This review is devoted to modern notions about autoantibodies (AAb) as one of classes of tumor biomarkers. Principles of humoral response by way of autoantibodies to different tumor-associated proteins in the process of malignant tumor progression are considered. During carcinogenesis self-proteins may become overexpressed, mutant, undergo posttranslational modification, localize abnormally, degrade aberrantly, becoming immunogenic and, as a result, be recognized by immune system as allogeneic. Advantages of AAb as biomarkers over its ligands – tumor antigens – are discussed.

The review analyzes literature data and the results of our own research on the role of reactive nitrogen species (NO, NO₂, N₂O₃) in the initiation and progression of tumors. The possibility of modulating the activity of inducible NO synthase by the biologically active components of plant products and their effect on carcinogenesis is analyzed. Possible mechanisms of the ambiguous action of NO and its metabolic products in the mechanisms of carcinogenesis are discussed. The generalization and analysis of these data allowed us to formulate some principles for the use of substances that modulate the activity of inducible NO synthase and affect the formation of NO and its metabolic products in inhibiting carcinogenesis.

The modern concept of therapy for intrahepatic cholangiocarcinoma including surgical treatment, must take into account the achievements of molecular biology and modern staging principles. A detailed understanding of the molecular genetic (genetic and epigenetic) disorders underlying the pathogenesis of cholangiocarcinoma is important, which will improve the results of surgical treatment and expand the possibilities of personalized (targeted) therapy. Based on new data on cholangiocarcinogenesis, molecular profiling of bile duct tumors may be most appropriate for the selection of treatment in cases refractory to standard therapy. Current potential target therapy targets include endothelial growth factor receptors, fibroblast growth factor, MET tyrosine kinase, PI3K/Akt/mTOR signaling pathway and isocitrate dehydrogenase mutation. The review considers the molecular-genetic aspects underlying the pathogenesis and modern principles of staging intrahepatic cholangiocarcinoma.

The expected effect of androgen-deprivation therapy is one of the important criteria when choosing therapy in patients with prostate cancer. No less significant factor is the time of its implementation. The study showed that high expression of androgen receptors (AR) in the tumor tissue against the background of low estrogen receptor α (ERα) expression is characteristic of patients in whom the effect of androgen-deprivation therapy was observed for 12 months. A set of parameters has been identified that makes it possible to predict the duration of response to androgen-deprivation therapy in patients with prostate cancer, which include the patient’s age, testosterone level, prostate specific antigen, expression level of AR, ERα. These data allow us to consider these parameters as additional informative markers, to predict not only the expected effect, but also its duration.

Background. In our work, we investigated the role of ABC transporters and the transcription factor YB-1 protein in the formation of drug resistance to the proteasome inhibitor bortezomib in multiple myeloma.

Materials  and methods. We used the RPMI8226 and NCI-H929  cultures and their bortezomib-resistant sublines as models.

Results. Two major ABC transporter proteins, P-glycoprotein and MRP1, are not involved in the emergence of resistance to bortezomib, moreover, bortezomib contributed to decrease of these genes expression. Expression of the MVP gene was increased only in the resistant RPMI8226/btz-6 variant, but not in H929/btz-6. The localization of the YB-1 protein, a transcription factor for the MDR1, MRP1 and MVP genes, changed only in RPMI8226/btz-6 cells, as well, it became diffuse in 20 % of the cells as compared to 7 % of the cells in the RPMI8226 parent line. The only ABC transporter gene, activated in both RPMI8226/btz-6 and H929/btz-6 sublines, was BCRP. Сross-resistance to doxorubicin is also shown for these sublines.

Conclusion. Thus, the activation of ABC transporters is not a key mechanism for the formation of bortezomib drug resistance. MVP protein may play certain role, and an increase in the BCRP expression explains the emergence of resistance to doxorubicin, but not to bortezomib, since the latter is not a substrate of BCRP.

Background. Worldwide, more than 300,000 women are diagnosed with uterine cancer each year. Currently, the problem of finding highly specific molecular tumor markers for this disease remains relevant. Screening for gene expression of transcription factors responsible for controlling the differentiation of cells of endometrial tissues may allow the formation of a tumor markers panel and explore the fundamental mechanisms of oncotransformation.

Objective of our study was to analyze changes in the expression of transcription factors OCT4, SOX2 and C-MYC in the tissues of the uterus (corpus uteri) during the process of their malignancy.

Materials  and methods. Uterus tissue biopsy specimens of 45 patients (tumor and non-tumor) were used for the study. To determine the relative expression of 3 genetic loci encoding the transcription factors OCT4, SOX2 and C-MYC the real-time polymerase chain reaction method, ACTB was used as the reference gene.

Results. A change of OCT4, SOX2 and C-MYC genes transcriptional activity in uterus tumor cells is found as the tumor develops. By reducing the tumor cells differentiation degree expression of OCT4 gene increases most significantly, that confirmsits status of undifferentiated cellsmarker. As the differentiation degree of tumor cells decreases, OCT4, SOX2 and C-MYC genes expression change affects the adjacent conditionally normal tissue of the uterus, but with less intensity, especially in the later stages of malignancy.

Conclusion. The obtained data makes it possible to use the OCT4, SOX2 and C-MYC genes as differential markers of the tumor process development, and the SOX2 gene expression as a predictive marker of malignancy.

Background. 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 (GSC). Molecular mechanisms of these cell interaction with extracellular matrix (ECM) are practically not studied. At present, it is also not clear the signaling of the ECM-receptor interaction (ECM-RI) differs for GSC and differentiated glioma cells (GDC).

Objective: using high-resolution proteomic mass spectrometry to study the determinant expression of the ECM-receptor interaction signaling cascade in CD133⁺ GSC and CD133^–    GDC.

Results. 1990 proteins are identified, 18 of which are associated with the ECM-RI process. Positive regulation of 14 ECM-RI proteins was found in CD133⁺ GSC compared with CD133^–    GDC, ten had more than 2 times increased expression. Increase in the CD133⁺ GSC level of 4 proteins activating the ECM-RI signaling cascade was noted.

Conclusion. Important regularities are determined that could be used for the development of new approaches for detection of potential therapy targets of glioblastoma multiforme.