Ce site (1) commente la "Chemoprevention Database" avec l'article "Corpet & Taché, Nutr.& Cancer, 2002"
(2) met online des outils d'enseignement du Prof.D.Corpet. Ce sont donc des
Pages pour étudiants & profs Toulouse
TDnutr MicroDiet / Sujets CEAV / Biblio M2R / Conseil Scientifique ENVT / Thèses SEVAB
This site gives a Commentary on
"Colon Cancer Prevention Database".
This is the HOME page (introduction). Next pages: methods, results, and discussion of data, including ACF MDF BCAC
Tumor Free Rats: Efficacy of Chemopreventive
Our goal is to stop cancer before it starts, in other words, to prevent colorectal cancer.
Agents on Experimental Neoplasms
We thus wanted to find the most potent agents to prevent intestinal tumors in preclinical studies. To reach this goal we had three minor aims:
-(1) to gather all published preclinical studies on the effect of dietary chemopreventive agents against colon carcinogenesis in rats or mice after carcinogen injection,
-(2) to rank the agents, according to their potency to inhibit tumors and aberrant crypt foci. Ranking is a critical step that can help to set priorities when selecting agents for human trials. These ranked lists could be used to choose an agent provided it is not toxic. A similar approach was the ranking of carcinogenic hazards (HE/RP) published by Ames & Gold
-(3) to correlate ACF and tumor data: are potencies in both assays correlated?
According to Cummings & Bingham, dietary changes might prevent 70-80% of colorectal cancer, a major cause of death in nonsmokers. Diet may carry chemopreventive agents that could reduce the cancer risk. These agents can inhibit the initiation of preneoplastic lesions by carcinogens, or reverse their progression to invasive cancers.
- The American National Cancer Institute tells that chemoprevention is the use of natural or synthetic substances to reduce the risk of developing cancer, or to reduce the chance that cancer will recur (come back).
- The I.A.R.C. uses the term chemoprevention for interventions with pharmaceuticals, vitamins, minerals or other chemicals (natural and synthetic) at any of the multiple stages of carcinogenesis to reduce cancer incidence.
- More than 300 agents have been tested in rodents: most of them were fed to rats, during or after the injection of a colon carcinogen. The aim of those animal studies is to detect potent and non-toxic chemopreventive agents that might eventually be given to people, to reduce their risk of colorectal cancer, a strategy conceived by W. Robert Bruce in Toronto, among others.
Tumors & cancers.
Before 1990, the gold standard endpoint for chemoprevention in rodents was the incidence of macroscopic tumors: colon adenomas and adenocarcinomas induced by a chemical carcinogen.
These endpoints are clearly related to cancer, but have three major drawbacks:
- (1) a tumor requires a long time to develop (usually 5-8 months),
- (2) each tumor must be confirmed by histology, which is long and costly, and
- (3) each animal brings little information to the study (each rat has either no tumor or a tumor), thus large groups of rats are needed for statistical analysis.
Aberrant crypt foci (ACF) are putative precursors of colon cancer. ACF were first detected in rodents in 1987 by Ranjana Bird, few weeks after carcinogen injection. The crypts in ACF are easy to score on whole mount colon:
- ACF are two to three times larger than normal crypts,
- ACF are microscopically elevated,
- ACF have a slit-like opening,
- ACF have a thick epithelial lining that stains darker than normal crypts, with a large pericryptal zone.
It was demonstrated that:
- (1) ACF were induced by all colon carcinogens in a dose- and species-dependant manner;
- (2) ACF number and growth were modified by the modulators of colon carcinogenesis, and they predicted the tumor outcome in several rodent studies;
- (3) ACF correlate with colon cancer risk, and adenoma size and number in humans;
- (4) the morphological and genotypic features of ACF in human colons were similar to those in animal colons, and many alterations are similar in ACF and in tumors;
- (5) some ACF show dysplasia, and carcinoma were observed in rodents and humans' ACF.
The use of the ACF system to study modulators of carcinogenesis has accelerated for the last 10 years, for it provides a simple and economical tool for preliminary screening of potential chemopreventive agents, and it allows a quantitative assessment of the mechanisms of colon carcinogenesis.
To know how was done the bibliographic search, and built the tables, see the Methods.
To read a commentary on the data that are presented in the tables, see the Results.
To discuss a little more with me on those data, see the Discussion
L'auteur, Denis Corpet, prof à l'Ecole Nationale Vétérinaire de Toulouse et Downshifteur, donne des cours d'Hidaoa
Outdated Blogs: G-Blog cancer prevention blogspot &
U-blog prevention cancer