Radiation and Angiostatin Target the Tumor Vasculature: A New Paradigm for Prostate Cancer Treatment
Abstract
Our laboratory has investigated the interaction of angiostatin and ionizing radiation (IR) both in vivo and in vitro. We proposed the hypothesis that interactive killing between angiostatin and fractionated radiation in murine tumors and human xenografts may overcome radioresistance by targeting the prostate tumor neovasculature. We have demonstrated enhanced tumor regression in PC3 (human prostate carcinoma) xenografts and in murine Lewis lung carcinomas (LLC) treated with the combination of angiostatin and IR when compared with either treatment alone. We have shown in vitro that angiostatin was cytotoxic to endothelial cells but not to tumor cells. Additive cytotoxicity was seen in endothelial cells when angiostatin was combined with IR. This cytotoxic interaction was absent in tumor cells treated with angiostatin and IR suggesting specificity of targeting tumor endothelium. We investigated the hypothesis that DNA damaging agents other than IR will interact with angiostatin. Cyclophosphamide was employed in combination with angiostatin to assess primary tumor regression using PC3 xenografts and LLC tumors and to assess growth of metastases using LLC. These data may lead to increased efficacy of localized radiotherapy for prostate cancer and may be beneficial in the adjuvant treatment of prostate cancer and possibly in some forms of metastatic prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA391980
Entities
People
- Ralph Weichselbaum
Organizations
- University of Chicago