Are activated stellate cells producing Cytoglobin directly involved in hepatocarcinogenesis?

• Project/Area Number: 19H03641
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Osaka City University
• Principal Investigator: Kawada Norifumi 大阪市立大学, 大学院医学研究科, 教授 (30271191)
• Co-Investigator(Kenkyū-buntansha): 松原 三佐子 (佐藤三佐子 / 佐藤) 大阪市立大学, 大学院医学研究科, 特任講師 (00635120) ; LE THITHANHTHUY 大阪市立大学, 大学院医学研究科, 特任講師 (10572175)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000); Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2020: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2019: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: 肝星細胞 / 肝線維化 / Cytoglobin / コラーゲン / TGF-β / ROS / 星細胞 / TGFβ / 肝硬変 / 肝がん / サイトグロビン / ヒドロキシラジカル

Outline of Research at the Start

肝がんは病因を問わず線維化肝から出芽するが、線維化やその主役の活性化星細胞（hepatic stellate cells, HSCs）の発がんへの直接的関与については不明である。我々はHSCsに発現するCytoglobin（CYGB）を発見し、Cygb欠損マウスを用いたin vivo肝障害モデルによりCYGB欠損が肝炎症・線維化反応を増強させ、肝発がんを促進することを証明した。また、CYGBはHSCs活性化の鍵因子であり、その欠損は活性酸素や生理活性因子、細胞外マトリックスの過剰産生を惹起する。本研究はHSCsにおけるCYGBの発現調節機構の詳細な解析と同時に、CYGB-HSC軸が隣接する肝細胞のDNA損傷を通じた発がんへの寄与について明らかにする。

Outline of Final Research Achievements

CYGB is a respiratory protein that acts as a scavenger of reactive oxygen species (ROS) and protects cells from oxidative DNA damage. Cygb-overexpressing mice exhibited reduced liver inflammation and fibrosis, but high levels of quiescent HSCs compared to wild-type mice following 10 weeks of thioacetamide (TAA) induced advanced liver fibrosis. Similarly, Cygb-overexpressing mice showed attenuation of liver damage, fibrosis and ROS formation induced by 16 weeks of choline deficient amino acid define diet (CDAA) feeding or 12 months after diethylnitrosamine (DEN) treatment. We further found that the cytokine TGF-β1 downregulates human CYGB expression. In culture, TGF-β1-pretreated human HSCs exhibited lower CYGB levels - together with increased NADPH oxidase 4 expression leading to oxidative DNA damage in activated hepatic stellate cells - and were primed for H2O2-triggered -OH production and 8-OHdG generation; overexpression of human CYGB in human HSCs reversed these effects.

Academic Significance and Societal Importance of the Research Achievements

これまで上皮細胞ばかりに焦点が集められていた発がんの分子機構について、間質細胞の重要性をグロビン蛋白との絡みで研究できれば、新たなパラダイムが広がる。肝がんは高度線維化や肝硬変を母地に発生するため、HSCsや筋線維芽細胞のがん発生における役割をCYGBと絡めて研究する意義は大きい。さらに、本研究を通じて肝脱線維化剤が開発されれば、治療法のない肝硬変に対して一矢を報いることになり臨床医学的にも極めて有用で、社会貢献度が高い。

Research Products

• [Journal Article] Soluble programmed cell death-1 predicts hepatocellular carcinoma development during nucleoside analogue treatment. (2022)
  • Author(s): Ritsuzo Kozuka, Masaru Enomoto, Minh Phuong Dong, Hoang Hai, Le Thi Thanh Thuy, Naoshi Odagiri, Kanako Yoshida, Kohei Kotani, Hiroyuki Motoyama, Etsushi Kawamura, Atsushi Hagihara, Hideki Fujii, Sawako Uchida-Kobayashi, Akihiro Tamori, Norifumi Kawada
  • Journal Title: Scientific reports Volume: 12 Issue: 1 Pages: 105-105
  • DOI: 10.1038/s41598-021-03706-w
  • Peer Reviewed / Open Access
• [Journal Article] Capacity of extracellular globins to reduce liver fibrosis via scavenging reactive oxygen species and promoting MMP-1 secretion. (2022)
  • Author(s): Hieu VN, Thuy LTT, Hai H, Dat NQ, Hoang DV, Hanh NV, Phuong DM, Hoang TH, Sawai H, Shiro Y, Sato-Matsubara M, Oikawa D, Tokunaga F, Yoshizato K, Kawada N.
  • Journal Title: Redox Biol. Volume: 52 Pages: 102286-102286
  • DOI: 10.1016/j.redox.2022.102286
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cytoglobin Attenuated Pancreatic Cancer Growth in vitro and in vivo via Scavenging Function for Reactive Oxygen Species. (2022)
  • Author(s): 2.Dinh VH*, Thuy LTT*, Hai H, Hieu VN, Kimura K, Oikawa D, Ikura Y, Ninh QD, Hoang TH, Sato-Matsubara M, Dong MP, Hanh NV, Uchida-Kobayashi S, Tokunaga F, Kubo S, Ohtani N, Yoishizato K, and Kawada N.
  • Journal Title: Oncogenesis, accepted manuscript. Volume: 0 Pages: 0-0
• [Journal Article] 6His-tagged Recombinant Human Cytoglobin Deactivates Hepatic Stellate Cells and Inhibits Liver Fibrosis by Scavenging Reactive Oxygen Species (2021)
  • Author(s): Ninh Quoc Dat, Le Thi Thanh Thuy, Vu Ngoc Hieu, Fuminori Tokunaga, Massimo Pinzani, and Norifumi Kawada
  • Journal Title: Hepatology Volume: 0-0 Issue: 6 Pages: 0-0
  • DOI: 10.1002/hep.31752
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cytoglobin expression in pericyte and its role in pancreatic cancer. (2021)
  • Author(s): Thuy le TT, Hai H, Dinh VH, Ngo VH, Uchida-Kobayashi S, Kawada N.
  • Journal Title: Gastroenterology & Hepatology Volume: 10 Pages: 354-362
• [Journal Article] 【膵癌研究最前線】膵星細胞に発現するサイトグロビンの膵癌における役割 (2021)
  • Author(s): Le Thi Thanh Thuy、Hoang Hai、Dinh Viet Hoang、Ngo Vinh Hanh、打田佐和子（小林）、河田則文
  • Journal Title: 消化器・肝臓内科 Volume: 10 Pages: 354-362
• [Journal Article] TGF-β1-driven reduction of cytoglobin leads to oxidative DNA damage in stellate cells during non-alcoholic steatohepatitis. (2020)
  • Author(s): Okina Y, Sato-Matsubara M, Matsubara T, Daikoku A, Longato L, Rombouts K, Thanh Thuy LT, Ichikawa H, Minamiyama Y, Kadota M, Fujii H, Enomoto M, Ikeda K, Yoshizato K, Pinzani M, Kawada N.
  • Journal Title: J Hepatol. Volume: 20 Pages: 30228-30228
  • NAID: 120006900885
• [Journal Article] Clinical significance of circulating soluble immune checkpoint proteins in sorafenib-treated patients with advanced hepatocellular carcinoma. (2020)
  • Author(s): Dong MP, Enomoto M, Thuy LTT, Hai H, Hieu VN, Hoang DV, Iida-Ueno A, Odagiri N, Amano-Teranishi Y, Hagihara A, Fujii H, Uchida-Kobayashi S, Tamori A, Kawada N.
  • Journal Title: Sci Rep Volume: 10 Issue: 1 Pages: 3392-3392
  • DOI: 10.1038/s41598-020-60440-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Long-term outcome of pediatric non-cirrhotic portal fibrosis from the viewpoint of endoscopic profile. (2020)
  • Author(s): Kotani K, Kawada N.
  • Journal Title: Hepatol Int. Volume: 14 Issue: 2 Pages: 164-166
  • DOI: 10.1007/s12072-020-10028-y
• [Journal Article] 【肝線維化をめぐる最新情報】抗線維化薬開発の最新情報 (2020)
  • Author(s): 松原三佐子、河田則文
  • Journal Title: 日本消化器病学会雑誌 Volume: 117 Pages: 52-63
• [Journal Article] C型肝炎 HCV排除は肝がんを抑制するのか 外来でのフォローはどうするか (2019)
  • Author(s): 榎本 大(大阪市立大学 大学院医学研究科肝胆膵病態内科学), 伊倉 義弘, 田守 昭博, 河田 則文
  • Journal Title: 内科 Volume: 123 Pages: 1081-1085
• [Journal Article] 肝機能障害を契機に診断されたサルコイドーシス5例の検討 (2019)
  • Author(s): 焦 光裕、榎本 大、小谷 晃平、小田 桐直志、吉田 香奈子、元山 宏行、小塚 立蔵、藤井 英樹、萩原 淳司、打田 佐和子、森川 浩安、村上 善基、田守 昭博、河田 則文
  • Journal Title: 肝臓 Volume: 60 Pages: 405-413
  • NAID: 130007741895
• [Journal Article] 肝星細胞の活性化の仕組み サイトグロビンの作用から見えてくる新しい視点 (2019)
  • Author(s): 松原 三佐子, 河田 則文, 吉里 勝利
  • Journal Title: 細胞 Volume: 51 Pages: 530-534
• [Journal Article] Intention-to-treat assessment of glecaprevir + pibrentasvir combination therapy for patients with chronic hepatitis C in the real world. (2019)
  • Author(s): Tamori A, Inoue K, Kagawa T, Takaguchi K, Nouso K, Iwasaki Y, Minami M, Hai H, Enomoto M, Kawada N.
  • Journal Title: Hepatol Res Volume: 49 Issue: 12 Pages: 1365-1373
  • DOI: 10.1111/hepr.13410
  • Peer Reviewed
• [Journal Article] Switching to tenofovir disoproxil fumarate vs continuing treatment in patients with chronic hepatitis B who maintain long-term virological response to entecavir therapy: A randomized trial. (2019)
  • Author(s): Iida-Ueno A, Enomoto M, Kozuka R, Tamori A, Kawada N.
  • Journal Title: J Med Virol Volume: 91 Issue: 7 Pages: 1295-1300
  • DOI: 10.1002/jmv.25442
  • Peer Reviewed
• [Journal Article] Obesity and hiatal hernia may be non-allergic risk factors for esophageal eosinophilia in Japanese adults. (2019)
  • Author(s): Tanaka F, Fukumoto S, Morisaki T, Otani K, Hosomi S, Nagami Y, Kamata N, Taira K, Nakano A, Kimura T, Yamagami H, Tanigawa T, Morikawa H, Watanabe T, Kawada N, Hirata K, Fujiwara Y.
  • Journal Title: Esophagus Volume: 16 Issue: 3 Pages: 309-315
  • DOI: 10.1007/s10388-019-00662-3
  • NAID: 120006876362
  • Peer Reviewed
• [Journal Article] Last crusade against HCV: Direct-acting antiviral treatment for marginalized populations. (2019)
  • Author(s): Fujii H, Enomoto M, Murakami Y, Hagihara A, Kawada N, Saito S.
  • Journal Title: J Viral Hepat Volume: 26 Issue: 12 Pages: 1501-1501
  • DOI: 10.1111/jvh.13190
  • Peer Reviewed
• [Journal Article] Hepatitis C virus recurrence in two patients who achieved sustained viral response with interferon-free direct-acting antiviral therapy: reinfection or relapse? (2019)
  • Author(s): Yukawa Y, Tamori A, Iio E, Ogawa S, Yoshida K, Uchida-Kobayashi S, Enomoto M, Tanaka Y, Kawada N.
  • Journal Title: Clin J Gastroenterol Volume: 12 Issue: 6 Pages: 598-602
  • DOI: 10.1007/s12328-019-01001-w
  • NAID: 120006866793
  • Peer Reviewed
• [Journal Article] Interstitial pneumonia suspected during regorafenib administration and exacerbated by subsequent therapy with lenvatinib for unresectable hepatocellular carcinoma. (2019)
  • Author(s): Kotani K, Enomoto M, Okada M, Yoshida K, Motoyama H, Fiji H, Hagihara A, Uchida-Kobayashi S, Mordkawa H, Murakami Y, Tamori A, Kanada N.
  • Journal Title: Clinical Journal of Gastroenterology. Volume: - Issue: 4 Pages: 355-360
  • DOI: 10.1007/s12328-019-00983-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of the Gut-Liver Axis in Liver Inflammation, Fibrosis, and Cancer: A Special Focus on the Gut Microbiota Relationship. (2019)
  • Author(s): Ohtani N, Kawada N.
  • Journal Title: Hepatol Commun Volume: 3 Issue: 4 Pages: 456-470
  • DOI: 10.1002/hep4.1331
  • Peer Reviewed / Open Access
• [Journal Article] HOMA-IR: An independent predictor of advanced liver fibrosis in nondiabetic non-alcoholic fatty liver disease. (2019)
  • Author(s): Fujii H, Yoneda M, et al.
  • Journal Title: J Gastroenterol Hepatol. Volume: in press Issue: 8 Pages: 1-6
  • DOI: 10.1111/jgh.14595
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association between Functional Dyspepsia and Gastric Depressive Erosions in Japanese Subjects. (2019)
  • Author(s): Tanaka F, Tominaga K, Fujikawa Y, Morisaki T, Otani K, Hosomi S, Nagami Y, Kamata N, Taira K, Nakano A, Kimura T, Yamagami H, Tanigawa T, Morikawa H, Fukumoto S, Watanabe T, Kawada N, Hirata K, Fujiwara Y.
  • Journal Title: Intern Med Volume: 58 Pages: 321-328
  • NAID: 130007588506
  • Peer Reviewed
• [Presentation] Cytoglobin inhibits pancreatic cancer growth in vitro and in vivo (2021)
  • Author(s): Dinh Viet Hoang, Le Thi Thanh Thuy, Hoang Hai, Vu Ngoc Hieu, Ninh Quoc Dat, Truong Huu Hoang, Dong Minh Phuong, Ngo Vinh Hanh, Yoshihiro Ikura, Kenjiro Kimura, and Norifumi Kawada
  • Organizer: 第107回 日本消化器病学会総会
• [Presentation] Intracellular gap formation of the liver sinusoidal endothelial cells facilitates the liver metastasis ability of cancer cells (2021)
  • Author(s): ruong Huu Hoang, Misako Sato-Matsubara, Yuasa Hideto, Tsutomu Matsubara, Hayato Urushima, Le Thi Thanh Thuy, Atsuko Daikoku, Yoshinori Okina, Akihiro Tamori, Katsutoshi Yoshizato, Norifumi Kawada
  • Organizer: 第107回 日本消化器病学会総会
• [Presentation] Recombinant human Cytoglobin Deactivates Hepatic Stellate Cells and Prevents Fibrosis Aggravation by Scavenging ROS and Inducing Interferon-Beta (2021)
  • Author(s): Vu Ngoc Hieu, Ninh Quoc Dat, Le Thi Thanh Thuy, Hoang Hai, Dinh Viet Hoang, Katsutoshi Yoishizato and Norifumi Kawada
  • Organizer: 第107回 日本消化器病学会総会
• [Presentation] Levels of soluble immune checkpoint proteins associate with hepatocellular arcinoma development in patients with chronic hepatitis C (2021)
  • Author(s): Dong Minh Phuong, Le Thi Thanh Thuy, Hoang Hai, Akihiro Tamori, Masaru Enomoto, Sawako Uchida-Kobayashi and Norifumi Kawada
  • Organizer: 第57回 日本肝臓学会総会
• [Presentation] 肝細胞と肝星細胞との細胞膜を介した直接的なクロストーク (2021)
  • Author(s): 井上喜来々、松原三佐子、Truong Huu Hoang、松原勤、宇留島隼人、湯浅秀人、大黒敦子、池田一雄、吉里勝利、河田則文
  • Organizer: 第28回 肝細胞研究会
• [Presentation] Intracellular gaps formation of liver sinusoidal endothelial cells facilitates cancer cell engraftment in liver (2021)
  • Author(s): Truong Huu Hoang, Misako Sato-Matsubara, Yuasa Hideto, Tsutomu Matsubara, Hayato Urushima, Le Thi Thanh Thuy, Atsuko Daikoku, Yoshinori Okina, Akihiro Tamori, Katsutoshi Yoshizato, Norifumi Kawada
  • Organizer: 第53回 日本臨床分子形態学会総会・学術集会
• [Presentation] Circulating soluble immune checkpoint proteins as biomarkers for predicting the outcome of antiviral treatment of chronic hepatitis B (2021)
  • Author(s): Hoang Hai, Masaru Enomoto, Minh Phuong Dong, Le Thi Thanh Thuy, Atsushi Hagihara, Sawako Uchida-Kobayashi, Akihiro Tamori, and Norifumi Kawada
  • Organizer: JDDW 2021 KOBE
• [Presentation] Anti-fibrosis application of overexpression and recombinant human CYGB in multiple models of advanced fibrosis (2021)
  • Author(s): Le Thi Thanh Thuy, Ninh Quoc Dat, Vu Ngoc Hieu, Hoang Hai, Dinh Viet Hoang, Katsutoshi Yoishizato and Norifumi Kawada
  • Organizer: JDDW 2021 KOBE
• [Presentation] Interaction between CD4+T cells and tumor cells in hepatocellular carcinoma microenvironment (2021)
  • Author(s): Ngo Vinh Hanh, Le Thi Thanh Thuy, Hoang Hai, Vu Ngoc Hieu, Sawako Uchida-Kobayashi, Masaru Enomoto, Akihiro Tamori, and Norifumi Kawada
  • Organizer: 第35回 肝類洞壁細胞研究会
• [Presentation] Novel Anti-Fibrotic Function of Neuroglobin in vitro and in vivo (2021)
  • Author(s): Vu Ngoc Hieu, Le Thi Thanh Thuy, Hoang Hai, Dinh Viet Hoang, Ninh Quoc Dat, Katsutoshi Yoishizato and Norifumi Kawada
  • Organizer: 第35回 肝類洞壁細胞研究会
• [Presentation] Intracellular gap formation of the liver sinusoidal endothelial cells facilitates the liver metastasis ability of cancer cell (2021)
  • Author(s): Truong Huu Hoang, Misako Sato-Matsubara, Yuasa Hideto, Tsutomu Matsubara, Hayato Urushima, Le Thi Thanh Thuy, Atsuko Daikoku, Yoshinori Okina, Akihiro Tamori, Katsutoshi Yoshizato, Norifumi Kawada
  • Organizer: American Association for Cancer Research (AACR) Annual Meeting 2021
  • Int'l Joint Research
• [Presentation] Cytoglobin impairs pancreatic cancer growth in vitro and in vivo. (2021)
  • Author(s): Dinh Viet Hoang, Le Thi Thanh Thuy, Hoang Hai, Vu Ngoc Hieu, Ninh Quoc Dat, Truong Huu Hoang, Dong Minh Phuong, Ngo Vinh Hanh, Yoshihiro Ikura, Kenjiro Kimura, and Norifumi Kawada
  • Organizer: Virtual Annual Meeting of the Digestive Disease Week (DDW)
  • Int'l Joint Research
• [Presentation] Capacity of Extracellular Globins in suppression of Collagen Production from activated Hepatic Stellate cells via Scavenging ROS and Promoting MMP-1 Secretion. (2021)
  • Author(s): Vu Ngoc Hieu, Le Thi Thanh Thuy, Ninh Quoc Dat, Hoang Hai, Dinh Viet Hoang, Katsutoshi Yoshizato and Norifumi Kawada
  • Organizer: Asian Pacific Association for the Study of the Liver (APASL) Single Topic Conference 2021 Osaka
  • Int'l Joint Research
• [Presentation] Changes of soluble immune checkpoint proteins following antiviral treatment in chronic hepatitis C patients and the roles of the CD27-CD70 pathway in hepatocellular carcinoma development (2021)
  • Author(s): Minh Phuong Dong, Le Thi Thanh Thuy, Hoang Hai, Vu Ngoc Hieu, Dinh Viet Hoang, Sawako Uchida-Kobayashi, Masaru Enomoto, Akihiro Tamori and Norifumi Kawada
  • Organizer: Asian Pacific Association for the Study of the Liver (APASL) Single Topic Conference 2021 Osaka
  • Int'l Joint Research
• [Presentation] Role of CD40 in Hepatocellular Carcinoma (2021)
  • Author(s): Ngo Vinh Hanh, Le Thi Thanh Thuy, Hoang Hai, Vu Ngoc Hieu, Sawako Uchida-Kobayashi, Masaru Enomoto, Akihiro Tamori, and Norifumi Kawada
  • Organizer: Asian Pacific Association for the Study of the Liver (APASL) Single Topic Conference 2021 Osaka
  • Int'l Joint Research
• [Presentation] Intracellular gaps formation of liver sinusoidal endothelial cells facilitates cancer cell engraftment in liver (2021)
  • Author(s): Truong Huu Hoang, Misako Sato-Matsubara, Yuasa Hideto, Tsutomu Matsubara, Hayato Urushima, Le Thi Thanh Thuy, Atsuko Daikoku, Yoshinori Okina, Akihiro Tamori, Katsutoshi Yoshizato, Norifumi Kawada
  • Organizer: Asian Pacific Association for the Study of the Liver (APASL) Single Topic Conference 2021 Osaka
  • Int'l Joint Research
• [Presentation] Cell membrane-mediated direct crosstalks between hepatocytes and HSCs (2021)
  • Author(s): Kirara Inoue, Misako Sato-Matsubara, Truong Huu Hoang, Tsutomu Matsubara, Hayato Urushima, Atsuko Daikoku, Kazuo Ikeda, Katsutoshi Yoshizato, Norifumi Kawada
  • Organizer: Asian Pacific Association for the Study of the Liver (APASL) Single Topic Conference 2021 Osaka
  • Int'l Joint Research
• [Presentation] Anti-fibrotic Capacity of Extracellular Globins via Scavenging ROS and Promoting MMP-1 Secretion (2021)
  • Author(s): Vu Ngoc Hieu, Le Thi Thanh Thuy, Ninh Quoc Dat, Hoang Hai, Dinh Viet Hoang, Katsutoshi Yoshizato and Norifumi Kawada
  • Organizer: American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2021
  • Int'l Joint Research
• [Presentation] Levels of soluble immune checkpoint proteins following antiviral treatment in chronic hepatitis C patients and the roles of sCD27 in hepatocellular carcinoma development (2021)
  • Author(s): Minh Phuong Dong, Le Thi Thanh Thuy, Hoang Hai, Vu Ngoc Hieu, Dinh Viet Hoang, Sawako Uchida-Kobayashi, Masaru Enomoto, Akihiro Tamori and Norifumi Kawada
  • Organizer: American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2021
  • Int'l Joint Research
• [Presentation] Investigation of CYGB promoter methylation as a biomarker for hepatocellular carcinoma (2021)
  • Author(s): Hoang Hai, Le Thi Thanh Thuy, Akihiro Tamori, Shoji Kubo, Shigekazu Takemura, Shogo Tanaka, Atsushi Hagihara, Etsushi Kawamura, Sawako Uchida-Kobayashi, Masaru Enomoto and Norifumi Kawada
  • Organizer: American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2021
  • Int'l Joint Research
• [Presentation] Intracellular gap formation of the liver sinusoidal endothelial cells facilitates the liver metastasis ability of cancer cells (2021)
  • Author(s): Truong Huu Hoang, Misako Sato-Matsubara, Yuasa Hideto, Tsutomu Matsubara, Hayato Urushima, Le Thi Thanh Thuy, Atsuko Daikoku, Yoshinori Okina, Akihiro Tamori, Katsutoshi Yoshizato, Norifumi Kawada
  • Organizer: American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2021
  • Int'l Joint Research
• [Presentation] 肝硬変治療薬開発を見据えた肝星細胞活性化抑制物質の同定 (2020)
  • Author(s): 松原三佐子、河田則文
  • Organizer: 第56回 日本肝臓学会総会
• [Presentation] NAFLD/NASHの肝線維化進展におけるCYGB依存的酸化ストレス応答と発現制御機構の解明 (2020)
  • Author(s): 翁良徳、松原三佐子、河田則文
  • Organizer: 第56回 日本肝臓学会総会
• [Presentation] Intracellular gap formation of the liver sinusoidal endothelial cells facilitates the liver metastasis ability of cancer (2020)
  • Author(s): チュンフーホアン、松原三佐子、湯浅秀人、松原勤、宇留島隼人、リーツイ、大黒敦子、翁良徳、吉里勝利、河田則文
  • Organizer: 第34回 肝類洞壁細胞研究会学術集会
• [Presentation] Recombinant human Cytoglobin scavenging ROS and inducing Interferon-Beta mediated hepatic stellate cells activation and liver fibrosis. (2020)
  • Author(s): Vu Ngoc Hieu, Ninh Quoc Dat, Le Thi Thanh Thuy, Hoang Hai,Dinh Viet Hoang, Katsutoshi Yoishizato and Norifumi Kawada
  • Organizer: 第34回 肝類洞壁細胞研究会学術集会
• [Presentation] Recombinant Human Cytoglobin Protects Mice from Chemical Induced Liver Fibrosis (2019)
  • Author(s): Ninh Quoc Dat, Le Thi Thanh Thuy, Hoang Hai, Vu Ngoc Hieu, Dinh Viet Hoang, Katsutoshi Yoshizato, Norifumi Kawada
  • Organizer: JSH international Liver Conference
  • Int'l Joint Research
• [Presentation] Profiling of Circulating Immune Checkpoint Proteins in Advanced HCC Patients (2019)
  • Author(s): Minh Phuong Dong, Masaru Enomoto, Thi Thanh Thuy Le, Hai Hoang, Atsushi Hagihara, Sawako Uchida-Kobayashi, Akihiro Tamori, Norifumi Kawada
  • Organizer: JSH international Liver Conference
  • Int'l Joint Research
• [Presentation] Establishment of Orthotopic Hepatocellular Carcinoma on the Background of Fibrosis by Intrahepatic and Intrasplenic Tumor Inoculation in Mice. (2019)
  • Author(s): Hoang Huu Truong1, Misako Sato-Matsubar, Thuy Thi Thanh Le, Tsutomu Matsubara, Hai Hoang, Atsuko Daikoku, Yoshinori Okina, Hoang Viet Dinh, Norifumi Kawada
  • Organizer: JSH international Liver Conference
  • Int'l Joint Research
• [Presentation] Identification of Gut Bacteria Involved in Hepatic Encephalopathy by the Analysis of Rifaximin Administrated Patients (2019)
  • Author(s): Yoshimi Yukawa, Naoko Ohtani, Norifumi Kawada
  • Organizer: JSH international Liver Conference
  • Int'l Joint Research
• [Presentation] Downregulation of Cytoglobin by TGF-β Leads to Hydroxyl Radical-induced Oxidative DNA Damage in Human HSCs. (2019)
  • Author(s): Yoshinori Okina, Misako Sato-Matsubara, Tsutomu Matsubara, Atsuko Daikoku, Hideki Fujii, Kazuo Ikeda, Katsutoshi Yoshizato, Massimo Pinzani, Norifumi Kawada
  • Organizer: JSH international Liver Conference
  • Int'l Joint Research
• [Presentation] Identification of Lawsone as an Anti-fibrotic Agent based on High-Throughput Screening System with Human COL1A2 Promoter Activity. (2019)
  • Author(s): Misako Sato-Matsubara, Tsutomu Matsubara, Atsuko Daikoku, Kazuo Ikeda, Katsutoshi Yoshizato, Norifumi Kawada
  • Organizer: JSH international Liver Conference
  • Int'l Joint Research
• [Presentation] Putative Role of ERK1/2 Signaling of Senescent Human Hepatic Stellate Cells in Hepatocellular Carcinoma derived from Liver Cirrhosis. (2019)
  • Author(s): Naoshi Odagiri, Tsutomu Matsubara, Kazuo Ikeda, Norifumi Kawada
  • Organizer: JSH international Liver Conference
  • Int'l Joint Research
• [Presentation] Renal Shear Wave Velocity Measurement can Predict the Response to Tolvaptan Treatment for Hepatic Ascites (2019)
  • Author(s): Hiroyuki Motoyama, Koji Rinka, Ayane Kasamatsu, Hiroko Ikenaga, Maito Suoh, Naoshi Odagiri, Kanako Yoshida, Kohei Kotani, Atsushi Hagihara, Sawako Uchida-Kobayashi, Masaru Enomoto, Akihiro Tamori, Norifumi Kawada
  • Organizer: JSH international Liver Conference
  • Int'l Joint Research
• [Presentation] Wisteria Floribunda Agglutinin Positive MAC-2-Binding Protein Predicts Esophagogastric Varices in Cirrhotic Patients with Chronic Hepatitis C Virus Infection Treated with IFN-Free Direct-Acting Antiviral Agent (2019)
  • Author(s): Sawako Uchida-Kobayashi, Kanako Kikukawa, Akihiro Tamori, Naoshi Odagiri, Kanako Yoshida, Kohei Kotani, Hiroyuki Motoyama, Atsushi Hagihara, Hideki Fujii, Masaru Enomoto, Norifumi Kawada
  • Organizer: JSH international Liver Conference
  • Int'l Joint Research
• [Presentation] Histological Evaluations after Achieving a Sustained Virologic Response to DirectActing Antiviral Treatment for Chronic Hepatitis C in a Short Term (2019)
  • Author(s): Masaru Enomoto, Yutaka Yasui, Misako Sato-Matsubara, Yoshihiro Ikura, Akihiro Tamori, Ritsuzo Kozuka, Etsushi Kawamura, Atsushi Hagihara, Hideki Fujii1, Sawako Uchida-Kobayashi, Yoshiki Murakami, Norifumi Kawada
  • Organizer: JSH international Liver Conference
  • Int'l Joint Research
• [Presentation] Noninvasive Assessment of Portal Hemodynamics Using Per-Rectal Portal Scintigraphy: A Comparison with Hepatic Venous Pressure Gradient (2019)
  • Author(s): Kohei Kotani, Sawako Uchida-Kobayashi, Naoshi Odagiri, Kanako Yoshida, Hiroyuki Motoyama, Atsushi Hagihara, Hideki Fujii, Masaru Enomoto1, Shinichi Hamamoto, Atsushi Jogo, Akira Yamamoto, Shigeaki Higashiyama, Joji Kawabe, Akihiro Tamori, Norifumi Kawada
  • Organizer: JSH international Liver Conference
  • Int'l Joint Research
• [Presentation] Direct-Acting Antiviral Treatment can Prolong Disease-free Survival after Curative Treatment of HCV-related, Primary Hepatocellular Carcinoma in Patient with Advanced Fibrosis (2019)
  • Author(s): Hiroko Ikenaga, SawakoUchida-Kobayashi, Naoshi Odagiri, Kanako Yoshida, Kohei Kotani, Hiroyuki Motoyama, Atsushi Hagihara, Hideki Fuji, Masaru Enomoto, Akihiro Tamori, Norifumi Kawada
  • Organizer: JSH international Liver Conference
  • Int'l Joint Research
• [Presentation] TGF-β1 transcriptionally repressed cytoglobin expression and enhanced H2O2-induced oxidative DNA damage in activated HSCs. (2019)
  • Author(s): Misako Sato-Matsubara, Yoshinori Okina, Tsutomu Matsubara, Atsuko Daikoku1, Krista Rombouts, Le Thi Thanh Thuy, Hideki Fujii1, Kazuo Ikeda, Katsutoshi Yoshizato, Massimo Pinzani, and Norifumi Kawada
  • Organizer: JSH international Liver Conference
  • Int'l Joint Research
• [Presentation] Cytoglobin suppresses liver fibrosis and cancer in mice by regulating oxidative stress (2019)
  • Author(s): Le Thi Thanh Thuy, Ninh Quoc Dat, Hoang Hai, Dinh Viet Hoang, Katsutoshi Yoishizato and Norifumi Kawada
  • Organizer: JSH international Liver Conference
  • Int'l Joint Research
• [Presentation] Deletion Mutations in HCV NS5A Persist and Resist to Subsequent Treatment (2019)
  • Author(s): Hai H, Tamori A, Thuy LTT, Yoshida K, Uchida-Kobayashi S, Enomoto M, Kozuka R, Motoyama H, Murakami Y, Kawada N.
  • Organizer: JSH international Liver Conference
  • Int'l Joint Research
• [Presentation] Role of cytoglibin, the fourth globin in mammals, in liver diseases. (2019)
  • Author(s): Le Thi Thanh Thuy, Hoang Hai, and Norifumi Kawada
  • Organizer: VJST2019
  • Int'l Joint Research
• [Presentation] Does liver cirrhosis regress? Consideration based on DAA therapy to type C advanced chronic liver disease in Japan (2019)
  • Author(s): Kawada N.
  • Organizer: CHESS Forum 2019 for Portal Hypertension
  • Int'l Joint Research
• [Presentation] Identification of gut bacteria involved in hepatic encephalopathy from the analysis of patients administered rifaximin (2019)
  • Author(s): Yoshimi Yukawa Muto, Tomonori Kamiya, Shinji Fukuda, Norifumi Kawada , Naoko Ohtani
  • Organizer: Cold Spring Harbor Asia
  • Int'l Joint Research
• [Presentation] Prospective Multicenter study of Glecaprevir plus Pibrentasvir combination therapy for patients with chronic hepatitis C (2019)
  • Author(s): Tamori A, Iwasa M, Inoue K, Kagawa T, Takaguchi K, Minami M, Iwasaki Y, Nouso K, Hai H, Enomoto M, Kawada N.
  • Organizer: 54th European Association for the study of the liver diseases (Vienna)
  • Int'l Joint Research
• [Presentation] TGF-βとサイトグロビンの拮抗作用はヒトNASHにおける星細胞活性化と肝線維化に影響する (2019)
  • Author(s): 翁良徳、松原三佐子、藤井英樹、河田則文
  • Organizer: 第55回 日本肝臓学会総会
• [Presentation] 肝表面直下の血流評価による門脈圧亢進症診断 (2019)
  • Author(s): 打田佐和子,菊川 佳菜子, 河田 則文
  • Organizer: 第55回 日本肝臓学会総会
• [Presentation] 切除不能肝細胞癌に対する 1 次から 3 次治療の全身化学療法としてのレンバチニブ治療 (2019)
  • Author(s): 周防舞仁, 萩原 淳司, 笠松 彩音, 岡田 雅子, 小田桐 直志, 吉田 香奈子, 小谷 晃平, 元山 宏行, 藤井 英樹, 打田 佐和子, 榎本 大, 森川 浩安, 村上 善基, 田守 昭博, 新川 寛二, 田中 肖吾, 竹村 茂一, 久保 正二, 河田 則文
  • Organizer: 第55回 日本肝臓学会総会
• [Presentation] Standardized uptake valueを用いたアシアロシンチグラフィによる新たな肝予備能評価 (2019)
  • Author(s): 小谷晃平,打田 佐和子, 小田桐 直志, 吉田 香奈子, 元山 宏行, 藤井 英樹, 萩原 淳司, 森川 浩安, 榎本 大, 田守 昭博, 河田 則文
  • Organizer: 第55回 日本肝臓学会総会
• [Presentation] 成因不明の肝疾患に対するTransient elastographyの使用経験 (2019)
  • Author(s): 藤井英樹,森川 浩安, 河田 則文
  • Organizer: 第55回 日本肝臓学会総会
• [Presentation] Cytoglobin suppresses liver fibrosis and cancer in mice by regulating oxidative stress (2019)
  • Author(s): Thi Le,河田 則文
  • Organizer: 第55回 日本肝臓学会総会
• [Presentation] Selective overexpression of Cytoglobin in stellate cells attenuates their activation and fibrosis development in mice (2019)
  • Author(s): Ninh Quoc Dat,河田則文
  • Organizer: 第55回 日本肝臓学会総会
• [Presentation] 保険診療下におけるパンジェノ型抗HCV治療の効果と安全性―他施設共同研究・第2報― (2019)
  • Author(s): 田守昭博,榎本大,河田則文
  • Organizer: 第55回 日本肝臓学会総会
• [Presentation] DAA治療過去4年間からみた治療不成功因子の検討 (2019)
  • Author(s): 吉田香奈子,田守昭博,河田則文
  • Organizer: 第55回 日本肝臓学会総会
• [Presentation] 肝炎ウイルス制御下における組織学的な脂肪沈着の程度と関連因子の検討 (2019)
  • Author(s): 岡田雅子,小谷 晃平, 田守 昭博, 笠松 彩音, 周防 舞仁, 小田桐 直志, 吉田 香奈子, 元山 宏行, 藤井 英樹, 打田 佐和子, 榎本 大, 村上 善基, 河田 則文
  • Organizer: 第55回 日本肝臓学会総会
• [Presentation] HCV genotype2型に対するDAA治療の効果と安全性に関する薬剤レジメンの比較 (2019)
  • Author(s): 和田 響子, 田守 昭博, 小谷 晃平, 吉田 香奈子, 元山 宏行, 藤井 英樹, 石津 弘隆, 萩原 淳司, 打田 佐和子, 森川 浩安, 榎本 大, 村上 善基, 河田 則文
  • Organizer: 第55回 日本肝臓学会総会
• [Presentation] リファキシミンの使用経験と腸内細菌叢に与える影響 (2019)
  • Author(s): 湯川芳美,大谷直子,河田則文
  • Organizer: 第105回日本消化器病学会総会