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Background. Colorectal cancer is ranked third in terms of incidence and second in terms of mortality around the world. Molecular markers of chemoresistance allow to determine the prognosis of the disease and sensitivity of the tumor to drugs.Aim. To assess the predictive value of expression of regulators of tumor-associated inflammation TGFb1 and CXCL8 in the tumor tissue in colorectal cancer.Materials and methods. Patients were divided into 3 groups: group I included patients without relapse of the disease, group II encompassed patients with relapse of the disease (within 6–16 months after the end of chemotherapy), group III included patients with disease progression. Expression of TGFb1 and CXCL8 in the tumor tissue before treatment in patients with stage II–III colorectal cancer (n = 77) was determined using quantitative realtime polymerase chain reaction (PCR) on the Bio-Rad CFX-96 Touch Real-Time PCR Detection System (USA). Statistical data processing was performed using Statistica 13.0 software (StatSoft, USA).Results. We found that in samples of poorly differentiated colorectal cancer, the level of TGFb and CXCL8 mRNA was significantly higher than in moderately and well differentiated tumors. We did not reveal any relationship of the level of TGFb1 and CXCL8 transcripts in tumor samples of patients with stage II–III colorectal cancer with age and the presence of mutations in the EGFR (Epidermal Growth Factor Receptor) signaling pathway (RAS, BRAF). We found a strong positive correlation between the levels of TGFb1 and CXCL8 transcripts for the entire sample of patients with colorectal cancer. We have found that the expression of TGFb1 and CXCL8 genes was significantly higher in the tumor tissue of patients with disease progression.Conclusion. Overexpression of TGFb1 and CXCL8, which are involved in the mechanism of tumor-associated inflammation, can be considered as a negative prognostic factor for the progression-free interval when using the FOLFOX / XELOX regimen for the treatment of colorectal cancer.

Melanoma is the most dangerous type of cancer, with a high rate of metastasis. The conventional method of treating skin melanoma is photodynamic therapy, yet this type of phototherapy has several side effects. In addition, the photosensitizers used are relatively expensive and toxic. Thus, developing methods of treating melanoma cancer using laser only is a promising area of research. Here we present in vitro effects in melanoma cell culture after 1265 nm laser irradiation exposure.

The prognostic factors that determine colorectal cancer (CRC) treatment are disease status, tumor grade, microsatellite instability, invasion degree, and the index of proliferative activity. However, the assessment of the adjuvant chemotherapy in colorectal cancer does not imply the assessment of angiogenic factors in a primary tumor. The aim of the paper is to evaluate the prognostic role of PDGFAA and VEGFA expression in tumor tissue of stages II/III colorectal cancers. Materials and Methods. Paraffin blocks of primary CRC tumor (n=50) were used as study material. Immunohistochemistry (IHC) was used to examine the expression of vasculoendothelial and platelet growth factors and calculate IHC score in the tumor parenchyma and CRC stroma. Results. According to IHC staining, CRC tumor expresses VEGFA and PDGFAA factors in 92 % of cases, in the resection line – in 37 % of the samples. There were no differences in VEGFA and PDGFAA expression in tumor parenchyma in CRC, depending on the process stage and grade degree. The cumulative risk of disease progression within a year after surgery in patients with stage II/III CRC with VEGFA+PDGFAA overexpression in the primary tumor is 4.9 times higher (CI 2.123–11.089, p=0.011) compared to the group of patients with reduced expression of the studied angiogenic factors. Conclusions. The data obtained suggest that co-expression of angiogenic VEGFA and PDGFAA factors in the tumor may reflect the initial CRC regarding neoangiogenesis. If VEGFA and/or PDGFAA IHC score is more or equal to 6, the risk of disease recurrence within 1 year from the start of medical observation increases, which is an unfavorable prognostic factor. Keywords: colorectal cancer, vasculoendothelial growth factor, platelet growth factor, adjuvant chemotherapy. Прогностическими факторами, определяющими тактику лечения при колоректальном раке (КРР), являются стадия заболевания, степень дифференцировки опухоли, микросателлитная нестабильность, степень инвазии, индекс пролиферативной активности. При этом оценка эффективности адъюватной химиотерапии при КРР не предполагает оценку ангиогенных факторов в первичной опухоли. Цель работы – оценить прогностическую роль экспрессии PDGFAA и VEGFA в опухолевой ткани на II–III стадиях колоректального рака. Материалы и методы. В качестве материала для исследования использованы парафиновые блоки первичной опухоли КРР (n=50). С помощью метода ИГХ исследована экспрессия васкулоэндотелиального и тромбоцитарного факторов роста путем расчета ИГХ-балла в опухолевой паренхиме и строме КРР. Результаты. По результатам ИГХ-окрашивания опухоль КРР экспрессирует факторы VEGFA и PDGFAA в 92 % случаев, в линии резекции – в 37 % образцов. Отличий в экспрессии VEGFA и PDGFAA в опухолевой паренхиме при КРР в зависимости от стадии процесса, степени дифференцировки выявлено не было. Кумулятивный риск прогрессирования заболевания в течение года после операции у больных с КРР II–III стадий при гиперэкспрессии VEGFA+PDGFAA в первичной опухоли выше в 4,9 раза (ДИ 2,123–11,089, р=0,011) по сравнению с группой пациентов со сниженной продукцией изученных ангиогенных факторов. Выводы. Полученные данные позволяют предполагать, что коэкспрессия ангиогенных факторов VEGFA и PDGFAA в опухоли может отражать исходный профиль КРР в отношении неоангиогенеза. При ИГХ-балле VEGFA и/или PDGFAA выше или равном 6 возрастает риск рецидива заболевания в течение 1 года от момента начала наблюдения, что является неблагоприятным прогностическим фактором. Ключевые слова: колоректальный рак, васкулоэндотелиальный фактор роста, тромбоцитарный фактор роста, адъювантная химиотерапия.

At the present time, there is no common point of view to the role of circulating neutrophils (NP) in emergence and development of neoplasia. It is suggested that due to high functional plasticity, the neutrophils may exhibit both pro- and antitumor activity. In order to study the NP phenotype at different stages of cervical neoplasia (CN), we have evaluated their absolute and relative amounts, myeloperoxidase activity, spontaneous and induced NST-test markers, and the level of intracellular cationic proteins. Spontaneous production of elastase and active forms of matrix metalloproteinases, the levels of IL-2, IL-8, IL-18, IFNy, G-CSF were determined in the NP cell lysates and in blood serum. The formation of extracellular traps (NET) was evaluated using 1-day cultures of Saccharomyces cerevisiae as an inducer. We examined 31 patients with cervical intraepithelial neoplasia (CIN) and 21 primary patients with cervical cancer (CC, Ia stage according to FIGO scale), as well as 25 practically healthy women. We revealed increased spontaneous and inducible oxygen-dependent cytolytic and phagocytic activity and spontaneous production of NET if compared to normal values, along with decreased absolute NP numbers in patients with CIN, thus suggesting the antitumor activity of NP. The levels of “pro-tumor” cytokines (MMP-9, IL-2 and G-CSF) become increased over normal levels as early as at the CIN stage, both for the neutrophils and blood plasma. High levels of regulatory IFNy and neutrophil-priming IL-8 in blood plasma do not presume any use of exogenous NP-activating factors at the stage of cervical dysplasia. At the initial stage of cervical cancer, the absolute NP amounts are significantly increased compared to normal counts. However, despite increased spontaneous oxygen-dependent cytolytic activity, the NPs have a significantly reduced activity of phagocytosis and sharply increased spontaneous production of NET, thus, generally, being characteristic to the “pro-tumorous” NP phenotype. IL-2 levels are elevated, and MMP-9 values are still increased in NP and blood plasma of patients with CC (stage Ia). Hence, the obtained results suggest some changes of NP phenotype to a pro-tumorous pattern during transition from intraepithelial dysplasia to cervical cancer. These results allowed us to design an algorithm for examining women with suspected cervical cancer, including IL-2 measurement in blood serum, and MMP-9 amounts in the NP lysates.

Circulating tumor cells (CTCs) are essential for hematogenous metastasis. In 2003, it was found out that such cells were present in the blood of patients diagnosed with ovarian cancer (OC). It is known that inflammation plays an important role in tumor progression. There are CSCs with a large number of components in the blood, e.g. cytokines that can modulate the metastatic potential of a tumor cell. The aim of the study is to assess the blood serum cytokine status in ovarian cancer patients with different levels of circulating tumor cells. Materials and Methods. Untreated primary patients (n=24) with histologically or cytologically verified ovarian cancer, stage II–IV according to FIGO classification, were the trial subjects. Flow cytometry was used to detect the number of circulating tumor cells in the blood from the patients; the authors also determined IL-6, IL-17A, IL-1β, TGF-α, IL-4, VEGF, TNF-α, HGF, IL-18, IL-10, IL-8 levels. The results were processed using the Statistica Windows software package. Results. The authors determined that TNF-α, HGF, IL-10, IL-18 cytokine level in the blood serum from OC patients significantly increased, and IL-8 level decreased with CTC increase. Conclusion. The obtained results suggest a correlation of CTC level with TNF-α, HGF, IL-10, IL-18, IL-8 cytokine serum level in patients diagnosed with advanced ovarian cancer. At the same time, a sharp and significant increase in TNF-α level accompanied with CTC increase may indicate a change in the phenotypes of TNF-producing cells in OC. Keywords: ovarian cancer, cytokines, circulating tumor cells. Циркулирующие опухолевые клетки (ЦОК) представляют собой основу гематогенного метастазирования. В 2003 г. было продемонстрировано их существование в крови больных раком яичников (РЯ). Известно, что воспаление играет важную роль в прогрессировании опухолей. В крови ЦОК встречаются с большим количеством компонентов, в т.ч. с цитокинами, которые способны модулировать метастатический потенциал опухолевой клетки. Целью данного исследования была оценка цитокинового статуса сыворотки крови больных раком яичников с различным уровнем циркулирующих опухолевых клеток. Материалы и методы. Объектом исследования явились первичные больные с верифицированным (гистологически либо цитологически) раком яичников II–IV степеней по FIGO (n=24) до лечения. В крови пациенток определяли число циркулирующих опухолевых клеток методом проточной цитофлюориметрии и уровни IL-6, IL-17A, IL-1β, TGF-α, IL-4, VEGF, TNF-α, HGF, IL-18, IL-10, IL-8. Обработку результатов проводили с использованием пакета программ Statistica Windows. Результаты. Было установлено, что уровень цитокинов TNF-α, HGF, IL-10, IL-18 в сыворотке крови больных РЯ статистически значимо повышался, а уровень IL-8 снижался с увеличением количества ЦОК. Выводы. Полученные результаты позволяют предполагать корреляцию уровня ЦОК с сывороточным уровнем цитокинов TNF-α, HGF, IL-10, IL-18, IL-8 у больных распространенным РЯ. При этом резкое и значимое возрастание уровня TNF-α при увеличении числа ЦОК может свидетельствовать о смене фенотипов TNF-продуцирующих клеток при РЯ. Ключевые слова: рак яичников, цитокины, циркулирующие опухолевые клетки.

The purpose of the paper is to evaluate the relationship between the expression of drug resistance genes in the tumor tissue of patients with ovarian cancer after neoadjuvant chemotherapy (NAChT) with clinical and pathological disease parameters. Materials and Methods. The study included 26 patients with ovarian cancer who had undergone NAChT according to the AP scheme. The authors used paired samples of normal and tumor ovatian tissue as material for their study. The expression level of ABCB1, ERCC1, and TOP2A genes was evaluated by real-time PCR. Results. It was found out that in patients under 60 years of age, the level of ABCB1 expression is higher than in patients over 60. ERCC1 and TOP2A expression in different age groups was the same. The linkage between the studied genes, tumor size and metastasis was not discovered. TOP2A and ABCB1 expression levels in patients with and without relapses did not differ significantly. In patients with relapses, the level of ERCC1 expression is higher than in patients without relapses. In patients with a normal CA-125 value, the level of ERCC1 expression is lower than in patients with a high CA-125 value. An analysis of the linkage between the expression of the studied genes and the general and relapse-free patient survival did not give significant results. Conclusion. The level of ABCB1expression is associated with the patients’ age, while the level of ERCC1expression is connected with disease recurrence and CA-125. In general, the expression of the studied genes weakly correlates with the main clinical and pathological disease parameters. Keywords: ovarian cancer, neoadjuvant chemotherapy, expression, drug resistance genes ABCB1, ERCC1, TOP2A. Цель работы – оценка связи экспрессии генов лекарственной устойчивости в опухолевой ткани больных раком яичников после проведения неоадъювантной химиотерапии (НАХТ) с клинико-патологическими параметрами заболевания. Материалы и методы. В исследование вошли 26 больных раком яичников после НАХТ по схеме АР. Материал для исследования – парные образцы нормальной и опухолевой ткани яичников. Уровень экспрессии генов ABCB1, ERCC1 и TOP2A оценивали при помощи ПЦР в реальном времени. Результаты. Выявлено, что у больных до 60 лет уровень экспрессии гена ABCB1 выше, чем у больных старше 60 лет. Экспрессия ERCC1 и TOP2A в разных возрастных группах не отличалась. Не установлена связь изучаемых генов с размером опухоли и метастазированием. Уровень экспрессии генов TOP2A и ABCB1 у больных с рецидивами и без них достоверно не отличался. У больных с рецидивами уровень экспрессии ERCC1 выше, чем у больных без рецидивов. У больных с нормальным значением СА-125 уровень экспрессии ERCC1 ниже, чем у больных с высоким показателем. Анализ связи экспрессии исследуемых генов с общей и безрецидивной выживаемостью больных не дал значимых результатов. Выводы. Уровень экспрессии гена ABCB1 связан с возрастом пациентов, а уровень экспрессии ERCC1 – с рецидивом заболевания и СА-125. В целом экспрессия изучаемых генов слабо коррелирует с основными клинико-патологическими параметрами заболевания. Ключевые слова: рак яичников, неоадъювантная химиотерапия, экспрессия, гены лекарственной устойчивости ABCB1, ERCC1, ТОР2А.

Aim. To assess the morphology of circulating red blood cells in patients with stage III ovarian cancer. Methods. The object of the study was the peripheral blood erythrocytes of primary patients with ovarian cancer (n=25) who had stage III according to International Federation of Gynecology and Obstetrics. Patients were examined in the gynecological department of Ulyanovsk Regional Clinical Oncology Center. The control group included 25 somatically healthy women. Morphological studies were performed using light microscopy. The number of red blood cells with an unchanged and altered shape was expressed as a percentage. By the method of atomic force microscopy, the topology and rigidity of red blood cells was studied. Results. A statistically significant decrease in the number of circulating blood erythrocytes was found in patients with ovarian cancer compared to somatically healthy women. At the same time, the number of discocytes is markedly reduced while the number of morphologically altered forms: echinocytes, stomatocytes, spherocytes and erythrocyte rigidity are increased. Conclusion. With the appearance of altered forms of red blood cells and increase of the transformation index and erythrocyte rigidity in patients with stage III ovarian cancer, total number of red blood cells decreases in circulating blood compared to somatically healthy women.

Aim. Study of the relationship of vascular endothelial growth factor expression in tumor cells of ascites and primary tumor in patients with ascitic form of ovarian cancer undergoing neoadjuvant chemotherapy according to the AP scheme (doxorubicin + cisplatin). Methods. The level of vascular endothelial growth factor messenger ribonucleic acid (mRNA) was assessed using PCR-RT in epithelial cells of ascites and primary tumor tissue obtained intraoperatively after 2–4 courses of neoadjuvant chemotherapy according to the AP scheme from 25 patients with a verified diagnosis of ovarian cancer (serous adenocarcinoma) at stage III–IV according to the International Federation of Gynecology and Obstetrics. Processing of the results was performed using the software package Statistica 10. Results. An increase in the expression of vascular endothelial growth factor mRNA in epithelial cells of ascites in 60% of samples was established. In the intraoperatively obtained tumor tissue after 2–4 courses of neoadjuvant chemotherapy according to the AP scheme, vascular endothelial growth factor expression was increased in 73% of the samples. At the same time, the increase of relative expression in the tumor after neoadjuvant chemotherapy did not depend on the degree of therapeutic pathomorphosis but was related to early relapse and increased level of cancer antigen-125 (CA-125). Median of relapse-free survival in vascular endothelial growth factor-positive ovarian cancer was less than 5 months. Conclusion. Neoadjuvant chemotherapy according to the AP scheme increases the expression of vascular endothelial growth factor in the tumor tissue in advanced ovarian cancer; the degree of vascular endothelial growth factor overexpression in ovarian tumor is related to the presence of early relapse and an increase in the serum CA-125 level.

In Russia, ovarian cancer (OC) is the first cause of mortality from vaginal cancer. Ascitic form of OC is considered to be the most malignant. The ascites composition is determined by the neoplasm biological properties in its development. The aim of the study was to evaluate the redox status ofascitic fluid at various stages of experimental OC. Materials and Methods. The work was performed on white outbred rats, 180–200 g, with a transplanted ascitic ovarian tumor. Ascites was taken from animals in the stationary and terminal stages of tumor growth. After removal of tumor cells, lipid peroxidation parameters were biochemically determined in it: diene conjugates, ketodienes, Schiff bases, malondialdehyde, levels of protein oxidative modification (346 nm – neutral aldehyde groups; 370 nm – neutral ketone groups; 430 nm – basic aldehyde groups; 530 nm – basic ketones) and antioxidant defense components – catalase and glutathione-S-transferase activity. The results were evaluated by means of Mann-Whitney U test (Stata 6.0). Results. As a result of the research conducted, the authors determined a significant reduction in the level of protein oxidative modification, a decrease in the catalase activity and a decrease in the malondialdehyde level at the terminal stage of tumor growth as compared with the stationary stage indices. Conclusion The redox status of ascitic fluid in experimental OC is characterized by a decrease in the oxidative modification of proteins, a decrease in the intensity of lipid peroxidation and a constant catalase and glutathione-S-transferase activity in the dynamics of neoplasm progression. Keywords: ovarian cancer, ascitic fluid, protein oxidative modification, lipid peroxidation, antioxidant system. В России рак яичников (РЯ) занимает первое место среди причин смертности от рака гениталий. Асцитная форма РЯ оценивается как наиболее злокачественная. Состав асцита при этом определяется биологическими свойствами неоплазмы в динамике ее развития. Целью исследования была оценка редокс-статуса асцитической жидкости на различных стадиях экспериментального РЯ. Материалы и методы. Работа выполнена на белых беспородных крысах массой 180–200 г с перевиваемой асцитной опухолью яичников. У животных в стационарную и терминальную стадии роста опухоли отбирался асцит, в котором после удаления опухолевых клеток биохимически определяли параметры перекисного окисления липидов: диеновые конъюгаты, кетодиены, основания Шиффа, малоновый диальдегид, уровни окислительной модификации белков (346 нм – альдегидные группы нейтрального характера; 370 нм – кетонные группы нейтрального характера; 430 нм – альдегидные группы основного характера; 530 нм – кетонные группы основного характера) и компоненты антиоксидантной защиты – активность каталазы и глутатион-S-трансферазы. Полученные результаты оценивались с использованием непараметрического критерия Манна–Уитни (Stata 6.0). Результаты. В результате проведенных исследований было установлено в терминальной стадии роста опухоли значимое по сравнению с показателями в стационарной стадии снижение уровня окислительной модификации белков, снижение активности каталазы и тенденция к снижению уровня малонового диальдегида. Заключение. Редокс-статус асцитической жидкости при экспериментальном РЯ характеризуется снижением окислительной модификации белков, тенденцией к снижению интенсивности перекисного окисления липидов и постоянной активностью каталазы и глутатион-S-трансферазы в динамике прогрессирования неоплазмы. Ключевые слова: рак яичников, асцитическая жидкость, окислительная модификация белков, перекисное окисление липидов, антиоксидантная система.

Developing neoplasm can affect the erythropoiesis of the tumor-bearer. It is found out that the degree and nature of such effect depend on tumor biological characteristics. The purpose of the study is to examine erythrocyte morphometric parameters and erythropoiesis change in tumor-bearing animals under neoplastic process development. Materials and Methods. Peripheral blood of experimental animals was used as trial material. Blood sampling was carried out during stationary (n=64) and terminal (n=64) tumor growth phases. Healthy adult rats (n=62) composed the control group. To assess erythropoiesis, the authors determined erythrocyte content, hemoglobin level, reticulocyte count, and erythropoietin concentration in the peripheral blood of tumor-bearing animals. Cytoarchitectonics was studied using atomic force microscopy. Results. Significant reduction in the number of red blood cells and decrease in hemoglobin level was established. The erythropoietin level in blood plasma increased during the stationary phase as well as the number of reticulocytes in blood during all periods of tumor growth. Erythrocyte cytoarchitectonics changed: echinocytes prevailed in the stationary phase (52%), spherocytes – in the terminal phase (50.8 %). Conclusion. The data obtained suggest that, on the background of intense erythropoiesis, the number of erythrocytes in peripheral blood falls, the hemoglobin level decreases, there is some change in cytoarchitectonics, which may indicate a toxic effect of the tumor on the hematopoietic system. Keywords: erythrocytes, erythropoietin, ovarian ascites tumor.

Chemoresistance is one of the main causes of treatment failure in advanced ovarian cancer (OC). In order to identify predictors of chemoresistance, 30 patients with ascitic form of OC, who received neoadjuvant chemotherapy (NACT) according to AP regimen, were examined. In the epithelial cells of ascites and in tumor tissue after NACT, expression of the VEGFa, ABCB1 and ERCC1 genes was assessed by PCR-RT. The effectiveness of NACT was assessed using the criteria of therapeutic pathomorphosis, survival - using the Kaplan-Meier criterion, the relationship of clinical and molecular parameters - using the Mann-Whitney criterion. Results. We established that in 43% of patients the response to NACT was absent (CRS1), the significant response (CRS2) was in 35% of cases, and the complete response (CRS3) was in 21% of cases. VEGFa expression was increased in ascites in 17% of cases, in tumor tissue - in 33% in the CRS1 group. In groups with CRS 2,3, overexpression of VEGFa in ascites was detected in 25% of cases, in tumor tissue in 37.5%. ABCB1 mRNA expression was increased after NACT in 50% of cases in the CRS1 group and in 25% of cases in the CRS 2,3 group. Thus, platinum-based NACT initiates an increase in the expression of VEGFa and ABCB1 in tumor tissue. We established that in case of high expression (ERCC + / VEGF + / ABCB1 +) in ascites, there is a statistically significant increase in relapse-free survival compared with the group with low or absent expression (p = 0.012). The overall survival rate was 41.8 months in patients with overexpression of the studied genes in the tissue of the primary tumor after NACT and 25.3 months in patients with low expression (p = 0.058). Conclusion. The levels of ERCC1, VEGFa and ABCB1 mRNA in ascitic cells before NACT and in the primary tumor after NACT according to the AP scheme can serve as a predictor of the effectiveness of this treatment in ascitic OC.

Chemotherapeutic treatment using standard solvents is stopped in every fourth ovarian cancer patient because of significant side effects. The autohemochemotherapy method alters the pharmacokinetics of the drug, and significantly reduces the frequency and severity of side effects. In order to compare the effects of neoadjuvant chemotherapy using autologous liquid tissues or standard solvents on cytokine status and neutrophils in the peripheral blood we evaluated the number of neutrophils and their ability to generate reactive oxygen species, and levels of interleukin-1p, IL-1Ra, IL-6, IL-10, IL-18 and TNF-a in 244 primary stage III-IV ovarian cancer patients during chemotherapy according to the AP scheme (cisplatin 75 mg/m2, doxorubicin 50 mg/m2) with infusion by standard intravenous method or as autohemochemotherapy. We established that the effectiveness of chemotherapy was associated with the redox status of neutrophils and cytokine status of peripheral blood, registered prior to neoadjuvant chemotherapy. For patients with tumor progression, increased absolute and relative number of neutrophils with reduced ability to produce reactive oxygen species is significant. For patients with a lack of tumor response, significant are the high levels of serum IL-10 and IL-18. For patients with complete or partial tumor response, significant is the decrease of IL-6 level, compared to the norm. No significant differences in neutrophil and cytokine status in both modes of infusion of chemodrugs have been established. Thus, serum IL-10, IL-18 and IL-6 may be used to predict tumor response to neoadjuvant chemotherapy according to the AP scheme.

Background The role of neoangiogenesis in progression of solid tumors is crucial [Han J.M., 2017]. Activated neutrophils (Nph) can synthesize vascular endothelial growth factor (VEGF) and interleukine-8 (IL-8) [Merritt W.M., 2008], regulated by nuclear factor-kappa B (NF-κB) [Annunziata C.M., 2010]. The aim of the study was to assess the role of pro-angiogenic factors of circulating Nph in the progression of ovarian cancer (OC). Methods We isolated circulating Nph from the peripheral blood of 97 OC patients (stage I-IV FIGO) 36-76 years old on a double layer of ficoll-urographin. Using ELISA, the VEGF-A (RayBiotech, USA) and IL-8 (Vector-Best-Volga CJSC, Russia) levels were determined in the Nph lysate, and the expression of NF-kB (eBioscience, USA) was determined in the Nph nuclear fraction. The control group included 30 healthy women 23-65 years old. The study was conducted in accordance with the requirements of the IMEPC ULSU ethics commission (protocol №3 from 15.03.2015). The correlation between the parameters was evaluated using the Spearman coefficient, the statistical significance of the differences was evaluated using the nonparametric Mann-Whitney U-test (p ≤ 0.05). Results We detected a statistically significant increase in the level of VEGF in Nph already at the initial stage of the OC compared to the control (469.764±185.028 pg/ml vs 50.483±9.505 pg/ml, p = 0.0053). With more advanced OC stage, the VEGF level in Nph decreased by 2 times, but remained statistically significantly high compared to control. An average correlation was revealed between the level of VEGF in Nph and the stage of OC (p = 0.5196). The level of NF-kB in the nuclear fraction of Nph was statistically significantly increased in I stage OC (0.589±0.129 mg/ml vs 0.166±0.028 mg/ml in the control, p = 0.0253) and decreased statistically significantly with the OC spread. A weak correlation between the level of NF-kB in Nph lyzate and the OC stage was revealed. The level of IL-8 in Nph did not significantly change in OC. An average correlation was found between the NF-kB level and IL-8 level in Nph (p = 0.6914). Conclusion The results obtained indicate an increase in the pro-angiogenic activity of circulating Nph with the progression of OC. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Recently, many interdisciplinary community researchers have focused their efforts on study of the low-level light irradiation effects (photobiomodulation, PBM) as a promising therapeutic technology. Among the priorities, a search of new wavelength ranges of laser radiation to enhance the laser prospects in treatment of autoimmune and cancer diseases commonly accompanied by disorders in the antioxidant system of the body. The laser wavelengths within 1265-1270 nm corresponds to the maximum oxygen absorption band. Therefore, PBM effects on a model organism within this spectrum range are of particular interest for preclinical research. Here, we report comprehensive biomolecular studies of the changes in the BALB/c nude mice skin after an exposure to the continuous laser radiation at the 1270 nm wavelength and energy densities of 0.12 and 1.2 J/cm(2). Such regime induces both local and systemic PBM effects, presumably due to the short-term increase in ROS levels, which in turn activate the cell antioxidative system.

Peripheral blood neutrophils of 123 patients in stage Ia of the endometrial cancer have been assayed. The receptor system and ability of neutrophils to form extracellular traps (NET activity) were assessed by fluorescence microscopy, and spontaneous production of IL-2, IFN-γ, matrix metalloproteinase (MMP), G-CSF was found to exist determined with enzyme-linked immunosorbent assay. Phagocytic and myeloperoxidase activity, the level of cationic proteins, and neutrophil activity were evaluated in an NBT test determining the oxygen-dependent bactericidal action of neutrophils. Topology and rigidity of neutrophil membranes were assessed using scanning probe microscopy. It was established that an increased number of neutrophils was accompanied by changes of their receptor system, aerobic and anaerobic cytotoxicity, enhanced phagocytic activity, and reduced NET activity. The secretory activity of neutrophils changed. An increased level of MMP-1, possibly by enhanced production of reactive oxygen species, reduced IL-2 level, and a drastic increase in G-CSF were observed. The architectonics of neutrophils at stage Ia of endometrial cancer was characterized by altered cell shape and granularity loss. The rigidity of the cell membrane decreased. The changes in neutrophil morphology and persistent hyperactivity suggest the existence of the equilibrium between the immune system and the tumor in stage Ia of endometrial cancer.

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.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.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/cmA 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.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/mОбоснование. Эффекты воздействия на кожу низкоинтенсивного лазерного излучения (НИЛИ) определяются длиной волны и плотностью потока облучения. Также обширное рецепторное поле кожи обусловливает системное влияние на организм. Цель исследования - изучить влияние НИЛИ инфракрасного диапазона с длиной волны 1270 нм на кожу мышей линии Balb/cNude. Методы. Объектом исследования послужили линейные иммунодефицитные мыши Balb/cNude (питомник лабораторных животных 'Пущино' филиала ФГБУН 'Институт биоорганической химии им. акад. М.М. Шемякина и Ю.А. Овчинникова' РАН). Животных однократно облучали волоконным лазером вынужденного комбинационного рассеивания с длиной волны 1270 нм, мощностью 1,96 мВт, экспозицией 2 мин при интенсивности 10 мВт/см

Background Long non-coding RNAs (lncRNAs) appear to be one of the key regulators of cellular signaling processes. According to several authors, they play a crucial role in the regulation of the antitumor immune response. Dysregulation of lncRNA profile is associated with carcinogenesis. Alteration of the lncRNA profile in ovarian cancer (OC) tumor tissue was shown. The aim of our study was to identify serum lncRNAs as potential biomarkers in ovarian cancer. Methods The study included 34 patients with verified ovarian cancer II-IV FIGO stage. Blood sampling was performed before treatment and after 3 courses of standard neoadjuvant (paclitaxel 175 mg/m² + carboplatin AUC 6 every 3 weeks) chemotherapy. To isolate free-circulating RNA from serum, the SileksMagNA-Direct magnetic particle kit was used. Analysis of the normalized expression of lncRNA MALAT, HOTAIR and PVT1 was carried out using qPCR method with normalization by 18S. We assessed the correlations between lncRNA levels and the patient age, tumor stage and CA-125 level. For statistical analysis, the ANOVA criterion (Statistika 13.0) was used. Results We have established strong correlations between the HOTAIR plasma level and age (p = 0.120) and CA-125 level (p = 0.082), and weak correlation with a relapse-free period duration (p = 0.167). The level of MALAT strongly correlated with age (p = 0.050) and with a relapse-free period duration (p = 0.014) and weakly correlated with the stage of ovarian cancer (p = 0.140). PVT1 expression did not reliably correlate with any of the studied clinical and biological parameters. Conclusion The revealed relationships between the levels of circulating MALAT and HOTAIR in the blood plasma of patients with OC require further study of these epigenetic regulators in OC carcinogenesis and chemoresistance. Free circulating lncRNA MALAT and HOTAIR, as an element of a liquid biopsy, are potential prognostic and predictive biomarkers for OC. Legal entity responsible for the study The authors. Funding RFBR (project number 19-315-50012). Disclosure All authors have declared no conflicts of interest.

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.

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.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.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.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.

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.

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.

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 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.

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 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.

Background: The aim of the study was to elaborate a method of specific diagnostics of progressive ovarian cancer. Methods and Findings: We observed 21 parameters in plasma of 300 primary ovarian cancer patients, stage III and IV. Using the least squares method, approximation of the relative frequencies by the Rayleigh distribution density was conducted for each parameter. The likelihood functions were constructed and intervals for each measurement on each stage were determined. Approximation accuracy was identified while checking the hypothesis of correspondence of parameter practical value to the theoretical law of density distribution by Pearson criterion. Conclusions: The obtained results suggest that the level of the oxidative modification of proteins may serve as a reliable indicator for the differential diagnosis of stages III and IV ovarian cancer.

The possibility of laser initiation of oxidative stress was studied by the example of the tumour tissue of cervix. The laser facility with the operating wavelength 1265 nm that falls within the region of resonance absorption of molecular oxygen was used for initiation. The source of radiation in the experiments was a fibre SRS laser with the repeated cascade conversion of radiation of a 1125-nm ytterbium laser.

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 present work discusses effect of infrared (IR) femtosecond laser irradiation on neoplasm of white mice with experimental cervical cancer- 5 (CC-5 on the 20th and 30th days after tumor transplantation). Tumor tissue was irradiated by femtosecond erbium doped fiber laser: the wavelength is 1.55 μm, average and peak powers are1,25 mW and 6kW, respectively, irradiation trials n=10. The average energy density (energy dose) on a tissue for two groups of animals was 0,24 J/cm2 and 0,36 J/cm2 for a single trial. Irradiation was followed by biochemical determination of LPO AOS parameters (“Lipid peroxidation-antioxidants” system): malondialdehyde (MDA), activity of superoxide dismutase (SOD), catalase and glutathione-reductase (GR), glutathione-S-transferase (GST). A subsequent morphological study of tumor tissue was performed. Mathematical analysis of data demonstrates a weak dependence of the studied parameters on energy dose. The latter implies the trigger effect of IR femtosecond laser irradiation on redox-dependent processes in neoplasm at experimental cervical cancer.

The purpose of the study was to evaluate the morphofunctional state of polymorphonuclear neutrophils and cytokine levels in the lysate of blood neutrophils of ovarian cancer patients. The absolute and the relative number of peripheral blood polymorphonuclear neutrophils in 120 primary ovarian cancer patients (III-IV clinical stage FIGO) and 80 healthy women were determined. The expression of CD11a, 11b, 15 and CD95 in polymorphonuclear neutrophils was assessed by fluorescent microscopy. Cytochemically the myeloperoxidase activity, the content of cationic proteins, the activity in the spontaneous NBT-test and phagocytic activity in polymorphonuclear neutrophils was determined. The amounts of cytokines TNF-α, IL-1β, 1Ra, 6, 18, and G-CSF in serum were measured by the enzyme immunoassay method. Rigidity and topology of native polymorphonuclear neutrophils were assessed by scanning probe microscopy. To detect the differences between the data obtained in the evaluation of ovarian cancer patients and healthy people, a non-parametric U-Mann-Whitney test was used. Reliable difference was considered at p ≤ 0.05. These studies found an increase of the total number of polymorphonuclear neutrophils in peripheral blood, while reducing their cytotoxicity parameters. We observed reduced myeloperoxidase activity and level of cationic proteins. Reducing in the levels of CD15 and CD95 expression on the background of increasing polymorphonuclear neutrophils activity in the spontaneous NBT-test may indicate a decrease in ability to complete phagocytosis. The dynamics of CD11a and CD11b expression in polymorphonuclear neutrophils was multidirectional, and the changes were not statistically significant. Polymorphonuclear neutrophils membrane stiffness decreased in stage IV ovarian cancer. We also observed the levels of IL-1β reduced up to 248.5 ± 9.00 pg / ml in stage III ovarian cancer, up to 230.9 ± 15.04 pg / ml in stage IV ovarian cancer vs 36.8 ± 10.74 pg / ml in control, reduced levels of 1Ra, and IL-18. We found that the level of IL-6 increased at stage III ovarian cancer up to 34.38 ± 9.74 pg / ml vs 7.66 ± 2.28 pg / ml in control, and the levels of TNF-α and G-CSF decreased. Thus, these results suggest a state of secondary immunodeficiency in patients with ovarian cancer at III-IV clinical stages of the disease.

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.