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

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

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

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

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

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

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

The 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.

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