Le Pecq J B, Gosse C, Cros S, Paoletti C
Cancer Res. 1976 Sep;36(9 pt.1):3067-76.
The antitumor activity of a new derivative of ellipticine, 9-hydroxyellipticine (NSC 210717), was studied using L1210 mouse leukemia. Low doses of this drug have a high antileukemic activity, whereas high doses have less activity than expected because of a leveling off in the antitumor activity-dose relationship, as if a few cells were resistant to the treatment. The possible causes of this apparent resistance were investigated. It is suggested that this apparent resistance is related to the sequestration of a small number of cells in compartments inaccessible to the drug. A model was developed which takes into account the distribution of cells in various compartments and their drug sensitivity therein. It was predicted and observed that the activity of drugs acting on cells in the small compartments can be observed only in conjunction with the presence of drugs acting on the cells in the major compartment. The importance of this observation in the screening procedures of new drugs, the clinical trial of new chemotherapeutic agents, and the association of anticancer drugs are discussed within this context. 9-Hydroxyellipticine is of interest because it acts on leukemic cells in the brain.
使用L1210小鼠白血病模型研究了玫瑰树碱的一种新衍生物9-羟基玫瑰树碱（NSC 210717）的抗肿瘤活性。低剂量的这种药物具有较高的抗白血病活性，而高剂量时活性低于预期，因为抗肿瘤活性与剂量的关系趋于平稳，就好像有一些细胞对该治疗具有抗性。研究了这种明显抗性的可能原因。有人认为这种明显的抗性与少量细胞隔离在药物无法到达的区室有关。建立了一个模型，该模型考虑了细胞在各个区室中的分布及其在其中的药物敏感性。预测并观察到，只有在作用于主要区室细胞的药物存在的情况下，才能观察到作用于小区室细胞的药物的活性。在此背景下讨论了这一观察结果在新药筛选程序、新化疗药物的临床试验以及抗癌药物联合使用方面的重要性。9-羟基玫瑰树碱之所以令人感兴趣，是因为它作用于脑中的白血病细胞。
