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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

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

Background. The arsenal of antitumor drug therapy for melanoma brain metastases is limited. The search and study of new agents capable to penetrate the blood-brain barrier and provide a therapeutic effect against intracranial tumors remains an unmet clinical need. The aim is to evaluate the antitumor activity of the domestic derivative of nitrosoalkylureas, chlonisol, in mice with intracranially transplanted syngeneic B16 melanoma. Methods. The experiment was carried out in 18 female inbred C57BL/6 mice. After intracranial tumor transplantation, performed according to modified technique, the animals were randomized into two groups: I. Control (n = 10) – the animals were injected with normal saline 10 ml/kg intraperitoneally; II. Chlonisol (n = 8) – the animals were treated with the test compound at a dose of 15 mg/kg in normal saline intraperitoneally. The single administration of normal saline and chlonisol was performed 24 hours after tumor transplantation. The end point of the study was overall survival (OS) of the animals. Results. Compared with the control group, administration of chlonisol significantly increased the median OS of mice from 13 to 18 days (log rank test, p = 0.0005). Chlonisol significantly decreased the risk of death by 71 % compared with the control group (HR = 0.29; 95 %CI 0.10–0.82). By the 15th day after intracranial transplantation of B16 melanoma, all 10 mice in the control group died from intracerebral tumors (100 %), whereas in the chlonisol group only 2 out of 8 (25 %) mice died (Fisher's exact test, p = 0.0015). Conclusion. Despite the exploratory nature of the present study, it provides a good starting point for further research of chlonisol in brain tumors.

Because of the high risk of brain metastases from HER2-positive breast cancer, the study of the anticancer activity of drugs used to treat brain tumors, in particular lomustine, is of great importance. In the FVB/N Her-2 transgenic mice bearing HER2-positive breast cancer (BC HER2+), a single oral administration of lomustine at a dose of 50 mg/kg resulted in a significant tumor growth inhibition (up to 96 %, p

The purpose of this work was to study changes in the level of cell-free DNA (cfDNA) in the blood of young and old rats in the normal state and with induced benign prostatic hyperplasia (BPH). Male Wistar rats were divided into 4 groups—young (3 months), old (20 months), intact, or with testosterone-induced BPH. Groups with BPH were subjected to surgical castration and administration of testosterone esters at a dose of 25 mg/kg for a total of 7 injections for 20 days. In intact animals, the level of cfDNA in old rats (2.00±0.14 ng/μl) was significantly higher than that in the young (1.02±0.30 ng/μl). The body and the prostate weights of old rats were 1.6 and 1.4 times larger than those of the young, without an increase in the prostate index (PI). The testosterone level in the blood of young rats was 1.6 times higher than that of old (6.20±0.93 nmol/l vs. 3.77±0.55 nmol/l; NS). In animals with BPH, the level of cfDNA in old rats (3.14±0.76 ng/μl) was significantly higher than that in young rats (0.80±0.14 ng/μl). The body and the prostate weights in old rats were 1.8 and 2.3 times larger, than those in young rats, with an increase in the PI. The level of testosterone in the blood of young (15.76±0.51 nmol/l) and old (16.99±1.1 nmol/l) rats was not significantly different. Morphological signs of BPH were observed in the prostate of both young and old rats. During the induction of BPH in the experiment, according to the level of cfDNA, cell death processes have not changed significantly in young rats but significantly increased in old rats. A similar trend was observed in the group of intact animals. The obtained data indicate that apoptosis processes are enhanced during the development of BPH despite the growth of tissues in the prostate itself.