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Dig Dis Sci. 2013 Sep;58(9):2615-22. doi: 10.1007/s10620-013-2670-5. Epub 2013 Apr 27.

Colonic 15-PGDH levels are stable across distance and time and are not perturbed by aspirin intervention.

Author information

1
Department of Medicine, Case Western Reserve University and Case Medical Center, 10900 Euclid Ave., Wolstein Research Building, Rm 3-128, Cleveland, OH 44106-7285, USA. stephen.fink@case.edu

Abstract

BACKGROUND AND AIMS:

15-Hydroxprostaglandin dehydrogenase (15-PGDH) mediates a colon neoplasia suppressor pathway, acting through metabolic antagonism of cyclooxygenase-mediated colon carcinogenesis. To determine whether the colon tumor prevention activity of 15-PGDH acts as a constant or variable effect among individuals, we determined whether 15-PGDH levels remain stable over subsite and time in the human colon, determined the extent of differences in 15-PGDH levels between different individuals, and determined whether 15-PGDH modulation mediates any part of the anti-colon tumor effect of aspirin.

METHODS:

Using real-time PCR, we measured 15-PGDH mRNA to determine the correlation of 15-PGDH level in replicate colon biopsies, in biopsies from throughout the length of the colon, in repeat biopsies taken 4 months apart, and in paired biopsies of individuals taken before and after aspirin treatment, and by Western-blot for 15-PGDH protein in mice.

RESULTS:

Colonic 15-PGDH levels varied 4.4-fold across the human population. Within individuals, 15-PGDH levels proved highly reproducible (r=0.81 in duplicate biopsies) and stable along the length of the colon, with average 15-PGDH levels deviating by only 17% from rectum to cecum. An individual's 15-PGDH levels are also highly stable over time, with a median coefficient of variation over a 4-month interval of only 12%. Last, colonic 15-PGDH levels proved resistant to alteration by aspirin, with only a 10% difference in 15-PGDH levels measured before and after aspirin treatment.

CONCLUSIONS:

15-PGDH levels vary across the population in a stable and reproducible manner, and are resistant to alteration by aspirin. 15-PGDH represents an independent target for modulation by candidate colon tumor chemopreventive agents.

PMID:
23625286
PMCID:
PMC3769508
DOI:
10.1007/s10620-013-2670-5
[Indexed for MEDLINE]
Free PMC Article
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