美诺加里尔和N-去甲基美诺加里尔在人肿瘤克隆试验中的体外活性。

In vitro activity of menogaril and N-demethylmenogaril in a human tumor cloning assay.

作者信息

Dodion P, Sanders C, Rombaut W, Rozencweig M, Kitt M M, Kenis Y, Klastersky J

出版信息

Eur J Cancer Clin Oncol. 1986 Mar;22(3):245-9. doi: 10.1016/0277-5379(86)90387-1.

Abstract

The activity of menogaril and its major metabolite in animals and humans, N-demethylmenogaril, has been investigated in the human stem cell assay as developed by Salmon et al. Among 31 evaluable samples, four were sensitive to menogaril, including one which responded to N-demethylmenogaril. Three samples resistant to menogaril responded to N-demethylmenogaril. None was sensitive to doxorubicin. Overall, one out of seven ovarian samples and one out of three breast samples responded to menogaril. Our data confirm the in vitro activity of menogaril in ovarian and breast cancer; in addition, they suggest incomplete cross-resistance between doxorubicin and menogaril and, considering the concentrations of N-demethylmenogaril in animals and humans, a minor role for this metabolite in the overall antitumor activity of the parent compound.

摘要

已按照Salmon等人开发的人类干细胞试验方法，对美诺立尔及其主要代谢物N -去甲基美诺立尔在动物和人体内的活性进行了研究。在31个可评估样本中，有4个对美诺立尔敏感，其中1个对N -去甲基美诺立尔有反应。3个对美诺立尔耐药的样本对N -去甲基美诺立尔有反应。无一例对多柔比星敏感。总体而言，7个卵巢样本中有1个、3个乳腺样本中有1个对美诺立尔有反应。我们的数据证实了美诺立尔在卵巢癌和乳腺癌中的体外活性；此外，数据表明多柔比星与美诺立尔之间存在不完全交叉耐药性，并且考虑到动物和人体内N -去甲基美诺立尔的浓度，该代谢物在母体化合物的总体抗肿瘤活性中作用较小。