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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.

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.

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.

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.

We performed clinical observations and laboratory examination of 22 patients with chronic pyelonephritis (chronic renal failure, CRF) and 30 healthy individuals. The patients with CRF were examined twice. The first group (Group I) included patients with exacerbation of the disease. The comparison series (Group II) was represented by the same patients who were examined 1.5-3 months after completion of treatment, without clinical exacerbation of chronic pyelonephritis (CPN). Laboratory signs of acute renal damage were not detectable in all the patients examined. Concentrations of VEGF, MCP-1, IL-8 and IL-18 were determined in urine samples of all examined persons by ELISA technique. Protein spectrum of urine was assessed in six patients from Group I, and in six cases of Group II by means of mass spectrometry, using Agilent 1100 chromatographic device, and LTQ-FT Ultra hybrid mass spectrometer. The results of parallel determination of urine proteins by the two methods have shown that the evolving CPN exacerbation is associated with local secondary immune deficiency at the level of renal tubular urothelium. Determination of urine proteome by means of mass spectrometry in exacerbating disease allows identify the proteins associated with damage to epithelial lining of renal tubules and development of local immune response.

Aim. Investigation of the influence of canceroembryonic antigen (CEA) on the immune cells in patients with breast tumors.Materials and methods. Peripheral blood of 67 patients with invasive ductal carcinoma (n = 44), fibroadenoma (n = 12) and breast pre-cancer (n = 11). In the supernatants of the blood cells cytokine production induced by CEA was determined by ELISA.Results.It was found that CEA stimulated production of IL-6, IL-8, IL-10, IL-1β, IL-1Ra, TNFα, G-CSF, GM-CSF and the protein MCP-1 by blood immune cells in patients with fibroadenoma compared with groups of patients with invasive ductal carcinoma and precancerous lesions. Stimulation index of CEA on cytokine production by immunocompetent cells in patients in these groups was lower than in groups of patients with fibroadenoma due to initially high levels of spontaneous cytokine production.Results. In patients with fibroadenoma CEA was found to stimulate the production of IL-6, IL-8, IL-10, IL-1β, IL-1Ra, TNFa, G-CSF, GM-CSF and MCP-1 compared with groups of patients with invasive ductal carcinoma and precancerous conditions. Indexes of the influence of CEA on cytokine production by immunocompetent cells in these groups was lower than in the fibroadenoma due to initially high spontaneous production of cytokines.Conclusion. Evident spontaneous cytokine-producing function of immunocompetent blood cells was revealed in patients with invasive ductal carcinoma and precancerous conditions compared to patients with fibroadenoma. The differences between the indices of CEA influence on cytokine production in patients with malignant, benign and precancerous conditions can serve as a basis for the development of methods of differential diagnosis of breast tumors.

It is known that a relationship exists between patient’s age and pathogenesis of malignant tumors associated with ability of tumor and its microenvironment to secrete cytokines that may play an important role in carcinogenesis. The aim of present study was a comparative analysis of cytokine production by peripheral blood cells and tumor samples when exposed to polyclonal activators (PA) in patients of different age groups with invasive ductal carcinoma. Peripheral blood samples of 54 women with invasive ductal carcinoma were under study. The patients were divided into the following groups: I, 40-60 years old; II, 61 year and older. Metastases into lymph nodes were revealed at the moment of study in 13 patients (42%) from group I. By contrast, only 3 of 23 (10%) patients with metastases were revealed in group II. Fisher’s ratio test showed significant differences between occurrence of metastases in lymph nodes, and patient age (p = 0.034). In both groups of patients, there was an increase of IL-6, IL-8, IL-10, IL-17, IL-18, IL-1ra, G-CSF, GM-CSF and VEGF concentrations in tumor supernates and its microenvironment, when compared with the production of cytokines by blood cells, thus indicating to high functional activity of tumor together with its microenvironment. Effect of PA led to increase of IL-2, IL-10, IL-17, IL-1β, IL-1ra, TNFα and IFNγ concentrations in blood cells supernatant which suggested their high ability to produce cytokines. In the group of patients who were 40-60 years old, the stimulatory index of PA (SIPA) for IFNγ production was several times higher than similar index in patients aged 61 years or more. Increase of SIPA for all cytokines in blood cells supernates, in comparison to SIPA of tumor supernates, could be explained by initially high levels of spontaneous cytokine production by the tumor and its microenvironment that are able to promote tumor growth. Therefore, effect of PA upon tumor tissue was not so expressed as its effect upon immunocompetent blood cells. Both tumor and microenvironment maintained high ability of IL-18 production, thus confirming its important role in carcinogenesis. In summary, these findings suggest that circulating immunocompetent cells may serve as an additional factor providing tumor progression, due to their high ability to secrete cytokines.

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. This result indicates likely secretion of interferon γ in younger patients. The relation among the production of angiogenic factors by tumor cells, age of the patients, and presence or absence of lymph node metastases shows that in such studies, patients have to be stratified by age.

We studied biological effects of Human Leukemia Differentiation Factor (HLDF), first derived from the cultural media of human myelogenous HL-60 leukemia cells, on the production of IL-1β, IL-1ra and IL-8 by immune cells from the patients with chronic atrophic gastritis, adenomas and adenocarcinomas of the stomach. To evaluate the influence of HLDF on cytokine-producing function of the whole blood cells, the latter were incubated with this factor or without it. The levels of IL-1β, IL-1ra and IL-8 were determined in supernates of these cells. The stimulation indices of HLDF upon cytokine production were estimated as a cytokine production ratio of stimulated versus resting cells. Histological analysis of gastric mucous tissue samples and removed tumors was also performed. It was revealed that, in chronic atrophic gastritis, HLDF significantly increased IL-1ra and IL-8production. In patients with stomach adenomas and adenocarcinomas, HLDF increased IL-1ra, IL-8 and IL-1β production. In cases of stomach adenomas, the indices of HLDF stimulation upon blood cells cytokine production are significant higher than in patients with chronic atrophic gastritis. Interdependence study between the stimulation indices of HLDF and histological parameters of gastric mucosa and tumor samples have shown a negative correlations between the stimulation index of HLDF upon IL-1ra production and the grade of intestinal metaplasia and dysplasia of the adenoma epithelium, and a positive correlation between the stimulation index of HLDF on IL-8 production and the intensity of lymphoid infiltration of the adenomas. In patients with gastric adenocarcinomas, a positive correlation between the stimulation index of HLDF on IL-8 production and number of blood vessels with tumor embolus was revealed. One may presume that immune cells activation caused by HLDF may exert following actions: (1) triggering some processes of chronic inflammation that underly malignancy development, and (2) the mechanisms restricting the disturbances of epithelial regeneration. Finally, the results of HLDF effects depend on balance between proand antioncogenic cytokines produced by immune cells.

Аbstract. The aim of present study was to investigate an influence of polyclonal activators upon cytokine-producing function of peripheral blood cells in the patients with colorectal adenocarcinomas. It was revealed that the stimulated production of IL-1β, IL-1ra, IL-2, IL-17, IL-18 and IFNγ by whole blood cells treated with polyclonal activators was significantly decreased in colorectal cancer patients, as compared to healthy individuals. The stimulated IL-1ra and IL-17 production was depressed during the tumor progression, along with increased release of TNFα and IL-8. It was found that the stimulation index of polyclonal activators upon production of IL-17 by whole blood cells (i.e., a cytokine production ratio of stimulated versus resting cells) may be used as a reliable pre-surgery predictor of tumor invasion, the latter being an important histopathological parameter for clinical oncologists. ( Med. Immunol., 2011, vol. 13, N 2-3, pp 197-204

Antibodies to leukemia differentiation factor (HLDF) in patients with gastrointestinal cancer Abstract. Patients with gastric cancer exhibit higher levels of IgG4-antibodies to human leukemia differentiation factor (HLDF), as compared with healthy individuals, whereas, in patients with colorectal cancer, one may detect high levels of IgA anti-HDLF antibodies, along with lower levels of IgG1 class antibodies against HLDF than in control group. Among patients with gastrointestinal cancer, a positive correlation is revealed between contents of highly differentiated cells in the tumor, and IgM antibodies to HDLF. Meanwhile, a reverse relationship is noted between low differentiation of tumor cells and levels of IgG2 antibodies to HDLF in gastric cancer patients, or IgG3 antibodies to HDLF in patients with colorectal cancer.

Cytokine-producing potential of peripheral blood cells was determined as a stimulation index with polyclonal activators (i.e., a cytokine production ratio of stimulated versus resting cells), as well as concentrations of cytokines were investigated in blood serum of patients with chronic atrophic gastritis. It was revealed that the stimulation indices concerning production of TNFα, IL-1β, IL-6, IL-8 and IL-10 by whole blood cells, along with serum concentrations of IL-8 and IL-18BP were increased in patients with epithelial dysplasia of stomach mucosa, as compared to patients without dysplasia. It was sahown, that the patients with higher polyclonal stimulation indices for IL-6 and IL-8 (resp., > 164 and > 38 arbitrary units) should be referred to a high-risk group for development of mucous epithelial dysplasia of stomach.

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).

The technology developed in the SRC VB “Vector“ made it possible to create the encapsulated form of the live measles vaccine for oral administration. The vaccine no contains pathogenic bacteria, alien viruses, mycoplasmas, and in the studied parameters meets the requirements of the national control institution of Russia to measles vaccines. Immunization of monkeys with the encapsulated form of the vaccine of measles viruses results in the induction of humoral, secretory, and cell-mediated imm unity.