Development of novel gene therapies in the field of liver surgery

肝脏外科领域新型基因疗法的开发

• 批准号: 09557104
• 负责人: ARII Shigeki
• 金额: $ 8万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09557104/
• 关键词: liver Surgery; gene therapy; VEGF; p53; cre-loxp; Flt-1; IL-12; アデノウィルスベクター; IL-12; HSV-tkプロモーター

There are many diseases and pathophysiological status for the liver surgery. Particulary, the most frequent diseases in this field are primary and secondary liver cancers. Furthermore, novel strategies against the liver failure due to various causes should be also resolved.In the present study, we attempted to develop new strategies against. The above diseases by gene therapies.We obtained the following results which included the development of the gene therapies in the fields other than liver surgery.1) We clarified the efficacy of VEGF gene therapy for prevention of sinusoidal endothelial cell damage during cold preservation.2) We clarified the efficacy of VEGF gene therapy-for prevention of endotoxin induced liver failure.3) We developed P53 expression of suicide gene with on/off switch by CreィイD1-ィエD1loxp system.4) We developed gene therapy using soluble Flt-1 expression vector for peritoneal dissemination of cancer.5) We developed immunogene therapy by using IL-12 gene transfected dendritic cells

肝脏手术有多种疾病和病理生理状态。特别地，该领域最常见的疾病是原发性和继发性肝癌。此外，还应解决针对各种原因引起的肝功能衰竭的新策略。在本研究中，我们试图开发新的策略。通过基因治疗治疗上述疾病。我们获得了以下结果，其中包括肝脏外科以外领域的基因治疗的发展。1）我们阐明了VEGF基因治疗对于预防冷藏过程中肝窦内皮细胞损伤的功效。2）我们阐明了VEGF基因治疗对于预防内毒素引起的肝衰竭的功效。3）我们开发了P53表达 CreiD1-ィエD1loxp系统具有开/关开关的自杀基因。4)我们开发了使用可溶性Flt-1表达载体用于癌症腹膜传播的基因疗法。5)我们通过使用IL-12基因转染的树突状细胞开发了免疫基因疗法

项目成果

MJ. Gorrin-Rives: "Macropage metalloelastase gene transfer into melanoma cells suppresses primary tumor growth by halting angiogenesis"Clinical Cancer Res. (in press).

乔丹。

T.Harada: "Memhane-type matrix metalbopiteinase gene is overexpresed in highly invasive hepatocellular carcinoma" Journal of Hepatology. 28. 231-239 (1998)

T.Harada：“Memhane 型基质金属蛋白酶基因在高度侵袭性肝细胞癌中过度表达”《肝脏病学杂志》。

Masaharu Furutani: "Decreased expression and rare mutation of the CIP/WAF 1 gone in humon hepatocellular carcinoma" Cancer Letter. 111. 191-197 (1997)

Masaharu Furutani：“人类肝细胞癌中 CIP/WAF 1 的表达减少和罕见突变”《癌症通讯》。

Toshiya Kawaguchi: "Expression of FAS-estrogen recepton fusion protein induces cell deall in pancreatic cancer cell lines" Cancer Letter. 116. 53-59 (1997)

Toshiya Kawaguchi：“FAS-雌激素受体融合蛋白的表达诱导胰腺癌细胞系中的细胞处理”《癌症通讯》。

Mototaka Niwano: "The inhibition of tumor growth and microvascular angiogenesis by the potent angiogenesis inhibitor,TNP-470 in rats" Surgery Today. (in press).

Mototaka Niwano：“强效血管生成抑制剂 TNP-470 在大鼠体内抑制肿瘤生长和微血管生成”《今日外科》。