Prevention of hepatitis and Hepatocellular carcinoma by regulation of cytokine signaling

2008 Fiscal Year Final Research Report

• Project/Area Number: 18790483
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Kurume University
• Principal Investigator: YOSHIDA Takafumi Kurume University, 医学部, 助教 (30368899)
• Project Period (FY): 2006 – 2008
• Keywords: サイトカイン / シグナル伝達 / 肝炎 / 肝癌

Research Abstract

肝炎、肝癌の進行においてJAK-STATおよびRas-MAPKシグナルの活性化と、これらのシグナルの抑制因子SOCS、SpredがDNAメチル化などによる発現低下が関与していることを証明した。また、糖尿病や肥満や肝炎、肝癌の増悪に終末糖化産物(AGEs)が関与していることを証明し、さらに網膜色素上皮因子(PEDF)による抑制効果も証明した。

Research Products

• [Journal Article] Pigment epithelium-derived factor (PEDF) ameliorates advanced glycation end product (AGE)-induced hepatic insulin resistance in vitro by suppressing Rac-1 activation. (2008)
  • Author(s): Yoshida T, Yamagishi S, Nakamura K, Matsui T, Imaizumi T, Takeuchi M, Koga H, Ueno T, Sata M.
  • Journal Title: Horm Metab Res 40(9) Pages: 620-5
  • Peer Reviewed
• [Journal Article] Telmisartan, an angiotensin II type 1 receptor blocker, inhibits advanced glycation end-product (AGE)-elicited hepatic insulin resistance via peroxisome proliferator-activated receptor-gamma activation. (2008)
  • Author(s): Yoshida T, Yamagishi S, Matsui T, Nakamura K, Ueno T, Takeuchi M, Sata M.
  • Journal Title: J Int Med Res 36(2) Pages: 237-43
  • Peer Reviewed
• [Journal Article] Pigment epithelium-derived factor inhibits neointimal hyperplasia after vascular injury by blocking NADPH oxidase-mediated reactive oxygen species generation. (2007)
  • Author(s): Nakamura K, Yamagishi S, Matsui T, Yoshida T, Takenaka K, Jinnouchi Y, Yoshida Y, Ueda S, Adachi H, Imaizumi T.
  • Journal Title: Am J Pathol. 170(6) Pages: 2159-70
  • Peer Reviewed
• [Journal Article] Serum C-reactive protein levels predict survival in hepatocellular carcinoma. (2007)
  • Author(s): Nagaoka S, Yoshida T, Akiyoshi J, Akiba J, Torimura T, Adachi H, Kurogi J, Tajiri N, Inoue K, Niizeki T, Koga H, Imaizumi T, Kojiro M, Sata M.
  • Journal Title: Liver Int. 27(8) Pages: 1091-7
  • Peer Reviewed
• [Journal Article] Oxidative stress induces the endoplasmic reticulum stress and facilitates inclusion formation in cultured cells. (2007)
  • Author(s): Hanada S, Harada M, Kumemura H, Bishr Omary M, Koga H, Kawaguchi T, Taniguchi E, Yoshida T, Hisamoto T, Yanagimoto C, Maeyama M, Ueno T, Sata M.
  • Journal Title: J Hepatol. 47(1) Pages: 93-102
  • Peer Reviewed
• [Journal Article] Telmisartan inhibits AGE-induced C-reactive protein production through downregulation of the receptor for AGE via peroxisome proliferator-activated receptor-gamma activation. (2006)
  • Author(s): Yoshida T, Yamagishi S, Nakamura K, Matsui T, Imaizumi T, Takeuchi M, Koga H, Ueno T, Sata M.
  • Journal Title: Diabetologia. 49(12) Pages: 3094-9
  • Peer Reviewed
• [Journal Article] Pigment epithelium-derived factor (PEDF) blocks the interleukin-6 signaling to C-reactive protein expression in Hep3B cells by suppressing Rac-1 activation. (2006)
  • Author(s): Yoshida T, Yamagishi S, Nakamura K, Matsui T, Imaizumi T, Inoue H, Ueno T, Sata M.
  • Journal Title: Life Sci. 19 ; 79(21) Pages: 1981-7
  • Peer Reviewed
• [Journal Article] Pigment epithelium-derived factor (PEDF) inhibits advanced glycation end product (AGE)-induced C-reactive protein expression in hepatoma cells by suppressing Rac-1 activation. (2006)
  • Author(s): Yoshida T, Yamagishi S, Nakamura K, Matsui T, Imaizumi T, Takeuchi M, Ueno T, Sata M.
  • Journal Title: FEBS Lett. 15 ; 580(11) Pages: 2788-96
  • Peer Reviewed
• [Journal Article] Luteolin promotes degradation in signal transducer and activator of transcription 3 in human hepatoma cells: an implication for the antitumor potential of flavonoids. (2006)
  • Author(s): Selvendiran K, Koga H, Ueno T, Yoshida T, Maeyama M, Torimura T, Yano H, Kojiro M, Sata M.
  • Journal Title: Cancer Res. 1 ; 66(9) Pages: 4826-34
  • Peer Reviewed
• [Journal Article] Spreds, inhibitors of the Ras/ERK signal transduction, are dysregulated in human hepatocellular carcinoma and linked to the malignant phenotype of tumors. (2006)
  • Author(s): Yoshida T, Hisamoto T, Akiba J, Koga H, Nakamura K, Tokunaga Y, Hanada S, Kumemura H, Maeyama M, Harada M, Ogata H, Yano H, Kojiro M, Ueno T, Yoshimura A, Sata M.
  • Journal Title: Oncogene. 5 ; 25(45) Pages: 6056-66
  • Peer Reviewed
• [Journal Article] Loss of SOCS3 in the liver promotes fibrosis by enhancing STAT3-mediated TGF-beta1 production. (2006)
  • Author(s): Ogata H, Chinen T, Yoshida T, Kinjyo I, Takaesu G, Shiraishi H, Iida M, Kobayashi T, Yoshimura A.
  • Journal Title: Oncogene. 25(17) Pages: 2520-30
  • Peer Reviewed
• [Presentation] 肝におけるAGEs (Advanced end glycation products : 終末糖化産物)によるインスリン抵抗性と、PEDFによるその抑制効果の検討 (2008)
  • Author(s): 吉田隆文
  • Organizer: 京都肝セルバイオロジー研究会
  • Year and Date: 2008-07-14
• [Presentation] Overexpression of pigment epithelium-derived factor (PEDF) prevents fat storage, inflammation and neoplastic formation in the liver of mice steatohepatitis model. (2007)
  • Author(s): Yoshida Takafumi
  • Organizer: EASL
  • Place of Presentation: Barcelona
  • Year and Date: 20070000
• [Presentation] 肝線維化、肝癌におけるサイトカインシグナルとその抑制機構の役割 (2007)
  • Author(s): 吉田隆文
  • Place of Presentation: 九州、北海道がんフォーラム
  • Year and Date: 2007-01-13
• [Presentation] Telmisartan inhibits AGE-induced C-reactive protein (CRP) production through down-regulation of receptor for AGE (RAGE) via peroxisome proliferator-activated receptor-gamma activation. (2006)
  • Author(s): Yoshida Takafumi
  • Organizer: EUGMS. 4th Congress of the European Union Geriatric Medicine Society.
  • Place of Presentation: Geneva, Switzerland
  • Year and Date: 20060823-26
• [Presentation] Spreds, inhibitors of the Ras/ERK signal transduction, are dysregulated in human hepatocellular carcinoma and linked to the malignant phenotype of tumors. (2006)
  • Author(s): Yoshida Takafumi, Hisamoto Takao, Akiba Jun, Koga Hironori, Nakamura Kazuo, Yano Hirohisa, Kojiro Masamichi, Ueno Takato, Yoshimura Akihiko, Sata Michio.
  • Organizer: DDW-USA 2006
  • Place of Presentation: Los Angels, USA
  • Year and Date: 20060522-25
• [Book] 糖尿病ファーマナビゲーター「NASHとインスリン抵抗性について」 (2006)
  • Author(s): 吉田隆文
  • Total Pages: 326-329
  • Publisher: メディカルレビュー社