Antiangiogenic gene therapy in a rat glioma model using a dominant-negative vascular endothelial growth factor receptor 2.

摘要: Malignant gliomas are a prominent target for cancer gene therapy approaches because of their poor prognosis despite all currently available therapies. Gene strategies developed to interfere with the normal function vascular endothelial growth factor receptors have been successfully used in different experimental models block tumor angiogenesis and inhibit growth. In this study we examined whether retroviruses encoding mutant VEGF receptor 2 (VEGFR-2) could suppress thereby prolong survival rats bearing syngeneic intracerebral glioma tumors. Survival time tumors was significantly prolonged dose-dependent manner when carrying VEGFR-2 were cotransplanted cells. No effect on observed that received virus-producing cells or virus supernatant intracerebrally after 5 days injection. established subcutaneous treatment multiple injections also inhibited manner. After implantation stably transfected truncated form VEGFR-2, exhibited rate similar animals treated high numbers VEGFR-2. Morphologically, showed signs impaired angiogenesis, such as extensive necrosis reduced density. These results suggest dual mode namely dominant-negative inhibition depletion by binding. We further explored safety retrovirus-mediated transfer. Although sequences found tissues injection cells, no morphological changes any tissue follow-up 6 months. Our indicate is useful malignant gliomas.