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Prostaglandin Levels in Human Colorectal Mucosa (Effects of Sulindac in Patients with Familial Adenomatous Polyposis)

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Abstract

Recent evidence suggests that nonsteroidalantiinflammatory drugs (NSAIDs) may prevent colorectalcancer. The mechanism of action of NSAIDs inchemoprevention is unknown but may be linked to theireffect on mucosal prostaglandin levels. Levels of fivemajor prostaglandin metabolites were measured by gaschromatography-mass spectrometry in biopsy specimens offlat rectal mucosa from four patients with familial adenomatous polyposis (FAP) before and aftersulindac therapy and from five healthy individuals. Theprostaglandin present at highest concentration in rectalmucosa from FAP and control subjects was prostaglandin E2. The concentration of thromboxaneB2 alone was significantly elevated in FAPpatients compared to controls (P = 0.016). In FAPpatients treated with sulindac, all prostaglandinmetabolite levels were significantly reduced compared to pretreatmentlevels (P < 0.05) except prostaglandin D2(P = 0.07). Prostaglandins D2, E2,F2α, and 6-keto-F1αlevels also were significantly reduced in FAP patients on sulindac compared to healthy controls (P< 0.05). However, interpatient heterogeneity ofresponse to sulindac was evident with changes rangingfrom +19% to –89%, and the patient with thegreatest reductions after sulindac developed colorectal cancerafter 35 months of therapy. Sulindac treatment, at drugdoses shown to regress colorectal adenomas in FAPpatients, has heterogeneous effects on the level ofmajor prostaglandins in their rectal mucosa and maynot prevent colorectal cancer due to uncoupling ofprostaglandin levels and carcinogenesis.

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Authors
  1. Raymond N. Dubois
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  2. Linda M. Hylind
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  3. C. Rahj Robinson
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  4. Walter C. Hubbard
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  5. Stanley R. Hamilton
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  6. Vincent W. Yang
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  7. Francis M. Giardiello
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  8. Ernst W. Spannhake
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Dubois, R.N., Hylind, L.M., Robinson, C.R. et al. Prostaglandin Levels in Human Colorectal Mucosa (Effects of Sulindac in Patients with Familial Adenomatous Polyposis). Dig Dis Sci 43, 311–316 (1998). https://doi.org/10.1023/A:1018898120673

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