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.

The heterogeneity of diffuse large B-cell lymphoma (DLBCL) is the reason for an unfavorable response to therapy in 40 % of patients. Thus, the search for prognostic markers is relevant. Цель. Изучить содержание в сыворотке крови больных ДВКЛ некоторых факторов роста и их рецепторов для выявления прогностической значимости в течении заболевания. The aim of the study is to examine the content of some growth factors and their receptors in the blood serum of patients with DLBCL and to identify prognostic significance during the disease progression. Materials and methods. The ELISA method was used to determine the level of growth factors VEGF-A, VEGF-C, EGF, TGFβ1, IGF-I, IGF-II and their soluble receptors sVEGFR3, sEGFR, sTGFβR2 in the blood serum of patients with DLBCL after 4 courses of polychemotherapy, R-CHOP regimen. Thirty-two men and thirty-one women were enrolled in the study, average age 55.6 years. The parameters of healthy donors were considered the norm. STATISTICA 10.0 was used for data processing. Results. Before treatment, VEGF-A, IGF-I, IGF-II and TGFβ1 levels in the blood serum of all patients exceeded the norm by 2.1–4.3 times; the content of soluble receptors sEGFR and sTGFβR2 was lower by 1.4 and 3 times, respectively; EGF/ sEGFR and TGFβ1/ sTGFβR2 increased by 1.8 and 6.1 times, respectively. After 4 cycles of R-CHOP VEGF-A and sEGFR levels normalized in patients with subsequent remission; IGF-I, IGF-II, EGF/sEGFR and TGFβ1/sTGFβR2 decreased by 1.6, 1.8, 1.6 and 2.7 times, respectively, compared with the parameters before treatment; sTGFβR2 increased by 2.4 times. Normalization of indicators was not observed in patients with an unfavorable outcome. Conclusion. Minimally invasive and effective method for determining the content of certain growth factors and their receptors, in particular TGFβ1, sTGFβR2, VEGF-A, EGF, and sEGFR, in patients with DLBCL can be effective for predicting the disease progression.

Purpose of the study. To determine the thyroid status of primary cancer patients in the early stages of uterine body cancer, kidney cancer, breast cancer, skin melanoma and lung cancer without a history of endocrine pathology.Patients and methods. The content levels of thyroid-stimulating hormone (TSH), thyroid hormones (THs) T4 and T3 of total and free forms were determined in the blood serum by RIA method in 132 patients with breast cancer, uterine body cancer, lung cancer, kidney cancer and skin melanoma (average age 55 years). The comparison group consisted of practically healthy donors.Results. Only in skin melanoma, serum TSH levels were reduced by 1.5 times (p < 0.05). The T4 content was reduced by 1.4–1.7 times (p < 0.05) in uterine body cancer and kidney cancer, increased in lung cancer patients and 16 % of breast cancer patients by 1.4–1.7 times though (p < 0.05). A 1.3–1.5‑fold low (p < 0.05) T3 level was found in breast cancer, kidney cancer, and skin melanoma, while an 1.6‑fold increase (p < 0.05) was found in uterine body cancer. The revealed changes in THs by the type of clinical hyperthyroidism are an increase of 1.8 times (p < 0.05) FT3 on the background of low TSH in the blood in patients with skin melanoma, and by the type of hyperthyroxinemia in patients with lung cancer and breast cancer, consisting in increased concentrations of T4 and FT3, and with free and total T3 levels in patients uterine body cancer, as well as FT4, without changes in TSH in the blood serum of patients, may be associated with the features of malignant pathology, since it is known that THs are proliferation stimulants and can build up in tumors.Conclusion. The development of a malignant tumor even in the early stages of the disease is perceived by the body as a threat for homeostasis and the response to the occurrence of neoplasm is the reaction of the hypothalamicpituitary-thyroid regulatory axis. As an outcome, patients develop euthyroid disorder syndrome.

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.

СОДЕРЖАНИЕ ФАКТОРОВ РОСТА И ИХ РЕЦЕПТОРОВ В ОБРАЗЦАХ ОПУХОЛИ, ПЕРИФОКАЛЬНОЙ ЗОНЕ И ЛИНИИ РЕЗЕКЦИИ У БОЛЬНЫХ БАЗАЛЬНОКЛЕТОЧНЫМ РАКОМ КОЖИ Бандовкина В.А. 1 , Франциянц Е.М. 1 , Ларина Н.И. 1 , Пржедецкий Ю.В. 1 , Каплиева И.В. 1 , Погорелова Ю.А

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.

Endometrial cancer (EC) is one of the most common cancers with a constantly and steadily growing incidence worldwide. The main reason for EC development, in addition to the female population aging, involves the obesity epidemic and associated hyperinsulinemia. Screening for EC has not been developed. However, endometrial carcinoma (ECa) demonstrates a specific symptomatology and clinical picture, and diagnostic methods are available, sensitive and defined by a certain range of comorbid diseases. These factors allow early ECa diagnosis in 80 %. The methods of treatment are standardized, depending on the stage of RTM and the morphological structure of EC, the age of the patient and allow to achieve 72–76 % of the overall 5-year survival rate. The methods of treatment are standardized, depending on the EC stage, the morphological structure of ECa, and the patient’s age, and allow achieving the 5-year overall survival of 72–76 %. The disease promised a favorable outcome and seemed to be controlled. However, at the end of the last century, researchers started to report the clinical and morphological heterogeneity of ECa, which allowed Ya. V. Bohman to propose a dichotomous division of EC into clinical and pathological variants. Such a division was accepted all over the world and required re-evaluation of the prognostic value of various endometrial adenocarcinoma histotypes depending on the phenotype and hormonogenesis of ECa. Initially, adenosquamous cancer (or endometrioid adenocarcinoma with squamous metaplasia, in the modern classification) was also classified as estrogen-dependent endometrioid adenocarcinoma, and squamous cell endometrial cancer was classified as an unfavorable type with a poor prognosis and without hormonal influence. Interest in the squamous cell component in dimorphic endometrial adenocarcinoma has repeatedly arisen over the past decades due to its unpredictable clinical course. The newest TCGA molecular classification of EC did not clarify the issues, but gave rise to new ones related to the etiology and carcinogenesis of this ECa histotype and its clinical interpretation.

Purpose of the study. To study the intensity of lipid peroxidation (LPO) and the activity of antioxidant protection components in tumor tissues, peritumoral zone and conditionally healthy skin tissue in basal cell carcinoma, depending on the type of tumor growth, gender of patients, and the presence of concomitant diseases. Materials and methods. Tissues from 34 patients with basal cell carcinoma (BCC) were studied, including 17 women (10 with superficial tumor growth and 7 with solid growth) and 17 men (5 and 12 patients, respectively). We used skin flaps obtained during operations on 12 men and 10 women without malignant pathology (“norm”) as a comparison material. The content of malondialdehyde (MDA), diene conjugates (DC), superoxide dismutase (SOD) activity and total peroxidase activity (TPA) were determined. Statistical processing of the results was carried out using the Statistica 10.0 program. Results. In women, the level of MDA was increased in all tissues: with superficial growth of BCC by 2.1–2.5 times (p ≤ 0.05), with solid growth by 1.6–2.1 times (p < 0.05) relative to the “norm”. In men with superficial growth, an MDA increase by 3.2 and 3.1 times in tumor tissue and conditionally healthy tissue was observed (p < 0.02), and no increase in MDA in the tumor was detected in 11 of 12 patients with solid growth. An increase in DC (on average 2–5 times) in BCC patients with concomitant hypertension and diabetes mellitus was observed mainly in women. Activation of SOD in tumor tissue, to a greater extent in men (2.4 times with superficial growth and 1.7 times with solid growth, p < 0.05 relative to conditionally healthy tissue), can be considered as a mechanism of antiradical protection of the tumor. Conclusions. An increase in the level of MDA in BCC was observed in tumor and nearby tissues in women with both types of growth, in men only with superficial growth. Analysis of individual characteristics of LPO indicators in patients with skin carcinoma revealed a dependence of the severity of the increase in MDA and especially DC on the presence of concomitant pathology (hypertension, diabetes mellitus).

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.

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.

Over the past decades, endometrial cancer has become the most common gynecological cancer worldwide. Its increasing incidence cannot be attributed only to the increasing age of women in socially secure countries. The leading risk factor for the endometrial cancer development is obesity, and its epidemic is gradually covering the female population of North Africa, Europe and Asia. Endometrial cancer is pathogenetically associated with hyperestrogenism, and this was the basis for the dualistic theory of clinical and pathological variants proposed by Ya.V. Bohman. The foundations of this theory about the hormonal dependence of endometrial cancer are now being actively supplemented by molecular genetic parameters of the TCGA classification. Recent studies show steroid dependence of endometrial cancer both on estrogens and, to a large extent, on androgens which are directly involved in the complex processes of transformation into estrogens. Published research data, rather contradictory and ambiguous, confirm the antiproliferative role of androgens in the pathogenesis of endometrial cancer. This review analyzes papers on the role of androgens in pathogenesis and their potential clinical antitumor application. Keywords: endometrial cancer, androgens, androgen receptor, classification of endometrial cancer.

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.

Purpose of the study. An analysis of IGF and their carrying proteins levels in blood serum of patients with non‑small cell lung cancer (NSCLC), depending on the severity of the previous COVID-19 infection. Materials and methods. 60 patients with histologically verified NSCLC T 2–3 N х M 0 receiving treatment at the Thoracic Department (National Medical Research Centre for Oncology, 2020–2021), were included in the study. The control group included 30 NSCLC patients after asymptomatic or mild COVID-19 disease (15 men and 15 women); the main group included 30 (15 men and 15 women) patients after severe or moderate to severe COVID-19. The mean age of patients was 59.11 ± 2.89 years. Blood counts of donors of the same age were used as the norm. Results. The levels of IGF-I, IGF-II, IGFBP2 and IGFBP3 in the blood serum of patients with NSCLC of the main and control groups were higher than those of donors by an average of 2.5, 2.1, 1.7 and 2.7 times, respectively ( p < 0.05). The concentration of IGFBP1 was higher in the control group compared to the main group, and decreased in relation to donors: in the control in men and women by 1.4 and 1.9 times, and in the main group by 3.0 and 6.4 times, respectively ( p < 0.05). The ratios of IGF and IGFBP1 increased in both groups: IGF-I/IGFBP1 – in the control group from 3.8 to 4.2 times, and in the main group from 7.9 to 14.4 times; IGF-II/IGFBP1 – in the control from 2.4 to 4.5 times, and in the main group from 6.6 to 12.7 times in men and women, respectively ( p < 0.05). Conclusions. The level of ligands and almost all of the studied carrier proteins, except for IGFBP1, increases in the blood of patients with NSCLC of both sexes, regardless of the severity of COVID-19. The ratio of IGF-I/IGFBP1 and IGF-II/IGFBP1 in the blood increases in both groups, most significantly in the group with severe and moderate COVID-19, which indicates excessive accumulation of IGF levels and may contribute to a more aggressive course of the malignant process.

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.

The aim of our research work was to study the level of sex steroids in blood, the tumor and the perifocal zone in rats of both sexes with Guerin’s carcinoma against the background of hypothyroidism. Materials and methods. The experiment was performed in 110 outbred rats of both sexes. Hypothyroidism was induced in animals for 30 days with Mercazolil medication, and then Guerin’s carcinoma was transplanted (the main group). The reference groups included animals with an independent growth of Guerin’s carcinoma and with independent hypothyroidism, as well as intact animals (the norm). On the 18th day of the tumor growth, the animals were sacrificed, and, using standard RIA kits, in the serum, the tumor homogenates and the perifocal zone, the levels of estradiol (E2), testosterone (T) and progesterone (P4) were determined. Results. In comparison with intact animals, hypothyroidism caused an increase in the blood content of E2 in animals of both sexes by 2.2-2.4 times and T by 1.4-16 times, and P4 by 1.7 times only in females, but recorded was a decrease therein in males by 2.4 times. The growth of Guerin’s carcinoma resulted in a 2.5-5.5-fold decrease in E2 in blood of the animals of both sexes, an increase in T by 2.1 times and P4 by 3 times in the females, but a decrease in T by 2.6 times without changing P4 in the males. In the main group, in the animals of both sexes, similarly to the processes in hypothyroidism, the level of E2 and P4 increased by 1.4-1.6 times, and in females also T by 4.4 times, compared with the intact animals. Conclusion. Hypothyroidism and the growth of Guerin’s carcinoma changed E2 in different directions in animals of both sexes the level of sex hormones in blood and shifted the steroid balance in the tumor and its perifocal zone. In the females of the main group, the saturation of the tumor with estrogens, androgens and progesterone decreased, while in the males, on the contrary, the concentration of steroids increased.

The aim was to study changes in the functioning of the hypothalamic-pituitary-gonadal (HPG) axis in BALB/c Nude mice of both sexes with multiple primary malignant tumors (MPMTs). The BALB/c Nude mice (n=84) of both sexes were divided into groups as follows: intact males and females (n=14), a reference group of mice of both sexes with standard subcutaneous inoculation of B16/F10 melanoma (n=14); the main group of mice with the reproduction of the MPMT model (n=14); B16/ F10 melanoma and Lewis carcinoma were inoculated into mice sequentially subcutaneously on two sides: one on the left side and the other on the right side. After 15 days of the growth of the malignant tumors, GnRH, LH and FSH contents were determined by ELISA using standard kits in 1% of the homogenates of the hypothalamic and pituitary tissues, and estradiol content (E2) was determined in 10% homogenates of ovaries and testes, as well concentrations of testosterone (T) and progesterone (P4) were identified in blood serum with the standard RIA kits (Immunotech, Czech Republic). Results. In the hypothalamus in females of the reference and main groups, the level of GnRH increased by 2.5-4 times, and in males it decreased by an average of 3.1 times; in response to those changes in animals of both sexes in the reference group and in the main group only in females in the pituitary gland the level of LH increased by 1.3-1.6 times, however a decrease in FSH in all groups was more pronounced in females: by 7.8-13.7 times and less pronounced in males: by 1.4-1.7 times (р˂0, 05). In the gonads of females, the level of E2 increased, but the levels of T and P4 decreased, while P4 increased in males. Blood parameters did not reflect hormonal changes in the organs. Conclusion. Abnormalities in the HHG axis performance, along with primary immunodeficiency, play a decisive role in overcoming antitumor protection for uncharacteristic malignant tumors.