DRUG-COMBINATION TESTING IN ACUTE LYMPHOBLASTIC-LEUKEMIA USING THE MTT ASSAY
DRUG-COMBINATION TESTING IN ACUTE LYMPHOBLASTIC-LEUKEMIA USING THE MTT ASSAY
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DOI：
10.1016/0145-2126(94)00126-u
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发表时间：
1995-03-01
影响因子：
2.7
通讯作者：
VANWERING, ER
中科院分区：
文献类型：
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作者：
KASPERS, GJL;VEERMAN, AJP;VANWERING, ER
耐药试验可能有助于确定药物相互作用。为此，我们研究了三种药物组合，每种药物浓度为8-12，并对34名初次诊断时获得的急性淋巴细胞白血病（ALL）样本进行了MTT测定。这导致在预期和观察到的白血病细胞存活率之间总共进行了518次比较。泼尼松龙（PRD）与长春新碱（VCR）、PRD与马环磷酰胺（MAF）以及PRD与柔红霉素（DNR）的联合试验没有技术上的困难，与单一药物相比，没有增加的测定变化。我们观察到患者之间、组合之间以及特定组合内不同浓度的药物相互作用存在明显的异质性。在228个观察结果中，PRD+VCR有46%的增效作用，18%的拮抗作用和36%的可加性。在140个观察结果中，PRD+MAF的增效性为51%，拮抗性为20%，可加性为29%。在150个观察结果中，PRD+DNR的增效性为35%，拮抗性为31%，可加性为34%。与PRD+DNR相比，PRD+VCR和PRD+MAF表现出更多的协同作用，而PRD+DNR之间表现出更多的拮抗作用(p
Drug resistance assays may be useful to identify drug interactions. For this purpose, we studied three drug combinations, each at 8-12 concentrations, with the MTT assay in acute lymphoblastic leukemia (ALL) samples from 34 children obtained at initial diagnosis. This resulted in a total of 518 comparisons between expected and observed leukemic cell survivals.The combinations prednisolone (PRD) with vincristine (VCR), PRD with mafosfamide (MAF), and PRD with daunorubicin (DNR) were tested without technical difficulties, and without an increased assay variation as compared to single drugs. We observed a marked heterogeneity in drug interactions between patients, between combinations, and between different concentrations within one specific combination. Between PRD+VCR, synergism was found in 46%, antagonism in 18%, and additivity in 36% of the 228 observations. Between PRD+MAF, synergism was found in 51%, antagonism in 20%, and additivity in 29% of the 140 observations. Between PRD+DNR, synergism was found in 35%, antagonism in 31%, and additivity in 34% of the 150 observations. PRD+VCR and PRD+MAF showed more often synergism than PRD+DNR, while antagonism was observed more frequently between PRD+DNR (p