Angiosuppressive treatment of malignant glioma - analysis of molecular mechanisms for clinical implication -

1)胶质瘤的血管生成平衡：研究了多种血管生成因子和抑制物在一系列胶质瘤组织和胶质瘤细胞中的表达。血管内皮生长因子/凝血酶敏感蛋白-1的表达平衡控制着胶质瘤的血管生成。在胶质瘤细胞中，干扰素β可抑制血管内皮生长因子的表达，并抑制血管生成抑制因子的过表达。3)构建了鼠、人血管内皮细胞生长因子报告基因表达载体。通过荧光素酶活性测定，对抑制血管内皮生长因子启动子活性的物质进行了研究。凝血酶敏感蛋白、金雀异黄素、米曲霉素和茶红素可抑制血管内皮生长因子启动子的活性，从而抑制胶质瘤细胞的血管内皮生长因子基因和蛋白表达，并诱导血管内皮细胞迁移。4)采用小鼠颅窗移植瘤U87肿瘤模型，研究了上述几种血管内皮生长因子活性抑制剂的体内抗血管生成活性。

1) Angiogenic balance in gliomas : Expression of various angiogenic factor and inhibitors was investigated in a series of glioma tissues and glioma cells. The expression balance of VEGF / thrombospondin-1 controlled glioma angiogenesis. Interferon β resulted in inhibition of VEGF expression as well as angiogenic inhibitor, IP102) Overexpression of thrombospondin in glioma cells : Thronbospondin-1 expressed plasmid DNA has been used for the transfection (ripofectin method & electroporation). The experiment has been repeated in order to acquire the stable transfectant.3) Mouse & human VEGF / reporter plasmid was constructed. Using luciferase assay, the materials that inhibit VEGF promoter activity was investigated. Thrombospondin, genistein, mithramycin, and theobromin inhibited the VEGF promoter activity, resulting in inhibition of VEGF mRNA and protein expression of glioma cells and glioma induced endothelial cell migration. Pentoxyfillin also inhibited VEGF mRNA and protein expression of glioma cells, resulting in inhibition of glioma induced endothelial cell migration.4) Using mouse cranial window model implanted U87 tumor fragment, above-mentioned inhibitors of VEGF activity have been investigated for their intravital anti-angiogenic activity.