Sensitivity and resistance to chemotherapy in acute leukemia: Correlation within vitro drug uptake and lack of potentiation by verapamil
Sensitivity and resistance to chemotherapy in acute leukemia: Correlation within vitro drug uptake and lack of potentiation by verapamil
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急性白血病化疗的敏感性和耐药性：体外药物摄取与维拉帕米增强作用缺乏的相关性
DOI：
10.1007/bf02934930
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
G. Mavligit
中科院分区：
文献类型：
--
作者：
B. Andersson;M. Beran;Sarah E. Stuckey;K. McCredie;G. Mavligit
钙离子通道阻滞剂维拉帕米在体外可逆转肿瘤细胞对不同抗肿瘤药物的获得性耐药。本文研究了它对11例白血病患者新鲜白血病细胞摄取间苯二甲酰氨基水杨酸（m-AMSA）和阿霉素（ADM）的影响。六名先前未经治疗的患者对AMSA敏感（获得缓解）。四个临床耐药tom-AMSA，其中两个也阿霉素。白血病细胞在药理学剂量的14 C-阿霉素和14 C-m-AMSA中孵育2小时。在加入m-AMSA或阿霉素前30分钟，向样品中补充维拉帕米（750 ng ml-1）。以15分钟的间隔测量药物摄取直至2小时，并且在孵育结束后的30分钟期间测量药物保留，随后洗涤并重悬于不含细胞毒性药物的新鲜培养基中。在所有四个细胞样本中，无论维拉帕米如何，阿霉素摄取都是相同的，其中两个来自对阿霉素耐药的患者。临床敏感患者的细胞对细胞臂AMSA的摄取高于耐药患者（510±155 fg cell−1 vs 275±125 fg cell−1;P<0.01）。与耐药患者相比，敏感患者细胞孵育30 min后m-AMSA的保留率更高（187±78 vs 25±7;P<0.05）。我们的数据表明：（1）体外摄取≥350 fg cell-1和随后的滞留>75 fg cell-1与药物的临床敏感性相关;（2）维拉帕米可显著增加neitherm-AMSA和阿霉素的摄取。
The calcium channel blocker verapamil has been reported to circumvent acquired resistance to different antitumor agents in tumor cell linesin vitro. We studied its effect onin vitro uptake ofm-AMSA and adriamycin in fresh leukemic cells from 11 leukemia patients. Six previously untreated patients were sensitive tom-AMSA (obtained remission). Four were clinically resistant tom-AMSA, and two of these also to adriamycin. Leukemic cells were incubated in pharmacological doses of14C-adriamycin and14C-m-AMSA for up to 2 h. Samples were supplemented with verapamil (750 ng ml−1) 30 min prior to the addition ofm-AMSA or adriamycin. Drug uptake was measured at 15 min intervals up to 2 h and drug retention was measured during 30 min after the end of incubation, following washing and resuspension in fresh medium without cytotoxic drugs. Adriamycin uptake was the same irrespective of verapamil in all four cell samples, two of which were derived from patients resistant to adriamycin. The cellularm-AMSA uptake was higher in cells from clinically sensitive than from resistant patients (510±155 fg cell−1 vs 275±125 fg cell−1;P<0.01). Retention ofm-AMSA 30 min after incubation was higher in cells from sensitive compared to resistant patients (187±78 vs 25±7;P<0.05). Our data suggest: (1)in vitro uptake ≥350 fg cell−1 and subsequent retention >75 fg cell−1 correlate to clinical sensitivity to the drug; and (2) neitherm-AMSA nor adriamycin uptake could be significantly increased by verapamil.
P388 小鼠白血病的蒽环类药物耐药性及其钙拮抗剂的规避。
影响因子：
11.2
作者：
Kessel,D;Wilberding,C
通讯作者：
Wilberding,C
通过 DNA 荧光染料竞争分析核 m-AMSA 含量。
DOI：
10.1016/0277-5379(86)90378-0
发表时间：
1986
期刊：
European journal of cancer & clinical oncology
影响因子：
--
作者：
Andersson,BS;Beran,M;Barlogie,B;Van,NT;McCredie,KB
通讯作者：
McCredie,KB