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The study presents the killer functions of circulating neutrophils: myeloperoxidase activity, the ability to generate ROS, phagocytic activity, receptor status, NETosis, as well as the level of cytokines IL-2, IL-4, IL-6, IL-17A, and IL-18, granulocyte CSF, monocyte chemotactic protein 1, and neutrophil elastase in the serum of patients with uterine myoma and endometrial cancer (FIGO stages I-III). The phagocytic ability of neutrophils in uterine myoma was influenced by serum levels of granulocyte CSF and IL-2 in 54% of the total variance. The degranulation ability of neutrophils in endometrial cancer was determined by circulating IL-18 in 50% of the total variance. In uterine myoma, 66% of the total variance in neutrophil myeloperoxidase activity was explained by a model dependent on blood levels of IL-17A, IL-6, and IL-4. The risk of endometrial cancer increases when elevated levels of monocyte chemotactic protein 1 in circulating neutrophils are associated with reduced ability to capture particles via extracellular traps (96% probability)., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Stem properties allow circulating tumor cells (CTCs) to survive in the bloodstream and initiate cancer progression. We aimed to assess the numbers of stem-like CTCs in patients with ovarian cancer (OC) before treatment and during first-line chemotherapy (CT). Flow cytometry was performed (Cytoflex S (Beckman Coulter, CA, USA)) using antibodies against CD45; epithelial markers EpCAM and cytokeratin (CK) 8,18; mesenchymal vimentin (vim); and stem-like CD44, CD133 and ALDH. This study included 38 stage I-IV OC patients (median age 66 (Q1-Q3 53-70)). The CK+vim- counts were higher ( p = 0.012) and the CD133+ALDHhigh counts were lower ( p = 0.010) before treatment in the neoadjuvant CT group than in the adjuvant group. The patients with ascites had more CK+vim- cells before treatment ( p = 0.009) and less EpCAM-vim+ cells during treatment ( p = 0.018) than the patients without ascites. All the CTC counts did not differ significantly in paired samples. Correlations were found between the CK-vim+ and CD133+ALDHhigh (r = 0.505, p = 0.027) and EpCAM-vim+ and ALDHhigh (r = 0.597, p = 0.004) cells before but not during treatment. Multivariate Cox regression analysis showed that progression-free survival was longer with the presence of surgical treatment (HR 0.06 95% CI 0.01-0.48, p = 0.009) and fewer CD133+ALDHveryhigh cells (HR 1.06 95% CI 1.02-1.12, p = 0.010). Thus, CD133+ALDH+ CTCs have the greatest prognostic potential in OC among the phenotypes studied.

Ovarian cancer (OC) is able to develop implantation metastases in the abdominal cavity. Ascites is potentially useful for evaluating cancer features. The aim of the study was to assess the content of stem-like tumor cells and inflammatory mediators in ascites of OC. The prospective study included 11 patients with primary OC having ascites, 8 patients with benign ovarian tumors having ascites and 22 healthy women. In ascitic fluid obtained by laparocentesis, the populations of tumor stem-like cells were determined on a Cytoflex S` flow cytometer (Beckman Coulter, USA) and CytExpert Software using monoclonal antibodies to CD45, CD44 and CD133. The cytokine profiles of ascitic fluid and blood serum (IL-1β, IL-18, IL-4, IL-10 and VEGF) were assessed by ELISA. Stem-like cells were found in all samples. 5 cell populations were evaluated. The number of cells expressing both markers: CD44 + and CD133+, was the lowest. The highest, about 32%, was the number of CD44+ cells. The number of cells CD45-CD44+CD133- in ascites strongly positively correlated with the content of IL-10 in ascites, and the numbers of CD45-CD133+ and CD45-CD44-CD133+ - with the level of VEGF in blood serum. No correlations were found between the numbers of stem-like cells and the disease stage or the level of CA125 in blood. The combination of IL-4 and IL-10 in ascites had the greatest significance in predicting the disease stage. These results suggest a relationship between the levels of VEGF, IL-10, and cancer stem cells in the OC ascites. Stem-like cells in OC ascites are heterogeneous and are present even at an early stage of the disease. It seems promising to study cell populations and cytokine profile of ascites together, to assess the biomarker potential of their combination., Competing Interests: The authors declare no conflict of interest.

Background: Circulating Tumor Cells (CTCs) are a potential source of metastases and relapses. The data on molecular characteristics of Ovarian Cancer (OC) CTCs are limited., Objective: This study aims to assess the TGFβ, CXCL2, VEGFA and ERCC1 expressions in two OC CTC subpopulations before and during chemotherapy (CT), and their relation to clinical characteristics., Methods: Two CTCs subpopulations (EpCAM+CK18+E-cadherin+; EpCAM+CK18+Vimentin+) were enriched using immunomagnetic separation before treatment and after 3 cycles of platinumcontaining CT. The expression of mRNA was assessed using RT-qPCR., Results: The study included 31 I-IV stage OC patients. During CT, TGFβ levels increased in both fractions (p=0.054) compared with the initial levels. ERCC1 expression in E-cadherin+ CTCs was higher during neoadjuvant than adjuvant CT (p=0.004). CXCL2 level in E-cadherin+ CTCs increased (p=0.038) during neoadjuvant CT compared with the initial. TGF-β expression in vimentin+ CTCs during CT was negatively correlated to disease stage (p=0.003). Principal component analysis before CT revealed a component combining VEGFA, TGFβ, CXCL2, and a component with ERCC1 and VEGFA; during CT, component 1 contained ERCC1 and VEGFA, and component 2 - TGFβ and CXCL2 in both fractions. Increased ERCC1 expression in E-cadherin+ CTCs during CT was associated with decreased Progression-Free Survival (PFS) (HR 1.11 (95% CI 1.03-1.21, p=0.009) in multivariate analysis., Conclusion: EpCAM+ OC CTCs are phenotypically heterogeneous, which may reflect variability in their metastatic potential. CT changes the molecular characteristics of CTCs. Expression of TGFβ in EpCAM+ CTCs increases during CT. High ERCC1 expression in EpCAM+CK18+E-cadherin+ CTCs during CT is associated with decreased PFS in OC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: To assess the risk of exacerbations of bronchial asthma (BA) in smoking patients with the asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) after inpatient treatment., Materials and Methods: 36 smokers with ACO (main group) and 36 non-smoking patients (control group) with severe or moderate exacerbation of bronchial asthma were examined. Assessment of the severity of exacerbation of BA before treatment, levels of control and risk of exacerbations of BA after treatment was determined according to the Federal clinical guidelines for the diagnosis and treatment of BA (2016). Spirometry, monitoring of blood oxygenation using transcutaneous spectral pulse oximetry and enzyme immunoassay for determination of matrix metalloproteinases 9 were performed. Smoking experience, smoking index and pack/years index were taken into account in patients with ACO. The carboxyhaemoglobin level was analyzed by the carbon monoxide fraction in the exhaled air., Results: For the first time in patients with the ACO, the ability of heavy tobacco smoking and associated decrease in blood oxygenation to potentiate the negative impact of other predictors on the risk of exacerbations of the underlying disease was revealed. In smoking patients with the ACO, for the first time, a direct association of higher levels of matrix metalloproteinases 9 (measured before inpatient treatment) with such a predictor of the risk of further exacerbations of the disease as more frequent detection of symptoms of uncontrolled BA was revealed. In non-smoking patients with BA, a direct relationship between increased sputum secretion and eosinophilia of blood and/or sputum (a predictor of exacerbation of BA) and the relative duration of episodes of decreased blood oxygenation was established., Conclusion: It was found that intensive and prolonged smoking increases the duration and reduces the effectiveness of inpatient treatment of patients with ACO, contributing to the preservation of air traps and low (forced expiratory volume in 1 second 60%) ventilation capacity of the lungs with the persistence of moderately reduced blood oxygenation; the risk of further exacerbations of BA in this phenotype of patients is significantly higher than in non-smoking patients with BA without combination with COPD.

Background: It is shown that each type of human malignancies has a unique set of expressed miRNAs, and tumor-specific miRNAs in biological tissues of a patient are stable. The aim of this study was to determine the differences in the expression of miRNAs in tumor tissue of invasive breast carcinoma compared to normal tissue, as well as to analyze the variable expression of miRNAs in molecular genetic subtypes of breast cancer., Methods: We determined differences in mRNA expression in 35 biopsies of tumor tissue of various molecular genetic subtypes of breast cancer and 35 biopsies of adjacent conventionally normal breast tissue by RT-PCR in real time. We assessed the expression levels of miRNA-21, 221, 222, 155, 205, 20a , 125b and 200a., Results: A significant increase in the level of expression of the oncogenic miRNA-20a (p=0.000141) and miRNA-221 (p=0.037777) in the triple negative cancer in comparison with the luminal A and luminal B/HER2/neu-negative breast cancer subtypes was established. Assessment of significance of the results was conducted using ROC analysis. For miRNA-221 AUC value was 0.772, for miRNA-20a AUC value was 0.949. The obtained results suggest the possibility of using the levels of miRNA-21, 155, 205, 125b expression in tumor tissue to assess a malignant potential of a breast carcinoma. The levels of expression of oncogenic miRNA-221 and miRNA-20a are increased in TNBC compared with luminal A and luminal B/HER2/neu-negative breast cancer subtypes, supporting the characteristic of TNBC as the most aggressive subtype of breast cancer. MiRNA-20a is a marker of TNBC compared with luminal subtypes of breast cancer., Micro Abstract: To identify markers for breast cancer with triple-negative phenotype, we evaluated expression levels of siRNA-21, 221, 222, 155, 205, 20a, 125b, 200a and 146b in the tumor tissue of 35 patients by RT-PCR. AUC value equal to 0.949 in the ROC-analysis allows us to recommend the miRNA-20a as a marker of triple negative breast cancer to differentiate it from the luminal subtypes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The effects of low-intensity laser radiation (LILR) on the skin depend on the wavelength and density of the irradiation flux. Moreover, the vast receptor field of the skin facilitates the systemic influence of irradiation on the body., Aims: The objective of the present study was to evaluate the effects of low-intensity laser irradiation (LIRI) of the infrared range with a wavelength of 1270 nm on the skin of mice Balb/cNude., Material and Methods: The study was carried out with the use of the linear immunodeficient mice Balb/c nude obtained from the animal house of the Pushchino branch of the Academicians M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Biorganic Chemistry. The animals were irradiated once with a fiber laser of stimulated Raman scattering with a wavelength (λ) of 1270 nm, a power of 1.96 mW during the 2 min exposure at an intensity of 10 mW/cm 2 , and an energy flux density of 1.2 J/cm 2 . The histological studies and morphometry of the skin autoptate were performed. In adition, the expression of microRNA-21, -31, -130a, -191, -200c, -205, -218 was determined in the skin. Reverse transcription and real-time PCR reactions with Taq-Man probes and primers were performed on the nucleic acid amplifier CFX96 ('BioRad', USA).MicroRNA-191 was chosen as the reference gene. The bioinformation analysis of signaling pathways involving the studied microRNAs was performed using the DJANA miRPath database v.3.0., Results: A significant increase in the amount of keratinocytes of the basal layer was documented together with diffuse lymphoid-leukocyte infiltration of the interlobular connective tissue of the subcutaneous fat and endomysium after LILR. The pattern of microRNA expression was tissue-specific. An increase in the expression of micro-RNA-31 and-21 in the skin and a multidirectional change in miRNA-200 and -218 levels were shown. The bioinformation analysis showed that miR21 and miR31 were involved in the regulation of such signaling pathways as PI3K-Akt, Jak-STAT, MAPK, and mTOR of importance for carcinogenesis. Also, they have a signaling significance in the development of melanoma, kidney cancer, prostate cancer and malignant glioma., Conclusion: The data obtained in this study suggest activation of the tumor cell-specific and basic processes in the skin of immunodeficient Balb/cNude mice under the influence of low-intensity laser radiation with a wavelength of 1270 nm applied at a dose of 1.2 J/m 2 .

Antiangiogenic therapy requires to search for molecular markers of angiogenesis in ovarian cancer (OC). The diagnostic and prognostic role of VEGFA in OC is controversial today. The aim of the study was to compare the serum level of VEGF, the cytoplasmic protein content and VEGF transcript in the tumor tissue of primary patients with advanced ovarian cancer and to analyze the relationship between these parameters and the response to standard polychemotherapy using the AP scheme. 82 primary patients with advanced OC were incladed in the study. The control group included 30 healthy women. All patients received adjuvant chemotherapy according to the AP scheme after surgery. The serum VEGF-A level was determined by direct immunoassay analysis "Human VEGF ELISA Kit" ("RayBiotech", USA). Analysis of the VEGF transcript in tumor tissue was performed by PCR-RT using TaqMan® Gene Expression Assay (Thermo Scientific) probes, and for the data normalization the 18S and GAPDH referee genes were used. To calculate the IHC score of cytoplasmic expression of VEGF, immunohistochemical reactions were performed in paired samples of OC patients using antibodies (GeneTex, USA). For the genotyping of patients' DNA, test systems for the analysis of functional polymorphisms of the VEGF-A C12143A, G634C (LLC "Sintol", Moscow) were used. The level of VEGF-A in the serum of patients with OC was increased in comparison with the norm and depended on the response to chemotherapy according to the AP scheme. However, the specificity of this indicator is insufficient for use in prognostic purposes. There are no significant differences in the cytoplasmic expression of VEGF-A, depending on the response to chemotherapy. VEGF mRNA level was increased in 58% of patients. There was no correlation between serum VEGF levels and the transcript in the tumor tissue. Genotyping showed that the combination of genotypes of CC / GG reduces the risk of recurrence by 2.6 times. The results obtained make it possible to question the value of studying the serum level of VEGF for evaluating the sensitivity of patients with OС to anti-angiogenic drugs., Competing Interests: The authors declare no conflict of interest.

Background: Polychemotherapy in ovarian cancer (OC) is the second major component of treatment. However, treatment with cytostatics is stopped in 25% of cases because of significant side effects. It is shown that concentration of certain cytokines and their balance is largely formed in accordance with a genetic polymorphism., Objective: The objective of the study was to evaluate the cytokine status of blood serum of patients with ovarian cancer with different tumor response to neoadjuvant chemotherapy (NACT)., Method: Patients received 2 courses NACT according to the scheme AP. The levels of IL-1β and IL-1Ra, IL-10, TNF-α in blood serum were determined by solid phase ELISA. For molecular genetic studies we selected polymorphic variants in the promoters of the gene represented in dbS`NP NCBI and SNP500 Cancer databases., Results: The sharply declined in patients with ovarian cancer compared with the normal, level of IL-1β correlates with increased levels of IL-1RA. It is found that 75% of patients who had progression of the disease after NACT bear CT genotype of gene IL-1β associated with a low expression of the cytokine, while the TT genotype, providing a high level of the expression of IL-1β gene had met only 25% among patients in this group. At the same time 70% of patients with a complete response are the carriers of the T allele, while a complete response was associated with a higher level of IL-1β than in the progression group. Low secretion of TNF-α in all types of tumor response when testing TNF-α G-308A gene polymorphisms was associated with carriage of GA and AA genotypes, which are associated with low production of this cytokine. Increased compared to the control IL-10 production in patients with ovarian cancer associated with genotype replacement at position 1082 G/A IL-10 gene, which occured in 10% of patients with a complete response and 25% of patients with tumor progression after NACT., Conclusion: All the studied polymorphisms of IL-1β, IL-10 and TNF-α genes in patients with OC are associated with the level of these cytokines and tumor NACT response., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The study was carried out to evaluate characteristics of redox-status in erythrocytes of peripheral blood of patients with ovarian cancer, uterine body cancer and cervix cancer using evaluation of products of peroxide oxidation of lipids: diene conjugates, ketodienes, Schiff's bases by Volchegorskii, malonic di-aldehyde by L.I. Andreieva, content of products of oxidizing modification of proteins by E.E. Dubinina; activity of anti-oxidant enzymes: superoxiddismutase by Nishikimi, catalase, glutathione-S'-transferase, glutathionereductase and level of reduced glutathione by A.I. Karpischenko. The evaluation of architectonics of erythrocytes and rigidity of membrane was implemented using a scanning probing microscope SolverPro (NT-MDT, Zelenograd, Russia). The statistical processing of obtained data was implemented using non-parametric Mann-Whitney U-test. The increasing of products of initial stages of peroxide oxidation of lipids - diene conjugates and malonic di-aldehyde and decreasing of level of interim (ketodienes) and tertiary ( Schiff's bases) products of peroxide oxidation of lipids have been established. Against this background a multi-directional alteration of superoxiddismutase and decreasing of catalase occurred. Simultaneously, increasing of activity of glutathione-transferase and level of reduced glutathione under all analyzed localizations of neoplasm were noted. The level of products of oxidizing modification of proteins depended on localization of primary tumor and it was minimal in case of cervix cancer. Also such an alteration of cyto-architectonics of erythrocytes was established as development of reversible deformed echinocytes in patients in case of ovarian cancer and irreversible deformed spherocytes in patients with cervix cancer and uterine body cancer and also abrupt increasing of rigidity of membrane of erythrocytes. The obtained data permits to surmise as a capacity of para-neoplastic processes development of oxidative and carbonyl stress in erythrocytes of peripheral blood of patients with ovarian cancer, cervix cancer and uterine body cancer at extensive stage of disease. The mentioned stress is accompanied by formation of echinocytes and spherocytes and significant increasing of rigidity of membrane. However, intensity of these processes is determined by localization of primary neoplasm and it can be applied for characteristic of biological portrait of tumor in case of consideration of schemes of anti-oxidant therapy., Competing Interests: The authors declare no conflict of interest.

The Purpose: The purpose of the study was to investigate the effect of the scheme autohemochemotherapy ATS on redox-dependent processes in red blood cells of tumor-bearing organism at an experimental ovarian cancer., Methods: We studied the dynamics of redox-dependent processes in red blood cells of rats with experimental ascitic ovarian tumor during CAP-regimen autohemochemotherapy (cyclophosphamide, doxorubicin and cisplatin). We assessed the indicators of oxidative modification of proteins in erythrocytes - carbonyl derivatives at l = 346 nm, 370 nm, 430 nm and 530 nm, the parameters of lipid peroxidation - malondialdehyde, ketodienes, diene conjugates, Schiff bases; the enzymatic part of antioxidant system - the activity of catalase, glutathione transferase and superoxide dismutase biochemically., Results: The red blood cells of tumor-bearing animals were found having increased the products of lipid peroxidation and oxidative modification of proteins while reducing the activity of antioxidant enzymes, suggesting a state of oxidative and carbonyl stress., Conclusion: We showed that extracorporeal incubation of cytotoxic drugs used in the CAP scheme with autoblood prior to infusion - the method of autohemochemotherapy - either in monochemotherapy, or in CAP-regimen, decreases the levels of lipid peroxidation, oxidative modification of proteins and increases activity of first line antioxidant defense enzymes - catalase and superoxide dismutase in circulating red blood cells. Such dynamics of redox-dependent processes suggests a stabilizing effect of autohemochemotherapy on circulating erythrocytes in a tumor-bearing organism.

We have examined peripheral blood neutrophils from 123 patients with primary endometrial cancer at stage Ia. Receptor system and the ability of neutrophils to form extracellular traps were assessed by fluorescence microscopy, the spontaneous production of cytokines IL-2, IFN-γ, g-CSF, matrix metalloproteinases-1,9,13 by the method of enzyme-linked immunosorbent assay, phagocytic activity, myeloperoxidase activity, the level of cationic proteis activity in NBT-test were evaluated by cytochemical methods, activity of neutrophils in the spontaneous NBT-test was used to evaluate the oxygen-dependent bactericidal action of neutrophils. The topology and the rigidity of the membrane of neutrophils were assessed by scanning probe microscopy. We have shown that the increase in the relative number of neutrophils lead to a change in their receptor system, aerobic and anaerobic cytotoxicity and ability to phagocytosis are enchanced while reducing NET-activity. We have observed a change in the secretory activity of neutrophils, which is characterized by increased level of MMP-1, possibly initiated by enhanced production of reactive oxygen species, by a reduction in the IL-2 level (inductor of cytotoxic activity) and a sharp increase in the level of the G-CSF. Architectonics of neutrophils in the case of endonetrial cancer at stage Ia is characterized by changing the shape and loss of grit. The rigidity of the cell membrane decreased. Changes in the morphology of neutrophils on the background of the continuing hyperactivity suggests that a state of balance between the immune system and the tumor is already in stage Ia endometrial cancer.

The ovarian carcinoma is the most frequent cause of death because of malignant neoplasins in women. At that, there is no pathognomonic symptoms permitting diagnosing stage of process with sufficient degree of confidence. This is a determinative not only for choosing treatment regimen but also for correlation of expected results of treatments with economic factors with purpose to evaluate cost effectiveness under monitoring of these patients. The study was carried out to develop mode of clarifying diagnostic of progressing forms of ovarian carcinoma on the basis of evaluation of oxidative modification of proteins in blood plasma. In 100 female patients with primary ovarian carcinoma (stage III and IV according FIGO,) in blood plasma 21 indicators were determined in blood plasma using standardized techniques: absolute number of leukocytes, absolute and relative number of neutrophils, products of oxidative modification of proteins of basic and ketonic character (under wavelength of 356, 370, 430, 530 nm), Her-2/neu CA-125, matrix metalloproteinase 2 and 9 in blood serum and neutrophils, interleukin-6, interleukin-10, interleukin-1β, interferon-γ, tumor necrosis factor-α, malonic dialdehyde, catalase, glutaihione transferase, glutathione reductase. The least squares method was applied to every parameter to appmximnate relative rates by density of Rayleigh distribution. For every indicator likelihood ratio functions of likelihood ratio were constructed and intervals at every stage were determined. The reliability of approximation was proved under testing with Pirson criterion hypothesis of compliance of practical values of parameters to theoretical law of density of distribution. The results permit to assert that level of oxidative modification of proteins cab be used as a reliable indicator for differentiated diagnostic of stage III and IV of ovarian carcinoma.

Background: Ovarian cancer (OC) is the most lethal of gynecologic tumors because women generally present with advanced stage disease. Platinum-based chemotherapy play a pivotal role in OC treatment. The aim of the study was to assess the effects of CAP-regimen chemotherapy on blood redox status in patients with ovarian cancer., Materials and Methods: Patients were 132 women with primary OC with FIGO stage III-IV. Patients were examined before treatment, 3 and 14 days after the first and 3 and 14 days after the second course of CAP-regimen chemotherapy. The activity of antioxidant enzymes, the intensity of lipid peroxidation, the level of oxidative modification of proteins (OMP) were evaluated., Results: We have found elevated levels of OMP products in plasma and erythrocytes of patients with ovarian cancer in comparison with donors. Our results suggest activation of lipid peroxidation in plasma and erythrocytes of ovarian cancer patients in comparison with healthy women. Sensitive and specific indicators of oxidative stress are levels of glutathione-S-transferase (sensitivity 80%, specificity 89%), diene conjugates (sensitivity 85,71%, specificity 72,73%) and OMP 430 nm (sensitivity 80%, specificity 90%) in blood plasma and the activity of catalase in erythrocytes (sensitivity 100%, specificity 89%)., Conclusion: CAP chemotherapy in patients with ovarian cancer with FIGO stage III-IV induces radical formation and changes the homeostasis of the patient. The lipid peroxidation and antioxidant system in plasma move to a higher level of functioning, and the erythrocytes develop oxidative stress.

The neutrophil is considered as the peculiar monocelled sekretorny gland realizing the effector potential including by secretion of soluble products - cytokines and for today. Influence of a tumor on functional activity of neutrophils depends on type, localization and a stage of its development. In our research dynamics of metabolic and of neutrophils of peripheral blood, the contents in a lysate and serums of blood of cytokines of IL-1β, 1Ra, 2, 6, 10, 18, TNF-α, IFN-γ and is studied when progressing a cervical cancer. Cytokines and metabolism indicators - activity of, determined by an immunofermental method, level of cationic proteins, a share of active cages in the spontaneous NST-test were cytochemical. It is shown that when progressing cervical cancer against increase in total of neutrophils significant decrease in their, aerobic and anaerobic bacterial action, decrease in the IL-1β and IL-1 Ra level, and also IFN-γ takes place at TNF-α increase, increase of production of matrix metalloproteinas-2 on Ib-IIa of a stage of a disease that allows to assume emergence at this stage of cervical cancer of pro-tumoral effect of neutrophils.

In order to evaluate the role of cytokines in the development of polymodal local and distant effects in patients with stages I-IV cervical cancer, the following parameters were measured: serum concentrations of TNF-α, IFN-γ, IL-1β, IL-6, and IL-10; levels of malondialdehyde, activities of catalase, superoxide dismutase, glutathione reductase, and glutathione-S-reductase in the plasma, erythrocyte, and cervix uteri homogenate. The expression of p53, Bcl-2, VEGF, and Ki-67 in tumor tissue was evaluated. High levels of malondialdehyde in tumor tissue and erythrocyte were paralleled by low levels of superoxide dismutase and catalase and high activities of glutathiones. Medium correlations between Ki-67, Bcl-2, and p53 and the levels of IL-6, IL-10, and TNF-α at stages Ib-IIa were detected. The results indicated that the progress of cervical cancer was associated with the neoplasm integration in the host homeostasis by using the regional and systemic cytokine functions. These effects, amplifying the biological potential of the tumor, were the most significant at stages Ib-IIa.

The dynamics of the redox-dependent processes in blood plasma, neutrophils and erythrocytes of the patients with ovary cancer of the IIIrd clinical stage by FIGO after polychemotherapy according to the CAP scheme is considered. In the blood plasma and erythrocytes there were estimated the values of protein oxidative modification: carbonyl derivatives at λ = 346 nm, 370 nm, 430 nm and 530 nm; the lipid peroxidation parameters: malonic dialdehyde, dienic conjugates, ketodiens, shiff's bases; the fermentative chain of the antioxidant system: activities of catalase, glutationtransferase and superoxide dismutase. In the peripheral blood neutrophils there were cytochemically determined the myeloperoxidase activity and the number of the active neutrophils in the spontaneous NBTR-test. After the polychemotherapy there were detected higher levels of the protein oxidative modification products and the products of the lipid peroxidation in the blood plasma and erythrocytes of the patients. Simultaneous increase of the activity of the antioxidant enzymes in the blood plasma could be evident of a high level of the lipid antioxidants peroxidation system functioning, whereas the simultaneous decrease of the activity of the antioxidant enzymes in the erythrocytes was indicative of passible development of oxidative stress in them. After the chemotherapy there was observed a significant and reliable decrease of the total number of the neutrophils. After the second course of the chemotherapy the activity of myeloperoxidase in them in the spontaneous NBTR-test as well decreased. Such a dynamics of the redox-depended processes in various components of the blood in the tumour carrier was characteristic of the tumor biological picture and required the use of differential multicomponent antioxidant therapy in patients with ovary cancer.

Aim: To assess the role of matrix metalloproteinases (MMP) in the clinical and functional status of smoking patients with persistent asthma., Subjects and Methods: Examinations were made in 16 healthy smokers (a control group), 22 healthy nonsmoking volunteers (a volunteer group), and 16 patients with endogenous (n = 6) and mixed (n = 10) persistent asthma (a study group) with varying disease control. The investigators used the following techniques: spirometry; determination of airway resistance and FeCO in the expired air; 30-minute percutaneous monitoring of blood oxygenation and 6-minute walk test; enzyme immunoassay for matrix metalloproteinase levels., Results: The longer duration and higher intensity of smoking increase airway inflammation in the asthmatic patients and the length of blood oxygenation within the very low range. The combined negative influence of tobacco smoking and the underlying disease leads to a clinically significant decrease in pulmonary ventilation ability and basic levels of blood oxygenation, the occurring asthma control reduction being correlating with the longer duration of treatment. The investigators revealed the predictors of lowering the mean level of blood oxygenation (MMP-9, FeCO, and airway resistance), as well as the factors that negatively influence the level of dyspnea and fatigue in asthmatic smokers., Conclusion: The serum levels of FeCO and MMP-9 may serve as markers reflecting the intensity of airway inflammation in smokers with persistent asthma.

There were assessed morphofunctional state of peripheral blood neutrophils and cytokine status in the serum of primary patients with progression of cervical cancer in the dynamics. Against the background of increasing the total number of neutrophils, a significant reduction occurred in the phagocytic activity, aerobic and anaerobic bactericidal activity, an increase of the rigidity of the membrane and the change of cell cytoarchitectonics at Ib-IIa stage of the disease. At the same stage, in neutrophils there were reduced the level of IL-1β and its receptor IL-1Ra as well as the number of IFN-γ. Wherein there was increased the level of pro-inflammatory cytokine TNF-α. Cytokine status of the serum, characterized by sig- nificant boosting of IL-1Ra and IL-18 while lowering TNF-α, IFN-γ and IL-2, was advantageous for tumor progression and was detected at Ib-IIa stage of cervical cancer. The observed changes of cytokine status in the serum and morphofunctional state of neutrophils were discussed in the light of connection with the possibility of potential pro-tumor effect of the latter.

The studies determining phagocytic activity, the levels of myeloperoxidase (MPO) and cationic proteins (CP), and the results of the spontaneous and induced NST tests of peripheral neutrophilic granulocytes (NGC) revealed their functional changes in the course of tumor progression in patients with ovarian cancer. There was an increase in the total count of NGC with simultaneous reductions in the levels of CP, the activity of MPO and in the absorptive capacity of NGC at the late clinical stages of the disease. The results of the NST test did not change. The findings suggest that a growing tumor affects NGC reproduction.

Changes in the cardiorespiratory function in obese persons exposed to different combinations of normobaric hypoxia and physical exercise were studied. The results show a positive effect of combined use of normobaric hypoxic exercise on functional reserves of cardiorespiratory system, physical performance and aerobic potentialities in obese patients. The highest effect is achieved in combination of physical exercise with hypoxic gas mixtures breathing.

Tissue distribution of erythrocyte membrane-bound gentamicin was studied in non-inbred albino rats. Gentamicin was administered to the animals intravenously in single doses of 3.3 mg/kg as a free substance of the antibiotic or in carrier erythrocytes. The gentamicin concentration was determined in serum, blood and tissues of the liver, kidneys, lungs, spleen and the skeletal muscles by fluorescence polarization immunoassay (TDx, Abbott). Encapsulation of gentamicin in erythrocytes caused changes in its pharmacokinetics: the antibiotic half-life and mean retention time appeared to be higher and the antibiotic accumulation in the liver, spleen and kidneys increased 1.7-3.0, 19-27 and 1.5 times respectively depending on the technique of the carrier erythrocytes preparation. Exposure of the erythrocytes to tannin led to an increase in the rate of the antibiotic release from the carrier erythrocytes.

Incorporation of rubomycin into exclusive shades of erythrocytes amounted to 7.1 per cent, that of tetracyclines to 6.9-8.9 per cent. Determination of stability of the erythrocyte containers showed that leakage of the antibiotics proceeded during the first 30 minutes of incubation at 37 degrees C when titrated with the Hanks solution. It varied with respect to different antibiotics. With the use of blood serum for titration stability of the erythrocyte containers probably increased. After incubation for 30 minutes only traces of the tetracycline derivatives were detected in the supernatant liquid while rubomycin was not detectable at all. Therefore, the study showed that the exclusive shades of autologous erythrocytes may be in principle used for transport of water-soluble antibiotics.