Prevention of hepatitis and Hepatocellular carcinoma by regulation of cytokine signaling

• 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
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,540,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥240,000); Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2007: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
• Keywords: サイトカイン / シグナル伝達 / 肝炎 / 肝癌 / サイトカインシグナル伝達 / 終末糖化産物 / SOCS-1 / Spred

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 (PEDF) ameliorates advanced glycation end product (AGE)-induced hepatic insulin resistance in vitro by suppressing Rac-1 activation (2008)
  • Author(s): Yoshida T., et.al.
  • Journal Title: Hormone and Metabolic Research. 31 Pages: 2115-27
  • 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., et.al.
  • Journal Title: Journal of International Medical Research. 36 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] Pigment epithelium-derived factor inhibits neointimal hyperplasia after vascular injury by blocking NADPH oχidase-mediated reactive oxygen species generation (2007)
  • Author(s): Nakamura K, Yoshida T, et. al.
  • Journal Title: American journal of pathology 170 Pages: 2159-70
  • Peer Reviewed
• [Journal Article] Elevation of soluble form of receptor for advanced glycation end products in diabetic subiects with coronary artery disease. (2007)
  • Author(s): Nakamura K, Yoshida T, et. al.
  • Journal Title: Diabetes metabolic research review 23 Pages: 368-71
  • Peer Reviewed
• [Journal Article] Serum C-reactive protein levels predicts survival in hepatocellular carcinoma (2007)
  • Author(s): Nagaoka S, Yoshida T, et. al.
  • Journal Title: Liver international 27 Pages: 1091-7
  • Peer Reviewed
• [Journal Article] Hydrogen peroxide stimulates pigment epithelium-derived factor gene and protein expression in the human hepatocyte cell line OUMS-29. (2007)
  • Author(s): Nakamura K, Yoshida T, et. al.
  • Journal Title: J Int Med Res. 35 Pages: 427-32
  • Peer Reviewed
• [Journal Article] Serum levels of sRAGE, the soluble form of receptor for advanced glycation end products, are associated with inflammatory markers in patients with tvpe 2 diabetes. (2007)
  • Author(s): Nakamura K, Yoshida T, et. al.
  • Journal Title: Mol Med. 13 Pages: 185-9
  • Peer Reviewed
• [Journal Article] Oxidative stress induces the endoplasmic reticxilum stress and facilitates inclusion formation in cultured cells. (2007)
  • Author(s): Hanada S, Yoshida T, et. al.
  • Journal Title: J Hepatol. 47 Pages: 93-102
  • Peer Reviewed
• [Journal Article] Pigment epithelium・derived factor (PEDF) blocks advanced glycation end DrodUct (AGE)-induced angiogenesis in vitro. (2007)
  • Author(s): Yamagishi SI, Yoshida T, et. al.
  • Journal Title: Horm Metab Res. 39 Pages: 233-5
  • Peer Reviewed
• [Journal Article] Pigment-epithelium-derived factor suppresses expression of receptor for advanced glycation end products in the eye of diabetic rats. (2007)
  • Author(s): Yamagishi SI, Yoshida T, et. al.
  • Journal Title: Ophthalmic Res. 39 Pages: 92-7
  • 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
• [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 Takafumi, et al.
  • Journal Title: Oncogene 25・45 Pages: 6056-6066
• [Journal Article] 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, et al.
  • Journal Title: Diabetologia 49・12 Pages: 3094-3099
• [Journal Article] Loss of SOCS3 in the liver promotes fibrosis by enhancing STAT3-mediated TGF-b1 production. (2006)
  • Author(s): Ogata Hisanobu, Chinen Takatoshi, Yoshida Takafumi, et al.
  • Journal Title: Oncogene 25・17 Pages: 2520-2530
• [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 Takafumi, et al.
  • Journal Title: FEBS Letter 580・11 Pages: 2788-2796
• [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 Takafumi, et al.
  • Journal Title: Life Sciences 79・12 Pages: 1981-1987
• [Journal Article] Luteolin promotes degradation in signal transducer and activator of transcription (STAT) 3 in human hepatoma cells : an implication for the antitumor potential of flavonoids. (2006)
  • Author(s): Selvendiran K, Koga H, Ueno T, Yoshida T, et al.
  • Journal Title: Cancer Research 166・9 Pages: 4826-4834
• [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] 肝におけるAGEsによるインスリン抵抗性と、PEDFによる抑制効果の検討 (2007)
  • Author(s): 吉田隆文
  • Organizer: 京都肝セルバイオロジー研究会
  • Place of Presentation: 京都市
  • Year and Date: 2007-07-14
• [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] 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
• [Presentation] Overexpression of pigment epithelium-derived factor prevents fat storage Inflammation and neoplastic formation in the liver of mice steatohepatitis model (2007)
  • Author(s): Yoshida T, et. al.
  • Organizer: European association study of liver (EASL)
  • Place of Presentation: Barcelona, Spain
• [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
• [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
• [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
  • Publisher: メディカルレビュー社