ABSTRACT
Measurements of cell proliferation and differentiation have identified changes in gastrointestinal epithelial cells that are associated with increased susceptibility to neoplasia. Early in the development of precancerous diseases, DNA synthesis continues in the cells as they migrate to the surface of the epithelial lining, and the cells do not differentiate normally. Further changes occur in advanced stages of precancerous diseases, and gastrointestinal cells exhibit progressively increasing degrees of abnormally delayed maturation. Intestinal metaplasia increases in the gastric mucosa of patients with cancer compared with individuals with gastric ulcer, suggesting that metaplasia may be a biomarker of precancerous disease. Measurements of the proliferation and differentiation of epithelial cells have served as "intermediate biomarkers", analyzing the early effects of chemopreventive interventions in the cells of both human subjects and animal models. Because of the results of these studies, larger randomized clinical trials have been started with administration of supplemental dietary calcium or placebos to human subjects.
