Cancer cell adaptation to chemotherapy.
Cancer cell adaptation to chemotherapy.
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癌细胞适应化学疗法。
DOI：
10.1186/1471-2407-5-78
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发表时间：
2005-07-18
期刊：
影响因子：
3.8
通讯作者：
Cree, IA
中科院分区：
文献类型：
--
作者：
Di Nicolantonio, F;Mercer, SJ;Knight, LA;Gabriel, FG;Whitehouse, PA;Sharma, S;Fernando, A;Glaysher, S;Di Palma, S;Johnson, P;Somers, SS;Toh, S;Higgins, B;Lamont, A;Gulliford, T;Hurren, J;Yiangou, C;Cree, IA
肿瘤对化疗的耐药性可能在治疗开始时就存在，在治疗过程中发展，或者在患者重新治疗时变得明显。所涉及的机制通常是从细胞系实验中推断出来的，因为对肿瘤来源的细胞进行研究很困难。对人类肿瘤的研究表明，细胞适应化疗，但人们在很大程度上认为克隆选择会导致复发性肿瘤的耐药性。来自 47 个乳腺癌、卵巢癌、食管癌和结直肠癌来源的肿瘤和 16 个配对食管活检的细胞在短期细胞培养（6 天）中暴露于抗癌药物（顺铂、5-氟尿嘧啶、表柔比星、阿霉素、紫杉醇、伊立替康和拓扑替康）。使用实时定量 PCR 来测量 16 种不同抗性/靶基因的上调或下调，当获得组织时，使用免疫组织化学来评估蛋白质水平。在 8/16 配对的食管活检中，表阿霉素 + 顺铂 + 5-氟尿嘧啶 (ECF) 化疗后，多药耐药基因 1 (MDR1) 的表达增加，同时 MDR-1 编码蛋白 P-gp 的表达增加。体外暴露于阿霉素后，13/14 的乳腺癌和 9/12 的卵巢癌显示拓扑异构酶 IIα (TOPOIIα) 下调 2 倍以上。体外暴露于拓扑替康导致 6/7 的结直肠肿瘤和 8/10 的卵巢肿瘤中 TOPOIIα 下调 4 倍以上。这项研究表明，在治疗开始后的几天内，人类实体瘤中可能会迅速发生耐药基因的上调或靶基因的下调，并且化疗前和化疗后活检材料中也存在类似的变化。每个肿瘤使用的分子过程似乎与所使用的药物有关，但各个肿瘤之间也存在异质性，即使是具有相同组织学类型的肿瘤，对相同药物的反应模式和程度也存在异质性。对化疗的适应可以解释为什么仅根据肿瘤类型或个体标志物很难预测耐药机制，并表明需要更复杂的预测方法来提高化疗的反应率。
Tumor resistance to chemotherapy may be present at the beginning of treatment, develop during treatment, or become apparent on re-treatment of the patient. The mechanisms involved are usually inferred from experiments with cell lines, as studies in tumor-derived cells are difficult. Studies of human tumors show that cells adapt to chemotherapy, but it has been largely assumed that clonal selection leads to the resistance of recurrent tumors. Cells derived from 47 tumors of breast, ovarian, esophageal, and colorectal origin and 16 paired esophageal biopsies were exposed to anticancer agents (cisplatin; 5-fluorouracil; epirubicin; doxorubicin; paclitaxel; irinotecan and topotecan) in short-term cell culture (6 days). Real-time quantitative PCR was used to measure up- or down-regulation of 16 different resistance/target genes, and when tissue was available, immunohistochemistry was used to assess the protein levels. In 8/16 paired esophageal biopsies, there was an increase in the expression of multi-drug resistance gene 1 (MDR1) following epirubicin + cisplatin + 5-fluorouracil (ECF) chemotherapy and this was accompanied by increased expression of the MDR-1 encoded protein, P-gp. Following exposure to doxorubicin in vitro, 13/14 breast carcinomas and 9/12 ovarian carcinomas showed >2-fold down-regulation of topoisomerase IIα (TOPOIIα). Exposure to topotecan in vitro, resulted in >4-fold down-regulation of TOPOIIα in 6/7 colorectal tumors and 8/10 ovarian tumors. This study suggests that up-regulation of resistance genes or down-regulation in target genes may occur rapidly in human solid tumors, within days of the start of treatment, and that similar changes are present in pre- and post-chemotherapy biopsy material. The molecular processes used by each tumor appear to be linked to the drug used, but there is also heterogeneity between individual tumors, even those with the same histological type, in the pattern and magnitude of response to the same drugs. Adaptation to chemotherapy may explain why prediction of resistance mechanisms is difficult on the basis of tumor type alone or individual markers, and suggests that more complex predictive methods are required to improve the response rates to chemotherapy.
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影响因子：
2.2
作者：
Buchholz, TA;Stivers, DN;Pusztai, L
通讯作者：
Pusztai, L
影响因子：
2.3
作者：
Cree, IA;Kurbacher, CM;Bruckner, HW
通讯作者：
Bruckner, HW
影响因子：
15.9
作者：
DABHOLKAR, M;VIONNET, J;REED, E
通讯作者：
REED, E
DOI：
10.1111/j.1349-7006.2000.tb00866.x
发表时间：
2000-01
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Ishikawa Y;Kubota T;Otani Y;Watanabe M;Teramoto T;Kumai K;Takechi T;Okabe H;Fukushima M;Kitajima M
通讯作者：
Kitajima M
影响因子：
5.8
作者：
COPUR, S;AIBA, K;CHU, E
通讯作者：
CHU, E