Study the effect of single nucleotide polymorphism genes TP53 (rs1042522, rs1800371), CDKN2A (rs3731217, rs3088440) and MDM2 (rs2279744) on the risk of development of color- ectal cancer (CRC) in population of Perm Region.

Epstein-Barr virus (EBV) - the etiological agent of a number of human benign and malignant tumors including infectious mononucleosis (IM), Burkitt lymphoma (BL), Hodgkin (HL) and non-Hodgkin (NLH) lymphomas, nasopharyngeal carcinoma (NPC), and many other tumors. Latent membrane protein 1 (LMPl) encoded by the gene of the same name (LMP I) is the main oncoprotein of EBV. LMP1 is a transmembrane protein capable of activating many signaling pathways and transcription factors of the cells, which leads to its transformation. Molecular analysis of LMP1 of various clinical origins identified many variants with different types of amino acid mutations that influence its biological activity. Since the role of LMPl in the development of NPC is still not fully understood, it is important to find out how LMPl samples from patients with EBV-associated form of NPC differ from those of patients with other tumors also located in the oral cavity (OTOC), but not associated with this virus. Unlike most investigations conducted in endemic regions, the present work is intended to compare the genetic structure and the transforming activity of LMPl variants from NPC and OTOC patients has been carried out in a non-endemic region of Russia, where NPC is rarely diagnosed. The obtained data show structural and functional similarities of LMP1 variants in the two groups of patients and, accordingly, a genetic relationship of EBV strains persisting in these patients. Our work suggests that in non-endemic regions any EBV strain with any structure of LMP1 may become the etiologic agent of NPC. However, based on modem concepts, the cancer can occur only if EBV-infected persons have a unique pattern of HLA associated with a high sensitivity to the development of NPC combined with exposure to harmful environmental factors (chemical or physical carcinogens) and lifestyle.

The results of the whole-exome DNA sequencing of eight prostate adenocarcinoma patients are presented. DNA was isolated from the peripheral blood as well as healthy and tumor prostate tissue from each patient. Bioinformatics analysis was conducted and the most significant mutations in prostate cancer patients were revealed. The obtained data could be important for understanding of the molecular mechanisms of prostate cancer pathogenesis and facilitate development of new approaches for treatment of the disease.

The implementation of biochemical laboratory tests in oncology practice increased exponentially during last decades and continues to be in progress nowadays. The application of modern molecular genetic technologies permits using diagnostic systems with greater diagnostic sensitivity and specificity. The new tests are actively implemented permitting to diagnose physical presence of tumor systemic manifestations of malignant neoplasm (cachexia, pyrexia), paraneoplastic syndromes and also to detect tumor markers. The oncomarker permits to differentiate malignant from benign tumor on the basis of quantitative differences in content of corresponding antigene-tumor marker in blood serum independently of localization of tumor nidus. The prostate cancer is a medical social problem of male population. On initial stages, this disease can take its course asymptomatically or with symptomatic conditioned by such concomitant and more prevalent pathologies as chronic prostatitis and prostate benign hyperplasia. The early diagnostic ofprostate cancer permits implementing timely radical treatment frequently contributing to total recovery of patients. The article presents detailed description of evolutionary conception of markers using in diagnostic, staging and prognostication of course of prostate cancer. The acid phosphatase was applied for the first time in early diagnostic of staging of prostate cancer in 1974. Nowadays, in century of "OMX"-technologies, in common clinical practice detection of RNA in urine of patient is used for staging diagnostic and prognostication of progression of process of tissue neotransformation.

The RARa is a transcription factor playing important role in such processes as proliferation, differentiation and apoptosis of cells in norm and in tumor. At the same time, it is little known about significance of expression of two major products of transcription of gene RARa - isoforms RARa and RARa - in pathogenesis of solid and non-solid tumors, including multiple myeloma. The actual data testify ambiguity of input made by isoforms RARa and RARa into processes of tumor development and progression of malignant tumors.

Secondary myeloid neoplasia may be a complication of intensive cytostatic therapy. The most common types of secondary neoplasias are acute myeloid leukemia and myelodysplastic syndrome. The development of secondary atypical chronic myeloid leukemia (aCML) is an extremely rare phenomenon. The paper describes transformation of secondary myelodysplastic syndrome to aCML 6 months after its diagnosis. The development of aCML was accompanied by additional chromosomal aberration as monosomy of chromosome 17. No mutations in the JAK2, MPL, and CalR genes were detected. It is concluded that the clinical course of secondary myeloid neoplasias is variable.

to investigate the methylation status of the SOX7 and p15NK4b genes and Wnt signaling pathway antagonists in patients with acute myeloid leukemia (AML) in order to assess the association of the rate of aberrant methylation (AM) with the morphological variant and pattern of chromosomal aberrations, as well as the impact of the methylation status on survival.

to identify the clinical features of latent polycythemia vera (PV) as an independent nosological entity.

All around the world, more than 330 thousands cases of bladder cancer are registered annually hence representing actual problem of modern oncology. Still in demand are search and characteristic of new molecular markers of bladder cancer detecting in tumor cells from urinary sediment and having high diagnostic accuracy. The studies of last decade, especially using methods of genome-wide sequencing, permitted to receive a large amount of experimental data concerning development and progression of bladder cancer The review presents systematic analysis of publications available in PubMed data base mainly of last five years. The original studies of molecular genetic disorders under bladder cancer and meta-analyzes were considered This approach permitted to detected the most common local alterations of DNA under bladder cancer which can be detected using routine genetic methods indifferent clinical material and present prospective interest for development of test-systems. The molecular genetic markers of disease can be activating missense mutations in 7 and 10 exons of gene of receptor of growth factor of fibroblasts 3 (FGFR3), 9 and 20 exons of gene of Phosphatidylinositol-4,5-bi-phosphate-3-kinase (PIK3CA) and mutation in -124 and -146 nucleotides in promoter of gene of catalytic subunit telomerase (TERT). The development of test-systems on the basis of aberrant methylation of CpG-islets of genes-suppressors still is seemed as a difficult task because of differences in pattern of methylation of different primary tumors at various stages of clonal evolution of bladder cancer though they can be considered as potential markers.

Breast cancer is the most frequent cancer and the leading cause of cancer-related deaths in women worldwide. We determined the expression of COX2, COX1, 15-HPGDH mRNA and miRNAs (miR-21, miR-155) in three estrogen positive human breast cancer cell lines (MCF-7, BT-474, ZR-75-1). According to the results of three independent experiments the amount of COX1 and COX2 mRNA was significantly higher in the ZR-75-1 than in MCF-7 and BT-474 cells. Levels of total 15-HPGDH; functional 15-HPGDH mRNA in BT-474 cell line were lower than in MCF-7 and ZR-75-1 ones. The synthesis of 15-HPGDH enzyme in BT-474 line was blocked at the nuclear immature pre-mRNA processing level. miR-155 expression level was significantly lower than miR-21 in breast cancer cell lines. Correlations between the dysregulation of miR-21, miR-155 and 15-HPGDH, COX-1, COX-2 mRNA were identified. Expression of miR-21 was high in MCF-7, ZR-75-1 and BT-474 cell lines. Our results show that miR-21 and miR-155 regulate activity of several genes in cancer cells, their effect on the individual genes was in some cases cumulative. Based on our results, we concluded that miR-21, miR-155 suppress the work of tumor suppressor gene 15-HPGDH and induce potential oncogene COX-2 that promotes cell malignancy and metastasis of breast cancer.

A biochip-based method was developed to identify the BCR-ABL mutations that affect the thyrosine kinase domain and determine resistance to targeted therapy with thyrosine kinase inhibitors. The method is based on RT-PCR followed by allele-specific hybridization on a biochip with immobilized oligonucleotide probes. The biochip addresses 11 mutations, which are responsible for up to 85% of imatinib resistance cases. A method to decect the clinically significant mutation T315I was designed on the basis of LNA-clamped PCR and proved highly sensitive, detecting the mutation in clinical samples with a leukemic cell content of 5% or higher. The method was validated using clinical samples from chronic myeloid leukemia (CML) patients with acquired resistance to imatinib. The results of hybridization on biochip were verified by Sanger sequencing.

The main objective of anticancer treatment is the elimination of degenerated cells by the induction of programmed cell death. Various chemotherapy drugs and radiation are able to activate cell death mechanisms in tumors. However, unfortunately, monotherapy will always be insufficiently effective because of the variety and virulence of tumors, as well as their ability to develop resistance to drugs. Moreover, monotherapy might constrain many negative side effects. Therefore, the combination of different approaches and/or drugs will increase the efficiency of treatment. One such promising approach is the combination of nutrient restriction (NR) and various chemotherapeutic drugs. This approach may not only affect the autophagy but also influence apoptotic cell death. This review is focused on the potential of NR use in anticancer therapy, as well as the molecular mechanisms underlying this approach.

Cancer, along with cardiovascular disorders, is one of the most important problems of healthcare. Pathologies of the hematopoietic system are the most prevalent in patients under 30 years of age, including acute myeloid leukemia (AML), which is widespread and difficult to treat. The review considers the mechanisms that play a significant role in AML cell malignant transformation and shows the contributions of certain genes to both remission and resistance of AML cells to various treatments.

As previously indicated, side population cells (side population, SP) of breast cancer line MCF-7 have greater resistance to the action of low-LET radiation compared to other tumor cells (non SP, NSP). One can assume that one possible reason for the high radioresistance of this fraction of tumor cells is the increased expression of different heat shock proteins (HSP) before and/or after radiation exposure. To verify this hypothesis, we investigated the expression of HSP27 and HSP70 in these populations of cells-before and after irradiation at a dose of 5.0 Gy. The study was performed using scanning microscopy for NSP and SP cells after sorting and immunocytochemical staining. A substantial increase of HSP27 and HSP70 in SP cells was found after irra- diation as'compared with the control. In NSP cells the HSP27 level increased in response to radiation exposure, but to a lesser extent than in SP cells, while the content of HSP70 did not change after irradiation. The results confirm the assumption about HSP27 and HSP70 participation in the formation of SP cell radioresistance by the example of MCF-7 line.

An association between polymorphic variants of key genes of base excision repair (BER) and lung cancer was studied in "Mayak" workers occupationally exposed to prolonged external y-rays and internal α-radiation from incorporated (239)Pu. The study was "case-control". The group of "cases" consists of 75 "Mayak" workers with the verified diagnosis of "lung cancer". At the moment of diagnosis the mean total absorbed dose from external y-rays to whole body was 1.19 Gy; the mean total absorbed dose from internal α-radiation due to incorporated (239)Pu in lung was 0.31 Gy. The group of "controls" includes "Mayak" workers matched by sex and birth year without lung cancer and other cancers during the study period (141 individuals). Increased lung cancer risk was revealed in workers-carriers of homozygous minor genotype of genes OGG] Ser326Cys (OR - 4.67, p = 0.007), APEI Asp148Glu (OR = 1.82, p = 0.063) and XRCC1 Gln399Arg (OR = 2.86, p = 0.026). Increased lung cancer risk was revealed in carriers of different pairwise combinations of minor genotypes of the studied genes of BER or in carriers of pairwise combinations with one homozygous minor mm-genotype and the other homozygous major ww genotype. Thus, OR of lung cancer in carriers of pairwise genotypes of mm genes OGG] Ser326Cys and APE] Asp 148Glu was 12.17.

In the last years it was shown that autoantibodies to the extracellular regions of the ionotropic receptors, such as glutamate AMPA- and NMDA-receptors, GABAA-receptors, glycine and nicotinic acetylcholine receptors, induce a wide spectrum of autoimmune diseases, including limbic encephalitis, Rasmussen's encephalitis, systemic lupus erythematosus, myasthenia gravis, encephalomyelitis, and stiff-man syndrome. In the review the literature data concerning the autoimmune processes provoking autoantibodies formation to the ionotropic receptors, the epitopes participating in the induction of pathogenic autoantibodies, and the effects of these antibodies on the functions of nervous cells and their role in the development of autoimmune diseases were analyzed and systematized. The possible role of oncology diseases in the generation of autoantibodies to the ionotropic receptors was discussed. Approaches that are currently being developed to inhibit the synthesis of pathogenic autoantibodies and to their neutralization were considered. These approaches may be subsequently used to treat the autoimmune diseases caused by the antibodies to ionotropic receptors.

The review discusses the causes of multiple failures in cancer treatment, which might primarily result from the excessive variability of cancer genomes. They are capable of changing their spatial and temporal architecture during tumor development. The key reasons of irreproducibility of biomedical data and the presumable means for improvement of therapeutic results aiming at targeting the most stable tumor traits are suggested.

To present a clinical case of serrated colon adenocarcinoma. To demonstrate morphological and genetic features of these tumors and to determine their clinical management.

Non-small cell lung cancer (NSCLC) is a main group of lung malignancies. Epigenetic changes are as important as genome structural changes in carcinogenesis. MicroRNA (miRNA) is a class of non-coding single-stranded RNAs that play an important role in the regulation of matrix RNA (mRNA) translation and degradation. MicroRNA expression changes occur in many cancers. According to the field cancerization theory, tumor-adjacent histologically normal tissue takes part in tumor progression by triggering cell transformation. The important clinical implication is that the fields may serve as the basis for a recurrence after surgery. Thus, the aim of our study was to determine the expression levels of miRNAs let-7a, miR-155, and miR-205 in tumor and tumor-adjacent apparently normal tissues to evaluate these changes as potential prognostic markers in NSCLC patients.

On the basis of all possible publications on the theme included in the previously formed base of sources on molecular epidemiology of RET/PTC rearrangements in thyroid papillary carcinoma a pooled analysis ("simple pooling data") on determination of the dose-effect dependences for RET/PTC frequency in radiogenic carcinomas of various irradiated groups was performed. (They are groups subjected to radiotherapeutic exposure, residents near the Chernobyl nuclear power plant (CNPP) and victims of nuclear bombing). The tendency to Pearson linear correlation (r = 0.746; p = 0.148) between the frequency of RET/PTC and the estimated dose on thyroid in the regions affected by the CNPP accident was revealed. But this tendency was recognized to be random owing to abnormally low values of the indicator for the most contaminated Gomel region. The method tentatively called "case-control" showed reliable differences in thyroid dose values for carcinomas with RET/PTC and without those. The versatility of changes was found: the lack of RET/PTC for radiotherapeutic impacts was associated with higher doses, whereas in case of the CNPP accident and for nuclear bombing victims it was the opposite. Probably, in the first case the "cellular cleaning" phenomenon after exposure to very high doses took place. Search of direct Pearson correlations between average/median thyroid doses on groups and RET/PTC frequency in carcinomas of these groups showed a high reliability for the dose-effect dependences- at the continuous dose scale (for RET/PTC in total and RET/PTC1 respectively: r = 0.830; p = 0.002 and r = 0.906; p = 0.0003); while there was no significant correlation received for RET/PTC3. When using the weighting least square regression analysis (proceeding from the number of carcinomas in samples), the specified regularities remained. Attempts to influence the strength of correlation by exception ofthe data of all the samples connected with the accident on the CNPP did not significantly reduce the strength of associations for RET/PTC in total. On the basis of ordinal scale doses (background, "low" (0.1 Gy), "middle" (0.1-1 Gy) and "large" (1-10 Gy) dose) also found was a significant correlation (Spearman) with the dose for the frequency RET/PTC in total (r = 0.736; p = 0.0098), but for certain types of rearrangements the results were reverse to the previous analysis (the effect was significant only for the RET/PTC3: r = 0.731; p = 0.024). The linear dose-response trends of the Cochrane-Armitage-test for the frequency of RET/PTC in total, RET/PTC1 and RET/PTC3 depending on the dose to the thyroid in the ordinal scale were registered (p, respectively: < 0.0001 < 0.0001 and 0.007). Thus; after more than 20 years of the molecular and epidemiological research of RET/PTC in thyroid radiogenic carcinomas the comprehensive evidence of the dose-effect dependence existence indicating a real relationship between the studied parameters and a radiation factor was obtained for the first time.