In accordance with Russian Federal program of import substitution of foreign medicines quality of Russian drugs in the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, played vincristine-RONC (VC-RONC), which as a drug – the generic’s passed preclinical pharmacological and toxicological testing in comparison with foreign firms vincristine Teva of Israel (VC-Teva). The aim. The aim of present study was the comparative pathomorphological evaluation of the effect of VC-RONC and VC-Teva on the internal organs of rats. Materials and methods. Used 50 weinbrenner male rats, at 10 rats per group. VC-RONC and VC-Teva rats were administered intravenously 3 times daily at aquatoxicity total dose corresponding to the MTD and 1/2 MTD. Control rats in the same regime intravenously administered of 0,9 % sodium chloride solution. Rats were deduced from the experience of 3 and 30 days after the end of administration of the drugs. Conducted macroscopic and histological examination of internal organs by conventional methods, including fixation of the material in 10 % formalin and coloring sections with hematoxylin and eosin. The micropreparations of the internal organs was analyzed under light microscope at magnifications of 100, 400, 1000. Results. VC-RONC, as VC-Teva in cumulative doses of 0,5 and 0,25 mg/kg in 3 days after the end of introductions in the internal organs of rats cause similar slightly pronounced morphological changes: hypoplasia in the bone marrow and spleen, destructive changes in the testes, focal degenerative changes in the kidney and liver of individual rats. On the 30th day after the application of both drugs, some rats regardless of the dose occurred similar symptoms residual morphological changes in the bone marrow, testes, kidneys and liver. Conclusion. Based on the results of macroscopic and histological examination the conclusion about the similarity of the influence of VC-RONC and VC-Teva on the internal organs of rats was made.

Background. The new anticancer chemical compound LHS-1269 from the class of indolocarbazoles is undergoing preclinical studies at the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia. LHS-1269 has a high antitumor activity on transplanted tumors of mice, showed high cytotoxic activity on many tumor cells lines in vitro, and has shown an inhibitory effect on vasculogenic mimicry in tumors in vitro. LHS-1269 does not affect the catalytic activity of human topoisomerases I and IIα. An antiangiogenic mechanism of the drug’s antitumor action is suggested.Aim. To evaluate the effect of LHS-1269 on the morphological features and angiogenesis of transplanted Lewis lung carcinoma (LLC) in BDF1 mice.Materials and methods. In BDF1 mice (n = 20) with transplanted LLC tumor on days 1 and 3 after 5-fold intraperitoneal administration of LHS-1269 in a single dose of 60 mg (total dose – 300 mg/kg), mice (n = 20) on days 5 and 8 after a single intravenous injection of LHS-1269 at a dose of 100 mg/kg, mice (n = 20) with transplanted LLC tumor without administration of LHS-1269 (control). The assessment of the antitumor effect was carried out according to the criterion of inhibition of tumor growth (%) and the study of the morphological features of the tumors. To assess the effect of LHS-1269 on tumor angiogenesis in LLC tumor sections, a visual calculation of the average number (density) of blood vessels and immunohistochemical detection of expression of the CD31+ endothelial marker were performed.Results. The LHS-1269 compound in animal groups with 5-fold and 1-fold use caused tumor growth inhibition – 59–70 and 67–79 %, with pronounced morphological changes and tumor cell death. There is an uneven distribution of blood vessels in tumors and surrounding tissues in all groups. LHS-1269 caused a statistically significant decrease in the average number of blood vessels in the tumor both after 5-fold and after 1-fold administration. The statistically significant decrease in the average number of blood vessels in the surrounding connective tissue tumor was observed only after 5-fold administration of the drug. The decrease in the average number of CD31+ endothelial cells after five times intraperitoneal administration was statistically insignificant compared to control (83.1 ± 8.7 and 59.6 ± 18.9, respectively). The increase in this indicator after a single intravenous injection of LHS-1269 was statistically significant.Conclusion. LHS-1269, when administered five times and once in mice, caused pronounced morphological changes in the form of damage and death of LLC tumor cells. The results of a study of angiogenesis in a tumor do not allow an unambiguous conclusion about the inhibitory effect of LHS-1269 on angiogenesis in LLC tumors in mice.