Advances in brain tumor vascular biology may lead to new brain tumor therapies targeting the vasculature. The microvasculature of the central nervous system differs morphologically and functionally from that of other organs in: 1) its expression of a blood brain barrier; and (2) the important role of astroglia in regulation of microvessel formation. Tumor-stimulated neovascularization (angiogenesis) dramatically alters these unique properties and is critical to brain tumor growth. Inhibition of angiogenesis may control the growth of brain tumors. Therefore, elucidation of the interaction between the tumor and the vasculature in the microvessel environment, of the role of the microvasculature in energy delivery, and of the impact on the tumor of restricting neovascularization is needed in order to develop angiogenesis inhibition as an approach for brain tumor therapy. Project I, "Biochemistry of Brain Tumor Microvessel Development," will investigate the mechanisms by which glioma cells alter the microvasculature. Project II, "Development of Anti-angiogenesis agents for Brain Tumors, " will identify inhibitors of angiogenesis that are effective against brain tumors and explore their biological characteristics. Project III "Brain Tumor Metabolism and Perfusion" will investigate how inadequate perfusion affects tumor cell growth and tumor metabolism by use of nuclear magnetic resonance spectroscopy. Project IV, "Glucose Metabolism of Brain Tumors; Role of Microvasculature, " will explore the role of microvessels in delivering glucose to human brain tumors by correlating functional imaging data related to glucose metabolism and immunohistopathologic measures of blood brain barrier expression, cell division, and neovascularity. The Core Support will maintain a well characterized library of cell cultures and xenografts of human astrocytomas, and provide pathological and statistical expertise. Through an integrated program in a "Vascular Biology of Brain Tumors" Center, the four projects and the core are designed to provide insight into angiogenesis, blood- brain barrier expression, endothelial cell biology, tumor metabolism, and imaging, so that new diagnostic and therapeutic modalities can be developed for future clinical application.