Celecoxib pre-treatment in human colorectal adenocarcinoma patients is associated with gene expression alterations suggestive of diminished cellular proliferation
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作者:
Auman, James Todd
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Univ N Carolina, UNC Inst Pharmacogenom & Individualized Therapy, Chapel Hill, NC 27599 USAUniv N Carolina, UNC Inst Pharmacogenom & Individualized Therapy, Chapel Hill, NC 27599 USA
Auman, James Todd
[1
]
Church, Robert
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Washington Univ, Sch Med, Div Colorectal Surg, St Louis, MO USAUniv N Carolina, UNC Inst Pharmacogenom & Individualized Therapy, Chapel Hill, NC 27599 USA
Church, Robert
[2
]
Lee, Soo-Youn
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Univ N Carolina, UNC Inst Pharmacogenom & Individualized Therapy, Chapel Hill, NC 27599 USAUniv N Carolina, UNC Inst Pharmacogenom & Individualized Therapy, Chapel Hill, NC 27599 USA
Lee, Soo-Youn
[1
]
Watson, Mark A.
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Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA
Siteman Canc Ctr, St Louis, MO USAUniv N Carolina, UNC Inst Pharmacogenom & Individualized Therapy, Chapel Hill, NC 27599 USA
Watson, Mark A.
[3
,4
]
Fleshman, James W.
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Washington Univ, Sch Med, Div Colorectal Surg, St Louis, MO USA
Siteman Canc Ctr, St Louis, MO USAUniv N Carolina, UNC Inst Pharmacogenom & Individualized Therapy, Chapel Hill, NC 27599 USA
Fleshman, James W.
[2
,4
]
Mcleod, Howard L.
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Univ N Carolina, UNC Inst Pharmacogenom & Individualized Therapy, Chapel Hill, NC 27599 USAUniv N Carolina, UNC Inst Pharmacogenom & Individualized Therapy, Chapel Hill, NC 27599 USA
Mcleod, Howard L.
[1
]
机构:
[1] Univ N Carolina, UNC Inst Pharmacogenom & Individualized Therapy, Chapel Hill, NC 27599 USA
[2] Washington Univ, Sch Med, Div Colorectal Surg, St Louis, MO USA
[3] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA
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 (400 mg 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. (C) 2008 Elsevier Ltd. All rights reserved.