[Analysis of carrying clinically significant allelic variants of TPMT and DPYD genes associated with the response to drug therapy in cancer practice among 9 ethnic groups of the Russian Federation].

AIM: To study the peculiarities of carrying clinically significant allelic variants of TPMT and DPYD genes associated with the response to drug therapy in cancer practice among 9 ethnic groups of the Russian Federation. MATERIALS AND METHODS: The study included 1446 conditionally healthy volunteers from 9 ethnic groups. Carriage of polymorphic TPMT and DPYD gene markers was detected by the Real-Time PCR (polymerase chain reaction) method. RESULTS: In all ethnic groups, the distribution of genotypes and alleles matched the equilibrium of Hardy-Weinberg. TPMT*3A (rs1800460) and TPMT*3C (rs1142345) were observed in heterozygous state in all investigated ethnic groups. In the Kabardinian group (n=204) the frequency of the TPMT*3A minor allele (MAF, %) was 2.94%; Balkars (n=200) 1.25%; Ossetians (n=239) 1.67%; Chuvashes (n=238) 1.89%: Mari (n=206) 1.21%; Tatars (n=141) 1.77%; Russians (n=134) 4.85%. The frequency of the TPMT*3C minor allele (MAF, %) in the Kabardinian group (n=204) MAF was 4.90%; Balkars (n=200) 1. 75%; Buryats (n=114) 0.44%; Ossetians (n=239) 1.88%; Chuvashes (n=238) 1.68%: Mari (n=206) 1.21%; Tatars (n=141) 1.42%; Russians (n=134) 4.48%. The results of the analysis of DPYD*2A polymorphism (rs3918290) demonstrated ethnic peculiarities of distribution. In the heterozygous state it was found only in the groups of Kabardins (n=204, MAF 1.22%), Balkars (n=200, MAF 2.00%), and Ossetians (n=239, MAF 0.63%). CONCLUSION: The results obtained in the study will be useful for developing personalized algorithms of antitumor therapy in cancer practice, including those aimed at increasing the safety of chemotherapy.

[Effects of cascatol and sodium selenite on the onset and development of breast tumors induced in rats by N-methyl-N-nitrosourea].

Experimental evidence is presented on effects of the vitamin complex cascatol containing vitamins E, C, beta-carotin and sodium selenite on the onset and development of breast tumors induced in rats by N-methyl-N-nitrosourea. Cascatol used in combination with sodium selenite significantly reduced the incidence of tumors from 95.5% in the control group to 50% in the test group, prolonged a latent period of tumor development and inhibited growth of breast tumor.

[New approaches to the drug prophylaxis of mammary tumor: evaluation of the prophylactic effect of lovastatin and captopril in rats with experimental mammary gland tumors].

Effects of the GABA-CoA reductase inhibitor lovastatin and the ACE inhibitor captopril on the induction and growth of mammary gland tumors induced by N-methyl-N-nitrosourea in Wistar rats have been studied. It is established that lovastatin administered in a doze of 80 mg/kg two times a week exhibits anticarcinogenic activity, which is manifested by a significant decrease in the incidence of neoplasms and an increase in the survival lifetime in the experimental animals. Captopril administered in a doze of 50 mg/kg two times a week significantly decreased the tumor growth rate. The chemopreventive activity of these drugs can be due to their possible regulatory influence on the processes of cell proliferation, differentiation, neoangiogenesis, and apoptosis. The results of this investigation show good prospects for the further investigation of lovastatin and captopril as chemotherapeutic agents for the prophylaxis of mammary tumor.

Effects of acetylsalicylic acid and celecoxib on the N-nitrosodiethylamine induced carcinogenesis in rat liver and esophagus.

The effects of nonsteroid antiinflammatory drugs (acetylsalicylic acid and celecoxib) on N-nitrosodiethylamine-induced carcinogenesis in the liver and esophagus were studied in rats. The inhibitory effect of celecoxib on carcinogenesis was more pronounced (in comparison with acetylsalicylic acid), which manifested in a significantly decreased incidence of neoplastic changes in the liver tissue (from 91.7 to 65.2%), number of tumors in the esophagus (from 4.13 to 2.61 tumor/rat), and in delayed malignization in the liver and esophagus. The incidence of erosions and ulcers of the gastric mucosa was significantly lower after celecoxib treatment. These data indicate that celecoxib inhibits N-nitrosodiethylamine-induced carcinogenesis in the liver and esophagus.