Langmuir V K, Rooker J A, Osen M, Mendonca H L, Laderoute K R
SRI International, Menlo Park, California 94025.
Cancer Res. 1994 Jun 1;54(11):2845-7.
This study examined the efficacy of combining cyclophosphamide and the hypoxic cytotoxin, tirapazamine, in the treatment of human breast cancer xenografts grown in nude mice. A single dose of tirapazamine was followed 2 h later by a single dose of cyclophosphamide. As determined from tumor regrowth delay, the effectiveness of combined therapy was greater than the additive effects of each treatment given alone. Possible mechanisms of this synergistic interaction include enhancement of DNA damage, inhibition of repair of DNA damage, or induction of apoptosis. Apart from some loss in body weight, the only other toxicity of interest in mice treated with tirapazamine was necrosis of the skin on the distal tail, which appeared to be vascular in origin.
本研究检测了环磷酰胺与低氧细胞毒素替拉扎明联合应用于裸鼠体内人乳腺癌异种移植瘤治疗的疗效。先给予单剂量替拉扎明，2小时后再给予单剂量环磷酰胺。根据肿瘤再生长延迟情况判断，联合治疗的效果优于单独使用每种治疗方法的相加效果。这种协同相互作用的可能机制包括增强DNA损伤、抑制DNA损伤修复或诱导细胞凋亡。除体重有所减轻外，用替拉扎明治疗的小鼠唯一其他值得关注的毒性反应是尾端皮肤坏死，其似乎起源于血管。
