Effect of the Tumor Vascular-Damaging Agent, ZD6126, on the Radioresponse of U87 Glioblastoma

摘要: Purpose: The effect of ZD6126 on tumor oxygen tension and growth delay in combination with ionizing radiation was examined the human U87 glioblastoma model. Resistance to treatment investigated nitric oxide synthase inhibitor, l-NG-nitroarginine methyl ester (hydrochloride; l-NAME/active form, l-NNA). Methods: xenografts were grown athymic nude mice. given or without l-NNA. Tumor measured using Oxford Oxylite (Oxford, England) fiberoptic probe system. volume determined by direct measurement calipers calculated formula [(smallest diameter2 × widest diameter)/2]. Results: Multiple doses (three doses) had a significant delay, reducing average daily rate from 29% 16%. When 1 hour before radiation, caused an acute increase hypoxia tumors, reduced compared that alone. after either as single dose multiple doses, greater similar antitumor activity Twenty-four hours administration, induced little (10 ± 8%) necrosis xenografts. l-NNA, when ZD6126, significantly enhanced effectiveness inducing necrosis. Conclusions: Our observation ZD6126-induced can decrease response is prior indicates importance scheduling. findings suggest optimal therapeutic benefit plus may require dosing be scheduled following radiotherapy.