Clinical and Genomic Influence of Sulindac on Rectal Mucosa in Familial Adenomatous Polyposis | oneFAPvoice

welcome to oneFAPvoice

- a positively charged Familial Adenomatous Polyposis community.
  • join today!
scientific articles

Clinical and Genomic Influence of Sulindac on Rectal Mucosa in Familial Adenomatous Polyposis

key information

source: Diseases of the colon and rectum

year: 1997

authors: Winde G, Schmid K W, Brandt B, Müller O, Osswald H

summary/abstract:

PURPOSE : A study was performed to evaluate the antiproliferative effects of low doses of the nonsteroidal drug, sulindac, on adenomas and rectal mucosa in familial adenomatous polyposis and to analyze the influence on tumor-suppressor genes and on apoptosis.

METHODS : This was a prospective, controlled, nonrandomized Phase II dose-finding study for sulindac. The study group (n = 28) and control group (n = 10) underwent colectomy and ileorectal anastomoses, with repeated proctoscopy with endoluminal ultrasound and biopsies every three months. Dose-reduction of sulindac according to adenoma reversion was predetermined. Proliferation marker, Ki-67 (MIB1 and 5), on frozen or paraffin sections evaluated the antiproliferative effects; mutant p21ras, pantropic p53, mutant p53, and anti-bcl-2 were performed as enzyme-linked immunosorbent assay procedures and/or immunohistochemistry on paraffin sections.

RESULTS : All patients responded to sulindac after 24 weeks (at the latest). There was a significant reduction of adenomas and dose reduction to 67 mg/day after three years of therapy (Mann’s test for trend, P < 0.001). Results consisted of 78 percent complete reversions, 22 percent partial reversions of adenomas at latest re-examination, and no influence on upper gastrointestinal tract adenomas. No influence was detected on repeated hemograms, liver, or renal function at high or low doses. There was a permanent antiproliferative effect (Ki-67) of low-dose sulindac, significant blocking of ras mutation activation, and a significant difference of untreated and treated mucosa in mutant p53 content (Wilcoxon’s or Kruskal-Wallis each, P < 0.05). Reverse correlation of anti-bcl-2 and p53 immunostaining on mucosa sections was an indication of adenoma relapse.

CONCLUSIONS : Low-dose antiproliferative sulindac therapy is highly effective in adenoma reversion in familial adenomatous polyposis patients. Sulindac shows influence on tumor-suppressor genes and on apoptosis markers. An immunostaining correlation indicates adenoma relapse in flat microadenomas in advance of macroscopic appearance. Low-dose sulindac treatment may develop into an additive permnanent therapy for colectomized familial adenomatous polyposis patients.

organization: University of Münster

read more

expertly curated content related to this topic

To improve your experience on this site, we use cookies. This includes cookies essential for the basic functioning of our website, cookies for analytics purposes, and cookies enabling us to personalize site content. By clicking on 'Accept' or any content on this site, you agree that cookies can be placed. You may adjust your browser's cookie settings to suit your preferences.
More information

The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.

Close