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= 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=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= 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=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=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=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=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=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=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=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=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=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=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=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=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=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=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=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=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=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=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=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=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= 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=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=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=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=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=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=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=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=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=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=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= 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=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=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=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=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=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 start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=2 article-no= start-page=139 end-page=145 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=Evaluation of the Imaging Process for a Novel Subtraction Method Using Apparent Diffusion Coefficient Values en-subtitle= kn-subtitle= en-abstract= kn-abstract=Diffusion-weighted imaging may be used to obtain the apparent diffusion coefficient (ADC), which aids the diagnosis of cerebral infarction and tumors. An ADC reflects elements of free diffusion. Diffusion kurtosis imaging (DKI) has attracted attention as a restricted diffusion imaging technique. The ADC subtraction method (ASM) was developed to visualize restricted diffusion with high resolution by using two ADC maps taken with different diffusion times. We conducted the present study to provide a bridge between the reported basic ASM research and clinical research. We developed new imaging software for clinical use and evaluated its performance herein. This software performs the imaging process automatically and continuously at the pixel level, using ImageJ software. The new software uses a macro or a plugin which is compatible with various operating systems via a Java Virtual Machine. We tested the new imaging software’s performance by using a Jurkat cell bio-phantom, and the statistical evaluation of the performance clarified that the ASM values of 99.98% of the pixels in the bio-phantom and physiological saline were calculated accurately (p<0.001). The new software may serve as a useful tool for future clinical applications and restricted diffusion imaging research. en-copyright= kn-copyright= en-aut-name=HamadaKentaro en-aut-sei=Hamada en-aut-mei=Kentaro 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=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=TekikiNouha en-aut-sei=Tekiki en-aut-mei=Nouha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=9 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=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=KurozumiAkira en-aut-sei=Kurozumi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=14 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=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=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=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Radiological Technology, Graduate School of Health Sciences, 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=Central Division of Radiology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Central Division of Radiology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Central Division of Radiology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= en-keyword=apparent diffusion coefficient kn-keyword=apparent diffusion coefficient en-keyword=ADC subtraction method kn-keyword=ADC subtraction method en-keyword=restricted diffusion kn-keyword=restricted diffusion en-keyword=ImageJ kn-keyword=ImageJ en-keyword=plugin kn-keyword=plugin 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=20210303 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=RFX1‐mediated CCN3 induction that may support chondrocyte survival under starved conditions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cellular communication network factor (CCN) family members are multifunctional matricellular proteins that manipulate and integrate extracellular signals. In our previous studies investigating the role of CCN family members in cellular metabolism, we found three members that might be under the regulation of energy metabolism. In this study, we confirmed that CCN2 and CCN3 are the only members that are tightly regulated by glycolysis in human chondrocytic cells. Interestingly, CCN3 was induced under a variety of impaired glycolytic conditions. This CCN3 induction was also observed in two breast cancer cell lines with a distinct phenotype, suggesting a basic role of CCN3 in cellular metabolism. Reporter gene assays indicated a transcriptional regulation mediated by an enhancer in the proximal promoter region. As a result of analyses in silico, we specified regulatory factor binding to the X‐box 1 (RFX1) as a candidate that mediated the transcriptional activation by impaired glycolysis. Indeed, the inhibition of glycolysis induced the expression of RFX1, and RFX1 silencing nullified the CCN3 induction by impaired glycolysis. Subsequent experiments with an anti‐CCN3 antibody indicated that CCN3 supported the survival of chondrocytes under impaired glycolysis. Consistent with these findings in vitro, abundant CCN3 production by chondrocytes in the deep zones of developing epiphysial cartilage, which are located far away from the synovial fluid, was confirmed in vivo. Our present study uncovered that RFX1 is the mediator that enables CCN3 induction upon cellular starvation, which may eventually assist chondrocytes in retaining their viability, even when there is an energy supply shortage. en-copyright= kn-copyright= en-aut-name=MizukawaTomomi en-aut-sei=Mizukawa en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishidaTakashi en-aut-sei=Nishida en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AkashiSho en-aut-sei=Akashi en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawataKazumi en-aut-sei=Kawata en-aut-mei=Kazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikuchiSumire en-aut-sei=Kikuchi en-aut-mei=Sumire kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawakiHarumi en-aut-sei=Kawaki en-aut-mei=Harumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakigawaMasaharu en-aut-sei=Takigawa en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KubotaSatoshi en-aut-sei=Kubota en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan kn-affil= affil-num=4 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan kn-affil= affil-num=5 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan kn-affil= affil-num=6 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan kn-affil= affil-num=7 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School kn-affil= affil-num=8 en-affil=Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue= article-no= start-page=100330 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The HMGB1/RAGE axis induces bone pain associated with colonization of 4T1 mouse breast cancer in bone en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bone pain is a common complication of breast cancer (BC) bone metastasis and is a major cause of increased morbidity and mortality. Although the mechanism of BC-associated bone pain (BCABP) remains poorly understood, involvement of BC products in the pathophysiology of BCABP has been proposed. Aggressive cancers secrete damage-associated molecular patterns (DAMPs) that bind to specific DAMP receptors and modulate cancer microenvironment. A prototypic DAMP, high mobility group box 1 (HMGB1), which acts as a ligand for the receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs), is increased in its expression in BC patients with poor outcomes. Here we show that 4T1 mouse BC cells colonizing bone up-regulate the expression of molecular pain markers, phosphorylated ERK1/2 (pERK) and pCREB, in the dorsal root ganglia (DRGs) innervating bone and induced BCABP as evaluated by hind-paw mechanical hypersensitivity. Importantly, silencing HMGB1 in 4T1 BC cells by shRNA reduced pERK and pCREB and BCABP with decreased HMGB1 levels in bone. Further, administration of a neutralizing antibody to HMGB1 or an antagonist for RAGE, FPS-ZM1, ameliorated pERK, pCREB and BCABP, while a TLR4 antagonist, TAK242, showed no effects. Consistent with these in vivo results, co-cultures of F11 sensory neuron-like cells with 4T1 BC cells in microfluidic culture platforms increased neurite outgrowth of F11 cells, which was blocked by HMGB1 antibody. Our results show that HMGB1 secreted by BC cells induces BCABP via binding to RAGE of sensory neurons and suggest that the HMGB1/RAGE axis may be a potential novel therapeutic target for BCABP. en-copyright= kn-copyright= en-aut-name=OkuiTatsuo en-aut-sei=Okui en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiasaMasahiro en-aut-sei=Hiasa en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RyumonShoji en-aut-sei=Ryumon en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OnoKisho en-aut-sei=Ono en-aut-mei=Kisho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunisadaYuki en-aut-sei=Kunisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SasakiAkira en-aut-sei=Sasaki en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=RoodmanG. David en-aut-sei=Roodman en-aut-mei=G. David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WhiteFletcher A. en-aut-sei=White en-aut-mei=Fletcher A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YonedaToshiyuki en-aut-sei=Yoneda en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Biomaterials and Bioengineerings, University of Tokushima Graduate School of Dentistry kn-affil= affil-num=3 en-affil= kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=8 en-affil=Department of Medicine, Hematology Oncology, Indiana University School of Medicine kn-affil= affil-num=9 en-affil=Department of Anesthesia, Paul and Carole Stark Neurosciences Research Institute kn-affil= affil-num=10 en-affil=Department of Cellular and Molecular Biochemistry, Osaka University Graduate School of Dentistry kn-affil= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Bone pain kn-keyword=Bone pain en-keyword=Sensory neurons kn-keyword=Sensory neurons en-keyword=HMGB1 kn-keyword=HMGB1 en-keyword=RAGE kn-keyword=RAGE 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=20210318 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Role of surgery in a novel multimodal therapeutic approach to complete cure of advanced lung cancer: current and future perspectives en-subtitle= kn-subtitle= en-abstract= kn-abstract=Non-small cell lung cancer (NSCLC) is considered potentially curable by multimodal therapy in a subset of patients, including those with locally advanced (LA) disease or nodal spread, who would otherwise have a poor prognosis. Guidelines recommend perioperative chemotherapy with platinum-based regimens, with or without radiotherapy, as the standard treatment modality for high-risk resectable LA-NSCLC. Although the classical regimens of adjuvant chemotherapy have been platinum-based doublet or oral agents such as tegafur/uracil, some molecular targeted therapeutic agents and immune checkpoint inhibitors have been developed recently with an expected favorable effect. Recent trials of perioperative therapy using these agents have demonstrated favourable anticancer efficacy for LA-NSCLC with an acceptable adverse events profile. The ideal timing of perioperative therapy administration, before or after surgery, is still controversial. Because some speculation and concepts have arisen from basic research, several trials are ongoing to clarify the efficacy of newly developed agents in the adjuvant or neoadjuvant setting. This review discusses the role of surgery in the new era and analyzes when and which optimal perioperative multimodal therapy, including chemotherapy, radiotherapy, molecular-targeted therapy, and immunotherapy, should be administered for resectable or potentially resectable NSCLC to provide possible complete cure. en-copyright= kn-copyright= en-aut-name=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= affil-num=1 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=2 en-affil=Departments of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Perioperative therapy kn-keyword=Perioperative therapy en-keyword=Surgery kn-keyword=Surgery END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=2 article-no= start-page=e042099 end-page= 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=Protocol for a multicentre, prospective, cohort study to investigate patient satisfaction and quality of life after immediate breast reconstruction in Japan: the SAQLA study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction The aim of breast reconstruction (BR) is to improve patients' health-related quality of life (HRQOL). Therefore, measuring patient-reported outcomes (PROs) would clarify the value and impact of BR on a patient's life and thus would provide evidence-based information to help decision-making. The Satisfaction and Quality of Life After Immediate Breast Reconstruction study aimed to investigate satisfaction and HRQOL in Japanese patients with breast cancer who undergo immediate breast reconstruction (IBR). Methods and analysis This ongoing prospective, observational multicentre study will assess 406 patients who had unilateral breast cancer and underwent mastectomy and IBR, and were recruited from April 2018 to July 2019. All participants were recruited from seven hospitals: Okayama University Hospital, Iwate Medical University Hospital, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Showa University Hospital, University of Tsukuba Hospital, Osaka University Hospital and Yokohama City University Medical Center. The patients will be followed up for 36 months postoperatively. The primary endpoint of this study will be the time-dependent changes in BREAST-Q satisfaction with breast subscale scores for 12 months after reconstructive surgery, which will be collected via an electronic PRO system. Ethics and dissemination This study will be performed in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects published by Japan's Ministry of Education, Science and Technology and the Ministry of Health, Labour and Welfare, the modified Act on the Protection of Personal Information and the Declaration of Helsinki. This study protocol was approved by the institutional ethics committee at the Okayama University Graduate School of Medicine, Dentistry, on 2 February 2018 (1801-039) and all other participating sites. The findings of this trial will be submitted to an international peer-reviewed journal. 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=HosoyaYuko en-aut-sei=Hosoya en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UtsunomiyaHiroki en-aut-sei=Utsunomiya en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuramotoYukiko en-aut-sei=Kuramoto en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=TomitaKoichi en-aut-sei=Tomita en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AiharaYukiko en-aut-sei=Aihara en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MutoMayu en-aut-sei=Muto en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HikosakaMakoto en-aut-sei=Hikosaka en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawaguchiTakashi en-aut-sei=Kawaguchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MiyajiTempei en-aut-sei=Miyaji en-aut-mei=Tempei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=ZendaSadamoto en-aut-sei=Zenda en-aut-mei=Sadamoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=GotoAya en-aut-sei=Goto en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SakurabaMinoru en-aut-sei=Sakuraba en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KusanoTaro en-aut-sei=Kusano en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MiyabeKenta en-aut-sei=Miyabe en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KurokiTomoaki en-aut-sei=Kuroki en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YanoTomoyuki en-aut-sei=Yano en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TaminatoMifue en-aut-sei=Taminato en-aut-mei=Mifue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=SekidoMitsuru en-aut-sei=Sekido en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=TsunodaYui en-aut-sei=Tsunoda en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=SatakeToshihiko en-aut-sei=Satake en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 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=24 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=25 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, Iwate Medical University kn-affil= affil-num=3 en-affil=Department of Surgery and Plastic Surgery, Showa University Koto Toyosu Hospital kn-affil= affil-num=4 en-affil=Department of Plastic and Reconstructive Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research 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, Graduate School of Medicine, Osaka University kn-affil= affil-num=7 en-affil=Department of Plastic and Reconstructive Surgery, Faculty of Medicine, University of Tsukuba kn-affil= affil-num=8 en-affil=Department of Plastic and Reconstructive Surgery, Yokohama City University Medical Center kn-affil= affil-num=9 en-affil=Department of Plastic and Reconstructive Surgery, National Center for Child Health and Development kn-affil= affil-num=10 en-affil=Department of Practical Pharmacy, Tokyo University of Pharmacy and Life Sciences kn-affil= affil-num=11 en-affil=Department of Clinical Trial Data Management, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=12 en-affil=Division of Biostatistics, Tohoku University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Division of Radiation Oncology, National Cancer Center Hospital East kn-affil= affil-num=14 en-affil=Department of Plastic and Reconstructive Surgery, Iwate Medical University kn-affil= affil-num=15 en-affil=Department of Plastic and Reconstructive Surgery, Iwate Medical University kn-affil= affil-num=16 en-affil=Kusano Taro Clinic kn-affil= affil-num=17 en-affil=Department of Plastic and Reconstructive Surgery, Showa University Hospital kn-affil= affil-num=18 en-affil=Department of Plastic and Reconstructive Surgery, Showa University Hospital kn-affil= affil-num=19 en-affil=Department of Plastic and Reconstructive Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=20 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Osaka University kn-affil= affil-num=21 en-affil=Department of Plastic and Reconstructive Surgery, Faculty of Medicine, University of Tsukuba kn-affil= affil-num=22 en-affil=Department of Plastic and Reconstructive Surgery, Yokohama City University Medical Center kn-affil= affil-num=23 en-affil=Department of Plastic and Reconstructive Surgery, Toyama University Hospital kn-affil= affil-num=24 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=25 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Hospital kn-affil= en-keyword=plastic & reconstructive surgery kn-keyword=plastic & reconstructive surgery en-keyword=breast surgery kn-keyword=breast surgery en-keyword=breast tumours kn-keyword=breast tumours END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=213 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Investigation of Factors Affecting Early Quality of Life of Patients after Breast Cancer Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: The purpose of this study was to investigate factors related to early quality of life (QOL) three months after surgery in breast cancer patients with axillary lymph node dissection. Methods: The subjects of this study were 195 consecutive patients who underwent axillary lymph node dissection for breast cancer. Age, body mass index, level of lymph node dissection, marriage, children, co-resident household members, neoadjuvant chemotherapy, postoperative chemotherapy, postoperative hormonal therapy, postoperative radiotherapy, upper limb function (disabilities of the arm, shoulder, and hand (DASH)), and QOL (European Organization for the Treatment and Research of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)) were evaluated. For each item of the EORTC QLQ-C30, compared with preoperative status and three months after surgery, those who improved or remained unchanged in the three months after surgery were classified as the maintenance and improved groups, and those with worsening status were classified as the worsened group. Results: Age, level of lymph node dissection, DASH, neoadjuvant chemotherapy, postoperative chemotherapy, and postoperative radiotherapy were significantly associated with QOL (p < 0.05). Conclusions: The early QOL of postoperative patients with breast cancer is affected by multiple factors, such as upper limb function and postoperative chemotherapy, and thus comprehensive intervention is required. 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, 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= 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=quality of life kn-keyword=quality of life en-keyword=breast cancer kn-keyword=breast cancer en-keyword=neoadjuvant chemotherapy kn-keyword=neoadjuvant chemotherapy en-keyword=postoperative chemotherapy kn-keyword=postoperative chemotherapy en-keyword=postoperative radiotherapy kn-keyword=postoperative radiotherapy END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=1 article-no= start-page=39 end-page=44 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202102 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Influence of and Risk Factors for Axillary Web Syndrome Following Surgery for Breast Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this study, we examined whether axillary web syndrome (AWS) in patients with breast cancer following axil-lary lymph node dissection affects range of motion (ROM), upper extremity function, and quality of life (QOL). The risk factors for AWS were also evaluated in a total of 238 consecutive breast cancer patients follow-ing axillary lymph node dissection. At 1, 2, and 3 months after surgery, there were no significant differences between the AWS group and the non-AWS group in upper-limb function or QOL. At 2 months after surgery, shoulder flexion and abduction ROM were significantly higher in the AWS group than in the non-AWS group (p < 0.05). Self-training time at home was not significantly different between the groups at 1, 2, or 3 months. Only age was a significant predictor of AWS at 1 month after surgery (p < 0.05). The AWS group in the present study did not have worse results for shoulder joint ROM, upper-limb function, and QOL than the non-AWS group. Younger age should be useful for predicting the development of AWS in the early postoperative period. 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=HamadaMakiko en-aut-sei=Hamada en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=9 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=Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=8 en-affil=Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=9 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=axillary web syndrome kn-keyword=axillary web syndrome en-keyword=age kn-keyword=age en-keyword=upper limb function kn-keyword=upper limb function en-keyword=quality of life kn-keyword=quality of life END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=1 article-no= start-page=15 end-page=23 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202102 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Volumetric PET Parameters Predict Prognosis after Definitive Chemoradiotherapy with Cisplatin/Docetaxel for Stage III Non-Small Cell Lung Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=The aim of this study was to investigate whether volumetric positron emission tomography (PET) parameters are prognostic predictors in stage III non-small cell lung cancer patients receiving definitive concurrent chemo-radiotherapy (CCRT) with cisplatin/docetaxel. Cases involving definitive CCRT were reviewed retrospectively, and the maximum standardized uptake value, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated. The relationships between these PET parameters and prognosis were analyzed. MTV and TLG were significant predictors of distant metastasis-free survival (DMFS) (p = 0.0003 and 0.0005, respectively) and progression-free survival (PFS) (p = 0.001 and 0.0007, respectively). The three-year DMFS rates in patients with low and high MTV were 13.3% and 64.6%, respectively, and the corresponding values in those with low and high TLG were 13.3% and 65.2%, respectively. The three-year PFS rates in patients with low and high MTV were 13.3% and 57.8%, respectively, and the corresponding values in patients with low and high TLG were 13.3% and 57.8%, respectively. However, MTV and TLG were not predictors of local control or overall sur-vival. We demonstrated that volumetric PET parameters were predictors of patients receiving definitive CCRT. Our findings contradict the findings of previous reports and warrant further research to validate them. 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=TadaAkihiro en-aut-sei=Tada en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=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=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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 Diagnostic Imaging Center kn-affil= affil-num=4 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=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=Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=volumetric positron emission tomography parameters kn-keyword=volumetric positron emission tomography parameters en-keyword=distant metastasis-free survival kn-keyword=distant metastasis-free survival en-keyword=chemoradiotherapy kn-keyword=chemoradiotherapy en-keyword=cisplatin/docetaxel kn-keyword=cisplatin/docetaxel en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=6 article-no= start-page=461 end-page=466 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Reality of Gastric Cancer in Young Patients: The Importance and Difficulty of the Early Diagnosis, Prevention and Treatment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gastric cancer usually arises in middle-aged to older patients, and is rarely found in younger patients. The clin-ical characteristics, etiology, prognosis, preventive methods and treatment of gastric cancer in young patients have not been fully investigated because of its low prevalence. In this review, we discuss the current under-standing and clinical problems associated with gastric cancer in young patients. Helicobacter pylori (H. pylori), which is a major cause of gastric cancer, especially in older populations, is closely associated with gastric cancer in young patients as well as in older patients. Gastric cancer in young patients tends to be diagnosed at an advanced stage with alarm symptoms. However, young patients with advanced gastric cancer tend to have a favorable general condition and organ function, so they can tolerate intensive systematic chemotherapy. Unfortunately, the prognosis of gastric cancer in young patients with an advanced stage is not favorable. We should not take this rare disease lightly, given its poor prognosis if patients are diagnosed at an unresectable stage. The evaluation of the H. pylori infection status and performance of H. pylori eradication therapy to prevent gastric cancer in young patients as well as the development of more intensive chemotherapy regimens for unre-sectable gastric cancer in young patients are warranted. en-copyright= kn-copyright= en-aut-name=KonoYoshiyasu en-aut-sei=Kono en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanzakiHiromitsu en-aut-sei=Kanzaki en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=young patients kn-keyword=young patients en-keyword=Helicobacter pylori kn-keyword=Helicobacter pylori END start-ver=1.4 cd-journal=joma no-vol=55 cd-vols= no-issue= article-no= start-page=63 end-page=68 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Chemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX.
Methods
We compared three different doses of q3w nab-PTX (Standard: 260 mg/m2 [SD260] vs Medium: 220 mg/m2 [MD220] vs Low: 180 mg/m2 [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was <0.75 or >1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded.
Results
One hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42–1.28) in MD220 vs SD260, 0.77 (95% CI 0.47–1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56–1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180.
Conclusions
Intravenous administration of low-dose nab-PTX at 180 mg/m2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC. en-copyright= kn-copyright= en-aut-name=TsurutaniJunji en-aut-sei=Tsurutani en-aut-mei=Junji 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=KitadaMasahiro en-aut-sei=Kitada en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 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=7 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=8 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=9 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=10 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=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=TakashimaTsutomu en-aut-sei=Takashima en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=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= affil-num=1 en-affil=Advanced Cancer Translational Research Institute, Showa University kn-affil= affil-num=2 en-affil=Department of Breast Medical Oncology, Cancer Institute Hospital of JFCR kn-affil= affil-num=3 en-affil=Department of Breast Disease Center, Asahikawa Medical University Hospital kn-affil= affil-num=4 en-affil=NHO Hokkaido Cancer Center kn-affil= affil-num=5 en-affil=Department of Breast Surgery, Kobe City Medical Center General Hospita kn-affil= affil-num=6 en-affil=Teine Keijinkai Hospital kn-affil= affil-num=7 en-affil=Niigata City General Hospital kn-affil= affil-num=8 en-affil=Department of Breast and Medical Oncology, National Cancer Center Hospital East kn-affil= affil-num=9 en-affil=Department of Breast Surgery, Hirosaki Municipal Hospital kn-affil= affil-num=10 en-affil=Japanese Red Cross Saitama Hospital kn-affil= affil-num=11 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=12 en-affil=Okayama University Hospital kn-affil= affil-num=13 en-affil=Osaka City University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Clinical Research Promotion Center, The University of Tokyo Hospital kn-affil= affil-num=15 en-affil=Breast Center, Aihara Hospital kn-affil= affil-num=16 en-affil=National Cancer Center Hospital East, Kashiwa kn-affil= en-keyword=Nab-paclitaxel kn-keyword=Nab-paclitaxel en-keyword=Nanoparticle albumin–bound paclitaxel kn-keyword=Nanoparticle albumin–bound paclitaxel en-keyword=Metastatic breast cancer kn-keyword=Metastatic breast cancer en-keyword=Solvent-base paclitaxel kn-keyword=Solvent-base paclitaxel en-keyword=Chemotherapy-induced peripheral neuropathy kn-keyword=Chemotherapy-induced peripheral neuropathy 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=2020 dt-pub=20201009 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Germline multigene panel testing revealed a BRCA2 pathogenic variant in a patient with suspected Lynch syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=There has been a rapid advance in germline multigene panel testing by next-generation sequencing, and it is being widely used in clinical settings. A 56-year-old woman suspected of having Lynch syndrome was identified as a BRCA2 pathogenic variant carrier by multigene panel testing. The patient was diagnosed with endometrial cancer at the age of 39 years, and total laparoscopic hysterectomy and bilateral salpingectomy were performed at the age of 49 years; however, bilateral oophorectomy was not performed at that time. As she had a family history of colorectal cancer and a history of endometrial cancer, Lynch syndrome was suspected. However, germline multigene panel testing revealed a pathogenic BRCA2 variant rather than pathogenic variants in mismatch repair genes. In this case, with conventional genetic risk assessment, we were unable to determine whether the patient had a high risk of hereditary breast and ovarian cancer; thus, germline multigene panel testing may provide valuable information to improve disease management strategies for patients in clinical settings. Particularly, germline multigene panel testing may be useful for detecting hereditary tumor syndromes if a patient does not present with a typical family history of cancer. en-copyright= kn-copyright= en-aut-name=YoshihamaTomoko en-aut-sei=Yoshihama en-aut-mei=Tomoko 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= SuganoKokichi en-aut-sei= Sugano en-aut-mei=Kokichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaTeruhiko en-aut-sei=Yoshida en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UshiamaMineko en-aut-sei=Ushiama en-aut-mei=Mineko 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=AkahaneTomoko en-aut-sei=Akahane en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NankiYoshiko en-aut-sei=Nanki en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SakaiKensuke en-aut-sei=Sakai en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MakabeTakeshi en-aut-sei=Makabe en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamagamiWataru en-aut-sei=Yamagami en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SusumuNobuyuki en-aut-sei=Susumu en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KameyamaKaori en-aut-sei=Kameyama en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KosakiKenjiro en-aut-sei=Kosaki en-aut-mei=Kenjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AokiDaisuke en-aut-sei=Aoki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine 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=Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute kn-affil= affil-num=4 en-affil=Department of Genetic Medicine and Services, National Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Genetic Medicine and Services, National Cancer Center Hospital kn-affil= affil-num=6 en-affil=Center for Medical Genetics, Keio University School of Medicine kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=10 en-affil= Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=11 en-affil= Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=12 en-affil= Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=13 en-affil=Department of Pathology, Showa University Northern Yokohama Hospital kn-affil= affil-num=14 en-affil=Center for Medical Genetics, Keio University School of Medicine kn-affil= affil-num=15 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= en-keyword=BRCA2 kn-keyword=BRCA2 en-keyword=Hereditary breast and ovarian cancer kn-keyword=Hereditary breast and ovarian cancer en-keyword=Multigene panel testing kn-keyword=Multigene panel testing en-keyword=Genetic counseling kn-keyword=Genetic counseling en-keyword=Lynch syndrome kn-keyword=Lynch syndrome END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=5 article-no= start-page=455 end-page=459 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Study Protocol for Assessing the Efficacy of Compression Therapy Using Stockings and Sleeves 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 associated with the administration of the taxane docetaxel is chemotherapy-induced peripheral neuropathy (CIPN). We are conducting a singlecenter, single-arm, open-label historical control trial to evaluate the ability of compression therapy using stockings or sleeves to prevent CIPN due to docetaxel treatment. The primary endpoint is the incidence of all-grade CIPN according to patients’ records until 3 weeks after the fourth docetaxel administration. This study’s results will clarify whether compression therapy using stockings or sleeves can prevent CIPN in breast cancer patients. 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=KanetakaKengo en-aut-sei=Kanetaka en-aut-mei=Kengo 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=9 cd-vols= no-issue=8 article-no= start-page=5102 end-page=5107 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202008 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of local surgery on outcomes of stage IV breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Metastatic breast cancer (MBC), including de novo stage IV, is regarded as being incurable and the mainstay of clinical management is systemic therapy. Traditionally, locoregional surgery is performed only for local control, such as to prevent ulceration and bleeding. In recent years, however, both retrospective and prospective studies have demonstrated the prognostic efficacy of primary surgery for de novo stage IV patients. Therefore, we conducted a meta-analysis to evaluate whether surgical therapy contributes to overall survival (OS) extension. We searched for clinical trials published in electronic databases (PubMed, Embase, and the Cochrane databases) and performed a meta-analysis of the data collected. There were five prospective randomized controlled phase III trials (RCTs). The results of three have been reported. According to our meta-analysis of these RCTs, primary surgery for de novo stage IV breast cancer patients significantly improves OS. However, the Tata trial showed that systemic therapy does not achieve a sufficient effect. Another trial, conducted in Turkey, had statistical shortcomings and patient randomization was not adequately performed The ABCSG (Austrian Breast and Colorectal Cancer Study Group) trial had too few subjects. Meta-analysis of 12 retrospective studies showed that patients with stage IV breast cancer receiving surgery as the initial treatment experienced longer OS (HR: 0.65, P<0.00001). Based on our meta-analysis of three reported 'RCTs, surgery as the primary treatment does not significantly impact the outcomes of de novo stage IV breast cancer patients. However, these trials had limitations. We await the results of the remaining two ongoing RCTs (ECOG 2108 and JCOG 1017). These trials are anticipated to resolve current controversies and provide many eagerly awaited answers. 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=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=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=metastatic kn-keyword=metastatic en-keyword=stage IV kn-keyword=stage IV en-keyword=local therapy kn-keyword=local therapy en-keyword=locoregional therapy kn-keyword=locoregional therapy en-keyword=surgery kn-keyword=surgery en-keyword=survival kn-keyword=survival END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=8 article-no= start-page=5028 end-page=5031 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202008 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oligometastases: history and future vision of breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oligometastases, oligo-recurrence, sync-oligometastases and metachronous oligometastases were proposed based on the spectrum theory. This review article, first, described the history of cancer theory. Second, we described the history of the concepts of oligometastases, oligo-recurrence and sync-oligometastases. Finally, we prospect future visions of breast cancer of oligometastases. en-copyright= kn-copyright= en-aut-name=NiibeYuzuru en-aut-sei=Niibe en-aut-mei=Yuzuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=JinguKeiichi en-aut-sei=Jingu en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OnishiHiroshi en-aut-sei=Onishi en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Primary Care and Medical Education, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiation Oncology, Graduate School of Medicine, Tohoku University kn-affil= affil-num=3 en-affil=Department of Radiology, Graduate School of Medicine, Yamanashi University kn-affil= en-keyword=Oligometastases kn-keyword=Oligometastases en-keyword=oligo-recurrence kn-keyword=oligo-recurrence en-keyword=sync-oligometastases kn-keyword=sync-oligometastases en-keyword=metachronous oligometastases kn-keyword=metachronous oligometastases en-keyword=breast cancer kn-keyword=breast cancer END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=8 article-no= start-page=5063 end-page=5076 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202008 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neurosurgery for brain metastasis from breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Breast cancer is the most common malignancy among women worldwide, and the main cause of death in patients with breast cancer is metastasis. Metastasis to the central nervous system occurs in 10% to 16% of patients with metastatic breast cancer, and this rate has increased because of recent advancements in systemic chemotherapy. Because of the various treatments available for brain metastasis, accurate diagnosis and evaluation for treatment are important. Magnetic resonance imaging (MRI) is one of the most reliable preoperative examinations not only for diagnosis of metastatic brain tumors but also for estimation of the molecular characteristics of the tumor based on radiographic information such as the number of lesions, solid or ring enhancement, and cyst formation. Surgical resection continues to play an important role in patients with a limited number of brain metastases and a relatively good performance status. A single brain metastasis is a good indication for surgical treatment followed by radiation therapy to obtain longer survival. Surgical removal is also considered for two or more lesions if neurological symptoms are caused by brain lesions of >3 cm with a mass effect or associated hydrocephalus. Although maximal safe resection with minimal morbidity is ideal in the surgical treatment of brain tumors, supramarginal resection can be achieved in select cases. With respect to the resection technique, en bloc resection is generally recommended to avoid leptomeningeal dissemination induced by piecemeal resection. An operating microscope, neuronavigation, and intraoperative neurophysiological monitoring are essential in modern neurosurgical procedures, including tumor resection. More recently, supporting surgical instruments have been introduced. The use of endoscopic surgery has dramatically increased, especially for intraventricular lesions and in transsphenoidal surgery. An exoscope helps neurosurgeons to comfortably operate regardless of patient positioning or anatomy. A tubular retractor can prevent damage to the surrounding brain tissue during surgery and is a useful instrument in combination with both an endoscope and exoscope. Additionally, 5-aminolevulinic acid (5-ALA) is a promising reagent for photodynamic detection of residual tumor tissue. In the near future, novel treatment options such as high-intensity focused ultrasound (HIFU), laser interstitial thermal therapy (LITT), oncolytic virus therapy, and gene therapy will be introduced. en-copyright= kn-copyright= en-aut-name=TomitaYusuke en-aut-sei=Tomita en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurozumiKazuhiko en-aut-sei=Kurozumi en-aut-mei=Kazuhiko 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=ShimazuYosuke en-aut-sei=Shimazu en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= 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= en-keyword=Metastatic brain tumor kn-keyword=Metastatic brain tumor en-keyword=breast cancer kn-keyword=breast cancer en-keyword=neurosurgical technique kn-keyword=neurosurgical technique END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=8 article-no= start-page=5096 end-page=5101 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202008 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Radiation therapy for oligometastatic bone disease in breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Breast cancer (BCa) frequently metastasizes to the bone. BCa patients with oligometastatic bone diseases have much more favorable outcomes than those with metastatic bone disease. Radiation therapy (RT), especially stereotactic body radiation therapy (SBRT), is advised for the treatment of patients with oligometastatic bone disease in other primary sites. "This line of treatment provided favorable outcomes in patients and resulted in only mild toxicities. A similar strategy has been suggested for treatment of BCa patients with oligometastatic bone disease. BCa, bone-only, or high radiation dose are reported to have been associated with good outcomes in RT for metastatic disease. Furthermore, based on the guidelines provided by the BCa expert panel of the German Society for Radiation Oncology and members of the Working Party of Gynecologic Oncology Breast Committee and in line of the results obtained in other primary sites, our group supports the use of high-dose RT or SBRT for the treatment of BCa patients with oligometastatic bone disease. Additionally, the use of magnetic resonance imaging (MRI) for proper target volume definition and three-dimensional (3D) treatment planning especially for lesions of the trunk are essential for the treatment planning of RT. Of note, several clinical trials have combined RT with immune checkpoint inhibitors for the treatment of BCa patients with metastatic disease. Based on this, we anticipate that combined RT and ICI may serve as a better treatment modality for BCa patients with oligometastatic bone disease. en-copyright= kn-copyright= en-aut-name=KatayamaNorihisa en-aut-sei=Katayama en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=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=NagaoRyota en-aut-sei=Nagao en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtsukiKaho en-aut-sei=Otsuki en-aut-mei=Kaho 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=KanazawaSusumu en-aut-sei=Kanazawa en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Radiology, Okayama University Medical School kn-affil= affil-num=2 en-affil=Department of Radiology, Okayama University Medical School kn-affil= affil-num=3 en-affil=Department of Radiology, Okayama University Medical School kn-affil= affil-num=4 en-affil=Department of Radiology, Okayama University Medical School kn-affil= affil-num=5 en-affil=Department of Radiology, Okayama University Medical School kn-affil= affil-num=6 en-affil=Department of Radiology, Okayama University Medical School kn-affil= affil-num=7 en-affil=Department of Radiology, Okayama University Medical School kn-affil= en-keyword=Bone metastasis kn-keyword=Bone metastasis en-keyword=breast cancer (BCa) kn-keyword=breast cancer (BCa) en-keyword=oligometastatic kn-keyword=oligometastatic en-keyword=radiation therapy (RT) kn-keyword=radiation therapy (RT) en-keyword=stereotactic body radiation therapy (SBRT) kn-keyword=stereotactic body radiation therapy (SBRT) END start-ver=1.4 cd-journal=joma no-vol=529 cd-vols= no-issue=3 article-no= start-page=760 end-page=765 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200827 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Overcoming epithelial-mesenchymal transition-mediated drug resistance with monensin-based combined therapy in non-small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
The epithelial-mesenchymal transition (EMT) is a key process in tumor progression and metastasis and is also associated with drug resistance. Thus, controlling EMT status is a research of interest to conquer the malignant tumors.
Materials and methods
A drug repositioning analysis of transcriptomic data from a public cell line database identified monensin, a widely used in veterinary medicine, as a candidate EMT inhibitor that suppresses the conversion of the EMT phenotype. Using TGF-β-induced EMT cell line models, the effects of monensin on the EMT status and EMT-mediated drug resistance were assessed.
Results
TGF-β treatment induced EMT in non-small cell lung cancer (NSCLC) cell lines and the EGFR-mutant NSCLC cell lines with TGF-β-induced EMT acquired resistance to EGFR-tyrosine kinase inhibitor. The addition of monensin effectively suppressed the TGF-β-induced-EMT conversion, and restored the growth inhibition and the induction of apoptosis by the EGFR-tyrosine kinase inhibitor.
Conclusion
Our data suggested that combined therapy with monensin might be a useful strategy for preventing EMT-mediated acquired drug resistance. 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=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=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=TakanoJui en-aut-sei=Takano en-aut-mei=Jui 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=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=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=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=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=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko 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=AzumaKazuo en-aut-sei=Azuma en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=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 Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Thoracic, 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 Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Veterinary Clinical Medicine, Joint School of Veterinary Medicine, Tottori University kn-affil= affil-num=17 en-affil=Department of Veterinary Clinical Medicine, Joint School of Veterinary Medicine, Tottori University kn-affil= affil-num=18 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Monensin kn-keyword=Monensin en-keyword=Epithelial-mesenchymal transition kn-keyword=Epithelial-mesenchymal transition en-keyword=Non-small cell lung cancer kn-keyword=Non-small cell lung cancer en-keyword=Drug repositioning kn-keyword=Drug repositioning en-keyword=Drug resistance kn-keyword=Drug resistance END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=1 article-no= start-page=521 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prognostic value of OCT4A and SPP1C transcript variant co-expression in early-stage lung adenocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Octamer-binding transcription factor 4A (OCT4A) is essential for cell pluripotency and reprogramming both in humans and mice. To date, however, the function of human OCT4 in somatic and/or tumour tissues is largely unknown.
Methods
RT-PCR was used to identify full-length splice forms of OCT4 transcripts in normal and cancer cells. A FLAG-tagged OCT4 genomic transgene was used to identify OCT4-positive cancer cells. A potential role for OCT4 in somatic cancer cells was examined by cell ablation of OCT4-positive cells using promoter-driven diphtheria toxin A. OCT4 and secreted phosphoprotein 1 (SPP1) transcripts in early-stage lung adenocarcinoma tumours were analysed and compared with pathohistological features.
Results
The results show that, unlike in murine cells, OCT4A and OCT4B variants are transcribed in both human cancer cells and in adult tissues such as lung, kidney, uterus, breast, and eye. We found that OCT4A and SPP1C are co-expressed in highly aggressive human breast, endometrial, and lung adenocarcinoma cell lines, but not in mesothelial tumour cell lines. Ablation of OCT4-positive cells in lung adenocarcinoma cells significantly decreased cell migration and SPP1C mRNA levels. The OCT4A/SPP1C axis was found in primary, early-stage, lung adenocarcinoma tumours.
Conclusions
Co-expression of OCT4 and SPP1 may correlate with cancer aggressiveness, and the OCT4A/SPP1C axis may help identify early-stage high-risk patients with lung adenocarcinoma. Contrary to the case in mice, our data strongly suggest a critical role for OCT4A and SPP1C in the development and progression of human epithelial cancers. en-copyright= kn-copyright= en-aut-name=KoshimuneSeijiro en-aut-sei=Koshimune en-aut-mei=Seijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KosakaMitsuko en-aut-sei=Kosaka en-aut-mei=Mitsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MizunoNobuhiko en-aut-sei=Mizuno en-aut-mei=Nobuhiko 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=MiyamotoTomoyuki en-aut-sei=Miyamoto en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EbisuiKohta en-aut-sei=Ebisui en-aut-mei=Kohta 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=OhtsukaAiji en-aut-sei=Ohtsuka en-aut-mei=Aiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Okayama Univ, Dept Human Morphol, Grad Sch Med Dent & Pharmaceut Sci kn-affil= affil-num=3 en-affil=Department of Human Morphology, 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 Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Human Morphology, 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 Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=OCT4 kn-keyword=OCT4 en-keyword=SPP1 kn-keyword=SPP1 en-keyword=lung adenocarcinoma kn-keyword=lung adenocarcinoma en-keyword=tumour-initiating cell kn-keyword=tumour-initiating cell en-keyword=cancer stem cell kn-keyword=cancer stem cell en-keyword=cell migration kn-keyword=cell migration END start-ver=1.4 cd-journal=joma no-vol=86 cd-vols= no-issue=1 article-no= start-page=55 end-page=63 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Influences of preoperative metformin on immunological factors in early breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose
Metformin has been suggested to possibly reduce cancer risk. However, the mechanism underlying the positive effects of metformin on cancer treatment remains unclear. We conducted a prospective study to evaluate the effects of preoperative metformin in patients with early breast cancer.
Method
We evaluated the effects on immunological factors (TILs, CD4 + , CD8 + , PD-L1, IFNγ and IL-2) by comparing core needle biopsies (CNB) obtained before metformin treatment with surgical specimens. Seventeen patients were enrolled in this prospective study from January to December 2016. We also analyzed 59 patients undergoing surgery during the same period to reveal the correlation of immune factors between CNB and surgical specimen.
Result
There was a moderate correlation between CNB and surgical specimens on TILs and CD8 + lymphocyte. (TILs Rs = 0.63, CD4 + Rs = 0.224, CD8 + Rs = 0.42) In the metformin group, TILs increases were confirmed in five (29%) patients, while a decrease was confirmed in two (12%). The expressions of CD4 + and CD8 + by TILs were increased in 41% and 18% of surgical specimens, respectively. However, TILs number (p = 0.0554), CD4+ (p = 0.0613) and CD8 + (p = 0.0646) expressions did not significantly increased. Furthermore, IFNγ expression appeared to be increased in response to metformin (p = 0.08).
Conclusion
Preoperative metformin tends to increase TILs, as well as the numbers of CD4 and CD8 positive lymphocytes, and IFNγ levels. Metformin might improve immune function and have a possibility of chemo-sensitivity and thereby increase the effectiveness of immunotherapy, based on the results of this preliminary study. 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=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=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=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=KajiharaYukiko en-aut-sei=Kajihara en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=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=IwamotoTakayuki en-aut-sei=Iwamoto en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=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=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=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Metformin kn-keyword=Metformin en-keyword=Preoperative kn-keyword=Preoperative en-keyword=Tils kn-keyword=Tils en-keyword=CD8 kn-keyword=CD8 en-keyword=PD-L1 kn-keyword=PD-L1 END start-ver=1.4 cd-journal=joma no-vol=182 cd-vols= no-issue=2 article-no= start-page=325 end-page=332 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200528 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=NSAS-BC02 substudy of chemotherapy-induced amenorrhea (CIA) in premenopausal patients who received either taxane alone or doxorubicin(A) cyclophosphamide(C) followed by taxane as postoperative chemotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Chemotherapy-induced amenorrhea (CIA) is one of the critical side effects from the chemotherapy in premenopausal patients with breast cancer. The goals of our study are the following: (1) to investigate the factors affecting the incidence of CIA; and (2) to evaluate the prognostic role of CIA in premenopausal patients with breast cancer.
Methods
We conducted a post hoc retrospective substudy to examine the incidence of the CIA and the relationship between CIA and prognosis in NSAS-BC02 that compared taxane alone to Doxorubicin(A) Cyclophosphamide(C) followed by taxane in postoperative patients with node-positive breast cancer
Results
Of 395 premenopausal women, 287 (72.7%) had CIA due to protocol treatment. Regarding type of protocol regimen, proportion of CIA was 76.9% in AC Paclitaxel(P), 75.2% in AC Docetaxel(D), 62.8% in PTX, and 75.2% in DTX. Predictive factors of CIA were age increase by 5 years (OR 1.50), ER positivity (OR 2.08), and HER2 3 + ( OR 0.40) according to logistic regression analysis. According to the log rank test and the Cox proportional hazards model, CIA group had significantly better disease-free survival than non-CIA group (P < .0001). However, according to time-dependent Cox model that was used to reduce guarantee-time bias, CIA was not a statistically significant prognostic factor in both ER-positive and ER-negative patients.
Conclusion
Treatment with taxane alone caused high frequency of CIA in premenopausal women with breast cancer. CIA did not turn out to be an independent prognostic factor, taking guarantee-time bias into consideration. Further clinical studies are needed to validate these findings. en-copyright= kn-copyright= en-aut-name=IwamotoTakayuki en-aut-sei=Iwamoto en-aut-mei=Takayuki 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=UemuraYukari en-aut-sei=Uemura en-aut-mei=Yukari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=WatanabeToru en-aut-sei=Watanabe en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhashiYasuo en-aut-sei=Ohashi en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Breast Medical Oncology Department, Cancer Institute Hospital of JFCR kn-affil= affil-num=3 en-affil=Department of Clinical Research, National Center for Global Health and Medicine kn-affil= affil-num=4 en-affil=Department of Breast and Medical Oncology, National Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Medical Oncology, Hamamatsu Oncology Center kn-affil= affil-num=6 en-affil=Department of Integrated Science and Engineering for Sustainable Society, Chuo University kn-affil= en-keyword=Chemotherapy-induced amenorrhea kn-keyword=Chemotherapy-induced amenorrhea en-keyword=Taxane kn-keyword=Taxane en-keyword=Taxane kn-keyword=Taxane en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Guarantee-time bias kn-keyword=Guarantee-time bias en-keyword=Premenopause kn-keyword=Premenopause END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=Suppl. 2 article-no= start-page=S118 end-page=S119 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201903 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of breast surgery in de novo stage IV breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=The article, entitled “Impact of Breast Surgery in Primary Metastasized Breast Cancer Outcomes of the Prospective Randomized Phase III ABCSG-28 POSYTIVE Trial,” published in the /i>Annals of Surgery (1), is the third to study to prospectively evaluate the prognostic efficacy of breast surgery in patients with metastases (Table 1). 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= affil-num=1 en-affil=Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=50 cd-vols= no-issue=3 article-no= start-page=225 end-page=229 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Adjuvant and neoadjuvant therapy for breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Systemic therapies for operable breast cancer patients have improved outcomes and have thus become standard treatments. Recently, new molecular target drugs and regimens are being developed based on the predicted sensitivity for specific breast cancer histological types. Systemic therapy is selected according to recurrence risk, with the treatment for low-risk patients being de-escalated, while high-risk patients receive aggressive systemic treatment with an adequate dose and duration. Neoadjuvant systemic therapy has a different aim. The efficacy of systemic therapies, based on the sensitivities to drugs, is supported by improvements in the rate of breast-conserving therapy. The response to neoadjuvant systemic therapy is the most important factor for predicting outcomes and selecting the optimal adjuvant therapy. Novel biological markers unique to individual patients allow appropriate targeted therapy, which can achieve optimal efficacy. 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=IwataHiroji en-aut-sei=Iwata en-aut-mei=Hiroji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Okayama University Hospital kn-affil= affil-num=2 en-affil=Okayama University Hospital kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=adjuvant kn-keyword=adjuvant en-keyword=neoadjuvant kn-keyword=neoadjuvant END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=2 article-no= start-page=109 end-page=114 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202004 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Risk of Gynecologic Cancer as Second versus First Primary Cancer in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract= This study aimed to determine whether the risk conferred by gynecologic cancer (GC) as second primary cancer (SPC) differs from that associated with GC as first primary cancer (FPC). We investigated the correlations between FPC/SPC and the characteristics and prognoses of 1,645 GC patients (701 with cervical cancer [CC], 641 with endometrial cancer [EM], and 303 with ovarian cancer [OV]). The χ2 test and the Kaplan–Meier method were used to determine whether FPC/SPC and the characteristics and prognoses of GC patients. Of the SPC patients, 26 (3.7%) had CC, 53 (8.3%) had EM, and 31 (10.2%) had OV. The most common previous cancer type in SPC of GC patients was breast cancer, which was observed in 13 patients (50.0%) with CC, 23 (43.4%) with EM, and 16 (51.6%) with OV. In all patients with CC, EM, and OV as SPC, the stage was significantly associated with recurrence. There were no significant differences in the morbidity or mortality of CC, EM, or OV patients between those with FPC and those with SPC. The risk of SPC development in GC patients varied, ranging from 3.5% (CC) to 10.3% (OV) of patients. 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=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=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=MatsubaraYuko en-aut-sei=Matsubara en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaragaJunko en-aut-sei=Haraga en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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= en-keyword=second primary cancer kn-keyword=second primary cancer en-keyword=gynecologic cancer kn-keyword=gynecologic cancer en-keyword=prognosis kn-keyword=prognosis END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=2 article-no= start-page=95 end-page=101 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202004 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Efficacy of Software to Help Patients Understand Drug for Adjuvant Treatment for Breast Cancer: A Pilot Randomized Controlled Trial en-subtitle= kn-subtitle= en-abstract= kn-abstract= We assessed the usefulness of ChemoCalc, a software package for calculating drug costs, in helping patients understand these costs. We randomly assigned, in a 1 : 1 ratio, 20 women who had undergone surgery for early breast cancer to a group that discussed adjuvant treatment with their physicians using the ChemoCalc software (ChemoCalc group) or a group that discussed adjuvant treatment without ChemoCalc (Usual Explanation group). The participants completed a five-grade evaluation questionnaire after these discussions. The primary endpoint was the intergroup comparison of the questionnaire scores regarding participants’ understanding of their treatment-associated drug costs. Median age was not significantly different between the ChemoCalc group and Usual Explanation group (57 vs. 50, respectively; p=0.27). Patients in the ChemoCalc group had a significantly higher perceived level of understanding of the drug cost than those in the Usual Explanation group (5 [4-5] vs. 2.5 [1-5], respectively; p=0.002). Scores related to the patients’ perception that understanding drug costs is an important part of breast cancer treatment were also higher in the ChemoCalc group than the Usual Explanation group (5 [2-5] vs. 3 [1-5], respectively; p=0.049). ChemoCalc was found to be useful for understanding drug costs. en-copyright= kn-copyright= en-aut-name=KubaSayaka en-aut-sei=Kuba en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamanouchiKosho en-aut-sei=Yamanouchi en-aut-mei=Kosho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 ORCID= en-aut-name=InamasuEiko en-aut-sei=Inamasu en-aut-mei=Eiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HatachiToshiko en-aut-sei=Hatachi en-aut-mei=Toshiko 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=MatsumotoMegumi en-aut-sei=Matsumoto en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=MiyamotoJunya en-aut-sei=Miyamoto en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SatoShuntaro en-aut-sei=Sato en-aut-mei=Shuntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakagawaHiroo en-aut-sei=Nakagawa en-aut-mei=Hiroo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KanetakaKengo en-aut-sei=Kanetaka en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TakatsukiMitsuhisa en-aut-sei=Takatsuki en-aut-mei=Mitsuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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=16 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 Surgery, Nagasaki University Graduate School of Biomedical Science kn-affil= affil-num=4 en-affil=Department of Surgery, Nagasaki University Graduate School of Biomedical Science kn-affil= affil-num=5 en-affil=Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science kn-affil= affil-num=6 en-affil=Department of Surgical Oncology, 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 Surgical Oncology, 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 Clinical Research Center, Nagasaki University Graduate School of Biomedical Science kn-affil= affil-num=11 en-affil=Department of Clinical Research Center, Nagasaki University Graduate School of Biomedical Science kn-affil= affil-num=12 en-affil=Department of Pharmacy, Nagasaki University Graduate School of Biomedical Science kn-affil= affil-num=13 en-affil=Department of Surgery, Nagasaki University Graduate School of Biomedical Science kn-affil= affil-num=14 en-affil=Department of Surgery, Nagasaki University Graduate School of Biomedical Science kn-affil= affil-num=15 en-affil=Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science kn-affil= affil-num=16 en-affil=Department of Surgery, Nagasaki University Graduate School of Biomedical Science kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=drug costs kn-keyword=drug costs en-keyword=ChemoCalc kn-keyword=ChemoCalc END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=13 article-no= start-page=2495 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190708 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Alpinia zerumbet (Pers.): Food and Medicinal Plant with Potential In Vitro and In Vivo Anti-Cancer Activities en-subtitle= kn-subtitle= en-abstract= kn-abstract=BACKGROUND/AIM:Plants play an important role in anti-cancer drug discovery, therefore, the current study aimed to evaluate the biological activity of Alpinia zerumbet (A. zerumbet) flowers.
METHODS:The phytochemical and biological criteria of A. zerumbet were in vitro investigated as well as in mouse xenograft model.
RESULTS:A. zerumbet extracts, specially CH2Cl2 and MeOH extracts, exhibited the highest potent anti-tumor activity against Ehrlich ascites carcinoma (EAC) cells. The most active CH2Cl2 extract was subjected to bioassay-guided fractionation leading to isolatation of the naturally occurring 5,6-dehydrokawain (DK) which was characterized by IR, MS, 1H-NMR and 13C-NMR. A. zerumbet extracts, specially MeOH and CH2Cl2 extracts, exhibited significant inhibitory activity towards tumor volume (TV). Furthermore, A. zerumbet extracts declined the high level of malonaldehyde (MDA) as well as elevated the levels of superoxide dismutase (SOD) and catalase (CAT) in liver tissue homogenate. Moreover, DK showed anti-proliferative action on different human cancer cell lines. The recorded IC50 values against breast carcinoma (MCF-7), liver carcinoma (Hep-G2) and larynx carcinoma cells (HEP-2) were 3.08, 6.8, and 8.7 µg/mL, respectively.
CONCLUSION:Taken together, these findings open the door for further investigations in order to explore the potential medicinal properties of A. zerumbet. en-copyright= kn-copyright= en-aut-name=ZahraMaram Hussein en-aut-sei=Zahra en-aut-mei=Maram Hussein kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SalemTarek A. R. en-aut-sei=Salem en-aut-mei=Tarek A. R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=El-AaragBishoy en-aut-sei=El-Aarag en-aut-mei=Bishoy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YosriNermeen en-aut-sei=Yosri en-aut-mei=Nermeen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=ZakiKholoud en-aut-sei=Zaki en-aut-mei=Kholoud kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MareiAmel H. en-aut-sei=Marei en-aut-mei=Amel H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Abd El-WahedAida en-aut-sei=Abd El-Wahed en-aut-mei=Aida kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SaeedAamer en-aut-sei=Saeed en-aut-mei=Aamer kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KhatibAlfi en-aut-sei=Khatib en-aut-mei=Alfi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AlAjmiMohamed F. en-aut-sei=AlAjmi en-aut-mei=Mohamed F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShathiliAbdulrahman M. en-aut-sei=Shathili en-aut-mei=Abdulrahman M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=XiaoJianbo en-aut-sei=Xiao en-aut-mei=Jianbo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KhalifaShaden A. M. en-aut-sei=Khalifa en-aut-mei=Shaden A. M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=El-SeediHesham R. en-aut-sei=El-Seedi en-aut-mei=Hesham R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Biochemistry, College of Medicine, Qassim University kn-affil= affil-num=3 en-affil=Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Chemistry, Faculty of Science, Menoufia University kn-affil= affil-num=5 en-affil=Biochemistry Division, Chemistry Department, Faculty of Science, Menoufia University kn-affil= affil-num=6 en-affil=Department of Chemistry, Faculty of Science, Menoufia University kn-affil= affil-num=7 en-affil=Department of Chemistry, Faculty of Science, Menoufia University kn-affil= affil-num=8 en-affil=Department of Chemistry, Faculty of Science, Menoufia University kn-affil= affil-num=9 en-affil=Department of Chemistry, Quaid-i-Azam University kn-affil= affil-num=10 en-affil=Department of Pharmaceutical Chemistry, Faculty of Pharmacy, International Islamic University Malaysia kn-affil= affil-num=11 en-affil=Pharmacognosy Group, College of Pharmacy, King Saud University kn-affil= affil-num=12 en-affil=Al-Rayan Research and Innovation Center, Al-Rayan Colleges kn-affil= affil-num=13 en-affil=Institute of Chinese Medical Sciences, University of Macau kn-affil= affil-num=14 en-affil=Clinical Research Centre, Karolinska University Hospital kn-affil= affil-num=15 en-affil=Department of Chemistry, Faculty of Science, Menoufia University kn-affil= en-keyword=Alpinia zerumbet kn-keyword=Alpinia zerumbet en-keyword=5,6-dehydrokawain kn-keyword=5,6-dehydrokawain en-keyword=Ehrlich ascites carcinoma kn-keyword=Ehrlich ascites carcinoma en-keyword=anti-tumor kn-keyword=anti-tumor en-keyword=anti-oxidant kn-keyword=anti-oxidant END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=24 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cancer Cell-Derived Granulocyte-Macrophage Colony-Stimulating Factor Is Dispensable for the Progression of 4T1 Murine Breast Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=We previously reported that 4T1 murine breast cancer cells produce GM-CSF that up-regulates macrophage expression of several cancer promoting genes, including Mcp-1/Ccl2, Ccl17 and Rankl, suggesting a critical role of cancer cell-derived GM-CSF in cancer progression. Here, we attempted to define whether 4T1 cell-derived GM-CSF contributes to the expression of these genes by 4T1tumors, and their subsequent progression. Intraperitoneal injection of anti-GM-CSF neutralizing antibody did not decrease the expression of Mcp-1, Ccl17 or Rankl mRNA by 4T1 tumors. To further examine the role of cancer cell-derived GM-CSF, we generated GM-CSF-deficient 4T1 cells by using the Crisper-Cas9 system. As previously demonstrated, 4T1 cells are a mixture of cells and cloning of cells by itself significantly reduced tumor growth and lung metastasis. By contrast, GM-CSF-deficiency did not affect tumor growth, lung metastasis or the expression of these chemokine and cytokine genes in tumor tissues. By in-situ hybridization, the expression of Mcp-1 mRNA was detected in both F4/80-expressing and non-expressing cells in tumors of GM-CSF-deficient cells. These results indicate that cancer cell-derived GM-CSF is dispensable for the tuning of the 4T1 tumor microenvironment and the production of MCP-1, CCL17 or RANKL in the 4T1 tumor microenvironment is likely regulated by redundant mechanisms. 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=NakamuraKaoru en-aut-sei=Nakamura en-aut-mei=Kaoru 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=ShiinaTsuyoshi en-aut-sei=Shiina en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ImamuraMayu en-aut-sei=Imamura en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=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 Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa 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=macrophages kn-keyword=macrophages en-keyword=chemokines kn-keyword=chemokines en-keyword=cytokines kn-keyword=cytokines en-keyword=inflammation kn-keyword=inflammation en-keyword=tumor microenvironment kn-keyword=tumor microenvironment en-keyword=breast cancer kn-keyword=breast cancer END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=1 article-no= start-page=89 end-page=94 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202002 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Multicenter, Open-label, Clinical Trial to Assess the Effectiveness and Safety of Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced-intensity Conditioning in Relapsed/refractory Anaplastic Large-cell Lymphoma in Children en-subtitle= kn-subtitle= en-abstract= kn-abstract= No standard treatment for relapsed or refractory anaplastic large-cell lymphoma (ALCL) has been established. This study is a multicenter, open-label trial to examine the effectiveness and safety of transplantation with reduced-intensity conditioning (RIC) for patients under 20 years old with relapsed or refractory ALCL. We defined RIC as the administration of fludarabine (30 mg/m2/day) for five days plus melphalan (70 mg/m2/day) for two days and total body irradiation at 4 Gy, followed by allogeneic hematopoietic stem cell transplantation. en-copyright= kn-copyright= en-aut-name=KadaAkiko en-aut-sei=Kada en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukanoReiji en-aut-sei=Fukano en-aut-mei=Reiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriTetsuya en-aut-sei=Mori en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KameiMichi en-aut-sei=Kamei en-aut-mei=Michi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaFumiko en-aut-sei=Tanaka en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UeyamaJunichi en-aut-sei=Ueyama en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SekimizuMasahiro en-aut-sei=Sekimizu en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OsumiTomoo en-aut-sei=Osumi en-aut-mei=Tomoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoriTakeshi en-aut-sei=Mori en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KogaYuhki en-aut-sei=Koga en-aut-mei=Yuhki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhkiKentaro en-aut-sei=Ohki en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujitaNaoto en-aut-sei=Fujita en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MitsuiTetsuo en-aut-sei=Mitsui en-aut-mei=Tetsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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=15 ORCID= en-aut-name=KobayashiRyoji en-aut-sei=Kobayashi en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Clinical Research Center, NHO Nagoya Medical Center kn-affil= affil-num=2 en-affil=Department of Pediatrics, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Pediatrics, St. Marianna University School of Medicine Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=5 en-affil=Department of Pediatrics, Saiseikai Yokohamashi Nanbu Hospital kn-affil= affil-num=6 en-affil=Department of Pediatrics, Tottori University Hospital, kn-affil= affil-num=7 en-affil=Department of Pediatrics, NHO Nagoya Medical Center kn-affil= affil-num=8 en-affil=Children’s Cancer Center, National Center for Child Health and Development kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Children’s Cancer Center, Kobe Children’s Hospital kn-affil= affil-num=10 en-affil=Department of Pediatrics, Graduate School of Medical Sciences Kyushu University kn-affil= affil-num=11 en-affil=Department of Pediatric Hematology and Oncology Research, National Center for Child Health and Development kn-affil= affil-num=12 en-affil=Department of Pediatrics, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital kn-affil= affil-num=13 en-affil=Department of Pediatrics, Yamagata University Hospital kn-affil= affil-num=14 en-affil=Clinical Research Center, NHO Nagoya Medical Center kn-affil= affil-num=15 en-affil=Clinical Research Center, NHO Nagoya Medical Center kn-affil= affil-num=16 en-affil=Department of Pediatrics and Adolescence, Sapporo Hokuyu Hospital kn-affil= en-keyword=anaplastic large-cell lymphoma kn-keyword=anaplastic large-cell lymphoma en-keyword=relapsed/refractory kn-keyword=relapsed/refractory en-keyword=fludarabine kn-keyword=fludarabine en-keyword=melphalan kn-keyword=melphalan en-keyword=total body irradiation kn-keyword=total body irradiation END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=1 article-no= start-page=1 end-page=6 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202002 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Promising New Anti-Cancer Strategy: Iron Chelators Targeting CSCs en-subtitle= kn-subtitle= en-abstract= kn-abstract= Iron is a trace but vital element in the human body and is necessary for a multitude of crucial processes in life. However, iron overload is known to induce carcinogenesis via oxidative stress. Cancer cells require large amounts of iron for their rapid division and cell growth. Iron was recently found to play a role in cancer stem cells (CSCs); it maintains stemness during development. Iron also plays an important role in stemness by moderating reactive oxygen species. Thus, iron metabolism in CSCs is a promising therapeutic target. In this review, we summarize the roles of iron in cancer cells and CSCs. We also summarize anti-cancer therapeutic studies with iron chelators and describe our expectation of a new therapeutic strategy for CSCs on the basis of our findings. en-copyright= kn-copyright= en-aut-name=ChenYuehua en-aut-sei=Chen en-aut-mei=Yuehua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=XingBoyi en-aut-sei=Xing en-aut-mei=Boyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=QiJiping en-aut-sei=Qi en-aut-mei=Jiping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=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= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pathology, the First Affiliated Hospital of Harbin Medical University 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 Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=cancer stem cell kn-keyword=cancer stem cell en-keyword=stemness kn-keyword=stemness en-keyword=iron kn-keyword=iron en-keyword=chelation kn-keyword=chelation en-keyword=chemotherapy kn-keyword=chemotherapy END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=2 article-no= start-page=2177 end-page=2186 dt-received= dt-revised= dt-accepted= dt-pub-year=2018 dt-pub=20181219 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Associations in tumor infiltrating lymphocytes between clinicopathological factors and clinical outcomes in estrogen receptor-positive/human epidermal growth factor receptor type 2 negative breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= The value of assessing tumor infiltrating lymphocytes (TILs) in estrogen receptor (ER) positive/human epidermal growth factor receptor type 2 (HER2) negative breast cancer has yet to be determined. In the present study, a total of 184 cases with early distant recurrence detected within 5 years following the primary operation, 134 with late distant recurrence diagnosed following 5 years or longer and 321 controls without recurrence for >10 years following starting the initial treatment for ER-positive/HER2 negative breast cancer, registered in 9 institutions, were analyzed. The distributions of TILs and their clinical relevance were investigated. TIL distributions did not differ significantly among the early, late and no recurrence groups, employing a 30% cut-off point as a dichotomous variable. In those who had received adjuvant chemotherapy as well as endocrine therapy, a trend toward higher TIL proportions was detected when the early recurrence group was compared with the no recurrence group employing the 30% cut-off point (P=0.064). The TIL distributions were significantly associated with nodal metastasis (P=0.004), ER status (P=0.045), progesterone receptor (PgR) status (P=0.002), tumor grade (P=0.021), and the Ki67 labeling index (LI) (P=0.002) in the no recurrence group and with the Ki67 LI in the recurrence groups (P=0.002 in early recurrence group, P=0.023 in late recurrence group). High TIL distributions also predicted shorter survival time following the detection of recurrence (P=0.026). However, these prognostic interactions were not significant in multivariate analysis (P=0.200). The present retrospective study demonstrated no significant interaction between TIL proportions and the timing of recurrence. However, higher TIL proportions were observed in breast cancer patients with aggressive biological phenotypes, which tended to be more responsive to chemotherapy. The clinical relevance of stromal TILs for identifying patients who would likely benefit from additional therapies merits further investigation in a larger patient population. en-copyright= kn-copyright= en-aut-name=MiyoshiYuichiro en-aut-sei=Miyoshi en-aut-mei=Yuichiro 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=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=IshidaNaoko en-aut-sei=Ishida en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamazakiKieko en-aut-sei=Yamazaki en-aut-mei=Kieko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoriiRie en-aut-sei=Horii en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HorimotoYoshiya en-aut-sei=Horimoto en-aut-mei=Yoshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=YasojimaHiroyuki en-aut-sei=Yasojima en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=InaoTouko en-aut-sei=Inao en-aut-mei=Touko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OsakoTomofumi en-aut-sei=Osako en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=TomiokaNobumoto en-aut-sei=Tomioka en-aut-mei=Nobumoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Wanifuchi‑EndoYumi en-aut-sei=Wanifuchi‑Endo en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HosodaMitsuchika en-aut-sei=Hosoda en-aut-mei=Mitsuchika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 ORCID= en-aut-name=YamashitaHiroko en-aut-sei=Yamashita en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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 Surgical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research kn-affil= affil-num=4 en-affil=Department of Breast Surgery, Hokkaido University Hospital kn-affil= affil-num=5 en-affil= Department of Breast Surgical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research kn-affil= affil-num=6 en-affil=Division of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research kn-affil= affil-num=7 en-affil= Department of Breast Oncology, Juntendo University School of Medicine kn-affil= affil-num=8 en-affil=Department of Surgery, Breast Oncology, NHO Osaka National Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, Breast Oncology, NHO Osaka National Hospital kn-affil= affil-num=10 en-affil=Department of Breast and Endocrine Surgery, Graduate School of Medical Science Kumamoto University kn-affil= affil-num=11 en-affil=Department of Breast and Endocrine Surgery, Kumamoto City Hospital kn-affil= affil-num=12 en-affil=Department of Breast Surgery, NHO Hokkaido Cancer Center kn-affil= affil-num=13 en-affil=Department of Breast Surgery, NHO Hokkaido Cancer Center kn-affil= affil-num=14 en-affil=Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=15 en-affil=Department of Breast Surgery, Hokkaido University Hospital kn-affil= affil-num=16 en-affil= Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=17 en-affil=Department of Breast Surgery, Hokkaido University Hospital kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=estrogen receptor positive kn-keyword=estrogen receptor positive en-keyword=human epidermal growth factor receptor type 2 negative kn-keyword=human epidermal growth factor receptor type 2 negative en-keyword=prognosis kn-keyword=prognosis en-keyword=tumor infiltrating lymphocytes kn-keyword=tumor infiltrating lymphocytes END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=7 article-no= start-page=627 end-page=640 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201907 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Critical role of the MCAM-ETV4 axis triggered by extracellular S100A8/A9 in breast cancer aggressiveness en-subtitle= kn-subtitle= en-abstract= kn-abstract=Metastatic breast cancer is the leading cause of cancer-associated death in women. The progression of this fatal disease is associated with inflammatory responses that promote cancer cell growth and dissemination, eventually leading to a reduction of overall survival. However, the mechanism(s) of the inflammation-boosted cancer progression remains unclear. In this study, we found for the first time that an extracellular cytokine, S100A8/A9, accelerates breast cancer growth and metastasis upon binding to a cell surface receptor, melanoma cell adhesion molecule (MCAM). Our molecular analyses revealed an important role of ETS translocation variant 4 (ETV4), which is significantly activated in the region downstream of MCAM upon S100A8/A9 stimulation, in breast cancer progression in vitro as well as in vivo. The MCAM-mediated activation of ETV4 induced a mobile phenotype called epithelial-mesenchymal transition (EMT) in cells, since we found that ETV4 transcriptionally upregulates ZEB1, a strong EMT inducer, at a very high level. In contrast, downregulation of either MCAM or ETV4 repressed EMT, resulting in greatly weakened tumor growth and lung metastasis. Overall, our results revealed that ETV4 is a novel transcription factor regulated by the S100A8/A9-MCAM axis, which leads to EMT through ZEB1 and thereby to metastasis in breast cancer cells. Thus, therapeutic strategies based on our findings might improve patient outcomes. 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=SumardikaI Wayan en-aut-sei=Sumardika en-aut-mei=I Wayan 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=InoueYusuke en-aut-sei=Inoue en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IiokaHidekazu en-aut-sei=Iioka en-aut-mei=Hidekazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MitsuiYosuke en-aut-sei=Mitsui en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SaitoKen en-aut-sei=Saito en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 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=12 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=13 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=14 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=15 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=16 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=17 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=18 ORCID= en-aut-name=KuboMiyoko en-aut-sei=Kubo en-aut-mei=Miyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=PutrantoEndy Widya en-aut-sei=Putranto en-aut-mei=Endy Widya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MurakamiTakashi en-aut-sei=Murakami en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=LiuMing en-aut-sei=Liu en-aut-mei=Ming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HibinoToshihiko en-aut-sei=Hibino en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 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=24 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=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= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 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=Faculty of Science and Technology, Division of Molecular Science, Gunma University kn-affil= affil-num=6 en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental 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=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental 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=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=12 en-affil=Department of Cell Biology, 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 Biobank, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Pediatrics, Dr. Sardjito Hospital/Faculty of Medicine, Universitas Gadjah Mada kn-affil= affil-num=21 en-affil=Department of Microbiology, Faculty of Medicine, Saitama Medical University kn-affil= affil-num=22 en-affil=Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University kn-affil= affil-num=23 en-affil=Department of Dermatology, Tokyo Medical University kn-affil= affil-num=24 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=25 en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=26 en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=27 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=1 article-no= start-page=51 end-page=59 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201902 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Body Mass Index of Japanese Gallbladder Cancer Patients on their Postoperative Outcomes en-subtitle= kn-subtitle= en-abstract= kn-abstract=　We investigated the relationship between body mass index (BMI) and postoperative outcomes in 450 gallbladder cancer patients in Japan. We collected patient information, including sex, age, underlying disease, BMI, stage, surgery method, postoperative time to discharge, and postoperative Medicare fees, from the Japanese administrative database associated with the Diagnosis Procedure Combination system. We classified patient BMIs as underweight (BMI<18.5 kg/m2), normal (BMI≥18.5 kg/m2 and <25 kg/m2) or overweight/obese (BMI≥25 kg/m2), then investigated the relationship between these categories and two postoperative outcomes: time to discharge and postoperative Medicare fees. The median postoperative time to discharge was 12 days in all patients, and 12 days in each of the three weight groups (p=0.62, n.s.). The median postoperative Medicare fees from surgery until discharge were (USD): all patients, $5,002; underweight, $5,875; normal weight, $4,797; and overweight/obese, $5,179 (p=0.146, n.s.). A multivariate analysis with adjustment for competing risk factors revealed that BMI was not associated with increased risk of longer postoperative time to discharge (normal weight: HR 1.17, p=0.29; overweight/obese: HR 1.17, p=0.37) or higher postoperative Medicare fees (OR 0.99, p=0.86, n.s.). Thus, high BMI was not found to be a factor for poor postoperative outcomes in Japanese patients with gallbladder cancer. en-copyright= kn-copyright= en-aut-name=FujiiMasakuni en-aut-sei=Fujii en-aut-mei=Masakuni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujimotoKenji en-aut-sei=Fujimoto en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YabeSyuntaro en-aut-sei=Yabe en-aut-mei=Syuntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NasuJunichiro en-aut-sei=Nasu en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyaikeJiro en-aut-sei=Miyaike en-aut-mei=Jiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshiokaMasao en-aut-sei=Yoshioka en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShiodeJunji en-aut-sei=Shiode en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoKazuhide en-aut-sei=Yamamoto en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsudaShinya en-aut-sei=Matsuda en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=2 en-affil=Department of Public Health, University of Occupational and Environmental Health kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Imabari Saiseikai General Hospital kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=7 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=8 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=9 en-affil=Department of Public Health, University of Occupational and Environmental Health kn-affil= en-keyword=body mass index kn-keyword=body mass index en-keyword=gallbladder cancer kn-keyword=gallbladder cancer en-keyword=surgery kn-keyword=surgery en-keyword=obesity kn-keyword=obesity END start-ver=1.4 cd-journal=joma no-vol=72 cd-vols= no-issue=4 article-no= start-page=369 end-page=374 dt-received= dt-revised= dt-accepted= dt-pub-year=2018 dt-pub=201808 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hormonal Therapy Resistant Estrogen-receptor Positive Metastatic Breast Cancer Cohort (HORSE-BC) Study : Current Status of Treatment Selection in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract= The Hormonal therapy resistant estrogen-receptor positive metastatic breast cancer cohort (HORSE-BC) study is a multicenter observational study evaluating the efficacy and safety of secondary endocrine therapy (ET) for postmenopausal cases of metastatic breast cancer (MBC) with poor response to primary ET. In this initial report we analyze the HORSE-BC baseline data to clarify the current status of treatment selection for MBC in Japan. Baseline data for the 50 patients enrolled in HORSE-BC were analyzed, including patient characteristics, types of secondary ET, and reasons for selecting secondary ET. Postoperative recurrence was detected in 84% of patients (42/50) and de novo stage IV breast cancer in 16% (8/50). Forty-one patients (41/50; 82%) received fulvestrant, 5 patients (10%) received selective estrogen receptor modulators (SERMs), 3 patients (6%) received ET plus a mammalian target of rapamycin (mTOR) inhibitor, and 1 patient received an aromatase inhibitor (AI) as the secondary ET. Forty-five patients selected their secondary ET based on its therapeutic effect, while 14 patients selected it based on side effects. Most patients with progression after primary ET selected fulvestrant as the secondary ET based on its therapeutic and side effects. We await the final results from the HORSE-BC study. en-copyright= kn-copyright= en-aut-name=IwamotoTakayuki en-aut-sei=Iwamoto en-aut-mei=Takayuki 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=Fujisawa Tomomi en-aut-sei=Fujisawa en-aut-mei= Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Araki Kazuhiro en-aut-sei=Araki en-aut-mei= Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakamakiKentaro en-aut-sei=Sakamaki en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SangaiTakafumi en-aut-sei=Sangai en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Kikawa Yuichiro en-aut-sei=Kikawa en-aut-mei= Yuichiro 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=TakaoShintaro en-aut-sei=Takao en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatoMasako en-aut-sei=Sato en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=GotoYoshinari en-aut-sei=Goto en-aut-mei=Yoshinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YoshidaTakashi en-aut-sei=Yoshida en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=Aihara Tomohiko en-aut-sei=Aihara en-aut-mei= Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=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, Gunma Prefectural Cancer Center kn-affil= affil-num=4 en-affil=Department of Breast Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research kn-affil= affil-num=5 en-affil=Department of Biostatistics and Bioinformatics, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Department of Breast and Thyroid Surgery, Chiba University Hospital kn-affil= affil-num=7 en-affil=Department of Breast Surgery, Kobe City Medical Center General 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 Surgery, Hyogo Cancer Center kn-affil= affil-num=10 en-affil=Department of Breast Surgery, National Hospital Organization Hokkaido Cancer Center kn-affil= affil-num=11 en-affil=Department of Breast Surgery, Ota Memorial Hospital kn-affil= affil-num=12 en-affil=Department of Breast Surgery, Ota Memorial Hospital kn-affil= affil-num=13 en-affil=Department of Breast Surgery, National Hospital Organization Hokkaido Cancer Center kn-affil= affil-num=14 en-affil=Breast Center, Aihara Hospital kn-affil= affil-num=15 en-affil=Division of Breast and Medical Oncology, National Cancer Center Hospital East kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword= secondary endocrine therapy kn-keyword= secondary endocrine therapy en-keyword=low sensitivity kn-keyword=low sensitivity en-keyword=primary endocrine therapy kn-keyword=primary endocrine therapy en-keyword=fulvestrant kn-keyword=fulvestrant END start-ver=1.4 cd-journal=joma no-vol=116 cd-vols= no-issue=10 article-no= start-page=2146 end-page=2154 dt-received= dt-revised= dt-accepted= dt-pub-year=2015 dt-pub=20150421 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Role and Regulation of Myeloid Zinc Finger Protein 1 in Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= Myeloid zinc finger 1 (MZF1) belongs to the SCAN-Zinc Finger (SCAN-ZF) transcription factor family that has recently been implicated in a number of types of cancer. Although the initial studies concentrated on the role of MZF1 in myeloid differentiation and leukemia, the factor now appears to be involved in the etiology of major solid tumors such as lung, cervical, breast, and colorectal cancer. Here we discuss the regulation of MZF1 that mediated its recruitment and activation in cancer, concentrating on posttranslational modification by phosphorylation, and sumoylation, formation of promyelocytic leukemia nuclear bodies and its association with co-activators and co-repressors. en-copyright= kn-copyright= en-aut-name=Eguchi Taka en-aut-sei=Eguchi en-aut-mei=Taka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PrinceThomas en-aut-sei=Prince en-aut-mei=Thomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WegielBarbara en-aut-sei=Wegiel en-aut-mei=Barbara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=CalderwoodStuart K. en-aut-sei=Calderwood en-aut-mei=Stuart K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute kn-affil= affil-num=3 en-affil=Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=4 en-affil=Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= en-keyword=CANCER kn-keyword=CANCER en-keyword=FINGER-1 kn-keyword=FINGER-1 en-keyword=INVASION kn-keyword=INVASION en-keyword=MYELOID kn-keyword=MYELOID en-keyword=NUCLEAR BODY kn-keyword=NUCLEAR BODY en-keyword=SUMO kn-keyword=SUMO en-keyword=ZINC kn-keyword=ZINC 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=2018 dt-pub=20180323 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=原発性乳癌における腫瘍浸潤リンパ球（TILs）関連遺伝子マーカーは化学療法の治療効果を予測する kn-title=Tumour-infiltrating lymphocytes (TILs)-related genomic signature predicts chemotherapy response in breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KochiMariko en-aut-sei=Kochi en-aut-mei=Mariko kn-aut-name=河内麻里子 kn-aut-sei=河内 kn-aut-mei=麻里子 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=129 cd-vols= no-issue=2 article-no= start-page=89 end-page=91 dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=20170801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2016 Incentive Award of the Okayama Medical Association in Cancer Research (2016 Hayashibara Prize and Yamada Prize) kn-title=平成28年度岡山医学会賞 がん研究奨励賞（林原賞・山田賞） en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=藤田洋史 kn-aut-sei=藤田 kn-aut-mei=洋史 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Cytology and Histology, 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　細胞組織学 END start-ver=1.4 cd-journal=joma no-vol=71 cd-vols= no-issue=3 article-no= start-page=233 end-page=240 dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=201706 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lesion Size on Ultrasonography Predicts Potential Invasion in Ductal Carcinoma in situ Preoperatively Diagnosed by Breast Needle Biopsy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ductal carcinoma in situ (DCIS) of the breast has no potential to metastasize, but over 20% of cases preoperatively diagnosed as DCIS are upstaged on final pathology. The rates of upstaging and the predictors for invasion on final pathology were evaluated. For 240 primary breast cancers, radiological findings on mammography, ultrasonography, and magnetic resonance imaging were investigated along with pathological and clinical information. Univariate and multivariate analyses were performed to identify predictors of potential invasion. Of the 240 breast cancers, 68 (28.3%) showed invasion on final pathology, and 5 (2.5%) had sentinel node metastasis. The multivariate analysis identified five independent predictors: non-mass lesions >2.4 cm on ultrasonography (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.02-7.95, p=0.047), comedo-type histology (OR 6.89, 95% CI 1.89-25.08, p<0.01), solid-type histology (OR 7.97, 95% CI 2.08-30.49, p<0.01), palpable mass (OR 2.63, 95% CI 1.05-6.64, p=0.04), and bloody nipple discharge (OR 4.61, 95% CI 1.20-17.66, p=0.02). These five predictors were associated with invasion on final pathology and may help select candidates for sentinel node biopsy. 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=OsakoTomo en-aut-sei=Osako en-aut-mei=Tomo 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=AkiyamaFutoshi en-aut-sei=Akiyama en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwaseTakuji en-aut-sei=Iwase en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Breast Surgery, Takatsuki General Hospital kn-affil= affil-num=2 en-affil=Department of Pathology, the Cancer Institute Hospital of the Japanese Foundation for Cancer Research kn-affil= affil-num=3 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Division of Pathology, the Cancer Institute of the Japanese Foundation for Cancer Research kn-affil= affil-num=5 en-affil=Breast Oncology Center, the Cancer Institute Hospital of the Japanese Foundation for Cancer Research kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=DCIS kn-keyword=DCIS en-keyword=breast needle biopsy kn-keyword=breast needle biopsy en-keyword=imaging examination kn-keyword=imaging examination en-keyword=sentinel node biopsy kn-keyword=sentinel node biopsy 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=2017 dt-pub=20170324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=ER陽性HER2陰性乳癌・早期再発群、晩期再発群、無再発群においての癌幹細胞マーカーALDH1発現率の差異 kn-title=Differences in expression of the cancer stem cell marker aldehyde dehydrogenase 1 among estrogen receptor-positive/human epidermal growth factor receptor type 2-negative breast cancer cases with early, late, and no recurrence en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MiyoshiYuichiro en-aut-sei=Miyoshi en-aut-mei=Yuichiro kn-aut-name=三好雄一郎 kn-aut-sei=三好 kn-aut-mei=雄一郎 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=128 cd-vols= no-issue=3 article-no= start-page=237 end-page=239 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20161201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Biobank kn-title=バイオバンク en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MoritaMizuki en-aut-sei=Morita en-aut-mei=Mizuki kn-aut-name=森田瑞樹 kn-aut-sei=森田 kn-aut-mei=瑞樹 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 Biorepository Research and Networking, 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　クリニカルバイオバンクネットワーキング事業化研究講座 affil-num=2 en-affil=Department of Clinical Genomic Medicine, 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　臨床遺伝子医療学 END start-ver=1.4 cd-journal=joma no-vol=128 cd-vols= no-issue=3 article-no= start-page=179 end-page=182 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20161201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2015 Incentive Award of the Okayama Medical Association in Cancer Research (2015 Hayashibara Prize and Yamada Prize) kn-title=平成27年度岡山医学会賞 がん研究奨励賞（林原賞・山田賞） en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name=重安邦俊 kn-aut-sei=重安 kn-aut-mei=邦俊 aut-affil-num=1 ORCID= affil-num=1 en-affil=Baylor University Medical Center kn-affil=ベイラー大学メディカルセンター END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=5 article-no= start-page=425 end-page=427 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=201610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Phase I Trial of 100mg/m2 Docetaxel in Patients with Advanced or Recurrent Breast Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Docetaxel is a standard treatment for patients with advanced or recurrent breast cancer. The recommended dose is 60 to 100 mg/m2. Previous study have shown that the tumor response rates of patients who received docetaxel monotherapy at doses of 60, 75, and 100 mg/m2 were 22.1% , 23.3% , and 36.0% , respectively, and there was a significant relationship between the dose and response. In Europe and the United States, docetaxel is approved at a dose of 100 mg/m2, and Japanese guidelines also recommend a dose of 100 mg/m2. However, the approved dose in Japan is up to 75 mg/m2. We have launched a phase I trial evaluating 100 mg/m2 docetaxel in patients with advanced or relapsed breast cancer. The major eligibility criteria are as follows: age ≥20 years, pathologically diagnosed breast cancer, recurrent or advanced breast cancer, a good performance status, and HER2 [human epidermal growth factor receptor 2] negative. The primary endpoint is demonstrated safety of 100 mg/m2 docetaxel. This study will clarify whether 100mg/m2 docetaxel can be administrated safely in Japanese patients with advanced or recurrent breast cancer. en-copyright= kn-copyright= en-aut-name=TamuraTomoki en-aut-sei=Tamura en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HirataTaizo en-aut-sei=Hirata en-aut-mei=Taizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 ORCID= en-aut-name=HamadaAkinobu en-aut-sei=Hamada en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= en-aut-name=MizooTaeko en-aut-sei=Mizoo en-aut-mei=Taeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NogamiTomohiro en-aut-sei=Nogami en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 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=12 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=13 ORCID= affil-num=1 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Medical Oncology, National Hospital Organization Kure Medical Center kn-affil= affil-num=3 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Division of Clinical Pharmacology & Translational Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center kn-affil= affil-num=6 en-affil=Department of Breast and Endocrinological Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Breast and Endocrinological Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Breast and Endocrinological Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Breast and Endocrinological Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Breast and Endocrinological Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Breast and Endocrinological Surgery, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Breast and Endocrinological Surgery, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Breast and Endocrinological Surgery, Okayama University Hospital kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=phase I trial kn-keyword=phase I trial en-keyword=docetaxel kn-keyword=docetaxel END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=3 article-no= start-page=e58791 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130318 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=MCP-1/CCL2 plays an important role in the initiation and progression of cancer. Since tumor cells produce MCP-1, they are considered to be the main source of this chemokine. Here, we examined whether MCP-1 produced by non-tumor cells affects the growth and lung metastasis of 4T1 breast cancer cells by transplanting them into the mammary pad of WT or MCP-1−/− mice. Primary tumors at the injected site grew similarly in both mice; however, lung metastases were markedly reduced in MCP-1−/− mice, with significantly longer mouse survival. High levels of MCP-1 mRNA were detected in tumors growing in WT, but not MCP-1−/− mice. Serum MCP-1 levels were increased in tumor-bearing WT, but not MCP-1−/− mice. Transplantation of MCP-1−/− bone marrow cells into WT mice did not alter the incidence of lung metastasis, whereas transplantation of WT bone marrow cells into MCP-1−/− mice increased lung metastasis. The primary tumors of MCP-1−/− mice consistently developed necrosis earlier than those of WT mice and showed decreased infiltration by macrophages and reduced angiogenesis. Interestingly, 4T1 cells that metastasized to the lung constitutively expressed elevated levels of MCP-1, and intravenous injection of 4T1 cells producing a high level of MCP-1 resulted in increased tumor foci in the lung of WT and MCP-1−/− mice. Thus, stromal cell-derived MCP-1 in the primary tumors promotes lung metastasis of 4T1 cells, but tumor cell-derived MCP-1 can also contribute once tumor cells enter the circulation. A greater understanding of the source and role of this chemokine may lead to novel strategies for cancer treatment. 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=HowardO. M. Zack en-aut-sei=Howard en-aut-mei=O. M. Zack kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItoToshihiro en-aut-sei=Ito en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuwabaraMasaki en-aut-sei=Kuwabara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=ChenKeqiang en-aut-sei=Chen en-aut-mei=Keqiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LiuYing en-aut-sei=Liu en-aut-mei=Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=LiuMingyong en-aut-sei=Liu en-aut-mei=Mingyong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OppenheimJoost J. en-aut-sei=Oppenheim en-aut-mei=Joost J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WangJi Ming en-aut-sei=Wang en-aut-mei=Ji Ming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute affil-num=2 en-affil= kn-affil=Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute affil-num=3 en-affil= kn-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University affil-num=4 en-affil= kn-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University affil-num=5 en-affil= kn-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University affil-num=6 en-affil= kn-affil=Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute affil-num=7 en-affil= kn-affil=Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute affil-num=8 en-affil= kn-affil=Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute affil-num=9 en-affil= kn-affil=Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute affil-num=10 en-affil= kn-affil=Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute 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=2015 dt-pub=20150930 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=HER2陰性乳癌細胞に対する遺伝子導入技術を用いたHER2標的療法適応拡大の試み kn-title=Viral transduction of the HER2-extracellular domain expands trastuzumab-based photoimmunotherapy for HER2-negative breast cancer cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ShimoyamaKyoko en-aut-sei=Shimoyama en-aut-mei=Kyoko kn-aut-name=下山京子 kn-aut-sei=下山 kn-aut-mei=京子 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院 END start-ver=1.4 cd-journal=joma no-vol=127 cd-vols= no-issue=1 article-no= start-page=41 end-page=45 dt-received= dt-revised= dt-accepted= dt-pub-year=2015 dt-pub=20150401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A phase I trial of 100㎎/㎡ docetaxel in advanced or recurrent breast cancer patients kn-title=アンメットメディカルニーズを克服するためのプロジェクト「進行・再発乳癌に対するドセタキセル100㎎/㎡の第Ⅰ相試験」 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HirataTaizo en-aut-sei=Hirata en-aut-mei=Taizo kn-aut-name=平田泰三 kn-aut-sei=平田 kn-aut-mei=泰三 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学病院　新医療研究開発センター en-keyword=進行・再発乳癌 kn-keyword=進行・再発乳癌 en-keyword=ドセタキセル kn-keyword=ドセタキセル en-keyword=100㎎/㎡ kn-keyword=100㎎/㎡ en-keyword=医師主導治験 kn-keyword=医師主導治験 END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue= article-no= start-page=415 end-page=423 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20140711 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Up-regulation of brain-derived neurotrophic factor in the dorsal root ganglion of the rat bone cancer pain model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Metastatic bone cancer causes severe pain, but current treatments often provide insufficient pain relief. One of the reasons is that mechanisms underlying bone cancer pain are not solved completely. Our previous studies have shown that brain-derived neurotrophic factor (BDNF), known as a member of the neurotrophic family, is an important molecule in the pathological pain state in some pain models. We hypothesized that expression changes of BDNF may be one of the factors related to bone cancer pain; in this study, we investigated changes of BDNF expression in dorsal root ganglia in a rat bone cancer pain model. As we expected, BDNF mRNA (messenger ribonucleic acid) and protein were significantly increased in L3 dorsal root ganglia after intra-tibial inoculation of MRMT-1 rat breast cancer cells. Among the eleven splice-variants of BDNF mRNA, exon 1–9 variant increased predominantly. Interestingly, the up-regulation of BDNF is localized in small neurons (mostly nociceptive neurons) but not in medium or large neurons (non-nociceptive neurons). Further, expression of nerve growth factor (NGF), which is known as a specific promoter of BDNF exon 1–9 variant, was significantly increased in tibial bone marrow. Our findings suggest that BDNF is a key molecule in bone cancer pain, and NGF-BDNF cascade possibly develops bone cancer pain. en-copyright= kn-copyright= en-aut-name=TomotsukaNaoto en-aut-sei=Tomotsuka en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KakuRyuji en-aut-sei=Kaku en-aut-mei=Ryuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ObataNorihiko en-aut-sei=Obata en-aut-mei=Norihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuokaYoshikazu en-aut-sei=Matsuoka en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanzakiHirotaka en-aut-sei=Kanzaki en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TaniguchiArata en-aut-sei=Taniguchi en-aut-mei=Arata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MutoNoriko en-aut-sei=Muto en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OmiyaHiroki en-aut-sei=Omiya en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ItanoYoshitaro en-aut-sei=Itano en-aut-mei=Yoshitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatoTadasu en-aut-sei=Sato en-aut-mei=Tadasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IchikawaHiroyuki en-aut-sei=Ichikawa en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MizobuchiSatoshi en-aut-sei=Mizobuchi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil= kn-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Department of Pharmacy, Okayama University Hospital affil-num=6 en-affil= kn-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=7 en-affil= kn-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=8 en-affil= kn-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=9 en-affil= kn-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=10 en-affil= kn-affil=Department of Oral and Craniofacial Anatomy, Tohoku University Graduate School of Dentistry affil-num=11 en-affil= kn-affil=Department of Oral and Craniofacial Anatomy, Tohoku University Graduate School of Dentistry affil-num=12 en-affil= kn-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=13 en-affil= kn-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=BDNF kn-keyword=BDNF en-keyword=bone cancer pain kn-keyword=bone cancer pain en-keyword=chronic pain kn-keyword=chronic pain en-keyword=nerve growth factor kn-keyword=nerve growth factor END start-ver=1.4 cd-journal=joma no-vol=126 cd-vols= no-issue=3 article-no= start-page=187 end-page=190 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20141201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2013 Incentive Award of the Okayama Medical Association in General Medical Science (2013 Yuuki Prize) kn-title=平成25年度岡山医学会賞 総合研究奨励賞（結城賞） en-subtitle= kn-subtitle= en-abstract= kn-abstract=受賞対象論文: Yamamoto H, Higasa K, Sakaguchi M, Shien K, Soh J, Ichimura K, Furukawa M, Hashida S, Tsukuda K, Takigawa N, Matsuo K, Kiura K, Miyoshi S, Matsuda F, Toyooka S：Novel germline mutation in the transmembrane domain of HER2 in familial lung adenocarcinomas. J Natl Cancer Inst (2014) 106, djt338 en-copyright= kn-copyright= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name=山本寛斉 kn-aut-sei=山本 kn-aut-mei=寛斉 aut-affil-num=1 ORCID= affil-num=1 en-affil= 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=143 cd-vols= no-issue=2 article-no= start-page=403 end-page=409 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=201401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Estrogen receptor (ER) mRNA expression and molecular subtype distribution in ER-negative/progesterone receptor-positive breast cancers en-subtitle= kn-subtitle= en-abstract= kn-abstract=We examined estrogen receptor (ER) mRNA expression and molecular subtypes in stage I-III breast cancers that are progesterone receptor (PR) positive but ER and HER2 negative by immunohistochemistry (IHC) or fluorescent in situ hybridization. The ER, PR, and HER2 status was determined by IHC as part of routine clinical assessment (N = 501). Gene expression profiling was done with the Affymetrix U133A gene chip. We compared expressions of ESR1 and MKI67 mRNA, distribution of molecular subtypes by the PAM50 classifier, the sensitivity to endocrine therapy index, and the DLDA30 chemotherapy response predictor signature among ER/PR-positive (n = 223), ER-positive/PR-negative (n = 73), ER-negative/PR-positive (n = 20), and triple-negative (n = 185) cancers. All patients received neoadjuvant chemotherapy with an anthracycline and taxane and had adjuvant endocrine therapy only if ER or PR > 10 % positive. ESR1 expression was high in 25 % of ER-negative/PR-positive, in 79 % of ER-positive/PR-negative, in 96 % of ER/PR-positive, and in 12 % of triple-negative cancers by IHC. The average MKI67 expression was significantly higher in the ER-negative/PR-positive and triple-negative cohorts. Among the ER-negative/PR-positive patients, 15 % were luminal A, 5 % were Luminal B, and 65 % were basal like. The relapse-free survival rate of ER-negative/PR-positive patients was equivalent to ER-positive cancers and better than the triple-negative cohort. Only 20-25 % of the ER-negative/PR-positive tumors show molecular features of ER-positive cancers. In this rare subset of patients (i) a second RNA-based assessment may help identifying the minority of ESR1 mRNA-positive, luminal-type cancers and (ii) the safest clinical approach may be to consider both adjuvant endocrine and chemotherapy. en-copyright= kn-copyright= en-aut-name=ItohMitsuya en-aut-sei=Itoh en-aut-mei=Mitsuya 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=MatsuokaJunji en-aut-sei=Matsuoka en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NogamiTomohiro en-aut-sei=Nogami en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=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=TairaNaruto en-aut-sei=Taira en-aut-mei=Naruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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=10 ORCID= en-aut-name=HigakiKenji en-aut-sei=Higaki en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=13 ORCID= en-aut-name=SymmansW. Fraser en-aut-sei=Symmans en-aut-mei=W. Fraser kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=PusztaiLajos en-aut-sei=Pusztai en-aut-mei=Lajos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ affil-num=2 en-affil= kn-affil=Okayama Univ affil-num=3 en-affil= kn-affil=Okayama Univ affil-num=4 en-affil= kn-affil=Okayama Univ affil-num=5 en-affil= kn-affil=Okayama Univ affil-num=6 en-affil= kn-affil=Okayama Univ affil-num=7 en-affil= kn-affil=Okayama Univ affil-num=8 en-affil= kn-affil=Tokai Univ affil-num=9 en-affil= kn-affil=St Lukes Int Hosp affil-num=10 en-affil= kn-affil=Hiroshima City Hosp affil-num=11 en-affil= kn-affil=Hiroshima City Hosp affil-num=12 en-affil= kn-affil=Okayama Univ affil-num=13 en-affil= kn-affil=Okayama Univ affil-num=14 en-affil= kn-affil=Univ Texas MD Anderson Canc Ctr affil-num=15 en-affil= kn-affil=Yale Univ en-keyword=Estrogen receptor kn-keyword=Estrogen receptor en-keyword=Progesteron receptor kn-keyword=Progesteron receptor en-keyword=cDNA microarray kn-keyword=cDNA microarray en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Hormone therapy kn-keyword=Hormone 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=2014 dt-pub=20140630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=エストロゲン受容体（ER）陰性／プロゲステロン受容体陽性乳癌におけるER mRNA発現と分子サブタイプの分布 kn-title=Estrogen receptor (ER) mRNA expression and molecular subtype distribution in ER-negative/progesterone receptor-positive breast cancers en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ItoMitsuya en-aut-sei=Ito en-aut-mei=Mitsuya kn-aut-name=伊藤充矢 kn-aut-sei=伊藤 kn-aut-mei=充矢 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=138 cd-vols= no-issue=5 article-no= start-page=799 end-page=809 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=DNA methylation status of REIC/Dkk-3 gene in human malignancies en-subtitle= kn-subtitle= en-abstract= kn-abstract=The REIC (reduced expression in immortalized cells)/Dkk-3 is down-regulated in various cancers and considered to be a tumor suppressor gene. REIC/Dkk-3 mRNA has two isoforms (type-a,b). REIC type-a mRNA has shown to be a major transcript in various cancer cells, and its promoter activity was much stronger than that of type-b. In this study, we examined the methylation status of REIC/Dkk-3 type-a in a broad range of human malignancies. We examined REIC/Dkk-3 type-a methylation in breast cancers, non-small-cell lung cancers, gastric cancers, colorectal cancers, and malignant pleural mesotheliomas using a quantitative combined bisulfite restriction analysis assay and bisulfate sequencing. REIC/Dkk-3 type-a and type-b expression was examined using reverse transcriptional PCR. The relationships between the methylation and clinicopathological factors were analyzed. The rate of REIC/Dkk-3 type-a methylation ranged from 26.2 to 50.0% in the various primary tumors that were examined. REIC/Dkk-3 type-a methylation in breast cancer cells was significantly heavier than that in the other cell lines that we tested. REIC/Dkk-3 type-a methylation was inversely correlated with REIC/Dkk-3 type-a expression. There was a correlation between REIC/Dkk-3 type-a and type-b mRNA expression. REIC/Dkk-3 type-a expression was restored in MDA-MB-231 cells using 5-aza-2'-deoxycytidine treatment. We found that estrogen receptor-positive breast cancers were significantly more common among the methylated group than among the non-methylated group. REIC/Dkk-3 type-a methylation was frequently detected in a broad range of cancers and appeared to play a key role in silencing REIC/Dkk-3 type-a expression in these malignancies. en-copyright= kn-copyright= en-aut-name=HayashiTatsuro en-aut-sei=Hayashi en-aut-mei=Tatsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsanoHiroaki en-aut-sei=Asano en-aut-mei=Hiroaki 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= en-aut-name=TsukudaKazunori en-aut-sei=Tsukuda en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=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=TairaNaruto en-aut-sei=Taira en-aut-mei=Naruto 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=TanakaNorimitsu en-aut-sei=Tanaka en-aut-mei=Norimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=NasuYasutomo en-aut-sei=Nasu en-aut-mei=Yasutomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HuhNam-ho en-aut-sei=Huh en-aut-mei=Nam-ho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MiyoshiShinichiro en-aut-sei=Miyoshi en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=2 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=3 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=4 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=5 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=6 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=7 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=8 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=9 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=10 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg affil-num=11 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Urol affil-num=12 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cell Biol affil-num=13 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg en-keyword=DNA methylation kn-keyword=DNA methylation en-keyword=REIC/Dkk-3 kn-keyword=REIC/Dkk-3 en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Mesothelioma kn-keyword=Mesothelioma END start-ver=1.4 cd-journal=joma no-vol=126 cd-vols= no-issue=2 article-no= start-page=103 end-page=107 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20140801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Induction therapy followed by surgery for non small-cell lung cancer kn-title=非小細胞肺癌に対する術前治療後外科切除療法 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= 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=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　臨床遺伝子医療学 en-keyword=非小細胞肺癌 kn-keyword=非小細胞肺癌 en-keyword=導入療法 kn-keyword=導入療法 en-keyword=放射線化学療法 kn-keyword=放射線化学療法 en-keyword=外科切除 kn-keyword=外科切除 END start-ver=1.4 cd-journal=joma no-vol=124 cd-vols= no-issue=3 article-no= start-page=231 end-page=238 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=20121203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=HuH-7 cell line established from a highly differentiated human hepatocellular carcinoma kn-title=高分化型ヒト肝癌由来細胞株“HuH-7” en-subtitle= kn-subtitle= en-abstract= kn-abstract=高分化型ヒト肝癌由来細胞株“HuH-7”は，1982年にCancer Researchにその樹立を報告した．HuH-7は，当時の岡山大学医学部附属癌源研究施設病理部門（故佐藤二郎教授）の下で樹立し，これまで多くの研究分野で利用され，世界的に有名な肝癌細胞株となっている．本稿では，有用性の高い分化機能を有するヒト肝癌細胞株HuH-7について，肝細胞癌の腫瘍マーカーであるα-fetoprotein（AFP）を中心に，この細胞株を用いた研究分野に関する詳細を紹介する． en-copyright= kn-copyright= en-aut-name=NakabayashiHidekazu en-aut-sei=Nakabayashi en-aut-mei=Hidekazu kn-aut-name=中林秀和 kn-aut-sei=中林 kn-aut-mei=秀和 aut-affil-num=1 ORCID= en-aut-name=TaketaKazuhisa en-aut-sei=Taketa en-aut-mei=Kazuhisa kn-aut-name=武田和久 kn-aut-sei=武田 kn-aut-mei=和久 aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=北海道情報大学　医療情報学科 affil-num=2 en-affil= kn-affil=介護老人保健施設　仁和の里 en-keyword=肝細胞癌 kn-keyword=肝細胞癌 en-keyword=培養細胞 kn-keyword=培養細胞 en-keyword=α-フェトプロテイン kn-keyword=α-フェトプロテイン en-keyword=HuH-7 kn-keyword=HuH-7 END start-ver=1.4 cd-journal=joma no-vol=128 cd-vols= no-issue=3 article-no= start-page=735 end-page=747 dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=201108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Associations among baseline variables, treatment-related factors and health-related quality of life 2 years after breast cancer surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=Provision of social support and rehabilitation for patients with physical, mental, and functional problems after cancer treatment is important for long-term health-related quality of life (HRQOL). Effective use of human and financial healthcare resources requires identification of patients requiring rehabilitation. The objectives of the current study were to clarify the patterns of physical and psychosocial recovery over time, to evaluate the associations among baseline variables, treatment-related factors and HRQOL at 6 months, 1, and 2 years after breast cancer surgery, and to identify the significant factors predicting HRQOL at each point. A multicenter longitudinal study was performed to evaluate physical conditions, anxiety, depression, and HRQOL at 1 month (baseline), 6 months, 1, and 2 years after surgery in 196 patients (mean age: 53.3 years old) with early breast cancer and no postoperative recurrence. Physical conditions were evaluated using a patient-reported symptom checklist. HRQOL was rated using the functional assessment of cancer treatment scalegeneral (FACT-G) and the breast cancer subscale (FACTB). Anxiety and depression were rated using the hospital anxiety and depression scale (HADS). More than 50% of patients had local problems of "tightness", "arm weakness." and "arm lymphedema", and systemic problems of "reduced energy, fatigue, and general weakness" postoperatively. The HRQOL score significantly improved 1 year after surgery, and scores for physical, emotional and functional well-being also increased with time, whereas the score for social well-being was the highest at baseline and decreased with time. Depression and anxiety significantly improved with time. Concomitant disease, marital status, and the presence of a partner, anxiety and depression at baseline, pathological lymph node involvement, and adjuvant intravenous chemotherapy were significant factors predicting FACT-G scores at 6 months, 1, and 2 years after surgery. Depression at baseline was a strong predictor of HRQOL up to 2 years after surgery. These results suggest that physical rehabilitation is required for tightness and lymphedema to improve long-term postoperative physical function. A further study of psychosocial interventions is required to improve depression and social well-being after breast cancer surgery. 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=ShimozumaKojiro en-aut-sei=Shimozuma en-aut-mei=Kojiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 ORCID= en-aut-name=KuroiKatsumasa en-aut-sei=Kuroi en-aut-mei=Katsumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=SaitoMitsue en-aut-sei=Saito en-aut-mei=Mitsue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IhaShigemichi en-aut-sei=Iha en-aut-mei=Shigemichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WatanabeTakanori en-aut-sei=Watanabe en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatsumataNoriyuki en-aut-sei=Katsumata en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital affil-num=2 en-affil= kn-affil=Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University affil-num=3 en-affil= kn-affil=Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University affil-num=4 en-affil= kn-affil=Department of Breast Surgery, National Hospital Organization, National Shikoku Cancer Center affil-num=5 en-affil= kn-affil=Division of Clinical Trials and Research, Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital affil-num=6 en-affil= kn-affil=Division of Clinical Trials and Research, Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital affil-num=7 en-affil= kn-affil=Department of Breast Oncology, Juntendo University affil-num=8 en-affil= kn-affil=Department of Breast Surgery, Okayama Ofuku Clinic affil-num=9 en-affil= kn-affil=Department of Surgery, National Hospital Organization, Sendai Medical Center affil-num=10 en-affil= kn-affil=Department of Medical Oncology, National Cancer Center Hospital en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=HRQOL kn-keyword=HRQOL en-keyword=Depression kn-keyword=Depression en-keyword=Anxiety kn-keyword=Anxiety en-keyword=Chemotherapy kn-keyword=Chemotherapy END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=5 article-no= start-page=285 end-page=291 dt-received= dt-revised= dt-accepted= dt-pub-year=2010 dt-pub=201010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cancer of Unknown Primary Site:A Review of 28 Cases and the Efficacy of Cisplatin/Docetaxel Therapy at a Single Institute in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=We evaluated the efficacy and toxicity of cisplatin/docetaxel (CDDP/TXT) chemotherapy and identified prognostic factors in Japanese patients with cancer of unknown primary site (CUP). Twenty-eight consecutive patients seen at a single institute were reviewed retrospectively. Sixteen patients were treated with TXT 80mg/m2, followed by CDDP 75mg/m2. The overall response rate to CDDP/TXT treatment was 62.5%, with a median survival time (MST) of 22.7 months. Common adverse reactions were myelosuppression and hyponatremia. The MST of all 28 patients with CUP was 8.3 months, and the 1-year overall survival rate was 45.6%. Univariate analysis identified 5 prognostic factors:performance status, liver involvement, bone involvement, pleural involvement, and lymph node involvement. In conclusion, CDDP/TXT chemotherapy is effective with tolerable toxicity in patients with CUP. Japanese patients with CUP might be chemosensitive and may survive longer. en-copyright= kn-copyright= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiShunji en-aut-sei=Takahashi en-aut-mei=Shunji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=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=KobayashiTakayuki en-aut-sei=Kobayashi en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SanoKoji en-aut-sei=Sano en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShinozakiEiji en-aut-sei=Shinozaki en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YokoyamaMasahiro en-aut-sei=Yokoyama en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MishimaYuko en-aut-sei=Mishima en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TeruiYasuhito en-aut-sei=Terui en-aut-mei=Yasuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ChinKeisho en-aut-sei=Chin en-aut-mei=Keisho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MizunumaNobuyuki en-aut-sei=Mizunuma en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ItoYoshinori en-aut-sei=Ito en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=TakeuchiKengo en-aut-sei=Takeuchi en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IshikawaYuichi en-aut-sei=Ishikawa en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OguchiMasahiko en-aut-sei=Oguchi en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TanimotoMitsune en-aut-sei=Tanimoto en-aut-mei=Mitsune kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HatakeKiyohiko en-aut-sei=Hatake en-aut-mei=Kiyohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil= kn-affil=Department of Hematology, Oncology, Allergy, and Respiratory Medicine, Okayama University Hospital affil-num=2 en-affil= kn-affil=Division of Medical Oncology and Hematology, Cancer Institute Hospital affil-num=3 en-affil= kn-affil=Department of Hematology, Oncology, Allergy, and Respiratory Medicine, Okayama University Hospital affil-num=4 en-affil= kn-affil=Department of Hematology, Oncology, Allergy, and Respiratory Medicine, Okayama University Hospital affil-num=5 en-affil= kn-affil=Division of Medical Oncology and Hematology, Cancer Institute Hospital affil-num=6 en-affil= kn-affil=Division of Medical Oncology and Hematology, Cancer Institute Hospital affil-num=7 en-affil= kn-affil=Division of Medical Oncology and Hematology, Cancer Institute Hospital affil-num=8 en-affil= kn-affil=Division of Medical Oncology and Hematology, Cancer Institute Hospital affil-num=9 en-affil= kn-affil=Division of Medical Oncology and Hematology, Cancer Institute Hospital affil-num=10 en-affil= kn-affil=Division of Medical Oncology and Hematology, Cancer Institute Hospital affil-num=11 en-affil= kn-affil=Division of Medical Oncology and Hematology, Cancer Institute Hospital affil-num=12 en-affil= kn-affil=Division of Medical Oncology and Hematology, Cancer Institute Hospital affil-num=13 en-affil= kn-affil=Division of Medical Oncology and Hematology, Cancer Institute Hospital affil-num=14 en-affil= kn-affil=Division of Breast Surgery, Cancer Institute Hospital affil-num=15 en-affil= kn-affil=Division of Pathology, Cancer Institute of the Japanese Foundation for Cancer Research affil-num=16 en-affil= kn-affil=Division of Pathology, Cancer Institute of the Japanese Foundation for Cancer Research affil-num=17 en-affil= kn-affil=Division of Radiology, Cancer Institute Hospital affil-num=18 en-affil= kn-affil=Department of Hematology, Oncology, Allergy, and Respiratory Medicine, Okayama University Hospital affil-num=19 en-affil= kn-affil=Division of Medical Oncology and Hematology, Cancer Institute Hospital en-keyword=cancer of unknown primary site (CUP) kn-keyword=cancer of unknown primary site (CUP) en-keyword=cisplatin kn-keyword=cisplatin en-keyword=docetaxel kn-keyword=docetaxel en-keyword=prognosis kn-keyword=prognosis END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=4 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2004 dt-pub=20040615 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Addition of granulocyte-colony stimulating factor (G-CSF) may further increase chemosensitive state in premenopausal node-positive breast cancer patients with induced angiogenesis after surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=AltundagKadri en-aut-sei=Altundag en-aut-mei=Kadri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AltundagOzden en-aut-sei=Altundag en-aut-mei=Ozden kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GunduzMehmet en-aut-sei=Gunduz en-aut-mei=Mehmet kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Department of Medical Oncology, Hacettepe University Faculty of Medicine affil-num=2 en-affil= kn-affil=Department of Medical Oncology, Hacettepe University Faculty of Medicine affil-num=3 en-affil= kn-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine and Dentistry, Okayama University END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=4 article-no= start-page=R291 end-page=R299 dt-received= dt-revised= dt-accepted= dt-pub-year=2004 dt-pub=20040426 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Introduction The present study was conducted to examine the effect of conjugated docosahexaenoic acid (CDHA) on cell growth, cell cycle progression, mode of cell death, and expression of cell cycle regulatory and/or apoptosis-related proteins in KPL-1 human breast cancer cell line. This effect of CDHA was compared with that of docosahexaenoic acid (DHA).
Methods KPL-1 cell growth was assessed by colorimetric 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; cell cycle progression and mode of cell death were examined by flow cytometry; and levels of expression of p53, p21Cip1/Waf1, cyclin D1, Bax, and Bcl-2 proteins were examined by Western blotting analysis. In vivo tumor growth was examined by injecting KPL-1 cells subcutaneously into the area of the right thoracic mammary fat pad of female athymic mice fed a CDHA diet.
Results CDHA inhibited KPL-1 cells more effectively than did DHA (50% inhibitory concentration for 72 hours: 97 μmol/l and 270 μmol/l, respectively). With both CDHA and DHA growth inhibition was due to apoptosis, as indicated by the appearance of a sub-G1 fraction. The apoptosis cascade involved downregulation of Bcl-2 protein; Bax expression was unchanged. Cell cycle progression was due to G0/G1 arrest, which involved increased expression of p53 and p21Cip1/Waf1, and decreased expression of cyclin D1. CDHA modulated cell cycle regulatory proteins and apoptosis-related proteins in a manner similar to that of parent DHA. In the athymic mouse system 1.0% dietary CDHA, but not 0.2%, significantly suppressed growth of KPL-1 tumor cells; CDHA tended to decrease regional lymph node metastasis in a dose dependent manner.
Conclusion CDHA inhibited growth of KPL-1 human breast cancer cells in vitro more effectively than did DHA. The mechanisms of action involved modulation of apoptosis cascade and cell cycle progression. Dietary CDHA at 1.0% suppressed KPL-1 cell growth in the athymic mouse system.

en-copyright= kn-copyright= en-aut-name=Tsujita-KyutokuMiki en-aut-sei=Tsujita-Kyutoku en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YuriTakashi en-aut-sei=Yuri en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DanbaraNaoyuki en-aut-sei=Danbara en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SenzakiHideto en-aut-sei=Senzaki en-aut-mei=Hideto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KiyozukaYasuhiko en-aut-sei=Kiyozuka en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UeharaNorihisa en-aut-sei=Uehara en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakadaHideho en-aut-sei=Takada en-aut-mei=Hideho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HadaTakahiko en-aut-sei=Hada en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyazawaTeruo en-aut-sei=Miyazawa en-aut-mei=Teruo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OgawaYutaka en-aut-sei=Ogawa en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsuburaAiro en-aut-sei=Tsubura en-aut-mei=Airo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil= kn-affil=Department of Pathology II, Kansai Medical University affil-num=2 en-affil= kn-affil=Department of Pathology II, Kansai Medical University affil-num=3 en-affil= kn-affil=Department of Pathology II, Kansai Medical University affil-num=4 en-affil= kn-affil=Department of Pathology II, Kansai Medical University affil-num=5 en-affil= kn-affil=Department of Pathology II, Kansai Medical University affil-num=6 en-affil= kn-affil=Department of Pathology II, Kansai Medical University affil-num=7 en-affil= kn-affil=Division of Surgery, Kansai Medical University Kori Hospital affil-num=8 en-affil= kn-affil=R&D Division, Bizen Chemical Co., Ltd affil-num=9 en-affil= kn-affil=Laboratory of Biodynamic Chemistry, Tohoku University Graduate School of Life Science and Agriculture affil-num=10 en-affil= kn-affil=Department of Plastic and Reconstructive Surgery, Kansai Medical University affil-num=11 en-affil= kn-affil=Department of Pathology II, Kansai Medical University en-keyword=apoptosis kn-keyword=apoptosis en-keyword=breast cancer kn-keyword=breast cancer en-keyword=conjugated docosahexaenoic acid kn-keyword=conjugated docosahexaenoic acid en-keyword=docosahexaenoic acid kn-keyword=docosahexaenoic acid en-keyword=human kn-keyword=human END start-ver=1.4 cd-journal=joma no-vol=104 cd-vols= no-issue=9-10 article-no= start-page=897 end-page=904 dt-received= dt-revised= dt-accepted= dt-pub-year=1992 dt-pub=199210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on cell biology and chemotherapy of lung cancer using tissue culture techniques Part 1. Drug sensitivity test in lung cancer using human tumor clonogenic assay kn-title=組織培養法を用いた肺癌の細胞生物学並びに治療に関する研究 第1編 Human Tumor Clonogenic Assay を用いた制癌剤感受性試験の検討―肺癌を中心として― en-subtitle= kn-subtitle= en-abstract= kn-abstract=The selection of a series of effective drugs for individual patients in advance of drug therapy should increase the success of cancer chemotherapy. The human tumor clonogenic assay was evaluated as a drug sensitivity test mainly in patients with lung cancer. Tumor cells from malignant pleural effusion, tumor-positive bone marrow aspirates, and tumor tissues from the primary or metastases were used as sepcimens. Prior to plating, tumor cells were exposed to 4-hydroperoxy ifosfamide, adriamycin, mitomycin C, methotrerxate, and cisplatin for one hour at graded concentrations which were achievable in man. Of 151 specimens tested, 93(62%) yielded at least 5 colonies in the control plates containing no durgs. Colony growth (≧5/plate) was seen in 80% of squamous cell carcinoma, in 73% of small cell carcinoma, in 62% of adenocarcinoma, and in 40% of large cell carcinoma. Among the 93 specimens with colony growth, 62 yielded more than 30 colonies in the control plates and were put in force for drug sensitivity testing. Of 37 instances in which the clinical response to a certain drug was examined, 34(92%) showed an in vitro-in vivo correlation, showing a true positive rate of 57% and a true negative rate of 100%. In summary, the human tumor clonogenic assay would be an excellent technique for testing the drug sensitivity of the tumor in individual patients tumor. en-copyright= kn-copyright= en-aut-name=KishimotoNobuyasu en-aut-sei=Kishimoto en-aut-mei=Nobuyasu kn-aut-name=岸本信康 kn-aut-sei=岸本 kn-aut-mei=信康 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第二内科学教室 en-keyword=human tumor clonogenic assay kn-keyword=human tumor clonogenic assay en-keyword=drug sensitivity kn-keyword=drug sensitivity en-keyword=lung cancer kn-keyword=lung cancer END start-ver=1.4 cd-journal=joma no-vol=105 cd-vols= no-issue=11-12 article-no= start-page=1009 end-page=1017 dt-received= dt-revised= dt-accepted= dt-pub-year=1993 dt-pub=19931231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on chemotherapy for malignant lymphoma Part 1. Salvage chemotherapy for non-Hodgkin's lymphoma ; MEPP : Combination of mitoxantrone, etoposide, cisplatin and prednisolone kn-title=悪性リンパ腫の化学療法に関する研究　第1編　Mitoxantrone, Etoposide, Cisplatin, Prednisolone 併用療法(MEPP) による non-Hodgkin's lymphoma の salvage 治療の検討 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Twenty six patients with non-Hodgkin's lymphoma (NHL), who failed to achieve complete remission or had relapsed after conventional chemotherapy (CHOP or CHOP-Bleo) were treated with a four-drug combination of mitoxantrone, etoposide, cisplatin and prednisolone (MEPP). Of 24 patients evaluated, five (21%) achieved complete remission and seven (29%) responded partially. The median duration of remission was 25 weeks, 38 weeks for complete responders (CRs), 24 weeks for partial responders (PRs). The median survival time after initiation of therapy was 93 weeks for CRs, 50 weeks for PRs and 25 weeks for non-responders (NRs). The difference in survival time between CRs and NRs was statistically significant. Myelosuppression was the major dose-limiting toxicity ; WBC nadir below 1,000/μl occurred in 66.2% of evaluable courses. Two patients with bone marrow involvement died of infection due to granulocytopenia. Renal toxicity of cisplatin was moderate and there was no cardiotoxicity of mitoxantrone detected. Despite severe myelotoxicity, these results indicate that MEPP regimen is useful as a salvage therapy for relapsed or refractory NHL. en-copyright= kn-copyright= en-aut-name=UenoKunio en-aut-sei=Ueno en-aut-mei=Kunio kn-aut-name=上野邦夫 kn-aut-sei=上野 kn-aut-mei=邦夫 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第二内科学教室 en-keyword=非ホジキンリンパ腫 kn-keyword=非ホジキンリンパ腫 en-keyword=salvage 治療 kn-keyword=salvage 治療 END start-ver=1.4 cd-journal=joma no-vol=105 cd-vols= no-issue=5-6 article-no= start-page=475 end-page=487 dt-received= dt-revised= dt-accepted= dt-pub-year=1993 dt-pub=1993 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Flow cytometric DNA analysis in thyroid tumors kn-title=甲状腺腫瘍の核DNA量と生物学的悪性度に関する研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract=To evaluate the biological malingnacy of differentiated thyroid cancer, we determined the nuclear DNA content in thyroid tumors by flow cytometry using paraffin-enbedded materials. The subjects were 80 patients with thyroid tumors. The thyroid tumors were follicular adenoma in 11 cases and thyroid cancer in 69 cases. Of the 69 cases of thyroid cancer, 42 were histologically classfied as papillary carcinoma, 18 as follicular carcinoma, 3 as medullary carcinoma and 6 as anaplastic carcinoma. DNA ploidy pattern and the percentage of proliferating phase cells were analyzed in relation to the prognosis and the following clinicopathological findings : age, gender, histological type, tumor size (t), extrathyroidal invasion (Ex), lymph node metastases (n) and distant metastases (M). DNA ploidy pattern correlated with histological type (p<0.005), but did not correlate with other clinicopathological findings. The percentage of prolipherating phase cells correlated with age (p<0.01) and the histlogical type (p<0.05), but did not correlate with other clinicopathological findings. The percentage of proliferating phase cells correlated with age (p<0.01) and the histological type (p<0.05), but did not correlate with other clinicopathological findings. The comulative survival rate (Kaplan- Meier) of differentiated carcinomas was worse in the aneuploid group than in the diploid group (p<0.0001). the percentage of proliferaging phase cells increased as the prognosis deteriorated. The results suggest that flow cytometric DNA analysis may be useful to evaluate biological malignancy of thyroid tumors. en-copyright= kn-copyright= en-aut-name=OnodaYuji en-aut-sei=Onoda en-aut-mei=Yuji kn-aut-name=小野田裕士 kn-aut-sei=小野田 kn-aut-mei=裕士 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第二外科学教室 en-keyword=甲状腺癌 kn-keyword=甲状腺癌 en-keyword=フローサイトメトリー kn-keyword=フローサイトメトリー en-keyword=生物学的悪性度 kn-keyword=生物学的悪性度 en-keyword=プロイディパターン kn-keyword=プロイディパターン en-keyword=増殖期細胞 kn-keyword=増殖期細胞 END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=3-4 article-no= start-page=391 end-page=399 dt-received= dt-revised= dt-accepted= dt-pub-year=1994 dt-pub=1994 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Neutrophil chemotactic factors induced by OK-432 in the treatment of malignant pleural effusion kn-title=癌性胸膜炎胸水中の好中球遊走因子に関する研究―溶連菌製剤OK-432による好中球遊走因子の誘導― en-subtitle= kn-subtitle= en-abstract= kn-abstract=To investigate the mechanism of neutrophil migration into the pleural effusion in patients undergoing intrapleural immunotherapy with the streptococal agent OK-432 for malignant pleurisy, we examined the levels of neutrophil chemotactic factor in the pleural fluid. Pleural fluid was collected before and after instillation of OK-432 in 19 patients with lung cancer, one with breast cancer, and one with gastric cancer. First we evaluated the neutrophil chemotactic activity measured by Byoden's method and the change of the cellular compositition of pleural fluid. Neutrophil chemotactic activity was significantly increased 6 hours after the instillation of OK-432, as were the differential neutrophil count and the absolute number of neutrophils. Moreover, there was a close correlation between the absolute neutrophil count and the neutrophil chemotactic activity. We also measured the levels of complement compo-nent C5a and interleukin-8 (IL-8), which are thought to be neutrophil chemotactic factor, before and after intrapleural injection of OK-432. The IL-8 and C5a levels were significantly elevated after OK-432 injection. The change of the IL-8 level was associated with a marked increase both in the neutrophil chemotactic activity and in the neutrophil absolute count. In addition, we evaluated the cytokine levels (IL-1β, IL-6 and soluble interleukin-2 receptor) of pleural fluid before and after OK-432 treatment. The OK-432 treatment induced a marked increase in the levels of IL-1β and IL-6. However, the pleural fluid level of sIL-2R was not significantly elevated, although it was significantly higher than the serum level. These findings suggest that OK-432 intrapleural injection induces neutrophil chemotactic factors (IL-8 and C5a) and cytokines (IL-1β and Il-6), which attracts neutrophils into the pleural space, which may be involved in the mechanism of the sclerosing effect of OK-432. en-copyright= kn-copyright= en-aut-name=MorishitaRyouji en-aut-sei=Morishita en-aut-mei=Ryouji kn-aut-name=森下亮二 kn-aut-sei=森下 kn-aut-mei=亮二 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第二内科学教室 en-keyword=malignant pleural effusin kn-keyword=malignant pleural effusin en-keyword=OK-432 kn-keyword=OK-432 en-keyword=neutrophil chemotactic factor kn-keyword=neutrophil chemotactic factor en-keyword=C5a kn-keyword=C5a en-keyword=IL-8 kn-keyword=IL-8 END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=3-4 article-no= start-page=379 end-page=389 dt-received= dt-revised= dt-accepted= dt-pub-year=1994 dt-pub=1994 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Chemothrapy of small cell lung cancer : Comparative phase Ⅱ study of CAV-PVP hybrid regimen and CAV-PVP sequential regimen in patients with small cell lung cancer(SCLC) kn-title=肺小細胞癌の化学療法の関する研究―肺小細胞癌に対するCAV-PVP hybrid療法とCAV-PVP sequential療法の無作為化比較試験― en-subtitle= kn-subtitle= en-abstract= kn-abstract=One hundred and forty three patients with previously untreated SCLC were randomly allocated to receive either the CAV-PVP hybrid (Hyb) regimen or CAV-PVP sequential(Seq) regimen between November 1987 and October 1992. The Hyb regimen consisted of CAV (cyclophosphamide 700mg/㎡,iv,day 1 ; adriamycin 30mg/㎡,iv,day 1 ; and vincristine 1.4mg/㎡,iv,day 1) and PVP (cisplatin 60mg/㎡,iv,day 8 ; and etoposide 100mg/㎡,iv,days 8 and 9), and was repeated up to 6 cycles at 4-week intervals. The Seq regimen consisted of an initial 3 cycles of CAV (cyclophosphamide 700mg/㎡,iv,days 1 and 8 ; adriamycin 30mg/㎡,iv days 1 and 8 ; and vincristine 1.4mg/㎡,iv,day 8 ; and vincristine 1.4mg/㎡,iv days 1 and 8) followed by 3 cycles of PVP (cisplatin 60mg/㎡,iv,days 1 and 8 ; and etoposide 100mg/㎡,iv,days 1, 2, 8 and 9) at 4-week intervals. For patients with limited disease (LD), thoracic irradiation at a dose of 50 Gy was given after a maximal response with chemotherapy, and LD patients achieving a complete response (CR) received prophylactic cranial irradiation at a dose of 30 Gy. For the LD patients, the overall response rate was 97% for the Hyb regimen with a CR rate of 59% and 100% for the Seq regimen with a CR rate of 45%. For the patients with extensive disease (ED), the overall response rate was 94% for the Hyb regimen with a CR rate of 21% and 78% for the Seq regimen with a CR rate of 16%. The median survival time (MST) for the LD patients was 17.9 months for the Hyb group and 20.9 months for the Seq group, and the MST for the ED patients was 9.7 months for the Hyb group and 12.2 months for the Seq group. The 3-year survival rate for the LD patients was 21.9% for the Hyb group and 18.8% for the Seq group. There was a trend favoring the Hyb regimen in terms of overal response rate, CR rate, and 3-year survival rate for the LD patients as well, but there was no significant difference in survival between the two treatment groups. Hematologic toxicity was the major dose-limiting toxicity, but it was generally well-tolerated in both treatment groups. These findings indicate that both Hyb and Seq regimens are equally effective for the prolongation of life in patients with SCLC. en-copyright= kn-copyright= en-aut-name=KameiHaruhito en-aut-sei=Kamei en-aut-mei=Haruhito kn-aut-name=亀井治人 kn-aut-sei=亀井 kn-aut-mei=治人 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第二内科学教室 en-keyword=肺小細胞癌 kn-keyword=肺小細胞癌 en-keyword=CAV-PVP hybrid療法 kn-keyword=CAV-PVP hybrid療法 en-keyword=CAV-PVP sequential療法 kn-keyword=CAV-PVP sequential療法 en-keyword=無作為化比較試験 kn-keyword=無作為化比較試験 en-keyword=dose-intensity kn-keyword=dose-intensity END start-ver=1.4 cd-journal=joma no-vol=120 cd-vols= no-issue=2 article-no= start-page=135 end-page=141 dt-received= dt-revised= dt-accepted= dt-pub-year=2008 dt-pub=20080801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Adenovirus-mediated REIC/Dkk-3 gene therapy for prostate tumor in vivo and in vitro kn-title=アデノウイルスベクターを用いた REIC/Dkk-3遺伝子導入による前立腺癌の転移抑制効果について en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=EdamuraKohei en-aut-sei=Edamura en-aut-mei=Kohei kn-aut-name=枝村康平 kn-aut-sei=枝村 kn-aut-mei=康平 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　泌尿器病態学 en-keyword=Dkk-3 kn-keyword=Dkk-3 en-keyword=REIC kn-keyword=REIC en-keyword=前立腺癌 kn-keyword=前立腺癌 en-keyword=転移 kn-keyword=転移 END start-ver=1.4 cd-journal=joma no-vol=119 cd-vols= no-issue=3 article-no= start-page=285 end-page=292 dt-received= dt-revised= dt-accepted= dt-pub-year=2008 dt-pub=20080104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=II Standard treatment for advanced lung cancer kn-title=II 肺癌の内科的治療 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name=木浦勝行 kn-aut-sei=木浦 kn-aut-mei=勝行 aut-affil-num=1 ORCID= en-aut-name=TakigawaNagio en-aut-sei=Takigawa en-aut-mei=Nagio kn-aut-name=瀧川奈義夫 kn-aut-sei=瀧川 kn-aut-mei=奈義夫 aut-affil-num=2 ORCID= en-aut-name=OzeIsao en-aut-sei=Oze en-aut-mei=Isao kn-aut-name=尾瀬功 kn-aut-sei=尾瀬 kn-aut-mei=功 aut-affil-num=3 ORCID= en-aut-name=YasugiMasayuki en-aut-sei=Yasugi en-aut-mei=Masayuki kn-aut-name=八杉昌幸 kn-aut-sei=八杉 kn-aut-mei=昌幸 aut-affil-num=4 ORCID= en-aut-name=OchiNobuaki en-aut-sei=Ochi en-aut-mei=Nobuaki kn-aut-name=越智宣昭 kn-aut-sei=越智 kn-aut-mei=宣昭 aut-affil-num=5 ORCID= en-aut-name=HaradaDaijiro en-aut-sei=Harada en-aut-mei=Daijiro kn-aut-name=原田大二郎 kn-aut-sei=原田 kn-aut-mei=大二郎 aut-affil-num=6 ORCID= en-aut-name=TanimotoMitsune en-aut-sei=Tanimoto en-aut-mei=Mitsune kn-aut-name=谷本光音 kn-aut-sei=谷本 kn-aut-mei=光音 aut-affil-num=7 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 血液・腫瘍・呼吸器内科学 affil-num=2 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 血液・腫瘍・呼吸器内科学 affil-num=3 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 血液・腫瘍・呼吸器内科学 affil-num=4 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 血液・腫瘍・呼吸器内科学 affil-num=5 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 血液・腫瘍・呼吸器内科学 affil-num=6 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 血液・腫瘍・呼吸器内科学 affil-num=7 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 血液・腫瘍・呼吸器内科学 en-keyword=放射線化学療法 kn-keyword=放射線化学療法 en-keyword=分子標的治療 kn-keyword=分子標的治療 en-keyword=血管新生阻害薬 kn-keyword=血管新生阻害薬 en-keyword=受容体チロシンキナーゼ阻害薬 kn-keyword=受容体チロシンキナーゼ阻害薬 END