Development of metastasis is determined by both the accretion of essential changes in cancerous cells and by their communications with different stromal elements in the tumor microenvironment. Specifically, inflammatory response and emergence of immune regulatory cells, such and myeloid regulatory cells (macrophages, dendritic cells, neutrophils, myeloid-derived suppressor cells) and lymphoid regulatory cells (regulatory T, B and NK cells) to the tumor site have been reported to support tumor growth in addition to spreading and metastasis. Every phase of tumor progression, from its initiation through metastatic expansion, is endorsed by interaction between malignant and immune cells mediated by a number of growth factors, cytokines, proteases and other molecules that modify the tumor microenvironment. Invasion and metastasis depend on intratumoral vascularization, alterations of the basement membrane and degradation of the extracellular matrix for tumor cell spreading, invasion and extravasation into the blood and lymphatic vessels. The consequent dissemination of cancerous cells to distant tissues and organs necessitates a trafficking through the vasculature, which is promoted by further interactions with cells of the immune system, including myeloid regulatory cells. Moreover, the formation of the pre-metastatic niche and specific metastasis organ tropism is also regulated and controlled by bone marrow-derived hematopoietic immune progenitor cells, immature myeloid cells and certain cytokines, chemokines and growth factors derived from tumor and immune cells, which amend the local microenvironment of the organ or tissue to promote adhesion and survival of circulating cancerous cells. Although the potential role for myeloid regulatory cells in tumor spreading and development of pre-metastatic niche has been suggested, the concept still requires further supportive experimental and clinical data, as well as data related to specific factors and mechanisms responsible for myeloid regulatory cell functioning at malignant sites.

Aim. To study the epidemiological characteristics and changes of hypertension (HTN), as well as factors associated with HTN in the Russian population aged 35-74 years.Material and methods. The Epidemiology of Cardiovascular Diseases and their Risk Factors in Regions of Russian Federation-3 (ESSE-RF3) study examined a representative sample of the population aged 35-74 years of 15 Russian regions with a response >70% (n=28611). Modular design questionnaire was used. Blood pressure (BP) was measured twice after a 5-minute rest in a sitting position on the right arm with an Omron blood pressure monitor. There were following criteria for hypertension: systolic blood pressure (SBP) ≥140 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg, and/or antihypertensive therapy. The effectiveness of treatment was considered the proportion (%) of people who achieved target blood pressure values among those being treated, while the control was considered the proportion (%) of patients with a BP <140/90 mm Hg of the total number of hypertensive patients. HTN changes were studied in a single age range of 35-64 years with the inclusion of materials from the ESSE-RF (2012-14) and ESSE-RF2 (2017) studies, carried out using the same methodology as ESSE-RF3. Statistical analysis was carried out using the open-source R 3.6.1 environment. Analysis of the association between factors and a binary variable was performed using logistic regression. The significance level for all tested hypotheses was 0,05.Results. According to ESSE-RF3, the average levels of SBP and DBP in the population were 131,9±18,7 and 84,4±10,9 mm Hg, respectively, while the proportion of those with BP ≥140/90 mm Hg — 38,8% (men: 44,8%, women: 33,9%). Prevalence of hypertension was 53,9% (men: 56,0%, women: 52,1%), awareness — 77,7% (men: 71,5%, women: 82,3%), while the treatment received 63,4%, significantly higher among women than among men: 72,3 vs 53,3%. The effectiveness of treatment was 44,0%, higher among women compared to men (48,2 vs 37,4%). In addition, 27,9% of patients have controlled HTN.Conclusion. The problem of controlled HTN in Russia remains unresolved in the 21st century. The following significant sex differences remain: the prevalence of HTN is higher among men, but awareness of the disease, treatment rate and its effectiveness are lower compared to women.

The main concept of radiosensitization is making the tumor tissue more responsive to ionizing radiation, which leads to an increase in the potency of radiation therapy and allows for decreasing radiation dose and the concomitant side effects. Radiosensitization by metal oxide nanoparticles is widely discussed, but the range of mechanisms studied is not sufficiently codified and often does not reflect the ability of nanocarriers to have a specific impact on cells. This review is focused on the magnetic iron oxide nanoparticles while they occupied a special niche among the prospective radiosensitizers due to unique physicochemical characteristics and reactivity. We collected data about the possible molecular mechanisms underlying the radiosensitizing effects of iron oxide nanoparticles (IONPs) and the main approaches to increase their therapeutic efficacy by variable modifications.

Protumorigenic activity of immune regulatory cells has been proven to play a major role in precluding immunosurveillance and limiting the efficacy of anticancer therapies. Although several approaches have been offered to deplete myeloid‐derived suppressor cells (MDSC) and regulatory T cells, there are no data on how to control suppressive dendritic cell (DC) accumulation or function in the tumor environment. Although immunosuppressive function of DC in cancer was implicated to immature and plasmacytoid DC, details of how conventional DC (cDC) develop immunosuppressive properties remain less understood. Here, we show that the development of lung cancer in mice was associated with fast accumulation of regulatory DC (regDC) prior to the appearance of MDSC. Using the in vitro and in vivo approaches, we demonstrated that (i)both cDC and MDSC could be polarized into protumor regDC in the lung cancer environment; (ii) cDC → regDC polarization was mediated by the small Rho GTPase signaling, which could be controlled by noncytotoxic doses of paclitaxel; and (iii) prevention of regDC appearance increased the antitumor potential of DC vaccine in lung cancer. These findings not only bring new players to the family of myeloid regulatory cells and provide new targets for cancer therapy, but offer novel insights into the immunomodulatory capacity of chemotherapeutic agents used in low, noncytotoxic doses.

Nerve endings are often identified within solid tumors, but their impact on the tumor growth and progression remains poorly understood. Emerging data suggests that the central nervous system may affect cancer development and spreading via the hypothalamic-pituitary-adrenal axis and autonomous nervous system. However, the role of the afferent sensory neurons in tumor growth is unclear, except some reports on perineural invasion in prostate and pancreatic cancer and cancer-related pain syndrome. Here, we provide the results of primary testing of the concept that the interaction between melanoma cells and sensory neurons may induce the formation of tumor-supporting microenvironment via attraction of immune regulatory cells by the tumor-activated dorsal root ganglion (DRG) neurons. We report that despite DRG cells not directly up-regulating proliferation of melanoma cells in vitro, presence of DRG neurons allows tumors to grow significantly faster in vivo. This effect has been associated with increased production of chemokines by tumor-activated DRG neurons and attraction of myeloid-derived suppressor cells both in vitro and in vivo. These initial proof-of-concept results justify further investigations of the sensory (afferent) nervous system in the context of tumorigenesis and the local protumorigenic immunoenvironment.

Aim. To study the prevalence of dyslipidemias and their association with various risk factors in the Russian population of men and women aged 35-74 years in 2020-2022.Material and methods. This work was carried out as part of the Epidemiology of Cardiovascular Diseases and their Risk Factors in Regions of Russian Federation-3 (ESSE-RF3) study. The sample included 28731 men and women aged 35-74 years living in 15 Russian regions. Hypercholesterolemia (HC) was diagnosed with total cholesterol (TC) ≥5,0 mmol/l, while elevated low-density lipoprotein cholesterol (LDL-C) was considered ≥3,0 mmol/l, hypertriglyceridemia — with triglyceride levels ≥1,7 mmol/l, reduced high-density lipoprotein cholesterol (HDL-C) <1,0 mmol/l in men and <1,2 mmol/l in women. Associations were assessed using logistic regression after adjustment for socio-demographic characteristics, drinking status, presence of hypertension (HTN) and stroke.Results. The prevalence of hypertriglyceridemia in the Russian Federation in 2020-2022 was 58,8%, hypertriglyceridemia — 32,2%. The incidence of lipid-lowering therapy increased with age from 1% in the group of 35-44 years to 16% in the group of 65-74 years. On average, only 7,6% of study participants received lipid-lowering therapy. Significant associations of HC with HTN, obesity and alcohol abuse were identified. Similar results were obtained for elevated LDL-C levels, with the exception of alcohol abuse. In turn, a reduced HDL-C level was significantly associated with the lack of higher education, marriage, physical activity, smoking and the presence of diseases.Conclusion. The prevalence of lipid disorders in the Russian Federation in 2020-2022 remained at a high level. These disorders occurred more often in women, and they were better informed about their cholesterol levels and more often received lipid-lowering therapy. HTN, obesity, and some behavioral and social risk factors were associated with dyslipidemia.