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Background. Human papillomavirus (HPV) has been established to be the etiological factor of cervical cancer (CC). HPV infection and CC progression involve the direct participation of the E6 oncoprotein. Aim. An analysis of the E6 oncoprotein levels in tissues of the tumor and its perifocal area in HPV-associated cervical squamous cell cancer as an objective indicator of the effect of treatment depending on preoperative chemotherapy. Material and methods. The study included clinical and laboratory data of 237 patients with high-risk HPV infection of the cervix. The patients were divided into 4 groups: two main groups (CC T2а2–2bN0–1M0) and two control groups. Patients in the main group 1 (n=84) received standard neoadjuvant chemotherapy (NACT), in the main group 2 (n=93) — modified NACT with prior plasmapheresis session and a parallel course of nonspecific immunotherapy with Allokin-alpha. Control group 1 (n=40) included patients with CC T1b2–2a1N0–1M0, surgical treatment; control group 2 (n=20) — HPV-positive patients without CC. Levels of E6 were measured in samples of the cervical tumor and perifocal tissues. Results. The lowest levels of the E6 oncoprotein were registered in the group of HPV-positive patients without CC. After modified NACT, E6 levels in tumor tissues remained 4.6 times higher than in intact tissues, and even so, these patients demonstrated minimal E6 levels compared to other CC patients. E6 in tumor tissues was significantly lower than in main group 1 (by 3.3 times) and 8 times lower than in control group 1. E6 levels in the perifocal tissues of patients in main group 2 were 1.9 times lower than in the corresponding tissues of patients in main group 1 and 2.2 times lower than in control group 1. Conclusions. Inclusion of plasmapheresis and inducers of endogenous interferonogenesis into neoadjuvant treatment for cervical cancer can be considered pathogenetically justified, since it affects the key unit of cervical carcinogenesis.

e15078 Background: It is known that berberine inhibits oxidative phosphorylation by suppressing respiratory complex I function, but the exact mechanism of this phenomenon has not yet been described. The aim of the study was to evaluate the effect of residues in positions 8 and 13 of berberine molecule on the energy metabolism of HeLa cells. Methods: HeLa cells were seeded in an amount of 2*104 cells per well in a Seahorse XFp Analyzer plate (Agilent, USA) in DMEM medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA). After cell adhesion, the medium was decanted, and the medium with test substances at a concentration of 5 µM was added. Four variants of the experiment, 3 repetitions each, were set up: 1) control; 2) berberine without modification; 3) modification 1 (M1) with the addition of 7-nitrobenzo[c][1,2,5]oxadiazol-4-yl residue at position 13 and malononitrile residue to position 8; 4) modification 2 (M2) with the addition of dicyanovinyl residue at position 13. After 24 hours the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were measured on Seahorse XFp Analyzer (Agilent, USA) using a Seahorse XFp Cell Energy Phenotype Test (Agilent, USA), with 2 µM FCCP and 1 µM oligomycin. Results: Incubation with the original berberine resulted in a significant decrease in baseline OCR by 39.3±2.8% (M±SD) compared to control (α = 0.05, df = 4), but the maximum OCR did not change significantly. At the same time, a significant increase in the baseline level of glycolysis was observed proportional to the decrease in the baseline OCR, as can be seen from the increase in ECAR by 32.9±5.3% compared with the control (α = 0.05, df = 4). Berberine M1 modification led to a significant increase in baseline OCR by 49.1±2.1% compared with the control (α = 0.05, df = 4), which was also accompanied by a significant increase in maximum OCR by 22.8±3.8% (α = 0.05, df = 4), while the increase in the baseline level of ECAR by 9.7±4.2% was not significant. The addition of the M2 modification did not significantly change the measured parameters compared to the control. Conclusions: The introduction of a dicyanovinyl residue into the berberine molecule at position 13 abrogated its ability to inhibit cellular respiration, possibly due to disturbing its interaction with the proteins of the respiratory complex I. Introduction of the bicyclic residue 7-nitrobenzo[c][1,2,5]oxadiazol-4- yl at position 13 and a malononitrile residue at position 8 caused an increase in baseline and maximum respiration levels, that means thereby berberine activity reversal. This effect can be associated either with the ability to uncouple oxidative phosphorylation (similar to FCCP) or to enhance the expression of electron transport chain proteins.

e15077 Background: Plant metabolites are traditionally a valuable source of anticancer drugs. The huge variety of molecular structures found in plants makes it possible to isolate substances that possess not only antimitotic, but also anti-migratory properties on cancer cells. The objective of this study was to evaluate the anti-migratory activity of selected metabolites from Petasítes sp. plants. Methods: Cells of cancer cell cultures PC3 (prostate cancer), A431 (skin cancer), CaCo-2 (colorectal cancer), HeLa (cervical cancer) and T98G (glioma) were seeded in an amount of 15*104 cells per well of a 24-well plate (Biofil, China) in DMEM medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA). After cell adhesion the test substances at a concentration of 40 µM were added, and a wound healing assay was performed according to the standard procedure. The study included the following metabolites: 1) substance 1 (S1) - 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one; 2) substance 2 (S2) - 5-(hydroxymethyl)furan-2-carbaldehyde; 3) substance 3 (S3) - corynan. The wound area was measured using a Lionheart FX imager (BioTek, USA) at starting time point and after 48 hours of cultivation. Data are presented as mean±95% confidence interval (n = 12). Results: The studied cultures were found to be differently sensitive to the tested substances. Cells of CaCo-2 and PC3 cultures did not demonstrate a significant decrease in mobility, as the degree of scratch overgrowth did not decrease compared to the control without the addition of substances (α = 0.05, df = 22) in all variants of the experiment. However, the A431 skin cancer culture showed reduced motility in all three trials compared to the no-substance control. Namely, the wound area reduction was 81.52 ± 9.6% in the control, 63.77 ± 8.4% in S1 variant, 62.42 ± 6.3% in S2 variant, and 12.05 ± 7.1% in S3 variant. Also, a slowdown in cell motility was observed in HeLa (28.92±5.1% compared to 37.0±6.3% in control) and T98G cells (82.41±9.1% compared to with 97.35±1.9% in control) when incubated with S1. Taking into account the correction for multiple comparisons, only the results for A431 turned out to be significant, but the results obtained for HeLa and T98G cultures were not significant at a corrected significance level (α = 0.003, df = 22). Conclusions: Further studies of 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one anti-migratory properties are of particular interest, since it showed promising results in three of the five studied cancer cell cultures.

e15003 Background: Taxanes and platinum compounds are widely used in cervical cancer chemotherapy. In particular, a combination of 75 mg/m2cisplatin and 175 mg/m2 paclitaxel, which suggests a doses ratio of 1:2.3, is recommended as first-line systemic chemotherapy. Although this combination has performed well in clinical practice, little is known about its effect on cervical cancer cell biology in vitro. This study assessed the effect of combined application of cisplatin and paclitaxel in a dose ratio of 1:2.3 on HeLa cells. Methods: HeLa cells were seeded at 3000 cells per well in a 96-well plate (Eppendorf, Germany) and incubated for 24 hours in DMEM medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA) at 37°C in an atmosphere containing 5.0% CO2. After 24 hours, the culture medium was replaced with a medium containing chemotherapy drugs in combination or as standalone agents in a series of two-fold dilutions: 0.03 - 32 µg/mL cisplatin and 0.07 - 73.6 µg/mL paclitaxel. After 2 h exposition to studied compounds the medium was replaced and cells were incubated for another 72 hours. At the end of the experiment, the number of living cells was assessed using the MTT test. Viability was determined as the number of living cells in % of the control without the addition of chemotherapy drugs. Results: The combination of cisplatin with paclitaxel demonstrated significantly greater efficacy than pure cisplatin in the concentration range from 0.03 μg/ml to 8 μg/ml. The difference between the mean viability values for each concentration between pure cisplatin and its 1:2.3 mixture with paclitaxel was significant at α = 0.05 (df = 14). The decrease in viability is especially dramatic at non-toxic concentrations of cisplatin (0.03 - 0.5 μg/ml) and is about 60% over this concentration range. However, when moving to toxic concentrations of cisplatin (0.5-32 μg/ml), the difference in the viability of HeLa cells between pure cisplatin and its combination with paclitaxel linearly decreases with increasing cisplatin concentration, becoming insignificant in the range of 8-32 µg/ml. However, when comparing the dose-response curves for pure paclitaxel and its combination with cisplatin, we see a significant reduction in cytotoxic activity compared with pure paclitaxel. The difference in cell viability reaches its maximum (45%) at a paclitaxel concentration of 2.3 µg/ml and is significant at α = 0.05 (df = 14). Conclusions: The combined use of cisplatin and paclitaxel in a dose ratio of 1:2.3 on HeLa culture has a greater cytotoxic activity compared to pure cisplatin. However, compared with pure paclitaxel, the effectiveness of its combination with cisplatin is significantly lower, which indicates the antagonism of the two substances.

e17500 Background: Our purpose was to analyze the rates of polymorphic allelic variants of genes of hemostasis system and methionine exchange in patients with female reproductive tumors. Methods: The study included 51 patients with histologically verified gynecologic tumors (group 1), including 28 patients (group 1a) with malignant tumors (cervical cancer (CC) n = 8, ovarian cancer (OC) n = 8, endometrial cancer (EC) n = 8, other cancers n = 4) and 23 patients (group 1b) with benign tumors, and 47 women without tumors (group 2). 12 polymorphic loci were studied by RT-PCR in genomic DNA samples: F2 (G20210А, rs1799963), F5 (G1691A, rs6025), F7 (G10976A, rs6046), F13 (G226A, rs5985), FGB G(-455)A (rs1800790), ITGA2-α2 (C807T, rs1126643), ITGB3-b (Т1565С, rs5918), PAI-1 4G(-675)5G, rs1799889), MTHFR (С677Т, rs 1801133 and A1298C, rs1801131), MTR (А2756G, rs1805087), MTRR (A66G, rs1801394). Groups 1, 1a and 1b were compared with controls (p1) and among themselves (p2). Results: The ratio of genotype frequencies maintained in the Hardy-Weinberg equilibrium in all gene loci except F7 (G10976A) in group 1 (p = 0.03). An alternative allele in the F2 gene was found only in group 2 (1.1%). The frequency of an alternative allele in the F5 gene in group 1 was 2.9%, including 1a – 1.8%, 1b – 4.3%, group 2 – 2.1%; F7 – 16.7%, 14.3%, 19.6% and 17.0%; F13 – 23.5%, 23.2%, 23.9% and 34%; FGB – 26.5%, 25.0, 28.3% and 25.5%; ITGA2 – 53.9% (p1= 0.03, OR = 1.89 (1.07-3.33), 48.2%, 60.9% (p1= 0.01, OR = 5.21 (1.22-5.17) and 38.3%; ITGB3 – 13.7%, 10.7%, 17.4% and 16.0%; PAI-1 – 47.1% (p1= 0.03, OR = 0.53 (0.30-0.93), 46.4%, 47.8% and 62.8%; MTHFR (Т) – 28.4%, 30.4%, 26.1%, 34.0%; MTHFR (С) – 34.3%, 28.6%, 41.3% (p1= 0.04, OR = 2.17 (1.02-4.61) and 24.5%; MTR – 18.6%, 19.6%, 17.4% and 27.7%; MTRR – 63.7%, 71.4%, 54.3% and 62.8%, respectively. TT genotype at the ITGA2-α2 (C807T) locus was more frequent in group 1 than in group 2 (23.5% vs 19.1%, p1= 0.01, OR = 6.54 (2.61-16.40); CT genotype was more frequent in group 1a than in group 2 (67.9% vs 38.3%, p1= 0.004, OR = 3.40 (1.27-9.13), and more frequent in EC than in group 2 (87.5% vs 38.3%, p1= 0.03, OR = 11.28 (1.28-99.40). GG genotype at the MTRR (A66G) locus was more frequent in group 1a than in group 1b (53.6% vs 26.4%, p2= 0.042). 5G5G genotype at the PAI-1 4G(-675)5G locus was more frequent in group 1 than in group 2 (31.4% vs 10.6%, p1= 0.04, OR = 3.84 (1.28-11.53), and more frequent in OC than in group 2 (75% vs 11%, p1= 0.0001, OR = 25.50 (3.96-160.20). AA genotype at the F7 (G10976A) locus was more frequent in CC patients than in group 2 (31.3% vs 17%, p1= 0.03, OR = 15.33 (1.20-195.75). Conclusions: Carriage of the AA genotype at the F7 (G10976A) locus may increase the risk of developing CC, and the CT genotype at the ITGA2-α2 (C807T) locus may increase the risk of EC. On the contrary, the alternative 4G allele at the PAI-1 4G(-675)5G locus was less common in patients with malignant tumors, especially OC, than in the group without cancer.

e17549 Background: The question of the mechanisms of platinum resistance development in advanced ovarian cancer (OC) remains open. The aim of the study was to reveal the relationship between the proliferative activity of OC cells, the disruption of apoptosis processes and the changes in the activity of transporter proteins that provide the efflux of chemotherapy drugs. Methods: Patients with advanced OC (T3-4N0-3M0-1) of postmenopausal age, sensitive (SPtPs, n = 23) and resistant to platinum drugs (RPtPs, n = 17), operated on after 3-6 cycles of neoadjuvant chemotherapy, were retrospectively studied. The parameters of proliferative activity (ki67), apoptosis disturbances (p53), as well as the expression of BCRP and Pgp transporter proteins were evaluated in OC tissue using immunohistochemistry methods. Statistical analysis was performed using the Mann-Whitney and Pearson tests (χ2), as well as the Spearman's rank correlation coefficient (SC). Results: In total, the dominance of the RPtPs over the SPtPs was noted in terms of intensity of the studied indicators (p < 0.05-0.003), the most significant for Pgp expression. At the same time, moderate and high values of these indicators were observed in SPtPs in 42-61% of cases, which reduced the predictive value of the revealed differences. It was of interest that statistically significant correlations between the indicators in SPtPs differed from those in RPtPs. Thus, the following values of the SC were observed in SPtPs: +0.848 (ki67-p53), -0.675 (ki67-BCRP), -0.575 (p53-BCR). In RPtPs, another intensity and/or direction of these relations were noted: +0.521 (ki 67-p53), +0.500 (ki 67-BCRP), +0.705 (p53-BCR). There were no statistically significant relationships between ki67-Pgp expression in SPtPs and RPtPs. The direction and intensity of the studied relationships could indicate changes in cell regulation in primary OC in SPtPs compared to RPtPs. Thus, in SPtPs, they reflected a significant contribution of apoptotic disturbances to the enhancement of OC cell proliferation, which was limited by the negative feedback mechanism via BCRP activity suppression indicated by the presence of an inverse correlation ki67-BCRP. In RPtPs, this mechanism was apparently already lost, which resulted in a change in the direction of the statistical relationship ki67-BCRP from reverse to direct one. Under these conditions, the positive contribution of apoptosis disruption to the proliferative activity of OC cells could obviously be supplemented by a synergistic increase in the activity of the BCRP transporter protein, which removes platinum drugs from OC cells. Conclusions: Patients with advanced OC may develop platinum resistance due to discoordination of proliferation, apoptosis, and regulation of the activity of the BCRP transporter protein.

e15002 Background: Bleomycin is a glycopeptide antibiotic with anticancer properties. Clinical data indicate a relatively low efficacy of bleomycin in mono regimen, which is also accompanied by side effects from high doses. That’s why so it is more often used in relatively low doses in combination with other chemotherapy drugs. In particular, in cervical cancer, bleomycin is used in combination with cisplatin in a dose ratio of 0.8:1. Despite good clinical results, it is not known how the two drugs interact in vitro. The aim of this study was to evaluate the effect of combined application of bleomycin and cisplatin on HeLa cells. Methods: HeLa cells were seeded at 3000 cells per well in a 96-well plate (Eppendorf, Germany) and incubated for 24 hours in DMEM medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA) at 37°C in an atmosphere containing 5.0% CO2. After 24 hours, the culture medium was replaced with a medium containing chemotherapy drugs in combination or as standalone agents in a series of two-fold dilutions: 0.03 - 32 µg/mL cisplatin and 0.012 – 12.8 µg/mL bleomycin. After 2 h exposition to studied compounds the medium was replaced and cells were incubated for another 72 hours. At the end of the experiment, the number of living cells was assessed using the MTT test. Viability was determined as the number of living cells in % of the control without the addition of chemotherapy drugs. Results: The combination of cisplatin with bleomycin demonstrated significantly greater efficacy than pure cisplatin in the concentration range from 0.03 µg/ml to 8 µg/ml, and pure bleomycin in the range of 0.012 - 12.8 µg/ml. The difference between the mean viability values for each concentration of pure bleomycin or pure cisplatin and their 0.8:1 mixture was significant at α = 0.05 (df = 14). Observed decrease in the viability of HeLa cells in comparison with pure substances is most pronounced in the range of non-toxic concentrations for both substances in mono regimen, namely 0.03 - 0.5 μg/ml for cisplatin, and at concentrations less than 0.125 μg/ml for bleomycin. Here, the increase in the difference between the dose-response curves grows as the concentration of the studied drugs increases. At cisplatin concentrations of 0.5–32 μg/ml, the difference in HeLa cell viability between pure cisplatin and its combination with bleomycin, on the contrary, decreases linearly with increasing cisplatin concentration, becoming insignificant above 16 μg/ml. Conclusions: The combined use of bleomycin and cisplatin on HeLa culture in a dose ratio of 0.8:1 exhibits synergistic properties that are most pronounced in the concentration ranges of both substances that do not have a cytotoxic effect in mono regimen.

e17554 Background: Thrombosis in patients with gynecologic cancers worsens the outcome of antitumor treatment and is one of the leading causes of their death. The kallikrein-kinin system (KKS) is involved in both the regulation of thrombus formation and the development of cancer. The purpose of this study was to analyze characteristics of the KKS components in the blood in patients with endometrial cancer (EM) and ovarian cancer (OC) with and without secondary thrombosis (VTEC). Methods: The study included 39 patients, mean age 58.0±4.2 years: main groups – patients with OC T1c-3cN0M0 (n = 10) or EC T1a-2N0M0 (n = 9) with VTEC; comparison groups - patients with OC (n = 10) or EC (n = 10) without VTEC. EC was represented by adenocarcinomas (G1-G3), OC by serous carcinomas (90%) and clear cell adenocarcinomas (10%). The control group included healthy women of the corresponding age (n = 10). Blood levels of kallikrein 1 (K1), kallikrein 14 (K14), and kininogen (KG) were measured by ELISA after the surgery. Results: EC patients with VTEC showed 1.5 times (p < 0.05) higher blood levels of K1, compared to donors, while other indices were unchanged. EC patients without VTEC had 4 times lower KG levels, compared to donors and EC+VTEC. In OC, regardless of the presence or absence of VTEC, levels of K1 in the blood increased, as well as in women with EC+VTEC, by 1.5 times (p < 0.05) compared with donors, which was combined with a twofold increase in KG in OC+VTEC and a decrease in KG by 1.4 times in OC patients without VTEC. Blood levels of K14 increased only in OC patients without VTEC by an average of 1.9 times (p < 0.05) compared with donors and OC+VTEC. Conclusions: The revealed changes in some KKS components in the blood demonstrate the similarity (K1 increase) and differences (KG increase only in OC) in the pathogenesis of thrombosis associated with gynecologic cancers. The mechanisms of protection against VTEC in the early postoperative period also showed common (KG decrease) and specific features associated with the characteristics of cancer (K14increase only in OC). The development of therapy aimed at correcting the identified disorders will allow an antitumor treatment program for this category of patients with maximum efficiency improving their quality of life and survival.

e17621 Background: An imbalance of sex hormones in endometrial cancer (EC) towards hyperestrogenism together with progesterone deficiency is considered to stimulate proliferation and suppress endometrial apoptosis. EC with squamous metaplasia is characterized by a more severe clinical course and the lack of an adequate response to standard treatment. The purpose of this study was to analyze the local hormonal profiles of tumors with squamous metaplasia in patients with obesity. Methods: The main group included 20 EC patients with squamous metaplasia, and control group included 35 patients with endometrioid adenocarcinoma: T1-3N0-1M0, mean age 64±3.2 years. Intact endometrial tissues were obtained during surgical treatment of patients with uterine fibroids (n = 20). All patients gave their written informed consent for the study. Levels of estradiol (E2), estrone (E1), testosterone (T), progesterone (P4), estrogen receptors ERα and ERβ, progesterone receptor RP4 and androgen receptors RA were measured by ELISA in samples of tumor and peritumoral (PT) tissues. Statistical processing of results was performed using the Statistica 10. Results: Tumor tissues of patients with EC, regardless of the histological structure, showed higher levels of estrogens and androgens and their receptors, compared with the intact endometrium, without significant changes in levels of progesterone and its receptor. In the main group, compared with the control group, E1 levels in tumors were lower by 1.6 times, E2 by 1.3 times (p < 0.05), but T higher by 2.4 times, ERα by 1.7 times, ERβ by 1.5 times (p < 0.05). PT, compared with the intact endometrium, had lower levels of E1 and E2 by 2 times and 1.5 times, P4 by 5.1 times, and T was lower only in PT with squamous metaplasia by 2.8 times. Levels of all steroid hormone receptors in PT were higher, regardless of the histological type of tumors. In PT of the main group, levels of E1 were 1.3 times lower (p < 0.05) than in controls, P4 – by 2.2 times, T – by 2.8 times, RP4 – by 1.7 times and ERβ by 1.8 times (p < 0.05), but ERα was 3.2 times higher. Conclusions: Tumors with squamous metaplasia, compared with endometrioid adenocarcinoma, are characterized by an imbalance of steroid hormones towards the predominance of androgens, and ERα plays a dominant role among estrogen receptors. The tumor probably synthesizes sex steroids independently and also pumps them over from the surrounding area. At the same time, malignant endometrial tumors, regardless of their histological structure, are more saturated with estrogens, androgens and their receptors, compared with the intact endometrium.

Ovarian carcinoma is the leading cause of death from gynecological cancer. Aim of the study is to reveal the role of VEGF-C comparing to VEGF-А in the progression of ovarian cancer. Material and methods. Tissue samples obtained from 76 patients with epithelial ovarian cancer (serous cystadenocarcinoma: T1N0M0; T2N0M0; T3NxM0; T4Nx-1M0) and 47 patients with cystadenoma were studied. Histological control was performed in all cases. Ovaries of 20 patients obtained during the surgery for uterine myoma were used as the intact tissue. All patients were 50.9 ± 2.9 years old. Levels of the growth factor as VEGF-A and its receptor VEGF-R1, as well VEGF-С and its receptor sVEGF-R3 - were measured by ELISA with the use of standard test systems. Results. VEGF-А levels in cystadenomas and intact tissue were similar, while in cystadenocarcinomas VEGF-А was significantly higher at all stages of the tumor development. sVEGF-R1 receptor in cystadenomas was lower in comparison with the intact tissue, in the contralateral ovary in T1N0M0 and in the tumorous ovary in T4Nx-1M0. VEGF-С level was higher significantly in all tumors, in cystadenocarcinomas it was higher if compared to cystadenomas. Its increase in the contralateral ovary in T1N0M0 differed from other tissue values being average. sVEGF-R3 receptor increased significantly at the later stages of ovarian cancer - T3NxM0 and T4Nx-1M0; its level was low only in the contralateral ovary in T1N0M0, and the values in other tissues were similar to the intact ones. Conclusion. The results show a high rate of lymphatic vessel formation in benign tumors at all stages of the development of the malignant tumor. The significant increase in VEGF-C level in the contralateral (non-tumorous) ovaries, compared to the intact tissue, allows considering VEGF-C, along with VEGF-А, as a pathogenetic factor of ovarian tumor development.

e17516 Background: The combination treatment with plasmapheresis and non-specific immunotherapy for locally advanced cervical cancer (CC) is shown to be effective. We studied the effect of immunotherapy with dendritic cell vaccine (DCV) as a part of combination therapy on the intensity of the lipid peroxidation (LPO) and activity of antioxidant enzymes. Methods: Plasma and erythrocyte content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD), catalase, glutathione dependent enzymes and the content of reduced glutathione (GSH) in erythrocytes were determined in 24 patients with CC of T2a-2bN0-1M0 stages and in 25 women without cancer. The patients underwent neoadjuvant chemotherapy (CT) with cisplatin and bleomycin, followed by 2 cycles of DCV, for a total of 6 courses of CT and 12 cycles of DCV. Results: Initially, patients demonstrated intensification of free radical processes enhancing after PCT and the first two DCV: MDA in erythrocytes elevated by 52.2-111.7%, in the blood plasma by 2.2-3.5 times. Subsequent DCV cycles normalized the LPO. MDA levels after 4 DCV cycles were lower than the initial values in erythrocytes by 30.4% (p = 0.04), in plasma by 55.6% (p = 0.007), i.e. were similar to the levels in healthy women. The SOD activity was decreased by 16.7-27.3% (p < 0.005) after 4-6 DCV cycles and normalized after the 7th cycle. The catalase activity in erythrocytes was decreased before treatment and after PCT by 42.4% (p = 0.000000), during vaccine therapy by 20.5-37.7% (p < 0.0005). In reduced catalase activity, inactivation of hydrogen peroxide was realized, apparently, by glutathione peroxidase (GPO), and its increased activity (by 37-102.3%, p≤0.00005) was supported by a high GSH content - by 11.6-52.4% (p < 0.02) above the norm at all stages after the 2nd DCV cycle. And only with the complete normalization of the erythrocyte MDA content, the GPO activity after the 7th DCV cycle decreased by 46.7% (p = 0.000000) relative to the levels before the treatment and did not differ significantly from the values in donors. Conclusions: Vaccine therapy helped to enhance the activity of the glutathione system becoming the most important component of antioxidant protection in the blood of CC patients. Already 3-4 DCV cycles normalized the LPO sharply increased in CC patients during CT. Multi-course vaccine therapy allowed maintaining the optimal oxidative status of the blood.

e17535 Background: Analysis of the nature of cancer cell release and interaction with the microenvironment determines the fundamental basis of ovarian cancer pathogenesis, which is necessary for the development of new methods for peritoneal dissemination treatment and prevention. The purpose of the study was to analyze levels of VEGF-A, VEGFR1, VEGF-C, VEGFR3, TGF-β, IGF-1, IGF-2 and IGFBP3 in omental tissues (O) with and without metastasis (Mts) in ovarian cancer patients. Methods: Samples of O tissues were obtained from 51 ovarian cancer patients aged 60±1.9 years (G2-G3 serous cystadenocarcinoma – AC, Т2-3NxM0-1). 17 non-cancer patients of similar age were controls (C). Levels of VEGF-A, VEGFR1, VEGF-C, VEGFR3, IGF-1, IGF-2, IGFBP3 and TGF-β1 were measured in Mts and O tissues by standard ELISA test systems. Results: VEGF-A levels in O of AC patients were 2.6 times higher than in C. In Mts, VEGF-A and VEGFR1 exceeded the levels in C (by 6.3 and 3.1 times) and O (by 2.5 and 2.8 times, respectively). VEGF-C in O was lower than in C by 5.5 times, while VEGFR3 was 2.2 times higher. In Mts, VEGF-C and VEGFR3 exceeded the levels in C (by 7.8 and 3.6 times) and O (by 43.3 and 1.6 times, respectively, p

e18022 Background: Locally advanced and progressive cervical cancer is always accompanied by the pain syndrome. The common analgesics include non-steroidal anti-inflammatory drugs and opioids. The purpose of the study was to assess allogeneic dendritic cell vaccine (DCV) as an alternative analgesic in patients with advanced cervical cancer. Methods: The pain syndrome dynamics was assessed in 20 patients with advanced T3-4N1M0-1 cervical cancer receiving subcutaneous paravertebral injections of allogeneic DCV in a total alternating dose of 5-10 million cells every 2 weeks. Patients received DCV for one year, with a total of 24 vaccine therapy sessions and a total dosage of 180 million dendritic cells. The pain intensity was assessed on a verbal rating scale: 0 – no pain; 1 – mild pain; 2 – moderate pain; 3 – severe pain; 4 – extremely intense pain. Results: Prior to the therapy, 15 patients (75%) had severe pain; 2 (10%) - moderate pain; 3 (15%) - extremely intense pain. After 4-6 DCV injections, the pain intensity decreased, patients refused opioid analgesics. After 10-12 DCV sessions, 19 (95%) (p < 0.05) women had no pain at all, patients denied additional pain relief with non-opioid analgesics. Unrelieved pain was registered only in one cervical cancer patient. Conclusions: DCV injections in patients with advanced cervical cancer provide pain relief thereby improving their quality of life.

e18037 Background: Renal dysfunction in cancer patients is an urgent problem of clinical practice in oncology which can often challenge the efficacy of anticancer treatment and the disease prognosis. The purpose of the study was to reveal risk factors for renal dysfunction in oncogynecological patients. Methods: A prospective randomized study of the renal function included 174 patients aged 54-82 years with reproductive tumors. The control group included 34 patients with benign uterine tumors. Glomerular filtration rate (GFR) was estimated using the CKD-EPI equation. Results: GFR in the main group was 71.6±2.3 mL/min/1.73m2. Renal dysfunction was found in 42.5%. The majority of patients (115 patients, 66.1%) had concomitant diseases classified as modifiable risk factors for the development and progression of chronic kidney disease (KDIGO, 2017), including hypertonic disease in 46.6% (χ2= 4.4, p < 0.05), diabetes in 39.1% (χ2= 7.9, p < 0.05), cardiovascular diseases in 27.6% (χ2= 3.9, p < 0.05), and morbid obesity in 68.9%. This confirmed the decisive importance of hypercholesterolemia, hyperglycemia and hypertension as risk factors for reduced GFR. 52.9% of patients had a combination of these factors, which together with the initial renal dysfunction suggested a high probability of acute renal failure in the perioperative period. Conclusions: The assessment of kidney function in patients with gynecological cancers is required to determine the intensity of treatment in the perioperative period, the general disease prognosis and risks of possible complications.

e17129 Background: An important principle of analgesia is its effect on each component of the pain formation. The purpose of the study was to improve analgesia in the perioperative period in patients with gynecological cancer. Methods: This prospective randomized study of the quality and effectiveness of various analgesics included 97 patients aged 22-67 years receiving surgery for gynecological cancer. The patients were divided into two groups. Group 1 (n = 47): patient-controlled analgesia with trimeperidine and nonsteroidal anti-inflammatory drugs (NSAIDs); group 2 (n = 50): preemptive analgesia based on lidocaine, magnesium sulphate, nefopam and NSAIDs. Results and pain syndrome were assessed by levels of glucose, cortisol, insulin, lactate, C-reactive protein (CRP), Kerdo autonomic index, visual analogue scale (VAS), levels of personal and reactive anxiety and depression. Results: Analgesic effect of trimeperidine was obtained in 83.3% (p < 0.05). However, the effect was less pronounced, compared to non-opioid analgesics, and did not reduce the psychosomatic component of pain after surgical treatment. In group 2, non-opioid analgesia limited the increase of cortisol, glucose, insulin, CRP and lactate (p < 0.05) providing effective pain relief in the perioperative period. Non-opioid analgesics promoted an optimal analgesic effect, did not cause residual sedation, anxiety, depressive effects and cognitive impairments, which showed their obvious advantage over opioids. Opioid-sparing effect was 96.3% (p < 0.05). Reducing the consumption of narcotic analgesics without worsening the quality of postoperative analgesia and the patient's well-being is an important advantage which allows minimizing the negative effects of opioids, facilitating the early rehabilitation of patients. Conclusions: Non-opioid analgesics can significantly limit endocrine and metabolic changes without worsening the quality of analgesia in the perioperative period.

e17005 Background: The purpose of the study was to determine the influence of complex treatment with dendritic cell vaccine on the dynamics of the immune status of patients with cervical cancer. Methods: 17 patients with cervical cancer (CC) T2b-4аN0-1M0-1 received chemotherapy with combined radiotherapy to the pelvic area. Between courses of cytostatic treatment, patients underwent dendritic cell vaccination (DCV) planned individually depending on the treatment effect, which was evaluated by the results of examination, US, CT and MRI. A control group included 19 patients with locally advanced CC receiving standard polychemotherapy (PCT) and radiotherapy. Immune status of patients was evaluated by flow cytometry (FACSCantoII BD) including T, B, NK cells, Tregs (CD4+CD25+CD127dim), memory T cells (Тm) and naïve T lymphocytes (Th0) was determined in the dynamics of the treatment. Results were calculated as a percentage from the total number of lymphocytes, for Tregs – in % from CD3+CD4+ cells, for Тm and Th0 – in % from CD3+CD4+ and CD3+CD8+ cells. Results: 1 to 4 cycles of PCT with DCV caused a transient increase in Tregs after the 1st cycle, with further regression to the initial levels; other studied lymphocyte subsets remained unchanged. Only after 8 or more DCV cycles, a favorable immunological dynamics developed; however, it was not observed in controls. DCV increased levels of lymphocytes with potential cytotoxicity: CD3+CD8+ (from 19.0±2.0 to 28.8±1.5%), NK cells (from 12.0±2.0 to 21.2±1.9%). During DCV courses helper-inducer Tm amount rose from 51.7±6.3 to 69.7±4.3%, while in remission – CD8+Tm grew from 28.5±2.1 to 40.4±5.3% (p < 0.05 for all cases). Repeated DCV was satisfactorily tolerated by CC patients and, when used in complex treatment, caused a pronounced clinical effect. DCV did not lead to serious adverse events. Patients in remission are still observed. Conclusions: Treatment for CC with DCV causes a positive dynamics of the immune status, with the maximal effect after 8 and more DCV cycles. Remission is apparently maintained due to an increase in the level of TmCD8+ cells.

e17019 Background: The purpose of the study was to analyze hormonal disorders in tissues of histologically unchanged ovaries of patients with cervical cancer infected with HPV/Chlamydia trachomatis. Methods: We studied levels of estrone (E1), estradiol (E2), free estriol (E3), free (fT) and total (T) testosterone, progesterone (P4), steroid-binding globulin (SBG) and prolactin (PRL) by the ELISA in intact ovaries of 25 patients aged 53.4±3.2 years with cervical cancer T1b-2aN0M0. HPV presence was determined by Е7 protein expression, Chlamydia trachomatis (Ch. tr.) – by IgG and IgА to Ch. tr. and antigen/DNA by ELISA and Real-time PCR. Tissues of intact ovaries obtained during hysterectomy from 22 non-infected women of similar age with endometrial cancer T1N0M0 were used as the control. Results: The data demonstrated a sharp decrease in E2 level by 9.3 times and increase in E1 by 2.3 times in intact ovaries of cervical cancer patients infected with HPV and Ch. tr., compared with the values in controls. Changes were noted in the balance between some estrogen fractions: E1 percentage increased by 5 times, E3 – by 2.4 times and E2 percentage decreased by 4 times. Androgenic status in intact ovaries in cervical cancer was characterized with increased levels of T (by 5.1 times) and fT (by 1.6 times). We noted an increase in SBG concentration by more than 3 times in response to the release of androgens registered in ovarian tissue, as well as significant (by 4.4 times) increase in PRL and decrease in P4 by 1.5 times compared with non-infected tissues. Estrogens to P4 ratio in co-infected patients reduced by 1.6 times, while the PRL to P4 ratio increased by 6.4 times, mainly due to disorders in hormone-producing ovarian function. Conclusions: The development of malignant process in the cervix in a combined HPV and Chlamydia trachomatis infection is accompanied by disorders of the endocrine status in tissues of intact ovaries and shows the undeniable role of consequences of HPV/Chlamydia trachomatis coinfection in this process.

e23180 Background: Sex hormones are known to be able to influence the synthesis of growth factors in breast and uterine tumors; however, their relationship in multiple primary tumors is poorly studied. The purpose of the study was to analyze correlations between sex steroids and growth factors in tissues of solitary and synchronous breast cancer and uterine myoma. Methods: Levels of estrogens (E1, E2, E3), 2OHE1 and 16α-OHE1, Р4, VEGА and EGF were measured by ELISA in tissues of breast cancer (BC, n = 37), uterine myoma (n = 27) and in synchronous BC and uterine myoma (n = 36). Results: Strong positive correlations were observed in synchronous BC and uterine myoma: E3 with VEGF (r1= 83, r2= 79; p1,2< 0.05) and EGF (r1= 78, r2= 82; p1,2< 0.05), Е1 with VEGF ( r1= 81, r2= 77; p1,2< 0.05) and EGF (r1= 76, r2= 80; p1,2< 0.05), 16-OHE1 with VEGF and EGF (r1= 80, r2= 77; p1,2< 0.05 and r1= 79 r2= 80; p1,2< 0.05). We found strong negative correlations of Е3 and VEGF (r1= 80, r2= 77; p1,2< 0.05) and EGF (r1= 79 r2= 80; p1,2< 0.05), Р4 and VEGF (r1= - 81, r2= -79; p1,2< 0.05) and EGF (r1= - 77, r2= -80; p1,2< 0.05). Solitary breast tumors showed moderate positive correlations of E2 and E1 with VEGF (r1= 56, r2= 63; p1,2< 0.05) and EGF (r1= 61, r2= 65; p1,2< 0.05) and a moderate negative correlation between VEGF and EGF and Р4 (r1= - 61, r2= -59; p1,2< 0,05). A strong negative correlation of EGF with Е1 and 16-OHE1 (r1= -79, r2= -76; р1,2< 0.05) was registered in uterine myoma. Conclusions: Tissues of synchronous primary breast tumors and uterine myoma had similar correlations between levels of growth factors and sex hormones. Solitary breast tumors and uterine myoma showed correlations typical of the tumor type. Thus, expression of growth factors in multiple primary tumors, but not in solitary ones, is subject to a clearly determined regulatory role of sex steroids and their metabolites.

e17067 Background: Our purpose was to study VEGF-A, VEGF-R1, VEGF-C and FGF21 in the blood serum (BS) and ascitic fluid (AF) in stage I-IV ovarian cancer. Methods: BS in serous cystadenocarcinoma (CAC, n=76) and cystadenoma (CA, n=47) was studied. Histological control was performed in all cases. The data were compared to BS in uterine myoma (UM, n=20) and in 36 healthy donors (N), all women aged 51.5±2.6 years. Native AF was studied in patients with CAC affecting one ovary without treatment (n=26, T3-4N0M0) and ovarian CA (n=12). Levels of VEGF-А, VEGF-R1, VEGF-С and FGF21 were measured by ELISA. Results: Levels of VEGF-A in CA BS exceeded N by 1.8, sVEGF-R1 – by 2, VEGF-C – by 1.7 and FGF21 – by 2.6 times. VEGF-A in T1N0M0 CAC exceeded N and CA by 2.9 and 1.6, in T2N0M0 – by 3.1 and 1.7, in T3NxM0 – by 5.5 and 3, in T4Nx-1M0 – by 5.8 and 3.1 times. sVEGF-R1 was similar in all CAC stages, on average twice higher than N, and similar to CA and UM. Differences were found between VEGF-А in CAC, CA and UM. sVEGF-R1 in all BS exceeded N (Р˂0.05 in all cases). VEGF-С in CA and UM BS exceeded N on average by 1.7 times, and in CAC it was significantly higher than in CA, UM and N. VEGF-С in BS in T1N0M0 was higher than in N and CA by 2.0 and 1.2, in T2N0M0 – by 2.6 and 1.6, in T3NxM0 – by 2.5 and 1.5, in T4Nx-1M0 – by 2.5 and 1.5 times, respectively. Differences in VEGF-С were found only in T1N0M0 and T2N0M0 by 1.3 times (Р˂0.05 in all cases). FGF21 in BS in UM and CA was similar, but differed from N by 2.6 times. FGF21 in all CAC stages exceeded BS and CA by 4 and 1.5 times. VEGF-А in CAC AF exceeded CA by 9.8, sVEGF-R1 – by 3.9; VEGF-C – by 1.6; FGF21 – by 1.7 times. VEGF-А, sVEGF-R1, FGF21 and VEGF-А/sVEGF-R1 in AF in UM and CA were similar to BS, and VEGF-С was lower than in BS by 1.7 times (Р˂0.05 in all cases). VEGF-А and sVEGF-R1 in BS in CAC were higher than in N by 2.9-5.8 and 2 times; in AF – higher than in UM by 9.9 and 4 times. VEGF-С in AF in CAC was lower than in BS on average by 1.6 times (Р˂0.05), and FGF21 did not differed in AF and BS. Conclusions: VEGF in SВ correlates with CAC stages distinguishing early and later ones. VEGF-А is higher than VEGF-C in BS and AF in all tumors. The VEGF family regulates functions of the endothelium of lymphatic and blood vasculature influencing oncogenesis and the occurrence of ascites.

e17018 Background: The purpose of the study was to analyze the effect of HPV/Chlamydia trachomatis co-infection on the hormonal status of tumor and visually unchanged cervical tissues in cervical cancer patients. Methods: We studied levels of estrone (E1), estradiol (E2), free estriol (E3), free (fT) and total (T) testosterone, progesterone (P4) and prolactin (PRL) by the ELISA in tumors and visually unchanged cervical tissues of 49 patients with cervical cancer T1b-2aN0M0 with endophytic (25 patients) and exophytic (24 patients) patterns of tumor growth. 13 patients with endophytic tumors and 12 patients with exophytic ones were infected with HPV and Сhlamydia trachomatis (Ch.tr.). HPV infection was determined by Е7 protein expression, Ch.tr. – by IgG and IgА and antigen/DNA in ELISA and PCR. Intact cervical tissues obtained during hysterectomy from 22 non-infected women with endometrial cancer were used as the control. Results: Tumor tissues of the cervix without infection demonstrated increased levels of all sex steroids: estrogens by 3 times, androgens by 3.1 times and progestins by 1.8 times. Co-infected tissues were characterized by the sex-steroid imbalance. We observed reduced coefficients of estrogens to T and fT by 1.6 and 6 times, respectively, compared to intact tissues (most significant in a tumor with endophytic growth pattern) and an increase in the estrogens to P4 ratio by 1.5 times – only in endophytic growth pattern. Androgenic status in co-infected tumor tissues increased by 1.7 in endophytic and by 3.1 times in exophytic growth pattern. PRL level was increased only in co-infected tumors (by 2.5 times). Unchanged co-infected tissues, unlike non-infected samples, showed E2 increase by 2.6 times in exophytic and by 1.5 times in endophytic growth pattern, T increase by 1.6 times only in endophytic tumors and P4 decrease by 1.5 times and PRL increase by 1.8 times regardless the tumor growth pattern. Conclusions: Hormonal profile of both tumor and unchanged cervical tissues was dependent on HPV/Ch. tr. co-infection and tumor growth patterns. The changes could result from HPV and Ch. tr. interaction triggering malignant processes.

e17030 Background: The kallikrein (KLKs) family is considered to be a regulator of many systems of limited proteolysis but can also be involved into pathology. Plasmin (P) regulates functions and density of the extracellular matrix, angiogenesis, maturation of gametes, sanation of cavities, tissues and body fluids, development of inflammation and malignant tumors. α2-Macroglobulin (α2M) is a molecular component of the body's endogenous protection. Ascitic fluid (AF) in various diseases of the ovaries is the biological environment valuable for the study of the affected organism containing protein about 20-50 g/L. KLKs, their proenzymes (pro-KLKs), Р, plasminogen (PG) and α2М in AF are poorly studied. Our purpose was to analyze the proteinase-inhibitory balance in AF of patients with ovarian cystadenocarcinoma (CAC) and tuberculosis of the uterine appendages (TA) to reveal its role in the development of the diseases and targets for the therapy. Methods: KLKs, pro-KLKs, Р, PG and α2М in AF in CAC of one ovary (n=26, T3-4N0M0) were compared with the levels in AF of TA patients before treatment (n=11). All women were menopausal, aged 56.5±2.6 years. KLKs, pro-KLKs, Р, PG and α2М were determined before treatment using the U-2900 UV Solutions double-beam spectrophotometer (USA), the result was calculated per 1 mg of protein (by Lowry). The protein content in AF was comparable to the blood plasma one, so we took the values in the plasma of healthy donors as the norm (N). The data were processed using the Statistica 10 program. Results: The exudate is believed to occur mainly from inflammation-damaged vessels. High protein content in AF in CAC and TA allowed us to consider AF as the exudates. The pro-KLKs/KLKs ratio reflecting the rates of KLKs formation in AF was decreased in TA and CAC by 4.6 and 6.7 times compared to N. The РG/Р ratio in AF in CAC was decreased by 3.8 times; in TA it was similar to N with increased PG and P. The KLKs/α2М ratio in TA and CAC exceeded N by 4.6 and 2.7 times. The Р/α2М ratio in TA and CAC was 6.5 and 4.5 times higher than N. Conclusions: Activity of KLKs and P in AF in CAC and TA was higher than in the blood plasma of healthy donors. Activity of α2М in AF in CAC and TA was not sufficient to control KLKs and P.

e17126Background: Uterine cancer ranks 6th among the most common cancers affecting women in developed countries. Hyperestrogenia plays a leading role in the pathogenesis of this disease. The purpos...

e17125Background: Changes in apoptosis signaling pathways are now considered to play a significant role in uterine tissue malignization process. Therefore, the purpose of our study was the screenin...

e22244 Background: Higher quantity ofIGF-1R expresses in tumor tissue in breast cancer in comparison with benign tumor or normal breast tissue. At the same time, IGF-1 stimulates proliferation of n...

e18025 Background: Young patients with early stages of gynecological cancers often go through surgical menopause which worsens the quality of life affecting social, sexual, psycho-emotional, cognitive spheres, and causes somatic diseases rare in a young age. The purpose of the study was to evaluate the clinical effectiveness of medical and hormone replacement therapy (HRT) in patients with endothelial (EC) and cervical cancers (CC) of the reproductive age after surgical treatment. Methods: Clinical data and adaptive reactions were studied in 346 patients with stage Ia-IIa EC and CC aged 20-45 years after combination treatment. Patients were divided into 3 groups: group 1 – 192 patients, estrogen/gestagen HRT; group 2 – 112 patients, treatment with phytoestrogens; group 3 – 42 patients choosing not to have any adjuvant therapy. The Kupperman index was used to evaluate the severity of a post-castration syndrome. Results: In group 1, 158 women (82.3%) showed normal somatic and psychoemotional status and adequate cognitive functions, the Kupperman index ≤20; 34 (17.7%) patients of group 1 needed additional sedation, the Kupperman index = 30; adaptive reactions included reactions of training and adaptation. In group 2, 112 patients (100%) demonstrated moderate hormonal imbalance signs: vegetative and emotional disorders, decreased libido, manifestations of the metabolic syndrome, the Kupperman index = 30-35; adaptive reactions included reactions of training and stress. All patients of group 3 (n = 42) developed metabolic disorders shortly after surgical castration, with social, sexual and psycho-emotional disadaptation, the Kupperman index = 35 (reactions of stress). Conclusions: Combination HRT after surgical castration contributes to full adaptation in the social, sexual, psycho-emotional spheres of life in patients of the reproductive age, restoring the quality of life without affecting the prognosis.

e17552 Background: Perioperative (PO) pain management is one of the most important issues in cancer treatment. The purpose of the study was to improve the quality of PO analgesia in cancer patients. Methods: A prospective randomized study of the quality and efficacy of various analgesics included 104 patients aged 34 to 77 years who underwent surgical interventions for ovarian cancer. The patients were divided into 2 groups. Group 1 (n = 49): patient-controlled analgesia with trimeperidine and nonsteroidal anti-inflammatory drugs (NSAIDs); group 2 (n = 55): preemptive analgesia based on a continuous infusion of lidocaine, magnesium sulphate, microdoses of fentanyl (4 µg/h) and NSAIDs. Results and pain syndrome were assessed by the visual analogue scale (VAS), personal and reactive anxiety, levels of glucose, cortisol, insulin, lactate, and the Kerdo index. Results: Analgesic effect of trimeperidine was obtained in 85.7% (p < 0.05). However, the effect was less pronounced, compared to OSMMA, and did not reduce the cognitive component of pain after surgical treatment. In group 2, opioid-sparing analgesic effect was 96.4% (p < 0.05). OSMMA limited the increase of cortisol, glucose, insulin, CRP and lactate (p < 0.05) providing effective PO pain relief. OSMMA did not cause residual sedation, anxiety, depressive effects and cognitive impairments, which showed its advantages over trimeperidine. Therefore, despite the minimal doses of narcotic analgesics in group 2, OSMMA improved the quality of pain relief and the well-being of patients in perioperative period being a significant advantage in minimizing the negative effects of opioids. Conclusions: Lidocaine-based PO analgesia with microdoses of fentanyl can significantly limit endocrine and metabolic changes and improve the quality of pain relief contributing to the early rehabilitation of cancer patients.

e18081 Background: Ovarian cancer spreads intraperitoneally due to the interaction of tumor cells and the omental mesothelium, creating a metastatic niche and supporting elements of cancer cell expansion such as adhesion, proliferation, migration, and neoangiogenesis. The purpose of the study was to analyze levels of VEGFA, IGF-I, IGF-II and TGFβ1 in omental tissues in ovarian cancer (OC). Methods: The main group included 23 patients with metastatic OC T3-4аN0-3M1; the comparison group – 21 patients with non-metastatic OC T3-4аN0-3M0; the control group – 19 non-cancer patients. Levels of VEGFA, IGF-I, IGF-II and TGFβ1 were measured by standard ELISA methods in tissues of primary tumors and the omentum. Results: Levels of growth factors in the comparison group were not elevated compared to control values. Growth factors in omental tissues in the main group were increased compared to control values: VEGFA – by 2.5 times, IGF-I – by 3.4 times, IGF-II – by 2.5 times, TGFβ1 - by 3.1 times. In the comparison group, the levels in omental tissues were lower than in the main group: VEGFA – by 1.7 times (p < 0.05), IGF-I – by 2.1 times, IGF-II – by 1.6 times (p < 0.05); TGFβ1 did not differ from the levels in the main group. Conclusions: Higher expression of VEGFА in the omentum with metastases can be considered a significant factor in the formation of signaling pathways between metastatic tumor cells and local non-cancer cells. IGF-I and IGF-II trigger the endothelial growth factor. The TGFβ1 activation in the omentum in metastatic ovarian cancer is necessary for the paracrine induction and transition of disseminated tumor and/or stem cells from the "sleeping" to the active state.

e17516 Background: Cancer stem cells (CSCs) are being actively studied as a possible origin of malignant neoplasms. Research of the properties of CSCs and mechanisms of their regulation holds the promise of the development of new approaches to antitumor therapy. The most frequently detected CSC markers in different tumors are CD44 and CD133. In this regard, the aim of our study was to identify characteristics of expression of CSC markers in cervical cancer treatment and their possible predictive value. Methods: The study included 237 patients with locally advanced cervical cancer T2a-2bNx-1M0. Patients were divided depending on the treatment: neoadjuvant chemotherapy with cisplatin and bleomycin (NACT, n = 84); plasmapheresis (PA) in combination with NACT (PA+NACT, n = 60); PA+NACT with nonspecific immunotherapy with an interferon inducer (PA+NACT+IT, n = 93). Immunohistochemical study was performed on sections from paraffin blocks of tumors using anti-CD44 monoclonal mouse antibodies (156-3C11, Thermo Scientific) at a dilution of 1:2500 and anti-CD133 polyclonal rabbit antibodies (AF5120, Affinity Biosciences) at a dilution of 1:400 (Thermo autostainer Scientific 480S). Membrane staining and staining intensity were evaluated: 0, 1+ weak, 2+ moderate, 3+ strong staining. Protein expression was defined as positive when staining was detected in ≥10% of all tumor cells with a staining intensity ≥2. Statistical analysis of the results was performed with the STATISTICA 13.0 program (StatSoftInc., USA) using the Mann-Whitney U-test. Results: Tumors with positive CD133 and CD44 expression were observed in all groups of patients. However, only PA+NACT+IT patients had CD133- (57%) and CD44- (43%) tumors. Median expression of CD133: in NACT - 70 [60;80]; PA+NACT - 60 [37;70], PA+NACT+IT - 25 [5;60]. Median expression of CD44: in NACT - 30 [10;40]; PA+NACT - 30 [13;65], PA+NACT+IT - 20 [2; 40]. CD133 expression in PA+NACT+IT patients was significantly lower than in PA+NACT and NACT patients by 2.4 times (*p = 0.009) and 2.8 times (*p = 0.002), respectively. CD44 expression in tumors of patients with PA+NACT+IT was 1.5 times lower (statistically non-significant). Differences in tumors of NACT and PA+NACT patients were not found. Conclusions: The immunohistochemical study revealed a decline in the expression of CSC markers (CD133 and CD44) in tumors of patients who received PA+NAPCT+IT. The results obtained for the CD133 marker show its possible value as a predictive factor in the treatment of cervical cancer.