Publications [#168959] of Mark W. Dewhirst

Papers Published

1. BJ Moeller, MR Dreher, ZN Rabbani, T Schroeder, Y Cao, CY Li, MW Dewhirst, Pleiotropic effects of HIF-1 blockade on tumor radiosensitivity., Cancer cell, vol. 8 no. 2 (August, 2005), pp. 99-110, ISSN 1535-6108 [doi]
   (last updated on 2013/05/16)

   Abstract:
   We have previously shown that radiation increases HIF-1 activity in tumors, causing significant radioprotection of the tumor vasculature. The impact that HIF-1 activation has on overall tumor radiosensitivity, however, is unknown. We reveal here that HIF-1 plays an important role in determining tumor radioresponsiveness through regulating four distinct processes. By promoting ATP metabolism, proliferation, and p53 activation, HIF-1 has a radiosensitizing effect on tumors. Through stimulating endothelial cell survival, HIF-1 promotes tumor radioresistance. As a result, the net effect of HIF-1 blockade on tumor radioresponsiveness is highly dependent on treatment sequencing, with "radiation first" strategies being significantly more effective than the alternative. These data provide a strong rationale for pursuing sequence-specific combinations of HIF-1 blockade and conventional therapeutics.

   Keywords:
   Adenosine Triphosphate • Animals • Apoptosis • Cell Proliferation • DNA-Binding Proteins • Endothelium, Vascular • Energy Metabolism • Humans • Hypoxia-Inducible Factor 1 • Hypoxia-Inducible Factor 1, alpha Subunit • Mice • Neoplasms • Neovascularization, Pathologic • Nuclear Proteins • RNA Interference • Radiation Tolerance* • Transcription Factors • Tumor Suppressor Protein p53 • antagonists & inhibitors* • genetics • metabolism • radiation effects • radiotherapy*