Background: The microbiota is an important element of the tumor microenvironment and is able to influence the biological properties of malignant cells, which determine their malignancy and sensitivity to anticancer therapy. Aim : To investigate the effect of the microbiota member Bifidobacterium animalis (B. animalis) on glucose metabolism, the expression of genes regulating these processes, ROS levels, and the expression of EMT-associated proteins in breast cancer (BC)cells of different molecular subtypes. Materials and methods: BC cell lines: T47D, MCF-7, MDA-MB-231; prokaryotic cells: Bifidobacterium animalis subsp. lactis BB-12 . Metabolic activity of BC cells was determined by biochemical methods. Expression levels of glucose transporters and key enzymes of glycolysis genes were assessed by real-time PCR. Viability of BC cells and ROS production were determined by flow cytometry. Expression of EMT-associated proteins was analyzed by immunocytochemical analysis. Results: BCcells treated with B. animalis are characterized by a shift in the metabolic profile towards increased glycolysis, inhibition of proliferation and induction of changes in the redox state of cells.A statistically significant increase in glucose consumption and lactate production rate, lactate dehydrogenase activity was observed in B. animalis-treated BC cells of all three lines. The detected changes in mRNA expression of the glucose transporter genes GLUT1 and GLUT4 and the lactate dehydrogenase isoforms LDHA and LDHB confirm that B. animalis does not simply modulate individual metabolic or signaling pathways, but triggers a complex reprogramming of BC cells in a direction characteristic of their molecular subtype. In B. animalis-treated BCcells G6PD activity correlates with the level of ROS production in a feedback loop. The multidirectional influence of prokaryotic members of the microbiome was also revealed when studying the EMT-associated profile of breast cancer cells of different molecular subtypes: the expression of biomarkers differed depending on the initial dominance of epithelial or mesenchymal characteristics. Conclusions: The data support the concept that bifidobacteria can act as modulator of the tumor microenvironment and metabolic plasticity of breast cancer cells, and open prospects for further study of bacterial metabolites as potential regulators of tumor growth, their metastatic properties, and response to therapy.

A key challenge that complicates early diagnosis, choice of treatment tactics, and prognosis of the course of breast cancer (BC) is its heterogeneity. Today, many researchers focus on the TME as an environment that directly determines the development and progression of BC. Given this, it is necessary to deepen our understanding of the features of the TME and its interaction with tumor cells. to characterize the cellular and molecular composition of the TME in early-stage BC, stratified by PD-L1 expression status, with a focus on immune cell infiltration (CD68 + and CD163 + cells, mast cells (MCs)), cytokine profiles (IL-6, IL-10 and TNF-α), and extracellular matrix (vimentin (VIM), TGF-β1, collagen type 1 alpha 1 chain (COL1A1), collagen type 3 alpha 1 chain (COL3A1), matrix metalloproteinases (MMP) both collagenases (MMP-1, MMP-8, and MMP-13) and gelatinases (MMP-2 and MMP-9), lysyl oxidase (LOX), and Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1 (PLOD, to identify features associated with an immunosuppressive and tumor-promoting phenotype. The study was conducted on the postoperative material of 124 patients with stage I-II BC. The expression of TME markers was analyzed immunohistochemically. The mRNA gene expression was estimated using the real-time RT-PCR method. Serum cytokines levels were assessed by the ELISA method. We found an association between high PD-L1 expression and increased levels of infiltration of BC tissue with CD163 + macrophages and MCs by 2.9 and 2.5 times, respectively. At the same time, it was shown that BC with high PD-L1 expression is characterized by a significant increase in serum interleukin-10 (IL-10) levels against the background of decreasing the interleukin-6 (IL6) levels. Simultaneously, high PD-L1 expression is associated with a 2.13-fold increase in transforming growth factor-β1 (TGF-β1) and a 13.24

BACKGROUND:The development of human breast cancer (BC) is known to be closely related to disturbances in the mammary gland microbiota. Bacteria of the genus Bifidobacterium are an important component of normal breast microbiota and exert antitumor activity. The molecular-biological mechanisms of interaction between BC cells and microbiota members remain poorly studied yet. The aim of this study was to develop and optimize an experimental model system for the co-cultivation of BC cells with Bifidobacterium animalis in vitro.MATERIALS AND METHODS:Human ВС cells of the MCF-7, T47D, and MDA-MB-231 lines, as well as live and heat-inactivated bacteria of Bifidobacterium animalis subsp. lactis (B. animalis) were used as research objects. The growth kinetics and viability of B. animalis in the presence of different ВС cell lines and without them were determined by both the turbidimetry method and seeding on an elective nutrient medium. Glucose consumption and lactate production by bifidobacteria were assessed by biochemical methods. The viability of BC cells was determined by a standard colorimetric method.RESULTS:The growth kinetics of B. animalis in the complete DMEM nutrient medium showed standard patterns. The indicators of glucose consumption and lactate production of B. animalis confirm its physiological metabolic activity under the growth conditions. The presence of BC cells in the model system did not affect the duration of the growth phases of the B. animalis cells' population but contributed to the increase in their counts. A significant decrease in the number of live BC cells of all studied lines was observed only after 48 h of co-cultivation with live B. animalis. To achieve similar suppression of the BC cell viability, 10-30-fold higher counts of heatinactivated bacteria were required compared to live ones.CONCLUSIONS:The optimal conditions for co-cultivation of human BC cells and living B. animalis cells in vitro have been identified.

Background Prostate cancer (PCa) is common malignancy among men worldwide. To date only few molecular markers are available to predict its course and outcome. SPARC is considered to be promising prognostic marker of PCa due to its involvement in various cancer processes. Materials and methods study was conducted on PCa surgical primary tumor samples, obtained from 84 patients. Level of SPARC mRNA expression was estimated using RT-qPCR. To identify SPARC protein (osteonectin) in prostate tissue, immunohistochemical analysis was conducted. Bioinformatical analysis was performed on UALCAN and TNMplot resources. Results bioinformatical analysis demonstrated that SPARC mRNA levels are decreased in PCa samples, in comparison to normal tissue. In patients with lymph node metastases its levels are 1.26 times higher; p = 4.66E(-02), than in N0 category. Ex vivo study demonstrated that SPARC expression was elevated on both mRNA and protein levels in PCa patients with lymph node metastases (by 2.34 and 1.91, respectively, p < 0.05). We established higher levels of SPARC mRNA and protein in PCa patients with T3 tumors, as well as high Gleason score. Estimation of survival rates demonstrated that PCa patients with a high level of SPARC mRNA and protein have decreased overall 2-year survival. Conclusions SPARC protein was overexpressed on mRNA and protein levels in patients with presence of lymph node metastases and higher Gleason score of tumors. Also, both mRNA and protein upregulation were associated with worse survival rates. The current study has therefore provided further evidence that SPARC is indeed linked to the prognosis and aggressiveness of human PCa.

Collagen, the main component of the tumor microenvironment, plays a key role in the development of breast cancer (BCa); however, the specific changes in its spatial organization during tumor progression have not been definitively elucidated. The existing and available methods for assessing the morphometric parameters of the stroma's fibrous component are insufficient for a detailed description of the state of collagen fibers and for assessing its changes to evaluate the aggressiveness of the BCa course. The aim of the work was to develop an algorithm for microphoto analysis to assess the spatial organization of collagen in BCa tissue of patients with different clinical statuses. The study was conducted on 60 tissue samples of stage I‐II BCa. The processed images were analyzed using the software packages CurveAlign v4.0 and imagej. We established that the increase in BCa stage and the decrease in tumor differentiation grade are associated with decreased length, width, and straightness of collagen fibers, as well as their increased density. The formation of an aggressive basal molecular BCa subtype was accompanied by an increase in tumor‐stroma ratio. The obtained results indicate the possibility of practical application of the developed algorithm for evaluating the spatial organization of collagen in BCa tissue to predict the aggressiveness of the disease course.

Summary. Aim: to determine the quality of life, progression-free (PFS) and overall survival (OS) of patients with localized prostate cancer (PC) with existing metabolic syndrome (MS) and the development of bone metastases (BM) after radical prostatectomy (RP). Objects and methods: а retrospective clinical study diagnosed in 35 patients with localized PC and development of BM. Patients with a moderate (Grade group 2.3) and high (Grade group 4.5) risk of disease progression are divided into subgroups based on the presence and absence of MS. Analyzed indicators of recurrence-free and overall survival; the quality of life of patients was assessed using the QLQ-C30 questionnaire. Results: among 35 study participants after RP with the development of BM – 27 (77.1%) have MS, 8 (22.9%) haven’t features of MS. MS was found in 25.9% of patients with GG 2.3 and 74.1% of GG 4.5; the absence of MS was observed in 62.5 and 37.5% of patients, respectively. The median progression-free survival of patients with РС GG 2.3 and existing MS was 13.3% lower compared to the rate of patients without MS; in patients with PС GG 4.5 – by 10.5%. They also noted a decrease in the median overall survival of patients with MS compared to the rate of patients without MS by 6.4 (GG 2.3) and by 23.9% (GG 4.5). The data of the study demonstrate a decrease in the general health status of patients before RP and at the time of development of BM with existing MS by 27.6%, without MS by 5.5%. Decrease in quality-of-life indicators was noted in the following indicators: social status, fatigue, lack of appetite and the presence of financial difficulties. Conclusion: the investigation analysis showed that presence of metabolic syndrome influence on decreasing quality of life, progression-free survival and overall survival rates in patients with prostate cancer.

Summary. Breast cancer (BCa) is the most common cancer among women both in Ukraine and in the world. Extracellular matrix remodeling has been shown to play a crucial role in tumor progression. Collagenases are one of the main drivers of this process, providing collagen degradation and directly affecting the invasion and metastasis of neoplastic cells. Aim: to study the features of collagenase gene expression and their regulatory factors in BC tissue as possible drivers of tumor growth. Objects and methods: a comparison of collagenase gene expression levels in normal and malignant breast tissue was performed using the GEPIA, UALCAN, and TNMplot resources. The methylation levels of collagenase gene promoters were determined using the UALCAN database. The identification of microRNAs and transcription factors involved in the regulation of collagenase expression was performed based on the information provided on the miRNet v2.0 platform using the TarBase v.8.0 and JASPAR databases. The miRNA level study was performed using the miR-TV online resource. Results: it was found that BCa tissue is characterized by significantly higher MMP1, MMP8, and MMP13 mRNA expression levels compared to normal breast tissue. It was demonstrated that the methylation levels of MMP1 and MMP13 promoters in tumor cells were significantly lower compared to non-transformed breast cells. Using the TarBase v.8.0 and JASPAR databases, transcription factors and miRNAs involved in the regulation of MMP1, MMP8, and MMP13 expression were identified. Analysis of the expression levels of miRNAs involved in the regulation of collagenase expression showed that the levels of miR-155-5p, miR-200b-3p, and miR-210-5p in BCa tissue were 2.26 (p = 2.2e-16), 2.95 (p = 2.2e-16), and 5.90 (p = 2.2e-16) times higher, respectively, compared to non-transformed breast tissue. It was shown that BC tissues compared to healthy donor tissues were characterized by significantly lower expression levels of miR-100-5p, miR-127-3p, and miR-539-5p by 4.19 (p = 2.2e-16), 2.05 (p = 3.9e-12), and 1.70 (p = 2.5e-5), respectively. Conclusions: the obtained results indicate the involvement of collagenases in the development and progression of malignant tumors and indicate the need for further research on their role in the formation of the aggressive potential of BC.

BACKGROUND:Breast cancer (BC) in young women remains a significant public health concern. While progress has been made in understanding the etiology, diagnosis, and treatment of BC in this population, challenges persist. The identification and utilization of prognostic biomarkers offer valuable tools for tailoring treatment strategies and improving outcomes for BC patients.AIM:To evaluate the relationship between the expression of tumor-associated microRNAs and the clinical and pathological features of BC in young patients.MATERIALS AND METHODS:The work is based on the results of the examination and treatment of 50 women younger than 45 years with stage I-II BC. miR-145, -182, -21, -27a, -29b, and -34a expression in tumor samples was analyzed by the real-time reverse transcription polymerase chain reaction.RESULTS:Higher expression of miR-182, -21, and -29b and lower levels of miR-27a were associated with tumor stage in young BC patients. Patients without lymph node metastases (N0) had significantly higher levels of miR-182, -27a, and -34a and lower levels of miR-29b compared to N1 cases (p < 0.05). Expression of miR-145, -182, -21, -27a, and -29b was associated with molecular BC subtypes.CONCLUSION:Obtained results show that a high malignancy degree of BC in young women is associated with an increase in the miR-182, -21, -29b, and -34a expressions and a decrease in the miR-27a level in the tumor tissue, which indicates the prospects of the use of them for predicting the aggressiveness of the disease.

Summary. Aim: to investigate of the effect of bacteria of the genus Bifidobacterium and the extracellular metabolite B. subtilis IMV B-7724 on the process of macrophage polarization in mice with a model tumor. Object and methods: the study was conducted on Balb/c mice (n = 52). Ehrlich adenocarcinoma (ACE) was used as an experimental model. Starting from the 2nd day after the transplantation of tumor cells, animals of the experimental groups were treated with lectin of B. subtilis IMV B-7724 (s/c, 1 mg/kg of weight), B. animalis subsp. lactis BB-12 (per os, 7×105 CFU/mouse) or their combination. On the 21st and 28th days of tumor growth, the parameters of the functional activity of macrophages (Mph) were determined by the level of NO production, arginase (Arg) and cytotoxic activity. Statistical processing of the results was performed using generally accepted methods of variational statistics. Results: at the terminal stage of ACE growth, cells with the M2 phenotype prevailed among the Mph of the peritoneal cavity and tumor tissue. The introduction of the lectin of B. subtilis IMV B-7724 (both separately and in combination with B. animalis) promoted the polarization of peritoneal Mph to the M1 phenotype, as evidenced by an increase (p < 0.05) in the NO/Arg ratio by 5.2 times (on day 21) and by 6.9 times (on day 28). The introduction of B. animalis alone led to the polarization of peritoneal Mph to the M2 phenotype, as evidenced by a significant increase (p < 0.05) in Arg activity and a decrease in the NO/Arg index compared with the indicators of both intact mice and animals of other experimental groups. The polarization of Mph obtained from tumor tissue changed in a similar way. Conclusions: the introduction of lectin of the B. subtilis IMV B-7724 alone or in combination with B. animalis subsp. lactis BB-12 contributed to the change in the polarization state of Mphs of animals with a model tumor. Regardless of the anatomical niche of functioning, cells with the phenotype and functional properties of M1 prevailed among Mphs.

Background: This study aims to investigate the influence of metabolic syndrome on pathological response in young patients with HER2-neu negative breast cancer after preoperative chemotherapy (4ddAC-12Tweekly). Understanding the relationship between metabolic status and treatment efficacy is key to personalized care for cancer patients.

Background. Breast cancer (BCa) is one of the most common oncological diseases in women in Ukraine and worldwide, which determines the need to search for new diagnostic and prognostic markers. In this aspect, the study of multicellular proteins, in particular osteopontin (OPN) and osteonectin (ON), in BCа tissue is relevant. The aim of the work was to investigate the expression of SPP1 and SPARC at the mRNA and protein levels in BCa tissue and to assess their relationship with the main clinicopathological BCa characteristics and the survival rates of patients. Materials and Methods. The work was based on the analysis of the results of the examination and treatment of 60 patients with stage II—III BCa and 15 patients with breast fibroadenomas. SPP1 and SPARC mRNA levels were determined by real-time PCR. The study of the expression of protein products of the SPP1 and SPARC genes was carried out by the immunohistochemical method. Results. We have established that the BCa tissue was characterized by 3.5 (p < 0.05) and 7.4 (p < 0.05) lower levels of SPP1 and SPARC mRNA, respectively, compared to the tissue of benign neoplasms, while OPN and ON expression levels were 1.6 (p < 0.05) and 5.6 (p < 0.05) times higher, respectively, compared to fibroadenoma tissue. The analysis of the relationship between the expression of SPP1 and SPARC at the protein and mRNA levels in BCa tissue and the main clinicopathological BCa characteristics revealed its dependence on the presence of metastases in regional lymph nodes, differentiation grade, and the molecular BCa subtype. Also, high expression levels of SPP1 and OPN were associated with worse patient survival rates. Conclusion. The obtained results indicate the perspective of using SPP1 and SPARC expression indices in BCa tissue to assess the aggressiveness of the cancer course and optimize the tactics of treating patients.

Identification of leukemic stem cells (LSCs) distinguishing them from hematopoietic stem cells (HSCs) remains the topical problem of modern biology and medicine. The current data on the immunophenotype of LSCs and HSCs as well as bulk of leukemic cells in acute myeloid leukemia (AML) are presented supplemented with our own data on the CD150 expression on cells of different forms of AML. The data on the expression of miRNA-29b, -125b, -142, -155, -210, -223 and -370 in the blast cells of AML categorized to different forms according to FAB classification are also given. The detailed knowledge of immunophenotype and miRNA profile of HSCs and blast cells could be a prerequisite for the efficient targeted therapy of AML.

Summary. The review of the literature draws attention to the fact that, from the modern point of view, oncogenesis is a multistage process in which, along with numerous factors of various origins, stress occupies a prominent place. It has been established that stress triggers mechanisms that lead to the activation of programs such as proliferation, invasion, migration of tumor cells at various stages of neoplasm formation, and due to the integration of these actions, the spread of malignantly transformed cells in the body occurs, namely the recurrence of removed tumors and metastasis. In addition, it has recently been shown that as a result of chronic stress, the polarization of tumor cells towards a more mesenchymal phenotype and the release of proteases, in particular the gelatinases MMP-2 and MMP-9, which carry out the destruction and remodeling of the extracellular matrix, and this promotes the metastasis of malignantly transformed cells. Objective indicators of changes under the influence of stress are given, which, after checking their significance, can be used as prognostic criteria and targets for personalized treatment tactics for patients with breast cancer.

Aim. To investigate the effect of bacteria of the genus Bifidobacterium and the extracellular metabolite of B. subtilis IMV B-7724 on the antitumor immune response of mice with a model tumor. Materials and Methods. The study was conducted on Balb/c mice with transplanted solid Ehrlich adenocarcinoma (ACE). Starting from the 2nd day after the transplantation of tumor cells, the animals of the experimental groups were treated with lectin of B. subtilis IMV B-7724 (s/c, 1 mg/kg of weight), Bifidobacterium animalis (per os, 7 × 105 CFU/mouse) or their combination. The immunological studies were performed on the 21st and 28th days of tumor growth. The functional activity of natural killer cells (NK), cytotoxic T-lymphocytes (CTL), as well as the ability of lymphocytes from the peripheral lymph nodes (PLN) to transform into blast cells under the influence of T- (Con A) and B-cell (LPS) mitogens were determined. Results. Administration of probiotic components to the mice with ACE led to the activation of innate immune responses, that is, to a significant increase in the cytotoxic activity of NK, especially in the case of their combined use. The NK cytotoxicity index was higher than that in the non-treated ACE-bearing mice and the intact control by 3.7 and 2.1 times, respectively (p < 0.05). Similarly, the highest specific cytotoxic activity of spleen lymphocytes was observed upon the combined use of the microbial preparations: the CTL cytotoxicity index was nearly 2.5-fold higher than in the non-treated ACE-bearing mice. The data on the ability of PLN lymphocytes to transform into blast cells under the influence of Con A and LPS indicated the preservation of the functional activity of lymphocytes in the animals of the experimental groups during ACE growth. Conclusion. Both B. animalis and lectin of B. subtilis IMV B-7724 have a significant influence on the effectors of the natural and adaptive immunity of mice with ACE. Their combined use was found to be the most effective.

Summary. Aim: to determine at the optical level the role of the fibrillar organization of the collagen-containing connective tissue component of the primary tumor focus in prostate cancer (PCa) progression. Objects and methods: the morphological study is based on the analysis of the histological material of the primary tumor foci of 55 PCa patients without tumor progression in the postoperative period and bone metastases. The tumors were graded Gleason 6–9 at surgery. The features of the architecture of collagen-containing connective tissue in tumors were determined in histological slides stained by Van-Gieson. Results: the remodeling of the collagen-containing stromal component located both around the glandular structures (increase in the percentage of straight and aligned collagen fibers compared to the curved ones) and in the stroma itself has been found. Such remodeling is manifested by an increase in the total mass of fibrous structures, an increase in the width of collagen fibrils, their compaction in relation to the density of their location, peculiarities of desmoplasia, alignment and elongation. The specified features are consistent with the Gleason score and the postoperative disease course, namely, the occurrence of metastases. Conclusions: the desmoplastically changed collagen-containing connective tissue component of the PCa creates favorable conditions for the unimpeded migration and realization of the invasive potential of cancer cells, in particular those expressing bone tissue remodeling proteins.

The widespread introduction of nuclear technologies in industry, medicine, science, etc. increases the number of professionals subjected to additional radiation exposure. Moreover, the problem of occupational cancer is the most complicated in occupational pathology due to the multifactorial nature of the etiology of this disease. The radiation accidents in Chornobyl and Fukushima-1 showed that nuclear reactors cannot guarantee absolutely safe operation. At present, the threat of nuclear terrorism is increasing. Occupational radiation exposure and its consequences are also of great concern worldwide. Based on the literature data and our own studies on the effects of various types of radiation exposure, especially stochastic effects of radiation, it seems reasonable to develop a scientific basis for the optimization of radiation protection of various categories of population, first of all, medical personnel and patients. The complex assessment of radiation risks and reconstruction of the total ionizing radiation dose from all types of irradiation will allow optimizing radiation protection of the population and reducing carcinogenic risk..

BACKGROUND:In the last decades, the incidence of breast cancer (BCa) in young women has been increasing steadily. The quantitative indicators of expression of collagen, which play important role in stromal microenvironment, and their association with the age and survival rates of BCa patients have not been yet definitively clarified.AIM:To investigate the relationship between the COL1A1 gene expression at the mRNA and protein levels in BCa tissue and the clinicopatological features and survival rates of BCa patients of different age groups.MATERIALS AND METHODS:The study was conducted on the clinical material of 50 patients with stage I-III BCa. COL1A1 gene expression at the mRNA and protein levels in BCa tissue were studied using the real-time PCR and immunohistochemical methods, as well as the bioinformatic analysis (UALCAN and Kaplan - Meier Plotter databases).RESULTS:The bioinformatic analysis showed that BCa tissue is characterized by 6.0 times (p < 0.05) higher level of COL1A1 mRNA compared to normal breast tissue. The correlation of COL1A1 expression at the mRNA and protein levels with the molecular subtype of neoplasms was demonstrated. According to Kaplan - Meier Plotter database, a low level of expression of COL1A1 protein level in BCa tissue is associated with lower rates of relapse-free survival of patients. The ex vivo study of the clinical material revealed a decrease in COL1A1 protein expression in tumor tissue of young patients with BCa of T3 category (p < 0.0374), low differentiation grade (p < 0.0163) and basal molecular subtype (p < 0.0001). A correlation between the expression of COL1A1 at the mRNA and protein levels and the expression status of estrogen receptors (p < 0.0001) and progesterone receptors (p < 0.0040) was established. The relapse-free 3-year survival rate of young BCa patients is significantly lower in the presence of a low COL1A1 optical density index in the tumor tissue.CONCLUSIONS:The identified relationship between COL1A1 expression and such indicators of BCa malignancy as tumor size, differentiation grade, molecular subtype, receptor status, and the recurrencefree survival of patients indicates the prospects of its use to predict the aggressiveness of the BCa course in young patients.

The effects of insulin on the doxorubicin (Dox) sensitivity of breast cancer cell line MCF-7 and its Dox-resistant counterpart MCF-7/Dox were studied and glucose metabolism, content of essential minerals, and the expression of several microRNAs in these cells upon exposure to insulin and Dox were compared. Cell viability colorimetric assay, colorimetric enzymatic technique, flow cytometry, immunocytochemical techniques, inductively-coupled plasma atomic emission spectroscopy, and quantitative polymerase chain reaction were used in the study. We found that insulin in high concentration significantly suppressed Dox toxicity, especially in parental MCF-7 cell line. The increase in proliferative activity triggered by insulin in MCF-7 but not MCF-7/Dox cells occurred in the setting of the increased level of specific binding sites for insulin and increased glucose uptake. Insulin treatment of MCF-7 cells in low and high concentrations resulted in the increase of Mg, Ca, and Zn content while in DOX-resistant cells, only Mg content increased upon exposure to insulin. High concentration of insulin increased the expression of kinase Akt1, P-glycoprotein 1 (P-gp1) and DNA excision repair protein ERCC-1 in MCF-7 cells, while in MCF-7/Dox cells, Akt1 expression decreased, and cytoplasmic expression of P-gp1 increased. In addition, insulin treatment affected expression of miR-122-5p, miR-133a-3p, miR-200b-3p, and miR-320a-3p. The decreased manifestation of biological effects of insulin in Dox-resistant cells could be partly explained by the different patterns of energy metabolism in MCF-7 cells and their Dox-resistant counterpart.

Summary. Prostate cancer (PCa) is one of the most common oncological diseases in men both in Ukraine and in the world, which determines the need to search for new diagnostic and prognostic markers. According to the data of modern literature, a characteristic feature of malignant growth and progression is the remodeling of the extracellular matrix on the background of an increase in the expression of matricellular proteins (MCP). Aim: to conduct a comparative study of the expression of matricellular genes at the level of mRNA (SPP1 and SPARC) and protein (OPN and ON) in the tissue of benign and malignant tumors of the prostate gland. Objects ОРИГІНАЛЬНІ ДОСЛІДЖЕННЯ 5 4 ОНКОЛОГІЯ • Т. 25 • № 1 • 2023 Одержано: 25.04.2023 and methods: the work is based on the analysis of the results of examination and treatment of 50 patients with stage II–III prostate cancer and 20 patients with benign prostatic hyperplasia (BPH), who were treated during 2015–2021 at the National Cancer Institute of the Ministry of Health of Ukraine. The study of the expression of matricellular genes at the level of mRNA and protein in the PCa and BPH tissues was carried out using the methods of real-time polymerase chain reaction and immunohistochemistry, respectively. The bioinformatical study of SPP1 and SPARC expression in the tissue of BPH and PCa was carried out using the сamсАРP resource on the Cambridge Dataset (2015). The analysis of the recurrence-free survival rates of patients with PCa depending on the expression of SPP1 and SPARC was carried out using the PROGgeneV2 (GSE40272 Dataset). Statistical analysis was performed using GraphPad Prism v. 8.00. Results: the analysis of the results of the immunohistochemical study of the MCP established that the PCa tissue is characterized by a high level of OPN and ON. It has been demonstrated that the level of ON expression in the PCa tissue is 2.5 (p < 0.05) times higher compared to BPH tissue. It was found that the level of SPP1 and SPARC in the PCa tissue was 3.9 (p < 0.05) and 28.9 (p < 0.05) times higher compared to the corresponding expression indicators of the studied genes in the tissue of the BPH. It is shown that the rate of recurrence-free 5-year survival decreased by 20.0% (p < 0.05) in patients with PCa with a high level of SPARC mRNA in the tumor tissue. Conclusions: the obtained results indicate the need for further study of the role of MCP genes in the mechanisms of the development of PCa with the aim of using these indicators as markers for the differential diagnosis of the tumor process.

Summary. Aim: to investigate the influence of human microbiota element Lactobacillus rhamnosus on the viability, proliferation and apoptosis of breast cancer (BC) cells with various degrees of malignancy in vitro. Objects and methods: human breast cancer cells of the MCF-7, T47D and MDA-MB-231 lines, as well as live and pasteurized bacteria cells of Lactobacillus rhamnosus or their secreted metabolites, were used as research objects. The expression of proteins associated with the proliferation and apoptosis regulation in breast cancer cells was assessed by immunocytochemical analysis. Results: the direct interaction of Lactobacillus rhamnosus live cells and BC cells leads to the most significant effect on the viability and proliferation of malignant cells, compared to the action of their secreted metabolites (contactless cocultivation in the Insert system) or pasteurized microorganisms. Incubation of luminal-type breast cancer cells with Lactobacillus rhamnosus was accompanied by suppression of the proliferation marker Ki-67expression. Co-cultivation of T47D cells and Lactobacillus rhamnosus led to increased expression of both the pro-apoptotic proteins Bax and p21WAF1, as well as the anti-apoptotic protein Bcl-2. In MCF-7 cells lactobacilli increased the expression of p21WAF1, but did not affect the expression of Bcl-2. In MDA-MB-231 cells, which are characterized by the highest degree of malignancy, Lactobacillus rhamnosus caused only an increase in the anti-apoptotic marker Bcl-2 expression. Conclusions: in human ВС cells with various degrees of malignancy after their cultivation with Lactobacillus rhamnosus, various vector mechanisms of modification of the vital activity system of malignant cells by changing their proliferative activity and initiating their apoptotic program were revealed. Key words: microbiota, Lactobacillus, breast