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人结肠肿瘤细胞系体外克隆形成存活研究:热疗、5-氟尿嘧啶/亚叶酸、卡铂与肿瘤坏死因子联合应用

Clonogenic survival studies of human colon tumor cell lines in vitro: combined hyperthermia, 5-fluorouracil/leucovorin, carboplatin and tumor necrosis factor.

作者信息

Klostergaard J, Leroux M E, Tomasovic S P

机构信息

Department of Tumor Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.

出版信息

Radiat Res. 1995 Jan;141(1):44-8.

PMID:7997513
Abstract

The responses of DLD-1 and HCT-15 human colon adenocarcinoma cells to hyperthermia, 5-fluorouracil (5-FU)/leucovorin, carboplatin and tumor necrosis factor-alpha, singly and in multiple combinations, were evaluated in clonogenic assays. The combination of hyperthermia with the lower dose combination resulted in a survival fraction of about 0.005 to 0.001 for both cell types, whereas estimated additive interactions alone would have resulted in a survival fraction of about 0.5 (DLD-1) or 0.05 (HCT-15). A survival fraction of 0.00001 or greater was observed when the higher dose levels were combined with hyperthermia, whereas additive interactions alone would have achieved a decrease of only 0.001 or 0.0001 in the surviving fraction. The combination of the three other modalities at either dose level under conditions of hyperthermia or normothermia achieved statistically significant apparently supra-additive losses of clonogenicity in HCT-15 cells; similar results were obtained with the lower dose level in DLD-1 cells. Our results suggest that human colon tumor cells are markedly sensitive to this combination of modalities when used at clinically achievable dose levels.

摘要

在克隆形成试验中评估了DLD-1和HCT-15人结肠腺癌细胞对热疗、5-氟尿嘧啶(5-FU)/亚叶酸、卡铂和肿瘤坏死因子-α单独及多种组合的反应。热疗与低剂量组合相结合,两种细胞类型的存活分数约为0.005至0.001,而仅估计的相加相互作用会导致存活分数约为0.5(DLD-1)或0.05(HCT-15)。当高剂量水平与热疗联合时,观察到存活分数为0.00001或更高,而仅相加相互作用只会使存活分数降低0.001或0.0001。在热疗或正常体温条件下,其他三种治疗方式在任一剂量水平的组合在HCT-15细胞中均实现了具有统计学意义的明显超相加性克隆形成能力损失;在DLD-1细胞中使用较低剂量水平也获得了类似结果。我们的结果表明,当以临床可达到的剂量水平使用时,人结肠肿瘤细胞对这种治疗方式的组合明显敏感。

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