Final results of pharmacokinetic study of oxaliplatin and capecitabine combination for advanced colorectal cancer

Final results of pharmacokinetic study of oxaliplatin and capecitabine combination for advanced colorectal cancer
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DOI:
10.1111/j.1472-8206.2007.00462.x
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发表时间:
2007-04-01
影响因子:
2.9
通讯作者:
Bastian, Gerard
Bastian, Gerard
中科院分区:
医学4区
文献类型:
--
作者:
William-Faltaos, Sara;Rouillard, Dany;Bastian, Gerard

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奥沙利铂(L-OHP)是唯一在结直肠癌中显示活性的铂化合物。我们研究了L-羟基喜树碱在长时间(72 H)和不同孵育时间(24或72 h)下对四种人癌细胞的细胞毒作用及其对细胞周期的影响。我们使用了一组细胞系:HT29(结肠癌)、MCF7(乳腺癌)、Hela(子宫颈)和A549(肺腺癌)。用四甲基偶氮唑盐比色法测定抑制浓度(IC)(50)。用双参数溴脱氧尿苷和碘化丙啶测定细胞周期的改变。L-OHP对HT29和MCF7细胞的杀伤作用强于Hela和A549,培养后的细胞生长抑制对HT29和Hela细胞株的生长抑制是不可逆的。L-OHP的主要作用是G2/M期阻滞和一过性S期延迟。综上所述,L-OHP对HT29、MCF7和Hela的治疗结果有利于在进一步的临床试验中延长患者的输液持续时间。
Oxaliplatin (L-OHP) is the only platinum compound to show activity in colorectal cancer. We evaluated the cytotoxicity of L-OHP on four human cancer cell lines and its influence on the cell cycle, when treated during long exposure (72 h) and different post-incubation times (24 or 72 h). We used a panel of cell lines: HT29 (colon cancer), MCF7 (breast cancer), Hela (uterine cervix) and A549 (lung adenocarcinoma). Inhibition concentration (IC)(50) was assessed by MTT assay. Cell cycle modifications were determined using dual parameter bromodeoxyuridine and propidium iodide. L-OHP yielded a superior cytotoxicity on HT29 and MCF7 relative to Hela and A549 after treatment, the post-incubations demonstrate that growth inhibition was irreversible for HT29 and Hela cell lines contrary to MCF7 and A549. The main effects of L-OHP are G2/M cell cycle arrest and transient S phase delay. Taken together, L-OHP treatment results on HT29, MCF7 and Hela, are in favor of lengthening the infusion duration to patients during further clinical trials.