Chemopreventive efficacy of all-trans-retinoic acid in biodegradable microspheres against epithelial cancers: results in a 4-nitroquinoline 1-oxide-induced oral carcinogenesis model.

Retinoids are known to suppress carcinogenesis in various epithelial tissues. Among them, all-trans-retinoic acid (atRA) is recognized as one such active retinoid. However, despite the known anticarcinogenic activity of atRA, it exhibits its short plasma half-life during repeated oral administration due to the "acute retinoid resistance" in the liver. This has been the major limitation in clinical applications of atRA. Therefore, in order to render atRA more suitable for clinical uses, sustained delivery of atRA using biodegradable microspheres is suggested in this study. When 50 mg atRA/kg of atRA-loaded microspheres were subcutaneously administered to rats once, the atRA concentration in plasma was maintained around 6.5 ng/ml for 7 weeks, with only minor signs of toxicity. When the chemopreventive efficacy of atRA-loaded microspheres was evaluated using a model of 4-nitroquinoline 1-oxide-induced oral carcinogenesis in F344 rats, a single injection of atRA-loaded microspheres significantly suppressed oral carcinogenesis. Additional injections of atRA-loaded microspheres, however, did not indicate further suppression of carcinogenesis.

Intervention study for primary prevention of oral cancer among 36 000 Indian tobacco users.

In a house-to-house survey, 36 471 tobacco chewers and smokers were selected from the rural population in three areas of India. These individuals were interviewed for their tobacco habits and examined for the presence of oral leukoplakia and other precancerous lesions, first in a baseline survey, and then annually over a 5-year period. By personal advice and via the mass media they were encouraged to give up their tobacco habits. The follow-up rate was 97%. The control cohort was provided by the first 5-year results from a 10-year follow-up study conducted earlier in the same areas with the same methodology but on different individuals without any educational intervention. In Ernakulam district (Kerala) and Srikakulam district (Andhra) substantially more people stopped their tobacco habit and reduced the frequency of tobacco use in the intervention cohort than in the control cohort; in Bhavnagar district (Gujarat) the intervention group showed only a slightly higher proportion stopping their tobacco habits and no difference in the proportion reducing them. The 5-year age-adjusted incidence rate of leukoplakia in Ernakulam district was 11.4 in the intervention group versus 47.8 among men, and 5.8 versus 33.0 among women; and for palatal lesions in Srikakulam district the corresponding figures were 59.8 versus 260.8 among men and 289.5 versus 489.5 among women. In Bhavnagar the incidence rate of leukoplakia did not differ between the cohorts. Since most oral cancers are preceded by precancerous lesions, education on tobacco habits should be a feasible and effective approach to primary prevention of oral cancer.