Effect of 2-(carboxyphenyl) retinamide and genistein on the formation of early lesions in 1,2-dimethylhydrazine-induced colon carcinogenesis in rats.

Aberrant crypt foci (ACF) are recognized as preneoplastic lesions for colon cancer, and ACF in rodents are widely used as an intermediate biomarker to predict tumorigenicity in the colon. However, a lack of correlations between the formation of ACF and the development of colonic tumors has been reported in several studies. For example, 2-(carboxyphenyl) retinamide (2-CPR) and genistein were reported to inhibit the carcinogen-induced formation of ACF, whereas both of them were later found to enhance colon tumorigenesis in rats treated with azoxymethane (AOM). Recently, we have identified b-catenin-accumulated crypts (BCAC) in the colon of rats shortly after administration of AOM, and provided evidence that these are independent early lesions of classical ACF, and BCAC might be direct precursors for colon cancers. In the present study, we performed a comparative analysis of the modifying effects of 2-CPR and genistein on 1,2-dimethylhydrazine (DMH)-induced BCAC and ACF in male F344 rats. Dietary administration of 2-CPR (315 ppm) significantly reduced the total number, multiplicity and size of ACF in DMH-exposed colonic mucosa, while genistein (250 ppm) had no significant effects on DMH-induced ACF formation. In contrast, both of 2-CPR and genistein significantly enhanced the multiplicity and size of DMH-induced BCAC when compared with DMH alone group. In addition, both 2-CPR and genistein significantly increased the proliferating cell nuclear antigen (PCNA) index preferentially in BCAC. Together with previous findings that 2-CPR and genistein are tumor promoters in the colon, our results support the concept that BCAC are precursors of colon tumors and suggest that these lesions are more reliable short-term biomarkers for colon carcinogenesis in rodents than ACF.

The aromatic ethylamide derivative of retinoic acid in the treatment of acne vulgaris.

A clinical trial on the aromatic ethylamide derivative of retinoic acid (Ro. 11-1430) applied topically was carried out for 10 weeks on 50 ambulatory patients suffering from various degrees of acne vulgaris. This clinical trial assessed the efficacy and side reactions of Ro. 11-1430 in the treatment of acne vulgaris, especially when used in the tropics. A comparison was made between the results obtained in this trial and those in another trial using topical retinoic acid. Analysis made in terms of efficacy, drug tolerance, patients' complaints and duration of treatment for achieving obvious alleviation of symptoms shows that Ro. 11-1430, with the exception of side reactions due to the drugs applied, was inferior to retinoic acid. Relapses as well as remissions often occurred during the period of maintenance therapy. Like retinoic acid, Ro. 11-1430 has a palliative effect only and not a curative one.