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Pathogenesis of liver injury and carcinogenesis in HCV-expressing model animals by in vivo gene transfer.

Research Project

Project/Area Number 05404030
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionOsaka University

Principal Investigator

KAMADA Takenobu  Osaka University Medical School, Professor, 医学部, 教授 (80028399)

Co-Investigator(Kenkyū-buntansha) MITA Eiji  Osaka University Hospital, Medical Staff, 医学部附属病院, 医員
TAKEHARA Tetsuo  Osaka University Hospital, Medical Staff, 医学部附属病院, 医員
KATAYAMA Kazuhiro  Osaka University Hospital, Medical Staff, 医学部附属病院, 医員
KASAHARA Akinori  Osaka University Medical School, Assistant Professor, 医学部, 助手 (70214286)
HAYASHI Norio  Osaka University Medical School, Associate Professor, 医学部, 講師 (00144478)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥22,800,000 (Direct Cost: ¥22,800,000)
Fiscal Year 1995: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1994: ¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1993: ¥11,500,000 (Direct Cost: ¥11,500,000)
Keywordsin vivo gene transfer / hepatitis C virus / cationic liposome / asialoglycoprotein / rat / liver injury / hepatocarcinogenesis / expression vector / 肝発泡機構 / β-ガラクトシダーゼ / C形肝炎ウィルス / in vivo遺伝子導入 / リポソーム / PCR / 免疫組織化学 / Lac Z / 肝炎 / 肝癌
Research Abstract

The lack of small animal model of hepatitis C virus (HCV) infection impeded elucidation of the pathogenesis of this virus. The aim of this study is to develop HCV-expressing model animals using in vivo gene transfer and use them to study the pathogenesis of liver injury and hepatocarcinogenesis. In this study, we used cationic liposome-mediated and asialoglycoprotein receptor-mediatd in vivo gene transfer. To examine the feasibility of these procedures, pActLacZ in which the LacZ gene was driven by the beta-actin promoter was used as an reporter vector and successful transfection into rat hepatocytes in vivo was confermed by X-Gal histochemistry. For expression of HCV,HCV-expression vector in which the full-coding sequence of the HCV genome was driven by the beta-actin promoter was used. The expression of HCV in rat hepatocytes in vivo was confermed by RT/PCR and immunohistochemical staining using anti-HCV core monoclonal antibody. These HCV-expressing model rats will be useful for determining the pathological role of HCV in vivo.

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Yuki N, et al.: "Hepatitis C virus replication and antibody responses toward specific hepatitis C proteins." HEPATOLOGY. 20. 1360-1365 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kanto T., et al.: "Buoant density of hepatitis C virus recovered from infected hosts." HEPATOLOGY. 19. 296-302 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takehara T., et al.: "Expression of the hepatitis C virus genome in rat liver after cationic liposome-mediated in vivo gene transfer." HEPATOLOGY. 21. 746-751 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yamamoto M., et al.: "In vivo transfection of hepatitis C virus cDNA into rodent liver by asialoglycoprotein receptor mediated gene delivery." HEPATOLOGY. 22. 847-855 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kasahara A., et al.: "Ability of prolonged interferon treatment to suppress relapse after cessation of therapy in patients with chronic hepatitis C." HEPATOLOGY. 21. 291-297 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hagiwara H., et al.: "Quantitation of hepatitis C viru RNA in serum of asymptomatic blood donors and patients with type C chronic liver disease." HEPATOLOGY. 17. 545-550 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hagiwara H,Hayashi N,et al.: "Quantitation of hepatitis C virus RNA in serum of asymptomatic blood donors and patients with type C chronic liver disease." HEPATOLOGY. 17. 545-550 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yuki.N,Hayashi N,et al.: "Quantitative analysis of antibodies to hepatitis C virus during interferon-a tharapy." HEPATOLOGY. 17. 960-965 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kanto T,Hayashi N,et al.: "Buoyant density of hepatitis C virus recovered from infected hosts." HEPATOLOGY. 19. 296-302 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hiramatsu N,Hayashi N,et al.: "Immunohistochemical detection of Fas actigen in liver tissue patients with chronic hepatitis C." HEPATOLOGY. 19. 1354-1359 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yuki N,Hayashi N,et al.: "Hepatitis C virus replication and antibody responses toward specific hepatitis C virus proteins." HEPATOLOGY. 19. 1360-1365 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kanazawa Y,Hayashi N,et al.: "Influence of viral quasispecies of effectiveness of interferon therapy in chronic hepatitis C patients." HEPATOLOGY. 20. 1121-1130 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Oshita M,Hayashi N,et al.: "Increased serum hepatitis C virus RNA levels among alcoholic patients with chronic hepatitis C." HEPATOLOGY. 20. 1115-1120 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takehara T,Hayashi N,et al.: "Expression of the hepatitis C virus genome in rat liver after cationic liposome-mediated in vivo gene transfer." HEPATOLOGY. 21. 746-751 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yamamoto M,Hayashi N,et al.: "In vivo transfection of hepatitis C virus cDNA into rodent liver by asialoglycoprotein receptor mediated gene delivery." HEPATOLOGY. 22. 847-855 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kasahara A,Hayashi N,et al.: "Ability of prolonged interferon treatment to suppress relapse after cessation of therapy in patients with chronic hepatitis C." HEPATOLOGY. 21. 291-297 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yuki N,Hayashi N,et al.: "Thesignificance of IgM antibody response to hepatitis C virus core protein in patients with chronic hapatitis C." HEPATOLOGY. 22. 402-406 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Naito M,Hayashi N,et al.: "Hepatitis C virus quasispecies in hepatitis C virus carriers with normal liver enzymes and patients with type C chronic liver disease." HEPATOLOGY. 22. 407-412 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takehara T,et al.: "Expression of the hepatitis C virus genome in rat liver after cationic liposome-mediated in vivo gene transfer." Hepatology. 21. 746-751 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamamoto M,et al.: "In vivo transfection of hepatitis C virus cDNA into rodent liver by asialoglycoprotein receptor mediated gene delivery." Hepatology. 22. 847-855 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kasahara A,et al.: "Ability of prolonged interferon treatment to suppress relapse after cessation of therapy in patients with chronic hepatitis C." Hepatology. 21. 291-297 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yuki N,et al.: "The significance of IgM antibody response to hepatitis C virus core protein in patients with chronic hepatitis C." Hepatology. 22. 402-406 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Naito M,et al.: "Hepatitis C viral quasispecies in hepatitis C virus carriers with normal liver enzymes and patients with type C chronic liver disease." Hepatology. 22. 407-412 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Moribe T,et al.: "Hepatitis C viral complexity detected by single-strand conformation polymorphism and response to interferon therapy." Gastroenterology. 108. 789-795 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kanto T,Hayashi N,Takehara T,etk al.: "Buoyant density of hepatitis C virus recovered from infected hosts." Hepatoloqy. 19. 296-302 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Naito M,Hayashi N,Hagiwara H,et al.: "Serial quantitative analysis of serum hepatitis C." Journal of Hepatoloqy. 20. 755-759 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yuki N,Hayashi N,Kasahara A,et al.: "Hepatitis C virus replication and antibody responses toward specific hepatitis C Proteins." Hepatology. 19. 1360-1365 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Haruna Y, Hayashi N,Kamada T,et al.: "Expression of hepatitis C virus hepatocellular" Cancer. 73. 2253-2258 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Osita M, Hayashi N,Kasahara A,et al.: "Increased serum hepatitis C Virus RNA levels among alcoholic patients with chronic hepatitis C." Hepatology. 20. 1115-1120 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takehara T,Hayashi N, Miyamoto Y,et al.: "Expression of the hepatitis C virus genome in ratliver after cationic liposome-mediated in vivo gene transfer" Hepatology. in press.

    • Related Report
      1994 Annual Research Report
  • [Publications] Yuki N.et al.: "Changes in antibodies to specific hepatitis C virus antigens with interferon alpha therapy" American Journal of Gastroenterology. 88. 914-918 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Oshita, M.et al.: "Prevalence of hepatitis C virus in family members of patients with hepatitis C" Journal of Medical Virology. 41. 251-255 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hagiwara, H.et al.: "Quantitation of hepatitis C virus RNA in serum of asymptomatic blood donors and patients with type C chronic liver disease" Hepatology. 17. 545-550 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yuki N.et al.: "Quantitative analysis of antibodies to hepatitis C virus during interferon alpha therapy" Hepatology. 17. 960-965 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hagiwara, H.et al: "Quantitative analysis of hepatitis C virus RNA in serum during interferon therapy" Gastroenterology. 104. 877-883 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Haruna Y.et al.: "Detection of hepatitis C virus RNA in liver tissues by an in situ hybridization technique" Journal of Hepatology. 18. 96-100 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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