start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=10 article-no= start-page=e95411 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Primary Lacrimal Sac Diffuse Large B-cell Lymphoma Treated With Local Radiotherapy Alone: A Case With No Relapse After 21 Years of Follow-Up en-subtitle= kn-subtitle= en-abstract= kn-abstract=Primary lacrimal sac lymphoma is rare and diagnosed as diffuse large B-cell lymphoma in a predominant histopathological type. Systemic chemotherapy would be the standard of care, but local radiotherapy may be a treatment option toward a localized lesion. The present patient is a 54-year-old otherwise healthy woman with a right lacrimal sac mass, which was proven by excisional biopsy to be diffuse large B-cell lymphoma. Since she did not have any other systemic lesions on gallium scintigraphy and neck-to-abdominal computed tomography scans, which were the standard procedure at that time, she underwent local radiotherapy at 40 Gy. Two years later, at the age of 56 years, she developed radiation retinopathy with macular edema in the right eye and had spotty laser photocoagulation in the nasal half of the fundus. At the age of 57 years, she developed radiation cataract and underwent cataract surgery with intraocular lens implantation in the right eye. At the age of 58 years, the macular edema in the right eye became worse and remained active, resulting in poor visual acuity of 0.1. She thus underwent 25-gauge vitrectomy in the right eye to peel off the adhering posterior vitreous surface, together with the internal limiting membrane, as the standard procedure at that time. The visual acuity in the right eye was elevated to 0.6. She maintained the visual acuity afterward and had no relapse of lymphoma in 21 years from the diagnosis of primary right lacrimal sac diffuse large B-cell lymphoma. Local radiotherapy would still be a treatment option for localized lymphoma lesions such as primary lacrimal sac lymphoma. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakemotoMitsuhiro en-aut-sei=Takemoto en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Healthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Radiotherapy, Himeji Red Cross Hospital kn-affil= en-keyword=diffuse large b-cell lymphoma kn-keyword=diffuse large b-cell lymphoma en-keyword=excisional biopsy kn-keyword=excisional biopsy en-keyword=lacrimal sac kn-keyword=lacrimal sac en-keyword=laser photocoagulation kn-keyword=laser photocoagulation en-keyword=macular edema kn-keyword=macular edema en-keyword=pathology kn-keyword=pathology en-keyword=radiation cataract kn-keyword=radiation cataract en-keyword=radiation retinopathy kn-keyword=radiation retinopathy en-keyword=radiotherapy kn-keyword=radiotherapy en-keyword=vitrectomy kn-keyword=vitrectomy END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251014 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparative analysis of interactions between five strains of Pseudomonas syringae pv. tabaci and Nicotiana benthamiana en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pseudomonas syringae pv. tabaci 6605 (Pta 6605), the agent of wildfire disease in tobacco, has been used as a model strain for elucidating the virulence mechanisms of Pta. However, the host genes involved in resistance or susceptibility to Pta remain largely unknown. Nicotiana benthamiana is a model plant species in the Solanaceae family and is useful in functional analyses of genes. We herein compared five Pta strains (6605, 6823, 7372, 7375, and 7380) in terms of their phenotypes on medium and interactions with N. benthamiana. Pta 6605 and Pta 6823 showed more active proliferation than the other strains in a high cell density culture. Moreover, Pta 6605 exhibited markedly higher swarming motility than the other strains. In inoculated leaves of N. benthamiana, Pta 6605 and Pta 6823 caused more severe disease symptoms and proliferated to a higher cell density than the other strains. However, Pta 6823 as well as Pta 7372 and Pta 7380 induced the high accumulation of salicylic acid (SA). Moreover, the inoculations of Pta 6823 and Pta 7372 resulted in the upregulation of ethylene biosynthesis genes. On the other hand, Pta 6605 induced neither SA accumulation nor the expression of ethylene biosynthesis genes, and suppressed the expression of jasmonate biosynthesis genes. Moreover, chlorosis was clearly induced in the upper uninoculated leaves of Pta 6605-infected plants. These results suggest that Pta 6605 escapes from or suppresses plant immune systems and, thus, is the most virulent on N. benthamiana among the five strains tested. en-copyright= kn-copyright= en-aut-name=NakaoYuna en-aut-sei=Nakao en-aut-mei=Yuna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsaiShuta en-aut-sei=Asai en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuiHidenori en-aut-sei=Matsui en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IchinoseYuki en-aut-sei=Ichinose en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatouShinpei en-aut-sei=Katou en-aut-mei=Shinpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Science and Technology, Shinshu University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Science and Technology, Shinshu University kn-affil= en-keyword=Chlorosis kn-keyword=Chlorosis en-keyword=Nicotiana benthamiana kn-keyword=Nicotiana benthamiana en-keyword=Phytohormones kn-keyword=Phytohormones en-keyword=Pseudomonas syringae pv. tabaci kn-keyword=Pseudomonas syringae pv. tabaci END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=20 article-no= start-page=10072 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251016 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neurofibromin Encoded by the Neurofibromatosis Type 1 (NF1) Gene Promotes the Membrane Translocation of SPRED2, Thereby Inhibiting the ERK Pathway in Breast Cancer Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neurofibromin (NF) inhibits the RAS/RAF/ERK pathway through its interaction with SPRED1 (Sprouty-related EVH1 domain-containing protein 1). Here, we investigated the functional relationship between NF and SPRED2 in breast cancer (BC). Human BC cell lines were transfected to downregulate or overexpress NF and SPRED2 and subsequently subjected to functional assays. Protein and mRNA levels were analyzed by Western blotting and RT-qPCR, respectively. Protein?protein interactions were examined by immunoprecipitation. Database analyses and immunohistochemistry (IHC) of BC tissues were performed to validate the in vitro findings. Downregulating NF or SPRED2 expression in BC cells enhanced cell proliferation, migration and invasion accompanied by RAF/ERK activation, whereas overexpression produced opposite effects. NF formed a protein complex with SPRED2 and facilitated its translocation to the plasma membrane. By IHC, SPRED2 membrane localization was absent in NF-negative luminal A and triple-negative BC (TNBC) but present in a subset of luminal A BC. By database analyses, both NF1 and SPRED2 mRNA levels were reduced in BC tissues, and luminal A BC patients with high expression of both NF1 and SPRED2 mRNA exhibited improved relapse-free survival. These results suggest a critical role for the NF?SPRED2 axis in BC progression and highlight it as a potential therapeutic target. en-copyright= kn-copyright= en-aut-name=Su PwintNang Thee en-aut-sei=Su Pwint en-aut-mei=Nang Thee kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiChunning en-aut-sei=Li en-aut-mei=Chunning kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GaoTong en-aut-sei=Gao en-aut-mei=Tong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangYuze en-aut-sei=Wang en-aut-mei=Yuze kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=SPRED2 kn-keyword=SPRED2 en-keyword=neurofibromatosis type 1 kn-keyword=neurofibromatosis type 1 en-keyword=neurofibromin kn-keyword=neurofibromin en-keyword=RAS/RAF/ERK kn-keyword=RAS/RAF/ERK END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251017 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ATPase copper transporting beta contributes to cisplatin resistance as a regulatory factor of extracellular vesicles in head and neck squamous cell carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cisplatin (CDDP) resistance remains a major clinical challenge in the treatment of head and neck squamous cell carcinoma (HNSC). Our group identified ATPase copper transporting beta (ATP7B) as a mediator of CDDP resistance through its role in drug efflux and small extracellular vesicle (sEV) secretion. Herein, we uncovered a novel mechanism by which ATP7B regulates sEV dynamics and the intercellular transmission of CDDP resistance. Using transcriptomic analyses of HNSC datasets, we demonstrate that ATP7B expression correlates with endocytosis- and epithelial-mesenchymal transition (EMT)-related gene sets and with elevated levels of EV-associated proteins. CDDP-resistant HNSC cells exhibited upregulated ATP7B, Rab5/Rab7, and preferentially secreted HSP90- and EpCAM-rich sEVs. These sEVs were leading to increased ATP7B expression and reduced CDDP sensitivity in recipient cells. A pharmacological inhibition of sEV biogenesis with GW4869 suppressed ATP7B and Atox1 expressions, inhibited late endosome maturation, and significantly enhanced CDDP-induced apoptosis in HNSC cells. In vivo, GW4869 reduced the sEV protein content and ATP7B expression in xenograft tumors. These findings establish that ATP7B is a critical modulator of sEV cargo and resistance propagation. Our results highlight a previously unrecognized ATP7B?sEV axis driving chemoresistance and identify sEV inhibition as a promising strategy to overcome therapeutic failure in HNSC. en-copyright= kn-copyright= en-aut-name=OgawaTatsuo en-aut-sei=Ogawa en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnoKisho en-aut-sei=Ono en-aut-mei=Kisho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RyumonShoji en-aut-sei=Ryumon en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoKohei en-aut-sei=Sato en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UmemoriKoki en-aut-sei=Umemori en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaKunihiro en-aut-sei=Yoshida en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ObataKyoichi en-aut-sei=Obata en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KunisadaYuki en-aut-sei=Kunisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkuiTatsuo en-aut-sei=Okui en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OkamotoKuniaki en-aut-sei=Okamoto en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Momen-HeraviFatemeh en-aut-sei=Momen-Heravi en-aut-mei=Fatemeh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=11 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Orofacial Sciences, School of Dentistry, University of California San Francisco kn-affil= affil-num=14 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=399 end-page=404 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Epstein-Barr Virus-Associated Early Gastric Carcinoma with Lymphoid Stroma Mimicking a Submucosal Tumor: A Typical Case Diagnosed by Endoscopic Resection and Treated by Local Resection with Sentinel Node Navigation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gastric cancer with lymphoid stroma (GCLS) accounts for 1%-7% of gastric cancers; ~80% are Epstein-Barr virus (EBV)-positive. The rate of lymph node metastasis is relatively low, even when an early GCLS has invaded the submucosa. We report an early GCLS with massive submucosal invasion mimicking a submucosal tumor (SMT), diagnosed by endoscopic submucosal resection (ESD) and treated with local resection and sentinel node navigation surgery (SNNS). The patient was a 40-year-old Japanese man. A protruding lesion on the greater curvature of the middle part of his stomach was detected by X-ray, and an endoscopic examination revealed a 2.5-cm protruding tumor covered with a normal mucosa and small ulcers at the apex. ESD was performed for a diagnosis. The pathological diagnosis was lymphoepithelioma-like gastric cancer (GCLS), pT1b(SM2), Ly0, V0, pHM1, pVM1. EBV infection in the cancer cells was confirmed pathologically by EBV-encoded RNA. The local resection was performed using SNNS. The patient has had no recurrence or post-gastrectomy syndrome 4 years postsurgery. EBV-associated early GCLS resembling an SMT is relatively rare, and clinicians need to be aware of this disease. Local resection using SNNS may be a surgical option for GCLS cases with a low rate of lymphatic metastasis. en-copyright= kn-copyright= en-aut-name=IsozakiHiroshi en-aut-sei=Isozaki en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoSasau en-aut-sei=Matsumoto en-aut-mei=Sasau kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakamaTakehiro en-aut-sei=Takama en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IsozakiYuka en-aut-sei=Isozaki en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiShigeki en-aut-sei=Murakami en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=2 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=3 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=4 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, Oomoto Hospital kn-affil= en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=gastric cancer with lymphoid stroma kn-keyword=gastric cancer with lymphoid stroma en-keyword=lymphoepithelioma-like carcinoma kn-keyword=lymphoepithelioma-like carcinoma en-keyword=Epstein Barr virus kn-keyword=Epstein Barr virus en-keyword=sentinel node navigation surgery kn-keyword=sentinel node navigation surgery END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=381 end-page=385 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immunoglobulin G4-related Disease Mimicking Portal Vein Tumor Thrombus en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report the case of a 72-year-old Japanese man with an incidental portal vein mass that was surgically resected and diagnosed as immunoglobulin G4 (IgG4)-related disease. The mass was discovered during an atrial fibrillation examination. The patient had a history of gastric cancer and was also diagnosed with rectal cancer, raising concerns about metastasis. Due to technical challenges, a biopsy was not feasible. Imaging findings suggested portal vein tumor thrombosis, complicating the diagnosis. This case highlights a rare presentation of IgG4-related disease mimicking portal vein tumor thrombus. en-copyright= kn-copyright= en-aut-name=SakuraiAtsunobu en-aut-sei=Sakurai en-aut-mei=Atsunobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YabukiTakayuki en-aut-sei=Yabuki en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AokiHideki en-aut-sei=Aoki en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IsekiAkiko en-aut-sei=Iseki en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Radiology, NHO Iwakuni Clinical Center kn-affil= affil-num=2 en-affil=Department of Radiology, NHO Iwakuni Clinical Center kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, NHO Iwakuni Clinical Center kn-affil= affil-num=4 en-affil=Department of Pathology, NHO Iwakuni Clinical Center kn-affil= en-keyword=immunoglobulin G4-related disease kn-keyword=immunoglobulin G4-related disease en-keyword=inflammatory pseudotumor kn-keyword=inflammatory pseudotumor en-keyword=mass kn-keyword=mass en-keyword=portal vein kn-keyword=portal vein en-keyword=pericarditis kn-keyword=pericarditis END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=2 article-no= start-page=1 end-page=13 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Advancements in systemic therapy for muscle-invasive bladder cancer: A systematic review from the beginning to the latest updates en-subtitle= kn-subtitle= en-abstract= kn-abstract=Context: Several phase III randomized controlled trials (RCTs) have shown the importance of perioperative systemic therapy, especially for the efficacy of immune checkpoint inhibitors (ICIs) in both neoadjuvant and adjuvant settings for muscle-invasive bladder cancer (MIBC).
Objective: To synthesize the growing evidence on the efficacy and safety of systemic therapies for MIBC utilizing the data from RCTs.
Evidence acquisition: Three databases and ClinicalTrials.gov were searched in October 2024 for eligible RCTs evaluating oncologic outcomes in MIBC patients treated with systemic therapy. We evaluated pathological complete response (pCR), disease-free survival (DFS), progression-free survival (PFS), event-free survival (EFS), overall survival (OS), and adverse events (AEs).
Evidence synthesis: Thirty-three RCTs (including 14 ongoing trials) were included in this systematic review. Neoadjuvant chemotherapy improved OS compared to radical cystectomy alone. Particularly, the VESPER trial demonstrated that dd-MVAC provided oncological benefits over GC alone in terms of pCR rates, OS (HR: 0.71), and PFS (HR: 0.70). Recently, the NIAGARA trial showed that perioperative durvalumab plus GC outperformed GC alone in terms of pCR rates, OS (HR: 0.75), and EFS (HR: 0.68). Despite the lack of data on overall AE rates in the VESPER trial, differential safety profiles in hematologic toxicity were reported between dd-MVAC and durvalumab plus GC regimens. In the adjuvant setting, no study provided the OS benefit from adjuvant chemotherapy. However, only adjuvant nivolumab had significant DFS and OS benefits compared to placebo.
Conclusions: Neoadjuvant chemotherapy remains the current standard of care for MIBC. Durvalumab shed light on the promising impact of ICIs added to neoadjuvant chemotherapy. Nivolumab is the only ICI recommended as adjuvant therapy in patients who harbored adverse pathologic outcomes. Ongoing trials will provide further information on the impact of combination therapy, including chemotherapy, ICIs, and enfortumab vedotin, in both neoadjuvant and adjuvant settings. en-copyright= kn-copyright= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TeohJeremy Yuen-Chun en-aut-sei=Teoh en-aut-mei=Jeremy Yuen-Chun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriKeiichiro en-aut-sei=Mori en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=RajwaPawe? en-aut-sei=Rajwa en-aut-mei=Pawe? kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=QuhalFahad en-aut-sei=Quhal en-aut-mei=Fahad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=PradereBenjamin en-aut-sei=Pradere en-aut-mei=Benjamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MoschiniMarco en-aut-sei=Moschini en-aut-mei=Marco kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShariatShahrokh F. en-aut-sei=Shariat en-aut-mei=Shahrokh F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MikiJun en-aut-sei=Miki en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KimuraTakahiro en-aut-sei=Kimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=3 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=4 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=8 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=9 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=10 en-affil=Department of Urology, San Raffaele Hospital and Scientific Institute kn-affil= affil-num=11 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=12 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=13 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= en-keyword=immune checkpoint inhibitors kn-keyword=immune checkpoint inhibitors en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=urothelial carcinoma kn-keyword=urothelial carcinoma en-keyword=muscle-invasive kn-keyword=muscle-invasive en-keyword=neoadjuvant kn-keyword=neoadjuvant en-keyword=adjuvant kn-keyword=adjuvant END start-ver=1.4 cd-journal=joma no-vol=39 cd-vols= no-issue=5 article-no= start-page=2787 end-page=2793 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Accuracy of Contrast-enhanced CT in Diagnosing Small-sized cT3a Renal Cell Carcinoma and Analysis of Factors Predicting Downstaging to pT1 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: This study assessed the accuracy of preoperative contrast-enhanced computed tomography (CECT) scans in staging small-sized, locally advanced (cT3a) renal cell carcinoma (RCC) and identified predictors of pathological downstaging following surgery.
Patients and Methods: Seventy-six patients who underwent radical nephrectomy for cT3aN0M0 RCC with tumors ?7 cm were analyzed. Preoperative CECT evaluated features such as venous, peritumoral, or renal sinus fat, and urinary tract invasion, predictive values, and concordance index between radiological and pathological findings were calculated for these categories. The study also examined the impact of clinicopathologic factors on downstaging.
Results: Of 76 patients with cT3 RCC, 37% were down-staged to pT1. Down-staged cases had a higher proportion of male patients and non-clear cell carcinoma (86% vs. 58%, 32% vs. 6%; p=0.02, p=0.007, respectively). Multiple cT3a factors were less common in down-staged cases (4% vs. 23%, p=0.04). Non-clear cell carcinoma was significantly associated with downstaging compared to clear cell carcinoma (75% vs. 30%, p=0.006). Multivariate analysis confirmed non-clear cell carcinoma as an independent predictor (odds ratio=8.2, p=0.01). For venous invasion, CECT sensitivity and positive predictive value were high (73.5% and 83.3%, respectively) and the degree of agreement was substantial (=0.62).
Conclusion: The accuracy of preoperative CECT was acceptable for detecting venous invasion. The downstaging to pT1 occurred in 37% of cT3a RCC cases in the final pathology, with non-clear cell carcinoma being a significant predictor.
en-copyright= kn-copyright= en-aut-name=BEKKUKENSUKE en-aut-sei=BEKKU en-aut-mei=KENSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YOSHINAGAKASUMI en-aut-sei=YOSHINAGA en-aut-mei=KASUMI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=INOUESHOTA en-aut-sei=INOUE en-aut-mei=SHOTA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MITSUIYOSUKE en-aut-sei=MITSUI en-aut-mei=YOSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YAMANOITOMOAKI en-aut-sei=YAMANOI en-aut-mei=TOMOAKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KAWADATATSUSHI en-aut-sei=KAWADA en-aut-mei=TATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TOMINAGAYUSUKE en-aut-sei=TOMINAGA en-aut-mei=YUSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SADAHIRATAKUYA en-aut-sei=SADAHIRA en-aut-mei=TAKUYA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KATAYAMASATOSHI en-aut-sei=KATAYAMA en-aut-mei=SATOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IWATATAKEHIRO en-aut-sei=IWATA en-aut-mei=TAKEHIRO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NISHIMURASHINGO en-aut-sei=NISHIMURA en-aut-mei=SHINGO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=EDAMURAKOHEI en-aut-sei=EDAMURA en-aut-mei=KOHEI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KOBAYASHITOMOKO en-aut-sei=KOBAYASHI en-aut-mei=TOMOKO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ARAKIMOTOO en-aut-sei=ARAKI en-aut-mei=MOTOO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Contrast?enhanced CT kn-keyword=Contrast?enhanced CT en-keyword=renal cell carcinoma kn-keyword=renal cell carcinoma en-keyword=staging kn-keyword=staging en-keyword=T3a kn-keyword=T3a en-keyword=downstaging kn-keyword=downstaging END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=20 article-no= start-page=2979 end-page=2984 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251015 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Two Cases of Esophageal Mucosal Damage Observed after Peroral Endoscopic Myotomy for Esophageal Motility Disorders en-subtitle= kn-subtitle= en-abstract= kn-abstract=This report presents two cases of esophageal mucosal damage following peroral endoscopic myotomy (POEM) for esophageal motility disorders. In the first case, delayed perforation and mediastinitis occurred on postoperative day 15 and the patient was treated with endoscopic clipping and antibiotics. In the second case, although no perforation was observed, extensive mucosal injury developed the day after POEM which was successfully managed by fasting and antibiotic therapy. These findings highlight the need for careful patient management to minimize the risks associated with POEM, while maximizing its therapeutic benefits. en-copyright= kn-copyright= en-aut-name=HirataShoichiro en-aut-sei=Hirata en-aut-mei=Shoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KamioTomohiro en-aut-sei=Kamio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatomiTakuya en-aut-sei=Satomi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HamadaKenta en-aut-sei=Hamada en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakaeHiroyuki en-aut-sei=Sakae en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ManabeNoriaki en-aut-sei=Manabe en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=esophagogastroduodenoscopy kn-keyword=esophagogastroduodenoscopy en-keyword=hypercontractile esophagus kn-keyword=hypercontractile esophagus en-keyword=jackhammer esophagus kn-keyword=jackhammer esophagus en-keyword=peroral endoscopic myotomy kn-keyword=peroral endoscopic myotomy END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=34964 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251007 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Periodontitis associated with Porphyromonas gingivalis infection is a risk factor for infertility through uterine hypertrophy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Periodontitis has recently been recognized as a potential risk factor for infertility due to its adverse effect on conception, although the underlying mechanisms remain unclear. This study investigated serum IgG antibody titers against periodontopathogenic bacteria in women with unexplained infertility and investigated how periodontal inflammation affects pregnancy and uterine function using a ligature-induced periodontitis mouse model infected with Porphyromonas gingivalis (Pg). IgG antibody titers against seven periodontopathogenic bacteria strains were measured by ELISA in 76 spontaneously pregnant women and 70 women undergoing infertility treatment. In the in vivo study, periodontitis mice were bred four weeks after periodontitis induction. Birth numbers, newborn weights, and gestation periods were assessed. To evaluate periodontal inflammation, alveolar bone, serum, and uterus was collected before mating. Uterine tissue was evaluated through histological and immunohistochemical staining. Women receiving infertility treatment were significantly older and had higher IgG titers against three Pg strains. Periodontitis mice had fewer births, lower newborn weights, and increased uterine cross-sectional areas. Additionally, elevated estrogen receptor and progesterone receptor expression levels were observed in endometrial and stromal tissues. These results suggest that periodontitis may cause uterine hypertrophy and hormone receptor changes, potentially impairing pregnancy. en-copyright= kn-copyright= en-aut-name=Kamei-NagataChiaki en-aut-sei=Kamei-Nagata en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakoHidefumi en-aut-sei=Sako en-aut-mei=Hidefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakaidaKyosuke en-aut-sei=Sakaida en-aut-mei=Kyosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakayamaMasa-aki en-aut-sei=Nakayama en-aut-mei=Masa-aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MandaiHiroki en-aut-sei=Mandai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Kubota-TakamoriMoyuka en-aut-sei=Kubota-Takamori en-aut-mei=Moyuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KiyamaFumiko en-aut-sei=Kiyama en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HiraiKimito en-aut-sei=Hirai en-aut-mei=Kimito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IkedaAtsushi en-aut-sei=Ikeda en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Takeuchi-HatanakaKazu en-aut-sei=Takeuchi-Hatanaka en-aut-mei=Kazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=Tai-TokuzenMasako en-aut-sei=Tai-Tokuzen en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SakamotoAi en-aut-sei=Sakamoto en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KiyokawaMachiko en-aut-sei=Kiyokawa en-aut-mei=Machiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YamanishiTomomi en-aut-sei=Yamanishi en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OdaTakashi en-aut-sei=Oda en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TakigawaMasayuki en-aut-sei=Takigawa en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MiyakeTakahito en-aut-sei=Miyake en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science kn-affil= affil-num=8 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=16 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=17 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=18 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=19 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=20 en-affil=Miyake Hello Dental Clinic, Pediatric Dentistry and Orthodontics kn-affil= affil-num=21 en-affil=The Center for Graduate Medical Education (Dental Division), Okayama University Hospital kn-affil= affil-num=22 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=23 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Infertility kn-keyword=Infertility en-keyword=Periodontitis kn-keyword=Periodontitis en-keyword=Porphyromonas gingivalis kn-keyword=Porphyromonas gingivalis en-keyword=Chronic inflammation kn-keyword=Chronic inflammation en-keyword=Uterus kn-keyword=Uterus en-keyword=Sex hormone receptor kn-keyword=Sex hormone receptor END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=4 article-no= start-page=51 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250930 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cancer-associated fibroblast-derived SOD3 enhances lymphangiogenesis to drive metastasis in lung adenocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Despite advancements in diagnostic and therapeutic strategies, lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality due to its aggressive metastatic potential. Extracellular superoxide dismutase (SOD3) is an antioxidant enzyme that regulates oxidative stress and is regarded as a tumor suppressor. However, studies have demonstrated that SOD3 can either promote or inhibit cell proliferation and survival in various cancers, and its molecular mechanisms within the tumor microenvironment are poorly understood. In this study, we report a breakthrough in uncovering the role of SOD3 derived from cancer-associated fibroblasts (CAFs) in LUAD. Using LUAD xenograft models co-implanted with SOD3-overexpressing CAFs (CAFSOD3), we observe an aggressive tumor phenotype characterized by increased lymphangiogenesis and lymphatic vessel invasion (LVI) of the tumor. Additionally, LUAD patients with elevated SOD3 levels exhibit a higher incidence of LVI and metastasis. Notably, RNA sequencing of CAFSOD3 reveals that SOD3-mediated VEGF-dependent tumor progression and lymphangiogenesis are up-regulated. Furthermore, single-cell transcriptomic analysis of LUAD clinical samples confirms a strong correlation between SOD3 expression in fibroblasts and characteristics of tumor exacerbation, such as lymphangiogenesis and metastasis. These findings underscore new insights into the role of CAF-derived SOD3 in LUAD progression and highlight its potential as a biomarker and therapeutic target. en-copyright= kn-copyright= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HikitaTakao en-aut-sei=Hikita en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MashimaTomoha en-aut-sei=Mashima en-aut-mei=Tomoha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TorigataKosuke en-aut-sei=Torigata en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ThuYin Min en-aut-sei=Thu en-aut-mei=Yin Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HabuTomohiro en-aut-sei=Habu en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItoSachio en-aut-sei=Ito en-aut-mei=Sachio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakayamaMasanori en-aut-sei=Nakayama en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=School of Medicine, Kobe University kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Thoracic Surgery, National Hospital Organization, Shikoku Cancer Center kn-affil= affil-num=13 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Cancer-associated fibroblast kn-keyword=Cancer-associated fibroblast en-keyword=Superoxide dismutase 3 kn-keyword=Superoxide dismutase 3 en-keyword=Lymphangiogenesis kn-keyword=Lymphangiogenesis en-keyword=Angiogenesis kn-keyword=Angiogenesis en-keyword=Metastasis kn-keyword=Metastasis en-keyword=Lung adenocarcinoma kn-keyword=Lung adenocarcinoma END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=19 article-no= start-page=9347 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: From Sarcomere to Clinic en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease characterized by unexplained left ventricular hypertrophy, often resulting from pathogenic variants of sarcomeric protein genes. Conventional treatments, such as the use of beta blockers or calcium channel blockers, focus on symptomatic control but do not address the underlying hypercontractility at the sarcomere level. Recent advances in molecular understanding have led to the development of cardiac myosin inhibitors that directly modulate sarcomeric function by reducing myosin?actin cross-bridge formation and adenosine triphosphatase (ATPase) activity. Mavacamten and aficamten have shown promising results in phase 2 and 3 clinical trials, improving symptoms, exercise capacity, and left ventricular outflow tract gradients in patients with obstructive HCM. This review summarizes the current understanding of HCM pathophysiology, diagnostic strategies, and conventional treatments with a focus on the mechanisms of action of myosin inhibitors, clinical evidence supporting their use, and future directions for improvement. We also discuss their potential applications in non-obstructive HCM and the importance of precision medicine guided by genetic profiling. en-copyright= kn-copyright= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkumuraTakahiro en-aut-sei=Okumura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatoSeiya en-aut-sei=Kato en-aut-mei=Seiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OnoueKenji en-aut-sei=Onoue en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KuboToru en-aut-sei=Kubo en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KouzuHidemichi en-aut-sei=Kouzu en-aut-mei=Hidemichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YanoToshiyuki en-aut-sei=Yano en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InomataTakayuki en-aut-sei=Inomata en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Advanced Cardiovascular Therapeutics, Nagoya University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Division of Pathology, Saiseikai Fukuoka General Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Nara Medical University kn-affil= affil-num=5 en-affil=Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University kn-affil= affil-num=6 en-affil=Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine kn-affil= affil-num=7 en-affil=Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= en-keyword=hypertrophic cardiomyopathy kn-keyword=hypertrophic cardiomyopathy en-keyword=myosin inhibitors kn-keyword=myosin inhibitors en-keyword=sarcomere kn-keyword=sarcomere en-keyword=mavacamten kn-keyword=mavacamten en-keyword=aficamten kn-keyword=aficamten en-keyword=heart failure kn-keyword=heart failure END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=18 article-no= start-page=2927 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250911 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lacticaseibacillus rhamnosus Probio-M9 Alters the Gut Microbiota and Mitigates Pulmonary Hypertension in a Rat Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Intestinal microbiota plays an important role in the progression of pulmonary hypertension (PH). Colostrum-derived Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9) has shown protective effects against inflammation and remodeling. We investigated whether Probio-M9 supplementation could improve the pathology of PH. Methods: The monocrotaline (MCT)-induced PH model rats are created followed by Probio-M9 treatment. Microbiota and pathological analyses were performed to investigate the therapeutic effects of Probio-M9. Results: Probio-M9 significantly suppressed cardiovascular remodeling and reduced mortality in rats. Analysis of the fecal microbiota revealed that Probio-M9 significantly altered the gut microbiota of MCT model rats. Specifically, Alistipes sp009774895 and Duncaniella muris populations increased, whereas Limosilactobacillus reuteri_D, Ligilactobacillus apodeme and Monoglobus sp900542675 decreased compared to those in the MCT group. Focusing on the expression of GPNMB in macrophages and the localization of CD44, we found that the number of these cells increased in the MCT group but significantly decreased with Probio-M9 treatment. In lung tissue from PH patients, more GPNMB-positive macrophages were found than non-PH lungs, and an increase in CD44-positive cells was confirmed in the vicinity of GPNMB. Conclusions: Probio-M9 had a significant impact on the intestinal microbiota and GPNMB/CD44 positive cells in the lungs of PH rats. en-copyright= kn-copyright= en-aut-name=ZhaoZhixin en-aut-sei=Zhao en-aut-mei=Zhixin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiGaopeng en-aut-sei=Li en-aut-mei=Gaopeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhmichiKiyomi en-aut-sei=Ohmichi en-aut-mei=Kiyomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LiXiaodong en-aut-sei=Li en-aut-mei=Xiaodong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZhaoFeiyan en-aut-sei=Zhao en-aut-mei=Feiyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshikawaKaori en-aut-sei=Ishikawa en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshikawaRyou en-aut-sei=Ishikawa en-aut-mei=Ryou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YokotaNaoya en-aut-sei=Yokota en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SunZhihong en-aut-sei=Sun en-aut-mei=Zhihong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KuraharaLin Hai en-aut-sei=Kurahara en-aut-mei=Lin Hai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=3 en-affil=Department of Diagnostic Pathology, Kagawa University Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=5 en-affil=Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University kn-affil= affil-num=6 en-affil=Department of General Medicine, Kagawa University Hospital kn-affil= affil-num=7 en-affil=Department of Diagnostic Pathology, Kagawa University Hospital kn-affil= affil-num=8 en-affil=Center for Advanced Heart Failure, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University kn-affil= affil-num=10 en-affil=Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University kn-affil= affil-num=11 en-affil=Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University kn-affil= en-keyword=pulmonary artery remodeling kn-keyword=pulmonary artery remodeling en-keyword=probiotics kn-keyword=probiotics en-keyword=gut microbiota kn-keyword=gut microbiota en-keyword=macrophages kn-keyword=macrophages en-keyword=GPNMB kn-keyword=GPNMB en-keyword=CD44 kn-keyword=CD44 END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=20056 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pharmacokinetics and the effectiveness of pyrogen-free bioabsorbable wet adhesives en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bioabsorbable materials are essential for advanced therapies, including surgical sealing, cell therapy, and drug delivery. Natural bioabsorbable materials, including collagen and hyaluronic acid, have better biocompatibility than synthetic bioabsorbable polymers; however, they are mainly derived from animals, presenting infection risks. Non-animal origin polymers have a lower molecular weight than those of animal origins. Their viscosity increases with increase in molecular weight, making endotoxin removal difficult. Here, using the phosphoryl chloride disposal method, we present a strategy for synthesizing pyrogen-free bioabsorbable adhesives with controlled molecular weight. Phosphopullulan, a polysaccharide derivative, had less than detectable endotoxin levels and controllable average molecular weight of approximately 300,000 to over 1,400,000. Furthermore, it is important to ensure the safety as well as efficacy of bio-implantable materials. We have evaluated the biosafety of polysaccharide derivatives we are developing, and have examined their cell phagocytosis and pharmacokinetics in vitro and in vivo, and have confirmed that they are safe. We have also evaluated their adhesion to wet tissue adhesions and confirmed that they leak less than existing materials. en-copyright= kn-copyright= en-aut-name=OshimaRisa en-aut-sei=Oshima en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshiharaKumiko en-aut-sei=Yoshihara en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanishiKo en-aut-sei=Nakanishi en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkasakaTsukasa en-aut-sei=Akasaka en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimojiShinji en-aut-sei=Shimoji en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraTeppei en-aut-sei=Nakamura en-aut-mei=Teppei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkiharaTakumi en-aut-sei=Okihara en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraMariko en-aut-sei=Nakamura en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TamadaIkkei en-aut-sei=Tamada en-aut-mei=Ikkei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=Van MeerbeekBart en-aut-sei=Van Meerbeek en-aut-mei=Bart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SugayaTsutomu en-aut-sei=Sugaya en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YoshidaYasuhiro en-aut-sei=Yoshida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Periodontology, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=4 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=5 en-affil=Department of Periodontology, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=6 en-affil=Department of Applied Veterinary Science, Faculty of Veterinary Medicine, Hokkaido University kn-affil= affil-num=7 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Department of Clinical Psychology, School of Clinical Psychology, Kyushu University of Medical and Science kn-affil= affil-num=9 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Plastic and Reconstructive Surgery, Tokyo Metropolitan Childrenfs Medical Center kn-affil= affil-num=11 en-affil=BIOMAT, Department of Oral Health Sciences, & UZ Leuven, Dentistry, KU Leuven kn-affil= affil-num=12 en-affil=Department of Periodontology, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=13 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= en-keyword=Phosphopullulan kn-keyword=Phosphopullulan en-keyword=Polysaccharide kn-keyword=Polysaccharide en-keyword=ADME kn-keyword=ADME en-keyword=Animal study kn-keyword=Animal study en-keyword=Endodontic sealer kn-keyword=Endodontic sealer END start-ver=1.4 cd-journal=joma no-vol=142 cd-vols= no-issue= article-no= start-page=104967 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cross-feeding between beneficial and pathogenic bacteria to utilize eukaryotic host cell-derived sialic acids and bacteriophages shape the pathogen-host interface milieu en-subtitle= kn-subtitle= en-abstract= kn-abstract=Under an inflamed-intestinal milieu, increased free sialic acids are associated with the overgrowth of some pathogenic bacterial strains. Recently, the protective immunomodulatory activity of gut bacteriophages (phages) has also been highlighted. However, the role of phages in triple reciprocal interactions between pathogenic bacteria, beneficial bacteria, and their host cell sialic acids has not been studied so far. We established a sialidase-explicit model in which beneficial and pathogenic bacteria interact through cross-feeding and competition for free sialic acid using a human triple co-culture cell model incorporating colonocytes (T84 cells), monocytes (THP-1 cells), and hepatocytes (Huh7 cells). Triple co-cultured cells were challenged with Gram-positive Bifidobacterium bifidum (B. bifidum) and Gram-negative Pseudomonas aeruginosa PAO1 (P. a PAO1) in the absence or presence of its KPP22 phage in two different cell culture mediums: 1) standard Dulbecco's Modified Eagle Medium (DMEM) and 2) DMEM with 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA). Changes in physiological, functional, and structural health markers of stimulated cocultured cells were evaluated. The concentrations of sialic acid and pro-inflammatory cytokines in the cell culture supernatants were quantified. P. a PAO1 triggered the release of interleukin 6 and 8 (IL-6 and IL-8), accompanied by increased levels of free sialic acid, reduced viability of co-cultured cells, and disrupted the integrity of the cellular monolayer. These disruptive effects were markedly attenuated by KPP22 phage and B. bifidum. In addition to well-documented differences in the structure and composition of the bacterial cell walls of Gram-negative pathogenic bacteria and bifidobacteria, two distinct factors seem to be pivotal in modulating the pathogen-host interface milieu: (i) the presence of phages and (ii) the utilization of free sialic acids secreted from host cells by bifidobacteria. en-copyright= kn-copyright= en-aut-name=GhadimiDarab en-aut-sei=Ghadimi en-aut-mei=Darab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=F?lster-HolstRegina en-aut-sei=F?lster-Holst en-aut-mei=Regina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Bl?merSophia en-aut-sei=Bl?mer en-aut-mei=Sophia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EbsenMichael en-aut-sei=Ebsen en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=R?ckenChristoph en-aut-sei=R?cken en-aut-mei=Christoph kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuzakiShigenobu en-aut-sei=Matsuzaki en-aut-mei=Shigenobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BockelmannWilhelm en-aut-sei=Bockelmann en-aut-mei=Wilhelm kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= affil-num=2 en-affil=Clinic of Dermatology, Venerology und Allergology, University Hospital Schleswig-Holstein kn-affil= affil-num=3 en-affil=Clinic of Dermatology, Venerology und Allergology, University Hospital Schleswig-Holstein kn-affil= affil-num=4 en-affil=St?dtisches MVZ Kiel GmbH (Kiel City Hospital), Department of Pathology kn-affil= affil-num=5 en-affil=Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein kn-affil= affil-num=6 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University kn-affil= affil-num=8 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= en-keyword=Bacterial sialidase kn-keyword=Bacterial sialidase en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Cytokines kn-keyword=Cytokines en-keyword=Infection kn-keyword=Infection en-keyword=Bifidobacteria kn-keyword=Bifidobacteria en-keyword=Phages kn-keyword=Phages END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=3 article-no= start-page=e70004 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oregon Wolfe barley genetic stocks ? Research and teaching tools for next generation scientists en-subtitle= kn-subtitle= en-abstract= kn-abstract=The Oregon Wolfe Barley (OWB) mapping population (Reg. no. MP-4, NSL 554937 MAP) is a resource for genetics research and instruction. The OWBs are a set of doubled haploid barley (Hordeum vulgare L.) lines developed at Oregon State University from the F1 of a cross between Dr. Robert Wolfe's dominant and recessive marker stocks. Exhibiting a high level of genetic and phenotypic diversity, the OWBs are used throughout the world as a research tool for barley genetics. To date, these endeavors have led to 56 peer-reviewed publications, as well as three reports in the Barley Genetics Newsletter. At the same time, the OWBs are widely used as an instructor resource at the K?12, undergraduate, graduate, and professional levels. They are currently used at universities and/or institutes in German, Italy, Norway, Spain, and the United States and are currently being developed further for educational use in other countries. Genotype and phenotype data, lesson plans, and seed availability information are available herein and online. en-copyright= kn-copyright= en-aut-name=KrauseMargaret R. en-aut-sei=Krause en-aut-mei=Margaret R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ArbelaezJuan David en-aut-sei=Arbelaez en-aut-mei=Juan David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Asdal?smund en-aut-sei=Asdal en-aut-mei=?smund kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BelkodjaRamzi en-aut-sei=Belkodja en-aut-mei=Ramzi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BouryNancy en-aut-sei=Boury en-aut-mei=Nancy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BlakeVictoria C. en-aut-sei=Blake en-aut-mei=Victoria C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BrownPatrick J. en-aut-sei=Brown en-aut-mei=Patrick J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CasasAna en-aut-sei=Casas en-aut-mei=Ana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Cistu?Luis en-aut-sei=Cistu? en-aut-mei=Luis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Farr?]Mart?nezAlba en-aut-sei=Farr?]Mart?nez en-aut-mei=Alba kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FiskScott en-aut-sei=Fisk en-aut-mei=Scott kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FuerstGregory S. en-aut-sei=Fuerst en-aut-mei=Gregory S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Gim?nezEstela en-aut-sei=Gim?nez en-aut-mei=Estela kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Guijarro]RealCarla en-aut-sei=Guijarro]Real en-aut-mei=Carla kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=GuthrieKaty en-aut-sei=Guthrie en-aut-mei=Katy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HalsteadMargaret en-aut-sei=Halstead en-aut-mei=Margaret kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HelgersonLaura en-aut-sei=Helgerson en-aut-mei=Laura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IgartuaErnesto en-aut-sei=Igartua en-aut-mei=Ernesto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=LillemoMorten en-aut-sei=Lillemo en-aut-mei=Morten kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=Mart?nez]Garc?aMarina en-aut-sei=Mart?nez]Garc?a en-aut-mei=Marina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=Mart?nez]Subir?Mariona en-aut-sei=Mart?nez]Subir? en-aut-mei=Mariona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=McCouchSusan en-aut-sei=McCouch en-aut-mei=Susan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=McGheeLaurie en-aut-sei=McGhee en-aut-mei=Laurie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=NickolsTravis en-aut-sei=Nickols en-aut-mei=Travis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=PetersNick en-aut-sei=Peters en-aut-mei=Nick kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=PorterRaymond en-aut-sei=Porter en-aut-mei=Raymond kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=RomagosaIgnacio en-aut-sei=Romagosa en-aut-mei=Ignacio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=RuudAnja Karine en-aut-sei=Ruud en-aut-mei=Anja Karine kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SatoKazuhiro en-aut-sei=Sato en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=SalviSilvio en-aut-sei=Salvi en-aut-mei=Silvio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=SangiorgiGiuseppe en-aut-sei=Sangiorgi en-aut-mei=Giuseppe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=Sch?llerRebekka en-aut-sei=Sch?ller en-aut-mei=Rebekka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=SenTaner Z. en-aut-sei=Sen en-aut-mei=Taner Z. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=SorianoJos? Miguel en-aut-sei=Soriano en-aut-mei=Jos? Miguel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=StuparRobert M. en-aut-sei=Stupar en-aut-mei=Robert M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=TingTo]Chia en-aut-sei=Ting en-aut-mei=To]Chia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=ViningKelly en-aut-sei=Vining en-aut-mei=Kelly kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=von KorffMaria en-aut-sei=von Korff en-aut-mei=Maria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=WallaAgatha en-aut-sei=Walla en-aut-mei=Agatha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=WangDiane R. en-aut-sei=Wang en-aut-mei=Diane R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=WaughRobbie en-aut-sei=Waugh en-aut-mei=Robbie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=WiseRoger P. en-aut-sei=Wise en-aut-mei=Roger P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=WolfeRobert en-aut-sei=Wolfe en-aut-mei=Robert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=YaoEric en-aut-sei=Yao en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=HayesPatrick M. en-aut-sei=Hayes en-aut-mei=Patrick M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= affil-num=1 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=2 en-affil=Department of Crop Sciences, University of Illinois at Urbana-Champaign kn-affil= affil-num=3 en-affil=Nordic Genetic Resource Centre kn-affil= affil-num=4 en-affil=CIHEAM-Zaragoza kn-affil= affil-num=5 en-affil=Department of Plant Pathology, Entomology, and Microbiology, Iowa State University kn-affil= affil-num=6 en-affil=Department of Plant Sciences and Plant Pathology, Montana State University kn-affil= affil-num=7 en-affil=Department of Plant Sciences, University of California-Davis kn-affil= affil-num=8 en-affil=Departamento de Gen?tica y Producci?n Vegetal, Estaci?n Experimental Aula Dei?CSIC kn-affil= affil-num=9 en-affil=Departamento de Gen?tica y Producci?n Vegetal, Estaci?n Experimental Aula Dei?CSIC kn-affil= affil-num=10 en-affil=AGROTECNIO-CERCA Center, Universidad de Lleida kn-affil= affil-num=11 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=12 en-affil=U.S. Department of Agriculture-Agricultural Research Service, Corn Insects and Crop Genetics Research Unit, Iowa State University kn-affil= affil-num=13 en-affil=Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Polit?cnica de Madrid kn-affil= affil-num=14 en-affil=Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Polit?cnica de Madrid kn-affil= affil-num=15 en-affil=Department of Agronomy and Plant Genetics, University of Minnesota kn-affil= affil-num=16 en-affil=Aardevo North America kn-affil= affil-num=17 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=18 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=19 en-affil=Departamento de Gen?tica y Producci?n Vegetal, Estaci?n Experimental Aula Dei?CSIC kn-affil= affil-num=20 en-affil=Department of Plant Sciences, Norwegian University of Life Sciences kn-affil= affil-num=21 en-affil=Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Polit?cnica de Madrid kn-affil= affil-num=22 en-affil=AGROTECNIO-CERCA Center, Universidad de Lleida kn-affil= affil-num=23 en-affil=Plant Breeding and Genetics Section, School of Integrative Plant Science, Cornell University kn-affil= affil-num=24 en-affil=Colfax-Mingo Community High School kn-affil= affil-num=25 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=26 en-affil=Department of Plant Pathology, Entomology, and Microbiology, Iowa State University kn-affil= affil-num=27 en-affil=Haupert Institute for Agricultural Studies, Huntington University kn-affil= affil-num=28 en-affil=AGROTECNIO-CERCA Center, Universidad de Lleida kn-affil= affil-num=29 en-affil=Department of Plant Sciences, Norwegian University of Life Sciences kn-affil= affil-num=30 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=31 en-affil=Department of Agricultural and Food Sciences, University of Bologna kn-affil= affil-num=32 en-affil=Department of Agricultural and Food Sciences, University of Bologna kn-affil= affil-num=33 en-affil=Department of Crop Sciences, University of Illinois at Urbana-Champaign kn-affil= affil-num=34 en-affil=Crop Improvement and Genetics Research Unit, U.S. Department of Agriculture-Agricultural Research Service kn-affil= affil-num=35 en-affil=AGROTECNIO-CERCA Center, Universidad de Lleida kn-affil= affil-num=36 en-affil=Department of Agronomy and Plant Genetics, University of Minnesota kn-affil= affil-num=37 en-affil=Agronomy Department, Purdue University kn-affil= affil-num=38 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=39 en-affil=Institute of Plant Genetics, Heinrich-Heine-Universit?t D?sseldorf kn-affil= affil-num=40 en-affil=Institute of Plant Genetics, Heinrich-Heine-Universit?t D?sseldorf kn-affil= affil-num=41 en-affil=Agronomy Department, Purdue University kn-affil= affil-num=42 en-affil=Division of Plant Sciences, School of Life Sciences, University of Dundee kn-affil= affil-num=43 en-affil=Department of Plant Pathology, Entomology, and Microbiology, Iowa State University kn-affil= affil-num=44 en-affil=Agriculture and Agri-Food Canada kn-affil= affil-num=45 en-affil=Crop Improvement and Genetics Research Unit, U.S. Department of Agriculture-Agricultural Research Service kn-affil= affil-num=46 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=1869 cd-vols= no-issue=12 article-no= start-page=130860 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250913 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The F54L mutation of Thioredoxin shows protein instability and increased fluctuations of the catalytic center en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thioredoxin is a ubiquitous redox protein that acts as an electron donor via its conserved dithiol motif (C32GPC35), catalyzing dithiol?disulfide exchange to regulate the redox state of target proteins. It supports antioxidant defense via peroxiredoxins, facilitates DNA synthesis by donating electrons to ribonucleotide reductase, and regulates redox-sensitive signaling pathways, including those controlling transcription and apoptosis. Neuronal degeneration and chronic kidney disease have been observed in Txn-F54L mutant rats; however, the details of why the Txn mutation causes these phenomena remain unknown. The present study aimed to elucidate the functional and structural changes caused by the F54L mutation. The Thioredoxin-F54L showed less insulin-reducing activity and more thermosensitivity to denaturation in the body temperature range compared to the wild type. The crystal structure revealed that F54 forms hydrophobic interactions with the surrounding hydrophobic amino acids. In addition, molecular dynamics simulation predicts increased fluctuations around the F54L mutation and a tendency for the distance between residues C32 and C35 at the catalytic center to be widened. The increased distance between residues C32 and C35 of the catalytic center may affect the reducing activity of the enzyme on the substrate. The finding that Thioredoxin-F54L is prone to denaturation at normal body temperature may reduce the normally functioning Thioredoxin. These molecular characteristics of Thioredoxin-F54L may be related to brain and kidney disease development in the Txn-F54L rats. en-copyright= kn-copyright= en-aut-name=BabaTakumi en-aut-sei=Baba en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UenoGo en-aut-sei=Ueno en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OheChika en-aut-sei=Ohe en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SajiShuku en-aut-sei=Saji en-aut-mei=Shuku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoSachiko en-aut-sei=Yamamoto en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoMasaki en-aut-sei=Yamamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakagawaHiroshi en-aut-sei=Nakagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkazakiNobuo en-aut-sei=Okazaki en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OuchidaMamoru en-aut-sei=Ouchida en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Kawasaki-OhmoriIori en-aut-sei=Kawasaki-Ohmori en-aut-mei=Iori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakeshitaKohei en-aut-sei=Takeshita en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=2 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=3 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=4 en-affil=Structural Biology Division, Japan Synchrotron Radiation Research Institute kn-affil= affil-num=5 en-affil=Structural Biology Division, Japan Synchrotron Radiation Research Institute kn-affil= affil-num=6 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=7 en-affil=Materials Sciences Research Center, Japan Atomic Energy Agency kn-affil= affil-num=8 en-affil=Neutron Science and Technology Center, Comprehensive Research Organization for Science and Society (CROSS) kn-affil= affil-num=9 en-affil=Department of Molecular Oncology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Section of Developmental Physiology and Pathology, Faculty of Education, Okayama University kn-affil= affil-num=11 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= en-keyword=Txn kn-keyword=Txn en-keyword=Thioredoxin kn-keyword=Thioredoxin en-keyword=Protein instability kn-keyword=Protein instability en-keyword=Thermosensitivity kn-keyword=Thermosensitivity en-keyword=Crystal structure kn-keyword=Crystal structure en-keyword=Molecular dynamics simulation kn-keyword=Molecular dynamics simulation END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250909 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=S100A8/A9-MCAM signaling promotes gastric cancer cell progression via ERK-c-Jun activation en-subtitle= kn-subtitle= en-abstract= kn-abstract=S100 protein family members S100A8 and S100A9 function primarily as a heterodimer complex (S100A8/A9) in vivo. This complex has been implicated in various cancers, including gastric cancer (GC). Recent studies suggest that these proteins play significant roles in tumor progression, inflammation, and metastasis. However, the exact mechanisms by which S100A8/A9 contributes to GC pathogenesis remain unclear. This study investigates the role of S100A8/A9 and its receptor in GC. Immunohistochemical analysis was performed on GC tissue samples to assess the expression of the S100A8/A9 receptor melanoma cell adhesion molecule (MCAM). In vitro transwell migration and invasion assays were used to evaluate the motility and invasiveness of GC cells. Cell proliferation was assessed using a growth assay, and Western blotting (WB) was employed to examine downstream signaling pathways, including ERK and the transcription factor c-Jun, in response to S100A8/A9?MCAM interaction. S100A8/A9 stimulation enhanced both proliferation and migration through MCAM binding in GC cell lines. These cellular events were accompanied by ERK activation and c-Jun induction. Downregulation of MCAM suppressed both ERK phosphorylation and c-Jun expression, highlighting the importance of the S100A8/A9?MCAM?ERK?c-Jun axis in promoting GC progression. These findings indicate that S100A8/A9 contributes to GC progression via MCAM, which activates the ERK?c-Jun pathway. The S100A8/A9?signaling axis may represent a novel therapeutic target in GC. en-copyright= kn-copyright= en-aut-name=ChenYouyi en-aut-sei=Chen en-aut-mei=Youyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YangXu en-aut-sei=Yang en-aut-mei=Xu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KinoshitaRie en-aut-sei=Kinoshita en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=PanBo en-aut-sei=Pan en-aut-mei=Bo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WuFangping en-aut-sei=Wu en-aut-mei=Fangping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhangXu en-aut-sei=Zhang en-aut-mei=Xu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SagayamaKazumi en-aut-sei=Sagayama en-aut-mei=Kazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SunBei en-aut-sei=Sun en-aut-mei=Bei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=2 en-affil=Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=3 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=6 en-affil=School of Pharmaceutical Sciences, Zhejiang Chinese Medical University kn-affil= affil-num=7 en-affil=Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=8 en-affil=Faculties of Educational and Research Management Field, Okayama University kn-affil= affil-num=9 en-affil=Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University kn-affil= affil-num=10 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Gastric cancer kn-keyword=Gastric cancer en-keyword=S100 protein kn-keyword=S100 protein en-keyword=MCAM kn-keyword=MCAM en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Metastasis kn-keyword=Metastasis END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=3 article-no= start-page=412 end-page=437 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biophysical regulation of extracellular matrix in systemic lupus erythematosus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by immune dysregulation and multi-organ damage. Recent advances have underscored the critical involvement of extracellular matrix (ECM) biophysical properties in shaping immune cell behavior and metabolic states that contribute to disease progression. This review systematically delineates the pathological remodeling of ECM biophysics in SLE, with a focus on their roles in mechanotransduction, immune-metabolic interplay, and organ-specific tissue injury. By integrating current evidence, we highlight how ECM-derived mechanical cues orchestrate aberrant immune responses and propose new perspectives for targeting ECM-immune crosstalk in the development of organ-specific, mechanism-based therapies for SLE. en-copyright= kn-copyright= en-aut-name=LiQiwei en-aut-sei=Li en-aut-mei=Qiwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiQiang en-aut-sei=Li en-aut-mei=Qiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=XiaoZhaoyang en-aut-sei=Xiao en-aut-mei=Zhaoyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NARUSEKeiji en-aut-sei=NARUSE en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiKen en-aut-sei=Takahashi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Anesthesiology, The Second Affiliated Hospital of Dalian Medical University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=systemic lupus erythematosus (SLE) kn-keyword=systemic lupus erythematosus (SLE) en-keyword=extracellular matrix (ECM) kn-keyword=extracellular matrix (ECM) en-keyword=mechanotransduction kn-keyword=mechanotransduction en-keyword=mechanism kn-keyword=mechanism en-keyword=immune regulation kn-keyword=immune regulation en-keyword=fibrosis kn-keyword=fibrosis en-keyword=organ-specific damage kn-keyword=organ-specific damage END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=17 article-no= start-page=6207 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250902 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of the Diagnostic Performance of the Brush/Biopsy Rapid On-Site Evaluation (B-ROSE) in Cases of Bile Duct Stricture: A Prospective, Pilot Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=settingsOrder Article Reprints Open AccessArticle Evaluation of the Diagnostic Performance of the Brush/Biopsy Rapid On-Site Evaluation (B-ROSE) in Cases of Bile Duct Stricture: A Prospective, Pilot Study by Nao Hattori 1,Daisuke Uchida 1,2,*,Kei Harada 1,Ryosuke Sato 1ORCID,Taisuke Obata 1,Akihiro Matsumi 1ORCID,Kazuya Miyamoto 1ORCID,Hiroyuki Terasawa 1ORCID,Yuki Fujii 1,Koichiro Tsutsumi 1ORCID,Shigeru Horiguchi 1,Kazuyuki Matsumoto 1ORCID andMotoyuki Otsuka 1 1 Department of Gastroenterology, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan 2 Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan * Author to whom correspondence should be addressed. J. Clin. Med. 2025, 14(17), 6207; https://doi.org/10.3390/jcm14176207 Submission received: 23 June 2025 / Revised: 21 August 2025 / Accepted: 26 August 2025 / Published: 2 September 2025 (This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine) Downloadkeyboard_arrow_down Browse Figures Versions Notes Abstract Background: Biliary strictures are diagnosed using endoscopic retrograde cholangiopancreatography (ERCP) with brush cytology and biopsy. However, brush cytology shows a sensitivity of 9?56.1% and a diagnostic accuracy of 43?65.4%, while biopsy demonstrates a sensitivity of 48%. Both methods exhibit high specificity but limited sensitivity. While rapid on-site evaluation (ROSE) is effective in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), its application in ERCP-obtained samples remains underexplored. Methods: This prospective pilot study was conducted at Okayama University Hospital from April 2019 to July 2024. Patients requiring ERCP-guided sampling for bile duct strictures were included. ROSE was applied to brush cytology with up to three additional attempts and to imprint cytology from biopsy samples with up to two attempts. Diagnostic accuracy was assessed based on pathology and clinical course. Results: Among 37 patients (median age: 73 years, add range, and male?female ratio: 27:10), 18 had hilar and 19 had distal bile duct strictures. Brush cytology required one, two, or three attempts in twenty-six, six, and five cases, respectively, whereas biopsy required one or two attempts in thirty-five and two cases, respectively. Among the thirty-seven cases, thirty-five were malignant and two were benign. The B-ROSE group showed a sensitivity, specificity, and accuracy of 71.4%, 100.0%, and 73.0%, respectively, compared to lower accuracy in the conventional group, where single brush cytology attempts yielded a sensitivity of 48.6% and an accuracy of 48.6%, and single biopsy attempts showed a sensitivity of 68.6% and an accuracy of 70.3%. Conclusions: B-ROSE improves diagnostic accuracy, reduces repeat sampling, and minimizes patient burden in ERCP-based diagnosis of bile duct strictures, making it a valuable addition to current diagnostic protocols. en-copyright= kn-copyright= en-aut-name=HattoriNao en-aut-sei=Hattori en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaKei en-aut-sei=Harada en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ObataTaisuke en-aut-sei=Obata en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumiAkihiro en-aut-sei=Matsumi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyamotoKazuya en-aut-sei=Miyamoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TerasawaHiroyuki en-aut-sei=Terasawa en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= en-keyword=bile duct stricture kn-keyword=bile duct stricture en-keyword=ERCP (endoscopic retrograde cholangiopancreatography) kn-keyword=ERCP (endoscopic retrograde cholangiopancreatography) en-keyword=rapid on-site evaluation (ROSE) kn-keyword=rapid on-site evaluation (ROSE) en-keyword=B-ROSE kn-keyword=B-ROSE END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250830 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pseudohypoxia induced by iron chelator activates tumor immune response in lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hypoxia-inducible factor (HIF) signaling plays a critical role in immune cell function. Pseudohypoxia is characterized as iron-mediated stabilization of HIF-1 under normoxic conditions, which can be induced by iron chelators. This study explored whether iron chelators exert antitumor effects by enhancing tumor immune responses and elucidating the underlying mechanisms. The iron chelators Super?polyphenol 10 (SP10) and Deferoxamine (DFO) were used to create iron-deficient and pseudohypoxia conditions. Pseudohypoxia induced by iron chelators stimulates IL-2 secretion from T cells and from both human and murine nonsmall cell lung cancer (NSCLC) cell lines (A549, PC-3, and LLC). Administration of SP10 reduced tumor growth when LLC tumors were implanted in C57BL/6 mice; however, this was not observed in immunodeficient RAG1-deficient C57BL/6 mice. SP10 itself did not directly inhibit LLC cells proliferation in vitro, suggesting an activation of the tumor immune response. SP10 synergistically enhanced the efficacy of PD-1 antibody therapy in lung cancer by increasing the number of tumor-infiltrating lymphocytes (TILs). In conclusion, iron chelation-induced pseudohypoxia activates tumor immune responses by directly upregulating HIF-1, augmenting T cell function, and inducing IL-2 secretion from T cells, and cancer cells, thereby amplifying the immune efficacy of the PD-1 antibody in lung cancer treatment. en-copyright= kn-copyright= en-aut-name=HamadaYusuke en-aut-sei=Hamada en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChenYuehua en-aut-sei=Chen en-aut-mei=Yuehua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TeradaManato en-aut-sei=Terada en-aut-mei=Manato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangYuze en-aut-sei=Wang en-aut-mei=Yuze kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=iron kn-keyword=iron en-keyword=hypoxia-inducible factor kn-keyword=hypoxia-inducible factor en-keyword=immune checkpoint inhibitors kn-keyword=immune checkpoint inhibitors END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=27047 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prevalence of Streptococcus mutans harboring the cnm gene encoding cell surface protein Cnm in Japanese children en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dental caries is a highly prevalent infectious disease primarily caused by the pathogenic bacterium Streptococcus mutans, which has also been associated with systemic disease. A 120-kDa collagen-binding protein (Cnm) produced by S. mutans contributes to cardiovascular disease pathogenicity. Few studies have addressed the current prevalence of S. mutans and the cnm gene in Japanese children or examined caries pathology in relation to cnm presence. Here, we investigated the prevalence of S. mutans and the distribution of cnm-positive S. mutans among 490 children who visited two university hospitals in Japan. The caries experience index (dmft/DMFT) was calculated, and the collagen-binding ability of cnm-positive S. mutans strains was assessed. S. mutans was isolated from the oral cavities of 158 patients (36.8%); 10.1% (16/158) harbored cnm-positive S. mutans. When caries experience indices were compared across dentitions, patients harboring cnm-positive strains had significantly higher dmft/DMFT scores than those with cnm-negative strains (P? Methods: Between June 2019 and April 2024, 119 samples of 22G EUS-TA collected for F1CDx testing at Himeji Red Cross Hospital were retrospectively reviewed. Tissue adequacy was only assessed based on tumor cell percentage (?20%). The procedure stopped when white tissue fragments reached 20 mm during macroscopic on-site evaluation. The specimens were prepared using both etissue preserving sectioningf to retain tissue within formalin-fixed paraffin-embedded blocks and the ethin sectioning matched needle gauge and tissue lengthf method with calculation to ensure minimal unstained slides for the 1 mm3 sample volume criterion. Tissue area from HE slides and sample volume were measured, and F1CDx reports were analyzed.
Results: Of 119 samples, 108 (90.8%) were suitable for F1CDx. Excluding the cases not submitted for testing, in the 45 cases where F1CDx was done using 22G EUS-TA samples, eight (17.8%) had a sum of tissue area tissue of 25 mm2 or greater in the HE-stained sample. However, all cases met the F1CDx 1 mm3 volume criterion by submitting > 30 unstained slides per sample. As a result, 43 of 45 cases (95.6%) were successfully analyzable.
Conclusions: The 22G EUS-TA needle is an effective tool for providing the sufficient tissue volume required for F1CDx. en-copyright= kn-copyright= en-aut-name=NagataniTami en-aut-sei=Nagatani en-aut-mei=Tami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WaniYoji en-aut-sei=Wani en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakataniMasahiro en-aut-sei=Takatani en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FushimiSoichiro en-aut-sei=Fushimi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueHirofumi en-aut-sei=Inoue en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoriShinichiro en-aut-sei=Hori en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KaiKyohei en-aut-sei=Kai en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkazakiTetsuya en-aut-sei=Okazaki en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TaniokaMaki en-aut-sei=Tanioka en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology, Japanese Red Cross Society, Himeji Red Cross Hospital kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Japanese Red Cross Society, Himeji Red Cross Hospital kn-affil= affil-num=4 en-affil=Department of Pathology, Japanese Red Cross Society, Himeji Red Cross Hospital kn-affil= affil-num=5 en-affil=Division of Medical Support, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Japanese Red Cross Society, Himeji Red Cross Hospital kn-affil= affil-num=7 en-affil=Department of Genetic Medicine, Japanese Red Cross Society, Himeji Red Cross Hospital kn-affil= affil-num=8 en-affil=Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Internal Medicine, Japanese Red Cross Society, Himeji Red Cross Hospital kn-affil= affil-num=12 en-affil=Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=biliary tract cancer kn-keyword=biliary tract cancer en-keyword=comprehensive genomic profiling kn-keyword=comprehensive genomic profiling en-keyword=endoscopic ultrasound-guided fine needle aspiration kn-keyword=endoscopic ultrasound-guided fine needle aspiration en-keyword=endoscopic ultrasound-guided fine needle biopsy kn-keyword=endoscopic ultrasound-guided fine needle biopsy en-keyword=pancreatic cancer kn-keyword=pancreatic cancer END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=8 article-no= start-page=e91072 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250826 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Craniofacial Fibrous Dysplasia to Affect or Not the Optic Nerve in Long-Term Follow-Up of Three Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fibrous dysplasia of the bone is characterized by immature fibrous bones of trabeculae and fibrovascular proliferation in the medulla. In this study, we report three consecutive patients with craniofacial fibrous dysplasia with or without optic nerve involvement. In Case 1, a 43-year-old man with blurred vision in the right eye at the first visit was well until the age of 54 years, when he came back with symptoms suggestive of paranasal sinusitis. Computed tomography scans disclosed a mucocele in the right sphenoid sinus and thickened bilateral ethmoid, sphenoid, and frontal bones. He underwent an emergency nasal endoscopic surgery to make a drainage opening to the sphenoid and ethmoid sinuses on the right side with incomplete success. The pathology of the resected tissue confirmed fibrous dysplasia. With intravenous antibiotics, he recovered from blepharoptosis, complete ophthalmoplegia, and visual acuity decrease on the right side. He was well until the age of 71 years when he had a self-limiting episode of visual field cloudiness caused by the right sphenoid sinus mucocele. At the age of 75 years, he developed abrupt vision loss to no light perception in the right eye. He underwent an open skull surgery to extirpate the sphenoid mucocele on the right side and died of an unknown cause two years later. In Case 2, a 29-year-old man had a two-week-long headache, and computed tomography scans revealed fibrous dysplasia in the bilateral sphenoid bones. Nasal biopsy at the spheno-ethmoid recess proved a pathological diagnosis of fibrous dysplasia. Goldmann perimetry showed normal visual fields in both eyes. He was followed every year by magnetic resonance imaging to maintain normal visual fields until the latest visit at the age of 41 years. In Case 3, a 12-year-old girl was referred to an ophthalmologist to check her vision. She had been diagnosed with fibrous dysplasia of the left maxillary bone at the age of six years by a dentist. She had a gingival resection on the left maxilla at the age of 15 years and had a left maxillary bone resection at 18 years at another hospital. One month after the resection, Goldmann perimetry showed superior peripheral field depression in the left eye, in contrast with the normal visual field in the right eye. She maintained the visual acuity of 1.5 in both eyes until the last visit at the age of 21 years. In fibrous dysplasia as a rare disease, functional and cosmetic problems, including vision problems, should be considered in a case-based approach. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaKiyoshi en-aut-sei=Yamada en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkanoMitsuhiro en-aut-sei=Okano en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Otorhinolaryngology, School of Medicine, International University of Health and Welfare kn-affil= en-keyword=computed tomography (ct) scan kn-keyword=computed tomography (ct) scan en-keyword=craniofacial bone kn-keyword=craniofacial bone en-keyword=fibrous dysplasia kn-keyword=fibrous dysplasia en-keyword=goldmann perimetry kn-keyword=goldmann perimetry en-keyword=magnetic resonance imaging kn-keyword=magnetic resonance imaging en-keyword=monostotic kn-keyword=monostotic en-keyword=optic nerve kn-keyword=optic nerve en-keyword=pathology kn-keyword=pathology en-keyword=visual acuity kn-keyword=visual acuity en-keyword=visual field kn-keyword=visual field END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=10 article-no= start-page=2373 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241017 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development and Characterization of a Three-Dimensional Organotypic In Vitro Oral Cancer Model with Four Co-Cultured Cell Types, Including Patient-Derived Cancer-Associated Fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Cancer organoids have emerged as a valuable tool of three-dimensional (3D) cell cultures to investigate tumor heterogeneity and predict tumor behavior and treatment response. We developed a 3D organotypic culture model of oral squamous cell carcinoma (OSCC) to recapitulate the tumor?stromal interface by co-culturing four cell types, including patient-derived cancer-associated fibroblasts (PD-CAFs). Methods: A stainless-steel ring was used twice to create the horizontal positioning of the cancer stroma (adjoining normal oral mucosa connective tissue) and the OSCC layer (surrounding normal oral mucosa epithelial layer). Combined with a structured bi-layered model of the epithelial component and the underlying stroma, this protocol enabled us to construct four distinct portions mimicking the oral cancer tissue arising in the oral mucosa. Results: In this model, -smooth muscle actin-positive PD-CAFs were localized in close proximity to the OSCC layer, suggesting a crosstalk between them. Furthermore, a linear laminin-2 expression was lacking at the interface between the OSCC layer and the underlying stromal layer, indicating the loss of the basement membrane-like structure. Conclusions: Since the specific 3D architecture and polarity mimicking oral cancer in vivo provides a more accurate milieu of the tumor microenvironment (TME), it could be crucial in elucidating oral cancer TME. en-copyright= kn-copyright= en-aut-name=AizawaYuka en-aut-sei=Aizawa en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagaKenta en-aut-sei=Haga en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshibaNagako en-aut-sei=Yoshiba en-aut-mei=Nagako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YortchanWitsanu en-aut-sei=Yortchan en-aut-mei=Witsanu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakadaSho en-aut-sei=Takada en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaRintaro en-aut-sei=Tanaka en-aut-mei=Rintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NaitoEriko en-aut-sei=Naito en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Ab?Tatsuya en-aut-sei=Ab? en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaruyamaSatoshi en-aut-sei=Maruyama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamazakiManabu en-aut-sei=Yamazaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TanumaJun-ichi en-aut-sei=Tanuma en-aut-mei=Jun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IgawaKazuyo en-aut-sei=Igawa en-aut-mei=Kazuyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TomiharaKei en-aut-sei=Tomihara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TogoShinsaku en-aut-sei=Togo en-aut-mei=Shinsaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IzumiKenji en-aut-sei=Izumi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=2 en-affil=Division of Reconstructive Surgery for Oral and Maxillofacial Region, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=3 en-affil=Department of Oral Health and Welfare, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=4 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=5 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=6 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=7 en-affil=Division of Oral and Maxillofacial Surgery, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=8 en-affil=Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=9 en-affil=Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=10 en-affil=Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=11 en-affil=Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=12 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=13 en-affil=Division of Oral and Maxillofacial Surgery, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Graduate School of Medicine, Juntendo University kn-affil= affil-num=15 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= en-keyword=oral cancer kn-keyword=oral cancer en-keyword=cancer-associated fibroblasts kn-keyword=cancer-associated fibroblasts en-keyword=oral mucosa kn-keyword=oral mucosa en-keyword=patient-derived kn-keyword=patient-derived en-keyword=organotypic culture kn-keyword=organotypic culture en-keyword=3D in vitro model kn-keyword=3D in vitro model en-keyword=polarity kn-keyword=polarity END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=9 article-no= start-page=4310 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Possibility of Plasma Membrane Transporters as Drug Targets in Oral Cancers en-subtitle= kn-subtitle= en-abstract= kn-abstract=Plasma membrane transporters are increasingly recognized as potential drug targets for oral cancer, particularly oral squamous cell carcinoma (OSCC). These transporters play crucial roles in cancer cell metabolism, drug resistance, and the tumor microenvironment, making them attractive targets for therapeutic intervention. Among the two main families of plasma membrane transporters, ATP-binding cassette (ABC) transporters have long been known to be involved in drug efflux and contribute to chemoresistance in cancer cells. On the other hand, solute carriers (SLCs) are also a family of transporters that facilitate the transport of various substrates, including nutrients and drugs, and have recently been shown to contribute to cancer chemosensitivity, metabolism, and proliferation. SLC transporters have been identified as potential cancer biomarkers and therapeutic targets, and their expression profiles suggest that they could be utilized in precision oncology approaches. We summarize previous reports on the expression and role of ABC and SLC transporters in oral cancer and discuss their potential as therapeutic targets. en-copyright= kn-copyright= en-aut-name=SogawaChiharu en-aut-sei=Sogawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimadaKatsumitsu en-aut-sei=Shimada en-aut-mei=Katsumitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of Technology kn-affil= affil-num=2 en-affil=Department of Clinical Phathophysiology, Matsumoto Dental University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=SLC transporter kn-keyword=SLC transporter en-keyword=ABC transporter kn-keyword=ABC transporter en-keyword=oral cancer kn-keyword=oral cancer en-keyword=oral squamous cell carcinoma kn-keyword=oral squamous cell carcinoma END start-ver=1.4 cd-journal=joma no-vol=189 cd-vols= no-issue= article-no= start-page=67 end-page=74 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250822 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Educational Support Based on an Understanding of the Pathology of Spina Bifida kn-title=񕪐Ғŏǂ̕aԗɊÂ猻ł̎x en-subtitle= kn-subtitle= en-abstract= kn-abstract=@񕪐Ғŏǂ̂qǂ́AǏ̌l傫A̕sRʎxwZłȂʊwɂݐЂĂB{̖ړÍC񕪐Ғŏǂ̕aԂɊÂA猻ł̎x݂̍ɂ‚āAs̒m܂Ƃ߁Ảۑ炩ɂ邱ƂłB
@񕪐Ғŏǂɂ́Ả^QƊoQArQɉAǂ͂߂ƂlXȍǂ邱ƂA^ʁAʁAFmʂɂēK؂ȎxvBɁAvtȍ~ɂȂƁAҐWɂuɂ̏oAs\͂̒ቺɒӂKvB_oNɂrAQꍇ́AԌAsBwZyƍmIɑĂqǂ̂قƂǂ́AԌA邢͈ꕔ̉݂̂ŔrA邱ƂłĂB̂ƂASĆAg̓IAFmIȎxƔzɉAEƖȘAgȂ琴ԌȓAڎw̎wi߂邱ƂƁAǍDȗFl֌Wz߂̎xsƂdvƎvꂽB en-copyright= kn-copyright= en-aut-name=OHMORI (KAWASAKI)Iori en-aut-sei=OHMORI (KAWASAKI) en-aut-mei=Iori kn-aut-name=ijɐD kn-aut-sei=ij kn-aut-mei=ɐD aut-affil-num=1 ORCID= en-aut-name=YAMANAKAMitsuko en-aut-sei=YAMANAKA en-aut-mei=Mitsuko kn-aut-name=RÎq kn-aut-sei=R kn-aut-mei=Îq aut-affil-num=2 ORCID= affil-num=1 en-affil=Faculty of EducationCOkayama University kn-affil=Rwwp@w affil-num=2 en-affil=Okayama prefectural Okayama east special needs school kn-affil=RRxwZ en-keyword=񕪐Ғŏ kn-keyword=񕪐Ғŏ en-keyword=ԌA kn-keyword=ԌA en-keyword=wZ kn-keyword=wZ en-keyword=EAg kn-keyword=EAg END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=e003250 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical impact of combined assessment of myocardial inflammation and fibrosis using myocardial biopsy in patients with dilated cardiomyopathy: a multicentre, retrospective cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Among patients with dilated cardiomyopathy (DCM), myocardial inflammation and fibrosis are risk factors for poor clinical outcomes. Here, we investigated the combined prognostic value of these two factors, as evaluated using myocardial biopsy samples.
Methods This retrospective and multicentre study included patients with DCM?defined as LVEF of ?45% and left diastolic diameter of >112% of predicted value, without evidence of secondary or ischaemic cardiomyopathy. In myocardial biopsy samples, inflammatory cells were counted using immunohistochemistry, and Massonfs Trichrome staining was performed to quantify the myocardial fibrosis as collagen area fraction (CAF). Higher myocardial inflammation was defined as leucocytes of ?14/mm?, including ?4 monocytes/mm?, with CD3+ T lymphocytes of?7/mm?. Greater myocardial fibrosis was defined as CAF of>5.9% by the Youdenfs index. The primary endpoint was cardiac death or left ventricular assist device implantation.
Results A total of 255 DCM patients were enrolled (average age, 53.1 years; 78% males). Within this cohort, the mean LVEF was 28.0%, mean CAF was 10.7% and median CD3+ cell count was 8.3/mm2. During the median follow-up period of 2688 days, 46 patients met the primary endpoint. Multivariable Cox proportional hazard analyses revealed that CD3+ cell count and CAF were independent determinants of the primary endpoint. Kaplan?Meier analysis showed that patients with both higher myocardial inflammation and greater fibrosis had the worst prognosis (log-rank p<0.001). When myocardial inflammation was graded as one of three degrees: T lymphocytes of <13/mm? (low); 13 of 13.1?23.9/mm? (moderate); and T lymphocytes of ?24?/mm? (high), patients with moderate inflammation exhibited a superior survival rate when CAF was ?5.9%, but a worse survival rate when CAF was >5.9%.
Conclusions Having both biopsy-proven higher myocardial inflammation and greater fibrosis predicted the worst clinical prognosis in patients with DCM. en-copyright= kn-copyright= en-aut-name=NakayamaTakafumi en-aut-sei=Nakayama en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgoKeiko Ohta en-aut-sei=Ogo en-aut-mei=Keiko Ohta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuganoYasuo en-aut-sei=Sugano en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YokokawaTetsuro en-aut-sei=Yokokawa en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanamoriHiromitsu en-aut-sei=Kanamori en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkedaYoshihiko en-aut-sei=Ikeda en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiroeMichiaki en-aut-sei=Hiroe en-aut-mei=Michiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HatakeyamaKinta en-aut-sei=Hatakeyama en-aut-mei=Kinta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Ishibashi-UedaHatsue en-aut-sei=Ishibashi-Ueda en-aut-mei=Hatsue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DohiKaoru en-aut-sei=Dohi en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AnzaiToshihisa en-aut-sei=Anzai en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SeoYoshihiro en-aut-sei=Seo en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Imanaka-YoshidaKyoko en-aut-sei=Imanaka-Yoshida en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Cardiology, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology, National Cerebral and Cardiovascular Center kn-affil= affil-num=3 en-affil=Department of Cardiology, Keiyu Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Fukushima Medical University kn-affil= affil-num=5 en-affil=Department of Cardiology, Gifu University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Pathology, National Cerebral and Cardiovascular Center kn-affil= affil-num=7 en-affil=Department of Cardiology, National Center for Global Health and Medicine kn-affil= affil-num=8 en-affil=Department of Pathology, National Cerebral and Cardiovascular Center kn-affil= affil-num=9 en-affil=Department of Pathology, National Cerebral and Cardiovascular Center kn-affil= affil-num=10 en-affil=Center for Advanced Heart Failure, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Cardiology and Nephrology, Mie University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Cardiology, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=14 en-affil=Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=10 article-no= start-page=1151 end-page=1159 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=NCF-1 plays a pivotal role in the survival of adenocarcinoma cells of pancreatic and gastric origins en-subtitle= kn-subtitle= en-abstract= kn-abstract=Reactive oxygen species (ROS) play a pivotal biological role in cells, with ROS function differing depending on cellular conditions and the extracellular environment. Notably, ROS act as cytotoxic factors to eliminate infectious pathogens or promote cell death under cellular stress, while also facilitating cell growth (via ROS-sensing pathways) by modifying gene expression. Among ROS-related genes, neutrophil cytosolic factor-1 (NCF-1; p47phox) was identified as a ROS generator in neutrophils. This product is a subunit of a cytosolic NADPH oxidase complex activated in response to pathogens such as bacteria and viruses. NCF-1 has been examined primarily in terms of ROS-production pathways in macrophages and neutrophils; however, the expression of this protein and its biological role in cancer cells remain unclear. Here, we report expression of NCF-1 in pancreatic and gastric cancers, and demonstrate its biological significance in these tumor cells. Abundant expression of NCF-1 was observed in pancreatic adenocarcinoma (PDAC) lines and in patient tissues, as well as in gastric adenocarcinomas. Accumulation of the protein was also detected in the invasive/metastatic foci of these tumors. Unexpectedly, BxPC-3 underwent apoptotic cell death when transfected with a small interfering RNA (siRNA) specific to NCF-1, whereas the cells treated with a control siRNA proliferated in a time-dependent manner. A similar phenomenon was observed in HSC-58, a poorly differentiated gastric adenocarcinoma line. Consequently, the tumor cells highly expressing NCF-1 obtained coincident accumulation of ROS and reduced glutathione (GSH) with expression of glutathione peroxidase 4 (GPX4), a quencher involved in ferroptosis. Unlike the conventional role of ROS as a representative cytotoxic factor, these findings suggest that NCF-1-mediated ROS generation may be required for expansive growth of PDAC and gastric cancers. en-copyright= kn-copyright= en-aut-name=Furuya-IkudeChiemi en-aut-sei=Furuya-Ikude en-aut-mei=Chiemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KittaAkane en-aut-sei=Kitta en-aut-mei=Akane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomonobuNaoko en-aut-sei=Tomonobu en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawasakiYoshihiro en-aut-sei=Kawasaki en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KondoEisaku en-aut-sei=Kondo en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University kn-affil= affil-num=2 en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University kn-affil= affil-num=3 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University kn-affil= affil-num=5 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University kn-affil= en-keyword=NCF-1 (p47phox) kn-keyword=NCF-1 (p47phox) en-keyword=ROS kn-keyword=ROS en-keyword=Cancer kn-keyword=Cancer en-keyword=Tumor growth kn-keyword=Tumor growth en-keyword=Apoptosis kn-keyword=Apoptosis END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue=12 article-no= start-page=1697 end-page=1702 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240615 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gastric Mucosa-associated Lymphoid Tissue Lymphoma That Relapsed after 11 Years Subsequent to Achieving Complete Remission en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 38-year-old Japanese man was diagnosed with extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue in the stomach (gastric MALT lymphoma). Fluorescence in situ hybridization analysis revealed the absence of t (11;18) (q21;q21) translocation but the presence of extra copies of MALT1, indicating tetrasomy 18. Helicobacter pylori eradication led to complete remission (CR). However, the gastric MALT lymphoma relapsed after 11 years old. This case underscores the need for long-term observation (>10 years) of patients with gastric MALT lymphoma. Further investigation is warranted to elucidate the correlation between trisomy/tetrasomy 18 and the recurrence propensity. en-copyright= kn-copyright= en-aut-name=InooShoko en-aut-sei=Inoo en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OotukaMotoyuki en-aut-sei=Ootuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=gastric MALT lymphoma kn-keyword=gastric MALT lymphoma en-keyword=H. pylori kn-keyword=H. pylori en-keyword=relapse kn-keyword=relapse END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue=10 article-no= start-page=1367 end-page=1371 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250515 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Idiopathic Gastric Antral Ulcers en-subtitle= kn-subtitle= en-abstract= kn-abstract=A Japanese woman presented with gastric antral ulcers accompanied by erosion and edema, demonstrating a chronic pattern of improvement and recurrence for more than six years. The patient had no relevant treatment history, and Helicobacter pylori infection was ruled out. Other potential etiologies contributing to gastric ulcers were eliminated on the basis of endoscopic biopsy and blood laboratory findings. Consequently, the patient was diagnosed with idiopathic gastric antral ulcer. This disease is often overlooked, and the chronological endoscopic images provided in this report can be used as a reference. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=esophagogastroduodenoscopy kn-keyword=esophagogastroduodenoscopy en-keyword=gastric ulcer kn-keyword=gastric ulcer en-keyword=diopathic ulcer kn-keyword=diopathic ulcer en-keyword=Helicobacter pylori kn-keyword=Helicobacter pylori END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=305 end-page=309 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Rare Presentation of Pneumonic-Type Adenocarcinoma Hidden behind Empyema en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pneumonic-type adenocarcinoma (P-ADC) can closely mimic pneumonia. We report a P-ADC initially diagnosed as pneumonia which developed into a pulmonary abscess and empyema. A 50-year-old Japanese male diagnosed with pneumonia, pulmonary abscess, and empyema was administered antibiotics and a chest tube for drainage, which improved his symptoms and blood test results. However, chest computed tomography showed an enlarged infiltrative shadow. The patient underwent bronchoscopy and was diagnosed with an adenocarcinoma. This case highlights the importance of considering P-ADC in differential diagnoses when a pneumonia-like shadow enlarges post-empyema treatment. Diagnostic and clinical tests, e.g., bronchoscopy, should be performed in such cases. en-copyright= kn-copyright= en-aut-name=SenooSatoru en-aut-sei=Senoo en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NimanEito en-aut-sei=Niman en-aut-mei=Eito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsujiRyoko en-aut-sei=Tsuji en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakataKohei en-aut-sei=Takata en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumoriShunsuke en-aut-sei=Matsumori en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MuranoFumika en-aut-sei=Murano en-aut-mei=Fumika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugisakiYuka en-aut-sei=Sugisaki en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OmoriHiroki en-aut-sei=Omori en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TaniguchiAkihiko en-aut-sei=Taniguchi en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OmoteRika en-aut-sei=Omote en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakahashiKenji en-aut-sei=Takahashi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkadaToshiaki en-aut-sei=Okada en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=10 en-affil=Department of Diagnostic Pathology, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=12 en-affil=Department of General Thoracic Surgery, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= en-keyword=pneumonic type adenocarcinoma kn-keyword=pneumonic type adenocarcinoma en-keyword=empyema kn-keyword=empyema en-keyword=bronchoscopy kn-keyword=bronchoscopy en-keyword=lung cancer diagnosis kn-keyword=lung cancer diagnosis en-keyword=cavity formation kn-keyword=cavity formation END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=299 end-page=303 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pulmonary Calcium Phosphate Cement Embolism After Percutaneous Vertebroplasty for Thoracic Vertebrae Fractures en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pulmonary cement embolism (PCE) is a rare but severe complication following percutaneous vertebroplasty (PVP). Calcium phosphate cement (CPC) has emerged as an alternative to traditional materials for vertebral augmentation. There appear to be no established guidelines for managing symptomatic PCE, and there is scarce literature on CPC embolisms. This is a first report of a case of pulmonary CPC embolism following PVP. The patient, a 63-year-old Chinese female, was administered anticoagulant treatment and achieved a satisfactory outcome. Her case highlights the severe potential morbidity associated with CPC leakage and emphasizes the efficacy of anticoagulant treatment for managing pulmonary CPC embolisms. en-copyright= kn-copyright= en-aut-name=FengRuibin en-aut-sei=Feng en-aut-mei=Ruibin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ZhuBikang en-aut-sei=Zhu en-aut-mei=Bikang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WeiDanyun en-aut-sei=Wei en-aut-mei=Danyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhuDingjiao en-aut-sei=Zhu en-aut-mei=Dingjiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChenCairu en-aut-sei=Chen en-aut-mei=Cairu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical University kn-affil= affil-num=2 en-affil=Department of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical University kn-affil= affil-num=3 en-affil=Department of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical University kn-affil= affil-num=4 en-affil=Department of Radiology, the Ninth Affiliated Hospital of Guangxi Medical University kn-affil= affil-num=5 en-affil=Department of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical University kn-affil= en-keyword=percutaneous vertebroplasty kn-keyword=percutaneous vertebroplasty en-keyword=thoracic vertebrae fracture kn-keyword=thoracic vertebrae fracture en-keyword=calcium phosphate cement kn-keyword=calcium phosphate cement en-keyword=pulmonary embolism kn-keyword=pulmonary embolism END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=283 end-page=286 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Anterior Uveitis Secondary to an Infected Postoperative Maxillary Cyst en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 76-year-old man presented with right eyelid swelling and deteriorated vision. Examination revealed anterior uveitis with hypopyon and a visual acuity of 20/2,000 in the right eye, with no abnormalities in the left. Computed tomography revealed enlargement of the right maxillary sinus and internal fluid accumulation, suggesting a postoperative maxillary cyst (POMC). Nasal endoscopic surgery drained the pus by opening the lower wall of the maxillary cyst. Following the procedure, intraocular inflammation resolved, and visual acuity in the right eye improved to 24/20. This is the first reported case of uveitis secondary to POMC. en-copyright= kn-copyright= en-aut-name=ImamuraYuta en-aut-sei=Imamura en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraShuhei en-aut-sei=Kimura en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HosokawaMio en-aut-sei=Hosokawa en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KanzakiYuki en-aut-sei=Kanzaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KindoHiroya en-aut-sei=Kindo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MoritaTetsuro en-aut-sei=Morita en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MuraiAya en-aut-sei=Murai en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=anterior uveitis kn-keyword=anterior uveitis en-keyword=hypopyon kn-keyword=hypopyon en-keyword=maxillary sinus kn-keyword=maxillary sinus en-keyword=postoperative maxillary cyst kn-keyword=postoperative maxillary cyst END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=1 article-no= start-page=104318 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hypotheses of pathophysiological mechanisms in epileptic encephalopathies: A review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Epileptic encephalopathy (EE) is a serious clinical issue that manifests as part of developmental and epileptic encephalopathy (DEE), particularly in childhood epilepsy. In EE, neurocognitive functions and behavior are impaired by intense epileptiform electroencephalogram (EEG) activity. Hypotheses of pathophysiological mechanisms behind EE are reviewed to contribute to an effective solution for EE.
Review: Current hypotheses are as follows: 1) neuronal dysfunction based on genetic abnormalities that may affect neurocognitive functions and epilepsy separately; 2) impairment of synaptic homeostasis during sleep that may be responsible for DEE/EE with spike-and-wave activation in sleep; 3) abnormal subcortical regulation of the cerebral cortex; 4) abnormal cortical metabolism and hemodynamics with impairment of the neural network including default mode network; 5) neurotransmitter imbalance and disordered neural excitability; 6) the effects of neuroinflammation that may be caused by epileptic seizures and in turn aggravate epileptogenesis; 7) the interaction between physiological and pathological high-frequency EEG activity; etc. The causal relationship between epileptiform EEG activity and neurocognitive dysfunctions is small in DEE based on genetic abnormalities and it is largely unestablished in the other hypothetical mechanisms.
Conclusion: We have not yet found answers to the question of whether the single-central or multiple derangements are present and what seizures and intense epileptiform EEG abnormalities mean in EE. We need to continue our best efforts in both aspects to elucidate the pathophysiological mechanisms of DEE/EE and further develop epilepsy treatment and precision medicine. en-copyright= kn-copyright= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShibataTakashi en-aut-sei=Shibata en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsuchiyaHiroki en-aut-sei=Tsuchiya en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkiyamaMari en-aut-sei=Akiyama en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Pediatrics, Asahigawaso Rehabilitation and Medical Center kn-affil= affil-num=2 en-affil=Department of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Behavior kn-keyword=Behavior en-keyword=Childhood epilepsy kn-keyword=Childhood epilepsy en-keyword=Cognitive function kn-keyword=Cognitive function en-keyword=Developmental and epileptic encephalopathy kn-keyword=Developmental and epileptic encephalopathy en-keyword=Regression kn-keyword=Regression END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=15 article-no= start-page=e71098 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real]World Data of Comprehensive Cancer Genomic Profiling Tests Performed in the Routine Clinical Setting in Sarcoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Next-generation sequencing-based comprehensive cancer genomic profiling (CGP) tests are beneficial for refining diagnosis and personalized treatment of various cancers. However, the clinical impact of CGP, as covered by public health insurance in the management of sarcomas, remains unknown. Especially, the data on the utility of the newly emerging dual DNA?RNA panel compared to the conventional DNA-only panel in clinical settings is lacking. Therefore, we evaluated the utility of CGP in routine clinical practice for sarcoma treatment.
Patients and Methods: In this study, three types of DNA panel and one DNA?RNA panel, reimbursed by Japanese public health insurance, were utilized. We detected oncogenic and druggable gene mutations and genotype-matched therapies.
Results: One hundred and thirty-six patients were included in this study. Based on the detection of highly histology-specific translocations in the sequencing results, 2.2% of patients were re-classified. In patients with translocation-related sarcomas, a DNA?RNA panel identified more histology-specific fusion genes than DNA panels (p?=?0.0035). Specifically, 86.8% and 39.0% of patients had oncogenic and druggable genomic alterations, respectively. Of these, 9.6% underwent genotype-matched therapy, with a 36.3% response rate and an 81.8% disease control rate. Patients who were administered genomically matched therapy had better overall survival (OS) than those who did not in patients with metastatic or advanced sarcoma with no prior chemotherapy (3-year OS: 83.3% vs. 48.0%, p?=?0.42). Patients with TP53 and RB1 mutations had worse OS than those without. Germline findings were detected in 11.0% of the patients, one of whom had a truly germline origin.
Conclusions: This study suggests that publicly reimbursed CGP tests, particularly the dual DNA?RNA panel, could be beneficial for refining diagnostic precision in selected sarcoma subtypes, treatment decisions, detecting the germline findings, and prognosis prediction in routine clinical settings for sarcoma. The implementation of genotype-matched therapies showed favorable clinical outcomes and improved the prognosis. en-copyright= kn-copyright= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OsoneTatsunori en-aut-sei=Osone en-aut-mei=Tatsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItanoTakuto en-aut-sei=Itano en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IdaNaoyuki en-aut-sei=Ida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FutagawaMashu en-aut-sei=Futagawa en-aut-mei=Mashu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShimoiTatsunori en-aut-sei=Shimoi en-aut-mei=Tatsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Medical Oncology, National Cancer Center Hospital kn-affil= affil-num=13 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Center for Clinical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=comprehensive genomic profiling kn-keyword=comprehensive genomic profiling en-keyword=genotype-matched therapy kn-keyword=genotype-matched therapy en-keyword=multiplex gene panel test kn-keyword=multiplex gene panel test en-keyword=sarcoma kn-keyword=sarcoma END start-ver=1.4 cd-journal=joma no-vol=638 cd-vols= no-issue=8049 article-no= start-page=225 end-page=236 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immune evasion through mitochondrial transfer in the tumour microenvironment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer cells in the tumour microenvironment use various mechanisms to evade the immune system, particularly T?cell attack1. For example, metabolic reprogramming in the tumour microenvironment and mitochondrial dysfunction in tumour-infiltrating lymphocytes (TILs) impair antitumour immune responses2,3,4. However, detailed mechanisms of such processes remain unclear. Here we analyse clinical specimens and identify mitochondrial DNA (mtDNA) mutations in TILs that are shared with cancer cells. Moreover, mitochondria with mtDNA mutations from cancer cells are able to transfer to TILs. Typically, mitochondria in TILs readily undergo mitophagy through reactive oxygen species. However, mitochondria transferred from cancer cells do not undergo mitophagy, which we find is due to mitophagy-inhibitory molecules. These molecules attach to mitochondria and together are transferred to TILs, which results in homoplasmic replacement. T?cells that acquire mtDNA mutations from cancer cells exhibit metabolic abnormalities and senescence, with defects in effector functions and memory formation. This in turn leads to impaired antitumour immunity both in vitro and in vivo. Accordingly, the presence of an mtDNA mutation in tumour tissue is a poor prognostic factor for immune checkpoint inhibitors in patients with melanoma or non-small-cell lung cancer. These findings reveal a previously unknown mechanism of cancer immune evasion through mitochondrial transfer and can contribute to the development of future cancer immunotherapies. en-copyright= kn-copyright= en-aut-name=IkedaHideki en-aut-sei=Ikeda en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaseKatsushige en-aut-sei=Kawase en-aut-mei=Katsushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiTatsuya en-aut-sei=Nishi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeTomofumi en-aut-sei=Watanabe en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakenagaKeizo en-aut-sei=Takenaga en-aut-mei=Keizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InozumeTakashi en-aut-sei=Inozume en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshinoTakamasa en-aut-sei=Ishino en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AkiSho en-aut-sei=Aki en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=LinJason en-aut-sei=Lin en-aut-mei=Jason kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawashimaShusuke en-aut-sei=Kawashima en-aut-mei=Shusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SuzukiShinichiro en-aut-sei=Suzuki en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MakinoshimaHideki en-aut-sei=Makinoshima en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ItamiMakiko en-aut-sei=Itami en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NakamuraYuki en-aut-sei=Nakamura en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TatsumiYasutoshi en-aut-sei=Tatsumi en-aut-mei=Yasutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SuenagaYusuke en-aut-sei=Suenaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MorinagaTakao en-aut-sei=Morinaga en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=Honobe-TabuchiAkiko en-aut-sei=Honobe-Tabuchi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=OhnumaTakehiro en-aut-sei=Ohnuma en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KawamuraTatsuyoshi en-aut-sei=Kawamura en-aut-mei=Tatsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=UmedaYoshiyasu en-aut-sei=Umeda en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=NakamuraYasuhiro en-aut-sei=Nakamura en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KiniwaYukiko en-aut-sei=Kiniwa en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=HayashiHidetoshi en-aut-sei=Hayashi en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=IkedaJun-ichiro en-aut-sei=Ikeda en-aut-mei=Jun-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=HanazawaToyoyuki en-aut-sei=Hanazawa en-aut-mei=Toyoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=ManoHiroyuki en-aut-sei=Mano en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=SuzukiTakuji en-aut-sei=Suzuki en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=OsawaTsuyoshi en-aut-sei=Osawa en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=KawazuMasahito en-aut-sei=Kawazu en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= affil-num=1 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=2 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=3 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Division of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute kn-affil= affil-num=6 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=7 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Division of Nutriomics and Oncology, RCAST, The University of Tokyo kn-affil= affil-num=9 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=10 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan Department of Dermatology, Graduate School of Medicine, Chiba University kn-affil= affil-num=11 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Tsuruoka Metabolomics Laboratory, National Cancer Center kn-affil= affil-num=15 en-affil=Department of Surgical Pathology, Chiba Cancer Center kn-affil= affil-num=16 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=17 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=18 en-affil=Laboratory of Evolutionary Oncology, Chiba Cancer Center Research Institute kn-affil= affil-num=19 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=20 en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=21 en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=22 en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=23 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=24 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=25 en-affil=Department of Dermatology, Shinshu University School of Medicine kn-affil= affil-num=26 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=27 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=28 en-affil=Department of Diagnostic Pathology, Graduate School of Medicine, Chiba University kn-affil= affil-num=29 en-affil=Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine kn-affil= affil-num=30 en-affil=Department of General Thoracic Surgery and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=31 en-affil=Division of Cellular Signalling, National Cancer Center Research Institute kn-affil= affil-num=32 en-affil=Department of Respirology, Graduate School of Medicine, Chiba University kn-affil= affil-num=33 en-affil=Division of Nutriomics and Oncology, RCAST, The University of Tokyo kn-affil= affil-num=34 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=35 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=6 article-no= start-page=1008 end-page=1016 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240422 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High risk of multiple gastric cancers in Japanese individuals with Lynch syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aim: Lynch syndrome (LS) is a dominantly inherited syndrome characterized by an increased risk for LS associated tumors such as colorectal cancer (CRC) and gastric cancer (GC). However, the clinical benefit of surveillance for GC remains unclear while it has already been recommended for CRC. This study aimed to elucidate the clinical features of GC in Japanese individuals with LS, and the risk of developing multiple GCs to build regional-tailored surveillance programs in LS patients with GC.
Methods: Data on Japanese individuals with LS were retrospectively collected from a single institution. The clinical features of GC, including the cumulative risk of multiple GCs, were analyzed.
Results: Among 96 individuals with LS (MLH1/MSH2/MSH6, 75:20:1), 32 GC lesions were detected in 15 individuals with LS (male/female, 11:4). The median age at initial GC diagnosis was 52.7?y (range: 28?71). Histological examination revealed a predominance of intestinal type (19/24: 87.5%). Moreover, the majority of the GC lesions (82%) were determined to have high-frequency of microsatellite instability. The cumulative risk of individuals with LS developing GC at 70?y was 31.3% (MLH1 36.1%, MSH2 18.0%). Notably, the cumulative risk of individuals with LS developing metachronous and/or synchronous GCs at 0, 10 and 20?y after initial diagnosis of GC was 26.7%, 40.7%, and 59.4%, respectively.
Conclusion: Due to a higher risk of developing multiple GCs, intensive surveillance might be especially recommended for Japanese individuals with LS associated initial GC. en-copyright= kn-copyright= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=van SchaikThijs A. en-aut-sei=van Schaik en-aut-mei=Thijs A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AokiHideki en-aut-sei=Aoki en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoYumiko en-aut-sei=Sato en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TaniguchiFumitaka en-aut-sei=Taniguchi en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuganoKokichi en-aut-sei=Sugano en-aut-mei=Kokichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AkagiKiwamu en-aut-sei=Akagi en-aut-mei=Kiwamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshidaHideyuki en-aut-sei=Ishida en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakayaKohji en-aut-sei=Tanakaya en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School kn-affil= affil-num=3 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=4 en-affil=Department of Pathology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=5 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Genetic Medicine, Kyoundo Hospital, SSasaki Foundation kn-affil= affil-num=8 en-affil=Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center kn-affil= affil-num=9 en-affil=Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=10 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= en-keyword=cumulative risk kn-keyword=cumulative risk en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=Japanese individuals kn-keyword=Japanese individuals en-keyword=Lynch syndrome kn-keyword=Lynch syndrome en-keyword=multiple gastric cancers kn-keyword=multiple gastric cancers END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=3 article-no= start-page=79 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association of the expression of 5?FU biomarkers with aging and prognosis in elderly patients with lung cancer treated with S?1 adjuvant chemotherapy: Follow?up results of the Setouchi Lung Cancer Group Study 1201 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Managing elderly patients presents several challenges because of age?related declines; however, age should not be the sole determinant for adjuvant treatment decisions in patients with non?small cell lung cancer (NSCLC). Moreover, age may affect the expression of 5?fluorouracil (5?FU) biomarkers. The present study assessed: i) The effect of age on the expression levels of 5?FU biomarkers by analyzing a public database; and ii) the ability of these biomarkers to predict clinical outcomes in elderly patients with NSCLC who underwent complete resection in the Setouchi Lung Cancer Group Study 1201 (SCLG1201) followed by S?1 adjuvant chemotherapy. Changes in gene expression levels across age groups were assessed by analyzing The Cancer Genome Atlas (TCGA) database. The expression of 5?FU biomarkers, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase, epidermal growth factor receptor (EGFR) and excision repair cross?complementation group 1 (ERCC1), were assessed via quantitative reverse?transcription PCR assays in 89 elderly patients (?75 years) with NSCLC who received adjuvant chemotherapy with oral fluoropyrimidine prodrug S?1 in the SLCG1201 trial. TCGA database analysis (n=955) showed that TS expression decreased significantly with aging, especially in the age group ?75. In the SCLG1201 trial, univariate analysis revealed that EGFR upregulation and TS downregulation were correlated with favorable recurrence?free survival (RFS) and overall survival (OS), respectively. Multivariate analysis demonstrated that pathological stage was an independent prognostic factor for both RFS and OS. EGFR mutations were associated with upregulation of DPD and EGFR, and downregulation of TS and ERCC1. In conclusion, although pathological stage is an independent prognostic factor for survival, EGFR upregulation and TS downregulation may be a greater predictor of clinical outcomes in elderly patients with NSCLC treated with S?1 adjuvant chemotherapy. The age?related decrease in TS expression supports the potential benefit of 5?FU therapies in elderly patients. Nonetheless, further research is warranted to validate these results. en-copyright= kn-copyright= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkumuraNorihito en-aut-sei=Okumura en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiHiroyuki en-aut-sei=Suzuki en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakataMasao en-aut-sei=Nakata en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraToshiya en-aut-sei=Fujiwara en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GembaKenicehi en-aut-sei=Gemba en-aut-mei=Kenicehi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SanoIsao en-aut-sei=Sano en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujinagaTakuji en-aut-sei=Fujinaga en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KataokaMasafumi en-aut-sei=Kataoka en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TerasakiYasuhiro en-aut-sei=Terasaki en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujimotoNobukazu en-aut-sei=Fujimoto en-aut-mei=Nobukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KataokaKazuhiko en-aut-sei=Kataoka en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KosakaShinji en-aut-sei=Kosaka en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=InokawaHidetoshi en-aut-sei=Inokawa en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakamuraHiroshige en-aut-sei=Nakamura en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamashitaYoshinori en-aut-sei=Yamashita en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TakahashiYuta en-aut-sei=Takahashi en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TorigoeHidejiro en-aut-sei=Torigoe en-aut-mei=Hidejiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=SatoHiroki en-aut-sei=Sato en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=MoritaSatoshi en-aut-sei=Morita en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=MatsuoKeitaro en-aut-sei=Matsuo en-aut-mei=Keitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=SakamotoJunichi en-aut-sei=Sakamoto en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=DateHiroshi en-aut-sei=Date en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Department of Chest Surgery, Fukushima Medical University Hospital kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Hiroshima 720?0001, Japan; 8Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery, National Hospital Organization Nagara Medical Center kn-affil= affil-num=10 en-affil=Department of Surgery and Respiratory Center, Okayama Saiseikai General Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Surgery, Saga Medical Center Koseikan kn-affil= affil-num=12 en-affil=Department of Medical Oncology and Respiratory Medicine, Okayama Rosai Hospital kn-affil= affil-num=13 en-affil=Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=14 en-affil=Department of Thoracic Surgery, Shimane Prefectural Central Hospital kn-affil= affil-num=15 en-affil=Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=16 en-affil=Department of Thoracic Surgery, National Hospital Organization Yamaguchi?Ube Medical Center kn-affil= affil-num=17 en-affil=Department of Thoracic Surgery, Shimonoseki City Hospital kn-affil= affil-num=18 en-affil=Division of General Thoracic Surgery, Tottori University Hospital kn-affil= affil-num=19 en-affil=Department of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center kn-affil= affil-num=20 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=21 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=22 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=23 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=24 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=25 en-affil=Department of Thoracic Oncology, Kansai Medical University Hospital kn-affil= affil-num=26 en-affil=Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine kn-affil= affil-num=27 en-affil=Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute kn-affil= affil-num=28 en-affil=Tokai Central Hospital kn-affil= affil-num=29 en-affil=Department of Thoracic Surgery, Kyoto University Hospital kn-affil= affil-num=30 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=non?small cell lung cancer kn-keyword=non?small cell lung cancer en-keyword=elderly patients kn-keyword=elderly patients en-keyword=adjuvant chemotherapy kn-keyword=adjuvant chemotherapy en-keyword=S?1 kn-keyword=S?1 en-keyword=EGFR kn-keyword=EGFR en-keyword=TP kn-keyword=TP en-keyword=TS kn-keyword=TS en-keyword=OPRT kn-keyword=OPRT en-keyword=ERCC1 kn-keyword=ERCC1 en-keyword=DPD kn-keyword=DPD END start-ver=1.4 cd-journal=joma no-vol=120 cd-vols= no-issue=1 article-no= start-page=87 end-page=98 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparable Clinical Outcomes Between Segmentectomy and Lobectomy for NSCLC With Unsuspected N1/N2: A Multicenter Real-World Data Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Segmentectomy for lung cancer has been increasingly performed. However, evidence regarding the necessity of additional surgical resection after the diagnosis of unsuspected N1 or N2 lymph node metastasis is limited.
Methods We conducted a multicenter, real-world data study of patients with any clinical T and N0 non-small cell lung cancer (NSCLC) who underwent lobectomy or segmentectomy between 2012 and 2021 and who subsequently received a diagnosis of pathologic N1 or N2 lymph node metastasis. Patients were categorized into lobectomy and segmentectomy groups. We analyzed overall survival (OS), recurrence-free survival (RFS), cumulative recurrence rates, and recurrence patterns using both unadjusted and propensity score?adjusted cohorts.
Results A total of 736 patients were in the lobectomy group, and 70 were in the segmentectomy group. In the unadjusted cohort, segmentectomy-treated patients were older, had a lower preoperative percentage of vital capacity, had smaller tumors, and received less postoperative adjuvant chemotherapy. The 5-year OS was significantly worse in the segmentectomy group (P = .011), with no significant differences in 5-year RFS or cumulative recurrence rates. In the propensity score?adjusted cohort, there were no significant differences in OS, RFS, or recurrence rates; however, the segmentectomy group had a higher rate of local recurrence.
Conclusions In patients with unsuspected N1 or N2 NSCLC, analysis using a cohort adjusted for patient background with propensity scores revealed no differences in OS, RFS, or cumulative recurrence rates between segmentectomy and lobectomy. This finding suggests that additional resection of the remaining segments may not be necessary for these patients. However, the higher rate of local recurrence in the segmentectomy group warrants careful consideration. en-copyright= kn-copyright= en-aut-name=RyukoTsuyoshi en-aut-sei=Ryuko en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UenoTsuyoshi en-aut-sei=Ueno en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiwaraToshiya en-aut-sei=Fujiwara en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeMototsugu en-aut-sei=Watanabe en-aut-mei=Mototsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=InokawaHidetoshi en-aut-sei=Inokawa en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MisaoTakahiko en-aut-sei=Misao en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TorigoeHidejiro en-aut-sei=Torigoe en-aut-mei=Hidejiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WashioKazuhiro en-aut-sei=Washio en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TaoHiroyuki en-aut-sei=Tao en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OkutaniDaisuke en-aut-sei=Okutani en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HayamaMakio en-aut-sei=Hayama en-aut-mei=Makio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=UomotoMasashi en-aut-sei=Uomoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YamadaEiji en-aut-sei=Yamada en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OtaniShinji en-aut-sei=Otani en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KurosakiTakeshi en-aut-sei=Kurosaki en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YaginumaYuji en-aut-sei=Yaginuma en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NimanEito en-aut-sei=Niman en-aut-mei=Eito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KawamataOsamu en-aut-sei=Kawamata en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=NishikawaHitoshi en-aut-sei=Nishikawa en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OtsukaTomoaki en-aut-sei=Otsuka en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YoshikawaTakeshi en-aut-sei=Yoshikawa en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=HayashiTatsuro en-aut-sei=Hayashi en-aut-mei=Tatsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=7 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=8 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=9 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=10 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=11 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=12 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=13 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=14 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=15 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=16 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=17 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=18 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=19 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=20 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=21 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=22 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=23 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=24 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=25 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=26 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=27 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=10 article-no= start-page=1215 end-page=1227 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Enhanced design of pCMViR-TSC plasmid vector for sustainably high cargo gene expression in mammalian cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=The first-generation pCMViR-TSC, implemented through the promoter sandwich rule, yields 10- to 100-fold higher gene expression than the standard plasmid used with the CMV (cytomegalovirus) or CAG promoter. However, the vectorfs shortcomings limit its utility to transient expression only, as it is not suitable for establishing stable transformants in mammalian cells. To overcome this weakness, we here introduce the improved plasmid vector pSAKA-4B, derived from pCMViR-TSC as a second-generation chromosome-insertable vector. This vector facilitates the linear entry of the expression unit into the TTAA site of DNA universally with transposase assistance. The vector is helpful for the indefinite expression of our target gene. The new vector system is proven here to be efficient in establishing stable transformants with a high likelihood of positive clones that exhibit significantly elevated expression levels of the delivered foreign gene. This system, alongside the first-generation vector, is therefore instrumental for diverse basic research endeavors concerning genes, proteins, cells, and animals, and potentially for clinical applications such as gene therapy. en-copyright= kn-copyright= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KinoshitaRie en-aut-sei=Kinoshita en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakaguchiYoshihiko en-aut-sei=Sakaguchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FutamiJunichiro en-aut-sei=Futami en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamauchiAkira en-aut-sei=Yamauchi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MurataHitoshi en-aut-sei=Murata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoKen-ichi en-aut-sei=Yamamoto en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakahashiTetta en-aut-sei=Takahashi en-aut-mei=Tetta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GoharaYuma en-aut-sei=Gohara en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OchiToshiki en-aut-sei=Ochi en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=JiangFan en-aut-sei=Jiang en-aut-mei=Fan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KomalasariNi Luh Gede Yoni en-aut-sei=Komalasari en-aut-mei=Ni Luh Gede Yoni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ChenYouyi en-aut-sei=Chen en-aut-mei=Youyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=RumaI Made Winarsa en-aut-sei=Ruma en-aut-mei=I Made Winarsa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SumardikaI Wayan en-aut-sei=Sumardika en-aut-mei=I Wayan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ZhouJin en-aut-sei=Zhou en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HonjoTomoko en-aut-sei=Honjo en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KuribayashiFutoshi en-aut-sei=Kuribayashi en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SagayamaKazumi en-aut-sei=Sagayama en-aut-mei=Kazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KondoEisaku en-aut-sei=Kondo en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=InoueYusuke en-aut-sei=Inoue en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Microbiology, Tokushima Bunri University kn-affil= affil-num=5 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=14 en-affil=Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=15 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=16 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=17 en-affil=Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of Technology kn-affil= affil-num=18 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=19 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=20 en-affil=Organization for Research and Innovation Strategy, Okayama University kn-affil= affil-num=21 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=22 en-affil=Division of Tumor Pathology, Near InfraRed Photo-Immuno-Therapy Research Institute, Kansai Medical University kn-affil= affil-num=23 en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University kn-affil= en-keyword=Plasmid kn-keyword=Plasmid en-keyword=Gene engineering kn-keyword=Gene engineering en-keyword=Cancer kn-keyword=Cancer en-keyword=Cell culture kn-keyword=Cell culture END start-ver=1.4 cd-journal=joma no-vol=150 cd-vols= no-issue=1 article-no= start-page=19 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250813 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biallelic variants in DNAJC7 cause familial amyotrophic lateral sclerosis with the TDP-43 pathology en-subtitle= kn-subtitle= en-abstract= kn-abstract=Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons. ALS pathology primarily involves the failure of protein quality control mechanisms, leading to the accumulation of misfolded proteins, particularly TAR DNA-binding protein 43 (TDP-43). TDP-43 aggregation is a central pathological feature of ALS. Maintaining protein homeostasis is critical and facilitated by heat shock proteins (HSPs), particularly the HSP40 family, which includes co-chaperones such as DNAJC7. Here, we report a family with three siblings affected by ALS who carry a homozygous c.518dupC frameshift variant in DNAJC7, a member of the HSP40 family. All three patients exhibited progressive muscle weakness, limb atrophy, bulbar palsy, and respiratory failure. Pathological examination revealed degeneration of both upper and lower motor neurons, with phosphorylated TDP-43-positive neuronal cytoplasmic inclusions in the frontal and temporal cortices. Immunoblot analysis were consistent with a type B pattern of phosphorylated TDP-43 in the precentral gyrus. Immunohistochemistry and RNA sequencing analyses demonstrated a substantial reduction in DNAJC7 expression at both the protein and RNA levels in affected brain regions. In a TDP-43 cell model, DNAJC7 knockdown impaired the disassembly of TDP-43 following arsenite-induced stress, whereas DNAJC7 overexpression suppressed the assembly and promoted the disassembly of arsenite-induced TDP-43 condensates. Furthermore, in a zebrafish ALS model, dnajc7 knockdown resulted in increased TDP-43 aggregation in motor neurons and reduced survival. To the best of our knowledge, this study provides the first evidence linking biallelic loss-of-function variants in DNAJC7 to familial ALS with TDP-43 pathology. en-copyright= kn-copyright= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokotaOsamu en-aut-sei=Yokota en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OusakaDaiki en-aut-sei=Ousaka en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SunHongming en-aut-sei=Sun en-aut-mei=Hongming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraguchiTakashi en-aut-sei=Haraguchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Ota-ElliottRicardo Satoshi en-aut-sei=Ota-Elliott en-aut-mei=Ricardo Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuokaChika en-aut-sei=Matsuoka en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawanoTomohito en-aut-sei=Kawano en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Nakashima-YasudaHanae en-aut-sei=Nakashima-Yasuda en-aut-mei=Hanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FukuiYusuke en-aut-sei=Fukui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakanoYumiko en-aut-sei=Nakano en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HasegawaMasato en-aut-sei=Hasegawa en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HosonoYasuyuki en-aut-sei=Hosono en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TeradaSeishi en-aut-sei=Terada en-aut-mei=Seishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurology, National Hospital Organisation Minami-Okayama Medical Centre kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Psychiatry, Zikei Hospital kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Brain and Neurosciences, Tokyo Metropolitan Institute of Medical Science kn-affil= affil-num=14 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Amyotrophic lateral sclerosis kn-keyword=Amyotrophic lateral sclerosis en-keyword=Heat shock protein kn-keyword=Heat shock protein en-keyword=DNAJC7 kn-keyword=DNAJC7 en-keyword=TDP-43 kn-keyword=TDP-43 en-keyword=Live-cell imaging kn-keyword=Live-cell imaging en-keyword=Zebrafish disease model kn-keyword=Zebrafish disease model END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=6 article-no= start-page=e00110-25 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250519 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mycobacterium tuberculosis bacillus induces pyroptosis in human lung fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=We previously reported that live, but not dead, virulent Mycobacterium tuberculosis (Mtb) H37Rv bacilli induce cell death in human lung fibroblast cell lines, MRC-5, MRC-9, and TIG-1. Here, using two distinct Mtb strains from two different lineages (HN878 lineage 2 and H37Rv lineage 4), we confirmed cell death at day 2 after infection with a device that measures cell growth/cytotoxicity in real time (Maestro-Z [AXION]). Mtb bacilli uptake by the fibroblast was confirmed with a transmission electron microscope on day 2. Expressions of inflammatory cytokines and interleukin (IL)?1, IL-6, and IL-8 were observed when exposed to live, but not dead bacteria. The cell death of fibroblasts induced by both Mtb strains tested was prevented by caspase-1/4 and NLRP3 inflammasome inhibitors, but not by caspase-3 and caspase-9 inhibitors. Therefore, we classified the fibroblast cell death by Mtb infection as pyroptosis. To investigate the biological and pathological relevance of fibroblast cell death by Mtb infection, we performed dual RNA-Seq analysis on Mtb within fibroblasts and Mtb-infected fibroblasts at day 2. In Mtb bacilli tcrR, secE2, ahpD, and mazF8 genes were highly induced during infection. These genes play roles in survival in a hypoxic environment, production of a calcium-binding protein-inducing cytokine, and regulation of transcription in a toxin-antitoxin system. The gene expressions of IL-1, IL-6, and IL-8, caspase-4, and NLRP3, but not of caspase-3 and caspase-9, were augmented in Mtb bacilli-infected fibroblasts. Taken together, our study suggests that Mtb bacilli attempt to survive in lung fibroblasts and that pyroptosis of the host fibroblasts activates the immune system against the infection. en-copyright= kn-copyright= en-aut-name=TakiiTakemasa en-aut-sei=Takii en-aut-mei=Takemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamadaHiroyuki en-aut-sei=Yamada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotozonoChihiro en-aut-sei=Motozono en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamasakiSho en-aut-sei=Yamasaki en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TorrellesJordi B. en-aut-sei=Torrelles en-aut-mei=Jordi B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TurnerJoanne en-aut-sei=Turner en-aut-mei=Joanne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimishimaAoi en-aut-sei=Kimishima en-aut-mei=Aoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AsamiYukihiro en-aut-sei=Asami en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OharaNaoya en-aut-sei=Ohara en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HidaShigeaki en-aut-sei=Hida en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HayashiHidetoshi en-aut-sei=Hayashi en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OnozakiKikuo en-aut-sei=Onozaki en-aut-mei=Kikuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=2 en-affil=Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=3 en-affil=Department of Molecular Immunology, Research Institute for Microbial Diseases, The University of Osaka kn-affil= affil-num=4 en-affil=Department of Molecular Immunology, Research Institute for Microbial Diseases, The University of Osaka kn-affil= affil-num=5 en-affil=Texas Biomedical Research Institute and International Center for the Advancement of Research & Education (I?CARE) kn-affil= affil-num=6 en-affil=Texas Biomedical Research Institute and International Center for the Advancement of Research & Education (I?CARE) kn-affil= affil-num=7 en-affil=Laboratory of Applied Microbial Chemistry, ?mura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=8 en-affil=Laboratory of Applied Microbial Chemistry, ?mura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=9 en-affil=Department of Oral Microbiology, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=11 en-affil=Department of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=12 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= en-keyword=Mycobacterium tuberculosis kn-keyword=Mycobacterium tuberculosis en-keyword=pyroptosis kn-keyword=pyroptosis en-keyword=caspase kn-keyword=caspase en-keyword=RNA-Seq kn-keyword=RNA-Seq en-keyword=cytokine kn-keyword=cytokine en-keyword=fibroblasts kn-keyword=fibroblasts END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=11 article-no= start-page=348 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Coronal Cementum and Reduced Enamel Epithelium on Occlusal Surface of Impacted Wisdom Tooth in a Human en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: There is only limited research on the coronal cementum of a tooth, and the mechanisms of its forming process are not well-defined. This report presents a coronal cementum on the occlusal surfaces of enamel in an impacted wisdom tooth in a human, which is not nearly the cervical portion. Materials and Methods: The tooth (Tooth #1) was derived from a 46-year-old female. Histological analysis, including hematoxylin and eosin (HE) and toluidine blue (TB) staining, and Scanning Electron Microscopy and Energy Dispersive X-ray Spectrometer (SEM-EDS) analysis of the extracted tooth were conducted. Radiographic examination showed that Tooth #1 was horizontally impacted in the maxilla and had the apex of a single root placed between the buccal and palatal roots of Tooth #2. Results: Coronal cementum was distributed widely on the enamel, and reduced enamel epithelium was also found with enamel matrix proteins histologically. The formation of acellular cementum was observed to be more predominant than that of the cellular cementum in Tooth #1. SEM showed that the occlusal cementum connected directly with enamel. Calcium mapping revealed an almost similar occlusal cementum and enamel. In addition, the spectrum of elements in coronal cementum resembled the primary cementum according to SEM-EDS. Discussion: Thus, coronal cementogenesis in impacted human teeth might be related to the existence of reduced enamel epithelium. en-copyright= kn-copyright= en-aut-name=HorieNaohiro en-aut-sei=Horie en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MurataMasaru en-aut-sei=Murata en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MinamidaYasuhito en-aut-sei=Minamida en-aut-mei=Yasuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagayasuHiroki en-aut-sei=Nagayasu en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimoTsuyoshi en-aut-sei=Shimo en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkazawaToshiyuki en-aut-sei=Akazawa en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujigiwaHidetsugu en-aut-sei=Tsujigiwa en-aut-mei=Hidetsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaikelYoussef en-aut-sei=Haikel en-aut-mei=Youssef kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Division of Reconstructive Surgery for Oral and Maxillofacial Region, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=2 en-affil=Division of Regenerative Medicine, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=3 en-affil=Division of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=4 en-affil=Division of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=5 en-affil=Division of Reconstructive Surgery for Oral and Maxillofacial Region, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=6 en-affil=Industrial Technology and Environment Research Development, Hokkaido Research Organization kn-affil= affil-num=7 en-affil=Department of Life Science, Faculty of Science, Okayama University of Science kn-affil= affil-num=8 en-affil=Department of Biomaterials and Bioengineering, Institut National de la Sant? et de la Recherche m?dicale Unit? Mixte de Recherche (INSERM UMR) _S 1121, University of Strasbourg kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=coronal cementum kn-keyword=coronal cementum en-keyword=human kn-keyword=human en-keyword=reduced epithelium kn-keyword=reduced epithelium en-keyword=impacted tooth kn-keyword=impacted tooth END start-ver=1.4 cd-journal=joma no-vol=218 cd-vols= no-issue= article-no= start-page=104922 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Alteration of perineuronal nets and parvalbumin interneurons in prefrontal cortex and hippocampus, and correlation with blood corticosterone in activity-based anorexia model mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Anorexia nervosa (AN) is an eating disorder characterized by restricted energy intake, severely underweight status, and frequent hyperactivity. Previous research has shown structural and functional alterations in the medial prefrontal cortex (mPFC) and hippocampus of AN patients. To investigate the pathological mechanism of AN, we analyzed the expression and distribution of parvalbumin (PV) interneurons and perineuronal nets (PNNs), which are implicated in the pathology of neuropsychiatric disorders, in the mPFC and hippocampus dorsal (HPCd) and ventral (HPCv) using an activity-based anorexia (ABA) mouse model. We found that PNN expression and density increased in the mPFC, with minor alterations in the HPCd and HPCv of ABA mice. The expression and distribution of PV neurons were unchanged in the brains of ABA mice, except for a regional decrease in PV-expressing neuron density in the HPCd. Co-localization analysis showed an increased number of PNNs enwrapping PV-negative neurons in the mPFC of ABA mice. Furthermore, the upregulation of PNN expression in the mPFC was positively correlated with elevated blood corticosterone levels, a well-known stress indicator, in ABA mice. Our findings suggest that the increased expression and distribution of PNNs surrounding PV-negative neurons in the mPFC may indicate the pathological mechanisms of AN. en-copyright= kn-copyright= en-aut-name=NguyenHoang Duy en-aut-sei=Nguyen en-aut-mei=Hoang Duy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiHaruko en-aut-sei=Miyazaki en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaiHiroki en-aut-sei=Kawai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakamotoShinji en-aut-sei=Sakamoto en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OohashiToshitaka en-aut-sei=Oohashi en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=anorexia nervosa kn-keyword=anorexia nervosa en-keyword=activity-based anorexia kn-keyword=activity-based anorexia en-keyword=perineuronal nets kn-keyword=perineuronal nets en-keyword=parvalbumin kn-keyword=parvalbumin en-keyword=corticosterone kn-keyword=corticosterone en-keyword=prefrontal cortex kn-keyword=prefrontal cortex en-keyword=hippocampus kn-keyword=hippocampus END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=1 article-no= start-page=e70146 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Gastric Atypical Lipomatous Tumor/Well]Differentiated Liposarcoma With Endoscopic Morphological Changes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Atypical lipomatous tumor/well-differentiated liposarcoma is a locally aggressive mesenchymal neoplasm composed of adipocytes and stromal cells. Gastric cases are exceedingly rare, and their malignant potential remains unclear. We report a case of a woman in her 60s who was found to have multiple submucosal tumor-like lesions of the stomach. Over time, the tumors increased in size, requiring a laparoscopic partial gastrectomy. Histological examination revealed a tumor composed of both fatty tissue and fibrous stroma with nuclear atypia. Immunohistochemistry showed positivity for CDK4 and MDM2, and fluorescence in situ hybridization confirmed MDM2 amplification, leading to a diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma. This case presented an unusual gastric manifestation, with multiple submucosal tumor-like lesions on endoscopy and exhibiting progressive morphological changes over several years. en-copyright= kn-copyright= en-aut-name=OmoteRika en-aut-sei=Omote en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OmoteShizuma en-aut-sei=Omote en-aut-mei=Shizuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SonobeHiroshi en-aut-sei=Sonobe en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HamanoRyosuke en-aut-sei=Hamano en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToyokawaTatsuya en-aut-sei=Toyokawa en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtsukaShinya en-aut-sei=Otsuka en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=InagakiMasaru en-aut-sei=Inagaki en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Diagnostic Pathology, NHO Fukuyama Medical Center kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Fukuyama Minami Hospital kn-affil= affil-num=3 en-affil=Department of Diagnostic Pathology, NHO Fukuyama Medical Center kn-affil= affil-num=4 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=5 en-affil=Department of Gastroenterology, NHO Fukuyama Medical Center kn-affil= affil-num=6 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=7 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=10 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=atypical lipomatous tumor kn-keyword=atypical lipomatous tumor en-keyword=CDK4 kn-keyword=CDK4 en-keyword=MDM2 kn-keyword=MDM2 en-keyword=stomach kn-keyword=stomach en-keyword=well-differentiated liposarcoma kn-keyword=well-differentiated liposarcoma END start-ver=1.4 cd-journal=joma no-vol=199 cd-vols= no-issue= article-no= start-page=108027 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real-world status of multimodal treatment of Stage IIIA-N2 non-small cell lung cancer in Japan: Results from the SOLUTION study, a non-interventional, multicenter cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: There is limited consensus on resectability criteria for Stage IIIA-N2 non-small cell lung cancer (NSCLC). We examined the patient characteristics, N2 status, treatment decisions, and clinical outcomes according to the treatment modality for Stage IIIA-N2 NSCLC in Japan.
Materials and methods: Patients with Stage IIIA-N2 NSCLC in Japan were consecutively registered in the SOLUTION study between 2013 and 2014. Patients were divided according to treatment (chemoradiotherapy [CRT], surgery + perioperative therapy [neoadjuvant and/or adjuvant therapy], surgery alone). Demographic characteristics, N2 status (number and morphological features), pathological information, and treatments were analyzed descriptively. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) were estimated using the Kaplan?Meier method.
Results: Of 227 patients registered, 133 underwent CRT, 56 underwent surgery + perioperative therapy, and 38 underwent surgery alone. The physicians reported the following reasons for unresectability for 116 of 133 CRT patients: large number of metastatic lymph nodes (70.7 %), extranodal infiltration (25.0 %), poor surgical tolerance (19.0 %), or other reasons (18.1 %). CRT was more frequently performed in patients whose lymph nodes had an infiltrative appearance (64.3 %) and was the predominant treatment in patients with multiple involved stations (discrete: 60.0 %; infiltrative: 80.4 %). Distant metastasis with/without local progression was found in 50.4 %, 50.0 %, and 36.8 % of patients in the CRT, surgery + perioperative therapy, and surgery alone groups, respectively. The respective 3-year OS and DFS/PFS rates (median values) were as follows: surgery + perioperative therapy?61.9 % (not reached) and 37.1 % (22.4 months; DFS); CRT group?42.2 % (31.9 months) and 26.8 % (12.0 months; PFS); surgery alone group?37.7 % (26.5 months) and 28.7 % (12.6 months; DFS).
Conclusion: This study has illuminated the real-world decision rules for choosing between surgical and non-surgical approaches in patients with Stage IIIA-N2 NSCLC. Our landmark data could support treatment decision making for using immune checkpoint inhibitors and targeted therapy for driver oncogenes in the perioperative therapy era. en-copyright= kn-copyright= en-aut-name=HorinouchiHidehito en-aut-sei=Horinouchi en-aut-mei=Hidehito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MurakamiHaruyasu en-aut-sei=Murakami en-aut-mei=Haruyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaHideyuki en-aut-sei=Harada en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SobueTomotaka en-aut-sei=Sobue en-aut-mei=Tomotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoTomohiro en-aut-sei=Kato en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AtagiShinji en-aut-sei=Atagi en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KozukiToshiyuki en-aut-sei=Kozuki en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TokitoTakaaki en-aut-sei=Tokito en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OizumiSatoshi en-aut-sei=Oizumi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SeikeMasahiro en-aut-sei=Seike en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MioTadashi en-aut-sei=Mio en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SoneTakashi en-aut-sei=Sone en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwaoChikako en-aut-sei=Iwao en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IwaneTakeshi en-aut-sei=Iwane en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KotoRyo en-aut-sei=Koto en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TsuboiMasahiro en-aut-sei=Tsuboi en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Oncology, Shizuoka Cancer Center kn-affil= affil-num=3 en-affil=Division of Radiation Therapy, Shizuoka Cancer Center kn-affil= affil-num=4 en-affil=Division of Environmental Medicine and Population Sciences, Graduate School of Medicine, Osaka University kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, National Hospital Organization Himeji Medical Cente kn-affil= affil-num=6 en-affil=Department of Thoracic Oncology, National Hospital Organization Kinki-Chuo Chest Medical Center kn-affil= affil-num=7 en-affil=Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=8 en-affil=Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center kn-affil= affil-num=10 en-affil=Department of Pulmonary Medicine and Oncology, Nippon Medical School Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, National Hospital Organization Kyoto Medical Center kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Kanazawa University Hospital kn-affil= affil-num=14 en-affil=Department of Medical, AstraZeneca K.K. kn-affil= affil-num=15 en-affil=Department of Medical, AstraZeneca K.K. kn-affil= affil-num=16 en-affil=Department of Medical, AstraZeneca K.K. kn-affil= affil-num=17 en-affil=Department of Thoracic Surgery, National Cancer Center Hospital East kn-affil= en-keyword=Non-small cell lung cancer kn-keyword=Non-small cell lung cancer en-keyword=Surgery kn-keyword=Surgery en-keyword=Adjuvant therapy kn-keyword=Adjuvant therapy en-keyword=Neoadjuvant therapy kn-keyword=Neoadjuvant therapy en-keyword=Chemoradiotherapy kn-keyword=Chemoradiotherapy en-keyword=Observational study kn-keyword=Observational study en-keyword=Retrospective study kn-keyword=Retrospective study END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=5 article-no= start-page=594 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Review Article: Diagnostic Paradigm Shift in Spine Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=Meticulous clinical examination is essential for spinal disorders to utilize the diagnostic methods and technologies that strongly support physicians and enhance clinical practice. A significant change in the approach to diagnosing spinal disorders has occurred in the last three decades, which has enhanced a more nuanced understanding of spine pathology. Traditional radiographic methods such as conventional and functional X-rays and CT scans are still the first line in the diagnosis of spinal disorders due to their low cost and accessibility. As more advanced imaging technologies become increasingly available worldwide, there is a constantly increasing trend in MRI scans for detecting spinal pathologies and making treatment decisions. Not only do MRI scans have superior diagnostic capabilities, but they also assist surgeons in performing meticulous preoperative planning, making them currently the most widely used diagnostic tool for spinal disorders. Positron Emission Tomography (PET) can help detect inflammatory lesions, infections, and tumors. Other advanced diagnostic tools such as CT/MRI fusion image, Functional Magnetic Resonance Imaging (fMRI), Upright and Kinetic MRI, magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI) could play an important role when it comes to detecting more special pathologies. However, some technical difficulties in the daily praxis and their high costs act as obstacles to their further spread. Integrating artificial intelligence and advancements in data analytics and virtual reality promises to enhance spinal proceduresf precision, safety, and efficacy. As these technologies continue to develop, they will play a critical role in transforming spinal surgery. This paradigm shift emphasizes the importance of continuous innovation and adaptability in improving the diagnosis and treatment of spinal disorders. en-copyright= kn-copyright= en-aut-name=LeventAras Efe en-aut-sei=Levent en-aut-mei=Aras Efe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaMasato en-aut-sei=Tanaka en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KumawatChetan en-aut-sei=Kumawat en-aut-mei=Chetan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HengChristian en-aut-sei=Heng en-aut-mei=Christian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NikolaosSalamalikis en-aut-sei=Nikolaos en-aut-mei=Salamalikis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=LatkaKajetan en-aut-sei=Latka en-aut-mei=Kajetan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyamotoAkiyoshi en-aut-sei=Miyamoto en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KomatsubaraTadashi en-aut-sei=Komatsubara en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AratakiShinya en-aut-sei=Arataki en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OdaYoshiaki en-aut-sei=Oda en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShinoharaKensuke en-aut-sei=Shinohara en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=10 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= en-keyword=diagnosis kn-keyword=diagnosis en-keyword=spine surgery kn-keyword=spine surgery en-keyword=innovative technique kn-keyword=innovative technique en-keyword=MRI kn-keyword=MRI en-keyword=myelography kn-keyword=myelography END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=7 article-no= start-page=002112 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses (ICTV) from the Animal dsRNA and ssRNA(?) Viruses Subcommittee, 2025 en-subtitle= kn-subtitle= en-abstract= kn-abstract=RNA viruses are ubiquitous in the environment and are important pathogens of humans, animals and plants. In 2024, the International Committee on Taxonomy of Viruses Animal dsRNA and ssRNA(?) Viruses Subcommittee submitted 18 taxonomic proposals for consideration. These proposals expanded the known virosphere by classifying 9 new genera and 88 species for newly detected virus genomes. Of note, newly established species expand the large family of Rhabdoviridae to 580 species. A new species in the family Arenaviridae includes a virus detected in Antarctic fish with a unique split nucleoprotein ORF. Additionally, four new species were established for historically isolated viruses with previously unsequenced genomes. Furthermore, three species were abolished due to incomplete genome sequence information, and one family was moved from being unassigned in the phylum Negarnaviricota into a subphylum and order. Herein, we summarize the 18 ratified taxonomic proposals and the general features of the current taxonomy, thereby supporting public and animal health responses. en-copyright= kn-copyright= en-aut-name=HughesHolly R. en-aut-sei=Hughes en-aut-mei=Holly R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BallingerMatthew J. en-aut-sei=Ballinger en-aut-mei=Matthew J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BaoYiming en-aut-sei=Bao en-aut-mei=Yiming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BejermanNicolas en-aut-sei=Bejerman en-aut-mei=Nicolas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BlasdellKim R. en-aut-sei=Blasdell en-aut-mei=Kim R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BrieseThomas en-aut-sei=Briese en-aut-mei=Thomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BrignoneJulia en-aut-sei=Brignone en-aut-mei=Julia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CarreraJean Paul en-aut-sei=Carrera en-aut-mei=Jean Paul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=De ConinckLander en-aut-sei=De Coninck en-aut-mei=Lander kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=de SouzaWilliam Marciel en-aut-sei=de Souza en-aut-mei=William Marciel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DebatHumberto en-aut-sei=Debat en-aut-mei=Humberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DietzgenRalf G. en-aut-sei=Dietzgen en-aut-mei=Ralf G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=D?rrwaldRalf en-aut-sei=D?rrwald en-aut-mei=Ralf kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ErdinMert en-aut-sei=Erdin en-aut-mei=Mert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FooksAnthony R. en-aut-sei=Fooks en-aut-mei=Anthony R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ForbesKristian M. en-aut-sei=Forbes en-aut-mei=Kristian M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=Freitas-Ast?aJuliana en-aut-sei=Freitas-Ast?a en-aut-mei=Juliana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=GarciaJorge B. en-aut-sei=Garcia en-aut-mei=Jorge B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=GeogheganJemma L. en-aut-sei=Geoghegan en-aut-mei=Jemma L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=GrimwoodRebecca M. en-aut-sei=Grimwood en-aut-mei=Rebecca M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HorieMasayuki en-aut-sei=Horie en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HyndmanTimothy H. en-aut-sei=Hyndman en-aut-mei=Timothy H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=JohneReimar en-aut-sei=Johne en-aut-mei=Reimar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KlenaJohn D. en-aut-sei=Klena en-aut-mei=John D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KooninEugene V. en-aut-sei=Koonin en-aut-mei=Eugene V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KostygovAlexei Y. en-aut-sei=Kostygov en-aut-mei=Alexei Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=KrupovicMart en-aut-sei=Krupovic en-aut-mei=Mart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=KuhnJens H. en-aut-sei=Kuhn en-aut-mei=Jens H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=LetkoMichael en-aut-sei=Letko en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=LiJun-Min en-aut-sei=Li en-aut-mei=Jun-Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=LiuYiyun en-aut-sei=Liu en-aut-mei=Yiyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=MartinMaria Laura en-aut-sei=Martin en-aut-mei=Maria Laura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=MullNathaniel en-aut-sei=Mull en-aut-mei=Nathaniel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=NazarYael en-aut-sei=Nazar en-aut-mei=Yael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=NowotnyNorbert en-aut-sei=Nowotny en-aut-mei=Norbert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=NunesM?rcio Roberto Teixeira en-aut-sei=Nunes en-aut-mei=M?rcio Roberto Teixeira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=?klandArnfinn Lodden en-aut-sei=?kland en-aut-mei=Arnfinn Lodden kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=RubbenstrothDennis en-aut-sei=Rubbenstroth en-aut-mei=Dennis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=RussellBrandy J. en-aut-sei=Russell en-aut-mei=Brandy J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=SchottEric en-aut-sei=Schott en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=SeifertStephanie en-aut-sei=Seifert en-aut-mei=Stephanie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=SenCarina en-aut-sei=Sen en-aut-mei=Carina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=ShedroffElizabeth en-aut-sei=Shedroff en-aut-mei=Elizabeth kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=SironenTarja en-aut-sei=Sironen en-aut-mei=Tarja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=SmuraTeemu en-aut-sei=Smura en-aut-mei=Teemu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=TavaresCamila Prestes Dos Santos en-aut-sei=Tavares en-aut-mei=Camila Prestes Dos Santos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=TeshRobert B. en-aut-sei=Tesh en-aut-mei=Robert B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=TilstonNatasha L. en-aut-sei=Tilston en-aut-mei=Natasha L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=TordoNo?l en-aut-sei=Tordo en-aut-mei=No?l kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=VasilakisNikos en-aut-sei=Vasilakis en-aut-mei=Nikos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=WalkerPeter J. en-aut-sei=Walker en-aut-mei=Peter J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=52 ORCID= en-aut-name=WangFei en-aut-sei=Wang en-aut-mei=Fei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=53 ORCID= en-aut-name=WhitfieldAnna E. en-aut-sei=Whitfield en-aut-mei=Anna E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=54 ORCID= en-aut-name=WhitmerShannon L.M. en-aut-sei=Whitmer en-aut-mei=Shannon L.M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=55 ORCID= en-aut-name=WolfYuri I. en-aut-sei=Wolf en-aut-mei=Yuri I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=56 ORCID= en-aut-name=XiaHan en-aut-sei=Xia en-aut-mei=Han kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=57 ORCID= en-aut-name=YeGong-Yin en-aut-sei=Ye en-aut-mei=Gong-Yin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=58 ORCID= en-aut-name=YeZhuangxin en-aut-sei=Ye en-aut-mei=Zhuangxin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=59 ORCID= en-aut-name=YurchenkoVyacheslav en-aut-sei=Yurchenko en-aut-mei=Vyacheslav kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=60 ORCID= en-aut-name=ZhaoMingli en-aut-sei=Zhao en-aut-mei=Mingli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=61 ORCID= affil-num=1 en-affil=Centers for Disease Control and Prevention kn-affil= affil-num=2 en-affil=Biological Sciences, Mississippi State University kn-affil= affil-num=3 en-affil=National Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of Sciences kn-affil= affil-num=4 en-affil=Consejo Nacional de Investigaciones Cient?ficas y T?cnicas (CONICET) and Instituto Nacional de Tecnolog?a Agropecuaria (INTA) kn-affil= affil-num=5 en-affil=CSIRO Health and Biosecurity kn-affil= affil-num=6 en-affil=Center for Infection and Immunity, and Department of Epidemiology, Mailman School of Public Health, Columbia University kn-affil= affil-num=7 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=8 en-affil=Instituto Conmemorativo Gorgas de Estudios de la Salud kn-affil= affil-num=9 en-affil=Division of Clinical and Epidemiological Virology, KU Leuven kn-affil= affil-num=10 en-affil=Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky kn-affil= affil-num=11 en-affil=Instituto Nacional de Tecnolog?a Agropecuaria (INTA) kn-affil= affil-num=12 en-affil=QAAFI, The University of Queensland kn-affil= affil-num=13 en-affil=Robert Koch Institut kn-affil= affil-num=14 en-affil=Department of Virology, University of Helsinki kn-affil= affil-num=15 en-affil=Animal and Plant Health Agency (APHA) kn-affil= affil-num=16 en-affil=Department of Biological Sciences, University of Arkansas kn-affil= affil-num=17 en-affil=Embrapa Cassava and Fruits kn-affil= affil-num=18 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=19 en-affil=Department of Microbiology and Immunology, University of Otago kn-affil= affil-num=20 en-affil=Department of Microbiology and Immunology, University of Otago kn-affil= affil-num=21 en-affil=Osaka International Research Center for Infectious Diseases, Osaka Metropolitan University kn-affil= affil-num=22 en-affil=School of Veterinary Medicine, Murdoch University kn-affil= affil-num=23 en-affil=German Federal Institute for Risk Assessment kn-affil= affil-num=24 en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention kn-affil= affil-num=25 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=26 en-affil=Computational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of Health kn-affil= affil-num=27 en-affil=University of Ostrava kn-affil= affil-num=28 en-affil=Institut Pasteur, Universit? Paris Cit?, CNRS UMR6047, Archaeal Virology Unit kn-affil= affil-num=29 en-affil=Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health kn-affil= affil-num=30 en-affil=Paul G. Allen School for Global Health, Washington State University kn-affil= affil-num=31 en-affil=Institute of Plant Virology, Ningbo University kn-affil= affil-num=32 en-affil=National Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of Sciences kn-affil= affil-num=33 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=34 en-affil=Department of Natural Sciences, Shawnee State University kn-affil= affil-num=35 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=36 en-affil=College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health kn-affil= affil-num=37 en-affil=Universidade Federal do Par? kn-affil= affil-num=38 en-affil=Pharmaq Analytiq kn-affil= affil-num=39 en-affil=Institute of Diagnostic Virology, Friedrich-Loeffler-Institut kn-affil= affil-num=40 en-affil=Centers for Disease Control and Prevention kn-affil= affil-num=41 en-affil=Institute of Marine and Environmental Technology, University of Maryland Center for Environmental Science kn-affil= affil-num=42 en-affil=Paul G. Allen School for Global Health, Washington State University kn-affil= affil-num=43 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=44 en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention kn-affil= affil-num=45 en-affil=Department of Virology, University of Helsinki kn-affil= affil-num=46 en-affil=Department of Virology, University of Helsinki kn-affil= affil-num=47 en-affil=Integrated Group of Aquaculture and Environmental Studies, Federal University of Paran? kn-affil= affil-num=48 en-affil=Department of Pathology, The University of Texas Medical Branch kn-affil= affil-num=49 en-affil=Department of Microbiology and Immunology, Indiana University School of Medicine kn-affil= affil-num=50 en-affil=Institut Pasteur kn-affil= affil-num=51 en-affil=Department of Pathology, The University of Texas Medical Branch kn-affil= affil-num=52 en-affil=University of Queensland kn-affil= affil-num=53 en-affil=Wuhan Institute of Virology, Chinese Academy of Sciences kn-affil= affil-num=54 en-affil=North Carolina State University kn-affil= affil-num=55 en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention kn-affil= affil-num=56 en-affil=Computational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of Health kn-affil= affil-num=57 en-affil=Wuhan Institute of Virology, Chinese Academy of Sciences kn-affil= affil-num=58 en-affil=Institute of Insect Sciences, Zhejiang University kn-affil= affil-num=59 en-affil=Institute of Plant Virology, Ningbo University kn-affil= affil-num=60 en-affil=University of Ostrava kn-affil= affil-num=61 en-affil=Department of Pathobiology and Population Sciences, Royal Veterinary College kn-affil= END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=7 article-no= start-page=002114 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses from the Plant Viruses Subcommittee, 2025 en-subtitle= kn-subtitle= en-abstract= kn-abstract=In March 2025, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote, newly proposed taxa were added to those under the mandate of the Plant Viruses Subcommittee. In brief, 1 new order, 3 new families, 6 new genera, 2 new subgenera and 206 new species were created. Some taxa were reorganized. Genus Cytorhabdovirus in the family Rhabdoviridae was abolished and its taxa were redistributed into three new genera Alphacytorhabdovirus, Betacytorhabdovirus and Gammacytorhabdovirus. Genus Waikavirus in the family Secoviridae was reorganized into two subgenera (Actinidivirus and Ritunrivirus). One family and four previously unaffiliated genera were moved to the newly established order Tombendovirales. Twelve species not assigned to a genus were abolished. To comply with the ICTV mandate of a binomial format for virus species, eight species were renamed. Demarcation criteria in the absence of biological information were defined in the genus Ilarvirus (family Bromoviridae). This article presents the updated taxonomy put forth by the Plant Viruses Subcommittee and ratified by the ICTV. en-copyright= kn-copyright= en-aut-name=RubinoLuisa en-aut-sei=Rubino en-aut-mei=Luisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AbrahamianPeter en-aut-sei=Abrahamian en-aut-mei=Peter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AnWenxia en-aut-sei=An en-aut-mei=Wenxia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArandaMiguel A. en-aut-sei=Aranda en-aut-mei=Miguel A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Ascencio-Iba?ezJos? T. en-aut-sei=Ascencio-Iba?ez en-aut-mei=Jos? T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BejermanNicolas en-aut-sei=Bejerman en-aut-mei=Nicolas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BlouinArnaud G. en-aut-sei=Blouin en-aut-mei=Arnaud G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CandresseThierry en-aut-sei=Candresse en-aut-mei=Thierry kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=CantoTomas en-aut-sei=Canto en-aut-mei=Tomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=CaoMengji en-aut-sei=Cao en-aut-mei=Mengji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=CarrJohn P. en-aut-sei=Carr en-aut-mei=John P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ChoWon Kyong en-aut-sei=Cho en-aut-mei=Won Kyong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ConstableFiona en-aut-sei=Constable en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=DasguptaIndranil en-aut-sei=Dasgupta en-aut-mei=Indranil kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=DebatHumberto en-aut-sei=Debat en-aut-mei=Humberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=DietzgenRalf G. en-aut-sei=Dietzgen en-aut-mei=Ralf G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=DigiaroMichele en-aut-sei=Digiaro en-aut-mei=Michele kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=DonaireLivia en-aut-sei=Donaire en-aut-mei=Livia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ElbeainoToufic en-aut-sei=Elbeaino en-aut-mei=Toufic kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FargetteDenis en-aut-sei=Fargette en-aut-mei=Denis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=FilardoFiona en-aut-sei=Filardo en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=FischerMatthias G. en-aut-sei=Fischer en-aut-mei=Matthias G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FontdevilaNuria en-aut-sei=Fontdevila en-aut-mei=Nuria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=FoxAdrian en-aut-sei=Fox en-aut-mei=Adrian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=Freitas-AstuaJuliana en-aut-sei=Freitas-Astua en-aut-mei=Juliana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=FuchsMarc en-aut-sei=Fuchs en-aut-mei=Marc kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=GeeringAndrew D.W. en-aut-sei=Geering en-aut-mei=Andrew D.W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=GhafariMahan en-aut-sei=Ghafari en-aut-mei=Mahan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=Hafr?nAnders en-aut-sei=Hafr?n en-aut-mei=Anders kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=HammondJohn en-aut-sei=Hammond en-aut-mei=John kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=HammondRosemarie en-aut-sei=Hammond en-aut-mei=Rosemarie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=Hasi?w-JaroszewskaBeata en-aut-sei=Hasi?w-Jaroszewska en-aut-mei=Beata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=HebrardEugenie en-aut-sei=Hebrard en-aut-mei=Eugenie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=Hern?ndezCarmen en-aut-sei=Hern?ndez en-aut-mei=Carmen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=HilyJean-Michel en-aut-sei=Hily en-aut-mei=Jean-Michel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=HosseiniAhmed en-aut-sei=Hosseini en-aut-mei=Ahmed kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=HullRoger en-aut-sei=Hull en-aut-mei=Roger kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=Inoue-NagataAlice K. en-aut-sei=Inoue-Nagata en-aut-mei=Alice K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=JordanRamon en-aut-sei=Jordan en-aut-mei=Ramon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=KreuzeJan F. en-aut-sei=Kreuze en-aut-mei=Jan F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=KrupovicMart en-aut-sei=Krupovic en-aut-mei=Mart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=KubotaKenji en-aut-sei=Kubota en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=KuhnJens H. en-aut-sei=Kuhn en-aut-mei=Jens H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=LeisnerScott en-aut-sei=Leisner en-aut-mei=Scott kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=LettJean-Michel en-aut-sei=Lett en-aut-mei=Jean-Michel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=LiChengyu en-aut-sei=Li en-aut-mei=Chengyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=LiFan en-aut-sei=Li en-aut-mei=Fan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=LiJun Min en-aut-sei=Li en-aut-mei=Jun Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=L?pez-LambertiniPaola M. en-aut-sei=L?pez-Lambertini en-aut-mei=Paola M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=Lopez-MoyaJuan J. en-aut-sei=Lopez-Moya en-aut-mei=Juan J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=MaclotFrancois en-aut-sei=Maclot en-aut-mei=Francois kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=52 ORCID= en-aut-name=M?kinenKristiina en-aut-sei=M?kinen en-aut-mei=Kristiina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=53 ORCID= en-aut-name=MartinDarren en-aut-sei=Martin en-aut-mei=Darren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=54 ORCID= en-aut-name=MassartSebastien en-aut-sei=Massart en-aut-mei=Sebastien kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=55 ORCID= en-aut-name=MillerW. Allen en-aut-sei=Miller en-aut-mei=W. Allen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=56 ORCID= en-aut-name=MohammadiMusa en-aut-sei=Mohammadi en-aut-mei=Musa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=57 ORCID= en-aut-name=MollovDimitre en-aut-sei=Mollov en-aut-mei=Dimitre kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=58 ORCID= en-aut-name=MullerEmmanuelle en-aut-sei=Muller en-aut-mei=Emmanuelle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=59 ORCID= en-aut-name=NagataTatsuya en-aut-sei=Nagata en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=60 ORCID= en-aut-name=Navas-CastilloJes?s en-aut-sei=Navas-Castillo en-aut-mei=Jes?s kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=61 ORCID= en-aut-name=NeriyaYutaro en-aut-sei=Neriya en-aut-mei=Yutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=62 ORCID= en-aut-name=Ochoa-CoronaFrancisco M. en-aut-sei=Ochoa-Corona en-aut-mei=Francisco M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=63 ORCID= en-aut-name=OhshimaKazusato en-aut-sei=Ohshima en-aut-mei=Kazusato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=64 ORCID= en-aut-name=Pall?sVicente en-aut-sei=Pall?s en-aut-mei=Vicente kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=65 ORCID= en-aut-name=PappuHanu en-aut-sei=Pappu en-aut-mei=Hanu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=66 ORCID= en-aut-name=PetrzikKarel en-aut-sei=Petrzik en-aut-mei=Karel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=67 ORCID= en-aut-name=PoogginMikhail en-aut-sei=Pooggin en-aut-mei=Mikhail kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=68 ORCID= en-aut-name=PrigigalloMaria Isabella en-aut-sei=Prigigallo en-aut-mei=Maria Isabella kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=69 ORCID= en-aut-name=Ramos-Gonz?lezPedro L. en-aut-sei=Ramos-Gonz?lez en-aut-mei=Pedro L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=70 ORCID= en-aut-name=RibeiroSimone en-aut-sei=Ribeiro en-aut-mei=Simone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=71 ORCID= en-aut-name=Richert-P?ggelerKatja R. en-aut-sei=Richert-P?ggeler en-aut-mei=Katja R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=72 ORCID= en-aut-name=RoumagnacPhilippe en-aut-sei=Roumagnac en-aut-mei=Philippe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=73 ORCID= en-aut-name=RoyAvijit en-aut-sei=Roy en-aut-mei=Avijit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=74 ORCID= en-aut-name=SabanadzovicSead en-aut-sei=Sabanadzovic en-aut-mei=Sead kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=75 ORCID= en-aut-name=?af??ov?Dana en-aut-sei=?af??ov? en-aut-mei=Dana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=76 ORCID= en-aut-name=SaldarelliPasquale en-aut-sei=Saldarelli en-aut-mei=Pasquale kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=77 ORCID= en-aut-name=Sanfa?onH?l?ne en-aut-sei=Sanfa?on en-aut-mei=H?l?ne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=78 ORCID= en-aut-name=SarmientoCecilia en-aut-sei=Sarmiento en-aut-mei=Cecilia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=79 ORCID= en-aut-name=SasayaTakahide en-aut-sei=Sasaya en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=80 ORCID= en-aut-name=ScheetsKay en-aut-sei=Scheets en-aut-mei=Kay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=81 ORCID= en-aut-name=SchravesandeWillem E.W. en-aut-sei=Schravesande en-aut-mei=Willem E.W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=82 ORCID= en-aut-name=SealSusan en-aut-sei=Seal en-aut-mei=Susan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=83 ORCID= en-aut-name=ShimomotoYoshifumi en-aut-sei=Shimomoto en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=84 ORCID= en-aut-name=S?meraMerike en-aut-sei=S?mera en-aut-mei=Merike kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=85 ORCID= en-aut-name=StavoloneLivia en-aut-sei=Stavolone en-aut-mei=Livia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=86 ORCID= en-aut-name=StewartLucy R. en-aut-sei=Stewart en-aut-mei=Lucy R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=87 ORCID= en-aut-name=TeycheneyPierre-Yves en-aut-sei=Teycheney en-aut-mei=Pierre-Yves kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=88 ORCID= en-aut-name=ThomasJohn E. en-aut-sei=Thomas en-aut-mei=John E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=89 ORCID= en-aut-name=ThompsonJeremy R. en-aut-sei=Thompson en-aut-mei=Jeremy R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=90 ORCID= en-aut-name=TiberiniAntonio en-aut-sei=Tiberini en-aut-mei=Antonio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=91 ORCID= en-aut-name=TomitakaYasuhiro en-aut-sei=Tomitaka en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=92 ORCID= en-aut-name=TzanetakisIoannis en-aut-sei=Tzanetakis en-aut-mei=Ioannis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=93 ORCID= en-aut-name=UmberMarie en-aut-sei=Umber en-aut-mei=Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=94 ORCID= en-aut-name=UrbinoCica en-aut-sei=Urbino en-aut-mei=Cica kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=95 ORCID= en-aut-name=van den BurgHarrold A. en-aut-sei=van den Burg en-aut-mei=Harrold A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=96 ORCID= en-aut-name=Van der VlugtRen? A.A. en-aut-sei=Van der Vlugt en-aut-mei=Ren? A.A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=97 ORCID= en-aut-name=VarsaniArvind en-aut-sei=Varsani en-aut-mei=Arvind kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=98 ORCID= en-aut-name=VerhageAdriaan en-aut-sei=Verhage en-aut-mei=Adriaan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=99 ORCID= en-aut-name=VillamorDan en-aut-sei=Villamor en-aut-mei=Dan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=100 ORCID= en-aut-name=von BargenSusanne en-aut-sei=von Bargen en-aut-mei=Susanne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=101 ORCID= en-aut-name=WalkerPeter J. en-aut-sei=Walker en-aut-mei=Peter J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=102 ORCID= en-aut-name=WetzelThierry en-aut-sei=Wetzel en-aut-mei=Thierry kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=103 ORCID= en-aut-name=WhitfieldAnna E. en-aut-sei=Whitfield en-aut-mei=Anna E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=104 ORCID= en-aut-name=WylieStephen J. en-aut-sei=Wylie en-aut-mei=Stephen J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=105 ORCID= en-aut-name=YangCaixia en-aut-sei=Yang en-aut-mei=Caixia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=106 ORCID= en-aut-name=ZerbiniF. Murilo en-aut-sei=Zerbini en-aut-mei=F. Murilo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=107 ORCID= en-aut-name=ZhangSong en-aut-sei=Zhang en-aut-mei=Song kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=108 ORCID= affil-num=1 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=2 en-affil=USDA-ARS, BARC, National Germplasm Resources Laboratory kn-affil= affil-num=3 en-affil=Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University kn-affil= affil-num=4 en-affil=Centro de Edafolog?a y Biolog?a Aplicada del Segura-CSIC kn-affil= affil-num=5 en-affil=Department of Molecular and Structural Biochemistry, North Carolina State University kn-affil= affil-num=6 en-affil=Unidad de Fitopatolog?a y Modelizaci?n Agr?cola (UFYMA) INTA-CONICET kn-affil= affil-num=7 en-affil=Plant Protection Department kn-affil= affil-num=8 en-affil=UMR 1332 Biologie du Fruit et Pathologie, University of Bordeaux, INRAE kn-affil= affil-num=9 en-affil=Margarita Salas Center for Biological Research (CIB-CSIC) Spanish Council for Scientific Research (CSIC) kn-affil= affil-num=10 en-affil=National Citrus Engineering and Technology Research Center, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Citrus Research Institute, Southwest University kn-affil= affil-num=11 en-affil=Department of Plant Sciences, University of Cambridge kn-affil= affil-num=12 en-affil=Agriculture and Life Sciences Research Institute, Kangwon National University kn-affil= affil-num=13 en-affil=Agriculture Victoria Research, Department of Energy, Environment and Climate Action and School of Applied Systems Biology, La Trobe University kn-affil= affil-num=14 en-affil=University of Delhi South Campu kn-affil= affil-num=15 en-affil=Unidad de Fitopatolog?a y Modelizaci?n Agr?cola (UFYMA) INTA-CONICET kn-affil= affil-num=16 en-affil=Queensland Alliance for Agriculture and Food Innovation, The University of Queensland kn-affil= affil-num=17 en-affil=CIHEAM, Istituto Agronomico Mediterraneo of Bari kn-affil= affil-num=18 en-affil=Centro de Edafolog?a y Biolog?a Aplicada del Segura-CSIC kn-affil= affil-num=19 en-affil=CIHEAM, Istituto Agronomico Mediterraneo of Bari kn-affil= affil-num=20 en-affil=Virus South Data kn-affil= affil-num=21 en-affil=Queensland Department of Primary Industries kn-affil= affil-num=22 en-affil=Max Planck Institute for Marine Microbiology kn-affil= affil-num=23 en-affil=Plant Protection Department kn-affil= affil-num=24 en-affil=Fera Science Ltd (Fera), York Biotech Campus kn-affil= affil-num=25 en-affil=Embrapa Cassava and Fruits, Brazilian Agricultural Research Corporation kn-affil= affil-num=26 en-affil=Plant Pathology, Cornell University kn-affil= affil-num=27 en-affil=Queensland Alliance for Agriculture and Food Innovation, The University of Queensland kn-affil= affil-num=28 en-affil=Department of Biology, University of Oxford kn-affil= affil-num=29 en-affil=Swedish University of Agriculture kn-affil= affil-num=30 en-affil=USDA-ARS, USNA, Floral and Nursery Plants Research Unit kn-affil= affil-num=31 en-affil=USDA-ARS, BARC, Molecular Plant Pathology Laboratory kn-affil= affil-num=32 en-affil=Institute of Plant Protection-NRI kn-affil= affil-num=33 en-affil=PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute Agro kn-affil= affil-num=34 en-affil=Instituto de Biolog?a Molecular y Celular de Plantas (IBMCP), Universitat Polit?cnica de Valencia-CSIC kn-affil= affil-num=35 en-affil=Institut Fran?ais de la Vigne et du Vin kn-affil= affil-num=36 en-affil=Vali-e-Asr University of Rafsanjan, Department of Plant Protection kn-affil= affil-num=37 en-affil=Retired from John Innes Centre kn-affil= affil-num=38 en-affil=Embrapa Hortali?as kn-affil= affil-num=39 en-affil=USDA-ARS, USNA, Floral and Nursery Plants Research Unit kn-affil= affil-num=40 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=41 en-affil=International Potato Center (CIP) kn-affil= affil-num=42 en-affil=Institut Pasteur, Universit? Paris Cit?, CNRS UMR6047, Archaeal Virology Unit kn-affil= affil-num=43 en-affil=Institute for Plant Protection, NARO kn-affil= affil-num=44 en-affil=Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health kn-affil= affil-num=45 en-affil=Department of Biological Sciences, University of Toledo kn-affil= affil-num=46 en-affil=CIRAD, UMR PVBMT kn-affil= affil-num=47 en-affil=Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University kn-affil= affil-num=48 en-affil=State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University kn-affil= affil-num=49 en-affil=Institute of Plant Virology, Ningbo University kn-affil= affil-num=50 en-affil=Instituto de Patolog?a Vegetal (IPAVE), INTA, Unidad de Fitopatolog?a y Modelizaci?n Agr?cola (UFYMA) INTA-CONICET kn-affil= affil-num=51 en-affil=Centre for Research in Agricultural Genomics, CRAG (CSIC-IRTA-UAB-UB) kn-affil= affil-num=52 en-affil=UMR 1332 Biologie du Fruit et Pathologie, University of Bordeaux, INRAE kn-affil= affil-num=53 en-affil=Department of Agricultural Sciences, University of Helsinki kn-affil= affil-num=54 en-affil=Institute of Infectious Disease and Molecular Medicine, University of Cape Town kn-affil= affil-num=55 en-affil=Plant Pathology Laboratory, TERRA Gembloux Agro-Bio Tech, University of Liege kn-affil= affil-num=56 en-affil=Department of Plant Pathology, Entomology and Microbiology, Iowa State University kn-affil= affil-num=57 en-affil=Department of Plant Protection, Gorgan University of Agricultural Sciences and Natural Resources kn-affil= affil-num=58 en-affil=USDA-APHIS, Plant Protection and Quarantine kn-affil= affil-num=59 en-affil=CIRAD, AGAP Institut; AGAP Institut, University of Montpellier; CIRAD, INRAE kn-affil= affil-num=60 en-affil=Instituto de Ci?ncias Biol?gicas, Universidade de Bras?lia kn-affil= affil-num=61 en-affil=Instituto de Hortofruticultura Subtropical y Mediterr?nea gLa Mayorah (IHSM-UMA-CSIC), Consejo Superior de Investigaciones Cient?ficas kn-affil= affil-num=62 en-affil=Utsunomiya University kn-affil= affil-num=63 en-affil=Oklahoma State University, Institute for Biosecurity & Microbial Forensics kn-affil= affil-num=64 en-affil=Saga University kn-affil= affil-num=65 en-affil=Instituto de Biolog?a Molecular y Celular de Plantas (IBMCP), Universitat Polit?cnica de Valencia-CSIC kn-affil= affil-num=66 en-affil=Department of Plant Pathology, Washington State University kn-affil= affil-num=67 en-affil=Institute of Plant Molecular Biology kn-affil= affil-num=68 en-affil=PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD kn-affil= affil-num=69 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=70 en-affil=Applied Molecular Biology Laboratory, Instituto Biol?gico de S?o Paulo kn-affil= affil-num=71 en-affil=Embrapa Recursos Gen?ticos e Biotecnologia kn-affil= affil-num=72 en-affil=Julius K?hn Institute, Federal Research Centre for Cultivated Plants, Institute for Epidemiology and Pathogen Diagnostics kn-affil= affil-num=73 en-affil=CIRAD, UMR PHIM kn-affil= affil-num=74 en-affil=USDA-ARS, BARC, Molecular Plant Pathology Laboratory, Beltsville, MD, USA kn-affil= affil-num=75 en-affil=Department of Agricultural Science and Plant Protection, Mississippi State University kn-affil= affil-num=76 en-affil=Department of Cell Biology and Genetics, Faculty of Science, Palack? University Olomouc kn-affil= affil-num=77 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=78 en-affil=Summerland Research and Development Centre, Agriculture and Agri-Food Canada kn-affil= affil-num=79 en-affil=Department of Chemistry and Biotechnology, Tallinn University of Technology kn-affil= affil-num=80 en-affil=Strategic Planning Headquarters, NARO kn-affil= affil-num=81 en-affil=Department of Plant Pathology, Ecology and Evolution, Oklahoma State University kn-affil= affil-num=82 en-affil=Molecular Plant Pathology, University of Amsterdam kn-affil= affil-num=83 en-affil=Natural Resources Institute, University of Greenwich kn-affil= affil-num=84 en-affil=Kochi Agricultural Research Center kn-affil= affil-num=85 en-affil=Department of Chemistry and Biotechnology, Tallinn University of Technology kn-affil= affil-num=86 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=87 en-affil=Currently unaffiliated kn-affil= affil-num=88 en-affil=CIRAD, UMR PVBMT & UMR PVBMT, Universit? de la R?union kn-affil= affil-num=89 en-affil=Queensland Alliance for Agriculture and Food Innovation, The University of Queensland kn-affil= affil-num=90 en-affil=Plant Health and Environment Laboratory kn-affil= affil-num=91 en-affil=Council for Agricultural Research and Economics, Research Centre for Plant Protection and Certification kn-affil= affil-num=92 en-affil=Institute for Plant Protection, NARO kn-affil= affil-num=93 en-affil=Department of Entomology and Plant Pathology, Division of Agriculture, University of Arkansas System kn-affil= affil-num=94 en-affil=INRAE, UR ASTRO kn-affil= affil-num=95 en-affil=PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute Agro kn-affil= affil-num=96 en-affil=Molecular Plant Pathology, University of Amsterdam kn-affil= affil-num=97 en-affil=Wageningen University and Research kn-affil= affil-num=98 en-affil=The Biodesign Center for Fundamental and Applied Microbiomics, Center for Evolution and Medicine, School of Life Sciences, Arizona State University kn-affil= affil-num=99 en-affil=Rijk Zwaan Breeding B.V. kn-affil= affil-num=100 en-affil=Department of Entomology and Plant Pathology, Division of Agriculture, University of Arkansas System kn-affil= affil-num=101 en-affil=Humboldt-Universit?t zu Berlin, Thaer-Institute of Agricultural and Horticultural Sciences kn-affil= affil-num=102 en-affil=The University of Queensland kn-affil= affil-num=103 en-affil=Dienstleistungszentrum L?ndlicher Raum Rheinpfalz kn-affil= affil-num=104 en-affil=North Carolina State University kn-affil= affil-num=105 en-affil=Food Futures Institute, Murdoch University kn-affil= affil-num=106 en-affil=Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University kn-affil= affil-num=107 en-affil=Dep. de Fitopatologia/BIOAGRO, Universidade Federal de Vi?osa kn-affil= affil-num=108 en-affil=National Citrus Engineering and Technology Research Center, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Citrus Research Institute, Southwest University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=6 article-no= start-page=466 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250617 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Artificial Intelligence Approach in Machine Learning-Based Modeling and Networking of the Coronavirus Pathogenesis Pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=The coronavirus pathogenesis pathway, which consists of severe acute respiratory syndrome (SARS) coronavirus infection and signaling pathways, including the interferon pathway, the transforming growth factor beta pathway, the mitogen-activated protein kinase pathway, the apoptosis pathway, and the inflammation pathway, is activated upon coronaviral infection. An artificial intelligence approach based on machine learning was utilized to develop models with images of the coronavirus pathogenesis pathway to predict the activation states. Data on coronaviral infection held in a database were analyzed with Ingenuity Pathway Analysis (IPA), a network pathway analysis tool. Data related to SARS coronavirus 2 (SARS-CoV-2) were extracted from more than 100,000 analyses and datasets in the IPA database. A total of 27 analyses, including nine analyses of SARS-CoV-2-infected human-induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes and fibroblasts, and a total of 22 analyses of SARS-CoV-2-infected lung adenocarcinoma (LUAD), were identified as being related to ghumanh and gSARS coronavirus 2h in the database. The coronavirus pathogenesis pathway was activated in SARS-CoV-2-infected iPSC-derived cells and LUAD cells. A prediction model was developed in Python 3.11 using images of the coronavirus pathogenesis pathway under different conditions. The prediction model of activation states of the coronavirus pathogenesis pathway may aid in treatment identification. en-copyright= kn-copyright= en-aut-name=TanabeShihori en-aut-sei=Tanabe en-aut-mei=Shihori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=QuaderSabina en-aut-sei=Quader en-aut-mei=Sabina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OnoRyuichi en-aut-sei=Ono en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaHiroyoshi Y. en-aut-sei=Tanaka en-aut-mei=Hiroyoshi Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoAkihisa en-aut-sei=Yamamoto en-aut-mei=Akihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KojimaMotohiro en-aut-sei=Kojima en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=PerkinsEdward J. en-aut-sei=Perkins en-aut-mei=Edward J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CabralHoracio en-aut-sei=Cabral en-aut-mei=Horacio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences kn-affil= affil-num=2 en-affil=Innovation Centre of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion kn-affil= affil-num=3 en-affil=Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences kn-affil= affil-num=4 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Mechanical Systems Engineering, Graduate School of Systems Design Tokyo Metropolitan University kn-affil= affil-num=6 en-affil=Department of Surgical Pathology, Kyoto Prefecture University of Medicine kn-affil= affil-num=7 en-affil=US Army Engineer Research and Development Center kn-affil= affil-num=8 en-affil=Department of Bioengineering, Graduate School of Engineering, The University of Tokyo kn-affil= en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=coronavirus kn-keyword=coronavirus en-keyword=coronaviral infection kn-keyword=coronaviral infection en-keyword=machine learning kn-keyword=machine learning en-keyword=pathway analysis kn-keyword=pathway analysis en-keyword=predictionmodel kn-keyword=predictionmodel en-keyword=molecular network kn-keyword=molecular network en-keyword=molecular pathway image kn-keyword=molecular pathway image en-keyword=network analysis kn-keyword=network analysis END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=11 article-no= start-page=4984 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Induced Pluripotent Stem Cells in Cardiomyopathy: Advancing Disease Modeling, Therapeutic Development, and Regenerative Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cardiomyopathies are a heterogeneous group of heart muscle diseases that can lead to heart failure, arrhythmias, and sudden cardiac death. Traditional animal models and in vitro systems have limitations in replicating the complex pathology of human cardiomyopathies. Induced pluripotent stem cells (iPSCs) offer a transformative platform by enabling the generation of patient-specific cardiomyocytes, thus opening new avenues for disease modeling, drug discovery, and regenerative therapy. This process involves reprogramming somatic cells into iPSCs and subsequently differentiating them into functional cardiomyocytes, which can be characterized using techniques such as electrophysiology, contractility assays, and gene expression profiling. iPSC-derived cardiomyocyte (iPSC-CM) platforms are also being explored for drug screening and personalized medicine, including high-throughput testing for cardiotoxicity and the identification of patient-tailored therapies. While iPSC-CMs already serve as valuable models for understanding disease mechanisms and screening drugs, ongoing advances in maturation and bioengineering are bringing iPSC-based therapies closer to clinical application. Furthermore, the integration of multi-omics approaches and artificial intelligence (AI) is enhancing the predictive power of iPSC models. iPSC-based technologies are paving the way for a new era of personalized cardiology, with the potential to revolutionize the management of cardiomyopathies through patient-specific insights and regenerative strategies. en-copyright= kn-copyright= en-aut-name=VoQuan Duy en-aut-sei=Vo en-aut-mei=Quan Duy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=induced pluripotent stem cells kn-keyword=induced pluripotent stem cells en-keyword=cardiomyopathy kn-keyword=cardiomyopathy en-keyword=disease modeling kn-keyword=disease modeling en-keyword=drug screening kn-keyword=drug screening en-keyword=regenerative therapy kn-keyword=regenerative therapy END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=10 article-no= start-page=1444 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250516 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Canine c-kit Novel Mutation Isolated from a Gastrointestinal Stromal Tumor (GIST) Retains the Ability to Form Dimers but Lacks Autophosphorylation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that develop in the gastrointestinal tract; KIT mutations are present in both canine and human GISTs. In this study, genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) sections of 55 canine GIST cases, and mutation searches were performed for exons 8, 9, and 11. The results revealed novel mutations, A434T and F436S, in exon 8. In contrast to the A434T mutation without functional changes, the F436S mutant retained its dimerization ability, but lost its phosphorylation function and attenuated downstream Akt signaling, which is reflected in wound healing and migration activities. A comparison of the subcellular localization of WT KIT and the F436S mutant revealed no differences. In silico simulations indicated that the F436S mutation alters the structure of the near-membrane region and that its effects may extend to the transmembrane and intracellular domains compared to the WT. F436S is a point mutation that affects the entire molecule because co-mutation with the F436S mutation and the known autophosphorylation mutation reduces the autophosphorylation abilities. en-copyright= kn-copyright= en-aut-name=ShimakawaKei en-aut-sei=Shimakawa en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DogeSo en-aut-sei=Doge en-aut-mei=So kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MichishitaMasaki en-aut-sei=Michishita en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanabeEri en-aut-sei=Tanabe en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TajimaTsuyoshi en-aut-sei=Tajima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobayashiMasato en-aut-sei=Kobayashi en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BonkobaraMakoto en-aut-sei=Bonkobara en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OchiaiKazuhiko en-aut-sei=Ochiai en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaYoshikazu en-aut-sei=Tanaka en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Laboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=2 en-affil=Laboratory of Veterinary Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=3 en-affil=Laboratory of Veterinary Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=4 en-affil=Laboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=5 en-affil=Laboratory of Veterinary Pharmacology, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=6 en-affil=Laboratory of Veterinary Reproduction, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=7 en-affil=Laboratory of Veterinary Clinical Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=8 en-affil=Laboratory of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Laboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=10 en-affil=Laboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= en-keyword=autophosphorylation kn-keyword=autophosphorylation en-keyword=canine kn-keyword=canine en-keyword=c-kit kn-keyword=c-kit en-keyword=GIST kn-keyword=GIST en-keyword=KIT kn-keyword=KIT en-keyword=loss-of-function mutation kn-keyword=loss-of-function mutation END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=7 article-no= start-page=e88945 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Six-Year Remission With No Relapse After Four-Time Weekly Rituximab Only for Bilateral Ocular Adnexal Follicular Lymphoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Follicular lymphoma mostly takes an indolent course, and thus, observation with watchful waiting is a main therapeutic strategy. Recent long-term studies suggest earlier treatment with rituximab monotherapy may benefit patients by delaying the need for treatment in the later phase of exacerbation. In this study, we reported a patient with bilateral orbital follicular lymphoma who received four-time weekly rituximab monotherapy as an induction therapy only and maintained the remission for 5 years with no treatment. The patient was a 51-year-old woman who developed a right upper orbital mass and was diagnosed with follicular lymphoma grade 1 by the excisional biopsy. Two years later, at the age of 53 years, she developed a left lacrimal gland mass and underwent excision. The pathological diagnosis was follicular lymphoma grade 1. She did not have any other systemic lesions by fluorodeoxyglucose positron emission tomography. At the age of 54 years, she developed a new mass on the nasal side of the right orbit and underwent weekly rituximab monotherapy (375 mg/m2) four times a month, leading to the reduction of the mass in 3 months. Two high uptake sites on the temporal and nasal side of the right superior orbit by fluorodeoxyglucose positron emission tomography disappeared one year later at the age of 55 years. She was followed with no treatment for 6 years until the age of 60 years at the latest visit. In case of a local orbital relapse, local radiotherapy would be the standard, but rituximab monotherapy as an induction therapy only was chosen in the present patient. Rituximab monotherapy in place of local radiotherapy would be a treatment option for orbital follicular lymphoma. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, and Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Division of Transfusion and Cell Therapy, Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=claustrophobia kn-keyword=claustrophobia en-keyword=extranodal marginal zone b-cell lymphoma mucosa-associated lymphoid tissue (malt) type kn-keyword=extranodal marginal zone b-cell lymphoma mucosa-associated lymphoid tissue (malt) type en-keyword=fluorodeoxyglucose positron emission tomography kn-keyword=fluorodeoxyglucose positron emission tomography en-keyword=follicular lymphoma kn-keyword=follicular lymphoma en-keyword=magnetic resonance imaging kn-keyword=magnetic resonance imaging en-keyword=mucosaassociated lymphoid tissue (malt) lymphoma kn-keyword=mucosaassociated lymphoid tissue (malt) lymphoma en-keyword=ocular adnexa kn-keyword=ocular adnexa en-keyword=orbital mass kn-keyword=orbital mass en-keyword=radiotherapy kn-keyword=radiotherapy en-keyword=rituximab kn-keyword=rituximab END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250710 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tumor Microvessels with Specific Morphology as a Prognostic Factor in Esophageal Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Angiogenesis is essential for tumor progression. Microvessel density (MVD) is a widely used histological method to assess angiogenesis using immunostained sections, but its prognostic significance in esophageal cancer remains controversial. Recently, the evaluation of microvascular architecture has gained importance as a method to assess tumor aggressiveness. The present study aimed to identify the histological characteristics of tumor microvessels that are associated with the aggressiveness of esophageal squamous cell carcinoma.
Patients and Methods A total of 108 esophageal squamous cell carcinoma tissues were immunohistochemically stained with blood vessel markers and angiogenesis-related markers, including CD31, alpha smooth muscle actin, vascular endothelial growth factor A (VEGF-A), CD206, and D2-40. MVD, microvessel pericyte coverage index (MPI), and tumor vascular morphology were evaluated by microscopy.
Results MVD was significantly associated with patient outcomes, whereas neither MPI nor VEGF-A expression throughout the tumor showed a significant correlation. In addition, the presence of blood vessels encircling clusters of tumor cells, termed C-shaped microvessels, and excessively branching microvessels, termed X-shaped microvessels, was significantly associated with poor prognosis. These vessel types were also correlated with clinicopathological parameters, including deeper invasion of the primary tumor, presence of lymph node metastasis, advanced pathological stage, and distant metastasis. Focal VEGF-A immunoexpression in tumor cells was higher in areas containing C-shaped or X-shaped microvessels compared with areas lacking these vessel morphologies.
Conclusions The data suggest that tumor microvessels with specific morphologies (C-shaped and X-shaped microvessels) may serve as a promising prognostic factor in esophageal squamous cell carcinoma. en-copyright= kn-copyright= en-aut-name=TunHnin Thida en-aut-sei=Tun en-aut-mei=Hnin Thida kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraSeitaro en-aut-sei=Nishimura en-aut-mei=Seitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunitomoTomoyoshi en-aut-sei=Kunitomo en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Esophageal neoplasms kn-keyword=Esophageal neoplasms en-keyword=Angiogenesis kn-keyword=Angiogenesis en-keyword=Microvessel density kn-keyword=Microvessel density en-keyword=Pericytes kn-keyword=Pericytes en-keyword=VEGF-A kn-keyword=VEGF-A en-keyword=Immunohistochemistry kn-keyword=Immunohistochemistry en-keyword=Prognosis kn-keyword=Prognosis END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=18 article-no= start-page=2413456 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250320 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cryo-EM Analysis of a Tri-Heme Cytochrome-Associated RC-LH1 Complex from the Marine Photoheterotrophic Bacterium Dinoroseobacter Shibae en-subtitle= kn-subtitle= en-abstract= kn-abstract=The reaction center-light harvesting 1 (RC-LH1) complex converts solar energy into electrical energy, driving the initiation of photosynthesis. The authors present a cryo-electron microscopy structure of the RC-LH1 isolated from a marine photoheterotrophic bacterium Dinoroseobacter shibae. The RC comprises four subunits, including a three-heme cytochrome (Cyt) c protein, and is surrounded by a closed LH ring composed of 17 pairs of antenna subunits. Notably, a novel subunit with an N-terminal ghelix-turn-helixh motif embedded in the gap between the RC and the LH ring is identified. The purified RC-LH1 complex exhibits high stability in solutions containing Mg2+ or Ca2+. The periplasmic Cyt c2 is predicted to bind at the junction between the Cyt subunit and the membrane plane, enabling electron transfer from Cyt c2 to the proximal heme of the tri-heme Cyt, and subsequently to the special pair of bacteriochlorophylls. These findings provide structural insights into the efficient energy and electron transfer processes within a distinct type of RC-LH1, and shed light on evolutionary adaptations of photosynthesis. en-copyright= kn-copyright= en-aut-name=WangWeiwei en-aut-sei=Wang en-aut-mei=Weiwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiuYanting en-aut-sei=Liu en-aut-mei=Yanting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GuJiayi en-aut-sei=Gu en-aut-mei=Jiayi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AnShaoya en-aut-sei=An en-aut-mei=Shaoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaCheng en-aut-sei=Ma en-aut-mei=Cheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GaoHaichun en-aut-sei=Gao en-aut-mei=Haichun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=JiaoNianzhi en-aut-sei=Jiao en-aut-mei=Nianzhi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShenJian]Ren en-aut-sei=Shen en-aut-mei=Jian]Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BeattyJohn Thomas en-aut-sei=Beatty en-aut-mei=John Thomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Kobl??ekMichal en-aut-sei=Kobl??ek en-aut-mei=Michal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ZhangXing en-aut-sei=Zhang en-aut-mei=Xing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ZhengQiang en-aut-sei=Zheng en-aut-mei=Qiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ChenJing]Hua en-aut-sei=Chen en-aut-mei=Jing]Hua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=College of Life Sciences, Zhejiang University kn-affil= affil-num=2 en-affil=State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University kn-affil= affil-num=3 en-affil=College of Life Sciences, Zhejiang University kn-affil= affil-num=4 en-affil=Department of Pathology of Sir Run Run Shaw Hospital, Department of Biophysics, Zhejiang University School of Medicine kn-affil= affil-num=5 en-affil=Department of Pathology of Sir Run Run Shaw Hospital, Department of Biophysics, Zhejiang University School of Medicine kn-affil= affil-num=6 en-affil=College of Life Sciences, Zhejiang University kn-affil= affil-num=7 en-affil=State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University kn-affil= affil-num=8 en-affil=Research Institute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Department of Microbiology & Immunology, University of British Columbia kn-affil= affil-num=10 en-affil=Laboratory of Anoxygenic Phototrophs, Institute of Microbiology, Czech Academy of Science kn-affil= affil-num=11 en-affil=Department of Pathology of Sir Run Run Shaw Hospital, Department of Biophysics, Zhejiang University School of Medicine kn-affil= affil-num=12 en-affil=State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University kn-affil= affil-num=13 en-affil=College of Life Sciences, Zhejiang University kn-affil= en-keyword=energy transfer kn-keyword=energy transfer en-keyword=photoheterotrophic bacteria kn-keyword=photoheterotrophic bacteria en-keyword=photosynthesis kn-keyword=photosynthesis en-keyword=reaction center kn-keyword=reaction center en-keyword=structure kn-keyword=structure END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=4 article-no= start-page=510 end-page=524 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250626 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=C1orf50 Drives Malignant Melanoma Progression Through the Regulation of Stemness en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Recent advancements in omics analysis have significantly enhanced our understanding of the molecular pathology of malignant melanoma, leading to the development of novel therapeutic strategies that target specific vulnerabilities within the disease. Despite these improvements, the factors contributing to the poor prognosis of patients with malignant melanoma remain incompletely understood. The aim of this study was to investigate the role of C1orf50 (Chromosome 1 open reading frame 50), a gene previously of unknown function, as a prognostic biomarker in melanoma.
Materials and Methods: We performed comprehensive transcriptome data analysis and subsequent functional validation of the human Skin Cutaneous Melanoma project from The Cancer Genome Atlas (TCGA).
Results: Elevated expression levels of C1orf50 correlated with worse survival outcomes. Mechanistically, we revealed that C1orf50 plays a significant role in the regulation of cell cycle processes and cancer cell stemness, providing a potential avenue for novel therapeutic interventions in melanoma.
Conclusion: This study is the first to identify C1orf50 as a prognostic biomarker in melanoma. The clinical relevance of our results sheds light on the importance of further investigation into the biological mechanisms underpinning C1orf50fs impact on melanoma progression and patient prognosis. en-copyright= kn-copyright= en-aut-name=OTANIYUSUKE en-aut-sei=OTANI en-aut-mei=YUSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MAEKAWAMASAKI en-aut-sei=MAEKAWA en-aut-mei=MASAKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TANAKAATSUSHI en-aut-sei=TANAKA en-aut-mei=ATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PE?ATIRSO en-aut-sei=PE?A en-aut-mei=TIRSO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CHINVANESSA D. en-aut-sei=CHIN en-aut-mei=VANESSA D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ROGACHEVSKAYAANNA en-aut-sei=ROGACHEVSKAYA en-aut-mei=ANNA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TOYOOKASHINICHI en-aut-sei=TOYOOKA en-aut-mei=SHINICHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ROEHRLMICHAEL H. en-aut-sei=ROEHRL en-aut-mei=MICHAEL H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FUJIMURAATSUSHI en-aut-sei=FUJIMURA en-aut-mei=ATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=2 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=3 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=4 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=5 en-affil=UMass Chan Medical School, UMass Memorial Medical Center kn-affil= affil-num=6 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=9 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=C1orf50 kn-keyword=C1orf50 en-keyword=melanoma kn-keyword=melanoma en-keyword=cancer stem cells kn-keyword=cancer stem cells en-keyword=YAP/TAZ kn-keyword=YAP/TAZ END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=6 article-no= start-page=e86695 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250624 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Managing Persistent Pupillary Membranes With Surgery or Medication: A Report of Three Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=The persistent pupillary membrane, as a congenital anomaly, is a remnant of a network of feeding blood vessels for the lens of the eye, called tunica vasculosa lentis. This study reports three patients with persistent pupillary membrane in both eyes who presented in different situations and were managed differently to achieve better vision. The first child (Case 1) who had been seen initially at the age of two years complained of severe photophobia even though he had good visual acuity, and hence, he and his family chose surgical resection of the pupillary membrane in both eyes at the age of six years just before the admission to an elementary school. He did not develop any surgical complications, such as cataract and glaucoma, and maintained the visual acuity in decimals of 1.2 in both eyes at the age of 17 years.
The second child (Case 2), who was seen first at the age of one month, had persistent pupillary membranes in both eyes, together with Peters' anomaly in the left eye. The iris process adhesion to the corneal inner surface was visualized later by optical coherence tomography. She wore full-correction glasses and obtained the visual acuity of 0.7 in the right eye, so she had no problem studying at an elementary school. She used topical 1% atropine once a week in both eyes to maintain pupillary dilation and also used 0.5% timolol and 1% brinzolamide as pressure-lowering eye drops in the left eye with Peters' anomaly.
The third patient (Case 3) with persistent pupillary membranes in both eyes complained of vision problems for the first time at the age of 49 years when she developed cataract. Surgical resection of the pupillary membrane was done in the initial phase of cataract surgery with intraocular lens implantation in both eyes. At surgical resection of the pupillary membrane, a safe and efficient way was to cut the root of the pupillary membrane on the iris surface with scissors, and then the isolated tissues of the pupillary membrane were pulled out with forceps from the side port at the corneal limbus. Pathological examinations of the excised tissues showed blood vessels with red blood cells in the lumen. In such a rare congenital disease as the persistent pupillary membrane, a case-based approach to choose a better option in different conditions from individual to individual is still required to have a better vision in learning at school and in daily working life. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Division of Healthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=anterior segment dysgenesis kn-keyword=anterior segment dysgenesis en-keyword=cataract kn-keyword=cataract en-keyword=forceps kn-keyword=forceps en-keyword=optical coherence tomography kn-keyword=optical coherence tomography en-keyword=persistent pupillary membrane kn-keyword=persistent pupillary membrane en-keyword=peters anomaly kn-keyword=peters anomaly en-keyword=resection kn-keyword=resection en-keyword=scissors kn-keyword=scissors en-keyword=vitrectomy cutter kn-keyword=vitrectomy cutter END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=6 article-no= start-page=e85680 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Whole-Eye Radiation for the Local Control of Choroidal Lymphoma in Primary Central Nervous System Lymphoma: A 14-Year Case Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Involved-site radiation therapy is effective for curative and palliative treatments of cancers, including lymphoma. This case study describes the use of whole-eye radiation for primary intraocular lymphoma occurring during primary central nervous system lymphoma. The patient, a 68-year-old man, developed personality changes and apathy two weeks after cataract surgery combined with vitrectomy for vitreous opacity in the left eye. Magnetic resonance imaging revealed a mass lesion in the left frontal lobe, and biopsy by craniotomy confirmed diffuse large B-cell lymphoma. He underwent chemotherapy using rituximab combined with high-dose methotrexate and high-dose cytarabine in association with intrathecal methotrexate and cytarabine injections, leading to complete remission. At age 75, he noticed forgetfulness, and fluorodeoxyglucose positron emission tomography and magnetic resonance imaging revealed a relapse of lymphoma in the splenium of the corpus callosum. He underwent chemotherapy using rituximab combined with high-dose methotrexate, followed by monthly rituximab monotherapy for one year and then rituximab monotherapy every two months for one year. He maintained complete remission with no treatment until age 78, when he developed subretinal choroidal lesions in the left eye and underwent whole-eye radiation at 40 Gy. One year later, he developed subretinal choroidal lesions in the right eye and underwent whole-eye radiation at 40 Gy. At age 81, he had lower limb weakness with disorientation. Magnetic resonance imaging showed a relapse of lymphoma in the right frontal to temporal lobe. The brain lesions showed a marked response to four weeks of oral tirabrutinib as a salvage therapy, but the lesions regrew, and the patient died seven months later. Throughout the treatment, he maintained a visual acuity of 0.7 (decimal scale) in both eyes. In conclusion, whole-eye radiation should be considered as a treatment option for the local control of active intraocular lymphoma, especially choroidal lesions, for patients with primary central nervous system lymphoma with no active brain lesions and without systemic treatment. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YanoTomofumi en-aut-sei=Yano en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshioKotaro en-aut-sei=Yoshio en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimuraHirotake en-aut-sei=Nishimura en-aut-mei=Hirotake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Okayama Rosai Hospital kn-affil= affil-num=3 en-affil=Department of Radiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=brain biopsy kn-keyword=brain biopsy en-keyword=bruton tyrosine kinase (btk) inhibitor kn-keyword=bruton tyrosine kinase (btk) inhibitor en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=diffuse large b-cell lymphoma kn-keyword=diffuse large b-cell lymphoma en-keyword=fluorodeoxyglucose positron emission tomography kn-keyword=fluorodeoxyglucose positron emission tomography en-keyword=primary central nervous system lymphoma kn-keyword=primary central nervous system lymphoma en-keyword=primary intraocular (vitreoretinal) lymphoma kn-keyword=primary intraocular (vitreoretinal) lymphoma en-keyword=radiation therapy (radiotherapy) kn-keyword=radiation therapy (radiotherapy) en-keyword=tirabrutinib kn-keyword=tirabrutinib en-keyword=whole-eye radiation kn-keyword=whole-eye radiation END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=5 article-no= start-page=164 end-page=173 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nephronophthisis and Retinitis Pigmentosa (Senior-Loken Syndrome) After Living-Donor Kidney Transplantation: Twelve-Year Follow-Up in a Young Woman en-subtitle= kn-subtitle= en-abstract= kn-abstract=Senior-Loken syndrome is a hereditary ciliopathy with recessive trait that manifests as nephronophthisis and retinitis pigmentosa. This report described an 18-year-old woman who was referred to a University Hospital to set up a treatment plan for chronic renal failure of an unknown cause. She had experienced nocturnal polyurea from the age of 12 years and was found to have an elevated level of serum creatinine at 3 mg/dL at the age of 15 years. She underwent renal biopsy at a hometown regional hospital which showed global glomerulosclerosis in six of the 13 glomeruli examined, renal tubular dilation in irregular shape, and marked interstitial fibrosis with lymphocytic infiltration. At the age of 19 years, she received a living-donor kidney transplant from her 46-year-old father as a preemptive therapy. At surgery, biopsy of the fatherfs donor kidney showed two glomeruli with global sclerosis out of 24 glomeruli examined, in association with minimal interstitial fibrosis and lymphocytic infiltration. She began to have extended-release tacrolimus 4 mg daily and mycophenolate mofetil 1,000 mg daily. According to the standard protocol, she underwent biopsy of the transplanted donor kidney to reveal interstitial fibrosis and lymphocytic infiltration, in addition to no sign of rejection and no glomerular deposition of immunoglobulins and complements, both 4 weeks and 14 months after the kidney transplantation. At the age of 23 years, 4 years after the kidney transplantation, she was, for the first time, diagnosed retinitis pigmentosa, and hence, Senior-Loken syndrome. She was followed up in the stable condition with basal doses of tacrolimus 5 mg daily, mycophenolate mofetil 1,000 mg daily, and prednisolone 5 mg daily up until now in 12 years after the kidney transplantation. The interstitial fibrosis with lymphocytic infiltration in the donor kidney might be a milder presentation of the disease with recessive inheritance. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorinagaHiroshi en-aut-sei=Morinaga en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Retinitis pigmentosa kn-keyword=Retinitis pigmentosa en-keyword=Nephronophthisis kn-keyword=Nephronophthisis en-keyword=Senior-Loken syndrome kn-keyword=Senior-Loken syndrome en-keyword=Kidney transplantation kn-keyword=Kidney transplantation en-keyword=Living donor kn-keyword=Living donor en-keyword=Kidney biopsy kn-keyword=Kidney biopsy en-keyword=Pathology kn-keyword=Pathology en-keyword=Computed tomography scan kn-keyword=Computed tomography scan en-keyword=Ciliopathy kn-keyword=Ciliopathy en-keyword=Optical coherence tomography kn-keyword=Optical coherence tomography END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=5 article-no= start-page=e83484 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Detailed Ophthalmic and Pathological Features of Choroidal Metastasis From Breast Cancer: A Case Series of Five Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Breast cancer causes choroidal metastases on rare occasions. This study presented the eye manifestations of choroidal metastases from breast cancer and their response to treatments in detail as well as their pathological correlation in five patients. The patients' age at the diagnosis of breast cancer ranged from 24 to 69 years (median: 37 years). The time from the diagnosis of breast cancer to the detection of metastases was concurrent in one patient, two years later in three patients, and six years later in the other patient. The time from the detection of systemic metastases to the detection of choroidal metastases was the same in one patient, while it ranged from one to seven years later in four patients. Choroidal metastases were in the unilateral eye of four patients, whereas they were in both eyes of one patient. Choroidal metastases manifested as one or a few nodular or flat choroidal lesions with serous retinal detachment. As for the treatment of choroidal metastases, enucleation of the right eye was chosen based on the patient's wish as well as the family's wish in the earliest patient when cancer notification was not the norm in Japan. In the other four patients, whole-eye radiation was performed to reduce the choroidal metastatic lesions. As regards the prognosis, which was available in four patients, three patients died within one year from the diagnosis of choroidal metastases, while one patient died one year and eight months later. Regarding the pathology of breast cancer, which was available in four patients, immunostaining of the preserved enucleated eye in the earliest patient revealed that breast cancer cells in the choroidal metastatic lesion were positive for estrogen receptor and negative for progesterone receptor and human epidermal growth factor receptor 2 (HER2). Invasive ductal carcinoma in two patients was positive for estrogen receptor and negative for HER2, while invasive ductal carcinoma in the other patient was triple-negative for estrogen receptor, progesterone receptor, and HER2 with a high Ki-67 index. In conclusion, the prognosis for life was poor in patients with breast cancer who developed choroidal metastases. Choroidal metastatic lesions showed a response to whole-eye radiation to improve the quality of vision at the end of life. Vision-related symptoms should be monitored in the course of chemotherapy for systemic metastases. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MuraokaAtsushi en-aut-sei=Muraoka en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Division of Healthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Surgery, Kagawa Rosai Hospital kn-affil= affil-num=5 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=choroidal metastasis kn-keyword=choroidal metastasis en-keyword=estrogen receptor kn-keyword=estrogen receptor en-keyword=her2 kn-keyword=her2 en-keyword=immunostaining kn-keyword=immunostaining en-keyword=invasive ductal carcinoma kn-keyword=invasive ductal carcinoma en-keyword=ki-67 kn-keyword=ki-67 en-keyword=progesterone receptor kn-keyword=progesterone receptor en-keyword=radiation kn-keyword=radiation END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250620 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=International Consensus Histopathological Criteria for Subtyping Idiopathic Multicentric Castleman Disease Based on Machine Learning Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder classified into three recognized clinical subtypes?idiopathic plasmacytic lymphadenopathy (IPL), TAFRO, and NOS. Although clinical criteria are available for subtyping, diagnostically challenging cases with overlapping histopathological features highlight the need for an improved classification system integrating clinical and histopathological findings. We aimed to develop an objective histopathological subtyping system for iMCD that closely correlates with the clinical subtypes. Excisional lymph node specimens from 94 Japanese iMCD patients (54 IPL, 28 TAFRO, 12 NOS) were analyzed for five key histopathological parameters: germinal center (GC) status, plasmacytosis, vascularity, hemosiderin deposition, and gwhirlpoolh vessel formation in GC. Using hierarchical clustering, we visualized subgroups and developed a machine learning-based decision tree to differentiate the clinical subtypes and validated it in an external cohort of 12 patients with iMCD. Hierarchical cluster analysis separated the IPL and TAFRO cases into mutually exclusive clusters, whereas the NOS cases were interspersed between them. Decision tree modeling identified plasmacytosis, vascularity, and whirlpool vessel formation as key features distinguishing IPL from TAFRO, achieving 91% and 92% accuracy in the training and test sets, respectively. External validation correctly classified all IPL and TAFRO cases, confirming the reproducibility of the system. Our histopathological classification system closely aligns with the clinical subtypes, offering a more precise approach to iMCD subtyping. It may enhance diagnostic accuracy, guide clinical decision-making for predicting treatment response in challenging cases, and improve patient selection for future research. Further validation of its versatility and clinical utility is required. en-copyright= kn-copyright= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaratakeTomoka en-aut-sei=Haratake en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SumiyoshiRemi en-aut-sei=Sumiyoshi en-aut-mei=Remi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UjiieHideki en-aut-sei=Ujiie en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawaharaYuri en-aut-sei=Kawahara en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KogaTomohiro en-aut-sei=Koga en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UekiMasao en-aut-sei=Ueki en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LaczkoDorottya en-aut-sei=Laczko en-aut-mei=Dorottya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OksenhendlerEric en-aut-sei=Oksenhendler en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FajgenbaumDavid C. en-aut-sei=Fajgenbaum en-aut-mei=David C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=van RheeFrits en-aut-sei=van Rhee en-aut-mei=Frits kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawakamiAtsushi en-aut-sei=Kawakami en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease, TAFRO and Related Ddisease Research Group kn-affil= affil-num=6 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=7 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease, TAFRO and Related Ddisease Research Group kn-affil= affil-num=9 en-affil=School of Information and Data Sciences, Nagasaki University kn-affil= affil-num=10 en-affil=Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania kn-affil= affil-num=11 en-affil=Department of Clinical Immunology, H?pital Saint-Louis kn-affil= affil-num=12 en-affil=Center for Cytokine Storm Treatment and Laboratory, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=13 en-affil=Myeloma Center, University of Arkansas for Medical Sciences kn-affil= affil-num=14 en-affil=The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease, TAFRO and Related Ddisease Research Group kn-affil= affil-num=15 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=clinical subtype kn-keyword=clinical subtype en-keyword=histopathological criteria kn-keyword=histopathological criteria en-keyword=idiopathic multicentric castleman disease kn-keyword=idiopathic multicentric castleman disease en-keyword=lymphoproliferative disease kn-keyword=lymphoproliferative disease en-keyword=machine-learning kn-keyword=machine-learning END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=7 article-no= start-page=1152 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240717 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Metatranscriptomic Sequencing of Sheath Blight-Associated Isolates of Rhizoctonia solani Revealed Multi-Infection by Diverse Groups of RNA Viruses en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rice sheath blight, caused by the soil-borne fungus Rhizoctonia solani (teleomorph: Thanatephorus cucumeris, Basidiomycota), is one of the most devastating phytopathogenic fungal diseases and causes yield loss. Here, we report on a very high prevalence (100%) of potential virus-associated double-stranded RNA (dsRNA) elements for a collection of 39 fungal strains of R. solani from the rice sheath blight samples from at least four major rice-growing areas in the Philippines and a reference isolate from the International Rice Research Institute, showing different colony phenotypes. Their dsRNA profiles suggested the presence of multiple viral infections among these Philippine R. solani populations. Using next-generation sequencing, the viral sequences of the three representative R. solani strains (Ilo-Rs-6, Tar-Rs-3, and Tar-Rs-5) from different rice-growing areas revealed the presence of at least 36 viruses or virus-like agents, with the Tar-Rs-3 strain harboring the largest number of viruses (at least 20 in total). These mycoviruses or their candidates are believed to have single-stranded RNA or dsRNA genomes and they belong to or are associated with the orders Martellivirales, Hepelivirales, Durnavirales, Cryppavirales, Ourlivirales, and Ghabrivirales based on their coding-complete RNA-dependent RNA polymerase sequences. The complete genome sequences of two novel RNA viruses belonging to the proposed family Phlegiviridae and family Mitoviridae were determined. en-copyright= kn-copyright= en-aut-name=UrzoMichael Louie R. en-aut-sei=Urzo en-aut-mei=Michael Louie R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GuintoTimothy D. en-aut-sei=Guinto en-aut-mei=Timothy D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Eusebio-CopeAna en-aut-sei=Eusebio-Cope en-aut-mei=Ana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BudotBernard O. en-aut-sei=Budot en-aut-mei=Bernard O. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YanoriaMary Jeanie T. en-aut-sei=Yanoria en-aut-mei=Mary Jeanie T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JonsonGilda B. en-aut-sei=Jonson en-aut-mei=Gilda B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ArakawaMasao en-aut-sei=Arakawa en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Microbiology Division, Institute of Biological Sciences, College of Arts and Sciences, University of the Philippines Los Ba?os kn-affil= affil-num=2 en-affil=Microbiology Division, Institute of Biological Sciences, College of Arts and Sciences, University of the Philippines Los Ba?os kn-affil= affil-num=3 en-affil=Fit-for-Future Genetic Resources Unit, Rice Breeding Innovations Department, International Rice Research Institute (IRRI), University of the Philippines Los Ba?os kn-affil= affil-num=4 en-affil=Institute of Weed Science, Entomology, and Plant Pathology, College of Agriculture and Food Science, University of the Philippines Los Ba?os kn-affil= affil-num=5 en-affil=Traits for Challenged Environments Unit, Rice Breeding Innovations Department, International Rice Research Institute (IRRI), University of the Philippines Los Ba?os kn-affil= affil-num=6 en-affil=Traits for Challenged Environments Unit, Rice Breeding Innovations Department, International Rice Research Institute (IRRI), University of the Philippines Los Ba?os kn-affil= affil-num=7 en-affil=Faculty of Agriculture, Meijo University kn-affil= affil-num=8 en-affil=Plant-Microbe Interactions Group, Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=9 en-affil=Plant-Microbe Interactions Group, Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= en-keyword=Rhizoctonia solani kn-keyword=Rhizoctonia solani en-keyword=dsRNA kn-keyword=dsRNA en-keyword=mycovirus kn-keyword=mycovirus en-keyword=RNA virus kn-keyword=RNA virus en-keyword=metatranscriptome kn-keyword=metatranscriptome END start-ver=1.4 cd-journal=joma no-vol=38 cd-vols= no-issue=8 article-no= start-page=100782 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Involvement of PI3K?Akt Signaling in the Clinical and Pathological Findings of Idiopathic Multicentric Castleman Disease?Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis, and Organomegaly and Not Otherwise Specified Subtypes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Idiopathic multicentric Castleman disease is a rare lymphoproliferative disorder that is clinically classified into idiopathic plasmacytic lymphadenopathy (IPL); thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO); and not otherwise specified (NOS). Although each subtype shows varying degrees of hypervascularity, no statistical data on the degree of vascularization have been reported. Additionally, the mechanisms underlying vascularization in each clinical subtype are poorly understood. Here, we aimed to clarify these mechanisms by evaluating the histopathological characteristics of each clinical subtype across 37 patients and performing a whole-transcriptome analysis focusing on angiogenesis-related gene expression. Histologically, TAFRO and NOS exhibited a significantly higher degree of vascularization than IPL (IPL vs TAFRO, P < .001; IPL vs NOS, P = .002). In addition, the germinal centers (GCs) were significantly more atrophic in TAFRO than in IPL. In TAFRO and NOS, gwhirlpool vesselsh in GCs were seen in most cases (TAFRO, 9/9, 100%; NOS, 6/8, 75%) but not in IPL (IPL vs TAFRO, P < .001; IPL vs NOS, P = .007). Likewise, immunostaining for Ets-related gene revealed higher levels in endothelial cells of GCs in TAFRO than in IPL (P = .014), and TAFRO and NOS were associated with a significantly higher number of endothelial cells in interfollicular areas compared with that in IPL (TAFRO vs IPL, P < .001; NOS vs IPL, P = .002). Gene expression analysis revealed that the PI3K?Akt signaling pathway was significantly enriched in the TAFRO and NOS (TAFRO/NOS) groups. This pathway, which may be activated by vascular endothelial growth factor A and some integrins, is known to affect angiogenesis by increasing vascular permeability, which may explain the clinical manifestations of anasarca and/or fluid retention in TAFRO/NOS. These results suggest that the PI3K?Akt pathway plays an important role in the pathogenesis of TAFRO/NOS. en-copyright= kn-copyright= en-aut-name=HaratakeTomoka en-aut-sei=Haratake en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GonzalezMichael V. en-aut-sei=Gonzalez en-aut-mei=Michael V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=LaiYou Cheng en-aut-sei=Lai en-aut-mei=You Cheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OchiSayaka en-aut-sei=Ochi en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsunodaManaka en-aut-sei=Tsunoda en-aut-mei=Manaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FajgenbaumDavid C. en-aut-sei=Fajgenbaum en-aut-mei=David C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=van RheeFrits en-aut-sei=van Rhee en-aut-mei=Frits kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MomoseShuji en-aut-sei=Momose en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Center for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=5 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Medical Biotechnology and Laboratory Science, Chang Gung University kn-affil= affil-num=7 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=9 en-affil=Center for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=10 en-affil=Center for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=11 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=12 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=idiopathic multicentric Castleman disease kn-keyword=idiopathic multicentric Castleman disease en-keyword=integrin subunit alpha 5 kn-keyword=integrin subunit alpha 5 en-keyword=PI3K?Akt signaling pathway kn-keyword=PI3K?Akt signaling pathway en-keyword=platelet-derived growth factor receptor beta kn-keyword=platelet-derived growth factor receptor beta en-keyword=vascular endothelial growth factor A kn-keyword=vascular endothelial growth factor A en-keyword=vascularity kn-keyword=vascularity END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=3 article-no= start-page=213 end-page=219 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Chromophobe Renal Cell Carcinoma Metastasizing to the Cervical Lymph Nodes after Long-term Follow-up en-subtitle= kn-subtitle= en-abstract= kn-abstract=Renal cell carcinoma (RCC) can metastasize hematogenously and recur after a long dormancy. Chromophobe RCC metastasized to the cervical lymph nodes 10 years after the primary resection in a woman who underwent nephrectomy for RCC (T1aN0M0 stage I). Metastatic RCC diagnosis was confirmed by aspiration. The lymph node mass was resected, and the tumor cells matched chromophobe RCC metastasis. No adjuvant therapy was administered due to the lack of evidence regarding adjuvant therapy for chromophobe RCC. Long-term surveillance is crucial in RCC because of the possibility of late metastasis. We reviewed the clinical aspects and literature on metastatic cervical RCC. en-copyright= kn-copyright= en-aut-name=WatanabeMakoto en-aut-sei=Watanabe en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgawaTomoyuki en-aut-sei=Ogawa en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiKanao en-aut-sei=Kobayashi en-aut-mei=Kanao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsuyaNarutaka en-aut-sei=Katsuya en-aut-mei=Narutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshikawaAkira en-aut-sei=Ishikawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HamamotoTakao en-aut-sei=Hamamoto en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TaharaHiroaki en-aut-sei=Tahara en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UedaTsutomu en-aut-sei=Ueda en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakenoSachio en-aut-sei=Takeno en-aut-mei=Sachio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Otolaryngology, Chugoku Rosai Hospital kn-affil= affil-num=2 en-affil=Department of Otolaryngology, Chugoku Rosai Hospital kn-affil= affil-num=3 en-affil=Department of Nephrology and Urological Surgery, Chugoku Rosai Hospital kn-affil= affil-num=4 en-affil=Department of Molecular Pathology, Graduate School of Medical Sciences, Hiroshima University kn-affil= affil-num=5 en-affil=Department of Molecular Pathology, Graduate School of Medical Sciences, Hiroshima University kn-affil= affil-num=6 en-affil=Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital kn-affil= affil-num=7 en-affil=Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital kn-affil= affil-num=8 en-affil=Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital kn-affil= affil-num=9 en-affil=Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital kn-affil= en-keyword=renal cell carcinoma kn-keyword=renal cell carcinoma en-keyword=cervical lymph node metastasis kn-keyword=cervical lymph node metastasis en-keyword=late recurrence kn-keyword=late recurrence en-keyword=head and neck kn-keyword=head and neck END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=3 article-no= start-page=157 end-page=166 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Continuous Stimulation with Glycolaldehyde-derived Advanced Glycation End Product Reduces Aggrecan and COL2A1 Production via RAGE in Human OUMS-27 Chondrosarcoma Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chondrocytes are responsible for the production of extracellular matrix (ECM) components such as collagen type II alpha-1 (COL2A1) and aggrecan, which are loosely distributed in articular cartilage. Chondrocyte dysfunction has been implicated in the pathogenesis of rheumatic diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). With age, advanced glycation end products (AGEs) accumulate in all tissues and body fluids, including cartilage and synovial fluid, causing and accelerating pathological changes associated with chronic diseases such as OA. Glycolaldehyde-derived AGE (AGE3), which is toxic to a variety of cell types, have a stronger effect on cartilage compared with other AGEs. To understand the long-term effects of AGE3 on cartilage, we stimulated a human chondrosarcoma cell line (OUMS-27), which exhibits a chondrocytic phenotype, with 10 g/ml AGE3 for 4 weeks. As a result, the expressions of COL2A1 and aggrecan were significantly downregulated in the OUMS-27 cells without inducing cell death, but the expressions of proteases that play an important role in cartilage destruction were not affected. Inhibition of the receptor for advanced glycation end products (RAGE) suppressed the AGE3-induced reduction in cartilage component production, suggesting the involvement of RAGE in the action of AGE3. en-copyright= kn-copyright= en-aut-name=HatipogluOmer Faruk en-aut-sei=Hatipoglu en-aut-mei=Omer Faruk kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishinakaTakashi en-aut-sei=Nishinaka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YaykasliKursat Oguz en-aut-sei=Yaykasli en-aut-mei=Kursat Oguz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriShuji en-aut-sei=Mori en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeMasahiro en-aut-sei=Watanabe en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ToyomuraTakao en-aut-sei=Toyomura en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HirohataSatoshi en-aut-sei=Hirohata en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakahashiHideo en-aut-sei=Takahashi en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University kn-affil= affil-num=2 en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University kn-affil= affil-num=3 en-affil=Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-N?rnberg (FAU) and Universit?tsklinikum Erlangen kn-affil= affil-num=4 en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University kn-affil= affil-num=5 en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University kn-affil= affil-num=6 en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University kn-affil= affil-num=7 en-affil=Department of Translational Research & Dug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University kn-affil= affil-num=10 en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University kn-affil= en-keyword=advanced glycation end product kn-keyword=advanced glycation end product en-keyword=aging kn-keyword=aging en-keyword=cartilage kn-keyword=cartilage en-keyword=collagen kn-keyword=collagen en-keyword=aggrecan kn-keyword=aggrecan END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=3 article-no= start-page=147 end-page=155 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immunometabolic Regulation of Innate Immunity in Systemic Lupus Erythematosus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pathogens or their components can induce long-lasting changes in the behavior of innate immune cells, a process analogous to gtrainingh for future threats or environmental adaptation. However, such training can sometimes have unintended consequences, such as the development of autoimmunity. Systemic lupus erythematosus (SLE) is a chronic and heterogeneous autoimmune disease characterized by the production of autoantibodies and progressive organ damage. Innate immunity plays a central role in its pathogenesis, contributing through impaired clearance of apoptotic cells, excessive type I interferon production, and dysregulated formation of neutrophil extracellular traps. Recent studies have revealed that metabolites and nucleic acids derived from mitochondria, a crucial energy production site, directly regulate type I interferon and anti-inflammatory cytokine production. These insights have fueled interest in targeting metabolic pathways as a novel therapeutic approach for SLE, offering promise for improving long-term patient outcomes. en-copyright= kn-copyright= en-aut-name=WatanabeHaruki en-aut-sei=Watanabe en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=systemic lupus erythematosus kn-keyword=systemic lupus erythematosus en-keyword=interferon kn-keyword=interferon en-keyword=tricarboxylic acid cycle kn-keyword=tricarboxylic acid cycle en-keyword=innate immune memory kn-keyword=innate immune memory en-keyword=trained immunity kn-keyword=trained immunity END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=5 article-no= start-page=e70087 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genomic Islands of Pseudomonas syringae pv. tabaci 6605: Identification of PtaGI-1 as a Pathogenicity Island With Effector Genes and a Tabtoxin Cluster en-subtitle= kn-subtitle= en-abstract= kn-abstract=Genomic islands (GIs) are 20-500 kb DNA regions that are thought to be acquired by horizontal gene transfer. GIs that confer pathogenicity and environmental adaptation have been reported in Pseudomonas species; however, GIs that enhance bacterial virulence have not. Here, we identified 110 kb and 103 kb GIs in P. syringae pv. tabaci 6605 (Pta6605), the causative agent of tobacco wildfire disease, which has the ability to produce tabtoxin as a phytotoxin. These GIs are partially homologous to known genomic islands in Pseudomonas aeruginosa and P. syringae pv. phaseolicola and were designated PtaGI-1 and PtaGI-2. Both PtaGIs conserve core genes, whereas each GI possesses different accessory genes. PtaGI-1 contains a tabtoxin biosynthetic gene cluster and three type III effector genes among its accessory genes, whereas PtaGI-2 also contains homologous genes to hsvABC, pathogenicity-related genes in Erwinia amylovora. Inoculation revealed that the PtaGI-1 mutant, but not the PtaGI-2 mutant, lost the ability to biosynthesise tabtoxin and to cause disease. Therefore, PtaGI-1 is thought to be a pathogenicity island. Both PtaGI-1 and PtaGI-2 have a pseudogene of tRNALys on the left border and an intact tRNALys gene on the right border. In a colony of Pta6605, both GIs can be excised at tRNALys, and PtaGI-1 and PtaGI-2 exist in a circular form. These results indicate that tabtoxin biosynthesis genes in PtaGI-1 are required for disease development, and PtaGI-1 is necessary for Pta6605 virulence. en-copyright= kn-copyright= en-aut-name=WatanabeYuta en-aut-sei=Watanabe en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KunishiKotomi en-aut-sei=Kunishi en-aut-mei=Kotomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuiHidenori en-aut-sei=Matsui en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakataNanami en-aut-sei=Sakata en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NoutoshiYoshiteru en-aut-sei=Noutoshi en-aut-mei=Yoshiteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ToyodaKazuhiro en-aut-sei=Toyoda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IchinoseYuki en-aut-sei=Ichinose en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Agriculture,Okayama University kn-affil= affil-num=3 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=horizontal gene transfer kn-keyword=horizontal gene transfer en-keyword=integrative and conjugative elements kn-keyword=integrative and conjugative elements en-keyword=pathogenicity island kn-keyword=pathogenicity island en-keyword=Pseudomonas syringae kn-keyword=Pseudomonas syringae en-keyword=tabtoxin kn-keyword=tabtoxin END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=9 article-no= start-page=1559 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impacts of Dental Follicle Cells and Periodontal Ligament Cells on the Bone Invasion of Well-Differentiated Oral Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Oral squamous cell carcinoma (OSCC) frequently invades the jawbone, leading to diagnostic and therapeutic challenges. While tumor-bone interactions have been studied, the specific roles of dental follicle cells (DFCs) and periodontal ligament cells (PDLCs) in OSCC-associated bone resorption remain unclear. This study aimed to compare the effects of DFCs and PDLCs on OSCC-induced bone invasion and elucidate the underlying mechanisms. Methods: Primary human DFCs and PDLCs were isolated from extracted third molars and characterized by Giemsa and immunofluorescence staining. An in vitro co-culture system and an in vivo xenograft mouse model were established using the HSC-2 OSCC cell line. Tumor invasion and osteoclast activation were assessed by hematoxylin and eosin (HE) and tartrate-resistant acid phosphatase (TRAP) staining. Immunohistochemical analysis was performed to evaluate the expression of receptor activator of NF-kappa B ligand (RANKL) and parathyroid hormone-related peptide (PTHrP). Results: DFCs significantly enhanced OSCC-induced bone resorption by promoting osteoclastogenesis and upregulating RANKL and PTHrP expression. In contrast, PDLCs suppressed RANKL expression and partially modulated PTHrP levels, thereby reducing osteoclast activity. Conclusions: DFCs and PDLCs exert opposite regulatory effects on OSCC-associated bone destruction. These findings underscore the importance of stromal heterogeneity and highlight the therapeutic potential of targeting specific stromal-tumor interactions to mitigate bone-invasive OSCC. en-copyright= kn-copyright= en-aut-name=ChangAnqi en-aut-sei=Chang en-aut-mei=Anqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PiaoTianyan en-aut-sei=Piao en-aut-mei=Tianyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArashimaTakuma en-aut-sei=Arashima en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EainHtoo Shwe en-aut-sei=Eain en-aut-mei=Htoo Shwe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SoeYamin en-aut-sei=Soe en-aut-mei=Yamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MinZin Zin en-aut-sei=Min en-aut-mei=Zin Zin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= en-keyword=oral squamous cell carcinoma kn-keyword=oral squamous cell carcinoma en-keyword=dental follicle cells kn-keyword=dental follicle cells en-keyword=periodontal ligament cells kn-keyword=periodontal ligament cells en-keyword=bone invasion kn-keyword=bone invasion en-keyword=receptor activator of NF-kappa B ligand kn-keyword=receptor activator of NF-kappa B ligand en-keyword=parathyroid hormone-related peptide kn-keyword=parathyroid hormone-related peptide END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=7 article-no= start-page=192 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=HIF-PH inhibitors induce pseudohypoxia in T cells and suppress the growth of microsatellite stable colorectal cancer by enhancing antitumor immune responses en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Recent studies have revealed that CD8+ T cells can be activated via genetic upregulation of HIF-1 alpha, thereby augmenting antitumor effector functions. HIF-1 alpha upregulation can be attained by inhibiting HIF-prolyl hydroxylase (HIF-PH) under normoxic conditions, termed pseudohypoxia. This study investigated whether pseudohypoxia induced by HIF-PH inhibitors suppresses Microsatellite stable (MSS) colorectal cancer (CRC) by affecting tumor immune response.
Methods The HIF-PH inhibitors Roxadustat and Vadadustat were utilized in this study. In vitro, we assessed the effects of HIF-PH inhibitors on human and murine colon cancer cell lines (SW480, HT29, Colon26) and murine T cells. In vivo experiments were performed with mice bearing Colon26 tumors to evaluate the effect of these inhibitors on tumor immune responses. Tumor and spleen samples were analyzed using immunohistochemistry, RT-qPCR, and flow cytometry to elucidate potential mechanisms.
Results HIF-PH inhibitors demonstrated antitumor effects in vivo but not in vitro. These inhibitors enhanced the tumor immune response by increasing the infiltration of CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs). HIF-PH inhibitors induced IL-2 production in splenic and intratumoral CD4+ T cells, promoting T cell proliferation, differentiation, and immune responses. Roxadustat synergistically enhanced the efficacy of anti-PD-1 antibody for MSS cancer by increasing the recruitment of TILs and augmenting effector-like CD8+ T cells.
Conclusion Pseudohypoxia induced by HIF-PH inhibitors activates antitumor immune responses, at least in part, through the induction of IL-2 secretion from CD4+ T cells in the spleen and tumor microenvironment, thereby enhancing immune efficacy against MSS CRC. en-copyright= kn-copyright= en-aut-name=ChenYuehua en-aut-sei=Chen en-aut-mei=Yuehua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamadaYusuke en-aut-sei=Hamada en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangYuze en-aut-sei=Wang en-aut-mei=Yuze kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TianMiao en-aut-sei=Tian en-aut-mei=Miao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Colorectal cancer kn-keyword=Colorectal cancer en-keyword=Microsatellite stable kn-keyword=Microsatellite stable en-keyword=Hypoxia-inducible factor kn-keyword=Hypoxia-inducible factor en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=5 article-no= start-page=e70091 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pseudomonas syringae pv. tabaci 6605 Requires Seven Type III Effectors to Infect Nicotiana benthamiana en-subtitle= kn-subtitle= en-abstract= kn-abstract=Type III effectors (T3Es), virulence factors injected into plant cells via the type III secretion system (T3SS), play essential roles in the infection of host plants. Pseudomonas syringae pv. tabaci 6605 (Pta 6605) is the causal agent of wildfire disease in tobacco and harbours at least 22 T3Es in its genome. However, the specific T3Es required by Pta 6605 to infect Nicotiana benthamiana remain unidentified. In this study, we investigated the T3Es that contribute to Pta 6605 infection of N. benthamiana. We constructed Pta 6605 poly-T3E-deficient mutants (Pta DxE) and inoculated them into N. benthamiana. Flood assay, which mimics natural opening-based entry, showed that mutant strains lacking 14-22 T3Es, namely, Pta D14E-D22E mutants, exhibited reduced disease symptoms. By contrast, infiltration inoculation, which involves direct injection into leaves, showed that the Pta D14E to Pta D20E mutants developed disease symptoms. Notably, the Pta D20E, containing AvrE1 and HopM1, induced weak but observable symptoms upon infiltration inoculation. Conversely, no symptoms were observed in either the flood assay or infiltration inoculation for Pta D21E and Pta D22E. Taken together, these findings indicate that the many T3Es such as AvrPto4/AvrPtoB, HopW1/HopAE1, and HopM1/AvrE1 in Pta 6605 collectively contribute to invasion through natural openings and symptom development in N. benthamiana. This study provides the basis for understanding virulence in the host by identifying the minimum T3E repertoire required by Pta 6605 to infect N. benthamiana. en-copyright= kn-copyright= en-aut-name=KuroeKana en-aut-sei=Kuroe en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraTakafumi en-aut-sei=Nishimura en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KashiharaSachi en-aut-sei=Kashihara en-aut-mei=Sachi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakataNanami en-aut-sei=Sakata en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoMikihiro en-aut-sei=Yamamoto en-aut-mei=Mikihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NoutoshiYoshiteru en-aut-sei=Noutoshi en-aut-mei=Yoshiteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyodaKazuhiro en-aut-sei=Toyoda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IchinoseYuki en-aut-sei=Ichinose en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsuiHidenori en-aut-sei=Matsui en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=poly T3E mutant kn-keyword=poly T3E mutant en-keyword=type III effector kn-keyword=type III effector en-keyword=type III secretion system kn-keyword=type III secretion system END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=3 article-no= start-page=343 end-page=350 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characteristics of Early Gastric Cancer in a Patient with a History of Helicobacter pylori Infection and No History of Eradication Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective The characteristics of gastric cancer in patients with atrophic mucosa and no apparent history of Helicobacter pylori eradication have not been thoroughly investigated. Therefore, this study examined the clinicopathological characteristics of gastric cancer in these patients.
Methods We retrospectively examined the endoscopic and pathological characteristics of gastric cancer in patients who underwent endoscopic submucosal dissection.
Patients We divided the patients into 2 groups: those with gastric atrophy and no history of eradication (group A; n=102) and those with a history of eradication (group B; n=161). In group A, patients were further divided into mild atrophy (group C) and severe atrophy (group D) groups, while group B was further divided into those who underwent eradication treatment >5 years ago (group E) and those who underwent eradication 1-5 years ago (group F).
Results Group A comprised significantly older individuals (75}8.0 vs. 71}7.5 years old, p<0.001) with a higher frequency of elevated gastric cancer than group B (32.4% vs. 17.4%, p=0.006). Compared with group E, group A was older and had a greater incidence of elevated gastric cancer. The incidence of gastric cancer in the U or M region was lower in group C than in group D.
Conclusion Gastric cancer in patients with gastric atrophy and no history of eradication was associated with an older age and higher frequency of elevated-type morphology than in those with a history of eradication. en-copyright= kn-copyright= en-aut-name=KuraokaSakiko en-aut-sei=Kuraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InoShoko en-aut-sei=Ino en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatomiTakuya en-aut-sei=Satomi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HamadaKenta en-aut-sei=Hamada en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KonoYoshiyasu en-aut-sei=Kono en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=autoimmune gastritis kn-keyword=autoimmune gastritis en-keyword=eradication kn-keyword=eradication en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=Helicobacter pylori kn-keyword=Helicobacter pylori END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=4 article-no= start-page=e70151 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Frequency and Characteristics of Gastrointestinal Diseases in Patients With Neurofibromatosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aim: Patients with neurofibromatosis (NF) frequently experience gastrointestinal symptoms, but the specific characteristics of these lesions are not well understood.
Methods: To investigate the prevalence and nature of gastrointestinal diseases in this population, we analyzed the gastrointestinal lesions identified through endoscopic examinations in patients with NF.
Results: We included 225 patients with NF type 1 (NF1) and 15 with NF type 2 (NF2). None of the NF2 patients underwent endoscopy. Among the NF1 patients, 27 received endoscopies, and 13 (59%) had gastrointestinal lesions. These 13 patients were predominantly male (10 males and three females), with a median age of 53 years (range: 19-76 years). The identified lesions included colorectal polyps (n = 6), gastrointestinal stromal tumors ([GIST], n = 4), subepithelial lesions (n = 3), gastric fundic gland polyps (n = 3), diffuse intestinal ganglioneuromatosis (n = 2), esophageal polyps (n = 2), a Schwann cell hamartoma (n = 1), esophageal cancer (n = 1), and a gastric hyperplastic polyp (n = 1). All GISTs and one case of diffuse intestinal ganglioneuromatosis were surgically resected. Interestingly, six out of 13 patients were asymptomatic. Additionally, all patients who required surgery were 40 years of age or older.
Conclusions: These findings suggest that routine endoscopic examinations, along with imaging techniques like computed tomography and magnetic resonance imaging, could be beneficial for the early detection of gastrointestinal lesions in NF1 patients aged 40 and above. en-copyright= kn-copyright= en-aut-name=HondaManami en-aut-sei=Honda en-aut-mei=Manami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamasakiYasushi en-aut-sei=Yamasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Practical Gastrointestinal Endoscopy,Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=colonoscopy kn-keyword=colonoscopy en-keyword=esophagogastroduodenoscopy kn-keyword=esophagogastroduodenoscopy en-keyword=gastrointestinal neoplasms kn-keyword=gastrointestinal neoplasms en-keyword=gastrointestinal stromal tumor kn-keyword=gastrointestinal stromal tumor en-keyword=neurofibromatosis kn-keyword=neurofibromatosis END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=81 end-page=92 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical Outcomes of Neoadjuvant Paclitaxel/Cisplatin/Gemcitabine Compared with Gemcitabine/Cisplatin for Muscle-Invasive Bladder Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=We retrospectively evaluated the oncologic outcomes of paclitaxel, cisplatin, and gemcitabine (PCG) with those of gemcitabine and cisplatin (GC) as neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients. The primary outcome was efficacy: pathological complete response (pCR), ypT0N0; and pathological objective response (pOR), ypT0N0, ? ypT1N0, or ypT0N1. Secondary outcomes included overall survival (OS), recurrence-free survival (RFS), predictive factors for pOR, OS, and RFS, and hematologic adverse events (AEs). Among 113 patients treated (PCG, n=28; GC, n=85), similar pOR and pCR rates were achieved by the groups (pOR: PCG, 57.1% vs. GC, 49. 4%; p=0.52; pCR: PCG, 39.3% vs. GC, 29.4%; p=0.36). No significant differences were observed in OS (p=1.0) or RFS (p=0.20). Multivariate logistic regression analysis showed that hydronephrosis (odds ratio [OR] 0.32, 95%CI: 0.11-0.92) and clinical node-positive status (cN+) (OR 0.22, 95%CI: 0.050-0.99) were significantly associated with a decreased probability of pOR. On multivariate Cox regression analyses, pOR achievement was associated with improved OS (hazard ratio [HR] 0.23, 95%CI: 0.10-0.56) and RFS (HR 0.30, 95%CI: 0.13-0.67). There were no significant between-group differences in the incidence of grade ? 3 hematologic AEs or dose-reduction required, but the PCG group had a higher incidence of grade 4 neutropenia. en-copyright= kn-copyright= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiYasuyuki en-aut-sei=Kobayashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsugawaTakuji en-aut-sei=Tsugawa en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuboiKazuma en-aut-sei=Tsuboi en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KobayashiTomoko en-aut-sei=Kobayashi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=EdamuraKohei en-aut-sei=Edamura en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EbaraShin en-aut-sei=Ebara en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=11 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=urothelial carcinoma kn-keyword=urothelial carcinoma en-keyword=paclitaxel kn-keyword=paclitaxel en-keyword=cisplatin kn-keyword=cisplatin en-keyword=gemcitabine kn-keyword=gemcitabine en-keyword=neoadjuvant kn-keyword=neoadjuvant END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=2 article-no= start-page=100016 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Changes in adrenoceptor expression level contribute to the cellular plasticity of glioblastoma cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Glioblastoma cells are known to regulate their cellular plasticity in response to their surrounding microenvironment, but it is not fully understood what factors contribute to the cells' changing plasticity. Here, we found that glioblastoma cells alter the expression level of adrenoreceptors depending on their differentiation stage. Catecholamines are abundant in the central nervous system, and we found that noradrenaline, in particular, enhances the stemness of glioblastoma cells and promotes the dedifferentiation potential of already differentiated glioblastoma cells. Antagonist and RNAi experiments revealed that signaling through alpha 1D-adrenoreceptor is important for noradrenaline action on glioblastoma cells. We also found that high alpha 1Dadrenoreceptor expression was associated with poor prognosis in patients with gliomas. These data suggest that glioblastoma cells increase the expression level of their own adrenoreceptors to alter the surrounding tumor microenvironment favorably for survival. We believe that our findings will contribute to the development of new therapeutic strategies for glioblastoma. en-copyright= kn-copyright= en-aut-name=AsakaYutaro en-aut-sei=Asaka en-aut-mei=Yutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MasumotoToshio en-aut-sei=Masumoto en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UnedaAtsuhito en-aut-sei=Uneda en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChinVanessa D. en-aut-sei=Chin en-aut-mei=Vanessa D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtaniYusuke en-aut-sei=Otani en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=PenaTirso en-aut-sei=Pena en-aut-mei=Tirso kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatayamaHaruyoshi en-aut-sei=Katayama en-aut-mei=Haruyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ItanoTakuto en-aut-sei=Itano en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AndoTeruhiko en-aut-sei=Ando en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HuangRongsheng en-aut-sei=Huang en-aut-mei=Rongsheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Division of Health Administration and Promotion, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=3 en-affil=Department of Neurosurgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=UMass Chan Medical School, UMass Memorial Medical Center kn-affil= affil-num=5 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=6 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Trauma Orthopedics, The Second Hospital of Dalian Medical University kn-affil= affil-num=11 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Adrenoceptors kn-keyword=Adrenoceptors en-keyword=Glioma stem-like cells kn-keyword=Glioma stem-like cells en-keyword=Differentiated glioma cells kn-keyword=Differentiated glioma cells en-keyword=Noradrenaline kn-keyword=Noradrenaline en-keyword=Cellular plasticity kn-keyword=Cellular plasticity END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=4 article-no= start-page=e82348 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bilateral Scleritis and Neutrophilic Dermatosis With Cytogenetic Chromosomal Aberrancy Related to Pyoderma Gangrenosum: A Case Report of a 20-Year Follow-Up en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pyoderma gangrenosum is a non-infectious autoimmune disease with skin plaques and ulcers in the entity of neutrophilic dermatosis and may have a background of myelodysplastic syndromes. This study reported a 20-year follow-up of a patient with pyoderma gangrenosum and scleritis who showed chromosomal aberrancy from the initial phase and later in the course developed thrombocythemia. A 51-year-old man presented with widespread indurated erythematous plaques with scaling and pustules on the forehead, bilateral eyelids, and nasal bridge, in addition to nodular scleritis in the left eye and ulcer formation of the plaques in the lower legs. Skin biopsy revealed massive dermal infiltration mainly with neutrophils in the absence of neutrophilic vasculitis. Suspected of myelodysplastic syndromes, bone marrow biopsy was normal, while chromosomal aberrancy, 46, XY, del (20) (q11q13.3), was detected. In the diagnosis of neutrophilic dermatosis, probably of pyoderma gangrenosum, he began to have oral prednisolone 20 mg daily and colchicine 1 mg daily, leading to the subsidence of skin lesions. Four months later, he developed nodular scleritis in the right eye and began to use topical 0.1% betamethasone in both eyes. He was stable with only prednisolone 12.5 mg daily until the age of 55.5 years, when he showed an increase of serum lactate dehydrogenase. The bone marrow aspirate disclosed neither blast cell increase nor atypical cells. The same chromosomal aberrancy was repeatedly detected. One year later, he developed breathing difficulty and underwent tracheostomy. Laryngeal lesion biopsy disclosed squamous cell papilloma with human papillomavirus-6. At 60 years old, he showed marginal corneal infiltration in the left eye, and at 61 years old, hypopyon in the right eye. Platelets tended to increase up to 1000 ~ 103/?L, and bone marrow examinations were recommended but refused by the patient. At the latest follow-up at 71 years old, he was ambulatory in health and stable with a tracheostomy cannula. In conclusion, pyoderma gangrenosum with scleritis occurred in an undetermined hematological malignancy with chromosomal aberrancy. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ObikaMikako en-aut-sei=Obika en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OmichiRyotaro en-aut-sei=Omichi en-aut-mei=Ryotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwatsukiKeiji en-aut-sei=Iwatsuki en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of General Internal Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=corneal infiltration kn-keyword=corneal infiltration en-keyword=hypopyon kn-keyword=hypopyon en-keyword=myelodysplastic syndromes kn-keyword=myelodysplastic syndromes en-keyword=neutrophilic dermatosis kn-keyword=neutrophilic dermatosis en-keyword=peripheral keratitis kn-keyword=peripheral keratitis en-keyword=pyoderma gangrenosum kn-keyword=pyoderma gangrenosum en-keyword=scleritis kn-keyword=scleritis en-keyword=sweet syndrome kn-keyword=sweet syndrome END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=6 article-no= start-page=790 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250320 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Improving Diagnostic Performance for Head and Neck Tumors with Simple Diffusion Kurtosis Imaging and Machine Learning Bi-Parameter Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Mean kurtosis (MK) values in simple diffusion kurtosis imaging (SDI)-a type of diffusion kurtosis imaging (DKI)-have been reported to be useful in the diagnosis of head and neck malignancies, for which pre-processing with smoothing filters has been reported to improve the diagnostic accuracy. Multi-parameter analysis using DKI in combination with other image types has recently been reported to improve the diagnostic performance. The purpose of this study was to evaluate the usefulness of machine learning (ML)-based multi-parameter analysis using the MK and apparent diffusion coefficient (ADC) values-which can be acquired simultaneously through SDI-for the differential diagnosis of benign and malignant head and neck tumors, which is important for determining the treatment strategy, as well as examining the usefulness of filter pre-processing. Methods: A total of 32 pathologically diagnosed head and neck tumors were included in the study, and a Gaussian filter was used for image pre-processing. MK and ADC values were extracted from pixels within the tumor area and used as explanatory variables. Five ML algorithms were used to create models for the prediction of tumor status (benign or malignant), which were evaluated through ROC analysis. Results: Bi-parameter analysis with gradient boosting achieved the best diagnostic performance, with an AUC of 0.81. Conclusions: The usefulness of bi-parameter analysis with ML methods for the differential diagnosis of benign and malignant head and neck tumors using SDI data were demonstrated. en-copyright= kn-copyright= en-aut-name=YoshidaSuzuka en-aut-sei=Yoshida en-aut-mei=Suzuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaMasahiro en-aut-sei=Kuroda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraYoshihide en-aut-sei=Nakamura en-aut-mei=Yoshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukumuraYuka en-aut-sei=Fukumura en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamitsuYuki en-aut-sei=Nakamitsu en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Al-HammadWlla E. en-aut-sei=Al-Hammad en-aut-mei=Wlla E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurodaKazuhiro en-aut-sei=Kuroda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimizuYudai en-aut-sei=Shimizu en-aut-mei=Yudai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanabeYoshinori en-aut-sei=Tanabe en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OitaMasataka en-aut-sei=Oita en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SugiantoIrfan en-aut-sei=Sugianto en-aut-mei=Irfan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=BarhamMajd en-aut-sei=Barham en-aut-mei=Majd kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TekikiNouha en-aut-sei=Tekiki en-aut-mei=Nouha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KamaruddinNurul N. en-aut-sei=Kamaruddin en-aut-mei=Nurul N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HisatomiMiki en-aut-sei=Hisatomi en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YanagiYoshinobu en-aut-sei=Yanagi en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=AsaumiJunichi en-aut-sei=Asaumi en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University kn-affil= affil-num=11 en-affil=Department of Oral Radiology, Faculty of Dentistry, Hasanuddin University kn-affil= affil-num=12 en-affil=Department of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An-Najah National University kn-affil= affil-num=13 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=head and neck tumors kn-keyword=head and neck tumors en-keyword=mean kurtosis kn-keyword=mean kurtosis en-keyword=simple diffusion kurtosis imaging kn-keyword=simple diffusion kurtosis imaging en-keyword=magnetic resonance imaging kn-keyword=magnetic resonance imaging en-keyword=apparent diffusion coefficient value kn-keyword=apparent diffusion coefficient value en-keyword=diffusion kurtosis imaging kn-keyword=diffusion kurtosis imaging en-keyword=machine learning kn-keyword=machine learning en-keyword=bi-parameter analysis kn-keyword=bi-parameter analysis en-keyword=gradient boosting kn-keyword=gradient boosting en-keyword=differential diagnosis of benign and malignant kn-keyword=differential diagnosis of benign and malignant END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=3 article-no= start-page=e81476 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250330 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Natural Course From Primary Intraocular Lymphoma to Brain Lymphoma in Four Years According to Patient's Choice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Primary intraocular lymphoma or vitreoretinal lymphoma is a rare entity of diffuse large B-cell lymphoma that presents vitreous opacity and retinal and choroidal infiltration. Primary central nervous system lymphoma would occur previously, later, or concurrently with respect to primary intraocular lymphoma. This study reported a 72-year-old patient with a pathological diagnosis of primary intraocular lymphoma who developed central nervous system lymphoma four years later in the course of no treatment. She presented with a four-year history of blurred vision in both eyes after cataract surgeries. Three weeks previously, she underwent a vitrectomy in the left eye at a clinic, and measurements of the vitreous fluid showed a high level of interleukin-10 at 5739 pg/mL, in contrast with interleukin-6 at 142 pg/mL. Cytology of the vitreous fluid was class III on the Papanicolaou classification. Head magnetic resonance imaging detected nothing abnormal. She underwent vitrectomy in the right eye as a diagnostic procedure to show large cells in the vitreous which were positive for CD20 and Ki-67 and negative for CD3, leading to a pathological diagnosis of large B-cell lymphoma. Prophylactic chemotherapy with high-dose methotrexate was recommended as a therapeutic option, but she chose observation since she did not have any eye or systemic symptoms. In the follow-up every three months by an oncologist and an ophthalmologist, she did not have any symptoms, and serum levels of soluble interleukin-2 receptor were in the normal range at each visit. She was well for four years until the age of 76 years when she fell and hit her head, and an emergency head computed tomography scan showed a mass in the left occipital lobe. Magnetic resonance imaging demonstrated a well-defined circular mass in the left occipital lobe with a hyperintense signal in the T2-weighted fluid-attenuated inversion recovery (FLAIR) image and diffusion-weighted image. Fluorodeoxyglucose positron emission tomography showed no abnormal uptake systemically, except for the left occipital lesion. She underwent a brain biopsy by craniotomy to pathologically prove diffuse large B-cell lymphoma. She was recommended to receive first-line chemotherapy as the standard treatment but chose observation with no treatment and died of brain lymphoma nine months later. This case happened to illustrate a natural course of primary intraocular lymphoma which proceeded to central nervous system lymphoma four years later. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoShotaro en-aut-sei=Kondo en-aut-mei=Shotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Kurashiki Municipal Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=brain biopsy kn-keyword=brain biopsy en-keyword=cell block pathology kn-keyword=cell block pathology en-keyword=diffuse large b-cell lymphoma kn-keyword=diffuse large b-cell lymphoma en-keyword=natural course kn-keyword=natural course en-keyword=primary central nervous system lymphoma kn-keyword=primary central nervous system lymphoma en-keyword=primary intraocular (vitreoretinal) lymphoma kn-keyword=primary intraocular (vitreoretinal) lymphoma en-keyword=vitrectomy kn-keyword=vitrectomy en-keyword=vitreous opacity kn-keyword=vitreous opacity END start-ver=1.4 cd-journal=joma no-vol=85 cd-vols= no-issue=6 article-no= start-page=1082 end-page=1096 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250314 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Myeloid Cells Induce Infiltration and Activation of B Cells and CD4+ T Follicular Helper Cells to Sensitize Brain Metastases to Combination Immunotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Brain metastasis is a poor prognostic factor in patients with cancer. Despite showing efficacy in many extracranial tumors, immunotherapy with anti?PD-1 mAb or anti?CTLA4 mAb seems to be less effective against intracranial tumors. Promisingly, recent clinical studies have reported that combination therapy with anti?PD-1 and anti?CTLA4 mAbs has a potent antitumor effect on brain metastasis, highlighting the need to elucidate the detailed mechanisms controlling the intracranial tumor microenvironment (TME) to develop effective immunotherapeutic strategies. In this study, we analyzed the tumor-infiltrating lymphocytes in murine models of brain metastasis that responded to anti?CTLA4 and anti?PD-1 mAbs. Activated CD4+ T follicular helper (TFH) cells with high CTLA4 expression characteristically infiltrated the intracranial TME, which were activated by combination anti?CTLA4 and anti?PD-1 treatment. The loss of TFH cells suppressed the additive effect of CTLA4 blockade on anti?PD-1 mAb. B-cell?activating factor belonging to the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) produced by abundant myeloid cells, particularly CD80hiCD206lo proinflammatory M1-like macrophages, in the intracranial TME induced B-cell and TFH-cell infiltration and activation. Furthermore, the intracranial TME of patients with non?small cell lung cancer featured TFH- and B-cell infiltration as tertiary lymphoid structures. Together, these findings provide insights into the immune cell cross-talk in the intracranial TME that facilitates an additive antitumor effect of CTLA4 blockade with anti?PD-1 treatment, supporting the potential of a combination immunotherapeutic strategy for brain metastases.
Significance: B-cell and CD4+ T follicular helper cell activation via BAFF/APRIL from abundant myeloid cells in the intracranial tumor microenvironment enables a combinatorial effect of CTLA4 and PD-1 blockade in brain metastases. en-copyright= kn-copyright= en-aut-name=NinomiyaToshifumi en-aut-sei=Ninomiya en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KemmotsuNaoya en-aut-sei=Kemmotsu en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MukoharaFumiaki en-aut-sei=Mukohara en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MagariMasaki en-aut-sei=Magari en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyamotoAi en-aut-sei=Miyamoto en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshinoTakamasa en-aut-sei=Ishino en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HayashiHidetoshi en-aut-sei=Hayashi en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TachibanaKota en-aut-sei=Tachibana en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OkamotoIsamu en-aut-sei=Okamoto en-aut-mei=Isamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Medical Protein Engineering, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=12 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=18 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue=9 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20160908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=S-nitrosylation of laforin inhibits its phosphatase activity and is implicated in Lafora disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recently, the relation between S-nitrosylation by nitric oxide (NO), which is over?produced under pathological conditions and neurodegenerative diseases, includingAlzheimerfs and Parkinsonfs diseases, has become a focus of attention. Although mostcases of Parkinsonfs disease are known to be caused by mutations in the Parkin gene, arecent finding has indicated that S-nitrosylation of Parkin affects its enzymatic activityand leads to the Parkinsonian phenotype. Therefore, it is important to understand thefunction of S-nitrosylated proteins in the pathogenesis of neurodegenerative diseases.Lafora disease (LD, OMIM 254780) is a neurodegenerative disease characterized by theaccumulation of insoluble glucans called Lafora bodies (LBs). LD is caused by mutationsin genes that encode the glucan phosphatase, Laforin, or the E3 ubiquitin ligase, Malin.In this study, we hypothesized that LD may be caused by S-nitrosylation of Laforin,which is similar to the finding that Parkinsonfs disease is caused by S-nitrosylation ofParkin. To test this hypothesis, we first determined whether Laforin was S-nitrosylatedusing a biotin switch assay, and compared the three main functions of unmodified andS-nitrosylated Laforin, namely glucan- and Malin-binding activity and phosphataseactivity. Furthermore, we examined whether the numbers of LBs were changed byNO in the cells expressing wild-type Laforin. Here, we report for the first time thatS-nitrosylation of Laforin inhibited its phosphatase activity and that LB formation wasincreased by an NO donor. Our results suggest a possible hypothesis for LD pathogenesis; that is, the decrease in phosphatase activity of Laforin by S-nitrosylation leads toincreased LB formation. Therefore, LD may be caused not only by mutations in theLaforin or Malin genes, but also by the S-nitrosylation of Laforin. en-copyright= kn-copyright= en-aut-name=ToyotaRikako en-aut-sei=Toyota en-aut-mei=Rikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HonjoYasuko en-aut-sei=Honjo en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ImajoRisa en-aut-sei=Imajo en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University; Research Institute for Radiation Biology and Medicine, Hiroshima University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University; Research Institute for Radiation Biology and Medicine, Hiroshima University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University; Research Institute for Radiation Biology and Medicine, Hiroshima University kn-affil= en-keyword=S-Nitrosylation Of Laforin kn-keyword=S-Nitrosylation Of Laforin en-keyword=Post-Translational Modification kn-keyword=Post-Translational Modification en-keyword=Nitrosylation kn-keyword=Nitrosylation en-keyword=Phosphatase kn-keyword=Phosphatase en-keyword=Glucan-Binding kn-keyword=Glucan-Binding END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=5248 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Changes of leucine-rich alpha 2 glycoprotein could be a marker of changes of endoscopic and histologic activity of ulcerative colitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Leucine-rich alpha 2 glycoprotein (LRG) is one of the serum biomarkers for disease activity of ulcerative colitis (UC). We focused on the correlation between the changes of LRG and the changes of endoscopic and histologic activity of UC, in comparison to the changes of fecal calprotectin (Fcal), fecal immunochemical test (FIT), and C-reactive protein (CRP). Seventy-nine patients with two or more colonoscopies were enrolled, and 123 paired colonoscopies and 121 paired biopsies were examined. With regard to the change of endoscopic/histologic activity between the preceding and subsequent colonoscopy, there was improvement (n = 29/45), unchanging (n = 63/36), and worsening (n = 31/40). The correlations between the changes of marker levels and endoscopic/histologic activity were Fcal; r = 0.50/0.39 and FIT; r = 0.41/0.40, LRG; r = 0.42/0.40 and CRP; r = 0.22/0.17. Furthermore, when the correlation between the changes of LRG levels and the changes of endoscopic/histological activity was compared with those of other markers, the correlation of LRG tended to be superior to those of CRP (CRP vs. LRG; p = 0.08/0.01). LRG is equivalent to fecal markers and superior to CRP, when inferring changes in disease activity of UC based on changes in its level. en-copyright= kn-copyright= en-aut-name=AoyamaYuki en-aut-sei=Aoyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasutomiEriko en-aut-sei=Yasutomi en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InokuchiToshihiro en-aut-sei=Inokuchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakeiKensuke en-aut-sei=Takei en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IgawaShoko en-aut-sei=Igawa en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiKeiko en-aut-sei=Takeuchi en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakaharaMasahiro en-aut-sei=Takahara en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ToyosawaJunki en-aut-sei=Toyosawa en-aut-mei=Junki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamasakiYasushi en-aut-sei=Yamasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KinugasaHideaki en-aut-sei=Kinugasa en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KatoJun en-aut-sei=Kato en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Gastroenterology, Graduate School of Medicine, Chiba University kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Ulcerative colitis kn-keyword=Ulcerative colitis en-keyword=Leucine-rich alpha 2 glycoprotein kn-keyword=Leucine-rich alpha 2 glycoprotein en-keyword=Biomarker kn-keyword=Biomarker END start-ver=1.4 cd-journal=joma no-vol=96 cd-vols= no-issue=10 article-no= start-page=1241 end-page=1252 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype (TAFRO) of idiopathic multicentric Castleman disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly (TAFRO) syndrome is a heterogeneous entity manifesting with a constellation of symptoms described above that can occur in the context of idiopathic multicentric Castleman disease (iMCD) as well as infectious diseases, malignancies, and rheumatologic disorders. So, iMCD-TAFRO is an aggressive subtype of iMCD with TAFRO syndrome and often hyper-vascularized lymph nodes. Since we proposed diagnostic criteria of iMCD-TAFRO in 2016, we have accumulated new insights on the disorder and additional cases have been reported worldwide. In this systematic review and cohort analysis, we established and validated a definition for iMCD-TAFRO. First, we searched PubMed and Japan Medical Abstracts Society databases using the keyword gTAFROh to extract cases. Patients with possible systemic autoimmune diseases and hematologic malignancies were excluded. Our search identified 54 cases from 50 articles. We classified cases into three categories: (1) iMCD-TAFRO (TAFRO syndrome with lymph node histopathology consistent with iMCD), (2) possible iMCD-TAFRO (TAFRO syndrome with no lymph node biopsy performed and no other co-morbidities), and (3) TAFRO without iMCD or other co-morbidities (TAFRO syndrome with lymph node histopathology not consistent with iMCD or other comorbidities). Based on the findings, we propose an international definition requiring four clinical criteria (thrombocytopenia, anasarca, fever/hyperinflammatory status, organomegaly), renal dysfunction or characteristic bone marrow findings, and lymph node features consistent with iMCD. The definition was validated with an external cohort (the ACCELERATE Natural History Registry). The present international definition will facilitate a more precise and comprehensive approach to the diagnosis of iMCD-TAFRO. en-copyright= kn-copyright= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FajgenbaumDavid C. en-aut-sei=Fajgenbaum en-aut-mei=David C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PiersonSheila K. en-aut-sei=Pierson en-aut-mei=Sheila K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwakiNoriko en-aut-sei=Iwaki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawanoMitsuhiro en-aut-sei=Kawano en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraNaoya en-aut-sei=Nakamura en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IzutsuKoji en-aut-sei=Izutsu en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakeuchiKengo en-aut-sei=Takeuchi en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YoshizakiKazuyuki en-aut-sei=Yoshizaki en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OksenhendlerEric en-aut-sei=Oksenhendler en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=van RheeFrits en-aut-sei=van Rhee en-aut-mei=Frits kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Center for Cytokine Storm Treatment & Laboratory, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=3 en-affil=Center for Cytokine Storm Treatment & Laboratory, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=4 en-affil=Hematology/Respiratory Medicine, Kanazawa University Graduate School of Medical Science kn-affil= affil-num=5 en-affil=Division of Pathophysiology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Department of Rheumatology, Kanazawa University Graduate School of Medical Science kn-affil= affil-num=7 en-affil=Department of Pathology, Tokai University School of Medicine kn-affil= affil-num=8 en-affil=Department of Hematology, National Cancer Center Hospital kn-affil= affil-num=9 en-affil=Department of Pathology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=10 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Organic Fine Chemicals, Institute of Scientific and Industrial Research, Osaka University kn-affil= affil-num=14 en-affil=Department of Clinical Immunology, H?pital Saint-Louis kn-affil= affil-num=15 en-affil=Myeloma Center, University of Arkansas for Medical Sciences kn-affil= affil-num=16 en-affil=Division of Pathophysiology, Okayama University Graduate School of Health Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=2 article-no= start-page=97 end-page=106 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=2024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Atypical lymphoplasmacytic and immunoblastic proliferation: A Systematic Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) was first reported in 1984 as characteristic histological findings in lymph nodes associated with autoimmune diseases, but it has not been clearly defined to date. To summarize the histological characteristics and clinical diagnoses associated with ALPIBP, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including gatypical lymphoplasmacytic and immunoblastic lymphadenopathyh from their inception to December 27, 2023. We also summarized the courses of three cases with a pathological diagnosis of ALPIBP. Nine articles with 52 cases were included. Among the total of 55 cases, including the three from our institution, the median age of the cases was 63.5 years with a female predominance (69.5%). Lymphadenopathy was generalized in 65.6% and regional in 34.4% of cases. RA (24.4%), SLE (24.4%), and autoimmune hemolytic anemia (20.0%), were common clinical diagnoses. A combination of cytotoxic chemotherapy was used in 15.6% of cases due to the suspicion of malignancy. Nodal T-follicular helper cell lymphoma, angioimmunoblastic type, methotrexate-associated lymphoproliferative disorders, and IgG4-related diseases were listed as important diseases that need to be pathologically differentiated from ALPIBP. This review summarizes the current understanding of the characteristics of ALPIBP. Given that underrecognition of ALPIBP could lead to overdiagnosis of hematological malignancy and unnecessary treatment, increased awareness of the condition in pathologists and clinicians is crucial. en-copyright= kn-copyright= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiToshiaki en-aut-sei=Takahashi en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakaokaKensuke en-aut-sei=Takaoka en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MacapagalSharina en-aut-sei=Macapagal en-aut-mei=Sharina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WannaphutChalothorn en-aut-sei=Wannaphut en-aut-mei=Chalothorn kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TodaHiroko en-aut-sei=Toda en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawaifi kn-affil= affil-num=3 en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawaifi kn-affil= affil-num=4 en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawaifi kn-affil= affil-num=5 en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawaifi kn-affil= affil-num=6 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=7 en-affil=Department of Pathology, Chugoku Central Hospital kn-affil= affil-num=8 en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawaifi kn-affil= affil-num=9 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=systematic review kn-keyword=systematic review en-keyword=atypical lymphoplasmacytic and immunoblastic proliferation kn-keyword=atypical lymphoplasmacytic and immunoblastic proliferation en-keyword=IgG4-related disease kn-keyword=IgG4-related disease en-keyword=angioimmunoblastic T-cell lymphoma kn-keyword=angioimmunoblastic T-cell lymphoma END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=2 article-no= start-page=e79852 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Presumed Autoimmune Keratitis in Both Eyes Without Systemic Manifestations: A 40-Year Course of a Patient With Corneal Infiltrates and Melt en-subtitle= kn-subtitle= en-abstract= kn-abstract=Peripheral corneal infiltration, corneal ulcer, and melt are recognized complications linked to systemic immunological diseases, such as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. These manifestations, which occur in isolation, might be autoimmune keratitis but are difficult to prove underlying immunological abnormalities. This report described a patient with presumed autoimmune keratitis who repeatedly presented corneal infiltration and perforation in both eyes even after penetrating keratoplasty. The 68-year-old patient with a stable condition of keratoconjunctivitis sicca, in a 28-year follow-up, abruptly developed mild infiltrates in the corneal center of the right eye and white dense infiltrates in the peripheral and central cornea of the left eye. He was treated with topical 0.1% betamethasone eye drops and oral prednisolone tapering from 30 mg daily. The patient underwent cataract surgeries in both eyes 10 months after the onset of corneal infiltration and subsequently underwent penetrating keratoplasty in both eyes due to abrupt corneal perforation in the left eye 14 months after the onset of corneal infiltration. Six months post-keratoplasty, he experienced a recurrence of infiltrates in the corneal grafts in both eyes, leading to corneal leukoma in the left eye. The corneal graft in the right eye maintained its integrity with relatively mild opacity until approximately 3.5 years post-keratoplasty, when he abruptly developed white dense infiltration of both the corneal graft and his own peripheral cornea at the age of 73. In response to oral prednisolone tapered from 15 mg daily, the corneal infiltration in the right eye resolved but resulted in graft failure. Since he did not exhibit systemic symptoms and signs throughout the course, the repeat episodes of infiltration in both his own cornea and the corneal graft would be the manifestations of autoimmune keratitis. The entity of autoimmune keratitis in isolation would be beneficial to establish a therapeutic strategy for long-term immunosuppression in light of a risk for steroid side effects and a high rate of corneal graft failure. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=autoimmune keratitis kn-keyword=autoimmune keratitis en-keyword=corneal graft kn-keyword=corneal graft en-keyword=corneal infiltration kn-keyword=corneal infiltration en-keyword=corneal melt kn-keyword=corneal melt en-keyword=penetrating keratoplasty kn-keyword=penetrating keratoplasty END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250217 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Kikuchi]Fujimoto disease: investigating comprehensive clinicopathological features and risk factors for recurrence en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims: Kikuchi-Fujimoto disease (KFD) is a rare disease that typically manifests with fever and cervical lymphadenopathy. Little is known about the risk factors associated with recurrence and their correlation with clinicopathologic features.
Methods and Results: We analysed 112 patients with KFD, predominantly female (61/112, 54.5%), with an average age of 29.4?years. The incidence was higher in males up to the age of 20 and higher in females from their 30s onwards. Of the 70 patients with follow-up data, 23% experienced recurrence. Recurrence was associated with lower C4 levels (P?=?0.038) and higher antinuclear antibody (ANA) rates (P?=?0.007) compared to transient disease. The mean duration of symptoms was 71.5?days. Lymph node histology in 98 cases (excluding 14 needle biopsy specimens) was classified into three patterns: proliferative (n?=?75, 77%), necrotizing (n?=?22, 22%), and xanthomatous (n?=?1, 1%). The necrotizing pattern associated with significantly enlarged lymph nodes (P?=?0.047) and a longer symptom duration (P?=?0.009) than the proliferating pattern. The number of CD4-positive lymphocytes was significantly lower in the necrotizing type than in the proliferative type (P? Conclusion: These results indicated that low C4 levels and positive ANA were associated with KFD recurrence. Although the aetiology of KFD remains elusive, given that some cases develop autoimmune disease, the results suggest that patients with recurrent KFD represent an intermediate status between those with transient KFD and those with overt autoimmune disease. The comprehensive clinicopathological findings of this study may be useful for elucidating its pathogenesis and predicting the clinical course. en-copyright= kn-copyright= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakaoChikako en-aut-sei=Sakao en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurokawaYuka en-aut-sei=Kurokawa en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=histiocytic necrotizing lymphadenitis kn-keyword=histiocytic necrotizing lymphadenitis en-keyword=histological subtypes kn-keyword=histological subtypes en-keyword=Kikuchi-Fujimoto disease kn-keyword=Kikuchi-Fujimoto disease en-keyword=necrotizing type kn-keyword=necrotizing type en-keyword=proliferating type kn-keyword=proliferating type en-keyword=recurrent kn-keyword=recurrent en-keyword=xanthomatous type kn-keyword=xanthomatous type END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=2 article-no= start-page=376 end-page=382 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A case of pancreatic ductal adenocarcinoma growing within the pancreatic duct mimicking an intraductal tubulopapillary neoplasm en-subtitle= kn-subtitle= en-abstract= kn-abstract=We herein report a case of pancreatic ductal adenocarcinoma (PDAC) that developed within the pancreatic duct and was initially diagnosed as an intraductal tubulopapillary neoplasm (ITPN). A 76-year-old man presented with weight loss and main pancreatic duct dilation. The imaging studies revealed a 30-mm hypovascular tumor within the main duct of the pancreatic head. An endoscopic examination with a biopsy revealed high-grade atypical epithelial cells with immunostaining patterns suggestive of ITPN. Following robot-assisted pancreaticoduodenectomy, postoperative pathology revealed conflicting features: nodular/cribriform infiltrations typical of ITPN and non-lobular replacement with scattered infiltrations characteristic of PDAC. A comprehensive genomic profiling test detected KRAS and TP53 mutations, leading to the final diagnosis of PDAC (fT3N1aM0, stage IIB). The patient received adjuvant S-1 chemotherapy and remained recurrence-free for 15 months post-surgery. This case highlights the diagnostic challenges of differentiating intraductal pancreatic tumors and demonstrates the utility of integrating genetic testing with conventional diagnostic modalities for an accurate diagnosis and appropriate treatment selection. en-copyright= kn-copyright= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UkaMayu en-aut-sei=Uka en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishidaKenji en-aut-sei=Nishida en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pathology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Pathology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=Pancreatic intraductal neoplasms kn-keyword=Pancreatic intraductal neoplasms en-keyword=Pancreatic carcinoma kn-keyword=Pancreatic carcinoma en-keyword=Intraductal tubulopapillary neoplasm kn-keyword=Intraductal tubulopapillary neoplasm en-keyword=Genetic testing kn-keyword=Genetic testing END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=3 article-no= start-page=96 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cancer-associated fibroblasts promote pro-tumor functions of neutrophils in pancreatic cancer via IL-8: potential suppression by pirfenidone en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The mechanisms by which neutrophils acquire pro-tumor properties remain poorly understood. In pancreatic cancer, cancer-associated fibroblasts (CAFs) may interact with neutrophils, directing them to promote tumor progression.
Methods To validate the association between CAFs and neutrophils, the localization of neutrophils was examined in clinically resected pancreatic cancer specimens. CAFs were produced by culturing in cancer-conditioned media, and the effects of these CAFs on neutrophils were examined. In vitro migration and invasion assays assess the effect of CAF-activated neutrophils on cancer cells. The factors secreted by the activated neutrophils were also explored. Finally, pirfenidone (PFD) was tested to determine whether it could suppress the pro-tumor functions of activated neutrophils.
Results In pancreatic cancer specimens, neutrophils tended to co-localize with IL-6-positive CAFs. Neutrophils co-cultured with CAFs increased migratory capacity and prolonged life span. CAF-affected neutrophils enhance the migratory and invasive activities of pancreatic cancer cells. IL-8 is the most upregulated cytokine secreted by the neutrophils. PFD suppresses IL-8 secretion from CAF-stimulated neutrophils and mitigates the malignant traits of pancreatic cancer cells.
Conclusion CAFs activate neutrophils and enhance the malignant phenotype of pancreatic cancer. The interactions between cancer cells, CAFs, and neutrophils can be disrupted by PFD, highlighting a potential therapeutic approach. en-copyright= kn-copyright= en-aut-name=YagiTomohiko en-aut-sei=Yagi en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NogiShohei en-aut-sei=Nogi en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaniguchiAtsuki en-aut-sei=Taniguchi en-aut-mei=Atsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshimotoMasashi en-aut-sei=Yoshimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuemoriKanto en-aut-sei=Suemori en-aut-mei=Kanto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujitaShuto en-aut-sei=Fujita en-aut-mei=Shuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Departments of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Cancer-associated fibroblasts kn-keyword=Cancer-associated fibroblasts en-keyword=Neutrophil kn-keyword=Neutrophil en-keyword=Anti-fibrotic agent kn-keyword=Anti-fibrotic agent en-keyword=Pirfenidone kn-keyword=Pirfenidone END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=1 article-no= start-page=1 end-page=7 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Endothelial Cell Polarity in Health and Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Endothelial cell polarity is fundamental to the organization and function of blood vessels, influencing processes such as angiogenesis, vascular stability, and response to shear stress. This review elaborates on the molecular mechanisms that regulate endothelial cell polarity, focusing on key players like the PAR polarity complex and Rho family GTPases. These pathways coordinate the front?rear, apical?basal and planar polarity of endothelial cells, which are essential for the proper formation and maintenance of vascular structures. In health, endothelial polarity ensures not only the orderly development of blood vessels, with tip cells adopting distinct polarities during angiogenesis, but also ensures proper vascular integrity and function. In disease states, however, disruptions in polarity contribute to pathologies such as coronary artery disease, where altered planar polarity exacerbates atherosclerosis, and cancer, where disrupted polarity in tumor vasculature leads to abnormal vessel growth and function. Understanding cell polarity and its disruption is fundamental not only to comprehending how cells interact with their microenvironment and organize themselves into complex, organ-specific tissues but also to developing novel, targeted, and therapeutic strategies for a range of diseases, from cardiovascular disorders to malignancies, ultimately improving patient outcomes. en-copyright= kn-copyright= en-aut-name=ThihaMoe en-aut-sei=Thiha en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HikitaTakao en-aut-sei=Hikita en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakayamaMasanori en-aut-sei=Nakayama en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=blood vessel kn-keyword=blood vessel en-keyword=endothelial cell kn-keyword=endothelial cell en-keyword=cell polarity kn-keyword=cell polarity en-keyword=atherosclerosis kn-keyword=atherosclerosis en-keyword=cancer kn-keyword=cancer END start-ver=1.4 cd-journal=joma no-vol=121 cd-vols= no-issue=35 article-no= start-page=e2320189121 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240821 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Somatic mutations in tumor-infiltrating lymphocytes impact on antitumor immunity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immune checkpoint inhibitors (ICIs) exert clinical efficacy against various types of cancers by reinvigorating exhausted CD8+ T cells that can expand and directly attack cancer cells (cancer-specific T cells) among tumor-infiltrating lymphocytes (TILs). Although some reports have identified somatic mutations in TILs, their effect on antitumor immunity remains unclear. In this study, we successfully established 18 cancer-specific T cell clones, which have an exhaustion phenotype, from the TILs of four patients with melanoma. We conducted whole-genome sequencing for these T cell clones and identified various somatic mutations in them with high clonality. Among the somatic mutations, an SH2D2A loss-of-function frameshift mutation and TNFAIP3 deletion could activate T cell effector functions in vitro. Furthermore, we generated CD8+ T cell?specific Tnfaip3 knockout mice and showed that Tnfaip3 function loss in CD8+ T cell increased antitumor immunity, leading to remarkable response to PD-1 blockade in vivo. In addition, we analyzed bulk CD3+ T cells from TILs in additional 12 patients and identified an SH2D2A mutation in one patient through amplicon sequencing. These findings suggest that somatic mutations in TILs can affect antitumor immunity and suggest unique biomarkers and therapeutic targets. en-copyright= kn-copyright= en-aut-name=MukoharaFumiaki en-aut-sei=Mukohara en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwataKazuma en-aut-sei=Iwata en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshinoTakamasa en-aut-sei=Ishino en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InozumeTakashi en-aut-sei=Inozume en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UenoToshihide en-aut-sei=Ueno en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IkedaHideki en-aut-sei=Ikeda en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawaseKatsushige en-aut-sei=Kawase en-aut-mei=Katsushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SaekiYuka en-aut-sei=Saeki en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawashimaShusuke en-aut-sei=Kawashima en-aut-mei=Shusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamashitaKazuo en-aut-sei=Yamashita en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawaharaYu en-aut-sei=Kawahara en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakamuraYasuhiro en-aut-sei=Nakamura en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=Honobe-TabuchiAkiko en-aut-sei=Honobe-Tabuchi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=WatanabeHiroko en-aut-sei=Watanabe en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=DansakoHiromichi en-aut-sei=Dansako en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KawamuraTatsuyoshi en-aut-sei=Kawamura en-aut-mei=Tatsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SuzukiYutaka en-aut-sei=Suzuki en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HondaHiroaki en-aut-sei=Honda en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ManoHiroyuki en-aut-sei=Mano en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KawazuMasahito en-aut-sei=Kawazu en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= affil-num=1 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University kn-affil= affil-num=8 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=9 en-affil=Division of Cell Therapy, Chiba Cancer Research Institute kn-affil= affil-num=10 en-affil=Division of Cell Therapy, Chiba Cancer Research Institute kn-affil= affil-num=11 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=13 en-affil=KOTAI Biotechnologies, Inc. kn-affil= affil-num=14 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=16 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=17 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=18 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=19 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=20 en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa kn-affil= affil-num=21 en-affil=Department of Pathology, Tokyo Women's Medical University kn-affil= affil-num=22 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=23 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University kn-affil= affil-num=24 en-affil=Division of Cell Therapy, Chiba Cancer Research Institute kn-affil= affil-num=25 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=cancer immunology kn-keyword=cancer immunology en-keyword=somatic mutation kn-keyword=somatic mutation en-keyword=T cell kn-keyword=T cell en-keyword=tumor-infiltrating lymphocytes kn-keyword=tumor-infiltrating lymphocytes END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=3267 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250125 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel treatment strategy targeting interleukin-6 induced by cancer associated fibroblasts for peritoneal metastasis of gastric cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer-associated fibroblasts (CAFs) are a crucial component in the tumor microenvironment (TME) of peritoneal metastasis (PM), where they contribute to tumor progression and metastasis via secretion of interleukin-6 (IL-6). Here, we investigated the role of IL-6 in PM of gastric cancer (GC) and assessed whether anti-IL-6 receptor antibody (anti-IL-6R Ab) could inhibit PM of GC. We conducted immunohistochemical analysis of IL-6 and alpha-smooth muscle (alpha-SMA) expressions in clinical samples of GC and PM, and investigated the interactions between CAFs and GC cells in vitro. Anti-tumor effects of anti-IL-6R Ab on PM of GC were investigated in an orthotopic murine PM model. IL-6 expression was significantly correlated with alpha-SMA expression in clinical samples of GC, and higher IL-6 expression in the primary tumor was associated with poor prognosis of GC. Higher IL-6 and alpha-SMA expressions were also observed in PM of GC. In vitro, differentiation of fibroblasts into CAFs and chemoresistance were observed in GC cells cocultured with fibroblasts. Anti-IL-6R Ab inhibited the progression of PM in GC cells cocultured with fibroblasts in the orthotopic mouse model but could not inhibit the progression of PM consisting of GC cells alone. IL-6 expression in the TME was associated with poor prognosis of GC, and CAFs were associated with establishment and progression of PM via IL-6. Anti-IL-6R Ab could inhibit PM of GC by the blockade of IL-6 secreted by CAFs, which suggests its therapeutic potential for PM of GC. en-copyright= kn-copyright= en-aut-name=MitsuiEma en-aut-sei=Mitsui en-aut-mei=Ema kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkuraTomohiro en-aut-sei=Okura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UneYuta en-aut-sei=Une en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishiwakiNoriyuki en-aut-sei=Nishiwaki en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhtsukaJunko en-aut-sei=Ohtsuka en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OhkiRieko en-aut-sei=Ohki en-aut-mei=Rieko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Laboratory of Fundamental Oncology, National Cancer Center Research Institute kn-affil= affil-num=12 en-affil=Laboratory of Fundamental Oncology, National Cancer Center Research Institute kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Peritoneal metastasis kn-keyword=Peritoneal metastasis en-keyword=Gastric cancer kn-keyword=Gastric cancer en-keyword=Interleukin-6 kn-keyword=Interleukin-6 en-keyword=Cancer-associated fibroblasts kn-keyword=Cancer-associated fibroblasts en-keyword=Interleukin-6 receptor antibody kn-keyword=Interleukin-6 receptor antibody END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=2486 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nomogram models for predicting outcomes in thyroid cancer patients with distant metastasis receiving 131iodine therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study aimed to establish and validate prognostic nomogram models for patients who underwent I-131 therapy for thyroid cancer with distant metastases. The cohort was divided into training (70%) and validation (30%) sets for nomogram development. Univariate and multivariate Cox regression analyses were used to identify independent predictors for overall survival (OS) and progression-free survival (PFS). Nomograms were developed based on these predictors, and Kaplan-Meier curves were constructed for validation. Among 451 patients who were screened, 412 met the inclusion criteria and were followed-up for a median duration of 65.2 months. The training and validation sets included 288 and 124 patients, respectively. Pathological type, first I-131 administrated activity, and lesion I-131 uptake in lesions were independent predictors for PFS. For OS, predictors included gender, age, metastasis site, first I-131 administrated activity, I-131 uptake, pulmonary lesion size, and stimulated thyroglobulin levels. These predictors were used to construct nomograms for predicting PFS and OS. Low-risk patients had significantly longer PFS and OS compared to high-risk patients, with 10-year PFS rates of 81.1% vs. 51.9% and 10-year OS rates of 86.2% vs. 37.4%. These may aid individualized prognostic assessment and clinical decision-making, especially in determining the prescribed activity for the first I-131 treatment. en-copyright= kn-copyright= en-aut-name=JinShui en-aut-sei=Jin en-aut-mei=Shui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YeXuemei en-aut-sei=Ye en-aut-mei=Xuemei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YeTing en-aut-sei=Ye en-aut-mei=Ting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChenXinyu en-aut-sei=Chen en-aut-mei=Xinyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=JiJianfeng en-aut-sei=Ji en-aut-mei=Jianfeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WangJinyu en-aut-sei=Wang en-aut-mei=Jinyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhuXin en-aut-sei=Zhu en-aut-mei=Xin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaoXiaochun en-aut-sei=Mao en-aut-mei=Xiaochun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiguchiTakahiro en-aut-sei=Higuchi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YiHeqing en-aut-sei=Yi en-aut-mei=Heqing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Nuclear Medicine, Zhejiang Cancer Hospital kn-affil= affil-num=2 en-affil=Department of Nuclear Medicine, Zhejiang Cancer Hospital kn-affil= affil-num=3 en-affil=Department of Nuclear Medicine, Zhejiang Cancer Hospital kn-affil= affil-num=4 en-affil=Nuclear Medicine, Faculty of Medicine, University of Augsburg kn-affil= affil-num=5 en-affil=Department of Nuclear Medicine, Zhejiang Cancer Hospital kn-affil= affil-num=6 en-affil=Medical records and statistics office, Zhejiang Cancer Hospital kn-affil= affil-num=7 en-affil=Key Laboratory of Head and Neck Cancer Translational Research of Zhejiang Province, Zhejiang Cancer Hospital kn-affil= affil-num=8 en-affil=Department of Thyroid Surgery, Zhejiang Cancer Hospital kn-affil= affil-num=9 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Nuclear Medicine, Zhejiang Cancer Hospital kn-affil= en-keyword=131iodine kn-keyword=131iodine en-keyword=Activity kn-keyword=Activity en-keyword=Distant metastasis kn-keyword=Distant metastasis en-keyword=Iodine radioisotopes kn-keyword=Iodine radioisotopes en-keyword=Thyroid cancer kn-keyword=Thyroid cancer END start-ver=1.4 cd-journal=joma no-vol=2025 cd-vols= no-issue=1 article-no= start-page=5556176 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250111 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of an Oral Elastofibromatous Lesion: A Clinicopathological Analysis With a Literature Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Elastofibromatous changes of the oral mucosa, such as an elastofibroma (EF) or an elastofibromatous lesion (EFL), are not well recognized, and the second such case in Japan is reported. A 72-year-old man wearing a complete maxillary denture presented with a small nodule on the hard palate. Histopathological examination showed abundant fibrous tissue with numerous elastic fibers on Elastica van Gieson (EvG) staining. The diagnosis of an oral EFL was made. In the review of oral EF and EFL, no cases with recurrence were identified, but such lesions may resemble neoplastic lesions macroscopically. Accurate diagnosis using EvG stain is needed to recognize oral EFs and EFLs. en-copyright= kn-copyright= en-aut-name=OnoSawako en-aut-sei=Ono en-aut-mei=Sawako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MasuiMasanori en-aut-sei=Masui en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ObataKyoichi en-aut-sei=Obata en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamuraTomoya en-aut-sei=Nakamura en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FurukiYoshihiko en-aut-sei=Furuki en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraSatoko en-aut-sei=Nakamura en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=6 en-affil=Department of Pathology, Kagawa Prefectural Central Hospital kn-affil= affil-num=7 en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=elastofibroma kn-keyword=elastofibroma en-keyword=oral elastofibromatous lesion kn-keyword=oral elastofibromatous lesion en-keyword=oral mucosa kn-keyword=oral mucosa END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=23 article-no= start-page=7078 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241123 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical Characteristics of Persistent Hypophosphatasemia Uncovered in Adult Patients: A Retrospective Study at a Japanese Tertiary Hospital en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Hypophosphatasemia is often overlooked despite its potential to indicate underlying pathologies. The aim of this study was to determine the prevalence of persistent hypophosphatasemia in a large, urban, multi-specialty hospital population and characterize the clinical and laboratory findings in adult patients with this condition. Methods: In this retrospective observational study, the results of 424,434 alkaline phosphatase (ALP) tests in 50,136 patients aged >= 18 years that were performed at Okayama University Hospital between July 2020 and October 2023 were analyzed. Persistent hypophosphatasemia was defined as consistently low ALP levels (<= 40 IU/L) for 28 days with a minimum recorded level of <= 35 IU/L. Results: Persistent hypophosphatasemia was detected in 273 patients (0.54% of the tested patients), and the patients with persistent hypophosphatasemia included a higher proportion of females (72.5% vs. 52.9% in the people without persistent hypophosphatasemia; chi-squared test, p < 0.01) and had a younger median age (51 years vs. 63 years; Mann-Whitney U test, p < 0.01) than those in the overall tested population. The common causes of persistent hypophosphatasemia were cancer (30%), glucocorticoid use (21%), and immunosuppressants (16%). Notably, 38 patients (14%) had no apparent cause for low ALP values. These patients were categorized on the basis of their clinical characteristics, with some patients presenting symptoms potentially related to adult hypophosphatasia. Conclusions: This study provides prevalence and insights into the causes and characteristics of persistent hypophosphatasemia in a Japanese tertiary care setting. While most cases were associated with known causes, patients with unexplained hypophosphatasemia and symptoms such as chronic pain, muscle weakness, and general fatigue could have adult hypophosphatasia. In such cases, comprehensive evaluation and further investigation for hypophosphatasia should be considered. Persistent hypophosphatasemia of undetermined etiology could be a crucial initial step in diagnostic algorithms for this condition. en-copyright= kn-copyright= en-aut-name=FujiwaraShintaro en-aut-sei=Fujiwara en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtsukaYuki en-aut-sei=Otsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FurukawaMasanori en-aut-sei=Furukawa en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HigashikageAkihito en-aut-sei=Higashikage en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Laboratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Laboratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=chronic fatigue syndrome kn-keyword=chronic fatigue syndrome en-keyword=chronic pain kn-keyword=chronic pain en-keyword=hypophosphatasemia kn-keyword=hypophosphatasemia en-keyword=alkaline phosphatase kn-keyword=alkaline phosphatase en-keyword=hypophosphatasia kn-keyword=hypophosphatasia END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue=21 article-no= start-page=2875 end-page=2884 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Endoscopic and Histological Gastritis in University Students with Helicobacter pylori Infection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective Although the characteristics of Helicobacter pylori infection have been extensively reported, there is a lack of consensus regarding its characteristics in young adults. The present study examined the endoscopic and histological characteristics of young adults who underwent eradication therapy for H. pylori infection.
Methods We examined the H. pylori infection status of first-year students at Okayama University School of Medicine and Dentistry between 2014 and 2020. A total of 152 (6.8%) students who were positive for H. pylori antibody or pepsinogen tests were enrolled in the study. Among them, 107 students underwent endoscopy, and their biopsy samples were investigated. Seventy-five students were diagnosed with H. pylori infections.
Results Of 75 H. pylori-positive patients, 57 (76.0%) had endoscopic atrophic gastritis, and 42 (56.0%) had histological atrophy. A few patients had severe atrophic gastritis. All 65 patients who underwent an eradication assessment were successfully treated. After successful eradication, 26 patients underwent endoscopic follow-up. The mean follow-up period was 32.9 months. A histological evaluation revealed that gastric antrum atrophy had subsided in 11 of 14 patients, and atrophy in the lesser curvature of the gastric body had subsided in 7 of 8 patients.
Conclusion More than half of young adults with H. pylori infection had atrophic gastritis. We found mild atrophy in young adults, which subsided shortly after eradication treatment. This study provides a foundation for future studies to evaluate the validity of eradication therapy in preventing gastric cancer in patients. en-copyright= kn-copyright= en-aut-name=OkanoueShotaro en-aut-sei=Okanoue en-aut-mei=Shotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakaeHiroyuki en-aut-sei=Sakae en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YokotaKenji en-aut-sei=Yokota en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ObayashiYuka en-aut-sei=Obayashi en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AbeMakoto en-aut-sei=Abe en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KonoYoshiyasu en-aut-sei=Kono en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanzakiHiromitsu en-aut-sei=Kanzaki en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=atrophic gastritis kn-keyword=atrophic gastritis en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=Helicobacter pylori kn-keyword=Helicobacter pylori en-keyword=young adults kn-keyword=young adults en-keyword=eradication kn-keyword=eradication END start-ver=1.4 cd-journal=joma no-vol=145 cd-vols= no-issue=8 article-no= start-page=881 end-page=896 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oral Inflammation and Microbiome Dysbiosis Exacerbate Chronic Graft-versus-host Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated antigen-presenting cells, thereby promoting the expansion of donor-derived inflammatory T cells. Based on these results, we hypothesize that pathogenic bacteria increase in the oral cavity might not only exacerbate local inflammation but also enhance systemic inflammation throughout the HCT course. Additionally, these bacteria translocated to the gut and formed ectopic colonies, further amplifying systemic inflammation. Furthermore, interventions targeting the oral microbiome mitigated murine cGVHD. Collectively, our findings highlight the importance of oral dysbiosis in cGVHD and suggest that modulation of the oral microbiome during transplantation may be an effective approach for preventing or treating cGVHD. en-copyright= kn-copyright= en-aut-name=KambaraYui en-aut-sei=Kambara en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoAkira en-aut-sei=Yamamoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KunihiroMari en-aut-sei=Kunihiro en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OyamaTadashi en-aut-sei=Oyama en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TeraoToshiki en-aut-sei=Terao en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatoAyame en-aut-sei=Sato en-aut-mei=Ayame kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=PeltierDaniel en-aut-sei=Peltier en-aut-mei=Daniel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SogaYoshihiko en-aut-sei=Soga en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ReddyPavan en-aut-sei=Reddy en-aut-mei=Pavan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YoshinobuMaeda en-aut-sei=Yoshinobu en-aut-mei=Maeda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Medical School kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of Microbiology and Genetics, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatrics, Herman B Wells Center for Pediatric Research, Simon Cancer Center, Indiana University School of Medicine kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=17 en-affil=Division of Blood Transfusion, Okayama University Hospital kn-affil= affil-num=18 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=19 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=20 en-affil=Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine kn-affil= affil-num=21 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=2 article-no= start-page=249 end-page=260 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241005 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Loss of Nr4a1 ameliorates endothelial cell injury and vascular leakage in lung transplantation from circulatory-death donor en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Ischemia-reperfusion injury (IRI) stands as a major trigger for primary graft dysfunction (PGD) in lung transplantation (LTx). Especially in LTx from donation after cardiac death (DCD), effective control of IRI following warm ischemia (WIRI) is crucial to prevent PGD. This study aimed to identify the key factors affecting WIRI in LTx from DCD.
Methods: Previously reported RNA-sequencing dataset of lung WIRI was reanalyzed to identify nuclear receptor subfamily 4 group A member 1 (NR4A1) as the immediate early gene for WIRI. Dynamics of NR4A1 expression were verified using a mouse hilar clamp model. To investigate the role of NR4A1 in WIRI, a mouse model of LTx from DCD was established using Nr4a1 knockout (Nr4a1?/?) mice.
Results: NR4A1 was located around vascular cells, and its protein levels in the lungs increased rapidly and transiently during WIRI. LT from Nr4a1?/? donors significantly improved pulmonary graft function compared to wild-type donors. Histological analysis showed decreased microvascular endothelial cell death, neutrophil infiltration, and albumin leakage. Evans blue permeability assay demonstrated maintained pulmonary microvascular barrier integrity in grafts from Nr4a1?/? donors, correlating with diminished pulmonary edema. However, NR4A1 did not significantly affect the inflammatory response during WIRI, and IRI was not suppressed when a wild-type donor lung was transplanted into the Nr4a1?/? recipient.
Conclusions: Donor NR4A1 plays a specialized role in the positive regulation of endothelial cell injury and microvascular hyperpermeability. These findings demonstrate the potential of targeting NR4A1 interventions to alleviate PGD and improve outcomes in LTx from DCD. en-copyright= kn-copyright= en-aut-name=KawanaShinichi en-aut-sei=Kawana en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakaueTomohisa en-aut-sei=Sakaue en-aut-mei=Tomohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HashimotoKohei en-aut-sei=Hashimoto en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakataKentaro en-aut-sei=Nakata en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ChoshiHaruki en-aut-sei=Choshi en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhtaniShinji en-aut-sei=Ohtani en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Surgery, Division of Cardiovascular and Thoracic Surgery, Duke University School of Medicine kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University kn-affil= affil-num=10 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=lung transplantation kn-keyword=lung transplantation en-keyword=ischemia-reperfusion injury kn-keyword=ischemia-reperfusion injury en-keyword=donation after circulatory death kn-keyword=donation after circulatory death en-keyword=nuclear receptor subfamily 4 group A member 1 kn-keyword=nuclear receptor subfamily 4 group A member 1 en-keyword=endothelial cell kn-keyword=endothelial cell END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=1 article-no= start-page=102494 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cryptococcal prostatitis in an immunocompromised patient with tocilizumab and glucocorticoid therapy: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cryptococcus prostatitis is an uncommon manifestation of cryptococcal infection that occurs mostly in immunocompromised patients. Tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, has been associated with an increased risk of cryptococcal infections. However, there have been no documented cases of cryptococcal prostatitis in patients receiving tocilizumab therapy. We report a case of cryptococcal prostatitis in a 72-year-old man treated with glucocorticoids and tocilizumab for giant cell arteritis and granulomatosis with polyangiitis. The patient presented dysuria and his serum level of prostate-specific antigen was elevated. Magnetic resonance imaging revealed a prostate mass, and a prostate biopsy was performed, leading to a pathologic diagnosis of cryptococcal prostatitis. Fungal cultures for blood and urine were negative, while the cryptococcal antigen for both serum and urine showed positive results. There were no particular findings in the pulmonary and central nervous systems. The patient was successfully treated with oral fluconazole (400 mg/day) and was discharged. Although cryptococcal prostatitis is a rare entity, clinicians should note that an immunosuppressed patient may develop such a difficult-to-diagnose disease. en-copyright= kn-copyright= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatoAtsushi en-aut-sei=Kato en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuyamaAtsuhito en-aut-sei=Suyama en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyawakiYoshia en-aut-sei=Miyawaki en-aut-mei=Yoshia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OnoSawako en-aut-sei=Ono en-aut-mei=Sawako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Cryptococcosis kn-keyword=Cryptococcosis en-keyword=Fluconazole kn-keyword=Fluconazole en-keyword=Glucocorticoids kn-keyword=Glucocorticoids en-keyword=Prostatitis kn-keyword=Prostatitis en-keyword=Tocilizumab kn-keyword=Tocilizumab END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=e70097 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250107 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Eyelid Spindle Cell Lipoma: Case Report and Review of Three Patients in Literature en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 39-year-old woman presented a saucer-shaped mass in the left upper eyelid and underwent the extirpation at local anesthesia. Pathologically, collagen fibers, capillaries, small vessels, and CD34-positive spindle cells were dispersed among mature adipose tissues, indicative of spindle cell lipoma. Long-lasting cyst-like eyelid masses would be usually dermoid cysts, and spindle cell lipoma would be listed as a rare pathological diagnosis in differential diagnoses of cyst-like lesions in the upper and lower eyelid. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamadaKiyoshi en-aut-sei=Yamada en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MonobeYasumasa en-aut-sei=Monobe en-aut-mei=Yasumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Plastic and Reconstructive Surgery, Kousei Hospital kn-affil= affil-num=3 en-affil=Department of Pathology, General Medical Center, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=CD34 kn-keyword=CD34 en-keyword=eyelid kn-keyword=eyelid en-keyword=orbital bony edge kn-keyword=orbital bony edge en-keyword=pathology kn-keyword=pathology en-keyword=spindle cell lipoma kn-keyword=spindle cell lipoma END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=4 article-no= start-page=213 end-page=218 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=2024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=-catenin Binds to Gsk-3 in Liquid-Liquid Phase Separation Compartment in HEK293 Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Liquid-liquid phase separation (LLPS) has emerged as a significant mechanism for cellular organization, impacting various biological processes, including Wnt/-catenin signaling. This study investigates the role of LLPS in the regulation of -catenin in HEK293 cells, particularly in response to Wnt3a signaling. Our findings demonstrate that -catenin is regulated by LLPS, forming spherical droplets indicative of this phenomenon. Fluorescence recovery after photobleaching (FRAP) assays revealed that these droplets exhibit reversible dynamics, further confirming their phase-separated nature. Importantly, treatment with Wnt3a led to an increase in -catenin levels, while simultaneously reducing the recovery of fluorescence intensity in FRAP experiments, suggesting that enhanced Wnt signaling may stimulate the release of -catenin from LLPS. Immunoprecipitation studies indicated that -catenin binds to glycogen synthase kinase 3 (Gsk-3) within the LLPS state, highlighting a potential regulatory mechanism whereby LLPS facilitates the phosphorylation and subsequent degradation of -catenin. The addition of 1,6-hexanediol disrupted the -catenin/Gsk-3 interaction, reinforcing the idea that LLPS plays a critical role in modulating these biochemical interactions. The findings presented in this study suggest that LLPS is not only crucial for the spatial organization of -catenin but also serves as a regulatory mechanism for its signaling functions in the Wnt pathway. Given the association of aberrant Wnt signaling with various diseases, including cancer and neurodegenerative disorders, understanding the role of LLPS in this context may provide new insights into therapeutic strategies targeting these pathological conditions. en-copyright= kn-copyright= en-aut-name=KatoMari en-aut-sei=Kato en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanaiAiri en-aut-sei=Tanai en-aut-mei=Airi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukuharaYoko en-aut-sei=Fukuhara en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhengXinyu en-aut-sei=Zheng en-aut-mei=Xinyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SitosariHeriati en-aut-sei=Sitosari en-aut-mei=Heriati kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IkegameMika en-aut-sei=Ikegame en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamuraHirohiko en-aut-sei=Okamura en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=The Center for Graduate Medical Education (Dental Division), Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=-catenin kn-keyword=-catenin en-keyword=Gsk-3 kn-keyword=Gsk-3 en-keyword=LLPS kn-keyword=LLPS en-keyword=Wnt kn-keyword=Wnt END start-ver=1.4 cd-journal=joma no-vol=126 cd-vols= no-issue= article-no= start-page=110572 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Laparoscopic resection for oesophageal duplication cyst: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Oesophageal duplication cyst is a congenital malformation and rare tumour, clinically manifesting as dysphagia, epigastric pain, or respiratory distress. Duplicate cysts associated with abscess formation or mediastinal penetration and malignancies have been reported, necessitating surgical resection.
Presentation of case: A 55-year-old woman had chest discomfort for 1 year. Preoperative imaging, including computed tomography (CT), upper gastrointestinal endoscopy, and endoscopic ultrasound, revealed a tumour extending from the anterior wall to the lesser curvature of the near the oesophagogastric junction (OGJ) and a suspected mural nodule within the tumour. Contrast-enhanced CT revealed a cystic nodule on the wall of the lesser curvature of the OGJ, with an unclear boundary between the cystic nodule and the oesophageal wall. Magnetic resonance imaging showed an isointense signal on T1-weighted imaging and hyperintensity on T2weighted imaging. Laparoscopic lower oesophagectomy and proximal gastrectomy with lymph node dissection were performed to the confirm mucinous cyst. Pathological findings revealed a cystic lesion in the muscularis propria of the OGJ filled with mucinous components and lined with multilayered columnar epithelial cells. The cyst was diagnosed as a duplicate without malignancy.
Discussion: Since the border between the cyst and the oesophageal walls was unclear, and the cyst potentially contained a malignant component, instead of cystectomy, lower oesophagectomy and proximal gastrectomy with lymph node dissection were performed with oesophagogastric anastomosis using the double-flap technique, tailored specifically for OGJ cancer.
Conclusions: Oesophageal duplication cysts are rare. Lower oesophagectomy and proximal gastrectomy are selective surgical approaches for cyst duplication at the OGJ. en-copyright= kn-copyright= en-aut-name=HamazakiTomohiro en-aut-sei=Hamazaki en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawasakiKento en-aut-sei=Kawasaki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Oesophageal duplication cyst kn-keyword=Oesophageal duplication cyst en-keyword=Laparoscopic surgery kn-keyword=Laparoscopic surgery en-keyword=Lower oesophagectomy kn-keyword=Lower oesophagectomy END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=28 end-page=36 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Local Control of Conjunctival Malignant Melanoma by Proton Beam Therapy in a Patient With No Metastasis in Six Years From in Situ to Nodular Lesions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Conjunctival malignant melanoma is extremely rare, with no standard of care established at moment. Here we report a 65-year-old woman, as a hepatitis B virus (HBV) carrier, who presented concurrently a liver mass and lower bulbar conjunctival pigmented lesions in the right eye. Needle liver biopsy and excisional conjunctival biopsy showed hepatocellular carcinoma and conjunctival malignant melanoma in situ, respectively. The priority was given to segmental liver resection for hepatocellular carcinoma after transcatheter arterial chemoembolization. In 1 year, she underwent second and third resection of bulbar conjunctival pigmented lesions, and the pathological examinations constantly showed melanoma in situ. In the course, she showed gradual widening of pigmented lesions to upper bulbar conjunctiva and lower palpebral conjunctiva and lower eyelid. About 2.5 years from the initial visit, the lower eyelid lesion was resected for a genomic DNA-based test of BRAF mutations which turned out to be absent, and then, she began to have intravenous anti-programmed cell death-1 (PD-1), nivolumab every 3 or 4 weeks. She developed iritis in the right eye with conjunctival melanoma as an immune-related adverse event, 3 months after the beginning of nivolumab, and so she used daily topical 0.1% betamethasone eye drops to control the intraocular inflammation. She showed no metastasis in 6 years of follow-up, but later in the course, 5 years from the initial visit, she developed abruptly a non-pigmented nodular lesion on the temporal side of the bulbar conjunctiva along the corneal limbus, accompanied by two pigmented nodular lesions in the upper and lower eyelids in a few months. She thus, underwent proton beam therapy toward the conjunctival melanoma and achieved the successful local control. Proton beam therapy is a treatment option in place of orbital exenteration, and multidisciplinary team collaboration is desirable to achieve better cosmetic and functional outcomes in conjunctival malignant melanoma. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgataTakeshi en-aut-sei=Ogata en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WakiTakahiro en-aut-sei=Waki en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TachibanaKota en-aut-sei=Tachibana en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AdachiTakuya en-aut-sei=Adachi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamasakiOsamu en-aut-sei=Yamasaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Regenerative and Reconstructive Medicine (Ophthalmology), Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiology, Proton Beam Center, Tsuyama Chuo Hospital kn-affil= affil-num=3 en-affil=Department of Radiology, Proton Beam Center, Tsuyama Chuo Hospital kn-affil= affil-num=4 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Ocular surface kn-keyword=Ocular surface en-keyword=Conjunctiva kn-keyword=Conjunctiva en-keyword=Malignant melanoma kn-keyword=Malignant melanoma en-keyword=Proton beam therapy kn-keyword=Proton beam therapy en-keyword=Nivolumab kn-keyword=Nivolumab en-keyword=PD-1 inhibitor kn-keyword=PD-1 inhibitor en-keyword=Immune checkpoint inhibitor kn-keyword=Immune checkpoint inhibitor END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=6 article-no= start-page=469 end-page=474 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Treatment of Tenosynovial Giant Cell Tumor of the Cervical Spine with Postoperative Anti-RANKL Antibody (Denosumab) Administration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tenosynovial giant cell tumor (TGCT) is a fibrous histiocytic tumor originating in the synovial membrane. While cervical TGCT may not be considered a common diagnosis preoperatively because it is relatively rare, it has a high recurrence rate and should be considered. Total resection is preferable, but it can be challenging due to the risk of damaging the vertebral artery. Denosumab has shown effectiveness as a postoperative treatment for osteolytic bone lesion. Denosumab administration coupled with close follow-up might offer an effective postoperative treatment option for unresectable TGCT with bone invasion. en-copyright= kn-copyright= en-aut-name=HirataYuichi en-aut-sei=Hirata en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagaseTakayuki en-aut-sei=Nagase en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SasadaSusumu en-aut-sei=Sasada en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AyadaYoshiyuki en-aut-sei=Ayada en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyakeHayato en-aut-sei=Miyake en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugaharaChiaki en-aut-sei=Sugahara en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OdaYoshinao en-aut-sei=Oda en-aut-mei=Yoshinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=tenosynovial giant cell tumor kn-keyword=tenosynovial giant cell tumor en-keyword=bone tumor kn-keyword=bone tumor en-keyword=spine kn-keyword=spine END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=6 article-no= start-page=459 end-page=464 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Traumatic Neuroma Arising from Surgical Trauma during Conversion from Laparoscopic to Open Cholecystectomy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Traumatic neuroma is an abnormal proliferation of injured nerves resulting from trauma or surgery. We present a case of traumatic neuroma arising in the cystic duct after cholecystectomy. A 66-year-old man was referred to our department due to a biliary tumor. He had undergone cholecystectomy 20 years prior. Cholangioscopy showed an elevated lesion covered with smooth mucosa. Histological examination revealed normal bile duct mucosa. Although benign disease was suspected, the possibilities of malignant disease could not be excluded. Extrahepatic bile duct resection was planned to include intraoperative rapid-freezing of a biopsy specimen followed by histopathological examination. These intraoperative histology results showed proliferation of nerve and fibrous tissue only, resulting in the diagnosis of traumatic neuroma, so no lymph nodes were removed. To avoid excessive surgical intervention, histopathological examination of an intraoperative rapid-frozen biopsy specimen may be important for diagnosing traumatic neuroma. en-copyright= kn-copyright= en-aut-name=SakamotoShinya en-aut-sei=Sakamoto en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TabuchiMotoyasu en-aut-sei=Tabuchi en-aut-mei=Motoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshimatsuRika en-aut-sei=Yoshimatsu en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoManabu en-aut-sei=Matsumoto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwataJun en-aut-sei=Iwata en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkabayashiTakehiro en-aut-sei=Okabayashi en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=3 en-affil=Department of Radiology, Kochi Health Sciences Center kn-affil= affil-num=4 en-affil=Department of Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=5 en-affil=Department of Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= en-keyword=traumatic neuroma kn-keyword=traumatic neuroma en-keyword=biliary stricture kn-keyword=biliary stricture en-keyword=cholecystectomy kn-keyword=cholecystectomy en-keyword=cholangiography kn-keyword=cholangiography en-keyword=intraoperative rapid-frozen biopsy kn-keyword=intraoperative rapid-frozen biopsy END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=6 article-no= start-page=453 end-page=458 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Case of Radiation-Induced Angiosarcoma after Breast-Conserving Surgery with Hypofractionated Radiotherapy in a Japanese Patient en-subtitle= kn-subtitle= en-abstract= kn-abstract=Radiation-induced angiosarcoma (RIAS) is a rare, late adverse event of radiotherapy comprising approximately half of all radiation-induced sarcomas. It has a relatively short latency period and generally unfavorable prognosis. This study presents a case of RIAS that developed 5 years and 11 months after the completion of hypofractionated radiotherapy (42.56 Gy/16 fractions) following partial mastectomy. The patient was diagnosed with RIAS 10 months after the onset of skin redness. She underwent skin tumor resection, followed by paclitaxel, then pazopanib administration, but no radiotherapy. At 6 years and 2 months after surgery, no RIAS recurrence has been detected. en-copyright= kn-copyright= en-aut-name=KawataYujiro en-aut-sei=Kawata en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeKenta en-aut-sei=Watanabe en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TokiyaRyoji en-aut-sei=Tokiya en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsunoTakeshi en-aut-sei=Matsuno en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaRyo en-aut-sei=Tanaka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TairaNaruto en-aut-sei=Taira en-aut-mei=Naruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatsuiKuniaki en-aut-sei=Katsui en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=2 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Pathology, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Dermatology, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=hypofractionated radiotherapy kn-keyword=hypofractionated radiotherapy en-keyword=radiation-induced angiosarcoma kn-keyword=radiation-induced angiosarcoma END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=6 article-no= start-page=439 end-page=447 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Risk Factors for Gangrenous Cholecystitis and the Outcomes of Early Cholecystectomy: A Retrospective Study of a Single-Center City General Hospital en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gangrenous cholecystitis (GC) is classified as moderate acute cholecystitis according to the Tokyo Guidelines from 2018 (TG18). We evaluated the risk factors for GC and the outcomes of early cholecystectomy. A total of 136 patients who underwent emergency cholecystectomy for acute cholecystitis were retrospectively analyzed; 58 of these patients (42.6%) were diagnosed with GC (GC group) based on our retrospective pathologic diagnosis. We comparatively evaluated the patient backgrounds and surgical outcomes between the GC group and non-GC group. The GC group was significantly older and included more hypertensive patients than the non-GC group. The GC group was prescribed more antibiotics as initial treatment than the non-GC group, and they had more days between onset and surgery. The preoperative white blood cell count and C-reactive protein values were significantly higher in the GC group than in the non-GC group, and these values were predictive factors for GC. Cholecystectomy required a longer operation time and caused greater blood loss in the GC group. The GC group also had longer hospitalization times than the non-GC group; however, no significant differences were observed in terms of postoperative complications. In conclusion, gangrenous changes should be assessed when diagnosing cholecystitis, and appropriate treatment, such as surgery or drainage, should be undertaken. en-copyright= kn-copyright= en-aut-name=YamashitaMampei en-aut-sei=Yamashita en-aut-mei=Mampei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakayuki en-aut-sei=Tanaka en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SumidaYorihisa en-aut-sei=Sumida en-aut-mei=Yorihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamazakiShoto en-aut-sei=Yamazaki en-aut-mei=Shoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraYuki en-aut-sei=Hara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukudaAkiko en-aut-sei=Fukuda en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HisanagaMakoto en-aut-sei=Hisanaga en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WakataKoki en-aut-sei=Wakata en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ArakiMasato en-aut-sei=Araki en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EguchiSusumu en-aut-sei=Eguchi en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Surgery, Sasebo City General Hospital kn-affil= affil-num=2 en-affil=Department of Surgery, Sasebo City General Hospital kn-affil= affil-num=3 en-affil=Department of Surgery, Sasebo City General Hospital kn-affil= affil-num=4 en-affil=Department of Surgery, Sasebo City General Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, Sasebo City General Hospital kn-affil= affil-num=6 en-affil=Department of Surgery, Sasebo City General Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, Sasebo City General Hospital kn-affil= affil-num=8 en-affil=Department of Surgery, Sasebo City General Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, Sasebo City General Hospital kn-affil= affil-num=10 en-affil=Department of Surgery, Nagasaki University Graduate School of Biomedical Science kn-affil= en-keyword=gangrenous kn-keyword=gangrenous en-keyword=cholecystitis kn-keyword=cholecystitis en-keyword=acute cholecystitis kn-keyword=acute cholecystitis en-keyword=laparoscopic cholecystectomy kn-keyword=laparoscopic cholecystectomy END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=2 article-no= start-page=292 end-page=305 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The role of C1orf50 in breast cancer progression and prognosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although the prognosis of breast cancer has significantly improved compared to other types of cancer, there are still some patients who expire due to recurrence or metastasis. Therefore, it is necessary to develop a method to identify patients with poor prognosis at the early stages of cancer. In the process of discovering new prognostic markers from genes of unknown function, we found that the expression of C1orf50 determines the prognosis of breast cancer patients, especially for those with Luminal A breast cancer. This study aims to elucidate the molecular role of C1orf50 in breast cancer progression. Bioinformatic analyses of the breast cancer dataset of TCGA, and in vitro analyses, reveal the molecular pathways influenced by C1orf50 expression. C1orf50 knockdown suppressed the cell cycle of breast cancer cells and weakened their ability to maintain the undifferentiated state and self-renewal capacity. Interestingly, upregulation of C1orf50 increased sensitivity to CDK4/6 inhibition. In addition, C1orf50 was found to be more abundant in breast cancer cells than in normal breast epithelium, suggesting C1orf50fs involvement in breast cancer pathogenesis. Furthermore, the mRNA expression level of C1orf50 was positively correlated with the expression of PD-L1 and its related factors. These results suggest that C1orf50 promotes breast cancer progression through cell cycle upregulation, maintenance of cancer stemness, and immune evasion mechanisms. Our study uncovers the biological functions of C1orf50 in Luminal breast cancer progression, a finding not previously reported in any type of cancer. en-copyright= kn-copyright= en-aut-name=OtaniYusuke en-aut-sei=Otani en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaAtsushi en-aut-sei=Tanaka en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaekawaMasaki en-aut-sei=Maekawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Pe?aTirso en-aut-sei=Pe?a en-aut-mei=Tirso kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RogachevskayaAnna en-aut-sei=Rogachevskaya en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AndoTeruhiko en-aut-sei=Ando en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ItanoTakuto en-aut-sei=Itano en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatayamaHaruyoshi en-aut-sei=Katayama en-aut-mei=Haruyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=RoehrlMichael H. en-aut-sei=Roehrl en-aut-mei=Michael H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=2 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=3 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=4 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=5 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of General Surgery, Kawasaki Medical School General Medical Center kn-affil= affil-num=13 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=14 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=C1orf50 kn-keyword=C1orf50 en-keyword=Luminal A breast cancer kn-keyword=Luminal A breast cancer en-keyword=Cell cycle kn-keyword=Cell cycle en-keyword=Immune evasion kn-keyword=Immune evasion en-keyword=YAP/TAZ kn-keyword=YAP/TAZ END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=60 end-page=63 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241129 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Successful immunotherapy with ipilimumab and nivolumab in a patient with pulmonary sclerosing pneumocytoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pulmonary sclerosing pneumocytoma (PSP) is a rare form of lung cancer that occasionally presents with lymph node and extrapulmonary metastases, and multiple lesions. The treatment of metastatic PSP remains undefined. This study reports the case of a 48-year-old female patient diagnosed with PSP following surgical intervention for a solitary nodule in the left lower lobe. Four years later, recurrence occurred in the left hilar and mediastinal lymph nodes, necessitating an additional resection. Concurrently, sacral metastases developed and required palliative radiotherapy. Genetic analysis identified an AKT1 E17K mutation, characteristic of PSP, and absence of programmed cell death ligand 1 (PD-L1) expression in the tumor. Two years post-recurrence, the tumor recurred in the left mammary gland and mediastinal lymph nodes. Combination immunotherapy with ipilimumab and nivolumab yielded a significantly positive response in this metastatic PSP case. This is the first reported case of successful treatment of multiple distant metastatic PSP with ipilimumab and nivolumab, following the failure of various local treatments. Further case series are warranted to validate the efficacy of immunotherapy in metastatic PSP. en-copyright= kn-copyright= en-aut-name=Inukai-MotokuraYumi en-aut-sei=Inukai-Motokura en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BabaTakahiro en-aut-sei=Baba en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OmoriHiroki en-aut-sei=Omori en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakeguchiTetsuya en-aut-sei=Takeguchi en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UnoMari en-aut-sei=Uno en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AyadaYoshiyuki en-aut-sei=Ayada en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=Pulmonary sclerosing pneumocytoma kn-keyword=Pulmonary sclerosing pneumocytoma en-keyword=Ipilimumab kn-keyword=Ipilimumab en-keyword=Nivolumab kn-keyword=Nivolumab en-keyword=Programmed cell death ligand 1 kn-keyword=Programmed cell death ligand 1 en-keyword=Case report kn-keyword=Case report END start-ver=1.4 cd-journal=joma no-vol=2024 cd-vols= no-issue= article-no= start-page=8836103 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241028 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Rare Case of Multiple Myeloma Identified Following the Diagnosis of Amyloidosis of the Tongue en-subtitle= kn-subtitle= en-abstract= kn-abstract=Amyloidosis is a disease in which amyloid protein is deposited in organs and tissues, resulting in functional impairment. Amyloidosis occurs in 12%-30% of patients with multiple myeloma, but in rare cases, amyloidosis may precede the diagnosis of multiple myeloma. Our patient was a 76-year-old Japanese male on dialysis. Multiple nodules accompanied by ulcers were observed on his tongue. He had no subjective symptoms or clinical findings associated with multiple myeloma. The histopathological findings suggested amyloidosis. We suspected both systemic and localized amyloidosis and performed a comprehensive systemic examination. Since the patient had been on dialysis for only a short period of time (similar to 3 months), dialysis-related amyloidosis was ruled out. After blood and urine tests, a diagnosis of multiple myeloma was made. Chemotherapy treatment was started, but the patient's multiple myeloma could not be suppressed and the tongue amyloidosis worsened, leading to his death 2 years and 2 months after the initial diagnosis. en-copyright= kn-copyright= en-aut-name=KanemotoHideka en-aut-sei=Kanemoto en-aut-mei=Hideka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ObataKyoichi en-aut-sei=Obata en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KadoyaKoichi en-aut-sei=Kadoya en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OnoKisho en-aut-sei=Ono en-aut-mei=Kisho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KunisadaYuki en-aut-sei=Kunisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YaoMayumi en-aut-sei=Yao en-aut-mei=Mayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Tsuyama Chuo Hospital kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=11 article-no= start-page=e73775 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241115 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Axillary Reactive Lymphoid Hyperplasia, Likely Due to Unicentric Castleman Disease, and the Concurrent Presence of Orbital Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma: A Six-Year Follow-Up Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Castleman disease is a lymphadenopathy of unknown cause at a single site, which is designated as unicentric Castleman disease, or at multiple sites designated as multicentric Castleman disease. We present a patient who showed axillary reactive lymphoid hyperplasia, likely due to unicentric Castleman disease, and orbital extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma in a six-year follow-up. A 76-year-old man had a painless left axillary mass for an unknown period and also left complete blepharoptosis with no other systemic symptoms. Suspected of lymphoma, iliac bone marrow biopsy showed no anomalous cells, and positron emission tomography demonstrated abnormal uptake at the left axilla and in the left superior anterior orbit. Incisional biopsy of the left axillary mass demonstrated hyperplastic lymphoid follicles with an atrophic germinal center and prominent small vessels in the follicular center, indicative of unicentric Castleman disease. One year later, annual follow-up positron emission tomography disclosed a high uptake site, next to the previously-identified cyst, in the pancreatic body. Trans-gastric fine needle pancreatic biopsy proved adenocarcinoma and he underwent subtotal stomach-preserving pancreaticoduodenectomy with jejunal anastomosis. He was well for six months after the surgery and thus, underwent resection of the left orbital lesion at 78 years old. The pathology of the orbital lesion showed ambiguous nodular structure with massive infiltration with CD20-positive medium-sized lymphoid cells which were monotype in immunoglobulin light chain restriction, indicative of MALT lymphoma. In the four-year period of the COVID-19 pandemic, he was healthy and followed with no treatment until the age of 82 years when he underwent radiation (46 Gy) to the left axillary lesion which did not regress. He then underwent eyelid levator muscle plication for left blepharoptosis since the left orbital lesion remained unpalpable. The six-year follow-up showed that concurrent and independent orbital MALT lymphoma and axillary reactive lymphoid hyperplasia, likely due to unicentric Castleman disease, were both stable. The present case illustrates how important it is to make pathological diagnoses in different anatomical lesions after the initial diagnosis of Castleman disease. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= en-keyword=blepharoptosis kn-keyword=blepharoptosis en-keyword=castleman disease kn-keyword=castleman disease en-keyword=extranodal marginal zone b-cell lymphoma of mucosa-associated lymphoid tissue (malt) lymphoma kn-keyword=extranodal marginal zone b-cell lymphoma of mucosa-associated lymphoid tissue (malt) lymphoma en-keyword=pancreatic cancer kn-keyword=pancreatic cancer en-keyword=radiation kn-keyword=radiation en-keyword=reactive lymphoid hyperplasia kn-keyword=reactive lymphoid hyperplasia END start-ver=1.4 cd-journal=joma no-vol=42 cd-vols= no-issue=1 article-no= start-page=1 end-page=11 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tectal glioma: clinical, radiological, and pathological features, and the importance of molecular analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tectal glioma (TG) is a rare lower grade glioma (LrGG) that occurs in the tectum, mainly affecting children. TG shares pathological similarities with pilocytic astrocytoma (PA), but recent genetic analyses have revealed distinct features, such as alterations in KRAS and BRAF. We conducted a retrospective review of cases clinically diagnosed as TG and treated at our institute between January 2005 and March 2023. Six cases were identified and the median age was 30.5 years. Four patients underwent biopsy and two patients underwent tumor resection. Histological diagnoses included three cases of PA, one case of astrocytoma, and two cases of high-grade glioma. The integrated diagnosis, according to the fifth edition of the World Health Organization Classification of Tumours of the central nervous system, included two cases of PA and one case each of diffuse high-grade glioma; diffuse midline glioma H3 K27-altered; glioblastoma; and circumscribed astrocytic glioma. Among the three patients who underwent molecular evaluation, two had KRAS mutation and one had H3-3A K27M mutation. Our results demonstrate the diverse histological and molecular characteristics of TG distinct from other LrGGs. Given the heterogeneous pathological background and the risk of pathological progression in TG, we emphasize the importance of comprehensive diagnosis, including molecular evaluation. en-copyright= kn-copyright= en-aut-name=ImotoRyoji en-aut-sei=Imoto en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiiKentaro en-aut-sei=Fujii en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HiranoShuichiro en-aut-sei=Hirano en-aut-mei=Shuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KemmotsuNaoya en-aut-sei=Kemmotsu en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SurugaYasuki en-aut-sei=Suruga en-aut-mei=Yasuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MizutaRyo en-aut-sei=Mizuta en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KegoyaYasuhito en-aut-sei=Kegoya en-aut-mei=Yasuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=InoueYohei en-aut-sei=Inoue en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UmedaTsuyoshi en-aut-sei=Umeda en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HokamaMadoka en-aut-sei=Hokama en-aut-mei=Madoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WashioKana en-aut-sei=Washio en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SatomiKaishi en-aut-sei=Satomi en-aut-mei=Kaishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=IchimuraKoichi en-aut-sei=Ichimura en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Pathology, Kyorin University Faculty of Medicine kn-affil= affil-num=17 en-affil=Department of Brain Disease Translational Research, Juntendo University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Tectal glioma kn-keyword=Tectal glioma en-keyword=Lower grade glioma kn-keyword=Lower grade glioma en-keyword=KRAS kn-keyword=KRAS en-keyword=H3 K27M kn-keyword=H3 K27M en-keyword=Molecular analysis kn-keyword=Molecular analysis END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=4 article-no= start-page=297 end-page=306 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=2024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Transcriptome analysis of the cytokine storm-related genes among the subtypes of idiopathic multicentric Castleman disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Idiopathic multicentric Castleman disease (iMCD) is a type of Castleman disease unrelated to the Kaposi sarcoma-associated herpesvirus/human herpesvirus type 8 (KSHV/HHV8) infection. Presently, iMCD is classified into iMCD-IPL (idiopathic plasmacytic lymphadenopathy), iMCD-TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly), and iMCD-NOS (not otherwise specified). The most common treatment for iMCD is using IL-6 inhibitors; however, some patients resist IL-6 inhibitors, especially for iMCD-TAFRO/NOS. Nevertheless, since serum IL-6 levels are not significantly different between the iMCD-IPL and iMCD-TAFRO/NOS cases, cytokines other than IL-6 may be responsible for the differences in pathogenesis. Herein, we performed a transcriptome analysis of cytokine storm-related genes and examined the differences between iMCD-IPL and iMCD-TAFRO/NOS. The results demonstrated that counts per million of STAT2, IL1R1, IL1RAP, IL33, TAFAIP1, and VEGFA (P < 0.001); STAT3, JAK2, MAPK8, IL17RA, IL18, TAFAIP2, TAFAIP3, PDGFA, VEGFC, CXCL10, CCL4, and CXCL13 (P < 0.01); and STAT1, STAT6, JAK1, MAPK1, MAPK3, MAPK6, MAPK7, MAPK9, MAPK10, MAPK11, MAPK12, MAPK14, NFKB1, NFKBIA, NFKBIB, NFKBIZ, MTOR, IL10RB, IL12RB2, IL18BP, TAFAIP6, TNFAIP8L1, TNFAIP8L3, CSF2RBP1, PDGFB, PDGFC, and CXCL9 (P < 0.05) were significantly increased in iMCD-TAFRO/NOS. Particularly, upregulated IL33 expression was demonstrated for the first time in iMCD-TAFRO/NOS. Thus, inflammatory signaling, such as JAK-STAT and MAPK, may be enhanced in iMCD-TAFRO/NOS and may be a cytokine storm. en-copyright= kn-copyright= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChijimatsuRyota en-aut-sei=Chijimatsu en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UetaHimawari en-aut-sei=Ueta en-aut-mei=Himawari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=LaiYou Cheng en-aut-sei=Lai en-aut-mei=You Cheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawaharaYuri en-aut-sei=Kawahara en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakedaYudai en-aut-sei=Takeda en-aut-mei=Yudai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OchiSayaka en-aut-sei=Ochi en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HaratakeTomoka en-aut-sei=Haratake en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakamuraNaoya en-aut-sei=Nakamura en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MomoseShuji en-aut-sei=Momose en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Department of Medical Biotechnology and Laboratory Science, Chang Gung University kn-affil= affil-num=7 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=9 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=10 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=11 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Pathology, Tokai University School of Medicine kn-affil= affil-num=13 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=14 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=idiopathic multicentric Castleman disease kn-keyword=idiopathic multicentric Castleman disease en-keyword=cytokine storm kn-keyword=cytokine storm en-keyword=transcriptome analysis kn-keyword=transcriptome analysis END start-ver=1.4 cd-journal=joma no-vol=68 cd-vols= no-issue=6 article-no= start-page=603 end-page=613 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241028 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Epiretinal membrane: an overview and update en-subtitle= kn-subtitle= en-abstract= kn-abstract=Epiretinal membrane (ERM) is a frequently diagnosed macular disease associated with aging, characterized by a fibrous membrane forming on the internal limiting membrane (ILM) and leading to visual dysfunctions such as metamorphopsia. Various hypotheses regarding the pathology of metamorphopsia have been proposed; however, the complete pathophysiologic mechanism underlying ERM remains unclear. Optical coherence tomography (OCT) provides detailed images enabling precise diagnosis and characterization of ERM, with several recent studies using the latest OCT imaging techniques. Surgical removal of ERM is the only treatment option; however, criteria for surgical intervention are not established, complicating the decision-making processes. Furthermore, the debate on whether simultaneous peeling of the ILM during ERM surgery enhances outcomes or poses unnecessary risks is ongoing, with no definite conclusion having yet been reached. This review also focuses on epiretinal proliferation, which is different from ERM and is characteristic of lamellar macular hole (LMH). Recently, diagnostic criteria for LMH and related diseases were proposed. Reports on effective surgical procedures for LMH exist, although more research is needed to confirm the long-term outcomes. Thus, this review article aims to provide an overview and updated knowledge of ERM, LMH, and related diseases. en-copyright= kn-copyright= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=En face imaging kn-keyword=En face imaging en-keyword=Epiretinal membrane kn-keyword=Epiretinal membrane en-keyword=Epiretinal proliferation kn-keyword=Epiretinal proliferation en-keyword=Internal limiting membrane kn-keyword=Internal limiting membrane en-keyword=Lamellar macular hole kn-keyword=Lamellar macular hole END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=5 article-no= start-page=423 end-page=428 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Occult Nesidioblastosis Detected by 111In-Pentetreotide Single-Photon Emission Computed Tomography en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nesidioblastosis, also known as persistent hyperinsulinemic hypoglycemia, is usually observed in children and infants, although more recently adult-onset nesidioblastosis has also been described. We present a case of nesidioblastosis in a 78-year-old man that was detected by 111In-pentetreotide single photon emission computed tomography (SPECT/CT). The patient was transferred to our hospitalfs emergency department in a hypoglycemic coma. Dynamic enhanced CT could detect no lesion in the pancreas, but an 111In-pentetreotide SPECT/CT scan performed after a similar episode four weeks later showed increased focal uptake at the head of the pancreas. The results of a selective arterial calcium injection test were negative. After careful consideration and discussion among colleagues, surgical intervention was selected, and a pancreaticoduodenectomy was performed. On histology, there were elevated numbers of Langerhans islets in the pancreatic head, and the islets themselves appeared enlarged. Hypertrophic -cells comprised the majority, but -cells, -cells and pancreatic polypeptide were also detected in the islets. Based on the histopathological results and repeated hyperinsulinemic hypoglycemic crises, the patient was finally diagnosed with adult-onset nesidioblastosis. He had no hypoglycemic symptoms during outpatient follow-up examination. Since 111In-pentetreotide SPECT/CT may be able to detect nesidioblastosis, clinicians should consider this relatively new-modality examination when encountering such cases. en-copyright= kn-copyright= en-aut-name=SakamotoShinya en-aut-sei=Sakamoto en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TabuchiMotoyasu en-aut-sei=Tabuchi en-aut-mei=Motoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshimatsuRika en-aut-sei=Yoshimatsu en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HishidaAi en-aut-sei=Hishida en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoManabu en-aut-sei=Matsumoto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwataJun en-aut-sei=Iwata en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkabayashiTakehiro en-aut-sei=Okabayashi en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Gastroenteorlogical Surgery, Kochi Health Sciences Center kn-affil= affil-num=2 en-affil=Department of Gastroenteorlogical Surgery, Kochi Health Sciences Center kn-affil= affil-num=3 en-affil=Department of Radiology, Kochi Health Sciences Center kn-affil= affil-num=4 en-affil=Department of Endocrinology and Metabolism, Kochi Health Sciences Center kn-affil= affil-num=5 en-affil=Department of Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=7 en-affil=Department of Gastroenteorlogical Surgery, Kochi Health Sciences Center kn-affil= en-keyword=111In-pentetreotide kn-keyword=111In-pentetreotide en-keyword=nesidioblastosis kn-keyword=nesidioblastosis en-keyword=single-photon emission computed tomography kn-keyword=single-photon emission computed tomography en-keyword=hyperinsulinemic hypoglycemia kn-keyword=hyperinsulinemic hypoglycemia END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue= article-no= start-page=e2400228 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240919 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Response to Imatinib in a Patient With Gastric Adenocarcinoma With KIT Q556_K558 In-Frame Deletion: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkamotoKunio en-aut-sei=Okamoto en-aut-mei=Kunio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AndoMidori en-aut-sei=Ando en-aut-mei=Midori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraSatoko en-aut-sei=Nakamura en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AyadaYoshiyuki en-aut-sei=Ayada en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkitaNatsuko en-aut-sei=Okita en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Medical Oncology, Kagawa Prefectural Central Hospital kn-affil= affil-num=4 en-affil=Department of Pathology, Kagawa Prefectural Central Hospital, kn-affil= affil-num=5 en-affil=Department of Pathology, Kagawa Prefectural Central Hospital kn-affil= affil-num=6 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Research Management Division, Clinical Research Support Office, National Cancer Center Hospital kn-affil= affil-num=11 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=22441 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240928 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effectiveness of data-augmentation on deep learning in evaluating rapid on-site cytopathology at endoscopic ultrasound-guided fine needle aspiration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rapid on-site cytopathology evaluation (ROSE) has been considered an effective method to increase the diagnostic ability of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA); however, ROSE is unavailable in most institutes worldwide due to the shortage of cytopathologists. To overcome this situation, we created an artificial intelligence (AI)-based system (the ROSE-AI system), which was trained with the augmented data to evaluate the slide images acquired by EUS-FNA. This study aimed to clarify the effects of such data-augmentation on establishing an effective ROSE-AI system by comparing the efficacy of various data-augmentation techniques. The ROSE-AI system was trained with increased data obtained by the various data-augmentation techniques, including geometric transformation, color space transformation, and kernel filtering. By performing five-fold cross-validation, we compared the efficacy of each data-augmentation technique on the increasing diagnostic abilities of the ROSE-AI system. We collected 4059 divided EUS-FNA slide images from 36 patients with pancreatic cancer and nine patients with non-pancreatic cancer. The diagnostic ability of the ROSE-AI system without data augmentation had a sensitivity, specificity, and accuracy of 87.5%, 79.7%, and 83.7%, respectively. While, some data-augmentation techniques decreased diagnostic ability, the ROSE-AI system trained only with the augmented data using the geometric transformation technique had the highest diagnostic accuracy (88.2%). We successfully developed a prototype ROSE-AI system with high diagnostic ability. Each data-augmentation technique may have various compatibilities with AI-mediated diagnostics, and the geometric transformation was the most effective for the ROSE-AI system. en-copyright= kn-copyright= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ObataTaisuke en-aut-sei=Obata en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkihiroMatsumi en-aut-sei=Akihiro en-aut-mei=Matsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyamotoKazuya en-aut-sei=Miyamoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MorimotoKosaku en-aut-sei=Morimoto en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TerasawaHiroyuki en-aut-sei=Terasawa en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamazakiTatsuhiro en-aut-sei=Yamazaki en-aut-mei=Tatsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KatoHironari en-aut-sei=Kato en-aut-mei=Hironari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=InoueHirofumi en-aut-sei=Inoue en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ChoTen en-aut-sei=Cho en-aut-mei=Ten kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TanimotoTakayoshi en-aut-sei=Tanimoto en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OhtoAkimitsu en-aut-sei=Ohto en-aut-mei=Akimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=14 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=15 en-affil=Business Strategy Division, Ryobi Systems Co., Ltd. kn-affil= affil-num=16 en-affil=Business Strategy Division, Ryobi Systems Co., Ltd. kn-affil= affil-num=17 en-affil=Business Strategy Division, Ryobi Systems Co., Ltd. kn-affil= affil-num=18 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=19 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=10 article-no= start-page=e70865 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241004 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Presumed Choroidopathy of IgG4-Related Disease Discovered During 16-Year Follow-Up of a Patient With Polycystic Kidney Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immunoglobulin G4 (IgG4)-related disease is characterized by infiltration with IgG4-producing plasma cells in different organs and the elevation of serum IgG4. We present a patient with polycystic kidney disease in long-term follow-up who developed bilateral lacrimal gland enlargement and presumed IgG4-related choroidopathy at different time points. A 45-year-old woman developed bilateral upper eyelid swelling. Head MRI showed bilateral lacrimal gland enlargement, and the resection on both sides revealed foci of infiltration with lymphocytes and plasma cells in bilateral lacrimal glands. The IgG4-immunostaining did not satisfy the diagnostic criteria. She had been taking oral valsartan 40 mg daily for hypertension with polycystic kidney disease.

The patient was well until the age of 49 years, when she noticed yellowish vision in the right eye compared to the left eye. The right eye showed multiple yellowish spotty lesions in the deep retina to choroid with a mildly hyperemic optic disc, while the left eye showed the normal fundus. No inflammation was noted in the anterior segments of both eyes. Fundus angiography demonstrated early-phase no-filling with late-phase leakage by fluorescein dye and both early-phase and late-phase no-filling by indocyanine green dye, leading to the diagnosis of acute posterior multifocal placoid pigment epitheliopathy (APMPPE). She began to have oral prednisolone tapered from 30 mg daily and discontinued in a year. At the age of 52 years, she switched to candesartan 8 mg daily and began to have tolvaptan (a selective competitive vasopressin receptor 2 (V2) antagonist) 90 mg daily for polycystic kidney disease with liver cysts. At that time, the lesions in the right eye had mild degeneration.

The patient was followed once a year ophthalmologically to maintain good vision. At 57 years, serum IgG4, which was measured for the first time on suspicion of IgG4-related disease, was elevated to 269.6 mg/dL. In the following four years to the latest visit at 61 years, she kept stable but high levels of serum IgG4 around 300 mg/dL. Serum IgG4 measurement is helpful to make a clinical diagnosis and, hence, a clinical decision since the spectrum of IgG4-related disease remains obscure. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Pathology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Nephrology, Okayama University Hospital kn-affil= en-keyword=acute posterior multifocal placoid pigment epitheliopathy kn-keyword=acute posterior multifocal placoid pigment epitheliopathy en-keyword=choroidopathy kn-keyword=choroidopathy en-keyword=uveitis kn-keyword=uveitis en-keyword=lacrimal gland tumor kn-keyword=lacrimal gland tumor en-keyword=igg4-related disease kn-keyword=igg4-related disease END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=1099 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240916 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Histological differences related to autophagy in the minor salivary gland between primary and secondary types of Sj?gren's syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Some forms of Sj?grenfs syndrome (SS) follow a clinical course accompanied by systemic symptoms caused by lymphocyte infiltration and proliferation in the liver, kidneys, and other organs. To better understand the clinical outcomes of SS, here we used minor salivary gland tissues from patients and examine their molecular, biological, and pathological characteristics. A retrospective study was performed, combining clinical data and formalin-fixed paraffin-embedded (FFPE) samples from female patients over 60 years of age who underwent biopsies at Okayama University Hospital. We employed direct digital RNA counting with nCounter? and multiplex immunofluorescence analysis with a PhenoCycler? on the labial gland biopsies. We compared FFPE samples from SS patients who presented with other connective tissue diseases (secondary SS) with those from stable SS patients with symptoms restricted to the exocrine glands (primary SS). Secondary SS tissues showed enhanced epithelial damage and lymphocytic infiltration accompanied by elevated expression of autophagy marker genes in the immune cells of the labial glands. The close intercellular distance between helper T cells and B cells positive for autophagy-associated molecules suggests accelerated autophagy in these lymphocytes and potential B cell activation by helper T cells. These findings indicate that examination of FFPE samples from labial gland biopsies can be an effective tool for evaluating molecular histological differences between secondary and primary SS through multiplexed analysis of gene expression and tissue imaging. en-copyright= kn-copyright= en-aut-name=Ono-MinagiHitomi en-aut-sei=Ono-Minagi en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NohnoTsutomu en-aut-sei=Nohno en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatsuyamaTakayuki en-aut-sei=Katsuyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyawakiKohta en-aut-sei=Miyawaki en-aut-mei=Kohta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IidaSeiji en-aut-sei=Iida en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SakaiTakayoshi en-aut-sei=Sakai en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OhuchiHideyo en-aut-sei=Ohuchi en-aut-mei=Hideyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Cytology and Histology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Cytology and Histology, Okayama University Medical School kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Precision Medicine, Kyushu University School of Medicine kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Rehabilitation for Orofacial Disorders, Osaka University Graduate School of Dentistry kn-affil= affil-num=13 en-affil=Department of Cytology and Histology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Autoimmune disease kn-keyword=Autoimmune disease en-keyword=Xerostomia kn-keyword=Xerostomia en-keyword=Multiplex immunostaining kn-keyword=Multiplex immunostaining en-keyword=Spatial analysis kn-keyword=Spatial analysis en-keyword=Autophagy kn-keyword=Autophagy END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=17 article-no= start-page=4368 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240904 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Antibacterial Dental Adhesive Containing Cetylpyridinium Chloride Montmorillonite en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oral bacteria cause tooth caries and periodontal disease. Much research is being conducted to prevent both major oral diseases by rendering dental materials' antimicrobial potential. However, such antimicrobial materials are regarded as 'combination' products and face high hurdles for regulatory approval. We loaded inorganic montmorillonite with the antimicrobial agent cetylpyridinium chloride, referred to below as 'CPC-Mont'. CPC-Mont particles in a 1, 3 and 5 wt% concentration were added to the considered gold-standard self-etch adhesive Clearfil SE Bond 2 ('CSE2'; Kuraray Noritake) to render its antibacterial potential (CSE2 without CPC-Mont served as control). Besides measuring (immediate) bonding effectiveness and (aged) bond durability to dentin, the antibacterial activity against S. mutans and the polymerization-conversion rate was assessed. Immediate and aged bond strength was not affected by 1 and 3 wt% CPC-Mont addition, while 5 wt% CPC-Mont significantly lowered bond strength and bond durability. The higher the concentration of the antimicrobial material added, the stronger the antimicrobial activity. Polymerization conversion was not affected by the CPC-Mont addition in any of the three concentrations. Hence, adding 3 wt% CPC-Mont to the two-step self-etch adhesive rendered additional antimicrobial potential on top of its primary bonding function. en-copyright= kn-copyright= en-aut-name=OkazakiYohei en-aut-sei=Okazaki en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamoriKiichi en-aut-sei=Nakamori en-aut-mei=Kiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YaoChenmin en-aut-sei=Yao en-aut-mei=Chenmin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AhmedMohammed H. en-aut-sei=Ahmed en-aut-mei=Mohammed H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MercelisBenjamin en-aut-sei=Mercelis en-aut-mei=Benjamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MaruoYukinori en-aut-sei=Maruo en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshidaYasuhiro en-aut-sei=Yoshida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AbeYasuhiko en-aut-sei=Abe en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Van MeerbeekMeerbeek, Bart en-aut-sei=Van Meerbeek en-aut-mei=Meerbeek, Bart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshiharaKumiko en-aut-sei=Yoshihara en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Oral Health Sciences, BIOMAT, KU Leuven kn-affil= affil-num=2 en-affil=Department of Advanced Prosthodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=3 en-affil=Department of Oral Health Sciences, BIOMAT, KU Leuven kn-affil= affil-num=4 en-affil=Department of Oral Health Sciences, BIOMAT, KU Leuven kn-affil= affil-num=5 en-affil=Department of Oral Health Sciences, BIOMAT, KU Leuven kn-affil= affil-num=6 en-affil=Advanced Research Center for Oral and Craniofacial Science, Okayama University Dental School kn-affil= affil-num=7 en-affil=Department of Prosthodontics, Okayama University kn-affil= affil-num=8 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=9 en-affil=Department of Advanced Prosthodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=10 en-affil=Department of Oral Health Sciences, BIOMAT, KU Leuven kn-affil= affil-num=11 en-affil=Department of Pathology & Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=dental adhesive kn-keyword=dental adhesive en-keyword=antibacterial agent kn-keyword=antibacterial agent en-keyword=dentin kn-keyword=dentin en-keyword=degree of conversion kn-keyword=degree of conversion en-keyword=micro tensile bond strength kn-keyword=micro tensile bond strength en-keyword=scanning microscopy kn-keyword=scanning microscopy END start-ver=1.4 cd-journal=joma no-vol=90 cd-vols= no-issue=6 article-no= start-page=371 end-page=373 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240827 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Morphogenesis and adaptive strategies for infection in plant pathogenic fungi en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=FukadaFumi en-aut-sei=Fukada en-aut-mei=Fumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=16 article-no= start-page=4108 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240819 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of Scaffold Geometrical Structure on Macrophage Polarization during Bone Regeneration Using Honeycomb Tricalcium Phosphate en-subtitle= kn-subtitle= en-abstract= kn-abstract=The polarization balance of M1/M2 macrophages with different functions is important in osteogenesis and bone repair processes. In a previous study, we succeeded in developing honeycomb tricalcium phosphate (TCP), which is a cylindrical scaffold with a honeycomb arrangement of straight pores, and we demonstrated that TCP with 300 and 500 mu m pore diameters (300TCP and 500TCP) induced bone formation within the pores. However, the details of the influence of macrophage polarization on bone formation using engineered biomaterials, especially with respect to the geometric structure of the artificial biomaterials, are unknown. In this study, we examined whether differences in bone tissue formation due to differences in TCP geometry were due to the polarity of the assembling macrophages. Immunohistochemistry for IBA-1, iNOS, and CD163 single staining was performed. The 300TCP showed a marked infiltration of iNOS-positive cells, which are thought to be M1 macrophages, during the osteogenesis process, while no involvement of CD163-positive cells, which are thought to be M2 macrophages, was observed in the TCP pores. In addition, 500TCP showed a clustering of iNOS-positive cells and CD163-positive cells at 2 weeks, suggesting the involvement of M2 macrophages in the formation of bone tissue in the TCP pores. In conclusion, we demonstrated for the first time that the geometrical structure of the artificial biomaterial, i.e., the pore size of honeycomb TCP, affects the polarization of M1/2 macrophages and bone tissue formation in TCP pores. en-copyright= kn-copyright= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujigiwaHidetsugu en-aut-sei=Tsujigiwa en-aut-mei=Hidetsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChangAnqi en-aut-sei=Chang en-aut-mei=Anqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=PiaoTianyan en-aut-sei=Piao en-aut-mei=Tianyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InadaYasunori en-aut-sei=Inada en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ArashimaTakuma en-aut-sei=Arashima en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MorimatsuAyumi en-aut-sei=Morimatsu en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaAyumi en-aut-sei=Tanaka en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Life Science, Faculty of Science, Okayama University of Science kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=honeycomb TCP kn-keyword=honeycomb TCP en-keyword=bone formation kn-keyword=bone formation en-keyword=macrophages kn-keyword=macrophages en-keyword=polarization kn-keyword=polarization END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=4 article-no= start-page=349 end-page=355 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202408 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Middle-Ear Salivary Gland Choristoma with Congenital, Single-Sided Hearing Loss en-subtitle= kn-subtitle= en-abstract= kn-abstract=Middle-ear salivary gland choristoma (SGCh) is a rare, benign tumor that causes conductive hearing loss owing to middle-ear morphological abnormalities. Early diagnosis is challenging, and surgical resection is indispensable for a definitive diagnosis. We report the case of a 3-year-old boy diagnosed with middle-ear SGCh during the follow-up period for left-sided hearing loss discovered at newborn hearing screening (NHS). Long-term follow-up after the NHS result, subsequent computed tomography/magnetic resonance imaging, and surgical resection led to its relatively early diagnosis and treatment. en-copyright= kn-copyright= en-aut-name=TominagaYuichiro en-aut-sei=Tominaga en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugayaAkiko en-aut-sei=Sugaya en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KariyaShin en-aut-sei=Kariya en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShimizuAiko en-aut-sei=Shimizu en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KataokaYuko en-aut-sei=Kataoka en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Otolaryngology, Head and Neck Surgery, Hiroshima City, Hiroshima Citizens Hospital kn-affil= affil-num=2 en-affil=Department of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Otolaryngology, Head and Neck Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=4 en-affil=Department of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=middle-ear salivary gland choristoma kn-keyword=middle-ear salivary gland choristoma en-keyword=middle-ear morphological abnormalities kn-keyword=middle-ear morphological abnormalities en-keyword=newborn hearing screening kn-keyword=newborn hearing screening en-keyword=unilateral hearing loss kn-keyword=unilateral hearing loss en-keyword=surgical resection kn-keyword=surgical resection END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=4 article-no= start-page=337 end-page=343 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202408 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pneumocephalus with Inverted Papilloma in the Frontoethmoidal Sinus: Case Report and Literature Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Here, we describe the unique case of a pneumocephalus originating from an inverted papilloma (IP) in the frontoethmoidal sinus. A 71-year-old man with diabetes presented with headaches and altered consciousness. Imaging revealed the pneumocephalus together with bone destruction in the left frontal sinus. He underwent simultaneous endoscopic endonasal and transcranial surgery using an ORBEYE exoscope. Pathological diagnosis of the tumor confirmed IP. Post-surgery, the pneumocephalus was significantly resolved and the squamous cell carcinoma antigen level, which had been elevated, decreased. This case underscores the importance of a multidisciplinary approach and innovative surgical methods in treating complex sinonasal pathologies. en-copyright= kn-copyright= en-aut-name=MakiharaSeiichiro en-aut-sei=Makihara en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UraguchiKensuke en-aut-sei=Uraguchi en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OnoSawako en-aut-sei=Ono en-aut-mei=Sawako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimizuAiko en-aut-sei=Shimizu en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkemachiRyosuke en-aut-sei=Ikemachi en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkazakiYosuke en-aut-sei=Okazaki en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OtaTomoyuki en-aut-sei=Ota en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsumotoHiroshi en-aut-sei=Matsumoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyamotoShotaro en-aut-sei=Miyamoto en-aut-mei=Shotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsumuraMunechika en-aut-sei=Tsumura en-aut-mei=Munechika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HayashiSeiya en-aut-sei=Hayashi en-aut-mei=Seiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=UmakoshiMichiari en-aut-sei=Umakoshi en-aut-mei=Michiari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HirashitaKoji en-aut-sei=Hirashita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital kn-affil= affil-num=11 en-affil=Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital kn-affil= affil-num=12 en-affil=Department of Neurosurgery, Kagawa Rosai Hospital kn-affil= affil-num=13 en-affil=Department of Neurosurgery, Kagawa Rosai Hospital kn-affil= affil-num=14 en-affil=Department of Neurosurgery, Kagawa Rosai Hospital kn-affil= affil-num=15 en-affil=Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=pneumocephalus kn-keyword=pneumocephalus en-keyword=inverted papilloma kn-keyword=inverted papilloma en-keyword=frontoethmoidal sinus kn-keyword=frontoethmoidal sinus en-keyword=endoscopic endonasal and transcranial surgery kn-keyword=endoscopic endonasal and transcranial surgery END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=4 article-no= start-page=331 end-page=335 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202408 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Rare Subglottic Pleomorphic Adenoma: Magnetic Resonance Findings en-subtitle= kn-subtitle= en-abstract= kn-abstract=No previous study has published magnetic resonance imaging (MRI) findings for a subglottic pleomorphic adenoma. Here, we describe the case of a 62-year-old man with a subglottic pleomorphic adenoma. Endoscopic findings revealed a smooth-surfaced tumor arising from the subglottic posterior wall. MRI revealed the lesion as an isointense region on T1-weighted images, which was homogeneously enhanced. This lesion showed a heterogeneously hyperintense region on T2-weighted images. Diffusion-weighted imaging (DWI) showed slightly high intensity in the same area, with a normal or only slightly high apparent diffusion coefficient (ADC). Laryngomicrosurgery was performed for transoral excision of the subglottic tumor, resulting in a postsurgical diagnosis of pleomorphic adenoma. en-copyright= kn-copyright= en-aut-name=FurukawaChieko en-aut-sei=Furukawa en-aut-mei=Chieko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TachibanaTomoyasu en-aut-sei=Tachibana en-aut-mei=Tomoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NobuhisaTetsuji en-aut-sei=Nobuhisa en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanieYuichiro en-aut-sei=Kanie en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WaniYoji en-aut-sei=Wani en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoJun-Ya en-aut-sei=Matsumoto en-aut-mei=Jun-Ya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KariyaAkifumi en-aut-sei=Kariya en-aut-mei=Akifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SatoAsuka en-aut-sei=Sato en-aut-mei=Asuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshikawaIichiro en-aut-sei=Ishikawa en-aut-mei=Iichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaoiYuto en-aut-sei=Naoi en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Otolaryngology Head and Neck Surgery, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=2 en-affil=Department of Otolaryngology Head and Neck Surgery, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=3 en-affil=Department of Surgery, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=4 en-affil=Department of Radiology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=5 en-affil=Department of Pathology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=6 en-affil=Department of Otolaryngology Head and Neck Surgery, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=7 en-affil=Department of Otolaryngology Head and Neck Surgery, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=8 en-affil=Department of Otolaryngology Head and Neck Surgery, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=10 en-affil=Department of Otolaryngology Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Otolaryngology Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=subglottis kn-keyword=subglottis en-keyword=pleomorphic adenoma kn-keyword=pleomorphic adenoma en-keyword=MRI kn-keyword=MRI en-keyword=transoral surgery kn-keyword=transoral surgery END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=4 article-no= start-page=253 end-page=256 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230614 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A case of mucosal-associated lymphoid tissue lymphoma of the urachus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Urachus carcinoma is a rare malignancy with an aggressive potential and a poor prognosis, and evidence is limited for its diagnosis and treatment.
Case presentation: A 75-year-old man underwent fluorodeoxyglucose positron emission tomography/computed tomography for staging prostate cancer, and a mass (standardized uptake value max 9.5) was observed on the outside of the urinary bladder dome. T2-weighted magnetic resonance imaging showed the urachus and a low-intensity tumor, which suggested a malignant tumor. We suspected urachal carcinoma and performed total resection of the urachus and partial cystectomy. Pathological examination revealed mucosa-associated lymphoid tissue lymphoma with cells positive for CD20 and negative for CD3, CD5, and cyclin D1. After the surgery, no recurrence has been observed for more than 2 years.
Conclusion: We encountered an extremely rare case of mucosa-associated lymphoid tissue lymphoma of the urachus. Surgical resection of the tumor provided an accurate diagnosis and good disease control. en-copyright= kn-copyright= en-aut-name=TsuboiKazuma en-aut-sei=Tsuboi en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaisaKohei en-aut-sei=Haisa en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KajiharaYuta en-aut-sei=Kajihara en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsugawaTakuji en-aut-sei=Tsugawa en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InoueYosuke en-aut-sei=Inoue en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakoTomoko en-aut-sei=Sako en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MuraoWataru en-aut-sei=Murao en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=EbaraShin en-aut-sei=Ebara en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Urology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=4 en-affil=Department of Urology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=5 en-affil=Department of Urology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=6 en-affil=Department of Urology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=7 en-affil=Department of Urology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=8 en-affil=Department of Urology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=9 en-affil=Department of Urology, Hiroshima City Hiroshima Citizens Hospital kn-affil= en-keyword=bladder cancer kn-keyword=bladder cancer en-keyword=malignant lymphoma kn-keyword=malignant lymphoma en-keyword=MALT lymphoma kn-keyword=MALT lymphoma en-keyword=urachal cancer kn-keyword=urachal cancer en-keyword=urachal remnant kn-keyword=urachal remnant END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=17591 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240730 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Training high-performance deep learning classifier for diagnosis in oral cytology using diverse annotations en-subtitle= kn-subtitle= en-abstract= kn-abstract=The uncertainty of true labels in medical images hinders diagnosis owing to the variability across professionals when applying deep learning models. We used deep learning to obtain an optimal convolutional neural network (CNN) by adequately annotating data for oral exfoliative cytology considering labels from multiple oral pathologists. Six whole-slide images were processed using QuPath for segmenting them into tiles. The images were labeled by three oral pathologists, resulting in 14,535 images with the corresponding pathologists' annotations. Data from three pathologists who provided the same diagnosis were labeled as ground truth (GT) and used for testing. We investigated six models trained using the annotations of (1) pathologist A, (2) pathologist B, (3) pathologist C, (4) GT, (5) majority voting, and (6) a probabilistic model. We divided the test by cross-validation per slide dataset and examined the classification performance of the CNN with a ResNet50 baseline. Statistical evaluation was performed repeatedly and independently using every slide 10 times as test data. For the area under the curve, three cases showed the highest values (0.861, 0.955, and 0.991) for the probabilistic model. Regarding accuracy, two cases showed the highest values (0.988 and 0.967). For the models using the pathologists and GT annotations, many slides showed very low accuracy and large variations across tests. Hence, the classifier trained with probabilistic labels provided the optimal CNN for oral exfoliative cytology considering diagnoses from multiple pathologists. These results may lead to trusted medical artificial intelligence solutions that reflect diverse diagnoses of various professionals. en-copyright= kn-copyright= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaFuta en-aut-sei=Tanaka en-aut-mei=Futa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HaraTakeshi en-aut-sei=Hara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OchiaiTakanaga en-aut-sei=Ochiai en-aut-mei=Takanaga kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimadaKatsumitsu en-aut-sei=Shimada en-aut-mei=Katsumitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=InoueYuta en-aut-sei=Inoue en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakiYoshihiro en-aut-sei=Taki en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakaiFumi en-aut-sei=Nakai en-aut-mei=Fumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakaiYasuhiro en-aut-sei=Nakai en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IshihamaTakanori en-aut-sei=Ishihama en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MiyazakiRyo en-aut-sei=Miyazaki en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MurakamiSatoshi en-aut-sei=Murakami en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MiyakeMinoru en-aut-sei=Miyake en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University kn-affil= affil-num=5 en-affil=Division of Oral Pathogenesis and Disease Control, Department of Oral Pathology, Asahi University School of Dentistry kn-affil= affil-num=6 en-affil=Department of Oral Pathology, Graduate School of Oral Medicine, Matsumoto Dental University kn-affil= affil-num=7 en-affil=Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University kn-affil= affil-num=8 en-affil=Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine kn-affil= affil-num=11 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine kn-affil= affil-num=12 en-affil=Stony Brook Cancer Center, Stony Brook University kn-affil= affil-num=13 en-affil=Department of Oral Pathology, Graduate School of Oral Medicine, Matsumoto Dental University kn-affil= affil-num=14 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine kn-affil= en-keyword=Deep learning kn-keyword=Deep learning en-keyword=Oral cytology kn-keyword=Oral cytology en-keyword=Classification kn-keyword=Classification en-keyword=Convolutional neural network kn-keyword=Convolutional neural network en-keyword=Probabilistic labeling kn-keyword=Probabilistic labeling END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=341 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240813 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pathological findings in enucleated eyes of patients with neurofibromatosis type 1: report of a case with 15-year follow-up and review of 14 patients in the literature en-subtitle= kn-subtitle= en-abstract= kn-abstract=Backgrounds Iris nodules are frequently noted as clinical manifestations of neurofibromatosis type 1 but the other intraocular manifestations are rare. The purpose of this study is to present a patient with a phthisic eye who underwent enucleation for a cosmetic reason after 15-year follow-up and also to review 14 patients with enucleation described in the literature.
Case presentation A 17-year-old man with neurofibromatosis type 1 from infancy underwent the enucleation of phthisic left eye and also had the resection of eyelid subcutaneous mass lesions on the left side for a cosmetic reason. He had undergone four-time preceding surgeries for eyelid and orbital mass reduction on the left side in childhood and had developed total retinal detachment 10 years previously. Pathologically, the enucleated eye showed massive retinal gliosis positive for both S-100 and glial fibrillary acidic protein (GFAP) in the area with involvement of the detached retinal neuronal layer, together with a more fibrotic lesion along the choroid which were, in contrast, negative for both S-100 and GFAP. The choroid, ciliary body, and iris did not show apparent neurofibroma while episcleral neurofibroma was present.
Literature review In review of enucleated eyes of 14 patients in the literature, buphthalmic eyes with early-onset glaucoma on the unilateral side was clinically diagnosed in 9 patients who frequently showed varying extent of hemifacial neurofibromatosis which involved the eyelid and orbit on the same side. Pathologically, neurofibromas in varying extent were found in the choroid of 12 patients. One patient showed choroidal malignant melanoma on the left side and fusiform enlargement of the optic nerve on the right side suspected of optic nerve glioma. The phthisic eye in another patient showed massive retinal gliosis similar to the present patient.
Conclusions In summary of the 15 patients with neurofibromatosis type 1, including the present patient, buphthalmic or phthisic eyes with no vision were enucleated for cosmetic reasons and showed choroidal neurofibroma in most patients and massive retinal gliosis in two patients including the present patient. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishidaKenji en-aut-sei=Nishida en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SenoTakaya en-aut-sei=Seno en-aut-mei=Takaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamadaKiyoshi en-aut-sei=Yamada en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OnoShigeki en-aut-sei=Ono en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, General Medical Center, Kawasaki Medical School kn-affil= en-keyword=Neurofibromatosis type 1 kn-keyword=Neurofibromatosis type 1 en-keyword=Enucleation kn-keyword=Enucleation en-keyword=Eye kn-keyword=Eye en-keyword=Pathology kn-keyword=Pathology en-keyword=Massive retinal gliosis kn-keyword=Massive retinal gliosis en-keyword=Choroidal neurofibroma kn-keyword=Choroidal neurofibroma en-keyword=Phthisis kn-keyword=Phthisis en-keyword=Buphthalmos kn-keyword=Buphthalmos en-keyword=Malignant melanoma kn-keyword=Malignant melanoma en-keyword=Cosmetic surgery kn-keyword=Cosmetic surgery END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=8 article-no= start-page=208 end-page=214 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202408 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Anterior Uveitis After Discontinuation of Janus Kinase Inhibitor, Ruxolitinib en-subtitle= kn-subtitle= en-abstract= kn-abstract=Primary myelofibrosis shows widespread fibrosis in the bone marrow and is part of myeloproliferative neoplasms in which gene mutations in hematopoietic stem cells lead to abnormal clonal expansion of one or more lineage of myeloid and erythroid cells and megakaryocytes. Janus kinase (JAK) inhibitors are the main therapeutic regimen for primary myelofibrosis which harbors gene mutations, resulting in continuous activation of JAK-STAT signaling pathway. Since JAK inhibitors modulate immunological state, the administration would have a potential for uveitis. A 67-year-old patient presented with weight loss of 10 kg in the past 2 years after his retirement. He showed normocytic anemia with anisocytosis and abnormal shape, as well as hepatosplenomegaly. Suspected of hematological malignancy, bone marrow biopsy led to the diagnosis of primary myelofibrosis (grade 2) with bizarre megakaryocytes and relative maintenance of myeloid and erythroid lineage. He started to have blood transfusion. Genomic DNA analysis of the peripheral blood showed a pathogenic variant in the exon 9 of calreticulin (CALR) gene while pathogenic variants in Janus kinase-2 (JAK2), and myeloproliferative leukemia virus oncogene (MPL) were absent. He began to have oral ruxolitinib 10 mg daily at the timepoint of 5 months after the initial visit and the dose was increased to 20 mg daily 8 months later but was discontinued further 4 months later because he showed the limited effect of ruxolitinib. He had blood transfusion every week or every 2 weeks in the following 2 months until he noticed blurred vision in the right eye. The right eye showed thick fibrin membrane formation in the anterior chamber in front of the pupil which prevented the fundus from visualization. The left eye showed no inflammation and optic nerve atrophy, sequel to tuberculous meningitis in childhood. The patient started to use 0.1% betamethasone six times daily and 1% atropine once daily as eye drops. A week later, fibrin membrane disappeared and the pupillary area with total iris posterior synechia was visible in the right eye. He regained the vision in the right eye and did not show relapse of uveitis only with topical 0.1% betamethasone. Uveitis might be related with the administration and discontinuation of ruxolitinib. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkedaNaoto en-aut-sei=Ikeda en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MonobeYasumasa en-aut-sei=Monobe en-aut-mei=Yasumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Kaneda Hospital kn-affil= affil-num=3 en-affil=Department of Pathology, General Medical Center, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Janus kinase inhibitor kn-keyword=Janus kinase inhibitor en-keyword=Ruxolitinib kn-keyword=Ruxolitinib en-keyword=Anemia kn-keyword=Anemia en-keyword=Myelofibrosis kn-keyword=Myelofibrosis en-keyword=Anterior uveitis kn-keyword=Anterior uveitis END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=7 article-no= start-page=e70003 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240719 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rare case of rectal carcinoid with synchronous primary carcinoid tumors of the lung misdiagnosed as lung metastases en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 68-year-old woman was referred to our hospital for rectal surgery after a pathological diagnosis of rectal carcinoid with venous invasion following endoscopic submucosal dissection of a 5?mm-sized submucosal tumor in the lower rectum. Chest CT showed nodules in the left upper lobe and right lower lobe, but positron emission tomography and somatostatin receptor scintigraphy showed no hyperaccumulation in the lung nodules. CT-guided needle biopsy was performed on the nodular lesion in the left upper lobe, which showed focal growth of tumor cells with a high N/C ratio and positive synaptophysin, leading to a diagnosis of pulmonary metastasis of rectal carcinoid. Since the patient was asymptomatic and did not wish to undergo surgery or chemotherapy, she was followed up strictly with sufficient informed consent. Three years have passed since the diagnosis, and there is no tendency for the lung metastasis to increase, and no other new lesions have been observed. The disease had not progressed and remained stable. Therefore, immunohistological analysis of the lung biopsy specimen was performed again, which was positive for TTF-1 and negative for CDX2. Consequently, the diagnosis was changed to primary lung carcinoid tumors, and the patient remains under follow-up with no disease progression. en-copyright= kn-copyright= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShojiRhohei en-aut-sei=Shoji en-aut-mei=Rhohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School kn-affil= en-keyword=lung metastases kn-keyword=lung metastases en-keyword=neuroendocrine tumor kn-keyword=neuroendocrine tumor en-keyword=rectal carcinoid kn-keyword=rectal carcinoid END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=13 article-no= start-page=2326 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240625 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy of Cisplatin-CXCR4 Antagonist Combination Therapy in Oral Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cisplatin is a platinum-based compound that is widely used for treating inoperable oral squamous cell carcinoma (OSCC) in Japan; however, resistance to cisplatin presents a challenge and innovative approaches are required. We aimed to investigate the therapeutic potential of targeting the chemokine receptor CXCR4, which is involved in angiogenesis and tumor progression, using the CXCR4 inhibitor AMD3100, in combination with cisplatin. AMD3100 induced necrosis and bleeding in OSCC xenografts by inhibiting angiogenesis. We investigated the combined ability of AMD3100 plus cisplatin to enhance the antitumor effect in cisplatin-resistant OSCC. An MTS assay identified HSC-2 cells as cisplatin-resistant cells in vitro. Mice treated with the cisplatin-AMD combination exhibited the most significant reduction in tumor volume, accompanied by extensive hemorrhage and necrosis. Histological examination indicated thin and short tumor vessels in the AMD and cisplatin?AMD groups. These results indicated that cisplatin and AMD3100 had synergistic antitumor effects, highlighting their potential for vascular therapy of refractory OSCC. Antitumor vascular therapy using cisplatin combined with a CXCR4 inhibitor provides a novel strategy for addressing cisplatin-resistant OSCC. en-copyright= kn-copyright= en-aut-name=YoshidaSaori en-aut-sei=Yoshida en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SoeYamin en-aut-sei=Soe en-aut-mei=Yamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EainHtoo Shwe en-aut-sei=Eain en-aut-mei=Htoo Shwe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SanouSho en-aut-sei=Sanou en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HisatomiMiki en-aut-sei=Hisatomi en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AsaumiJunichi en-aut-sei=Asaumi en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YanagiYoshinobu en-aut-sei=Yanagi en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Preliminary Examination Room, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Preliminary Examination Room, Okayama University Hospital kn-affil= en-keyword=oral squamous cell carcinoma kn-keyword=oral squamous cell carcinoma en-keyword=CXCR4 kn-keyword=CXCR4 en-keyword=cisplatin kn-keyword=cisplatin en-keyword=antitumor vascular therapy kn-keyword=antitumor vascular therapy END start-ver=1.4 cd-journal=joma no-vol=100 cd-vols= no-issue=1 article-no= start-page=219 end-page=228 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240625 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Novel Peptidome Technology for the Diagnosis of Mild Cognitive Impairment and Alzheimerfs Disease by Selected Reaction Monitoring en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background:With the aging of populations worldwide, Alzheimerfs disease (AD) has become a concern due to its high prevalence and the continued lack of established treatments. Early diagnosis is required as a preventive intervention to modify the diseasefs progression. In our previous study, we performed peptidomic analysis of serum samples obtained from AD patients and age-matched healthy subjects to seek peptide biomarker candidates for AD by using BLOTCHIP-MS analysis, and identified four peptides as AD biomarker candidates.
Objective:The objective was to validate the serum biomarker peptides to distinguish mild cognitive impairment (MCI) and AD in comparison to cognitively healthy controls using a new peptidome technology, the Dementia Risk Test.
Methods:We enrolled 195 subjects with normal cognitive function (NC; n?=?70), MCI (n?=?55), and AD (n?=?70), The concentrations of cognitive impairment marker peptides (Fibrinogen chain (FAC), Fibrinogen chain (FBC), Plasma protease C1 inhibitor (PPC1I), 2-HS-glycoprotein (AHSG)) were quantified by using a selected reaction monitoring assay based on liquid chromatography-MS/MS.
Results:The present study confirmed that three peptides, FAC, FBC, and PPC1I, were significantly upregulated during the onset of AD. This three-peptide set was both highly sensitive in determining AD (sensitivity: 85.7%, specificity: 95.7%, AUC: 0.900) and useful in distinguishing MCI (sensitivity: 61.8%, specificity: 98.6%, AUC: 0.824) from NC.
Conclusions:In this validation study, we confirmed the high diagnostic potential of the three peptides identified in our previous study as candidate serum biomarkers for AD. The Dementia Risk Test may be a powerful tool for detecting AD-related pathological changes. en-copyright= kn-copyright= en-aut-name=FukuiYusuke en-aut-sei=Fukui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TadokoroKoh en-aut-sei=Tadokoro en-aut-mei=Koh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamadaMinaki en-aut-sei=Hamada en-aut-mei=Minaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AsadaKyoichi en-aut-sei=Asada en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LeeLyang-Ja en-aut-sei=Lee en-aut-mei=Lyang-Ja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TachikiHidehisa en-aut-sei=Tachiki en-aut-mei=Hidehisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Protosera, Inc. kn-affil= affil-num=4 en-affil=Protosera, Inc. kn-affil= affil-num=5 en-affil=Protosera, Inc. kn-affil= affil-num=6 en-affil=Protosera, Inc. kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Neurology, National Center of Neurology and Psychiatry kn-affil= affil-num=9 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Alzheimerfs disease kn-keyword=Alzheimerfs disease en-keyword=biochemical marker kn-keyword=biochemical marker en-keyword=dementia risk test kn-keyword=dementia risk test en-keyword=liquid chromatography-MS/MS kn-keyword=liquid chromatography-MS/MS en-keyword=mild cognitive impairment kn-keyword=mild cognitive impairment en-keyword=peptidome kn-keyword=peptidome en-keyword=selected reaction monitoring kn-keyword=selected reaction monitoring END start-ver=1.4 cd-journal=joma no-vol=208 cd-vols= no-issue= article-no= start-page=145- end-page=154 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240627 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparison of proportions and prognostic impact of pathological complete response between evaluations of representative specimen and total specimen in primary breast cancer after neoadjuvant chemoradiotherapy: an ancillary study of JCOG0306 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background In JCOG0306 trial, a phase II study to examine the efficacy of neoadjuvant chemotherapy followed by radiation therapy (NAC-RT) to primary breast cancer, pathological complete response (pCR) was evaluated from specimens of the representative cross-section including the tumor center that had been accurately marked [representative specimen (RS) method]. In this ancillary study, we examined if the RS method was comparable to the conventional total specimen (TS) method, which is widely employed in Japan, to identify the pCR group showing excellent prognosis.
Methods We obtained long-term follow-up data of 103 patients enrolled in JCOG0306 trial. As histological therapeutic effect, pCR (ypT0 and ypT0/is) and quasi-pCR [QpCR, ypT0/is plus Grade 2b (only a few remaining invasive cancer cells)] were evaluated with RS and TS methods. Concordance of pCR between these two methods and associations of the pCR with prognosis were examined.
Results ypT0, ypT0/is, and QpCR were observed in 28 (27.2%), 39 (37.9%), and 45 (43.7%) patients with RS method, whereas these were 20 (19.4%), 25 (24.3%) and 40 (38.9%) with TS method, respectively. Between RS and TS methods, concordance proportions of ypT0 and ypTis were 92.2% and 86.4%, respectively. Risk of recurrence of ypT0/is group was lower than that of non-ypT0/is group (HR 0.408, 95% CI [0.175?0.946], P?=?0.037) and risk of death of ypT0/is group was lower than that of non-ypT0/is group (HR 0.251, 95% CI [0.073?0.857], P?=?0.027). The ypT0 and ypT0/is groups with RS method showed excellent prognosis similarly with those with TS method, and RS method was able to differentiate the OS and RFS between pCR and non-pCR than TS method significantly even if pCR was classified ypT0 or ypT0/is. With TS method, QpCR criteria stratified patients into the better and worse prognosis groupsmore clearly than pCR criteria of ypT0 or ypT0/is.
Conclusions RS method was comparable to TS method for the evaluation of pCR in the patients who received NAC-RT to primary breast cancer provided the tumor center was accurately marked. As pCR criteria with RS method, ypT0/is appeared more appropriate than ypT0. en-copyright= kn-copyright= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsudaHitoshi en-aut-sei=Tsuda en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SasakiKeita en-aut-sei=Sasaki en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MizusawaJunki en-aut-sei=Mizusawa en-aut-mei=Junki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkiyamaFutoshi en-aut-sei=Akiyama en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurosumiMasafumi en-aut-sei=Kurosumi en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SawakiMasataka en-aut-sei=Sawaki en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TamuraNobuko en-aut-sei=Tamura en-aut-mei=Nobuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaKiyo en-aut-sei=Tanaka en-aut-mei=Kiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KogawaTakahiro en-aut-sei=Kogawa en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakahashiMina en-aut-sei=Takahashi en-aut-mei=Mina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HayashiNaoki en-aut-sei=Hayashi en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MukaiHirofumi en-aut-sei=Mukai en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MasudaNorikazu en-aut-sei=Masuda en-aut-mei=Norikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IwataHiroji en-aut-sei=Iwata en-aut-mei=Hiroji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Basic Pathology, National Defense Medical College kn-affil= affil-num=3 en-affil=JCOG Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=4 en-affil=JCOG Data Center/Operations Office, National Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Pathology, Cancer Institute Hospital kn-affil= affil-num=6 en-affil=Department of Diagnostic Pathology, Kameda Kyobashi Clinic kn-affil= affil-num=7 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Breast Surgery, Toranomon Hospital kn-affil= affil-num=9 en-affil=Department of Breast Surgery, Toranomon Hospital kn-affil= affil-num=10 en-affil=Department of Breast Medical Oncology, Cancer Institute Hospital kn-affil= affil-num=11 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=12 en-affil=Department of Breast Surgery Oncology, St Lukes International Hospital kn-affil= affil-num=13 en-affil=Department of Breast and Medical Oncology, National Cancer Center Hospital East kn-affil= affil-num=14 en-affil=Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital kn-affil= affil-num=15 en-affil=Department of Breast Medical Oncology, Cancer Institute Hospital kn-affil= affil-num=16 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Neoadjuvant chemoradiotherapy kn-keyword=Neoadjuvant chemoradiotherapy en-keyword=Pathological therapeutic effect kn-keyword=Pathological therapeutic effect en-keyword=Specimen sampling method kn-keyword=Specimen sampling method END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=12 article-no= start-page=6648 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240617 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Local E-rhBMP-2/-TCP Application Rescues Osteocyte Dendritic Integrity and Reduces Microstructural Damage in Alveolar Bone Post-Extraction in MRONJ-like Mouse Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=The pathology of medication-related osteonecrosis of the jaw (MRONJ), often associated with antiresorptive therapy, is still not fully understood. Osteocyte networks are known to play a critical role in maintaining bone homeostasis and repair, but the exact condition of these networks in MRONJ is unknown. On the other hand, the local application of E-coli-derived Recombinant Human Bone Morphogenetic Protein 2/beta-Tricalcium phosphate (E-rhBMP-2/beta-TCP) has been shown to promote bone regeneration and mitigate osteonecrosis in MRONJ-like mouse models, indicating its potential therapeutic application for the treatment of MRONJ. However, the detailed effect of BMP-2 treatment on restoring bone integrity, including its osteocyte network, in an MRONJ condition remains unclear. Therefore, in the present study, by applying a scanning electron microscope (SEM) analysis and a 3D osteocyte network reconstruction workflow on the alveolar bone surrounding the tooth extraction socket of an MRONJ-like mouse model, we examined the effectiveness of BMP-2/beta-TCP therapy on the alleviation of MRONJ-related bone necrosis with a particular focus on the osteocyte network and alveolar bone microstructure (microcrack accumulation). The 3D osteocyte dendritic analysis showed a significant decrease in osteocyte dendritic parameters along with a delay in bone remodeling in the MRONJ group compared to the healthy counterpart. The SEM analysis also revealed a notable increase in the number of microcracks in the alveolar bone surface in the MRONJ group compared to the healthy group. In contrast, all of those parameters were restored in the E-rhBMP-2/beta-TCP-treated group to levels that were almost similar to those in the healthy group. In summary, our study reveals that MRONJ induces osteocyte network degradation and microcrack accumulation, while application of E-rhBMP-2/beta-TCP can restore a compromised osteocyte network and abrogate microcrack accumulation in MRONJ. en-copyright= kn-copyright= en-aut-name=DangAnh Tuan en-aut-sei=Dang en-aut-mei=Anh Tuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnoMitsuaki en-aut-sei=Ono en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TosaIkue en-aut-sei=Tosa en-aut-mei=Ikue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraEmilio Satoshi en-aut-sei=Hara en-aut-mei=Emilio Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MikaiAkihiro en-aut-sei=Mikai en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KitagawaWakana en-aut-sei=Kitagawa en-aut-mei=Wakana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YonezawaTomoko en-aut-sei=Yonezawa en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KubokiTakuo en-aut-sei=Kuboki en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OohashiToshitaka en-aut-sei=Oohashi en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=medication-related osteonecrosis of the jaw kn-keyword=medication-related osteonecrosis of the jaw en-keyword=BMP-2 kn-keyword=BMP-2 en-keyword=osteocyte dendritic network kn-keyword=osteocyte dendritic network en-keyword=microcrack accumulation kn-keyword=microcrack accumulation en-keyword=bone remodeling kn-keyword=bone remodeling END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=6 article-no= start-page=2497 end-page=2509 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240531 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Senescent Fibroblasts Potentiate Peritoneal Metastasis of Diffuse-type Gastric Cancer Cells via IL-8?mediated Crosstalk en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Diffuse-type gastric cancer (DGC) often forms peritoneal metastases, leading to poor prognosis. However, the underlying mechanism of DGC-mediated peritoneal metastasis is poorly understood. DGC is characterized by desmoplastic stroma, in which heterogeneous cancer-associated fibroblasts (CAFs), including myofibroblastic CAFs (myCAFs) and senescent CAFs (sCAFs), play a crucial role during tumor progression. This study investigated the CAF subtypes induced by GC cells and the role of sCAFs in peritoneal metastasis of DGC cells. Materials and Methods: Conditioned medium of human DGC cells (KATOIII, NUGC-4) and human intestinal-type GC (IGC) cells (MKN-7, N87) was used to induce CAFs. CAF subtypes were evaluated by analyzing the expression of ?smooth muscle actin (-SMA), senescence-associated -galactosidase (SA--gal), and p16 in human normal fibroblasts (GF, FEF-3). A cytokine array was used to explore the underlying mechanism of GC-induced CAF subtype development. The role of sCAFs in peritoneal metastasis of DGC cells was analyzed using a peritoneally metastatic DGC tumor model. The relationships between GC subtypes and CAF-related markers were evaluated using publicly available datasets. Results: IGC cells significantly induced -SMA+ myCAFs by secreting transforming growth factor?, whereas DGC cells induced SA--gal+/p16+ sCAFs by secreting interleukin (IL)-8. sCAFs further secreted IL-8 to promote DGC cell migration. In vivo experiments demonstrated that co-inoculation of sCAFs significantly enhanced peritoneal metastasis of NUGC-4 cells, which was attenuated by administration of the IL-8 receptor antagonist navarixin. p16 and IL-8 expression was significantly associated with poor prognosis of DGC patients. Conclusion: sCAFs promote peritoneal metastasis of DGC via IL-8?mediated crosstalk. en-copyright= kn-copyright= en-aut-name=LIYUNCHENG en-aut-sei=LI en-aut-mei=YUNCHENG kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TAZAWAHIROSHI en-aut-sei=TAZAWA en-aut-mei=HIROSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NAGAIYASUO en-aut-sei=NAGAI en-aut-mei=YASUO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FUJITASHUTO en-aut-sei=FUJITA en-aut-mei=SHUTO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OKURATOMOHIRO en-aut-sei=OKURA en-aut-mei=TOMOHIRO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SHOJIRYOHEI en-aut-sei=SHOJI en-aut-mei=RYOHEI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YAMADAMOTOHIKO en-aut-sei=YAMADA en-aut-mei=MOTOHIKO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KIKUCHISATORU en-aut-sei=KIKUCHI en-aut-mei=SATORU kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KURODASHINJI en-aut-sei=KURODA en-aut-mei=SHINJI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OHARATOSHIAKI en-aut-sei=OHARA en-aut-mei=TOSHIAKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NOMAKAZUHIRO en-aut-sei=NOMA en-aut-mei=KAZUHIRO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NISHIZAKIMASAHIKO en-aut-sei=NISHIZAKI en-aut-mei=MASAHIKO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KAGAWASHUNSUKE en-aut-sei=KAGAWA en-aut-mei=SHUNSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FUJIWARATOSHIYOSHI en-aut-sei=FUJIWARA en-aut-mei=TOSHIYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Gastric cancer kn-keyword=Gastric cancer en-keyword=peritoneal metastasis kn-keyword=peritoneal metastasis en-keyword=senescent fibroblast kn-keyword=senescent fibroblast en-keyword=IL-8 kn-keyword=IL-8 en-keyword=CXCR1/2 kn-keyword=CXCR1/2 END start-ver=1.4 cd-journal=joma no-vol=65 cd-vols= no-issue=3 article-no= start-page=276 end-page=281 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202405 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Postnatal longitudinal analysis of serum nitric oxide and eosinophil counts in extremely preterm infants en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Nitric oxide (NO) may be related to the pathogenesis of several morbidities in extremely preterm infants, including late-onset adrenal insufficiency. However, eosinophilia is observed under pathological conditions with adrenal insufficiency. Therefore, this study explored postnatal changes in NO levels and eosinophil counts in extremely preterm infants with and without morbidities.
Methods: Nineteen extremely preterm infants with a median gestational age of 27.0 weeks and median birth weight of 888 g were enrolled in this study. Serum levels of nitrogen oxides (NOx) and peripheral blood eosinophil counts were measured at birth and every 2 weeks thereafter. Morbidities of the study group were diagnosed using a single criterion.
Results: Serum NOx levels (mean } standard deviation) were 22.5 } 14.9 mol/L, 51.2 } 23.7 mol/L, 42.4 } 15.2 mol/L, and 33.8 } 9.4 mol/L at birth and 2, 4, and 6 weeks of age, respectively. The serum NOx level at 2 weeks of age was significantly higher than that at birth and 6 weeks of age. Eosinophil counts, which increase with adrenal insufficiency, were measured simultaneously and were 145 } 199/L, 613 } 625/L, 466 } 375/L, and 292 } 228/L at birth and 2, 4, and 6 weeks of age, respectively. These values showed that the eosinophil count was significantly higher at 2 weeks of age than at birth and 6 weeks of age. The serum NOx level of infants without chorioamnionitis was significantly increased at 4 weeks of age, and the eosinophil count of infants with necrotizing enterocolitis was significantly increased at 2 weeks of age. No correlation with the NOx level or eosinophil count was observed in infants with late-onset circulatory collapse.
Conclusion: The postnatal serum NOx level and eosinophil count were significantly correlated with each other and peaked at 2 weeks of age. en-copyright= kn-copyright= en-aut-name=WatanabeHirokazu en-aut-sei=Watanabe en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WashioYosuke en-aut-sei=Washio en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TamaiKei en-aut-sei=Tamai en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorimotoDaisaku en-aut-sei=Morimoto en-aut-mei=Daisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkamuraTomoka en-aut-sei=Okamura en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshimotoJunko en-aut-sei=Yoshimoto en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakanishiHidehiko en-aut-sei=Nakanishi en-aut-mei=Hidehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KageyamaMisao en-aut-sei=Kageyama en-aut-mei=Misao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchiyamaAtsushi en-aut-sei=Uchiyama en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KusudaSatoshi en-aut-sei=Kusuda en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Neonatology, Okayama Medical Center, National Hospital Organization kn-affil= affil-num=4 en-affil=Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=7 en-affil=Department of Neonatology, Maternal and Perinatal Center, Tokyo Womenfs Medical University kn-affil= affil-num=8 en-affil=Department of Neonatology, Okayama Medical Center, National Hospital Organization kn-affil= affil-num=9 en-affil=Department of Neonatology, Maternal and Perinatal Center, Tokyo Womenfs Medical University kn-affil= affil-num=10 en-affil=Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=11 en-affil=Department of Neonatology, Maternal and Perinatal Center, Tokyo Womenfs Medical University kn-affil= en-keyword=eosinophils kn-keyword=eosinophils en-keyword=extremely preterm infant kn-keyword=extremely preterm infant en-keyword=nitric oxide kn-keyword=nitric oxide en-keyword=relative adrenal insufficiency kn-keyword=relative adrenal insufficiency END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=5938 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240311 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Palaeoproteomic investigation of an ancient human skeleton with abnormal deposition of dental calculus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Detailed investigation of extremely severe pathological conditions in ancient human skeletons is important as it could shed light on the breadth of potential interactions between humans and disease etiologies in the past. Here, we applied palaeoproteomics to investigate an ancient human skeletal individual with severe oral pathology, focusing our research on bacterial pathogenic factors and host defense response. This female skeleton, from the Okhotsk period (i.e., fifth to thirteenth century) of Northern Japan, poses relevant amounts of abnormal dental calculus deposition and exhibits oral dysfunction due to severe periodontal disease. A shotgun mass-spectrometry analysis identified 81 human proteins and 15 bacterial proteins from the calculus of the subject. We identified two pathogenic or bioinvasive proteins originating from two of the three "red complex" bacteria, the core species associated with severe periodontal disease in modern humans, as well as two additional bioinvasive proteins of periodontal-associated bacteria. Moreover, we discovered defense response system-associated human proteins, although their proportion was mostly similar to those reported in ancient and modern human individuals with lower calculus deposition. These results suggest that the bacterial etiology was similar and the host defense response was not necessarily more intense in ancient individuals with significant amounts of abnormal dental calculus deposition. en-copyright= kn-copyright= en-aut-name=Uchida-FukuharaYoko en-aut-sei=Uchida-Fukuhara en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimamuraShigeru en-aut-sei=Shimamura en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SawafujiRikai en-aut-sei=Sawafuji en-aut-mei=Rikai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishiuchiTakumi en-aut-sei=Nishiuchi en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YonedaMinoru en-aut-sei=Yoneda en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshidaHajime en-aut-sei=Ishida en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumuraHirofumi en-aut-sei=Matsumura en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsutayaTakumi en-aut-sei=Tsutaya en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Oral Morphology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Institute for Extra-Cutting-Edge Science and Technology Avant-Garde Research (X-STAR), Japan Agency for Marine-Earth Science and Technology (JAMSTEC) kn-affil= affil-num=3 en-affil=Research Center for Integrative Evolutionary Science, The Graduate University for Advanced Studies (SOKENDAI) kn-affil= affil-num=4 en-affil=Research Center for Experimental Modeling of Human Disease, Kanazawa University kn-affil= affil-num=5 en-affil=The University Museum, The University of Tokyo kn-affil= affil-num=6 en-affil=Department of Human Biology and Anatomy, Graduate School of Medicine, University of the Ryukyus kn-affil= affil-num=7 en-affil=School of Health Sciences, Sapporo Medical University kn-affil= affil-num=8 en-affil=Research Center for Integrative Evolutionary Science, The Graduate University for Advanced Studies (SOKENDAI) kn-affil= END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue= article-no= start-page=1371307 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240528 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dissection of the signal transduction machinery responsible for the lysyl oxidase-like 4-mediated increase in invasive motility in triple-negative breast cancer cells: mechanistic insight into the integrin-1-NF-B-MMP9 axis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Triple-negative breast cancer (TNBC) cells are a highly formidable cancer to treat. Nonetheless, by continued investigation into the molecular biology underlying the complex regulation of TNBC cell activity, vulnerabilities can be exposed as potential therapeutic targets at the molecular level. We previously revealed that lysyl oxidase-like 4 (LOXL4) promotes the invasiveness of TNBC cells via cell surface annexin A2 as a novel binding substrate of LOXL4, which promotes the abundant localization of integrin-beta 1 at the cancer plasma membrane. However, it has yet to be uncovered how the LOXL4-mediated abundance of integrin-beta 1 hastens the invasive outgrowth of TNBC cells at the molecular level.
Methods LOXL4-overexpressing stable clones were established from MDA-MB-231 cells and subjected to molecular analyses, real-time qPCR and zymography to clarify their invasiveness, signal transduction, and matrix metalloprotease (MMP) activity, respectively.
Results Our results show that LOXL4 potently promotes the induction of matrix metalloprotease 9 (MMP9) via activation of nuclear factor-kappa B (NF-kappa B). Our molecular analysis revealed that TNF receptor-associated factor 4 (TRAF4) and TGF-beta activated kinase 1 (TAK1) were required for the activation of NF-kappa B through I kappa beta kinase kinase (IKK alpha/beta) phosphorylation.
Conclusion Our results demonstrate that the newly identified LOXL4-mediated axis, integrin-beta 1-TRAF4-TAK1-IKK alpha/beta-I kappa beta alpha-NF-kappa B-MMP9, is crucial for TNBC cell invasiveness. en-copyright= kn-copyright= en-aut-name=JiangFan en-aut-sei=Jiang en-aut-mei=Fan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChenYouyi en-aut-sei=Chen en-aut-mei=Youyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KinoshitaRie en-aut-sei=Kinoshita en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KomalasariNi Luh Gede Yoni en-aut-sei=Komalasari en-aut-mei=Ni Luh Gede Yoni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Kasano-CamonesCarlos Ichiro en-aut-sei=Kasano-Camones en-aut-mei=Carlos Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NinomiyaKazumi en-aut-sei=Ninomiya en-aut-mei=Kazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MurataHitoshi en-aut-sei=Murata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoKen-Ichi en-aut-sei=Yamamoto en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GoharaYuma en-aut-sei=Gohara en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OchiToshiki en-aut-sei=Ochi en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=RumaI. Made Winarsa en-aut-sei=Ruma en-aut-mei=I. Made Winarsa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SumardikaI. Wayan en-aut-sei=Sumardika en-aut-mei=I. Wayan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ZhouJin en-aut-sei=Zhou en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HonjoTomoko en-aut-sei=Honjo en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SakaguchiYoshihiko en-aut-sei=Sakaguchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YamauchiAkira en-aut-sei=Yamauchi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KuribayashiFutoshi en-aut-sei=Kuribayashi en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FutamiJunichiro en-aut-sei=Futami en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KondoEisaku en-aut-sei=Kondo en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=InoueYusuke en-aut-sei=Inoue en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=3 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=6 en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University kn-affil= affil-num=7 en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University kn-affil= affil-num=8 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=13 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=14 en-affil=Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of Technology kn-affil= affil-num=15 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=16 en-affil=Department of Microbiology, Tokushima Bunri University kn-affil= affil-num=17 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=18 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=19 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=20 en-affil=Division of Tumor Pathology, Near InfraRed Photo-Immuno-Therapy Research Institute, Kansai Medical University kn-affil= affil-num=21 en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University kn-affil= affil-num=22 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=23 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=invasion kn-keyword=invasion en-keyword=lysyl oxidase kn-keyword=lysyl oxidase en-keyword=NF-B kn-keyword=NF-B en-keyword=MMP9 kn-keyword=MMP9 END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=11 article-no= start-page=6269 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=SPRED2 Is a Novel Regulator of Autophagy in Hepatocellular Carcinoma Cells and Normal Hepatocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sprouty-related enabled/vasodilator-stimulated phosphoprotein homology 1 domain containing 2 (SPRED2) is an inhibitor of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and has been shown to promote autophagy in several cancers. Here, we aimed to determine whether SPRED2 plays a role in autophagy in hepatocellular carcinoma (HCC) cells. The Cancer Genome Atlas (TCGA) Liver Cancer Database showed a negative association between the level of SPRED2 and p62, a ubiquitin-binding scaffold protein that accumulates when autophagy is inhibited. Immunohistochemically, accumulation of p62 was detected in human HCC tissues with low SPRED2 expression. Overexpression of SPRED2 in HCC cells increased the number of autophagosomes and autophagic vacuoles containing damaged mitochondria, decreased p62 levels, and increased levels of light-chain-3 (LC3)-II, an autophagy marker. In contrast, SPRED2 deficiency increased p62 levels and decreased LC3-II levels. SPRED2 expression levels were negatively correlated with translocase of outer mitochondrial membrane 20 (TOM20) expression levels, suggesting its role in mitophagy. Mechanistically, SPRED2 overexpression reduced ERK activation followed by the mechanistic or mammalian target of rapamycin complex 1 (mTORC1)-mediated signaling pathway, and SPRED2 deficiency showed the opposite pattern. Finally, hepatic autophagy was impaired in the liver of SPRED2-deficient mice with hepatic lipid droplet accumulation in response to starvation. These results indicate that SPRED2 is a critical regulator of autophagy not only in HCC cells, but also in hepatocytes, and thus the manipulation of this process may provide new insights into liver pathology. en-copyright= kn-copyright= en-aut-name=WangTianyi en-aut-sei=Wang en-aut-mei=Tianyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GaoTong en-aut-sei=Gao en-aut-mei=Tong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=autophagy kn-keyword=autophagy en-keyword=mitophagy kn-keyword=mitophagy en-keyword=SPRED proteins kn-keyword=SPRED proteins en-keyword=MAPK/ERK kn-keyword=MAPK/ERK en-keyword=mTOR kn-keyword=mTOR en-keyword=hepatocellular carcinoma kn-keyword=hepatocellular carcinoma END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=3 article-no= start-page=285 end-page=290 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202406 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Organized Chronic Subdural Hematoma (OCSDH) Mimicking Meningioma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Organized chronic subdural hematoma (OCSDH) is a relatively rare condition that forms over a longer period of time compared to chronic subdural hematoma and is sometimes difficult to diagnose with preoperative imaging. We resected an intracranial lesion in a 37-year-old Japanese man; the lesion had been increasing in size for >17 years. The preoperative diagnosis based on imaging findings was meningioma; however, pathological findings revealed OCSDH. Clinicians should be aware that OCSDH mimics other tumors and consider surgical strategies for this disease. en-copyright= kn-copyright= en-aut-name=HiranoShuichiro en-aut-sei=Hirano en-aut-mei=Shuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiiKentaro en-aut-sei=Fujii en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=meningioma kn-keyword=meningioma en-keyword=organized chronic subdural hematoma kn-keyword=organized chronic subdural hematoma END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=7 article-no= start-page=394 end-page=407 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240531 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The specific shapes of capillaries are associated with worse prognosis in patients with invasive breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Angiogenesis is considered essential for tumor progression; however, whether histological counting of blood vessel numbers, expressed as microvessel density (MVD), can be a prognostic factor in breast cancer remains controversial. It has been suggested that the specific morphology of blood vessels such as glomeruloid microvascular proliferation (GMP) is associated with clinical parameters. Here, we aimed to clarify the significance of MVD with revised immunohistochemistry and to identify new blood vessel shapes that predict prognosis in breast cancer. Four hundred and eleven primary breast cancer specimens were collected, and the sections were immunohistochemically stained with CD31 (single staining) and CD31 and Collagen IV (double staining). The prognosis of patients was examined based on the MVD value, and the presence of GMP and other blood vessels with other specific shapes. As a result, high MVD value and the presence of GMP were not associated with worse prognosis. By contrast, patients with deep-curved capillaries surrounding tumor cell nests (C-shaped) or excessively branched capillaries near tumor cell nests showed a significantly poor prognosis. The presence of these capillaries was also correlated with clinicopathological parameters such as Ki-67 index. Thus, the morphology of capillaries rather than MVD can be a better indicator of tumor aggressiveness. en-copyright= kn-copyright= en-aut-name=SweHnin]Wint]Wint en-aut-sei=Swe en-aut-mei=Hnin]Wint]Wint kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KomatsubaraYu en-aut-sei=Komatsubara en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=angiogenesis kn-keyword=angiogenesis en-keyword=blood vessels kn-keyword=blood vessels en-keyword=breast cancer kn-keyword=breast cancer en-keyword=CD31 antigen kn-keyword=CD31 antigen en-keyword=immunohistochemistry kn-keyword=immunohistochemistry en-keyword=microvessel density kn-keyword=microvessel density en-keyword=survival analysis kn-keyword=survival analysis END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=10 article-no= start-page=e174618 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Double-faced CX3CL1 enhances lymphangiogenesis-dependent metastasis in an aggressive subclone of oral squamous cell carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Because cancer cells have a genetically unstable nature, they give rise to genetically different variant subclones inside a single tumor. Understanding cancer heterogeneity and subclone characteristics is crucial for developing more efficacious therapies. Oral squamous cell carcinoma (OSCC) is characterized by high heterogeneity and plasticity. On the other hand, CX3C motif ligand 1 (CX3CL1) is a double-faced chemokine with anti- and pro -tumor functions. Our study reported that CX3CL1 functioned differently in tumors with different cancer phenotypes, both in vivo and in vitro. Mouse OSCC 1 (MOC1) and MOC2 cells responded similarly to CX3CL1 in vitro. However, in vivo, CX3CL1 increased keratinization in indolent MOC1 cancer, while CX3CL1 promoted cervical lymphatic metastasis in aggressive MOC2 cancer. These outcomes were due to double-faced CX3CL1 effects on different immune microenvironments indolent and aggressive cancer created. Furthermore, we established that CX3CL1 promoted cancer metastasis via the lymphatic pathway by stimulating lymphangiogenesis and transendothelial migration of lymph -circulating tumor cells. CX3CL1 enrichment in lymphatic metastasis tissues was observed in aggressive murine and human cell lines. OSCC patient samples with CX3CL1 enrichment exhibited a strong correlation with lower overall survival rates and higher recurrence and distant metastasis rates. In conclusion, CX3CL1 is a pivotal factor that stimulates the metastasis of aggressive cancer subclones within the heterogeneous tumors to metastasize, and our study demonstrates the prognostic value of CX3CL1 enrichment in long-term monitoring in OSCC. en-copyright= kn-copyright= en-aut-name=EainHtoo Shwe en-aut-sei=Eain en-aut-mei=Htoo Shwe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakayamaMasaaki en-aut-sei=Nakayama en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukuharaYoko en-aut-sei=Fukuhara en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShanQuisheng en-aut-sei=Shan en-aut-mei=Quisheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SoeYamin en-aut-sei=Soe en-aut-mei=Yamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OnoKisho en-aut-sei=Ono en-aut-mei=Kisho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MizukawaNobuyoshi en-aut-sei=Mizukawa en-aut-mei=Nobuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IidaSeiji en-aut-sei=Iida en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama Universit kn-affil= affil-num=6 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=2 article-no= start-page=86 end-page=96 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=2024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Spontaneous regression and rare relapse after excisional biopsy in long-term observation of 31 patients with primary conjunctival lymphoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=To elucidate long-term outcome in primary conjunctival lymphoma, a review was conducted of 31 consecutive patients: 21 men and 10 women with an age range of 28 to 85 (median, 61) years at presentation and follow-up periods ranging from 1 to 19 (median, 7) years. Conjunctival lymphoma was on the right side in 10 patients, on the left side in 12, and on both sides in 9. Upper, lower, or both fornix lesions in 28 patients were all diagnosed as extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), while thick nasal bulbar conjunctival lesions in 3 patients were differently diagnosed as MALT lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma, respectively. Seven patients underwent local radiation (30 Gy): as initial treatment in 5 patients and treatment for relapse in 2 patients. The remaining 24 patients were observed without additional treatment after excisional biopsy: 5 of these 24 patients showed relapse 0.5 to 6 years later and underwent excisional biopsy again that revealed MALT lymphoma. Of the 5 patients with relapse, only one with second-time relapse underwent radiation. Fluorodeoxyglucose positron emission tomography was performed in 18 patients and showed no systemic lesions: high uptake was noted in the residual conjunctival lesions of 4 patients and in the relapsed conjunctival lesions of 3 patients. One patient died of rectal cancer while no patients died of lymphoma. Observation is an option in patients with primary conjunctival lymphoma after excisional biopsy. Radiation is a treatment option in the case of relapse. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword= conjunctival lymphoma kn-keyword= conjunctival lymphoma en-keyword=extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) kn-keyword=extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) en-keyword=follicular lymphoma kn-keyword=follicular lymphoma en-keyword=diffuse large B-cell lymphoma kn-keyword=diffuse large B-cell lymphoma en-keyword=fluorodeoxyglucose positron emission tomography (FDG-PET) kn-keyword=fluorodeoxyglucose positron emission tomography (FDG-PET) END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=1 article-no= start-page=271 end-page=273 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trousseau's syndrome in diffuse large B-cell lymphoma en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatoYumiko en-aut-sei=Sato en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuyamaShoichi en-aut-sei=Kuyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center kn-affil= en-keyword=diffuse large B-cell lymphoma kn-keyword=diffuse large B-cell lymphoma en-keyword=multiple cerebral infarctions kn-keyword=multiple cerebral infarctions en-keyword=Trousseau's syndrome kn-keyword=Trousseau's syndrome END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue=2 article-no= start-page=e177 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230328 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical application of pancreatic juice-derived small extracellular vesicles of pancreatic ductal adenocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Recent imaging modalities have helped inthe early detection of pancreatic ductal adenocarcinoma (PDAC), resulting inimproved survival rates for patients with early-stage PDAC. However, preoperative pathological diagnosis of early-stage PDAC remains a challenge, particularly for small PDAC that is difficult to diagnose through standardendoscopic ultrasound-guided fine-needle biopsy. In this context, pancreaticjuice cytology has been re-evaluated as an important tool for the preoperativediagnosis of early-stage PDAC.
Main: Pancreatic juice (PJ) comes in directcontact with PDAC lesions in the pancreatic duct and thus may contain a fewHG-PanIN/PDAC cells and specific molecules. Additionally, the PJ may containconcentrated small extracellular vesicles (sEVs) that are released from cancerlesions. sEVs are double-layered lipid-bound particles that contain cargoassociated with the cell-of-origin, including proteins, microRNA, and RNA. sEVsreleased from cancer lesions found in body fluids, such as blood, urine, andsaliva, have already been studied as potential sources of diagnostic biomarkersfor cancer. PJ-derived sEVs could serve as a gliquid biopsyh for theearly diagnosis of PDAC. However, little is known about the existence,physiological status, and function of PJ-derived sEVs and their potentialutility as biomarkers for diagnostic, surveillance, and monitoring purposes oras therapeutic targets.
Conclusion: PJ-derived sEVs represent a promisingavenue for the early diagnosis of PDAC. The utility of these particles as biomarkersfor diagnostic, surveillance, and monitoring purposes, or as therapeutictargets, warrants further research. Understanding the existence, physiologicalstatus, and function of PJ-derived sEVs is crucial to unlocking their potentialas a valuable tool for overcoming PDAC. en-copyright= kn-copyright= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= en-keyword=biomarker kn-keyword=biomarker en-keyword=early diagnosis kn-keyword=early diagnosis en-keyword=high-grade PanIN kn-keyword=high-grade PanIN en-keyword=IPMN kn-keyword=IPMN en-keyword=liquid biopsy kn-keyword=liquid biopsy en-keyword=pancreatic ductal carcinoma kn-keyword=pancreatic ductal carcinoma en-keyword=pancreatic juice kn-keyword=pancreatic juice en-keyword=small extracellular vesicle kn-keyword=small extracellular vesicle en-keyword=treatment kn-keyword=treatment END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=5 article-no= start-page=e8933 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202405 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Decades of stability of conjunctival vascular malformations in two patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 65-year-old woman with diabetic retinopathy underwent glaucoma surgery to construct a filtering bleb adjacent to conjunctival hemangioma, and showed bleb function and stable hemangioma for a decade. A 1.5-year-old girl with right eye lid and cheek swelling by orbital to facial lymphangioma was followed for visual acuity development. Conjunctival lymphangioma was stable in 20?years. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimataYoshihiro en-aut-sei=Kimata en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=hemangioma kn-keyword=hemangioma en-keyword=lymphangioma kn-keyword=lymphangioma en-keyword=lymphatic malformation kn-keyword=lymphatic malformation en-keyword=pathology kn-keyword=pathology en-keyword=trabeculectomy kn-keyword=trabeculectomy en-keyword=vascular malformation kn-keyword=vascular malformation END start-ver=1.4 cd-journal=joma no-vol=120 cd-vols= no-issue=1 article-no= start-page=128 end-page=134 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240415 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Spontaneous regression of multiple solitary plasmacytoma harboring Epstein?Barr virus: a case report and literature review en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report a rare case of spontaneous regression (SR) in an elderly untreated patient with multiple solitary plasmacytoma (MSP). Diagnosis of MSP was confirmed through surgical resection of the left nasal cavity mass and subsequent biopsy of the right humerus. The patient was considered ineligible for chemotherapy due to poor performance status. At 3-month post-diagnosis, the patientfs condition worsened with deteriorating bone lesions and emergence of a new serum monoclonal protein. However, these clinical findings completely disappeared at 6 months, and positron emission tomography?computed tomography at 1 year confirmed complete metabolic remission. Notably, peripheral blood lymphocyte counts were inversely correlated with tumor progression and remission. Pathological re-evaluation of the initial biopsy specimens revealed programmed cell death protein 1 (PD-1) expression in tumor-infiltrating CD8+ T cells. In addition, tumor cells were infected with Epstein?Barr virus (EBV) but were negative for programmed cell death ligand 1 (PD-L1) expression, which is the most potent immune escape mechanism in tumor cells. While the mechanism underlying SR remains unclear, our findings suggest that host immune response as well as EBV infection may contribute to SR. Further studies are needed to elucidate the clinicopathologic mechanisms of tumor regression in plasma cell neoplasms. en-copyright= kn-copyright= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NodaMinori en-aut-sei=Noda en-aut-mei=Minori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IsekiAkiko en-aut-sei=Iseki en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoYumi en-aut-sei=Sato en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KuyamaShoichi en-aut-sei=Kuyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Otorhinolaryngology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=4 en-affil=Department of Pathology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=5 en-affil=Department of Pathology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center kn-affil= en-keyword=Plasmacytoma kn-keyword=Plasmacytoma en-keyword=Epstein?Barr virus kn-keyword=Epstein?Barr virus en-keyword=Spontaneous regression kn-keyword=Spontaneous regression END start-ver=1.4 cd-journal=joma no-vol=72 cd-vols= no-issue=11 article-no= start-page=3787 end-page=3802 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230905 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=PD-L1-expressing cancer-associated fibroblasts induce tumor immunosuppression and contribute to poor clinical outcome in esophageal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=The programmed cell death 1 protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays a crucial role in tumor immunosuppression, while the cancer-associated fibroblasts (CAFs) have various tumor-promoting functions. To determine the advantage of immunotherapy, the relationship between the cancer cells and the CAFs was evaluated in terms of the PD-1/PD-L1 axis. Overall, 140 cases of esophageal cancer underwent an immunohistochemical analysis of the PD-L1 expression and its association with the expression of the smooth muscle actin, fibroblast activation protein, CD8, and forkhead box P3 (FoxP3) positive cells. The relationship between the cancer cells and the CAFs was evaluated in vitro, and the effect of the anti-PD-L1 antibody was evaluated using a syngeneic mouse model. A survival analysis showed that the PD-L1+ CAF group had worse survival than the PD-L1- group. In vitro and in vivo, direct interaction between the cancer cells and the CAFs showed a mutually upregulated PD-L1 expression. In vivo, the anti-PD-L1 antibody increased the number of dead CAFs and cancer cells, resulting in increased CD8+ T cells and decreased FoxP3+ regulatory T cells. We demonstrated that the PD-L1-expressing CAFs lead to poor outcomes in patients with esophageal cancer. The cancer cells and the CAFs mutually enhanced the PD-L1 expression and induced tumor immunosuppression. Therefore, the PD-L1-expressing CAFs may be good targets for cancer therapy, inhibiting tumor progression and improving host tumor immunity. en-copyright= kn-copyright= en-aut-name=KawasakiKento en-aut-sei=Kawasaki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatoTakuya en-aut-sei=Kato en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakedaYasushige en-aut-sei=Takeda en-aut-mei=Yasushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoHijiri en-aut-sei=Matsumoto en-aut-mei=Hijiri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishimuraSeitaro en-aut-sei=Nishimura en-aut-mei=Seitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KunitomoTomoyoshi en-aut-sei=Kunitomo en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AkaiMasaaki en-aut-sei=Akai en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KobayashiTeruki en-aut-sei=Kobayashi en-aut-mei=Teruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NishiwakiNoriyuki en-aut-sei=Nishiwaki en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KashimaHajime en-aut-sei=Kashima en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MaedaNaoaki en-aut-sei=Maeda en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Esophageal cancer kn-keyword=Esophageal cancer en-keyword=Cancer-associated fibroblasts kn-keyword=Cancer-associated fibroblasts en-keyword=Programmed cell death 1 kn-keyword=Programmed cell death 1 en-keyword=Program cell death ligand 1 kn-keyword=Program cell death ligand 1 en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=140 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240422 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Endoscopic manifestation of intestinal transplant-associated microangiopathy after stem cell transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Endoscopic features of intestinal transplant-associated microangiopathy (iTAM) have not been comprehensively investigated. This study aimed to examine the endoscopic characteristics of patients diagnosed with iTAM.
Methods This retrospective analysis included 14 patients pathologically diagnosed with iTAM after stem cell transplantation for hematolymphoid neoplasms (n = 13) or thalassemia (n = 1). The sex, age at diagnosis, endoscopic features, and prognosis of each patient were assessed. Serological markers for diagnosing transplant-associated thrombotic microangiopathy were also evaluated.
Results The mean age at the time of iTAM diagnosis was 40.2 years. Patients diagnosed based on the pathognomonic pathological changes of iTAM presented with diverse symptoms at the times of endoscopic examinations, including diarrhea (n = 10), abdominal pain (n = 5), nausea (n = 4), appetite loss (n = 2), bloody stools (n = 2), abdominal discomfort (n = 1), and vomiting (n = 1). At the final follow-up, six patients survived, while eight patients succumbed, with a median time of 100.5 days (range: 52-247) post-diagnosis. Endoscopic manifestations included erythematous mucosa (n = 14), erosions (n = 13), ulcers (n = 9), mucosal edema (n = 9), granular mucosa (n = 9), and villous atrophy (n = 4). Erosions and/or ulcers were primarily observed in the colon (10/14, 71%), followed by the ileum (9/13, 69%), stomach (4/10, 40%), cecum (5/14, 36%), duodenum (3/10, 30%), rectum (4/14, 29%), and esophagus (1/10, 10%). Cytomegalovirus infection (n = 4) and graft-versus-host disease (n = 2) coexisted within the gastrointestinal tract. Patients had de novo prolonged or progressive thrombocytopenia (6/14, 43%), decreased hemoglobin concentration (4/14, 29%), reduced serum haptoglobin level (3/14, 21%), and a sudden and persistent increase in lactate dehydrogenase level (2/14, 14%). Peripheral blood samples from 12 patients were evaluated for schistocytes, with none exceeding 4%.
Conclusions This study provides a comprehensive exploration of the endoscopic characteristics of iTAM. Notably, all patients exhibited erythematous mucosa throughout the gastrointestinal tract, accompanied by prevalent manifestations, such as erosions (93%), ulcers (64%), mucosal edema (64%), granular mucosa (64%), and villous atrophy (29%). Because of the low positivity for serological markers of transplant-associated thrombotic microangiopathy in patients with iTAM, endoscopic evaluation and biopsy of these lesions are crucial, even in the absence of these serological features. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuokaKen-Ichi en-aut-sei=Matsuoka en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InokuchiToshihiro en-aut-sei=Inokuchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Colonoscopy kn-keyword=Colonoscopy en-keyword=Esophagogastroduodenoscopy kn-keyword=Esophagogastroduodenoscopy en-keyword=Graft-versus-host disease kn-keyword=Graft-versus-host disease en-keyword=Hematopoietic stem cell transplantation kn-keyword=Hematopoietic stem cell transplantation en-keyword=Intestinal transplant-associated microangiopathy kn-keyword=Intestinal transplant-associated microangiopathy en-keyword=iTAM kn-keyword=iTAM END start-ver=1.4 cd-journal=joma no-vol=174 cd-vols= no-issue=6 article-no= start-page=533 end-page=548 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230919 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phosphorylated SARM1 is involved in the pathological process of rotenone-induced neurodegeneration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sterile alpha and Toll/interleukin receptor motif-containing protein 1 (SARM1) is a NAD+ hydrolase that plays a key role in axonal degeneration and neuronal cell death. We reported that c-Jun N-terminal kinase (JNK) activates SARM1 through phosphorylation at Ser-548. The importance of SARM1 phosphorylation in the pathological process of Parkinsonfs disease (PD) has not been determined. We thus conducted the present study by using rotenone (an inducer of PD-like pathology) and neurons derived from induced pluripotent stem cells (iPSCs) from healthy donors and a patient with familial PD PARK2 (FPD2). The results showed that compared to the healthy neurons, FPD2 neurons were more vulnerable to rotenone-induced stress and had higher levels of SARM1 phosphorylation. Similar cellular events were obtained when we used PARK2-knockdown neurons derived from healthy donor iPSCs. These events in both types of PD-model neurons were suppressed in neurons treated with JNK inhibitors, Ca2+-signal inhibitors, or by a SARM1-knockdown procedure. The degenerative events were enhanced in neurons overexpressing wild-type SARM1 and conversely suppressed in neurons overexpressing the SARM1-S548A mutant. We also detected elevated SARM1 phosphorylation in the midbrain of PD-model mice. The results indicate that phosphorylated SARM1 plays an important role in the pathological process of rotenone-induced neurodegeneration. en-copyright= kn-copyright= en-aut-name=MurataHitoshi en-aut-sei=Murata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PhooMay Tha Zin en-aut-sei=Phoo en-aut-mei=May Tha Zin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OchiToshiki en-aut-sei=Ochi en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoKen-ichi en-aut-sei=Yamamoto en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KinoshitaRie en-aut-sei=Kinoshita en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=JNK kn-keyword=JNK en-keyword=PARK2 kn-keyword=PARK2 en-keyword=Parkinsonfsdisease kn-keyword=Parkinsonfsdisease en-keyword=Phosphorylation kn-keyword=Phosphorylation en-keyword=SARM1 kn-keyword=SARM1 END start-ver=1.4 cd-journal=joma no-vol=37 cd-vols= no-issue=9 article-no= start-page=6736 end-page=6748 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Diagnostic accuracy of frozen section biopsy for early gastric cancer extent during endoscopic submucosal dissection: a prospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Accurate diagnosis of the lateral extent of early gastric cancer during endoscopic submucosal dissection (ESD) is crucial to achieve negative resection margins. Similar to intraoperative consultation with a frozen section in surgery, rapid frozen section diagnosis with endoscopic forceps biopsy may be useful in assessing tumor margins during ESD. This study aimed to evaluate the diagnostic accuracy of frozen section biopsy.
Methods We prospectively enrolled 32 patients undergoing ESD for early gastric cancer. Biopsy samples for the frozen sections were randomly collected from fresh resected ESD specimens before formalin fixation. Two different pathologists independently diagnosed 130 frozen sections as gneoplasia,h gnegative for neoplasia,h or gindefinite for neoplasia,h and the frozen section diagnosis was compared with the final pathological results of the ESD specimens.
Results Among the 130 frozen sections, 35 were from cancerous areas, and 95 were from non-cancerous areas. The diagnostic accuracies of the frozen section biopsies by the two pathologists were 98.5 and 94.6%, respectively. Cohenfs kappa coefficient of diagnoses by the two pathologists was 0.851 (95% confidence interval: 0.837?0.864). Incorrect diagnoses resulted from freezing artifacts, a small volume of tissue, inflammation, the presence of well-differentiated adenocarcinoma with mild nuclear atypia, and/or tissue damage during ESD.
Conclusions Pathological diagnosis of frozen section biopsy is reliable and can be applied as a rapid frozen section diagnosis for evaluating the lateral margins of early gastric cancer during ESD. en-copyright= kn-copyright= en-aut-name=KobashiMayu en-aut-sei=Kobashi en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshikawaShigenao en-aut-sei=Ishikawa en-aut-mei=Shigenao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InabaTomoki en-aut-sei=Inaba en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AoyamaYuki en-aut-sei=Aoyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KagawaTomo en-aut-sei=Kagawa en-aut-mei=Tomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeuchiYasuto en-aut-sei=Takeuchi en-aut-mei=Yasuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AndoMidori en-aut-sei=Ando en-aut-mei=Midori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraSatoko en-aut-sei=Nakamura en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology, Kagawa Prefectural Central Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology, Kagawa Prefectural Central Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Kagawa Prefectural Central Hospital kn-affil= affil-num=7 en-affil=Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pathology, Kagawa Prefectural Central Hospital kn-affil= affil-num=9 en-affil=Department of Pathology, Kagawa Prefectural Central Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Frozen section kn-keyword=Frozen section en-keyword=Pathological diagnosis kn-keyword=Pathological diagnosis en-keyword=Diagnostic accuracy kn-keyword=Diagnostic accuracy en-keyword=Early gastric cancer kn-keyword=Early gastric cancer en-keyword=Endoscopic submucosal dissection kn-keyword=Endoscopic submucosal dissection en-keyword=Lateral margin kn-keyword=Lateral margin END start-ver=1.4 cd-journal=joma no-vol=42 cd-vols= no-issue=3 article-no= start-page=319 end-page=325 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231014 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prospective evaluation of core number of biopsy for renal tumor: are multiple cores preferable? en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose This single-center, single-arm, prospective, open-label study was conducted to evaluate the optimal number of cores (single or multiple) in renal tumor biopsy.
Materials and methods Forty-four biopsies of 44 tumors (mean diameter, 2.7?}?1.0 cm; range, 1.6?5.0 cm) were included. Biopsy was performed under ultrasound or computed tomography fluoroscopy guidance using an 18-gauge cutting needle and the co-axial method. Two or more specimens were obtained, which were divided into first and subsequent specimens. gFirst specimenh and gall specimensh were histologically evaluated (i.e., appropriateness of specimen, histological diagnosis, subtype, and Fuhrman grade of renal cell carcinoma [RCC]) blindly and independently by two board-certified pathologists.
Results Multiple specimens were successfully and safely obtained in all the biopsies. All tumors were histologically diagnosed; 40 malignancies included 39 RCCs and 1 solitary fibrous tumor, and 4 benign lesions included 2 angiomyolipomas, 1 oncocytoma, and 1 capillary hemangioma. In all RCCs, the subtype could be determined (32 clear cell RCCs, 4 chromophobe RCCs, and 3 papillary RCCs), and the Furman grade was determined in 38 RCCs. When only the first specimen was evaluated, 22.7% of the specimens were inappropriate for diagnosis, and 34 (77.3%) were histologically diagnosed. The diagnostic yield was significantly lower than that of all specimens (P?=?0.0044). Univariate analysis revealed that smaller lesions were a significant predictor of diagnostic failure (P?=?0.020).
Conclusion Biopsy with multiple cores significantly improved diagnostic yield. Thus, operators should obtain multiple cores during renal tumor biopsy. en-copyright= kn-copyright= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuiYusuke en-aut-sei=Matsui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TojiTomohiro en-aut-sei=Toji en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakuraiJun en-aut-sei=Sakurai en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TomitaKoji en-aut-sei=Tomita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UkaMayu en-aut-sei=Uka en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UmakoshiNoriyuki en-aut-sei=Umakoshi en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawabataTakahiro en-aut-sei=Kawabata en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MunetomoKazuaki en-aut-sei=Munetomo en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Biopsy kn-keyword=Biopsy en-keyword=Kidney kn-keyword=Kidney en-keyword=Tumor kn-keyword=Tumor en-keyword=Computed tomography kn-keyword=Computed tomography en-keyword=Ultrasound kn-keyword=Ultrasound END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=2 article-no= start-page=201 end-page=204 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Gallbladder Cancer with Trousseau Syndrome Successfully Treated Using Radical Resection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Trousseau syndrome is characterized by cancer-associated systemic thrombosis. We describe the first case of a successfully treated gallbladder adenocarcinoma accompanied by Trousseau syndrome. A 66-year-old woman presented with right hemiplegia. Magnetic resonance imaging identified multiple cerebral infarctions. Her serum carbohydrate antigen 19-9 and D-dimer levels were markedly elevated, and a gallbladder tumor was detected via abdominal computed tomography. Venous ultrasonography of the lower limbs revealed a deep venous thrombus in the right peroneal vein. These findings suggested that the brain infarctions were likely caused by Trousseau syndrome associated with her gallbladder cancer. Radical resection of the gallbladder tumor was performed. The resected gallbladder was filled with mucus and was pathologically diagnosed as an adenocarcinoma. Her postoperative course was uneventful, and she received a one-year course of adjuvant therapy with oral S-1. No cancer recurrence or thrombosis was noted 26 months postoperatively. Despite concurrent Trousseau syndrome, a radical cure of the primary tumor and thrombosis could be achieved with the appropriate treatment. en-copyright= kn-copyright= en-aut-name=MasunagaAkari en-aut-sei=Masunaga en-aut-mei=Akari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TabuchiMotoyasu en-aut-sei=Tabuchi en-aut-mei=Motoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakamotoShinya en-aut-sei=Sakamoto en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshimatsuRika en-aut-sei=Yoshimatsu en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoManabu en-aut-sei=Matsumoto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwataJun en-aut-sei=Iwata en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkabayashiTakehiro en-aut-sei=Okabayashi en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=4 en-affil=Department of Radiology, Kochi Health Sciences Center kn-affil= affil-num=5 en-affil=Department of Radiology, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= en-keyword=gallbladder cancer kn-keyword=gallbladder cancer en-keyword=Trousseau syndrome kn-keyword=Trousseau syndrome en-keyword=radical surgery kn-keyword=radical surgery END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=2 article-no= start-page=143 end-page=149 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Travel Distance on Surgical Outcomes of Patients Surgically Treated for Non-Small Cell Lung Cancer: A Single-Center Study in Ehime, Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Travel burden is a poor prognostic factor for many cancers worldwide because it hinders optimal diagnosis and treatment planning. Currently, the impact of travel burden on survival after surgery for non-small cell lung cancer (NSCLC) in Japan is largely unexplored. We examined the impact of travel distance on the postoperative outcomes of patients with NSCLC in Ehime Prefecture, Japan. The data of 1212 patients who underwent surgical resection for NSCLC were retrospectively reviewed. Patients were divided into quartiles based on the travel distance from their home to the hospital (? 13 km, 13-40 km, 40-57 km, and > 57 km) in Ehime Prefecture. We found no significant differences among the quartiles in baseline clinicopathological characteristics, including sex, smoking status, histology, surgical procedure, clinical stage, and pathological stage. Overall survival (OS) and relapse-free survival (RFS) also were not significantly different among the travel distance quartiles. We conclude that travel distance did not impact OS or RFS among patients with NSCLC who underwent surgical resection at our institution. en-copyright= kn-copyright= en-aut-name=ShigematsuHisayuki en-aut-sei=Shigematsu en-aut-mei=Hisayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamashitaNatsumi en-aut-sei=Yamashita en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuehisaHiroshi en-aut-sei=Suehisa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UenoTsuyoshi en-aut-sei=Ueno en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RyukoTsuyoshi en-aut-sei=Ryuko en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugiharaTakahito en-aut-sei=Sugihara en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakashimaShohei en-aut-sei=Nakashima en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SanoYoshifumi en-aut-sei=Sano en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, NHO Shikoku Cancer Center kn-affil= affil-num=2 en-affil=Clinical Research Center, NHO Shikoku Cancer Center kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, NHO Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Thoracic Surgery, NHO Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Thoracic Surgery, NHO Shikoku Cancer Center kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, NHO Shikoku Cancer Center kn-affil= affil-num=7 en-affil=Department of Thoracic Surgery, NHO Shikoku Cancer Center kn-affil= affil-num=8 en-affil=Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Thoracic Surgery, NHO Shikoku Cancer Center kn-affil= en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=travel distance kn-keyword=travel distance en-keyword=travel burden kn-keyword=travel burden en-keyword=lung surgery kn-keyword=lung surgery en-keyword=surgical outcome kn-keyword=surgical outcome END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=7 article-no= start-page=1298 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Copy Number Analysis of 9p24.1 in Classic Hodgkin Lymphoma Arising in Immune Deficiency/Dysregulation en-subtitle= kn-subtitle= en-abstract= kn-abstract=A subset of patients with rheumatoid arthritis receiving methotrexate develop immune deficiencies and dysregulation-associated lymphoproliferative disorders. Patients with these disorders often exhibit spontaneous regression after MTX withdrawal; however, chemotherapeutic intervention is frequently required in patients with classic Hodgkin lymphoma arising in immune deficiency/dysregulation. In this study, we examined PD-L1 expression levels and 9p24.1 copy number alterations in 27 patients with classic Hodgkin lymphoma arising from immune deficiency/dysregulation. All patients demonstrated PD-L1 protein expression and harbored 9p24.1 copy number alterations on the tumor cells. When comparing clinicopathological data and associations with 9p24.1 copy number features, the copy gain group showed a significantly higher incidence of extranodal lesions and clinical stages than the amplification group. Notably, all cases in the amplification group had latency type II, while 6/8 (75%) in the copy gain group had latency type II, and 2/8 (25%) had latency type I. Thus, a subset of the copy-gain group demonstrated more extensive extranodal lesions and higher clinical stages. This finding speculates the presence of a genetically distinct subgroup within the group of patients who develop immune deficiencies and dysregulation-associated lymphoproliferative disorders, which may explain certain characteristic features. en-copyright= kn-copyright= en-aut-name=OhsawaKumiko en-aut-sei=Ohsawa en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MomoseShuji en-aut-sei=Momose en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GionYuka en-aut-sei=Gion en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SawadaKeisuke en-aut-sei=Sawada en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigashiMorihiro en-aut-sei=Higashi en-aut-mei=Morihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TokuhiraMichihide en-aut-sei=Tokuhira en-aut-mei=Michihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TamaruJun-Ichi en-aut-sei=Tamaru en-aut-mei=Jun-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=3 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health Sciences kn-affil= affil-num=6 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=7 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=8 en-affil=Department of Hematology, Japan Community Health Care Organization Saitama Medical Center kn-affil= affil-num=9 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=10 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=classic Hodgkin lymphoma kn-keyword=classic Hodgkin lymphoma en-keyword=methotrexate kn-keyword=methotrexate en-keyword=immunodeficiency kn-keyword=immunodeficiency en-keyword=programmed cell death-ligand 1 kn-keyword=programmed cell death-ligand 1 en-keyword=rheumatoid arthritis kn-keyword=rheumatoid arthritis END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=2 article-no= start-page=rkae045 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ANCA-associated vasculitis with isolated splenomegaly as the initial organ presentation en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuratsuneMasatoshi en-aut-sei=Kuratsune en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IsekiAkiko en-aut-sei=Iseki en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuyamaShoichi en-aut-sei=Kuyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=3 en-affil=Department of Pathology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center kn-affil= END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=2 article-no= start-page=123 end-page=134 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sigle Agent of Posttransplant Cyclophosphamide Without Calcineurin Inhibitor Controls Severity of Experimental Chronic GVHD en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HCT), but its pathogenesis remains unclear. Recently, haplo-identical HCT with post-transplant cyclophosphamide (Haplo-HCT with PTCY) was found to achieve a low incidence rate of acute GVHD and chronic GVHD. However, while the pathogenesis of acute GVHD following Haplo-HCT with PTCY has been well investigated, that of chronic GVHD remains to be elucidated, especially in HLA-matched HCT with PTCY. Based on its safety profile, PTCY is currently applied for the human leucocyte antigen (HLA)-matched HCT setting. Here, we investigated the mechanisms of chronic GVHD following HLA-matched HCT with PTCY using a well-defined mouse chronic GVHD model. PTCY attenuated clinical and pathological chronic GVHD by suppressing effector T-cells and preserving regulatory T-cells compared with a control group. Additionally, we demonstrated that cyclosporine A (CsA) did not show any additional positive effects on attenuation of GVHD in PTCY-treated recipients. These results suggest that monotherapy with PTCY without CsA could be a promising strategy for the prevention of chronic GVHD following HLA-matched HCT. en-copyright= kn-copyright= en-aut-name=SaekiKyosuke en-aut-sei=Saeki en-aut-mei=Kyosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuroiTaiga en-aut-sei=Kuroi en-aut-mei=Taiga kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Division of Transfusion, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=GVHD kn-keyword=GVHD en-keyword=posttransplant cyclophosphamide kn-keyword=posttransplant cyclophosphamide en-keyword=hematopoietic cell transplantation kn-keyword=hematopoietic cell transplantation en-keyword=HLA-identical kn-keyword=HLA-identical END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=2 article-no= start-page=115 end-page=122 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impacts of Age and Gender on Brain Edema in a Mouse Water Intoxication Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Brain edema causes abnormal fluid retention and can be fatal in severe cases. Although it develops in various diseases, most treatments for brain edema are classical. We analyzed the impacts of age and gender on the characteristics of a water intoxication model that induces pure brain edema in mice and examined the modelfs usefulness for research regarding new treatments for brain edema. C57BL/6J mice received an intraperitoneal administration of 10% body weight distilled water, and we calculated the brain water content by measuring the brain-tissue weight immediately after dissection and after drying. We analyzed 8-OHdG and caspase-3 values to investigate the brain damage. We also applied this model in aquaporin 4 knockout (AQP4?) mice and compared these mice with wild-type mice. The changes in water content differed by age and gender, and the 8-OHdG and caspase-3 values differed by age. Suppression of brain edema by AQP4? was also confirmed. These results clarified the differences in the onset of brain edema by age and gender, highlighting the importance of considering the age and gender of model animals. Similar studies using genetically modified mice are also possible. Our findings indicate that this water intoxication model is effective for explorations of new brain edema treatments. en-copyright= kn-copyright= en-aut-name=Nakamura-MaruyamaEmi en-aut-sei=Nakamura-Maruyama en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IrieKeiichiro en-aut-sei=Irie en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NaritaKazuhiko en-aut-sei=Narita en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HimiNaoyuki en-aut-sei=Himi en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyamotoOsamu en-aut-sei=Miyamoto en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraTakehiro en-aut-sei=Nakamura en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Physiology2, Kawasaki Medical School kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Kagawa University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Physiology2, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Physiology2, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Physiology2, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Physiology2, Kawasaki Medical School kn-affil= en-keyword=brain edema kn-keyword=brain edema en-keyword=water intoxication model kn-keyword=water intoxication model en-keyword=age kn-keyword=age en-keyword=gender kn-keyword=gender en-keyword=AQP4 kn-keyword=AQP4 END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=2 article-no= start-page=95 end-page=106 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Roles of Neuropeptide Y in Respiratory Disease Pathogenesis via the Airway Immune Response en-subtitle= kn-subtitle= en-abstract= kn-abstract=The lungs are very complex organs, and the respiratory system performs the dual roles of repairing tissue while protecting against infection from various environmental stimuli. Persistent external irritation disrupts the immune responses of tissues and cells in the respiratory system, ultimately leading to respiratory disease. Neuropeptide Y (NPY) is a 36-amino-acid polypeptide and a neurotransmitter that regulates homeostasis. The NPY receptor is a seven-transmembrane-domain G-protein-coupled receptor with six subtypes (Y1, Y2, Y3, Y4, Y5, and Y6). Of these receptors, Y1, Y2, Y4, and Y5 are functional in humans, and Y1 plays important roles in the immune responses of many organs, including the respiratory system. NPY and the Y1 receptor have critical roles in the pathogenesis of asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis. The effects of NPY on the airway immune response and pathogenesis differ among respiratory diseases. This review focuses on the involvement of NPY in the airway immune response and pathogenesis of various respiratory diseases. en-copyright= kn-copyright= en-aut-name=ItanoJunko en-aut-sei=Itano en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyaharaNobuaki en-aut-sei=Miyahara en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=neuropeptide y kn-keyword=neuropeptide y en-keyword=Y1 receptor kn-keyword=Y1 receptor en-keyword=airway immune response kn-keyword=airway immune response en-keyword=bronchial epithelial cells kn-keyword=bronchial epithelial cells en-keyword=respiratory disease kn-keyword=respiratory disease END start-ver=1.4 cd-journal=joma no-vol=53 cd-vols= no-issue=11 article-no= start-page=1009 end-page=1018 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230825 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Advances in treatment of alveolar soft part sarcoma: an updated review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Alveolar soft part sarcoma is a rare neoplasm of uncertain histogenesis that belongs to a newly defined category of ultra-rare sarcomas. The neoplasm is characterized by a specific chromosomal translocation, der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1?TFE3 gene fusion. The natural history of alveolar soft part sarcoma describes indolent behaviour with slow progression in deep soft tissues of the extremities, trunk and head/neck in adolescents and young adults. A high rate of detection of distant metastasis at presentation has been reported, and the most common metastatic sites in decreasing order of frequency are the lung, bone and brain. Complete surgical resection remains the standard treatment strategy, whereas radiotherapy is indicated for patients with inadequate surgical margins or unresectable tumours. Although alveolar soft part sarcoma is refractory to conventional doxorubicin-based chemotherapy, monotherapy or combination therapy using tyrosine kinase inhibitors and immune checkpoint inhibitors have provided antitumor activity and emerged as new treatment strategies. This article provides an overview of the current understanding of this ultra-rare sarcoma and recent advancements in treatments according to the clinical stage of alveolar soft part sarcoma. en-copyright= kn-copyright= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishidaKenji en-aut-sei=Nishida en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraTomoki en-aut-sei=Nakamura en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaKazuhiro en-aut-sei=Tanaka en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Mie University kn-affil= affil-num=7 en-affil=Department of Advanced Medical Sciences, Oita University kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=alveolar soft part sarcoma kn-keyword=alveolar soft part sarcoma en-keyword=surgery kn-keyword=surgery en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=targeted therapy kn-keyword=targeted therapy en-keyword=immunotherapy kn-keyword=immunotherapy END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue= article-no= start-page=1371342 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240326 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lysyl oxidase-like 4 promotes the invasiveness of triple-negative breast cancer cells by orchestrating the invasive machinery formed by annexin A2 and S100A11 on the cell surface en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Our earlier research revealed that the secreted lysyl oxidase-like 4 (LOXL4) that is highly elevated in triple-negative breast cancer (TNBC) acts as a catalyst to lock annexin A2 on the cell membrane surface, which accelerates invasive outgrowth of the cancer through the binding of integrin-1 on the cell surface. However, whether this machinery is subject to the LOXL4-mediated intrusive regulation remains uncertain.

Methods: Cell invasion was assessed using a transwell-based assay, protein?protein interactions by an immunoprecipitation?Western blotting technique and immunocytochemistry, and plasmin activity in the cell membrane by gelatin zymography.

Results: We revealed that cell surface annexin A2 acts as a receptor of plasminogen via interaction with S100A10, a key cell surface annexin A2-binding factor, and S100A11. We found that the cell surface annexin A2/S100A11 complex leads to mature active plasmin from bound plasminogen, which actively stimulates gelatin digestion, followed by increased invasion.

Conclusion: We have refined our understanding of the role of LOXL4 in TNBC cell invasion: namely, LOXL4 mediates the upregulation of annexin A2 at the cell surface, the upregulated annexin 2 binds S100A11 and S100A10, and the resulting annexin A2/S100A11 complex acts as a receptor of plasminogen, readily converting it into active-form plasmin and thereby enhancing invasion. en-copyright= kn-copyright= en-aut-name=TakahashiTetta en-aut-sei=Takahashi en-aut-mei=Tetta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KinoshitaRie en-aut-sei=Kinoshita en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoKen-Ichi en-aut-sei=Yamamoto en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurataHitoshi en-aut-sei=Murata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KomalasariNi Luh Gede Yoni en-aut-sei=Komalasari en-aut-mei=Ni Luh Gede Yoni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ChenYouyi en-aut-sei=Chen en-aut-mei=Youyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=JiangFan en-aut-sei=Jiang en-aut-mei=Fan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=GoharaYuma en-aut-sei=Gohara en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OchiToshiki en-aut-sei=Ochi en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=RumaI. Made Winarsa en-aut-sei=Ruma en-aut-mei=I. Made Winarsa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SumardikaI. Wayan en-aut-sei=Sumardika en-aut-mei=I. Wayan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ZhouJin en-aut-sei=Zhou en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HonjoTomoko en-aut-sei=Honjo en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SakaguchiYoshihiko en-aut-sei=Sakaguchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YamauchiAkira en-aut-sei=Yamauchi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KuribayashiFutoshi en-aut-sei=Kuribayashi en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KondoEisaku en-aut-sei=Kondo en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=InoueYusuke en-aut-sei=Inoue en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FutamiJunichiro en-aut-sei=Futami en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=7 en-affil=Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=8 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=12 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=13 en-affil=Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of Technology kn-affil= affil-num=14 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=15 en-affil=Department of Microbiology, Tokushima Bunri University kn-affil= affil-num=16 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=17 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=18 en-affil=Division of Tumor Pathology, Near InfraRed Photo-Immuno-Therapy Research Institute, Kansai Medical University kn-affil= affil-num=19 en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University kn-affil= affil-num=20 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=21 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=22 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=23 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=lysyl oxidase kn-keyword=lysyl oxidase en-keyword=annexin A2 kn-keyword=annexin A2 en-keyword=S100A11 kn-keyword=S100A11 en-keyword=plasmin kn-keyword=plasmin en-keyword=cancer microenvironment kn-keyword=cancer microenvironment END start-ver=1.4 cd-journal=joma no-vol=65 cd-vols= no-issue=3 article-no= start-page=100510 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202403 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nuclear SphK2/S1P signaling is a key regulator of ApoE production and A uptake in astrocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=The link between changes in astrocyte function and the pathological progression of Alzheimer's disease (AD) has attracted considerable attention. Interestingly, activated astrocytes in AD show abnormalities in their lipid content and metabolism. In particular, the expression of apolipoprotein E (ApoE), a lipid transporter, is decreased. Because ApoE has anti-inflammatory and amyloid (A)-metabolizing effects, the nuclear receptors, retinoid X receptor (RXR) and LXR, which are involved in ApoE expression, are considered promising therapeutic targets for AD. However, the therapeutic effects of agents targeting these receptors are limited or vary considerably among groups, indicating the involvement of an unknown pathological factor that modifies astrocyte and ApoE function. Here, we focused on the signaling lipid, sphingosine-1-phosphate (S1P), which is mainly produced by sphingosine kinase 2 (SphK2) in the brain. Using astrocyte models, we found that upregulation of SphK2/S1P signaling suppressed ApoE induction by both RXR and LXR agonists. We also found that SphK2 activation reduced RXR binding to the APOE promoter region in the nucleus, suggesting the nuclear function of SphK2/S1P. Intriguingly, suppression of SphK2 activity by RNA knockdown or specific inhibitors upregulated lipidated ApoE induction. Furthermore, the induced ApoE facilitates A uptake in astrocytes. Together with our previous findings that SphK2 activity is upregulated in AD brain and promotes A production in neurons, these results indicate that SphK2/S1P signaling is a promising multifunctional therapeutic target for AD that can modulate astrocyte function by stabilizing the effects of RXR and LXR agonists, and simultaneously regulate neuronal pathogenesis. en-copyright= kn-copyright= en-aut-name=KomaiMasato en-aut-sei=Komai en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NodaYuka en-aut-sei=Noda en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IkedaAtsuya en-aut-sei=Ikeda en-aut-mei=Atsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KaneshiroNanaka en-aut-sei=Kaneshiro en-aut-mei=Nanaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KamikuboYuji en-aut-sei=Kamikubo en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakuraiTakashi en-aut-sei=Sakurai en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UeharaTakashi en-aut-sei=Uehara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakasugiNobumasa en-aut-sei=Takasugi en-aut-mei=Nobumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cellular and Molecular Pharmacology, Juntendo University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Cellular and Molecular Pharmacology, Juntendo University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=alzheimer's disease kn-keyword=alzheimer's disease en-keyword=apolipoproteins kn-keyword=apolipoproteins en-keyword=nuclear receptors/RXR kn-keyword=nuclear receptors/RXR en-keyword=transcription kn-keyword=transcription en-keyword=sphingosine phosphate kn-keyword=sphingosine phosphate en-keyword=astrocytes kn-keyword=astrocytes en-keyword=amyloid kn-keyword=amyloid en-keyword=sphingosine kinase 2 kn-keyword=sphingosine kinase 2 en-keyword=low-density lipoprotein receptor-related protein 4 kn-keyword=low-density lipoprotein receptor-related protein 4 END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=4953 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240229 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-term monitoring of gastric mucosa-associated lymphoid tissue lymphoma in patients with extra copies of the MALT1 gene en-subtitle= kn-subtitle= en-abstract= kn-abstract=The objective of this study was to clarify the long-term prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma with additional copies of MALT1. In this multicenter retrospective study, we enrolled 145 patients with gastric MALT lymphoma who underwent fluorescence in situ hybridization (FISH) analysis to detect t(11;18) translocation. The patient cohort was divided into three groups: Group A (n?=?87), comprising individuals devoid of the t(11;18) translocation or extra MALT1 copies; Group B (n?=?27), encompassing patients characterized by the presence of the t(11;18) translocation; and Group C (n?=?31), including patients with extra MALT1 copies. The clinical outcomes in each cohort were collected. Over the course of a mean follow-up of 8.5?}?4.2 years, one patient died of progressive MALT lymphoma, while 15 patients died due to etiologies unrelated to lymphoma. The progression or relapse of MALT lymphoma was observed in 11 patients: three in Group A, two in Group B, and six in Group C. In Groups A, B, and C, the 10-year overall survival rates were 82.5%, 93.8%, and 86.4%, respectively, and the 10-year event-free survival rates were 96.1%, 96.0%, and 82.9%, respectively. The event-free survival rate in Group C was significantly lower than that in Group A. However, no differences were observed in the 10-year event-free survival rates among individuals limited to stage I or II1 disease (equivalent to excluding patients with stage IV disease in this study, as there were no patients with stage II2), with rates of 98.6%, 95.8%, and 92.3% for Groups A, B, and C, respectively. In conclusion, the presence of extra copies of MALT1 was identified as an inferior prognostic determinant of event-free survival. Consequently, trisomy/tetrasomy 18 may serve as an indicator of progression and refractoriness to therapeutic intervention in patients with gastric MALT lymphoma, particularly stage IV gastric MALT lymphoma. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakenakaRyuta en-aut-sei=Takenaka en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyaharaKoji en-aut-sei=Miyahara en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkanoueShotaro en-aut-sei=Okanoue en-aut-mei=Shotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshiokaMasao en-aut-sei=Yoshioka en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakaguchiChihiro en-aut-sei=Sakaguchi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoKumiko en-aut-sei=Yamamoto en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaiYoshinari en-aut-sei=Kawai en-aut-mei=Yoshinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ToyokawaTatsuya en-aut-sei=Toyokawa en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil= Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Hiroshima City Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Mitoyo General Hospital kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Shikoku Cancer Center kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Kagawa Prefectural Central Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Onomichi Municipal Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology, Fukuyama Medical Center kn-affil= affil-num=10 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue kn-keyword=Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue en-keyword=Gastric neoplasms kn-keyword=Gastric neoplasms en-keyword=Esophagogastroduodenoscopy kn-keyword=Esophagogastroduodenoscopy en-keyword=t(11;18) translocation, kn-keyword=t(11;18) translocation, en-keyword=Trisomy 18 kn-keyword=Trisomy 18 END start-ver=1.4 cd-journal=joma no-vol=84 cd-vols= no-issue=7 article-no= start-page=1178 end-page=1191 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immunohistochemical p16 overexpression and Rb loss correlate with high]risk human papillomavirus infection in endocervical adenocarcinomas en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims: p16 is a sensitive surrogate marker for transcriptionally active high-risk human papillomavirus (HR-HPV) infection in endocervical adenocarcinoma (ECA); however, its specificity is not perfect.
Methods and results: We examined p16 and Rb expressions by immunohistochemistry (IHC) and the transcriptionally active HR-HPV infection by mRNA in-situ hybridisation (ISH) with histological review in 108 ECA cases. Thirteen adenocarcinomas of endometrial or equivocal origin (six endometrioid and seven serous carcinomas) were compared as the control group. HR-HPV was detected in 83 of 108 ECA cases (77%), including five HPV-associated adenocarcinomas in situ and 78 invasive HPV-associated adenocarcinomas. All 83 HPV-positive cases showed consistent morphology, p16 positivity and partial loss pattern of Rb. Among the 25 cases of HPV-independent adenocarcinoma, four (16%) were positive for p16, and of these four cases, three of 14 (21%) were gastric type adenocarcinomas and one of 10 (10%) was a clear cell type adenocarcinoma. All 25 HPV-independent adenocarcinomas showed preserved expression of Rb irrespective of the p16 status. Similarly, all 13 cases of the control group were negative for HR-HPV with preserved expression of Rb, even though six of 13 (46%) cases were positive for p16. Compared with p16 alone, the combination of p16 overexpression and Rb partial loss pattern showed equally excellent sensitivity (each 100%) and improved specificity (100 versus 73.6%) and positive predictive values (100 versus 89.2%) in the ECA and control groups. Furthermore, HR-HPV infection correlated with better prognosis among invasive ECAs.
Conclusions: The results suggest that the combined use of p16 and Rb IHC could be a reliable method to predict HR-HPV infection in primary ECAs and mimics. This finding may contribute to prognostic prediction and therapeutic strategy. en-copyright= kn-copyright= en-aut-name=YasutakeNobuko en-aut-sei=Yasutake en-aut-mei=Nobuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KugaRyosuke en-aut-sei=Kuga en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=JiromaruRina en-aut-sei=Jiromaru en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HongoTakahiro en-aut-sei=Hongo en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatayamaYoshihiro en-aut-sei=Katayama en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SonodaKenzo en-aut-sei=Sonoda en-aut-mei=Kenzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YahataHideaki en-aut-sei=Yahata en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatoKiyoko en-aut-sei=Kato en-aut-mei=Kiyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OdaYoshinao en-aut-sei=Oda en-aut-mei=Yoshinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=4 en-affil=Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=5 en-affil=Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=6 en-affil=Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=7 en-affil=Department of Gynecology and Obstetrics, National Kyushu Cancer Center kn-affil= affil-num=8 en-affil=Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=9 en-affil=Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=10 en-affil=Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University kn-affil= en-keyword=endocervical adenocarcinoma kn-keyword=endocervical adenocarcinoma en-keyword=human papillomavirus kn-keyword=human papillomavirus en-keyword=p16 kn-keyword=p16 en-keyword=Rb kn-keyword=Rb en-keyword=uterus kn-keyword=uterus END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=3 article-no= start-page=472 end-page=476 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Calcium polystyrene sulfonate-induced rectal ulcer causing E. coli native-valve infective endocarditis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Escherichia coli-associated native-valve infective endocarditis is a rare disease that affects elderly patients with underlying risk factors such as diabetes mellitus, malignancy, and renal failure. Long-term use of calcium polystyrene sulfonate is a potential risk factor for gastrointestinal mucosal damage or even colorectal ulcers. Herein, we describe a fatal case of a 66-year-old Japanese man with diabetes mellitus and renal failure who was prescribed calcium polystyrene sulfonate (CPS) for 11 years and developed a CPS-induced rectal ulcer, leading to E. coli native-valve infective endocarditis. The patient was admitted to our hospital due to acute-onset impaired consciousness. As a result of the systemic investigation, he was diagnosed with E. coli bacteremia accompanied by multiple cerebral infarctions and an acute hemorrhagic rectal ulcer. Transesophageal echocardiography revealed a 20-mm vegetative structure on the mitral valve, resulting in a final diagnosis of E. coli-associated infective endocarditis. After rectal resection, mitral valve replacement surgery was performed; however, the patient died shortly after surgery. Pathological findings of the resected rectum showed deposition of a basophilic crystalline material suggesting the presence of CPS. Our case highlights the potential risk of colorectal ulcers in a long-term CPS user, which can trigger bacterial translocation and endocarditis as fatal complications. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HondaHiroyuki en-aut-sei=Honda en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshidaTomoharu en-aut-sei=Ishida en-aut-mei=Tomoharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HasegawaKou en-aut-sei=Hasegawa en-aut-mei=Kou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Bacteremia kn-keyword=Bacteremia en-keyword=Calcium polystyrene sulfonate kn-keyword=Calcium polystyrene sulfonate en-keyword=Escherichia coli kn-keyword=Escherichia coli en-keyword=Infective endocarditis kn-keyword=Infective endocarditis en-keyword=Rectal ulcer kn-keyword=Rectal ulcer END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=11 article-no= start-page=4993 end-page=5001 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202311 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multimodal Prediction of Cervical Lymph Node Metastasis and Recurrence in Oral Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Oral squamous cell carcinoma (OSCC) is the most common malignancy in the head/neck region, and cervical lymph node (CLN) metastasis is a strong poor-prognosis factor. In addition, many patients with OSCC experience recurrence despite multidisciplinary treatment. We sought to identify factors associated with CLN metastasis and recurrence in patients with OSCC. Patients and Methods: We evaluated a total of 45 patients and 233 target CLNs. The longest diameter of the target CLN, the shortest diameter of the target CLN (LS), the area of the target CLN, and the relative computed tomography (CT) values of the target CLNs calculated based on the CT values of the internal jugular vein (LCT) were obtained from preoperative CT images, and the maximum standardized uptake values of the primary tumor (pSUV) and target CLN (nSUV) were obtained from preoperative 18F-fluorodeoxyglucose-positron emission tomography/CT images. We performed immunohistochemical staining for cytokeratin 13 (CK13) and 17 (CK17) on neck dissection tissues. Results: A discrimination equation was used that can predict CLN metastasis with a 92.2% discrimination rate using LS, LCT, pSUV, and nSUV. The CLNs were divided into discrimination and non-discrimination groups based on discriminant equations and CK13 and CK17 were used as the objective variables. A significantly higher recurrence rate was observed in the non-discrimination group (CK13: 5-year recurrence rate 28.6% vs. 64.3%, p<0.01; CK17: 5-year recurrence rate 28.0% vs. 76.0%, p<0.01). Conclusion: CLN metastases in OSCC can be assessed by combining preoperative imaging. The combined use of CK13 and CK17 expression with imaging findings offers an integrated approach to predict OSCC recurrence. en-copyright= kn-copyright= en-aut-name=KANEMOTOHIDEKA en-aut-sei=KANEMOTO en-aut-mei=HIDEKA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OBATAKYOICHI en-aut-sei=OBATA en-aut-mei=KYOICHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UMEMORIKOKI en-aut-sei=UMEMORI en-aut-mei=KOKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HASEGAWAKAZUAKI en-aut-sei=HASEGAWA en-aut-mei=KAZUAKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ONOSAWAKO en-aut-sei=ONO en-aut-mei=SAWAKO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ONOKISHO en-aut-sei=ONO en-aut-mei=KISHO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YUTORIHIROKAZU en-aut-sei=YUTORI en-aut-mei=HIROKAZU kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IBARAGISOICHIRO en-aut-sei=IBARAGI en-aut-mei=SOICHIRO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=5 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Oral cancer kn-keyword=Oral cancer en-keyword=head and neck squamous cell carcinoma kn-keyword=head and neck squamous cell carcinoma en-keyword=neck dissection kn-keyword=neck dissection en-keyword=lymph node kn-keyword=lymph node en-keyword=discriminant analysis kn-keyword=discriminant analysis en-keyword=cytokeratin kn-keyword=cytokeratin END start-ver=1.4 cd-journal=joma no-vol=150 cd-vols= no-issue=2 article-no= start-page=89 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical characteristics of patients treated with immune checkpoint inhibitors in EGFR-mutant non-small cell lung cancer: CS-Lung-003 prospective observational registry study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Immune checkpoint inhibitors (ICIs) are ineffective against epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical characteristics of patients who were treated or not treated with ICIs, and of those who benefit from immunotherapy in EGFR-mutant NSCLC.
Methods We analyzed patients with unresectable stage III/IV or recurrent NSCLC harboring EGFR mutations using a prospective umbrella-type lung cancer registry (CS-Lung-003).
Results A total of 303 patients who met the eligibility criteria were analyzed. The median age was 69 years; 116 patients were male, 289 had adenocarcinoma, 273 had major mutations, and 67 were treated with ICIs. The duration of EGFR-TKI treatment was longer in the Non-ICI group than in the ICI group (17.1 vs. 12.7 months, p? Conclusion ICIs were administered to only 22% of patients with EGFR-mutated lung cancer, and they had shorter TTNT of EGFR-TKI compared to other patients. ICI treatment should be avoided in EGFR mutated lung cancer with poor PS but can be considered for lung cancer with EGFR minor mutations. Pathological biomarker to predict long-term responders to ICI are needed.
en-copyright= kn-copyright= en-aut-name=KuribayashiTadahiro en-aut-sei=Kuribayashi en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiiKazuya en-aut-sei=Nishii en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsubataYukari en-aut-sei=Tsubata en-aut-mei=Yukari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshikawaNobuhisa en-aut-sei=Ishikawa en-aut-mei=Nobuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KodaniMasahiro en-aut-sei=Kodani en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanajiNobuhiro en-aut-sei=Kanaji en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamasakiMasahiro en-aut-sei=Yamasaki en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujitakaKazunori en-aut-sei=Fujitaka en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KuyamaShoichi en-aut-sei=Kuyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakigawaNagio en-aut-sei=Takigawa en-aut-mei=Nagio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujimotoNobukazu en-aut-sei=Fujimoto en-aut-mei=Nobukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KubotaTetsuya en-aut-sei=Kubota en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiwaraKeiichi en-aut-sei=Fujiwara en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HaritaShingo en-aut-sei=Harita en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TakataIchiro en-aut-sei=Takata en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TakadaKenji en-aut-sei=Takada en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OkawaSachi en-aut-sei=Okawa en-aut-mei=Sachi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Faculty of Medicine, Shimane University kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Hiroshima Prefectural Hospital kn-affil= affil-num=7 en-affil=Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=8 en-affil=Department of Internal Medicine, Division of Hematology, Rheumatology, and Respiratory Medicine, Faculty of Medicine, Kagawa University kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital kn-affil= affil-num=10 en-affil=Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=12 en-affil=Department of Internal Medicine 4, Kawasaki Medical School kn-affil= affil-num=13 en-affil=Department of Medical Oncology, Okayama Rosai Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine and Allergology, Kochi University Hospital kn-affil= affil-num=15 en-affil=Department of Chest Surgery, Shimonoseki City Hospital kn-affil= affil-num=16 en-affil=Department of Respiratory Medicine, NHO Okayama Medical Center kn-affil= affil-num=17 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=18 en-affil=Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=19 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=22 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=EGFR kn-keyword=EGFR en-keyword=EGFR-TKI kn-keyword=EGFR-TKI en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors en-keyword=Performance status kn-keyword=Performance status END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=1 article-no= start-page=89 end-page=93 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202402 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ectopic Breast Cancer Arising within an Axillary Lymph Node en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report our experience with the diagnosis and treatment of an ectopic breast cancer arising within an axillary lymph node. The patient was a 65-year-old woman diagnosed breast cancer and axillary lymph node metastasis. We performed a partial mastectomy and axillary lymph node dissection. Postoperative pathology revealed no malignant lesions in the breast; however, a nodule in one of axillary lymph nodes had mixed benign and malignant components, leading to a diagnosis of invasive ductal carcinoma derived from ectopic mammary tissue. This case represents a very rare form of breast cancer, and the malignancy was difficult to distinguish from metastasis. en-copyright= kn-copyright= en-aut-name=ToshimaKei en-aut-sei=Toshima en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiYoko en-aut-sei=Suzuki en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamotoShogo en-aut-sei=Nakamoto en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UnoMaya en-aut-sei=Uno en-aut-mei=Maya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshiokaRyo en-aut-sei=Yoshioka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsukiokiTakahiro en-aut-sei=Tsukioki en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakahashiYuko en-aut-sei=Takahashi en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IwamotoTakayuki en-aut-sei=Iwamoto en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IwataniTsuguo en-aut-sei=Iwatani en-aut-mei=Tsuguo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Molecular Hematopathology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Diagnostic Pathology, Okayama University Hospital kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=ectopic breast cancer kn-keyword=ectopic breast cancer en-keyword=axillary lymph node kn-keyword=axillary lymph node END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=1 article-no= start-page=85 end-page=88 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202402 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Idiopathic Peptic Ulcer Disease Treated Effectively with Trimebutine Maleat en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 30-year-old man with idiopathic peptic ulcer disease (IPUD) experienced repeated recurrence of ulcerative bleeding despite treatment with lansoprazole and then vonoprazan. Further evaluation suggested that the cause of the ulcer was strong contractile movements of the antrum. This prompted the co-administration of trimebutine maleate (TM) and vonoprazan to relieve the stomach contractions. TM was effective in preventing the recurrence of ulcerative bleeding, and the patient has remained in remission for 4 years. This case highlights the potential efficacy of TM in treating IPUD and the importance of considering hypercontractility as the underlying cause in cases of IPUD. en-copyright= kn-copyright= en-aut-name=MiyakeKeisuke en-aut-sei=Miyake en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanikawaTomohiro en-aut-sei=Tanikawa en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HarumaKen en-aut-sei=Haruma en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawadaMayuko en-aut-sei=Kawada en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshiiKatsunori en-aut-sei=Ishii en-aut-mei=Katsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UrataNoriyo en-aut-sei=Urata en-aut-mei=Noriyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishinoKen en-aut-sei=Nishino en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SuehiroMitsuhiko en-aut-sei=Suehiro en-aut-mei=Mitsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawanakaMiwa en-aut-sei=Kawanaka en-aut-mei=Miwa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ManabeNoriaki en-aut-sei=Manabe en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawamotoHirofumi en-aut-sei=Kawamoto en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Post graduate clinical education center, Kawasaki Medical School General Medical Center kn-affil= affil-num=2 en-affil=Department of General Internal Medicine 2, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of General Internal Medicine 2, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of General Internal Medicine 2, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of General Internal Medicine 2, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of General Internal Medicine 2, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of General Internal Medicine 2, Kawasaki Medical School kn-affil= affil-num=8 en-affil=Department of General Internal Medicine 2, Kawasaki Medical School kn-affil= affil-num=9 en-affil=Department of General Internal Medicine 2, Kawasaki Medical School kn-affil= affil-num=10 en-affil=Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School kn-affil= affil-num=11 en-affil=Department of General Internal Medicine 2, Kawasaki Medical School kn-affil= en-keyword=gastric ulcer kn-keyword=gastric ulcer en-keyword=idiopathic peptic ulcerative disease kn-keyword=idiopathic peptic ulcerative disease en-keyword=trimebutine maleate kn-keyword=trimebutine maleate END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=1 article-no= start-page=29 end-page=36 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202402 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Regression of Necrotic Lesions after Methotrexate Withdrawal in Patients with Methotrexate-Associated Lymphoproliferative Disorders: A Retrospective CT Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=This retrospective study investigated whether necrotic lesions detected on a computed tomography (CT) scan are more regressive than non-necrotic lesions after methotrexate withdrawal in patients pathologically diagnosed with methotrexate-associated lymphoproliferative disorders (MTX-LPD). In total, 89 lesions extracted from 24 patients on CT scans were included in the analysis. All patients had been evaluated for the presence of necrosis within lesions via CT scan upon first suspicion of MTX-LPD (baseline CT scan). The percentage lesion size reduction between the baseline and initial follow-up CT scan was calculated. The association between necrosis within lesions and size changes was estimated via linear regression analyses using both crude and adjusted models. Necrosis was significantly more common in extranodal lesions (27 out of 30 lesions, 90%) than in nodal lesions (9 out of 59 lesions, 15%, p<0.001). In the crude model, the regression of necrotic lesions was 58.5% greater than that of non-necrotic lesions; the difference was statistically significant (p<0.001). Additionally, the longest diameter of necrotic lesions at the baseline CT scan was significantly greater than that of non-necrotic lesions (p<0.001). Based on the adjusted model, necrotic lesions showed 49.3% greater regression than non-necrotic lesions (p=0.017). Necrosis detected on a CT scan was found to be an independent predictor of regression after MTX withdrawal in patients with MTX-LPD. en-copyright= kn-copyright= en-aut-name=KitayamaTakahiro en-aut-sei=Kitayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakashi en-aut-sei=Tanaka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanieYuichiro en-aut-sei=Kanie en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MarukawaYohei en-aut-sei=Marukawa en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KojimaKatsuhide en-aut-sei=Kojima en-aut-mei=Katsuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakaoSoshi en-aut-sei=Takao en-aut-mei=Soshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiology, Okayama City Hospital kn-affil= affil-num=3 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Radiology, Okayama Saiseikai General Hospital kn-affil= affil-num=5 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=methotrexate kn-keyword=methotrexate en-keyword=lymphoproliferative disorder kn-keyword=lymphoproliferative disorder en-keyword=computed tomography kn-keyword=computed tomography en-keyword=necrosis kn-keyword=necrosis END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=1 article-no= start-page=15 end-page=20 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202402 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lung Oligometastasis of Breast Cancer: Prospective Cohort Study of Treatment Strategies (SBP-06) en-subtitle= kn-subtitle= en-abstract= kn-abstract=While local treatment of metastases is considered to be unrelated to prognosis, previous studies have suggested that local treatment of isolated lung metastases may have positive prognostic impact. We designed this prospective cohort study to investigate the clinical situation and its outcomes. We enrolled patients with fewer than 3 lung nodules suspected of being oligometastases after curative breast cancer surgery. Treatments, including local and systemic therapy, were selected by the physician and patient in consultation. The primary outcome was overall survival (OS); secondary outcomes were the efficacy and the safety of the surgery for lung oligometastases. Between May 2015 and May 2019, 14 patients were enrolled. Resection of lung nodules (metastasectomy) was performed in 11 (78.6%) of 14 patients, and one of these cases was diagnosed as primary lung cancer. Metastasectomies were all performed employing video-assisted thoracic surgery (VATS) without perioperative complications. Systemic therapies were administered to all patients except one. The respective 3-year and 5-year OS rates of patients with lung oligometastases were 91.6% and 81.5%, respectively. Progression occurred in 6 patients: 3 of the 10 with metastasectomy and all 3 without this surgical procedure. Lung metastasectomy was worthwhile as a diagnostic evaluation and may provide long-term benefit in some patients. en-copyright= kn-copyright= en-aut-name=MaedaReina en-aut-sei=Maeda en-aut-mei=Reina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiMina en-aut-sei=Takahashi en-aut-mei=Mina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawadaKengo en-aut-sei=Kawada en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KajiwaraYukiko en-aut-sei=Kajiwara en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuboShinichiro en-aut-sei=Kubo en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakabatakeDaisuke en-aut-sei=Takabatake en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhtaniShoichiro en-aut-sei=Ohtani en-aut-mei=Shoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsuokaKinya en-aut-sei=Matsuoka en-aut-mei=Kinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HikinoHajime en-aut-sei=Hikino en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OgasawaraYutaka en-aut-sei=Ogasawara en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TairaNaruto en-aut-sei=Taira en-aut-mei=Naruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OsumiShozo en-aut-sei=Osumi en-aut-mei=Shozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IkedaMasahiko en-aut-sei=Ikeda en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Breast Oncology, NHO Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Breast and Endocrine Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=5 en-affil=Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=6 en-affil=Department of Breast and Thyroid Surgery, Fukuyama City Hospital kn-affil= affil-num=7 en-affil=Department of Breast Surgery, Kochi Health Sciences Center kn-affil= affil-num=8 en-affil=Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=9 en-affil=Department of Breast and Thyroid Surgery, Ehime Prefectural Central Hospital kn-affil= affil-num=10 en-affil=Department of Breast Surgery, Matsue Red Cross Hospital kn-affil= affil-num=11 en-affil=Department of Breast and Endocrine Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=12 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School kn-affil= affil-num=13 en-affil=Department of Breast Oncology, NHO Shikoku Cancer Center kn-affil= affil-num=14 en-affil=Department of Breast and Thyroid Surgery, Fukuyama City Hospital kn-affil= affil-num=15 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= en-keyword=oligometastasis kn-keyword=oligometastasis en-keyword=breast cancer kn-keyword=breast cancer en-keyword=lung kn-keyword=lung en-keyword=metastasectomy kn-keyword=metastasectomy END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=1 article-no= start-page=1 end-page=8 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202402 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Role of Macrophages in Liver Fibrosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Liver fibrosis, which ultimately leads to liver cirrhosis and hepatocellular carcinoma, is a major health burden worldwide. The progression of liver fibrosis is the result of the wound-healing response of liver to repeated injury. Hepatic macrophages are cells with high heterogeneity and plasticity and include tissue-resident macrophages termed Kupffer cells, and recruited macrophages derived from circulating monocytes, spleen and peritoneal cavity. Studies have shown that hepatic macrophages play roles in the initiation and progression of liver fibrosis by releasing inflammatory cytokines/chemokines and pro-fibrogenic factors. Furthermore, the development of liver fibrosis has been shown to be reversible. Hepatic macrophages have been shown to alternately regulate both the regression and turnover of liver fibrosis by changing their phenotypes during the dynamic progression of liver fibrosis. In this review, we summarize the role of hepatic macrophages in the progression and regression of liver fibrosis. en-copyright= kn-copyright= en-aut-name=SunCuiming en-aut-sei=Sun en-aut-mei=Cuiming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=ERK-MAPK kn-keyword=ERK-MAPK en-keyword=SPRED2 kn-keyword=SPRED2 en-keyword=fibrosis kn-keyword=fibrosis en-keyword=macrophages kn-keyword=macrophages END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=1 article-no= start-page=1 end-page=9 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=2024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Analysis of Notch1 protein expression in methotrexate-associated lymphoproliferative disorders en-subtitle= kn-subtitle= en-abstract= kn-abstract=Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a lymphoproliferative disorder in patients treated with MTX. The mechanism of pathogenesis is still elusive, but it is thought to be a complex interplay of factors, such as underlying autoimmune disease activity, MTX use, Epstein-Barr virus infection, and aging. The NOTCH genes encode receptors for a signaling pathway that regulates various fundamental cellular processes, such as proliferation and differentiation during embryonic development. Mutations of NOTCH1 have been reported in B-cell tumors, including chronic lymphocytic leukemia/ lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma (DLBCL). Recently, it has also been reported that NOTCH1 mutations are found in post-transplant lymphoproliferative disorders, and in CD20-positive cells in angioimmunoblastic T-cell lymphoma, which might be associated with lymphomagenesis in immunodeficiency. In this study, to investigate the association of NOTCH1 in the pathogenesis of MTX-LPD, we evaluated protein expression of Notch1 in nuclei immunohistochemically in MTX-LPD cases [histologically DLBCL-type (n = 24) and classical Hodgkin lymphoma (CHL)-type (n = 24)] and de novo lymphoma cases [DLBCL (n = 19) and CHL (n = 15)]. The results showed that among MTX-LPD cases, the expression of Notch1 protein was significantly higher in the DLBCL type than in the CHL type (P < 0.001). In addition, among DLBCL morphology cases, expression of Notch1 tended to be higher in MTX-LPD than in the de novo group; however this difference was not significant (P = 0.0605). The results showed that NOTCH1 may be involved in the proliferation and tumorigenesis of B cells under the use of MTX. Further research, including genetic studies, is necessary. en-copyright= kn-copyright= en-aut-name=OkataniTakeshi en-aut-sei=Okatani en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EgusaYuria en-aut-sei=Egusa en-aut-mei=Yuria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaSayako en-aut-sei=Yoshida en-aut-mei=Sayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=7 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=methotrexate-associated lymphoproliferative disorders kn-keyword=methotrexate-associated lymphoproliferative disorders en-keyword=other iatrogenic immunodeficiency-associated lymphoproliferative disorders kn-keyword=other iatrogenic immunodeficiency-associated lymphoproliferative disorders en-keyword=lymphoproliferative disorders arising in immune deficiency/dysregulation kn-keyword=lymphoproliferative disorders arising in immune deficiency/dysregulation en-keyword=NOTCH1 kn-keyword=NOTCH1 END start-ver=1.4 cd-journal=joma no-vol=115 cd-vols= no-issue=3 article-no= start-page=871 end-page=882 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Role of catecholamine synthases in the maintenance of cancer stem-like cells in malignant peripheral nerve sheath tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that are derived from Schwann cell lineage around peripheral nerves. As in many other cancer types, cancer stem cells (CSCs) have been identified in MPNSTs, and they are considered the cause of treatment resistance, recurrence, and metastasis. As an element defining the cancer stemness of MPNSTs, we previously reported a molecular mechanism by which exogenous adrenaline activates a core cancer stemness factor, YAP/TAZ, through 2 adrenoceptor (ADRB2). In this study, we found that MPNST cells express catecholamine synthases and that these enzymes are essential for maintaining cancer stemness, such as the ability to self-renew and maintain an undifferentiated state. Through gene knockdown and inhibition of these enzymes, we confirmed that catecholamines are indeed synthesized in MPNST cells. The results confirmed that catecholamine synthase knockdown in MPNST cells reduces the activity of YAP/TAZ. These data suggest that a mechanism of YAP/TAZ activation by de novo synthesized adrenaline, as well as exogenous adrenaline, may exist in the maintenance of cancer stemness of MPNST cells. This mechanism not only helps to understand the pathology of MPNST, but could also contribute to the development of therapeutic strategies for MPNST. en-copyright= kn-copyright= en-aut-name=KatayamaHaruyoshi en-aut-sei=Katayama en-aut-mei=Haruyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HuangRongsheng en-aut-sei=Huang en-aut-mei=Rongsheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtaniYusuke en-aut-sei=Otani en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ItanoTakuto en-aut-sei=Itano en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Trauma Orthopedics, The Second Hospital of Dalian Medical University kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=benserazide kn-keyword=benserazide en-keyword=cancer stem cell kn-keyword=cancer stem cell en-keyword=catecholamine synthase kn-keyword=catecholamine synthase en-keyword=malignant peripheral nerve sheath tumor kn-keyword=malignant peripheral nerve sheath tumor en-keyword=Schwann cell kn-keyword=Schwann cell en-keyword=vesicular monoamine transporter kn-keyword=vesicular monoamine transporter END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=55 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Influence of the coronavirus disease 2019 pandemic on the post-graduate career paths of medical students: a cross-sectional study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The World Health Organization first declared the coronavirus disease 2019 (COVID-19) pandemic in March 2020 and announced the end of the emergency in May 2023. Additionally, the COVID-19 pandemic significantly impacted individuals globally, including medical students. Although the COVID-19 pandemic increased online education, it restricted clinical training, extracurricular activities, and interprovincial travel. Therefore, this study aimed to examine whether the COVID-19 pandemic influenced the choice of training hospitals and career paths among 3rd- to 6th-year medical students in Japan.
Methods We developed a questionnaire comprising 21 multiple-choice and 1 open-ended questions, which was administered anonymously via online platforms. The survey targeted Japanese medical students to obtain insights into their preferences for training hospitals and career paths during the COVID-19 pandemic. Participants included 4th- to 6th-year medical students from 51 medical schools in Japan. The survey was conducted through student networks from 8 February 2022 to 20 March 2022.
Results Overall, 507 medical students participated in the survey, with representation from various academic years as follows: 102 (20.1%), 134 (26.4%), 121 (23.9%), and 150 (29.6%) students from the 3rd, 4th, 5th, and 6th year, respectively. Of these, 338 (66.6%) students reported that the COVID-19 pandemic had influenced their choice of training hospitals. The degree of the influence varied based on the university region and the student year. However, most of the students (473, 93.3%) did not change their course for clinical, basic research, or administrative pathways due to the COVID-19 pandemic. Among the clinically oriented students, 391 (77.2%) did not change their preferred speciality.
Conclusions The COVID-19 pandemic influenced medical students' choice of training hospitals. Although many students believed that the pandemic would not change their career choices, our results indicate a potential subconscious trend to avoid internal medicine, which is the speciality most directly involved in treating patients with COVID-19. en-copyright= kn-copyright= en-aut-name=NishimuraAyumu en-aut-sei=Nishimura en-aut-mei=Ayumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiTomoko en-aut-sei=Miyoshi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Okayama University Medical School Faculty of Medicine kn-affil= affil-num=2 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=COVID-19 pandemic kn-keyword=COVID-19 pandemic en-keyword=Medical students kn-keyword=Medical students en-keyword=Career path kn-keyword=Career path en-keyword=Training hospitals kn-keyword=Training hospitals END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=18 article-no= start-page=14128 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230915 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Advanced Techniques Using In Vivo Electroporation to Study the Molecular Mechanisms of Cerebral Development Disorders en-subtitle= kn-subtitle= en-abstract= kn-abstract=The mammalian cerebral cortex undergoes a strictly regulated developmental process. Detailed in situ visualizations, imaging of these dynamic processes, and in vivo functional gene studies significantly enhance our understanding of brain development and related disorders. This review introduces basic techniques and recent advancements in in vivo electroporation for investigating the molecular mechanisms underlying cerebral diseases. In utero electroporation (IUE) is extensively used to visualize and modify these processes, including the forced expression of pathological mutants in human diseases; thus, this method can be used to establish animal disease models. The advent of advanced techniques, such as genome editing, including de novo knockout, knock-in, epigenetic editing, and spatiotemporal gene regulation, has further expanded our list of investigative tools. These tools include the iON expression switch for the precise control of timing and copy numbers of exogenous genes and TEMPO for investigating the temporal effects of genes. We also introduce the iGONAD method, an improved genome editing via oviductal nucleic acid delivery approach, as a novel genome-editing technique that has accelerated brain development exploration. These advanced in vivo electroporation methods are expected to provide valuable insights into pathological conditions associated with human brain disorders. en-copyright= kn-copyright= en-aut-name=YangChen en-aut-sei=Yang en-aut-mei=Chen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShitamukaiAtsunori en-aut-sei=Shitamukai en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YangShucai en-aut-sei=Yang en-aut-mei=Shucai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawaguchiAyano en-aut-sei=Kawaguchi en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Human Anatomy and Histology and Embryology, School of Basic Medicine, Harbin Medical University kn-affil= affil-num=4 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences kn-affil= en-keyword=in vivo electroporation kn-keyword=in vivo electroporation en-keyword=in utero electroporation kn-keyword=in utero electroporation en-keyword=genome editing kn-keyword=genome editing en-keyword=IUE kn-keyword=IUE en-keyword=iON kn-keyword=iON en-keyword=TEMPO kn-keyword=TEMPO en-keyword=iGONAD kn-keyword=iGONAD END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue=4 article-no= start-page=246 end-page=250 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231226 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sutimlimab suppresses SARS-CoV-2 mRNA vaccine-induced hemolytic crisis in a patient with cold agglutinin disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cold agglutinin disease (CAD) is a rare form of acquired autoimmune hemolytic anemia driven mainly by antibodies that activate the classical complement pathway. Several patients with CAD experience its development or exacerbation of hemolysis after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or after receiving the SARS-CoV-2 mRNA vaccine. Therefore, these patients cannot receive an additional SARS-CoV-2 mRNA vaccination and have a higher risk of severe SARS-CoV-2 infection. Sutimlimab is a monoclonal antibody that inhibits the classical complement pathway of the C1s protein and shows rapid and sustained inhibition of hemolysis in patients with CAD. However, whether sutimlimab could also inhibit hemolysis caused by SARS-CoV-2 mRNA vaccination is uncertain. Here, we present the case of a 70-year-old man with CAD who repeatedly experienced a hemolytic crisis after receiving SARS-CoV-2 mRNA vaccines. The patient eventually underwent SARS-CoV-2 mRNA vaccination safely, without hemolytic attack, under classical pathway inhibition therapy with sutimlimab. This report suggests that appropriate sutimlimab administration can suppress SARS-CoV-2 mRNA vaccination-induced CAD exacerbation, and that it could be a preventive strategy to minimize hemolytic attacks in susceptible populations. en-copyright= kn-copyright= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OuchiTomoki en-aut-sei=Ouchi en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AsakuraShoji en-aut-sei=Asakura en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YanoTomofumi en-aut-sei=Yano en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakedaHiromasa en-aut-sei=Takeda en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TokudaYoshiyuki en-aut-sei=Tokuda en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Okayama Rosai Hospital kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Okayama Rosai Hospital kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=7 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=8 en-affil=Department of Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=cold agglutinin disease kn-keyword=cold agglutinin disease en-keyword=severe acute respiratory syndrome coronavirus 2 kn-keyword=severe acute respiratory syndrome coronavirus 2 en-keyword=sutimlimab kn-keyword=sutimlimab END start-ver=1.4 cd-journal=joma no-vol=117 cd-vols= no-issue=1 article-no= start-page=181 end-page=188 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical Features of Patients With Second Primary Lung Cancer After Head and Neck Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background In survivors of head and neck cancer (HNC), second primary lung cancer (SPLC) often develop as a result of a common risk factor, that is, smoking. A multicenter experience was reviewed to evaluate how the history of a diagnosis of HNC affects the outcomes of patients undergoing pulmonary resection for SPLC.
Methods A multicenter retrospective analysis of patients hospitalized between January 2012 and December 2018 was performed. From a cohort of 4521 patients undergoing therapeutic pulmonary resection for primary non-small cell lung cancer, 100 patients with a previous history of HNC (HNC group) were identified. These patients were compared with a control group consisting of 200 patients without an HNC history from the same cohort pair-matched with operating facility, age, sex, and pathologic stage of lung cancer.
Results At the time of surgery for SPLC, the HNC group showed malnutrition with a lower prognostic nutritional index compared with the control group (P < .001). The HNC group was determined to have postoperative complications more frequently (P = .02). The 5-year overall survival rates in the HNC and control groups were 59.0% and 83.2%, respectively (P < .001). Statistically, HNC history, lower prognostic nutritional index, squamous cell lung cancer, and TNM stage were identified to be independently associated with poor survival.
Conclusions Patients with SPLC after primary HNC often present with malnutrition and are predisposed to postoperative complications and poor survival after pulmonary resection. en-copyright= kn-copyright= en-aut-name=TakatsuFumiaki en-aut-sei=Takatsu en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WatanabeMototsugu en-aut-sei=Watanabe en-aut-mei=Mototsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HayamaMakio en-aut-sei=Hayama en-aut-mei=Makio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UenoTsuyoshi en-aut-sei=Ueno en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugimotoRyujiro en-aut-sei=Sugimoto en-aut-mei=Ryujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MakiYuho en-aut-sei=Maki en-aut-mei=Yuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiwaraToshiya en-aut-sei=Fujiwara en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OkitaRiki en-aut-sei=Okita en-aut-mei=Riki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=InokawaHidetoshi en-aut-sei=Inokawa en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaoHiroyuki en-aut-sei=Tao en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HiramiYuji en-aut-sei=Hirami en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MatsudaEisuke en-aut-sei=Matsuda en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KataokaKazuhiko en-aut-sei=Kataoka en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SanoYoshifumi en-aut-sei=Sano en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MatsuuraMotoki en-aut-sei=Matsuura en-aut-mei=Motoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MizutaniHisao en-aut-sei=Mizutani en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=7 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=8 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=9 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=10 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=11 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=12 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=13 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=14 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=15 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=16 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=17 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=18 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=19 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=20 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=21 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=22 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=24 article-no= start-page=7459 end-page=7470 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231214 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Distribution and clinical impact of molecular subtypes with dark zone signature of DLBCL in a Japanese real-world study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The distribution and clinical impact of cell-of-origin (COO) subtypes of diffuse large B-cell lymphoma (DLBCL) outside Western countries remain unknown. Recent literature also suggests that there is an additional COO subtype associated with the germinal center dark zone (DZ) that warrants wider validation to generalize clinical relevance. Here, we assembled a cohort of Japanese patients with untreated DLBCL and determined the refined COO subtypes, which include the DZ signature (DZsig), using the NanoString DLBCL90 assay. To compare the distribution and clinical characteristics of the molecular subtypes, we used a data set from the cohort of British Columbia Cancer (BCC) (n = 804). Through the 1050 patient samples on which DLBCL90 assay was successfully performed in our cohort, 35%, 45%, and 6% of patients were identified to have germinal center B-cell?like (GCB) DLBCL, activated B-cell?like (ABC) DLBCL, and DZsig-positive (DZsigpos) DLBCL, respectively, with the highest prevalence of ABC-DLBCL, differing significantly from the BCC result (P < .001). GCB-DLBCL, ABC-DLBCL, and DZsigpos-DLBCL were associated with 2-year overall survival rates of 88%, 75%, and 66%, respectively (P < .0001), with patients with DZsigpos-DLBCL having the poorest prognosis. In contrast, GCB-DLBCL without DZsig showed excellent outcomes after rituximab-containing immunochemotherapy. DZsigpos-DLBCL was associated with the significant enrichment of tumors with CD10 expression, concurrent MYC/BCL2 expression, and depletion of microenvironmental components (all, P < .05). These results provide evidence of the distinct distribution of clinically relevant molecular subtypes in Japanese DLBCL and that refined COO, as measured by the DLBCL90 assay, is a robust prognostic biomarker that is consistent across geographical areas. en-copyright= kn-copyright= en-aut-name=UrataTomohiro en-aut-sei=Urata en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaoiYusuke en-aut-sei=Naoi en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JiangAixiang en-aut-sei=Jiang en-aut-mei=Aixiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BoyleMerrill en-aut-sei=Boyle en-aut-mei=Merrill kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SunamiKazutaka en-aut-sei=Sunami en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ImaiToshi en-aut-sei=Imai en-aut-mei=Toshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NawaYuichiro en-aut-sei=Nawa en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiramatsuYasushi en-aut-sei=Hiramatsu en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoKazuhiko en-aut-sei=Yamamoto en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiiSoichiro en-aut-sei=Fujii en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshidaIsao en-aut-sei=Yoshida en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YanoTomofumi en-aut-sei=Yano en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ChijimatsuRyota en-aut-sei=Chijimatsu en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MurakamiHiroyuki en-aut-sei=Murakami en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IkeuchiKazuhiro en-aut-sei=Ikeuchi en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TaniKatsuma en-aut-sei=Tani en-aut-mei=Katsuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UjiieHideki en-aut-sei=Ujiie en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=InoueHirofumi en-aut-sei=Inoue en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YamamotoAkira en-aut-sei=Yamamoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=SawadaKeisuke en-aut-sei=Sawada en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=MomoseShuji en-aut-sei=Momose en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=TamaruJun-ichi en-aut-sei=Tamaru en-aut-mei=Jun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=ScottDavid W. en-aut-sei=Scott en-aut-mei=David W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=British Columbia Cancer, Centre for Lymphoid Cancer kn-affil= affil-num=4 en-affil=British Columbia Cancer, Centre for Lymphoid Cancer kn-affil= affil-num=5 en-affil=Department of Hematology, NHO Okayama Medical Center kn-affil= affil-num=6 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center kn-affil= affil-num=7 en-affil=Division of Hematology, Ehime Prefectural Central Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama City Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, Japanese Red Cross Okayama Hospital kn-affil= affil-num=11 en-affil=Department of Hematologic Oncology, NHO Shikoku Cancer Center kn-affil= affil-num=12 en-affil=Department of Internal Medicine, Okayama Rosai Hospital kn-affil= affil-num=13 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=19 en-affil=Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=20 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=21 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=22 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=23 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=24 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=25 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=26 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=27 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=28 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=29 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=30 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=31 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=32 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=33 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=34 en-affil=Department of Pathology, Okayama University kn-affil= affil-num=35 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=36 en-affil=British Columbia Cancer, Centre for Lymphoid Cancer kn-affil= affil-num=37 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=3 article-no= start-page=236 end-page=241 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202403 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relevance of complement immunity with brain fog in patients with long COVID en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction
This study aimed to elucidate the prevalence and clinical characteristics of patients with long COVID (coronavirus disease 2019), especially focusing on 50% hemolytic complement activity (CH50).

Methods
This retrospective observational study focused on patients who visited Okayama University Hospital (Japan) for the treatment of long COVID between February 2021 and March 2023. CH50 levels were measured using liposome immunometric assay (Autokit CH50 Assay, FUJIFILM Wako Pure Chemical Corporation, Japan); high CH50 was defined as ?59 U/mL. Univariate analyses assessed differences in the clinical background, long COVID symptoms, inflammatory markers, and clinical scores of patients with normal and high CH50. Logistic regression model investigated the association between high CH50 levels and these factors.

Results
Of 659 patients who visited our hospital, 478 patients were included. Of these, 284 (59.4%) patients had high CH50 levels. Poor concentration was significantly more frequent in the high CH50 group (7.2% vs. 13.7%), whereas no differences were observed in other subjective symptoms (fatigue, headache, insomnia, dyspnea, tiredness, and brain fog). Multivariate analysis was performed on factors that could be associated with poor concentration, suggesting a significant relationship to high CH50 levels (adjusted odds ratio [aOR], 2.70; 95% confidence interval [CI], 1.33?5.49). Also, high CH50 was significantly associated with brain fog (aOR, 1.66; 95% CI, 1.04?2.66).

Conclusions
High CH50 levels were frequently reported in individuals with long COVID, indicating a relationship with brain fog. Future in-depth research should examine the pathological role and causal link between complement immunity and the development of long COVID. en-copyright= kn-copyright= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TokumasuKazuki en-aut-sei=Tokumasu en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaYuki en-aut-sei=Otsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SunadaNaruhiko en-aut-sei=Sunada en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanoYasuhiro en-aut-sei=Nakano en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HondaHiroyuki en-aut-sei=Honda en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FurukawaMasanori en-aut-sei=Furukawa en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Complement immunity kn-keyword=Complement immunity en-keyword=Complement system kn-keyword=Complement system en-keyword=Coronavirus disease 2019 kn-keyword=Coronavirus disease 2019 en-keyword=Inflammation kn-keyword=Inflammation END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=10 article-no= start-page=100573 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immunologic Significance of CD80/CD86 or Major Histocompatibility Complex-II Expression in Thymic Epithelial Tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Unresectable or recurrent thymic epithelial tumors (TETs) have a poor prognosis, and treatment options are limited. This study aimed to investigate the immunologic significance of CD80/CD86 or major histocompatibility complex class II (MHC-II) expression in TETs, as potential predictive biomarkers for immune checkpoint inhibitors (ICIs).
Methods: We analyzed CD80, CD86, MHC class I (MHC-I), and MHC-II expression in TETs using immunohistochemistry and investigated their association with T-cell infiltration or ICI efficacy. In addition, we generated CD80- or MHC-II?expressing mouse tumors, evaluated the effects of ICIs, and analyzed tumor-infiltrating lymphocytes. We also performed tumor-rechallenge experiments in vivo.
Results: We found that approximately 50% and 30% of TETs had high expression of CD80/CD86 and MHC-II in tumor cells, respectively, and that this expression was related to T-cell infiltration in clinical samples. In mouse models, both CD80 and MHC-II increase the effects of ICIs. In addition, senescent T cells and long-lived memory precursor effector T cells were significantly decreased and increased, respectively, in tumor-infiltrating lymphocytes from CD80-expressing tumors, and rechallenged tumors were completely rejected after the initial eradication of CD80-expressing tumors by programmed cell death protein 1 blockade. Indeed, patients with CD80-high thymic carcinoma had longer progression-free survival with anti?programmed cell death protein 1 monoclonal antibody.
Conclusions: Half of the TETs had high expression of CD80/CD86 or MHC-II with high T-cell infiltration. These molecules could potentially increase the effects of ICIs, particularly inducing a durable response. CD80/CD86 and MHC-II can be predictive biomarkers of ICIs in TETs, promoting the development of drugs for such TETs. en-copyright= kn-copyright= en-aut-name=IkedaHideki en-aut-sei=Ikeda en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShimizuDaiki en-aut-sei=Shimizu en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsuyaYuki en-aut-sei=Katsuya en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HorinouchiHidehito en-aut-sei=Horinouchi en-aut-mei=Hidehito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HosomiYukio en-aut-sei=Hosomi en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanjiEtsuko en-aut-sei=Tanji en-aut-mei=Etsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwataTakekazu en-aut-sei=Iwata en-aut-mei=Takekazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ItamiMakiko en-aut-sei=Itami en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawazuMasahito en-aut-sei=Kawazu en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OheYuichiro en-aut-sei=Ohe en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SuzukiTakuji en-aut-sei=Suzuki en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=2 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=3 en-affil=Division of Thoracic Surgery, Chiba Cancer Center kn-affil= affil-num=4 en-affil=Department of Experimental Therapeutics, National Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=7 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=8 en-affil=Division of Thoracic Surgery, Chiba Cancer Center kn-affil= affil-num=9 en-affil=Department of Surgical Pathology, Chiba Cancer Center kn-affil= affil-num=10 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=11 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=12 en-affil=Department of Respirology, Graduate School of Medicine, Chiba University kn-affil= affil-num=13 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Thymic epithelial tumor kn-keyword=Thymic epithelial tumor en-keyword=Cancer immunotherapy kn-keyword=Cancer immunotherapy en-keyword=CD80/CD86 kn-keyword=CD80/CD86 en-keyword=MHC kn-keyword=MHC en-keyword=Memory precursor effector T cell kn-keyword=Memory precursor effector T cell END start-ver=1.4 cd-journal=joma no-vol=142 cd-vols= no-issue= article-no= start-page=106433 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202307 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=EpEX, the soluble extracellular domain of EpCAM, resists cetuximab treatment of EGFR-high head and neck squamous cell carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Cetuximab (Cmab) is a molecularly targeted monoclonal antibody drug for head and neck squamous cell carcinoma (HNSC), although cetuximab resistance is a serious challenge. Epithelial cell adhesion molecule (EpCAM) is an established marker for many epithelial tumors, while the soluble EpCAM extracellular domain (EpEX) functions as a ligand for epidermal growth factor receptor (EGFR). We investigated the expression of EpCAM in HNSC, its involvement in Cmab action, and the mechanism by which soluble EpEX activated EGFR and played key roles in Cmab resistance.
Materials and methods: We first examined EPCAM expression in HNSCs and its clinical significance by searching gene expression array databases. We then examined the effects of soluble EpEX and Cmab on intracellular signaling and Cmab efficacy in HNSC cell lines (HSC-3 and SAS).
Results: EPCAM expression was found to be enhanced in HNSC tumor tissues compared to normal tissues, and the enhancement was correlated with stage progression and prognosis. Soluble EpEX activated the EGFR-ERK signaling pathway and nuclear translocation of EpCAM intracellular domains (EpICDs) in HNSC cells. EpEX resisted the antitumor effect of Cmab in an EGFR expression-dependent manner.
Conclusion: Soluble EpEX activates EGFR to increase Cmab resistance in HNSC cells. The EpEX-activated Cmab resistance in HNSC is potentially mediated by the EGFR-ERK signaling pathway and the EpCAM cleavage-induced nuclear translocation of EpICD. High expression and cleavage of EpCAM are potential biomarkers for predicting the clinical efficacy and resistance to Cmab. en-copyright= kn-copyright= en-aut-name=UmemoriKoki en-aut-sei=Umemori en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnoKisho en-aut-sei=Ono en-aut-mei=Kisho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EguchiTakanori en-aut-sei=Eguchi en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraTomoya en-aut-sei=Nakamura en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OgawaTatsuo en-aut-sei=Ogawa en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaKunihiro en-aut-sei=Yoshida en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanemotoHideka en-aut-sei=Kanemoto en-aut-mei=Hideka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatoKohei en-aut-sei=Sato en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ObataKyoichi en-aut-sei=Obata en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=RyumonShoji en-aut-sei=Ryumon en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YutoriHirokazu en-aut-sei=Yutori en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KataseNaoki en-aut-sei=Katase en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OkuiTatsuo en-aut-sei=Okui en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Oral Pathology, Graduate School of Biomedical Sciences, Nagasaki University kn-affil= affil-num=14 en-affil=Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine kn-affil= affil-num=15 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Cetuximab kn-keyword=Cetuximab en-keyword=epithelial cell adhesion molecule (EpCAM) kn-keyword=epithelial cell adhesion molecule (EpCAM) en-keyword=EpEX kn-keyword=EpEX en-keyword=EpICD kn-keyword=EpICD en-keyword=epidermal growth factor receptor (EGFR) kn-keyword=epidermal growth factor receptor (EGFR) en-keyword=Drug resistance kn-keyword=Drug resistance en-keyword=Head and neck squamous cell carcinoma (HNSC) kn-keyword=Head and neck squamous cell carcinoma (HNSC) END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=7 article-no= start-page=100873 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202307 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of liquefied sake lees on growth performance and faecal and blood characteristics in Japanese Black calves en-subtitle= kn-subtitle= en-abstract= kn-abstract=Liquefied sake lees, a by-product of Japanese sake, is rich in Saccharomyces cerevisiae, proteins, and prebiotics derived from rice and yeast. Previous studies have reported that Saccharomyces cerevisiae fermentation products improved the health, growth, and faecal characteristics of preweaning calves. This study investigated the effects of adding liquefied sake lees to milk replacer on the growth performance, faecal characteristics, and blood metabolites of preweaning Japanese Black calves from 6 to 90 days of age. Twenty-four Japanese Black calves at 6 days of age were randomly assigned to one of three treatments: No liquefied sake lees (C, n = 8), 100 g/d (on a fresh matter basis) liquefied sake lees mixed with milk replacer (LS, n = 8), and 200 g/d (on a fresh matter basis) liquefied sake lees mixed with milk replacer (HS, n = 8). The intake of milk replacer and calf starter, as well as, the average daily gain did not differ between the treatments. The number of days counted with faecal score 1 in LS was higher than in HS (P < 0.05), while the number of days with diarrhoea medication in LS and C was lower than HS (P < 0.05). The faecal n-butyric acid concentration tended to be higher in LS compared to C (P = 0.060). The alpha diversity index (Chao1) was higher in HS than in C and LS at 90 days of age (P < 0.05). The principal coordinate analysis (PCoA) using weighted UniFrac distance showed that the bacterial community structures in faeces among the treatments at 90 days of age were significantly different (P < 0.05). The plasma -hydroxybutyric acid concentration, an indicator of rumen development, was higher for LS than in C throughout the experiment (P < 0.05). These results suggested that adding liquefied sake lees up to 100 g/d (on a fresh matter basis) might promote rumen development in preweaning Japanese Black calves. en-copyright= kn-copyright= en-aut-name=KatsumataS. en-aut-sei=Katsumata en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayashiY. en-aut-sei=Hayashi en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OishiK. en-aut-sei=Oishi en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsukaharaT. en-aut-sei=Tsukahara en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueR. en-aut-sei=Inoue en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ObataA. en-aut-sei=Obata en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HirookaH. en-aut-sei=Hirooka en-aut-mei=H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KumagaiH. en-aut-sei=Kumagai en-aut-mei=H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Shiga Prefectural Livestock Production Technology Promotion Center kn-affil= affil-num=3 en-affil=Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University kn-affil= affil-num=4 en-affil=Kyoto Institute of Nutrition and Pathology kn-affil= affil-num=5 en-affil=Department of Applied Biological Sciences, Faculty of Agriculture, Setsunan University kn-affil= affil-num=6 en-affil=Shiga Prefectural Livestock Production Technology Promotion Center kn-affil= affil-num=7 en-affil=Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University kn-affil= affil-num=8 en-affil=Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University kn-affil= en-keyword=By-products kn-keyword=By-products en-keyword=Faecal microbiota kn-keyword=Faecal microbiota en-keyword=Japanese Black cattle kn-keyword=Japanese Black cattle en-keyword=Preweaning calves kn-keyword=Preweaning calves en-keyword=Saccharomyces cerevisiae kn-keyword=Saccharomyces cerevisiae END start-ver=1.4 cd-journal=joma no-vol=135 cd-vols= no-issue=3 article-no= start-page=123 end-page=128 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Recent advances in molecular pathological findings in sinonasal carcinomas kn-title=@@oɂVqawIm en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name=Rp kn-aut-sei=R kn-aut-mei=p aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil=Rwwp@㎕w@awiᇕaj en-keyword=@@o kn-keyword=@@o en-keyword=G kn-keyword=G en-keyword=`qُ kn-keyword=`qُ en-keyword=HPV kn-keyword=HPV en-keyword=EGFR kn-keyword=EGFR END start-ver=1.4 cd-journal=joma no-vol=96 cd-vols= no-issue=2 article-no= start-page=609 end-page=622 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231107 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Protective Effects of Rivaroxaban on White Matter Integrity and Remyelination in a Mouse Model of Alzheimerfs Disease Combined with Cerebral Hypoperfusion en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background:Alzheimerfs disease (AD) is characterized by cognitive dysfunction and memory loss that is accompanied by pathological changes to white matter. Some clinical and animal research revealed that AD combined with chronic cerebral hypoperfusion (CCH) exacerbates AD progression by inducing blood-brain barrier dysfunction and fibrinogen deposition. Rivaroxaban, an anticoagulant, has been shown to reduce the rates of dementia in atrial fibrillation patients, but its effects on white matter and the underlying mechanisms are unclear.
Objective:The main purpose of this study was to explore the therapeutic effect of rivaroxaban on the white matter of AD+CCH mice.
Methods:In this study, the therapeutic effects of rivaroxaban on white matter in a mouse AD+CCH model were investigated to explore the potential mechanisms involving fibrinogen deposition, inflammation, and oxidative stress on remyelination in white matter.
Results:The results indicate that rivaroxaban significantly attenuated fibrinogen deposition, fibrinogen-related microglia activation, oxidative stress, and enhanced demyelination in AD+CCH mice, leading to improved white matter integrity, reduced axonal damage, and restored myelin loss.
Conclusions:These findings suggest that long-term administration of rivaroxaban might reduce the risk of dementia. en-copyright= kn-copyright= en-aut-name=BianZhihong en-aut-sei=Bian en-aut-mei=Zhihong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HuXinran en-aut-sei=Hu en-aut-mei=Xinran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiuXia en-aut-sei=Liu en-aut-mei=Xia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YuHaibo en-aut-sei=Yu en-aut-mei=Haibo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BianYuting en-aut-sei=Bian en-aut-mei=Yuting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SunHongming en-aut-sei=Sun en-aut-mei=Hongming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FukuiYusuke en-aut-sei=Fukui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Alzheimerfs disease kn-keyword=Alzheimerfs disease en-keyword=cerebral amyloid angiopathy kn-keyword=cerebral amyloid angiopathy en-keyword=chronic cerebral hypoperfusion kn-keyword=chronic cerebral hypoperfusion en-keyword=rivaroxaban kn-keyword=rivaroxaban en-keyword=white matter kn-keyword=white matter END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=12 article-no= start-page=e8364 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231221 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nontuberculous mycobacterial abscess of lacrimal sac and eyelid debridement: Case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 56-year-old otherwise healthy woman developed abscess from dacryocystitis in the right lower eyelid. The smear of puncture fluid showed acid-fast bacilli and Mycobacterium abscessus was identified after a month. The early start of clarithromycin/ethambutol was switched to clarithromycin/levofloxacin. Debridement specimen after 7-month treatment showed granulomatous tissue with no bacilli. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaKiyoshi en-aut-sei=Yamada en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NoseMotoko en-aut-sei=Nose en-aut-mei=Motoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanimotoYasushi en-aut-sei=Tanimoto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=debridement kn-keyword=debridement en-keyword=eyelid kn-keyword=eyelid en-keyword=lacrimal sac kn-keyword=lacrimal sac en-keyword=Mycobacterium abscessus kn-keyword=Mycobacterium abscessus en-keyword=nontuberculous mycobacteria kn-keyword=nontuberculous mycobacteria END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=1 article-no= start-page=843 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ligneous periodontitis exacerbated by Beh?etfs disease in a patient with plasminogen deficiency and a stop-gained variant PLG c.1468C?>?T: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Plasminogen serves as the precursor to plasmin, an essential element in the fibrinolytic process, and is synthesized primarily in the liver. Plasminogen activation occurs through the action of plasminogen activator, converting it into plasmin. This conversion greatly enhances the fibrinolytic system within tissues and blood vessels, facilitating the dissolution of fibrin clots. Consequently, congenital deficiency of plasminogen results in impaired fibrin degradation. Patients with plasminogen deficiency typically exhibit fibrin deposits in various mucosal sites throughout the body, including the oral cavity, eyes, vagina, and digestive organs. Behcet's disease is a chronic recurrent systemic inflammatory disease with four main symptoms: aphthous ulcers of the oral mucosa, vulvar ulcers, skin symptoms, and eye symptoms, and has been reported worldwide. This disease is highly prevalent around the Silk Road from the Mediterranean to East Asia.
We report a case of periodontitis in a patient with these two rare diseases that worsened quickly, leading to alveolar bone destruction. Genetic testing revealed a novel variant characterized by a stop-gain mutation, which may be a previously unidentified etiologic gene associated with decreased plasminogen activity.
Case presentation This case report depicts a patient diagnosed with ligneous gingivitis during childhood, originating from plasminogen deficiency and progressing to periodontitis. Genetic testing revealed a suspected association with the PLG c.1468C?>?T (p.Arg490*) stop-gain mutation. The patient's periodontal condition remained stable with brief intervals of supportive periodontal therapy. However, the emergence of Beh?et's disease induced acute systemic inflammation, necessitating hospitalization and treatment with steroids. During hospitalization, the dental approach focused on maintaining oral hygiene and alleviating contact-related pain. The patient's overall health improved with inpatient care and the periodontal tissues deteriorated.
Conclusions Collaborative efforts between medical and dental professionals are paramount in comprehensively evaluating and treating patients with intricate complications from rare diseases. Furthermore, the PLG c.1468C?>?T (p.Arg490*) stop-gain mutation could contribute to the association between plasminogen deficiency and related conditions. en-copyright= kn-copyright= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiraiAnna en-aut-sei=Hirai en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IdeguchiHidetaka en-aut-sei=Ideguchi en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatoFumino en-aut-sei=Kato en-aut-mei=Fumino kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ObataKyoichi en-aut-sei=Obata en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OgawaTatsuo en-aut-sei=Ogawa en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakadoiTakato en-aut-sei=Nakadoi en-aut-mei=Takato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KatsuyamaEri en-aut-sei=Katsuyama en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Pathophysiology?Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pathophysiology?Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Clinical Genomic Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=The Center for Graduate Medical Education (Dental Division), Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=The Center for Graduate Medical Education (Dental Division), Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Clinical Genomic Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of Pathophysiology?Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Ligneous periodontitis kn-keyword=Ligneous periodontitis en-keyword=Plasminogen deficiency kn-keyword=Plasminogen deficiency en-keyword=PLG kn-keyword=PLG en-keyword=Behcet's disease kn-keyword=Behcet's disease en-keyword=Gingival hyperplasia kn-keyword=Gingival hyperplasia END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=11 article-no= start-page=1562 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel Iron Chelators, Super-Polyphenols, Show Antimicrobial Effects against Cariogenic Streptococcus mutans en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dental caries are an oral infectious disease that can affect human health both orally and systemically. It remains an urgent issue to establish a novel antibacterial method to prevent oral infection for a healthy life expectancy. The aim of this study was to evaluate the inhibitory effects of novel iron chelators, super-polyphenols (SPs), on the cariogenic bacterium Streptococcus mutans, in vitro. SPs were developed to reduce the side effects of iron chelation therapy and were either water-soluble or insoluble depending on their isoforms. We found that SP6 and SP10 inhibited bacterial growth equivalent to povidone-iodine, and viability tests indicated that their effects were bacteriostatic. These results suggest that SP6 and SP10 have the potential to control oral bacterial infections such as Streptococcus mutans. en-copyright= kn-copyright= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItoTakashi en-aut-sei=Ito en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakayamaMasaaki en-aut-sei=Nakayama en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkedaAtsushi en-aut-sei=Ikeda en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItoMasahiro en-aut-sei=Ito en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Periodontics & Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=antimicrobial kn-keyword=antimicrobial en-keyword=iron chelator kn-keyword=iron chelator en-keyword=oral infection kn-keyword=oral infection en-keyword=Streptococcus mutans kn-keyword=Streptococcus mutans en-keyword=super-polyphenols kn-keyword=super-polyphenols END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=6 article-no= start-page=651 end-page=653 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prenatal Torsion of Radial Polydactyly: A Gangrenous Mass at the Base of the Thumb en-subtitle= kn-subtitle= en-abstract= kn-abstract=A patient was born with a mass at the base of the thumb approximately 1.5 cm in diameter on the radial side of the fingers. The mass had globular swelling filled with hemorrhagic fluid and was dark red. X-rays and histology of the excised specimen suggested the diagnosis of gangrene and torsion of polydactyly. Prenatal torsion of polydactyly is not a common occurrence; moreover, prenatal torsion of polydactyly has only been found in ulnar polydactyly. Our case is a novel case of radial polydactyly that was gangrenous at birth owing to prenatal torsion. Diagnosing such a mass at the base of the thumb is important. en-copyright= kn-copyright= en-aut-name=WatanabeDaisuke en-aut-sei=Watanabe en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HasebeYohei en-aut-sei=Hasebe en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuiHiroshi en-aut-sei=Mitsui en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OishiNaoki en-aut-sei=Oishi en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KasaiShin en-aut-sei=Kasai en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkahaneKoshi en-aut-sei=Akahane en-aut-mei=Koshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KojikaSatoru en-aut-sei=Kojika en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InukaiTakeshi en-aut-sei=Inukai en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pediatrics, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=2 en-affil=Department of Pediatrics, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=3 en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=4 en-affil=Department of Pathology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=5 en-affil=Department of Pediatrics, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=6 en-affil=Department of Pediatrics, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=7 en-affil=Department of Pediatrics, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=8 en-affil=Department of Pediatrics, Faculty of Medicine, University of Yamanashi kn-affil= en-keyword=infant kn-keyword=infant en-keyword=fingers kn-keyword=fingers en-keyword=thumb kn-keyword=thumb en-keyword=polydactyly kn-keyword=polydactyly en-keyword=torsion abnormality kn-keyword=torsion abnormality END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=6 article-no= start-page=627 end-page=634 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Abnormal Vaginal Cytology after Total Laparoscopic Hysterectomy in Patients with Cervical Intraepithelial Neoplasia en-subtitle= kn-subtitle= en-abstract= kn-abstract=To explore the incidence of abnormal vaginal cytology after total laparoscopic hysterectomy for the treatment of cervical intraepithelial neoplasia 3, we retrospectively analyzed the medical records of patients treated at NHO Shikoku Cancer Center (Japan) in 2014-2019. The cases of 99 patients who underwent a laparoscopic (n=36) or open (n=63) hysterectomy and postoperative follow-up were examined. Abnormal vaginal cytology was detected in 13.9% (5/36) of the laparoscopic-surgery (LS) group and 14.3% (9/63) of the open-surgery (OS) group. A vaginal biopsy was performed at the physiciansf discretion; one LS patient and six OS patients were diagnosed with vaginal intraepithelial neoplasia. The cumulative incidence of abnormal vaginal cytology at 3 years post-hysterectomy was 21.4% (LS group) and 20.5% (OS group), a nonsignificant difference. A multivariate analysis showed that age > 50 years was the only independent risk factor for abnormal vaginal cytology among the covariates examined including age; body mass index; histories of vaginal delivery, abdominal surgery, and smoking; and surgical approach (hazard ratio 8.11; 95% confidence interval 1.73-37.98; p=0.01). These results suggest that the occurrence of abnormal vaginal cytology after a hysterectomy may not be influenced by the laparoscopic procedure but is associated with older age. en-copyright= kn-copyright= en-aut-name=HibinoYumi en-aut-sei=Hibino en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Okazawa-SakaiMika en-aut-sei=Okazawa-Sakai en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YokoyamaTakanori en-aut-sei=Yokoyama en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujimotoEtsuko en-aut-sei=Fujimoto en-aut-mei=Etsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkameShinichi en-aut-sei=Okame en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TeramotoNorihiro en-aut-sei=Teramoto en-aut-mei=Norihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeharaKazuhiro en-aut-sei=Takehara en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Gynecologic Oncology, NHO Shikoku Cancer Center kn-affil= affil-num=2 en-affil=Department of Gynecologic Oncology, NHO Shikoku Cancer Center kn-affil= affil-num=3 en-affil=Department of Gynecologic Oncology, NHO Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Gynecologic Oncology, NHO Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Gynecologic Oncology, NHO Shikoku Cancer Center kn-affil= affil-num=6 en-affil=Department of Pathology, NHO Shikoku Cancer Center kn-affil= affil-num=7 en-affil=Department of Gynecologic Oncology, NHO Shikoku Cancer Center kn-affil= en-keyword=total laparoscopic hysterectomy kn-keyword=total laparoscopic hysterectomy en-keyword=vaginal intraepithelial neoplasia kn-keyword=vaginal intraepithelial neoplasia en-keyword=cervical intraepithelial neoplasia kn-keyword=cervical intraepithelial neoplasia en-keyword=vaginal cytology kn-keyword=vaginal cytology en-keyword=risk factor kn-keyword=risk factor END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=6 article-no= start-page=613 end-page=618 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Survey of Osteoarthritis of the Shoulder in Patients who Underwent Knee Arthroplasty for Knee Osteoarthritis en-subtitle= kn-subtitle= en-abstract= kn-abstract=The relationship between osteoarthritis (OA) of the lower extremity and shoulder OA has not been established. This study evaluated the prevalence of shoulder OA in patients with knee OA. We collected contrast-enhanced computed tomography (CECT) images of the shoulder joints of 105 patients with knee OA that were taken 1 week after they underwent primary knee arthroplasty to check for venous thromboembolism (VTE). The images were compared with CECT images of 110 control-group patients that were taken for the purpose of differentiating VTE. Shoulder OA was present in a significantly higher percentage of patients with knee arthroplasty than controls (29% versus 15%), and the difference was particularly pronounced in patients in their 70s (33%) compared to age-matched controls (11%). Patients with knee OA often use arm support to stand up or walk due to knee joint pain and muscle weakness, which places the weight-bearing shoulder at risk of developing OA. en-copyright= kn-copyright= en-aut-name=MiyakeYoshiaki en-aut-sei=Miyake en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NambaYoshifumi en-aut-sei=Namba en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitaniShigeru en-aut-sei=Mitani en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UmeharaNorifumi en-aut-sei=Umehara en-aut-mei=Norifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawamotoToyohiro en-aut-sei=Kawamoto en-aut-mei=Toyohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FuruichiShuro en-aut-sei=Furuichi en-aut-mei=Shuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Bone and Joint Surgery, Kawasaki Medical School kn-affil= affil-num=2 en-affil=Department of Bone and Joint Surgery, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Bone and Joint Surgery, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Bone and Joint Surgery, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Bone and Joint Surgery, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Bone and Joint Surgery, Kawasaki Medical School kn-affil= en-keyword=shoulder osteoarthritis kn-keyword=shoulder osteoarthritis en-keyword=knee osteoarthritis kn-keyword=knee osteoarthritis en-keyword=weight-bearing shoulder kn-keyword=weight-bearing shoulder en-keyword=knee arthroplasty kn-keyword=knee arthroplasty END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=05 article-no= start-page=E602 end-page=E608 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220513 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Resection depth for small colorectal polyps comparing cold snare polypectomy, hot snare polypectomy and underwater endoscopic mucosal resection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and study aims?Small colorectal polyps are removed by various methods, including cold snare polypectomy (CSP), hot snare polypectomy (HSP), and underwater endoscopic mucosal resection (UEMR), but the indications for using these methods are unclear. We retrospectively assessed the efficacy of CSP, HSP, and UEMR for small polyps, focusing on the depth of the resected specimens.
Patients and methods?Outpatients with non-pedunculated small polyps (endoscopically diagnosed as 6 to 9?mm), resected by two endoscopists between July 2019 and September 2020, were enrolled. We histologically evaluated the specimens resected via CSP, HSP, and UEMR. The main outcome was the containment rate of the muscularis mucosa (MM) and submucosa (SM) tissues.
Results?Forty polyps resected via CSP (n?=?14), HSP (n?=?12), or UEMR (n?=?14) were enrolled after excluding 13 polyps with resection depths that were difficult to determine. The rates of specimens containing MM and SM tissue differed significantly (57?% and 29?% for CSP, 92?% and 83?% for HSP, and 100?% and 100?% for UEMR, respectively (P?=?0.005 for MM and P? Conclusions?UEMR could be the best method to contain SM tissue without injection. Further studies are needed to evaluate the indication of UEMR for small polyps. en-copyright= kn-copyright= en-aut-name=ToyosawaJunki en-aut-sei=Toyosawa en-aut-mei=Junki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamasakiYasushi en-aut-sei=Yamasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujimotoTsuyoshi en-aut-sei=Fujimoto en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaShouichi en-aut-sei=Tanaka en-aut-mei=Shouichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology, Iwakuni Clinical Center kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Iwakuni Clinical Center kn-affil= affil-num=5 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=20 article-no= start-page=15450 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231022 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Roles of Oxidative Injury and Nitric Oxide System Derangements in Kawasaki Disease Pathogenesis: A Systematic Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Kawasaki disease (KD) is an acute febrile vasculitis that occurs mostly in children younger than five years. KD involves multiple intricately connected inflammatory reactions activated by a cytokine cascade. Despite therapeutic advances, coronary artery damage may develop in some patients, who will be at risk of clinical cardiovascular events and even sudden death. The etiology of KD remains unclear; however, it may involve both genetic and environmental factors leading to aberrant inflammatory responses. Given the young age of onset, prenatal or perinatal exposure may be etiologically relevant. Multisystem inflammatory syndrome in children, a post-infectious hyper-inflammatory disorder associated with severe acute respiratory syndrome coronavirus 2, has features that overlap with those of KD. Available evidence indicates that vascular endothelial dysfunction is a critical step in the sequence of events leading to the development of cardiovascular lesions in KD. Oxidative stress and the dysregulation of the nitric oxide (NO) system contribute to the pathogenesis of inflammatory responses related to this disease. This review provides current evidence and concepts highlighting the adverse effects of oxidative injury and NO system derangements on the initiation and progression of KD and potential therapeutic strategies for cardiovascular pathologies in affected children. en-copyright= kn-copyright= en-aut-name=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UdaKazuhiro en-aut-sei=Uda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EitokuTakahiro en-aut-sei=Eitoku en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatrics, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Epidemiology, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Epidemiology, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=biomarker kn-keyword=biomarker en-keyword=coronary artery lesions kn-keyword=coronary artery lesions en-keyword=Kawasaki disease kn-keyword=Kawasaki disease en-keyword=multisystem inflammatory syndrome in children kn-keyword=multisystem inflammatory syndrome in children en-keyword=nitric oxide kn-keyword=nitric oxide en-keyword=nitrosative stress kn-keyword=nitrosative stress en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=systemic inflammation kn-keyword=systemic inflammation en-keyword=vascular endothelial dysfunction kn-keyword=vascular endothelial dysfunction END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=1 article-no= start-page=24 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Connective tissue mast cells store and release noradrenaline en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mast cells are present in mucosal and connective tissues throughout the body. They synthesize and release a wide variety of bioactive molecules, such as histamine, proteases, and cytokines. In this study, we found that a population of connective tissue mast cells (CTMCs) stores and releases noradrenaline, originating from sympathetic nerves. Noradrenaline-storing cells, not neuronal fibers, were predominantly identified in the connective tissues of the skin, mammary gland, gastrointestinal tract, bronchus, thymus, and pancreas in wild-type mice but were absent in mast cell-deficient W-sash c-kit mutant KitW-sh/W-sh mice. In vitro studies using bone marrow-derived mast cells revealed that extracellular noradrenaline was taken up but not synthesized. Upon ionomycin stimulation, noradrenaline was released. Electron microscopy analyses further suggested that noradrenaline is stored in and released from the secretory granules of mast cells. Finally, we found that noradrenaline-storing CTMCs express organic cation transporter 3 (Oct3), which is also known as an extraneuronal monoamine transporter, SLC22A3. Our findings indicate that mast cells may play a role in regulating noradrenaline concentration by storing and releasing it in somatic tissues. en-copyright= kn-copyright= en-aut-name=OtaniYusuke en-aut-sei=Otani en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshikawaSoichiro en-aut-sei=Yoshikawa en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaoKei en-aut-sei=Nagao en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Mast cells kn-keyword=Mast cells en-keyword=Connective tissue mast cells kn-keyword=Connective tissue mast cells en-keyword=Noradrenaline kn-keyword=Noradrenaline en-keyword=Immunoelectron microscopy kn-keyword=Immunoelectron microscopy en-keyword=SLC22A3 kn-keyword=SLC22A3 END start-ver=1.4 cd-journal=joma no-vol=1821 cd-vols= no-issue= article-no= start-page=148565 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Injection of exogenous amyloid- oligomers aggravated cognitive deficits, and activated necroptosis, in APP23 transgenic mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by the loss of synapses and neurons in the brain, and the accumulation of amyloid plaques. A oligomers (AO) play a critical role in the pathogenesis of AD. Although there is increasing evidence to support the involvement of necroptosis in the pathogenesis of AD, the exact mechanism remains elusive. In the present study, we explored the effect of exogenous AO injection on cell necroptosis and cognitive deficits in APP23 transgenic mice. We found that intrahippocampal injection of AO accelerated the development of AD pathology and caused cognitive impairment in APP23 mice. Specifically, AO injection significantly accelerated the accumulation of AO and increased the expression level of phosphorylated-tau, and also induced necroptosis. Behavioral tests showed that AO injection was associated with cognitive impairment. Furthermore, necroptosis induced by AO injection occurred predominantly in microglia of the AD brain. We speculate that AO increased necroptosis by activating microglia, resulting in cognitive deficits. Our results may aid in an understanding of the role played by AO in AD from an alternative perspective and provide new ideas and evidence for necroptosis as a potential intervention and therapeutic target for AD. en-copyright= kn-copyright= en-aut-name=YuHaibo en-aut-sei=Yu en-aut-mei=Haibo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Ota-ElliottRicardo en-aut-sei=Ota-Elliott en-aut-mei=Ricardo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BianZhihong en-aut-sei=Bian en-aut-mei=Zhihong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BianYuting en-aut-sei=Bian en-aut-mei=Yuting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HuXinran en-aut-sei=Hu en-aut-mei=Xinran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SunHongming en-aut-sei=Sun en-aut-mei=Hongming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FukuiYusuke en-aut-sei=Fukui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=National Center Hospital, National Center of Neurology and Psychiatry kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Alzheimer's disease (AD) kn-keyword=Alzheimer's disease (AD) en-keyword=Amyloid-13 oligomers (A13O) kn-keyword=Amyloid-13 oligomers (A13O) en-keyword=Necroptosis kn-keyword=Necroptosis en-keyword=Microglia kn-keyword=Microglia en-keyword=Neurodegeneration kn-keyword=Neurodegeneration END start-ver=1.4 cd-journal=joma no-vol=50 cd-vols= no-issue= article-no= start-page=101990 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prognostic nutritional index is a prognostic factor for patients with gastric cancer and esophagogastric junction cancer undergoing proximal gastrectomy with esophagogastrostomy by the double-flap technique: A secondary analysis of the rD-FLAP study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: Although proximal gastrectomy (PG) is commonly used in patients with upper gastric cancer (GC) and esophagogastric junction (EGJ) cancer, long-term prognostic factors in these patients are poorly understood. The double-flap technique (DFT) is an esophagogastrostomy with anti-reflux mechanism after PG; we previously conducted a multicenter retrospective study (rD-FLAP) to evaluate the short-term outcomes of DFT reconstruction. Here, we evaluated the long-term prognostic factors in patients with upper GC and EGJ cancer.
Methods: The study was conducted as a secondary analysis of the rD-FLAP Study, which enrolled patients who underwent PG with DFT reconstruction, irrespective of disease type, between January 1996 and December 2015.
Results: A total of 509 GC and EGJ cancer patients were enrolled. Univariate and multivariate analyses of overall survival demonstrated that a preoperative prognostic nutritional index (PNI) < 45 (p < 0.001, hazard ratio [HR]: 3.59, 95% confidential interval [CI]: 1.93?6.67) was an independent poor prognostic factor alongside pathological T factor ([pT] ?2) (p = 0.010, HR: 2.29, 95% CI: 1.22?4.30) and pathological N factor ([pN] ?1) (p = 0.001, HR: 3.27, 95% CI: 1.66?6.46). In patients with preoperative PNI ?45, PNI change (<90%) at 1-year follow-up (p = 0.019, HR: 2.54, 95%CI: 1.16?5.54) was an independent poor prognostic factor, for which operation time (?300 min) and blood loss (?200 mL) were independent risk factors. No independent prognostic factors were identified in patients with preoperative PNI <45.
Conclusions: PNI is a prognostic factor in upper GC and EGJ cancer patients. Preoperative nutritional enhancement and postoperative nutritional maintenance are important for prognostic improvement in these patients. en-copyright= kn-copyright= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChodaYasuhiro en-aut-sei=Choda en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtsukaShinya en-aut-sei=Otsuka en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UeyamaSatoshi en-aut-sei=Ueyama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaNorimitsu en-aut-sei=Tanaka en-aut-mei=Norimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MuraokaAtsushi en-aut-sei=Muraoka en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HatoShinji en-aut-sei=Hato en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KamikawaYasuaki en-aut-sei=Kamikawa en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=4 en-affil=Department of Surgery, Fukuyama Medical Center kn-affil= affil-num=5 en-affil=Department of Surgery, Mihara Red Cross Hospital kn-affil= affil-num=6 en-affil=Department of Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, Kagawa Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Surgery, Shikoku Cancer Center kn-affil= affil-num=9 en-affil=Department of Surgery, Matsuda Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Double -flap technique kn-keyword=Double -flap technique en-keyword=Gastric cancer kn-keyword=Gastric cancer en-keyword=Prognostic factor kn-keyword=Prognostic factor en-keyword=Prognostic nutritional index kn-keyword=Prognostic nutritional index en-keyword=Proximal gastrectomy kn-keyword=Proximal gastrectomy END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=5 article-no= start-page=382 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220913 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Investigation of bone invasion and underlying mechanisms of oral cancer using a cell line?derived xenograft model en-subtitle= kn-subtitle= en-abstract= kn-abstract=The cancer stroma regulates bone invasion in oral squamous cell carcinoma (OSCC). However, data on normal stroma are limited. In the present study, the effects of gingival and periodontal ligament tissue?derived stromal cells (G?SCs and P?SCs, respectively) and human dermal fibroblasts (HDFs) on bone resorption and osteoclast activation were assessed using hematoxylin and eosin and tartrate?resistant acid phosphatase staining in a cell line?derived xenograft model. The results demonstrated that G?SCs promoted bone invasion and osteoclast activation and inhibited osteoclast proliferation following crosstalk with the human OSCC HSC?3 cell line, whereas P?SCs inhibited bone resorption and promoted osteoclast proliferation in vitro but had a minimal effect on osteoclast activation both in vitro and in vivo following crosstalk with HSC?3 cells. Furthermore, the effects of G?SCs, P?SCs and HDFs on protein expression levels of matrix metalloproteinase (MMP)?9, membrane type 1 MMP (MT1?MMP), Snail, parathyroid hormone?related peptide (PTHrP) and receptor activator of NF?B ligand (RANKL) in HSC?3 cells in OSCC bone invasion regions were assessed using immunohistochemistry. The results demonstrated that G?SCs had a more prominent effect on the expression of MMP?9, MT1?MMP, Snail, PTHrP, and RANKL, whereas P?SCs only promoted RANKL and PTHrP expression and exerted a minimal effect on MMP?9, MT1?MMP and Snail expression. The potential genes underlying the differential effects of G?SCs and P?SCs on bone invasion in OSCC were evaluated using a microarray, which indicated that cyclin?dependent kinase 1, insulin, aurora kinase A, cyclin B1 and DNA topoisomerase II alpha underlaid these differential effects. Therefore, these results demonstrated that G?SCs promoted bone invasion in OSCC by activating osteoclasts on the bone surface, whereas P?SCs exerted an inhibitory effect. These findings could indicate a potential regulatory mechanism for bone invasion in OSCC. en-copyright= kn-copyright= en-aut-name=ShanQiusheng en-aut-sei=Shan en-aut-mei=Qiusheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OmoriHaruka en-aut-sei=Omori en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiiMasae en-aut-sei=Fujii en-aut-mei=Masae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InadaYasunori en-aut-sei=Inada en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SanoSho en-aut-sei=Sano en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=oral squamous cell carcinoma kn-keyword=oral squamous cell carcinoma en-keyword=bone invasion kn-keyword=bone invasion en-keyword=gingival ligament tissue?derived stromal cell kn-keyword=gingival ligament tissue?derived stromal cell en-keyword=periodontal ligament tissue?derived stromal cell kn-keyword=periodontal ligament tissue?derived stromal cell en-keyword=xenograft model kn-keyword=xenograft model en-keyword=microarray kn-keyword=microarray END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=4 article-no= start-page=81 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Significance of cancer stroma for bone destruction in oral squamous cell carcinoma using different cancer stroma subtypes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Stromal cells in the tumor microenvironment (TME) can regulate the progression of numerous types of cancer; however, the bone invasion of oral squamous cell carcinoma (OSCC) has been poorly investigated. In the present study, the effect of verrucous SCC?associated stromal cells (VSCC?SCs), SCC?associated stromal cells (SCC?SCs) and human dermal fibroblasts on bone resorption and the activation of HSC?3 osteoclasts in vivo were examined by hematoxylin and eosin, AE1/3 (pan?cytokeratin) and tartrate?resistant acid phosphatase staining. In addition, the expression levels of matrix metalloproteinase (MMP)9, membrane?type 1 MMP (MT1?MMP), Snail, receptor activator of NF?B ligand (RANKL) and parathyroid hormone?related peptide (PTHrP) in the bone invasion regions of HSC?3 cells were examined by immunohistochemistry. The results suggested that both SCC?SCs and VSCC?SCs promoted bone resorption, the activation of osteoclasts, and the expression levels of MMP9, MT1?MMP, Snail, RANKL and PTHrP. However, SCC?SCs had a more prominent effect compared with VSCC?SCs. Finally, microarray data were used to predict potential genes underlying the differential effects of VSCC?SCs and SCC?SCs on bone invasion in OSCC. The results revealed that IL1B, ICAM1, FOS, CXCL12, INS and NGF may underlie these differential effects. In conclusion, both VSCC?SCs and SCC?SCs may promote bone invasion in OSCC by enhancing the expression levels of RANKL in cancer and stromal cells mediated by PTHrP; however, SCC?SCs had a more prominent effect. These findings may represent a potential regulatory mechanism underlying the bone invasion of OSCC. en-copyright= kn-copyright= en-aut-name=ShanQiusheng en-aut-sei=Shan en-aut-mei=Qiusheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InadaYasunori en-aut-sei=Inada en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FushimiShigeko en-aut-sei=Fushimi en-aut-mei=Shigeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=oral squamous cell carcinoma kn-keyword=oral squamous cell carcinoma en-keyword=bone invasion kn-keyword=bone invasion en-keyword=osteoclast kn-keyword=osteoclast en-keyword=receptor activator of NF?B ligand kn-keyword=receptor activator of NF?B ligand en-keyword=parathyroid hormone?related peptide kn-keyword=parathyroid hormone?related peptide en-keyword=microarray kn-keyword=microarray en-keyword=cancer?associated stromal cells kn-keyword=cancer?associated stromal cells END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=5 article-no= start-page=561 end-page=566 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effective Epilepsy Surgery for Post-Traumatic West Syndrome Following Abusive Head Trauma en-subtitle= kn-subtitle= en-abstract= kn-abstract=West syndrome, an infantile developmental and epileptic encephalopathy with a deleterious impact on long-term development, requires early treatment to minimize developmental abnormality; in such cases, epilepsy surgery should be considered a powerful therapeutic option. We describe a 10-month-old female admitted with West syndrome associated with a hemispheric lesion following abusive head trauma. Her seizures were suppressed by hemispherotomy at 12 months of age, leading to developmental improvement. Surgical treatment of West syndrome following traumatic brain injury has not been reported previously but is worth considering as a treatment option, depending on patient age and brain plasticity. en-copyright= kn-copyright= en-aut-name=TsuchiyaHiroki en-aut-sei=Tsuchiya en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShibataTakashi en-aut-sei=Shibata en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SasakiTatsuya en-aut-sei=Sasaki en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueTakushi en-aut-sei=Inoue en-aut-mei=Takushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics, National Hospital Organization Okayama Medical Center kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital kn-affil= en-keyword=abusive head trauma kn-keyword=abusive head trauma en-keyword=developmental and epileptic encephalopathy kn-keyword=developmental and epileptic encephalopathy en-keyword=epilepsy surgery kn-keyword=epilepsy surgery en-keyword=epileptic spasms kn-keyword=epileptic spasms en-keyword=hemispherotomy kn-keyword=hemispherotomy END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=5 article-no= start-page=553 end-page=559 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Favorable Outcome of Repeated Salvage Surgeries for Rare Metastasis to the Ligamentum Teres Hepatis and the Upper Abdominal Wall in a Stage IV Gastric Cancer Patient en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gastric cancer with peritoneal metastases is typically a devastating diagnosis. Ligamentum teres hepatis (LTH) metastasis is an extremely rare presentation with only four known cases. Herein, we report salvage surgery of successive metastases to the abdominal wall and LTH in a patient originally presenting with advanced gastric cancer with peritoneal metastasis, leading to long-term survival. A 72-year-old man with advanced gastric cancer underwent curative-intent distal gastrectomy with D2 lymph node dissection for gastric outlet obstruction. During this procedure, three small peritoneal metastases were detected in the lesser omentum, the small mesentery, and the mesocolon; however, intraoperative abdominal lavage cytology was negative. We added cytoreductive surgery for peritoneal metastasis. The pathological diagnosis of the gastric cancer was tubular adenocarcinoma with pT4aN1pM1(PER/P1b)CY0 stage IV (Japanese classification of gastric carcinoma/JCGC 15th), or T4N1M1b stage IV (UICC 7th). Post-operative adjuvant chemotherapy with S-1 (TS-1)+cisplatin (CDDP) was administered for 8 months followed by S-1 monotherapy for 4 months. At 28 months after the initial surgery, a follow-up computed tomography (CT) detected a small mass beneath the upper abdominal wall. The ass showed mild avidity on 18F-fluorodeoxyglucose positron-emission (FDG-PET) CT. Salvage resection was performed for diagnosis and treatment, and pathological findings were consistent with primary gastric cancer metastasis. At 49 months after the initial gastrectomy, a new lesion was detected in the LTH with a similar level of avidity on FDG-PET CT as the abdominal wall metastatic lesion. We performed a second salvage surgery for the LTH tumor, which also showed pathology of gastric cancer metastasis. There has been no recurrence up to 1 year after the LTH surgery. With multidisciplinary treatment the patient has survived almost 5 years after the initial gastrectomy. Curative-intent gastrectomy with cytoreductive surgery followed by adjuvant chemotherapy for advanced gastric cancer with localized peritoneal metastasis might have had a survival benefit in our patient. Successive salvage surgeries for oligometastatic lesions in the abdominal wall and the LTH also yielded favorable outcomes. en-copyright= kn-copyright= en-aut-name=MurokawaTakahiro en-aut-sei=Murokawa en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakamotoShinya en-aut-sei=Sakamoto en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TabuchiMotoyasu en-aut-sei=Tabuchi en-aut-mei=Motoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuiKenta en-aut-sei=Sui en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OzakiKazuhide en-aut-sei=Ozaki en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoManabu en-aut-sei=Matsumoto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwataJun en-aut-sei=Iwata en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkabayashiTakehiro en-aut-sei=Okabayashi en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshidaHiroshi en-aut-sei=Yoshida en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=7 en-affil=Department of Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=9 en-affil=Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School kn-affil= en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=peritoneal metastasis kn-keyword=peritoneal metastasis en-keyword=ligamentum teres hepatis kn-keyword=ligamentum teres hepatis en-keyword=oligometastasis kn-keyword=oligometastasis en-keyword=salvage surgery kn-keyword=salvage surgery END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=5 article-no= start-page=545 end-page=552 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Endoscopic Manifestations and Clinical Characteristics of Localized Gastric Light-Chain Amyloidosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=To determine the endoscopic and clinical features of localized gastric amyloid light-chain (AL) amyloidosis, we retrospectively examined the characteristics of nine patients (eight men and one woman) encountered by the hospitals in our network. Lesions were predominantly flat and depressed with surface vascular dilatation (n=5); others were characterized by subepithelial lesions (n=2), mucosal color change (n=1), and a mass-like morphology with swollen mucosal folds (n=1). Colonoscopy (n=7), video capsule enteroscopy (n=2), serum (n=5) and urine immunoelectrophoresis (n=4), and bone marrow examination (n=3) were performed to exclude involvement of organs other than the stomach. As treatment for gastric lesions of AL amyloidosis, one patient each underwent endoscopic submucosal dissection (n=1) and argon plasma coagulation (n=1), while the remaining seven patients underwent no specific treatment. During a mean follow-up of 4.2 years, one patient died 3.2 years after diagnosis, but the cause of death, which occurred in another hospital, was unknown. The remaining eight patients were alive at the last visit. In conclusion, although localized gastric AL amyloidosis can show various macroscopic features on esophagogastroduodenoscopy, flat, depressed lesions with vascular dilatation on the surface are predominant. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaShouichi en-aut-sei=Tanaka en-aut-mei=Shouichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ToyokawaTatsuya en-aut-sei=Toyokawa en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraMamoru en-aut-sei=Nishimura en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsuzukiTakao en-aut-sei=Tsuzuki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyaharaKoji en-aut-sei=Miyahara en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NegishiShin en-aut-sei=Negishi en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhyaShogen en-aut-sei=Ohya en-aut-mei=Shogen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=3 en-affil=Department of Gastroenterology, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Okayama City Hospital kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Kagawa Prefectural Central Hospital kn-affil= affil-num=8 en-affil=Kawaguchi Medical Clinic kn-affil= affil-num=9 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=esophagogastroduodenoscopy kn-keyword=esophagogastroduodenoscopy en-keyword=gastric lesion kn-keyword=gastric lesion en-keyword=amyloidosis kn-keyword=amyloidosis en-keyword=light chain kn-keyword=light chain END