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COX-2 expression is unexpectedly high in viable colorectal mucosal cells: is there life for chemoprophylaxis after VICTOR?
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McArthur, D. R., Leung, Edmund, Morris, A. G. (Alan George) and Williams, N.. (2009) COX-2 expression is unexpectedly high in viable colorectal mucosal cells: is there life for chemoprophylaxis after VICTOR? Colorectal Disease, Vol.11 (No.7). pp. 775-782. ISSN 1462-8910
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Official URL: http://dx.doi.org/10.1111/j.1463-1318.2008.01662.x
Abstract
Introduction Trials investigating colorectal cancer (CRC) chemoprophylaxis with cyclooxygenase-2 (COX-2) inhibitors have been discontinued because of adverse cardiovascular effects. Nevertheless, identification of patients where beneficial, chemo-prophylactic effects of COX-2 inhibitors outweigh side-effects may be possible; this study aimed to investigate whether such patient groups might exist. Method The COX-2 status of viable epithelial and inflammatory cells in freshly disaggregated CRC and paired normal colonic samples was assessed by three-colour flow cytometry. Results 21/31 (67.7%) CRCs expressed COX-2, with inflammatory cells positive in 19/31 (61.3%), epithelial cells in 12/31 (38.7%), and both positive in 10/31 (32.3%). 25/30 (83.33%) normal samples expressed COX-2, with epithelial cells positive in 18/30 (60%), inflammatory cells in 15/30 (50%) and both positive in 10/30 (33.3%). Strength of expression by CRC and normal was similar. More advanced cancers had higher expression rates (COX-2 in 12/13 (92.3%) with nodal disease vs 9/17 (52.9%) node-negative; P = 0.04). Conclusion Investigation of ex-vivo CRC cells by flow cytometry demonstrated COX-2 expression rates comparable to that previously reported. However, expression by paired live normal colon was significantly greater, suggesting that COX-2 may be expressed at higher rates in normal colonic cells in patients with CRC. Patients identified at resection as expressing COX-2 in normal colon may benefit from Coxib chemo-prophylaxis, thus potentially offering a refined approach to that adopted in the VICTOR trial.
| Item Type: | Journal Article |
|---|---|
| Subjects: | R Medicine > RC Internal medicine |
| Divisions: | Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010) |
| Journal or Publication Title: | Colorectal Disease |
| Publisher: | Wiley-Blackwell Publishing, Inc. |
| ISSN: | 1462-8910 |
| Date: | September 2009 |
| Volume: | Vol.11 |
| Number: | No.7 |
| Number of Pages: | 8 |
| Page Range: | pp. 775-782 |
| Identification Number: | 10.1111/j.1463-1318.2008.01662.x |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Restricted or Subscription Access |
| Funder: | Coventry Colorectal Research Fund |
| URI: | http://wrap.warwick.ac.uk/id/eprint/17485 |
Data sourced from Thomson Reuters' Web of Knowledge
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