Open Access. Powered by Scholars. Published by Universities.®

Medicine and Health Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 3 of 3

Full-Text Articles in Medicine and Health Sciences

Xenograft Tumors Vascularized With Murine Blood Vessels May Overestimate The Effect Of Anti-Tumor Drugs: A Pilot Study, Zhihong Dong, Atsushi Imai, Sudha Krishnamurthy, Zhaocheng Zhang, Benjamin David Zeitlin, Jacques E. Nör Oct 2017

Xenograft Tumors Vascularized With Murine Blood Vessels May Overestimate The Effect Of Anti-Tumor Drugs: A Pilot Study, Zhihong Dong, Atsushi Imai, Sudha Krishnamurthy, Zhaocheng Zhang, Benjamin David Zeitlin, Jacques E. Nör

Benjamin Zeitlin

Recent evidence demonstrated that endothelial cells initiate signaling events that enhance tumor cell survival, proliferation, invasion, and tumor recurrence. Under this new paradigm for cellular crosstalk within the tumor microenvironment, the origin of endothelial cells and tumor cells may have a direct impact on the pathobiology of cancer. The purpose of this pilot study was to evaluate the effect of endothelial cell species (i.e. murine or human) on xenograft tumor growth and response to therapy. Tumor xenografts vascularized either with human or with murine microvascular endothelial cells were engineered, side-by-side, subcutaneously in the dorsum of immunodefficient mice. When tumors reached …


Expanding Circle Of Inhibition: Small-Molecule Inhibitors Of Bcl-2 Asanticancer Cell And Antiangiogenic Agents, Benjamin David Zeitlin, Isaac J. Zeitlin, Jacques E. Nör Oct 2017

Expanding Circle Of Inhibition: Small-Molecule Inhibitors Of Bcl-2 Asanticancer Cell And Antiangiogenic Agents, Benjamin David Zeitlin, Isaac J. Zeitlin, Jacques E. Nör

Benjamin Zeitlin

The specific targeting of diseases, particularly cancer, is a primary aim in drug development, as specificity reduces unwelcome effects on healthy tissue and increases drug efficacy at the target site. Drug specificity can be increased by improving the delivery system or by selecting drugs with affinity for a molecular ligand specific to the disease state. The role of the prosurvival Bcl-2 protein in maintaining the normal balance between apoptosis and cellular survival has been recognized for more than a decade. Bcl-2 is vital during development, much less so in adults. It has also been noted that some cancers evade apoptosis …


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 Oct 2017

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 …