Killion J J, Kleinerman E S, Wilson M R, Tanaka M, Fidler I J
Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Oncol Res. 1992;4(10):413-8.
Three syngeneic murine tumor models were used to determine potential interactions between chemotherapeutic drugs and the synthetic liposome-encapsulated macrophage activator, muramyl tripeptide phosphatidylethanolamine (MLV-19835). Experiments were designed to maximize any additive toxicity of the simultaneous administration of MLV-19835 on the known myelosuppressive effects of doxorubicin, ifosfamide, and cisplatin. Treatment with these drugs resulted in diminished blood leukocyte counts, altered leukocyte differentials, and decreased hematocrits, but the systemic administration of MLV-19835 produced no additional deleterious effects. Myelosuppression normally observed at 2 weeks following treatment of mice with doxorubicin was prevented by combination treatment with MLV-19835. In addition, there was no interference of the antitumor activity of ifosfamide or doxorubicin against subcutaneous, kidney, and spleen tumors. These studies and the recent demonstration of the biological activity of MLV-19835 in phase II trials of osteosarcoma recommend clinical testing of these combined modalities.
使用三种同基因小鼠肿瘤模型来确定化疗药物与合成脂质体包裹的巨噬细胞激活剂——胞壁酰三肽磷脂酰乙醇胺（MLV - 19835）之间的潜在相互作用。实验旨在最大化同时给予MLV - 19835对阿霉素、异环磷酰胺和顺铂已知骨髓抑制作用的任何附加毒性。用这些药物治疗导致血液白细胞计数减少、白细胞分类改变和血细胞比容降低，但全身给予MLV - 19835未产生额外的有害影响。在用阿霉素治疗小鼠后2周通常观察到的骨髓抑制通过与MLV - 19835联合治疗得以预防。此外，异环磷酰胺或阿霉素对皮下、肾脏和脾脏肿瘤的抗肿瘤活性没有受到干扰。这些研究以及MLV - 19835在骨肉瘤II期试验中的生物活性的近期证明推荐对这些联合治疗方案进行临床测试。
