The (15)(16)(17). These factors include acidic fibroblast growth factor, basic fibroblast growth factor (bFGF), epidermal growth factor, transforming growth factors a and 13, tumor necrosis factor a, and vascular endothelial growth factor (VEGF). VEGF is secreted by a number of tumors and is normally expressed in the kidney, brain, and other tissues (18-22).VEGF is also markedly elevated in both VHL-associated and sporadic central nervous system hemangioblastomas (23, 24) and renal carcinomas (25,26). In addition to having mitogenic activity on endothelial cells, VEGF also induces vascular permeability, which may lead to extravasation of plasma proteins and deposition of fibrin, providing an extracellular support for tumor cell and endothelial cell growth.In the present study the effects of retroviral transduction of the VHL cDNA into renal carcinoma cell lines was evaluated. ITo whom reprint requests should be addressed

Optimal electrode location for thalamic DBS in essential tremor corresponds to the anterior margin of the ventralis intermedius nucleus. Leads located greater than 2 mm (in the plane of the commissures) from the optimal coordinates are more likely to be associated with poor tremor control than leads within 2 mm of the optimal location. The incidence of true physiological tolerance to the antitremor effect of thalamic DBS (defined as poor tremor control in spite of lead location within 2 mm of the optimal site) was found to be 9%.

Brain tumor-associated cerebral edema arises because tumor capillaries lack normal blood-brain barrier function; vascular permeability factor (VPF, also known as vascular endothelial growth factor, VEGF) is a likely mediator of this phenomenon. Clinically, dexamethasone reduces brain tumor-associated vascular permeability through poorly understood mechanisms. Our goals were to determine if suppression of permeability by dexamethasone might involve inhibition of VPF action or expression, and if dexamethasone effects in this setting are mediated by the glucocorticoid receptor (GR). In two rat models of permeability (peripheral vascular permeability induced by intradermal injection of 9L glioma cell-conditioned medium or purified VPF, and intracerebral vascular permeability induced by implanted 9L glioma), dexamethasone suppressed permeability in a dose-dependent manner. Since 80% of the permeability-inducing activity in 9L-conditioned medium was removed by anti-VPF antibodies, we examined dexamethasone effects of VPF expression in 9L cells. Dexamethasone inhibited FCS-and PDGF-dependent induction of VPF expression. At all levels (intradermal, intracranial, and cell culture), dexamethasone effects were reversed by the GR antagonist mifepristone (RU486). Dexamethasone may decrease brain tumor-associated vascular permeability by two GR-dependent mechanisms: reduction of the response of the vasculature to tumor-derived permeability factors (including VPF), and reduction of VPF expression by tumor cells. ( J. Clin. Invest . 1996. 98:1400-1408.)