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首页> 外文期刊>British Journal of Cancer >In vitro correlates of clinical response to methotrexate in acute leukaemia and Burkitt's lymphoma
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In vitro correlates of clinical response to methotrexate in acute leukaemia and Burkitt's lymphoma

机译:急性白血病和伯基特淋巴瘤对甲氨蝶呤临床反应的体外相关性

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The response of drug-resistant patients with acute leukaemia and Burkitt's lymphoma to treatment with a 24 h infusion of methotrexate (MTX) followed, in some cases,by cytosine arabinoside was correlated with in vitro measurements of total intracellular MTX, exchangeable intracellular MTX, and suppressibility of deoxyuridine (UdR) incorporation in isolated marrow blast cells at extracellular MTX concentrations of 10(-8)M, 10(-7)M, 10(-6)M and 10(-5)M. Total intracellular MTX levels and exchangeable intracellular MTX levels were not significantly different in responding or non-responding patients at any MTX concentration, but increased four-fold for every ten-fold concentration increment studied. Extracellular MTX levels in excess of 10(-7)M appeared necessary to allow accumulation of exchangeable intracellular MTX. UdR incorporation at 10(-6)M and 10(-5)M differed significantly between responding and non-responding patients, with responders having less than 20% of control values and non-responders having greater than 40% of control values. Further, increasing the extracellular MTX concentration from 10(-6)M to 10(-5)M produced no significant decrease in UdR incorporation in either group. The therapeutic implications of this apparent threshold are discussed.
机译:耐药性急性白血病和伯基特淋巴瘤患者对甲氨蝶呤(MTX)24小时输注治疗的反应,在某些情况下,胞嘧啶阿拉伯糖苷与体外细胞内总MTX,可交换细胞内MTX和在细胞外MTX浓度为10(-8)M,10(-7)M,10(-6)M和10(-5)M的分离的骨髓母细胞中,脱氧尿苷(UdR)掺入的抑制性。在任何MTX浓度下,反应或无反应患者的总细胞内MTX水平和可交换的细胞内MTX水平均无显着差异,但每研究十倍浓度增加,其四倍增加。超过10(-7)M的细胞外MTX水平似乎是必需的,以允许可交换的细胞内MTX积累。有反应的和无反应的患者在10(-6)M和10(-5)M的UdR掺入差异显着,反应者的控制值低于控制值的20%,无反应者的控制值高于控制值的40% 。此外,将细胞外MTX浓度从10(-6)M增加到10(-5)M均不会导致UdR掺入率显着降低。讨论了该明显阈值的治疗意义。

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