The aim of the study was to establish regularities of activated 3H-7,12-dimetilbenz(a)antratcene (DMBA) translocation in the major biopolymers of target and non-target organs at the initiation stage of transplacental carcinogenesis. DMBA was administered i.p. to rats on the 21th day of the pregnancy. Analysis of liver and kidney tissues of mothers, as well as liver, kidney, and brain of offspring was performed at temporal points of 1 hr to 14 days after single carcinogen administration. A regular, but transient non-specific accumulation of DMBA-radioactivity in the lipid fraction mainly embryonic tissues was observed during the first 6 hrs after administration of the labeled carcinogen. By 6 hrs, the maximum increase of label in RNA of embryonic brain and kidney (target organ for tumor induction) was observed and then, from 6 to 12 hrs, an increase occurred in the number of radioactive DNA adducts of fetus that was maintained for 24 hrs in these tissues. Increased accumulation of label in proteins of embryonic kidney was recorded from 6 to 24 hrs, and brain - from 12 to 24 hrs after administration of 3H-DMBA and on the 7th day in proteins of these organs of newborn rats.
Background. Alkylating drugs have been used in tumor chemo therapy for many decades, and the search for effective compounds continues.The aim of the study was to study the activity of the developed new compound – 2-[3-(2-chloroethyl)-3-nitrosoureido]-1,3-propanediol (chlonisol) in comparison with lomustine (CCNU) from the nitrosoalkylurea group, which is similar in chemical structure, in the model of intracranially transplanted Ehrlich's tumor and sarcoma 180 in mice.Methods. According to the developed technique, 64 female mice of the BALB/c line were punctured in the skull under anesthesia and inoculated with tumor cells of Ehrlich's carcinoma or sarcoma 180 in 0.9 % sodium chloride solution. After 24 hours, the test substances were administered at the maximum tolerated doses – chlonisol (20 mg/kg, i.p.) and lomustine (50 mg/kg, orally), once. The effect was compared with the control (solvent injection).Results. Chlonisol significantly increased the median overall survival (MOS) of animals after intracranial transplantation of both Ehrlich's tumor (by 39 %) and sarcoma 180 (by 84 %) compared with control (p<0.0001). Chlonisol reduced the risk of death in mice by 73 % compared to control in Ehrlich tumor transplantation and by 83 % in sarcoma 180 (p<0.0001). In contrast, lomustine did not show a significant therapeutic effect in intracranial transplantation of both tumors.Conclusion. The high activity of chlonisol in comparison with lomustine gives reason to consider it as a potential cytostatic agent in the treatment of nervous system tumors.
Background. Current treatment of HER2-positive metastatic breast cancer (BC) is based on the use of anti-HER2 blockers as pathogenic drugs, as well as the search for the optimal combination of anticancer drugs with different mechanisms of action. The potential activity of chlonisol in HER2+ ВС is of great interesting. The aim of the study was to evaluate the antitumor effect of 2-[3-(2-chloroethyl)-3-nitrosouriedo]-1,3-propanediol (chlonisol) on the growth of spontaneous mammary tumors in HER-2/neu transgenic FVB/N mice. Material and Methods. A prospective study used 5-month-old female mice with HER2-positive mammary tumors. Of these animals, ten pairs with almost the same size of tumors were formed (respectively, for the control group and the chlonisol treatment group). Chlonisol was administered at a dose of 20 mg/kg intraperitoneally, once. The animals were followed up for 30 days. Results. In all ten pairs of mice, chlonisol showed a significant antitumor effect, up to a complete temporary regression of the tumor. When summing the comparative results of all ten pairs of animals, the inhibition of tumor growth (ITG) in the chlonisol treatment group was 90-97 % (p<0.0001), and the area under the kinetic curve of tumor growth was 13.6 times less than in the control group (p<0.0001), thus indicating a significant effect. Conclusion. Chlonisol has a high therapeutic activity by inhibiting the growth of spontaneous HER2-positive breast tumors in FVB/N mice.
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