Verdonck L F, Lokhorst H M, Roovers D J, van Heugten H G
Department of Haematology, University Hospital Utrecht, The Netherlands.
Leuk Res. 1998 Mar;22(3):249-56. doi: 10.1016/s0145-2126(97)00160-4.
We examined the cytotoxic effects of free daunorubicin (DNR) and liposome-encapsulated DNR on multidrug-resistant (MDR1) leukemia cells of patients with acute leukemias who had failed primary induction treatment that included DNR. This was analyzed ex-vivo with DNR concentrations and exposure times that normally can be achieved in-vivo for both drugs with induction treatment. The leukemic blasts of patients both with drug-resistant AML and drug-resistant ALL were, ex-vivo, very sensitive to DNR concentrations and exposure times that can be achieved in-vivo by liposome-encapsulated DNR. However, under identical conditions, free DNR and liposome-encapsulated DNR had a similar cytotoxic profile, arguing against a unique mechanism of cytotoxicity by the liposomal constructure. These data suggest that liposome-encapsulated DNR may be preferable to free DNR for the treatment of acute leukemias.
我们研究了游离柔红霉素（DNR）和脂质体包裹的DNR对急性白血病患者多药耐药（MDR1）白血病细胞的细胞毒性作用，这些患者在包括DNR的初始诱导治疗中失败。使用诱导治疗时两种药物在体内通常可达到的DNR浓度和暴露时间进行体外分析。对耐药急性髓系白血病（AML）和耐药急性淋巴细胞白血病（ALL）患者的白血病原始细胞进行体外研究，结果显示，脂质体包裹的DNR在体内可达到的DNR浓度和暴露时间下，白血病原始细胞非常敏感。然而，在相同条件下，游离DNR和脂质体包裹的DNR具有相似的细胞毒性特征，这表明脂质体结构不存在独特的细胞毒性机制。这些数据表明，脂质体包裹的DNR在治疗急性白血病方面可能比游离DNR更具优势。
