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2005 Fiscal Year Final Research Report Summary

Combination gene therapy of HGF and truncated type II TGF-β receptor for rat liver cirrhosis after partial hepatectomy

Research Project

Project/Area Number 16591345
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionWakayama Medical University, School of Medicine

Principal Investigator

UCHIYAMA Kazuhisa  Wakayama Medical University, School of Medicine, Assistant Professor, 医学部, 助教授 (80232867)

Co-Investigator(Kenkyū-buntansha) YAMAUE Hiroki  Wakayama Medical University, School of Medicine, Professor, 医学部, 教授 (20191190)
IWAHASHI Makoto  Wakayama Medical University, School of Medicine, Lecturer, 医学部, 講師 (70244738)
Project Period (FY) 2004 – 2005
Keywordshepatectomy / liver cirrhosis / liver regeneration / adenovirus vector / HGF / TGF-β
Research Abstract

Background : In a cirrhotic liver, the regenerative ability and specific functions are impaires ; a hepatic resection increases the possibility of postoperative liver failure. Hepatocyte growth factor (HGF) stimulates liver regeneration, accelates restoration of hepatic function, and improves fibrosis. A truncated type II transforming growth factor-β receptor (TβTR), which specifically inhibits TGF-β signaling as a dominant-negative receptor, appears to prevent the progression of liver fibrosis. We demonstrated the therapeutic efficacy of adenovirus-mediated HGF and TβTR gene transducation after partial hepatectomy for liver cirrhosis.
Methods/Results : Rats were treated with dimethylnitrosamine for 3 weeks, and they all had severe cirrhosis. First, to examine the toxicity and the transduction efficiency of adenoviral (Ad) vector in this model, AdLacZ that ranged from 1.0×10^8 to 2.0×10^9 pfu was administered through the portal vein to the rats, and determined that the optimal dose of A … More d vector in cirrhotic rat was range from 5.0×10^8 to 1.0×10^9 pfu. Second, after the 10% partial hepatectomy in rats of this model, we injected AdLacZ (5.0×10^8 pfu), Ad TβTR, AdHGF, or Ad TβTR + AdHGF (1:1 total 1.0×10^9 pfu) into the portal vein, which was followed by an additionl 2-week dimethylnitrosamine treatment. On histologic examination, fibrotic tissue had decreased in the livers of the Ad TβTR + AdHGF-treated rats compared with rats that were treated by AdLacZ, Ad TβTR alone, and AdHGF alone. Liver function, which included serum levels of alanine aminotransferase, improved significantly in Ad TβTR + AdHGF -treated rats compared with all other groups. The number of hepatocytes that were positive for proliferating-cell nuclear antigen was greater (P<.05) in AdHGF alone and Ad TβTR + AdHGF -treated rat livers than in Ad LacZ-and TβTR-treated rats. All Ad TβTR + AdHGF -treated rats survived >60 days, and Ad TβTR + AdHGF treatment markedly improved the survival rate after a partial hepatectomy.
Conclusion : Our results suggest that the combination of HGF and TβTR gene therapy may increase the possibility of hepatectomy in a cirrhotic liver by improving fibrosis, hepatic function, and hepatocyte regeneration. Less

  • Research Products

    (10 results)

All 2006 2005

All Journal Article (10 results)

  • [Journal Article] Combination gene therapy of HGF and truncated type II TGF-β receptor for rat liver cirrhosis after partial hepatectomy2006

    • Author(s)
      Ozawa S et al.
    • Journal Title

      Surgery (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Combination gene therapy of HGF and truncated type II TGF-β receptor for rat liver cirrhosis after partial hepatectomy.2006

    • Author(s)
      Ozawa S, et al.
    • Journal Title

      Surgery (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The evaluation of duct-to-mucosal pancreaticojejunostomy in pancreaticoduodenectomy.2005

    • Author(s)
      Tani M et al.
    • Journal Title

      World J Surg 29

      Pages: 76-79

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Evaluation of chemosensitivity testing wuth highly purified tumor cells in 435 patients with gastric cancer using an MTT assay.2005

    • Author(s)
      Noguchi K et al.
    • Journal Title

      Anticancer Res 25

      Pages: 931-938

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Nitrite/nitrate oxide and cytokines changes in patients with surgical stress.2005

    • Author(s)
      Hirabayashi N et al.
    • Journal Title

      Dig Dis Sci 50

      Pages: 893-897

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Recurrence of primary hepatocellular carcinoma after hepatectomy-differences related to underlying hepatitis virus species.2005

    • Author(s)
      Uchiyama K et al.
    • Journal Title

      Hepato-Gastroenterology 52

      Pages: 591-595

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The evaluation of duct-to-mucosal pancreaticojejunostomy in pancreaticoduodenectomy.2005

    • Author(s)
      Tani M, et al.
    • Journal Title

      World J Surg 29

      Pages: 76-79

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Evaluation of chemosensitivity testing wuth highly purified tumor cells in 435 patients with gastric cancer using an MTT assay.2005

    • Author(s)
      Noguchi K, et al.
    • Journal Title

      Anticancer Res 25

      Pages: 931-938

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Nitrite/nitrate oxide and cytokines changes in patients with surgical stress.2005

    • Author(s)
      Hirabayashi N, et al.
    • Journal Title

      Dig Dis Sci 50

      Pages: 893-897

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Recurrence of primary hepatocellular carcinoma after hepatectomy-differences related to underlying hepatitis virus species.2005

    • Author(s)
      Uchiyama K, et al.
    • Journal Title

      Hepato-Gastfroenterology 52

      Pages: 591-595

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2007-12-13  

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