The issue of the peculiarities of the course of the malignant process and the informative value of hematological parameters in patients with non-small cell lung cancer (LC) considering gender specific difference, upon COVID-19 before the beginning of antitumor treatment, has been poorly studied.

This paper proposes bioluminescent enzymatic assay of saliva as a non-invasive method for monitoring the functional state of the body. The value of luminescence intensity from coupled enzyme-based reaction catalyzed by NADH:FMN oxidoreductase and luciferase, when exposed to saliva, served as an indicator of the state of the body of workers at work. The absence of a significant difference between profiles of bioluminescence before and after the shift and no changes in biochemical, physical and chemical parameters of saliva indicated that the bodies had adapted to a workload. An increased bioluminescent intensity value is typical for workers in a state of chronic fatigue, a decreased one points to the presence of chronic diseases and bad habits. The dependence of the bioluminescent intensity value on the concentration of lactate, lipid peroxidation products, ionic and mineral composition, the values of free radical oxidation and antiradical protection was identified. Thus, the dependence of the saliva constituents on conditions of life and health status of workers can be identified using bioluminescent enzyme bioassay that is suitable for rapid monitoring of the body at work.

The aim of the study was to evaluate a prognostic significance of immunohistochemical parameters in serous ovarian carcinomas and their statistical relationships after neoadjuvant treatment to assess the development of tumor resistance to platinum-containing adjuvant polychemotherapy regimens. Material and Methods. An immunohistochemical study of tumor tissue was carried out in patients with high-grade serous ovarian cancer (stage IIIC–IV). The age of the patients ranged from 49–72 years. There were 59 patients who were sensitive and 22 patients who were resistant to platinum-containing adjuvant polychemotherapy. In the tissue of ovarian tumors obtained during surgery after noadjuvant polychemotherapy, we studied immunohistochemical indicators of proliferative activity (Ki67), expression of the DNA excision repair protein ERCC1 and proteins of the ABC transporter family – Pgp and BCRP, as well as statistical relationships between these indicators (Spearman’s rank correlation coefficient). Results. After effective neoadjuvant polychemotherapy, more pronounced signs of activity in the processes of proliferation, DNA repair and xenobiotic efflux were noted in serous ovarian carcinomas, which subsequently demonstrated resistance to platinum-containing polychemotherapy regimens compared to tumors that retained platinum sensitivity. Moreover, in 40 % of cases or more, there was a coincidence in the ranges of values of the studied parameters in tumors with different sensitivity to platinum drugs. The expression of transporter proteins greater than 60 % for BCRP and 65 % for Pgp was shown to precede the development of resistance to adjuvant treatment with carboplatin. In the studied groups, differences in the number and significance of statistical relationships between the variables were observed. The most significant differences were noted for the Ki67 – BCRP correlation, which had the opposite direction in groups with different sensitivity to adjuvant treatment with carboplatin. Conclusion. A comprehensive immunohistochemical analysis of highgrade serous ovarian carcinomas after neoadjuvant polychemotherapy, which further demonstrated different sensitivity to platinum-containing adjuvant regimens, was carried out, and the prognostic value of the studied parameters was assessed. The revealed critical levels of Pgp and BCRP expression in tumor tissue may have a prognostic value regarding the effect of adjuvant polychemotherapy. The results of the correlation analysis suggest a relationship between the development of platinum resistance and changes in the nature of the regulatory relationships between proliferative activity and transport processes in tumor tissue.

Purpose of the study. This study aimed to identify the characteristics of the course of cell lung cancer (LC) and the information content of the indicators of the adaptation status of patients of different sexes who had COVID‑19, confirmed by PCR diagnostic results before the start of antitumor treatment. Patients and methods. We have studied traditional clinical and laboratory parameters, and the white blood cell count in patients with non‑small cell LC st. I–III, men (59) and women (32) aged 36–75 years. The main groups included 32 men and 16 women who had COVID‑19, confirmed by real‑time PCR, 2–9 months before hospitalization. Patients in the control groups denied having a history of diagnosed COVID‑19. Before the start of antitumor treatment, the percentage of lymphocytes in the blood was assessed. Cases of LC progression and mortality within a year after antitumor treatment were noted. Results. In men of the main group a 2.7‑fold increase (p < 0.05) in cases of early lung cancer stagings with a simultaneous tendency towards an increase in the number of incidences of metastasizing and mortality within a year after inpatient treatment in comparison with control indexes were observed. Signs of disease severity worsening and a decrease in the effectiveness of treatment were observed without significant changes in the ratio of the patients with tumors of various stagings in female patients. In patients of the main groups, a disturbance of the correspondence between the percentage of lymphocytes and the prevalence and dynamics of the malignant process was noted. In men of the main group who died within the first year after the end of antitumor treatment, the percentage of lymphocytes before the start of treatment reached 28–45 %, corresponding to antistress adaptational reactions, 4 times more often than in the control group (p < 0.01) Conclusion. COVID‑19 flow before the start of LC treatment contributes to a decrease in the body's antitumor resistance and a violation of the informativeness of the percentage of blood lymphocytes as an indicator of adaptation status. Changes depend on sex. In women, the observed changes reflected an aggravation of the malignant process and systemic disorders, as well as a decrease in the effectiveness of treatment. In men, a sharp increase in the number of cases of one year mortality with high percentage of blood lymphocytes before the start of treatment, as well as the number of cases of early‑ stage LC, indicates a more significant change in the state of lymphocytes compared to that observed only in LC, as well as the possibility of acceleration of the transition of precancerous cells into malignant process in the lungs under the influence of a previous coronavirus infection.

At present, there is a primacy of molecular and genetic concepts on the mechanism of the appearance and development of cancer. Much less attention is paid to an attention and an understanding of the metabolic features of malignant cells as a result of transformation at the genetic level.

Purpose of the study. Is to determine the features in the content and activity of some components of the plasminogen activation system in the blood of patients of different ages with leiomyomas (LM) and uterine corpus endometrial cancer (UCEC).Patients and methods. The study was carried out in patients with LM (n = 35) and UCEC T1a-2N0M0 (n = 56) of reproductive, perimenopausal and postmenopausal ages. Using ELISA methods, the content and activity of urokinase (u-PA), tissue plasminogen activator (t-PA), their inhibitor PAI-1, as well as the content of the soluble form of the u-PA receptor (su-PAR) were determined in the blood of patients. The Student´s test was used for statistical processing.Results. Regardless of the nature of the uterus tumor, it has been noted a significant increase in the activity and blood level of PAI-1 (up to 8 times, p < 0.01), especially pronounced in patients with UCEC of reproductive age. It was combined with the absence of changes or with a decreasing in blood level of su-PAR by more than 40 % (p < 0.05). We observed a rise of u-PA blood level without changes in one´s activity in patients with LM of perimenopausal age. And in patients with LM and UCEC of postmenopausal age an increase in u-PA blood level as well as elevation of u-PA activity (up to 3.9 times, p < 0.01–0.05) were noted. There was an increase in the calculated t-PA index (activity per unit mass) by 1.4–2.8 times (p < 0.05) in the most patients. The indicators of LM patients were characterized by the minimum value of the ratio “t-PA activity/u-PA activity in the blood” among all studied subgroups of patients. Age-related features of the researched parameters were observed more often in the cases of LM than in the cases of UCEC. The most pronounced differences between LM and UCEC were observed in patients of reproductive and postmenopausal age, characterized by stable hormonal levels.Conclusion. The participation of the plasminogen activation system in the pathogenesis of tumor lesions of the uterine body has been shown. The system’s “response” to the development of tumors in the uterus has both general characteristics and features that depend on the nature of the tumors and on the age-specific hormonal regulation of the body, which are most pronounced in postmenopausal women. The results obtained can be used in research aimed at clarifying the targets of targeted therapy for LM and UCEC in accordance with the age of patients.

Morphological studies represent the most important part of evidence-based medicine, and in oncology they are an essential attribute in the diagnostics of malignant neoplasms. In experimental oncology, current models of the tumor growth are developed to be as close as possible to the actual biological life conditions. There is a need to study the pathogenesis of tumors in various variants of their orthotopic growth, the formation of bi-model systems with a combination of the malignant growth and comorbid conditions (chronic neurogenic pain, diabetes mellitus, hypothyroidism, obesity), the use of subcellular substrates for the induction of carcinogenesis and biotherapy. Among the important methods for studying the pathogenesis of tumors, morphology is on a par with advanced molecular genetic and biochemical methods, as well as radioimmunoassay techniques.Morphological studies represent the most important part of evidence-based medicine, and in oncology they are an essential attribute in the diagnostics of malignant neoplasms. In experimental oncology, current models of the tumor growth are developed to be as close as possible to the actual biological life conditions. There is a need to study the pathogenesis of tumors in various variants of their orthotopic growth, the formation of bi-model systems with a combination of the malignant growth and comorbid conditions (chronic neurogenic pain, diabetes mellitus, hypothyroidism, obesity), the use of subcellular substrates for the induction of carcinogenesis and biotherapy. Among the important methods for studying the pathogenesis of tumors, morphology is on a par with advanced molecular genetic and biochemical methods, as well as radioimmunoassay techniques.

Purpose of the study. Was to study the values and variability of traditionally determined blood parameters and index of the adaption status in intact mature Balb/c mice of different sex. Materials and methods. Studies were carried out on 20 animals of mature age with spf-status, males (10) and females (10). Cytological and biochemical parameters of blood and weight characteristics of the organs of the immune system and adrenal glands were studied (considering the constitutional features of mice of this line). Statistica 10.0 software package was used for statistical analysis. The coefficient of variation (CV) was determined. The significance of statistical differences was assessed using the Mann-Whitney test. Results. Sex differences were found in the ratio of albumins and globulins, the content of urea and alkaline phosphatase, the relative proportion of lymphocytes and monocytes in the blood count, the erythrocytes’ count and the level of hemoglobin in erythrocytes. There were also indicators which had values of severe variability (CV up to 51 %), the number of those in males was higher than in females. The information content of the weight characteristics of the studied organs is reduced due to the constitutional features of Balb/c females. The identified sex differences indicated a higher adaptive status of female rodents compared to males and let to propose the prevalence of different activity of T-cell, B-cell and myeloid line in animals of different sexes. Conclusion. The study of weak and moderate shifts in traditional laboratory parameters reflecting the adaptive status and characteristics of the blood of sexually mature males and females of the Balb/c line under physiological conditions made it possible to identify the sex characteristics of systemic regulatory processes that may be important for the body's resistance to malignant growth and the effectiveness of antitumor treatment. The current areas of further research are also indicated.

В рамках настоящего сообщения освещены современные научные проблемы, связанные с влиянием хронической нейрогенной боли и иных коморбидных патологий на развитие злокачественного процесса, а также экспериментальные разработки по митохондриальной терапии опухолей. Фундаментальные исследования проводили на новых моделях: 1. Бимодельная система роста меланомы В16/F10 на фоне хронической нейрогенной боли. Генерализация болевого синдрома способствовала отмене генетической программы сдерживания канцерогенеза в экспериментах на мышах с нокаутом по гену uPA. 2. Бимодельная система роста карциномы Герена и развития сахарного диабета у крыс. Сочетание патологических процессов привело к различным последствиям у животных разного пола: у самцов отмечалась стимуляция роста первичной опухоли, а у самок при умеренном росте первичного очага наблюдалась обширное метастатическое поражение брюшины, яичников и почек, что указывало на выраженное проонкогенное влияние диабета. 3. Бимодельная система роста карциномы Герена или саркомы 45 и гипотериоза, на фоне которого у крыс-самцов наблюдалось усиление роста опухоли и снижение продолжительности жизни по сравнению с самками. Это было обусловлено превалированием у самок эстрогенов, участвующих в регуляции работы щитовидной железы и оказывающих разное пролиферативное и антиапоптотическое влияние на клетки рака. Разработаны новые способы патогенетической митохондриальной терапии для предотвращения развития инфаркта миокарда и блокирования метастатической агрессии меланомы В16/F10 с эффектом замедления роста опухоли, растущей на фоне хронической нейрогенной боли у мышей обоего пола.

Aims: to study the features of the functioning of the hypothalamic-pituitary-gonadal axis (HPGA) regulation in male rats at the stages of liver metastasizing. Materials and methods. Our research work was performed in 30 outbred male rats. Metastases in the liver were produced by implantation of sarcoma 45 (S45) cells into the spleen, which was previously positioned under the skin. The time spans of the study are 5 weeks (the pre-metastatic stage) and 7 weeks (the metastatic stage) after tumor cell transplantation. In the tissues, the content of the following hormones was determined by RIA: luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), total testosterone (Ttot), progesterone (P4); by ELISA we determined the content of the following hormones: gonadotropin-releasing hormone (GnRH), free testosterone (Tfr) and estrone (E1). Results. At all stages of the study, the level of GnRH in the hypothalamus decreased by more than 2.0 times; in the pituitary gland, the hormone levels had multidirectional dynamics: LH decreased by 1.6 times, and FSH increased by more than 6.0 times. Liver metastases were characterized by high levels of E1 and Ttot. In the gonads, a high level of P4 was recorded and concentrations of both forms of testosterone were reduced. The concentrations of E2 (by 1.6 times), Tfr (by 4.8 times) increased in blood, and the level of Ttot decreased (by 1.9 times). The salient features of HPGA in the presence of two metastasis sites (liver and lungs) were as follows: in blood, a 2.0 times lower increase in the LH and Tfr contents, a 1.6 times greater increase in E2, an increase in P4 (2.6 times), 1, 4 times lower level of FSH; in the gonads, there are found lower levels of P4, E1, but higher levels of Tfr and Ttot; in liver metastases, a greater increase in P4 (5.2 times), E1 (2.2 times) and Tfr (2.0 times) is recorded. Conclusion. Metastasizing to the liver was accompanied by activation of HPGA with the maximum accumulation of reactogenic E1 in liver metastases in rats with two metastasis sites that may indicate their more severe malignancy and ability to metastasize to the lungs.

Исследование проводилось на белых беспородных крысах. Метастазирование в печень моделировали путём введения клеток саркомы 45 (0,1 мл, 1*106) в селезёнку, за 3 недели выведенную под кожу. Изучали уровни рилизинг гормонов в гипоталамусе и тропных гормонов в гипофизе до развития первичной опухоли в селезёнке (через 1-2 недели после перевивки), в период сформированной первичной опухоли и до визуализации метастазов в печени (через 5 недель после перевивки). Установлено, что адаптационные реакции, разработанные для здорового организма, в условиях онкопатологии модифицируются с развитием нейроэндокринного диссонанса на центральном уровне гормональной регуляции, максимум - накануне метастазирования в печень. Ключевые слова: метастазы в печень, саркома 45, крысы, рилизинг-гормоны гипоталамуса, тропные гормоны гипофиза, адаптационные реакции.

Overloading a tumor with iron (Fe) is a promising strategy for cancer therapy. A number of papers have demonstrated a self-dependent anti-tumor effect of Fe nanoparticles (NPs) in vivo. However, an excessive amount of this trace metal can produce a negative effect on the organism.

Purpose of the study. A comparative analysis of blood parameters and some characteristics of the adaptation status of intact Balb/c and C57Bl/6 mice of both sexes. Materials and methods. We investigated intact mice of both sexes belonging to the C57Bl/6 ( n = 18) and Balb/c ( n = 20) lines. The age characteristics of these animals corresponded to the first half of the reproductive period. We studied the parameters of the complete and biochemical blood tests, the weight characteristics of the thymus, spleen and adrenal glands. The character and tension of general nonspecific adaptational reactions of the body (AR) were assessed as well. In statistical analysis we used the coefficient of variation (CV), Student's t-test, Mann-Whitney test. Results. In mice of both studied lines, the dominance of females over males was noted in terms of the weight characteristics of the thymus and spleen, the development of the most favorable antistress AR, and the number of indicators with low variability. At the same time, in C57Bl/6 mice, animals of different sexes had a similar nature of AR (AR of elevated activation),but differed in signs of tension, this might indicate the difference in the range of levels of reactivity, appropriate to AR in males and females C57Bl/6. Unlike C57Bl/6, mice Balb/c mice of different sexes were distinguished with the predominant antistress AR. Differences between C57Bl/6 mice and Balb/c mice in terms of amylase and ALT activity indicated a shift towards carbohydrate metabolism in Balb/c mice and a shift towards protein metabolism in C57Bl/6 mice. Animals of the С57Bl/6 line had an advantage over Balb/c mice (especially pronounced in females) in some indicators of the adaptation status. Conclusion. The results of the study indicated possible difference in the ratio of carbohydrate and protein metabolism in the animals of the studied lines and testified a more favorable state of the regulatory systems in C57Bl/6 mice compared to animals of the Balb/c line. The revealed regulatory and metabolic interlinear differences can determine the features in the reaction of the body of animals belonging to different lines to the malignant process and efficiency of antitumor therapy.

Гематологические показатели характера и напряженности общих неспецифических адаптационных реакций организма (АР) необходимо учитывать для адекватной оценки адаптационного статуса. Информативность отдельных гистохимических и биохимических показателей, рассматриваемых вне контекста характера и напряженности АР, недостаточна для объективной оценки адаптационного статуса и влияния внешних и внутренних факторов на состояния организма. Каждая из антистрессорных АР и реакция стресс характеризуются определенным комплексом показателей состояния регуляторных систем и метаболизма, что имеет большое значение для определения адекватной тактики лечения, реабилитации и выбора режимов трудовой деятельности и физической активности. Ключевые слова: общие неспецифические антистрессорные адаптационные реакции организма, регуляторные системы, трансплантируемые экспериментальные опухоли, лейкоцитарная формула крови, биогенные амины.

It is known about numerous regulatory disorders in the body during the development of a malignant process. However, in this case, the natural mechanisms of the anti-tumor resistance remain poorly understood. The concepts on the systemic processes during the development of general nonspecific adaptational reactions of the body (AR): stress and anti-stress ARs, discovered by G. Selye and Russian scientists L.Kh. Garkavi, E.B. Kvakina and M.A. Ukolova, have contributed to the development of effective technologies for preventive and complementary therapy for the purposes of clinical oncology.

Purpose of the study. To study the effect of copper nanoparticles on the characteristics of the transplanted tumors of rats, as well as to assess the dependence of the effect on the method of administration of nanoparticles.Materials and methods. In experiments on 163 white outbred male rats, 160–200 g, the size and growth rate of transplanted sarcoma 45 and Pliss' lymphosarcoma were determined in dynamics when a suspension of copper nanoparticles in physiological saline was injected intratumorally or intraperitoneally in a total dose of 10 mg/kg. Nanoparticles had a "core-shell" structure with variable diameter in the range of 30–75 nm. Contrary to other researches, we started the exposure to metal nanoparticles only when the tumors had become visible and had grown up to the sizes at which their spontaneous regression was unlikely.Results. In most animals (up to 89 %), significant antitumor effects of copper nanoparticles were obtained up to complete regression of tumors with large volumes. The effects of nanodispersed copper differed in tumors with different histological structures and growth patterns. Experiments on a transplantable, slowly growing sarcoma 45 showed a decrease in the specific tumor growth rate after a single injection of nanoparticles (1.25 mg/kg), a decrease in tumor size could be observed after 4 injections (a total dose of 5 mg/kg). In the case of a rapidly growing tumor model (Pliss' lymphosarcoma), a decrease in tumor growth rates caused by copper nanoparticles occurred at later stages of exposure, after the animals received nanoparticles at a total dose of 5–10 mg/kg. The efficiency depended on the approach of nanoparticles injection.Conclusion. In case of sarcoma 45, intraperitoneal injection of copper nanoparticles was more effective than intratumoral one, while in rats with Pliss' lymphosarcoma intratumoral injection of the nanoparticles had some advantages. The results indicate that nanodispersed copper is a promising antitumor factor. The mechanisms of regression of large transplanted tumors under the influence of copper nanoparticles are discussed.

The thyroid and the gonadal (HPG) regulatory axes are interconnected and act together as a single system and their imbalance leads to pathological responses of the organism [1, 2]. The involvement of thyroid and sex hormones in the development of the malignant process has been discussed for many decades.

Th e aim of the research was to evaluate the possibilities of using saliva as an indicator of mental and physical stress in the bioluminescent method. Material and methods. Th e object of the study was the saliva of schoolchildren (15-16 years old, n=15), students (19-20 years old, Krasnoyarsk State Medical University and Surgut State University, n=227) and athletes (19-20 years old, n=25). Saliva sampling was performed before and aft er muscle tension and psycho-emotional stress. Th e bacterial bioenzyme system NADH:FMN-oxidoreductase + luciferase was used as a test system. Th e residual glow intensity was used as an integral indicator of body fatigue [1, 2]. Results. It shows the greatest fatigue of schoolchildren aft er mental stress and the least fatigue aft er physical exertion. Boys got tired aft er physical exertion, girls aft er mental exertion. Physical activity tired the excellent schoolchildren. Mental stress caused fatigue of the good schoolchildren. Th e fatigue of students during the study session was revealed, regardless of the region of residence and the component composition of saliva. Students had the same index of stress resistance regardless of the state of rest or mental stress. Indicators of situational and personal anxiety were higher among students from the northern regions. For the fi rst time, the least fatigue of highly qualifi ed athletes was shown during high-intensity physical activity, which distinguishes them from low-skilled athletes. Th e concentration of lactate in the saliva of athletes increased with fatigue. Conclusion. Mental and physical overload aff ect schoolchildren regardless of their academic performance and length of study. Psychological or emotional stress causes fatigue of the students’ body, regardless of the component composition of their saliva and the region of residence. Physical (muscular) tension of varying intensity tires the body of highly qualifi ed athletes to a lesser extent, which makes it possible to reveal their high stress resistance to overloads. Th us, saliva can serve as an indicator of mental and physical stress in the bioluminescent method. It is planned to develop new express methods for pre-trip inspections of railway employees.

ОСОБЕННОСТИ СОДЕРЖАНИЯ НЕКОТОРЫХ КОМПОНЕНТОВ СИСТЕМЫ СОСУДИСТЫХ ЭНДОТЕЛИАЛЬНЫХ ФАКТОРОВ РОСТА В КРОВИ МУЖЧИН ЗРЕЛОГО И ПОЖИЛОГО ВОЗРАСТА С ПЕРВИЧНЫМИ И РЕЦИДИВНЫМИ САРКОМАМИ МЯГКИХ ТКАНЕЙКаплиева И.В. 1 , Жукова Г.В. 1 , Сагателян С