Retinoids and chemoprevention of aerodigestive tract cancers.
Natural and synthetic vitamin A metabolites and analogs (retinoids) were found to suppress head and neck and lung carcinogenesis in animal models and inhibit carcinogenesis in individuals with premalignant lesions and a high risk to develop cancer of the aerodigestive tract.
Likewise, retinoids prevent the development of second primary cancers in head and neck and lung cancer patients who had been treated for the first primary.
These effects are thought to result from changes in the expression of genes that regulate cell growth and differentiation.
Most of the effects of retinoids on gene expression are mediated by nuclear retinoic acid receptors RARs (alpha, bêta, and gamma) and retinoid X receptors (RXR alpha, bêta, and gamma), which function as retinoid-activated transcription factors.
Like vitamin A deficiency, alterations in receptor expression or function could interfere with the retinoid signaling pathway and thereby enhance cancer development even in vitamin A sufficient individuals.
We found that the expression of RARbêta was suppressed in more than 50% of oral and lung premalignant lesions in individuals without cancer (e.g., oral leukoplakia and squamous metaplasia), in dysplastic lesions adjacent to cancer, and in malignant oral and lung carcinomas.
The expression of the other receptors was not different among normal, dysplastic, and malignant oral tissues.
However, the expression of RARgamma and RXRbêta was somewhat decreased in lung cancers. (...)
Mots-clés Pascal : Tumeur maligne, Voie aérodigestive supérieure, Rétinoïde, Anticancéreux, Chimioprophylaxie, Prévention, Lésion précancéreuse, Etats Unis, Amérique du Nord, Amérique, Animal, Appareil respiratoire pathologie, Appareil digestif pathologie, ORL pathologie
Mots-clés Pascal anglais : Malignant tumor, Upper aerodigestive tract, Retinoids, Antineoplastic agent, Chemoprophylaxis, Prevention, Premalignant lesion, United States, North America, America, Animal, Respiratory disease, Digestive diseases, ENT disease
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 98-0067209
Code Inist : 002B02R02. Création : 14/05/1998.