Цель исследования. Изучить влияние эндопротезирования с применением имплантатов из никелида титана на течение процессов заживления раневой поверхности после удаления опухолей полости носа и околоносовых пазух и возможность управления последними. Материалы и методы. В исследование вошли 60 пациентов, получавших комбинированное лечение по поводу злокачественных опухолей полости носа и придаточных пазух Т3-4N0-1M0 в НИИ онкологии г. Томска с 2002 по 2021 гг. включительно. Все пациенты были подразделены на 3 группы в соответствии с видом имплантатов из никелида титана, которые использовались для восстановления стенок глазницы. Для купирования воспалительных изменений в послеоперационной полости, пациентам 1 и 2 групп проводилась магнитолазерная терапия с применением комбинированной установки «Милта-Ф». С целью определения влияния разных типов имплантатов на заживление раневой поверхности проводилось динамическое эндоскопическое наблюдение за послеоперационной полостью с забором материала на цитологическое и гистологическое исследование. Оценка эффективности проводимых реабилитационных мероприятий основывалась на данных клинических наблюдений за раневой поверхностью, изучения особенностей течения репаративных процессов и выявления осложнений, а также на основании изменений местного иммунитета на уровне цитокинового звена. Результаты исследования. В ходе исследования была установлена прямая взаимосвязь между структурой имплантата и количеством осложнений эндопротезирования. Наибольшее количество осложнений было выявлено при использовании пористых имплантатов (33 %). Применение тканевых имплантатов позволило снизить количество осложнений до 26 %. Наиболее хорошие результаты удалось достигнуть при использовании третьего вида имплантатов — тонкопрофильных имлантатов из никелида титана с памятью формы (6 %). Помимо этого, было установлено, что применение магнитолазерной терапии в послеоперационном периоде способствовало активизации факторов неспецифической защиты и оказывало положительное влияние на иммунный статус в области раневой поверхности.

Цель исследования. Изучить влияние эндопротезирования с применением имплантатов из никелида титана на течение процессов заживления раневой поверхности после удаления опухолей полости носа и околоносовых пазух и возможность управления последними.Материалы и методы. В исследование вошли 60 пациентов, получавших комбинированное лечение по поводу злокачественных опухолей полости носа и придаточных пазух Т3-4N0-1M0 в НИИ онкологии г. Томска с 2002 по 2021 гг. включительно. Все пациенты были подразделены на 3 группы в соответствии с видом имплантатов из никелида титана, которые использовались для восстановления стенок глазницы. Для купирования воспалительных изменений в послеоперационной полости, пациентам 1 и 2 групп проводилась магнитолазерная терапия с применением комбинированной установки «Милта-Ф». С целью определения влияния разных типов имплантатов на заживление раневой поверхности проводилось динамическое эндоскопическое наблюдение за послеоперационной полостью с забором материала на цитологическое и гистологическое исследование. Оценка эффективности проводимых реабилитационных мероприятий основывалась на данных клинических наблюдений за раневой поверхностью, изучения особенностей течения репаративных процессов и выявления осложнений, а также на основании изменений местного иммунитета на уровне цитокинового звена.Результаты исследования. В ходе исследования была установлена прямая взаимосвязь между структурой имплантата и количеством осложнений эндопротезирования. Наибольшее количество осложнений было выявлено при использовании пористых имплантатов (33 %). Применение тканевых имплантатов позволило снизить количество осложнений до 26 %. Наиболее хорошие результаты удалось достигнуть при использовании третьего вида имплантатов — тонкопрофильных имлантатов из никелида титана с памятью формы (6 %). Помимо этого, было установлено, что применение магнитолазерной терапии в послеоперационном периоде способствовало активизации факторов неспецифической защиты и оказывало положительное влияние на иммунный статус в области раневой поверхности.

Cirkuliruyushchie monocity — znachimye uchastniki patogeneza opuholevogo rosta. Pokazano, chto v krovi bol'nyh rakom molochnoj zhelezy nablyudayutsya osobennosti populyacij monocitov, ekspressiruyushchih receptory endocitoza, libo komponentov glavnogo kompleksa gistosovmestimosti. Cel'yu dannoj raboty bylo provedenie analiza vzaimosvyazi parametrov opuholi i citokinovogo profilya krovi s populyacionnym sostavom cirkuliruyushchih monocitov bol'nyh lokalizovannymi i mestno-rasprostranennymi formami raka molochnoj zhelezy. V issledovanii bylo pokazano, chto fenotipicheskie harakteristiki cirkuliruyushchih monocitov vzaimosvyazany s kliniko-morfologicheskimi osobennostyami opuholevogo processa. Soderzhanie populyacij s fenotipom CD14+CD16++CD163+ i CD14++CD16+CD163+ imelo polozhitel'nuyu korrelyaciyu so stadiej zabolevaniya, v to vremya kak bol'shij razmer pervichnogo opuholevogo uzla associirovan s bolee nizkim soderzhaniem CD14+CD16++-monocitov. U bol'nyh RMZH uvelicheno soderzhanie IL8 i MSR-1 v syvorotke krovi. Vysokij uroven' soderzhaniya IL6 u bol'nyh RMZH associirovan so snizheniem doli CD14++CD16-HLADR+ monocitov, CD14+CD16++HLA-DR+-monocitov i CD14++CD16-SD163+-monocitov. Takim obrazom, CD163+ i HLA-DR+-monocity svyazany s klinikomorfologicheskimi parametrami i urovnem citokinov krovi, chto svidetel'stvuet o vovlechenii dannyh populyacij v progressiyu raka molochnoj zhelezy i govorit o celesoobraznosti dal'nejshih issledovanij dlya translyacii poluchennyh rezul'tatov v klinicheskuyu praktiku.

Children obesity is becoming global and causing dysregulation throughout the immune system, affecting the balance and levels of cytokines and adipokines. The purpose of this research was to study the amount of CD14+CD163+ blood monocytes in obese children compared to practically healthy children of normal body weight (BW). Materials and methods used: 70 children aged 9 to 15 y/o were included in a cross-sectional single-center comparative study in parallel groups from Feb. to Nov., 2022. The main group consisted of 60 obese children aged 11.95 (9.45; 14.45) y/o, 43% boys/57% girls. The control group consisted of 10 children without signs of obesity aged 10.4 (9.3; 13.8) y/o, 40% boys/60% girls. The amount of CD14+CD163+ monocytes in peripheral blood was assessed using CytoFLEX platform flow cytometer. All participants have undergone bioimpedance measurement of adipose tissue parameters using InBody 770 body composition analyzer. Results: a statistically significant increase in the amount of CD14+CD163+ blood monocytes was connected with an increase in the obesity class (p=0.010) in children. Thus, in the 2nd and the 3rd obesity classes, an increase in the amount of blood monocytes was noted by 2.8 and 2.6 times, respectively, compared to the children with normal BW (p<0.05). There was also an increase in the amount of CD14+CD163+ monocytes in children with allergic diseases coupled with obesity - by 2.68 times compared to the children without this pathology (p=0.003). Conclusion: the connection between the amount of CD14+CD163+ peripheral blood monocytes, the obesity in children and the development of concomitant pathology was found. Therefore, reprogramming of blood monocytes would probably cause metabolic changes associated with obesity, which in its turn triggers various pathological processes. The results obtained are of a great practical importance for the purposes of treatment correction and undoubtedly require the continuation of the research in the field.

Background . Endometrial cancer (EC) is one of the most significant oncogynecological problems. The main mortality cause in this disease, as in the case of other malignant neoplasms, is the tumor progression. The presence of mutations associated with mismatch repair-deficient is of great prognostic importance. Immunotargeting therapy (ITT), lenvatinib in combination with pembrolizumab, seems to be the most effective solution in the second line treatment of advanced EC without microsatellite instability. At the same time, the group of such patients is heterogeneous in terms of progression-free survival (PFS) on ITT. So that it determines the continuing need to search for reliable parameters steadily associated with the PFS duration in this type of treatment. Aim . To analyze the clinical and morphological features in patients with advanced EC depending on the PFS duration on ITT. Materials and methods. The study included data on patients ( n = 36) with advanced EC who received ITT in oncological dispensaries in Siberia and the Russian Far East. The overall patients’ group was analyzed using the Kaplan-Meier method. PFS was defined as the time from the ITT initiation until progression or death against the background of treatment. The influence of the selected factors (clinical and morphological parameters, treatment features, and adverse events) on PFS was assessed using a log-rank criterion. The study participants were then divided into 2 subgroups (15 women and 9 women) according to median PFS. Mann–Whitney tests for independent samples (quantitative measures), and Fisher’s tests (qualitative measures) were used to identify significant differences in comparison subgroups for the selected factors. Differences were considered statistically significant when the significance level was reached ( p <0.05); data at the statistical trend level ( p <0.10) were also discussed. Results . In the study group, median PFS on ITT was 9.7 months (cut-off point), which was accepted as a response criterion. Among the 74 parameters reflecting clinical and morphological features in patients with advanced EC, metastatic lesions of pelvic lymph nodes ( p = 0.028), para-aortic lymph nodes ( p = 0.014), bone metastases ( p = 0.080), and degree of estrogen receptor expression in tumor cells ( p = 0.071) were associated with PFS. Partial regression as the maximal response to ITT (62.5 % vs 7.14 %, p = 0.011), as well as longer duration of response (median PFS 15.11 ± 1.10 months vs 4.47 ± 0.57 months, p = 0.00007), and the absence of foci in the pelvic/para-aortic lymph nodes (89 % vs 50 %, p = 0.069, and 89 % vs 47 %, p = 0.048, respectively), were more frequently observed in patients with a duration of median PFS ≥9.7 months compared to those with progression before 9.7 months. Stabilization as the maximum response to ITT (78.6 % vs 37.5 %, p = 0.072) was more frequently registered in the subgroup of patients with progression up to 9.7 months. Conclusion . ITT can be considered as a potentially promising therapeutic option in advanced EC. Further research in this direction should be aimed at finding criteria to identify patients with EC who would have most benefit from this type of therapy more accurately.

We previously exposed the role of actin-binding proteins (ABPs) in cancer development and progression. In this paper, we studied the relationship between circulating ABPs and the number of ABP-expressing leukocytes and circulating tumor cells (CTCs) in patients with highly aggressive laryngeal squamous cell carcinoma (LSCC). The levels of cofilin (CFL1), profilin (PFN1), ezrin (EZR), fascin (FSCN1), and adenylate cyclase-associated protein 1 (CAP1) were determined using enzyme immunoassay. The ABP expression by the cellular pools was analyzed by flow cytometry. The highest levels of FSCN1 and EZR were found in the blood serum of LSCC patients. There was a difference in ABP expression between the pools of leukocytes and CTCs. Leukocytes were mainly represented by CAP1+ and FSCN1+ pools, and CTCs contained CAP1+, FSCN1+, and EZR+ cells. The serum FSCN1 level correlated with the number of FSCN1-containing and CFL1-containing leukocytes. Thus, the level of circulating EZR is likely related to its expression in CTCs. The levels of CFL1 and PFN1 are likely to be supported by the expression of these proteins by leukocytes. Both CTCs and leukocytes can be a source of FSCN1 and CAP1 in blood serum. The results suggest that serum proteins can be produced by various cells, thus indicating both cancer development and the response of the immune system to this process.

The MYC and OCT4 genes are known factors associated with maintaining pluripotency and are linked with a more aggressive course, progression, and resistance to therapy in cancer. Determining the subpopulations of tumour cells expressing the Myc and Oct4 proteins will provide an opportunity to understand which tumour cell subpopulations expressing MYC and OCT4 are associated with metastasis and resistance and which subpopulations can be targeted by anti-MYC and anti-OCT4 therapy. The study included paraffin-embedded tissue from tumours from 27 patients with luminal B breast cancer obtained after neoadjuvant chemotherapy (NACT). Immunofluorescence staining was used to identify subpopulations of tumour cells expressing Myc, Oct4 and Snai2 (Opal™ 7-Color Kit (PerkinElmer, Hopkinton, MA). The following tumour cell subpopulations were identified with the Myc and Oct4 proteins and the Snai2 EMT marker: stem/progenitor tumour cells with/without Myc, Oct4 or Snai2 expression; differentiated tumour cells with/without Myc, Oct4 or Snai2 expression; and other nontumour cells (CK7−EpCAM−CD44+/−Myc+/−(Oct4, Snai2)+/−) within the inflammatory infiltrate in the tumour parenchyma and stroma. The circulating tumour cell subpopulations with Oct4 protein expression in the bloodstream were studied by flow cytometry. It was found that in patients with partial regression (PR) in response to NACT, the frequency of tumour stem cells was 3.6-fold increased (p = 0.038) in the non-EMT state (CK7+EpCam+CD44+Snai2−). In patients with metastases, there was a statistically significant 2.5-fold increase in the frequency of differentiated tumour cells with Myc expression (CK7+EpCam+CD44−Myc+) and a 2.7-fold increase in the frequency of cells with Oct4 expression (CK7+EpCam+CD44−OCT4+). In the next stage, the frequencies of subpopulations with expression of the Oct4 protein and signs of EMT among circulating tumour cells (CTCs) were determined. In patients with metastases, the frequency of tumour stem cells in the EMT state (CD326+CD44+CD24−CD325+) (p = 0.015) was more than fourfold increased, and the frequency of progenitor tumour cells with expression of the Oct4 stem protein (CD326+CD44+CD24+Oct4+) (p = 0.016) was almost sixfold higher than that in patients without metastases. Nonstem (differentiated) tumour cells with expression of the stemness proteins Myc and Oct4 were present in the breast tumour. Their content was significantly higher in residual tumours after NACT in patients who subsequently developed metastases compared with that in patients without metastases. Such cells are a new in situ marker of metastasis.

Interrelationship between a malignant tumor and the immunity are provided by the involvement of both adaptive and innate immune systems. Monocytes are major participants in nonspecific immune response and mediate their key function through refilling the pool of tumor-associated macrophages, dendritic cells and myeloid suppressor cells. All these populations regulate the relationship of tumor-infiltrating immunocompetent cells with tumor cells and with other components of the microenvironment, as well as tumor cell proliferation, angiogenesis, and dissemination. Monocytes, being direct participants of the chronic persistent inflammation, are involved in the inflammation impact on both tumor origin and progression. The study of the molecular mechanisms of monocyte recruitment and differentiation in malignant neoplasms seems to be a promising direction, both for a diagnostic purpose and as a search for targeting molecules for the control of macrophages and dendritic cells in the tumor microenvironment. In this review, the characteristics of peripheral blood monocytes are given, taking into account the heterogeneity of their population. Tie2+ cells and macrophage-polarized CD163+ and CD204+ -monocytes, as well as cancer-associated macrophage-like cells (CAMLs), are described as contributors to cancer disease progression and outcome. The involvement of monocyte subpopulations in the pathogenesis of oncological diseases of different localizations at the stages of the formation of monocyte precursors in the bone marrow, circulation in peripheral blood and differentiation in tumor tissue is shown.

According to the current paradigm proposed by Piter Novell [1], carcinogenesis is a process of clonal evolution in which consequent cycles of clonal selection in the adaptive tissue microenvironment give rise to tumors with a variety of genetic and other molecular changes determining the biological behavior of each individual tumor. Selection of clones with different properties provides heterogeneity of cancer cells within one tumor and thus results in a low effectiveness of chemotherapy.On the average, only 40–60% of cancer patients respond to chemotherapy, and even in the case of complete regression, there is a high probability of tumor recurrence [2, 3]. Increasing the effectiveness of solid tumor therapy and reducing the possibility of recurrence requires not only the use of optimal individual schemes of therapy for each patient, but also the development of combined approaches aimed at both the destruction of tumor cells and antitumor programming of the microenvironment, where immune cells plays a prominent regulatory role. The key cells of the immune system that determine the relationship between tumor cells and the microenvironment, from early stages of tumor growth, including the regulation of neoangiogenesis, and to terminal stage of dissemination of malignant process, are tumor-associated macrophages (TAM) [4– 6]. Identification of the pathways responsible for the tumor-supporting function of macrophages makes it possible to develop therapeutic approaches combining chemotherapy with the macrophage blocking strategy. Inhibition of macrophage infiltration into tumor, their removal with anti-macrophagal agents, and switching off the function of the macrophage colony-stimulating factor can be the macrophage blocking tools. Approaches of simultaneous alteration of cancer stem cells and TAM to abolish chemoresistance and inhibit tumor progression are promising. Strategies for reprogramming of macrophages to switch off towards the antitumor phenotype are developing.Thus, an extremely wide range of regulatory and effector activity and high functional plasticity of macrophages promise the development of macrophage-targeted therapeutic agents to modulate relationships between tumor and microenvironment to prevent the tumor progression.

A simple approach for isolation of exosomes from blood plasma samples has been proposed. Using this approach it is possible to obtain highly purified preparations of microvesicles no larger than 100 nm. The presence of different subpopulations of exosomes isolated by this method has been recognized in the blood plasma of healthy donors and cancer patients. Universal markers CD9, CD24, and CD81 are applicable for routine typing of exosomes isolated from blood plasma samples.

Tumor cells can maintain their growth via immunosuppression and escape from host antitumor immunity by controlling the PD-1/PD-L1 system. Expression of PD-L1 (CD274) is an inhibitory signal for T cells, while the increase in CD326 expression in the tumor tissue correlates with metastasis development. The experimental preparation on the basis of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronan from Acorus calamus L. produces an antitumor effect: it reduces tumor node size and the number and area of metastases after transplantation of Lewis lung carcinoma. Using flow cytometry, we demonstrated a decrease in the population of tumor cells expressing surface CD274 (PD-L1) and CD326 antigens after 20-day course of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronan.

Exosomes are extracellular membrane structures involved in many physiological and pathological processes including cancerogenesis and metastasis. The purpose of the study was to isolate, identify and analyze the total content of exosomes in biological fluids. The exosomes from the plasma and ascites samples of the patients with ovarian cancer, from the blood plasma of the patients with colorectal and head and neck squamous cell cancer as well as from the blood plasma of healthy donors were characterized using transmission electron microscopy and flow cytometry. The subpopulations of the exosomes in the biological fluids of the patients with different types of cancer were similar, but the protein concentrations of exosomes were different. In this paper we present the methodological approaches allowing us to obtain high quality exosome preparations from biological fluids.

The exosomes containing tumor-specific protein represent a valuable source of material for the non-invasive diagnosis of malignant neoplasms. The exosomes from plasma and cell-associated exosomes from blood of healthy women, the patients with mastopathy and breast cancer patients were studied with the nanoparticle tracking analysis, transmission electron microscopy, flow cytometry and protein profiling. The exposure of CD63, CD24, CD9, and CD81 demonstrates isolation of mainly exosomes. A major part of exosomes in the blood of healthy women, patients with mastopathy and breast cancer patients is shown to be associated with the surface of blood cells. The concentration of the exosomes in the plasma of the breast cancer patients is higher than in the healthy women's plasma. The proteins ranged from 10 to 250 kDa were found in the exosomes by gradient SDS PAAGE; 8 regions of electrophoregram differ between healthy and illness patients in the expression level and number of proteins. These proteins are planned to be identified by MALDI TOF and studied as potential breast cancer markers.

The comparative analysis of the efficacy of anesthetic management in 53 patients with operable rectal cancer was carried out. In the study group patients (n=29), preemptive thoracic epidural analgesia was used. In the control group, (n=24), anesthesia was induced with sevofluorane and fentanyl. Preemptive thoracic epidural analgesia provided a reliable blockade of nociceptors and neural pathways, normalized stress response and decreased the severity of the systemic inflammatory response by stimulating the production of antiinflammatory cytokines.

The model of streptozotocin-induced diabetes mellitus in C57Bl/6 mice was employed to study the role of precursors of insulin-producing β-cells, hematopoietic stem cells, and progenitor hematopoietic cells in inflammation. In addition to provoking hyperglycemia, streptozotocin elevated serum levels of IL-1β and hyaluronic acid, induced edema in the pancreatic insular tissue and its infiltration by inflammatory cells (neutrophils, lymphocytes, and macrophages) and fibroblasts. Inflammation in pancreatic islets was accompanied by necrotic processes and decreasing counts of multipotent progenitor β-cells (CD45 – , TER119 – , c-kit-1 – , and Flk-1 – ), oligopotent progenitor β-cells (CD45 – , TER119 – , CD133 + , and CD49f low ), and insulinproducing β-cells (Pdx1 + ). Pancreatic infl ammation was preceded by elevation of the number of short-term hematopoietic stem cells (Lin–Sca-1 + c-kit + CD34 + ) relative to long-term cells (Lin – Sca-1 + c-kit + CD34 – ) in the bone marrow as well as recruitment of hematopoietic stem and progenitor cells into circulation. Transplantation of bone marrow hematopoietic stem and progenitor cells from diabetic C57Bl/6 donor mice to recipient CBA mice with 5 - fluorouracilinduced leukopenia accelerated regeneration of granulocytopoiesis in recipient mice.

Experimental and clinical evidence suggests that the immune system when exposed to conventional cancer chemotherapy is involved in the antitumor effect. A study is conducted to assess the relationship between immunological parameters and effectiveness of neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients. The study included 269 patients with BC (T1–4N0–3M0) and 24 practically healthy comparable age women. The estimation of the subpopulation composition of blood mononuclear cells, their functional activity, apoptosis markers, allelic polymorphism of cytokine genes, depending on the presence or absence of clinical response to NAC was done. Complete tumor regression was associated with an increase in the number of cytotoxic CD8+-cells, high functional activity of lymphocytes (proliferation in response to mitogen, the secretion of cytokines TNFα, IL-1β and IL-10, IFN-γ) and neutrophils. Close relation of highly functional cytokine genotype and high cytokine secretion in blood cells with an objective clinical response to chemotherapy was revealed. Thus, the findings suggest that an objective clinical response to NAC is associated with structural and functional preservation of the immune system. Constitutive characteristics of the patient’s organism, responsible for the level of expression of pathogenetically relevant cytokines that play a key role in the functioning of the immune system are have important meaning.

Increasing the efficiency of antitumor therapy is one of major relevant tasks of oncology today. During recent years experimental evidence for active involvement of immune system in the regulation antitumor effects of cytostatic thereby has been obtained and theoretically justified. It was demonstrated that efficient cytostatic treatment is related to the cytotoxic activities of immune cells targeted against tumor cells. Such cytotoxic activities of immune cells are induced by radiotherapy or chemotherapy, where both innate and adaptive immune mechanisms are involved. However the disturbance in the functions of immune system can result in the impaired efficiency of cytostatic anti-tumor therapy. Cytotoxic agents can affect immune reactions by increasing the antigenic properties of tumor cells, facilitating their recognition of immune system, by stimulation of functional activation effector immune cells, elimination of immunosuppressive factors as well as systemic effects of antitumor therapy. A consideration of the crucial role of immune system in the providing of the efficiency of cytostatic antitumor therapy develops novel therapeutic approaches for treatment of malignant disorders based on balanced synergistic action of cytostatic agents and innovative immunomodulatory approaches.

И 53 Работа поддержана грантом Российского научного фонда №14-15-00350 «Молекулярный механизм действия регуляторных белков макрофагов второго типа на формирование опухолевого микроокружения