Vol 18, No 2 (2020)

The review describes the characteristics of the ubiquitin-proteasome system involved in proteins degradation and its role in the transition of pretumor changes of the epithelium to cancer. According to modern concepts, the ubiquitin-proteasome system is actively involved in the regulation of numerous intracellular processes, such as proliferation, apoptosis, differentiation, which play an important role in the development of tumors. Main target proteins which have been shown to be cleaved in proteasomes, can participate in carcinogenesis. Detailed research of the ubiquitin-proteasome system will reveal the specific mechanisms involved in the transition of precancerous diseases to malignant neoplasms.

Neurodegenerative diseases are a group of pathologies of the nervous system, which are characterized by progressive death of nerve cells and gradually increasing atrophy of the corresponding parts of the brain or spinal cord. In developed countries, an increase in average life expectancy is observed. The frequency of neurodegenerative diseases also has a pronounced upward trend. Currently, the treatment of neurodegenerative diseases is ineffective, especially at the advanced stages. Pathology of the nervous system is included in the list of global problems facing humanity in the 21st century. To solve such problems, funded programs are organized around the world. The development of regenerative medicine will allow developing in the near future new technologies for the diagnosis and treatment of neurodegenerative diseases. The review provides priority data on the prospects of using mesenchymal stem cell transplantation as replacement therapy for the treatment of neurodegenerative diseases.

Aim. Comparative evaluation of FcγRIIIb (CD16) expression level on the surface of blood neutrophils in vaccinated and unvaccinated people before and after the interaction of cells in vitro with the plague microbe allergen (pestin). Materials and methods. Blood samples of 25 healthy donors not vaccinated against the plague were examined, as well as 40 volunteers who were vaccinated once and several times with the plague vaccine alive, before and during different periods (1, 6 months) after the vaccination. The expression of CD16 on the surface of neutrophil granulocytes was determined by flow cytometry before and after incubation of blood samples for 4 hours with pestin. Results. After vaccination in all subjects there was registered a significant increase in the expression level of the CD16 molecule on the surface of blood neutrophils. After in vitro contact with pestin, the expression level of the FcγRIIIb molecule (CD16) decreased on the surface of neutrophils only in blood samples of people vaccinated against the plague. Conclusion. The change in the neutrophil phenotype from CD16bright to CD16dim, revealed by in vitro interaction with blood pestin grafted against the plague of people, mimics the response of these cells in anaphylactic shock mediating with specific IgG, and apparently represent the result of the functioning of the FcγRIIIb (CD16) as a trigger for netosis.

Currently, glioblastoma is an extremely malignant tumor, for which treatment only temozolomide is relatively effective. Aim to study the expression and variants of coexpression of transcription factors NeuroD1, Prox1, FoxM1, somatostatin receptors of the 2nd and 5th type, CD38 and CXCR4 receptors in glioblastoma. The methods included an immunohistochemicalstudy with antibodies to Neuro1l, CXCR4, Prox1, FoxM1, CD38, SSTR2, SSTR5and morphometric analysis of glioblastoma fragments from 22 patients (surgical material). Results. A high level of expression (>50% of the cells) of FoxM1 was detected in 85,7% of glioblastomas samples. The average expression level of FoxM1 accouned of 82,8±5,5%. NeuroD1 was expressed in the nuclei of glioblastoma cells in l00% of cases, the average level of its expression was 95,4±0,7%. High levels of CXCR4 expression were detected in l6 tumors (76,2%). The average expression level of CXCR4 was 76,2±6,1%. Proxl was expressed in 57,l% of cases with an average expression level of 58,4±7,0%. All of the above proteins were found in the tumor cells and the walls of its vessels. SSTRs of the 2nd and 5th types were expressed in the cells of the vascular walls in all cases, the expression level was 2,2±1,1 and 6,7±1,2%, respectively. Marked expression of CD38 was observed in only 9,5% of cases. The average level of expression of CD38 - l0,8±3,4%. When analyzing combinations of marker expression, FoxM1+/NeuroD1+/Prox1-/CXCR4+/ CD38- immunophenotype was most often found (in 38,1% of cases). Conclusion. As a result of the study, the expression of CD38 was detected for the first time in glioblastoma cells. High levels of expression of the studied proteins were recorded in the tumor cells and in walls of its vessels. The immunophenotypic heterogeneity of glioblastoma was determined, the most common variant of protein combination in one tumor, FoxM1+/NeuroD1+/Prox1-/CXCR4+/CD38-, was revealed. According to the data obtained, a new personalized approach to treatment is required with the definition of targets for exposure and the corresponding spectrum of drugs in each individual case.

Introduction. Multiple primary malignant neoplasms (MPMN) most often develop in individuals with a hereditary predisposition to oncological diseases. There are inherited allelic variants of oncogenes, tumor suppressor genes and their combinations which disrupt the functional activity of the corresponding proteins. This leads to the development of certain tumors and is clinically manifested as familial oncological syndromes. Materials and methods. Fifty key genes associated with carcinogenesis were sequenced for 8 women, developed MPMN and have a family tumor history. Results. A total of 26 polymorphic variants were identified in l8 genes. Ten of them are located in introns, one - in the regulatory region of the gene, ten of them are silent-mutations, five - are missense-mutations. Each patient has from 9 to l7 such variants. Probably the polymorphism RET rsl800863 in the existing genomic context in Patient № l predetermined the development of medullary thyroid cancer in her and her daughter. Family of patient №2 shows a picture typical of Li-Fraumeni-like syndrome. We assume that due to either the single homozygous TP53 rsl800372 polymorphism, or its combination with TP53 rsl042522 polymorphism, determines the presence of Li-Fraumeni-like syndrome in this family. Conclusion. The frequency of rs55986963, rsl050l7l, rsl2628 polymorphisms in the sample exceeds that in the population. It is necessary to expand the sample at the expense of MPMN-patients and healthy women for further discussion.