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

Koyamangalath Krishnan, Mack T. Ruffin, Daniel Normolle, Imad Shureiqi, Kimberley Burney, Joann Bailey, Marc Peters-Golden, Cheryl L. Rock, C. Richard Boland, Dean E. Brenner

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)447-453
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume10
Issue number5
StatePublished - Jan 1 2001

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Prostaglandin-Endoperoxide Synthases
Dinoprostone
Aspirin
Colorectal Neoplasms
Biomarkers
Proteins
Pharmaceutical Preparations
Cyclooxygenase 1
Drug Evaluation
Sigmoid Colon
Drug-Related Side Effects and Adverse Reactions
Prostaglandins
Estradiol
Biopsy
Population
Neoplasms

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology

Cite this

Krishnan, Koyamangalath ; Ruffin, Mack T. ; Normolle, Daniel ; Shureiqi, Imad ; Burney, Kimberley ; Bailey, Joann ; Peters-Golden, Marc ; Rock, Cheryl L. ; Boland, C. Richard ; Brenner, Dean E. / 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. In: Cancer Epidemiology Biomarkers and Prevention. 2001 ; Vol. 10, No. 5. pp. 447-453.
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title = "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",
abstract = "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.",
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Krishnan, K, Ruffin, MT, Normolle, D, Shureiqi, I, Burney, K, Bailey, J, Peters-Golden, M, Rock, CL, Boland, CR & Brenner, DE 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, no. 5, pp. 447-453.

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. / Krishnan, Koyamangalath; Ruffin, Mack T.; Normolle, Daniel; Shureiqi, Imad; Burney, Kimberley; Bailey, Joann; Peters-Golden, Marc; Rock, Cheryl L.; Boland, C. Richard; Brenner, Dean E.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 10, No. 5, 01.01.2001, p. 447-453.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Krishnan, Koyamangalath

AU - Ruffin, Mack T.

AU - Normolle, Daniel

AU - Shureiqi, Imad

AU - Burney, Kimberley

AU - Bailey, Joann

AU - Peters-Golden, Marc

AU - Rock, Cheryl L.

AU - Boland, C. Richard

AU - Brenner, Dean E.

PY - 2001/1/1

Y1 - 2001/1/1

N2 - 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.

AB - 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.

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