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Therapetic strategy for chronic hepatitis C by inducing apoptosis of hepatocyte infected with hepatitis C virus

Research Project

Project/Area Number 11470132
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionOsaka University

Principal Investigator

HAYASHI Norio  Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (00144478)

Co-Investigator(Kenkyū-buntansha) MOCHIZUKI Kiyosi  Osaka University Hospital, Clinical Staff, 医学部・附属病院, 医員
HIRAMATSU Naoki  Osaka University Hospital, Clinical Staff, 医学部・附属病院, 医員
SASAKI Yutaka  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (70235282)
OKAWA Kazuyoshi  Osaka University Hospital, Clinical Staff, 医学部・附属病院, 医員
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2000: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1999: ¥9,200,000 (Direct Cost: ¥9,200,000)
KeywordsHepatitis C virus / Apoptosis / Cell cycle / Hepatocyte / Core / Microarray / 樹状細胞 / IL-12 / 抗アポト-シス
Research Abstract

To investigate influence of hepatitis C virus (HCV) infection on hepatocyte, we established several permanent hepatocyte clones that express HCV core gene. Microarray analysis of these clones revealed a couple of gene of which expression was modulated in HCV core-expressing clones. We applied Nothern blot analysis to confirm 2 genes of which expression was downrgulated as well as 3 genes of which expression was upregulated in HCV core-expressing clones. We are currently analyzing the role of these genes in hepatocytes. We also investigated the effect of HCV core expression on apoptosis as well as cell proliferation. Expression of HCV core gene did not affect apoptosis, but significantly retarded proliferation of hepatocyte by inhibiting G1/S transition. These results suggest that infection of HCV inhibits hepatocyte proliferation but does not affect apoptosis of hepatocytes, raising the possibility that HCV-infected hepatocytes can be eradicated by apoptotic stimuli.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Kitada T, et al.: "The addition of bisecting N-acetylglucosamine residues to E-cadherin down-regulaes the tyrosine phosphorylation of β-catenin."J Biol Chem. 276. 475-480 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Horimoto M, et al.: "A novel strategy for cancer therapy by mutated mammalian degenerin gene transfer."Cancer Gene Ther. 7. 1341-1347 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka H, et al.: "Effect of interferon therapy on the incidence of hepatocellular carcinoma and mortality of patients with chronic hepatitis C ; A retrospective cohort study of 738 patients"Int J Cancer. 87. 741-749 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishida H, et al.: "Identification of multiple transcription factors, HLF, FTF, and E4BP4, controlling hepatitis B virus enhancer."J Virol. 74. 1241-1251 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka Y, et al.: "Probability of hepatocellular carcinoma of small hepatocellular nodules undetectable by computed tomography during arterial portography."Hepatology. 31. 890-898 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishida H, Ueda K, Ohkawa K, Kanazawa Y, Hosui A, Nakanishi F, Mita E, Kasahara A, Sasaki Y, Hori M, Hayashi N.: "Identification of multiple transcription factors, HLF, FTF, and E4BP4, controlling hepatitis B virus enhancer II."J Virol. 74. 1241-1251 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kasahara A, Hayashi N, Mochizuki K, Hiramatsu N, Kato M,. Masuzawa M, Oshita M, Naito M, Kashiwagi T, Yoshihara H, Hori M, Kamada T: "Pretreatment viral load and response to interferon therapy for liver cirrhosis caused by hepatitis C virus : a multicenter controlled study."Hepatol Res. 16. 124-138 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kasahara A, Hayashi N, Mochizuki K, Hiramatsu N, Sasaki Y, Kakumu S, Kiyosawa K, Okita K, Osaka Liver Disease Study Group.: "Clinical charactertistics of patients with chronic hepatitis C showing biochemical remission, without hepatitis C virus eradication, as a result of interferon therapy."J Viral Hep. 7. 343-351 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka Y, Sasaki Y, Katayama K, Hiramatsu N, Ito A, Murata H, Enomoto N, Oshita M, Mochizuki K, Ysujii M, Tsuji S, Kasahara A, Tomoda K, Nakamura H, Hayashi N, Hori M.: "Probability of hepatocellular carcinoma of small hepatocellular nodules undetectable by computed tomography during arterial portography."Hepatology. 31. 890-898 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yuki N, Ishida H, Inoue T, Tabata T, Matsushita Y, Kishimoto H, Kato M, Masuzawa M, Sasaki Y, Hayashi N, Hori M.: "Reappraisal of biochemical hepatitis C activity in hemodialysis patients."J Clin Gastroenterol. 30. 187-194 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yasuda K, Ohashi Y, Matsushima T, Kumada H, Hino K, Ito M, Takeuchi T, Kakumu S, Kuroki T, Hayashi N, Sata M, Iino S.: "Low-dose oral interferon-α in the treatment of chronic viral hepatitis type B : A double-blind, randomized, placebo-controlled, clinical trial."Curr Ther Res Clin Exp. 61. 245-254 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka H, Tsukuma H, Kasahara A, Hayashi N, Yoshihara H, Masuzawa M, Kanda T, Kashiwagi T, Inoue A, Kato M, Oshita A, Kinoshita Y, Kamada T.: "Effect of interferon therapy on the incidence of hepatocellular carcinoma and mortality of patients with chronic hepatitis C : A retrospective cohort study of 738 patients."Int J Cancer. 87. 741-749 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Horimoto M, Sasaki Y, Ugawa S, Wada S, Toyama T, Iyoda K, Yakushijin T, Minami Y, Ito T, Hijioka T, Eguchi A, Nakanishi M, Shimada S, Tohyama M, Hayashi N, Hori M.: "A novel strategy for cancer therapy by mutated mammalian degenerin gene transfer."Cancer Gene Ther. 7. 1341-1347 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katayama K, Kasahara A, Sasaki Y, Kashiwagi T, Naito M, Masuzawa M, KatohM, Yoshihara H, Kamada T, Mukuda T, Hijioka T, Hori M, Hayashi N: "Immunological response to interferon-γ priming prior to interferon-α treatment in refractory chronic hepatitis C in relation to viral clearance."J Viral Hep. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kitada T, Miyoshi E, Noda K, Higashiyama S, Ihara H, Matsuura N, Hayashi N, Kawata S, Matsuzawa Y, Taniguchi N.: "The addition of bisecting N-acetylglucosamine residues to E-cadherin down-regulaes the tyrosine phosphorylation of β-catenin."J Biol Chem. 276. 475-480 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kitada T, et al.: "The addition of bisecting N-acetylglucosamine residues to E-cadherin down-regulaes the tyrosine phosphorylation of β-catenin."J Biol Chem. 276. 475-480 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Horimoto M, et al.: "A novel strategy for cancer therapy by mutated mammalian degenerin gene transfer."Cancer Gene Ther. 7. 1341-1347 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tanaka H, et al.: "Effect of interferon therapy on the incidence of hepatocellular carcinoma and mortality of patients with chronic hepatitis C ; A retrospective cohort study of 738 patier"Int J Cancer. 87. 741-749 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishida H, et al.: "Identification of multiple transcription factors, HLF, FTF,and E4BP4, controlling hepatitis B virus enhancer."J Virol. 74. 1241-1251 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tanaka Y, et al.: "Probability of hepatocellular carcinoma of small hepatocellular nodules undetectable bu computed tomography during arterial portography."Hepatology. 31. 890-898 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kuzushita N.: "Involvement of transporter associated with antigen processing (TAP2)gene polymorphisims in hepatitis C virus infection"Gastroenterology. 116. 1149-1154 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tatsumi T.: "B7-1(CD80)-gene transfer combined with interleukin 12 administration elicits protective and therapeutic immunity against mouse hepatocellular carcinoma"Hepatology. 30. 422-429 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamamoto M.: "Intarcellular single-chain antibody against hepatitis B virus cultured cells"Hepatology. 30. 300-307 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takehara T.: "Interleukin-1 beta protects mice from Fas-mediated apoptosis and death"Gastroenterology. 117. 661-668 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyoshi E.: "Overexpression of alpha 1-6 fucosyltransferase in hepatoma cells suppresses intrahepatic metastasis after splanchnic injection in athymic mice"Cancer Res.. 59(9). 2237-2243 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishida H.: "Identification of multiple transcription factors, HLF, FTF, and E4BP4,controlling hepatitis B virus enhancer II."J Virology. 74(3). 1241-1251 (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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