Objective. Review of the modern methodological approaches for testing and studying the epigenetic activity of xenobiotics.

Materials and methods. In preparing the review, we used information databases of biomedical literature SciVerse Scopus (538), PubMed (746), Web of Science (625), RSCI (45). To obtain full-text documents, electronic resources of PubMed Central (PMC), Research Gate, RSCI, CyberLeninka were used. In the text of the review, 87 modern publications (2010–2019) were cited, as well as 17 earlier articles published by the founders of the methods, which are used today.

Results. In the review, current data on epigenetic regulation for gene expression at the level of DNA methylation and histone modification are discussed, in vitro model systems and model organisms are described, and modern methods for screening of epigenetically active xenobiotics are presented.

Conclusion. Modern data concerning the mechanisms of epigenetic regulation of gene expression, the usage of existing model systems and model organisms, as well as the application of various methodological approaches and techniques, allow extensive screening of xenobiotics (including drugs and compounds synthesized for national economic tasks) for epigenetic activity. The identification of epigenetically active compounds is important in terms of improving the prevention and treatment of a number of diseases and, in particular, malignant neoplasms.

The objective is to evaluate the contents of matrix metalloproteinases (MMP) MMP9, MMP2, as well as their inducer EMMPRIN in circulating exosomes of patients with colorectal cancer in relation with clinical and morphological parameters, as well as with the presence of metabolic syndrome to search for promising exosomal markers associated with invasion, metastasis and metabolic disorders.

Materials and methods. The study included 40 patients with colorectal cancer (T2–4N0–2M0–1) and 10 control patients. Exosomes of blood plasma were isolated by ultrafiltration with ultracentrifugation. The level of MMP9, MMP2 and their inducer EMMPRIN in exosomes was evaluated by flow cytometry.

Results and conclusion. The level of MMP9‑positive exosomes was significantly higher in patients with colorectal cancer compared with patients with colorectal polyps. The proportion of MMP9‑negative and triple positive MMP9 + / MMP2+ / EMMPRIN+ exosomes, on the contrary, was higher in patients with polyps compared with patients with colorectal cancer. Mixed subpopulation of MMP9+ / MMP2– / EMMPRIN-exosomes prevailed both in patients with colorectal cancer and in control patients. There were no significant differences in the subpopulations of MMP and EMMPRIN in the exosomes of colorectal cancer patients depending on the age, stage, grade and localization. Gender differences in the occurrence of a triple-positive exosome subpopulation in colorectal cancer patients have been revealed. No relationship was found between the expression of MMP and EMMPRIN in exosomes and the presence of the metabolic syndrome, anthropometric parameters, the level of total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol. However, the relationships between MMP9+ / MMP2– / EMMPRIN–, MMP9+ / MMP2– / EMMPRIN– and the level of triglycerides and glucose in blood serum were revealed. Further studies are needed to study the characteristics of exosomes associated with metabolic disorders and the possibility of their use as diagnostic, prognostic, or predictor biomarkers.

Background. Leiomyosarcoma is one of the most common types of soft tissue sarcomas. Radical surgical resection with subsequent adjuvant chemotherapy remain the most effective treatment approach. Immunotherapy based on inhibition of PD-L1 (programmed death ligand 1) or its receptor PD1 (programmed death 1) is considered a promising treatment option. Level of PD-L1 expression in tumor cells and presence of microsatellite instability (МSI) could be considered prognostic and predictive markers of disease progression and effectiveness of immunotherapy.

The study objective is to determine PD-L1 expression level and МSI status in patients with retroperitoneal leiomyosarcomas and evaluate their effect on overall and recurrence-free survival.

Materials and methods. The study included 57 patients with retroperitoneal leiomyosarcomas who underwent surgical or combination treatment. Analysis of clinical and morphological characteristics was performed; results of surgical treatment were researched. Evaluation of PD-L1 expression and MSI status was performed using immunohistochemical and molecular genetic analysis.

Results. PD-L1 expression and MSI status were evaluated in 41 patients of 57. In 10 (24 %) of 41 cases, positive PD-L1 expression was observed (expression level 3–50 %). In 1 (2.4 %) patient, the primary tumor and metastatic lesion had low MSI level (MSI-low, MSI-L). Median follow-up was 31 months. In patients with positive PD-L1 expression, higher Ki-67 proliferative index was observed compared to patients with PD-L1 negative tumors (58.8 and 47.8 % respectively; р = 0.02), as well as significantly lower median overall survival for grade II tumors (30 and 105 months; p = 0.043). In grade III leiomyosarcomas, a trend towards lower median overall survival in patients with PD-L1‑negative tumors (31.0 months) compared to patients with PD-L1 expression (61.2 months) (р = 0.11) was observed.

Conclusion. Among patients with retroperitoneal leiomyosarcomas, positive expression of PD-L1 was observed in 24 % (10 / 41) of cases and MSI-low status was found in 2.4 % (1 / 41) of cases. In patients with grade 2 tumors, positive PD-L1 expression is associated with significantly lower overall survival. PD-L1 expression in patients with retroperitoneal leiomyosarcomas could be considered a prognostic marker and a potential therapeutic target.

Background. Tumors influence on various vital processes in organism leading to cachexia, immunosuppression, anemia, changes in humoral regulation etc. Inflammation is one of the well-known etiological factors of carcinogenesis, including for cervical cancer, so we suggest that some blood serum inflammatory factors in patients with cervical cancer influence are associated with the level of tumor progression.

The objective of our study was to analyze the level of some hematological markers of inflammation in the blood serum of patients with cervical cancer in dependence on the histological characteristics of the primary tumors.

Materials and methods. In the study we analyzed the blood serum of patients with invasive cervical cancer I–IV stage (4 patients with verrucous cancer and 26 – with cervical cancer among them 10 – of G1 stage, 6 – of G2 stage, 10 – G3 stage) using flow cytometry. We studied the value of myoglobin, calprotectin, lipocalin, matrix metalloperoxidase 2, matrix metalloperoxidase 9, osteopontin, myeloperoxidase, serum amyloid A, protein 4, insulin-like growth factor-binding protein 4, cell-cell adhesion molecule 1, vascular cell adhesion molecule, cystatin С.

Results. We revealed the changes of some serum markers of inflammation in patients with G3 and verrocous cervical cancer.

Conclusion. The obtained dates demonstrate that further study of blood inflammatory markers as an additional differential and prognostic criteria in patients with cervical cancer should be considered as reasonable.

Background. Clarification of the mechanisms of carcinogenesis induced by foreign bodies is one of the urgent problems of modern oncology. This is due to the fact that there is a relationship between the processes of inflammation and carcinogenesis. Today, there is no doubt the fact that cytokines and signal molecules in the focus of inflammation (products of inflammation) can contribute to the initiation of carcinogenesis, as well as stimulate tumor progression. In the case of carcinogenesis induced by foreign bodies, the key issue is understanding the differences in the body’s response to the implantation of foreign bodies that can cause tumor formation and do not have this ability. One of the phenomena of this type of carcinogenesis is the occurrence of sarcoma after the subcutaneous implantation in mice of hydrophilic millipore filters with a pore diameter not exceeding 0.1 μm and the inability to induce tumors of one’s with a pore diameter greater than or equal to 0.22 μm.

The objective of our work was to study the differences between oncogenic and non-oncogenic filters at the molecular level.

Materials and methods. Reverse transcription polymerase chain reaction method was used to study the expression of a number of cytokines that are products of macrophage cells that live on the surface of implanted filters and in the surrounding capsule. Filters with pore diameters of 0.025 μm (carcinogenic) and 0.45 μm (non-carcinogenic) were compared in 8, 35 days and 5.5 months after implantation.

Results and conclusion. After 8 days we observed significant (p <0.01) excess of expression of two cytokines interleukin 1β (IL-1β) by cells around oncogenic filters (with pore of 0.025 μm) compared to non-oncogenic one’s (with pore of 0.45 μm) After 35 days, significant (p <0.01) excess of expression of IL-1β, Tnf-α, iNOS (induced nitric oxide synthase), and IL-6 by cells around the oncogenic filters (0.025 μm) compared to non-oncogenic one’s (0.45 μm) was observed. There was no quantitative difference in the expression of Nf-κB1 and Nf-κB2 (nuclear factor κ-B1, κ-B2), Tgf-β (transforming growth factor β), IL-10. After 5.5 months the expression of IL-1β by cells on oncogenic filters was still significant; for Tnf-α, iNOS, IL-6 and IL-10 there was no practically difference in expression. For Nf-κB1 and Nf-κB2, Tgf-β and COX-2 (cyclooxygenase 2) the difference was significant, cells on non-oncogenic filters are expressed more then on oncogenic one’s.

Based on the results of cancer monitoring in the staff of a large Cancer Center cancer risk research was performed using the method of nested “case–control” study within a cohort. The cohort comprised 7269 persons who were followed up through the cancer-register of the Cancer Center. Four hundred eighty-four (139 male and 345 female) cancer cases were revealed. For every case a control individual of the same sex and age was randomly selected from the staff who had no cancer as of January 1, 2019. A statistically insignificant increase in the overall cancer risk was observed in male operational staff (odds ratio (OR) being 1.14, 95 % confidence interval (CI) 0.64–2.05) and other doctorsclinicians (OR 1.36; 95 % CI 0.68–2.73). In a combined group of male clinicians and experimenters 4 cases of thyroid cancer were revealed and no members of this group were present in controls. An insignificantly increased risk of hemoblastoses, skin and brain cancer were also observed in this group. In the female stuff an insignificantly increased risk of all cancer sites combined was recorded in operational group (OR 1.28; 95 % CI 0.58–2.87) and nurses (OR 1.21; 95 % CI 0.85–1.72), as well as in the female stuff of experimental scientific units (OR 1.31; 95 % CI 0.90–1.92). An insignificant increase in breast cancer risk was observed in women clinicians and experimenters, exposed to the occupational factors. Female employees of experimental scientific units demonstrated a statistically significant increased risk of digestive organs cancer (OR 2.95; 95 % CI 1.14–7.67) and hemoblastoses (OR 5.71; 95 % CI 1.05–31.07). The results of the study demonstrate the need for epidemiological monitoring and data accumulation on cancer risk in different groups of medical workers.