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Enzastaurin, An Inhibitor Of Pkc Beta, Enhances Antiangiogenic Effects And Cytotoxicity Of Radiation Against Endothelial Cells., Aaron C. Spalding, Benjamin David Zeitlin, Kari Wilder-Romans, Mary Ellen Davis, Jacques E. Nör, Theodore S. Lawrence, Edgar Ben-Josef
Enzastaurin, An Inhibitor Of Pkc Beta, Enhances Antiangiogenic Effects And Cytotoxicity Of Radiation Against Endothelial Cells., Aaron C. Spalding, Benjamin David Zeitlin, Kari Wilder-Romans, Mary Ellen Davis, Jacques E. Nör, Theodore S. Lawrence, Edgar Ben-Josef
Benjamin Zeitlin
PURPOSE: Angiogenesis plays an important role in pancreas cancer pathobiology. Pancreatic tumor cells secrete vascular endothelial growth factor (VEGF), activating endothelial cell protein kinase C beta (PKC beta) that phosphorylates GSK3 beta to suppress apoptosis and promote endothelial cell proliferation and microvessel formation. We used Enzastaurin (Enz) to test the hypothesis that inhibition of PKC beta results in radiosensitization of endothelial cells in culture and in vivo. MATERIALS/METHODS: We measured PKC beta phosphorylation, VEGF pathway signaling, colony formation, and capillary sprout formation in primary human dermal microvessel endothelial cells (HDMECs) after Enz or radiation (RT) treatment. Microvessel density and tumor …