1. Local irradiation in combination with bevacizumab enhances radiation control of bone destruction and cancer-induced pain in a model of bone metastases.
- Author
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Zwolak P, Dudek AZ, Bodempudi VD, Nguyen J, Hebbel RP, Gallus NJ, Ericson ME, Goblirsch MJ, and Clohisy DR
- Subjects
- Animals, Antibodies, Monoclonal, Humanized, Bevacizumab, Bone Neoplasms drug therapy, Bone Neoplasms radiotherapy, Bone and Bones pathology, Combined Modality Therapy, Female, Mammary Neoplasms, Experimental pathology, Mammary Neoplasms, Experimental therapy, Mice, Mice, Inbred C3H, Mice, SCID, Pain etiology, Angiogenesis Inhibitors therapeutic use, Antibodies, Monoclonal therapeutic use, Bone Neoplasms secondary, Bone Neoplasms therapy, Bone and Bones radiation effects, Disease Models, Animal, Pain radiotherapy
- Abstract
Skeletal metastases are a major source of morbidity for cancer patients. The purpose of this study was to evaluate the effects of megavoltage irradiation and antiangiogenic therapy on metastatic bone cancer. A tumor xenograft model was prepared in C3H/Scid mice using 4T1 murine breast carcinoma cells. Twenty-eight mice bearing tumors were treated with either bevacizumab (15 mg/kg), local megavoltage irradiation (30 Gy in 1 fraction), combination of bevacizumab and local megavoltage irradiation or physiologic saline solution (control group). Tumor area, bone destruction, tumor microvessel density, pain-associated behaviors and expression of substance P were assessed. Combined modality treatment reduced the frequency of pain-associated behaviors, decreased levels of nociceptive protein expression in the spinal cord, maintained cortical integrity and decreased the density of microvessels as compared to single modality treatments. We conclude that concurrent antiangiogenic therapy and localized radiotherapy for the treatment of bone metastases warrants further evaluation in human clinical trials., ((c) 2007 Wiley-Liss, Inc.)
- Published
- 2008
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