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The cross-interaction between BMP, Wnt and Shh signalling pathways in developing epithelial skin tumours remains poorly understood. To study the role of Wnt and Shh signalling pathways in tumour development upon BMP inhibition, we utilized a transgenic mouse model, overexpressing BMP antagonist noggin in the skin epithelium and leading to the development of hair follicle-derived tumours shortly after birth. Comparative gene and protein expression analyses revealed up-regulation of Wnt and Shh signalling systems in the skin of transgenic mice at various stages of follicular tumour development. Furthermore, recombinant BMP-4 suppresses the expression of Shh in the culture of tumor cells, while pharmacological inhibitors of Wnt and Shh significantly slow down the formation and development of tumors in noggin-expressing transgenic mice. These results enhance our knowledge about the role of growth factors in carcinogenesis and may lead to finding new targets for specific therapies for oncological diseases.

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

Alzheimer's disease (AD) is the most common proteinopathy, which is accompanied by a steady decrease in the patient's cognitive functions with a simultaneous accumulation of amyloid plaques in brain tissues. Amyloid plaques are extracellular aggregates of amyloid β (Aβ) and are associated with neuroinflammation and neurodegeneration. Unlike humans and all other mammals, rats and mice do not reproduce AD-like pathology because there are three amino acid substitutions in their Aβ. Amyloid plaques form in the brains of transgenic mice with overexpression of human Aβ, and such mice are therefore possible to use in biomedicine to model the key features of AD. The transgenic mouse line APPswe/PS1dE9 is widely used as an animal model to study the molecular mechanisms of AD. A study was made to characterize the APPswe/PS1dE9/Blg subline, which was obtained by crossing APPswe/PS1dE9 mice on a CH3 genetic background with C57Bl6/Chg mice. No difference in offspring's survival and fertility was observed in the subline compared to wild-type control mice. Histological analysis of the brain in the APPswe/PS1dE9/Blg line confirmed the main neuromorphological features of AD and showed that amyloid plaques progressively increase in number and size during aging. The APPswe/PS1dE9/Blg line was assumed to provide a convenient model for developing therapeutic strategies to slow down AD progression.

Aim: To evaluate an effect of dimebon on the onset of symptomatic stage in FUS.1-513 transgenic mice - a new genetic model of neurodegeneration, and to study the dynamics of disease progression in the terminal stage., Material and Methods: The study was carried out on males of line FUS1-513 with the contribution of genes from CD1 strains. Mice of the experimental group (n=28) received dimebon with water in the concentration of 70 mcg/ml starting from the 35th day of life. The control group (n=25) did not receive the drug. Age, body mass of animals at the start of symptomatic stage and duration of symptomatic stage were assessed., Results: Application of dimebon can delay the onset of the manifestation of clinical symptoms of the neurodegenerative process in the experimental group (127.6±4.6 days) compared to the control group (110.6±4.2 days). The body mass was similar in both groups., Conclusion: Dimebon leads to an increase in the duration of presymptomatic stage and delays the manifestation of clinical symptoms. The changes in the dynamics of the pathological process in the symptomatic stage are not detected.