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Introduction. To a large extent, the resistance of glioblastoma multiforme to genotoxic therapy is associated with a dysregulation of responses to DNA damage and repair. Thus, suppression of DNA repair mechanisms is a priority pathway for increasing the survival rate of glioblastoma multiforme patients. Curcumin enhances the effectiveness of standard chemotherapy drugs, but its effect on DNA repair systems is not well understood.The study objective – to study the molecular mechanisms of curcumin action on excisional DNA repair in U251 glioblastoma multiforme cells.Materials and methods. high-resolution proteomic mass spectrometry, cell technologies.Results. In the proteomes of two types of glioblastoma multiforme cells (control and experiment), a total of 2757 proteins were identified, of which 39 % were differentially expressed. Significant changes have been found in many signaling cascades that play an important role in carcinogenesis.Conclusion. Curcumin suppressed excisional DNA repair by decreasing the expression of determinants APEX1, MSH6, PARP1. PCNA, POLD1, POLE3, RFC2, RPA.

Background. Glioblastoma multiforme (GBM) develops in the hypoxic microenvironment, which plays an important role in the pathogenesis of the disease and is closely associated with tumor growth, development and poor prognosis. Hypoxia increases the resistance of tumor cells (TC) to radiation therapy and chemotherapy, promotes the appearance of an aggressive TC phenotype, leading to the disease recurrence. The molecular mechanism of hypoxic action on the secretome of GBM cells, which is involved in the formation of the tumor microenvironment, remains unclear. Also, markers of the aggressive hypoxia-associated phenotype of tumor cells have not been established. The purpose of research – to study the molecular mechanisms of the hypoxia-associated effect on the secretome of the U251 GBM cells.Materials and method. High resolution proteomic mass spectrometry, cell technologies.Results. A total of 1432 proteins were identified in the secretomes of two types of GBM cells (control and experiment). After the action of hypoxia, statistically significant changes in the expression of 390 proteins were registered. 11 proteins showed increase in expression over two orders of magnitude. The intracellular signaling pathways which are responsible for the hypoxia-associated effects on the U251 GMB cells have been identified.Conclusions. Hypoxia significantly affected the proteomic composition of the GBM cells secretome. Five overexpressed secretome proteins, S100A6, HEY1, ZIP3, S100A4, ZEB2, have been proposed as potential markers of the hypoxiaassociated phenotype of GBM, for which participation in the pathogenesis of glioblastoma multiforme has been previously showed.

Glioblastoma multiforme (GBM), a grade IV astrocytoma, is the most common and deadly type of primary malignant brain tumor, with a patien’s median survival rate ranging from 12 to 15 months. Over the last fifteen years, the treatment for GBM has included maximal safe surgical resection with combination radiotherapy and adjuvant temozolomide chemotherapy. The low efficacy of mentioned therapies has forced researchers to explore an appropriate alternative or complementary treatment for GBM. It has been shown that curcumin has therapeutic potentials to fight against GBM via affecting on cell proliferation, apoptosis, cell cycle, invasion and angiogenesis pathways. In addition, curcumin possess a synergistic impact with chemotherapeutic agents. Herein, we summarized the current findings on curcumin as potential therapeutic agent in the treatment of GBM.

Breast cancer (ВС) is the most common form of cancer, leading to high mortality rates among women worldwide. Metastasis is the main cause of fatal outcomes in ВС. In this regard, of particular interest takes the study of molecular mechanisms of epithelial-mesenchymal transition (EMT). In the EMT processes involved in TGF-β1/SMAD-signaling pathway through the regulation of which can affect the processes of metastasis in ВС. In this study we have analyzed changes of mRNA expression of the mRNA SMADs, miR-21, and miR-155 of the tumor ВС cells with different metastatic potential MCF-7, BT-474, ZR-75-1. High expression of miR-21 was detected in all the tumor cell lines (MCF-7, ZR-75-1 and BT-474). In the ВС cell lines, the expression level of miR-155 was significantly lower than that of miR-21. Analysis of mRNA expression has clearly shown impairments of intracellular mechanisms of regulation of SMAD2, SMAD4, SMAD7 in ВС. Investigated the correlation of expression of miR-21 and miR-155 regulation of SMADs in TGF-β1/SMAD signaling pathway in three carcinomas lines of the human breast with different metastatic potential (MCF-7, ZR-75-1, BT-474). A significant inverse correlation was observed between SMAD4 and miR-155 in MCF-7 cells. Inverse correlation between the expression of SMAD2, SMAD4, SMAD7 and miR-155; miR21 was found in the BT-474 cells. The results obtained in this study showed that miR-21 and miR-155 regulate activity of several genes SMAD2, SMAD4, SMAD7 in the tumor cell ZR-75-1 and on some genes they exhibited a cumulative effect. It should be noted that the miR-155 and miR-21 in various degrees influenced the expression of SMAD2, SMAD4, SMAD7, blocking the work of these genes and, thereby exacerbating the progression and degree of malignancy of ВС cells human; in some cases their effects on individual genes were cumulative.

Breast malignancies hold the lead in the pattern of cancers among women worldwide. Currently used methods for the instrumental diagnosis of breast cancer (BC) and their related diagnostic procedures are not sophisticated. The common constraint of instrumental techniques is the ambiguity of resultы interpretation that is associated with a diversity of individual characteristics of the structure and morphology of the breast. There is a need to search for novel diagnostic methods and oncomarkers, which are highly specific, highly sensitive, and inexpensive and able to reveal early stages in tumor development. In our opinion, a search for BC biomarkers is a promising and relevant area in oncology. Mass spectrometric methods are used to detect and identify proteomic markers in blood, biological fluids, tumor tissue, lysates, and secretomes of cancer cell lines. State-of-the-art high tech proteomics and mass spectrometric studies are oriented to the analysis of biological fluids and blood in order to identify new biomarkers. It is really that a blood test does not require any material obtained directly from tumor tissue and hence it is independent of the site of a tumor, implies the early detection of primary tumors or secondary foci, and is required by a medical oncologist in current clinical practice. The given review deals with the analysis of current methods to diagnose BC and to evaluate the efficiency of its therapy, by applying proteomic markers and the latest advances in clinical oncoproteomics.

At present, there is no screening test for the early detecting of ovarian cancer, one of the most lethal form of gynaecological malignancy in the worldwide. In this study the new methodology for the search of tumor markers of ovarian cancer, involving profiling the low-molecular blood plasma proteomes, is developed, unified and approved. The given approach included three basic components: pre-preparation of samples, matrix-assisted laser desorption / ionization time-of-flight mass spectrometry and bioinformatics software for mass spectral data processing. Opportunities and prospects of the developed approach for the detection of potential ovarian cancer markers were shown. For search of potential tumor markers, screening of 56 blood plasma samples from ovarian cancer patients and 36 benign ovarian neoplasia samples were carried out.As a result of the present research, peptides / polypeptides which can be used in future for detecting this pathology were found out.

Identification of markers that will identify the disease at an early preclinical stage, is the main goal of our research. Diagnostic marker should have the following characteristics: high sensitivity and specificity, be readily accessible for the analysis of tissues and body fluids, and above all, be determined in blood plasma. Early detection of breast cancer markers in the blood – a promising trend in science, however, is technically challenging because of the heterogeneity of the disease and the variability of blood plasma proteins. Our review is devoted to theoretical assumptions and practical results of the search of new proteomic markers of breast cancer.

Purpose. To reveal prognostic factors of PSA-failure following radical prostatectomy in patients with localized and locally-advanced prostate cancer.Materials and methods. Medical data of 386 consecutive patients with localized and locally-advanced prostate cancer who underwent radical prostatectomy from 1997 to 2011 were analyzed. Median age was 61.0 years. Median PSA before surgery – 10.3 ng/ml. Plasma levels of VEGF, VEGFR2, VEGFR3, TGF-β1, CD105, IL-6 were measured using Enzyme Linked-Immuno-Sorbent Assay (ELISA) before radical prostatectomy in 77 patients. Postoperatively the tumours were categorized as pT2 in 288 (59.1 %), pT3 – in 144 (37.3 %), pT4 – in 14 (3.6); pN+ – in 34 (8.8 %) cases. Gleason score < 7 was present in 254 (65.8 %),  7 – in 132 (34.2 %) specimens. Perineural invasion was identified in 188 (48.7 %), angiolymphatic invasion – in 126 (32.6) cases.Results. Biochemical recurrence occurred in 64 (16.6 %) out of 386 patients at a median follow-up of 30.5 (12−164) months. Independent predictors of biochemical recurrence were PSA (HR 0.161 (95% CI:0.058−0.449); р = 0.001), Gleason sum in surgical specimens (HR 0.496 (95 % CI:0.268−0.917); p = 0.025), pN (HR 0.415 (95 % CI:0.181−0.955); p = 0.039). The patients were divided into 3 prognostic groups: good (0 factor), intermediate (1 factor), poor (2 factors) and very poor (3 factors) (AUC – 0.720 (95% CI: 0.656−0.784)). High preoperative levels VEGF ( 67 pg/ml) (р = 0.005), VEGFR2 ( 3149 pg/ml) (р = 0.036), VEGFR3 ( 2268 pg/ml) (р = 0.001), TGF-β1 ( 14473 pg/ml) (р = 0.052) were identified as unfavorable prognostic factors for survival without PSA-failure. Conclusion. Independent prognostic factors of biochemical recurrence after prostatectomy were PSA, Gleason sum and pN. Joint effect of the factors allows to predict PSA-relapse with accuracy 0.720. Preoperative serum levels VEGF, VEGFR2, VEGFR3, TGF-β1 potentially are perspective markers for PSA-failure after surgical treatment prostate cancer, further trials are needed.

Plasma proteome from patients with renal cell carcinoma (RCC) and controls underwent mass spectrometric mapping. A total of 247 proteins were identified; the expression of 12 proteins of them increased on transition from the controls to patients with Stages I–II and III–IV RCC. There was decreased expression of 14 proteins in this series. Out of the 26 proteins showing a change in their expressions, 7 proteins belong to acute-phase ones, 3 proteins are associated with the intercellular matrix. These proteins can be potential markers for RCC.

The proteome of ascites and pleural fluids (AF and PF) was mapped in patients with ovarian cancer (OC). 240 and 190 proteins were identi- fied with a high degree of assurance in A F and PF, respectively . The major portion w as extracellular and membrane proteins, whi ch ac- counted for 45 and 49 % in AF and PF, respectively. Analysis of the proteomic maps of AF and PF indicated that 82 proteins were common to these biological fluids whereas 81 and 49 proteins were unique to A F and PF, respectively. A list of 46 potential markers for O C metastasis and potential markers for tropic OC metastasis over the peritoneal (17 proteins) and pleural (11 proteins) surfaces is given.

At present, there is no screening test for the early detecting and monitoring of ovarian cancer, one of the most lethal form of gynaecological malig- nancy in the worldwide. In this study, the new methodology for the search of tumor markers of ovarian cancer, involving profiling the low-molec- ular blood plasma proteomes, is developed, unified and approved. The given approach included three basic components: pre-preparation of samples, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and bioinformatics software for mass spectral data process- ing. Opportunities and prospects of the developed approach for the detection of potential ovarian cancer markers were shown. For search of po- tential tumor markers, screening of 40 blood plasma samples from ovarian cancer patients and 48 control samples were carried out. As a result of the present research, peptides/polypeptides which can be used in future for detecting this pathology were found out.

This paper analyzes 15-PGDH gene expression in the human breast cancer (BC) cell liness and describes the molecular principles through which the expression of the enzyme 15-PGDH is controlled in the tumor cells with a varying metastatic potential. There is an inverse correla- tion of 15-PGDH gene expression with COX-2 expression and the metastatic potential of tumor cells. Investigation of mechanisms for 15-PGDH regulation opens up new vistas and possibilities for the design of effective drugs for the targeted therapy of metastatic forms of BC.

The expression of the SMAD2, SMAD4, SMAD7, and СOX-2 genes and the levels of Smad4, phosphorylated Smad2, and Smad7 proteins were analyzed in the human breast cancer (BC) cell lines MCF-7, BT-474, and ZR-75-1. The SMAD2 and SMAD4 genes were found to suppress COX-2 gene expression in the estrogen receptor-positive BC cells and to be linked to their metastatic potential. Smad4 and Smad2 apparently suppress COX-2 mRNA and protein synthesis and Smad7 is their antagonist and stimulates COX-2 formation. Smad2, Smad4, Smad7 proteins may be regarded as new potential targets for targeted BC therapy.

Proteomics has recently found wide application to account for the molecular mechanisms of cancer and to search for biomarkers that may be used to diagnose and/or predict the development of the disease. The paper briefly reviews proteomic studies to detect ovarian cancer biomarkers, by taking into account different types of biological samples.

The expression of СOX-2, VEGF, VEGFR-1, VEGFR-2, VEGFR-3, EGFR, endoglin (СD105), and IL-6 was analyzed in the human breast tumor cells having a varying metastatic potential. The role of these factors in the regulation of the metastatic potential of breast cancer cells, as well as that of COX-2 in the regulation of metastatic processes at the cellular level were examined. The potential capacity of human breast tumor cells to elaborate factors that stimulate tumor growth, angiogenesis, and metastasis was evaluated.

Currently, basic research in oncology focused on finding new potential markers of metastatic activity of tumor cells and rational approaches to cancer therapy. Constant search for biomarkers of endometrial cancer with high sensitivity and specificity, is a promising direction in medicine. Identification of new markers will identify the disease at an early stage and start early treatment.

The proteome of lysates of the breast tumor cell lines MCF-7, BT-474, and ZR-75-1 was mapped, resulting in the sequence of 340 proteins. The proteins associated with the biosynthesis of PGE2 and with the regulation of cyclooxygenase-2 expression were identified and their relative expression levels were determined. Potential goals for the targeted therapy of breast cancer, such as prostaglandin E2 and D2 receptors, pros- taglandin E synthase, 15-hydroxyprostaglandin dehydrogenase and leukotriene-A4 -hydrolase, are of special interest in this group.

The review covers the state-of-the-art of proteomic studies to seek and identify potential markers for kidney cancer. It considers the markers found in biological fluids and tumor tissues and those detected using the models of cultured kidney cancer cells.

In the cell there is a large class of regulatory molecules referred to as microRNA. Many investigators regard microRNA Mir and Mir-155 as new potential prognostic markers and targets for goal-oriented therapy for breast cancer (BC) these days. MiR-21 and MiR-155 have been found to regulate the metastatic potential of tumor cells and to be differentially expressed in the BC cells. Our review deals with the theoretical prerequisites for and practical results of studying MiR-21 and MiR-155 as potential molecular markers for BC.

Mass spectrometric mapping of proteomic lysate of a MCF-7 cancer cell line was carried out, which identified 153 proteins having molecular weights of 5000 to 630000 Da, a high proportion of which was cytoplasmic and nuclear proteins. The latter accounted for 60 % of their total number whereas the proportion of extracellular and membrane proteins constituted 13 %. After using some selection criteria to analyze the findings, the authors present a list of 31 potential biomarkers and describe 12 promising breast anticancer therapeutic targets.

Current therapeutic approaches based on a study of the genetic portrait of a tumor individualize treatment policy to a greater extent, which cre- ates real prospects for the increasing number of patients to recover. Experimental and clinical evidence suggest that the increased expression of the COX-2 gene increases the risk for breast cancer (BC) cell dissemination into distant organs. A number of recent studies have revealed that selec- tive COX-2 inhibitors are able to suppress proliferation, to induce apoptosis in the BC cells, and to inhibit tumor neoangiogenesis. However, this area contains many unclear and disputable problems to be still experimentally solved. Our review deals with the theoretical prerequisites for and the analysis of a role of COX-2 in BC cell dissemination.

Objective: to study the prognostic value of alterations in the VHL gene and the plasma markers hVEGF, hVEGFR2, and hVEGFR3 in patients with metastatic kidney cancer (KC) who receive targeted therapy.Subjects and methods. Paraffin blocks from 22 patients with metastatic KC who received targeted therapy were analyzed for VHL gene mutation/methylation. Polymerase chain reaction (PCR) products were sequenced using a BigDye® Terminator v 3.1, a Cycle Sequencing Kit, and an ABI3100 genetic analyzer in accordance with the Applied Biosystems protocols. VHL gene methylation was determined by methyl-sensitive PCR. The markers hVEGF, hVEGFR2, and hVEGFR3 were measured in the plasma of 43 patients before, during, and after targeted therapy, by applying the commercial DuoSet® ELISA kits (RnDSystems, USA). The results obtained were analyzed by known statistical methods, by using the package of statistical programs SPSS 13.0 for Windows. Survival was estimated by the Kaplan-Meier method. Survival differences were found by the log-rank test in the patient groups. Cox uni- and multi-factorial regression analyses were used to identify factors that were prognostically significant for survival.Results. Out of 22 patients, 10 (45.5 %) and 1 (4.5 %) were found to have VHL gene mutations or methylation, respectively. VHL gene inactivation did not affect prognosis in patients and the results of antiangiogenic therapy. Correlation analysis revealed no relationship between the concentrations of hVEGF and hVEGFR2 before and during therapy or absolute increases in hVEGF and hVEGFR2 concentrations during treatment with the frequency of progression during targeted therapy, with progression-free survival, and total life expectancy. No correlation was either found between the hVEGFR3 concentration and its changes and the results of antiangiogenic therapy. There was an inverse correlation between the pretreatment plasma hVEGFR3 level and lifetime without progression during antiangiogenic therapy (r = – 0.477, p = 0.039).Conclusion. VHL gene alterations and plasma hVEGF and hVEGFR2 levels are not predictors of a response to antiangiogenic therapy. The pretreatment plasma hVEGFR3 level correlates with progression-free survival in KC patients receiving targeted therapy.