Basic research and clinical approach of molecular therapy for liver cirrhosis and HCC

肝硬化和肝癌分子治疗的基础研究和临床途径

• 批准号: 14370395
• 负责人: FUJIMOTO Jiro
• 金额: $ 7.62万
• 依托单位: HYOGO COLLEGE OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370395/
• 关键词: Liver cirrhosis; Hepatoma; HGF; BMT; GVHG; Gene therapy; 肝再生

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.

肝脏肝硬化已成为恐怖的恐怖，没有建立一种新型的基因APY方法，用于通过介导的HVJ-脂质体介导的大鼠肝硬化。 2）骨髓衍生的细胞参与HGF基因治疗的肝纤维化重塑3）BMT介导的移植物 - 肿瘤egainst a s ofsper iments的结果，我们得到了许多新颖的发现。 HGF的MMP表达而不是抑制kuppfer细胞中的HGF。牢房似乎似乎似乎似乎似乎似乎似乎已经看似看似看似看似看似看似看似看似看似似乎是Semed F AmelyLiorialiorper take fr smale f s take f s take f a s take a take f a f s a take a f s s tause take f a f s s s s s s a the s s s s s s s s s s s s s s s s s s bmt s s tause。

项目成果

Fujimoto, J: "Extracellular Matrix and the Liver"Academic Press. 467 (2003)

Fujimoto, J：“细胞外基质和肝脏”学术出版社。

Iimuro, Y: "Delivery of matrix metalloproteinase-1 attenuates established liver fibrosis in the rat."Gastroenterology. 124. 445-458 (2003)

Iimuro, Y：“给予基质金属蛋白酶-1 可减轻大鼠已形成的肝纤维化。”胃肠病学。

平野公通: "肝臓外科領域における遺伝子治療応用の展望"外科治療. 89. 343-344 (2003)

Komichi Hirano：“基因治疗在肝脏外科领域的应用前景”Surgical Therapy 89. 343-344 (2003)。

Fujimoto J: "Possible gene therapy for liver cirrhosis. (Extracellular Matrix and the Liver)"Academic Press. 443-454

藤本 J：“肝硬化的可能基因疗法。（细胞外基质和肝脏）”学术出版社。

Iimuro, Y: "Strategy of gene therapy for liver cirrohosis and hepatocellular carcinoma."J.Hepatobiliary Pancreat.Surg. 10. 45-47 (2003)

Iimuro, Y：“肝硬化和肝细胞癌的基因治疗策略。”J. Hepatobiliary Pancreat. Surg。