Potentiation of Prostate Cancer Radiotherapy Using Combined Antiangiogenic and Antitumor Therapies
Annual rept. 10 Sep 2004-9 Sep 2005
ROCHESTER UNIV NY
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The purpose of this phase of the grant was to quantitate response to antiangiogenic and radiation therapy, in terms of changes in tumor vascular function and hypoxia, and to use the pathophysiological findings to optimally schedule combined therapies. Following a variety of treatments, -250 tumors were frozen for immunohistochemical staining and image analysis and stored for future molecular assays. Methods were developed for colocalized staining of a panel of pericyte markers, apoptosis, totalperfused vessels, hypoxia, and necrosis. A multiple receptor inhibitor, AG-0l3736, was shown to provide striking tumor response in the absence of marked pathophysiological alterations. Initial findings indicate that combining this drug with radiation may reduce some of the tumor volume-dependent resistance seen in single agent therapy. Ongoing studies will quantitate treatment-induced alterations in pericyte coverage in the initial DUl45 prostate tumors, as well as PC-3 and MDA-PDa-2b tumor models.
- Anatomy and Physiology
- Medicine and Medical Research