Ebrahim el-Zayat A A, Izquierdo M A, Clark G M, Von Hoff D D
Dept. of Experimental Pathology, New York Medical College, Valhalla 10595, USA.
Invest New Drugs. 1995;13(2):125-131. doi: 10.1007/BF00872860.
In several preclinical systems, the morpholino anthracycline MX2 has greater antitumor activity than doxorubicin, is less cardiotoxic, and is effective against multidrug resistant cancer cells. We used a human tumor soft-agar cloning assay to test the cytotoxicity of MX2 against single cell suspensions from freshly obtained human tumors. Tumor cells were exposed to MX2 at 0.05 and 0.5 micrograms/ml either for 1 hour (2-1 specimens; 77 [38%] assessable) or continuously (231 specimens; 91 [39%] assessable). Superior antitumor activity was observed with continuous exposure (19% in vitro response at 0.05 micrograms/ml and 69% at 0.5 micrograms/ml) than with 1-hour exposure (1.3% at 0.05 micrograms/ml and 12% at 0.5 micrograms/ml). Activity was seen against all types of cancer tested including renal (91%), melanoma (88%), ovarian (73%), breast (71%) and non-small-cell lung (67%) cancer at a MX2 concentration of 0.5 micrograms/ml after continuous exposure. If appropriate plasma levels can be achieved in patients, MX2 could have significant clinical activity with those tumors.
在多个临床前系统中，吗啉代蒽环类药物MX2比阿霉素具有更强的抗肿瘤活性，心脏毒性更小，并且对多药耐药癌细胞有效。我们使用人肿瘤软琼脂克隆试验来测试MX2对新鲜获取的人肿瘤单细胞悬液的细胞毒性。将肿瘤细胞以0.05和0.5微克/毫升的浓度暴露于MX2中，暴露时间为1小时（2 - 1个样本；77个[38%]可评估）或持续暴露（231个样本；91个[39%]可评估）。与1小时暴露相比，持续暴露观察到更高的抗肿瘤活性（0.05微克/毫升时体外反应率为19%，0.5微克/毫升时为69%），而1小时暴露时0.05微克/毫升时为1.3%，0.5微克/毫升时为12%。持续暴露后，在MX2浓度为0.5微克/毫升时，对所有测试的癌症类型均有活性，包括肾癌（91%）、黑色素瘤（88%）、卵巢癌（73%）、乳腺癌（71%）和非小细胞肺癌（67%）。如果在患者中能够达到合适的血浆水平，MX2对这些肿瘤可能具有显著的临床活性。
