Anti-angiogenic therapy for malignant gliomas using hypoxia-responsive soluble VEGF receptor

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Soluble form of VEGF receptor, sFlt1 and hypoxia indutible factor(HIF) were focused on the key molecules of antiangiogenic therapy for malignant gliomas.1.The role of sFlt1 and HIF in glioma tissues : The VEGF/sFlt1 ration over than 1 and high expression of HIF were bad prognostic factors in the patients with gliomas.2.Anti-glioma effect of over expression of sFlt1 : sFlt1 gene transfection into U87 human malignant glioma cell lines resulted in 30% decrease of tumor volume compared to control.3.Anti-angiogenic effect of CPT-11 : CPT-11 had potent angiosuppressive agent by inhibiting HIF and VEGF expression of glioma cells and inhibiting endothelial cell proliferation and tube formation.4.The effect of metronomic schedule of CPT-11 for glioma growth : Low dose (1mg/kg) and long term (77 days) administration of CPT-11 resulted in glioma growth which was similar to moderate dose (40mg/kg) and short term (10 days) administration without systemic side effect.5.JTT treatment caused to not only enhance immune function but also inhibit angiogenesis in mouse bearing glioma.Metronomic chemotherapy using CPT-11 is effective for glioma growth by inhibiting HIF and VEGF expression and by inhibiting endothelial cell proliferation and tube formation. sFlt1 and JTT are also candidates as angiosuppressive agent for glioma.