Enhancement of drug sensitivity and a bystander effect using gene tranfection

利用基因转染增强药物敏感性和旁观者效应

基本信息

批准号：
08457318
负责人：
HORIUCHI Tetsuya
金额：
$ 2.69万
依托单位：
Fukui Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457318/
关键词：
chemotherapy chemosensitivity gene therapy angiogenesis PD-ECGF cDNA By stander effect 5-FU dThdPase PD-ECGF cDNA by stander effect Thymidine Phosphorylase PD-ECGF Thymidine Kinase 5′DFUR Tegafur

项目摘要

Various type of chmosensitivity test assays have been developed to predict the human tumors to anticancer agents. Application of TIA (Tritium Incorporation Assay) has been developed to attain higher rates of evaluability and provide a rapid assessment of chmosensiytivities in our institute. However, even with such assays the chemotherapy to gastrointestinal cancers may not be always sufficient.Angiogenesis is essential for growth of solid tumors. Intratumoral microvessel count, which represents a measure of tumor angiogenesis, has been associated with the overall survival of patients with gastric carcinomas (Cancer Res, 1996), coloniccarcinomas (Cancer Res, 1997), esophageal carcinomas (cancer, 1997) and hepatocellular carcinomas (Hepatology, 1997). Vascular endothelial growth factor (VEGF) expression plays a role in promotion of angiogenesis and has strong correlation between overall survival and development of hematogenous metastasis in human gastric carcinomas (J Clin Oncol, 1997). On the other hand, platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) is also one of the potent angiogenic factors. The expression of VEGF,which correlates intratumoral microvessel count and the expression of PD-ECGF/TP,is an independent prognostic factor in colorectal carcinomas (Cncer Letters, 1997).PD-ECGF/TP is an enzyme that catalyzes the phosphorolysis of thymidine and converts 5' DFUR and tegafur to 5-FU.The tranfection of PD-ECGF gene to lung cancer cell line (PC-9) enhances the sensitivity to 5' DFUR,tegafur, and 5-FU.Besides this enhancement is promoted by non-contact type bystander effect (Br J Cancer, 1997).The tranfection of PD-ECGF gene may be useful as a gene therapy strategy for cancer treatment, especially in cancerous peritonitis, by enhancemenet of drug sensitivity.

已经开发出各种类型的化学敏感性试验来预测人类肿瘤对抗癌药物的影响。 TIA（氚掺入分析）的应用已得到开发，以获得更高的可评估率，并为我们研究所的化学敏感性提供快速评估。然而，即使采用此类检测，胃肠道癌症的化疗也可能并不总是足够的。血管生成对于实体瘤的生长至关重要。肿瘤内微血管计数代表肿瘤血管生成的量度，与胃癌（Cancer Res，1996）、结肠癌（Cancer Res，1997）、食管癌（cancer，1997）和肝细胞癌（Cancer Res，1997）患者的总生存期相关。肝病学，1997）。血管内皮生长因子（VEGF）表达在促进血管生成中发挥作用，并且与人胃癌的总生存率和血行转移的发展有很强的相关性（J Clin Oncol，1997）。另一方面，血小板源性内皮细胞生长因子/胸苷磷酸化酶（PD-ECGF/TP）也是有效的血管生成因子之一。 VEGF 的表达与肿瘤内微血管计数和 PD-ECGF/TP 的表达相关，是结直肠癌的独立预后因素 (Cncer Letters, 1997)。PD-ECGF/TP 是一种催化胸苷磷酸解和将5'DFUR和替加氟转化为5-FU。PD-ECGF基因转染肺癌细胞系(PC-9) 增强对 5' DFUR、替加氟和 5-FU 的敏感性。此外，这种增强是通过非接触型旁观者效应促进的（Br J Cancer，1997）。PD-ECGF 基因的转染可能有用通过增强药物敏感性作为癌症治疗的基因治疗策略，特别是癌性腹膜炎。