NATURAL-HISTORY OF INTRAEPITHELIAL NEOPLASIA IN HUMANS WITH IMPLICATIONS FOR CANCER CHEMOPREVENTION STRATEGY

Citation
Cw. Boone et al., NATURAL-HISTORY OF INTRAEPITHELIAL NEOPLASIA IN HUMANS WITH IMPLICATIONS FOR CANCER CHEMOPREVENTION STRATEGY, Cancer research, 52(7), 1992, pp. 1651-1659
Citations number
86
Language
INGLESE
art.tipo
Article
Journal title
ISSN journal
0008-5472
Volume
52
Issue
7
Year of publication
1992
Pages
1651 - 1659
Database
ISI
SICI code
0008-5472(1992)52:7<1651:NOINIH>2.0.ZU;2-9
Abstract
Intraepithelial neoplasia is of critical importance to the cancer chem oprevention field because it is a target condition for which drugs mus t be sought that will prevent its development or stop its progression. The term "dysplasia" refers to the morphological alterations that cha racterize intraepithelial neoplasia and according to many authors cons ists of seven basic morphological changes that occur in the majority o f human epithelia, as well as in the epithelium of mouse skin papillom as induced by 7,12-dimethylbenz(a)anthracene and 12-O-tetradecanoylpho rbol-13-acetate: increased nuclear size; altered nuclear shape; increa sed nuclear stain uptake; nuclear pleomorphism (increased variation in nuclear size, shape, and stain uptake); increased mitoses; abnormal m itoses; and disordered or absent maturation. Clonal evolution appears to begin early in the neoplastic process during intraepithelial neopla sia. Aneuploidy has been found during intraepithelial neoplasia in man y human epithelia, and, in association with other forms of genetic ins tability, may provide the increase in genetically variant cells requir ed for clonal evolution to occur. It is postulated that two major fact ors affecting the rate of progression of intraepithelial neoplasia are the cellular mutation rate, which is enhanced by environmental carcin ogens, and the cellular proliferation rate, which is enhanced by agent s that include sex hormones, inducers of chronic inflammation, and irr itant chemicals which stimulate reactive hyperproliferation. A preferr ed chemoprevention strategy should consist of the development of drugs and drug combinations which will block mutagenic carcinogens or preve nt epithelial hyperproliferation or its causes. Two examples of the in duction of regression of intraepithelial neoplasia by chemopreventive drugs are the regression of oral leukoplakia produced by beta-carotene and the regression of colorectal polyps in patients with familial pol yposis produced by sulindac. It is evident that there is a strong need for more research on the induction of regression of intraepithelial n eoplasia with chemopreventive agents. There is also a critical need to identify and develop biomarkers that correlate with the appearance an d regression of intraepithelial neoplasia.