Katsue Suzuki-Inoue, N. Tsukiji, Toshiaki Shirai, Tomoyuki Sasaki
{"title":"血小板活性化受容体CLEC-2の基礎研究から臨床応用に向けた取り組み","authors":"Katsue Suzuki-Inoue, N. Tsukiji, Toshiaki Shirai, Tomoyuki Sasaki","doi":"10.2491/jjsth.34.414","DOIUrl":"https://doi.org/10.2491/jjsth.34.414","url":null,"abstract":"","PeriodicalId":89444,"journal":{"name":"Nihon Kessen Shiketsu Gakkai shi = Japanese journal of thrombosis and hemostasis","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69242398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Description of the principles and applications of clot waveform analysis (CWA) and clot fibrinolysis waveform analysis (CFWA)","authors":"Tomoko Matsumoto, Daiki Shimomura","doi":"10.2491/jjsth.34.43","DOIUrl":"https://doi.org/10.2491/jjsth.34.43","url":null,"abstract":"","PeriodicalId":89444,"journal":{"name":"Nihon Kessen Shiketsu Gakkai shi = Japanese journal of thrombosis and hemostasis","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69243029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01Epub Date: 2022-03-30DOI: 10.1016/j.jbc.2022.101885
Zhihui Li, So Mee Kwon, Daochuan Li, Linhao Li, Xiwei Peng, Junran Zhang, Tatsuya Sueyoshi, Jean-Pierre Raufman, Masahiko Negishi, Xin Wei Wang, Hongbing Wang
The constitutive androstane receptor (CAR) is a nuclear receptor that plays a crucial role in regulating xenobiotic metabolism and detoxification, energy homeostasis, and cell proliferation by modulating the transcription of numerous target genes. CAR activation has been established as the mode of action by which phenobarbital-like nongenotoxic carcinogens promote liver tumor formation in rodents. This paradigm, however, appears to be unrelated to the function of human CAR (hCAR) in hepatocellular carcinoma (HCC), which remains poorly understood. Here, we show that hCAR expression is significantly lower in HCC than that in adjacent nontumor tissues and, importantly, reduced hCAR expression is associated with a worse HCC prognosis. We also show overexpression of hCAR in human hepatoma cells (HepG2 and Hep3B) profoundly suppressed cell proliferation, cell cycle progression, soft-agar colony formation, and the growth of xenografts in nude mice. RNA-Seq analysis revealed that the expression of erythropoietin (EPO), a pleiotropic growth factor, was markedly repressed by hCAR in hepatoma cells. Addition of recombinant EPO in HepG2 cells partially rescued hCAR-suppressed cell viability. Mechanistically, we showed that overexpressing hCAR repressed mitogenic EPO-EPO receptor signaling through dephosphorylation of signal transducer and activator of transcription 3, AKT, and extracellular signal-regulated kinase 1/2. Furthermore, we found that hCAR downregulates EPO expression by repressing the expression and activity of hepatocyte nuclear factor 4 alpha, a key transcription factor regulating EPO expression. Collectively, our results suggest that hCAR plays a tumor suppressive role in HCC development, which differs from that of rodent CAR and offers insight into the hCAR-hepatocyte nuclear factor 4 alpha-EPO axis in human liver tumorigenesis.
{"title":"Human constitutive androstane receptor represses liver cancer development and hepatoma cell proliferation by inhibiting erythropoietin signaling.","authors":"Zhihui Li, So Mee Kwon, Daochuan Li, Linhao Li, Xiwei Peng, Junran Zhang, Tatsuya Sueyoshi, Jean-Pierre Raufman, Masahiko Negishi, Xin Wei Wang, Hongbing Wang","doi":"10.1016/j.jbc.2022.101885","DOIUrl":"10.1016/j.jbc.2022.101885","url":null,"abstract":"<p><p>The constitutive androstane receptor (CAR) is a nuclear receptor that plays a crucial role in regulating xenobiotic metabolism and detoxification, energy homeostasis, and cell proliferation by modulating the transcription of numerous target genes. CAR activation has been established as the mode of action by which phenobarbital-like nongenotoxic carcinogens promote liver tumor formation in rodents. This paradigm, however, appears to be unrelated to the function of human CAR (hCAR) in hepatocellular carcinoma (HCC), which remains poorly understood. Here, we show that hCAR expression is significantly lower in HCC than that in adjacent nontumor tissues and, importantly, reduced hCAR expression is associated with a worse HCC prognosis. We also show overexpression of hCAR in human hepatoma cells (HepG2 and Hep3B) profoundly suppressed cell proliferation, cell cycle progression, soft-agar colony formation, and the growth of xenografts in nude mice. RNA-Seq analysis revealed that the expression of erythropoietin (EPO), a pleiotropic growth factor, was markedly repressed by hCAR in hepatoma cells. Addition of recombinant EPO in HepG2 cells partially rescued hCAR-suppressed cell viability. Mechanistically, we showed that overexpressing hCAR repressed mitogenic EPO-EPO receptor signaling through dephosphorylation of signal transducer and activator of transcription 3, AKT, and extracellular signal-regulated kinase 1/2. Furthermore, we found that hCAR downregulates EPO expression by repressing the expression and activity of hepatocyte nuclear factor 4 alpha, a key transcription factor regulating EPO expression. Collectively, our results suggest that hCAR plays a tumor suppressive role in HCC development, which differs from that of rodent CAR and offers insight into the hCAR-hepatocyte nuclear factor 4 alpha-EPO axis in human liver tumorigenesis.</p>","PeriodicalId":89444,"journal":{"name":"Nihon Kessen Shiketsu Gakkai shi = Japanese journal of thrombosis and hemostasis","volume":"18 1","pages":"101885"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91303751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The utility of comprehensive coagulation assays","authors":"S. Furukawa, K. Nogami","doi":"10.2491/jjsth.33.356","DOIUrl":"https://doi.org/10.2491/jjsth.33.356","url":null,"abstract":"","PeriodicalId":89444,"journal":{"name":"Nihon Kessen Shiketsu Gakkai shi = Japanese journal of thrombosis and hemostasis","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69236342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Disseminated intravascular coagulation in obstetrics: Diagnosis and up-to-date management strategies","authors":"K. Kawasaki","doi":"10.2491/jjsth.33.544","DOIUrl":"https://doi.org/10.2491/jjsth.33.544","url":null,"abstract":"","PeriodicalId":89444,"journal":{"name":"Nihon Kessen Shiketsu Gakkai shi = Japanese journal of thrombosis and hemostasis","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69237878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prevalence of VTE and prevention project after Kumamoto Earthquakes","authors":"K. Sakamoto, S. Hokimoto, Y. Hashimoto, K. Hanzawa, K. Tsujita","doi":"10.2491/jjsth.33.648","DOIUrl":"https://doi.org/10.2491/jjsth.33.648","url":null,"abstract":"要約:2016年 4月,2度の地震(震度 7)が熊本地方を襲った.本震から 2日後,車中泊の 51歳女性が急性肺 塞栓症(pulmonary thromboembolism: PTE)により死亡し,我々は避難所巡回での深部静脈血栓症スクリーニン グ検診を開始した.車中泊者を中心に要入院重症VTE患者が多数発生する中,のべ 136会場で 4,135名に下肢 静脈エコー検診を行なった.急性期検診(発災後 45日間)のDVT陽性率は 9.5%.予後調査で健診による 3名 の要入院者を同定できたが,死亡例はなかった.慢性期検診の検討では,DVT陽性率の検診時期毎の低下傾向 を認めなかったが,高齢者を除くと経時的な陽性率低下が確認できた.急性期に同定されたDVTの慢性期推移 を検討した結果,56%に消失が確認できた.血栓消失群における消失時期について検討したところ,49%は 2ヶ月以内,87%は 6ヶ月以内の追跡で血栓の消失が確認できており,発災直後からの予防啓発活動の重要性 が示唆された.","PeriodicalId":89444,"journal":{"name":"Nihon Kessen Shiketsu Gakkai shi = Japanese journal of thrombosis and hemostasis","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69238359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Practical key points of VWF multimer analysis","authors":"Yuka Eura","doi":"10.2491/jjsth.33.707","DOIUrl":"https://doi.org/10.2491/jjsth.33.707","url":null,"abstract":"","PeriodicalId":89444,"journal":{"name":"Nihon Kessen Shiketsu Gakkai shi = Japanese journal of thrombosis and hemostasis","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69239227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A research life in Scripps Research","authors":"Y. Morodomi","doi":"10.2491/jjsth.33.712","DOIUrl":"https://doi.org/10.2491/jjsth.33.712","url":null,"abstract":"","PeriodicalId":89444,"journal":{"name":"Nihon Kessen Shiketsu Gakkai shi = Japanese journal of thrombosis and hemostasis","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69239966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Congratulatory speech—The road to TMA analysis in Japan with Professor Miyata’s group—","authors":"Yoshihiro Fujimura","doi":"10.2491/jjsth.33.718","DOIUrl":"https://doi.org/10.2491/jjsth.33.718","url":null,"abstract":"","PeriodicalId":89444,"journal":{"name":"Nihon Kessen Shiketsu Gakkai shi = Japanese journal of thrombosis and hemostasis","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69240298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antibody testing as the guide to our living with COVID-19","authors":"N. Kaku, Y. Nakagama, Y. Nitahara, Y. Kido","doi":"10.2491/jjsth.33.338","DOIUrl":"https://doi.org/10.2491/jjsth.33.338","url":null,"abstract":"","PeriodicalId":89444,"journal":{"name":"Nihon Kessen Shiketsu Gakkai shi = Japanese journal of thrombosis and hemostasis","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69235736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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