Colonic Mucosal Prostaglandin E2 and Cyclooxygenase Expression Before and After Low Aspirin Doses in Subjects at High Risk or at Normal Risk for Colorectal Cancer1, 2
Document Type
Article
Publication Date
1-1-2001
Description
Development of potential cancer chemopreventive drugs involves the systematic evaluation of these drugs in preliminary Phase I and II studies in human beings to identify the optimal drug dose, drug toxicity, and surrogate end point biomarker modulation. Objectives: We tested the hypothesis that aspirin, at a single, once-daily 81-mg dose, will reduce colonic mucosal concentration of prostaglandin estradiol (E2) in individuals at high risk for colorectal cancer development similar to our prior observations in a young normal-risk population. Methods: Aspirin was administered at a dose of 81 mg once daily for 28 days in a cohort of 92 matched high-risk and normal-risk colorectal cancer subjects. Prostaglandin E2 and cyclooxygenase expression were assayed from distal sigmoid biopsies from all of the subjects before and after treatment. Results: The mean prostaglandin E2 for normal-risk subjects before aspirin treatment was 11.3 ± 1.7 pg/μg (mean ± SE) tissue protein and after aspirin treatment was 4.9 ± 0.91 pg/μg tissue protein (P & 0.0001). In high-risk subjects, mean pretreatment prostaglandin E2 was 14.4 ± 1.7 pg/μg tissue protein and after aspirin treatment was 4.7 ± 0.70 pg/μg tissue protein (P & 0.0001). Aspirin treatment did not alter cyclooxygenase-1 protein expression. Conclusions: Aspirin treatment at a dose of 81 mg reduces colorectal mucosal prostaglandin E2 concentration after 28 daily doses. Risk for colorectal carcinoma did not modify colorectal mucosal baseline or post-aspirin prostaglandin E2, or cyclooxygenase expression. Colorectal mucosal prostaglandin concentration may be used as a "drug-effect surrogate biomarker," that is, a surrogate to assess sufficient delivery and tissue effect of a chemopreventive agent.
Citation Information
Krishnan, Koyamangalath; Ruffin, Mack T.; Normolle, Daniel; Shureiqi, Imad; Burney, Kimberley; Bailey, Joann; Peters-Golden, Marc; Rock, Cheryl L.; Boland, C. Richard; and Brenner, Dean E.. 2001. Colonic Mucosal Prostaglandin E2 and Cyclooxygenase Expression Before and After Low Aspirin Doses in Subjects at High Risk or at Normal Risk for Colorectal Cancer1, 2. Cancer Epidemiology Biomarkers and Prevention. Vol.10(5). 447-453. https://cebp.aacrjournals.org/content/10/5/447.long PMID: 11352853 ISSN: 1055-9965