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BACKGROUND. The course and outcomes of primary IgA nephropathy in children are variable. Early therapy for high-risk individuals can help to delay the development of end-stage renal disease.THE AIM: to analysis of risk factors for progression and outcomes in children with IgA nephropathy, taking into account clinical and morphological data at the onset and during follow-up.PATIENTS AND METHODS. A retrospective study of 75 children was carried out; the median follow-up was 28 months. The median age of onset was 9.1 years. Patients were divided into 2 groups: 1st – patients with idiopathic IgA nephropathy (n= 53), 2nd – patients with Shenlein-Henoch purpura (n = 22). The diagnosis of primary IgA nephropathy was morphologically confirmed in all patients. Nephrobiopsy data were classified according to the Oxford scale (MEST-C score). The age of onset and first-time admission, the level of proteinuria and glomerular filtration rate (GFR) at the onset, at 12 months, at the end of follow-up, mean arterial blood pressure, MEST-C score, medication before nephrobiopsy were investigated. Progression was determined as a decrease in GFR less than 60 ml/min/1.73 m2. Outcomes were assessed by absence/presence of remission. We provided a search for factors influencing GFR at the end of the follow-up. Data analysis was performed using Student's t-test, Mann-Whitney, χ2, Fisher, linear regression model, binary logistic regression.RESULTS. Unlike adults, the predictive value of the MEST-C score in children has not been proven and is not associated with a decrease in GFR 2. GFR at the end of follow-up was lower in the idiopathic IgA nephropathy group than in group 2. The use of multiple linear regression predicts GFR on average after 28 months of observation.RESULTS. Unlike adults, the predictive value of the MEST-C scale in children has not been proven and is not associated with a decrease in GFR 2. GFR at the end of follow-up was lower in the idiopathic IgA nephropathy group. The use of multiple linear regression predicts GFR on average after 28 months of observation.CONCLUSIONS. The influence of morphological factors on the outcome and course of IgA nephropathy has not been proven. The level of GFR at the onset, mean blood pressure, and the age of the first-time admission turned out to be independent variables, which made it possible to identify children with an expected decrease in GFR less than 90 ml/min /1.73 m2 to the group of specific outpatient follow-up.

The relationship between the content of supernatant cytokines and the immune histochemical (IHC) expression of epithelial-mesenchymal transition (EMT) markers was studied in biopsy samples of invasive breast carcinoma of no special type (IBC-NST) from patients with and without lymphatic spread of metastases (group II and group I, respectively). 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 immunohistochemical (IHC) expression of EMT markers cadherin-E (CDH1), β-1 integrin (CD29) and type II collagen (CII) were assayed. Results have shown that the patients of these groups statistically significantly differed by spontaneous production of IL-18 and G-CSF, and by the index of the polyclonal activator influence (IPAI) on G-CSF production. The study of relationships between supernatant cytokine production and the IHC expression by biopsy samples revealed correlations between the parameter of CII expression in the tumor tissue and the cytokine production by tumor biopsy specimens; these correlation links were typical for all IBC-NST patients, while correlation links (both direct and reverse ones) between CDH1, CD29, and cytokine production varied in groups of patients with and without lymphatic spread of metastases. The study revealed the features of the correlation links between the cytokine production by the tumor, its microenvironment and the IHC expression of EMT markers in IBC-NST patients with and without lymphatic spread of metastasis.

To improve early detection of cancer, search for tumor markers in biological fluids is of great importance. A significant portion of exosomes is associated with the surface of blood cells, however, the protein spectrum of such exosomes has not been previously studied. The use of total blood exosomes (plasma exosomes and exosomes associated with the surface of blood cells) can not only significantly increase the specificity and sensitivity of existing methods, but also suggest new tumor markers for liquid biopsy. Objective. Search for candidate protein tumor markers of breast cancer by comparing 2D-proteomic maps of total blood exosomes of healthy females (HFs) and breast cancer patients (BCPs). Methods. Exosomes were isolated from plasma and total blood of HFs and BCPs by ultrafiltration followed by ultracentrifugation and were characterized using transmission electron microscopy (TEM) and immunocytochemistry. Protein concentration in exosomes was determined using the NanoOrange Protein Quantitation kit (Invitrogen) commercial kit. Proteomes of exosomes were studied using 2d electrophoresis followed by protein identification by mass spectrometry. Results. Highly purified samples of vesicles from plasma and total blood of no more than 100 nm in size were obtained, on the surface of which markers specific for exosomes were detected by monoclonal antibodies CD9. A comparative analysis of the proteomic maps of exosomal proteins of the HFs and BCPs obtained by 2D-electrophoresis allowed us to establish significant differences in the expression level and protein set in normal and pathological conditions. The 11 proteomic markers of breast cancer were identified by the peptide fingerprint method, of which LRG и у -chain FGB were detected in the composition of exosomes for the first time (according to the Exocarta database). Using MALDI-TOF mass spectrometry, 99 proteins were identified in the exosome preparations of the blood of HFs and BCPs, of which 35% were detected in the composition of the exosomes for the first time (according to the Exocarta database). 17 (53%) proteins associated with breast cancer were detected in total blood exosomes of cancer patients. Conclusion. The results obtained indicate that total blood exosomes are a promising source of diagnostic material for the search for proteomic markers of breast cancer. The identified proteomic tumor markers require further validation.

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.

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. Group IIA consisted of patients with T1-T2 tumor sizes, mainly with no metastases in the lymph nodes (in 11 out of 12 patients) and with a triple negative molecular subtype. Group IIB included patients with T2 tumor size, the presence of nodal metastasis and the expression of markers of ER-/PR-/HER2 - and ER-/PR-/HER2+. Group IIIA consisted of patients with tumor size T1-T3, with the presence of nodal metastasis and the expression of markers of ER-/PR+/HER2+ and ER-/PR-/HER2+. Group IIIC consisted of patients with T3 tumor size, lymphogenic metastasis, and expression of ER-/PR-/HER2-markers (triple negative molecular subtype). Due to a limited number of patients in the groups IIB, IIIA and IIIC, as well as due to more severe clinical and pathological stages, according to the prognostic Protocol of the 8th edition of the AJCC Committee, they were pooled into group III. Concentrations 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 were assayed in supernatants of biopsy specimens of breast tissue. Results have shown that with IBC-NST, a statistically significantly higher level of spontaneous production (SP) by biopsy specimens of IL-17, IL-18, IFN-γ and VEGF, and a lower level of SP IL-6 as compared with ND. Patients of all clinical and pathological groups showed a high VEGF spontaneous production as compared with ND, while statistically significant differences from patients with ND were not found in IL-17 spontaneous production in group IB patients, and IL-18 spontaneous production were absent in group IA. Only in patients with IA and IB, the IL-6 spontaneous production was lower as compared to ND, and the IL-8 spontaneous production was lower in the IA group. IFN-γ spontaneous production was higher in patients with IBC-NST group IIA as compared with ND. Under the influence of the HLDF differentiation factor, it was found that the parameters of IBC-NST patients were statistically significantly higher in the production of IL-1Ra, IL-17, IL-18 and VEGF, and statistically significantly lower in the production of IL-6 as compared to ND. HLDF had a higher impact on the content of IL-18 in IBC-NST patients than in ND. After HDLF sublimation IL-6 values were lower in patients of groups IA and IB, and HLDF-induced IL-17 production was higher only in patients of group IA. Statistically significant differences in the index of influence of HLDF (IVHLDF), representing ratio of the cytokine concentration in the supernatants of a biopsy specimen stimulated by HLDF to spontaneous cytokine production, were found between ND and IBC-NST in the case of on IFN-γ production, and also in the case of IL-4 production (between patients in the absence and presence of lymphogenic metastasis). IVHLDF for production of IL-6, IL-8 and TNF-α was lower in group IIA patients compared to group IA, and IVHLDF for production of GM-CSF and MCP-1 was lower in group IIA as compared to group III, in addition IVHLDF for MCP-1 products was lower in group IIA as compared to ND. The HLDF effect on the cytokine production by the tumor and its microenvironment was different in ND patients and IBC-NST patients. HDLF suppressed IFN-γ production in the pooled group of IBC-NST patients; HLDF mainly had a suppressive effect on the production of IL-6, IL-8, TNF-α, GM-CSF and MCP-1 in IBC-NST patients of group IIA.Issledovali vliianie faktora differentsirovki HLDF na produktsiiu tsitokinov bioptatami pri nezlokachestvennykh zabolevaniiakh molochnoĭ zhelezy (NZ) i pri invazivnoĭ kartsinome molochnoĭ zhelezy nespetsificheskogo tipa (IKNT), pri otsutstvii i nalichii limfogennogo metastazirovaniia, a takzhe u patsientov s IKNT, raspredelennykh po podtipam na osnove prognosticheskogo protokola 8 izdaniia komiteta AJCC. Gruppu IA sostavili patsienty s razmerami opukholi T1-T2 i preimushchestvenno s polozhitel'noĭ ékspressieĭ retseptorov éstrogena i progesterona (ER+/PR+/HER2-) i odin patsient s HER2+ (ER-/PR-/HER2+) molekuliarnym podtipom. V gruppu IB byli vkliucheny patsienty s razmerami opukholi T2, preimushchestvenno s nalichiem limfogennogo metastazirovaniia (8 iz 10) i s polozhitel'noĭ ékspressieĭ retseptorov éstrogena i progesterona (ER+/PR+/HER2-), a takzhe tri patsienta s molekuliarnym podtipom HER2+ (ER-/PR-/HER2+). Gruppu IIA sostavili patsienty s razmerami opukholi T1-T2, preimushchestvenno s otsutstviem metastazov v limfouzlakh (11 iz 12 bol'nykh) i s troĭnym negativnym molekuliarnym podtipom. Gruppu IIB sostavili patsienty s razmerami opukholi T2, nalichiem limfogennogo metastazirovaniia i ékspressieĭ markerov: ER-/PR-/HER2- i ER-/PR-/HER2+. Gruppu IIIA sostavili patsienty s razmerami opukholi T1-T3, nalichiem limfogennogo metastazirovaniia i ékspressieĭ markerov: ER-/PR+/HER2+ i ER-/PR-/HER2+. Gruppu IIIC sostavili patsienty s razmerami opukholi T3, s nalichiem limfogennogo metastazirovaniia i s ékspressieĭ markerov ER-/PR-/HER2- (troĭnoĭ negativnyĭ molekuliarnyĭ podtip). Vvidu malogo kolichestva patsientov v gruppakh IIB, IIIA i IIIC, a takzhe v sviazi s bolee tiazhelymi kliniko-patologicheskimi stadiiami soglasno prognosticheskomu protokolu 8 izdaniia komiteta AJCC oni byli ob"edineny v odnu gruppu III. Kontsentratsii 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 i MCP-1 opredeliali v supernatantakh bioptatov tkani molochnoĭ zhelezy. Issledovaniia pokazali, chto pri IKNT otmechalsia statisticheski znachimo bolee vysokiĭ uroven' spontannoĭ produktsii (SP) IL-17, IL-18, IFN-γ i VEGF i bolee nizkiĭ uroven' SP IL-6 po sravneniiu s NZ molochnoĭ zhelezy. U patsientov vsekh kliniko-patologicheskikh grupp IKNT otmechena vysokaia SP VEGF po sravneniiu s NZ, togda kak statisticheski znachimye razlichiia ot patsientov s NZ po SP IL-17 otsutstvovali u patsientov gruppy IB, a po SP IL-18 otsutstvovali u patsientov IA. Tol'ko u patsientov grupp IA i IB SP IL-6 byla nizhe po sravneniiu s NZ, a SP IL-8 byla nizhe u patsientov gruppy IA. SP IFN-γ byla vyshe u patsientov s IKNT gruppy IIA po sravneniiu s NZ. Pri vozdeĭstvii faktora differentsirovki HLDF ustanovleno, chto pokazateli patsientov s IKNT byli statisticheski znachimo bolee vysokimi po produktsii IL-1Ra, IL-17, IL-18 i VEGF i statisticheski znachimo bolee nizkimi po produktsii IL-6 po sravneniiu s NZ molochnoĭ zhelezy. Pri vozdeĭstvii HLDF na produktsiiu IL-18 ego soderzhanie okazalos' vyshe u patsientov vsekh kliniko-patologicheskikh grupp po sravneniiu s patsientami s NZ. Po sravneniiu s NZ tol'ko u patsientov grupp IA i IB pokazateli IL-6 pri vozdeĭstvii HLDF byli nizhe, a indutsirovannaia HLDF produktsiia IL-17 byla vyshe tol'ko u patsientov gruppy IA. Statisticheski znachimye razlichiia po indeksu vliianiia HLDF (IVHLDF), predstavliaiushchim soboĭ otnoshenie kontsentratsii tsitokinov v supernatante bioptata, pri vozdeĭstvii HLDF k spontannoĭ produktsii tsitokinov byli ustanovleny mezhdu NZ i IKNT po IVHLDF na produktsiiu IFN-γ, a takzhe po IVHLDF na produktsiiu IL-4 mezhdu patsientami pri otsutstvii i nalichii limfogennogo metastazirovaniia. IVHLDF na produktsiiu IL-6, IL-8 i TNF-α byl nizhe u patsientov gruppy IIA po sravneniiu s gruppoĭ IA, a IVHLDF na produktsiiu GM-CSF i MCP-1 byl nizhe u gruppy IIA po sravneniiu s pokazateliami gruppy III, krome togo, IVHLDF na produktsiiu MCP-1 byl nizhe u gruppy IIA po sravneniiu s NZ. Vliianie faktora differentsirovki HLDF na produktsiiu tsitokinov opukhol'iu i ee mikrookruzheniem razlichno dlia patsientov s NZ i IKNT. Faktor differentsirovki okazyval supressiruiushchee vliianie na produktsiiu IFN-γ u patsientov s IKNT i na produktsiiu IL-4 tol'ko u patsientov s limfogennym metastazirovaniem i na produktsiiu IL-6, IL-8, TNF-α, GM-CSF i MCP-1 u patsientov s IKNT gruppy IIA.

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. Group II was further subdivided into group IIa, which included only patients with fibroadenoma, and group IIb, which included the patients with leaf-shaped fibroadenoma, fibroadenomatosis, fibrocystic mastopathy, intraductal papillomatosis, sclerosing adenosis and fibrocystic mastopathy with microcalcifications. The 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, and MCP-1 were measured in tumor biopsy supernatants. When comparing groups I and II, higher indices of the polyclonal activators influence on the production of IL-17, IL-18 and TNF-α were observed in patients with benign diseases. Higher indices of the polyclonal activators influence on the production of IL-18, TNF-α, and IL-1β and the ratio of IL1β/IL1Ra were observed in patients with fibroadenoma as compared to those with invasive carcinoma of no special type. There were no significant differences in the indices of the polyclonal activators influence between groups I and IIb. This suggests the existence of changes in the mammary gland in patients of group IIb similar to those present in patients with invasive carcinoma of no special type. Higher indices of polyclonal activators influence on the production of IL-1β, as well as the ratio of IL1β/IL1Ra were observed in the patients of group IIa compared to the patients of group IIb. The results of the study identify the features of the cytokine-producing resource of tumor biopsy specimens in patients with invasive carcinoma of no special type and with benign breast tumors.Rak molochnoĭ zhelezy v bol'shinstve sluchaev iavliaetsia primerom zlokachestvennogo novoobrazovaniia, sviazannogo s infil'tratsieĭ opukholi kletkami, obrazuiushchimi mikrookruzhenie opukholi i produtsiruiushchimi razlichnye tsitokiny. Tsel'iu issledovaniia byla otsenka tsitokinprodutsiruiushcheĭ funktsii opukholevykh kletok i ikh mikrookruzheniia v bioptatakh opukholi patsientov s invazivnoĭ kartsinomoĭ nespetsificheskogo tipa (gruppa I) i u patsientov s nezlokachestvennymi zabolevaniiami molochnoĭ zhelezy (gruppa II). Bol'nye II gruppy byli razdeleny na gruppu IIa, v kotoruiu voshli patsienty tol'ko s fibroadenomoĭ, i gruppu IIb, v kotoruiu voshli ostal'nye patsienty s listovidnoĭ fibroadenomoĭ, fibroadenomatozom, fibrozno-kistoznoĭ mastopatieĭ, vnutriprotokovym papillomatozom, skleroziruiushchim adenozom i fibrozno-kistoznoĭ mastopatieĭ s mikrokal'tsinatami. Kontsentratsiiu 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 i MCP-1 opredeliali v supernatante bioptatov opukholeĭ. Dlia otsenki tsitokinprodutsiruiushcheĭ aktivnosti bioptatov opukholi i ee mikrookruzheniia opredeliali indeks vliianiia poliklonal'nykh aktivatorov na produktsiiu tsitokinov. Pri sravnenii I i II grupp byli polucheny vysokie indeksy vliianiia poliklonal'nykh aktivatorov na produktsiiu IL-17, IL-18 i TNF-α u patsientov s nezlokachestvennymi zabolevaniiami. Bolee vysokie znacheniia indeksov vliianiia poliklonal'nykh aktivatorov na produktsiiu IL-18, TNF-α, i IL-1β i sootnosheniia IL1β/IL1Ra byli u patsientov s fibroadenomoĭ po sravneniiu s invazivnoĭ kartsinomoĭ nespetsificheskogo tipa. Statisticheski znachimykh razlichiĭ v gruppakh I i IIb po indeksam vliianiia poliklonal'nykh aktivatorov obnaruzheno ne bylo. Éto pozvoliaet predpolozhit' sushchestvovanie analogichnykh invazivnoĭ kartsinome nespetsificheskogo tipa izmeneniĭ v molochnoĭ zheleze u patsientov IIb gruppy. Pri sravnenii grupp IIa i IIb byli polucheny bolee vysokie znacheniia indeksa vliianiia poliklonal'nykh aktivatorov na produktsiiu IL-1β, a takzhe sootnosheniia IL1β/IL1Ra u patsientov s fibroadenomoĭ molochnoĭ zhelezy. Provedennoe issledovanie pozvolilo vyiavit' osobennosti tsitokinprodutsiruiushchego resursa bioptatov opukholeĭ u patsientov s invazivnoĭ kartsinomoĭ nespetsificheskogo tipa i s dobrokachestvennymi opukholiami molochnoĭ zhelezy.

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. There was a correlation between the parameter of CII expression in tumor tissue and the production of cytokines by tumor biopsy specimens; it was characteristic of all patients with invasive carcinoma of a non-specific type, and correlations, both direct and reverse between the expression indices of CDH1, CD29 and cytokine production varied depending on the presence or the absence of lymphogenous metastasis. The study revealed the features of the correlation between the production of cytokines by the tumor, its microenvironment and the expression of IHC markers of the epithelial-mesenchymal transition in patients with invasive non-specific breast carcinoma in the presence and absence of lymphogenous metastasis.Izuchena vzaimosviaz' mezhdu soderzhaniem tsitokinov supernatantov i ékspressieĭ v bioptatakh invazivnoĭ kartsinomy molochnoĭ zhelezy nespetsificheskogo tipa markerov épitelial'no-mezenkhimal'nogo perekhoda pri nalichii (II gruppa) i otsutstvii (I gruppa) limfogennogo metastazirovaniia. Opredeliali kontsentratsiiu 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 i IL-1Ra, a takzhe ékspressiiu immuno-gistokhimicheskikh (IGKh) markerov épitelial'no-mezenkhimal'nogo perekhoda – kadgerina-E (CDH1), β-1-integrina (CD29) i kollagena II tipa (CII). Po rezul'tatam issledovaniia patsienty étikh grupp statisticheski znachimo otlichalis' po spontannoĭ produktsii IL-18 i G-CSF, po indeksu vliianiia poliklonal'nogo aktivatora na produktsiiu G-CSF. Pri izuchenii vzaimosviazi mezhdu produktsieĭ tsitokinov supernatantami i ékspressieĭ v nikh IGKh markerov ustanovleno, chto korreliatsionnye sviazi mezhdu pokazatelem ékspressii CII v tkani opukholi i produktsieĭ tsitokinov bioptatami opukholi kharakterny dlia vsekh patsientov s invazivnoĭ kartsinomoĭ nespetsificheskogo tipa, a korreliatsionnye sviazi, kak priamye, tak i obratnye mezhdu pokazateliami ékspressii CDH1, CD29 i produktsieĭ tsitokinov, razlichalis' v zavisimosti ot nalichiia ili otsutstviia limfogennogo metastazirovaniia. Provedennoe issledovanie pozvolilo vyiavit' osobennosti korreliatsionnykh sviazeĭ mezhdu produktsieĭ tsitokinov opukhol'iu, ee mikrookruzheniem i ékspressieĭ IGKh – markerov épitelial'no-mezenkhimal'nogo perekhoda u patsientov s invazivnoĭ kartsinomoĭ molochnoĭ zhelezy nespetsificheskogo tipa pri nalichii i otsutstvii limfogennogo metastazirovaniia.

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. This is evidence of the functional similarity of peripheral blood cells in patients with these conditions. Cytokine production under the influence of PA was different only in case of TNF-α in all study groups.

In this work, we have compared malignant and non-malignant diseases of the mammary gland using 8 proteins: HRG, MUC1, PAI-1, HSP90αA1, CDH1, ERα, PGR and IL-12. Their concentrations in the supernatants of blood cells and breast biopsies were compared in terms of spontaneous production, induced by a polyclonal activator and after exposure to biopsy samples of the HLDF differentiation factor, as well as the indices of the effect of the polyclonal activator and HLDF on the protein production. In addition, the correlation relationships of the above indicators with the expression of markers of the epithelial-mesenchymal transition: collagen type II (CII), β-1 integrin (CD29) and cadherin-E (CDH1) were studied. The study revealed statistically significant differences in the concentration of HRG in the supernatant of blood cells, IL-12 during spontaneous production by biopsy specimens, PGR production of biopsy specimens induced by the polyclonal activator, CDH1 and IL-12 production biopsy specimens exposed to HLDF. According to the influence index of the polyclonal activator and HLDF, statistically significant differences were found for CDH1production. Comparison of non-specific invasive carcinoma biopsy specimens and non-malignant breast diseases by means of the markers of the epithelial-mesenchymal transition revealed statistically significant differences in CD29 expression and the lack of differences in the expression of CDH1 and CII. This indicates the presence of cell atypia in samples of non-malignant breast diseases; it is confirmed by the recognized correlation between the production of certain proteins and the expression of the epithelial-mesenchymal transition markers.Provedeno sravnenie pokazateleĭ zlokachestvennykh i nezlokachestvennykh zabolevaniĭ molochnoĭ zhelezy po 8 belkam: gistidinbogatyĭ glikoprotein (HRG), mutsin 1 (MUC1), ingibitor aktivatora plazminogena 1 (PAI-1), belok teplovogo shoka 90αA1 (HSP90αA1), E-kadgerin (CDH1), retseptor éstrogena α (ERα), retseptor progesterona (PGR) i interleĭkin 12 (IL-12). Ikh kontsentratsii opredeliali v supernatantakh immunnokompetentnykh kletok krovi i bioptatov molochnoĭ zhelezy pri spontannoĭ, a takzhe indutsirovannoĭ poliklonal'nym aktivatorom produktsii i posle vozdeĭstviia na bioptaty faktora differentsirovki HLDF. Pomimo étogo rasschityvali indeksy vliianiia poliklonal'nogo aktivatora i HLDF na produktsiiu étikh belkov i issledovali korreliatsionnye sviazi perechislennykh vyshe pokazateleĭ s ékspressieĭ markerov épitelial'no-mezenkhimal'nogo perekhoda: kollagena II tipa (CII), β-1-integrina (CD29) i kadgerina-E (CDH1). Obnaruzheny statisticheski znachimye razlichiia v kontsentratsii HRG v supernatante immunnokompetentnykh kletok krovi, IL-12 pri spontannoĭ produktsii bioptatami, PGR pri indutsirovannoĭ poliklonal'nym aktivatorom produktsii bioptatami, CDH1 i IL-12 pri vozdeĭstvii HLDF na bioptaty. Po indeksam vliianiia poliklonal'nogo aktivatora i HLDF statisticheski znachimye razlichiia vyiavleny na produktsiiu CDH1. Pri sravnenii markerov épitelial'no-mezenkhimal'nogo perekhoda mezhdu bioptatami invazivnoĭ kartsinomy nespetsificheskogo tipa i nezlokachestvennymi zabolevaniiami molochnoĭ zhelezy obnaruzheny statisticheski znachimye razlichiia v pokazateliakh ékspressii CD29, v to vremia kak po ékspressii CDH1 i CII razlichiĭ polucheno ne bylo. Éto svidetel'stvuet o nalichii kletochnoĭ atipii v obraztsakh nezlokachestvennykh zabolevaniĭ molochnoĭ zhelezy i podtverzhdaetsia obnaruzhennymi korreliatsionnymi sviaziami mezhdu produktsieĭ nekotorykh belkov i ékspressieĭ markerov épitelial'no-mezenkhimal'nogo perekhoda.

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. The condition of fibrous component and presence of neutral glycoproteins and sulfated glycosaminoglycans were evaluated during the research of extracellular matrix. Regional lymphatic metastases were detected in 35 of 95 patients. It was shown that in the presence or absence of lymphatic metastases index of polyclonal activators influence on the production of cytokines by blood immune cells was different for IL-6, IL-8, and IL-1β; while in the case of cytokine production by tumor and its microenvironment the index of influence was different for IL-2 and IL-17. The presence of lymphatic metastases corresponded with the rise of cytokines spontaneous production, while the absence of lymphatic metastases corresponded with the rise of cytokines production stimulated by polyclonal activators. The value of indices of polyclonal activators influence on the production of cytokines by blood immune cells pointed to the highly stimulating effect of polyclonal activators while the value of indices of polyclonal activators influence on cytokines production by tumor and its microenvironments pointed to the low and sometimes even absent effect of polyclonal activators. Basing on these data we propose a ratio of indices of polyclonal activators influence for the better evaluation of the probability of lymphatic metastases during preoperative period. After characterizing extracellular matrix we found out a point threshold, which, in 100% of cases, predicted the presence of lymphatic metastases basing on the condition of extracellular matrix. Using the data acquired, we are proposing a risk group for metastasis among women with no lymphatic metastases in the moment of check-up.Issledovali spontannuiu i stimulirovannuiu poliklonal'nymi aktivatorami produktsiiu tsitokinov immunokompetentnymi kletkami krovi, opukhol'iu i ee mikrookruzheniem, a takzhe sostoianie vnekletochnogo matriksa u 95 patsientok s invazivnoĭ kartsinomoĭ molochnoĭ zhelezy nespetsificheskogo tipa pri limfogennom metastazirovanii. S pomoshch'iu immunofermentnogo analiza opredeliali kontsentratsiiu 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 i MCP-1. Pri izuchenii vnekletochnogo matriksa otsenivali sostoianie voloknistogo komponenta, soderzhanie neĭtral'nykh glikoproteinov i sul'fatirovannykh glikozaminoglikanov. Metastazy v regionarnye limfaticheskie uzly prisutstvovali u 35 iz 95 patsientok. Issledovanie pokazalo, chto pri nalichii ili otsutstvii limfogennogo metastazirovaniia indeks vliianiia poliklonal'nykh aktivatorov na produktsiiu tsitokinov immunokompetentnymi kletkami krovi razlichalsia po trem pokazateliam (IL-6, IL-8 i IL-1β), a indeks vliianiia poliklonal'nykh aktivatorov na produktsiiu tsitokinov kletkami opukholi i ee mikrookruzheniia po dvum (IL-2 i IL-17). Nalichiiu limfogennykh metastazov sootvetstvovalo povyshenie spontannoĭ produktsii tsitokinov, a ikh otsutstviiu – povyshenie produktsii, stimulirovannoĭ poliklonal'nymi aktivatorami. Znacheniia indeksov vliianiia poliklonal'nykh aktivatorov na produktsiiu tsitokinov immunokompetentnymi kletkami krovi svidetel'stvovali o vysokom stimuliruiushchem éffekte poliklonal'nykh aktivatorov, a znacheniia indeksov vliianiia poliklonal'nykh aktivatorov na produktsiiu tsitokinov kletkami opukholi i ee mikrookruzheniia – o nizkom i dazhe otsutstvuiushchem éffekte poliklonal'nykh aktivatorov. Na osnovanii poluchennykh dannykh bylo sostavleno sootnoshenie indeksov vliianiia poliklonal'nykh aktivatorov dlia otsenki veroiatnosti limfogennogo metastazirovaniia v dooperatsionnom periode. Pri otsenke sostoianiia vnekletochnogo matriksa byl vyiavlen porog, kotoryĭ v 100% sluchaev pokazal sootvetstvie sostoianiia vnekletochnogo matriksa nalichiiu metastazov v regionarnykh limfaticheskikh uzlakh. Na osnovanii poluchennykh rezul'tatov byla predlozhena gruppa riska po metastazirovaniiu sredi zhenshchin, ne imeiushchikh na moment issledovaniia metastazov v limfaticheskikh uzlakh.

To evaluate an effectiveness of simultaneous laparoscopic procedures in patients with synchronous multiple primary cancer (SMPC).We observed 3 patients (2 men and 1 woman) aged 61-78 years with synchronous multiple primary gastric and kidney cancer. Gastric tumors were localized in the lower third of the body (1) and the antrum (2), histological structure corresponded to adenocarcinoma G1 (1) and G2 (2). Kidney tumors were verified as light cell carcinoma and localized in the upper segment of the left kidney in 2 patient and right kidney in one patient. Mean dimension of tumor scheduled for resection was 4.65 cm, nephrectomy - 10.3 cm. Complexity of resection according to the RENAL scale was equal to 8 and 10.Three patients underwent laparoscopic Billroth-I distal gastrectomy, 2 - kidney resection and one patient - nephrectomy. Mean surgery time was 265±37 min, blood loss - 175±29 ml. There were no conversion and redo interventions within 30 days after surgery. Mean hospital-stay was 11±2 days.Minimally invasive technologies in patients with SMPC reduces blood loss, ICU- and hospital-stay. Earlier rehabilitation ensures the next stage of treatment in early postoperative period, while quality of life is better in comparison with traditional interventions.Оценить возможность и эффективность симультанных лапароскопических операций у больных первично-множественным синхронным раком (ПМСР).Мы наблюдали 3 пациентов (2 мужчин и 1 женщину) с ПМСР желудка и почки в возрасте от 61 до 78 лет. Опухоль желудка локализовывалась в нижней трети тела (1) и антральном отделе (2), гистологическое строение соответствовало аденокарциноме G1 (1) и G2 (2). Опухоль почки верифицирована как светлоклеточный рак и локализовывалась в верхнем сегменте левой почки у 2 пациентов, правой — у 1. Средний размер опухоли у пациентов, которым выполнена резекция почки, составил 4,65 см, при нефрэктомии — 10,3 см. Оценка сложности резекции по шкале RENAL — 8 и 10 баллов.Всех больных прооперировали: 3 выполнили лапароскопическую дистальную субтотальную резекцию желудка по Бильроту I; у 2 пациентов произвели резекцию почки, у 1 — нефрэктомию. Среднее время операции — 265±37 мин, кровопотеря в среднем составила 175±29 мл. Конверсии доступа, а также повторных хирургических вмешательств в течение 30 сут после операции не было. Среднее время пребывания в стационаре — 11±2 дня.Применение мини-инвазивных технологий у больных с ПМСР уменьшает кровопотерю, время пребывания в реанимации и стационаре. Более ранняя активизация и реабилитация позволяют приступить к следующему этапу лечения уже в раннем послеоперационном периоде, при этом качество жизни больных выше, чем при традиционных вмешательствах.

INTRODUCTION Traditionally, evaluation of the split renal function is performed using nephroscintigraphy. However, as shown in several studies, there might be quite significant inaccuracy in the interpretation of dynamic nephroscintigraphy results. But due to the lack of alternative methods for evaluation of split renal function, nephroscintigraphy remains the method of choice. AIM To investigate the feasibility of digital analysis of contrast-enhanced MSCT imaging for evaluation of the split renal function. MATERIALS AND METHODS This is a prospective study conducted at the R.M. Fronshteyn Clinic of Urology from November 2015 to February 2017. The study comprised 31 patients with urolithiasis (n=7), hydronephrosis (n=9), kidney cancer (n=14) and urinary bladder tumor (n=1). During the preoperative period, the patients underwent contrast-enhanced MSCT, 3D-reconstruction, and digital analysis. The obtained data were compared with the results of dynamic nephroscintigraphy. RESULTS Contrast-enhanced MSCT findings were not inferior to data obtained with dynamic nephroscintigraphy regarding information content (p