start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=7 article-no= start-page=3143 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260330 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CXCR2-Dependent Infiltration of Tumor-Associated Neutrophils Is Linked to Enhanced CD8+ T Cell Effector Function and Reduced Lung Metastasis in 4T1 Breast Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Triple-negative breast cancer (TNBC) is characterized by prominent neutrophil infiltration; however, its significance remains controversial. Here, we investigated the role of neutrophil chemoattractant receptors in TNBC progression and metastasis. In contrast to wild-type (WT), Fpr1−/−, and Fpr2−/− mice, neutrophils were almost completely absent in 4T1 tumors from Cxcr2−/− mice, indicating a dominant role for CXCR2 in the recruitment of tumor-associated neutrophils, leading us to use Cxcr2−/− mice for further studies. Primary tumor growth was comparable between WT and Cxcr2−/− mice, whereas lung metastasis was significantly increased in Cxcr2−/− mice, with reduced expression of inflammatory cytokines, chemokines and cytotoxic molecules, including granzyme B and perforin, in primary tumors and metastatic lungs of Cxcr2−/− mice. In vitro, WT, but not Cxcr2−/−, neutrophils enhanced CD8+ T cell activation, partly via ICAM-1, and directly induced tumor cell death, supporting their anti-tumor function. To assess clinical relevance, transcriptomic data were analyzed. High neutrophil infiltration combined with elevated CXCR2 expression, and to a lesser extent CXCR1 expression, was associated with improved prognosis in patients with basal-like BC that largely overlaps with TNBC. Collectively, these findings suggest that CXCR2-mediated neutrophil recruitment exerts protective, anti-tumor effects and may represent a new prognostic marker for TNBC patients. en-copyright= kn-copyright= en-aut-name=LiTiantian en-aut-sei=Li en-aut-mei=Tiantian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=NishidaGakushi en-aut-sei=Nishida en-aut-mei=Gakushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=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=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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 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= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=neutrophils kn-keyword=neutrophils en-keyword=CD8+ T cells kn-keyword=CD8+ T cells en-keyword=chemokines kn-keyword=chemokines en-keyword=chemokine receptors kn-keyword=chemokine receptors en-keyword=tumor microenvironment kn-keyword=tumor microenvironment END start-ver=1.4 cd-journal=joma no-vol=2025 cd-vols= no-issue= article-no= start-page=9884345 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparing the Activity of Peripheral Blood Mononuclear Cells Frozen Under Electromagnetic Field Freezing and Standard Slow-Freezing en-subtitle= kn-subtitle= en-abstract= kn-abstract=Peripheral blood mononuclear cells (PBMCs) are cells obtained from the blood that are used not only in clinical tests but also in various research applications. The slow-freezing (SLF) method, currently the standard for PBMC cryopreservation, involves extended storage at −80°C before transfer to liquid nitrogen. Delays in this transfer, such as overnight or weekend holds, risk a gradual decline in cell viability. Additionally, variability in freezing duration can lead to inconsistent cell quality, emphasizing the need for an alternative freezing method that allows for more timely transfer to liquid nitrogen. This study is aimed at clarifying whether the method of using a freezer with an applied electromagnetic field (EMF) is superior to the currently used standard SLF method for PBMC cryopreservation. A comparison of the number of viable cells, cell viability, and cell activity showed that the EMF method was equivalent to the SLF method. However, the shortest time required for freezing was significantly shorter with the EMF method than the SLF method (0.25 vs. 3 h), allowing for earlier transfer of PBMC to liquid nitrogen. This demonstrates that the EMF method offers an advantage in operational efficiency, particularly for facilities that routinely process and store PBMCs, such as biobanks and other storage-focused departments. en-copyright= kn-copyright= en-aut-name=MatsubaraTakehiro en-aut-sei=Matsubara en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakagiMina en-aut-sei=Takagi en-aut-mei=Mina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UwaboTakahiro en-aut-sei=Uwabo en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi 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=MoritaMizuki en-aut-sei=Morita en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Okayama University Hospital Biobank kn-affil= affil-num=2 en-affil=Faculty of Health Sciences, Okayama University Medical School kn-affil= affil-num=3 en-affil=Department of Biorepository Research and Networking, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Thoracic Surgery, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Okayama University Hospital Biobank kn-affil= affil-num=6 en-affil=Okayama University Hospital Biobank kn-affil= END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=50 article-no= start-page=e06926 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251031 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Collagen Signaling via DDR1 Exacerbates Barriers to Macromolecular Drug Delivery in a 3D Model of Pancreatic Cancer Fibrosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fibrosis is a significant barrier to drug delivery in pancreatic ductal adenocarcinoma (PDAC) and contributes to its dismal prognosis. Pancreatic stellate cells (PSCs) drive fibrosis by excessively secreting extracellular matrix proteins such as collagen I. Collagen I is thought to physically obstruct the delivery of macromolecules, such as albumin, antibodies, and nanomedicines. Apart from its structural role, collagen signals through dedicated cell surface receptors, such as the discoidin domain receptors (DDR) 1/2. However, whether and how collagen signaling contributes to fibrotic barrier generation remains uncharacterized. Here, a 3D culture model of PDAC fibrosis constructed from patient PSCs is used to assess the contribution of DDR1/2-mediated collagen signaling. DDR1/2 inhibition diminishes collagen I expression in PSCs to enhance macromolecular delivery. Moreover, MEK inhibitors exacerbate the fibrotic barrier by up-regulating collagen I, an effect reversed by inhibiting DDR1/2. Through isoform-specific targeting, inhibiting DDR1, but not DDR2, is shown to be effective. Downstream of DDR, the involvement of the PI3K/AKT/mTOR pathway is demonstrated, particularly alternative mTOR complexes involving MEAK7 and GIT1. Altogether, the results show in vitro that DDR1-mediated collagen signaling exacerbates the fibrotic barrier and may be targeted to enhance macromolecular drug delivery in PDAC. en-copyright= kn-copyright= en-aut-name=OhiraMayu en-aut-sei=Ohira en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitamuraMoe en-aut-sei=Kitamura en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IwasakiHiroyo en-aut-sei=Iwasaki en-aut-mei=Hiroyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Ohta‐OkanoHaruko en-aut-sei=Ohta‐Okano en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsujiiHiyori en-aut-sei=Tsujii en-aut-mei=Hiyori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraReika en-aut-sei=Nakamura en-aut-mei=Reika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakazawaTakuya en-aut-sei=Nakazawa en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishiguchiAkihiro en-aut-sei=Nishiguchi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoMasaya en-aut-sei=Yamamoto en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OsadaKensuke en-aut-sei=Osada en-aut-mei=Kensuke 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=CabralHoracio en-aut-sei=Cabral en-aut-mei=Horacio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MasamuneAtsushi en-aut-sei=Masamune en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KanoMitsunobu R. en-aut-sei=Kano en-aut-mei=Mitsunobu R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= affil-num=1 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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 Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Biomaterials Field, Research Center for Macromolecules and Biomaterials, National Institute for Materials Science kn-affil= affil-num=9 en-affil=Department of Materials Processing, Graduate School of Engineering, Tohoku University kn-affil= affil-num=10 en-affil=Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Sciences and Technology (QST) 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 Bioengineering, Graduate School of Engineering, The University of Tokyo kn-affil= affil-num=13 en-affil=Division of Gastroenterology, Graduate School of Medicine, Tohoku University kn-affil= affil-num=14 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=15 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=collagen kn-keyword=collagen en-keyword=fibrosis kn-keyword=fibrosis en-keyword=nanomedicine kn-keyword=nanomedicine en-keyword=pancreatic cancer kn-keyword=pancreatic cancer en-keyword=pancreatic stellate cell kn-keyword=pancreatic stellate cell 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=2026 dt-pub=20260225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical and Genetic Landscape of Glioblastoma, IDH-Wildtype With FGFR Gene Family Alterations en-subtitle= kn-subtitle= en-abstract= kn-abstract=Glioblastoma, isocitrate dehydrogenase wildtype (GBM, IDH-wt), is a highly aggressive brain tumor with a poor prognosis. Alterations in the fibroblast growth factor receptor (FGFR) gene family—such as FGFR::TACC fusions and FGFR1 mutations—have emerged as potential therapeutic targets; however, their clinical and genetic features in GBM, IDH-wt remain unclear. We analyzed 1076 GBM, IDH-wt cases using comprehensive genomic profiling data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database in Japan. FGFR alterations were detected in 8.0% of patients, including FGFR::TACC fusions (3.3%) and FGFR1 mutations (2.9%). The FGFR::TACC fusion-positive group was older at diagnosis and showed higher frequencies of TERT promoter mutation and MDM2 amplification, and lower frequencies of EGFR amplification and TP53 mutation, compared with the fusion-negative group. The FGFR1 mutation-positive group was enriched for ATRX, NF1, and PIK3CA mutations and had significantly fewer TERT promoter and PTEN mutations, compared with the mutation-negative group. No significant differences in overall survival were observed, although both groups tended to have longer median overall survival compared with their respective negative groups. This study represents the largest genomic cohort to date of FGFR alterations in GBM, IDH-wt. FGFR::TACC fusion-positive and FGFR1 mutation-positive GBMs exhibited distinct genetic profiles, highlighting the clinical relevance of molecular subclassification and providing insight for future therapeutic strategies. en-copyright= kn-copyright= en-aut-name=KegoyaYasuhito en-aut-sei=Kegoya en-aut-mei=Yasuhito 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=MizutaRyo en-aut-sei=Mizuta en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=KamiuraMako en-aut-sei=Kamiura en-aut-mei=Mako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=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=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke 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=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 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=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital 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=comprehensive genomic profiling kn-keyword=comprehensive genomic profiling en-keyword=copy number alteration kn-keyword=copy number alteration en-keyword=FGFR kn-keyword=FGFR en-keyword=glioblastoma kn-keyword=glioblastoma en-keyword=single-nucleotide variant kn-keyword=single-nucleotide variant END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=13 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pan-cancer profiling links C1orf50 to DNA repair and immune modulation in ovarian cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background C1orf50 encodes a small, evolutionarily conserved protein, the function of which remains unclear. Its significance across various human cancers, particularly its specific role in ovarian cancer within an immunogenomic context, is not yet fully understood. Utilizing The Cancer Genome Atlas and single-cell RNA sequencing (scRNA-seq) public datasets, we conducted a comprehensive profiling of C1orf50 across multiple cancer types, with a particular focus on ovarian cancer, to investigate its associations with copy-number status, genomic instability, tumor programs, and the immune microenvironment.
Results Across cancer types, copy-number gain or amplification of C1orf50 was most frequent in ovarian cancer and closely tracked with higher messenger RNA levels. Higher C1orf50 expression was associated with a greater tumor mutational burden and homologous recombination deficiency, as indicated by gene-set patterns that suggested heightened cell-cycle and cellular stress responses accompanied by reduced oxidative phosphorylation, enrichment of regulatory T cells, and depletion of resting memory CD4 T cells. In ovarian cancer, focal events at chromosome 1p34.2 were accompanied by stepwise increases in C1orf50 expression by clinical stage and were linked to higher tumor mutational burden, homologous recombination deficiency, and greater loss of heterozygosity, together with more frequent gene alterations in BRCA1 or BRCA2. Immune composition clustered into profiles consistent with an immunosuppressive context in tumors with higher C1orf50 expression. The scRNA-seq data further revealed that cancer cells enhanced immune-suppressive interactions with various immune cell populations and diminished antigen-presentation signals. Analyses of genomic instability in ovarian cancer suggested mutational processes compatible with base-substitution patterns associated with cytidine deaminase activity and with insertion-deletion patterns characteristic of homologous recombination failure, while transcript-level patterns pointed to a broad downshift of canonical DNA repair activity with apparent compensatory adjustments in related pathways rather than a uniform change in any single pathway.
Conclusions The overexpression of C1orf50 characterizes an aggressive immunogenomic phenotype in ovarian cancer, distinguished by genomic instability, impaired DNA repair mechanisms, and extensive immunosuppression. These findings indicate that C1orf50 warrants consideration as a potential biomarker and a prospective target for therapeutic investigation. Furthermore, they advocate for the progression to prospective validation and functional studies to ascertain its clinical significance. en-copyright= kn-copyright= en-aut-name=RogachevskayaAnna en-aut-sei=Rogachevskaya en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=OhtsuAkira en-aut-sei=Ohtsu en-aut-mei=Akira 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=PeñaTirso en-aut-sei=Peña en-aut-mei=Tirso kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AraiSeiji en-aut-sei=Arai en-aut-mei=Seiji 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=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=2 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=3 en-affil=Harvard Medical School 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 Urology, Gunma University Graduate School of Medicine 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 kn-affil= affil-num=8 en-affil=Department of Molecular Physiology, Faculty of Medicine, Graduate School of Medicine, Kagawa University kn-affil= affil-num=9 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= en-keyword=C1orf50 kn-keyword=C1orf50 en-keyword=Pan-cancer analysis kn-keyword=Pan-cancer analysis en-keyword=DNA repair kn-keyword=DNA repair en-keyword=Gene expression kn-keyword=Gene expression en-keyword=Tumor microenvironment kn-keyword=Tumor microenvironment en-keyword=Immune evasion kn-keyword=Immune evasion en-keyword=Single-cell RNA-seq kn-keyword=Single-cell RNA-seq END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=6 article-no= start-page=1128 end-page=1136 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250531 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Surgery for Older Cancer Patients: Cross‐Organ Review and Good Practice Statement by the Japanese Geriatric Oncology Guideline Committee en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Although the number of older people is increasing, there is a lack of evidence and insufficient consensus regarding postoperative complications and survival in older cancer patients. In this study, we conducted a literature search and systematic review focusing on the outcomes after surgery for older cancer patients.
Methods: Literature focusing on surgical treatment for older cancer patients was extracted from Japanese clinical practice guidelines for gastric cancer, lung cancer, colorectal cancer, liver cancer, and gynecological cancers (uterine body, uterine cervix, ovary, and external genitalia and vagina). Outcomes were reviewed, and committee members determined the strength of evidence on a four-point scale (A to D), with A being the highest and D being the lowest.
Results: Older cancer patients tend to have a higher incidence of postoperative complications and postoperative syndromes, and their expected survival is generally shorter compared to non-older patients. When extensive surgeries such as para-aortic lymph node dissection and/or resection with other organs are performed for older cancer patients, the postoperative mortality rates tend to increase compared to non-older patients.
Conclusion: Surgical treatments for older cancer patients tend to result in higher morbidity even when the patients are in good health status. Nevertheless, there is still a possibility that a certain fraction of the patients achieve treatment outcomes comparable to those of non-older patients. Therefore, surgical indication and procedure for older cancer patients should be carefully determined based on surgical invasiveness and patient tolerability. en-copyright= kn-copyright= en-aut-name=TanakaChie en-aut-sei=Tanaka en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OfuchiTakashi en-aut-sei=Ofuchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=InoueDaisuke en-aut-sei=Inoue en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugimotoKen en-aut-sei=Sugimoto en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MurofushiKeiko en-aut-sei=Murofushi en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkuyamaToru en-aut-sei=Okuyama en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanukiShigeaki en-aut-sei=Watanuki en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ImamuraChiyo en-aut-sei=Imamura en-aut-mei=Chiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SakaiDaisuke en-aut-sei=Sakai en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakuraiNaomi en-aut-sei=Sakurai en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WatanabeKiyotaka en-aut-sei=Watanabe en-aut-mei=Kiyotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TamuraKazuo en-aut-sei=Tamura en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SaekiToshiaki en-aut-sei=Saeki en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IshiguroHiroshi en-aut-sei=Ishiguro en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Surgery, Kyushu University Beppu Hospital kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, University of Fukui kn-affil= affil-num=5 en-affil=Department of General Geriatric Medicine, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Division of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=7 en-affil=Department of Psychiatry/Palliative Care Center, Nagoya City University West Medical Center kn-affil= affil-num=8 en-affil=National Center for Global Health and Medicine, National College of Nursing kn-affil= affil-num=9 en-affil=Advanced Cancer Translational Research Institute, Showa University kn-affil= affil-num=10 en-affil=Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Cancer Solutions Co. Ltd kn-affil= affil-num=12 en-affil=Division of Medical Oncology, Department of Medicine, School of Medicine, Teikyo University kn-affil= affil-num=13 en-affil=NPO Clinical Hematology/Oncology Treatment Study Group kn-affil= affil-num=14 en-affil=Breast Oncology Service, Saitama Medical University International Medical Center kn-affil= affil-num=15 en-affil=Breast Oncology Service, Saitama Medical University International Medical Center kn-affil= en-keyword=cancer kn-keyword=cancer en-keyword=older patients kn-keyword=older patients en-keyword=surgery kn-keyword=surgery END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=6 article-no= start-page=e86575 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250623 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Retreatment With EGFR-Tyrosine Kinase Inhibitor After Disease Progression Following Gefitinib Induction and Chemoradiotherapy in EGFR-Mutant Stage III Non-small Lung Cancer: An Efficacy and Safety Analysis of the LOGIK0902/OLCSG0905 Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and objective: We had previously conducted a phase II study (LOGIK0902/OLCSG0905 study) involving the eight-week administration of gefitinib, followed by cisplatin-based chemoradiotherapy, to treat locally advanced, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC). Despite favorable overall survival outcomes, more than half of the patients relapsed after the protocol therapy, highlighting the need to clarify the clinical significance of retreatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated the efficacy and safety of EGFR-TKI retreatment after disease progression.
Materials and methods: We included 14 patients who relapsed after the protocol treatment and received any type of EGFR-TKI as post-progression treatment in this sub-analysis. We evaluated the efficacy and safety of retreatment with EGFR-TKI in these patients.
Results: Among the 14 patients, 11 (78.6%) responded to the induction of gefitinib in the treatment protocol. After relapse, 9/14 patients (64.3%) received gefitinib, 3/14 (21.4%) received afatinib, and 2/14 (14.3%) received erlotinib monotherapy, respectively. The median duration of post-progression EGFR-TKI treatment was 17.9 (0.7-45.5) months. The overall response rate (ORR) and disease control rate were 64.3% [9/14 patients; 95% confidence interval (CI): 35.1%-87.2%] and 85.7% (12/14 patients; 95% CI: 57.2%-98.2%), respectively. The median progression-free survival (PFS) and median survival durations after the initiation of EGFR-TKI retreatment were 11.8 months (95% CI: 5.7-20.7 months) and 47.4 months (95% CI: 31.8 months to not estimable), respectively. Adverse events were comparable to those previously reported.
Conclusions: Patients with disease progression after protocol therapy demonstrated sensitivity to retreatment with an EGFR-TKI, with acceptable safety. en-copyright= kn-copyright= en-aut-name=SaekiSho en-aut-sei=Saeki en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=SakataShinya en-aut-sei=Sakata en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OdaNaohiro en-aut-sei=Oda en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueKoji en-aut-sei=Inoue en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TamuraTomoki en-aut-sei=Tamura en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyozawaRyo en-aut-sei=Toyozawa en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaradaDaijiro en-aut-sei=Harada en-aut-mei=Daijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaKentaro en-aut-sei=Tanaka en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=InoueKoji en-aut-sei=Inoue en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShioyamaYoshiyuki en-aut-sei=Shioyama en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GembaKenichi en-aut-sei=Gemba en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SasakiTomonari en-aut-sei=Sasaki en-aut-mei=Tomonari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=BesshoAkihiro en-aut-sei=Bessho en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KishimotoJunji en-aut-sei=Kishimoto en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 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=17 ORCID= en-aut-name=SugioKenji en-aut-sei=Sugio en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, Kumamoto University Hospital kn-affil= affil-num=2 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Kumamoto University Hospital kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Kitakyushu Municipal Medical Center kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center kn-affil= affil-num=8 en-affil=Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Ehime Prefectural Central Hospital kn-affil= affil-num=11 en-affil=Radiation Oncology, Ion Beam Therapy Center, SAGA HIMAT Foundation kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Chugoku Central Hospital kn-affil= affil-num=13 en-affil=Department of Radiation Oncology, Iizuka Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=15 en-affil=Center for Clinical and Translational Research, Kyushu University Hospital kn-affil= affil-num=16 en-affil=Department of Radiology, Division of Radiation Oncology, Kawasaki Medical School kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Thoracic and Breast Surgery, Oita University kn-affil= en-keyword=chemoradiotherapy kn-keyword=chemoradiotherapy en-keyword=egfr kn-keyword=egfr en-keyword=locally advanced setting kn-keyword=locally advanced setting en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=progression kn-keyword=progression en-keyword=retreatment kn-keyword=retreatment en-keyword=safety kn-keyword=safety en-keyword=targeted therapy kn-keyword=targeted therapy END start-ver=1.4 cd-journal=joma no-vol=112 cd-vols= no-issue=2 article-no= start-page=2301 end-page=2310 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Total thymectomy is oncologically superior to partial thymectomy in patients with thymic carcinoma: insights from a multicenter real-world data analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Although total thymectomy has been the standard surgical approach for thymic epithelial tumors, an increasing number of recent reports suggest that partial thymectomy for early-stage thymomas may yield outcomes comparable to those of total thymectomy. However, whether partial thymectomy is a viable alternative for thymic carcinoma remains unclear.
Materials and methods: A total of 106 patients with thymic carcinoma underwent curative intended resection at 19 institutions between January 2010 and December 2021. Excluding 14 patients with incomplete resection, 92 patients with thymic carcinoma who underwent total (n = 73) or partial thymectomy (n = 19) were compared. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan–Meier curves and Cox proportional hazard models. Overlap weighting was applied to adjust for potential confounding factors.
Results: Among patients with clinical stage I disease, 79.3% were upstaged to stage II or higher postoperatively. Unadjusted analyses revealed no statistically significant differences in OS and RFS between the total and partial thymectomy groups, although a trend toward poorer outcomes in the partial thymectomy group was observed. After overlap weighting, partial thymectomy was associated with significantly poorer OS (P = 0.0027) and higher recurrence risk (P < 0.0001). Early postoperative recurrence occurred more frequently in the partial thymectomy group.
Conclusion: Partial thymectomy was associated with significantly worse survival and recurrence outcomes in thymic carcinoma. Given the limitations of preoperative diagnosis, total thymectomy should remain the preferred surgical approach for undiagnosed thymic epithelial tumors to achieve optimal oncologic control and minimize the risk of recurrence. en-copyright= kn-copyright= en-aut-name=HayashiTatsuya en-aut-sei=Hayashi en-aut-mei=Tatsuya 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=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=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=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 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=12 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=13 ORCID= en-aut-name=HayashiTatsurou en-aut-sei=Hayashi en-aut-mei=Tatsurou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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=16 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=17 ORCID= en-aut-name=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=19 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=20 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=21 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=22 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=23 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=24 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=25 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=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 of Innovative Clinical Medicine, Okayama University Hospital 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=Okayama University Thoracic Surgery Study Group (OUTSSG) 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=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=9 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=10 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=11 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=12 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=13 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=14 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=15 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=16 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=17 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=18 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=19 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=20 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=21 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=22 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=23 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=24 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=25 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=26 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) 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= en-keyword=partial thymectomy kn-keyword=partial thymectomy en-keyword=real-world data analysis kn-keyword=real-world data analysis en-keyword=retrospective comparative cohort study kn-keyword=retrospective comparative cohort study en-keyword=thymic carcinoma kn-keyword=thymic carcinoma en-keyword=thymic epithelial tumors kn-keyword=thymic epithelial tumors en-keyword=total thymectomy kn-keyword=total thymectomy END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue= article-no= start-page=e2500182 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=Development and Validation of an Ipsilateral Breast Tumor Recurrence Risk Estimation Tool Incorporating Real-World Data and Evidence From Meta-Analyses: A Retrospective Multicenter Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Ipsilateral breast tumor recurrence (IBTR) remains a critical concern for patients undergoing breast-conserving surgery (BCS). Reliable risk estimation tools for IBTR risk can support personalized surgical and adjuvant treatment decisions, especially in the era of evolving systemic therapies. We aimed to develop and validate models to estimate IBTR risk.
Patients and Methods This multicenter retrospective cohort study included 8,938 women who underwent partial mastectomy for invasive breast cancer between 2008 and 2017. Prediction models were developed using Cox proportional hazards regression and validated via bootstrap resampling. Model performance was assessed using Harrell's C-index, Brier scores, calibration plots, and goodness-of-fit tests.
Results During a median follow-up of 9.0 years (IQR, 6.6-10.9), IBTR occurred in 320 patients (3.6%). The initial model, based on variables from Sanghani et al, achieved a Harrell's C-index of 0.74. Incorporating hormonal receptor status, human epidermal growth factor receptor 2 status, radiotherapy, and targeted therapy as predictors reduced the C-index to 0.65, despite their clinical relevance. Importantly, the inclusion of these factors improved calibration, demonstrating better alignment between predicted and observed IBTR probabilities. Although the hazard ratios (HRs) for radiotherapy aligned with the Early Breast Cancer Trialists’ Collaborative Group meta-analyses (MA), those for chemotherapy and endocrine therapy showed slight differences. Therefore, HRs from the MA were used to represent treatment effects in our model.
Conclusion We have developed and internally validated a new risk estimation model for IBTR using Cox regression and bootstrap methods. A Web-based risk estimation tool is now available to facilitate individualized risk assessment and treatment planning. en-copyright= kn-copyright= en-aut-name=SagaraYasuaki en-aut-sei=Sagara en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaAtsushi en-aut-sei=Yoshida en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraYuri en-aut-sei=Kimura en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshitobiMakoto en-aut-sei=Ishitobi en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OnoYuka en-aut-sei=Ono en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= en-aut-name=TakadaKoji en-aut-sei=Takada en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ItoYuri en-aut-sei=Ito en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OsakoTomo en-aut-sei=Osako en-aut-mei=Tomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakaiTakehiko en-aut-sei=Sakai en-aut-mei=Takehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Breast and Thyroid Surgical Oncology, Hakuaikai Sagara Hospital kn-affil= affil-num=2 en-affil=Department of Breast Surgical Oncology, St Luke's International Hospital kn-affil= affil-num=3 en-affil=Department of Breast Surgical Oncology, The Cancer Institute Hospital of JFCR kn-affil= affil-num=4 en-affil=Department of Breast Surgery, Osaka Habikino Medical Center kn-affil= affil-num=5 en-affil=Department of Radiation Oncology and Image-Applied Therapy, Kyoto 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 Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Breast Surgical Oncology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Medical Statistics, Osaka Medical and Pharmaceutical University kn-affil= affil-num=10 en-affil=Division of Pathology, The Cancer Institute of Japanese Foundation for Cancer Research kn-affil= affil-num=11 en-affil=Department of Breast Surgical Oncology, The Cancer Institute Hospital of JFCR kn-affil= 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=20251229 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genotype–Phenotype Correlations of Li–Fraumeni Syndrome in Japan Children's Cancer Group LFS20 Study Cohort en-subtitle= kn-subtitle= en-abstract= kn-abstract=Li–Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by germline pathogenic variants in the TP53 gene. With the increasing use of multi-gene panel testing, TP53 variants have been identified in individuals who do not meet established TP53 testing criteria, such as the Chompret criteria. The term “attenuated LFS” has been proposed for some of these cases, particularly those with adult-onset cancer. We analyzed participants of the Japanese nationwide prospective clinical trial of the cancer surveillance program (Japan Children's Cancer Group LFS-20), along with clinical information including their family histories, to better understand their genotypic and phenotypic characteristics. We identified 32 distinct TP53 variants from 41 families (45 participants), including four missense variants with conflicting classifications of pathogenicity in ClinVar. Among these families, 36 (88%) met the LFS criteria (hereafter referred to as “LFS” in contrast to attenuated LFS), while 5 (12%) were classified as attenuated LFS. Including 30 additional family members carrying the same variant, we analyzed 75 individuals with TP53 variants. Of these, 40 with LFS and 6 with attenuated LFS had cancer. Multiple primary cancers occurred in 22 individuals (21 LFS, 1 attenuated LFS). LFS-core tumors accounted for 66% (58/88) of cancers in the LFS group and 63% (5/8) in the attenuated LFS group; of note, all core tumors in the attenuated group were limited to breast cancer. Hotspot missense variants were detected in 11 of 36 LFS families and in none of 5 attenuated LFS families, and non-hotspot null variants were found in 14 and 1, respectively. Our study revealed genotype–phenotype correlations in several respects. UMIN-CTR: UMIN000045855. en-copyright= kn-copyright= en-aut-name=YamazakiFumito en-aut-sei=Yamazaki en-aut-mei=Fumito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakanoYoshiko en-aut-sei=Nakano en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SanadaMasashi en-aut-sei=Sanada en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KurahashiHiroki en-aut-sei=Kurahashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyaiShunsuke en-aut-sei=Miyai en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UekiArisa en-aut-sei=Ueki en-aut-mei=Arisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeYuko en-aut-sei=Watanabe en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HasegawaDaisuke en-aut-sei=Hasegawa en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KarakawaShuhei en-aut-sei=Karakawa en-aut-mei=Shuhei 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=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SaitoAkiko M. en-aut-sei=Saito en-aut-mei=Akiko M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=InoueEisuke en-aut-sei=Inoue en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KatoMotohiro en-aut-sei=Kato en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HattoriHiroyoshi en-aut-sei=Hattori 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 Pediatrics, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Department of Genetic Medicine and Services, National Cancer Center Hospital kn-affil= affil-num=3 en-affil=Department of Advanced Diagnosis, Clinical Research Center, NHO Nagoya Medical Center kn-affil= affil-num=4 en-affil=Division of Molecular Genetics, Center for Medical Science, Fujita Health University kn-affil= affil-num=5 en-affil=Division of Molecular Genetics, Center for Medical Science, Fujita Health University kn-affil= affil-num=6 en-affil=Department of Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=7 en-affil=Department of Pediatric Oncology, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Pediatrics, St. Luke's International Hospital kn-affil= affil-num=9 en-affil=Department of Pediatrics, Hiroshima University Hospital kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Clinical Research Center, NHO Nagoya Medical Center kn-affil= affil-num=13 en-affil=Showa Medical University Research Administration Center, Showa Medical University kn-affil= affil-num=14 en-affil=Department of Pediatrics, The University of Tokyo kn-affil= affil-num=15 en-affil=Department of Clinical Genetics, NHO Nagoya Medical Center kn-affil= en-keyword=cancer predisposition kn-keyword=cancer predisposition en-keyword=genotype–phenotype correlations kn-keyword=genotype–phenotype correlations en-keyword=hotspot variants kn-keyword=hotspot variants en-keyword=Li–Fraumeni syndrome kn-keyword=Li–Fraumeni syndrome en-keyword=TP53 kn-keyword=TP53 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=20251211 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Atezolizumab + Chemotherapy for Advanced Non-Small Cell Lung Cancer in Japanese Clinical Practice (J-TAIL-2) en-subtitle= kn-subtitle= en-abstract= kn-abstract=First-line atezolizumab combination therapies were approved for the treatment of metastatic non-small cell lung cancer (NSCLC) based on results from the global phase 3 trials IMpower130, IMpower132, and IMpower150. These trials reported 12-month overall survival (OS) rates of 60%–67% with atezolizumab combination therapy. J-TAIL-2 (NCT04501497), a prospective, multicenter, observational study, evaluated atezolizumab combination therapy in routine clinical practice in Japan. Patients ≥ 20 years old with NSCLC received atezolizumab plus carboplatin and nab-paclitaxel (atezo + CnP), atezolizumab plus carboplatin or cisplatin plus pemetrexed (atezo + PP), or atezolizumab plus bevacizumab plus carboplatin and paclitaxel (atezo + bev + CP) in clinical practice. The primary endpoint was the 12-month OS rate. Secondary endpoints included OS, progression-free survival, and subgroup analyses, including IMpower-unlike (did not meet the main eligibility criteria of each IMpower trial) and IMpower-like patients. In total, 814 patients were enrolled (atezo + CnP, n = 217; atezo + PP, n = 211; atezo + bev + CP, n = 386). The IMpower-unlike group included patients with Eastern Cooperative Oncology Group performance status ≥ 2, autoimmune disease, or interstitial lung disease. Twelve-month OS rates (95% confidence interval [CI]) were 62.9% (55.8–69.2), 72.1% (65.2–77.9), and 68.3% (63.2–72.9) with atezo + CnP, atezo + PP, and atezo + bev + CP, respectively. OS hazard ratios (95% CI) in the IMpower-unlike vs. -like subgroups were 1.36 (0.91–2.05), 1.08 (0.70–1.68), and 1.49 (1.09–2.06), respectively. No new safety signals were observed. Real-world efficacy and safety for each atezolizumab combination were comparable to those in the relevant IMpower trials. en-copyright= kn-copyright= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishioMakoto en-aut-sei=Nishio en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=OsoegawaAtsushi en-aut-sei=Osoegawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikuchiEiki en-aut-sei=Kikuchi en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KimuraHideharu en-aut-sei=Kimura en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GotoYasushi en-aut-sei=Goto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimizuJunichi en-aut-sei=Shimizu en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyauchiEisaku en-aut-sei=Miyauchi en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshinoIchiro en-aut-sei=Yoshino en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MisumiToshihiro en-aut-sei=Misumi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WatanabeYasutaka en-aut-sei=Watanabe en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HataAkito en-aut-sei=Hata en-aut-mei=Akito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KisoharaAkira en-aut-sei=Kisohara en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= en-aut-name=YamaguchiMasafumi en-aut-sei=Yamaguchi en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MiwaAsako en-aut-sei=Miwa en-aut-mei=Asako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IwasawaShunichiro en-aut-sei=Iwasawa en-aut-mei=Shunichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TanakaMisa en-aut-sei=Tanaka en-aut-mei=Misa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=GemmaAkihiko en-aut-sei=Gemma en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Thoracic Oncology, Kansai Medical University kn-affil= affil-num=2 en-affil=Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Kanazawa University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Thoracic Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Tohoku University Hospital kn-affil= affil-num=10 en-affil=International University of Health and Welfare, Narita Hospital kn-affil= affil-num=11 en-affil=Department of Data Science, National Cancer Center Hospital East kn-affil= affil-num=12 en-affil=Department of Thoracic Oncology, Saitama Cancer Center kn-affil= affil-num=13 en-affil=Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Kasukabe Medical Center kn-affil= affil-num=15 en-affil=Department of Respiratory Medicine, NHO Iwakuni Clinical Center kn-affil= affil-num=16 en-affil=Department of Thoracic Oncology, NHO Kyushu Cancer Center kn-affil= affil-num=17 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=18 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=19 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=20 en-affil=Nippon Medical School kn-affil= en-keyword=atezolizumab kn-keyword=atezolizumab en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=lung cancer kn-keyword=lung cancer en-keyword=non-small cell kn-keyword=non-small cell en-keyword=observational kn-keyword=observational END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=6 article-no= start-page=1405 end-page=1416 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical significance on switching CDK4/6 inhibitors among 13,284 patients with metastatic breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent clinical trials have shown that switching to a combination therapy of a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) prolongs progression-free survival (PFS) compared with ET monotherapy. Reports indicate that abemaciclib provides benefits regardless of the PIK3CA mutation status; however, its clinical benefits remain insufficient. This study aimed to evaluate the clinical significance of switching CDK4/6i + ET in a large real-world cohort. Using a medical database, we identified 13,284 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer who received CDK4/6i + ET between 2008 and 2022. Patients were categorized into five groups based on their first- and second-line therapy patterns. We compared the median time to discontinuation (TTD) among the groups. In patients who switched from one CDK4/6i + ET to another CDK4/6i + ET, the second-line TTD and total TTD of first- and second-line therapies (n = 542) were significantly longer than those in patients who switched from CDK4/6i + ET to ET monotherapy (n = 490) (the second-line TTD: 11.2 vs. 4.9 months, p < 0.01; total TTD: 25.1 vs. 20.5 months, p < 0.01). The order of palbociclib and abemaciclib administration did not significantly affect the second-line or total TTD in patients who switched from one CDK4/6i + ET to another CDK4/6i + ET. Switching from one CDK4/6i + ET to another CDK4/6i + ET resulted in a significantly longer TTD than switching to ET monotherapy. Considering the phase III clinical trial results of capivasertib, switching to CDK4/6i + ET is a viable therapeutic option regardless of the PIK3CA mutation status. en-copyright= kn-copyright= en-aut-name=NishinaTakuya en-aut-sei=Nishina en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 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=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=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 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=2 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=3 en-affil=Medical AI Project, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 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=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 General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Cyclin-dependent kinase 4/6 inhibitors kn-keyword=Cyclin-dependent kinase 4/6 inhibitors en-keyword=Endocrine therapy kn-keyword=Endocrine therapy en-keyword=HR-positive/HER2-negative advanced breast cancer kn-keyword=HR-positive/HER2-negative advanced breast cancer en-keyword=Progression-free survival kn-keyword=Progression-free survival en-keyword=Time to discontinuation kn-keyword=Time to discontinuation END start-ver=1.4 cd-journal=joma no-vol=36 cd-vols= no-issue= article-no= start-page=100857 end-page= 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=A multi-institutional dummy run on segmentation variability and plan quality of stereotactic body radiotherapy for oligometastatic disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and purpose: Oligometastatic disease represents limited metastatic burden, and local ablative therapies such as stereotactic body radiotherapy (SBRT) may improve survival. However, inter-institutional variability in target segmentation and treatment planning can compromise treatment quality. This study aimed to evaluate the segmentation variability and dose distribution quality of SBRT in oligometastatic settings using a multi-institutional dummy run approach.
Methods and materials: Sixty-nine institutions were provided with two anonymized cases of adrenal and spine metastases to delineate targets and organs at risk (OARs) and create intensity-modulated radiotherapy plans following a protocol. Variability was quantified using the Dice similarity coefficient (DSC), Hausdorff distance, and mean distance to agreement. Plan qualities were assessed using the Paddick conformity index, modified gradient index, and a new three-dimensional conformity–gradient index (3D-CGI). Knowledge-based planning (KBP) was applied to explore potential improvements in OAR sparing.
Results: All submitted plans met protocol dose constraints. However, substantial segmentation variability was observed, particularly for the spine case. Among 136 plans, 79% demonstrated acceptable conformity and dose gradients, with 3D-CGI < 6 correlating with favorable distributions. Mean DSC was 0.93 for the clinical target volume and 0.76 for the cauda equina, which showed the highest variability. KBP reduced OAR doses for the adrenal case but showed limited impact for the spine case.
Conclusions: Although dose constraints were achieved, segmentation variability remained substantial, particularly for the cauda equina in the spine case. These findings emphasize inter-institutional differences and the need for standardization and tools to improve SBRT consistency. en-copyright= kn-copyright= en-aut-name=HirashimaHideaki en-aut-sei=Hirashima en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuoYukinori en-aut-sei=Matsuo en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshikuraSatoshi en-aut-sei=Ishikura en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamuraMitsuhiro en-aut-sei=Nakamura en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishibuchiIkuno en-aut-sei=Nishibuchi en-aut-mei=Ikuno kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawaharaDaisuke en-aut-sei=Kawahara en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimadaYoshihisa en-aut-sei=Shimada en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakaharaYoshiro en-aut-sei=Nakahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishioTeiji en-aut-sei=Nishio en-aut-mei=Teiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShikamaNaoto en-aut-sei=Shikama en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WatanabeShun-ichi en-aut-sei=Watanabe en-aut-mei=Shun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=IshibaToshiyuki en-aut-sei=Ishiba en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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=15 ORCID= en-aut-name=MizowakiTakashi en-aut-sei=Mizowaki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University kn-affil= affil-num=2 en-affil=Department of Radiation Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Radiation Oncology, St. Luke’s International Hospital, St. Luke’s International University kn-affil= affil-num=4 en-affil=Department of Advanced Medical Physics, Graduate School of Medicine, Kyoto University kn-affil= affil-num=5 en-affil=Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University kn-affil= affil-num=6 en-affil=Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University kn-affil= affil-num=7 en-affil=Department of Surgery, Tokyo Medical University kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Kitasato University Hospital kn-affil= affil-num=9 en-affil=Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of Osaka kn-affil= affil-num=10 en-affil=Department of Radiation Oncology, Juntendo University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Thoracic Surgery, National Cancer Center Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=13 en-affil=Department of Breast Surgery, Institute of Science Tokyo kn-affil= affil-num=14 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=15 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University kn-affil= en-keyword=Oligometastatic disease kn-keyword=Oligometastatic disease en-keyword=Dummy run kn-keyword=Dummy run en-keyword=Segmentation variability kn-keyword=Segmentation variability en-keyword=Dose distribution accuracy kn-keyword=Dose distribution accuracy END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=3 article-no= start-page=132 end-page=136 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Advances in and future perspectives on robot-assisted surgery in the field of thoracic surgery kn-title=呼吸器外科領域におけるロボット支援手術の進化と展望 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name=岡﨑幹生 kn-aut-sei=岡﨑 kn-aut-mei=幹生 aut-affil-num=1 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name=豊岡伸一 kn-aut-sei=豊岡 kn-aut-mei=伸一 aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学学術研究院医歯薬学域 呼吸器・乳腺内分泌学 affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学学術研究院医歯薬学域 呼吸器・乳腺内分泌学 en-keyword=ロボット支援下手術 kn-keyword=ロボット支援下手術 en-keyword=RATS kn-keyword=RATS END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=3 article-no= start-page=95 end-page=97 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2024 Incentive Award of the Okayama Medical Association in Cardiovascular and Pulmonary Research (2024 Sunada Prize) kn-title=令和6年度岡山医学会賞 胸部・循環研究奨励賞(砂田賞) en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KawanaShinichi en-aut-sei=Kawana en-aut-mei=Shinichi kn-aut-name=川名伸一 kn-aut-sei=川名 kn-aut-mei=伸一 aut-affil-num=1 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=岡山大学大学院医歯薬学総合研究科 呼吸器・乳腺内分泌外科学 END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=11 article-no= start-page=105889 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association between adjuvant chemotherapy and outcomes in resected locoregional recurrence of hormone receptor-positive HER2-negative breast cancer: a multi-institutional retrospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: To evaluate the association of adjuvant chemotherapy and prognosis for locoregional recurrence (LRR) in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative subtype breast cancer.
Patients and methods: We carried out a multi-institutional retrospective cohort study in patients with breast cancer who developed HR-positive HER2-negative LRR. Patients who underwent curative surgery for LRR between 2014 and 2018 were categorized based on whether they received adjuvant chemotherapy for LRR (CTx versus no-CTx). Invasive disease-free survival (iDFS) was evaluated between the groups by Cox proportional hazards analysis. The primary analysis used a double-robust Cox model incorporating inverse probability of treatment weighting, and a sensitivity analysis using propensity score matching was also carried out.
Results: A total of 958 patients were included. The median time from the primary surgery to LRR diagnosis was 9.5 years (interquartile range 3.1-10.1 years). There were 235 patients (25%) in the CTx group and 722 (75%) in the no-CTx group. Among all patients, the 5-year iDFS rate was 75.4% [95% confidence interval (CI) 72.4% to 78.2%]. Multivariate analysis showed better iDFS in the CTx group (hazard ratio 0.70, 95% CI 0.49-0.99, P = 0.045). Sensitivity analysis supported these findings. Subgroup analyses showed that the CTx group had better iDFS in cases with non-ipsilateral breast tumor recurrence (IBTR), recurrences during adjuvant endocrine therapy for primary breast cancer, and without perioperative chemotherapy for primary breast cancer. Secondary analysis showed no significant difference with a worse trend toward overall survival in the CTx group with multivariate Cox proportional hazards analysis.
Conclusion: Adjuvant chemotherapy for HR-positive HER2-negative LRR was associated with better iDFS, particularly in cases of non-IBTR, recurrences during adjuvant endocrine therapy, and no prior perioperative chemotherapy for their primary tumor. However, the retrospective design and inability to distinguish true recurrences from new primary tumors in IBTR warrant cautious interpretation. en-copyright= kn-copyright= en-aut-name=OzakiY. en-aut-sei=Ozaki en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TokudaE. en-aut-sei=Tokuda en-aut-mei=E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SagaraY. en-aut-sei=Sagara en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HaraF. en-aut-sei=Hara en-aut-mei=F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SasadaS. en-aut-sei=Sasada en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SawakiM. en-aut-sei=Sawaki en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KanbayashiC. en-aut-sei=Kanbayashi en-aut-mei=C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamanakaT. en-aut-sei=Yamanaka en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OnishiT. en-aut-sei=Onishi en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujikiY. en-aut-sei=Fujiki en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SutoA. en-aut-sei=Suto en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakahashiY. en-aut-sei=Takahashi en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TokunagaE. en-aut-sei=Tokunaga en-aut-mei=E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ArugaT. en-aut-sei=Aruga en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakamuraR. en-aut-sei=Nakamura en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujisawaT. en-aut-sei=Fujisawa en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SajiS. en-aut-sei=Saji en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IwataH. en-aut-sei=Iwata en-aut-mei=H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShienT. en-aut-sei=Shien en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Breast Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=2 en-affil=Department of Medical Oncology, Fukushima Medical University kn-affil= affil-num=3 en-affil=Department of Breast Surgery, Social Medical Corporation Hakuaikai Sagara Hospital kn-affil= affil-num=4 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University kn-affil= affil-num=6 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=7 en-affil=Department of Breast Oncology, Niigata Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Breast Surgery and Oncology, Kanagawa Cancer Center kn-affil= affil-num=9 en-affil=Department of Breast Oncology, National Cancer Center Hospital East kn-affil= affil-num=10 en-affil=Department of Breast Surgery, Social Medical Corporation Hakuaikai Sagara Hospital kn-affil= affil-num=11 en-affil=Department of Breast Oncology, National Cancer Center Hospital kn-affil= affil-num=12 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Breast Oncology, National Hospital Organization Kyushu Cancer Center kn-affil= affil-num=14 en-affil=Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=15 en-affil=Division of Breast Surgery, Chiba Cancer Center kn-affil= affil-num=16 en-affil=Department of Breast Oncology, Gunma Prefectural Cancer Center kn-affil= affil-num=17 en-affil=Department of Medical Oncology, Fukushima Medical University kn-affil= affil-num=18 en-affil=Department of Advanced Clinical Research and Development, Nagoya City University kn-affil= affil-num=19 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=locoregional recurrence kn-keyword=locoregional recurrence en-keyword=adjuvant chemotherapy kn-keyword=adjuvant chemotherapy en-keyword=inverse probability of treatment weighting kn-keyword=inverse probability of treatment weighting END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=1 article-no= start-page=1773 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Single-cell and spatial transcriptomic characterization of pulmonary pleomorphic carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pulmonary pleomorphic carcinoma (PPC) is a rare subtype of lung cancer that comprises both epithelial and sarcomatoid components. The molecular basis of PPC, including the cellular dynamics of its components, remains largely unknown. To elucidate potential therapeutic targets for PPC, we perform a multi-omics analysis incorporating digital spatial profiling and single-cell RNA sequencing (scRNA-seq). PPC exhibits diverse driver gene alterations, including MET exon 14 skipping mutation (METex14) and ALK fusion. In spatial transcriptomics, MET gene and protein are overexpressed exclusively within the epithelial component and not in the sarcomatoid component, even in patients harboring METex14. Epithelial-mesenchymal transition (EMT)-related transcriptional changes, along with extracellular matrix (ECM) remodeling between the epithelial and sarcomatoid components, are observed. scRNA-seq identifies cell populations within the epithelial component that contribute to the malignant transformation and differentiation of the sarcomatoid component. They are characterized by an intermediate EMT state with ECM remodeling signature, suggesting their potential as novel therapeutic targets for PPC. en-copyright= kn-copyright= en-aut-name=MatsuokaAtsushi en-aut-sei=Matsuoka en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=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=OhkiMasayoshi en-aut-sei=Ohki en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HisamatsuKazuya en-aut-sei=Hisamatsu en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraRyota en-aut-sei=Fujiwara en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshimuraKosei en-aut-sei=Ishimura en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiiRyunosuke en-aut-sei=Fujii en-aut-mei=Ryunosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HigashiharaTomoaki en-aut-sei=Higashihara en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HayashiNaohiro en-aut-sei=Hayashi en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OkadaKazuhiro en-aut-sei=Okada en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YoshichikaRyo en-aut-sei=Yoshichika en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=YoshikawaMao en-aut-sei=Yoshikawa en-aut-mei=Mao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FukumotoYuma en-aut-sei=Fukumoto en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 ORCID= en-aut-name=TomiokaYasuaki en-aut-sei=Tomioka en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 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=19 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=20 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=21 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=22 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=23 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=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= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 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=27 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=28 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= 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=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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 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=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 Thoracic Surgery and Breast and Endocrinological Surgery, 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= affil-num=14 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=15 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=16 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=17 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=18 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=19 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=20 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=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 Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=23 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=24 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=25 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=26 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=27 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=28 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=55 cd-vols= no-issue=5 article-no= start-page=547 end-page=555 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250223 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multicenter, open-label, randomized, controlled study to test the utility of electronic patient-reported outcome monitoring in patients with unresectable advanced cancers or metastatic/recurrent solid tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Electronic patient-reported outcome (ePRO) monitoring for patients undergoing cancer chemotherapy may provide qualified and early detection of adverse events or disease-related symptoms, leading to improved patient care. The aim of this study is to examine whether addition of ePRO monitoring to routine medical care contributes to improved overall survival and quality of life of cancer patients undergoing chemotherapy. Patients with unresectable advanced cancers or metastatic/recurrent solid tumors receiving systemic chemotherapy will be randomized to an ePRO monitoring group and a usual care group. The ePRO group will conduct weekly symptom monitoring using an electronic device after study enrollment until the end of the study. Monitoring results will be returned to medical personnel and used as information for patient care. The primary endpoints are overall survival and health related quality of life. The initial target sample size for the study was 1500 patients. However, due to delays in enrollment, the target was readjusted to 500 patients. Enrollment has been completed, and the study is now in the follow-up phase. en-copyright= kn-copyright= en-aut-name=TairaNaruto en-aut-sei=Taira en-aut-mei=Naruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KiyotaNaomi en-aut-sei=Kiyota en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikawaYuichiro en-aut-sei=Kikawa en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=KatoKyoko en-aut-sei=Kato en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KubotaKaoru en-aut-sei=Kubota en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TateishiRyosuke en-aut-sei=Tateishi en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakataAkinobu en-aut-sei=Nakata en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaritaYukiya en-aut-sei=Narita en-aut-mei=Yukiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 ORCID= en-aut-name=GemmaAkihiko en-aut-sei=Gemma en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShimozumaKojiro en-aut-sei=Shimozuma en-aut-mei=Kojiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MuroKei en-aut-sei=Muro en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IwamotoTetsuya en-aut-sei=Iwamoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakumotoYuki en-aut-sei=Takumoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ShiroiwaTakeru en-aut-sei=Shiroiwa en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FukudaTakashi en-aut-sei=Fukuda en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YamaguchiTakuhiro en-aut-sei=Yamaguchi en-aut-mei=Takuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HagiwaraYasuhiro en-aut-sei=Hagiwara en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MinamiHironobu en-aut-sei=Minami en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School kn-affil= affil-num=2 en-affil=Department of Medical Oncology and Hematology, Cancer Center, Kobe University Hospital kn-affil= affil-num=3 en-affil=Department of Breast Surgery, Kansai Medical University kn-affil= affil-num=4 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Medical Oncology, National Hospital Organization Nagoya Medical Center kn-affil= affil-num=6 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine 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 Gastroenterology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Advanced Clinical Research and Development, Nagoya City University kn-affil= affil-num=13 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=14 en-affil=Department of Biomed Sciences, College of Life Sciences, Ritsumeikan University kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health kn-affil= affil-num=17 en-affil=Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health kn-affil= affil-num=18 en-affil=Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health kn-affil= affil-num=19 en-affil=Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health kn-affil= affil-num=20 en-affil=Division of Biostatistics, Tohoku University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Biostatistics, Division of Health Sciences and Nursing, The University of Tokyo Graduate School of Medicine kn-affil= affil-num=22 en-affil=Division of Medical Oncology and Hematology, Department of Medicine, Kobe University Graduate School of Medicine kn-affil= en-keyword=electronic patient-reported outcomes monitoring kn-keyword=electronic patient-reported outcomes monitoring en-keyword=advanced cancers kn-keyword=advanced cancers en-keyword=systemic chemotherapy kn-keyword=systemic chemotherapy en-keyword=randomized controlled study kn-keyword=randomized controlled study en-keyword=quality of life kn-keyword=quality of life en-keyword=overall survival kn-keyword=overall survival END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=12 article-no= start-page=1584 end-page=1595 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250906 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Combination chemotherapy for older patients with unresectable biliary tract cancer: a prospective observational study using propensity-score matched analysis (JON2104-B) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Systemic chemotherapy with gemcitabine plus S-1 (GEM + S-1), GEM + CDDP plus S-1 (GEM + CDDP + S-1), or gemcitabine plus cisplatin (GEM + CDDP) is standard treatment for advanced biliary tract cancer (aBTC). We aimed to evaluate the efficacy and safety of combination chemotherapy in older patients with aBTC.
Methods: This multicenter prospective observational study (JON2104-B, UMIN000045156) included patients aged ≥ 70 years with aBTC. Inverse-probability weighting propensity-score analyses (IPW) were used to compare overall survival (OS) as the primary endpoint and progression-free survival (PFS) across treatment groups.
Results: This study included 305 patients between August 2021 and January 2023. Of them, 75, 131, 26, 52, and 10 received GEM + CDDP + S-1, GEM + CDDP, GEM + S-1, gemcitabine, and S-1; their median ages were 74, 75, 77.5, 80, and 80 years, and approximately 24%, 16.8%, 23.1%, 9.6%, and 0% had G-8 scores of > 14, respectively. GEM + CDDP had a safety profile comparable to that of GEM + CDDP + S-1 but was more toxic than gemcitabine. Per IPW, the hazard ratio (HR) for GEM + CDDP + S-1 versus GEM + CDDP was 0.80 for OS (95% confidence interval [CI], 0.55–1.17) and 0.55 for PFS (95% CI 0.38–0.80). The HR for GEM + CDDP versus gemcitabine was 0.74 for OS (95% CI 0.42–1.29) and 0.79 for PFS (95% CI 0.42–1.49).
Conclusions: GEM + CDDP + S-1 was associated with longer PFS without additional toxicity than GEM + CDDP for fit older patients. However, the OS for both were not statistically different. The efficacies of GEM + CDDP and gemcitabine for vulnerable older patients did not also differ significantly. These findings highlight the importance of vulnerability in patients with aBTC. en-copyright= kn-copyright= en-aut-name=KobayashiSatoshi en-aut-sei=Kobayashi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakachiKohei en-aut-sei=Nakachi en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoKouji en-aut-sei=Yamamoto en-aut-mei=Kouji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UenoMakoto en-aut-sei=Ueno en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MarukiYuta en-aut-sei=Maruki en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkezawaKenji en-aut-sei=Ikezawa en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TerashimaTakeshi en-aut-sei=Terashima en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimizuSatoshi en-aut-sei=Shimizu en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OshimaKotoe en-aut-sei=Oshima en-aut-mei=Kotoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsujiKunihiro en-aut-sei=Tsuji en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MasakiYoshiharu en-aut-sei=Masaki en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TsumuraHidetaka en-aut-sei=Tsumura en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShibukiTaro en-aut-sei=Shibuki en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OzakaMasato en-aut-sei=Ozaka en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OkanoNaohiro en-aut-sei=Okano en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OkamuraYukiyasu en-aut-sei=Okamura en-aut-mei=Yukiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=UmemotoKumiko en-aut-sei=Umemoto en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SatohTatsunori en-aut-sei=Satoh en-aut-mei=Tatsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KojimaYasushi en-aut-sei=Kojima en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ShiojiKazuhiko en-aut-sei=Shioji en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NebikiHiroko en-aut-sei=Nebiki en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=DoiToshifumi en-aut-sei=Doi en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=NaganumaAtsushi en-aut-sei=Naganuma en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KataokaShigeki en-aut-sei=Kataoka en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KitaEmiri en-aut-sei=Kita en-aut-mei=Emiri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=AsamaHiroyuki en-aut-sei=Asama en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TsuchiyaKaoru en-aut-sei=Tsuchiya en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=UnnoMichiaki en-aut-sei=Unno en-aut-mei=Michiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=AshidaReiko en-aut-sei=Ashida en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 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=30 ORCID= en-aut-name=OhnoIzumi en-aut-sei=Ohno en-aut-mei=Izumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=ItoiTakao en-aut-sei=Itoi en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=NegoroYuji en-aut-sei=Negoro en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=SakamotoYasunari en-aut-sei=Sakamoto en-aut-mei=Yasunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=ArimaShiho en-aut-sei=Arima en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=AsagiAkinori en-aut-sei=Asagi en-aut-mei=Akinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=OkuyamaHiroyuki en-aut-sei=Okuyama en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=KomatsuYoshito en-aut-sei=Komatsu en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=KobayashiNoritoshi en-aut-sei=Kobayashi en-aut-mei=Noritoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=NaganoHiroaki en-aut-sei=Nagano en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=FuruseJunji en-aut-sei=Furuse en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= affil-num=1 en-affil=Department of Gastroenterology, Kanagawa Cancer Center kn-affil= affil-num=2 en-affil=Department of Medical Oncology, Tochigi Cancer Center kn-affil= affil-num=3 en-affil=Department of Biostatistics, Yokohama City University School of Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Kanagawa Cancer Center kn-affil= affil-num=5 en-affil= kn-affil= affil-num=6 en-affil=Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Kanazawa University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Kanazawa University Hospital kn-affil= affil-num=9 en-affil=Division of Gastrointestinal Oncology, Shizuoka Cancer Center kn-affil= affil-num=10 en-affil=Department of Gastroenterology, Ishikawa Prefectural Central Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine kn-affil= affil-num=12 en-affil=Department of Gastroenterological Oncology, Hyogo Cancer Center kn-affil= affil-num=13 en-affil=Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East kn-affil= affil-num=14 en-affil=Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=15 en-affil=Department of Medical Oncology, Kyorin University Faculty of Medicine kn-affil= affil-num=16 en-affil=Division of Digestive Surgery, Department of Surgery, Nihon University School of Medicine kn-affil= affil-num=17 en-affil=Department of Clinical Oncology, St. Marianna University School of Medicine kn-affil= affil-num=18 en-affil=Department of Gastroenterology, Shizuoka General Hospital kn-affil= affil-num=19 en-affil=Department of Gastroenterology, National Center for Global Health and Medicine kn-affil= affil-num=20 en-affil=Department of Gastroenterology, Niigata Cancer Center Hospital kn-affil= affil-num=21 en-affil=Department of Gastroenterology, Osaka City General Hospital kn-affil= affil-num=22 en-affil=Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine kn-affil= affil-num=23 en-affil=Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center kn-affil= affil-num=24 en-affil=Department of Clinical Oncology, Graduate School of Medicine Faculty of Medicine, Kyoto University kn-affil= affil-num=25 en-affil=Department of Gastroenterology, Chiba Cancer Center kn-affil= affil-num=26 en-affil=Department of Gastroenterology, Fukushima Medical University kn-affil= affil-num=27 en-affil=Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital kn-affil= affil-num=28 en-affil=Department of Surgery, Tohoku University Graduate School of Medicine kn-affil= affil-num=29 en-affil=Second Department of Internal Medicine, Wakayama Medical University kn-affil= affil-num=30 en-affil=Department of Gastroenterology, Okayama University Graduate School of Medicine kn-affil= affil-num=31 en-affil=Department of Gastroenterology, Chiba University Graduate School of Medicine kn-affil= affil-num=32 en-affil=Department of Gastroenterology, Tokyo Medical University kn-affil= affil-num=33 en-affil=Department of Oncologial Medicine, Kochi Health Sciences Center kn-affil= affil-num=34 en-affil=Department of Gastroenterology and Hepatology, International University of Health and Welfare Atami Hospital kn-affil= affil-num=35 en-affil=Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=36 en-affil=Department of Gastroenterology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=37 en-affil=Department of Medical Oncology, Kagawa University Hospital kn-affil= affil-num=38 en-affil=Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center kn-affil= affil-num=39 en-affil=Department of Oncology, School of Medicine Graduate School of Medicine, Yokohama City University kn-affil= affil-num=40 en-affil=Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=41 en-affil=Department of Gastroenterology, Kanagawa Cancer Center kn-affil= en-keyword=Biliary tract cancer kn-keyword=Biliary tract cancer en-keyword=Unresectable kn-keyword=Unresectable en-keyword=Chemotherapy kn-keyword=Chemotherapy en-keyword=Older kn-keyword=Older en-keyword=Survival kn-keyword=Survival END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=23 article-no= start-page=3413 end-page=3418 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Prompt Diagnosis of Ascites and Dramatic Effect of Alectinib for Advanced Lung Adenocarcinoma Harboring EML4-ALK Fusion en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 75-year-old never-smoker woman presented with dyspnea and loss of appetite. A mass was identified in the left upper lobe of the lung, and the patient was referred to our hospital. Despite the diagnosis of lung adenocarcinoma via bronchoscopy, anaplastic lymphoma kinase (ALK) immunostaining was negative. Rapid weight gain and abdominal distension caused by ascites prompted fluid testing using the AmoyDx® Pan Lung Cancer PCR Panel. EML4-ALK fusion was confirmed, and alectinib therapy was initiated immediately. The tumor size had decreased significantly, and the patient was discharged on day 34. This case highlights the necessity of multiplex genetic testing even when ALK immunostaining is negative. en-copyright= kn-copyright= en-aut-name=BabaTakahiro en-aut-sei=Baba en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=MatsuokaHiromi en-aut-sei=Matsuoka en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KyakunoMio en-aut-sei=Kyakuno en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshinagaYusuke en-aut-sei=Yoshinaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=FujiwaraMiho en-aut-sei=Fujiwara en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamadaKotaro en-aut-sei=Yamada en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraEri en-aut-sei=Nakamura en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MoritaAyako en-aut-sei=Morita en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HaraNaofumi en-aut-sei=Hara en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiiMasanori en-aut-sei=Fujii en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 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=18 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=19 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=20 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=21 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=22 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Medical Support, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Medical Support, 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 kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Geriatric Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=16 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=19 en-affil=Center for Clinical Oncology, Okayama University Hospital 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 Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=22 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=lung adenocarcinoma kn-keyword=lung adenocarcinoma en-keyword=EML4-ALK kn-keyword=EML4-ALK en-keyword=AmoyDxⓇ Pan Lung Cancer PCR Panel kn-keyword=AmoyDxⓇ Pan Lung Cancer PCR Panel en-keyword=alectinib kn-keyword=alectinib 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=20251023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparative Analysis of a Dual DNA–RNA Panel and a DNA-Only Panel for Sarcoma: Real-World Data From a Nationwide Genomic Database en-subtitle= kn-subtitle= en-abstract= kn-abstract=Next-generation sequencing-based comprehensive cancer genomic profiling is promising in cancer management; however, most studies rely on tumor-only DNA panels from single institutions. In 2023, Japan introduced an insurance-covered cancer genomic profiling test—the GenMine TOP Cancer Genome Profiling System—a dual DNA–RNA panel with matched tumor–normal testing. This study evaluated its utility compared to a conventional DNA-only test (FoundationOne CDx) in managing sarcoma patients using a nationwide genetic profiling database provided by the Center for Cancer Genomics and Advanced Therapeutics. This study included 1046 patients registered between August 2023 and October 2024. The dual DNA–RNA test identified significantly more fusion genes (20.3% vs. 7.4%, p < 0.001) and therapeutically targetable kinase fusions (3.5% vs. 1.2%, p = 0.019) than the DNA-only test. Among patients with translocation-related sarcomas, histology-specific fusion genes were identified in 77.5% using the dual panel, compared to 40.0% with the DNA-only panel (p < 0.001). In non-gastrointestinal stromal tumor sarcomas, the dual test showed a trend toward higher rates of genotype-matched therapy (4.3% vs. 2.6%, p = 0.25) and a significantly higher rate of molecular targeted therapy (4.3% vs. 1.5%, p = 0.03). Additionally, 5.7% of patients had pathogenic germline variants identified through tumor–normal matched analysis. These findings suggest that a dual DNA–RNA panel with matched tumor–normal testing may improve diagnostic accuracy and inform treatment decisions in the routine clinical management of sarcoma. 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=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=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=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke 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=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=FutagawaMashu en-aut-sei=Futagawa en-aut-mei=Mashu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 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 Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=comprehensive cancer genomic profiling (CGP) kn-keyword=comprehensive cancer genomic profiling (CGP) en-keyword=fusion genes kn-keyword=fusion genes en-keyword=gene alterations kn-keyword=gene alterations en-keyword=genotype-matched therapy kn-keyword=genotype-matched therapy en-keyword=potential germline variants (PGVs) kn-keyword=potential germline variants (PGVs) END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=6 article-no= start-page=836 end-page=849 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251028 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=C1orf50 Accelerates Epithelial-Mesenchymal Transition and the Cell Cycle of Hepatocellular Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Hepatocellular carcinoma (HCC) is a heterogeneous liver cancer with limited treatment options and a poor prognosis in advanced stages. To identify novel biomarkers and therapeutic targets, we investigated the role of chromosome 1 open reading frame 50 (C1orf50), a gene with a previously uncharacterized function in HCC.
Materials and Methods: We performed a comprehensive transcriptome data analysis of the human hepatocellular carcinoma project from The Cancer Genome Atlas (TCGA) and subsequently validated the oncogenic roles of C1orf50 using HCC cell lines.
Results: Using transcriptomic and clinical data from TCGA, we stratified 355 primary HCC samples based on C1orf50 expression levels. Patients with high C1orf50 expression exhibited significantly shorter overall survival, suggesting its association with aggressive tumor behavior. Differential expression and enrichment analyses revealed that C1orf50-high tumors were enriched in oncogenic pathways, including epithelial-mesenchymal transition (EMT), cell cycle activation, and stemness-related properties. Transcriptional regulatory network analysis detected 456 significantly dysregulated regulons, including ZEB1/2 and E2F2, key drivers of EMT and cell cycle, in the C1orf50-high group. In addition, we observed increased YAP1/TAZ signaling, further linking C1orf50 to stemness and therapeutic resistance. Functional data from CRISPR-based dependency screening suggested that several transcription factors up-regulated in the C1orf50-high state, such as ZBTB11 and CTCE, are essential for the survival of HCC cells. These findings indicate potential therapeutic vulnerabilities and support the rationale for targeting C1orf50-associated pathways.
Conclusion: C1orf50 is a novel biomarker of poor prognosis in HCC and a key regulator of oncogenic features such as EMT, cell cycle progression, and stemness. This study highlights the therapeutic potential of targeting C1orf50-related networks in aggressive subtypes of liver cancer. en-copyright= kn-copyright= en-aut-name=TANAKAATSUSHI en-aut-sei=TANAKA en-aut-mei=ATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=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=ROGACHEVSKAYAANNA en-aut-sei=ROGACHEVSKAYA en-aut-mei=ANNA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=PEÑATIRSO en-aut-sei=PEÑA en-aut-mei=TIRSO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=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=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=6 en-affil=UMass Chan Medical School, UMass Memorial 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=hepatocellular carcinoma kn-keyword=hepatocellular carcinoma en-keyword=stemness kn-keyword=stemness en-keyword=cell cycle kn-keyword=cell cycle en-keyword=epithelial‑mesenchymal transition kn-keyword=epithelial‑mesenchymal transition 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=79 cd-vols= no-issue=5 article-no= start-page=329 end-page=337 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=Current Status of Extracorporeal Membrane Oxygenation as a Treatment Strategy for Primary Graft Dysfunction after Lung Transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Primary graft dysfunction (PGD) is one of the major risk factors affecting patients’ short- and long-term survival after lung transplantation. No particular management strategy has been established for PGD; supportive care is the mainstay of PGD treatment. When a supportive strategy fails, the patient may require the introduction of extracorporeal membrane oxygenation (ECMO) as the last-resort measure for severe PGD. A variety of study of ECMO as a PGD treatment was reported and the management of PGD patients developed so far. Early recognition of a patient’s need for ECMO and its prompt initiation are critical to improved outcomes. The use of venovenous-ECMO became the preferred procedure for PGD rather than venoarterial-ECMO. However, the current ECMO strategy has limitations, and using ECMO to manage patients with PGD is not sufficiently effective. Further studies are required to develop this promising technology. en-copyright= kn-copyright= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital 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 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=primary graft dysfunction kn-keyword=primary graft dysfunction en-keyword=extracorporeal membrane oxygenation kn-keyword=extracorporeal membrane oxygenation en-keyword=ex vivo lung perfusion kn-keyword=ex vivo lung perfusion 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= 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=34 cd-vols= no-issue=2 article-no= start-page=67 end-page=73 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240701 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Depletion of Lysyl Oxidase-Like 4 (LOXL4) Attenuates Colony Formation in vitro and Collagen Deposition in vivo Breast Cancer Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Lysyl oxidase (LOX) family proteins have recently become a topic in cancer progression. Our recent study found a high expression of LOX-like 4 (LOXL4) in MDA-MB-231 cells. Objective: To reveal the impact of depleted LOXL4 in both in vitro and in vivo breast cancer models from a histological perspective. Material and Method: Endogenous LOXL4 was depleted using the CRISPR/Cas9 on MDA-MB-231 parental cells. Based on the LOXL4 protein expression, the clone was determined for the next experiment, thus generating MDA-MB-231 LOXL4 KO. Cell assay was conducted using colony formation assay (n=3) followed by crystal violet staining. The indicated cells were inoculated orthotopically to female BALB/c nude mice (n=5). At the end of the experiment, tumors were isolated, fixed, and prepared for Masson Trichrome staining. Result: CRISPR/Cas9 completely depleted LOXL4 expression on clone number #2-22. Depletion of LOXL4 reduced the colony size formed by MDA-MB-231 cells. MDA-MB-231 LOXL4 KO #2-22 derived tumors showed depressed tumor volume compared to the parental group. Reduced collagen was also observed from the Masson Trichrome staining (p<0.001). Conclusion: Depletion of LOXL4 downregulates the growth of MDA-MB-231 cells in vitro and collagen deposition in vivo. en-copyright= kn-copyright= en-aut-name=Ni Luh Gede Yoni Komalasari en-aut-sei=Ni Luh Gede Yoni Komalasari en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=I Gde Haryo Ganesha en-aut-sei=I Gde Haryo Ganesha en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=I Gusti Nyoman Sri Wiryawan en-aut-sei=I Gusti Nyoman Sri Wiryawan en-aut-mei= 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=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Cell Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Histology, Faculty of Medicine, Udayana University kn-affil= affil-num=3 en-affil=Department of Histology, Faculty of Medicine, Udayana University kn-affil= affil-num=4 en-affil=Department of Cell Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Cell Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University kn-affil= en-keyword=Good health kn-keyword=Good health en-keyword=Lysyl oxidase kn-keyword=Lysyl oxidase en-keyword=Extracellular matrix kn-keyword=Extracellular matrix END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=14 article-no= start-page=2406 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250721 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Definitions of, Advances in, and Treatment Strategies for Breast Cancer Oligometastasis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oligometastasis represents a clinically relevant state of limited metastatic disease that could be amenable to selected local therapies in carefully chosen patients. Although initial trials such as SABR-COMET demonstrated a survival benefit with aggressive local treatment, breast cancer was underrepresented. Subsequent breast cancer-specific trials, including NRG-BR002, failed to show a clear survival benefit, highlighting uncertainties and the need for further refinement in patient selection and integration with systemic approaches. The definitions of oligometastasis continue to evolve, incorporating radiological, clinical, and biological features. Advances in imaging and molecular profiling suggest that oligometastatic breast cancer might represent a distinct biological subtype, with potential biomarkers including PIK3CA mutations and YAP/TAZ expression. Organ-specific strategies using stereotactic radiotherapy, surgery, and proton therapy have shown favorable local control in certain settings, though their impact on the overall survival remains under investigation. Emerging techniques, including circulating tumor DNA (ctDNA) analysis, are being explored to improve patient selection and disease monitoring. Ongoing trials may provide further insight into the role of local therapy, particularly in hormone receptor-positive or HER2-positive subtypes. Local and systemic strategies need to be carefully coordinated to optimize the outcomes. This review summarizes the current definitions of and evidence and therapeutic considerations for oligometastatic breast cancer and outlines potential future directions. 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=NakamotoShogo en-aut-sei=Nakamoto en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiwaraYuki en-aut-sei=Fujiwara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KosakaMaya en-aut-sei=Kosaka en-aut-mei=Maya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaraharaYuki en-aut-sei=Narahara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiiKento en-aut-sei=Fujii en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MaedaReina en-aut-sei=Maeda en-aut-mei=Reina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatoShutaro en-aut-sei=Kato en-aut-mei=Shutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MimataAsuka en-aut-sei=Mimata en-aut-mei=Asuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=KuwaharaChihiro en-aut-sei=Kuwahara en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=13 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=14 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=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 and Endocrine Surgery, Okayama University Hospital 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 Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= en-keyword=oligo-recurrence kn-keyword=oligo-recurrence en-keyword=breast cancer kn-keyword=breast cancer en-keyword=local therapy kn-keyword=local therapy 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=20250704 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Primary tumour resection plus systemic therapy versus systemic therapy alone in metastatic breast cancer (JCOG1017, PRIM-BC): a randomised clinical trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Several prospective studies have evaluated the benefit of primary tumour resection (PTR) in de novo Stage IV breast cancer (BC) patients, but it remains controversial. We aimed to investigate whether PTR improves the survival of de novo stage IV BC patients.
Methods: De novo stage IV BC patients were enrolled in the first registration and received systemic therapies according to clinical subtypes. Patients without progression after primary systemic therapy for 3 months were randomly assigned 1:1 to systemic therapy alone (arm A) or PTR plus systemic therapy (arm B). The primary endpoint was overall survival (OS), and the secondary endpoints included local relapse-free survival (LRFS).
Results: Five hundred seventy patients were enrolled between May 5, 2011, and May 31, 2018. Of these, 407 were randomised to arm A (N = 205) or arm B (N = 202). The median follow-up time of all randomised patients was 60 months. The difference in OS was not statistically significant (HR 0.86 90% CI 0.69–1.07, one-sided p = 0.13). Median OS was 69 months (arm A) and 75 months (arm B). In the subgroup analysis, PTR was associated with improved OS in pre-menopausal patients, or those with single-organ metastasis. LRFS in arm B was significantly longer than that in arm A (median LRFS 20 vs. 63 months: HR 0.42, 95% CI 0.33–0.53, p < 0.0001). There were no treatment-related deaths.
Conclusions: PTR did not prolong OS. However, it improved local control and might benefit a subset of patients, such as those with premenopausal status or with single-organ metastasis. It also improved local relapse-free survival (LRFS), which is a clinically meaningful outcome in trials of systemic therapy.
Clinical trial registration: UMIN Clinical Trials Registry (UMIN000005586); Japan Registry of Clinical Trials (jRCTs031180151). 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=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AogiKenjiro en-aut-sei=Aogi en-aut-mei=Kenjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YanagidaYasuhiro en-aut-sei=Yanagida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsuneizumiMichiko en-aut-sei=Tsuneizumi en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoNaohito en-aut-sei=Yamamoto en-aut-mei=Naohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=SutoAkihiko en-aut-sei=Suto en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WatanabeKenichi en-aut-sei=Watanabe en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HaraoMichiko en-aut-sei=Harao en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KanbayashiChizuko en-aut-sei=Kanbayashi en-aut-mei=Chizuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ItohMitsuya en-aut-sei=Itoh en-aut-mei=Mitsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KadoyaTakayuki en-aut-sei=Kadoya en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AnanKeisei en-aut-sei=Anan en-aut-mei=Keisei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MaedaShigeto en-aut-sei=Maeda en-aut-mei=Shigeto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 ORCID= en-aut-name=OgawaGakuto en-aut-sei=Ogawa en-aut-mei=Gakuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SajiShigehira en-aut-sei=Saji en-aut-mei=Shigehira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FukudaHaruhiko en-aut-sei=Fukuda en-aut-mei=Haruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 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=20 ORCID= affil-num=1 en-affil=Okayama University Hospital kn-affil= affil-num=2 en-affil=Cancer Institute Hospital kn-affil= affil-num=3 en-affil=National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Shizuoka General Hospital kn-affil= affil-num=5 en-affil=Gunma Prefectural Cancer Center kn-affil= affil-num=6 en-affil=Chiba Prefectural Cancer Center kn-affil= affil-num=7 en-affil=Saitama Prefectural Cancer Center kn-affil= affil-num=8 en-affil=National Cancer Center Hospital kn-affil= affil-num=9 en-affil=Hokkaido Cancer Center kn-affil= affil-num=10 en-affil=Jichi Medical University Hospital kn-affil= affil-num=11 en-affil=Niigata Prefectural Cancer Center kn-affil= affil-num=12 en-affil=Hiroshima City Hiroshima Citizen’s Hospital kn-affil= affil-num=13 en-affil=Hiroshima University Hospital kn-affil= affil-num=14 en-affil=Kitakyushu Municipal Medical Center kn-affil= affil-num=15 en-affil=Nagasaki Municipal Medical Center kn-affil= affil-num=16 en-affil=National Cancer Center Hospital kn-affil= affil-num=17 en-affil=National Cancer Center Hospital kn-affil= affil-num=18 en-affil=Fukushima Medical University kn-affil= affil-num=19 en-affil=National Cancer Center Hospital kn-affil= affil-num=20 en-affil=Aichi Cancer Center Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=4 article-no= start-page=630 end-page=637 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250526 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immediate breast reconstruction surgery for breast cancer: current status and future directions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Immediate breast reconstruction (IBR) has become increasingly recognized in Japan as an important component of breast cancer care, improving patients’ quality of life after mastectomy. While the adoption of IBR is growing, the reconstruction rate in Japan remains lower than in Western countries. To clarify the current practice and challenges, the Japanese Breast Cancer Society (JBCS) conducted a nationwide survey.
Methods We conducted a comprehensive web-based questionnaire survey among all JBCS-certified institutions between December 2020 and February 2021. The survey assessed institutional capabilities, surgical techniques, decision-making criteria for BR, and the integration of adjuvant therapy.
Results A total of 429 institutions responded, with 72.5% offering BR and 61.7% capable of providing immediate reconstruction. Nipple-sparing mastectomy (NSM) was performed at 73.7% of institutions offering reconstruction. Multidisciplinary conferences with plastic surgeons were held at 70.5% of institutions. Approximately 30% of institutions discontinued IBR if sentinel lymph node metastases were detected intraoperatively, and 62.8% avoided recommending IBR for patients likely to require postoperative radiation therapy. In 94% of institutions, BR did not cause delays in the administration of adjuvant chemotherapy. However, 15% of institutions modified their radiation therapy approach in reconstructed patients. Additionally, 27% of physicians still believed that BR could negatively affect prognosis.
Conclusions The survey confirmed that IBR is widely performed and feasible in Japan. However, institutional differences, limited access to plastic surgeons, and persistent misconceptions remain significant barriers. Strengthening multidisciplinary collaboration and establishing standardized guidelines will help improve BR rates and patient outcomes in Japan. 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=NogiHiroko en-aut-sei=Nogi en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OgiyaAkiko en-aut-sei=Ogiya en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshitobiMakoto en-aut-sei=Ishitobi en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamauchiChikako en-aut-sei=Yamauchi en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimoAyaka en-aut-sei=Shimo en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NaruiKazutaka en-aut-sei=Narui en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NaguraNaomi en-aut-sei=Nagura en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SekiHirohito en-aut-sei=Seki en-aut-mei=Hirohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TerataKaori en-aut-sei=Terata en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SaigaMiho en-aut-sei=Saiga en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UchidaTatsuya en-aut-sei=Uchida en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SasadaShinsuke en-aut-sei=Sasada en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SakuraiTeruhisa en-aut-sei=Sakurai en-aut-mei=Teruhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NiikuraNaoki en-aut-sei=Niikura en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MoriHiroki en-aut-sei=Mori en-aut-mei=Hiroki 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 Breast and Endocrine Surgery, The Jikei University School of Medicine kn-affil= affil-num=3 en-affil=Department of Breast Surgery, Japanese Red Cross Medical Center kn-affil= affil-num=4 en-affil=Department of Breast Surgery, Mie University School of Medicine kn-affil= affil-num=5 en-affil=Department of Radiation Oncology, Shiga General Hospital kn-affil= affil-num=6 en-affil=Department of Breast and Endocrine Surgery, St. Marianna University School of Medicine kn-affil= affil-num=7 en-affil=Department of Breast and Thyroid Surgery, Medical Center, Yokohama City University kn-affil= affil-num=8 en-affil=Department of Breast Surgical Oncology, St Luke’s International Hospital kn-affil= affil-num=9 en-affil=Department of Breast Surgery, Kyorin University School of Medicine kn-affil= affil-num=10 en-affil=Department of Breast and Endocrine Surgery, Akita University Hospital kn-affil= affil-num=11 en-affil=Department of Plastic Surgery, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Plastic Surgery, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University kn-affil= affil-num=14 en-affil=Sakurai Breast Clinic kn-affil= affil-num=15 en-affil=Department of Breast Oncology, Tokai University School of Medicine kn-affil= affil-num=16 en-affil=Department of Plastic and Reconstructive Surgery, Tokyo Medical and Dental University kn-affil= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Immediate reconstruction surgery kn-keyword=Immediate reconstruction surgery en-keyword=Prognosis kn-keyword=Prognosis en-keyword=Complications kn-keyword=Complications END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue= article-no= start-page=100268 end-page= 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=Downward hyperinflation of the native lung after right single lung transplantation for COPD: A case report highlighting diaphragmatic mobility en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 60-year-old male with COPD underwent right single lung transplantation. Despite progressive hyperinflation of the native left lung, the transplanted lung maintained function, as downward expansion of the left lung displaced the diaphragm without compressing the mediastinum. This suggests diaphragm mobility, aided by the absence of the liver beneath the left diaphragm, contributes to favorable outcomes in right single lung transplantation by preventing mechanical compression of the transplanted lung. en-copyright= kn-copyright= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TomiokaYasuaki en-aut-sei=Tomioka en-aut-mei=Yasuaki 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=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 ORCID= affil-num=1 en-affil=Department of General Thoracic 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 and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Thoracic 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 and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Thoracic 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 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 and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Chronic obstructive pulmonary disease kn-keyword=Chronic obstructive pulmonary disease en-keyword=Single lung transplantation kn-keyword=Single lung transplantation en-keyword=Native lung hyperinflation kn-keyword=Native lung hyperinflation en-keyword=Diaphragm mobility kn-keyword=Diaphragm mobility END start-ver=1.4 cd-journal=joma no-vol=38 cd-vols= no-issue=2 article-no= start-page=ivae021 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Plasma concentrations of histidine-rich glycoprotein in primary graft dysfunction after lung transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=OBJECTIVES: Histidine-rich glycoprotein has been reported as an anti-inflammatory glycoprotein that inhibits acute lung injury in mice with sepsis and as a prognostic biomarker in patients with sepsis. We investigated the relationship between plasma concentrations of histidine-rich glycoprotein and the risk of occurrence of primary graft dysfunction.
METHODS: According to the primary graft dysfunction grade at post-transplant 72 h, patients who underwent lung transplantation were divided into three groups: non-primary graft dysfunction group (grade 0–1), moderate primary graft dysfunction group (grade 2), and severe primary graft dysfunction group (grade 3). The plasma concentrations of histidine-rich glycoprotein measured daily during the first post-transplant 7 days were compared among the three groups. Appropriate cutoff values of the concentrations were set for survival analyses after lung transplantation.
RESULTS: A total of 68 patients were included. The plasma histidine-rich glycoprotein concentration at post-transplant 72 h was significantly lower in the severe primary graft dysfunction group (n = 7) than in the other two groups [non-primary graft dysfunction group (n = 43), P = 0.042; moderate primary graft dysfunction group (n = 18), P = 0.040]. Patients with plasma histidine-rich glycoprotein concentration ≥34.4 µg/ml at post-transplant 72 h had significantly better chronic lung allograft dysfunction-free survival (P = 0.012) and overall survival (P = 0.037) than those with the concentration <34.4 µg/ml.
CONCLUSIONS: Plasma histidine-rich glycoprotein concentrations at post-transplant 72 h might be associated with the risk of development of primary graft dysfunction. en-copyright= kn-copyright= en-aut-name=ShiotaniToshio en-aut-sei=Shiotani en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TomiokaYasuaki en-aut-sei=Tomioka en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 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=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=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=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= affil-num=1 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=5 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= en-keyword=Lung transplantation kn-keyword=Lung transplantation en-keyword=Primary graft dysfunction kn-keyword=Primary graft dysfunction en-keyword=Histidine-rich glycoprotein kn-keyword=Histidine-rich glycoprotein en-keyword=Chronic lung allograft dysfunction kn-keyword=Chronic lung allograft dysfunction en-keyword=Overall survival kn-keyword=Overall survival END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=243 end-page=251 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 Work Productivity of Cancer-survivor and Non-cancer-survivor Workers en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated the work productivity levels of employed cancer survivors and non-cancer-survivor workers by conducting a cross-sectional study in Japan between February and March 2019, using an online survey. A total of 561 employed individuals aged 20-64 years were analyzed. Work productivity was assessed using the Work Productivity and Activity Impairment-General Health questionnaire which evaluates absenteeism, presenteeism, and overall work productivity loss. The questionnaire responses demonstrated that the cancer survivors within 1 year of diagnosis had significantly higher absenteeism compared to the non-cancer workers (p=0.048). Although presenteeism and overall work productivity loss were also higher in the non-cancer-survivor group, the differences were not significant. Cancer survivors within 1 year of diagnosis exhibited higher absenteeism, but their work productivity appeared to recover to levels comparable to those of the non-cancer workers over time. These findings may contribute to workplace policies supporting cancer survivors’ return to work. en-copyright= kn-copyright= en-aut-name=KamanoMika en-aut-sei=Kamano en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KandaKanae en-aut-sei=Kanda en-aut-mei=Kanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NgatuNlandu Roger en-aut-sei=Ngatu en-aut-mei=Nlandu Roger kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MurakamiAkitsu en-aut-sei=Murakami en-aut-mei=Akitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamadoriYusuke en-aut-sei=Yamadori en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HiraoTomohiro en-aut-sei=Hirao en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Public Health, Faculty of Medicine, Kagawa University kn-affil= affil-num=2 en-affil=Department of Public Health, Faculty of Medicine, Kagawa University kn-affil= affil-num=3 en-affil=Department of Public Health, Faculty of Medicine, Kagawa University kn-affil= affil-num=4 en-affil=Cancer Center, Kagawa University Hospital kn-affil= affil-num=5 en-affil=Department of Anesthesiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=6 en-affil=Department of Public Health, Faculty of Medicine, Kagawa University kn-affil= en-keyword=cancer survivor kn-keyword=cancer survivor en-keyword=work productivity kn-keyword=work productivity en-keyword=absenteeism kn-keyword=absenteeism en-keyword=presenteeism kn-keyword=presenteeism 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= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250613 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Distinct age-related effects of homologous recombination deficiency on genomic profiling and treatment efficacy in gastric cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The incidence of gastric cancer among younger patients is increasing globally, with growing attention being paid to the role of homologous recombination deficiency (HRD). However, the effect of HRD on treatment outcomes and prognosis in this population remains unclear.
Methods We analyzed clinical and genomic data from the Center for Cancer Genomics and Advanced Therapeutics database. Younger patients (≤ 39 years, n = 140) were compared with older patients (≥ 65 years, n = 1118) diagnosed with gastric cancer. This study focused on mutations in homologous recombination repair (HRR) genes and their association with tumor mutation burden (TMB), microsatellite instability (MSI), and treatment outcomes.
Results In older patients, HRD was associated with higher TMB and microsatellite instability-high (MSI-H) status, whereas no such correlations were observed in younger patients. Notably, MSI-H status was not observed in the younger group. Younger patients with HRD had a significantly shorter time to treatment failure (TTF) and overall survival (OS) than those without HRD. Conversely, in older patients, there was no significant difference in TTF or OS based on HRD status.
Conclusion HRR gene mutations influence genomic profiling, TMB, and MSI differently depending on the age of gastric cancer onset, suggesting potential effects on treatment efficacy and prognosis. en-copyright= kn-copyright= en-aut-name=MakiYoshie en-aut-sei=Maki en-aut-mei=Yoshie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=OzatoToshiki en-aut-sei=Ozato en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 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=7 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=8 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=9 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=10 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=11 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=12 ORCID= affil-num=1 en-affil=Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Faculty of Medicine, Department of Practical Gastrointestinal Endoscopy, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Homologous recombination repair gene kn-keyword=Homologous recombination repair gene en-keyword=Early-onset gastric cancer kn-keyword=Early-onset gastric cancer en-keyword=Comprehensive genomic profiling kn-keyword=Comprehensive genomic profiling 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=17 cd-vols= no-issue= article-no= start-page=1477 end-page=1486 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250719 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Predictive Value of Tumor ERCC1 Expression for Treatment Outcomes After Adjuvant Chemotherapy in Patients with Completely Resected Non-Small Cell Lung Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: To evaluate the predictive value of tumor expression of the excision repair cross-complementation group 1 gene (ERCC1) for the treatment outcomes after platinum-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC).
Methods: In this study, we conducted immunohistochemical analysis using a mouse monoclonal anti-ERCC1 antibody (clone 8F1) of operative specimens obtained from 238 patients enrolled in the SLCG0401 study which compared paclitaxel plus carboplatin (CBDCA+PTX) with uracil-tegafur (UFT) as adjuvant chemotherapy for stage IB-IIIA NSCLC. The overall survival (OS) of the patients was compared according to the ERCC1 expression status and adjuvant chemotherapy employed.
Results: Of the 238 specimens, 102 (42.9%) showed a positive result for ERCC1 expression. There were no significant differences in the patient characteristics or OS between the tumor ERCC1-positive and -negative patient groups. Among the patients with ERCC1-negative tumors, there was no significant difference in the survival between patient groups treated with CBDCA+PTX and UFT (HR=0.932, 95% CI: 0.52– 1.67, p=0.814). However, among the patients with ERCC1-positive tumors, CBDCA+PTX treatment tended to yield an inferior outcome, in terms of the OS, as compared with UFT treatment (HR=1.852, 95% CI: 0.92– 3.73, p=0.080). Multivariate analysis showed that ERCC1 expression was not an independent predictor of the OS following CBDCA+PTX treatment in completely resected NSCLC patients.
Conclusion: In completely resected NSCLC patients with positive tumor ERCC1 expression, adjuvant CBDCA+PTX treatment tended to yield an inferior outcome as compared with UFT treatment in terms of the OS. However, immunohistochemical analysis with the 8F1 antibody cannot be used for clinical decision making at this point. en-copyright= kn-copyright= en-aut-name=NakataMasao en-aut-sei=Nakata en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaishoShinsuke en-aut-sei=Saisho en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=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=DateHiroshi en-aut-sei=Date en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery, Kawasaki Medical School kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery, Kawasaki Medical School kn-affil= affil-num=3 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=4 en-affil=Department of Thoracic Surgery, Kurashiki Central Hospital kn-affil= affil-num=5 en-affil=Division of General Thoracic Surgery and Breast and Endocrine Surgery, Department of Surgery, Faculty of Medicine, Tottori University kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer 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 Thoracic Surgery, Kyoto University Graduate School of Medicine kn-affil= en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=postoperative adjuvant chemotherapy kn-keyword=postoperative adjuvant chemotherapy en-keyword=platinum-based chemotherapy kn-keyword=platinum-based chemotherapy en-keyword=excision repair crosscomplementation group 1 gene kn-keyword=excision repair crosscomplementation group 1 gene en-keyword=survival kn-keyword=survival 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 vector’s 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=156 cd-vols= no-issue= article-no= start-page=107913 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=Recurrent diffuse panbronchiolitis after lung transplantation: Off-label use of inhaled tobramycin for Pseudomonas aeruginosa control in a transplant recipient en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: This report highlights a clinical case of recurrent diffuse panbronchiolitis (DPB) after bilateral lung transplantation (LTx), with a focus on the therapeutic impact of off-label inhaled tobramycin solution for inhalation (TSI) in managing Pseudomonas aeruginosa colonization.
Methods: A Japanese woman with a history of DPB experienced disease recurrence following bilateral LTx. Persistent colonization by P. aeruginosa and recurrent respiratory symptoms were observed. Off-label TSI therapy, commonly used in cystic fibrosis, was introduced. Clinical response was assessed through radiologic imaging, bronchoscopy, and microbiological cultures.
Results: TSI administration led to significant clinical and radiological improvement. P. aeruginosa was eradicated from sputum cultures within one month and remained absent throughout six months of follow-up. No hospitalizations or adverse events were reported during therapy.
Conclusion: This case suggests the potential of TSI as a therapeutic approach for managing recurrent DPB and indicates its role in stabilizing post-transplant outcomes. Further studies may clarify its efficacy and expand its application in broader DPB management strategies. en-copyright= kn-copyright= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RyukoTuyoshi en-aut-sei=Ryuko en-aut-mei=Tuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomiokaYasuaki en-aut-sei=Tomioka en-aut-mei=Yasuaki 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=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 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=10 ORCID= affil-num=1 en-affil=Department of General Thoracic 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 and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Thoracic 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 and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Inhaled tobramycin kn-keyword=Inhaled tobramycin en-keyword=Lung transplantation kn-keyword=Lung transplantation en-keyword=Pseudomonas aeruginosa kn-keyword=Pseudomonas aeruginosa en-keyword=Recurrent diffuse panbronchiolitis kn-keyword=Recurrent diffuse panbronchiolitis END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue= article-no= start-page=31 end-page=42 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=Incidence, Management, and Prevention of Gynecomastia and Breast Pain in Patients with Prostate Cancer Undergoing Antiandrogen Therapy: A Systematic Review and Meta-analysis of Randomized Controlled Trials en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and objective: In patients with prostate cancer treated with antiandrogen monotherapy, gynecomastia and breast pain are relatively common. In the setting of androgen receptor pathway inhibitors (ARPIs), the incidence of these adverse events (AEs) remains unclear. In addition, the effect of prophylactic treatment on gynecomastia remains uncertain. We aimed to evaluate the incidence of gynecomastia and breast pain in prostate cancer patients treated with ARPIs compared with androgen deprivation therapy (ADT) and the effect of prophylactic treatment for these AEs due to antiandrogen therapy.
Methods: In June 2024, we queried four databases—PubMed, Scopus, Web of Science, and Embase—for randomized controlled trials (RCTs) investigating prostate cancer treatments involving antiandrogen therapy. The endpoints of interest were the incidence of these AEs due to ARPIs and the effect of prophylactic treatment for these.
Key findings and limitations: Eighteen RCTs, comprising 5036 patients, were included in the systematic review and meta-analysis. ARPIs included enzalutamide, darolutamide, and apalutamide. The results indicated that patients who received ARPI monotherapy had a significantly higher incidence of gynecomastia than those who received ADT monotherapy (risk ratio [RR]: 5.19, 95% confidence interval [CI]: 3.58–7.51, p < 0.001). There was no significant difference in the incidence of gynecomastia between ARPI plus ADT therapy and ADT monotherapy (RR: 1.27, 95% CI: 0.84–1.93, p = 0.2). Prophylactic tamoxifen or radiotherapy reduced significantly the incidence of gynecomastia and breast pain caused by bicalutamide monotherapy.
Conclusions and clinical implications: We found that ARPI monotherapy increases the incidence of these AEs significantly compared with ADT. In contrast, ARPI plus ADT therapy did not result in a higher incidence of AEs. The use of either tamoxifen or radiotherapy was effective in reducing the incidence of these AEs due to bicalutamide monotherapy. These prophylactic treatments could reduce the incidence of AEs due to ARPI monotherapy. However, further studies are needed to clarify their efficacy.
Patient summary: Although androgen deprivation therapy (ADT) improves overall survival in patients with prostate cancer, it is associated with several complications. Androgen receptor pathway inhibitor (ARPI) monotherapy has emerged as a promising strategy for improving oncological outcomes in these patients. However, ARPI monotherapy increases gynecomastia and breast pain in prostate cancer patients compared with ADT, while ARPI plus ADT did not result in a higher incidence of adverse events. en-copyright= kn-copyright= en-aut-name=TsuboiIchiro en-aut-sei=Tsuboi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SchulzRobert J. en-aut-sei=Schulz en-aut-mei=Robert J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LaukhtinaEkaterina en-aut-sei=Laukhtina en-aut-mei=Ekaterina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KarakiewiczPierre I. en-aut-sei=Karakiewicz en-aut-mei=Pierre I. 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= 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=7 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, Comprehensive Cancer Center, Medical University of Vienna 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, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=5 en-affil=Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre 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= en-keyword=Antiandrogen therapy kn-keyword=Antiandrogen therapy en-keyword=Androgen deprivation therapy kn-keyword=Androgen deprivation therapy en-keyword=Androgen receptor pathway inhibitors kn-keyword=Androgen receptor pathway inhibitors en-keyword=Breast pain kn-keyword=Breast pain en-keyword=Gynecomastia kn-keyword=Gynecomastia END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=311 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=Co-occurrence of interstitial lung disease and pulmonary embolism as adverse events of adjuvant osimertinib treatment for EGFR mutant non-small cell lung cancer: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Postoperative osimertinib for EGFR mutant non-small cell lung cancer has become the standard of care. However, its adverse events in clinical practice remain unclear. We report a case of interstitial lung disease and pulmonary embolism occurring simultaneously as adverse events during adjuvant osimertinib treatment.
Case presentation A 74-year-old woman, diagnosed with left lower lobe lung adenocarcinoma harboring an EGFR mutation, underwent a left lower lobectomy with lymph node dissection. During adjuvant osimertinib therapy, the patient developed respiratory distress with hypoxia, leading to the diagnosis of interstitial lung disease. Despite immediate steroid therapy, respiratory distress persisted, the patient developed leg edema. She was diagnosed with deep vein thrombosis and pulmonary embolism via contrast-enhanced computed tomography scan. Following treatment with steroid and anticoagulation, her clinical symptoms improved rapidly, and she showed no recurrence of interstitial lung disease, pulmonary embolism, or lung cancer over the following nine months.
Conclusions We encountered a case of interstitial lung disease and pulmonary embolism occurring simultaneously as adverse events during adjuvant osimertinib treatment. In patients with osimertinib-induced interstitial lung disease, particularly when respiratory symptoms show poor improvement with steroid treatment, the possibility of pulmonary embolism complications should be suspected. en-copyright= kn-copyright= en-aut-name=ManabeKenta en-aut-sei=Manabe en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=FurukawaShinichi en-aut-sei=Furukawa en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SenoTomoya en-aut-sei=Seno en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshimuraKousei en-aut-sei=Ishimura en-aut-mei=Kousei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=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=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=Osimertinib kn-keyword=Osimertinib en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Interstitial lung disease kn-keyword=Interstitial lung disease en-keyword=Pulmonary embolism kn-keyword=Pulmonary embolism END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=4 article-no= start-page=773 end-page=782 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Japanese translation of the Functional Assessment of Cancer Therapy-Breast + 4 (FACT-B + 4) following international guidelines: a verification of linguistic validity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background For breast cancer patients, postoperative lymphedema and upper limb movement disorders are serious complications that absolutely reduce their quality of life (QOL). To evaluate this serious complication, we used “Quick Dash” or “FACT-B”, which can assess a patient's physical, social, emotional, and functional health status. To evaluate their breast cancer surgery-related dysfunction correctly, “FACT-B + 4” was created by adding four questions about “arm swelling'' and “tenderness”. We have translated it into Japanese according to international translation guidelines.
Methods At the beginning, we contacted FACT headquarters that we would like to create a Japanese version of FACT-B + 4. They formed the FACIT Trans Team (FACIT) following international translation procedures, and then, we began translating according to them. The steps are 1: perform “Forward and Reverse translations” to create a “Preliminary Japanese version”, 2: request the cooperation of 5 breast cancer patients and “conduct a pilot study” and “questionnaire survey”, and 3: amendments and final approval based on pilot study results and clinical perspectives.
Result In Step1, FACIT requested faithful translation of the words, verbs, and nouns from the original text. In Step2, patients reported that they felt uncomfortable with the Japanese version words such as “numb'' and “stiffness'' and felt that it might be difficult to describe their symptoms accurately. In Step3, we readjusted the translation to be more concise and closer to common Japanese language, and performed “Step1” again to ensure that the translation definitely retained the meaning of the original.
Conclusion A Japanese version of FACT has existed until now, but there was no Japanese version of FACT-B + 4, which adds four additional items to evaluate swelling and pain in the upper limbs. This time, we have created a Japanese version that has been approved by FACT. en-copyright= kn-copyright= en-aut-name=TsukiokiTakahiro en-aut-sei=Tsukioki en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakataNozomu en-aut-sei=Takata en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DennisSaya R. en-aut-sei=Dennis en-aut-mei=Saya R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TerataKaori en-aut-sei=Terata en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SagaraYasuaki en-aut-sei=Sagara en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakaiTakehiko en-aut-sei=Sakai en-aut-mei=Takehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakayamaShin en-aut-sei=Takayama en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KitagawaDai en-aut-sei=Kitagawa en-aut-mei=Dai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KikawaYuichiro en-aut-sei=Kikawa en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=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=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujisawaTomomi en-aut-sei=Fujisawa en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= affil-num=1 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Simpson Querrey Biomedical Research Center, Northwestern University kn-affil= affil-num=3 en-affil=Department of Preventive Medicine Feinberg School of Medicine, Northwestern University kn-affil= affil-num=4 en-affil=Department of Breast and Endocrine Surgery, Akita University Hospital kn-affil= affil-num=5 en-affil=Department of Breast Surgical Oncology, Social Medical Corporation Hakuaikai Sagara Hospital kn-affil= affil-num=6 en-affil=Department of Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital of JFCR kn-affil= affil-num=7 en-affil=Department of Breast Surgery, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Breast Surgical Oncology, National Center for Global Health and Medicine kn-affil= affil-num=9 en-affil=Department of Breast Surgery, Kansai Medical 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 Breast Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=13 en-affil=Department of Breast Cancer, Gunma Prefectural Cancer Center kn-affil= affil-num=14 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=FACT-B kn-keyword=FACT-B en-keyword=FACT-B+4 kn-keyword=FACT-B+4 en-keyword=QOL kn-keyword=QOL 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 C1orf50’s 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=PEÑATIRSO en-aut-sei=PEÑA 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=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=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=原発性乳癌に対する術前化学療法の効果予測因子として腸内細菌叢の有用性の検討:多施設共同前向きコホート研究(SBP-14) kn-title=Baseline gut microbiota as a predictive marker for the efficacy of neoadjuvant chemotherapy in patients with early breast cancer: a multicenter prospective cohort study in the Setouchi Breast Project‑14 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NAKAMOTOShogo en-aut-sei=NAKAMOTO en-aut-mei=Shogo kn-aut-name=中本翔伍 kn-aut-sei=中本 kn-aut-mei=翔伍 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=3 article-no= start-page=185 end-page=195 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=Emotional Changes among Young Patients with Breast Cancer to Foster Relationship-Building with Their Partners: A Qualitative Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated the emotional changes that young patients with breast cancer need to undergo in order to foster relationship-building with their partners by conducting a qualitative descriptive study (March 1 to Nov. 26, 2021) and semi-structured interviews with eight postoperative patients (age 20-40 years) with breast cancer. The data were analyzed using the modified grounded theory approach (M-GTA), yielding five categories: (i) Awareness of being a breast cancer patient, (ii) Being at a loss, (iii) Support from significant others, (iv) The struggle to transition from being a patient with cancer to becoming “the person I want to be”, and (v) Reaching the “me” I want to be who can face building a relationship with a partner. These findings suggest that young breast cancer patients must feel that they can lead a normal life through activities such as work or acquiring qualifications before building relationships with their partners, and that getting closer to their desired selves is important. Nurses can provide information to young patients with breast cancer to assist them in building a solid relationship with their partners. We believe that this support may enhance the patients’ quality of life and help them achieve stronger relationships with their partners. en-copyright= kn-copyright= en-aut-name=YoshikawaAyumi en-aut-sei=Yoshikawa en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=OkanagaMayumi en-aut-sei=Okanaga en-aut-mei=Mayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaitoShinya en-aut-sei=Saito en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Faculty of Nursing, Osaka Dental University kn-affil= affil-num=2 en-affil=Kawasaki Medical School, Department of Breast and Thyroid Surgery kn-affil= affil-num=3 en-affil=Gifu College of Nursing, Nursing of Children and Child-Rearing Families kn-affil= affil-num=4 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=breast cancer patient kn-keyword=breast cancer patient en-keyword=young patient kn-keyword=young patient en-keyword=single kn-keyword=single en-keyword=partners kn-keyword=partners en-keyword=relationships kn-keyword=relationships 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=20250508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comprehensive analysis of adverse event profile changes with pertuzumab addition to trastuzumab‐based breast cancer therapy: Disproportionality analysis using VigiBase en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims: Pertuzumab is used in combination with trastuzumab-based therapy for HER2-positive breast cancer. However, real-world safety information on pertuzumab remains limited. This study assessed the safety of adding pertuzumab to trastuzumab-based therapy for HER2-positive breast cancer using real-world data.
Methods: VigiBase, the World Health Organization's global database of adverse events (AEs), containing reports from November 1967 to December 2023, was used. Signals for pertuzumab-associated AEs in breast cancer cases were detected using the reporting odds ratio (ROR).
Results: Signals of trastuzumab plus pertuzumab relative to trastuzumab alone were detected in gastrointestinal disorders (ROR: 1.45, 95% confidence interval: 1.26–1.67), including diarrhoea (3.49, 2.83–4.30); infections and infestations (1.54, 1.24–1.91); and skin and subcutaneous tissue disorders (ROR: 1.63, 1.40–1.90), including pruritus (1.96, 1.51–2.55) and rash (1.63, 1.20–2.23). Further, signals of trastuzumab plus docetaxel plus pertuzumab relative to those of trastuzumab plus docetaxel were detected in gastrointestinal disorders (1.63, 1.38–1.93), including nausea (1.72, 1.24–2.39) and vomiting (1.48, 1.01–2.17), and in nervous system disorders (1.50, 1.20–1.87), including paraesthesia (2.60, 1.33–5.08) and peripheral sensory neuropathy (5.94, 1.79–19.71). The frequency of AEs causing or prolonging hospitalization was increased with trastuzumab plus pertuzumab compared to that with trastuzumab alone (1.18, 1.00–1.38).
Conclusions: AE profiles after the addition of pertuzumab to trastuzumab-based therapy were comprehensively identified. The findings in this study highlight the importance of considering these AEs when selecting pertuzumab combination therapy to ensure the safety of patients with breast cancer. en-copyright= kn-copyright= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoJun en-aut-sei=Matsumoto en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakaiTomonori en-aut-sei=Sakai en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwataNaohiro en-aut-sei=Iwata en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KoyamaToshihiro en-aut-sei=Koyama en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AriyoshiNoritaka en-aut-sei=Ariyoshi en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= en-keyword=adverse event kn-keyword=adverse event en-keyword=breast cancer kn-keyword=breast cancer en-keyword=pertuzumab kn-keyword=pertuzumab en-keyword=trastuzumab kn-keyword=trastuzumab en-keyword=VigiBase kn-keyword=VigiBase END start-ver=1.4 cd-journal=joma no-vol=220 cd-vols= no-issue= article-no= start-page=115401 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genomic landscape and clinical impact of homologous recombination repair gene mutation in small bowel adenocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Small bowel adenocarcinoma (SBA) is a rare malignancy with a poor prognosis and limited treatment options. Although homologous recombination deficiency has been studied as a biomarker for other cancer types, the clinical and genomic implications of homologous recombination repair (HRR) gene mutations in SBA remain unclear.
Methods: We retrospectively analyzed the data of 628 patients with advanced or recurrent SBA from a nationwide genomic database. Patients were categorized into HRR mutation and non-HRR mutation groups and compared for their clinical and genomic characteristics including tumor mutational burden (TMB) and microsatellite instability-high (MSI-H) were compared. Treatment efficacy and overall survival (OS) were assessed based on HRR gene mutation status and primary tumor site (duodenal adenocarcinoma [DA] vs. small intestinal carcinoma [SIC]).
Results: Patients with the HRR mutations had higher frequencies of TMB and MSI-H than those without the mutation (P < 0.0001). In DA, HRR gene mutation positivity was associated with improved OS and higher overall response rates (ORR) to platinum-based chemotherapy (OS: not reached vs. 23.5 months, P = 0.040; ORR: 33 % vs. 19 %, P = 0.046), whereas no significant associations were observed with SIC.
Conclusion: HRR gene mutation may be a potential biomarker for platinum-based chemotherapy efficacy in SBA, especially in DA, highlighting the need for site-specific therapies. en-copyright= kn-copyright= en-aut-name=OzatoToshiki en-aut-sei=Ozato en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=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=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=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, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Homologous recombination repair kn-keyword=Homologous recombination repair en-keyword=Small bowel adenocarcinoma kn-keyword=Small bowel adenocarcinoma en-keyword=Genome kn-keyword=Genome END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=8 article-no= start-page=e70793 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250418 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genomic Differences and Distinct TP53 Mutation Site-Linked Chemosensitivity in Early- and Late-Onset Gastric Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Gastric cancer (GC) in younger patients often exhibits aggressive behavior and a poorer prognosis than that in older patients. Although the clinical differences may stem from oncogenic gene variations, it is unclear whether genetic differences exist between these groups. This study compared the genetic profiles of early- and late-onset GC and evaluated their impact on treatment outcomes.
Methods: We analyzed genetic data from 1284 patients with GC in the Japanese nationwide Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, comparing early-onset (<= 39 years; n = 143) and late-onset (>= 65 years; n = 1141) groups. The influence of TP53 mutations on the time to treatment failure (TTF) with platinum-based chemotherapy and the sensitivity of cancer cells with different TP53 mutation sites to oxaliplatin were assessed in vitro.
Results: Early- and late-onset GC showed distinct genetic profiles, with fewer neoantigen-associated genetic changes observed in early-onset cases. In particular, TP53 has distinct mutation sites; R175H and R273 mutations are more frequent in early- and late-onset GC, respectively. The R175H mutation showed higher sensitivity to oxaliplatin in vitro, consistent with the longer TTF in early-onset patients (17.3 vs. 7.0 months, p = 0.013) when focusing on the patients with TP53 mutations.
Conclusion: Genomic differences, particularly in TP53 mutation sites, between early- and late-onset GC support the need for age-specific treatment strategies. en-copyright= kn-copyright= en-aut-name=KamioTomohiro en-aut-sei=Kamio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=HirosunaKensuke en-aut-sei=Hirosuna en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OzatoToshiki en-aut-sei=Ozato en-aut-mei=Toshiki 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=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=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, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=comprehensive genomic profiling kn-keyword=comprehensive genomic profiling en-keyword=early-onset gastric cancer kn-keyword=early-onset gastric cancer en-keyword=oxaliplatin kn-keyword=oxaliplatin en-keyword=TP53 kn-keyword=TP53 END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=101 end-page=107 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=Effectiveness of Postoperative Irradiation in Patients with cN0 Early Breast Cancer Treated with Sentinel Lymph Node Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=To evaluate the effectiveness of postoperative irradiation (POI) for patients with cN0 early breast cancer, we retrospectively analyzed the cases of 650 consecutive breast cancer patients who underwent sentinel lymph node (SLN)-guided surgery (2005-2022) at our hospital. In this cohort, 53% (278/521) of the patients who underwent breast conservative surgery (BCS) and 96% (124/129) of those treated with mastectomy did not receive POI. The patients who underwent BCS were treated with POI using opposing tangential field irradiation. A false negative (FN) SLN was retrospectively defined as a negative metastasis in SLN plus positive recurrence in the axillary lymph nodes. Recurrence was detected in 83 patients. A logistic regression analysis revealed that the nuclear grade (odds ratio [OR] 1.69), POI (OR 0.41), and postoperative hormone therapy (OR 0.40) were each significantly related to recurrence. The 26.1% (12/46) FN rate of the non-POI patients decreased to 5.8% (1/17) compared to those treated with POI. The rate of axillary recurrence was significantly lower in the POI group (0.4%) versus the non-POI group (2.7%) (p=0.0355). The rate of locoregional recurrence was also significantly lower in the POI group (2.0%) versus the non-POI group (13.4%) (p<0.0001). No significant difference was observed in the rate of distant recurrence between the POI (4.0%) and non-POI (3.3%) (p=0.831) groups. These results indicated that the postoperative opposing tangential field irradiation of conserved breast tissue inhibited recurrence in the axillary lymph nodes. 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= 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= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=postoperative irradiation kn-keyword=postoperative irradiation en-keyword=radiation therapy kn-keyword=radiation therapy en-keyword=sentinel lymph nodes kn-keyword=sentinel lymph nodes en-keyword=recurrence kn-keyword=recurrence END start-ver=1.4 cd-journal=joma no-vol=35 cd-vols= no-issue=1 article-no= start-page=141 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Primary chest wall sarcoma: advances in surgical management and outcomes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Although rare, primary chest wall sarcomas are complex malignancies necessitating optimal local control and comprehensive treatment. This study aimed to review 9 years of cases of primary chest wall sarcomas at a single institution, focusing on their histology, surgical management, and prognosis.
Methods A retrospective analysis was performed on 19 patients undergoing chest wall resection for sarcoma from 2012 to 2020. Data on demographics, tumor specifics, resection extent, and adjuvant therapies were collected. Surgical and postoperative outcomes were also assessed.
Results The median patient age was 64 years. Chondrosarcoma was the most common histology. R0 resection was achieved in all patients, with early postoperative complications occurring in 11% of the patients. Robust chest wall reconstruction was performed, resulting in minimal respiratory complications. The 5-year overall survival and disease-free survival rates were 94% and 68%, respectively. Tumor size and patient age were significant prognostic factors for local recurrence.
Conclusion Comprehensive surgical resection, coupled with multidisciplinary preoperative planning, achieves favorable outcomes. Patients aged ≥ 70 years and with tumor size ≥ 5 cm (P = .047) should be carefully followed up for local recurrence. en-copyright= kn-copyright= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 ORCID= en-aut-name=TomiokaYasuaki en-aut-sei=Tomioka en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=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=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=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 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=12 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= kn-affil= affil-num=3 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=4 en-affil=Department of Orthopedic Surgery, Okayama University Hospital 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 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 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=11 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=12 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=Primary chest wall sarcomas kn-keyword=Primary chest wall sarcomas en-keyword=Chest wall resection kn-keyword=Chest wall resection en-keyword=Chondrosarcoma kn-keyword=Chondrosarcoma en-keyword=Robust chest wall reconstruction kn-keyword=Robust chest wall reconstruction END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=6 article-no= start-page=668 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Robustness of Machine Learning Predictions for Determining Whether Deep Inspiration Breath-Hold Is Required in Breast Cancer Radiation Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Deep inspiration breath-hold (DIBH) is a commonly used technique to reduce the mean heart dose (MHD), which is critical for minimizing late cardiac side effects in breast cancer patients undergoing radiation therapy (RT). Although previous studies have explored the potential of machine learning (ML) to predict which patients might benefit from DIBH, none have rigorously assessed ML model performance across various MHD thresholds and parameter settings. This study aims to evaluate the robustness of ML models in predicting the need for DIBH across different clinical scenarios. Methods: Using data from 207 breast cancer patients treated with RT, we developed and tested ML models at three MHD cut-off values (240, 270, and 300 cGy), considering variations in the number of independent variables (three vs. six) and folds in the cross-validation (three, four, and five). Robustness was defined as achieving high F2 scores and low instability in predictive performance. Results: Our findings indicate that the decision tree (DT) model demonstrated consistently high robustness at 240 and 270 cGy, while the random forest model performed optimally at 300 cGy. At 240 cGy, a threshold critical to minimize late cardiac risks, the DT model exhibited stable predictive power, reducing the risk of overestimating DIBH necessity. Conclusions: These results suggest that the DT model, particularly at lower MHD thresholds, may be the most reliable for clinical applications. By providing a tool for targeted DIBH implementation, this model has the potential to enhance patient-specific treatment planning and improve clinical outcomes in RT. en-copyright= kn-copyright= 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=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=Al JamalJamal, Ghaida en-aut-sei=Al Jamal en-aut-mei=Jamal, Ghaida kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujikuraMamiko en-aut-sei=Fujikura en-aut-mei=Mamiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KamizakiRyo en-aut-sei=Kamizaki en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=YoshidaSuzuka en-aut-sei=Yoshida en-aut-mei=Suzuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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=10 ORCID= en-aut-name=SugimotoKohei en-aut-sei=Sugimoto en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=13 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=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=AsaumiJunichi en-aut-sei=Asaumi en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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 Medicine and Oral Surgery, Faculty of Dentistry, Jordan University of Science and Technology 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=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical 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=Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University kn-affil= affil-num=10 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=11 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral Radiology, Faculty of Dentistry, Hasanuddin University kn-affil= affil-num=13 en-affil=Department of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An-Najah National University kn-affil= affil-num=14 en-affil=Department of Oral and Maxillofacial Radiology, 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= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=radiation therapy kn-keyword=radiation therapy en-keyword=heart dose kn-keyword=heart dose en-keyword=cut-off value kn-keyword=cut-off value en-keyword=machine learning kn-keyword=machine learning en-keyword=robustness kn-keyword=robustness en-keyword=instability kn-keyword=instability en-keyword=F2 score kn-keyword=F2 score en-keyword=deep inspiration breath-hold technique kn-keyword=deep inspiration breath-hold technique en-keyword=computed tomography kn-keyword=computed tomography 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= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250316 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel pulmonary abdominal normothermic regional perfusion circuit for simultaneous in-donor evaluation and preservation of lungs and abdominal organs in donation after circulatory death en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective To overcome limitations of traditional ex vivo lung perfusion (EVLP) for controlled donation after circulatory death (cDCD) lungs, this study aimed to evaluate a novel pulmonary abdominal normothermic regional perfusion (PANRP) technique, which we uniquely designed, for in situ assessment of lungs from cDCD donors.
Methods We modified the abdominal normothermic regional perfusion circuit for simultaneous lung and abdominal organ assessment using independent extracorporeal membrane oxygenation components. Blood was oxygenated via a membrane oxygenator and returned to the body, with pulmonary flow adjusted to maintain pressure < 25 mmHg. Femoral cannulation was performed, and the lungs were ventilated with standard settings. Organ function was assessed over 2 h using PaO2/FiO2, AST, ALT, BUN, and Cr measurements to monitor perfusion and oxygen delivery.
Results PANRP maintained stable lung function, with P/F ratios above 300, and preserved abdominal organ parameters, including stable AST, ALT, BUN, and Cr levels. Adequate urine output was observed, indicating normal renal function. Pulmonary artery pressure remained < 20 mmHg, and pulmonary vascular resistance was kept at 400 dyn・s/cm5, showing no signs of lung dysfunction or injury throughout the circuit.
Conclusions PANRP offers a promising alternative to traditional EVLP for cDCD lung evaluation, allowing in situ assessment of multiple organs simultaneously. This approach may overcome logistical and economic challenges associated with ex vivo techniques, enabling a more efficient evaluation process. Further studies are warranted to confirm its clinical applicability and impact on long-term outcomes. en-copyright= kn-copyright= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UmedaMasashi en-aut-sei=Umeda en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UjikeHiroyuki en-aut-sei=Ujike en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=TomiokaYasuaki en-aut-sei=Tomioka en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 ORCID= affil-num=1 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery, Shimane University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of General Thoracic and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Lung preservation kn-keyword=Lung preservation en-keyword=Donation after circulatory death kn-keyword=Donation after circulatory death en-keyword=Abdominal normothermic regional perfusion kn-keyword=Abdominal normothermic regional perfusion END start-ver=1.4 cd-journal=joma no-vol=209 cd-vols= no-issue= article-no= start-page=114663 end-page= 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=Repeated sequential administration of pegylated emulsion of SU5416 and liposomal paclitaxel enhances anti-tumor effect in 4T1 breast cancer-bearing mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=To improve vascular normalization strategy for intractable triple-negative breast cancer 4T1, we examined the anti-tumor effects of repeated sequential administration of polyethylene glycol (PEG)-modified emulsion of SU5416 (PE-SU5416), a vascular endothelial growth factor (VEGF) receptor-2 kinase inhibitor, and PEG-modified liposomal paclitaxel (PL-PTX) in mice bearing 4T1 cells. Three sequential administrations (Seq×3) of PE-SU5416 and PL-PTX exhibited significantly higher anti-tumor activity than a single sequential administration (Seq×1). The tumor vasculatures were structurally normalized until after two PE-SU5416 (PE-SU5416×2) or sequential (Seq×2) administrations, while the improvement in vascular function, such as oxygen supply, blood flow, and PEG-liposomal distribution, was evident until after three administrations of PE-SU5416 (PE-SU5416×3) and Seq×3. Although some discrepancies between the structural and functional improvement in tumor vasculatures were observed after PE-SU5416×3 and Seq×3, cancer-associated fibroblasts (CAFs) and collagen levels were significantly reduced after PE-SU5416×2, PE-SU5416×3, Seq×2, and Seq×3, suggesting that a possible decrease in interstitial fluid pressure due to the reduction in CAFs and collagen would have compensated for vascular function. Furthermore, PE-SU5416×2, PE-SU5416×3, Seq×2, and Seq×3 significantly decreased tumor growth factor-β (TGF-β), an activator of CAFs, in tumor tissues, suggesting that the reduction in TGF-β levels by PE-SU5416 suppresses CAF activation. en-copyright= kn-copyright= en-aut-name=MaruyamaMasato en-aut-sei=Maruyama en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ToriiReiya en-aut-sei=Torii en-aut-mei=Reiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuiHazuki en-aut-sei=Matsui en-aut-mei=Hazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HayashiHiroki en-aut-sei=Hayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OgawaraKen-ichi en-aut-sei=Ogawara en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HigakiKazutaka en-aut-sei=Higaki en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Laboratory of Pharmaceutics, Kobe Pharmaceutical University kn-affil= affil-num=6 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Drug delivery kn-keyword=Drug delivery en-keyword=Vascular normalization kn-keyword=Vascular normalization en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Liposome kn-keyword=Liposome en-keyword=Cancer-associated fibroblast kn-keyword=Cancer-associated fibroblast END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=1 article-no= start-page=51 end-page=58 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=Photoinitiators Induce Histamine Production in Human Mast Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photoinitiators are used in the manufacture of many daily products, and may produce harmful effects due to their cytotoxicity. They have also been detected in human serum. Here, we investigated the histamine-producing effects in HMC-1 cells and the inflammatory cytokine release effects in RAW264 cells for four photoinitiators: 1-hydroxycyclohexyl phenyl ketone; 2-isopropylthioxanthone; methyl 2-benzoylbenzoate; and 2-methyl-4´-(methylthio)-2-morpholinopropiophenone. All four promoted histamine production in HMC-1 cells; however, they did not significantly affect the release of inflammatory cytokines in RAW264 cells. These findings suggest that these four photoinitiators induce inflammatory cytokine-independent histamine production, potentially contributing to histamine-mediated chronic inflammation in vitro. en-copyright= kn-copyright= en-aut-name=MiuraTaro en-aut-sei=Miura en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawasakiYoichi en-aut-sei=Kawasaki en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=SendoToshiaki en-aut-sei=Sendo en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Laboratory of Clinical Pharmacology and Therapeutics, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University kn-affil= affil-num=3 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=photoinitiator kn-keyword=photoinitiator en-keyword=ink kn-keyword=ink en-keyword=injection kn-keyword=injection en-keyword=histamine kn-keyword=histamine en-keyword=inflammation kn-keyword=inflammation END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=1 article-no= start-page=9 end-page=19 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=Gastrectomy Causes an Imbalance in the Trunk Muscles en-subtitle= kn-subtitle= en-abstract= kn-abstract=Muscle loss negatively affects gastrectomy prognosis. However, muscle loss is recognized as a systemic change, and individual muscle function is often overlooked. We investigated changes in the muscle volume of individual muscles after gastrectomy to identify clues for prognostic factors and optimal rehabilitation programs. Patients who underwent R0 gastrectomy for Stage I gastric cancer at our hospital from 2015 to 2021 were retrospectively selected to minimize the effects of malignancy and chemotherapy. Trunk muscle volume was measured by computed tomography to analyze body composition changes. Statistical analysis was performed to identify risk factors related to body composition changes. We compared the preoperative and 6-month postoperative conditions of 59 patients after gastrectomy. There was no difference in the psoas major muscle, a conventional surrogate marker of sarcopenia. There were significant decreases in the erector spinae (p=0.01) and lateral abdominal (p=0.01) muscles, and a significant increase in the rectus abdominis muscle (p=0.02). No significant correlation was found between these muscle changes and nutritional status. Body composition imbalance may serve as a new indicator of the general condition of patients after gastrectomy. Rehabilitation to correct this imbalance may improve prognosis after gastrectomy. en-copyright= kn-copyright= en-aut-name=IkeyaNanami en-aut-sei=Ikeya en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkitaAtsushi en-aut-sei=Okita en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HashidaShinsuke en-aut-sei=Hashida en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoSumiharu en-aut-sei=Yamamoto en-aut-mei=Sumiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkedaHirokuni en-aut-sei=Ikeda en-aut-mei=Hirokuni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsukudaKazunori en-aut-sei=Tsukuda en-aut-mei=Kazunori 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= 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 Surgery, Okayama City Hospital kn-affil= affil-num=3 en-affil=Department of Surgery, Okayama City Hospital kn-affil= affil-num=4 en-affil=Department of Surgery, Okayama City Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, Okayama City Hospital kn-affil= affil-num=6 en-affil=Department of Surgery, Okayama City Hospital 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= en-keyword=sarcopenia kn-keyword=sarcopenia en-keyword=skeletal muscle kn-keyword=skeletal muscle en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=gastrectomy kn-keyword=gastrectomy en-keyword=erector spinae muscle kn-keyword=erector spinae muscle 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=4 cd-vols= no-issue=1 article-no= start-page=e70062 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trends in uptake of cancer screening among people with severe mental illness before and after the COVID-19 pandemic in Japan: A repeated cross-sectional study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aim: The aim of this study was to investigate trends in cancer screening participation among people with severe mental illness (PSMI) from periods before and after the COVID-19 pandemic.
Methods: In this repeated cross-sectional study, we used anonymized datasets on municipal cancer screening participation among PSMI in Okayama City. The data covered fiscal year (FY) 2018 to FY2022; we used the municipal cancer screening database and Medical Payment for Services and Supports for Persons with Disabilities. PSMI were defined as those with schizophrenia or related psychotic disorders (F20-29) or bipolar disorder (F30 or F31), identified using International Classification of Diseases, Tenth Revision, codes. The analysis included men and women aged 40-69 years for colorectal and lung cancer screening; men and women aged 50-69 years for gastric cancer screening; women aged 40-69 years for breast cancer screening; and women aged 20-69 years for cervical cancer screening. Municipal cancer screening rates among PSMI were calculated for each FY.
Results: For all cancer types, cancer screening rates for PSMI in FY2020 (colorectal: 9.0%; lung: 11.6%; gastric: 4.9%; breast: 6.2%; and cervical: 6.1%) were lower than the rates in FY2019 (11.5%, 14.0%, 6.5%, 9.3%, and 8.3%, respectively). In FY2022, the rates (9.9%, 12.9%; 5.3%; 8.0%, and 6.9%, respectively) recovered, but remained low.
Conclusion: This study showed that cancer screening rates among PSMI were very low, both before and after the COVID-19 pandemic. Efforts to encourage participation in cancer screening in this population are urgently needed. en-copyright= kn-copyright= en-aut-name=YamadaYuto en-aut-sei=Yamada en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakayaNaoki en-aut-sei=Nakaya en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtsukiKoji en-aut-sei=Otsuki en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimazuTaichi en-aut-sei=Shimazu en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujimoriMaiko en-aut-sei=Fujimori en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HinotsuShiro en-aut-sei=Hinotsu en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagoshiKiwamu en-aut-sei=Nagoshi en-aut-mei=Kiwamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchitomiYosuke en-aut-sei=Uchitomi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=InagakiMasatoshi en-aut-sei=Inagaki en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=4 en-affil=Department of Psychiatry, Faculty of Medicine, Shimane University kn-affil= affil-num=5 en-affil=Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=6 en-affil=Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=7 en-affil=Department of Biostatistics and Data Management, Sapporo Medical University kn-affil= affil-num=8 en-affil=Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University kn-affil= affil-num=9 en-affil=Department of Cancer Survivorship and Digital Medicine, The Jikei University School of Medicine kn-affil= affil-num=10 en-affil=Department of Psychiatry, Faculty of Medicine, Shimane University kn-affil= en-keyword=bipolar disorder kn-keyword=bipolar disorder en-keyword=cancer screening kn-keyword=cancer screening en-keyword=COVID-19 kn-keyword=COVID-19 en-keyword=healthcare disparities kn-keyword=healthcare disparities en-keyword=schizophrenia kn-keyword=schizophrenia END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=2577 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=Plasma S100A8/A9 level predicts response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Blood-based predictive markers for the efficacy of immune checkpoint inhibitors (ICIs) have not yet been established. We investigated the association of the plasma level of S100A8/A9 with the efficacy of immunotherapy. We evaluated patients with unresectable stage III/IV or recurrent non-small cell lung cancer (NSCLC) who were treated with ICIs at Okayama University Hospital. The pre-treatment plasma levels of S100A8/A9 were analyzed. Eighty-one eligible patients were included (median age, 69 years). Sixty-two patients were men, 54 had adenocarcinoma, 74 had performance status (PS) 0–1, and 47 received ICIs as first-line treatment. The median time to treatment failure (TTF) for ICIs was 5.7 months, and the median overall survival (OS) was 19.6 months. The TTF and OS were worse in patients with high plasma S100A8/A9 levels (≥ 2.475 µg/mL) (median TTF: 4.3 vs. 8.5 months, p = 0.009; median OS: 15.4 vs. 38.0 months, p = 0.001). Multivariate analysis revealed that PS ≥ 2, liver metastasis, and high plasma S100A8/A9 levels were significantly associated with short TTF and OS. In conclusion, plasma S100A8/A9 level may have a limited effect on ICI therapy for NSCLC. 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=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=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=9 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=10 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=11 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=12 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=13 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=14 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 Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 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=13 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=S100A8/A9 kn-keyword=S100A8/A9 en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors 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. LTx 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=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=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 C1orf50’s 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=PeñaTirso en-aut-sei=Peña 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=11 cd-vols= no-issue=1 article-no= start-page=42 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genotypes and phenotypes of neurofibromatosis type 1 patients in Japan: A Hereditary Tumor Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neurofibromatosis type 1 (NF1) presents with a broad spectrum of clinical manifestations, including an increased risk of tumor development and hypertension. Comprehensive data on genotype‒phenotype correlations in patients with NF1 are limited. Therefore, in this study, we aimed to elucidate the detailed genetic and clinical characteristics of NF1 in a hereditary tumor cohort. We performed sequencing and copy number assays in a clinical laboratory and analyzed the clinical data of 44 patients with suspected NF1. Germline pathogenic variants were detected in 36 patients (81.8%), and 20.7% of the variants were novel. Notably, 40.0% of adult patients presented with malignancies; female breast cancer occurred in 20.0% of patients, which was a higher rate than that previously reported. Hypertension was observed in 30.6% of the adult patients, with one patient experiencing sudden death and another developing pheochromocytoma. Three patients with large deletions in NF1 exhibited prominent cutaneous, skeletal, and neurological manifestations. These results highlight the importance of regular surveillance, particularly for patients with malignancies and hypertension. Our findings provide valuable insights for genetic counseling and clinical management, highlighting the multiple health risks associated with NF1 and the need for comprehensive and multidisciplinary care. en-copyright= kn-copyright= en-aut-name=FutagawaMashu en-aut-sei=Futagawa en-aut-mei=Mashu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=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=FukanoChika en-aut-sei=Fukano en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OsumiRisa en-aut-sei=Osumi en-aut-mei=Risa 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=UrakawaYusaku en-aut-sei=Urakawa en-aut-mei=Yusaku 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=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= affil-num=1 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Genetic Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=8 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= 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=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=浸潤性乳癌患者における毛細血管の特定の形状は、予後が悪いことと関連しています 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= en-copyright= kn-copyright= en-aut-name=HNIN WINT WINT SWE en-aut-sei=HNIN WINT WINT SWE en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 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=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Lysyl oxidase-like 4は、細胞表面にAnnexin A2/S100A11複合体形成を促進することで、トリプルネガティブ乳がん細胞の浸潤能を促進する 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= en-copyright= kn-copyright= en-aut-name=TAKAHASHITetta en-aut-sei=TAKAHASHI en-aut-mei=Tetta kn-aut-name=髙橋徹多 kn-aut-sei=髙橋 kn-aut-mei=徹多 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 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=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=LOXL4によるトリプルネガティブ乳がん細胞浸潤亢進のシグナル伝達機構の解明 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-β1-NF-κB-MMP9 axis en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=JIANGFAN en-aut-sei=JIANG en-aut-mei=FAN kn-aut-name=江帆 kn-aut-sei=江 kn-aut-mei=帆 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=39 cd-vols= no-issue=1 article-no= start-page=131 end-page=142 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241016 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real-World Comparative Analysis of Trastuzumab Originator and Biosimilars: Safety, Efficacy, and Cost Effectiveness en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Despite the global use of trastuzumab biosimilars, concerns remain regarding their efficacy and safety. In particular, when used concurrently with pertuzumab, trastuzumab biosimilars lack extensive real-world data and safety information. Additionally, as cancer drug expenditures continue to rise worldwide, cost savings from biosimilars have become increasingly important.
Objective This study aims to assess the safety, efficacy, and cost effectiveness of trastuzumab originators and their biosimilars in real-world clinical settings, focusing on a large patient population.
Methods The analysis included 31,661 patients with HER2-positive breast cancer from the Medical Data Vision Co., Ltd. database in Japan. Additionally, adverse event reports for the trastuzumab originator and its biosimilars were obtained for 58,799 patients from the World Health Organization’s VigiBase, the global adverse event reporting database.
Results No significant differences were observed in heart failure hospitalizations, liver dysfunction, or infusion reaction rates in both the Medical Data Vision Co., Ltd. database and the World Health Organization’s VigiBase. In the Medical Data Vision Co., Ltd. database, the addition of pertuzumab did not significantly influence the incidence of adverse events, and the use of biosimilars significantly reduced medical costs, with no significant difference in breast cancer recurrence rates.
Conclusions By analyzing two large and diverse datasets from multiple perspectives, we obtained reliable results that the trastuzumab originator and its biosimilars have similar safety profiles. The concurrent use of pertuzumab was also found to be safe. The use of biosimilars can lead to cost savings. These findings provide crucial insights for the evaluation and adoption of biosimilars in clinical practice. en-copyright= kn-copyright= en-aut-name=MamoriTomoka en-aut-sei=Mamori en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 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=8 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=9 ORCID= affil-num=1 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=2 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=3 en-affil=Medical AI Project, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmacy, Okayama University Hospital 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 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=9 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=47 end-page=57 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Deep learning-based approach for acquisition time reduction in ventilation SPECT in patients after lung transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=We aimed to evaluate the image quality and diagnostic performance of chronic lung allograft dysfunction (CLAD) with lung ventilation single-photon emission computed tomography (SPECT) images acquired briefly using a convolutional neural network (CNN) in patients after lung transplantation and to explore the feasibility of short acquisition times. We retrospectively identified 93 consecutive lung-transplant recipients who underwent ventilation SPECT/computed tomography (CT). We employed a CNN to distinguish the images acquired in full time from those acquired in a short time. The image quality was evaluated using the structural similarity index (SSIM) loss and normalized mean square error (NMSE). The correlation between functional volume/morphological volume (F/M) ratios of full-time SPECT images and predicted SPECT images was evaluated. Differences in the F/M ratio were evaluated using Bland–Altman plots, and the diagnostic performance was compared using the area under the curve (AUC). The learning curve, obtained using MSE, converged within 100 epochs. The NMSE was significantly lower (P < 0.001) and the SSIM was significantly higher (P < 0.001) for the CNN-predicted SPECT images compared to the short-time SPECT images. The F/M ratio of full-time SPECT images and predicted SPECT images showed a significant correlation (r = 0.955, P < 0.0001). The Bland–Altman plot revealed a bias of -7.90% in the F/M ratio. The AUC values were 0.942 for full-time SPECT images, 0.934 for predicted SPECT images and 0.872 for short-time SPECT images. Our findings suggest that a deep-learning-based approach can significantly curtail the acquisition time of ventilation SPECT, while preserving the image quality and diagnostic accuracy for CLAD. en-copyright= kn-copyright= en-aut-name=NakashimaMasahiro en-aut-sei=Nakashima en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukuiRyohei en-aut-sei=Fukui en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=3 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=4 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= en-keyword=Chronic lung allograft dysfunction kn-keyword=Chronic lung allograft dysfunction en-keyword=Lung transplantation kn-keyword=Lung transplantation en-keyword=Single photon emission computed tomography kn-keyword=Single photon emission computed tomography en-keyword=Deep learning kn-keyword=Deep learning en-keyword=Convolutional neural network kn-keyword=Convolutional neural network END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=5 article-no= start-page=407 end-page=412 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=The First Report of Bickerstaff Brainstem Encephalitis Induced by Atezolizumab for Metastatic Breast Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but they have been known to cause immune-related adverse events (irAEs) by promoting T-cell activation. Neurological irAEs are rare (1%) but have a high fatality rate (11.5%). Here we report the first case of Bickerstaff brainstem encephalitis (BBE) induced by an ICI. A woman in her 60s with metastatic breast cancer was treated with atezolizumab plus nab-paclitaxel once intravenously. Eighteen days later, she lost consciousness with ophthalmoplegia and was diagnosed with a neurological irAE. She recovered consciousness immediately with the administration of intravenous immunoglobulin (IVIG) but suffered severe permanent peripheral neuropathy. Although it is just one case, this experience shows that BBE occurring as a neurological irAE of ICI cancer treatment may be associated with more severe outcomes than conventional BBE in metastatic cancer. Creating a system for multidisciplinary treatment is essential for ICI therapy. en-copyright= kn-copyright= en-aut-name=ShimoyamaKyoko en-aut-sei=Shimoyama en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaAtsushi en-aut-sei=Nakajima en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MinariYoshimitsu en-aut-sei=Minari en-aut-mei=Yoshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Breast Surgery, Takatsuki General Hospital kn-affil= affil-num=2 en-affil=Department of Rehabilitation, Aijinkai Rehabilitation Hospital kn-affil= affil-num=3 en-affil=Department of Breast Surgery, Takatsuki General Hospital kn-affil= en-keyword=Bickerstaff brainstem encephalitis kn-keyword=Bickerstaff brainstem encephalitis en-keyword=immune checkpoint inhibitor kn-keyword=immune checkpoint inhibitor en-keyword=atezolizumab kn-keyword=atezolizumab en-keyword=neurological immune-related adverse event kn-keyword=neurological immune-related adverse event en-keyword=breast cancer kn-keyword=breast cancer 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=136 cd-vols= no-issue=2 article-no= start-page=54 end-page=56 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2023 Incentive Award of the Okayama Medical Association in Cardiovascular and Pulmonary Research (2023 Sunada Prize) kn-title=令和5年度岡山医学会賞 胸部・循環研究奨励賞(砂田賞) en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name=松原慧 kn-aut-sei=松原 kn-aut-mei=慧 aut-affil-num=1 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=岡山大学大学院医歯薬学総合研究科 呼吸器・乳腺・内分泌外科学 END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=15 article-no= start-page=8370 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240731 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Increased Oxidative Stress and Decreased Citrulline in Blood Associated with Severe Novel Coronavirus Pneumonia in Adult Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study investigated the correlation between oxidative stress and blood amino acids associated with nitric oxide metabolism in adult patients with coronavirus disease (COVID-19) pneumonia. Clinical data and serum samples were prospectively collected from 100 adult patients hospitalized for COVID-19 between July 2020 and August 2021. Patients with COVID-19 were categorized into three groups for analysis based on lung infiltrates, oxygen inhalation upon admission, and the initiation of oxygen therapy after admission. Blood data, oxidative stress-related biomarkers, and serum amino acid levels upon admission were compared in these groups. Patients with lung infiltrations requiring oxygen therapy upon admission or starting oxygen post-admission exhibited higher serum levels of hydroperoxides and lower levels of citrulline compared to the control group. No remarkable differences were observed in nitrite/nitrate, asymmetric dimethylarginine, and arginine levels. Serum citrulline levels correlated significantly with serum lactate dehydrogenase and C-reactive protein levels. A significant negative correlation was found between serum levels of citrulline and hydroperoxides. Levels of hydroperoxides decreased, and citrulline levels increased during the recovery period compared to admission. Patients with COVID-19 with extensive pneumonia or poor oxygenation showed increased oxidative stress and reduced citrulline levels in the blood compared to those with fewer pulmonary complications. These findings suggest that combined oxidative stress and abnormal citrulline metabolism may play a role in the pathogenesis of COVID-19 pneumonia. 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=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=KudoKenichiro en-aut-sei=Kudo en-aut-mei=Kenichiro 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= en-aut-name=NousoKazuhiro en-aut-sei=Nouso en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OdaNaohiro en-aut-sei=Oda en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MitsumuneSho en-aut-sei=Mitsumune en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KimuraGoro en-aut-sei=Kimura en-aut-mei=Goro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaHaruto en-aut-sei=Yamada en-aut-mei=Haruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 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=13 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AokageToshiyuki en-aut-sei=Aokage en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 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=17 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=18 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=19 ORCID= affil-num=1 en-affil=Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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 General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=5 en-affil=Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=7 en-affil=Department of Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=9 en-affil=Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=10 en-affil=Department of Infectious Disease, Okayama City Hospital kn-affil= affil-num=11 en-affil=Department of Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=12 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Department of General Thoracic Surgery and Breast and Endocrine Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=18 en-affil=Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=19 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=novel coronavirus disease 2019 kn-keyword=novel coronavirus disease 2019 en-keyword=pneumonia kn-keyword=pneumonia en-keyword=hydroperoxide kn-keyword=hydroperoxide en-keyword=nitric oxide kn-keyword=nitric oxide en-keyword=reactive oxygen species kn-keyword=reactive oxygen species en-keyword=citrulline kn-keyword=citrulline en-keyword=arginine kn-keyword=arginine en-keyword=asymmetric dimethylarginine kn-keyword=asymmetric dimethylarginine END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=9 article-no= start-page=884 end-page=890 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240731 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel strategy for activating gene expression through triplex DNA formation targeting epigenetically suppressed genes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Triplex DNA formation is a useful genomic targeting tool that is expected to have a wide range of applications, including the antigene method; however, there are fundamental limitations in its forming sequence. We recently extended the triplex DNA-forming sequence to methylated DNA sequences containing 5mCG base pairs by developing guanidino-dN, which is capable of recognizing a 5mCG base pair with high affinity. We herein investigated the effect of triplex DNA formation using TFOs with guanidino-dN on methylated DNA sequences at the promoter of the RASSF1A gene, whose expression is epigenetically suppressed by DNA methylation in MCF-7 cells, on gene expression. Interestingly, triplex DNA formation increased the expression of the RASSF1A gene at the transcript and protein levels. Furthermore, RASSF1A-activated MCF-7 cells exhibited cell growth suppressing activity. Changes in the expression of various genes associated with the promotion of apoptosis and breast cancer survival accompanied the activation of RASSF1A in cells exhibited antiproliferative activity. These results suggest the potential of increases in gene expression through triplex DNA formation as a new genomic targeting tool. en-copyright= kn-copyright= en-aut-name=NotomiRyotaro en-aut-sei=Notomi en-aut-mei=Ryotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SasakiShigeki en-aut-sei=Sasaki en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaniguchiYosuke en-aut-sei=Taniguchi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Pharmaceutical Sciences, Kyushu University kn-affil= affil-num=2 en-affil= Graduate School of Pharmaceutical Sciences, Nagasaki International University kn-affil= affil-num=3 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=62 cd-vols= no-issue=5 article-no= start-page=804 end-page=810 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202409 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Augmented humoral response to third and fourth dose of SARS-CoV-2 mRNA vaccines in lung transplant recipients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Since lung transplant recipients (LTRs) exhibit low immunogenicity after two doses of SARS-CoV-2 mRNA vaccines, optimal vaccine strategies for SARS-CoV-2 are required in LTRs. This study aimed to investigate the efficacy and safety of the third and fourth doses of the SARS-CoV-2 mRNA vaccines in LTRs.
Methods: We conducted a single-center study of 73 LTRs and 23 healthy controls (HCs). Participants received two-to-four doses of SARS-CoV-2 mRNA vaccines. The LTRs were divided into three groups based on the number of vaccine dose. IgG titers against SARS-CoV-2 spike protein were measured, and adverse events were assessed. Factors associated with humoral response were analyzed using univariate and multivariate analyses.
Results: The Dose 4 group (n = 27) had a higher humoral response rate (P = 0.018) and higher levels of anti-SARS-CoV-2 IgG antibody (P = 0.04) than the Dose 2 group (n = 14). The Dose 3 group (n = 32) had lower humoral response rates (P = 0.005) and levels of anti-SARS-CoV-2 IgG antibody (P = 0.0005) than the HCs (n = 23) even after the same dose. Systemic adverse events were milder in the LTRs than in the HCs (P < 0.05). Increased number of vaccine dose was identified as a predictor of positive humoral response (P = 0.021).
Conclusion: Booster doses of SARS-CoV-2 mRNA vaccines may enhance humoral response with mild adverse events in LTRs. Repeated vaccination might be warranted for LTRs to prevent SARS-CoV-2 infection. 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=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= en-aut-name=IshiharaMegumi en-aut-sei=Ishihara en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=9 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=10 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=11 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=12 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=13 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=14 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 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=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 Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University kn-affil= affil-num=14 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=Adverse events kn-keyword=Adverse events en-keyword=COVID-19 kn-keyword=COVID-19 en-keyword=Immunogenicity kn-keyword=Immunogenicity en-keyword=Lung transplantation kn-keyword=Lung transplantation en-keyword=mRNA vaccine kn-keyword=mRNA vaccine 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=19 cd-vols= no-issue=5 article-no= start-page=e0300644 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240517 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=PAI-1 mediates acquired resistance to MET-targeted therapy in non-small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mechanisms underlying primary and acquired resistance to MET tyrosine kinase inhibitors (TKIs) in managing non-small cell lung cancer remain unclear. In this study, we investigated the possible mechanisms acquired for crizotinib in MET-amplified lung carcinoma cell lines. Two MET-amplified lung cancer cell lines, EBC-1 and H1993, were established for acquired resistance to MET-TKI crizotinib and were functionally elucidated. Genomic and transcriptomic data were used to assess the factors contributing to the resistance mechanism, and the alterations hypothesized to confer resistance were validated. Multiple mechanisms underlie acquired resistance to crizotinib in MET-amplified lung cancer cell lines. In EBC-1-derived resistant cells, the overexpression of SERPINE1, the gene encoding plasminogen activator inhibitor-1 (PAI-1), mediated the drug resistance mechanism. Crizotinib resistance was addressed by combination therapy with a PAI-1 inhibitor and PAI-1 knockdown. Another mechanism of resistance in different subline cells of EBC-1 was evaluated as epithelial-to-mesenchymal transition with the upregulation of antiapoptotic proteins. In H1993-derived resistant cells, MEK inhibitors could be a potential therapeutic strategy for overcoming resistance with downstream mitogen-activated protein kinase pathway activation. In this study, we revealed the different mechanisms of acquired resistance to the MET inhibitor crizotinib with potential therapeutic application in patients with MET-amplified lung carcinoma. en-copyright= kn-copyright= 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=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=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=OchiKosuke en-aut-sei=Ochi en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsudakaShimpei en-aut-sei=Tsudaka en-aut-mei=Shimpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakatsuFumiaki en-aut-sei=Takatsu en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DateKeiichi en-aut-sei=Date en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsudaNaoki en-aut-sei=Matsuda en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 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=12 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=13 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=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= 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 Comprehensive Genomic 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=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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Surgery, Division of Cardiovascular and Thoracic Surgery, Duke University School of Medicine 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 Thoracic Surgery and Breast and Endocrinological Surgery, 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= affil-num=14 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=15 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=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-β1-NF-κB-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-κB kn-keyword=NF-κB en-keyword=MMP9 kn-keyword=MMP9 END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=9869 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Absolute lymphocyte count and neutrophil-to-lymphocyte ratio as predictors of CDK 4/6 inhibitor efficacy in advanced breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are the standard agents for treating patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer (ER + HER2 - ABC). However, markers predicting the outcomes of CDK4/6i treatment have yet to be identified. This study was a single-center retrospective cohort study. We retrospectively evaluated 101 patients with ER + HER2 - ABC receiving CDK4/6i in combination with endocrine therapy at Fukuyama City Hospital between November 2017 and July 2021. We investigated the clinical outcomes and the safety of CDK4/6i treatment, and the absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) as predictive markers for CDK4/6i. We defined the cut-off values as 1000/mu L for ALC and 3 for NLR, and divided into "low" and "high" groups, respectively. We evaluated 43 and 58 patients who received abemaciclib and palbociclib, respectively. Patients with high ALC and low NLR had significantly longer overall survival than those with low ALC and high NLR (high vs. low; ALC: HR 0.29; 95% CI 0.12-0.70; NLR: HR 2.94; 95% CI 1.21-7.13). There was no significant difference in efficacy between abemaciclib and palbociclib and both had good safety profiles. We demonstrated that ALC and NLR might predict the outcomes of CDK4/6i treatment in patients with ER + HER2 - ABC. en-copyright= kn-copyright= en-aut-name=NakamotoShogo en-aut-sei=Nakamoto en-aut-mei=Shogo 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=IwamotoTakayuki en-aut-sei=Iwamoto en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=YamamotoMari en-aut-sei=Yamamoto en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamashitaTetsumasa en-aut-sei=Yamashita en-aut-mei=Tetsumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KuwaharaChihiro en-aut-sei=Kuwahara en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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 and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Breast and Thyroid Surgery, Fukuyama City Hospital kn-affil= affil-num=5 en-affil=Department of Breast and Thyroid Surgery, Fukuyama City 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 and Thyroid Surgery, Fukuyama City Hospital kn-affil= affil-num=8 en-affil=Department of Breast and Thyroid Surgery, Fukuyama City Hospital kn-affil= 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= cd-vols= no-issue= article-no= start-page= end-page= 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=PRO-CTCAEを基にしたsymptom illustration scaleの開発と乳癌患者における検証 kn-title=Development and validation of a symptom illustration scale from the patient-reported outcome common terminology criteria for adverse events for patients with breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SUZUKIYoko en-aut-sei=SUZUKI en-aut-mei=Yoko kn-aut-name=鈴木陽子 kn-aut-sei=鈴木 kn-aut-mei=陽子 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=54 cd-vols= no-issue=11 article-no= start-page=1319 end-page=1328 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240418 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effective division of the intersegmental plane using a robotic stapler in robotic pulmonary segmentectomy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purposes Robot-assisted thoracoscopic (RATS) segmentectomy is becoming increasingly common because of the expanded indications for segmentectomy and the widespread adoption of robotic surgery. The precise division of the intersegmental plane is necessary to ensure oncologic margins from the tumor and to preserve the lung function. In this study, we present a strategy for accurately dividing the intersegmental plane using a robotic stapler and review the surgical outcomes.
Methods RATS portal segmentectomy was performed using the Da Vinci Xi system and the intersegmental plane was dissected using a robotic stapler. We evaluated the perioperative outcomes in 92 patients who underwent RATS portal segmentectomy between May 2020 and January 2023. These results were compared with those of 82 patients who underwent complete video-assisted thoracoscopic surgery (CVATS) during the same period.
Results The operative and console times were 162 and 97 min, respectively. No intraoperative complications occurred, and postoperative complications were observed in four cases (4.3%). The operative time, blood loss, postoperative complications, and maximum incision size were significantly lower in the RATS group than in the CVATS group. However, RATS requires a significantly higher number of staplers than CVATS.
Conclusions The division of the intersegmental plane using a robotic stapler in RATS portal segmentectomy was, therefore, found to be safe and effective. en-copyright= kn-copyright= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio 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=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko 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=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 ORCID= affil-num=1 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=2 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=3 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=4 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=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 General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 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=9 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Pulmonary segmentectomy kn-keyword=Pulmonary segmentectomy en-keyword=Robot-assisted thoracic surgery kn-keyword=Robot-assisted thoracic surgery en-keyword=Robotic segmentectomy kn-keyword=Robotic segmentectomy en-keyword=Robotic stapler kn-keyword=Robotic stapler END start-ver=1.4 cd-journal=joma no-vol=115 cd-vols= no-issue=7 article-no= start-page=2333 end-page=2345 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240427 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Adrenergic microenvironment driven by cancer-associated Schwann cells contributes to chemoresistance in patients with lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Doublecortin (DCX)-positive neural progenitor-like cells are purported components of the cancer microenvironment. The number of DCX-positive cells in tissues reportedly correlates with cancer progression; however, little is known about the mechanism by which these cells affect cancer progression. Here we demonstrated that DCX-positive cells, which are found in all major histological subtypes of lung cancer, are cancer-associated Schwann cells (CAS) and contribute to the chemoresistance of lung cancer cells by establishing an adrenergic microenvironment. Mechanistically, the activation of the Hippo transducer YAP/TAZ was involved in the acquisition of new traits of CAS and DCX positivity. We further revealed that CAS express catecholamine-synthesizing enzymes and synthesize adrenaline, which potentiates the chemoresistance of lung cancer cells through the activation of YAP/TAZ. Our findings shed light on CAS, which drive the formation of an adrenergic microenvironment by the reciprocal regulation of YAP/TAZ in lung cancer 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=KatayamaHaruyoshi en-aut-sei=Katayama en-aut-mei=Haruyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ZhuYidan en-aut-sei=Zhu en-aut-mei=Yidan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=ShigehiraTakafumi en-aut-sei=Shigehira en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=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=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=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 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 Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 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=4 en-affil=Department of Trauma Orthopedics, The Second Hospital of Dalian Medical University kn-affil= affil-num=5 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 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=11 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=adrenaline kn-keyword=adrenaline en-keyword=cancer-associated Schwann cells kn-keyword=cancer-associated Schwann cells en-keyword=doublecortin kn-keyword=doublecortin en-keyword=microenvironment kn-keyword=microenvironment en-keyword=YAP/TAZ kn-keyword=YAP/TAZ END start-ver=1.4 cd-journal=joma no-vol=202 cd-vols= no-issue=3 article-no= start-page=473 end-page=483 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230909 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Mammography screening has increased the detection of subcentimeter breast cancers. The prognosis for estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative T1a/bN0M0 breast cancers is excellent; however, the necessity of adjuvant endocrine therapy (ET) is uncertain.
Methods We evaluated the effectiveness of adjuvant ET in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer who underwent surgery from 2008 to 2012. Standard ET was administrated after surgery. The primary endpoint was the cumulative incidence of distant metastasis. All statistical tests were 2-sided.
Results Adjuvant ET was administered to 3991 (83%) of the 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%], diseases). The median follow-up period was 9.2 years. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32–0.93). In multivariate analysis, the independent risk factors for distant metastasis were no history of ET, mastectomy, high-grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% with and without ET, respectively (adjusted HR, 0.57; 95% CI, 0.39–0.83). In addition, adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs. 6.9%; sHR, 0.17, and 1.9% vs. 5.2%; sHR, 0.33).
Conclusions The prognosis was favorable in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, adjuvant ET reduced the incidence of distant metastasis with minimal absolute risk difference. These findings support considering the omission of adjuvant ET, especially for patients with low-grade and no lymphatic invasion disease. en-copyright= kn-copyright= en-aut-name=SasadaShinsuke en-aut-sei=Sasada en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KondoNaoto en-aut-sei=Kondo en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HashimotoHiroya en-aut-sei=Hashimoto en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=TerataKaori en-aut-sei=Terata en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KidaKumiko en-aut-sei=Kida en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SagaraYasuaki en-aut-sei=Sagara en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UenoTakayuki en-aut-sei=Ueno en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AnanKeisei en-aut-sei=Anan en-aut-mei=Keisei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SutoAkihiko en-aut-sei=Suto en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KanbayashiChizuko en-aut-sei=Kanbayashi en-aut-mei=Chizuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=NakamuraRikiya en-aut-sei=Nakamura en-aut-mei=Rikiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IshibaToshiyuki en-aut-sei=Ishiba en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TsuneizumiMichiko en-aut-sei=Tsuneizumi en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NishimuraSeiichiro en-aut-sei=Nishimura en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=NaitoYoichi en-aut-sei=Naito en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 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=19 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=20 ORCID= affil-num=1 en-affil=Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University kn-affil= affil-num=2 en-affil=Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=3 en-affil=Core Laboratory, Nagoya City University Graduate School of Medical Sciences 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, Akita University Hospital kn-affil= affil-num=6 en-affil=Department of Breast Surgical Oncology, St. Luke’s International Hospital kn-affil= affil-num=7 en-affil=Department of Breast and Thyroid Surgical Oncology, Social medical corporation Hakuaikai, Sagara Hospital kn-affil= affil-num=8 en-affil=Breast Oncology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=9 en-affil=Department of Surgery, Kitakyushu Municipal Medical Center kn-affil= affil-num=10 en-affil=Department of Breast Surgery, National Cancer Center Hospital kn-affil= affil-num=11 en-affil=Department of Breast Oncology, Niigata Cancer Center Hospital kn-affil= affil-num=12 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=13 en-affil=Department of Breast Surgery, Chiba Cancer Center kn-affil= affil-num=14 en-affil=Department of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=15 en-affil=Department of Breast Surgery, Shizuoka General Hospital kn-affil= affil-num=16 en-affil=Department of Breast Surgery, Shizuoka Cancer Center Hospital kn-affil= affil-num=17 en-affil=Department of General Internal Medicine, National Cancer Center Hospital East kn-affil= affil-num=18 en-affil=Breast Oncology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=19 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=20 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=T1a/b kn-keyword=T1a/b en-keyword=Endocrine therapy kn-keyword=Endocrine therapy en-keyword=Estrogen receptor kn-keyword=Estrogen receptor en-keyword=Prognosis kn-keyword=Prognosis END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=11 article-no= start-page=6697 end-page=6702 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230625 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=EGFR Mutation is a Prognostic Factor in Lung Cancer Patients with Pleural Dissemination Detected During or After Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background. Primary lung tumors are sometimes resected when either pleural dissemination (PD) or malignant pleural effusion (MPE) exists. This study clarified the prognostic factors for non-small cell lung cancer (NSCLC) with either PD and MPE, or both, detected during or after surgery.
Patients and Methods. We examined patients with NSCLC from a multicenter database who had either PD, MPE, or both, detected during or after surgery between 2005 and 2015. Hazard ratios and 95% confidence intervals were estimated using the Cox proportional hazards model adjusted for potential confounding factors.
Results. Among 9463 registered patients, PD, MPE, or both, were found in 114 patients with NSCLC during or after surgery. Primary tumor resection and exploratory thoracotomy were performed in 65 and 49 patients, respectively. In univariate analysis, adenocarcinoma, clinically undetected lymph node metastasis (c-N0 or unknown), EGFR mutation, and combination of chemotherapy or tyrosine kinase inhibitors after surgery were better prognostic factors for overall survival (OS), whereas in the multivariate analysis, adenocarcinoma, clinically undetected lymph node metastasis, and EGFR mutation were favorable independent prognostic factors in OS. Additionally, limited to patients with EGFR mutation, patients with primary lung tumor resection showed a significantly better 5-year OS than those with exploratory thoracotomy (86.4 vs. 44.8%; p < 0.001).
Conclusion. Our findings show that surgical resection of primary tumors could improve the prognosis of patients with PD, MPE, or both, detected during or after surgery when the tumors harbor an EGFR mutation. en-copyright= kn-copyright= en-aut-name=FujiwaraToshiya en-aut-sei=Fujiwara en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi 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=TakaoSoshi en-aut-sei=Takao en-aut-mei=Soshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=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=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 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=13 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=14 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=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=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 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=19 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=20 ORCID= affil-num=1 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=2 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=3 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=4 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=5 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=6 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=8 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=9 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=10 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=11 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=12 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=13 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=14 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=15 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=16 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=17 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=18 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=19 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=20 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= END start-ver=1.4 cd-journal=joma no-vol=101 cd-vols= no-issue=4 article-no= start-page=431 end-page=447 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel extracellular role of REIC/Dkk-3 protein in PD-L1 regulation in cancer cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=The adenovirus-REIC/Dkk-3 expression vector (Ad-REIC) has been the focus of numerous clinical studies due to its potential for the quenching of cancers. The cancer-suppressing mechanisms of the REIC/DKK-3 gene depend on multiple pathways that exert both direct and indirect effects on cancers. The direct effect is triggered by REIC/Dkk-3-mediated ER stress that causes cancer-selective apoptosis, and the indirect effect can be classified in two ways: (i) induction, by Ad-REIC-mis-infected cancer-associated fibroblasts, of the production of IL-7, an important activator of T cells and NK cells, and (ii) promotion, by the secretory REIC/Dkk-3 protein, of dendritic cell polarization from monocytes. These unique features allow Ad-REIC to exert effective and selective cancer-preventative effects in the manner of an anticancer vaccine. However, the question of how the REIC/Dkk-3 protein leverages anticancer immunity has remained to be answered. We herein report a novel function of the extracellular REIC/Dkk-3—namely, regulation of an immune checkpoint via modulation of PD-L1 on the cancer-cell surface. First, we identified novel interactions of REIC/Dkk-3 with the membrane proteins C5aR, CXCR2, CXCR6, and CMTM6. These proteins all functioned to stabilize PD-L1 on the cell surface. Due to the dominant expression of CMTM6 among the proteins in cancer cells, we next focused on CMTM6 and observed that REIC/Dkk-3 competed with CMTM6 for PD-L1, thereby liberating PD-L1 from its complexation with CMTM6. The released PD-L1 immediately underwent endocytosis-mediated degradation. These results will enhance our understanding of not only the physiological nature of the extracellular REIC/Dkk-3 protein but also the Ad-REIC-mediated anticancer effects. en-copyright= kn-copyright= en-aut-name=GoharaYuma en-aut-sei=Gohara en-aut-mei=Yuma 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=FutamiJunichiro en-aut-sei=Futami en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AudebertLéna en-aut-sei=Audebert en-aut-mei=Léna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=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=YoshizawaChikako en-aut-sei=Yoshizawa en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 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=12 ORCID= en-aut-name=KumonHiromi en-aut-sei=Kumon en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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 Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine 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 Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Innovation Center Okayama for Nanobio-Targeted Therapy, Okayama University kn-affil= affil-num=14 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=REIC/Dkk-3 kn-keyword=REIC/Dkk-3 en-keyword=PD-L1 kn-keyword=PD-L1 en-keyword=Immune checkpoint kn-keyword=Immune checkpoint en-keyword=Cancer therapy kn-keyword=Cancer therapy END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=7 article-no= start-page=847 end-page=859 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trends and issues in clinical research on satisfaction and quality of life after mastectomy and breast reconstruction: a 5-year scoping review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Breast reconstruction (BR) aims to improve the satisfaction and quality of life (QOL) of breast cancer survivors. Clinical studies using patient-reported outcomes (PROs) can therefore provide relevant information to the patients and support decision-making. This scoping review was conducted to analyze recent trends in world regions, methods used, and factors investigated. The literature search was conducted in August 2022. Databases of PubMed, MEDLINE, and CINAHL were searched for relevant English-language studies published from 2017 to 2022. Studies involving women with breast cancer who underwent BR after mastectomy and investigated PROs after BR using BR-specific scales were included. Data on the country, publication year, study design, PRO measures (PROMs) used, time points of surveys, and research themes were collected. In total, 147 articles met the inclusion criteria. BREAST-Q was the most widely used, contributing to the increase in the number and diversification of studies in this area. Such research has been conducted mainly in North America and Europe and is still developing in Asia and other regions. The research themes involved a wide range of clinical and patient factors in addition to surgery, which could be influenced by research methods, time since surgery, and even cultural differences. Recent BR-specific PROMs have led to a worldwide development of research on factors that affect satisfaction and QOL after BR. PRO after BR may be influenced by local cultural and social features, and it would be necessary to accumulate data in each region to draw clinically useful conclusion. en-copyright= kn-copyright= en-aut-name=SaigaMiho en-aut-sei=Saiga en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakagiriRyoko en-aut-sei=Nakagiri en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MukaiYuko en-aut-sei=Mukai en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= affil-num=1 en-affil=Department of Plastic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Plastic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Plastic Surgery, Okayama Rosai Hospital kn-affil= affil-num=4 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Patient-reported outcomes kn-keyword=Patient-reported outcomes en-keyword=Breast reconstruction kn-keyword=Breast reconstruction en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Quality of life kn-keyword=Quality of life en-keyword=Satisfaction kn-keyword=Satisfaction END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue=3 article-no= start-page=ezad048 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Surgical outcome of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy en-subtitle= kn-subtitle= en-abstract= kn-abstract=OBJECTIVES: Ipsilateral reoperation after pulmonary lobectomy is often challenging because of adhesions from the previous operation. We retrospectively examined the surgical outcome and prognosis of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy using a multicentre database.
METHODS: We evaluated the perioperative outcomes and overall survival of 51 patients who underwent pulmonary lobectomy followed by ipsilateral anatomical resection for lung cancer between January 2012 and December 2018. In addition, patients with stage I non-small-cell lung cancer (NSCLC) were compared with 3411 patients with stage I lung cancer who underwent pulmonary resection without a prior ipsilateral lobectomy.
RESULTS: Ipsilateral anatomical resections included 10 completion pneumonectomies, 19 pulmonary lobectomies and 22 pulmonary segmentectomies. Operative time was 312.2 ± 134.5 min, and intraoperative bleeding was 522.2 ± 797.5 ml. Intraoperative and postoperative complications occurred in 9 and 15 patients, respectively. However, the 5-year overall survival rate after anatomical resection followed by ipsilateral lobectomy was 83.5%. Furthermore, in patients with c-stage I NSCLC, anatomical resection followed by ipsilateral lobectomy was not associated with worse survival than anatomical resection without prior ipsilateral lobectomy.
CONCLUSIONS: Anatomical resection following ipsilateral lobectomy is associated with a high frequency of intraoperative and postoperative complications. However, the 5-year overall survival in patients with c-stage I NSCLC who underwent ipsilateral anatomical resection after pulmonary lobectomy is comparable to that in patients who underwent anatomical resection without prior pulmonary lobectomy. en-copyright= kn-copyright= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio 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=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=ArakiKota en-aut-sei=Araki en-aut-mei=Kota 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=OkadaMasanori en-aut-sei=Okada en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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=10 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=11 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=12 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=13 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=14 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=15 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=16 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=17 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=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=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 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=21 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=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= affil-num=1 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=6 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=7 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=8 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=9 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=10 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=11 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=12 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=13 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=14 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=15 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=16 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=17 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=18 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=19 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=20 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=21 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=22 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=23 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Surgical outcome kn-keyword=Surgical outcome en-keyword=ipsilateral anatomical resection kn-keyword=ipsilateral anatomical resection en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=pulmonary lobectomy kn-keyword=pulmonary lobectomy en-keyword=overall survival kn-keyword=overall survival END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=5 article-no= start-page=e1617 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=Postoperative Complications in Living Donors for Lung Transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background. Living donor lobar lung transplantation is a life-saving procedure for critically ill patients. This requires 2 healthy donors exposed to risks and without medical benefit. Therefore, the donor's safety and minimal postoperative complications are crucial. This study aimed to investigate the short-term outcomes and identify the risk factors affecting these outcomes. Methods. The data of 175 living donors enrolled between 1998 and 2022 were analyzed. Donors were divided into era 1 (1998-2009) and era 2 (2010-2022). Results. The overall incidence of postoperative complications was 39%, of which 7% were major complications. Donors who underwent surgery on the right side had a higher incidence of delayed pulmonary fistulae (P = 0.01) and elevated liver enzyme levels (P = 0.028). Living donor surgery on the right side (P = 0.01), era 2 (P = 0.01), and the need for plasty (P = 0.04) were predictors of postoperative complications. Conclusions. Updated data on complications and their correlation with postoperative quality of life from this study could aid in the selection of potential donors and facilitate informed consent. en-copyright= kn-copyright= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiKento en-aut-sei=Fujii en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshiharaMegumi en-aut-sei=Ishihara en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=OkaharaShuji en-aut-sei=Okahara en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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=10 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=11 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=12 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=13 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=14 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 General Thoracic Surgery and Organ Transplant Center, 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=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 Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 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=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 Thoracic Surgery and Breast and Endocrinological Surgery, 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= affil-num=14 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=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-β1 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=62 cd-vols= no-issue=2 article-no= start-page=240 end-page=246 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=Long-term outcomes of lung transplantation requiring renal replacement therapy: A single-center experience en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Life-long immunosuppressive therapy after lung transplantation (LT) may lead to end-stage renal disease (ESRD), requiring renal replacement therapy (RRT). We aimed to investigate the characteristics and long-term outcomes of patients undergoing LT and requiring RRT.

Methods
This study was a single-center, retrospective cohort study. The patients were divided into the RRT (n = 15) and non-RRT (n = 170) groups. We summarized the clinical features of patients in the RRT group and compared patient characteristics, overall survival, and chronic lung allograft dysfunction (CLAD)-free survival between the two groups.

Results
The cumulative incidences of ESRD requiring RRT after LT at 5, 10, and 15 years were 0.8 %, 7.6 %, and 25.2 %, respectively. In the RRT group, all 15 patients underwent hemodialysis but not peritoneal dialysis, and two patients underwent living-donor kidney transplantation. The median follow-up period was longer in the RRT group than in the non-RRT group (P < 0.001). The CLAD-free survival and overall survival did not differ between the two groups. The 5-year survival rate even after the initiation of hemodialysis was 53.3 %, and the leading cause of death in the RRT group was infection.

Conclusions
Favorable long-term outcomes can be achieved by RRT for ESRD after LT. en-copyright= kn-copyright= en-aut-name=TomiokaYasuaki en-aut-sei=Tomioka en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=ShiotaniToshio en-aut-sei=Shiotani en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=IshiharaMegumi en-aut-sei=Ishihara en-aut-mei=Megumi 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=OtaniShinji en-aut-sei=Otani en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 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=Dialysis kn-keyword=Dialysis en-keyword=Living-donor kidney transplantation kn-keyword=Living-donor kidney transplantation en-keyword=End -stage renal disease kn-keyword=End -stage renal disease en-keyword=Renal replacement therapy kn-keyword=Renal replacement therapy 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=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=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 β2 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=46 cd-vols= no-issue=2 article-no= start-page=536 end-page=541 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240119 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A comparison between the adverse event profiles of patients receiving palbociclib and abemaciclib: analysis of two real-world databases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Palbociclib and abemaciclib are cyclin-dependent kinase (CDK) 4/6 inhibitors currently used to treat breast cancer. Although their therapeutic efficacies are considered comparable, differences in adverse event (AE) profiles of the two drugs remain unclear.
Aim We analysed two real-world databases, the World Health Organization’s VigiBase and the Food and Drug Administration Adverse Event Reporting System (FAERS), to identify differences in AE profiles of palbociclib and abemaciclib.
Method Data of patients with breast cancer receiving palbociclib or abemaciclib recorded until December 2022 were extracted from the VigiBase and FAERS databases. In total, 200 types of AEs were analysed. The reporting odds ratios were calculated using a disproportionality analysis.
Results Cytopenia was frequently reported in patients receiving palbociclib, whereas interstitial lung disease and diarrhoea were frequently reported in those receiving abemaciclib. Moreover, psychiatric and nervous system disorders were more common in the palbociclib group, whereas renal and urinary disorders were more common in the abemaciclib group.
Conclusion This study is the first to show comprehensively the disparities in the AE profiles of palbociclib and abemaciclib. The findings highlight the importance of considering these differences when selecting a suitable CDK4/6 inhibitor to ensure safe and favourable outcomes for patients with breast cancer. en-copyright= kn-copyright= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugimotoShiho en-aut-sei=Sugimoto en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumotoJun en-aut-sei=Matsumoto en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwataNaohiro en-aut-sei=Iwata en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamotoAkihiko en-aut-sei=Nakamoto en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OzakiAya Fukuma en-aut-sei=Ozaki en-aut-mei=Aya Fukuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AriyoshiNoritaka en-aut-sei=Ariyoshi en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University of California kn-affil= affil-num=7 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= en-keyword=Abemaciclib kn-keyword=Abemaciclib en-keyword=Adverse event kn-keyword=Adverse event en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Cyclin-dependent kinase 4/6 inhibitor kn-keyword=Cyclin-dependent kinase 4/6 inhibitor en-keyword=Palbociclib kn-keyword=Palbociclib 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=45 cd-vols= no-issue=1 article-no= start-page=35 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Current status and challenges of breast cancer prevention∼DNA methylation would lead to groundbreaking progress in breast cancer prevention∼ en-subtitle= kn-subtitle= en-abstract= kn-abstract=The number of breast cancer patients is increasing worldwide. Furthermore, breast cancer often develops in young people, even those only in their 30s, who play a central role in their families and society. Results from many cohort studies suggest that dietary factors, alcohol consumption, lack of physical activity, obesity, nulliparity, breastfeeding, oral contraceptive use, fertility treatment and hormone replacement therapy are risk factors for breast cancer. However, the effects of lifestyle habits on the human body are complexly intertwined with various factors, and the effects vary from person to person depending on their constitution, etc., so there is no basis for this. Therefore, primary prevention of breast cancer is still not being implemented appropriately and efficiently. Furthermore, advances in genomic technology make it possible to assess the risk of developing breast cancer in some individuals. As a result, the establishment of breast cancer prevention methods has become a health priority for high-risk individuals. Drugs such as tamoxifen and raloxifene are known to prevent the development of breast cancer, based on the results of multiple randomized controlled trials, but there are concerns regarding the side effects of these powerful agents. In addition, several clinical studies have shown that prophylactic mastectomy for women who have BRCA mutations or who are identified as being at high risk reduces the incidence of breast cancer development. However, many issues, such as changes in long-term quality of life after preventive surgery, the optimal timing of surgery and the identification of women who are at high risk but will not develop breast cancer, remain uncertain. In other words, although many researchers have focused on chemoprevention and surgical prevention and clear preventive effects of these strategies have been confirmed, it cannot be said that they are widely accepted. Therefore, the current evidence for chemoprevention and surgical prevention, as well as highlights of several interesting lines of research currently underway, are summarized in this article. en-copyright= kn-copyright= en-aut-name=TsukiokiTakahiro en-aut-sei=Tsukioki en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KhanSeema A. en-aut-sei=Khan en-aut-mei=Seema A. 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= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrine Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Surgery, Feinberg School of Medicine of Northwestern University kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Breast and Endocrine Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Prevention kn-keyword=Prevention en-keyword=Risk reduction mastectomy kn-keyword=Risk reduction mastectomy en-keyword=Chemoprevention kn-keyword=Chemoprevention en-keyword=Methylation kn-keyword=Methylation END start-ver=1.4 cd-journal=joma no-vol=38 cd-vols= no-issue=1 article-no= start-page=e15169 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of changes in skeletal muscle mass and quality during the waiting time on outcomes of lung transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: The association of changes in skeletal muscle mass and quality during the waiting time with outcomes of lung transplantation (LT) remains unclear. We aimed to examine the association of changes in skeletal muscle mass and quality during the waiting time, as well as preoperative skeletal muscle mass and quality, with outcomes of LT.
Methods: This study included individuals who underwent LT from brain-dead donors. Skeletal muscle mass (cm2/m2) and quality (mean Hounsfield units [HU]) of the erector spinae muscle at the 12th thoracic level were evaluated using computed tomography. Preoperative skeletal muscle mass and quality, and their changes during the waiting time were calculated. We evaluated the associations among mechanical ventilation (MV) duration, intensive care unit (ICU) length of stay (LOS), hospital LOS, 6-minute walk distance at discharge, and 5-year survival after LT.
Results: This study included 98 patients. The median waiting time was 594.5 days (interquartile range [IQR], 355.0–913.0). The median changes in skeletal muscle mass and quality were −4.4% (IQR, −13.3–3.1) and −2.9% (IQR, −16.0–4.1), respectively. Severe low skeletal muscle mass at LT was associated with prolonged ICU LOS (B = 8.46, 95% confidence interval [CI]: .51–16.42) and hospital LOS (B = 36.00, 95% CI: 3.23–68.78). Pronounced decrease in skeletal muscle mass during the waiting time was associated with prolonged MV duration (B = 7.85, 95% CI: .89–14.81) and ICU LOS (B = 7.97, 95% CI: .83–15.10).
Conclusion: Maintaining or increasing skeletal muscle mass during the waiting time would be beneficial to improve the short-term outcomes of LT. en-copyright= kn-copyright= en-aut-name=HagiyamaAkikazu en-aut-sei=Hagiyama en-aut-mei=Akikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=KatayamaYoshimi en-aut-sei=Katayama en-aut-mei=Yoshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HamadaMasanori en-aut-sei=Hamada en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SendaMasuo en-aut-sei=Senda en-aut-mei=Masuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Division of Physical Medicine and Rehabilitation, Okayama University Hospital kn-affil= affil-num=2 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=3 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=4 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=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=Division of Physical Medicine and Rehabilitation, Okayama University Hospital kn-affil= affil-num=7 en-affil=Division of Physical Medicine and Rehabilitation, Okayama University Hospital kn-affil= affil-num=8 en-affil=Division of Physical Medicine and Rehabilitation, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=computed tomography kn-keyword=computed tomography en-keyword=lung transplantation kn-keyword=lung transplantation en-keyword=prognosis kn-keyword=prognosis en-keyword=skeletal muscle kn-keyword=skeletal muscle en-keyword=waiting time kn-keyword=waiting time END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=10 article-no= start-page=e0287501 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A randomized controlled trial of teprenone in terms of preventing worsening of COVID-19 infection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Some COVID-19 patients develop life-threatening disease accompanied by severe pneumonitis. Teprenone induces expression of heat-shock proteins (HSPs) that protect against interstitial pneumonia in preclinical models. We explored whether teprenone prevented worsening of COVID-19 infections.
Methods
This open-label, randomized, pilot phase 2 clinical trial was conducted at five institutions in Japan. We randomized patients hospitalized for COVID-19 with fever to teprenone or noteprenone groups in a 1:1 ratio. We stratified patients by sex, age < and >= 70 years and the existence (or not) of complications (hypertension, diabetes, ischemic heart disease, chronic pulmonary disease and active cancer). No limitation was imposed on other COVID-19 treatments. The primary endpoint was the intubation rate.
Results
One hundred patients were included, 51 in the teprenone and 49 in the no- teprenone groups. The intubation rate did not differ significantly between the two groups: 9.8% (5/51) vs. 2.0% (1/49) (sub-hazard ratio [SHR] 4.99, 95% confidence interval [CI]: 0.59-42.1; p = 0.140). The rates of intra-hospital mortality and intensive care unit (ICU) admission did not differ significantly between the two groups: intra-hospital mortality 3.9% (2/51) vs. 4.1% (2/ 49) (hazard ratio [HR] 0.78, 95%CI: 0.11-5.62; p = 0.809); ICU admission 11.8% (6/51) vs. 6.1% (3/49) (SHR 1.99, 95%CI: 0.51-7.80; p = 0.325).
Conclusion
Teprenone afforded no clinical benefit. en-copyright= kn-copyright= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KudoKenichiro en-aut-sei=Kudo en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=NousoKazuhiro en-aut-sei=Nouso en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OdaNaohiro en-aut-sei=Oda en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MitsumuneSho en-aut-sei=Mitsumune en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamadaHaruto en-aut-sei=Yamada en-aut-mei=Haruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 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=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=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AokageToshiyuki en-aut-sei=Aokage en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 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=17 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=18 ORCID= affil-num=1 en-affil=Department of Allergy and Respiratory Medicine, 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 Respiratory Medicine, National Hospital Organization Okayama Medical Center kn-affil= affil-num=4 en-affil=Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center kn-affil= affil-num=8 en-affil=Department of Infectious Disease, Okayama City Hospital kn-affil= affil-num=9 en-affil=Department of Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=10 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of General Thoracic Surgery and Breast and Endocrine Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= 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=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=乳がん進展におけるLysyl oxidase-like 4 (LOXL4) の新しい重要機能の発見−LOXL4はAnnexin A2を介して乳がんの増生を促進する− kn-title=Lysyl oxidase-like 4 exerts an atypical role in breast cancer progression that is dependent on the enzymatic activity that targets the cell-surface annexin A2 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NI LUH GEDE YONI KOMALASARI en-aut-sei=NI LUH GEDE YONI KOMALASARI en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 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=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=LOXL1 および LOXL4 は、ZEB1 の Zn²⁺結合型の新規標的遺伝子であり、トリプルネガティブ乳がん細胞における浸潤事象の加速に重要な役割を果たす kn-title=LOXL1 and LOXL4 are novel target genes of the Zn²⁺-bound form of ZEB1 and play a crucial role in the acceleration of invasive events in triple-negative breast cancer cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HIRABAYASHIDaisuke en-aut-sei=HIRABAYASHI en-aut-mei=Daisuke kn-aut-name=平林大輔 kn-aut-sei=平林 kn-aut-mei=大輔 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 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=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=一次乳房再建術が周術期炎症性サイトカインに与える影響に関する観察研究 kn-title=An observational study of the impact of immediate breast reconstruction on perioperative inflammatory cytokines en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MUKAIYuko en-aut-sei=MUKAI en-aut-mei=Yuko kn-aut-name=向井裕子 kn-aut-sei=向井 kn-aut-mei=裕子 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=5 article-no= start-page=536 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231002 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of the accuracy of heart dose prediction by machine learning for selecting patients not requiring deep inspiration breath‑hold radiotherapy after breast cancer surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=Increased heart dose during postoperative radiotherapy (RT) for left‑sided breast cancer (BC) can cause cardiac injury, which can decrease patient survival. The deep inspiration breath‑hold technique (DIBH) is becoming increasingly common for reducing the mean heart dose (MHD) in patients with left‑sided BC. However, treatment planning and DIBH for RT are laborious, time‑consuming and costly for patients and RT staff. In addition, the proportion of patients with left BC with low MHD is considerably higher among Asian women, mainly due to their smaller breast volume compared with that in Western countries. The present study aimed to determine the optimal machine learning (ML) model for predicting the MHD after RT to pre‑select patients with low MHD who will not require DIBH prior to RT planning. In total, 562 patients with BC who received postoperative RT were randomly divided into the trainval (n=449) and external (n=113) test datasets for ML using Python (version 3.8). Imbalanced data were corrected using synthetic minority oversampling with Gaussian noise. Specifically, right‑left, tumor site, chest wall thickness, irradiation method, body mass index and separation were the six explanatory variables used for ML, with four supervised ML algorithms used. Using the optimal value of hyperparameter tuning with root mean squared error (RMSE) as an indicator for the internal test data, the model yielding the best F2 score evaluation was selected for final validation using the external test data. The predictive ability of MHD for true MHD after RT was the highest among all algorithms for the deep neural network, with a RMSE of 77.4, F2 score of 0.80 and area under the curve‑receiver operating characteristic of 0.88, for a cut‑off value of 300 cGy. The present study suggested that ML can be used to pre‑select female Asian patients with low MHD who do not require DIBH for the postoperative RT of BC. en-copyright= kn-copyright= en-aut-name=KamizakiRyo en-aut-sei=Kamizaki en-aut-mei=Ryo 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=Al‑HammadWlla en-aut-sei=Al‑Hammad en-aut-mei=Wlla kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=IshizakaHinata en-aut-sei=Ishizaka en-aut-mei=Hinata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=SugimotoKohei en-aut-sei=Sugimoto en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=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=BarhamMajd en-aut-sei=Barham en-aut-mei=Majd 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=NakamitsuYuki en-aut-sei=Nakamitsu en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HiranoMasaki en-aut-sei=Hirano en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MutoYuki en-aut-sei=Muto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IharaHiroki en-aut-sei=Ihara en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SugiyamaSoichi en-aut-sei=Sugiyama en-aut-mei=Soichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University kn-affil= affil-num=9 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An‑Najah National 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 Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of Proton Beam Therapy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=BC kn-keyword=BC en-keyword=RT kn-keyword=RT en-keyword=heart dose kn-keyword=heart dose en-keyword=ML kn-keyword=ML en-keyword=DNN kn-keyword=DNN en-keyword=DIBH kn-keyword=DIBH 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=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=517 end-page=525 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=Association between BRCA Gene Variants and the Response to Modified FOLFIRINOX in Patients with Unresectable Pancreatic Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated the effect of modified FOLFIRINOX (mFFX) in unresectable pancreatic cancer by retrospectively analyzing the cases of 43 patients who underwent BRCA testing (germline, n=11; somatic, n=26; both germline and somatic, n=6). The association between BRCA mutations and therapeutic effect was clarified. Six patients tested positive for germline pathogenic variants. Familial pancreatic cancer (33% vs. 3%, p=0.006) and peritoneal disseminated lesions (66% vs. 8%, p<0.001) were significantly more common in patients with germline pathogenic variants. The partial response (PR) rate was 100% in the germline BRCA-positive patients, and 27% in the germline BRCA-negative patients (p<0.001). The median progression-free survival (PFS) was not reached for any germline BRCA-positive patients but was 9.0 months for the germline BRCA-negative patients (p=0.042). Patients with stage IV BRCA-associated pancreatic cancer had better overall survival than those with non-BRCA-associated pancreatic cancer, although the difference was nonsignificant (not reached vs. 655 days, p=0.061). Our results demonstrate that a PR and prolonged PFS can be expected in germline BRCA-positive patients after treatment with mFFX. Our findings also suggest that germline BRCA pathogenic variants may be useful as biomarkers for the therapeutic effect of mFFX in patients with pancreatic cancer. en-copyright= kn-copyright= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru 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=MorimotoKosaku en-aut-sei=Morimoto en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 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=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=KatoHironari en-aut-sei=Kato en-aut-mei=Hironari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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 Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital 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= en-keyword=BRCA kn-keyword=BRCA en-keyword=FOLFIRINOX kn-keyword=FOLFIRINOX en-keyword=pancreatic cancer kn-keyword=pancreatic cancer en-keyword=progression-free survival kn-keyword=progression-free survival en-keyword=pathogenic variant kn-keyword=pathogenic variant END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=13 article-no= start-page=8727 end-page=8734 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230901 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prognostic Impact of Tumor-Infiltrating Lymphocytes, Tertiary Lymphoid Structures, and Neutrophil-to-Lymphocyte Ratio in Pulmonary Metastases from Uterine Leiomyosarcoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The presence of tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) in tumor tissue has been related to the prognosis in various malignancies. Meanwhile, neutrophil-to-lymphocyte ratio (NLR) as a systemic inflammation marker also has been associated with the prognosis in them. However, few reports have investigated the relationship between pulmonary metastases from sarcoma and these biomarkers.
Methods We retrospectively recruited 102 patients undergoing metastasectomy for pulmonary metastases from uterine leiomyosarcoma at Okayama University Hospital from January 2006 to December 2019. TILs and TLSs were evaluated by immunohistochemical staining of surgically resected specimens of pulmonary metastases using anti-CD3/CD8/CD103/Foxp3/CD20 antibodies. NLR was calculated from the blood examination immediately before the most recent pulmonary metastasectomy. We elucidated the relationship between the prognosis and these factors. Because we considered that the status of tumor tissue and systemic inflammation were equally valuable, we also assessed the impact of the combination of TILs or TLSs and NLR on the prognosis.
Results As for TILs, CD3-positive cells and CD8-positive cells were correlated with the prognosis. The prognosis was significantly better in patients with CD3-high group, CD8-high group, TLSs-high group, and NLR-low group, respectively. The prognosis of CD8-high/NLR-low group and TLSs-high/NLR-low group was significantly better than that of CD8-low/NLR-high group and TLSs-low/NLR-high group, respectively.
Conclusions CD3-positive TILs, CD8-positive TILs, TLSs, and NLR are correlated with the prognosis, respectively. The combination of CD8-positive TILs or TLSs and NLR may be the indicators to predict the prognosis of patients with pulmonary metastases from uterine leiomyosarcoma. en-copyright= kn-copyright= en-aut-name=MatsudaNaoki en-aut-sei=Matsuda en-aut-mei=Naoki 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=HabuTomohiro en-aut-sei=Habu en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 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=10 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=11 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=12 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=13 ORCID= en-aut-name=TakahashiKatsuhito en-aut-sei=Takahashi en-aut-mei=Katsuhito 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= 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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=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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 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=11 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 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=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= affil-num=14 en-affil=Department of Sarcoma Medicine, Center for Sarcoma Multidisciplinary Treatment, Kameda Medical Center kn-affil= affil-num=15 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=65 cd-vols= no-issue=8 article-no= start-page=6039 end-page=6055 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220411 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of a Vitamin-D Receptor Antagonist, MeTC7, which Inhibits the Growth of Xenograft and Transgenic Tumors In Vivo en-subtitle= kn-subtitle= en-abstract= kn-abstract=Vitamin-D receptor (VDR) mRNA is overexpressed in neuroblastoma and carcinomas of lung, pancreas, and ovaries and predicts poor prognoses. VDR antagonists may be able to inhibit tumors that overexpress VDR. However, the current antagonists are arduous to synthesize and are only partial antagonists, limiting their use. Here, we show that the VDR antagonist MeTC7 (5), which can be synthesized from 7-dehydrocholesterol (6) in two steps, inhibits VDR selectively, suppresses the viability of cancer cell-lines, and reduces the growth of the spontaneous transgenic TH-MYCN neuroblastoma and xenografts in vivo. The VDR selectivity of 5 against RXRα and PPAR-γ was confirmed, and docking studies using VDR-LBD indicated that 5 induces major changes in the binding motifs, which potentially result in VDR antagonistic effects. These data highlight the therapeutic benefits of targeting VDR for the treatment of malignancies and demonstrate the creation of selective VDR antagonists that are easy to synthesize. en-copyright= kn-copyright= en-aut-name=KhazanNegar en-aut-sei=Khazan en-aut-mei=Negar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimKyu Kwang en-aut-sei=Kim en-aut-mei=Kyu Kwang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HansenJeanne N. en-aut-sei=Hansen en-aut-mei=Jeanne N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SinghNiloy A. en-aut-sei=Singh en-aut-mei=Niloy A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MooreTaylor en-aut-sei=Moore en-aut-mei=Taylor kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SnyderCameron W. A. en-aut-sei=Snyder en-aut-mei=Cameron W. A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=PanditaRavina en-aut-sei=Pandita en-aut-mei=Ravina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=StrawdermanMyla en-aut-sei=Strawderman en-aut-mei=Myla kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiharaMichiko en-aut-sei=Fujihara en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakamuraYuta en-aut-sei=Takamura en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=JianYe en-aut-sei=Jian en-aut-mei=Ye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=BattagliaNicholas en-aut-sei=Battaglia en-aut-mei=Nicholas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YanoNaohiro en-aut-sei=Yano en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TeramotoYuki en-aut-sei=Teramoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ArnoldLeggy A. en-aut-sei=Arnold en-aut-mei=Leggy A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HopsonRussell en-aut-sei=Hopson en-aut-mei=Russell kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KishorKeshav en-aut-sei=Kishor en-aut-mei=Keshav kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NayakSneha en-aut-sei=Nayak en-aut-mei=Sneha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OjhaDebasmita en-aut-sei=Ojha en-aut-mei=Debasmita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SharonAshoke en-aut-sei=Sharon en-aut-mei=Ashoke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=AshtonJohn M. en-aut-sei=Ashton en-aut-mei=John M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=WangJian en-aut-sei=Wang en-aut-mei=Jian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MilanoMichael T. en-aut-sei=Milano en-aut-mei=Michael T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MiyamotoHiroshi en-aut-sei=Miyamoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=LinehanDavid C. en-aut-sei=Linehan en-aut-mei=David C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=GerberScott A. en-aut-sei=Gerber en-aut-mei=Scott A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KawarNada en-aut-sei=Kawar en-aut-mei=Nada kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=SinghAjay P. en-aut-sei=Singh en-aut-mei=Ajay P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=TabdanovErdem D. en-aut-sei=Tabdanov en-aut-mei=Erdem D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=DokholyanNikolay V. en-aut-sei=Dokholyan en-aut-mei=Nikolay V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=KakutaHiroki en-aut-sei=Kakuta en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=JurutkaPeter W. en-aut-sei=Jurutka en-aut-mei=Peter W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=SchorNina F. en-aut-sei=Schor en-aut-mei=Nina F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=Rowswell-TurnerRachael B. en-aut-sei=Rowswell-Turner en-aut-mei=Rachael B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=SinghRakesh K. en-aut-sei=Singh en-aut-mei=Rakesh K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=MooreRichard G. en-aut-sei=Moore en-aut-mei=Richard G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= affil-num=1 en-affil=Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center kn-affil= affil-num=2 en-affil=Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center kn-affil= affil-num=3 en-affil=Department of Pediatrics, University of Rochester Medical Center kn-affil= affil-num=4 en-affil=Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center kn-affil= affil-num=5 en-affil=Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center kn-affil= affil-num=6 en-affil=Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center kn-affil= affil-num=7 en-affil=Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center kn-affil= affil-num=8 en-affil=Department of Biostatistics and Computational Biology, University of Rochester Medical Center kn-affil= affil-num=9 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center kn-affil= affil-num=12 en-affil=Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center kn-affil= affil-num=13 en-affil=Department of Surgery, Division of Surgical Research, Rhode Island Hospital, Alpert Medical School of Brown University kn-affil= affil-num=14 en-affil=Department of Pathology and Laboratory Medicine, University of Rochester Medical Center kn-affil= affil-num=15 en-affil=Department of Chemistry and Biochemistry, University of Wisconsin Milwaukee kn-affil= affil-num=16 en-affil=Department of Chemistry, Brown University kn-affil= affil-num=17 en-affil=Department of Chemistry, Birla Institute of Technology kn-affil= affil-num=18 en-affil=Department of Chemistry, Birla Institute of Technology kn-affil= affil-num=19 en-affil=Department of Chemistry, Birla Institute of Technology kn-affil= affil-num=20 en-affil=Department of Chemistry, Birla Institute of Technology kn-affil= affil-num=21 en-affil=Genomics Core Facility, Wilmot Cancer Center, University of Rochester Medical Center kn-affil= affil-num=22 en-affil=Department of Pharmacology and Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Penn State University kn-affil= affil-num=23 en-affil=Department of Radiation Oncology, University of Rochester Medical Center kn-affil= affil-num=24 en-affil=Department of Pathology and Laboratory Medicine, University of Rochester Medical Center kn-affil= affil-num=25 en-affil=Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center kn-affil= affil-num=26 en-affil=Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center kn-affil= affil-num=27 en-affil=Center for Breast Health and Gynecologic Oncology, Mercy Medical Center kn-affil= affil-num=28 en-affil=Rutgers, The State University of New Jersey kn-affil= affil-num=29 en-affil=CytoMechanobiology Laboratory, Department of Pharmacology, Penn State College of Medicine, Pennsylvania State University kn-affil= affil-num=30 en-affil=Department of Pharmacology and Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Penn State University kn-affil= affil-num=31 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=32 en-affil=School of Mathematical and Natural Sciences, Arizona State University, Health Futures Center kn-affil= affil-num=33 en-affil=Departments of Pediatrics, Neurology, and Neuroscience, University of Rochester Medical Center kn-affil= affil-num=34 en-affil=Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center kn-affil= affil-num=35 en-affil=Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center kn-affil= affil-num=36 en-affil=Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=5 article-no= start-page=e0285273 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230519 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Randomized phase II study of daily versus alternate-day administrations of S-1 for the elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm)-IIIA of non-small cell lung cancer: Setouchi Lung Cancer Group Study 1201 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
It is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC.

Methods
Elderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more.

Results
We enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11).

Conclusion
Although several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC. en-copyright= kn-copyright= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi 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=GembaKenichi en-aut-sei=Gemba en-aut-mei=Kenichi 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=TerazakiYasuhiro en-aut-sei=Terazaki 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=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 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=21 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=22 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=23 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=24 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=25 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=26 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Surgery, Division of Thoracic Surgery, Kindai University Faculty of Medicine 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 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 S0urgery, Saga-Ken Medical Centre 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 Chest 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=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=21 en-affil=Department of Thoracic Oncology, Kansai Medical University Hospital kn-affil= affil-num=22 en-affil=Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine kn-affil= affil-num=23 en-affil=Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute kn-affil= affil-num=24 en-affil=Tokai Central Hospital kn-affil= affil-num=25 en-affil=Department of Thoracic Surgery, Kyoto University Hospital kn-affil= affil-num=26 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=8 article-no= start-page=7412 end-page=7424 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230804 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mean Heart Dose Prediction Using Parameters of Single-Slice Computed Tomography and Body Mass Index: Machine Learning Approach for Radiotherapy of Left-Sided Breast Cancer of Asian Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Deep inspiration breath-hold (DIBH) is an excellent technique to reduce the incidental radiation received by the heart during radiotherapy in patients with breast cancer. However, DIBH is costly and time-consuming for patients and radiotherapy staff. In Asian countries, the use of DIBH is restricted due to the limited number of patients with a high mean heart dose (MHD) and the shortage of radiotherapy personnel and equipment compared to that in the USA. This study aimed to develop, evaluate, and compare the performance of ten machine learning algorithms for predicting MHD using a patient's body mass index and single-slice CT parameters to identify patients who may not require DIBH. Machine learning models were built and tested using a dataset containing 207 patients with left-sided breast cancer who were treated with field-in-field radiotherapy with free breathing. The average MHD was 251 cGy. Stratified repeated four-fold cross-validation was used to build models using 165 training data. The models were compared internally using their average performance metrics: F2 score, AUC, recall, accuracy, Cohen's kappa, and Matthews correlation coefficient. The final performance evaluation for each model was further externally analyzed using 42 unseen test data. The performance of each model was evaluated as a binary classifier by setting the cut-off value of MHD & GE; 300 cGy. The deep neural network (DNN) achieved the highest F2 score (78.9%). Most models successfully classified all patients with high MHD as true positive. This study indicates that the ten models, especially the DNN, might have the potential to identify patients who may not require DIBH. en-copyright= kn-copyright= 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=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=KamizakiRyo en-aut-sei=Kamizaki en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=IshizakaHinata en-aut-sei=Ishizaka en-aut-mei=Hinata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=SugimotoKohei en-aut-sei=Sugimoto en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=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=BarhamMajd en-aut-sei=Barham en-aut-mei=Majd 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=ShimizuYudai en-aut-sei=Shimizu en-aut-mei=Yudai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=14 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Radiological Technology, Graduate School of Health 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=Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, 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=Department of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An-Najah National 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 Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=radiotherapy kn-keyword=radiotherapy en-keyword=heart dose kn-keyword=heart dose en-keyword=machine learning kn-keyword=machine learning en-keyword=deep neural network kn-keyword=deep neural network en-keyword=deep inspiration breath-hold technique kn-keyword=deep inspiration breath-hold technique en-keyword=computed tomography kn-keyword=computed tomography END start-ver=1.4 cd-journal=joma no-vol=37 cd-vols= no-issue=11 article-no= start-page=e15077 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230717 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Percentage of low attenuation area on computed tomography detects chronic lung allograft dysfunction, especially bronchiolitis obliterans syndrome, after bilateral lung transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: The percentage of low attenuation area (%LAA) on computed tomography (CT) is useful for evaluating lung emphysema, and higher %LAA was observed in patients with chronic lung allograft dysfunction (CLAD). This study investigated the relationship between the %LAA and the development of CLAD after bilateral lung transplantation (LT).
Methods: We conducted a single-center retrospective study of 75 recipients who underwent bilateral LT; the recipients were divided into a CLAD group (n = 30) and a non-CLAD group (n = 45). The %LAA was calculated using CT and compared between the two groups from 4 years before to 4 years after the diagnosis of CLAD. The relationships between the %LAA and the percent baseline values of the pulmonary function test parameters were also calculated.
Results: The %LAA was significantly higher in the CLAD group than in the non-CLAD group from 2 years before to 2 years after the diagnosis of CLAD (P < .05). In particular, patients with bronchiolitis obliterans syndrome (BOS) exhibited significant differences even from 4 years before to 4 years after diagnosis (P < .05). Significant negative correlations between the %LAA and the percent baseline values of the forced expiratory volume in 1 s (r = −.36, P = .0031), the forced vital capacity (r = −.27, P = .027), and the total lung capacity (r = −.40, P < .001) were seen at the time of CLAD diagnosis.
Conclusion: The %LAA on CT was associated with the development of CLAD and appears to have the potential to predict CLAD, especially BOS, after bilateral LT. en-copyright= kn-copyright= en-aut-name=KuboYujiro en-aut-sei=Kubo en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=ShiotaniToshio en-aut-sei=Shiotani en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 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=8 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=9 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=10 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=11 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=12 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= en-keyword=bronchiolitis obliterans syndrome kn-keyword=bronchiolitis obliterans syndrome en-keyword=chronic lung allograft dysfunction kn-keyword=chronic lung allograft dysfunction en-keyword=computed tomography kn-keyword=computed tomography en-keyword=lung transplantation kn-keyword=lung transplantation en-keyword=restrictive allograft syndrome kn-keyword=restrictive allograft syndrome END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=9 article-no= start-page=5182 end-page=5194 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230627 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-term management and outcome of lung transplantation in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=The long-term survival after lung transplantation (LT) is favorable in Japan. However, longterm survivors after LT are subject to late complications, including chronic lung allograft dysfunction (CLAD), malignancy, infection, and chronic kidney disease (CKD) because of the need for lifelong immunosuppression. The rates of single cadaveric LT (CLT) and living-donor lobar LT (LDLLT) are higher than that of bilateral CLT in Japan. Here, we will describe the management of late complications and long-term outcome after LT in Japan. Attention should be paid to not only the phenotype of CLAD but also the difference in CLAD after CLT and after LDLLT as well as the timing of lung re-transplantation for advanced CLAD, especially after single CLT. Since post-transplant lymphoproliferative disorder is the most common malignancy after LT, infection monitoring for infection-related malignancies and appropriate screening are keys to the early diagnosis and treatment of malignancy after LT. The long-term management of infection after LT is also important, especially with regard to community-acquired pathogens, Aspergillus, and cytomegalovirus. When providing long-term care after LT, physicians should be aware of CKD and the timing of renal replacement therapy in cases with severe CKD. The widespread use of computed tomography and dialysis in Japan are beneficial for long-term survivors of LT. The similar survival outcomes of single CLT and LDLLT, compared with bilateral CLT, might contribute to improved long-term survival in Japan. Pulmonologists are encouraged to become further involved in long-term management after LT in Japan. en-copyright= kn-copyright= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 ORCID= en-aut-name=IshiharaMegumi en-aut-sei=Ishihara en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= en-keyword=Lung transplantation kn-keyword=Lung transplantation en-keyword=chronic lung allograft dysfunction kn-keyword=chronic lung allograft dysfunction en-keyword=infection kn-keyword=infection en-keyword=malignan kn-keyword=malignan en-keyword=cychronic kidney kn-keyword=cychronic kidney en-keyword=disease kn-keyword=disease END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230705 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bilateral Lacrimal Gland Mantle Cell Lymphoma in 11-Year Follow-Up: Case Report and Review of 48 Cases With Ocular Adnexal Presentation in the Literature en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 63-year-old woman, with 11-year history of breast cancer, showed bilateral lacrimal gland enlargement on magnetic resonance imaging. Gallium-67 scintigraphy, as the standard at that time in 2004, demonstrated abnormally high uptake only in bilateral lacrimal glands. The lacrimal glands were extirpated and the pathological diagnosis was mantle cell lymphoma (MCL). She underwent bilateral orbital radiation, based on no uptake of gallium-67 in other sites of the body. In a month, bone marrow biopsy revealed the infiltration with MCL, positive for cyclin D1. She showed hepatic lymphadenopathy and splenomegaly, and so received 2 cycles of alternating Hyper-CVAD therapy and high-dose methotrexate with cytarabine, combined with rituximab, in 2 months, leading to complete remission. She underwent autologous peripheral blood stem cell transplantation and was well until the age of 68 years when she showed a recurrent intratracheal submucosal lesion of lymphoma and underwent one course of reduced-dose CHOP combined with rituximab. Next year, the left rib resection revealed the metastasis of breast adenocarcinoma, leading to daily oral letrozole. Further 2 years later, computed tomographic scan demonstrated multiple submucosal nodular lesions in the trachea and bronchi, together with cervical and supraclavicular lymphadenopathy, and intratracheal lesion biopsy and bone marrow biopsy proved the involvement with MCL. She underwent 2 courses of bendamustine and rituximab, resulting in complete remission but died of metastatic breast cancer at the age of 74 years. Clinical features in 48 previous cases with ocular adnexal MCL in the literature were summarized in this study. 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=OkadaKazuya en-aut-sei=Okada en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NotoharaKenji en-aut-sei=Notohara en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 ORCID= affil-num=1 en-affil=Okayama University kn-affil= affil-num=2 en-affil=Okayama University kn-affil= affil-num=3 en-affil=Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Kurashiki Central Hospital kn-affil= affil-num=5 en-affil=Okayama University Hospital kn-affil= affil-num=6 en-affil=Okayama University Hospital kn-affil= en-keyword=mantle cell lymphoma kn-keyword=mantle cell lymphoma en-keyword=lacrimal gland kn-keyword=lacrimal gland en-keyword=autologous peripheral blood stem cell transplantation kn-keyword=autologous peripheral blood stem cell transplantation en-keyword=breast cancer kn-keyword=breast cancer en-keyword=tracheal and bronchial infiltration kn-keyword=tracheal and bronchial infiltration END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=5 article-no= start-page=101485 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230611 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Significance of the comprehensive geriatric assessment in the administration of chemotherapy to older adults with cancer: Recommendations by the Japanese Geriatric Oncology Guideline Committee en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: The number of older patients with cancer is expected to continue to increase owing to the aging population. Recently, the usefulness of geriatric assessment (GA) conducted by multiple staff members from different medical backgrounds has been reported; however, a consensus on the effectiveness of GA has not yet been achieved.
Materials and Methods: We, as the Japanese Geriatric Oncology Guideline Committee for elderly patients with cancer, conducted a literature search of randomized controlled trials published before August 2021 that used GA or comprehensive GA (CGA) as an intervention for patients with cancer undergoing chemotherapy. As the key outcomes for answering the clinical question, we focused on survival benefit, adverse events, and quality of life (QOL). After a systematic review of these studies, the expert panel member developed recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.
Results: For older patients with cancer, GA or CGA is suggested during or before chemotherapy (weakly recommended). Chemotherapy-induced adverse events were significantly reduced by GA/CGA interventions without any adverse effects on survival. Health-related QOL tended to improve with the GA/CGA interventions.
Discussion: Although, in our opinion, GA/CGA does require time and resources, it poses no harm patients. Therefore, we suggest expanding the human resources and educating skills of medical providers for clinical implementation of GA/CGA. 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=InoueDaisuke en-aut-sei=Inoue en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugimotoKen en-aut-sei=Sugimoto en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaChie en-aut-sei=Tanaka en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurofushiKeiko en-aut-sei=Murofushi en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkuyamaToru en-aut-sei=Okuyama en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanukiShigeaki en-aut-sei=Watanuki en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ImamuraChiyo K. en-aut-sei=Imamura en-aut-mei=Chiyo K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SakaiDaisuke en-aut-sei=Sakai en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SakuraiNaomi en-aut-sei=Sakurai en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WatanabeKiyotaka en-aut-sei=Watanabe en-aut-mei=Kiyotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TamuraKazuo en-aut-sei=Tamura en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SaekiToshiaki en-aut-sei=Saeki en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IshiguroHiroshi en-aut-sei=Ishiguro en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, University of Fukui kn-affil= affil-num=3 en-affil=Department of General Geriatric Medicine, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Division of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=6 en-affil=Department of Psychiatry / Palliative Care Center, Nagoya City University West Medical Center kn-affil= affil-num=7 en-affil=National Center for Global Health and Medicine, National College of Nursing kn-affil= affil-num=8 en-affil=Advanced Cancer Translational Research Institute, Showa University kn-affil= affil-num=9 en-affil=Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Cancer Solutions Co.,Ltd kn-affil= affil-num=11 en-affil=Division of Medical Oncology, Department of Medicine, School of Medicine, Teikyo University kn-affil= affil-num=12 en-affil=NPO Clinical Hematology/Oncology Treatment Study Group kn-affil= affil-num=13 en-affil=Breast Oncology Service, Saitama Medical University International Medical Center kn-affil= affil-num=14 en-affil=Breast Oncology Service, Saitama Medical University International Medical Center kn-affil= en-keyword=Comprehensive geriatric assessment kn-keyword=Comprehensive geriatric assessment en-keyword=Guideline kn-keyword=Guideline en-keyword=Systematic review kn-keyword=Systematic review END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=20628 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221130 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Early-stage antibody kinetics after the third dose of BNT162b2 mRNA COVID-19 vaccination measured by a point-of-care fingertip whole blood testing en-subtitle= kn-subtitle= en-abstract= kn-abstract=Amid the Coronavirus Disease 2019 pandemic, we aimed to demonstrate the accuracy of the fingertip whole blood sampling test (FWT) in measuring the antibody titer and uncovering its dynamics shortly after booster vaccination. Mokobio SARS-CoV-2 IgM & IgG Quantum Dot immunoassay (Mokobio Biotechnology R&D Center Inc., MD, USA) was used as a point-of-care FWT in 226 health care workers (HCWs) who had received two doses of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) at least 8 months prior. Each participant tested their antibody titers before and after the third-dose booster up to 14-days. The effect of the booster was observed as early as the fourth day after vaccination, which exceeded the detection limit (>30,000 U/mL) by 2.3% on the fifth day, 12.2% on the sixth day, and 22.5% after the seventh day. Significant positive correlations were observed between the pre- and post-vaccination (the seventh and eighth days) antibody titers (correlation coefficient, 0.405; p<0.001). FWT is useful for examining antibody titers as a point-of-care test. Rapid response of antibody titer started as early as the fourth day post-vaccination, while the presence of weak responders to BNT162b2 vaccine was indicated. 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=NakanoYasuhiro en-aut-sei=Nakano en-aut-mei=Yasuhiro 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=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=HasegawaToru en-aut-sei=Hasegawa en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakuradaYasue en-aut-sei=Sakurada en-aut-mei=Yasue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=YamamotoKoichiro en-aut-sei=Yamamoto en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OgawaHiroko en-aut-sei=Ogawa en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AgetaKouhei en-aut-sei=Ageta en-aut-mei=Kouhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=MatsuoRumi en-aut-sei=Matsuo en-aut-mei=Rumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KadowakiTomoka en-aut-sei=Kadowaki en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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=16 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=17 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=18 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=19 ORCID= en-aut-name=YokokuraYoshinori en-aut-sei=Yokokura en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 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=21 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=22 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=Clinical Laboratory, 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 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= affil-num=8 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=16 en-affil=Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University kn-affil= affil-num=17 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Departments of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Yokokura Hospital kn-affil= affil-num=21 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=22 en-affil=Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=8912 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of genetic loci associated with renal dysfunction after lung transplantation using an ethnic-specific single-nucleotide polymorphism array en-subtitle= kn-subtitle= en-abstract= kn-abstract=Renal dysfunction is a long-term complication associated with an increased mortality after lung transplantation (LT). We investigated the association of single-nucleotide polymorphisms (SNPs) with the development of renal dysfunction after LT using a Japanese-specific SNP array. First, eligible samples of 34 LT recipients were genotyped using the SNP array and divided into two groups, according to the presence of homozygous and heterozygous combinations of mutant alleles of the 162 renal-related SNPs. To identify candidate SNPs, the renal function tests were compared between the two groups for each SNP. Next, we investigated the association between the candidate SNPs and the time course of changes of the estimated glomerular filtration rate (eGFR) in the 99 recipients until 10 years after the LT. Delta eGFR was defined as the difference between the postoperative and preoperative eGFR values. Eight SNPs were identified as the candidate SNPs in the 34 recipients. Validation analysis of these 8 candidate SNPs in all the 99 recipients showed that three SNPs, namely, rs10277115, rs4690095, and rs792064, were associated with significant changes of the Delta eGFR. Pre-transplant identification of high-risk patients for the development of renal dysfunction after LT based on the presence of these SNPs might contribute to providing personalized medicine. en-copyright= kn-copyright= en-aut-name=TomiokaYasuaki en-aut-sei=Tomioka en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=YamamotoHaruchika en-aut-sei=Yamamoto en-aut-mei=Haruchika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=ShiotaniToshio en-aut-sei=Shiotani en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 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=10 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=11 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=12 ORCID= en-aut-name=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital 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 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 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=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 Thoracic Surgery and Breast and Endocrinological Surgery, 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= affil-num=14 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=20 cd-vols= no-issue=7 article-no= start-page=714 end-page=738 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230519 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The chemokine monocyte chemoattractant protein-1/CCL2 is a promoter of breast cancer metastasis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Breast cancer is the most prevalent cancer worldwide, and metastasis is the leading cause of death in cancer patients. Human monocyte chemoattractant protein-1 (MCP-1/CCL2) was isolated from the culture supernatants of not only mitogen-activated peripheral blood mononuclear leukocytes but also malignant glioma cells based on its in vitro chemotactic activity toward human monocytes. MCP-1 was subsequently found to be identical to a previously described tumor cell-derived chemotactic factor thought to be responsible for the accumulation of tumor-associated macrophages (TAMs), and it became a candidate target of clinical intervention; however, the role of TAMs in cancer development was still controversial at the time of the discovery of MCP-1. The in vivo role of MCP-1 in cancer progression was first evaluated by examining human cancer tissues, including breast cancers. Positive correlations between the level of MCP-1 production in tumors and the degree of TAM infiltration and cancer progression were established. The contribution of MCP-1 to the growth of primary tumors and metastasis to the lung, bone, and brain was examined in mouse breast cancer models. The results of these studies strongly suggested that MCP-1 is a promoter of breast cancer metastasis to the lung and brain but not bone. Potential mechanisms of MCP-1 production in the breast cancer microenvironment have also been reported. In the present manuscript, we review studies in which the role of MCP-1 in breast cancer development and progression and the mechanisms of its production were examined and attempt to draw a consensus and discuss the potential use of MCP-1 as a biomarker for diagnosis. en-copyright= kn-copyright= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo 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=WangYuze en-aut-sei=Wang en-aut-mei=Yuze 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=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= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=chemokines kn-keyword=chemokines en-keyword=chemokine receptors kn-keyword=chemokine receptors en-keyword=metastasis kn-keyword=metastasis en-keyword=macrophages kn-keyword=macrophages END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=3 article-no= start-page=331 end-page=334 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Endobronchial Metastasis with Bloody Sputum 20 Years after Complete Resection of type A Non-Invasive Thymoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Masaoka stage I type A thymomas rarely recur. We report the case of an 82-year-old man who developed endobronchial metastasis after thymothymectomy for Masaoka stage I type A thymoma. Twenty years after surgery, the patient developed bloody sputum, and chest computed tomography revealed a neoplasm obstructing the right upper lobe bronchus of the lung with enlarged mediastinal lymph nodes. He underwent right upper lobectomy and mediastinal lymph node dissection. Although preoperative pathological diagnosis was squamous cell carcinoma of the lung, postoperative histopathology revealed endobronchial metastasis of the thymoma. Nine years later, at age 89, the patient is alive and well. en-copyright= kn-copyright= en-aut-name=WatanabeMototsugu en-aut-sei=Watanabe en-aut-mei=Mototsugu 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=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=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= 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= en-keyword=endobronchial metastasis kn-keyword=endobronchial metastasis en-keyword=type A thymoma kn-keyword=type A thymoma en-keyword=bloody sputum kn-keyword=bloody sputum END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=1 article-no= start-page=596 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=NFYA promotes malignant behavior of triple-negative breast cancer in mice through the regulation of lipid metabolism en-subtitle= kn-subtitle= en-abstract= kn-abstract=Two splicing variants exist in NFYA that exhibit high expression in many human tumour types. The balance in their expression correlates with prognosis in breast cancer, but functional differences remain unclear. Here, we demonstrate that NFYAv1, a long-form variant, upregulates the transcription of essential lipogenic enzymes ACACA and FASN to enhance the malignant behavior of triple-negative breast cancer (TNBC). Loss of the NFYAv1-lipogenesis axis strongly suppresses malignant behavior in vitro and in vivo, indicating that the NFYAv1-lipogenesis axis is essential for TNBC malignant behavior and that the axis might be a potential therapeutic target for TNBC. Furthermore, mice deficient in lipogenic enzymes, such as Acly, Acaca, and Fasn, exhibit embryonic lethality; however, Nfyav1-deficient mice exhibited no apparent developmental abnormalities. Our results indicate that the NFYAv1-lipogenesis axis has tumour-promoting effects and that NFYAv1 may be a safe therapeutic target for TNBC. en-copyright= kn-copyright= en-aut-name=OkadaNobuhiro en-aut-sei=Okada en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UekiChihiro en-aut-sei=Ueki en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShimazakiMasahiro en-aut-sei=Shimazaki en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsujimotoGoki en-aut-sei=Tsujimoto en-aut-mei=Goki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KohnoSusumu en-aut-sei=Kohno en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MuranakaHayato en-aut-sei=Muranaka en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshikawaKiyotsugu en-aut-sei=Yoshikawa en-aut-mei=Kiyotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakahashiChiaki en-aut-sei=Takahashi en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Laboratory for Malignancy Control Research, Medical Innovation Center, Kyoto University kn-affil= affil-num=4 en-affil=Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Division of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa University kn-affil= affil-num=6 en-affil=Division of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa University kn-affil= affil-num=7 en-affil=Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts kn-affil= affil-num=8 en-affil=Division of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=3 article-no= start-page=281 end-page=290 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Immediate Breast Reconstruction on Survival of Breast Cancer Patients: A Single-Center Observational Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although immediate breast reconstruction following mastectomy has become increasingly common, its oncological safety has been debated. We enrolled patients with breast cancer who underwent surgery at Okayama University Hospital between 2007 and 2013. The primary outcome was relapse-free survival (RFS). Secondary outcomes were overall survival and the duration from the surgery to the initiation of adjuvant chemotherapy. We divided into immediate breast reconstruction, mastectomy alone, and breast conservative surgery groups. Outcomes were compared using Cox’s regression analysis. A total of 614 patients were included (reconstruction: 125, mastectomy: 128, breast conservative surgery: 361). The median follow-up duration was 79.0±31.9 months. The immediate-reconstruction patients were younger, had more lymph node metastases, and more often received postoperative chemotherapy. The RFS was better after the breast conservative surgery compared to after reconstruction (hazard ratio 0.33, 95% confidence interval: 0.144-0.763). The proportion of local recurrence was highest in the reconstruction group. No patients in the reconstruction group underwent postoperative radiation therapy. However, reconstruction did not affect overall survival or the time to the initiation of adjuvant chemotherapy. Surgeons should explain the risks of breast reconstruction to their patients preoperatively. Careful long-term follow-up is required after such procedures. en-copyright= kn-copyright= en-aut-name=MukaiYuko en-aut-sei=Mukai en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 ORCID= en-aut-name=KitaguchiYohei en-aut-sei=Kitaguchi en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SaigaMiho en-aut-sei=Saiga en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeSatoko en-aut-sei=Watanabe en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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=10 ORCID= affil-num=1 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=3 en-affil=Department of Breast Surgery, Hiroshima Citizens Hospital 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 Plastic and Reconstructive Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Plastic and Reconstructive 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 Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=immediate breast reconstruction kn-keyword=immediate breast reconstruction en-keyword=oncological safety kn-keyword=oncological safety en-keyword=local recurrence kn-keyword=local recurrence en-keyword=postoperative radiation therapy kn-keyword=postoperative radiation therapy en-keyword=time to initiation of adjuvant chemotherapy kn-keyword=time to initiation of adjuvant chemotherapy END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=4 article-no= start-page=e14903 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Diagnostic value of circulating microRNA-21 in chronic lung allograft dysfunction after bilateral cadaveric and living-donor lobar lung transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: MicroRNAs (miRNAs) involved in the pathogenesis of pulmonary fibrosis have been shown to be associated with the development of chronic lung allograft dysfunction (CLAD) after lung transplantation (LT). We investigated the role of circulating miRNAs in the diagnosis of CLAD after bilateral LT, including cadaveric LT (CLT) and living-donor lobar LT (LDLLT).
Methods: The subjects of this retrospective study were 37 recipients of bilateral CLT (n = 23) and LDLLT (n = 14), and they were divided into a non-CLAD group (n = 24) and a CLAD group (n = 13). The plasma miRNA levels of the two groups were compared, and correlations between their miRNAs levels and percent baseline forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and total lung capacity (TLC) values were calculated from one year before to one year after the diagnosis of CLAD.
Results: The plasma levels of both miR-21 and miR-155 at the time of the diagnosis of CLAD were significantly higher in the CLAD group than in the non-CLAD group (miR-21, P = 0.0013; miR155, P = 0.042). The miR-21 levels were significantly correlated with the percent baseline FEV1, FVC, and TLC value of one year before and at the time of diagnosis of CLAD (P < 0.05). A receiver operating characteristic curve analysis of the performance of miR-21 levels in the diagnosis of CLAD yielded an area under the curve of 0.89.
Conclusion: Circulating miR-21 appears to be of potential value in diagnosing CLAD after bilateral LT. en-copyright= kn-copyright= en-aut-name=ShiotaniToshio en-aut-sei=Shiotani en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TomiokaYasuaki en-aut-sei=Tomioka en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoHaruchika en-aut-sei=Yamamoto en-aut-mei=Haruchika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=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=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=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= affil-num=1 en-affil=Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=2 en-affil=Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=3 en-affil=Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=Biomarker kn-keyword=Biomarker en-keyword=Chronic lung allograft dysfunction kn-keyword=Chronic lung allograft dysfunction en-keyword=Lung transplantation kn-keyword=Lung transplantation en-keyword=Living -donor lobar lung transplantation kn-keyword=Living -donor lobar lung transplantation en-keyword=Micro-RNA kn-keyword=Micro-RNA 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=2023 dt-pub=20230324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=乳がんコホートより免疫関連遺伝子シグネチャーの化学療法の効果と予後予測能の検討 kn-title=Predictive value of immune genomic signatures from breast cancer cohorts containing data for both response to neoadjuvant chemotherapy and prognosis after surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ZHUYIDAN en-aut-sei=ZHU en-aut-mei=YIDAN kn-aut-name=朱一丹 kn-aut-sei=朱 kn-aut-mei=一丹 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 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=2023 dt-pub=20230324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=低転移性サブクローン由来のエキソソームwnt7aは、murine 4t1乳がんの高度転移性サブクローンの肺転移を促進する kn-title=Exosomal Wnt7a from a low metastatic subclone promotes lung metastasis of a highly metastatic subclone in the murine 4t1 breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=LICHUNNING en-aut-sei=LI en-aut-mei=CHUNNING kn-aut-name=李春寧 kn-aut-sei=李 kn-aut-mei=春寧 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=6 article-no= start-page=e01160 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230523 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pulmonary alveolar proteinosis after lung transplantation: Two case reports and literature review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pulmonary alveolar proteinosis (PAP) affecting transplanted lungs is not well recognized. Herein, we report two cases of PAP after lung transplantation (LTx). The first case was a 4-year-old boy with hereditary pulmonary fibrosis who underwent bilateral LTx and presented with respiratory distress on postoperative day (POD) 23. He was initially treated for acute rejection, died due to infection on POD 248, and was diagnosed with PAP at autopsy. The second case involved a 52-year-old man with idiopathic pulmonary fibrosis who underwent bilateral LTx. On POD 99, chest computed tomography revealed ground-glass opacities. Bronchoalveolar lavage and transbronchial biopsy led to a diagnosis of PAP. Follow-up with immunosuppression tapering resulted in clinical and radiological improvement. PAP after lung transplantation mimics common acute rejection; however, is potentially transient or resolved with tapering immunosuppression, as observed in the second case. Transplant physicians should be aware of this rare complication to avoid misconducting immunosuppressive management. 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=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 ORCID= en-aut-name=ShimizuDai en-aut-sei=Shimizu en-aut-mei=Dai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=HattoriNoboru en-aut-sei=Hattori en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Molecular and Internal Medicine, Hiroshima University, Graduate School of Biomedical and Health Sciences kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= en-keyword=graft dysfunction kn-keyword=graft dysfunction en-keyword=immunosuppression kn-keyword=immunosuppression en-keyword=lung transplantation kn-keyword=lung transplantation en-keyword=pulmonary alveolar proteinosis kn-keyword=pulmonary alveolar proteinosis END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=2 article-no= start-page=e35440 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Seat Belt Injury Causing a Large Breast Hematoma: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Seat belts with shoulder restraints have decreased the frequency of life-threatening severe chest trauma caused by car accidents. However, the introduction of seat belt legislation has led to an increase in a specific pattern of blunt trauma known as seat belt syndrome, which includes rib, clavicle, spine, and sternum fractures, as well as rupture of hollow pelvic and abdominal viscera, mesenteric tears, and major vessel injuries. The shoulder restraint part of the three-point seat belt commonly rests near or over the female and male breast. A 54-year-old female presented to our emergency department complaining of swelling and pain in her left breast immediately after a traffic accident. The patient had used a seat belt with a shoulder restraint. Bruising was noted along her chest where there had been seat belt contact. Her breast hematoma was most likely caused by breast tissue compression between her rib and the seat belt. Contrast-enhanced computed tomography demonstrated a sizable breast hematoma with active arterial contrast material extravasation, as well as multiple left rib fractures. The patient was conservatively treated with analgesic and anti-inflammatory drugs. Complete resolution was achieved, and her breast returned to its normal appearance. Although endovascular treatment and surgical hemostasis have been proposed for the treatment of breast injuries with active bleeding, conservative treatment such as compression hemostasis may be feasible. en-copyright= kn-copyright= en-aut-name=YamamotoShunki en-aut-sei=Yamamoto en-aut-mei=Shunki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KosakiYoshinori en-aut-sei=Kosaki en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UeharaTakenori en-aut-sei=Uehara en-aut-mei=Takenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=case report kn-keyword=case report en-keyword=breast hematoma kn-keyword=breast hematoma en-keyword=chest injury kn-keyword=chest injury en-keyword=seat belt injury kn-keyword=seat belt injury en-keyword=traffic injury kn-keyword=traffic injury END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=2 article-no= start-page=350 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220211 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association between Overall Survival and Activities of Daily Living in Patients with Spinal Bone Metastases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: This study aimed to investigate the association between overall survival (OS) and activities of daily living (ADL) in patients with skeletal-related events. In this study, 265 patients whose clinical parameters were available before radiotherapy were investigated. Methods: Age, sex, ADL, pain, the primary site, spinal level of bone metastases, spinal instability, treatment strategy, including chemotherapy or palliative treatment, and OS were investigated. ADL patients with a Barthel index of >= 90 were classified as the high ADL group, while those with a score < 90 were classified as the low ADL group. For OS, patients surviving >= 160 days were classified as the non-poor prognosis group, and those who survived <160 days were classified as the poor prognosis group. Results: Age, sex, ADL, pain, the primary site, and treatment strategy for OS were different between the two groups (p < 0.1). Logistic regression analysis revealed that ADL, the primary site, and treatment strategy were significant predictors of OS (p < 0.05). High ADL, breast cancer, and chemotherapy had a positive effect on OS. Conclusions: It is suggested that improvements may be obtained by performing rehabilitation interventions to maintain and improve ADL, by constructing a system for monitoring spinal bone metastases with images before ADL decreases, and by performing interventions such as changes in treatment methods such as RT or surgery at appropriate times. en-copyright= kn-copyright= en-aut-name=AkezakiYoshiteru en-aut-sei=Akezaki en-aut-mei=Yoshiteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KikuuchiMasato en-aut-sei=Kikuuchi en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SugiharaShinsuke en-aut-sei=Sugihara en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatayamaYoshimi en-aut-sei=Katayama en-aut-mei=Yoshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=HamadaMasanori en-aut-sei=Hamada en-aut-mei=Masanori 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=Division of Physical Therapy, Kochi Professional University of Rehabilitation kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= en-keyword=spinal bone metastases kn-keyword=spinal bone metastases en-keyword=radiotherapy kn-keyword=radiotherapy en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=activities of daily living kn-keyword=activities of daily living en-keyword=overall survival kn-keyword=overall survival END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=1142907 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lysyl oxidase-like 4 exerts an atypical role in breast cancer progression that is dependent on the enzymatic activity that targets the cell-surface annexin A2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: LOX family members are reported to play pivotal roles in cancer. Unlike their enzymatic activities in collagen cross-linking, their precise cancer functions are unclear. We revealed that LOXL4 is highly upregulated in breast cancer cells, and we thus sought to define an unidentified role of LOXL4 in breast cancer.
Methods: We established the MDA-MB-231 sublines MDA-MB-231-LOXL4 mutCA and -LOXL4 KO, which stably overexpress mutant LOXL4 that loses its catalytic activity and genetically ablates the intrinsic LOXL4 gene, respectively. In vitro and in vivo evaluations of these cells’ activities of cancer outgrowth were conducted by cell-based assays in cultures and an orthotopic xenograft model, respectively. The new target (s) of LOXL4 were explored by the MS/MS analytic approach.
Results: Our in vitro results revealed that both the overexpression of mutCA and the KO of LOXL4 in cells resulted in a marked reduction of cell growth and invasion. Interestingly, the lowered cellular activities observed in the engineered cells were also reflected in the mouse model. We identified a novel binding partner of LOXL4, i.e., annexin A2. LOXL4 catalyzes cell surface annexin A2 to achieve a cross-linked multimerization of annexin A2, which in turn prevents the internalization of integrin β-1, resulting in the locking of integrin β-1 on the cell surface. These events enhance the promotion of cancer cell outgrowth.
Conclusions: LOXL4 has a new role in breast cancer progression that occurs via an interaction with annexin A2 and integrin β-1 on the cell surface.
en-copyright= kn-copyright= 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=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=ChenYouyi en-aut-sei=Chen en-aut-mei=Youyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 ORCID= en-aut-name=YamamotoKen-Ich en-aut-sei=Yamamoto en-aut-mei=Ken-Ich kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 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=12 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=13 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=14 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=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=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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 General Surgery & Bio-Bank of General Surgery, TheFourth Affiliated Hospital of Harbin Medical University kn-affil= affil-num=5 en-affil=Department of Microbiology, Kitasato University School of Medicine 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 Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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=Faculty of Medicine, Udayana University kn-affil= affil-num=11 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=12 en-affil=Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology kn-affil= affil-num=13 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=14 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=15 en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University kn-affil= affil-num=16 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=17 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=integrin kn-keyword=integrin en-keyword=cancer microenvironment kn-keyword=cancer microenvironment END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=2 article-no= start-page=139 end-page=145 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prolonged Sedentary Bouts Are Critically Involved in All-Cause Mortality in Patients on Chronic Hemodialysis: A Prospective Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated the link between prolonged sedentary bouts and all-cause mortality in patients on chronic hemodialysis, using a prospective cohort. A total of 104 outpatients on chronic hemodialysis from 2013 to 2019, aged 71.4±11.4 years, were enrolled. Prolonged sedentary bouts (≥ 30 min and ≥60 min) (min and bouts) and relative prolonged sedentary bouts (≥ 30 min and ≥ 60 min) (%) on the patients’ non-hemodialysis days were measured by a tri-accelerometer, and we also analyzed the patients’ clinical parameters. The relationship between prolonged sedentary bouts and all-cause mortality was evaluated by a survival analysis and the Cox proportional hazard model. Thirty-five patients died during the follow-up period. A Kaplan-Meier analysis detected significant differences in the survival rate between two groups stratified by the median for all prolonged sedentary-bout parameters. After the adjustment for confounding factors, all of the prolonged sedentary-bout parameters were determinant factors for all-cause mortality. These results indicate that prolonged sedentary bouts on non-hemodialysis days were closely related to all-cause mortality in the patients on hemodialysis. en-copyright= kn-copyright= en-aut-name=NamioKeiichi en-aut-sei=Namio en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KondoTakashi en-aut-sei=Kondo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyatakeNobuyuki en-aut-sei=Miyatake en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HishiiShuhei en-aut-sei=Hishii en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiHiroyuki en-aut-sei=Nishi en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatayamaAkihiko en-aut-sei=Katayama en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UjikeKazuhiro en-aut-sei=Ujike en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SuzukiHiromi en-aut-sei=Suzuki en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KoumotoKiichi en-aut-sei=Koumoto en-aut-mei=Kiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=2 en-affil=Innoshima General Hospital kn-affil= affil-num=3 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=4 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=5 en-affil=Innoshima General Hospital kn-affil= affil-num=6 en-affil=Faculty of Social Studies, Shikokugakuin University kn-affil= affil-num=7 en-affil=Innoshima General Hospital kn-affil= affil-num=8 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=9 en-affil=Innoshima General Hospital kn-affil= en-keyword=sedentary bout kn-keyword=sedentary bout en-keyword=mortality kn-keyword=mortality en-keyword=hemodialysis kn-keyword=hemodialysis en-keyword=survival analysis kn-keyword=survival analysis END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=1142886 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230223 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=LOXL1 and LOXL4 are novel target genes of the Zn2+-bound form of ZEB1 and play a crucial role in the acceleration of invasive events in triple-negative breast cancer cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: EMT has been proposed to be a crucial early event in cancer metastasis. EMT is rigidly regulated by the action of several EMT-core transcription factors, particularly ZEB1. We previously revealed an unusual role of ZEB1 in the S100A8/A9-mediated metastasis in breast cancer cells that expressed ZEB1 at a significant level and showed that the ZEB1 was activated on the MCAM-downstream pathway upon S100A8/A9 binding. ZEB1 is well known to require Zn2+ for its activation based on the presence of several Zn-finger motifs in the transcription factor. However, how Zn2+-binding works on the pleiotropic role of ZEB1 through cancer progression has not been fully elucidated.
Methods: We established the engineered cells, MDA-MB-231 MutZEB1 (MDA-MutZEB1), that stably express MutZEB1 (Delta Zn). The cells were then evaluated in vitro for their invasion activities. Finally, an RNA-Seq analysis was performed to compare the gene alteration profiles of the established cells comprehensively.
Results: MDA-MutZEB1 showed a significant loss of the EMT, ultimately stalling the invasion. Inclusive analysis of the transcription changes after the expression of MutZEB1 (Delta Zn) in MDA-MB-231 cells revealed the significant downregulation of LOX family genes, which are known to play a critical role in cancer metastasis. We found that LOXL1 and LOXL4 remarkably enhanced cancer invasiveness among the LOX family genes with altered expression.
Conclusions: These findings indicate that ZEB1 potentiates Zn2+-mediated transcription of plural EMT-relevant factors, including LOXL1 and LOXL4, whose upregulation plays a critical role in the invasive dissemination of breast cancer cells. en-copyright= kn-copyright= en-aut-name=HirabayashiDaisuke en-aut-sei=Hirabayashi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=MaruyamaAkihiro en-aut-sei=Maruyama en-aut-mei=Akihiro 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=KinoshitaRie en-aut-sei=Kinoshita en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=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=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=JiangFan en-aut-sei=Jiang en-aut-mei=Fan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=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=YamauchiAkira en-aut-sei=Yamauchi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=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=InoueYusuke en-aut-sei=Inoue en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 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 General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University kn-affil= affil-num=7 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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=Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of Technology 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=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=15 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=16 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=17 en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University kn-affil= affil-num=18 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=epithelial-to-mesenchymal transition kn-keyword=epithelial-to-mesenchymal transition en-keyword=triple-negative breast cancer kn-keyword=triple-negative breast cancer en-keyword=zinc kn-keyword=zinc en-keyword=ZEB1 kn-keyword=ZEB1 en-keyword=metastasis kn-keyword=metastasis END start-ver=1.4 cd-journal=joma no-vol=85 cd-vols= no-issue=4 article-no= start-page=436 end-page=480 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Poor vaccine responsiveness towards third-dose mRNA vaccine of COVID-19 in Japanese older people en-subtitle= kn-subtitle= en-abstract= kn-abstract= 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=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=HabuTomohiro en-aut-sei=Habu en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AsadaMasaki en-aut-sei=Asada en-aut-mei=Masaki 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=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi 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= en-aut-name=NakayamaMasanori en-aut-sei=Nakayama en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University kn-affil= affil-num=3 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=4 en-affil=Departments of Medical Education, Kurashiki Central Hospital kn-affil= affil-num=5 en-affil=Department of Epidemiology, Dentistry and Pharmaceutical Sciences, Graduate 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 Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=1 article-no= start-page=37 end-page=43 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202302 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Efficacy of Inflammatory and Immune Markers for Predicting the Prognosis of Patients with Stage IV Breast Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Systemic therapy for stage IV breast cancer is usually an initial treatment and is based on findings regarding biomarkers (e.g., hormone receptors and human epidermal growth factor receptor-2 [HER2]). However, the response to therapy and outcomes sometime differ among patients with similar prognostic factors including grade, hormone receptor, HER2, and more. We conducted retrospective analyses to evaluate the correlations between the overall survival (OS) of 46 stage IV breast cancer patients and (i) the peripheral absolute lymphocyte count (ALC) and (ii) composite blood cell markers. The peripheral blood cell markers included the neutrophil- to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the systemic immune-inflammation index (SII), the systemic inflammation response index (SIRI), and the most recently introduced indicator, the pan-immune-inflammatory value (PIV). The SIRI and PIV showed prognostic impacts on the patients: those with a low SIRI or a low PIV showed significantly better OS than those with a high SIRI (5-year, 66.0% vs. 35.0%, p<0.05) or high PIV (5-year, 68.1% vs. 38.5%, p<0.05), respectively. This is the first report indicating the possible prognostic value of the PIV for OS in patients with stage IV breast cancer. Further studies with larger numbers of patients are necessary for further clarification. en-copyright= kn-copyright= en-aut-name=YamanouchiKosho en-aut-sei=Yamanouchi en-aut-mei=Kosho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaedaShigeto en-aut-sei=Maeda en-aut-mei=Shigeto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Surgery, National Hospital Organization, Nagasaki Medical Center kn-affil= affil-num=2 en-affil=Department of Surgery, National Hospital Organization, Nagasaki Medical Center kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=pan-immune-inflammatory value kn-keyword=pan-immune-inflammatory value en-keyword=prognosis kn-keyword=prognosis END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=1 article-no= start-page=11 end-page=19 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202302 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Safety and Efficacy of a Well-Fitting Brassiere after Breast Reconstruction: A Qualitative Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The importance of a well-fitted, comfortable brassiere to overall quality of life after breast reconstruction has not been evaluated. Our aim was to determine the impact of a semi-customized brassiere on patients’ health-related quality of life after breast reconstruction. The subjects were prospective patients with mastectomy who were to undergo immediate or delayed breast reconstruction at our hospital. After surgery, a professional bra fitter sized each patient for a semi-customized brassiere and provided follow-up consultations. A self-reported questionnaire on breast aesthetics, postoperative pain, and satisfaction was used to assess the primary outcomes. Data were prospectively collected at baseline (before surgery) and at 1, 3, 6, and 12 months after surgery and analyzed. Forty-six patients (50 breasts) were included in the analysis. Consistent wearing of the brassiere reduced pain (p<0.05), with good overall satisfaction (p<0.001). Aesthetic scores on breast shape and size were higher with than without the custom brassiere at 3 months (p=0.02) and 6 months (p=0.03) after surgery. Wearing the brassiere reduced anxiety at all time points of measurement. A well-fitting brassiere ensured safety and provided a high degree of satisfaction without anxiety for patients after breast reconstruction. en-copyright= kn-copyright= en-aut-name=WatanabeSatoko en-aut-sei=Watanabe en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaigaMiho en-aut-sei=Saiga en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotokiTakayuki en-aut-sei=Motoki en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 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=7 ORCID= affil-num=1 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of General Surgery, Okayama Saiseikai General Hospital 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 Plastic and Reconstructive Surgery, Okayama University Hospital kn-affil= en-keyword=breast reconstruction kn-keyword=breast reconstruction en-keyword=mastectomy kn-keyword=mastectomy en-keyword=brassiere kn-keyword=brassiere en-keyword=professional bra fitter kn-keyword=professional bra fitter END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=1 article-no= start-page=673 end-page=680 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characteristics of Postoperative Patients with Breast Cancer Aged 65 Years and Older en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: This study aimed to compare postoperative patients with breast cancer aged >= 65 years with those aged <65 years and clarify the characteristics of postoperative patients with breast cancer aged >= 65. Methods: In total, 376 patients in whom we were able to evaluate survey items one month after surgery were included in the study. Comorbidity, including diabetes mellitus and hypertension, shoulder range of motion (ROM), upper-limb function, and psychological problems, was evaluated. Results: Hypertension and diabetes mellitus were significantly higher in patients aged >= 65 years (the elderly group) than in those aged <65 years (the non-elderly group) (p < 0.05). Preoperative shoulder flexion ROM was significantly restricted in the elderly group compared with the non-elderly group (p < 0.05). Preoperative shoulder abduction ROM was significantly restricted in the elderly group compared with the non-elderly group (p < 0.05). At one month after surgery, upper-limb function was more impaired in the non-elderly group than in the elderly group (p < 0.05). In both groups, both ROM and upper-limb function were significantly impaired one month after surgery compared with before surgery (p < 0.05). Conclusions: Postoperative patients with breast cancer aged >= 65 years should be careful about risk management and intervention during rehabilitation. Preoperative evaluation of shoulder ROM should be performed because patients aged >= 65 years have limited ROM before surgery. en-copyright= kn-copyright= en-aut-name=AkezakiYoshiteru en-aut-sei=Akezaki en-aut-mei=Yoshiteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KikuuchiMasato en-aut-sei=Kikuuchi en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TominagaRitsuko en-aut-sei=Tominaga en-aut-mei=Ritsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurokawaHideaki en-aut-sei=Kurokawa en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkamotoMasaki en-aut-sei=Okamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=AogiKenjiro en-aut-sei=Aogi en-aut-mei=Kenjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhsumiShozo en-aut-sei=Ohsumi en-aut-mei=Shozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugiharaShinsuke en-aut-sei=Sugihara en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Physical Therapy, Kochi Professional University of Rehabilitation kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center, kn-affil= affil-num=6 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center, kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=9 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=10 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=elderly kn-keyword=elderly en-keyword=comorbidity kn-keyword=comorbidity en-keyword=upper-limb function kn-keyword=upper-limb function en-keyword=rehabilitation kn-keyword=rehabilitation END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=2 article-no= start-page=468 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Highly Metastatic Subpopulation of TNBC Cells Has Limited Iron Metabolism and Is a Target of Iron Chelators en-subtitle= kn-subtitle= en-abstract= kn-abstract=Simple Summary Excess iron is known to be a risk factor of carcinogenesis. Although iron chelators show anti-cancer effects, they have not been used successfully to treat cancer patients. Triple-negative breast cancer (TNBC) is a disease with poor prognosis without effective treatments. Thus, we aimed to evaluate the possibility of iron chelators as a therapy for TNBC. Deferasirox (DFX), an iron chelator, suppressed the growth of 4T1 murine TNBC cell line cells in vitro and in vivo lung metastatic model. We found that highly metastatic TNBC cells have limited iron metabolism and can be more effectively targeted by iron chelators. Excess iron is known to be a risk factor of carcinogenesis. Although iron chelators show anti-cancer effects, they have not been used successfully to treat cancer patients. Triple-negative breast cancer (TNBC) is a disease with poor prognosis without effective treatments. Thus, we aimed to evaluate a possibility of iron chelators as a therapy for TNBC. Deferasirox (DFX), an iron chelator, suppressed the growth of 4T1 murine TNBC cell line cells in vitro and in vivo. Lung metastasis was further significantly reduced, leading to the hypothesis that iron metabolism between metastatic and non-metastatic cells may be different. An analysis of existing database demonstrated that the expression of iron-uptake genes was significantly suppressed in TNBC cells that metastasized to lymph nodes or lungs compared to those in primary tumors. A highly metastatic clone of the murine 4T1 TNBC cells (4T1-HM) did not proliferate well under iron-rich or iron-depleted conditions by iron chelators compared to a low-metastatic clone (4T1-LM). Bulk RNA-seq analysis of RNA from 4T1-HM and 4T1-LM cells suggested that the PI3K-AKT pathway might be responsible for this difference. Indeed, DFX suppressed the proliferation via the AKT-mTOR pathway in 4T1-HM and the human MDA-MB-231 cells, a human mesenchymal-like TNBC cell line. DFX also suppressed the growth of 4T1-HM tumors in comparison to 4T1-LM tumors, and reduced lung metastases after surgical resection of primary 4T1 tumors. These results indicated, for the first time, that highly metastatic TNBC cells have limited iron metabolism, and they can be more effectively targeted by iron chelators. en-copyright= kn-copyright= en-aut-name=WangYuze en-aut-sei=Wang en-aut-mei=Yuze 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=HamadaYusuke en-aut-sei=Hamada en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 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=8 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, 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 Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=triple-negative breast cancer kn-keyword=triple-negative breast cancer en-keyword=iron metabolism kn-keyword=iron metabolism en-keyword=iron chelator kn-keyword=iron chelator en-keyword=phosphoinositide-3-kinase-protein kinase kn-keyword=phosphoinositide-3-kinase-protein kinase en-keyword=heterogeneity kn-keyword=heterogeneity en-keyword=metastasis kn-keyword=metastasis END start-ver=1.4 cd-journal=joma no-vol=2022 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221211 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Surgical site infections in thyroid and parathyroid surgery in Japan: An analysis of the Japan Nosocomial Infections Surveillance database from 2013 to 2020 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Surgical site infections (SSIs) after thyroid surgery are rare complications, with incidence rates of 0.3%-1.6%. Using a Japanese database, we conducted exploratory analyses on the incidence of SSIs, investigated the incidence of SSIs by the National Nosocomial Infections Surveillance risk index, and identified the causative bacteria of SSIs. SSIs occurred in 50 (0.7%) of 7388 thyroid surgery cases. Risk index-0 patients had the lowest incidence rate of SSIs (0.41%). The incidence of SSIs in risk index-1 patients was 3.05 times the incidence of SSIs in risk index-0 patients. The rate of SSI occurrence for risk index-2 patients was 4.22 times the rate of SSI occurrence for risk index-0 patients. Thirty-one bacterial species were identified as the cause of SSIs in thyroid surgery cases, of which 12 (38.7%) SSIs were caused by Staphylococcus aureus and Staphylococcus epidermidis. Of the nine SSIs caused by Staphylococcus aureus, 55.6% (five cases) were attributed to methicillin-resistant Staphylococcus aureus. Therefore, routine prophylactic antibiotic administration should be avoided, while the target for administration should be narrowed, according to the SSI risk. Administration of prophylactic antibiotics, such as 2 g piperacillin or 1 g cefazolin, is considered appropriate. en-copyright= kn-copyright= en-aut-name=IwataniTsuguo en-aut-sei=Iwatani en-aut-mei=Tsuguo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaitoShinya en-aut-sei=Saito en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=parathyroid surgery kn-keyword=parathyroid surgery en-keyword=prophylactic antibiotic kn-keyword=prophylactic antibiotic en-keyword=risk factor kn-keyword=risk factor en-keyword=surgical site infection kn-keyword=surgical site infection en-keyword=thyroid surgery kn-keyword=thyroid surgery END start-ver=1.4 cd-journal=joma no-vol=67 cd-vols= no-issue=6 article-no= start-page=654 end-page=665 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neuropeptide Y Antagonizes Development of Pulmonary Fibrosis through IL-1β Inhibition en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neuropeptide Y (NPY), a 36 amino acid residue polypeptide distributed throughout the nervous system, acts on various immune cells in many organs, including the respiratory system. However, little is known about its role in the pathogenesis of pulmonary fibrosis. This study was performed to determine the effects of NPY on pulmonary fibrosis. NPY-deficient and wild-type mice were intratracheally administered bleomycin. Inflammatory cells, cytokine concentrations, and morphological morphometry of the lungs were analyzed. Serum NPY concentrations were also measured in patients with idiopathic pulmonary fibrosis and healthy control subjects. NPY-deficient mice exhibited significantly enhanced pulmonary fibrosis and higher IL-1 beta concentrations in the lungs compared with wild-type mice. Exogenous NPY treatment suppressed the development of bleomycin-induced lung fibrosis and decreased IL-1 beta concentrations in the lungs. Moreover, IL-1 beta neutralization in NPY-deficient mice attenuated the fibrotic changes. NPY decreased IL-1 beta release, and Y1 receptor antagonists inhibited IL-1 beta release and induced epithelial-mesenchymal transition in human alveolar epithelial cells. Patients with idiopathic pulmonary fibrosis had lower NPY and greater IL-1 beta concentrations in the serums compared with healthy control subjects. NPY expression was mainly observed around bronchial epithelial cells in human idiopathic pulmonary fibrosis lungs. These data suggest that NPY plays a protective role against pulmonary fibrosis by suppressing IL-1 beta release, and manipulating the NPY-Y1 receptor axis could be a potential therapeutic strategy for delaying disease progression. 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=TaniguchiAkihiko en-aut-sei=Taniguchi en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SenooSatoru en-aut-sei=Senoo en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=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=EgusaYuria en-aut-sei=Egusa en-aut-mei=Yuria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GuoLili en-aut-sei=Guo en-aut-mei=Lili kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OdaNaohiro en-aut-sei=Oda en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ArakiKota en-aut-sei=Araki en-aut-mei=Kota 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= 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=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=14 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=7 en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=idiopathic pulmonary fibrosis kn-keyword=idiopathic pulmonary fibrosis en-keyword=NPY kn-keyword=NPY en-keyword=IL-1 beta; bleomycin kn-keyword=IL-1 beta; bleomycin en-keyword=bronchial epithelial cells kn-keyword=bronchial epithelial cells END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=11 article-no= start-page=673 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Functional Blockage of S100A8/A9 Ameliorates Ischemia-Reperfusion Injury in the Lung en-subtitle= kn-subtitle= en-abstract= kn-abstract=(1) Background: Lung ischemia-reperfusion (IR) injury increases the mortality and morbidity of patients undergoing lung transplantation. The objective of this study was to identify the key initiator of lung IR injury and to evaluate pharmacological therapeutic approaches using a functional inhibitor against the identified molecule. (2) Methods: Using a mouse hilar clamp model, the combination of RNA sequencing and histological investigations revealed that neutrophil-derived S100A8/A9 plays a central role in inflammatory reactions during lung IR injury. Mice were assigned to sham and IR groups with or without the injection of anti-S100A8/A9 neutralizing monoclonal antibody (mAb). (3) Results: Anti-S100A8/A9 mAb treatment significantly attenuated plasma S100A8/A9 levels compared with control IgG. As evaluated by oxygenation capacity and neutrophil infiltration, the antibody treatment dramatically ameliorated the IR injury. The gene expression levels of cytokines and chemokines induced by IR injury were significantly reduced by the neutralizing antibody. Furthermore, the antibody treatment significantly reduced TUNEL-positive cells, indicating the presence of apoptotic cells. (4) Conclusions: We identified S100A8/A9 as a novel therapeutic target against lung IR injury. en-copyright= kn-copyright= en-aut-name=NakataKentaro en-aut-sei=Nakata en-aut-mei=Kentaro 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=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=KomodaYuhei en-aut-sei=Komoda en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimizuDai en-aut-sei=Shimizu en-aut-mei=Dai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoHaruchika en-aut-sei=Yamamoto en-aut-mei=Haruchika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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=10 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=11 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=12 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=13 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=14 ORCID= en-aut-name=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 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=17 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=18 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 Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate 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=Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 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=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 Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 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=15 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=16 en-affil= Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 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=ischemia reperfusion injury kn-keyword=ischemia reperfusion injury en-keyword= S100A8/A9 kn-keyword= S100A8/A9 en-keyword=lung transplantation kn-keyword=lung transplantation en-keyword=damage-associated molecule patterns kn-keyword=damage-associated molecule patterns END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=6 article-no= start-page=689 end-page=694 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An Evaluation of the Efficacy of Compression Therapy Using Sleeves and Stockings to Prevent Docetaxel-induced Peripheral Neuropathy in Breast Cancer Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Taxanes are key drugs for patients with breast cancer. A major adverse effect of taxanes is peripheral neuropathy (PN). To investigate the ability of compression therapy using sleeves and stockings to prevent PN due to the taxane docetaxel, we conducted a single-center historical control trial. Patients receiving docetaxel at 75 mg/m2 every 3 weeks for 4 cycles as first-line chemotherapy for breast cancer were eligible. PN was evaluated using the common terminology criteria for adverse events version 4.0. The primary endpoint was the incidence of allgrade PN until 3 weeks after the fourth docetaxel administration. We evaluated 26 patients in the intervention group and compared their data to those collected retrospectively from 52 patients treated with docetaxel without compression. Neither the incidence of all-grade PN until 3 weeks after the fourth docetaxel administration (63.5% in the control group vs. 76.9% in the intervention group, p=0.31) nor that of PN grade ≥ 2 (13.5% vs. 15.4%, p=0.99) differed between the groups. In this study, the efficacy of compression therapy using sleeves and stockings to prevent PN induced by docetaxel was not demonstrated. Further clinical studies including medications or intervention are needed to reduce the incidence and severity of PN induced by chemotherapy. en-copyright= kn-copyright= en-aut-name=YamanouchiKosho en-aut-sei=Yamanouchi en-aut-mei=Kosho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KubaSayaka en-aut-sei=Kuba en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumotoMegumi en-aut-sei=Matsumoto en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YanoHiroshi en-aut-sei=Yano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoritaMichi en-aut-sei=Morita en-aut-mei=Michi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakimuraChika en-aut-sei=Sakimura en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OtsuboRyota en-aut-sei=Otsubo en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HidakaMasaaki en-aut-sei=Hidaka en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagayasuTakeshi en-aut-sei=Nagayasu en-aut-mei=Takeshi 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, Nagasaki University Graduate School of Biomedical Science kn-affil= affil-num=2 en-affil=Department of Surgery, Nagasaki University Graduate School of Biomedical Science kn-affil= affil-num=3 en-affil=Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science kn-affil= affil-num=4 en-affil=Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science kn-affil= affil-num=5 en-affil=Department of Surgery, Nagasaki University Graduate School of Biomedical Science kn-affil= affil-num=6 en-affil=Department of Surgery, Nagasaki University Graduate School of Biomedical Science kn-affil= affil-num=7 en-affil=Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science kn-affil= affil-num=8 en-affil=Department of Surgery, Nagasaki University Graduate School of Biomedical Science kn-affil= affil-num=9 en-affil=Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science kn-affil= affil-num=10 en-affil=Department of Surgery, Nagasaki University Graduate School of Biomedical Science kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=docetaxel kn-keyword=docetaxel en-keyword=neuropathy kn-keyword=neuropathy en-keyword=compression kn-keyword=compression END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=6 article-no= start-page=661 end-page=671 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association of Genetic Polymorphism with Taxane-induced Peripheral Neuropathy: Sub-analysis of a Randomized Phase II Study to Determine the Optimal Dose of 3-week Cycle Nab-Paclitaxel in Metastatic Breast Cancer Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chemotherapy-induced peripheral neuropathy (CIPN) is an important clinical challenge that threatens patients’ quality of life. This sub-study of the ABROAD trial investigated the influence of single nucleotide polymorphisms (SNPs) on CIPN, using genotype data from a randomized study to determine the optimal dose of a 3-week-cycle regimen of nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). Patients with HER2-negative MBC were randomly assigned to three doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2). Five SNPs (EPHA4-rs17348202, EPHA5-rs7349683, EPHA6-rs301927, LIMK2-rs5749248, and XKR4-rs4737264) were analyzed based on the results of a previous genome-wide association study. Per-allele SNP associations were assessed by a Cox regression to model the cumulative dose of nab-PTX up to the onset of severe or worsening sensory neuropathy. A total of 141 patients were enrolled in the parent study; 91(65%) were included in this sub-study. Worsening of CIPN was significantly greater in the cases with XKR4 AC compared to those with a homozygote AA (HR 1.86, 95%CI: 1.00001−3.46, p=0.049). There was no significant correlation of CIPN with any other SNP. A multivariate analysis showed that the cumulative dose of nab-PTX was most strongly correlated with CIPN (p<0.01). en-copyright= kn-copyright= en-aut-name=AbeYuko en-aut-sei=Abe en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KashiwabaraKosuke en-aut-sei=Kashiwabara en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsurutaniJunji en-aut-sei=Tsurutani en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitadaMasahiro en-aut-sei=Kitada en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakahashiMasato en-aut-sei=Takahashi en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatoHiroaki en-aut-sei=Kato en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KikawaYuichiro en-aut-sei=Kikawa en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SakataEiko en-aut-sei=Sakata en-aut-mei=Eiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaitoYoichi en-aut-sei=Naito en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HasegawaYoshie en-aut-sei=Hasegawa en-aut-mei=Yoshie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SaitoTsuyoshi en-aut-sei=Saito en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IwasaTsutomu en-aut-sei=Iwasa en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TakashimaTsutomu en-aut-sei=Takashima en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AiharaTomohiko en-aut-sei=Aihara en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 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=17 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=18 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=19 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=20 ORCID= affil-num=1 en-affil=Department of Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Breast and Endocrine surgery, Kawasaki Medical School Hospital kn-affil= affil-num=3 en-affil=Clinical Research Promotion Center, University of Tokyo Hospital kn-affil= affil-num=4 en-affil=Advanced Cancer Translational Research Institute, Showa University kn-affil= affil-num=5 en-affil=Breast Disease Center, Asahikawa Medical University Hospital kn-affil= affil-num=6 en-affil=Department of Breast Surgery, National Hospital Organization Hokkaido Cancer Center kn-affil= affil-num=7 en-affil=Department of Breast Surgery, Teine Keijinkai Hospital kn-affil= affil-num=8 en-affil=Department of Breast Surgery, Kansai Medical University Hospital kn-affil= affil-num=9 en-affil=Department of Breast Surgery, Niigata City General Hospital kn-affil= affil-num=10 en-affil=Department of Medical Oncology, National Cancer Center Hospital East kn-affil= affil-num=11 en-affil=Department of Breast Surgery, Hachinohe City Hospital kn-affil= affil-num=12 en-affil=Department of Breast Surgery, Japanese Red Cross Saitama Hospital kn-affil= affil-num=13 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Breast Center, Aihara Hospital kn-affil= affil-num=16 en-affil=Department of Medical Oncology, National Cancer Center Hospital East kn-affil= affil-num=17 en-affil=Breast Oncology Center, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=18 en-affil=Department of Breast and Endocrine surgery, Okayama University Hospital kn-affil= affil-num=19 en-affil=Department of Breast surgery, Kawasaki Medical School General Medical Center kn-affil= affil-num=20 en-affil=Department of Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=metastatic breast cancer kn-keyword=metastatic breast cancer en-keyword=taxane-induced peripheral neuropathy kn-keyword=taxane-induced peripheral neuropathy en-keyword=chemotherapy-induced peripheral neuropathy kn-keyword=chemotherapy-induced peripheral neuropathy en-keyword=nab-paclitaxel kn-keyword=nab-paclitaxel en-keyword=single nucleotide polymorphism kn-keyword=single nucleotide polymorphism END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=6 article-no= start-page=625 end-page=633 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Knockdown of LncRNA SBF2-AS1 Inhibited Gastric Cancer Tumorigenesis via the Wnt/LRP5 Signaling Pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=This investigation aimed to uncover the impact of a long noncoding RNA, SET-binding factor 2 antisense RNA1 (SBF2-AS1) on the malignant progression of gastric cancer (GC) and to further explore its underlying mechanism. SBF2-AS1 expression was quantified by qRT-PCR in GC cell lines and GC tissues. In vitro loss-of-function studies of SBF2-AS1, accompanied by flow cytometry, CCK-8, and cell invasion tests, were applied to elucidate the impact of SBF2-AS1 on the tumor progression of GC cells. Finally, Western blotting and a luciferase assay were used to detect WNT/LRP5 signaling pathway activation. SBF2-AS1 was aberrantly expressed in GC cell lines (p<0.05) and GC tissues (p<0.05). Cell invasive and proliferative capabilities were inhibited via SBF2-AS1 knockdown, resulting in apoptosis of NCI-N87 and MKN74 cells. Additionally, online database analysis uncovered a positive correlation between SBF2-AS1 and the Wnt/LRP5 signaling pathway (p<0.05). SBF2-AS1 knockdown blocked the Wnt/LRP5 signaling pathway, whereas the effects of SBF2-AS1 knockdown on the malignant genotype of MKN74 as well as NCI-N87 cells were partially restored by triggering the Wnt/ LRP5 signaling pathway. High expression of SBF2-AS1 was found in GC, the malignant progression of which was repressed via SBF2-AS1 knockdown by inhibiting the Wnt/LRP5 signaling pathway. en-copyright= kn-copyright= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=LiuZhisheng kn-aut-sei=Liu kn-aut-mei=Zhisheng aut-affil-num=1 ORCID= en-aut-name=LiQingmei en-aut-sei=Li en-aut-mei=Qingmei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangYe en-aut-sei=Wang en-aut-mei=Ye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GeYunjie en-aut-sei=Ge en-aut-mei=Yunjie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of General surgery, Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine) kn-affil= affil-num=2 en-affil=Department of General surgery, Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine) kn-affil= affil-num=3 en-affil=Department of General surgery, Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine) kn-affil= affil-num=4 en-affil=Department of Healthcare Internal Medicine, Affiliated Qingdao Municipal Hospital of Qingdao University kn-affil= en-keyword=gastric cancer (GC) kn-keyword=gastric cancer (GC) en-keyword=SET-binding factor 2 antisense RNA1 (SBF2-AS1) kn-keyword=SET-binding factor 2 antisense RNA1 (SBF2-AS1) en-keyword=invasion kn-keyword=invasion en-keyword=proliferation kn-keyword=proliferation en-keyword=signaling kn-keyword=signaling 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=2022 dt-pub=20220922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=HER2陽性乳癌におけるTrastuzumab・T-DM1耐性化獲得後の治療標的としてのYES1の役割 kn-title=YES1 as a Therapeutic Target for HER2-Positive Breast Cancer after Trastuzumab and Trastuzumab-Emtansine (T-DM1) Resistance Development en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=FUJIHARAMiwa en-aut-sei=FUJIHARA en-aut-mei=Miwa kn-aut-name=藤原みわ kn-aut-sei=藤原 kn-aut-mei=みわ aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 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=2022 dt-pub=20220922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=乳癌に対する術前短期アロマターゼ阻害剤投与後のKi67によって層別化される患者群間の遺伝子学的検討 kn-title=Gene Expression Profiling between Patient Groups with High and Low Ki67 Levels after Short-term Preoperative Aromatase Inhibitor Treatment for Breast Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KAJIWARAYukiko en-aut-sei=KAJIWARA en-aut-mei=Yukiko kn-aut-name=梶原友紀子 kn-aut-sei=梶原 kn-aut-mei=友紀子 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 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=2022 dt-pub=20220922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=早期乳癌患者における術前のメトホルミン内服が免疫応答因子に与える影響の検討 kn-title=Influences of preoperative metformin on immunological factors in early breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TSUKIOKITakahiro en-aut-sei=TSUKIOKI en-aut-mei=Takahiro kn-aut-name=突沖貴宏 kn-aut-sei=突沖 kn-aut-mei=貴宏 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 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=2022 dt-pub=20220922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=タキサン起因性末梢神経障害と遺伝子多型に関する検討:ABROAD試験付随研究結果 kn-title=Association of Genetic Polymorphism with Taxane-induced Peripheral Neuropathy: a Sub-analysis of a Randomized Phase II Study to Determine the Optimal Dose of 3-week Cycle Nab-Paclitaxel in Metastatic Breast Cancer Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ABEYuko en-aut-sei=ABE en-aut-mei=Yuko kn-aut-name=安部優子 kn-aut-sei=安部 kn-aut-mei=優子 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=5 article-no= start-page=593 end-page=596 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=COVID-19 Vaccine-Associated Lymphadenopathy Mimicking Regrowth of Axillary Lymph Node Metastasis of Lung Adenocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=We encountered a woman with re-enlarged axillary lymph nodes during a computed tomography (CT) scan for surveillance of lung adenocarcinoma with axillary lymph node metastasis at the initial diagnosis that had shrunk with standard chemotherapy. We first suspected cancer recurrence and considered a change in the chemotherapeutic regimen. However, after careful history taking regarding the timing of her Coronavirus Disease 2019 (COVID-19) vaccination, and subsequent careful, close follow-up, radiological shrinkage suggested a strictly benign cause. Especially in lung cancer with a medical history of axillary lymph node involvement, cliniciansshould be aware that vaccine-associated lymphadenopathy can mimic cancer recurrence and sometimesprompt serious misjudgment regarding a current treatment course and strategy. en-copyright= kn-copyright= en-aut-name=NoumiTaku en-aut-sei=Noumi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeHiromi en-aut-sei=Watanabe en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 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=5 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=KatoYuka en-aut-sei=Kato en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiMasanori en-aut-sei=Fujii en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=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=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, Okayama University Hospital 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=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 Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Okayama University Hospital 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 Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=lung cancer kn-keyword=lung cancer en-keyword=COVID-19 vaccination kn-keyword=COVID-19 vaccination en-keyword=axillary lymphadenopathy kn-keyword=axillary lymphadenopathy en-keyword=case report kn-keyword=case report END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=20 article-no= start-page=3307 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel Self-Forming Nanosized DDS Particles for BNCT: Utilizing A Hydrophobic Boron Cluster and Its Molecular Glue Effect en-subtitle= kn-subtitle= en-abstract= kn-abstract=BNCT is a non-invasive cancer therapy that allows for cancer cell death without harming adjacent cells. However, the application is limited, owing to the challenges of working with clinically approved boron (B) compounds and drug delivery systems (DDS). To address the issues, we developed self-forming nanoparticles consisting of a biodegradable polymer, namely, "AB-type Lactosome (AB-Lac)" loaded with B compounds. Three carborane isomers (o-, m-, and p-carborane) and three related alkylated derivatives, i.e., 1,2-dimethy-o-carborane (diC1-Carb), 1,2-dihexyl-o-carborane (diC6-Carb), and 1,2-didodecyl-o-carborane (diC12-Carb), were separately loaded. diC6-Carb was highly loaded with AB-Lac particles, and their stability indicated the "molecular glue" effect. The efficiency of in vitro B uptake of diC6-Carb for BNCT was confirmed at non-cytotoxic concentration in several cancer cell lines. In vivo/ex vivo biodistribution studies indicated that the AB-Lac particles were remarkably accumulated within 72 h post-injection in the tumor lesions of mice bearing syngeneic breast cancer (4T1) cells, but the maximum accumulation was reached at 12 h. In ex vivo B biodistribution, the ratios of tumor/normal tissue (T/N) and tumor/blood (T/Bl) of the diC6-Carb-loaded particles remained stably high up to 72 h. Therefore, we propose the diC6-Carb-loaded AB-Lac particles as a promising candidate medicine for BNCT. en-copyright= kn-copyright= en-aut-name=FithroniAbdul Basith en-aut-sei=Fithroni en-aut-mei=Abdul Basith kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiKazuko en-aut-sei=Kobayashi en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UjiHirotaka en-aut-sei=Uji en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshimotoManabu en-aut-sei=Ishimoto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkehiMasaru en-aut-sei=Akehi en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Collaborative Research Center for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Material Chemistry, Graduate School of Engineering, Kyoto University kn-affil= affil-num=4 en-affil=Fukushima SiC Applied Engineering Inc. kn-affil= affil-num=5 en-affil=Collaborative Research Center for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Department of Cell Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=boron neutron capture therapy (BNCT) kn-keyword=boron neutron capture therapy (BNCT) en-keyword=biologically self-degradable amphipathic polymer (Lactosome) kn-keyword=biologically self-degradable amphipathic polymer (Lactosome) en-keyword=hydrophobic boron cluster kn-keyword=hydrophobic boron cluster en-keyword=carborane isomers or o-carborane alkylated derivatives kn-keyword=carborane isomers or o-carborane alkylated derivatives en-keyword=molecular glue effect kn-keyword=molecular glue effect END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=19 article-no= start-page=11035 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220920 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immune State Conversion of the Mesenteric Lymph Node in a Mouse Breast Cancer Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Secondary lymphoid tissues, such as the spleen and lymph nodes (LNs), contribute to breast cancer development and metastasis in both anti- and pro-tumoral directions. Although secondary lymphoid tissues have been extensively studied, very little is known about the immune conversion in mesenteric LNs (mLNs) during breast cancer development. Here, we demonstrate inflammatory immune conversion of mLNs in a metastatic 4T1 breast cancer model. Splenic T cells were significantly decreased and continuously suppressed IFN-gamma production during tumor development, while myeloid-derived suppressor cells (MDSCs) were dramatically enriched. However, T cell numbers in the mLN did not decrease, and the MDSCs only moderately increased. T cells in the mLN exhibited conversion from a pro-inflammatory state with high IFN-gamma expression to an anti-inflammatory state with high expression of IL-4 and IL-10 in early- to late-stages of breast cancer development. Interestingly, increased migration of CD103(+)CD11b(+) dendritic cells (DCs) into the mLN, along with increased (1 -> 3)-beta-D-glucan levels in serum, was observed even in late-stage breast cancer. This suggests that CD103(+)CD11b(+) DCs could prime cancer-reactive T cells. Together, the data indicate that the mLN is an important lymphoid tissue contributing to breast cancer development. en-copyright= kn-copyright= en-aut-name=ShigehiroTsukasa en-aut-sei=Shigehiro en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UenoMaho en-aut-sei=Ueno en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KijihiraMayumi en-aut-sei=Kijihira en-aut-mei=Mayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiRyotaro en-aut-sei=Takahashi en-aut-mei=Ryotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UmemuraChiho en-aut-sei=Umemura en-aut-mei=Chiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TahaEman A. en-aut-sei=Taha en-aut-mei=Eman A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurosakaChisaki en-aut-sei=Kurosaka en-aut-mei=Chisaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AsayamaMegumi en-aut-sei=Asayama en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MurakamiHiroshi en-aut-sei=Murakami en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=NakamuraYoshimasa en-aut-sei=Nakamura en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=MasudaJunko en-aut-sei=Masuda en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Research Institute for Biomedical Sciences, Tokyo University of Science kn-affil= affil-num=2 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=3 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=8 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=12 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=13 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=breast cancer cells kn-keyword=breast cancer cells en-keyword=dendritic cells kn-keyword=dendritic cells en-keyword=mesenteric lymph node kn-keyword=mesenteric lymph node en-keyword=myeloid-derived suppressor cells kn-keyword=myeloid-derived suppressor cells END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=18 article-no= start-page=10300 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220907 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Histidine-Rich Glycoprotein Suppresses the S100A8/A9-Mediated Organotropic Metastasis of Melanoma Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=The dissection of the complex multistep process of metastasis exposes vulnerabilities that could be exploited to prevent metastasis. To search for possible factors that favor metastatic outgrowth, we have been focusing on secretory S100A8/A9. A heterodimer complex of the S100A8 and S100A9 proteins, S100A8/A9 functions as a strong chemoattractant, growth factor, and immune suppressor, both promoting the cancer milieu at the cancer-onset site and cultivating remote, premetastatic cancer sites. We previously reported that melanoma cells show lung-tropic metastasis owing to the abundant expression of S100A8/A9 in the lung. In the present study, we addressed the question of why melanoma cells are not metastasized into the brain at significant levels in mice despite the marked induction of S100A8/A9 in the brain. We discovered the presence of plasma histidine-rich glycoprotein (HRG), a brain-metastasis suppression factor against S100A8/A9. Using S100A8/A9 as an affinity ligand, we searched for and purified the binding plasma proteins of S100A8/A9 and identified HRG as the major protein on mass spectrometric analysis. HRG prevents the binding of S100A8/A9 to the B16-BL6 melanoma cell surface via the formation of the S100A8/A9 complex. HRG also inhibited the S100A8/A9-induced migration and invasion of A375 melanoma cells. When we knocked down HRG in mice bearing skin melanoma, metastasis to both the brain and lungs was significantly enhanced. The clinical examination of plasma S100A8/A9 and HRG levels showed that lung cancer patients with brain metastasis had higher S100A8/A9 and lower HRG levels than nonmetastatic patients. These results suggest that the plasma protein HRG strongly protects the brain and lungs from the threat of melanoma metastasis. en-copyright= kn-copyright= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko 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=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 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=7 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=8 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=9 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=10 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=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=ChenYouyi en-aut-sei=Chen en-aut-mei=Youyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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=15 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=16 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=17 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=18 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=19 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=20 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 Pharmacology, Kindai University Faculty of Medicine kn-affil= affil-num=4 en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University kn-affil= affil-num=5 en-affil=Faculty of Medicine, Udayana University 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 Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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=Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University 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 Biochemistry, Kawasaki Medical School kn-affil= affil-num=16 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=17 en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=18 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=19 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=S100A8/A9 kn-keyword=S100A8/A9 en-keyword=HRG kn-keyword=HRG en-keyword=metastasis kn-keyword=metastasis END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=60 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220912 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exosomal Wnt7a from a low metastatic subclone promotes lung metastasis of a highly metastatic subclone in the murine 4t1 breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Patients with triple-negative breast cancer (TNBC) often have poorer prognosis than those with other subtypes because of its aggressive behaviors. Cancer cells are heterogeneous, and only a few highly metastatic subclones metastasize. Although the majority of subclones may not metastasize, they could contribute by releasing factors that increase the capacity of highly metastatic cells and/or provide a favorable tumor microenvironment (TME). Here, we analyzed the interclonal communication in TNBC which leads to efficient cancer progression, particularly lung metastasis, using the polyclonal murine 4T1 BC model. Methods We isolated two 4T1 subclones, LM.4T1 and HM.4T1 cells with a low and a high metastatic potential, respectively, and examined the effects of LM.4T1 cells on the behaviors of HM.4T1 cells using the cell scratch assay, sphere-forming assay, sphere invasion assay, RT-qPCR, and western blotting in vitro. We also examined the contribution of LM.4T1 cells to the lung metastasis of HM.4T1 cells and TME in vivo. To identify a critical factor which may be responsible for the effects by LM.4T1 cells, we analyzed the data obtained from the GEO database. Results Co-injection of LM.4T1 cells significantly augmented lung metastases by HM.4T1 cells. LM.4T1-derived exosomes promoted the migration and invasion of HM.4T1 cells in vitro, and blocking the secretion of exosome abrogated their effects on HM.4T1 cells. Analyses of data obtained from the GEO database suggested that Wnt7a might be a critical factor responsible for the enhancing effects. In fact, a higher level of Wnt7a was detected in LM.4T1 cells, especially in exosomes, than in HM.4T1 cells, and deletion of Wnt7a in LM.4T1 cells significantly decreased the lung metastasis of HM.4T1 cells. Further, treatment with Wnt7a increased the spheroid formation by HM.4T1 cells via activation of the PI3K/Akt/mTOR signaling pathway. Finally, infiltration of alpha SMA-positive fibroblasts and angiogenesis was more prominent in tumors of LM.4T1 cells and deletion of Wnt7a in LM.4T1 cells markedly reduced angiogenesis. Conclusions We demonstrated, for the first time, that a low metastatic subclone can enhance lung metastasis of highly metastatic subclone via exosomal Wnt7a and propose Wnt7a as a molecular target to treat TNBC patients. en-copyright= kn-copyright= en-aut-name=LiChunning en-aut-sei=Li en-aut-mei=Chunning kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=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=KondoTakamasa en-aut-sei=Kondo en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=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=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=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo 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 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= 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 Cell Biology, 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=Breast cancer kn-keyword=Breast cancer en-keyword=Metastasis kn-keyword=Metastasis en-keyword=Exosomes kn-keyword=Exosomes en-keyword=Epithelial mesenchymal transition kn-keyword=Epithelial mesenchymal transition en-keyword=Tumor microenvironment kn-keyword=Tumor microenvironment END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=4 article-no= start-page=479 end-page=483 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Liquid Biopsy Revealed HBOC Pedigree and Led to Medical Management Among the Relatives en-subtitle= kn-subtitle= en-abstract= kn-abstract=A hereditary breast and ovarian cancer (HBOC) pedigree was detected via liquid biopsy, and cancer prevention was initiated for the patient’s daughter, after receiving a definitive result from BRCA genetic testing. A 48-yearold woman with ovarian cancer was administered precision medicine, which used cell-free DNA from plasma. The results revealed a pathogenic variant of BRCA1 as a presumed germline pathogenic mutation. We confirmed the germline pathological variant BRCA1 c.81-1G> A and suggested treatment with a PARP inhibitor. One of her three children had the variant, was diagnosed as an unaffected pathogenic variant carrier, and was advised to initiate surveillance. en-copyright= kn-copyright= en-aut-name=OgawaChikako en-aut-sei=Ogawa en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=SogawaReimi en-aut-sei=Sogawa en-aut-mei=Reimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HasuokaKayoko en-aut-sei=Hasuoka en-aut-mei=Kayoko 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=FutagawaMashu en-aut-sei=Futagawa en-aut-mei=Mashu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UrakawaYusaku en-aut-sei=Urakawa en-aut-mei=Yusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KochiMariko en-aut-sei=Kochi en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Nursing, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Center for Comprehensive Genomic Medicine, Okayama University Hospital Biobank, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Clinical Genetics and Genomic Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=hereditary breast and ovarian cancer (HBOC) kn-keyword=hereditary breast and ovarian cancer (HBOC) en-keyword=BRCA 1 kn-keyword=BRCA 1 en-keyword=presumed germline pathogenic variants (PGPV) kn-keyword=presumed germline pathogenic variants (PGPV) en-keyword=germline findings kn-keyword=germline findings en-keyword=cancer precision medicine kn-keyword=cancer precision medicine END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=4 article-no= start-page=399 end-page=408 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gene Expression Profiling between Patient Groups with High and Low Ki67 Levels after Short-term Preoperative Aromatase Inhibitor Treatment for Breast Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=According to a recent report, a low Ki67 level after short-term preoperative hormone therapy (post-Ki67) might suggest a more favorable prognosis compared with a high post-Ki67 level in patients with hormone receptorpositive/human epidermal growth factor 2-negative (HR+/HER2−) breast cancer with high levels of Ki67. This study aimed to evaluate the pre-treatment genetic differences between these two patient groups. Forty-five luminal B-like patients were stratified into two groups, namely, a group with high (H→H) and one with low (H→L) Ki67 levels after short-term preoperative aromatase inhibitor (AI) treatment. We compared pre-treatmentgene expression profiles between the two groups. In gene level analysis, there was no significant difference between the two groups by the class comparison test. In pathway analysis, five metabolism-related gene sets were significantly upregulated in the H→L group (p≤0.05). In the search for novel targets, five genes (PARP, BRCA2, FLT4, CDK6, and PDCD1LG2) showed significantly higher expression in the H→H group (p≤0.05). Several metabolism-related pathways were associated with sensitivity to AI. In the future, it will be necessary to seek out new therapeutic strategies for the poor prognostic group with high post-Ki67. en-copyright= kn-copyright= en-aut-name=KajiwaraYukiko en-aut-sei=Kajiwara en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=ZhuYidan en-aut-sei=Zhu en-aut-mei=Yidan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KochiMariko en-aut-sei=Kochi en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=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=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=Departments of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=3 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=4 en-affil=Departments of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Departments of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Departments of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Departments of Breast and Endocrine Surgery, Okayama University Hospital 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= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=short-term hormone therapy kn-keyword=short-term hormone therapy en-keyword=gene expression profiling kn-keyword=gene expression profiling en-keyword=Ki-67 kn-keyword=Ki-67 en-keyword=targeted therapy kn-keyword=targeted therapy END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=4 article-no= start-page=391 end-page=398 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Tanden Breathing on Constipation: A Randomized Controlled Trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tanden breathing, an ancient health technique, involves expiratory abdominal pressure breathing is practiced in Japan. In this study we examined the ability of Tanden breathing to relieve constipation. The study was designed as a stratified-block randomized controlled trial enrolling 20 participants. Nineteen were female and one was male, none were elderly. During the 6-week intervention period, the participants performed video-guided Tanden breathing about 10 min once day. We evaluated constipation using the Constipation Assessment Scale (CAS). There were significant differences in the mean CAS score between time points (baseline, 3 weeks after baseline, 6 weeks after baseline), groups (intervention and control), and their interaction (time×group) using repeated-measures analysis of variance. The control group showed no change in the mean CAS score; the mean CAS scores of the intervention group changed from 7.2 at baseline to 3.9 at 3 weeks and 3.1 at 6 weeks after baseline. A regression analysis of the difference in the mean CAS between baseline and 6 weeks later showed that the CAS of the intervention group was 4.3 points lower than that of the control group (95% confidence interval, 2.5-6.1). The results suggested that Tanden breathing is effective in relieving constipation among young women. en-copyright= kn-copyright= en-aut-name=HabuHiroshi en-aut-sei=Habu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TokinobuAkiko en-aut-sei=Tokinobu en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= affil-num=1 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Epidemiology and Public Health, Ehime University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Tanden breathing kn-keyword=Tanden breathing en-keyword=Dantian kn-keyword=Dantian en-keyword=breathing exercises kn-keyword=breathing exercises en-keyword=constipation kn-keyword=constipation en-keyword=mind−body therapy kn-keyword=mind−body therapy END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=4 article-no= start-page=359 end-page=371 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Therapeutic Approaches Targeting miRNA in Systemic Lupus Erythematosus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Systemic lupus erythematosus (SLE) is a potentially fatal systemic autoimmune disease, and its etiology involves both genetic and environmental factors such as sex hormone imbalance, genetic predisposition, epigenetic regulation, and immunological factors. Dysregulation of microRNA (miRNA) is suggested to be one of the epigenetic factors in SLE. miRNA is a 22-nucleotide single-stranded noncoding RNA that contributes to post-transcriptional modulation of gene expression. miRNA targeting therapy has been suggested to be useful for the treatment of cancers and other diseases. Gene knockout and miRNA targeting therapy have been demonstrated to improve SLE disease activity in mice. However, these approaches have not yet reached the level of clinical application. miRNA targeting therapy is limited by the fact that each miRNA has multiple targets. In addition, the expression of certain miRNAs may differ among cell tissues within a single SLE patient. This limitation can be overcome by targeted delivery and chemical modifications. In the future, further research into miRNA chemical modifications and delivery systems will help us develop novel therapeutic agents for SLE. en-copyright= kn-copyright= en-aut-name=Hiramatsu-AsanoSumie en-aut-sei=Hiramatsu-Asano en-aut-mei=Sumie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=systemic lupus erythematosus kn-keyword=systemic lupus erythematosus en-keyword=miRNA kn-keyword=miRNA en-keyword=miRNA targeting therapy kn-keyword=miRNA targeting therapy END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=8 article-no= start-page=1195 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220722 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Robotic Mediastinal Tumor Resections: Position and Port Placement en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study aimed to determine the optimal position and port placement during robotic resection for various mediastinal tumors. For anterior mediastinal tumors, total or extended thymectomy is commonly performed in the supine position using the lateral or subxiphoid approach. Although it is unclear which approach is better during robotic thymectomy, technical advantages of subxiphoid approach are beneficial for patients with myasthenia who require extended thymectomy. Partial thymectomy is performed in the supine position using a lateral approach. Superior, middle, and posterior mediastinal tumors are resected in the decubitus position using the lateral approach, whereas dumbbell tumor resection, which requires a posterior approach, can be performed in the prone position. The position and port placement should be chosen depending on the size, location, and aggressiveness of the tumor. In this study, we describe how to choose which of these different robotic approaches can be used based on our experience and previous reports. en-copyright= kn-copyright= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=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= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science 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 Science kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science 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 Science 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 Science kn-affil= en-keyword=robot kn-keyword=robot en-keyword=robot-assisted thoracic surgery kn-keyword=robot-assisted thoracic surgery en-keyword=mediastinal tumor kn-keyword=mediastinal tumor en-keyword=thymectomy kn-keyword=thymectomy en-keyword=port placement kn-keyword=port placement END start-ver=1.4 cd-journal=joma no-vol=2022 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220724 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Drug repositioning of tranilast to sensitize a cancer therapy by targeting cancer-associated fibroblast en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment that mediate resistance of cancer cells to anticancer drugs. Tranilast is an antiallergic drug that suppresses the release of cytokines from various inflammatory cells. In this study, we investigated the inhibitory effect of tranilast on the interactions between non-small cell lung cancer (NSCLC) cells and the CAFs in the tumor microenvironment. Three EGFR-mutant NSCLC cell lines, two KRAS-mutant cell lines, and three CAFs derived from NSCLC patients were used. To mimic the tumor microenvironment, the NSCLC cells were cocultured with the CAFs in vitro, and the molecular profiles and sensitivity to molecular targeted therapy were assessed. Crosstalk between NSCLC cells and CAFs induced multiple biological effects on the NSCLC cells both in vivo and in vitro, including activation of the STAT3 signaling pathway, promotion of xenograft tumor growth, induction of epithelial-mesenchymal transition (EMT), and acquisition of resistance to molecular-targeted therapy, including EGFR-mutant NSCLC cells to osimertinib and of KRAS-mutant NSCLC cells to selumetinib. Treatment with tranilast led to inhibition of IL-6 secretion from the CAFs, which, in turn, resulted in inhibition of CAF-induced phospho-STAT3 upregulation. Tranilast also inhibited CAF-induced EMT in the NSCLC cells. Finally, combined administration of tranilast with molecular-targeted therapy reversed the CAF-mediated resistance of the NSCLC cells to the molecular-targeted drugs, both in vitro and in vivo. Our results showed that combined administration of tranilast with molecular-targeted therapy is a possible new treatment strategy to overcome drug resistance caused by cancer-CAF interaction. en-copyright= kn-copyright= en-aut-name=OchiKosuke en-aut-sei=Ochi en-aut-mei=Kosuke 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=ThuYin Min en-aut-sei=Thu en-aut-mei=Yin Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakatsuFumiaki en-aut-sei=Takatsu en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsudakaShimpei en-aut-sei=Tsudaka en-aut-mei=Shimpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ZhuYidan en-aut-sei=Zhu en-aut-mei=Yidan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 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=12 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=13 ORCID= en-aut-name=OkamotoYoshiharu en-aut-sei=Okamoto en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=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= 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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=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=Departments of Pharmacy, Okayama University Hospital kn-affil= affil-num=9 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=10 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=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 Thoracic Surgery and Breast and Endocrinological Surgery, 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= affil-num=14 en-affil=Department of Veterinary Clinical Medicine, Joint School of Veterinary Medicine, Tottori University kn-affil= affil-num=15 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=16 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=cancer-associated fibroblast kn-keyword=cancer-associated fibroblast en-keyword=drug resistance kn-keyword=drug resistance en-keyword=tranilast kn-keyword=tranilast END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=4 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gefitinib induction followed by chemoradiotherapy in EGFR-mutant, locally advanced non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study (vol 6, 100191, 2021) en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HottaK. en-aut-sei=Hotta en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaekiS. en-aut-sei=Saeki en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamaguchiM. en-aut-sei=Yamaguchi en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HaradaD. en-aut-sei=Harada en-aut-mei=D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BesshoA. en-aut-sei=Bessho en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaK. en-aut-sei=Tanaka en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=InoueK. en-aut-sei=Inoue en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=GembaK. en-aut-sei=Gemba en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShiojiriM. en-aut-sei=Shiojiri en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatoY. en-aut-sei=Kato en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NinomiyaT. en-aut-sei=Ninomiya en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KuboT. en-aut-sei=Kubo en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KishimotoJ. en-aut-sei=Kishimoto en-aut-mei=J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShioyamaY. en-aut-sei=Shioyama en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KatsuiK. en-aut-sei=Katsui en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SasakiJ. en-aut-sei=Sasaki en-aut-mei=J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KiuraK. en-aut-sei=Kiura en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SugioK. en-aut-sei=Sugio en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Kumamoto University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center kn-affil= affil-num=4 en-affil=Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Kyushu University Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Kitakyushu Municipal Medical Center kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Chugoku Central Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama 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 Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Center for Clinical and Translational Research, Kyushu University Hospital kn-affil= affil-num=14 en-affil=Clinical Radiology, Radiology Informatics and Network, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=15 en-affil=Department of Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Department of Thoracic and Breast Surgery, Oita University kn-affil= 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=2022 dt-pub=20220712 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lung recruitment after cardiac arrest during procurement of atelectatic donor lungs is a protective measure in lung transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Brain-dead donors are susceptible to pulmonary atelectasis (AT). In procurement surgery, lung recruitment under circulatory conditions and cold-flushing for atelectatic donor lungs often provoke graft injury due to the acute blood inflow. We hypothesized that lung recruitment without blood circulation can mitigate graft injury. This study aimed to examine the benefits of lung recruitment subsequent to cardiac arrest using a porcine lung-transplant model.

Methods: Thirteen donor pigs were categorized into the non-atelectatic (No-AT) group (n=3) representing a healthy control group; AT-BCR group (n=5), in which AT was reverted by conventional blood-circulated recruitment (BCR); and AT-no-BCR group (n=5), in which AT was reverted by no-BCR following circulatory arrest. In the atelectatic donor models, the left main bronchus was ligated for 24 hours prior to lung procurement. Left lung transplantation (LTx) was subsequently performed in the thirteen recipient pigs. After 6 hours evaluation, the recipients were euthanized and the lung grafts were excised.

Results: The post-transplant PaO2/FiO(2) ratio was significantly higher in the AT-no-BCR group than in the AT-BCR group (P=0.015). Wet/dry ratio, histological findings of graft injury and tissue interleukin-8 expression in the AT-no-BCR group were similar to those of the No-AlT group.

Conclusions: Lung recruitment without circulation after circulatory arrest could be more protective for atelectatic donor lung than the conventional procedure. en-copyright= kn-copyright= en-aut-name=NimanEito en-aut-sei=Niman en-aut-mei=Eito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=ShiotaniToshio en-aut-sei=Shiotani en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=IgawaTakuro en-aut-sei=Igawa en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 ORCID= en-aut-name=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Diagnostic Pathology, Okayama University 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 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 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 (LTx) kn-keyword=Lung transplantation (LTx) en-keyword=lung recruitment maneuver kn-keyword=lung recruitment maneuver en-keyword=atelectasis kn-keyword=atelectasis en-keyword=protective procurement kn-keyword=protective procurement END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=3 article-no= start-page=297 end-page=305 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of Fast Diffusion Kurtosis Imaging Using New Software Designed for Widespread Clinical Use en-subtitle= kn-subtitle= en-abstract= kn-abstract=Clinical research using restricted diffusion-weighted imaging, especially diffusion kurtosis (DK) imaging, has been progressing, with reports on its effectiveness in the diagnostic imaging of cerebral infarctions, neurodegenerative diseases, and tumors, among others. However, the application of DK imaging in daily clinical practice has not spread because of the long imaging time required and the use of specific software for image creation. Herein, with the aim of promoting clinical research using DK imaging at any medical facility, we evaluated fast DK imaging using a new software program. We developed a new macro program that produces DK images using general-purpose, inexpensive software (Microsoft Excel and ImageJ), and we evaluated fast DK imaging using bio-phantoms and a healthy volunteer in clinical trials. The DK images created by the new software with diffusion-weighted images captured with short-time imaging sequences were similar to the original DK images captured with long-time imaging sequences. The DK images using three b-values, which can reduce the imaging time by 43%, were equivalent to the DK images using five b-values. The DK imaging technique developed herein might allow any medical facility to increase its daily clinical use of DK imaging and easily conduct clinical research. en-copyright= kn-copyright= en-aut-name=KurodaMasahiro en-aut-sei=Kuroda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KonishiKohei en-aut-sei=Konishi en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugimotoKohei en-aut-sei=Sugimoto en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshimuraYuuki en-aut-sei=Yoshimura en-aut-mei=Yuuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HamadaKentaro en-aut-sei=Hamada en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KhasawnehcAbdullah en-aut-sei=Khasawnehc en-aut-mei=Abdullah kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=9 ORCID= en-aut-name=BamgboseBabatunde O. en-aut-sei=Bamgbose en-aut-mei=Babatunde O. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IshizakaHinata en-aut-sei=Ishizaka en-aut-mei=Hinata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=13 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=14 ORCID= en-aut-name=KamizakiRyo en-aut-sei=Kamizaki en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KurozumiAkira en-aut-sei=Kurozumi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsushitaToshi en-aut-sei=Matsushita en-aut-mei=Toshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OhnoSeiichiro en-aut-sei=Ohno en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KanazawaSusumu en-aut-sei=Kanazawa en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 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=20 ORCID= affil-num=1 en-affil=Radiological Technology, Graduate School of Health 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=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Radiological Technology, Graduate School of Health 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, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=16 en-affil=Central Division of Radiology, Okayama University Hospital kn-affil= affil-num=17 en-affil=Central Division of Radiology, Okayama University Hospital kn-affil= affil-num=18 en-affil=Central Division of Radiology, Okayama University Hospital kn-affil= affil-num=19 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=fast diffusion kurtosis imaging kn-keyword=fast diffusion kurtosis imaging en-keyword=mean kurtosis kn-keyword=mean kurtosis en-keyword=restricted diffusion kn-keyword=restricted diffusion en-keyword=Excel kn-keyword=Excel en-keyword=ImageJ kn-keyword=ImageJ END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=10 article-no= start-page=2534 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220521 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Breast Cancer Awareness Month on Public Interest in the United States between 2012 and 2021: A Google Trends Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Simple Summary In this study, we quantified public awareness regarding breast cancer associated with Breast Cancer Awareness Month (BCAM) in October using Google Trends data and a joinpoint regression analysis. We analyzed the impact of BCAM, Lung Cancer Awareness Month (LCAM), and Prostate Cancer Awareness Month (PCAM) on public awareness of the top three most common cancers in the U.S. from 2012 to 2021 using the relative search volume of Google Trends. The results imply that BCAM has successfully improved the public awareness of breast cancer in the U.S., while LCAM and PCAM had no impact on the awareness of lung and prostate cancers. BCAM could serve as a good example for organizations working on health observances or awareness campaigns. Breast Cancer Awareness Month (BCAM) has a long history of over 30 years, established in 1985 to occur every October, and the National Breast Cancer Foundation now leads the operation. There have been no studies to evaluate the impact of the BCAM on public awareness of breast cancer. We analyzed the impact of BCAM on public awareness of breast cancer in the U.S. from 2012 to 2021 using the relative search volume (RSV) of Google Trends as a surrogate. We also analyzed the impact of Lung Cancer Awareness Month (LCAM) and Prostate Cancer Awareness Month (PCAM) on public awareness of lung and prostate cancer, respectively, to see differences in their effectiveness among the health observances for the top three most common cancers in the U.S. We performed a joinpoint regression analysis to identify statistically significant time points of a change in trend. There were joinpoints around BCAM for "Breast cancer" every year from 2012 to 2021, with a significant increase in the weekly RSVs from 21.9% to 46.7%. Except for 2013 and 2015 for "Lung cancer", when significant increases in the RSV at 1.8% and 1.2% per week were observed around LCAM, no joinpoints were noted around LCAM or PCAM. These results imply that BCAM has successfully improved the public awareness of breast cancer in the U.S. compared to other representative health observances, likely due to the effective involvement of non-medical industries, influencers affected by breast cancer, and an awareness symbol. 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=AcobaJared D. en-aut-sei=Acoba en-aut-mei=Jared D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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 Medicine, John A. Burns School of Medicine, University of Hawai’i kn-affil= en-keyword=Breast Cancer Awareness Month kn-keyword=Breast Cancer Awareness Month en-keyword=breast cancer kn-keyword=breast cancer en-keyword=Google Trends kn-keyword=Google Trends en-keyword=trend analysis kn-keyword=trend analysis END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=7297 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=One-step nucleic acid amplification for intraoperative diagnosis of lymph node metastasis in lung cancer patients: a single-center prospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=One-step nucleic acid amplification (OSNA) is a rapid intraoperative molecular detection technique for sentinel node assessment via the quantitative measurement of target cytokeratin 19 (CK19) mRNA to determine the presence of metastasis. It has been validated in breast cancer but its application in lung cancer has not been adequately investigated. 214 LNs from 105 patients with 100 primary lung cancers, 2 occult primary lung tumors, and 3 metastatic lung tumors, who underwent surgical lung resection with LN dissection between February 2018 and January 2020, were assessed. Resected LNs were divided into two parts: one was snap-frozen for OSNA and the other underwent rapidly frozen histological examination. Intraoperatively collected LNs were evaluated by OSNA using loop-mediated isothermal amplification and compared with intraoperative pathological diagnosis as a control. Among 214 LNs, 14 were detected as positive by OSNA, and 11 were positive by both OSNA and intraoperative pathological diagnosis. The sensitivity and specificity of OSNA was 84.6% and 98.5%, respectively. The results of 5 of 214 LNs were discordant, and the remainder all matched (11 positive and 198 negative) with a concordance rate of 97.7%. Although the analysis of public mRNA expression data from cBioPortal showed that CK19 expression varies greatly depending on the cancer type and histological subtype, the results of the five cases, except for primary lung cancer, were consistent. OSNA provides sufficient diagnostic accuracy and speed and can be applied to the intraoperative diagnosis of LN metastasis for non-small cell lung cancer. en-copyright= kn-copyright= en-aut-name=NambaKei en-aut-sei=Namba en-aut-mei=Kei 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=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiuraAkihiro en-aut-sei=Miura en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=MiyauchiShunsaku en-aut-sei=Miyauchi en-aut-mei=Shunsaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ArakiKota en-aut-sei=Araki en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=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=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 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=13 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=14 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=15 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 ORCID= affil-num=1 en-affil=Department of Pathology, Memorial Sloan Kettering Cancer Center 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 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=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=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=10 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=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 Thoracic Surgery and Breast and Endocrinological Surgery, 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= affil-num=14 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=15 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=16 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=17 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=18 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=76 cd-vols= no-issue=2 article-no= start-page=229 end-page=233 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Primary Osteosarcoma of the Mandible That Responded to Preoperative Chemotherapy: p16 as a Potential Prognostic Factor en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report a case of mandibular osteosarcoma in a Japanese woman in her 70s who was p16-positive. Despite the rapid growth of the tumor, the patient responded well to chemotherapy and was then able to undergo surgery. Head and neck osteosarcoma (HNOS) is a very rare cancer, and although the importance of surgery has been pointed out, the effectiveness of chemotherapy is unclear. Resection margin negativity and response to chemotherapy have been reported as prognostic factors; another report assessed the effectiveness of the immunohistochemical expression of p16 protein as a predictor of response to chemotherapy. en-copyright= kn-copyright= en-aut-name=KonoTakashi en-aut-sei=Kono en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MondenNobuya en-aut-sei=Monden en-aut-mei=Nobuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChikuieNobuyuki en-aut-sei=Chikuie en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaruyaTakayuki en-aut-sei=Taruya en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=IshinoTakashi en-aut-sei=Ishino en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= affil-num=1 en-affil=Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=2 en-affil=Division of Head and Neck Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=3 en-affil=Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=4 en-affil=Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=5 en-affil=Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=6 en-affil=Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=7 en-affil=Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=8 en-affil=Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= en-keyword=head and neck osteosarcomas kn-keyword=head and neck osteosarcomas en-keyword=tumor suppressor p16 kn-keyword=tumor suppressor p16 END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=2 article-no= start-page=203 end-page=215 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Overexpression of Adenovirus E1A Reverses Transforming Growth Factor-β-induced Epithelial-mesenchymal Transition in Human Esophageal Cancer Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=The epithelial-mesenchymal transition (EMT), a normal biological process by which epithelial cells acquire a mesenchymal phenotype, is associated with migration, metastasis, and chemoresistance in cancer cells, and with poor prognosis in patients with esophageal cancer. However, therapeutic strategies to inhibit EMT in tumor environments remain elusive. Here, we show the therapeutic potential of telomerase-specific replication- competent oncolytic adenovirus OBP-301 in human esophageal cancer TE4 and TE6 cells with an EMT phenotype. Transforming growth factor-β (TGF-β) administration induced the EMT phenotype with spindleshaped morphology, upregulation of mesenchymal markers and EMT transcription factors, migration, and chemoresistance in TE4 and TE6 cells. OBP-301 significantly inhibited the EMT phenotype via E1 accumulation. EMT cancer cells were susceptible to OBP-301 via massive autophagy induction. OBP-301 suppressed tumor growth and lymph node metastasis of TE4 cells co-inoculated with TGF-β-secreting fibroblasts. Our results suggest that OBP-301 inhibits the TGF-β-induced EMT phenotype in human esophageal cancer cells. OBP-301-mediated E1A overexpression is a promising antitumor strategy to inhibit EMT-mediated esophageal cancer progression. en-copyright= kn-copyright= en-aut-name=MasudaTomoya en-aut-sei=Masuda en-aut-mei=Tomoya 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=HashimotoYuuri en-aut-sei=Hashimoto en-aut-mei=Yuuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IedaTakeshi en-aut-sei=Ieda en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo 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=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 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=Oncolys BioPharma Inc. 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= en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=EMT kn-keyword=EMT en-keyword=TGF-β kn-keyword=TGF-β en-keyword=oncolytic adenovirus kn-keyword=oncolytic adenovirus en-keyword=E1A kn-keyword=E1A END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=1 article-no= start-page=114 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220408 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Survival and prognostic factors in patients undergoing pulmonary metastasectomy for lung metastases from retroperitoneal sarcoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Soft-tissue sarcomas are rare malignancies that consist of many different histologic subtypes and arise in various locations in the body. In patients with lung metastases from retroperitoneal sarcomas, the long-term outcomes and prognostic factors are unknown. This study is a retrospective review of patients undergoing pulmonary metastasectomy for retroperitoneal sarcoma metastases at one institution, with the purpose of determining prognostic factors and clinical outcomes. Methods This is a single-center, retrospective cohort study of patients undergoing pulmonary metastasectomy for lung metastases from various sarcomas at Okayama University Hospital from January 2006 to December 2018. The Kaplan-Meier method and log-rank test were used for the analyses, and cut-off values of continuous variables were determined by a receiver operating characteristic curve analysis. Results Twenty-four patients underwent the first pulmonary metastasectomy for lung metastases from retroperitoneal sarcoma in our hospital. Leiomyosarcoma was the most common histologic subtype of retroperitoneal sarcoma (79.2%, n = 19). Median overall survival was 49.9 months, and the 3-year and 5-year survival rates after the first pulmonary metastasectomy were 62.5% and 26.4% respectively. In univariate analysis, age >= 56 years, disease-free interval < 15 months, and size of metastasis (>= 27 mm) were associated with poor survival. Conclusion Pulmonary metastasectomy can be considered as an effective management strategy in retroperitoneal sarcoma patients with lung metastases in appropriately selected cases, just as it is for other sarcomas. 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=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=TomiokaYasuaki en-aut-sei=Tomioka en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=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=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=9 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=10 ORCID= en-aut-name=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakahashiKatsuhito en-aut-sei=Takahashi en-aut-mei=Katsuhito 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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=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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 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=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=Center for Sarcoma Multidisciplinary Treatment, Department of Sarcoma Medicine, Kameda Medical Center 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=Retroperitoneal sarcoma kn-keyword=Retroperitoneal sarcoma en-keyword=Lung metastasis kn-keyword=Lung metastasis en-keyword=Metastasectomy kn-keyword=Metastasectomy END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=2 article-no= start-page=129 end-page=135 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Combination of D-dimer and Glasgow Prognostic Score Can Be Useful in Predicting VTE in Patients with Stage IIIC and IVA Ovarian Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer patients have increased risk of venous thromboembolism (VTE) that must be assessed before treatment. This study aimed to determine effective VTE biomarkers in gynecologic cancer (GC). We investigated the correlation between D-dimer levels, Khorana risk score (KRS), Glasgow prognostic score (GPS), and VTE in 1499 GC patients (583 cervical cancer (CC), 621 endometrial cancer (EC), and 295 ovarian cancer (OC) patients) treated at our institution between January 2008 and December 2019. χ2 and Mann–Whitney U-tests were used to determine statistical significance. We used receiver operating characteristic-curve analysis to evaluate the discriminatory ability of each parameter. D-dimer levels were significantly correlated with KRS and GPS in patients with GC. VTE was diagnosed in 11 CC (1.9%), 27 EC (4.3%), and 39 OC patients (13.2%). Optimal D-dimer cut-off values for VTE were 3.1, 3.2, and 3.9 μg/ml in CC, EC and OC patients, respectively. D-dimer could significantly predict VTE in all GC patients. Furthermore, D-dimer combined with GPS was more accurate in predicting VTE than other VTE biomarkers in stage IIIC and IVA OC (AUC: 0.846; p<0.001). This study demonstrates that combined D-dimer and GPS are useful in predicting VTE in patients with OC. en-copyright= kn-copyright= en-aut-name=KuboKotaro en-aut-sei=Kubo en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkamotoKazuhiro en-aut-sei=Okamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuokaHirofumi en-aut-sei=Matsuoka en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=HarumaTomoko en-aut-sei=Haruma en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OgawaChikako en-aut-sei=Ogawa en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=D-dimer kn-keyword=D-dimer en-keyword=gynecologic cancer kn-keyword=gynecologic cancer en-keyword=venous thromboembolism kn-keyword=venous thromboembolism END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=2 article-no= start-page=105 end-page=111 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pathological Complete Response Patients after Neoadjuvant Chemotherapy in Breast Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cases of breast cancer metastasis after achieving a pathological complete response (pCR) with neoadjuvant chemotherapy (NAC) are sometimes encountered in clinical practice. We investigated the prognostic factors for pCR in patients with breast cancer after NAC. This retrospective cohort study included patients with localized breast cancer who underwent NAC followed by surgery between 2004 and 2020 and achieved a pCR. The associations between clinical factors and distant metastasis-free survival rate were statistically analyzed. We analyzed data for 127 patients. Twelve patients (9.4%) had distant metastases, and seven (5.5%) died. For estrogen receptor (ER)-positive patients, the distant metastasis-free survival rate was 94.6% for both 5 and 8 years. In contrast, ER-negative patients had a distant metastasis-free survival rate of 87.6% and 85.4% for 5 and 8 years (p=0.094), respectively. In cT0-2 patients, the distant metastasis-free survival rate was 92.4% for 5 years and 90.5% for 8 years, whereas in cT3-4 patients, the distant metastasis-free survival rate was 83.5% for 5 years and 83.5% for 8 years (p=0.301). This study suggested that patients with ER-negative, pre-NAC cT3 or T4 breast cancer who had achieved a pCR after NAC tended to have a worse prognosis. en-copyright= kn-copyright= en-aut-name=TakaokaMegumi en-aut-sei=Takaoka en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhsumiShozo en-aut-sei=Ohsumi en-aut-mei=Shozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IkejiriHaruka en-aut-sei=Ikejiri en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShidaharaTomohiro en-aut-sei=Shidahara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyoshiYuichiro en-aut-sei=Miyoshi en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=TakashimaSeiki en-aut-sei=Takashima en-aut-mei=Seiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AogiKenjiro en-aut-sei=Aogi en-aut-mei=Kenjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=2 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=3 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=6 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=7 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=8 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= en-keyword=breast kn-keyword=breast en-keyword=carcinoma kn-keyword=carcinoma en-keyword=neoadjuvant therapy kn-keyword=neoadjuvant therapy en-keyword=prognosis kn-keyword=prognosis END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=1 article-no= start-page=523 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ATM: Functions of ATM Kinase and Its Relevance to Hereditary Tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ataxia-telangiectasia mutated (ATM) functions as a key initiator and coordinator of DNA damage and cellular stress responses. ATM signaling pathways contain many downstream targets that regulate multiple important cellular processes, including DNA damage repair, apoptosis, cell cycle arrest, oxidative sensing, and proliferation. Over the past few decades, associations between germline ATM pathogenic variants and cancer risk have been reported, particularly for breast and pancreatic cancers. In addition, given that ATM plays a critical role in repairing double-strand breaks, inhibiting other DNA repair pathways could be a synthetic lethal approach. Based on this rationale, several DNA damage response inhibitors are currently being tested in ATM-deficient cancers. In this review, we discuss the current knowledge related to the structure of the ATM gene, function of ATM kinase, clinical significance of ATM germline pathogenic variants in patients with hereditary cancers, and ongoing efforts to target ATM for the benefit of cancer patients. en-copyright= kn-copyright= en-aut-name=UenoSayaka en-aut-sei=Ueno en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SudoTamotsu en-aut-sei=Sudo en-aut-mei=Tamotsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= affil-num=1 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Section of Translational Research, Hyogo Cancer Center kn-affil= affil-num=3 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=hereditary tumors kn-keyword=hereditary tumors en-keyword=ATM kn-keyword=ATM en-keyword=DNA damage kn-keyword=DNA damage en-keyword=redox homeostasis kn-keyword=redox homeostasis en-keyword=tumor profiling kn-keyword=tumor profiling en-keyword=precision therapy kn-keyword=precision therapy END start-ver=1.4 cd-journal=joma no-vol=61 cd-vols= no-issue=3 article-no= start-page=379 end-page=383 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pulmonary Aspergilloma and Allergic Bronchopulmonary Aspergillosis Following the 2018 Heavy Rain Event in Western Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 16-year-old boy with asthma participated in recovery volunteer work following the 2018 heavy rains in Japan. One month later, he experienced chest pain and dyspnea. Chest computed tomography revealed a cavity with a fungal ball, and Aspergillus fumigatus was detected in his bronchoalveolar lavage fluid. He was treated with voriconazole, but new consolidations appeared rapidly. He also experienced allergic bronchopulmonary aspergillosis. After prednisolone prescription, the consolidations improved; however, his asthma worsened. He underwent partial lung resection to avoid allergens, and his symptoms improved. We must recognize cases of infection after a disaster, especially in patients with chronic respiratory diseases. en-copyright= kn-copyright= en-aut-name=AndoEri en-aut-sei=Ando en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakasukaTakamasa en-aut-sei=Nakasuka en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= en-aut-name=KatoYuka en-aut-sei=Kato en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=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= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= affil-num=1 en-affil=Center for Graduate Medical Education, Okayama University Hospital kn-affil= affil-num=2 en-affil=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Departments 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=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=pulmonary aspergilloma kn-keyword=pulmonary aspergilloma en-keyword=allergic bronchopulmonary aspergillosis kn-keyword=allergic bronchopulmonary aspergillosis en-keyword=disaster kn-keyword=disaster END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=1 article-no= start-page=25 end-page=32 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development and Evaluation of a Short-time Imaging Method for the Clinical Study of the Apparent Diffusion Coefficient Subtraction Method en-subtitle= kn-subtitle= en-abstract= kn-abstract=The apparent diffusion coefficient subtraction method (ASM) was developed as a new restricted diffusionweighted imaging technique for magnetic resonance imaging (MRI). The usefulness of the ASM has been established by in vitro basic research using a bio-phantom, and clinical research on the application of the ASM for the human body is needed. Herein, we developed a short-time sequence for ASM imaging of the heads of healthy volunteers (n=2), and we investigated the similarity between the obtained ASM images and diffusion kurtosis (DK) images to determine the utility of the ASM for clinical uses. This study appears to be the first to report ASM images of the human head. We observed that the short-time sequence for the ASM imaging of the head can be scanned in approx. 3 min at 1.5T MRI. The noise reduction effect of median filter processing was confirmed on the ASM images scanned by this sequence. The obtained ASM images showed a weak correlation with the DK images, indicating that the ASM images are restricted diffusion-weighted images. The new shorttime imaging sequence could thus be used in clinical studies applying the ASM. en-copyright= kn-copyright= en-aut-name=SugimotoKohei en-aut-sei=Sugimoto en-aut-mei=Kohei 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=YoshimuraYuuki en-aut-sei=Yoshimura en-aut-mei=Yuuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HamadaKentaro en-aut-sei=Hamada en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KhasawnehAbdullah en-aut-sei=Khasawneh en-aut-mei=Abdullah kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= en-aut-name=KonishiKohei en-aut-sei=Konishi en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshizakaHinata en-aut-sei=Ishizaka en-aut-mei=Hinata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 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=12 ORCID= en-aut-name=KamizakiRyo en-aut-sei=Kamizaki en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KanazawaSusumu en-aut-sei=Kanazawa en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= affil-num=1 en-affil=Radiological Technology, Graduate School of Health 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=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Radiological Technology, Graduate School of Health 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=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=apparent diffusion coefficient kn-keyword=apparent diffusion coefficient en-keyword=apparent diffusion coefficient subtraction method kn-keyword=apparent diffusion coefficient subtraction method en-keyword=diffusion kurtosis imaging kn-keyword=diffusion kurtosis imaging en-keyword=restricted diffusion kn-keyword=restricted diffusion en-keyword=short-time imaging kn-keyword=short-time imaging END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=1 article-no= start-page=20 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220207 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of targetable kinases in idiopathic pulmonary fibrosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Tyrosine kinase activation plays an important role in the progression of pulmonary fibrosis. In this study, we analyzed the expression of 612 kinase-coding and cancer-related genes using next-generation sequencing to identify potential therapeutic targets for idiopathic pulmonary fibrosis (IPF). Methods Thirteen samples from five patients with IPF (Cases 1-5) and eight samples from four patients without IPF (control) were included in this study. Six of the thirteen samples were obtained from different lung segments of a single patient who underwent bilateral pneumonectomy. Gene expression analysis of IPF lung tissue samples (n = 13) and control samples (n = 8) was performed using SureSelect RNA Human Kinome Kit. The expression of the selected genes was further confirmed at the protein level by immunohistochemistry (IHC). Results Gene expression analysis revealed a correlation between the gene expression signatures and the degree of fibrosis, as assessed by Ashcroft score. In addition, the expression analysis indicated a stronger heterogeneity among the IPF lung samples than among the control lung samples. In the integrated analysis of the 21 samples, DCLK1 and STK33 were found to be upregulated in IPF lung samples compared to control lung samples. However, the top most upregulated genes were distinct in individual cases. DCLK1, PDK4, and ERBB4 were upregulated in IPF case 1, whereas STK33, PIM2, and SYK were upregulated in IPF case 2. IHC revealed that these proteins were expressed in the epithelial layer of the fibrotic lesions. Conclusions We performed a comprehensive kinase expression analysis to explore the potential therapeutic targets for IPF. We found that DCLK1 and STK33 may serve as potential candidate targets for molecular targeted therapy of IPF. In addition, PDK4, ERBB4, PIM2, and SYK might also serve as personalized therapeutic targets of IPF. Additional large-scale studies are warranted to develop personalized therapies for patients with IPF. en-copyright= kn-copyright= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao 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=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=OkawaSachi en-aut-sei=Okawa en-aut-mei=Sachi 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=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SenooSatoru en-aut-sei=Senoo en-aut-mei=Satoru 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=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakasukaTakamasa en-aut-sei=Nakasuka en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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=15 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=16 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=17 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=18 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=19 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 Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=18 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=19 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=Idiopathic pulmonary fibrosis kn-keyword=Idiopathic pulmonary fibrosis en-keyword=RNA sequencing kn-keyword=RNA sequencing en-keyword=Molecular therapeutic target kn-keyword=Molecular therapeutic target en-keyword=Personalized therapy kn-keyword=Personalized therapy END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=1 article-no= start-page=348 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211229 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Homologous Recombination Deficiencies and Hereditary Tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Homologous recombination (HR) is a vital process for repairing DNA double-strand breaks. Germline variants in the HR pathway, comprising at least 10 genes, such as BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK2, NBS1(NBN), PALB2, RAD51C, and RAD51D, lead to inherited susceptibility to specific types of cancers, including those of the breast, ovaries, prostate, and pancreas. The penetrance of germline pathogenic variants of each gene varies, whereas all their associated protein products are indispensable for maintaining a high-fidelity DNA repair system by HR. The present review summarizes the basic molecular mechanisms and components that collectively play a role in maintaining genomic integrity against DNA double-strand damage and their clinical implications on each type of hereditary tumor. en-copyright= kn-copyright= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= affil-num=1 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=homologous recombination deficiency (HRD) kn-keyword=homologous recombination deficiency (HRD) en-keyword=hereditary tumor kn-keyword=hereditary tumor en-keyword=germline kn-keyword=germline en-keyword=cancer predisposition kn-keyword=cancer predisposition en-keyword=multi-gene panel testing (MGPT) kn-keyword=multi-gene panel testing (MGPT) en-keyword=BRCAness kn-keyword=BRCAness END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=3 article-no= start-page=1726 end-page=1740 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211022 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Crosstalk between Cancer Cells and Fibroblasts for the Production of Monocyte Chemoattractant Protein-1 in the Murine 4T1 Breast Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=The chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) is shown to promote the progression of breast cancer. We previously identified cancer cell-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) as a potential regulator of MCP-1 production in the murine 4T1 breast cancer, but it played a minimum role in overall MCP-1 production. Here, we evaluated the crosstalk between 4T1 cells and fibroblasts. When fibroblasts were co-cultured with 4T1 cells or stimulated with the culture supernatants of 4T1 cells (4T1-sup), MCP-1 production by fibroblasts markedly increased. 4T1 cells expressed mRNA for platelet-derived growth factor (PDGF)-a, b and c, and the PDGF receptor inhibitor crenolanib almost completely inhibited 4T1-sup-induced MCP-1 production by fibroblasts. However, PDGF receptor antagonists failed to reduce MCP-1 production in tumor-bearing mice. Histologically, 4T1 tumors contained a small number of alpha SMA-positive fibroblasts, and Mcp-1 mRNA was mainly associated with macrophages, especially those surrounding necrotic lesions on day 14, by in situ hybridization. Thus, although cancer cells have the capacity to crosstalk with fibroblasts via PDGFs, this crosstalk does not play a major role in MCP-1 production or cancer progression in this model. Unraveling complex crosstalk between cancer cells and stromal cells will help us identify new targets to help treat breast cancer patients. en-copyright= kn-copyright= en-aut-name=ImamuraMayu en-aut-sei=Imamura en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiTiantian en-aut-sei=Li en-aut-mei=Tiantian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 ORCID= en-aut-name=MukaidaNaofumi en-aut-sei=Mukaida en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=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=Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa 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=breast cancer kn-keyword=breast cancer en-keyword=chemokine kn-keyword=chemokine en-keyword=lung metastasis kn-keyword=lung metastasis en-keyword=fibroblasts kn-keyword=fibroblasts en-keyword=macrophages kn-keyword=macrophages en-keyword=tumor microenvironment kn-keyword=tumor microenvironment END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=23 article-no= start-page=12809 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=YES1 as a Therapeutic Target for HER2-Positive Breast Cancer after Trastuzumab and Trastuzumab-Emtansine (T-DM1) Resistance Development en-subtitle= kn-subtitle= en-abstract= kn-abstract=Trastuzumab-emtansine (T-DM1) is a therapeutic agent molecularly targeting human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC), and it is especially effective for MBC with resistance to trastuzumab. Although several reports have described T-DM1 resistance, few have examined the mechanism underlying T-DM1 resistance after the development of acquired resistance to trastuzumab. We previously reported that YES1, a member of the Src family, plays an important role in acquired resistance to trastuzumab in HER2-amplified breast cancer cells. We newly established a trastuzumab/T-DM1-dual-resistant cell line and analyzed the resistance mechanisms in this cell line. At first, the T-DM1 effectively inhibited the YES1-amplified trastuzumab-resistant cell line, but resistance to T-DM1 gradually developed. YES1 amplification was further enhanced after acquired resistance to T-DM1 became apparent, and the knockdown of the YES1 or the administration of the Src inhibitor dasatinib restored sensitivity to T-DM1. Our results indicate that YES1 is also strongly associated with T-DM1 resistance after the development of acquired resistance to trastuzumab, and the continuous inhibition of YES1 is important for overcoming resistance to T-DM1. en-copyright= kn-copyright= en-aut-name=FujiharaMiwa en-aut-sei=Fujihara en-aut-mei=Miwa 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=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko 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=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ZhuYidan en-aut-sei=Zhu en-aut-mei=Yidan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MamoriTomoka en-aut-sei=Mamori en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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=10 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=11 ORCID= en-aut-name=AbeYuko en-aut-sei=Abe en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HatonoMinami en-aut-sei=Hatono en-aut-mei=Minami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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=15 ORCID= en-aut-name=KochiMariko en-aut-sei=Kochi en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 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=18 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=19 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=20 ORCID= affil-num=1 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=2 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=3 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=4 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=5 en-affil=Departments of Pharmacy, Okayama University Hospital 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 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=9 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=10 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=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 General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 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=16 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=17 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=18 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=19 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=20 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=YES1 kn-keyword=YES1 en-keyword=T-DM1 kn-keyword=T-DM1 en-keyword=dasatinib kn-keyword=dasatinib en-keyword=drug resistance kn-keyword=drug resistance END start-ver=1.4 cd-journal=joma no-vol=2021 cd-vols= no-issue=8 article-no= start-page=rjab336 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210814 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Robot-assisted thoracoscopic lobectomy for severe incomplete interlober fissure en-subtitle= kn-subtitle= en-abstract= kn-abstract=An incomplete interlobar fissure makes thoracoscopic lobectomy difficult and is predictive of morbidity after thoracoscopic lobectomy. This report demonstrates the robot-assisted thoracoscopic (RATS) lobectomy technique for patients with severe incomplete interlobar fissures. A fissureless approach was chosen for pulmonary resection. Near-infrared fluorescence imaging with intravenous indocyanine green (ICG) was used to detect the interlobar line after transection of the bronchus, pulmonary artery and vein. Interlobar fissure was identified and divided by robotic staplers. This combined technique using ICG and fissureless lobectomy made RATS lobectomy safe for patients with severe incomplete interlobar fissures. en-copyright= kn-copyright= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio 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=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 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=7 ORCID= en-aut-name=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=10 article-no= start-page=5658 end-page=5669 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Meticulous closure of collateral vessels in the perihilar mediastinal pleura to control intraoperative bleeding during lung transplantation for pulmonary hypertension en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Massive blood transfusion compensating hemorrhage during lung transplantation (LT) results in primary graft dysfunction (PGD) and worse outcomes after LT. Collateral vessels in the perihilar mediastinal pleura could be the source of hemorrhage during LT in patients with pulmonary hypertension (PH). The purpose of this study was to examine the effect of closure with hemoclips of the vessels in the perihilar mediastinal pleura on the risk of intraoperative hemorrhage and outcomes after LT in patients with PH.

Methods: We retrospectively reviewed 80 patients who underwent LT, including 13 patients with primary PH, 29 patients with secondary PH, and 38 patients with non-PH.

Results: The median number of hemoclips was significantly higher in the primary PH group than in the non-PH group (P=0.0045) or secondary PH group (P=0.0060). The intraoperative blood loss, transfusion volume, maximum PGD grade, and the 30-day and 90-day mortality rates in the primary PH group were equivalent to those in the other two groups.

Conclusions: Meticulous closure of collateral vessels in the perihilar mediastinal pleura during LT in patients with primary PH allowed intraoperative hemorrhage to be controlled and might be associated with acceptable mortality rate in these patients similar to that of LT in patients with other diseases. en-copyright= kn-copyright= en-aut-name=YamamotoHaruchika en-aut-sei=Yamamoto en-aut-mei=Haruchika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=ImanishiKentaro en-aut-sei=Imanishi en-aut-mei=Kentaro 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=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= en-keyword=Lung transplantation (LT) kn-keyword=Lung transplantation (LT) en-keyword=pulmonary hypertension (PH) kn-keyword=pulmonary hypertension (PH) en-keyword=collateral vessel kn-keyword=collateral vessel en-keyword=bleeding kn-keyword=bleeding en-keyword=mortality kn-keyword=mortality END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=48 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
RAD51D (RAD51 paralog D) is an intermediate cancer susceptibility gene for primary ovarian cancer, including fallopian tube and peritoneal carcinomas and breast cancer. Although gynecological non-epithelial tumors such as uterine sarcomas are associated with genomic instability, including BRCA impairment, there is no clear evidence of the relationship between RAD51D variants and the risk of sarcoma development.

Case presentation
A Japanese woman in her 50s underwent multiple surgical resections and several regimens of chemotherapy for tumors that originated in the retroperitoneum and recurred in the peritoneum over a clinical course of approximately 4 years. The peritoneal tumor was histologically diagnosed as a leiomyosarcoma and was genetically identified to show a splice variant of RAD51D c.904-2A > T [NM_002878] through tumor profiling performed as a part of cancer precision medicine. The confirmatory genetic test performed after genetic counseling revealed that the RAD51D splicing variant detected in her tumor was of germline origin. In silico analyses supported the possible pathogenicity of the detected splice variant of RAD51D with a predicted attenuation in mRNA transcription and truncated protein production due to frameshifting, which was attributed to a single-nucleotide alteration in the splicing acceptor site at the 3 '-end of intron 9 of RAD51D. Considering her unfavorable clinical outcome, which showed a highly aggressive phenotype of leiomyosarcoma with altered RAD51D, this case provided novel evidence for the relationship of a RAD51D splicing variant with malignant tumor development or progression. We report the findings of this rare case with possible involvement of the germline variant of RAD51D c.904-2A > T as a potential predisposing factor for malignant tumors, including leiomyosarcoma. Conclusions We present the findings of a case of leiomyosarcoma in the peritoneum of a female patient with a novel germline splicing variant of RAD51D as potential evidence for the pathogenicity of the variant and its involvement in the risk of sarcoma etiology and/or development. To the best of our knowledge, this is the first case report describing a leiomyosarcoma carrying a germline RAD51D splicing variant and elucidating its pathogenicity on the basis of computational prediction of the impairment of normal transcription and the presumed loss of functional protein production. en-copyright= kn-copyright= en-aut-name=FutagawaMashu en-aut-sei=Futagawa en-aut-mei=Mashu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KochiMariko en-aut-sei=Kochi en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UrakawaYusaku en-aut-sei=Urakawa en-aut-mei=Yusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SogawaReimi en-aut-sei=Sogawa en-aut-mei=Reimi 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=Okazawa-SakaiMika en-aut-sei=Okazawa-Sakai en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=ShinozakiKatsunori en-aut-sei=Shinozaki en-aut-mei=Katsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=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=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Division of Clinical Oncology, Hiroshima Prefecture Hospital kn-affil= affil-num=10 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=RAD51D kn-keyword=RAD51D en-keyword=Splice variant kn-keyword=Splice variant en-keyword=Leiomyosarcoma kn-keyword=Leiomyosarcoma en-keyword=Homologous recombination (HR) kn-keyword=Homologous recombination (HR) en-keyword=Cancer susceptibility kn-keyword=Cancer susceptibility en-keyword=Presumed germline pathogenic variant (PGPV) kn-keyword=Presumed germline pathogenic variant (PGPV) 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=2021 dt-pub=20210924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=乳腺脂肪組織の微小環境下で成長する乳がん幹細胞の病理組織学的および免疫組織化学的研究) kn-title=Histopathological and Immunohistochemical Studies on The Breast Cancer Stem Cells Developed in The Microenvironment of Mouse Mammary Fat Pads en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HAGAR ALI ABDUL RAHEEM ABU QUORA en-aut-sei=HAGAR ALI ABDUL RAHEEM ABU QUORA en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil=岡山大学大学院ヘルスシステム統合科学研究科 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=2021 dt-pub=20210924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=チロシンキナーゼABLはRUNX2のチロシンリン酸化により乳癌の浸潤を促進する kn-title=RUNX2 Phosphorylation by Tyrosine Kinase ABL Promotes Breast Cancer Invasion en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HeFang en-aut-sei=He en-aut-mei=Fang kn-aut-name=賀芳 kn-aut-sei=賀 kn-aut-mei=芳 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 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=2021 dt-pub=20210924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=イソフラボンの乳癌細胞増殖における効果と乳癌治療における影響 kn-title=Effect of isoflavones on breast cancer cell development and their impact on breast cancer treatments en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HatonoMinami en-aut-sei=Hatono en-aut-mei=Minami kn-aut-name=鳩野みなみ kn-aut-sei=鳩野 kn-aut-mei=みなみ aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=521 cd-vols= no-issue=28 article-no= start-page=142 end-page=154 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202111 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Chronic exposure to FGF2 converts iPSCs into cancer stem cells with an enhanced integrin/focal adhesion/PI3K/AKT axis en-subtitle= kn-subtitle= en-abstract= kn-abstract=We previously demonstrated the conversion of normal stem cells, including induced pluripotent stem cells (iPSCs), into cancer stem cells (CSCs) without genetic manipulation. Herein, we designed a meta-analysis to assess gene expression profiles in different breast cancer cell lines focusing on the secretory factors responsible for conversion. As a result, fibroblast growth factor 2 (FGF2) was found to be the best candidate in T47D and BT549 cells, of which conditioned medium was previously successful in inducing CSCs. When treated with 3.1 μg/ml FGF2, mouse iPSCs not only maintained survival without LIF for three weeks but also acquired growth ability independent of FGF2. The resultant cells exhibited expression of stemness and cancer stem cell markers, sphere-forming ability, differentiation, and tumorigenicity with malignancy. The primary cultures of the tumor confirmed the signatures of CSCs with two different phenotypes with or without GFP expression under control of the Nanog promoter. Bioinformatic analysis of gene expression profiles suggested constitutive autocrine activation of the FGF receptor, integrins, focal adhesions, and PI3K/AKT pathways. FGF2 could potently initiate cancer as a component of the inflammatory microenvironment. en-copyright= kn-copyright= en-aut-name=ShetaMona en-aut-sei=Sheta en-aut-mei=Mona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HassanGhmkin en-aut-sei=Hassan en-aut-mei=Ghmkin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AfifySaid M. en-aut-sei=Afify en-aut-mei=Said M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MonzurSadia en-aut-sei=Monzur en-aut-mei=Sadia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KumonKazuki en-aut-sei=Kumon en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Abu QuoraHagar A. en-aut-sei=Abu Quora en-aut-mei=Hagar A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FarahatMahmoud en-aut-sei=Farahat en-aut-mei=Mahmoud kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ZahraMaram H. en-aut-sei=Zahra en-aut-mei=Maram H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FuXiaoying en-aut-sei=Fu en-aut-mei=Xiaoying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SenoAkimasa en-aut-sei=Seno en-aut-mei=Akimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SenoMasaharu en-aut-sei=Seno en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=2 en-affil=Department of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=3 en-affil=Department of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=4 en-affil=Department of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=5 en-affil=Department of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=6 en-affil=Department of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=7 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=9 en-affil=Department of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=10 en-affil=Department of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=11 en-affil=Department of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= en-keyword=Cancer initiation kn-keyword=Cancer initiation en-keyword=Cancer stem cells kn-keyword=Cancer stem cells en-keyword=iPSCs kn-keyword=iPSCs en-keyword=FGF2 kn-keyword=FGF2 en-keyword=Chronic inflammation kn-keyword=Chronic inflammation END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=5 article-no= start-page=659 end-page=661 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Added Diagnostic Value of Cerebrospinal Fluid Carcinoembryonic Antigen in a Patient with Leptomeningeal Carcinomatosis as the Initial Manifestation of Gastric Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 77-year-old woman with no history of malignancy presented with anorexia and bilateral lower extremity weakness. Her consciousness level worsened daily, so we performed a lumbar puncture. Cerebrospinal fluid (CSF) analysis indicated meningitis, but three rounds of CSF cytology showed no malignant cells. The patient’s carcinoembryonic antigen (CEA) level was highly elevated in CSF, but normal in serum. Through gadolinium-enhanced brain/spinal magnetic resonance imaging and gastrointestinal endoscopy, she was diagnosed with leptomeningeal carcinomatosis (LC) from gastric cancer. CEA level in CSF facilitated the diagnosis of LC from gastric cancer because there were no malignant cells on CSF cytology. en-copyright= kn-copyright= en-aut-name=InoRiku en-aut-sei=Ino en-aut-mei=Riku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SadaKen-ei en-aut-sei=Sada en-aut-mei=Ken-ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyauchiAtsushi en-aut-sei=Miyauchi en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HashimotoDaisuke en-aut-sei=Hashimoto en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NojimaShigeru en-aut-sei=Nojima en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamanakaShingo en-aut-sei=Yamanaka en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawamuraMasafumi en-aut-sei=Kawamura en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital kn-affil= affil-num=7 en-affil=Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital kn-affil= en-keyword=leptomeningeal carcinomatosis kn-keyword=leptomeningeal carcinomatosis en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=carcinoembryonic antigen kn-keyword=carcinoembryonic antigen en-keyword=cerebrospinal fluid cytology kn-keyword=cerebrospinal fluid cytology END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=4 article-no= start-page=100191 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gefitinib induction followed by chemoradiotherapy in EGFR-mutant, locally advanced non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The role of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) induction coupled with standard concurrent chemoradiotherapy (CRT) is unclear in unresectable, stage III, EGFR-mutant non-small-cell lung cancer (NSCLC). Therefore, a phase II trial was conducted to evaluate the efficacy and safety of gefitinib induction followed by CRT in this disease setting.
Patients and methods: Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy (250 mg/day) for 8 weeks. Subsequently, patients without disease progression during induction therapy were administered cisplatin and docetaxel (40 mg/m(2) each) on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy. The primary endpoint was the 2-year overall survival (OS) rate, which was hypothesized to reach 85%, with a threshold of the lower limit of 60%.
Results: Twenty patients (median age: 66 years; male/female: 9/11; histology: 20 adenocarcinoma; stage IIIA/IIIB: 9/11; and exon 19/21: 10/10) were enrolled. The 2-year OS rate was 90% (90% confidence interval: 71.4% to 96.8%), indicating that this trial met the primary objective. The overall response rate and 1- and 2-year progression-free survival rates were 85.0%, 58.1%, and 36.9%, respectively. Grade >= 3 adverse events (>10%) included hepatic toxicity during the induction phase and neutropenia and febrile neutropenia in the CRT phase. Radiation pneumonitis grade >= 3 or treatment-related death did not occur.
Conclusions: This is the first prospective study to demonstrate the favorable efficacy and safety of EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III NSCLC. Further confirmatory studies are needed. en-copyright= kn-copyright= en-aut-name=HottaK. en-aut-sei=Hotta en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaekiS. en-aut-sei=Saeki en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamaguchiM. en-aut-sei=Yamaguchi en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HaradaD. en-aut-sei=Harada en-aut-mei=D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BesshoA. en-aut-sei=Bessho en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaK. en-aut-sei=Tanaka en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=InoueK. en-aut-sei=Inoue en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=GembaK. en-aut-sei=Gemba en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShiojiriM. en-aut-sei=Shiojiri en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatoY. en-aut-sei=Kato en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NinomiyaT. en-aut-sei=Ninomiya en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KuboT. en-aut-sei=Kubo en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KishimotoJ. en-aut-sei=Kishimoto en-aut-mei=J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShioyamaY. en-aut-sei=Shioyama en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KatsuiK. en-aut-sei=Katsui en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SasakiJ. en-aut-sei=Sasaki en-aut-mei=J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KiuraK. en-aut-sei=Kiura en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SugioK. en-aut-sei=Sugio en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Kumamoto University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center kn-affil= affil-num=4 en-affil=Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Kyushu University Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Kitakyushu Municipal Medical Center kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Chugoku Central Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama 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 Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Center for Clinical and Translational Research, Kyushu University Hospital kn-affil= affil-num=14 en-affil=Clinical Radiology, Radiology Informatics and Network, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=15 en-affil=Department of Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Department of Thoracic and Breast Surgery, Oita University kn-affil= en-keyword=non-small-cell lung cancer kn-keyword=non-small-cell lung cancer en-keyword=locally advanced setting kn-keyword=locally advanced setting en-keyword=chemoradiation kn-keyword=chemoradiation en-keyword=epidermal growth factor receptor kn-keyword=epidermal growth factor receptor END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=10 article-no= start-page=1784 end-page=1792 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202192 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hereditary pancreatic cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pancreatic cancer is associated with both family and hereditary cancer syndromes. Multigene panel testing for pancreatic cancer detected the germline variants BRCA1/2, PALB2, ATM, TP53, MLH1, STK11/LKB1, APC, CDKN2A, and SPINK1/ PRSS1 as high-risk genes. A latest genome-wide association study revealed the common, but low-risk germline variants in pancreatic cancer patients. Active pancreatic surveillance using magnetic resonance imaging and endoscopic ultrasound is recommended for high-risk individuals who have a family history of pancreatic cancer or harbor these germline pathogenic variants to improve the detection rate and prognosis of pancreatic cancer. Since poly-ADP-ribose polymerase (PARP) inhibitor has been shown to be effective in improving the prognosis of BRCA -positive pancreatic cancer as well as hereditary breast and ovarian cancer syndrome, PARP inhibitor therapy is currently being applied as precision medicine to pancreatic cancer patients harboring the BRCA1/2 germline variant. This review highlights the importance of surveillance for germline pathogenic variants in pancreatic cancer and is expected to lead to improvements in the diagnosis and prevention of pancreatic cancer as well as facilitate the development of effective therapeutic strategies and precision medicine. en-copyright= kn-copyright= en-aut-name=AbeKodai en-aut-sei=Abe en-aut-mei=Kodai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitagoMinoru en-aut-sei=Kitago en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KitagawaYuko en-aut-sei=Kitagawa en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= affil-num=1 en-affil=Department of Surgery, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Department of Surgery, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Department of Surgery, Keio University School of Medicine kn-affil= affil-num=4 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Cancer predisposition gene kn-keyword=Cancer predisposition gene en-keyword=Familial pancreatic cancer kn-keyword=Familial pancreatic cancer en-keyword=Hereditary pancreatic cancer kn-keyword=Hereditary pancreatic cancer en-keyword=Multigene panel kn-keyword=Multigene panel en-keyword=testing kn-keyword=testing en-keyword=Surveillance kn-keyword=Surveillance END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=4 article-no= start-page=461 end-page=469 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bendamustine Plus Rituximab as Salvage Treatment for Patients with Relapsed or Refractory Low-grade B-cell Lymphoma and Mantle Cell Lymphoma: A Single-Center Retrospective Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bendamustine plus rituximab (B-R) is an effective therapy for relapsed or refractory (r/r) low-grade B-cell lymphoma (LGBCL) and mantle cell lymphoma (MCL); however, clinical data from Japanese patients treated with B-R therapy are limited. We retrospectively evaluated the efficacy and safety of B-R therapy in 42 patients who received B-R therapy at our hospital for r/r LGBCL and MCL. All patients received intravenous (IV) ritux-imab 375 mg/m2 on day 1 and IV bendamustine 90 mg/m2 on days 2 and 3 every 28 days for up to 6 cycles. The common histologic subtypes were follicular lymphoma (n = 29, 70%), marginal zone lymphoma (n = 6, 14%), and MCL (n = 5, 12%). The overall response rate was 93%, with 62% complete response and complete response unconfirmed. The median progression-free survival (PFS) was 38 months (95% confidence interval [CI], 24.6 to not reached [NR]), and the median overall survival (OS) was 80 months (95% CI, 60.7 to NR). Patients receiving a cumulative dose of bendamustine ≥ 720 mg/m2 showed a significantly longer PFS and OS. Grade 3/4 adverse events (≥ 10%) included neutropenia (55%), lymphopenia (69%), and nausea (24%). B-R therapy was effective and well tolerated, and the cumulative dose of bendamustine was associated with a favorable outcome. en-copyright= kn-copyright= en-aut-name=MurakamiHiroyuki en-aut-sei=Murakami en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshiokaTakanori en-aut-sei=Yoshioka en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriyamaTakashi en-aut-sei=Moriyama en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshikawaTatsunori en-aut-sei=Ishikawa en-aut-mei=Tatsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MakitaMasanori en-aut-sei=Makita en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= affil-num=1 en-affil=Department of Hematology, National Hospital Organization Okayama Medical Center kn-affil= affil-num=2 en-affil=Department of Hematology, National Hospital Organization Okayama Medical Center kn-affil= affil-num=3 en-affil=Department of Hematology, National Hospital Organization Okayama Medical Center kn-affil= affil-num=4 en-affil=Department of Hematology, National Hospital Organization Okayama Medical Center kn-affil= affil-num=5 en-affil=Department of Hematology, National Hospital Organization Okayama Medical Center kn-affil= affil-num=6 en-affil=Department of Hematology, National Hospital Organization Okayama Medical Center kn-affil= en-keyword=bendamustine kn-keyword=bendamustine en-keyword=low grade B-cell lymphoma kn-keyword=low grade B-cell lymphoma en-keyword=mantle cell lymphoma kn-keyword=mantle cell lymphoma END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=4 article-no= start-page=431 end-page=437 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Differences in Attitudes and Practices of Cancer Pain Management between Medical Oncologists and Palliative Care Physicians en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study aimed to evaluate whether there are differences in the attitudes and practices of cancer pain manage-ment between medical oncologists and palliative care physicians. An online nationwide survey was used to collect responses from board-certified medical oncologists and palliative care physicians in Japan. The survey questionnaire comprised 30 questions. The differences in responses between medical oncologists and palliative care physicians were examined. Out of the 1,227 questionnaires sent, 522 (42.5%) were returned. After apply-ing the exclusion criteria, 445 questionnaires (medical oncologists: n = 283; palliative care physicians: n = 162) were retained for analysis. Among the questions about potential barriers to optimal cancer pain man-agement, both medical oncologists and palliative care physicians considered the reluctance of patients to take opioids due to fear of adverse effects as the greatest barrier. Significantly different ratings between medical oncologists and palliative care physicians were observed on 5 of the 8 questions in this area. Significantly differ-ent ratings were observed for all questions concerning pain specialists and their knowledge. For effective cancer pain management, it is important to account for differences in attitudes and practice between medical oncolo-gists and palliative care physicians. en-copyright= kn-copyright= en-aut-name=KunitomiToshiki en-aut-sei=Kunitomi en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NasuJunichirou en-aut-sei=Nasu en-aut-mei=Junichirou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MinamiDaisuke en-aut-sei=Minami en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=NishieHiroyuki en-aut-sei=Nishie en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SaitoShinya en-aut-sei=Saito en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=MatsuokaJunji en-aut-sei=Matsuoka en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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 Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=3 en-affil=Palliative Care Team, Okayama University Hospital 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=Palliative Care Team, Okayama University Hospital kn-affil= affil-num=6 en-affil=Palliative Care Team, Okayama University Hospital 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= en-keyword=cancer pain management kn-keyword=cancer pain management en-keyword=opioid kn-keyword=opioid en-keyword=medical oncologist kn-keyword=medical oncologist en-keyword=palliative care physician kn-keyword=palliative care physician en-keyword=barriers kn-keyword=barriers END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=8 article-no= start-page=1078 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210822 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Factors Affecting Participation in Leisure Activities in Patients after Breast Cancer Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The purpose of this study was to investigate the factors related to patient's participation in leisure activity in breast cancer patients with axillary lymph node dissection at 3 months after surgery. Methods: In total, 160 women who were employed before their surgery were evaluated. Age, body mass index (BMI), employment, level of lymph node dissection, marital status, children, coresident household members, preoperative chemotherapy, postoperative chemotherapy, postoperative hormonal therapy, postoperative radiotherapy, shoulder range of motion test, upper limb function, quality of life, and patient's participation in leisure activity were evaluated. Results: Patients who undertook leisure activities constituted the leisure activity group, and patients who did not constituted the non-leisure activity group. Global health status, emotional function, social function, and dyspnea were significantly different between the leisure activity group and the non-leisure activity group at 3 months after surgery (p < 0.05). Regarding factors that affected participation in leisure activities, logistic regression analysis showed that only participation in leisure activities before surgery was significantly associated with participation in leisure activities at 3 months after surgery (p < 0.05). Conclusion: Patients who did not participate in leisure activities prior to surgery were unlikely to participate 3 months after surgery and thus require intervention to encourage their involvement. en-copyright= kn-copyright= en-aut-name=AkezakiYoshiteru en-aut-sei=Akezaki en-aut-mei=Yoshiteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KikuuchiMasato en-aut-sei=Kikuuchi en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TominagaRitsuko en-aut-sei=Tominaga en-aut-mei=Ritsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurokawaHideaki en-aut-sei=Kurokawa en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkamotoMasaki en-aut-sei=Okamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HamadaMakiko en-aut-sei=Hamada en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AogiKenjiro en-aut-sei=Aogi en-aut-mei=Kenjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhsumiShozo en-aut-sei=Ohsumi en-aut-mei=Shozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugiharaShinsuke en-aut-sei=Sugihara en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Physical Therapy, Kochi Professional University of Rehabilitation kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=6 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=7 en-affil=Department of Rehabilitation Medicine, Higashi Tokushima Medical Center kn-affil= affil-num=8 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=9 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=10 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=leisure kn-keyword=leisure en-keyword=surgery kn-keyword=surgery en-keyword=rehabilitation kn-keyword=rehabilitation en-keyword=factor kn-keyword=factor END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=3 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021721 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=New field‑in‑field with two reference points method for whole breast radiotherapy: Dosimetric analysis and radiation‑induced skin toxicities assessment en-subtitle= kn-subtitle= en-abstract= kn-abstract=The usefulness of the field‑in‑field with two reference points (FIF w/ 2RP) method, in which the dose reference points are set simultaneously at two positions in the irradiation field and the high‑dose range is completely eliminated, was examined in the present study with the aim of decreasing acute skin toxicity in adjuvant breast radiotherapy (RT). A total of 573 patients with breast cancer who underwent postoperative whole breast RT were classified into 178 cases with wedge (W) method, 142 cases with field‑in‑field without 2 reference points (FIF w/o 2RP) method and 253 cases with FIF w/ 2RP method. Using the FIF w/ 2RP method, the high‑dose range was the lowest among the three irradiation methods. The planning target volume (PTV) V105% and the breast PTV for evaluation (BPe) V105% decreased to 0.09 and 0.10%, respectively. The FIF w/ 2RP method vs. the FIF w/o 2RP method had a strong association (η) with PTV V105% (η=0.79; P<0.001) and BPe V105% (η=0.76; P<0.001). The FIF w/ 2RP method had a significant impact on lowering the skin toxicity grade in weeks 3 and 4, and increasing the occurrence of skin toxicity grade 0. The FIF w/ 2RP method vs. the W method had a moderate association with skin toxicity grade at week 3 (η=0.49; P<0.001). Using the FIF w/ 2RP method, the high‑dose range V105% of the target decreased to 0%, and skin adverse events were decreased in conjunction. For patients with early‑stage breast cancer, particularly patients with relatively small‑sized breasts, the FIF w/ 2RP method may be an optimal irradiation method. en-copyright= kn-copyright= en-aut-name=TekikiNouha en-aut-sei=Tekiki en-aut-mei=Nouha 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=IshizakaHinata en-aut-sei=Ishizaka en-aut-mei=Hinata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KhasawnehAbdullah en-aut-sei=Khasawneh en-aut-mei=Abdullah kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=HamadaKentaro en-aut-sei=Hamada en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KonishiKohei en-aut-sei=Konishi en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugimotoKohei en-aut-sei=Sugimoto en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=SugiyamaSoichi en-aut-sei=Sugiyama en-aut-mei=Soichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 ORCID= en-aut-name=KatayamaNorihisa en-aut-sei=Katayama en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=IharaHiroki en-aut-sei=Ihara en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KanazawaSusumu en-aut-sei=Kanazawa en-aut-mei=Susumu 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, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=10 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Radiology, Kagawa Prefectural Central Hospital kn-affil= affil-num=14 en-affil=Department of Radiology, Iwakuni Clinical Center kn-affil= affil-num=15 en-affil=Department of Radiology, Tsuyama Chuo Hospital kn-affil= affil-num=16 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=field‑in‑field radiotherapy kn-keyword=field‑in‑field radiotherapy en-keyword=dose reference point kn-keyword=dose reference point en-keyword=acute skin toxicity kn-keyword=acute skin toxicity en-keyword=dose distribution kn-keyword=dose distribution en-keyword=high‑dose area kn-keyword=high‑dose area END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue= article-no= start-page=729192 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210720 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=RUNX2 Phosphorylation by Tyrosine Kinase ABL Promotes Breast Cancer Invasion (vol 11, 665273, 2021) en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HeFang en-aut-sei=He en-aut-mei=Fang 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=AsanoYosuke en-aut-sei=Asano en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamuraYuriko en-aut-sei=Yamamura en-aut-mei=Yuriko 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=RoseJose La en-aut-sei=Rose en-aut-mei=Jose La kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=9 ORCID= en-aut-name=RottapelRobert en-aut-sei=Rottapel en-aut-mei=Robert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Princess Margaret Cancer Center, University Health Network, University of Toronto kn-affil= affil-num=7 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 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=Princess Margaret Cancer Center, University Health Network, University of Toronto kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=ABL-Abelson murine leukemia viral oncogene homolog kn-keyword=ABL-Abelson murine leukemia viral oncogene homolog en-keyword=Runx2 (runt-related transcription factor 2) kn-keyword=Runx2 (runt-related transcription factor 2) en-keyword=tyrosine kn-keyword=tyrosine en-keyword=phosphorylation kn-keyword=phosphorylation en-keyword=invasion kn-keyword=invasion END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=7 article-no= start-page=3475 end-page=3495 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Microenvironment of mammary fat pads affected the characteristics of the tumors derived from the induced cancer stem cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Breast cancer is the first common cause of cancer-related death in women worldwide. Since the malignancy and aggressiveness of breast cancer have been correlated with the presence of breast cancer stem cells, the establishment of a disease model with cancer stem cells is required for the development of a novel therapeutic strategy. Here, we aimed to evaluate the availability of cancer stem cell models developed from mouse induced pluripotent stem cells with the conditioned medium of different subtypes of breast cancer cell lines, the hormonal-responsive T47D cell line and the triple-negative breast cancer BT549 cell line, to generate in vivo tumor models. When transplanted into the mammary fat pads of BALB/c nude mice, these two model cells formed malignant tumors exhibiting pronounced histopathological characteristics similar to breast cancers. Serial transplantation of the primary cultured cells into mammary fat pads evoked the same features of breast cancer, while this result was perturbed following subcutaneous transplantation. The tumors formed in the mammary fat pads exhibited immune reactivities to prolactin receptor, progesterone receptor, green florescent protein, Ki67, CD44, estrogen receptor alpha/beta and cytokeratin 8, while all of the tumors and their derived primary cells exhibited immunoreactivity to estrogen receptor alpha/beta and cytokeratin 8. Cancer stem cells can be developed from pluripotent stem cells via the secretory factors of cancer-derived cells with the capacity to inherit tissue specificity. However, cancer stem cells should be plastic enough to be affected by the microenvironment of specific tissues. In summary, we successfully established a breast cancer tumor model using mouse induced pluripotent stem cells developed from normal fibroblasts without genetic manipulation. en-copyright= kn-copyright= en-aut-name=Abu QuoraHagar A. en-aut-sei=Abu Quora en-aut-mei=Hagar A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ZahraMaram H. en-aut-sei=Zahra en-aut-mei=Maram H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=El-GhlbanSamah en-aut-sei=El-Ghlban en-aut-mei=Samah kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NairNeha en-aut-sei=Nair en-aut-mei=Neha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AfifySaid M. en-aut-sei=Afify en-aut-mei=Said M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HassanGhmkin en-aut-sei=Hassan en-aut-mei=Ghmkin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NawaraHend M. en-aut-sei=Nawara en-aut-mei=Hend M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShetaMona en-aut-sei=Sheta en-aut-mei=Mona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MonzurSadia en-aut-sei=Monzur en-aut-mei=Sadia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FuXiaoying en-aut-sei=Fu en-aut-mei=Xiaoying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OsmanAmira en-aut-sei=Osman en-aut-mei=Amira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SenoAkimasa en-aut-sei=Seno en-aut-mei=Akimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SenoMasaharu en-aut-sei=Seno en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Division of Biochemistry, Faculty of Science, Menoufia University kn-affil= affil-num=4 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=9 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=10 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=11 en-affil=Department of Histology, Faculty of Medicine, Kafr Elsheikh University kn-affil= affil-num=12 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=13 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=Mammary fat pad kn-keyword=Mammary fat pad en-keyword=microenvironment kn-keyword=microenvironment en-keyword=iPSCs kn-keyword=iPSCs en-keyword=CSCs kn-keyword=CSCs en-keyword=breast cancer kn-keyword=breast cancer END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=11882 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sarcopenia is associated with poor prognosis after chemoradiotherapy in patients with stage III non-small-cell lung cancer: a retrospective analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=We intended to investigate whether muscle and adipose masses were associated with prognosis among patients with stage III non-small-cell lung cancer (NSCLC) who were undergoing chemoradiotherapy (CCRT). We retrospectively explored data of patients with stage III NSCLC who underwent definitive CCRT (>= 60 Gy) between January 2004 and March 2018 at our hospital. We examined the relationship of overall survival (OS) with body mass index (BMI), skeletal muscle index (SMI), psoas muscle index (PMI), visceral adipose tissue index (VAI), subcutaneous adipose tissue index (SAI), and visceral-to-subcutaneous adipose tissue area ratio (VSR) using log-rank tests for the univariate analysis and Cox proportional hazard models for the multivariate analysis. Overall, 16, 32, and 12 patients had stage IIIA, IIIB, and IIIC NSCLC, respectively. The total radiotherapy dose ranged from 60 Gy/30 fractions to 66 Gy/33 fractions. In the univariate analysis, the performance status (PS), BMI, and SMI were associated with OS, whereas the PMI, VAI, SAI, and VSR were not. In the multivariate analysis, the PS and SMI were associated with OS. The hazard ratios and 95% confidence intervals were 2.91 and 1.28-6.64 for PS, and 2.36 and 1.15-4.85 for SMI, respectively. The 1, 3, and 5-year OS rates were 92.1%, 59.6%, and 51.0% in patients with high SMI, and 63.6%, 53.8%, and 17.9% in patients with low SMI, respectively. The SMI correlated with prognosis in our study population, whereas adipose mass did not. Therefore, sarcopenia should be considered while predicting the OS in such patients. en-copyright= kn-copyright= en-aut-name=KatsuiKuniaki en-aut-sei=Katsui en-aut-mei=Kuniaki 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=SugiyamaSoichi en-aut-sei=Sugiyama en-aut-mei=Soichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 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=7 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=8 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=9 ORCID= en-aut-name=KanazawaSusumu en-aut-sei=Kanazawa 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 Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Radiology, Iwakuni Clinical Center kn-affil= affil-num=3 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital 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=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=2 article-no= start-page=294 end-page=305 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021712 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Emphysematous changes and lower levels of plasma irisin are associated with bronchiolitis obliterans syndrome after bilateral living-donor lobar lung transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose
Decreased irisin levels may be associated with the development of emphysema. Similarly, emphysematous changes may develop in patients with chronic lung allograft dysfunction (CLAD) after living-donor lobar lung transplantation (LDLLT). We investigated the severity of emphysematous changes and the relationship between irisin levels and CLAD after bilateral LDLLT and cadaveric lung transplantation (CLT).

Methods
The subjects of this retrospective study were 59 recipients of bilateral LDLLT (n = 31) or CLT (n = 28), divided into a non-CLAD group (n = 41), a LDLLT-CLAD group (n = 11), and a CLT-CLAD group (n = 7). We compared the severity of emphysematous changes, the skeletal muscle mass, and the plasma irisin levels among the groups.

Results
The emphysematous changes were significantly more severe in the LDLLT-CLAD and CLT-CLAD groups (p = 0.046 and 0.036), especially in patients with bronchiolitis obliterans syndrome (BOS), than in the non-CLAD group. Although the skeletal muscle mass was similar in all the groups, the plasma irisin levels were significantly lower in the LDLLT-CLAD group (p = 0.022), especially in the patients with BOS after LDLLT, than in the non-CLAD group.

Conclusion
Emphysematous changes and lower levels of plasma irisin were associated with CLAD, especially in patients with BOS, after bilateral LDLLT. en-copyright= kn-copyright= en-aut-name=ShiotaniToshio en-aut-sei=Shiotani en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=YamamotoHaruchika en-aut-sei=Yamamoto en-aut-mei=Haruchika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 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=7 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=8 ORCID= en-aut-name=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=9 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=10 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=chronic lung allograft dysfunction kn-keyword=chronic lung allograft dysfunction en-keyword=emphysema kn-keyword=emphysema en-keyword=irisin kn-keyword=irisin en-keyword=living-donor kn-keyword=living-donor en-keyword=lung transplantation kn-keyword=lung transplantation END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=3 article-no= start-page=357 end-page=362 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Optimizing the timing of 3.6 mg Pegfilgrastim Administration for Dose-Dense Chemotherapy in Japanese Patients with Breast Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Perioperative dose-dense chemotherapy (DDCT) with pegfilgrastim (Peg) prophylaxis is a standard treatment for high-risk breast cancer. We explored the optimal timing of administration of 3.6 mg Peg, the dose approved in Japan. In the phase II feasibility study of DDCT (adriamycin+cyclophosphamide or epirubicin+cyclophosphamide followed by paclitaxel) for breast cancer, we investigated the feasibility, safety, neutrophil transition, and optimal timing of Peg treatment by administering Peg at days 2, 3, and 4 post-chemotherapy (P2, P3, and P4 groups, respectively). Among the 52 women enrolled, 13 were aged > 60 years. The anthracycline sequence was administered to P2 (n=33), P3 (n=5), and P4 (n=14) patients, and the taxane sequence to P2 (n=38) and P3 (n=6) patients. Both sequences showed no interaction between Peg administration timing and treatment discontinuation, treatment delay, or dose reduction. However, the relative dose intensity (RDI) was significantly different among the groups. The neutrophil count transition differed significantly among the groups receiving the anthracycline sequence. However, the neutrophil count remained in the appropriate range for both sequences in the P2 group. The timing of Peg administration did not substantially affect the feasibility or safety of DDCT. Postoperative day 2 might be the optimal timing for DDCT. en-copyright= kn-copyright= en-aut-name=TakabatakeDaisuke en-aut-sei=Takabatake en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=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=YamamotoMari en-aut-sei=Yamamoto en-aut-mei=Mari 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=IkedaMasahiko en-aut-sei=Ikeda en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= en-aut-name=AogiKenjiro en-aut-sei=Aogi en-aut-mei=Kenjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhsumiShozo en-aut-sei=Ohsumi en-aut-mei=Shozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=NishiyamaYoshitaka en-aut-sei=Nishiyama en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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=15 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=16 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=17 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=18 ORCID= affil-num=1 en-affil=Kochi Health Science Center kn-affil= affil-num=2 en-affil=Okayama University Hospital kn-affil= affil-num=3 en-affil=Hiroshima Citizens Hospital kn-affil= affil-num=4 en-affil=Okayama University Hospital kn-affil= affil-num=5 en-affil=Fukuyama Citizens Hospital kn-affil= affil-num=6 en-affil=Fukuyama Citizens Hospital kn-affil= affil-num=7 en-affil=Fukuyama Citizens Hospital kn-affil= affil-num=8 en-affil=Shikoku Cancer Center kn-affil= affil-num=9 en-affil=Cancer Institute Hospital kn-affil= affil-num=10 en-affil=Shikoku Cancer Center kn-affil= affil-num=11 en-affil=Shikoku Cancer Center kn-affil= affil-num=12 en-affil=Kagawa Prefectural Center Hospital kn-affil= affil-num=13 en-affil=Okayama Saiseikai General Hospital kn-affil= affil-num=14 en-affil=Matsue Red Cross General Hospital kn-affil= affil-num=15 en-affil=Ehime Prefectural Central Hospital kn-affil= affil-num=16 en-affil=Okayama University Hospital kn-affil= affil-num=17 en-affil=Okayama University Hospital kn-affil= affil-num=18 en-affil=Okayama University Hospital kn-affil= en-keyword=dose-dense chemotherapy kn-keyword=dose-dense chemotherapy en-keyword=breast cancer kn-keyword=breast cancer en-keyword=pegfilgrastim kn-keyword=pegfilgrastim END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=3 article-no= start-page=351 end-page=356 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Texture Indices of 18F-FDG PET/CT for Differentiating Squamous Cell Carcinoma and Non-Hodgkin’s Lymphoma of the Oropharynx en-subtitle= kn-subtitle= en-abstract= kn-abstract=We assessed the role of 18F-FDG PET/CT texture indices for the differentiation of squamous cell carcinoma (SCC) and non-Hodgkin’s lymphoma (NHL) in the oropharynx. 18F-FDG PET/CT data for 27 patients with SCC and 25 patients with NHL in the oropharynx were investigated. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and six texture indices (homogeneity, entropy, short-run emphasis, long-run emphasis, low gray-level zone emphasis [LGZE], and high graylevel zone emphasis [HGZE]) were derived from PET images. PET/CT parameters of the SCC patients were compared with those of the NHL patients. The diagnostic accuracy of the indices for differentiating SCC from NHL was calculated by a receiver operating characteristic curve analysis. 18F-FDG uptake in the oropharynx was observed in all of the patients. The SUVmax, MTV, and TLG did not differ significantly between the SCC and NHL groups, but two of the six texture indices (LGZE [p=0.004] and HGZE [p=0.03]) showed significant differences between the groups. LGZE was the best discriminative index for the differentiation of SCC and NHL (55.6% sensitivity, 88.0% specificity). The LGZE and HGZE texture indices derived from 18F-FDG PET/CT images may be useful in differentiating SCC and NHL in the oropharynx. en-copyright= kn-copyright= en-aut-name=MitamuraKatsuya en-aut-sei=Mitamura en-aut-mei=Katsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NorikaneTakashi en-aut-sei=Norikane en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoYuka en-aut-sei=Yamamoto en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Ihara-NishishitaAyumi en-aut-sei=Ihara-Nishishita en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobataTakuya en-aut-sei=Kobata en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujimotoKengo en-aut-sei=Fujimoto en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakamiYasukage en-aut-sei=Takami en-aut-mei=Yasukage kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KudomiNobuyuki en-aut-sei=Kudomi en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HoshikawaHiroshi en-aut-sei=Hoshikawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishiyamaYoshihiro en-aut-sei=Nishiyama en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Radiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=2 en-affil=Department of Radiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=3 en-affil=Department of Radiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=4 en-affil=Department of Radiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=5 en-affil=Department of Radiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=6 en-affil=Department of Radiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=7 en-affil=Department of Radiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=8 en-affil=Department of Medical Physics, Faculty of Medicine, Kagawa University kn-affil= affil-num=9 en-affil=Department of Otolaryngology, Faculty of Medicine, Kagawa University kn-affil= affil-num=10 en-affil=Department of Radiology, Faculty of Medicine, Kagawa University kn-affil= en-keyword=18F-FDG kn-keyword=18F-FDG en-keyword=PET/CT kn-keyword=PET/CT en-keyword=oropharyngeal squamous cell carcinoma kn-keyword=oropharyngeal squamous cell carcinoma en-keyword=malignant lymphoma kn-keyword=malignant lymphoma en-keyword=texture kn-keyword=texture END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=3 article-no= start-page=307 end-page=314 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Investigation into the Effect of Breast Volume on Irradiation Dose Distribution in Asian Women with Breast Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Reports on irradiation dose distribution in breast cancer radiotherapy with sufficient sample size are limited in Asian patients. Elucidating dose distribution in Asian patients is particularly important as their breast volume differs compared to patients in Europe and North America. Here, we examined dose distribution in the irradiation field relative to breast volume for three irradiation methods historically used in our facility. We investigated the influence of breast volume on each irradiation method for Asian women. A total of 573 women with early-stage breast cancer were treated with breast-conserving surgery and adjuvant radiotherapy. Three methods were compared: wedge (W), field-in-field (FIF), and wedge-field-in-field (W-FIF). In patients with small breast volume, FIF decreased low- and high-dose areas within the planning target volume, and increased optimal dose area more than W. In patients with medium and large breast volumes, FIF decreased high-dose area more than W. The absolute values of correlation coefficients of breast volume to low-, optimal-, and high-dose areas and mean dose were significantly lower in FIF than in W. The correlation coefficients of V107% were 0.00 and 0.28 for FIF and W, respectively. FIF is an excellent irradiation method that is less affected by breast volume than W in Asian breast cancer patients. en-copyright= kn-copyright= en-aut-name=IshizakaHinata en-aut-sei=Ishizaka en-aut-mei=Hinata 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=TekikiNouha en-aut-sei=Tekiki en-aut-mei=Nouha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KhasawnehAbdullah en-aut-sei=Khasawneh en-aut-mei=Abdullah kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=HamadaKentaro en-aut-sei=Hamada en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KonishiKohei en-aut-sei=Konishi en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugimotoKohei en-aut-sei=Sugimoto en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=SugiyamaSoichi en-aut-sei=Sugiyama en-aut-mei=Soichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 ORCID= en-aut-name=KatayamaNorihisa en-aut-sei=Katayama en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=IharaHiroki en-aut-sei=Ihara en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 ORCID= en-aut-name=KanazawaSusumu en-aut-sei=Kanazawa en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 ORCID= affil-num=1 en-affil=Radiological Technology, Graduate School of Health 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, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Radiological Technology, Graduate School of Health 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=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Proton Beam Therapy,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Radiology, Kagawa Prefectural Central Hospital kn-affil= affil-num=14 en-affil=Department of Radiology, Iwakuni Clinical Center kn-affil= affil-num=15 en-affil=Department of Radiology, Tsuyama Chuo Hospital kn-affil= affil-num=16 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=17 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=radiotherapy kn-keyword=radiotherapy en-keyword=dose distribution kn-keyword=dose distribution en-keyword=irradiation method kn-keyword=irradiation method en-keyword=breast volume kn-keyword=breast volume END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=3 article-no= start-page=269 end-page=277 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical Outcome of Palliative Concurrent Chemoradiotherapy with Cisplatin/Docetaxel for Stage III Non-small Cell Lung Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Palliative concurrent chemoradiotherapy (CCRT) is often administered to patients with stage III non-small cell lung cancer (NSCLC). We investigated the clinical outcomes of patients receiving palliative CCRT for NSCLC. Data of patients with NSCLC who underwent palliative CCRT (n=16), preoperative CCRT plus surgery (n=97), or definitive CCRT (n=48) were evaluated. In all groups, the concurrent chemotherapy regimens consisted of cisplatin and docetaxel. Rates of local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and prognosis were compared. The 2-year rates of LC, DMFS, PFS, and OS in 16 patients who underwent palliative CCRT were 44.4%, 12.5%, 12.5%, and 18.8%, respectively. Univariate analysis showed that palliative CCRT was associated with poor LC (p<0.001), DMFS (p<0.001), PFS (p<0.001), and OS (p<0.001) outcomes in patients who completed CCRT as a preoperative treatment and poor LC (p=0.01), DMFS (p=0.003), PFS (p=0.04), and OS (p=0.004) outcomes in patients who were considered for definitive CCRT. Although there were some long-term survivors, the clinical outcomes of palliative CCRT were significantly inferior to those of the ideal treatments. Therefore, careful determination of the appropriate treatment indications and further studies are warranted. en-copyright= kn-copyright= en-aut-name=KatsuiKuniaki en-aut-sei=Katsui en-aut-mei=Kuniaki 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=WatanabeKenta en-aut-sei=Watanabe en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 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=7 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=8 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=9 ORCID= en-aut-name=KanazawaSusumu en-aut-sei=Kanazawa 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 Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Radiology, Iwakuni Clinical Center kn-affil= affil-num=3 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital 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=General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=palliative concurrent chemoradiotherapy kn-keyword=palliative concurrent chemoradiotherapy en-keyword= cisplatin/docetaxel kn-keyword= cisplatin/docetaxel en-keyword=stage III non-small cell lung cancer kn-keyword=stage III non-small cell lung cancer END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue= article-no= start-page=665273 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210531 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=RUNX2 Phosphorylation by Tyrosine Kinase ABL Promotes Breast Cancer Invasion en-subtitle= kn-subtitle= en-abstract= kn-abstract=Activity of transcription factors is normally regulated through interaction with other transcription factors, chromatin remodeling proteins and transcriptional co-activators. In distinction to these well-established transcriptional controls of gene expression, we have uncovered a unique activation model of transcription factors between tyrosine kinase ABL and RUNX2, an osteoblastic master transcription factor, for cancer invasion. We show that ABL directly binds to, phosphorylates, and activates RUNX2 through its SH2 domain in a kinase activity-dependent manner and that the complex formation of these proteins is required for expression of its target gene MMP13. Additionally, we show that the RUNX2 transcriptional activity is dependent on the number of its tyrosine residues that are phosphorylated by ABL. In addition to regulation of RUNX2 activity, we show that ABL transcriptionally enhances RUNX2 expression through activation of the bone morphogenetic protein (BMP)-SMAD pathway. Lastly, we show that ABL expression in highly metastatic breast cancer MDA-MB231 cells is associated with their invasive capacity and that ABL-mediated invasion is abolished by depletion of endogenous RUNX2 or MMP13. Our genetic and biochemical evidence obtained in this study contributes to a mechanistic insight linking ABL-mediated phosphorylation and activation of RUNX2 to induction of MMP13, which underlies a fundamental invasive capacity in cancer and is different from the previously described model of transcriptional activation. en-copyright= kn-copyright= en-aut-name=HeFang en-aut-sei=He en-aut-mei=Fang 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=AsanoYosuke en-aut-sei=Asano en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamuraYuriko en-aut-sei=Yamamura en-aut-mei=Yuriko 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=La RoseJose en-aut-sei=La Rose en-aut-mei=Jose kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=9 ORCID= en-aut-name=RottapelRobert en-aut-sei=Rottapel en-aut-mei=Robert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Princess Margaret Cancer Center, University Health Network, University of Toronto kn-affil= affil-num=7 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 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=Princess Margaret Cancer Center, University Health Network, University of Toronto kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=ABL kn-keyword=ABL en-keyword=Abelson murine leukemia viral oncogene homolog kn-keyword=Abelson murine leukemia viral oncogene homolog en-keyword=Runx2 (runt-related transcription factor 2) kn-keyword=Runx2 (runt-related transcription factor 2) en-keyword=tyrosine kn-keyword=tyrosine en-keyword=phosphorylation kn-keyword=phosphorylation en-keyword=invasion kn-keyword=invasion 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=2021 dt-pub=20210325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=身体的及び乳癌の表現形と日本人女性の乳がんリスクと関連する3つの一塩基多型(rs2046210、rs3757318、rs3803662)との関連性 kn-title=Relationships of physical and breast cancer phenotypes with three single-nucleotide polymorphisms (rs2046210, rs3757318 and rs3803662) associated with breast cancer risk in jpnpanese women en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KawadaKengo en-aut-sei=Kawada en-aut-mei=Kengo kn-aut-name=河田健吾 kn-aut-sei=河田 kn-aut-mei=健吾 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=2 article-no= start-page=219 end-page=224 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Successful Treatment of Acute Promyelocytic Leukemia Complicated with Endometrial Cancer by Arsenic Trioxide en-subtitle= kn-subtitle= en-abstract= kn-abstract=Acute promyelocytic leukemia (APL) is a hematological emergency that requires urgent intervention because of the high incidence of early hemorrhagic death. When patients with APL experience a synchronous solid organ tumor, the tumor’s treatment must also be done properly. Differentiation-inducing therapy using arsenic trioxide (ATO) has less hematological toxicity compared to cytotoxic chemotherapy and might be preferable for untreated APL patients with a synchronous solid organ tumor. Here we describe the first successful case of untreated APL and synchronous endometrial cancer (in an adult Japanese woman) treated with ATO consolidation therapy and the subsequent surgery and chemotherapy for endometrial cancer. en-copyright= kn-copyright= en-aut-name=SugiuraHiroyuki en-aut-sei=Sugiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=MatsuokaHirofumi en-aut-sei=Matsuoka en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=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=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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 Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, 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=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=acute promyelocytic leukemia kn-keyword=acute promyelocytic leukemia en-keyword=endometrial cancer kn-keyword=endometrial cancer en-keyword=arsenic trioxide kn-keyword=arsenic trioxide en-keyword=synchronous multiple primary malignant tumor kn-keyword=synchronous multiple primary malignant tumor en-keyword=chemotherapy kn-keyword=chemotherapy END