Trimodal Cancer Treatment: Beneficial Effects of Combined Antiangiogenesis, Radiation, and Chemotherapy

摘要: It has been suggested that chemotherapy and radiotherapy could favorably be combined with antiangiogenesis in dual anticancer strategy combinations. Here we investigate the effects of a trimodal consisting all three therapy approaches administered concurrently. We found vitro vivo, antiendothelial antitumor triple combination SU11657 (a multitargeted small molecule inhibitor vascular endothelial growth factor platelet-derived receptor tyrosine kinases), Pemetrexed folate antimetabolite), ionizing radiation were superior to single The human umbilical vein cells tumor (A431) evident cell proliferation, migration, tube formation, clonogenic survival, apoptosis assays (sub-G1 caspase-3 assessment). Exploring potential on survival signaling, induced Akt phosphorylation, but attenuate this process vivo A431 xenografts growing s.c. BALB/c nu/nu mice. Triple further decreased proliferation (Ki-67 index) vessel count (CD31 staining), greater delay versus other regimens without increasing apparent toxicity. When testing different treatment schedules for tumor, regimen (7.5 Gy dose), given after institution treatment, was more effective than preceding treatment. Accordingly, markedly reduced intratumoral interstitial fluid pressure from 8.8 +/- 2.6 4.2 1.5 mm Hg 1 day. Likewise, quantitative T2-weighed magnetic resonance imaging measurements showed SU11657-treated mice had edema. Our data indicates inhibition signaling by antiangiogenic may result in: (a) normalization blood vessels cause prerequisite physiologic conditions subsequent radio/chemotherapy, (b) direct resensitization radio/chemotherapy. conclude cancer combining antiangiogenesis, chemotherapy, beneficial molecular emerge as clinically relevant strategy.