| Project/Area Number |
14370395
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Digestive surgery
|
|---|
| Research Institution | HYOGO COLLEGE OF MEDICINE |
|---|
Principal Investigator |
FUJIMOTO Jiro Hyogo College of Medicine, Faculty of Medicine, Professor, 医学部, 教授 (90199373)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TSUTSUI Hiroko Hyogo College of Medicine, Faculty of Medicine, Associate Professor, 医学部, 助教授 (40236914)
NAKANISHI Kenji Hyogo College of Medicine, Faculty of Medicine, Professor, 医学部, 教授 (60172350)
IIMURO Yuji Hyogo College of Medicine, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30252018)
HIRANO Tadamichi Hyogo College of Medicine, Faculty of Medicine, Research Associate, 医学部, 助手 (90340968)
IWASAKI Tsuyoshi Hyogo College of Medicine, Faculty of Medicine, Associate Professor, 医学部, 助教授 (10151721)
竹内 雅春 兵庫医科大学, 医学部, 助手 (00258162)
山中 潤一 兵庫医科大学, 医学部, 講師 (90289083)
植木 孝浩 兵庫医科大学, 医学部, 助手 (10309461)
|
|---|
| Project Period (FY) |
2002 – 2003
|
| Project Status |
Completed (Fiscal Year 2003)
|
| Budget Amount *help |
¥11,900,000 (Direct Cost: ¥11,900,000)
Fiscal Year 2003: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 2002: ¥6,200,000 (Direct Cost: ¥6,200,000)
|
|---|
| Keywords | Liver cirrhosis / Hepatoma / HGF / BMT / GVHG / Gene therapy / 肝再生 |
|---|
| 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). We also reported novel gene therapy for hepatoma. In this study, we performed following several experiments to apply these molecular therapy for human liver cirrhosis and hepatoma : 1)analysis of detail mechanism of HGF mediated anti-fibrogenesis 2)bone marrow-derived cells participate in the remodeling process of liver fibrosis with HGF gene therapy 3)BMT mediated graft-versus-tumor effect against 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. When HGF acts in NK cell in vitro, TGFβ1 was suppressed in mRNA and protein level. Bone marrow-derived cells appeared to participate in the remodeling process of liver fibrosis and HGF gene delivery accelerated this recruitment. As the most of bone marrow-derived cell were detected as endothelial cells, reconstruction of blood vessels seemed significantly important for recovery process of liver fibrosis. BMT with HGF therapy markedly inhibited growth of hepatoma. Moreover, HGF ameliorates GVHD effect that is main side effect of BMT.
These results suggested that these molecular therapy is capable for treatment of human liver cirrhosis and hepatoma.
|
