Dietary Fiber or Piroxicam as Potential Cancer Prevention Agents: Effects on Rectal Epithelial Cell Proliferation in Humans at Increased Risk of Colon Cancer

  • David L. Earnest
  • David S. Alberts
  • Lee J. Hixson
  • Frank L. Meyskens


Over the past decade, there has been little improvement in outcome of treatment for advanced colon cancer. The best chance for cure remains early removal of a localized malignant tumor. Accordingly, much emphasis has been focused on screening, early detection and removal of recognized precursor lesions, namely adenomatous colon polyps. However, this approach is problematic in that current methods, such as testing of stool for occult blood and periodic examination of the rectum and colon by fiberoptic endoscopy, have either less than desired sensitivity or are expensive, entail some risk, detect only gross macroscopic lesions and do not address the persistence of abnormal colonic mucosal biology which imparts a continued cancer risk. However, the demonstration that colonic crypt epithelial cell proliferative activity (labeling index) which is increased in colon cancer was also abnormal in colon mucosa of patients with familial polyposis coli, who are known to be at high risk for developing cancer, provided a tool to assess for the presence of a subclinical or microscopic abnormality (Lipkin 1983, 1984). The subsequent reports that crypt cell proliferative activity was also increased in patients with sporadic colon adenomas, and that the labeling index in patients with familial polyposis could be changed toward normal by addition of calcium to the diet, provides evidence that this marker of crypt cell epithelial proliferative activity might be useful to evaluate cancer risk in certain patient groups and for assessing the effects of treatment interventions aimed at decreasing cancer risk (Lipkin 1985). We have used the tritiated thymidine labeling index to evaluate the effects of two proposed cancer prevention strategies, namely increased dietary fiber and treatment with the nonsteroidal anti-inflammatory drug (NSAID) piroxicam.


Dietary Fiber Label Index Familial Polyposis Label Index Familial Polyposis Coli 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bennett A, Del Tacca M, Stamford IF, Zebro T (1977) Prostaglandins from tumors of human large bowel. Brit J Ca 35: 881–4CrossRefGoogle Scholar
  2. Buset M, Lipkin M, Winawer S, Swaroop S, Friedman E (1986) Inhibition of human colonic epithelial cell proliferation in vivo and in vitro by calcium. Ca Res 46: 5426–30Google Scholar
  3. DeCosse JJ, Miller HH, Lesser ML (1989) Effect of wheat bran fiber and vitamins C and E on rectal polyps in patients with familial adenomatous polyposis. J Natl Cancer Inst 81: 1290–7PubMedCrossRefGoogle Scholar
  4. Earnest DL, Hixson LJ, Sim WW, Ahnen D, Alberts DS (1989) Piroxicam as an agent to inhibit colonic neoplasia. Gastroenterology 96: A134Google Scholar
  5. Finley PR, Williams RJ, Earnest DL (1989) Rapid and sensitive HPLC assay for piroxicam in serum. (submitted)Google Scholar
  6. Goodwin JS (1984) Immunologie effects of nonsteroidal anti-inflammatory drugs. Am J Med 77: 7–15PubMedCrossRefGoogle Scholar
  7. Greenwald P, Lanza E, Eddy GA (1987) Dietary fiber in the reduction of colon cancer risk. J Amer Dietic Assoc 87: 1178–88Google Scholar
  8. Han T, Nemoto T, Ledesma EJ, Bruno S (1983) Enhancement of T lymphocyte proliferative response to mitogens by indomethacin in breast and colorectal cancer patients. Int J Immunopharmacology 5: 11–15CrossRefGoogle Scholar
  9. Ho EE, Atwood JR, Meyskens Jr FL (1988) Methodological development of dietary fiber intervention to lower colon cancer risk. In: Engstrom PF(ed) Advanced cancer control: the war on cancer — 15 years of progress. Liss, New York, pp 263–81Google Scholar
  10. Lipkin M, Blattner W, Fraumeni J, Lynch H, Deschner E, Winawer S (1983) Tritiated thymidine labeling distribution as a marker for hereditary predisposition to colon cancer. Ca Res 43: 1899–1904Google Scholar
  11. Lipkin M, Blattner WA, Gardner EJ, Bert RW, Lynch H, Deschner E, Winawer S, Fraumeni JF Jr (1984) Classification and risk assessment of individuals with familial polyposis, Gardner syndrome and familial nonpolyposis colon cancer from [3H]-dThd-labeling patterns in colonic epithelial cells. Ca Res 44: 4201–7Google Scholar
  12. Lipkin M, Newmark H (1985) Effect of added calcium on colonic epithelial cell proliferation in subjects at high risk for familial colonic cancer. N Engl J Med 313: 1381–4PubMedCrossRefGoogle Scholar
  13. Lipkin M, Enker WE, Winawer S (1987) Tritiated-thymidine labeling of rectal epithelial cells in “non-prep” biopsies of individuals at increased risk for colonic neoplasia. Ca Letters 37: 153–61CrossRefGoogle Scholar
  14. Pollard M, Luckert P (1980) Indomethacin treatment of rats with dimethylhydrazine-induced intestinal tumors. Ca Treat Rep 64:1323–7Google Scholar
  15. Ponz de Leon M, Roncucci L, Di Donato P, Tassi L, Smerieri O, De Maria D, Antonioli A, Chchin N, Perini M, Rigo G, Barberini G, Maneti A, Biasco G, Barbara L (1988) Pattern of epithelial cell proliferation in colorectal mucosa of normal subjects and of patients with adenomatous polyps or cancer of the large bowel. Ca Res 48: 4121–6Google Scholar
  16. Reddy BS, Maruyama H, Kelloff G (1987) Dose-related inhibition of colon carcinogenesis by dietary piroxicam, a nonsteroidal antiinflammatory drug, during different stages of rat colon tumor development. Ca Res 47: 5340–6Google Scholar
  17. Reddy BS, Engle A, Katsifis S, Simi B, Bartram H-P, Perrino P, Mahan C (1989) Biochemical epidemiology of colon cancer: effects of types of dietary fiber on fecal mutagens, acid and neutral sterols in healthy subjects. Ca Res 49: 4629–35Google Scholar
  18. Terpstra OT, van Blankenstein M, Dees J, Eilers GAM (1987) Abnormal pattern of cell proliferation in the entire colonic mucosa of patients with colon adenoma or cancer. Gastroenterology 92: 704–48PubMedGoogle Scholar

Copyright information

© Springer Japan 1990

Authors and Affiliations

  • David L. Earnest
  • David S. Alberts
  • Lee J. Hixson
  • Frank L. Meyskens

There are no affiliations available

Personalised recommendations