Potentiation of Prostate Cancer Radiotherapy Using Antiangiogenic and Antitumor Therapies
Abstract
The focus of this grant was to gauge the pathophysiological effects of combinations of radiotherapy and a variety of antiangiogenic agents by studying corresponding changes in vascular maturity and function in PC-3 and DU145 human prostate xenografts. Perfusion, apoptosis, proliferation, and hypoxia indices as well as pericyte and basement membrane coverage were quantified using image analysis of immunohistochemically stained frozen tumor sections. Results argue against a treatment-induced functional normalization of the tumor vasculature following combination therapy. Rather than tightening pericytes, combination treatments loosened pericyte-vessel and pericytebasement membrane associations. Despite reductions in oxygenation and vessel densities, tumor progression was minimal during extended combination treatment, most likely due to continued vascular destruction and the prevention of new vessel growth. Surprisingly, alternative scheduling of antiangiogenic drugs and radiation had minimal effects on tumor progression or pathophysiology.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2007
- Accession Number
- ADA477949
Entities
People
- Bruce M. Fenton
Organizations
- University of Rochester