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Novel strategies of cancer therapy combine irradiation and anti-angiogenicactive compounds. However, little is known concerning the undesired cellular andmolecular effects caused by this novel treatment concept. We used a mouse squamouscell carcinoma (SCC) xenotransplantation model to evaluate the potential undesiredeffects which compromise the success of this therapeutic combination. SCCs weresubcutanously implanted in nude mice. Animals were treated with a fractionatedirradiation scheme (5x4 Gy) alone or in combination with daily injections of anti-vascularendothelial growth factor (VEGF) antibodies. Controls remained untreated. Beforeand after treatment, resonance imaging (MRI), ultrasound and near-infrared spectrometrywere used to evaluate tumor vessel integrity. Finally, tumors were explanted andVEGF, basic fibroblast growth factor (bFGF), vessel density, proliferation andapoptotic activity were analyzed by immunohistochemistry. Irradiation caused VEGFrelease and we found evidence for VEGF-mediated vessel protection. In the tumorsderived from the combined treatment, blood volume was decreased, and apoptoticindices were increased. Remarkably, bFGF levels and proliferative indices werealso increased. Combined irradiation/anti-VEGF treatment resulted in the desiredVEGF depletion and increased tumor cell apoptosis. Nonetheless, bFGF and proliferationalso increased, possibly suggesting a compensatory response. The application ofadditional targeted drugs may help develop more effective SCC treatments.

oncology reports

Increased basic fibroblast growth factor release and proliferation in xenotransplanted squamous cell carcinoma after combined irradiation/anti-vascular endothelial growth factor treatment