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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.

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.

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.

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.

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.