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

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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.