Serum miR-181а and miR-25 Levels in Patients with Breast Cancer or Benign Breast Disease.

Circulating miR-181а and miR-25, which reflect regulation of the expression of carcinogenesis-related genes, were assayed in patients with invasive carcinoma of no specific type (ICNT) or benign breast diseases (BBDs) and in subjects without pathologies of the mammary gland (controls). miR-181а expression level proved to be higher compared to control in patients with fibroadenoma and adenosis with low, but not high, risk of malignant transformation, as well as in patients with luminal HER2-negative type B (Lum B HER2-), HER2-positive type (HER2+), and triple-negative breast cancer (TNBC) than in the controls and luminal-type (Lum A) breast cancer. MiR-25 expression level prevailed in patients with Lum B HER2- compared to control, Lum A, and TNBC patients compared to Lum A.

Serum miR-181a and miR-25 in patients with malignant and benign breast diseases.

Breast tumor diseases include a wide range of pathologies that require different approaches to their treatment. MicroRNA (miR) levels, reflecting regulation of the gene expression involved in tumorigenesis, can be diagnostic and prognostic markers of breast diseases. The levels of circulating miR-181a and miR-25 were measured in patients with benign breast diseases (BBD), patients with invasive carcinoma of a nonspecific type (ICNT) and also in conditionally healthy women.

[Expression of markers of epithelial-mesenchymal transition in breast cancer].

Objective: To study of the expression of epithelial-mesenchymal transition markers in various molecular subtypes of cancer and in benign breast diseases with different risks of malignant transformation.

Material And Methods: An immunohistochemical study of the expression of E-cadherin, collagen II, integrin 1β, cyclin D1 was carried out in breast tissue samples: 58 with invasive breast carcinoma of no special type and 17 with benign breast diseases with a high and low risk of malignant transformation.

Results: Patients with a triple negative molecular subtype are characterized by lower expression of collagen II compared with individuals with luminal A and B+ subtypes.

Cytokines in various molecular subtypes of breast cancer.

Introduction: Breast cancer is a heterogeneous disease that has multiple molecular and morphological subtypes. Nonetheless, the relation between various molecular subtypes and functional characteristics of a tumor in terms of cytokine secretion remains unknown.

Methods: We studied spontaneous and mitogen-induced cytokine secretion by invasive breast carcinoma of no special type (IBC NST; cultured tumors and cultured peripheral blood cells), depending on a molecular tumor subtype (where "mitogens" means "polyclonal activators" (PA): phytohemagglutinin , phytohemagglutinin M, concanavalin A, and lipopolysaccharide).

Analyzing the relationship between the cytokine profile of invasive breast carcinoma, its histopathological characteristics and metastasis to regional lymph nodes.

This study was aimed at analyzing the relations of metastasis to regional lymph nodes (RLNs) with histopathological indicators of invasive breast carcinoma of no special type (IC-NST) and its cytokine profile. Enzyme-linked immunosorbent assays were performed to determine concentrations of IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF-A, and MCP-1 in the culture supernatant of IC-NST samples from 48 female patients. Histopathological indicators (degree of tumor cell differentiation, mitoses, and others) and ER, PR, Her2/neu, Ki-67, and CD34 expression levels were determined.

Cytokine Production by Tumor Bioptate at Different Pathological Prognostic Stages in Breast Cancer.

Differences in the production of cytokines by tumor biopsy specimens were revealed depending on the pathological prognostic stages of The American Joint Committee on Cancer (AJCC) of invasive nonspecific breast carcinoma (INBC). The patients with a predominant absence of metastases in combination with a triple negative molecular subtype differ from the patients with other pathological prognostic stages in the cytokine-producing tumor resource of IL-18, IL-1β, IL-1Ra, TNF-α, GM-CSF, and MCP-1.

[Influence of the HLDF differentiation factor on the production of cytokines by bio-tissues of breast tissue in its non-malignant diseases and in invasive carcinoma of a non-specific type].

We studied the effect of the HLDF differentiation factor on production of cytokines by biopsy samples of nonmalignant breast diseases (ND) and invasive breast carcinoma of no special type (IBC-NST), in the absence and presence of lymphogenic metastasis: IBC-NST patients werw subdivided into groups on the prognostic protocol of the 8th edition of the AJCC committee. Group IA consisted of patients with T1-T2 tumor sizes, and predominantly with positive expression of estrogen and progesterone receptors (ER+/PR+/HER2-); it also included one patient with the HER2+ (ER-/PR-/HER2+) molecular subtype. The IB group was mainly composed of patients with T2 tumor size, with the presence of lymphogenic metastasis (in 8 out of 10) patients and with positive expression of estrogen and progesterone receptors (ER+/PR+/HER2-) and it also included three patients with the HER2+ (ER-/PR-/HER2+) molecular subtype.

Influence of HLDF Differentiation Factor on Nonspecific Invasive Breast Carcinoma in vitro.

The study was carried out on samples of invasive breast carcinoma of no special type from 36 patients aged 48.0 to 62.8 years.

Effects of polyclonal activators on cell differentiation and cytokine production of cultured invasive breast carcinoma of no special type, their association with tumour histopathological parameters and lymph node metastasis.

Currently, a number of promising strategies and approaches to cancer treatment include differentiation therapy. However, theoretical and methodological foundations of this field are not yet well developed. The objective of this study was to determine the effects of a mixture of polyclonal activators (PAs; phytohaemagglutinin, concanavalin A and lipopolysaccharide) on cytokine production by biopsy samples of invasive breast carcinoma of no special type (IBC-NST) having various differentiation abilities and metastatic potentials as well as on differentiation status of the IBC-NST biopsy samples.

Influence of Internal and External Factors on the Production of Cytokines by Peripheral Blood Cells in Breast Cancer.

The article focuses on the influence of human leukemia differentiation factor (HLDF), carcinoembryonic antigen (CEA), and polyclonal activators (PA) on cytokine production by peripheral blood cells in breast cancer and benign breast diseases. It was found that the influence of internal factors on the production of cytokines by the peripheral blood cells is associated with lymphatic metastasis (CEA: IL-10; HLDF: IL-6, IL-1β, TNF-α, and G-CSF). One special circumstance was that there were no differences between the production of cytokines by peripheral blood cells in the patients with breast cancer compared to the patients with benign breast diseases with a high risk of malignant transformation.

Personalized Approach to Determination of Histidine-Rich Glycoprotein and E-Cadherin in Supernatants of Immunocompetent Blood Cells and Breast Biopsy Specimens in Breast Malignant and Non-Malignant Disease.

The material of patients with invasive carcinoma of no special type (ICNT) and nonmalignant diseases (ND) of the mammary gland was studied. When comparing the concentrations of histidine-rich glycoprotein (HRG) and E-cadherin (CDH1), statistically significant differences between ICNT and ND by HRG in the supernatant of blood cells and its spontaneous production by biopsies and by CDH1 at its induced production, as well as by influence indices of polyclonal activators on the production of CDH1 were found. When comparing the expression of immunohistochemical markers, no statistically significant differences between ICNT and ND were obtained.

[Relationship between supernatant cytokines and expression of markers of epitelial-mesenchymal transition of invasive breast carcinoma of non-specific lymphynosis type].

The relationship between the content of supernatant cytokines and the expression of non-specific type of markers of epithelial-mesenchymal transition markers in the presence (group II) and the absence of lymphogenous metastasis (group I) were studied in biopsy specimens of mammary invasive breast carcinoma. The concentrations of TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, MCP-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β and IL-1Ra, as well as the expression of immunohistochemical (IHC) markers of the epithelial-mesenchymal transition - cadherin-E (CDH1), β-1 integrin (CD29) and type II collagen (CII) were assayed. Results have shown that patients of these groups statistically significantly differed in spontaneous production of IL-18 and G-CSF, in terms of the index of the effect of the polyclonal activator on G-CSF production.

[Cytokine production by blood immune cells, tumor and its microenvironment, characteristic of extracellular matrix in patients with invasive ductal carcinoma of no special type].

The aim of this research was to study cytokine production by blood immune cells, tumor, and its microenvironment, and characterize extracellular matrix of patients with invasive ductal carcinoma of no special type and lymphatic metastases. Spontaneous and polyclonal activators stimulated production of cytokines by blood immune cells, tumor and its microenvironment were studied in 95 patients with invasive ductal carcinoma of no special type. The concentration of IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF and MCP-1 was determined by the solid-phase enzyme-linked immunosorbent assay.

[Assessment of the cytokine-producing resource of tumor biopsy samples from patients with invasive carcinoma of no special type and with non-malignant breast diseases].

Breast cancer, in most cases, is a malignant neoplasm associated with infiltration of a tumor with the cells that form its microenvironment and produce various cytokines. The aim of the study was to evaluate the cytokine-producing function of tumor cells and their microenvironment in biopsy specimen of patients with invasive carcinoma of no special type and in patients with benign breast diseases. To assess the cytokine-producing activity of the tumor and its microenvironment, the index of polyclonal activators influence on cytokine production by biopsy specimens of patients with invasive carcinoma of no special type (group I) and in patients with benign breast tumors (group II) was calculated.

The Relationship Between Cytokine Production, CSF2RA, and IL1R2 Expression in Mammary Adenocarcinoma, Tumor Histopathological Parameters, and Lymph Node Metastasis.

Objective: The aim of this study was to evaluate the relationship between cytokine production, GM-CSF receptor (CSF2RA), and IL-1 receptor (IL1R2) expression in mammary adenocarcinoma and their association with it histopathological parameters and lymph node metastasis.

Methods: We analyzed tumor biopsy samples (cultured ) from 50 women (aged 43-75) with invasive ductal mammary adenocarcinomas. Enzyme-linked immunosorbent assay method the concentrations of interleukin 2, interleukin 6, interleukin 8, interleukin 10, interleukin 17, interleukin 18, interleukin 1β, interleukin 1Ra, tumor necrosis factor α, interferon γ, granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, and vascular endothelial growth factor A were determined in culture supernatants.

Personalized Approach to Assessing mRNA Expression of Histidine-Rich Glycoprotein and Immunohistochemical Markers in Diseases of the Breast.

Biopsy material of patients with malignant and benign breast diseases was examined. HRG mRNA expression was detected in 70% of cases in biopsy material obtained from patients with nonspecific invasive carcinoma and in 66.7% of cases in biopsy material of patients with benign breast diseases.

VEGF-R2 and TNF-R1 expression and cytokine production by samples of mammary adenocarcinomas and correlations with histopathological parameters of these malignant tumors.

Currently, the role of cytokines in the tumor progression, including breast cancer, is universally recognized. At the same time, there are still many questions concerning the role of individual cytokines and receptors for cytokines in various morphogenetic processes underlying the tumor progression. The objective of this work was to study cytokine production and vascular endothelial growth factor (VEGF)-R2 and VEGF-R1 expression by mammary adenocarcinoma (MAC) and the correlations with histopathological parameters of malignant tumors.

Messenger RNA of the Histidine-Rich Glycoprotein in Breast Tumors.

The content of mRNA of the histidine-rich glycoprotein (HRG), a potential marker of malignant neoplasia, which can be used in differential diagnosis of breast tumors, was determined in 110 breast tumor biopsy samples. The presence of HRG mRNA did not depend on the cancer type, on the preoperative treatment or its absence, as well as on the tumor progression stage and the presence of metastases.

Cytokine production by the tumor from patients with breast cancer in different age groups.

Dependence of cytokine pattern in the tumor supernatant obtained after cultivation of biopsy samples-on the patients' age was evaluated among patients with invasive ductal carcinoma of the breast. An increase in VEGF and IL-6 production in a group of younger patients was observed. An increase only in interferon γ concentration was revealed in the supernatants of the tumor after addition of polyclonal activators to the culture medium.

Cytokine production in mammary adenocarcinoma and its microenvironmental cells in patients with or without metastases in regional lymph nodes.

In recent years, the concept of formation of a sufficiently autonomous cytokine network in a malignant tumour has emerged. In this regard, the data on the role of this network and its signalling pathways in the process of metastasis are an interesting topic. The aim of this study was to evaluate the in vitro cytokine-producing potential of mammary adenocarcinoma (MAC; and cells of its microenvironment) from patients with or without metastases in regional lymph nodes (LNs).

Cytokine profiles of tumor supernatants in invasive ductal cancer and fibroadenoma of the breast and its relationship with VEGF-A expression in the tumors.

Interrelations between cytokines, produced by invasive ductal carcinoma (IDC) and fibroadenoma (FA) of the breast, and angiogenic growth factor VEGF-A, expressed in IDC and FA, were investigated. The analysis of the cytokine profiles of IDC and FA was performed by cultivation of tumor biopsy specimens in vitro. Testing of the cytokine-producing reserve of the tumors for production of VEGF-A was conducted by culturing samples of IDC and FA in a medium containing polyclonal activator (a complex of phytohemagglutinin, concanavalin A, and lipopolysaccharide).

Cytokine pattern of the breast tumor supernatant.

Cytokine production was evaluated in supernatants of cultured tumor cells that were obtained by biopsy of the breast invasive ductal carcinoma (IDC) and breast fibroadenoma (FA) and grown in vitro. In the IDC supernatants, the concentrations of pro-inflammatory (pro-oncogenic) cytokines IL-17, IL-18, and IFNγ and of IL-1 receptor antagonist were significantly higher than in the FA cell supernatants. The concentrations of anti-inflammatory cytokine IL-10 and MCP-1 protein in supernatants of IDC cells were significantly lower than those determined in FA supernatants.

Specific effect of the HLDF differentiation factor on the cytokine production potential of immunocompetent blood cells in stomach adenocarcinoma.

The cytokine production potential of immunocompetent cells from the blood of stomach adenocarcinoma patients was analyzed after the pretreatment of cells with the HLDF differentiation factor with subsequent exposure to polyclonal activators (HLDF+PA). IL-1β, IL-1Ra, TNFα, IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-18BPa, IFNγ, G-CSF, and GM-CSF were quantified in the supernatants after precipitation of the cells. Specific effects of HLDF+PA were manifested as an increase in the production of IL-8, IL-17, and GM-CSF due to suppression of Th1-dependent immune reactions in a Th17-mediated mechanism that is a part of a broader functional antagonism of Th1 and Th17 lymphocyte subpopulations.

Cytokine-producing function of human blood cells in chronic atrophic gastritis and gastric adenomas and adenocarcinomas.

The cytokine-producing potential of blood cells has been studied in the atrophic gastritis-adenoma-adenocarcinoma progression of pathological states of the stomach. It has been revealed that, at the initial stage of carcinogenesis, namely adenoma, immunocompetent cells have the highest cytokine-producing proto-oncogenic potential as compared to both atrophic gastritis, which presents a precancerous condition, and completely formed malignant tumor (gastric adenocarcinoma).

Effect of polyclonal activators on cytokine production by blood cells and by malignant breast cancer cells.

The production of cytokines by peripheral blood cells and biopsy specimens of tumors stimulated by polyclonal activators (PAs) was evaluated in 34 patients with invasive ductal breast carcinoma using enzyme-linked immunosorbent assay (ELISA). Positive correlation between the stimulation index of polyclonal activators (SIPA) for IL-18 production by the tumor and the relative content of poorly differentiated cells was revealed. The latter, in turn, was positively correlated with the numbers of normal and pathologic mitoses and the degree of malignancy.