Введение. Меланома представляет все больший интерес для исследований, особенно по мере выяснения конкретных биологических путей ее развития и прогрессирования. Важную роль в процессах развития меланомы играет митохондриальный метаболизм, перестройки которого влияют на выживаемость злокачественных клеток. Цель. Изучение способности митохондрий, изолированных из меланомы, образовывать опухолевые структуры в организме животных. Материалы и методы. В эксперименте использовали 17 самцов мышей линии С57ВL/6 и штамм меланомы кожи В16/F10. Из меланомы кожи В16/F10, взятой от самцов-доноров мышей линии С57ВL/6 (n = 3), выделяли митохондрии методом дифференциального центрифугирования. Мышам линии С57ВL/6 (n = 7) в мышцу одноразово трансплантировали свежеизолированные митохондрии меланомы В16/F10. Контролем служили мыши-самцы линии С57ВL/6 (n = 7), которым одноразово в мышцу вводили 0,4 мл физиологического раствора. Осуществляли морфологический контроль срезов внутренних органов и очагов меланомы В16/F10 после стандартной проводки, заливки в парафин и окраски препаратов гематоксилин-эозином с последующей микроскопией на Axiovert (Carl 44 Zeiss, Германия) на основе программы визуализации изображений Axiovision 4 (Carl Zeiss, Германия). Срезы исследовали и фотографировали с помощью электронного микроскопа JEM-1400 (JEOL Inc., Япония), оснащенный системой Quemesa CCD (OSIS, Германия) и работающий на 100 кВ. Результаты. Спустя 2 недели, при вскрытии животных в брюшной полости обнаружены множественные узлы меланомы с диссеминацией по брюшине, в брыжейке, толстой и тонкой кишке, печени. Морфологическое исследование крупного опухолевого узла, спаянного с почкой, а также небольшого узла на семенном канатике, подтвердило меланоцитарную природу клеток. Заключение. Полученный феномен отмечен впервые и требует дальнейшего изучения механизмов реализации митохондриальной программы злокачественной трансформации.

The purpose of this study was to establish a model of uterine carcinoma in female laboratory rats by transplanting Guerin carcinoma directly into the uterine horn. Material and Methods. Fifteen nonlinear white laboratory rats weighing 250 ± 25 g served as the subjects of surgical intervention. all operative interventions were performed under xylazine-zoletil anesthesia. Female white laboratory rats were laparotomized under aseptic conditions using anesthesia. the incision length was 2 cm, and a tumor suspension containing 2.5-3.5×106 cells was injected into the lumen of the right uterine horn using an intravenous catheter with a 22G injection port (0.9 × 25 mm). tumor cells were counted using the ADAMIILS cell analyzer (Nano Entek, Korea). the tumor progression was monitored for 21 days. after euthanizing the animals under ether anesthesia, median longitudinal histological sections, 5–7 μm thick, were made from the tumor node and stained with hematoxylin-eosin and Van-Gizon using standard techniques. Results. Following the transplantation of Guerin’s carcinoma cell suspension, a tumor node of approximately 25 mm in diameter was identified macroscopically in the region of the inferior aspect of the right uterine horn. additionally, the presence of haemorrhagic effusion was documented in the abdominal cavity and tumor screenings. at light microscopy, areas of neutrophilic infiltration, significant narrowing of the lumen of the uterine horn with signs of involution, and prismatic epithelium of papillary structures were observed. the tumor cell features characteristic of Guerin’s carcinoma are preserved in the tumor node induced in the uterus, with a cytoplasmic-nuclear ratio that remains close to 1:1. the shapes of the nuclei vary, but the irregular ovoid shape remains dominant, and pathological mitotic figures are observed. the tumor stroma includes cytoplasmic branched connections connecting the tumor conglomeration. Conclusion. therefore, according to the morphological description, the presented experimental model demonstrates the possibility of intrauterine growth of Guerin’s carcinoma in animals and is most similar to the localization of the tumor focus in patients with gynecological cancer.

Aim. To study the effect of malignant tumor growth on level of cAMP in mitochondria of cardiomyocytes in mice with chronic neuropathic pain. Materials and Methods. С57ВL/6 mice (n = 336) have been grouped as follows: intact mice (♂n = 21; ♀n = 21), mice with chronic neuropathic pain (♂n = 21; ♀n = 21), mice with melanoma В16/F10 (♂n=63; ♀n=63), and mice with melanoma В16/ F10 and chronic neuropathic pain (♂n=63; ♀n=63). After 1, 2, and 3 weeks of the melanoma growth, cardiac mitochondria of abovementioned mice have been isolated by the centrifugation with the following measurement of cAMP. Results. Chronic neuropathic pain has induced a 3.6-fold reduction in cAMP in cardiac mitochondria of female mice. In mice with melanoma В16/ F10, cardiac cAMP showed 4-fold average increase from the 2nd week of the tumor growth, while in mice with melanoma В16/F10 and chronic neuropathic pain a 2-4-fold increase in cAMP was recorded as soon as from the 1st week of tumor growth, eventually leading to the depletion of cAMP by the 3rd week of the experiment. Serum cAMP concentration did not correlate with the cAMP level in cardiac mitochondria and was reduced in both males and females. Conclusion. Alterations in cAMP concentration in cardiac mitochondria were gender-specific, as female mice responded to a chronic neuropathic pain without other triggers. In mice with melanoma and chronic neuropathic pain, cAMP level raised significantly earlier than in mice without chronic neuropathic pain, resulting in full cAMP depletion by the 3rd week of the experiment.

Nowadays, there is a new concept that says that mitochondria naturally circulate in the blood and this is characteristic of both human and animal bodies. It is believed that circulating mitochondria can easily pass through tissue barriers due to their small size (50–400 nm). The phenomenon of mitochondrial intercellular transfer, which is bidirectional, has been observed in vitro and in vivo , under both physiological and pathophysiological conditions, and among a variety of cells, including malignant tumor cells. Circulating cell-free intact mitochondria are thought to play an active biological and physiological role, as mitochondria are already known to be systemic mediators of intercellular communication, transmitting hereditary and non-hereditary biological components, including MtDN A. Mitochondrial components of cellular origin, including mitochondrial DNA, were detected in the extracellular space. There are about 50,000 times more copies of the mitochondrial genome than the nuclear genome in the blood plasma of healthy people. The researchers confirmed that mitochondrial cell-free DNA (McfDNA) is stable enough for detection and quantification, implying that there are stable structures protecting these DNA molecules. The circulating mitochondrial genome, which is released as a cell-free mitochondrial DNA, is recognized as a new biomarker of mitochondrial stress and signal transduction. McfDNA has become an attractive circulating biomarker because of its potential use in diagnostic programs for various diseases, e. g., diabetes, acute myocardial infarction, and cancer. There is no doubt that detection of circulating mitochondria and their DNA in body fluids opens up a new promising scientific direction in biology and medicine. The article analyzes modern scientific data devoted to proving the existence of extracellular mitochondria, their functions outside the cell and diagnostic value.

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.

Thyroid hormones (TH) influence the processes of cell proliferation and differentiation, but their role in the processes of carcinogenesis is contradictory.The purpose of the study. To study the effect of induced hyperthyroidism in mice of both sexes with intertwined Lewis carcinoma (LLC) on the activity of the hypothalamic-pituitary-thyroid axis (GGT).Materials and methods. The experimental model was mixed-sex mice of the C57BL/6 line with subcutaneously transplanted LLC on the background of induced hyperthyroidism (main group). Two control groups were used: control group I – mice with sodium liothyronine- induced hyperthyroidism and control group II – mice with subcutaneously transplanted LLC. On the 25th day after tumor transplantation, the level of thyrotropin- releasing hormone (TRH), thyroid- stimulating hormone (TSH), triiodothyronine (T3), total and free thyroxine (T4, FT4) was determined in the homogenates of GGT organs and in blood serum.Results. In female mice, hyperthyroidism caused an increase in the level of TRH in the hypothalamus and a decrease in TSH in the pituitary gland; in males, a decrease in TRH only in the hypothalamus. In control group II, euthyroid disorder syndrome developed: In mice of both sexes, serum levels of T4 and FT4 were found to decrease against the background of unchanged T3 levels and an increase in TSH content only in females. In the females of the main group, an increase in the level of TSH in the thyroid gland caused a decrease in T3 content in 73 % of animals against the background of normal T4 and elevated FT4 levels, in 27 % of females the T3 level increased. In males, in 73 % of the observations, the T3 level was increased against the background of high T4 and FT4 values and unchanged TSH levels. In the skin and LLC samples of the mice of the main group, an increase in T3 levels was noted.Conclusion. The growth of LLC against the background of hyperthyroidism is a process with multifactorial effects. High levels of T3 in blood serum and skin stimulated the proliferation of tumor cells, which led to the formation of subcutaneous tumors of a larger volume in the mice of the main group. Sex differences in the GGT response indicate different mechanisms that implement pathological processes.

Purpose of the study. To create a model of uterine sarcoma in female white mongrel rats and provide description of its morphological features. Materials and methods. In the in vivo experiment, white mongrel female laboratory rats (n = 20) weighing 250 ± 25 g were used, and the M1 strain of rat sarcoma was used as an experimental tumor model. The studied groups of animals: Group 1 (n = 10) – administration of 0.5 ml of tumor suspension containing 2.5–3.5 × 106 cells using an intravenous catheter with an injection port 22G, 0.9 × 25 mm; group 2 (n = 10) – donors of tumor material with subcutaneous M1 grafting according to the standard method. Xylazine‑ zolethyl anesthesia was used during surgical interventions. The duration of the experiment was 21 days. After killing the animals, median longitudinal histological sections were made from the tumor node, 5–7 microns thick, stained with hematoxylin‑ eosin. Results. Unlike subcutaneous grafting of sarcoma M1, the tumor growing in the uterine horn was characterized by the presence in the abdominal cavity of many nodules and tumor dropouts on the mesentery, i. e. lymph nodes. According to the cellular composition, tumors formed from a suspension of M1 sarcoma cells injected into the right horn of the uterus were characterized by a polymorphocellular type of structure against the background of pronounced neoangiogenesis. Necrosis and hemorrhages were noted in certain sections of the preparations with a polyp‑like tumor form, which corresponds to destructive signs of rapid growth and development of uterine sarcoma. Conclusion. The possibility of modeling a relatively rare tumor by introducing a suspension of M1 sarcoma cells into the right uterine horn of female rats has been established. The nature of multinodular tumor growth with pronounced polymorphism of the cellular composition, areas of necrotization and hemorrhage demonstrates the adequacy of the uterine sarcoma model for the implementation of research tasks in clinical oncology.

Central organelles in cells are mitochondria, which are essential for many fundamental biological processes. In the course of evolution, mitochondria have been transformed into signaling centers in biological systems that can cause changes in the cell via secreted factors and affect physiology of humans and animals. Along with performing many key functions for the cell, mitochondria have also evolved into active hubs that can both control cellular programs through interaction with other compartments, such as the endoplasmic reticulum, and affect tissues, determining the health of the body via mechanisms that we are only beginning to understand.

Purpose of the study. Was to reveal the effect of urokinase gene knockout in male and female mice with transplanted B16/F10 melanoma on the functions of the fibrinolytic system units. Materials and methods. Male and female mice were used: main group with genetically modified mice C57BL/6-Plautm1. 1Bug – ThisPlauGFDhu/GFDhu (uPA-/-); control group with С57Bl/6 (uPA+/+) mice. B16/F10 melanoma was transplanted by the standard methods to the animals, and levels of plasminogen (PG), plasmin (PAP), urokinase receptor uPAR, content (AG) and activity (act) of uPA, t-P A and PAI-I were measured with ELISA (Cussabio, China) in 10 % tumor homogenates and peritumoral area after 3 weeks of tumor growth. Results. The activity and levels of urokinase in intact uPA-/- animals were significantly (by 100–860 times) inhibited, compared to uPA+/+, but uPAR levels were unchanged in females and were 1.9 times lower in males. PAP levels in uPA-/- mice were 2.1–4.2 times higher than in uPA+/+ animals. The growth of B16/F10 melanoma in uPA-/- mice was slower and metastasizing was suppressed, but their survival was not improved. The dynamics of changes in components of the fibrinolytic system in presence of melanoma growth differed in uPA-/- mice, compared to uPA+/+ animals: PAP levels in tumor samples decreased by over 2 times, uPA levels and activity were not increased, PAI was practically unchanged, but activity of t-P A elevated by 3.8–8.2 times, as well as in uPA+/+ mice. Conclusion. Despite the suppression of the growth and metastasis of the primary tumor nodes in uPA-/- mice, their average survival was not improved, which indicates that the mechanisms of tumor are complex and there are alternative biological pathways supporting melanoma to survive in conditions of the urokinase gene knockout.

Experimental and clinical studies demonstrate the possibility of modulating the development of malignant tumors in thyroid imbalance, in particular hyperthyroidism, which negatively affects the electrophysiology of the heart. In an experimental model of tumor growth during of hyperthyroidism, activation of the tumor was shown.Aim: To study electrophysiological parameters of the mouse heart at the initial stages of transplantable tumor growth during of hyperthyroidism.Material and Methods. In female mice of the C57BL/6 line (n = 20) was created a model of melanoma B16/F10 growth during of hyperthyroidism, which was induced by daily intraperitoneal administration of liothyronine sodium (T3) for a long time and confirmed by determining the content of thyroid-stimulating hormone and triiodothyronine in the blood using the radioimmune method. On the 5th day of T3 administration, the melanoma was transplanted. ECG was recorded non-invasively (ecgTUN- NEL, ecgAVG software, emka TECHNOLOGIES, France) on the 1st and 3rd days of T3 administration, in groups with a tumor – on the 6th day after its transplantation.Results. Pathological changes were revealed: in the group with hyperthyroidism – rhythm irregularity, decrease the amplitude of P and T below the isoline, widening of the QRS, on the 3rd day – the death of 1 mouse was noted due to large-focal myocardial infarction; in the group with melanoma – only sinus arrhythmia and decreased heart rate; in the group with a combination of pathologies – an almost normal ECG, with the exception of an increase in P amplitude and a slight increase in QRS.Conclusion. Already in the early stages of hyperthyroidism or tumor growth, there was a violation of myocardial depolarization/ repolarization processes, capable of causing even death of the animal. In case of comorbidity, the majority of ECG parameters normalized, indicating the inclusion of compensatory mechanisms in the interaction of pathologies. The results demonstrate the need for a deeper study of the mechanisms of interaction of several simultaneously existing pathologies in the body.

Purpose of the study. Preclinical study in experiment of antitumor efficacy of a new substance synthesized on the basis of pyrimidin-4-one derivative.Materials and methods. The sodium salt of 4-{2-[2-[2-(4-hydroxy-3-methoxyphenyl)-vinyl]-6-ethyl-4-oxo-5-phenyl-4H-pyrimidin-1-yl}-benzsulfamide, a new inhibitor of the internal domain of the epidermal growth factor receptor (EGFR), was used in this study. All C57BL6 mice of both sexes were subcutaneously transplanted with B16/F10 melanoma. Twenty-four hours after tumor transplantation, mice in the main group (n = 18) were injected with a new EGFR inhibitor intramuscularly at a dose of 0.375 mg per mouse (15,0 mg/kg animal masses), while mice in the control group (n = 18) were injected with saline for injection. In both groups administration was carried out before natural death of animals according to the scheme: administration daily for 5 days, followed by 2 days of break. The dynamics of animal weight, dynamics of tumor node volume were evaluated, the tumor growth inhibition index (TGII) was calculated.Results. Tumor visualization time and animal weight did not statistically significantly differ between the groups during the whole study. In the main group there was a longer lifespan by 1.5 times on average (p ≤ 0.05), and smaller average tumor volume (by 19.2 times on 14 days in males, by 4.3 times in females, by 4.3 times on 28 days in males, by 2.5 times in females, p ≤ 0.05) than in the control group. At the same time, in the main group the tumor volume was smaller in males by 2.7 and 1.8 times (p ≤ 0.05), respectively on days 25 and 28 than in females. TGII in mice of both sexes was maximal on the 14th day with subsequent decrease by 40.3 % in females and only by 18.6 % in males, and during the whole experiment TGII in males was higher.Conclusion. The results showed inhibition of melanoma growth and increased lifespan of mice of both sexes (more pronounced in males) in the group with administration of a new EGFR inhibitor. This indicates the promising potential of this compound and the need to continue its preclinical study in other tumor models.

Serous endometrial intraepithelial carcinoma (SEIC) and clear cell carcinoma of the endometrium (CCEC) belong to pathogenetic type II without evidence of hyperestrogenism, are often detected late in the course of the disease, and are characterized by an aggressive course. Currently, there is increasing interest in the role of local content and metabolism of steroid hormones in organs and tissues in various pathologies, including the development of malignant tumors.Purpose of the study. To determine the local level of sex hormones in patients with SEIC and CCEC.Patients and methods. The study included 21 patients with SEIC and 20 patients with CCEC. The control group consisted of 20 patients who had undergone surgical treatment for uterine myoma. All patients were treated at the National Medical Research Center for Oncology, Rostov‑on‑ Don, the Russian Federation Ministry of Health. The local levels of estrogens and androgens were determined in the tumor tissue, the perifocal zone, endometrial tissue unaffected by the tumor process, and the fallopian tube tissue in patients with SEIC and CCEC. In the control group, the local level of sex hormones was determined in intact 10 % homogenic endometrial tissue.Results. The data were analyzed, and the results demonstrated that the tumors and peritumoral tissues exhibited a depletion of estradiol (E2), a saturation of testosterone, and an extreme saturation of estriol (E3). The consequence of this imbalance was the predominance of fetal placental estrogen (E3), which was detected not only in the tumor tissue but also in distant parts of the endometrium and uterine tubes. In these regions, the concentration of E3 exceeded that of intact endometrium by a factor of more than five. A comparison of estrogen receptor (ER) levels revealed elevated levels in samples of the tumor, its perifocal zone, distant endometrium, and fallopian tubes. This finding indicated a predominance of ERα over ERβ.Conclusion. The local hormonal background of rare forms of non‑endometrioid endometrial carcinomas exhibits distinctive characteristics, including the replacement of the influence of classical estrogen (E2) by fetal, placental E3. Additionally, there is a notable prevalence of the REα type over REβ, along with hyperandrogenization of tissues, which culminates in the formation of a unique low‑differentiated tumor with pronounced biological aggressiveness.

Understanding the mechanisms of colorectal cancer development and progression is important for disease management. Mitochondria being the energy source of eukaryotic cells play a significant role in intestinal homeostasis. Objective: The aim of the study is to examine cytochrome C level in mitochondria isolated from cells of different parts of the colon in men and women. Materials and Methods. The authors analyzed the materials obtained from 132 patients with colon cancer T2-3N0M0 (52 women and 80 men). Mitochondria from human intestinal and tumor tissue cells were isolated by differential centrifugation. Then, cytochrome C concentration (ng/mg protein) was determined by ELISA. Results. When studying the cytochrome C level in tumor tissue from various parts of the colon in men, we found that cytochrome C level in tumor mitochondria of the rectum, sigmoid colon and ascending colon was higher than that in the mitochondrial cells of the corresponding tissues by 1.8, 1.5 and 2.0 times, respectively. In women, cytochrome C level in the mitochondrial tumors of the same parts of the colon was higher than that in the mitochondria of the corresponding tissues by 2.9, 1.4 and 2.0 times, respectively. Conclusion. A common pathological characteristics of tumor mitochondria in all parts of the colon was a high cytochrome C level. It may be associated with the intensification of cellular respiration processes in the tumor contributing to its growth.

This review discusses the uniqueness of mitochondria providing normal cellular functions and at the same time involved in many pathological conditions, and also analyzes the scientific literature to clarify the effectiveness of mitochondrial transplantation in cancer treatment. Being important and semi-autonomous organelles in cells, they are able to adapt their functions to the needs of the corresponding organ. The ability of mitochondria to reprogram is important for all cell types that can switch between resting and proliferation. At the same time, tumor mitochondria undergo adaptive changes to accelerate the reproduction of tumor cells in an acidic and hypoxic microenvironment. According to emerging data, mitochondria can go beyond the boundaries of cells and move between the cells of the body. Intercellular transfer of mitochondria occurs naturally in humans as a normal mechanism for repairing damaged cells. The revealed physiological mitochondrial transfer has become the basis for a modern form of mitochondrial transplantation, including autologous (isogenic), allogeneic, and even xenogenic transplantation. Currently, exogenous healthy mitochondria are used in treatment of several carcinomas, including breast cancer, pancreatic cancer, and glioma. Investigation of the functional activity of healthy mitochondria demonstrated and confirmed the fact that female mitochondria are more efficient in suppressing tumor cell proliferation than male mitochondria. However, tissue-specific sex differences in mitochondrial morphology and oxidative capacity were described, and few studies showed functional sex differences in mitochondria during therapy. The reviewed studies report that mitochondrial transplantation can be specifically targeted to a tumor, providing evidence for changes in tumor function after mitochondrial administration. Thus, the appearance of the most interesting data on the unique functions of mitochondria indicates the obvious need for mitochondrial transplantation.

This review discusses issues related to mitochondrial dynamics. It also highlights mechanisms allowing these organelles to transcend cell boundaries and transfer between mammalian cells. Mitochondria play a key role in energy generation and cellular physiological processes. These organelles are highly dynamic; they constantly change their morphology, cellular location, and distribution in response to cellular stress. In recent years, the phenomenon of mitochondrial transfer has attracted significant attention and interest from biologists and medical investigators. Intercellular mitochondrial transfer occurs in a different way, including tunneling nanotubes (TNTs), extracellular vesicles (EVS), and gap junction channels (GJCs). According to research on intercellular mitochondrial transfer in physiological and pathological environments, mitochondrial transfer has great potential for maintaining body homeostasis and regulating pathological processes. Recent evidence also suggests, that cell-free mitochondria release into blood under normal and pathological conditions (stress, trauma). They were found as circulating extracellular mitochondria in blood samples from mica and humans. Multiple research groups have developed artificial mitochondrial transfer/transplantation (AMT/T) methods that transfer healthy mitochondria into damaged cells and recover cellular function. This paper reviews intercellular spontaneous mitochondrial transfer modes, mechanisms, and the latest methods of AMT/T. Furthermore, potential application value and mechanism of AMT/T in disease treatment (including malignant neoplasms) are also discussed.

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.

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.

Objective . Studying the levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF-β), and neurotrophin 3 (NT3) in the cerebral cortex and subcortical substance of female rats in an experimental model of extracerebral growth of malignant tumor under conditions of induced hypothyroidism. Materials and methods . An experiment was performed on 47 white non-linear female rats: 10 rats each in the intact group, control group 1 (induced hypothyroidism), control group 2 (subcutaneous growth of Guerin’s carcinoma), main group (combination of pathologies); 7 rats in the group with subcutaneous tumor growth to assess life expectancy. Hypothyroidism was induced by per os administration of thiamazole (mercazolil, Akrikhin, Russia), daily dose of 2.5 mg/100 g of body weight, course of 30 days; total thyroxine and thyroid stimulating hormone were determined in blood serum by RIA (Immunotech, Czech Republic). When persistent hypothyroidism was achieved, Guerin’s carcinoma was transplanted under the skin as standard. Aſter decapitation on the 18th day aſter transplantation, the content of BDNF, NGF-β, NT3 (R&D System, RayBiotech, USA) was determined in 10 % homogenates of the cortex and subcortical substance subcortex of the brain (R&D System, RayBiotech, USA). Results . In the cortex in control groups 1 and 2, the level of BDNF was 2.6- and 1.6-fold lower, respectively, and NGF-β was 2.2-fold higher on average than in the intact group. NT3 levels in the control group 1 were 3.0- and 1.6-fold lower in the cortex and subcortical substance, respectively. In the control group 2, the levels of NT3 and NGF-β were higher in the subcortical matter than in the intact group by 2.4-fold and 3.1-fold, respectively. In the cortex and subcortical substance in the main group, only NGF-β levels were higher on average by 1.7 times, with values being intermediate between the corresponding values in control groups 1 and 2. Conclusion . Changes in the levels of all neurotrophins in hypothyroidism were most pronounced in the cortex, while in independent tumor growth, NGF-β in the cortex and subcortical substance and NT3 only in subcortical substance changed the most. When the pathologies were combined, only NGF-β was altered in the cortex and subcortical substance. Apparently, there is an interaction of the tumor and the CNS with changes in the balance of regulatory signals in the subcortical areas of the brain, that reflecting the connection with the biological characteristics of an active or inhibited (in presence of hypothyroidism) tumor growth.