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Introduction. The article analyzes examples of procedures related to the implementation of anti-corruption standards, taking into account the specifi cs of offi cial relations, their administrative and intra-organizational nature. Theoretical analysis. The author reveals the problems of implementing anti-corruption standards. It is noted that in most cases the offi cial legislation provides that the conclusions drawn from the results of all inspections are not binding. The fi nal decision in relation to civil servants is made by the employer’s representative; the decision with regard to persons holding public positions is taken by the President of the Russian Federation; at the regional level, the heads of the constituent entities of the Russian Federation exercise control over compliance with anti-corruption standards. Empirical analysis. Currently, there is no specialized state anti-corruption body in the Russian Federation, but the need to create one is provided for by the UN Convention against Corruption. Results. The article concludes that the procedures for implementing anti-corruption standards in relation to persons holding public positions in the Russian Federation, as well as in relation to state and municipal employees, are essentially “internal” in nature. The constitutional and legal status of persons holding public offi ce requires monitoring their compliance with anti-corruption standards with the participation of various branches of government. To this end, a specialized anti-corruption body should be formed at the federal level in the Russian Federation, which may become an Interdepartmental Commission on Anti-Corruption.

Rationale: During neoplastic transformation, epithelial cells become mobile, which is one of the main mechanisms of metastatic disease and recurrence. Cell motility is regulated by actin-binding proteins, which ensure the association/dissociation of actin filaments and their interaction with the cell membrane. Previously, we have shown the presence of actin-binding proteins in the serum from patients with squamous cell carcinoma of the head and neck (HNSCC); however, their association with the development of metastases and relapses in cancer patients has not been sufficiently studied. Aim: To evaluate the serum levels of actin-binding proteins fascin-1 and ezrin in patients with HNSCC depending on the disease recurrence and lymphatic metastasis. Materials and methods: Serum fascin-1 and ezrin levels before combination therapy were measured with ELISA assay in 30 HNSCC (T1-4N0-2M0) patients (mean age 56 7 years). Results: The median fascin-1 level was significantly higher in the patients with lymphatic metastases, compared to those without metastases: 0.64 (0.40; 5.89) vs 6.35 (1.72; 8.35) ng/mL, respectively (p 0.001). At 12 to 36 months after combination therapy, the disease relapsed in 12 (40%) patients. Ezrin levels were significantly higher in the relapsed patients, compared to those without a relapse within 3 years after combination therapy: 2.55 (2.35; 2.75) vs 1.93 (1.87; 2.5) ng/mL (p = 0.02). The ROC analysis showed an association between fascin-1 serum levels with metastatic disease (AUC = 0.71, 95% confidence interval 0.570.85) and an association between ezrin levels and the disease relapse (AUC = 0.76, 95% confidence interval 0.570.94). Conclusion: These indicators can be used for the development of minimally invasive early detection of metastases in lymphatic nodes and for the prognosis of HNSCC recurrence.

Introduction. The relevance of the study is determined by the importance of the category “psychological safety” for the support of the life quality of modern people, which is influenced in a complicated way by physical health, psychological well-being, value preferences, features of social relations and their relation to the characteristic features of the environment. The state of psychological safety is a significant factor ensuring the effectiveness of еducation, upbrining and development of the younger generation. However, the personal resources that contribute to the support of this state among adolescents and young people in the educational environment are more understudied. The purpose of the article is to determine the resources of adolescents, which are the predictors of the state of psychological safety. Materials and Methods. The method “Psychological safety of the educational environmentˮ developed by I.А. Baeva was used to study students’ level of psychological safety. The method of S. Schwartz was used to assess the personality’s value orientations, to assess the level of psychological well-being – were used Ryff Scales of Psychological Well-Being (RPWB), the level of loneliness – UCLA Loneliness Scale (D. Russell, M. Ferguson), the level of hopelessness – Hopelessness Scale, Beck et al., the level of social intelligence – Tromsø Social Intelligence Scale, the level of aggression – Buss-Perry Aggression Questionnaire, hardiness – Hardiness Survey (S. Maddi). The methods of mathematical statistics used in the research (descriptive statistics, correlation and regression analyzes) are implemented by means of the IBM SPSS Statistics 19 package. Results. It has been proven that the resources of adolescents’ psychological safety in the educational environment are: values, psychological well-being, social intelligence, hardiness and a low level of aggressiveness. The state of psychological safety is influenced by such manifestations as conformity and following traditions, a positive image of the future, the experience of community with other people, the ability to understand and predict other people’s feelings and behavior, a sense of involvement in life events. Discussion and Conclusion. The article is of interest for researchers of psychological safety problems in education, practical psychologists and specialists of the education system for the evidence of prevention programs and ensuring the safety of the educational environment and its participants.

Der Aufsatz thematisiert das Verstehen fremdsprachiger Texte als eine der Schlüsselkompetenzen in der Germanisten-Ausbildung. Es wird sprachlichen Signalen nachgegangen, die der Text dem Rezipienten zur Verfügung stellt, um ihm den Zugang zu Textsinnen zu gewähren. Der zu untersuchende didaktisch angelegte Schwerpunkt ist für die Lehre von fremden Sprachen und Kulturen von großer Relevanz und besagt, dass Textverstehen im Fremdsprachenunterricht konsequent geschult werden soll. Im Aufsatz wird die interpretativ angelegte Herangehensweise an Texte mit impliziten Informationen zur Diskussion gestellt und das methodisch-didaktische Verfahren für Steuerung der rezeptiven Vorgänge im Deutschunterricht für Anfänger-vorgeschlagen. Eines solcher Zeichen, die verifizierbare Lesarten, von Studierenden aufgestellt, geltend macht, sind Sprichwörter als komplexe linguistische Entität und Träger kulturell relevanter Informationen. Am Beispiel der deutschen Volksmärchen in Bearbeitung von E. M. Arndt („Halt den Mittelweg!“), von den Brüdern Grimm („Der Nagel“) sowie von L. Bechstein („Bruder Sparer und Bruder Vertuer“) wird das textanalytische Verfahren vorgeführt, indem sich der Rezipient auf die in Märchen-Texte eingebetteten Sprichwörter in der Funktion des kognitiven “Schlüssels” stützt. Hierzu treten Sprichwörter als „Behälter“ soziokulturellen Wissens um ethische Normen und Wertvorstellungen auf. Im Bewusstsein des Rezipienten als mentale Einheiten gespeichert, werden die Sprichwörter vom ihm auf der formal-grammatischen und lexikalisch-semantischen Ebene mit Propositionen des Märchens als einer belehrenden Gattung in Korrelation gebracht. Dadurch wird Studierenden der Zugang zu verschlüsselten Botschaften gebahnt. Die vorgenommene Untersuchung wurde anhand der Methode der linguistischen Analyse, der Content-Analyse, der analytisch-hermeneutischen Methode und der Methode unausgelesener Stichprobe bei der Datenerhebung durchgeführt. Im Aufsatz wird ein Verfahren der linguokognitiven Analyse des Märchens als Genre der Folklore mit moralisierendem Hintergrund vorgeschlagen. Des Weiteren folgen didaktische Empfehlungen zur Wahl der Märchen-Texte zwecks deren Interpretation unter Einbezug der Sprichwörter und mit besonderer Berücksichtigung des Sprachniveaus der Studierenden.

Background. The calpain proteolytic system plays an important role in the development of cancer. Detection of early cancer in the upper respiratory tract is often challenging, as symptoms are largely non-specific, and most cases are diagnosed at an advanced stage.Aim. To identify candidate markers of transition from premalignant lesions to invasive carcinoma, we studied mRNA expression levels of CAPN1 and CAPN2 and the total activity of calpains in the tumor tissues of patients with head and neck squamous cell carcinoma (HNSCC) and in the epithelial dysplasia-affected tissues of patients with chronic diseases of the upper respiratory tract.Materials and methods. The study included 32 patients with HNSCC (Т1-3N0-1М0) and 12 patients with chronic diseases of the upper respiratory system associated with epithelial dysplasia. The expression levels of CAPN1 and CAPN2 were assessed using real-time polymerase chain reaction (PCR). The calpain activity was determined by hydrolysis of the fluorogenic Suc-LLVY-AMC oligopeptide.Results. The mRNA expression levels of CAPN1 and CAPN2 were respectively 3 and 4 times higher in the tumor tissue of patients with HNSCC than in the tissue of patients with endothelial dysplasia in the upper respiratory tract. The level of calpain activity was 4.4 times higher in patients with HNSCC than in patients with epithelial dysplasia of different severity.Conclusion. The elevated mRNA expression levels of CAPN1 and CAPN2 and their activity in the tumor tissues of patients with HNSCC compared to patients with chronic respiratory diseases associated with epithelial dysplasia are likely to characterize a high potential for transition from precancerous lesion to cancer. To clarify the role of calpains in the carcinogenesis of HNSCC, further studies of intact tissues using animal models are required.

The ubiquitin-proteasome system (UPS) controls the activity, subcellular localization, and stability of many cellular proteins that affect cellular homeostasis by regulating multiple signaling cascades. The activity of this system is associated with the emergence and progression of oral squamous cell carcinoma, since specific proteolysis of most intracellular proteins involved in the pathogenesis of cancer is implemented by this system.The review article presents data on the characteristics of proteasomes and the process of substrate protein ubiquitination. The role of the ubiquitin-proteasome system in the pathogenesis of oral squamous cell carcinoma is shown, and the prospects of its use in precancerous diseases are described. The literature search was carried out in the search engines Medline, eLIBRARY, Scopus, The Cochrane Library, and RSCI.

The paper presents results of a study on the relationship between the level of students’ psychological security in educational environment and their social intelligence.The aim of the study was to redefine this relationship and to test the hypothesis that different levels of psychological security in educational environment are connected with changes in the level of social intelligence and its components that happen in adolescence and young age.The data was obtained on a sample of students of secondary-level vocational training organizations (n=2,789 subjects) aged 12—25 years (M=17.13), 71,89% males.The following techniques were used: “Psychological Safety of Educational Environment” by I.А.Baeva; “The Tromsø Social Intelligence Scale” (TSIS) by D.H.Silvera, M.Martinussen, T.I.Dahl; sociodemographic information questionnaire.The study revealed that the level of social intelligence was higher among the students with high levels of psychological security in educational environment (U=114,56; p≤0,001).Higher social intelligence levels are based on the ability to understand and predict other people’s behaviours and feelings (U=101,25; p≤0,001) as well as on social skills (U=97,74; p≤0,001), whereas social awareness levels are the same in environments with different levels of psychological security.

Introduction. Identification of persons with a high oncological risk to squamous cell carcinoma of the head and neck region is an urgent problem for the early diagnosis of this disease. The activity of circulating proteasomes can be a criterion for predicting the risk of the larynx and oral cavity cancers in patients with precancerous diseases of the upper respiratory and gastrointestinal tracts. The aim of the study is to investigate the chymotrypsin-like and caspase-like activities of circulating serum proteasomes depending on the localization of precancerous and neoplastic diseases of the larynx and oral cavity. Material and Methods. The study population consisted of 35 patients with histologically verified HNSCC (T1–3N0–3M0), 15 patients with chronic hyperplastic laryngitis (CHL) and oral leukoplakia, and 10 healthy volunteers who did not have chronic upper respiratory tract diseases in the acute stage. The median age of the patients was 53 ± 5.3 years. Results. An increase in the studied proteasome activities was found in the blood serum of patients with malignant tumors as compared with patients with chronic hyperplastic diseases associated with precancerous changes, as well as in the larynx and oral cavity cancers groups as compared with healthy donors. At the same time, depending on the localization of the pathological process, it was shown that only the chymotrypsin-like activity of the circulating pool of proteasomes significantly differs both in the groups of oral cancer leukoplakia, and in the groups of laryngeal cancer chronic hyperplastic laryngitis with dysplastic epithelial lesions. In addition, differences were found between chymotrypsin-like and caspase-like activities of circulating serum proteasomes in patients with chronic hyperplastic laryngitis with oral dysplasia and leukoplakia. Conclusion. The results obtained indicate that the determination of the CTp activity of the circulating pool of proteasomes can be used as a criterion for predicting the risk of the larynx and oral cavity cancers in patients with precancerous diseases of the larynx and oral cavity.

Introduction.The biological heterogeneity of chronic lymphocytic leukemia (CLL) is reflected in the rate of progression, the need for therapy, and the response to treatment. Analysis of prognostic factors contributes to improving the quality of treatment and rational distribution of healthcare resources.Materials and methods. Among 890 patients with documented stage of CLL, 405 (45.5 %) received treatment. As the first-line of treatment, 173 patients received intensive regimens (FCR or BR), 6 – new agents, and 226 – all other regimens. The initial stage of the disease, mutation status of IGHV, del17p with or without complex karyotype were analyzed as prognostic markers.Results. Immunochemotherapeutic regimens were shown to be highly effective in case planned amount of treatment was completed. The combination of such prognostic parameters as the initial stage of the disease, the mutation status of IGHV, and the presence of del17p and/or complex karyotype allows us to clearly identify a group of patients with an unfavorable prognosis, for which it is advisable to use either intensive programs or new agents in the first-line therapy.

The article analyses the relation between psychological security (PS) and values in adolescent and young age. The value-semantic sphere of an individual determines his or her social behavior, and the strategic task of the education system is to create such educational environment that would promote the development of personal potential in students. The aim of the study is to identify the features and characteristics of students’ personal values in adolescence and young age depending on the level of their PS. The hypothesis was tested that the values of adolescents and young people with different levels of PS have different significance. The sample of the study consisted of 2789 first- year and second-year college students, aged 15-21 years. Significant differences in values at the level of normative ideals were found in groups with different levels of PS. There are also significant differences in the significance of values at the level of individual priorities which, in contrast to normative ideals, have a non-linear growth depending on the level of PS – the lowest values are observed in the group with an average level of PS. Values at the level of individual priorities in the group with a low level of PS are more significant than values at the level of normative ideals.

Analysis of cytokine profile markers in conjunction with the clinical manifestations of coronavirus disease 2019 (COVID-19) can provide valuable information about the pathogenetic manifestations of the disease, and therefore, in the future, determine drugs that affect the cytokine storm and have an anti-inflammatory effect.Aim. To identify correlations between the parameters of the developed cytokine profile and the clinical course in hospitalized patients with COVID-19 of different severity.Material and methods. The study included 70 hospitalized patients with a confirmed diagnosis of COVID-19, with a mean age of 58 [50;69] years, including 40 men (57%) and 30 women (43%). The average lung involvement according to computed tomography (CT) at admission was CT-2 [1;3]. Peripheral venous blood was taken at admission, which averaged 7 [6; 8] days from the symptom onset. Standard biochemical parameters were studied, as well as 47 cytokines and chemokines using the Multiplex system (Merck KGaA, Darmstadt, Germany).Results. Correlations was found between the lung involvement degree and the level of IL-8 (r=0,31, p

Introduction. Proteins associated with cellular motility are known to play an important role in invasion and metastasis of cancer, however there is no evidence of their association with the development of malignant tumors including endometrial cancer (EC).The aim of the present study was to investigate the levels of actin-binding proteins, p45-Ser-β-catenin, and calpain activity in endometrial hyperplasia and in EC.Material and Methods. Total calpain activity, p45-Ser β-catenin, Arp3, gelsolin, cofillin and thymosin β-4 levels were evaluated in 43 postmenopausal patients with stage I–II endometrioid EC and 40 endometrial hyperplasia patients. Flow cytometry and Western blotting were used for expression determination of p45 Ser β-catenin and actin-biding proteins. Total calpain activity was estimated by fluorimetric method.Results. Levels of cofilin-1, thymosin β-4 and calpain activity were higher in cancer tissues than in endometrial hyperplasia. Cofilin-1 and thymosin β-4 levels were associated with the depth of myometrial invasion. The thymosin β-4 expression was correlated with the presence of tumor cervical invasion. Revealed correlations between the actin-binding proteins, p45-Ser-β-catenin and total calpain activity in endometrial hyperplasia tissue, but not in the tissue of cancer, is evidence of the involvement of these proteases in regulation of cell migration in endometrial hyperplasia. Levels of thymosin β-4, cofilin and total calpain activity are independent cancer risk factors in patients with endometrial hyperplasia.Conclusion. The level of actin-binding proteins as well as the total calpain activity were enhanced in endometrium carcinoma tissues compared to endometrial hyperplasia. The levels of thymosinβ-4, cofilin and total calpain activity in endometrial hyperplasia tissues are associated with a hyperplasia transition to cancer and may be considered as predictive biomarkers.

High aggressiveness of laryngeal and hypopharyngeal squamous cell carcinomas dictates the necessity of studying the molecular mechanisms of metastasis. Cancer metastasis is associated with remodeling of the cytoskeleton, which is carried out by actin-binding proteins (ABPs). Currently, there is insufficient data on the feasibility of determining the level of circulating ASBs in lymphogenous metastasis of laryngeal cancer (LC). Material and Methods. Blood serum analysis was carried out in 42 LC patients and 15 healthy volunteers using ELISA kits on a microplate ELISA reader Multiskan FC 100 (ThermoFisher Scientific). Among ASBs, cofilin1 (CFL1), fascin1 (FSCN1), ezrin (EZR), profilin1 (PFN1), adenylyl cyclase associated protein 1 (CAP1) were studied. Statistical processing of the results was performed using the Statistica 6.0 software package. Results. It was shown that the serum level of CAP1 was significantly higher in patients with LC compared with the group of healthy volunteers (p=0.00). As the size of the primary tumor increased, the levels of FSCN1, CAP1 and PFN1 significantly increased. The level of FSCN1 was 10 times higher and the level of CAP1 was 40% higher in LC patients with metastases than in LC patients without metastases. Thus, among the studied ASBs, FSCN1, CAP1, and PFN1 play an important role in the pathogenesis of LC. Conclusion. The results of the serum level of ASB in LC were obtained for the first time, and they determine the fundamental basis for the development of new methods for predicting the development of metastases.

The purpose of the research is to study helminthofauna of Caucasian toad in vivo and in vitro. Materials and methods. Researches were conducted in vivo and in laboratory setting (Russian State Agrarian University – Moscow Timiryazev Agricultural Academy). Fecal from mature animals catching in six places in the north Caucasus and Transcaucasia during April–May 2012–2015 were investigated. Specimen of animals contained in laboratory during 1–4 years after catching and born in vitro have also be analyzed. Method of sequential irrigation was used for detachment helminths and their ootids. Died animals were anatomized according to Skryabin's method. Total 200 fecal samples of bufo in vivo and 150 samples of animals from laboratory have been studied.Results and discussion. Results and discussion. Eggs and adult proboscis worms of four species have been found in fecal of Caucasian toad: Acanthocephalus falcatus (Froelich, 1789), A. ranae (Schrank, 1788), Pseudoacanthocephalus bufonis (Shipley, 1903) и P. caucasicus (Petrochenko, 1953). Eggs of P. caucasicus were found in fecal masses of laboratory animals even in 4 years after catching. Helminths were not found in fecal of animals which were born in laboratory. Worms of four species were found in the process of helminthological autopsy of eight died species of Bufo caucasicus: Aplectana acuminata (Schrank, 1788), Cosmocerca commutata (Diesing, 1851), Oswaldocruzia filiformis Goeze 1782, Rhabdias bufonis (Schrank, 1788).

Autophagy is an important intracellular process that supports cell death and survival. Oncogenesis is associated with a change in the AKT/mTOR signaling pathway status. At the same time, the existence of protective autophagy, as one of the mechanisms of disease progression and the formation of resistance to treatment, has been proven. The review describes the significant mechanisms of the autophagy development, its association with AKT/mTOR signaling pathway. A molecule mTOR in TORC1 complex is associated with the oncogenesis, it provides the proliferation of transformed cells, apoptosis inhibition, and to the development of autophagy. The participation of this phenomenon at all stages of carcinogenesis, influencing on the main signal kinases: AKT, mTOR, is noted. It is shown that in most cases this mechanism is responsible for the progression of the disease and the development of resistance to treatment. The development of thyroid cancer associated with the BRAF mutation and with the activation of the RET oncoprotein, as well as with the formation of radio-resistant forms of the disease is associated with molecular peculiarities of autophagy. Given the inconsistency of this phenomenon regarding their influence on the processes of oncogenesis, its role in the development of thyroid cancer is still unknown.

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.

The use of time series of satellite images allows us to trace the dynamics in the processes of reforestation and forest formation. We estimated the use of the results of cluster analysis of the pixel distribution in the monitoring of post-fire forest restoration. We processed multispectral mid-resolution satellite images (and their fragments) of Landsat 8, Landsat TM/ЕТМ+, Landsat MSS taken in 1973–2016 using the following cluster analysis tools: unmanaged ISODATA classification and thematic difference. The thematic difference was calculated between the results of classifying data into two, four, six, and ten classes. We demonstrated that the post-fire forest restoration takes place in different burned areas with different wildfire intensity. It also depends on the proportion of post-fire wastelands. For example, greater areas of post-fire disturbance have been noted in conditions of a larger proportion of post-fire wastelands. In severely fire-damaged areas, the post-fire vegetation restoration was more intense than in slightly fire-damaged. We calculated the index characterising the forest cover in burned areas. We demonstrated its increase over the time. We considered the relationship between the change in the index characterising the forest cover over the time and the thematic difference of pixels.

The expected effect of androgen-deprivation therapy is one of the important criteria when choosing therapy in patients with prostate cancer. No less significant factor is the time of its implementation. The study showed that high expression of androgen receptors (AR) in the tumor tissue against the background of low estrogen receptor α (ERα) expression is characteristic of patients in whom the effect of androgen-deprivation therapy was observed for 12 months. A set of parameters has been identified that makes it possible to predict the duration of response to androgen-deprivation therapy in patients with prostate cancer, which include the patient’s age, testosterone level, prostate specific antigen, expression level of AR, ERα. These data allow us to consider these parameters as additional informative markers, to predict not only the expected effect, but also its duration.

Тhe protein TRIM16 is involved in key intracellular processes, such as proliferation, cell differentiation and programmed death, including intrinsic and extrinsic apoptosis, autophagy-dependent cell death and immunogenic cell death. The TRIM16 protein acts the proteins TPD43, Gli-1, RARβ, Snail components and MAPK signaling pathway, cadherins, caspases and is also associated with the regulation of the immune system via direct and indirect mechanisms. The influence of TRIM16 protein on the pathogenesis of hormone-dependent tumors is well-known. Further study of the TRIM16 role in the development and progression of malignant neoplasms will form the basis for the development of new methods for predicting the course of the malignant process.

The objective is to evaluate the level of ADAM10 and ADAM17 (a disintegrin and metalloproteinase) proteases, as well as 20S-proteasomes in blood plasma exosomes of patients with colorectal cancer.Materials and methods. The study included 60 patients with colorectal cancer (T2–4N0–2M0–1) and 10 control patients. The material for the study was EDTA blood plasma. Exosomes of blood plasma were isolated by ultrafiltration with ultracentrifugation. The level of tetraspanin-associated (ADAM10 and ADAM17) and tetraspanin-non-associated (20S-proteasome) proteases was evaluated by flow cytometry and Western blotting.Results. A twice negative subpopulation (ADAM10–/ADAM17–) predominated in blood plasma exosomes of colorectal cancer patients and control patients. The level of ADAM10+/ADAM17– exosomes was significantly higher in the exosomes of the plasma of control patients. There were no significant differences between the ADAM10/ADAM17 subpopulations and the 20S-proteasome level, depending on sex, age and tumor grade. A decrease in the ADAM10+/ADAM17– subpopulation was found in patients with metastatic colorectal cancer with hematogenous metastases compared with patients with T2–4N1–2M0 and 20S-proteasome compared to T2–4N0M0. A decrease in ADAM10–/ ADAM17+ exosomes and 20S-proteasomes level was found in exosomes of patients with colorectal cancer with a metabolic syndrome in comparison with patients without metabolic disorders.

Background . Using modern first-line chemotherapy more than 80 % of patients with classical Hodgkin’s lymphoma can be cured, however, in 15–20 % of cases there is a relapsed/refractory disease. The use of nivolumab in international clinical practice has significantly improved treatment results of patients with relapsed/refractory classical Hodgkin’s lymphoma.Objective of this study is to evaluate the results of therapy with nivolumab in the сlinic of Pavlov First Saint Petersburg State Medical University.Materials and methods . The retrospective analysis included treatment results of 101 patients with relapsed/refractory classical Hodgkin’s lymphoma who received nivolumab in Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation from February 2016 to August 2018. The group included 90 patients who received nivolumab as part of an named patient program. Therapy response was assessed using CT/PET-CT in accordance with LYRIC criteria for response assessment of malignant lymphomas to immunotherapy. Safety and tolerability were assessed by registering adverse events in accordance with NCI CTCAE version 4.03 criteria. Results . Median follow-up was 25 months. The response was registered in 64 % of patients: in 32 (31.6 %) – complete response and in 33 (32.7 %) – partial response. Stabilization and progression as the best response were registered in 5 (4.9 %) and 10 (9.8 %) patients, respectively. Indeterminate response was observed in 21 (20.6 %) patients. The 2-year overall survival was 96 %; the median of overall survival was not achieved. Progression-free survival (PFS) in studied patients was 40.6 %. The median of PFS was 17.9 months. There were no significant differences in PFS between patients with a partial and indeterminate response. Adverse events were reported in 87.1 % of patients. Severe adverse events (III–IV grade) occur in 18.8 % of patients.Conclusion . The results of a retrospective study of nivolumab therapy in Russian patients with relapsed/refractory classical Hodgkin’s lymphoma are consistent with published international data. Nivolumab demonstrates high efficacy as a monotherapy for relapsed/refractory classical Hodgkin’s lymphoma, regardless of previous therapy type and duration with well tolerance. Pseudo-progression phenomena during immunotherapy require revision of the traditional Hodgkin’s lymphoma therapy response criteria.

The article presents results of research of dynamics of morphological, biochemical, haematological and immunological parameters when changing the quantity and species of microorganisms of intestinal microbiocenosis of the rabbits. With the dominance of pathogenic bacteria in rabbit intestinal microbiocenoses, the titer of bifidumbacteria was 10-5-10-4, a decrease in the number of lactobacilli, an increase in the number of enterobacteria, a correlation between the colonization index and the degree of adhesion of bacteria was revealed; an increase in the total number of leukocytes, lymphocytes, erythrocytes, hematocrit, alanine aminotransferase level, aspartate aminotransferase, lactate dehydrogenase, total bilirubin, α-amylase, albumin, alkaline phosphatase, T-killer level, NK cells, concentration of C-reactive protein. We observed a decrease in the concentration of hemoglobin, monocytes, total protein level, T-lymphocytes, T-helpers, B-lymphocytes, phagocytic index, phagocytic activity of leukocytes, NST-spontaneous, NST-stimulated. Dynamics of morphological indicators was characterized by a disorder of the circulation of organs, a predominance of dystrophic and necrotic processes in the tissues and organs of the cardiovascular, respiratory, digestive, excretory system. Infiltration with mononuclear and segmented leukocytes was noted, diffuse lymphoid proliferation of the mucous membranes of the organs, hyperemia, edema, multiple hemorrhages, accumulation of hemorrhagic exudate in the lumen of the respiratory, digestive and urogenital tracts. Observed catarrhal-hemorrhagic inflammation of the gastrointestinal tract; mucous membrane of the stomach, small and large intestines edematic, hyperemic, with hemorrhages, covered with mucus, fibrinous films, with necrotic areas. The signs of acute diffuse interstitial nephritis, characterized by proliferation of connective tissue cells with a predominance of lipoblast and epithelioid cells, are revealed. In the presence of bacterial cells in the lumen of the tubules, the parenchyma of the cortical and medullar layers was marked by microabscesses. Accidental transformation of the thymus was observed, characterized by signs of a circulatory disorder, a decrease in the area of the cortex, the formation of cysts; signs of diffuse hyperplasia of the spleen with necrobiotic changes in the foci of proliferation, reduction of the area of lymphoid follicles, expansion of the area occupied by the red pulp of follicles, hyperplasia of follicles of white pulp with foci of necrosis. Identified multiple bacterial embolism of blood vessels, developed signs of hemorrhagic Diathesis, watched the development of sign infiltrative itch processes.

В статье представлено исследование традиционных гендерных стереотипов в тувинских паремиях и их оценке опрошенными респондентами — тувинцами. Использованы методы: интент-анализа с целью выявления интенций (скрытой направленности) пословиц и поговорок, шкала оценки гендерных стереотипов. Отобрано 75 пословиц и поговорок, содержащих описание мужского и женского поведения. Для последующей оценки и составления шкалы из них отобрано 45 паремий, отражающих гендерные стереотипы и социальное поведение мужчин и женщин. В июне 2018 г. опрошено 120 тувинцев обеих полов двух возрастных групп: от 18 до 35 лет, от 35 лет и старше. В паремиях тувинцев достаточно подробно отражено содержание и четко прослеживается скрытая направленность гендерных стереотипов. В паремиях отражены традиционные семейно-родовые отношения, основанные на патриархальных установках, регламентации гендерных различий и дихотомизации мужского и женского. В мужских стереотипах, отраженных в тувинских пословицах, скрыты интенции: «Восхваление», «Оценка», «Наставление», «Совет», «Поучение». Интенции женских стереотипов тувинцев: «Наставление», «Оценка», «Восхваление», «Поучение», «Обличение». Опрошенные тувинцы в целом согласны с традиционными представлениями о женском и мужском поведении и вполне допускают проявление сексизма в отношении к женщинам. Данные установки особенно выражены у мужчин и у людей старшего поколения. Существенных различий между половыми и возрастными выборками в оценке пословиц не обнаружено.

The aim of this investigation was to reveal the expression TRIM16, ERα, ERβ and AR in prostate cancer tissues compared to benign hyperplasia and clinical and morphological parameters.Materials and methods. Fifty patients with locally advanced prostate cancer with T2-3N0M0 and twenty patients with benign hyperplasia were included in the study. Prostate cancer patients were divided into subgroups according the Gleason score. Nine patients had Gleason score of 6, eighteen patients had 7 Gleason score, seven patients got 8 Gleason score and seven patients got 9 Gleason score. PSA level was from 4 to 100 ng/ml. TRIM16, ERα, ERβ and AR expression was determined by PCR in real time.Results. Increase of TRIM16 expression in prostate cancers was accompanied by high AR and ERα expression. The onco-suppressor ERβ was not changed in cancer tissues compared to benign hyperplasia. The Gleason score level was dependent on AR/ERβ relation. Associations between the PSA, AR, ERβ and TRIM16 were found in prostate cancersConclusion. Transcription factor TRIM16 participated in prostate cancer development. The connection between the ER and AR expression and clinical and morphological factors was found.

Introduction. The efficacy of anticancer treatment depends on biological factors of tumor.The aim of the study was to determine the activity of proteasomes and calpains and to reveal their association with VEGF, HIF-1α and NF-κΒ expressions in normal, primary and metastatic renal cell carcinoma (RCC) tissues.Methods. Ninety-three patients with renal cell carcinoma were included into the study. The expression levels of transcription factor and VEGF were measured using ELISA kits. The levels of proteasome subunits were measured by Western Blotting. Proteasome and calpain activities were determined using specific fluorogenic substrates.Results. We revealed inactivation of proteolysis in patients with kidney cancer. Disease advance was associated with a significant depression of cellular proteolysis and increase in transcription and growth factor levels in primary kidney cancer tissues. The proteolysis activation was found in metastatic tissues.Conclusions. Our results suggest that NF-κΒ, HIF-1α and VEGF transcription factors and intracellular proteolytic systems are involved in kidney cancer progression.

The objective of the study: to evaluate the possibility to enhance the clinical efficiency of treatment of pulmonary tuberculosis patients by adding bedaquiline to the fifth chemotherapy regimen.Subjects and methods. The presented results were obtained through dynamic follow-up and treatment of 68 respiratory tuberculosis patients, treated in St. Petersburg TB Dispensary from 2014 to 2016.Results. The clinical improvement manifested through relief of intoxication symptoms, normalization of blood count, reduction of infiltrate changes and healing of destruction. In a number of cases, relief of intoxication symptoms with reduction of bacillary excretion massiveness, infiltration and cavity sizes allowed preparing patients for the next stage of treatment – surgery.

Introduction. The transcription factor Brn-3α (product of the POU4F1) plays a significant role in carcinogenesis. The purpose of the study was to investigate Brn-3α, AR, ERα expressions in tissues of benign prostatic hyperplasia and prostate cancer as well as to determine their association with AKT/mTOR signaling pathway activation.Material and methods. The study included 30 patients with locally advanced prostate cancer and 15 patients with benign prostatic hyperplasia. The expression levels of Brn-3α, AR, ERα and the components of AKT/m-TOR signaling pathway were determined using RT-PCR assay.Results. Overexpression of Brn-3α in prostate cancer tissues was found to be associated with high level of ERα mRNA. High expression of AR was revealed in tissues of benign prostatic hyperplasia and prostate cancer. High expression levels of AKT, m-TOR and PTEN were observed in prostate cancer tissues. However, no significant changes in PTEN mRNA level were found in tissues of prostatic hyperplasia. Conclusion. Brn-3α transcription factor was associated with prostate cancer and accompanied with high expression levels of ERα, AKT and m-TOR.

The aim of the study was to evaluate the effect of nutrient restriction in combination with chemotherapy with methotrexate on the development of Lewis lung carcinoma (LLC) in mice.Material and methods. LLC cells were inoculated into the thigh of adult C57BL/6j mice. Mice fasted twice, for 2 days each, with a day interval. Methotrexate (MTX) was used alone and in combination with nutrient restriction. The drug was administered intraperitoneally at the maximally tolerated dose. Treatment efficacy was evaluated by the tumor growth inhibition (TGI), the level of inhibition of lung metastases (IM) and the kinetic tumor growth index (GI).Results. TGI was 34 %, 27 % and 46 % in mice with nutrient restriction alone, MTX alone and with combination of nutrient restriction and MTX, respectively. IM index was 90% and 70% in mice treated with MTX alone and in combination with nutrient restriction, respectively. There was no difference in IM index between mice subjected to restricted feeding and mice in the control group. GI was 0.7 in mice with nutrient restriction and combination of nutrient restriction and MTX. GI was 0.81 in mice treated with MTX monotherapy. The toxic effect of MTX was manifested by weight loss in mice. Weigh loss by 13% and 17% was observed in mice subjected to nutrient restriction alone and in combination with MTX, respectively.Conclusion. MTX inhibited cancer cell growth, however, the therapeutic effect of MTX was leveled by toxic effect on mice. Prolonged caloric restriction inhibited primary tumor growth. However, after returning to a normal diet, tumor growth resumed quickly. The use of MTX in combination with caloric restriction increased its anti-tumor effect on the primary tumor, decreased its toxic effect, but reduced its anti-metastatic activity by 20 %.

The article is devoted to results of the research of psychophysiological and adaptive characteristics of children and teenagers who constantly live in extreme weather conditions in the Far North. It was shown that children and teenagers living at high latitudes are characterized by higher sensorimotor reaction time in comparison to school children of middle latitudes. Results of the RRcardiointervalometry showed that for more than half of the children and teenagers the functional state of the nervous system characterized as “maximum permissible”. Tapping test showed prevalence of weak type of nervous system while the adaptation determined by a state of cardiovascular system was evaluated as satisfactory

To predict the development and clinical course of squamous cell head and neck carcinoma (SCHNC), we studied the level of protein phosphatase 1B (РРМ1В) using the proteomic analysis. Verification of the results of proteomic analysis by ELISA showed that the level of РРМ1В in blood serum of patients with SCHNC depended on the disease stage. The level of РРМ1В in the blood serum of patients with stage T1N0M0 cancer was higher than that observed in the control group and in patients with chronic hyperplastic laryngitis. In tumor tissue, the level of РРМ1В was associated with the size of the primary tumor and the presence of metastases. In tumor tissue, the level of РРМ1В was also higher in patients with stage T1N0M0 than in patients with chronic hyperplastic laryngitis. The data obtained indicate that the level of РРМ1В can be used for early detection and prediction of the clinical course of SCHNC. Further studies with larger cohorts of patients are required to evaluate the prognostic significance of the РРМ1В level.

The characteristics of calpain and proteasome systems in different molecular subtypes of breast cancer were studied. Tumor samples were obtained from 147 breast cancer patients, who were not previously treated with neoadjuvant therapy. Changes in the chymotrypsin-like proteasome activity and the correlation between proteasome and calpain activities were shown in different molecular subtypes of breast cancer. No changes in the calpain activity and proteasome subunits specific for various molecular subtypes of breast cancer were found. Our results show that the proteasome function undergoes changes depending on the receptor expression by tumor cells and this aspect should be further investigated.

Squamous cell carcinoma of head and neck (SCCHN) is often asymptomatic until it reaches the advanced stage. Currently, there are no available markers that can accurately predict the risk of progression of epithelial dysplasia to squamous cell carcinoma. The purpose of the study was to evaluate the feasibility of using the level of adenylyl cyclase-associated protein 1 (CAP-1) in the blood serum to identify groups of increased risk of cancer in patients with chronic laryngeal and hypopharyngeal hyperplasia associated with epithelial dysplasia. Material and methods. The blood serums from 45 patients with SCCHN (T1–4N0–3M0), 12 patients with chronic inflammatory laryngeal and hypopharyngeal diseases and 15 heath subjects were examined. The blood analysis was performed using the CAP1 ELISA kit (Cusabio) on the Biochrom Anthos 2020 Microplate IEA Reader. Results. The serum level of САР1 was higher by 75 % in patients with SCCHN (Т1N0M0) than in patients with chronic hyperplastic laryngitis. Moreover, differences in the serum level of САР1 were observed between healthy subjects and patients with chronic laryngeal hyperplasia. In SCCHN patients with regional metastases, CAP1 concentration in the blood serum was 2 times higher compared to that observed in SCCHN patients without regional metastases (p≤0.01). Conclusion. The study results showed the feasibility of using the level of CAP1 for distinguishing patients with chronic hyperplastic laryngitis from those with laryngeal cancer, as well as for early detection of SCCHN and the development of new method for prediction of disease.

Strains of microorganisms that have antagonistic and growth-stimulating activity (Pseudomonas sp., Bacillus sp., Bac. subtilis and Trichoderma harzianum) were added to the dark-gray soil of a forest nursery (Pogorelsky EEF) and to conifer seeds (Pinus sylvestris L., Larix sibirica L.). Pre-sowing seed treatments of Trichoderma harzianum, Bacillus sp., and Pseudomonas sp. strains increased Scots pine ground germination in 1.5–1.7 and Siberian larch – in 1.3–5.8 times; improved safety and quality of viable pine seedlings in the 1.4–11.0, larch – in 1.3–3.5 times in the end of the growing season, compared with the control. Morphometric parameters of the pine seedlings increased processing of Pseudomonas sp. and Bacillus subtilis, larch seedlings – Trichoderma harzianum and Bacillus sp. in 1.5–2.0 times (both). The pine and larch seeds bacterization, initially infected by Fusarium, reduced to 1.2–2.5 times the population of phytopathogen, which helped lower the death of coniferous seedlings. The biologically active microbial strains, which were introduced in the nursery soil, have increased and maintained the total number of microorganisms (ETGM) in conifer seedlings during the whole period of vegetation. It has had a positive effect of bacilli treatment (Bacillus sp. and Bac. subtilis) on the dynamics of microbial biomass content, the rate of basal respiration and microbial metabolic coefficient values (qCO2). In general, the introduction of spore bacteria (Bac. subtilis and Bacillus. sp.) and micromycetes (Trichoderma harzianum) populations with coniferous seeds increased the biogenetic and productivity of the nursery soil (MB, enzymatic activity, the ETGM number) to 1.5–3.0 times in comparison with the control and, despite of the high values of specific microbial respiration throughout the growing season, had a positive impact on the restoration of the ecophysiological functioning rule of soil microbial community.

The study was undertaken to analyse molecular markers associated with clinical response to preoperative chemotherapy in patients with muscle-invasive bladder cancer. the purpose of the study was to determine the relationship between the expression of transcription factors, vascular endothelial growth factor (VEGF), activity of proteasomes and calpaines in tumors and the response to neoadjuvant chemotherapy of patients with muscle-invasive bladder cancer. material and methods. The study included 50 patients with histologically verified transitional cell carcinoma of the bladder T2a–3bN0M0 (G2-G3). The levels of transcription and growth factors were determined by an immunoenzymatic assay. Proteasome activity was measured using the fluorometric method. results. Patients who achieved partial tumor regression demonstrated higher levels of VEGF and transcription factors (NF-κB and HIF-1), but lower levels of the 26S proteasome compared to those observed in patients with stable disease. Conclusion. Additional molecular markers that can be considered as predictors of response to neoadjuvant chemotherapy for bladder cancer were identified.

Life quality (LQ) is an integrated parameter of the health, applied for integral characterization of population health, and as the parameter of healthcare interventions effectiveness.Aim. To assess LQ in Russian population at the age 25-64 y. o. in general and in various socio-economical groups using EQ-5D, by the results of ESSE-RF (2012-2013) study.Material and methods. LQ was assessed on representative selections of inhabitants of 13 Russian Federation regions, aged 25-64 (males 8327, females 13497) with response 80%. LQ was assessed via international questionnaire EUROQOL — EQ-5D: 1) no decline; 2) mild decline; 3) significant decline; scoring also performed with visualanalogue scale (VAS). Integral LQ by EUROQOL performed with Shaw JW et al. method (ranging from 0,0 (death) to 1,0 (perfect health)).Result. EQ-5D index of Russian population was 0,87 with no gender difference. By the increase of the age LQ declines. Educational gradient of LQ was significant only in VAS (p

Aim. To assess rate of familiarity and specifics of treatment with statins among the citizens of economically active age with various cardiovascular risk by the data from epidemiological study ESSE-RF (Epidemiology of Cardiovascular Diseases in Different Russian Federation Regions). Material and methods. In the work the data from ESSE-RF study was used, of representative selection of non-organized male and female inhabitants aged 25-64 y.o. from 13 regions, investigated during 2012-2014. Responded ~80%. The study included questionning by standard scale that included data on the anamnesis, etc. Lipid profile, including total cholesterol (TC), cholesterol of lipoproteids low and high density were measured at SSRCPM and RSPCC.Results. Analysis of the whole selection showed that 20% of men and 32% of women knew their TC, and 13,6% and 18,2% were even familiar having increased level of TC. Part of those with high and very high risk was 31,3%, incl. men — 42,2%, women — 30,9%. Statins took ~7,0% of patients from this risk category. Effectiveness of treatment (target levels reached of low density cholesterol) in these groups of men and women was 14,4% and 4,8%, respectively.Conclusion. The data obtained in populational study points on insufficient knowledge and low rate of statin treatment of the persons with high and very high cardiovascular risk in RF, which confirms the anxiety provoking data of registries and other studies. The data dictates necessity of development and implementation of specific educational programs for citizens, of physician improvement and availability of cheap but effective lipid-lowering medications.

The purpose of the study was to evaluate the relationship between the levels of transcription factor, vascular endothelial growth factor (VEGF), serine/threonine-protein kinase (m-TOR), proteasome and calpain activities and the response to everolimus therapy in patients with disseminated renal cell carcinoma. Material and methods. The study included 18 patients with disseminated renal cell carcinoma. The expression of transcription and growth factors was studied using an immune enzymatic assay. Proteasome and calpain activities were evaluated using a fluorometric method. Results. Partial regression and stable disease were observed in 14 (78.8 %) of patients (tumor regression in 22.2 % of patients, stable disease in 56.6 % of patients). Disease progression occurred in 4 (22.2 %) of cases. The objective response to therapy with m-TOR inhibitor was observed in patients with high levels of NF-κB and HIF-1transcription factors, VEGF, VEGFR2 as well as with increased proteasome activity before treatment. Treatment response was also associated with low expression of phospho-m-TOR protein kinase. Conclusion. Additional predictive molecular markers of response to targeted therapy with evorolimus were revealed.

Aim of this study was to assess the possibility of using of the parameter of symmetry of pixel distribution in the forest condition monitoring. Multispectral satellite imagery and their fragments of high and medium resolution (Landsat TM/ЕТМ+, Aster, Spot, IRS), which have been made in 1995–2011, were processed in two stages. At the first stage, uncontrolled classification has been carried out using the method ISODATA (Iterative Self-Organizing Data Analysis Technigue). At the second stage, parameter of symmetry of pixel distribution was calculated. The results of classification were divided into two halves. Classes with lower optical density of the reflected light were concentrated in the upper half while classes with higher optical density of the reflected light were concentrated in the bottom half. The prospects for using the parameter symmetry of pixel distribution aim to assess the degree of forest disturbance after the fire impact was demonstrated. Disturbed forest areas a have larger sum of pixels in the bottom half of the classification results compared with the upper half. In contrast, undisturbed forest areas have a larger or equal sum of pixels in the upper half of the classification results compared with the bottom half. The prospects for using the parameter symmetry of pixel distribution in monitoring of seasonal changes of forest status were demonstrated. Comparison of two forest fragments with dominance of larch and Siberian pine showed that during the autumn months (September, October) after needle fall and leaf fall, there is a sharp decrease of the parameter "symmetry of pixel distribution" within the fragment with dominance of larch due to the increase of the proportion of pixels with high optical density. Seasonal changes in the parameter of symmetry of pixels distribution were less pronounced for the forest fragment with dominance of Siberian pine. We considered the prospect to use the parameter of symmetry of pixel distribution in the long-term monitoring of forest ecosystems status ( for example of the forest restoration process after fire impact). The rate of forest recovery was determined within the burned fragment with an area of 6.98 sq. km

The aim of the study was to investigate the NF-κB, HIF-1 and VEGF expressions and the proteasome and calpain activities in localized and disseminated kidney cancers.Material: The study included 87 patients with clear cell kidney cancer. Transcription factors and VEGF expression were measured by ELISA kits. Proteasome and calpain activity was determined using specific fluorogenic substrate.Results. The increase of NF-κB, HIF-1 expression in cancer tissues is associated with the development of hematogenic metastasis. Coefficient NF-κB р65/р50, referred to the level of active transcription factor forms, had the wave-like pattern and was increased in cancer tissues with single metastases and decreased in cancer tissues with multiple ones. The same trend of VEGF changes was revealed in kidney tissues. The low proteasome activity in metastatic cancer tissues was observed. The changes in calpain activity had the same dynamics as the expression of NF-κB and VEGF.Conclusion. The changes in NF-κB, HIF-1transcription factors, VEGF growth factor expressions and protease activities that could regulate their level, in localized and disseminated kidney cancer tissue were revealed. Coefficient NF-κB р65/р50, VEGF expression and proteases activities could be the potential prognostic molecular markers of hematogenic metastasis development in kidney cancer.

The role of circulating proteasomes (C-proteasomes) representing a multisubunit complex with several proteolytically active sites, and exosomes, which are extracellular vesicles providing intracellular and interstitial transfer of biologically important molecules (proteins and miRNAs) in the pathogenesis of ovarian cancer, has been described. Currently, there are prerequisites for further study of the role of C-proteasome and exosome not only as prognostic markers, but also as predictors of the effectiveness of neoadjuvant chemotherapy and optimal cytoreduction.

The role of growth factor receptors (insulin-like growth factor and transforming growth factor-beta) and adipokine receptors (leptin and adiponectin) in pathogenesis of endometrial cancer under conditions of metabolic syndrome is discussed. Cyclooxygenase-2 is an effector of signaling pathways activated by growth factors and cytokines. The detailed study of the mechanisms involving these proteins in pathogenesis of endometrial cancer in patients with metabolic syndrome and search for new biological prognostic markers appear to be promising.

The expression of matrix metalloproteinase (MMP) genes and activity of proteasomes and calpains were studied in patients with precancerous laryngeal lesions and laryngeal cancer. A significant increase in MMP-1 and MMp-14 gene expression was shown in laryngeal cancer tissue compared to that observed in dysplastic laryngeal tissue. Furthermore, the activity of proteasomes and calpains was significantly higher in laryngeal cancer tissue than in dysplastic laryngeal tissue. The results obtained indicate that extracellular and intracellular proteases play an important role in the development of laryngeal cancer. The detected features of pathogenesis of laryngeal dysplasia and laryngeal cancer will allow the additional objective criteria for predicting the risk for malignancy to be identified.

We compared the serum proteome profiles of squamous cell head and neck carcinoma patients with metastases, without metastases and healthy volunteers using the combination of gradient gel-electrophoresis (1D-SDS PAGE) and mass-spectrometry. The study showed the difference in the serum proteome between healthy volunteers and squamous cell head and neck carcinoma patients with metastases and without clinical evidence of disease progression. Proteins in the serum proteome of patients with squamous cell head and neck carcinoma that participate in various cellular processes can be suggested fur further study as potential markers of cancer progression.

The expression of motility-associated proteins in 18 patients with epithelial ovarian cancer was investigated. The study of actin-binding proteins (Arp3, gelsolin, cofilin-1 and thymosin-β4) and p45 Ser β-catenin revealed peculiarities of their expression with respect to clinicalmorphological parameters of ovarian cancer. Differences in cofilin expression with respect to histological type of the tumor were shown. The expression levels of Arp3, the most important protein of Arp2/3 actin-branching complex, and cofilin, which is able to break down actin filaments, were higher in peritoneal metastases than in omental metastases. It was found that the level of p45 Ser β-catenin and the percentage of cells expressing gelsolin and thymosin-4 were associated with pathological response to neoadjuvant chemotherapy (NACH) and were significantly higher in patients with complete and partial responses as compared to those observed in patients with no response. The obtained results can be used for identification of new prognostic factors, metastasis markers and predictive marker of pathological response after NACT.

The chymotrypsin-like and caspase-like proteasome activities were studied in tumor tissues of 74 patients with breast cancer (BC) NМin association with tumor size and lymph node involvement. Chymotrypsin-like and caspase-like proteasome activities were Т1-40-30 higher in breast cancer tissue than in adjacent tissues. We showed that advanced BC is accompanied by increase in chymotrypsin-like and caspase-like proteasome activities. In tumors with lymph node dissemination, proteasome activity was significantly decreased, which may have prospective prognostic value. Taken together, our data indicate an important role of intracellular proteolysis in BC progression.

The development of castration-resistant prostate cancer is an important problem of modern oncology. The review is focused on the system of growth factors – neuregulins and hepatocyte growth factor (HGF), direct pathligands of ErbB tyrosine protein kinases and hepatocyte growth factor receptor, c-Met, the activation of which triggers a cascade of signaling pathways, ending by the stimulation of proliferation of cancer cells, their migration under conditions of the development of tolerance to the treatment of castration.

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive disease with long asymptomatic course. New molecular prognostic markers are urgently needed to identify patients at high risk for developing lymph node metastasis. MicroRNAs (miRNAs) are a recently discovered class of small non-coding RNAs. Based on literature and our data, we have chosen 12 miRNAs (miRNA-21, -221, -222, -155, -205, -20a, -125b, -146b, -181b, -200a, -126, -451), involved in HNSCC carcinogenesis. Using real-time quantitative polymerase chain reaction analysis, we have shown a change in the expression miRNA in tumor tissue compared to unmodified tissue. Significant upregulation of five miRNAs: miRNA-21, -155, -181b, -126, -451 (p

Background. Search for more informative prognostic parameters in patients with renal cell carcinoma is an actual problem of modern oncology. Purpose: to study the prognostic significance of expression of transcription factors, VEGF growth factors, its receptors, m-TOR protein kinase and the activity of intracellular proteinases in patients with disseminated renal cell carcinoma. Material and methods. Forty patients with metastatic renal cell carcinoma (T3–4N0–1M1) were included into the study. In accordance with the MSKCC scale, all patients were divided into 3 groups: with good prognosis (n=13), intermediate (n=26) and unfavorable prognosis (n=1). Further, the analysis included patients with good and intermediate prognosis (n=39). All patients received targeted therapy with pazopanib or everolimus. Palliative nephrectomy was performed after completion of preoperative treatment. The level of transcription and growth factors was studied using IFA method. The proteasome and calpain activities were assayed fluorometrically. Results. Initially high levels of the expression of HIF-1 transcription factor and VEGF growth factor in renal cell carcinoma were associated with good disease prognosis evaluated according to the MSKCC scale. The targeted therapy with pazopanib/ everolimus resulted in decrease in the expression of HIF-1, NF-κB р65, NF-κB and р50 transcription factors, VEGF growth factor and the proteasome activity. The increased calpain activity in patients with intermediate prognosis was associated with disease progression. Conclusion. Additional molecular parameters that increase the informative value of the MSKCC scale were identified, allowing for more precise prediction of the disease outcome in patients with metastatic renal cell carcinoma.

This review presents the structure of the proteasome system, discusses its involvement in the pathogenesis of many cancers, including the process of metastasis. It describes the distinctive structural characteristics of intra- and extracellular pools of proteasomes, possible ways of their exit into the extracellular space and their forms of existence outside the cell. Also in the present review discusses the importance of circulating proteasomes for prognosis course of the cancer.