Prostaglandin levels in human colorectal mucosa: Effects of sulindac in patients with familial adenomatous polyposis

Francis M. Giardiello, Ernst W. Spannhake, Raymond N. Dubois, Linda M. Hylind, C. Rahj Robinson, Walter C. Hubbard, Stanley R. Hamilton, Vincent W. Yang

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Recent evidence suggests that nonsteroidal antiinflammatory drugs (NSAIDs) may prevent colorectal cancer. The mechanism of action of NSAIDs in chemoprevention is unknown but may be linked to their effect on mucosal prostaglandin levels. Levels of five major prostaglandin metabolites were measured by gas chromatography-mass spectrometry in biopsy specimens of flat rectal mucosa from four patients with familial adenomatous polyposis (FAP) before and after sulindac therapy and from five healthy individuals. The prostaglandin present at highest concentration in rectal mucosa from FAP and control subjects was prostaglandin E2. The concentration of thromboxane B2 alone was significantly elevated in FAP patients compared to controls (P = 0.016). In FAP patients treated with sulindac, all prostaglandin metabolite levels were significantly reduced compared to pretreatment levels (P < 0.05) except prostaglandin D2 (P = 0.07). Prostaglandins D2, E2, F(2α), and 6- keto-F(1α) levels also were significantly reduced in FAP patients on sulindac compared to healthy controls (P < 0.05). However, interpatient heterogeneity of response to sulindac was evident with changes ranging from +19% to -89%, and the patient with the greatest reductions after sulindac developed colorectal cancer after 35 months of therapy. Sulindac treatment, at drug doses shown to regress colorectal adenomas in FAP patients, has heterogeneous effects on the level of major prostaglandins in their rectal mucosa and may not prevent colorectal cancer due to uncoupling of prostaglandin levels and carcinogenesis.

Original languageEnglish (US)
Pages (from-to)311-316
Number of pages6
JournalDigestive Diseases and Sciences
Volume43
Issue number2
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

Sulindac
Adenomatous Polyposis Coli
Prostaglandins
Mucous Membrane
Prostaglandin D2
Colorectal Neoplasms
Dinoprostone
Anti-Inflammatory Agents
Pharmaceutical Preparations
Thromboxane B2
Chemoprevention
Adenoma
Gas Chromatography-Mass Spectrometry
Carcinogenesis
Therapeutics
Biopsy

Keywords

  • Familial adenomatous polyposis
  • Nonsteroidal antiinflammatory drugs
  • Polyps
  • Prostaglandins
  • Sulindac

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Giardiello, F. M., Spannhake, E. W., Dubois, R. N., Hylind, L. M., Robinson, C. R., Hubbard, W. C., ... Yang, V. W. (1998). Prostaglandin levels in human colorectal mucosa: Effects of sulindac in patients with familial adenomatous polyposis. Digestive Diseases and Sciences, 43(2), 311-316. https://doi.org/10.1023/A:1018898120673

Prostaglandin levels in human colorectal mucosa : Effects of sulindac in patients with familial adenomatous polyposis. / Giardiello, Francis M.; Spannhake, Ernst W.; Dubois, Raymond N.; Hylind, Linda M.; Robinson, C. Rahj; Hubbard, Walter C.; Hamilton, Stanley R.; Yang, Vincent W.

In: Digestive Diseases and Sciences, Vol. 43, No. 2, 1998, p. 311-316.

Research output: Contribution to journalArticle

Giardiello, FM, Spannhake, EW, Dubois, RN, Hylind, LM, Robinson, CR, Hubbard, WC, Hamilton, SR & Yang, VW 1998, 'Prostaglandin levels in human colorectal mucosa: Effects of sulindac in patients with familial adenomatous polyposis', Digestive Diseases and Sciences, vol. 43, no. 2, pp. 311-316. https://doi.org/10.1023/A:1018898120673
Giardiello, Francis M. ; Spannhake, Ernst W. ; Dubois, Raymond N. ; Hylind, Linda M. ; Robinson, C. Rahj ; Hubbard, Walter C. ; Hamilton, Stanley R. ; Yang, Vincent W. / Prostaglandin levels in human colorectal mucosa : Effects of sulindac in patients with familial adenomatous polyposis. In: Digestive Diseases and Sciences. 1998 ; Vol. 43, No. 2. pp. 311-316.
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