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Introduction. Treatment of glioblastoma multiforme remains little effective due to the rapidly developing recurrence of the tumor, due to its high tumorigenic potential, resistance to chemoradiation therapy and increased dissemination of glioma stem cells. The identification of potential therapeutic targets, which make it possible to more effectively destroy glioma stem cells, becomes topical. In this regard, the study of ferroptosis (FP), which can cause the death of tumor cells with a highly malignant phenotype, is of great importance. However, FP and its regulatory pathways in the GSC are not fully understood. At present, it is also not clear how FP differs for glioma stem cells and glioblastoma differentiated cells.Aim. To study the expression of ferroptosis signaling cascade determinants in CD133+ glioma stem cells and CD133- glioblastoma differentiated cells using high resolution proteomic mass spectrometry.Materials and methods. High-resolution proteomic mass spectrometry, cell technologies.Results. In total, 1970 proteins were identified, 15 of which are associated with ferroptosis and are present in both cell populations. Upregulation of 12 FP determinants (ACSL1, ACSL3, COPZ1, FTH1, FTL, GPX1, GPX4, PCBP1, SLC3A2, TFRC, VDAC1, VDAC2) was found in CD133+ glioblastoma stem cells compared to CD133- differential glioblastoma cells, 10 of which were more than 2-fold overexpressed.Conclusion. Important regularities have been established in the expression of ferroptosis determinants and proteins controlling this process in glioma stem cells, which can be used in the development of new approaches to the detection of potential targets for the therapy of glioblastoma multiforme.

Background. Multiple myeloma (MM) is a hematologic malignancy of plasma cells. The microenvironment plays a key role in MM cell survival and drug resistance through release of soluble factors, expression of adhesion molecules and release of exosomes (EXs). The role that EXs, released by MM cells have in cell-to-cell communication and signaling in the bone marrow is currently unknown. EXs as a source of markers for MM diagnostics are also not studied.Objective: to use proteomic profiling of EXs as a tool to identify circulating tumor associated markers in MM patients.Results. The proteome composition of EXs obtained from plasma of patients with MM and multiple sclerosis was studied for the first time. nano-HPLC–MS/MS analysis identified a total of 332 proteins in the EXs of both groups of patients and determined the proximity of their qualitative composition. For the first time, 12 differentially expressed proteins were detected, the levels of which were significantly increased in EXs from patients with MM. This allowed us to consider them as potential markers of the disease.Conclusion. Proteomic analysis of EXs obtained from plasma of patients with MM is an important method for finding disease markers.

Background. The transforming growth factor beta 1 (TGF-β1) is one of the most important tissue factors secreted by the development of epithelial tumors. Increased expression of TGF-β1 in lung tumors promotes cancer cells survival enhancing their growth, migration, invasion, angiogenesis, immune system suppression.Objective: to study molecular mechanisms of TGF-β1 action on A549 human lung adenocarcinoma cells by means of proteomic high-resolution mass spectrometry. Results. Intracellular signaling pathways responsible for the involvement of TGF-β1 in the oncogenesis of non-small cell lung cancer have been found, which include the differential expressed proteins of the families of cullin, ETS oncogenes, histone diacelases, cyclin-dependent kinases, and the signaling pathway phosphatidylinositol 3-kinase (PI3K).Conclusions. Important patterns are determined that could be used for the development of new approaches for detection of lung cancer metastasis candidate markers and potential therapy targets of this decease.

Background. Increased expression of transforming growth factor beta-1 (TGF-β1) in malignant brain tumors promotes cancer cells survival enhancing their growth, migration, invasion, angiogenesis, immune system suppression.Objective is to study molecular mechanisms of TGF-β1 action on U87 human glioblastoma cells by means of proteomic high-resolution massspectrometry.Results. We have identified intracell signal pathways responsible for TGF-β1 involvement in malignant gliomas oncogenesis including differential expressed proteins of tight cell junctions, focal adhesion, histone deacetylases, heat shock, S100 family.Conclusions. Important patterns are determined that could be used for the development of new approaches for detection of glioblastoma metastasis candidate markers and potential therapy targets of this decease.

Glioblastoma multiforme, a World Health Organization grade IV malignant glioma, is the most common and lethal primary brain tumor with the median survival of approximately 15–25 months after treatment. Glioblastoma multiforme has been shown to be resistant to radiotherapy and chemotherapy and invariably recurs following surgical resection and chemoradiation. The characteristics of this tumor are exemplified by heterogeneous cell population with diverse biologic properties and genetic changes, the ability to form cancer stem cells (CSC) and divided into four molecular subtypes – proneural, neural, classical and mesenchymal. Despite some success, the mechanisms leading to the formation of the most malignant tumor subtype are unclear. The aim of this review was a synthesis of modern information about the role and biological characteristics of tumor stem cells in tumor progression and the pathogenesis of glioblastoma multiforme. CSCs reside in niches, which are anatomically distinct regions within the tumor microenvironment. These niches maintain the principle properties of CSCs, preserve their phenotypic plasticity, adhesion, survival, resistance to standard cancer treatment and metastatic potential. The presence of aberrant signaling pathways (Notch, Hedgehog-Gli, Wnt/β-catenin, TGF-β/SMAD, PI3K/Akt/mTOR), both in the tumor and in the population of CSC, the dysregulation of microRNAs (miR-21, miR-128, miR-326, miR-34a), influence of epithelial-to-mesenchymal transition explains the availability of typical biological characteristics of the CSC. One needs to consider the influence of the therapy on normal stem cells in the development of drugs directed against the CSC. Regulatory mechanisms and markers found over the last decade can be used as the basis for creation of the new drugs with targeted action in the treatment of glioblastoma multiforme.

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.

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.

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.

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.

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.

В результате многочисленных клинических наблюдений установлено, что инфекции грибково-бактериальной природы являются одним из наиболее часто встречающихся осложнений после иммуносупрессивной полихимиотерапии (ПХТ) у онкогематологических больных на фоне нейтропении. В клинической онкологии широко используется рекомбинантный человеческий гранулоцитарный колониестимулирующий фактор ( рчГ- КСФ - нейпоген, граноцит ) с целью лечения нейтропении . Способность рчГ- КСФ стимулировать пролиферацию , дифференцировку и активность НЛ вызывает интерес к его потенциальному применению при лечении инфекционных осложнений. Тем не менее недостаточно ясна роль рчГ- КСФ в биохимических механизмах изменения кислородзависимой антикандидозной и антимикробной активности НЛ онкогематологических больных. Целью настоящей работы явилось изучение действия рчГ - КСФ -терапии на НАДФН - и миелопероксидазозависимое образование АФК НЛ онкогематологических больных со смешанной грибково-бактериальной инфекцией . Суммируя полученные данные , необходимо отметить , что комплексная терапия (антигрибковая , антибактериальная и рчГ - КСФ ) приводила к нормализаци и показателей генераци и АФК покоящимися НЛ и стимулировал а МПО -зависимую антикандидозную и антимикробную активность НЛ. Таким образом, применение рчГ- КСФ в комплексной терапии больных с инфекцией грибково-бактериальной природы является целесообразным.

Онкологические больные подвержены высокому риску развития грибковых инфекций . Важнейшим фактором риска возникновения инвазивного кандидоза является продолжительная нейтропения, индуцированная цитостатиками. В этой связи особое внимание уделяется гранулоцитарному колониестимулирующему фактору (Г-КСФ), который стимулирует пролиферацию и дифференциацию нейтрофилов и усиливает их функциональную активность. Тем не менее, не достаточно изучено влияние Г-КСФ на антикандидозну ю активность нейтрофилов у онкологических больных.Цель исследования - Оценить влияние Г-КСФ на изменение кислородзависимой антикандидозной активности нейтрофилов у онкологических больных после цитостатической терапии.