• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Modification of endoplasmic reticulum stress expands surgical indication in hepatocellular carcinom a

Research Project

Project/Area Number 20591609
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKyoto University

Principal Investigator

HATANO Etsuro  Kyoto University, 医学研究科, 講師 (80359801)

Co-Investigator(Kenkyū-buntansha) UEMOTO Shinji  京都大学, 医学研究科, 教授 (40252449)
NITTA Takashi  京都大学, 医学研究科, 助教 (40456877)
YASUCHIKA Kentaro  京都大学, 医学研究科, 助教 (00378895)
IKAI Iwao  京都大学, 医学研究科, 准教授 (60263084)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords癌 / ストレス / アポトーシス / 肝細胞癌 / 小胞体ストレス / CHOP / GADD153 / JNK
Research Abstract

C/EBP homologous protein (CHOP) is one of the key components of the endoplasmic reticulum (ER) stress-mediated apoptosis. We investigated the role of CHOP in cholestatic liver injury. Liver fibrosis was attenuated in CHOP knockout mice after bile duct ligation (BDL). Both apoptotic and necrotic hepatocyte deaths were attenuated in CHOP deficient mice. Cholestasis induces CHOP -mediated ER stress and t riggers hepatocyte death. CHOP deficiency attenuates hepatocyte death and subsequent liver fibrosis. CHOP expression was enhanced in human liver cirrhosis and hepatocellular carcinoma. Furthermore, inhibition of c-Jun NH_2-terminal kinase switches Smad3 signaling from oncogenesis to tumor-suppression in rat hepatocellular carcinoma. Taken together, we expect that modification of ER stress expands surgical indication in hepatocellular carcinoma.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (12 results)

All 2011 2009 2008 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (3 results)

  • [Journal Article] Olprinone attenuates excessive shear stress through up-regulation of endothelial nitric oxide synthase in a rat excessive hepatectomy model.2011

    • Author(s)
      K Yamanaka, E Hatano, M Narito, et al.
    • Journal Title

      Liver Transpl.

      Volume: 17 Pages: 60-69

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of c-Jun NH_2-Terminal Kinase Switches Smad3 Signaling from Oncogenesis to Tumor-suppression in Rat Hepatocellular Carcinoma2009

    • Author(s)
      Nagata, H., Hatano, E., Tada, M., Murata, M., Kitamura, K., Asechi, H., Narita, M., Yanagida, A., Tamaki, N., Yagi, S., Ikai, I., Matsuzaki, K., Uemoto, S.
    • Journal Title

      Hepatology 49(6)

      Pages: 1944-53

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of c-Jun NH_2-Terminal Kinase Switches Smad3 Signaling from Oncogenesis to Tumor- suppression in Rat Hepato cellular Carcinoma2009

    • Author(s)
      Nagata, H., Hatano, E., Tada, M., et al.
    • Journal Title

      Hepatology 49

      Pages: 1944-1953

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A phosphodiesterase III inhibitor protects rat liver from sinusoidal obstruction syndrome through heme oxygenase-1 induction.2009

    • Author(s)
      Narita M., Hatano, E., Ikai, I., et al.
    • Journal Title

      Ann Surg 249

      Pages: 1397-1401

    • NAID

      120001479079

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dai-kenchu-to attenuates rat sinusoidal obstruction syndrome by inhibiting the accumulation of neutrophils in the liver2009

    • Author(s)
      Narita M., Hatano, E., Tamaki, N., et al.
    • Journal Title

      J Gastoroen Hepatol, 24

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CHOP-deficiency attenuates cholestasis-induced liver fibrosis by redcution of hepatocyte injury.2008

    • Author(s)
      Tamaki, N., Hatano, E., Taura, K., Tada, M., Kodama Y., Nitta, T., Iwaisako, K., Seo, S., Nakajima, A., Ikai, I., Uemoto, S.
    • Journal Title

      Am J Physiol 294(2)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] CHOP-deficiency attenuates cholestasis-induced liver fibrosis by redcution of hepatocyte injury2008

    • Author(s)
      Tamaki, N., Hatano, E., Taura, K., et al.
    • Journal Title

      Am J Physiol 294

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss of Sept4 exacerbates liver fibrosis through the dysregulation of hepatic stellate cells2008

    • Author(s)
      54. Iwaisako, K., Hatano, E., Taura, K., et al
    • Journal Title

      J Hepatol 49

      Pages: 768-778

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proliferative activity in hepatocellular carcinoma is closely correlated with glucose metabolism but not angiogenesis.

    • Author(s)
      K Kitamura, E Hatano, T Higashi, et al.
    • Journal Title

      J Hepatology

      Volume: (印刷中)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] JNKの肝発癌過程における分子標的意義- JNK阻害剤による肝細胞癌治療の可能性-2009

    • Author(s)
      長田博光, 波多野悦朗, 阿世知弘行, 成田匡大, 柳田敦子, 玉置信行, 猪飼伊和夫, 松崎恒一, 上本伸二
    • Organizer
      第109回日本外科学会
    • Place of Presentation
      福岡
    • Year and Date
      2009-04-04
    • Related Report
      2010 Final Research Report
  • [Presentation] JNKの肝発癌過程における分子標的意義-JNK阻害剤による肝細胞癌治療の可能性-2009

    • Author(s)
      長田博光, 波多野悦朗, 阿世知弘行, 他
    • Organizer
      第109回日本外科学会
    • Place of Presentation
      福岡
    • Year and Date
      2009-04-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] ラット肝癌モデルにおけるJNK阻害剤による抗腫瘍効果2008

    • Author(s)
      長田博光、波多野悦朗、多田正晴、阿世知弘行、成田匡大、柳田敦子、玉置信行、猪飼伊和夫、松崎恒一、上本伸二
    • Organizer
      第63回日本消化器外科学会定期学術総会
    • Place of Presentation
      札幌
    • Year and Date
      2008-07-17
    • Related Report
      2010 Final Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi