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在人类结肠腺癌患者中,塞来昔布预处理与提示细胞增殖减少的基因表达改变有关。

Celecoxib pre-treatment in human colorectal adenocarcinoma patients is associated with gene expression alterations suggestive of diminished cellular proliferation.

作者信息

Auman James Todd, Church Robert, Lee Soo-Youn, Watson Mark A, Fleshman James W, Mcleod Howard L

机构信息

UNC Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599-7360, United States.

出版信息

Eur J Cancer. 2008 Aug;44(12):1754-60. doi: 10.1016/j.ejca.2008.05.010. Epub 2008 Jul 22.

Abstract

Cancer cells treated with the cyclooxygenase-2 inhibitor celecoxib show growth inhibition and induced apoptosis. This study was conducted to determine if the same processes are relevant to celecoxib's effects on human colorectal adenocarcinomas treated in vivo. A cohort of 23 patients with primary colorectal adenocarcinomas was randomised to receive a 7-d course of celecoxib (400mg b.i.d.) or no drug prior to surgical resection. Gene expression profiling was performed on resected adenocarcinomas from the cohort of patients. Using fold change (>1.5) and p-value (<0.05) cut-offs, 190 genes were differentially expressed between adenocarcinomas from patients receiving celecoxib and those that did not. The celecoxib pre-treated samples showed decreased expression levels in multiple genes involved in cellular lipid and glutathione metabolism; changes associated with diminished cellular proliferation. Celecoxib pre-treatment for 7 d in vivo is associated with alterations in colorectal adenocarcinoma gene expression which are suggestive of diminished cellular proliferation.

摘要

用环氧化酶-2抑制剂塞来昔布处理的癌细胞表现出生长抑制并诱导凋亡。本研究旨在确定这些相同的过程是否与塞来昔布对体内治疗的人类结肠腺癌的作用相关。一组23例原发性结肠腺癌患者在手术切除前被随机分配接受7天疗程的塞来昔布(400mg,每日两次)或不接受药物治疗。对该组患者切除的腺癌进行基因表达谱分析。使用变化倍数(>1.5)和p值(<0.05)作为截断值,接受塞来昔布治疗的患者与未接受治疗的患者的腺癌之间有190个基因差异表达。塞来昔布预处理的样本显示参与细胞脂质和谷胱甘肽代谢的多个基因表达水平降低;这些变化与细胞增殖减少有关。在体内进行7天的塞来昔布预处理与结肠腺癌基因表达的改变有关,这表明细胞增殖减少。

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