Tumor Growth Modulation by Sense and Antisense Vascular Endothelial Growth Factor Gene Expression: Effects on Angiogenesis, Vascular Permeability, Blood Volume, Blood Flow, Fluorodeoxyglucose Uptake, and Proliferation of Human Melanoma Intracerebral Xenografts

摘要: Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, has been investigated a potent mediator of brain tumor angiogenesis and growth. We evaluated the effect VEGF expression on pathophysiology in brain. Human SK-MEL-2 melanoma cells, with minimal expression, were stably transfected either sense or antisense mouse cDNA used to produce intracerebral xenografts. permeability, blood volume, flow, fluorodeoxyglucose metabolism assessed using tissue sampling quantitative autoradiography. Tumor proliferation was by measuring bromodeoxyuridine labeling indices. density morphological status blood-brain barrier immunohistochemistry. cells (V+) expressed large amounts human protein; V+ formed well-vascularized, rapidly growing tumors necrosis. had substantial significant increases compared wild-type and/or V- (antisense VEGF) tumors. no detectable protein minimally vascularized very low initial rate central necrosis; glucose levels A inhibition growth, well decrease vascularity, may be achieved down-regulation endogenous tissue. VEGF-targeted antiangiogenic gene therapy could an effective component combined strategy treat VEGF-producing