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| Status |
Public on Aug 21, 2008 |
| Title |
Celecoxib pre-treatment in human colorectal adenocarcinoma patients. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Pharmacological inhibition of cyclooxygenase-2 (COX-2) is being explored as a chemotherapeutic option because COX-2 protein expression is often elevated in many cancers. Cancer cells treated with COX-2 inhibitors, such as the selective COX-2 inhibitor celecoxib, show growth inhibition and the induction of apoptosis, through alterations in inflammatory processes, angiogenesis, cell adhesion and transforming growth factor-β signaling. 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 randomized to receive a 7-day course of celecoxib (400 mg b.i.d.) or no drug prior to surgical resection. Gene expression profiling was performed on resected adenocarcinomas from patients with and without celecoxib pre-treatment. 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. Of the differentially expressed genes, multiple genes involved in cellular lipid and glutathione metabolism showed decreased expression levels in celecoxib pre-treated samples; changes associated with diminished cellular proliferation. Other observed gene expression changes consistent with reduced proliferation include: altered expression of genes involved in cell adhesion (including collagen, laminin, von Willebrand factor and tenascin C), increased expression of inflammatory modulators (including inerleukin-6, S100 calcium binding protein A8, and several chemokines) and decreased expression of the pro-angiogenic gene, angiogenin. Celecoxib pre-treatment for 7 days in vivo is associated with alterations in colorectal adenocarcinoma gene expression which are suggestive of diminished cellular proliferation.
Keywords: treatment outcome
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| Overall design |
Patients undergoing surgical resection of histologically proven primary colorectal adenocarcinomas were consented for participation in the study. The patients enrolled in this study were randomized to receive either 400 mg celecoxib two times per day (n=11) or no COX-2 inhibitor (n=12) for 7 days prior to surgical resection. Total RNA (5 ug) from each sample was converted to double stranded cDNA using a dT-T7 promoter primer. The double stranded cDNA was then used as a template to synthesize biotinylated RNA, which was fragmented and hybridized to the Affymetrix HG_U95av2 microarray chip using Affymetrix’s labeling and hybridization protocol.
The array data was imported into GeneSpring GX 7.3 using the GC-RMA file preprocessor. The data was normalized by: (1) setting all expression measurements <0.01 to 0.01, (2) a per chip normalization to the 50th percentile, and (3) a per gene normalization to the median value across all chips.
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| Contributor(s) |
Auman JT |
| Citation(s) |
18653328 |
| Submission date |
Apr 22, 2008 |
| Last update date |
Dec 13, 2018 |
| Contact name |
James Todd Auman |
| E-mail(s) |
jtauman@email.unc.edu
|
| Phone |
(919) 966-9942
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| Organization name |
University of North Carolina at Chapel Hill
|
| Department |
Institute for Pharmacogenomics and Individualized Therapy
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| Street address |
3304 Kerr Hall, Campus Box 7360
|
| City |
Chapel Hill |
| State/province |
NC |
| ZIP/Postal code |
27599-7360 |
| Country |
USA |
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| Platforms (1) |
| GPL8300 |
[HG_U95Av2] Affymetrix Human Genome U95 Version 2 Array |
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| Samples (23)
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| Relations |
| BioProject |
PRJNA106739 |
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