An in vitro short time-high dose drug exposure assay for predicting 5FU-resistance of colorectal cancer
An in vitro short time-high dose drug exposure assay for predicting 5FU-resistance of colorectal cancer
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DOI：
10.1016/j.canlet.2004.06.004
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发表时间：
2004-10-28
期刊：
影响因子：
9.7
通讯作者：
Chan, EC
中科院分区：
文献类型：
--
作者：
Fan, CW;Fan, HA;Chan, EC
本研究的目的是开发一种简单快速的体外耐药性测定方法，以确定 5-氟尿嘧啶 (5-FU) 对结直肠癌个体化治疗的有效性。从肿瘤标本中分离出结直肠癌细胞，暴露于高剂量 5-FU 4 小时后，用 ATP 测定法测量细胞活力。 35 名患者肿瘤中 5-FU 的平均 IC50 浓度计算为 4000 μg/ml。肿瘤细胞被定义为极端耐药（存活率高于IC50 1个标准差（SD））、低耐药（LDR）（存活率低于TC50 1个标准差）和中度耐药（IDR）（存活率介于两者之间）。对102名患者癌细胞的耐药性测定显示，对5-氟尿嘧啶产生LDR的患者比例为19%。癌细胞的体外耐药性与癌症分期、患者性别或年龄无关。然而，大多数粘液性和低分化癌细胞表现出极端或IDR。 25 名接受术后 5-FU 化疗的 Duke's D 患者的体外 ATP 测定值与临床化疗后反应相当。该测定的灵敏度和特异性分别为 100% 和 95%。这种短时间高剂量药物暴露测定可能有助于改善个体化疗的 5-FU 治疗。 (C) 2004，Elsevier Ireland Ltd. 保留所有权利。
The goal of this study was to develop a simple and rapid in vitro drug resistance assay to ascertain the effectiveness of 5-fluorouracil (5-FU) for the individual therapy of colorectal cancer. Colorectal cancer cells were isolated from tumor specimens and, after 4 h exposure to high doses of 5-FU cell viability was measured with an ATP assay. The average IC50 concentration for 5-FU was calculated as 4000 mug/ml from 35 patients' tumors. The tumor cells were defined as extreme drug resistance with a survival rate 1 standard deviation (SD) over IC50, low drug resistance (LDR) with a survival rate 1 SD below TC50, and intermediate drug resistance (IDR) with survival rate between these two. The drug resistant assay for 102 patients' cancer cells showed that the proportion of patients with LDR to 5-fluorouracil was 19%. The in vitro drug resistance of the cancer cells was not correlated with cancer stages or by patient sex or age. However, most mucinous and poor differentiated cancer cells showed extreme or IDR. The in vitro ATP assay values for 25 Duke's D patients receiving postoperative 5-FU chemotherapy were comparable with clinical postchemotherapy responses. The sensitivity and specificity of the assay were 100 and 95%, respectively. This short time-high dose drug exposure assay may serve as an aid to improve 5-FU treatment for individual chemotherapy. (C) 2004, Elsevier Ireland Ltd. All rights reserved.