2001 Fiscal Year Final Research Report Summary
GENE THERAPY OF LIVER CIRRHOSIS ; BASIC RESEARCH AND A PROSPECT FOR CLINICAL TRIAL
| Project/Area Number |
11470266
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | HYOGO COLLEGE OF MEDICINE |
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Principal Investigator |
FUJIMOTO Jiro HYOGO COLLEGE OF MEDICINE, PROFESSOR, 医学部, 教授 (90199373)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANISHI Kenji Hyogo College of Medicine, Professor, 医学部, 教授 (60172350)
UEKI Takahiro Hyogo College of Medicine, Research Associate, 医学部, 助手 (10309461)
TAKEUTI Masaharu Hyogo College of Medicine, Research Associate, 医学部, 助手 (00258162)
OKAMURA Haruki Hyogo College of Medicine, Professor, 医学部, 教授 (60111043)
TUTSUI Hiroko Hyogo College of Medicine, Associate Professor, 医学部, 助教授 (40236914)
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| Project Period (FY) |
1999 – 2001
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| Keywords | LIVER CIRRHOSIS / GENE THERAPY / HGF / NAKED DNA / HVJ-LIPOSOME / LIVER FAILURE |
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| Research Abstract |
Liver cirrhosis has been regarded to be irreversible end of fibrous scaring with no effective therapy up to now.We recently established a novel gene therapy approach for rat liver cirrhosis by HVJ-liposome mediated muscle-directed gene transfer of hepatocyte growth facor (HGF). In this study, we performed following several experiments to apply this novel approach for human liver cirrhosis : a) analysis of detail mechanism of H.GF mediated anti-fibrogenesis b) safety evaluation of HVJ-liposome in nonhuman primates c) prevention of liver failure after hepatectomy in rat liver cirrhosis d) naked HGF gene therapy in rat liver cirrhosis e) naked HGF gene therapy in dog liver cirrhosis f) the effect of HGF gene expressionon growth of hepatoma.As the result of these experiments, we got much novel findings. HGF mediated anti-fibrogenesis was thought to act the enhancement of MMP expression by HGF rather than the suppression of TGFβ1 by activation of HGF in Kuppfer cells. Safety evaluation of HVJ-liposome showed the safety, feasiblity, and therapeutic potential of HVJ-liposome in primates. In liver cirrosis rats, HGF gene expression evaded liver failufe after hepatectomy. Naked HGF administration showed fine therapeutic effect not only rats but also dogs. HGF gene expression suppressed the tumor growth rather than tumor growing. These results suggested that HGF gene therapy is capable for treatment of human liver cirrhosis.
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