Anti-Vascular endothelial growth factor treatment augments tumor radiation response under normoxic or hypoxic conditions.

摘要: Recent studies in experimental animals have shown that combining antiangiogenic therapy with radiation can enhance tumor response. Whether this enhancement is mainly attributable to angiogenesis inhibition, endothelial cell radiosensitivity, apoptosis, or a decrease the number of hypoxic cells (improved oxygenation) not known. We designed study discern role oxygenation. We chose an anti-vascular growth factor (anti-VEGF) monoclonal antibody (mAb) which has a known target, human VEGF. also measured interstitial fluid pressure (IFP) test hypothesis that the decreased vascular permeability induced by anti-VEGF mAb can lower IFP. The effect on density, partial oxygen tension (pO2), and apoptosis was also measured. Athymic NCr/Sed nu/nu mice bearing 6-mm xenograft human glioblastoma multiforme (U87), or colon adenocarcinoma (LS174T) were treated injected i.p. alternate days for total of six injections at dosage 100 μg/injection/mouse. For combined anti-VEGF radiation, single doses were given under normal blood flow (20 30 Gy) clamped conditions (30 40 Gy) 24 h after sixth injection mAb. inhibition the growth U87 LS174T tumors associated with significant reduction density relatively small increase apoptotic cells. Compared with size-matched controls, IFP 74% LS174T, 73% U87 in treated After treatment pO2 increased significantly U87, but did not change in LS174T tumors. Combined treatment tumor-growth delay (TGD) greater than additive; except the 40-Gy group, only additive. In both and LS174T TGD independent oxygen levels in time radiation. fact in TGD occurred normoxic suggests that anti-VEGF compensate resistance radiation induced hypoxia.