Altered interactions between the extracellular matrix and cells play an important part in tumorigenesis and metastasis. As a member of matricellular glycoprotein, fibulin-5 is expressed in elastin-rich tissues and organizes the matrix structures by interacting with many extracellular proteins. Fibulin-5 expression is closely associated with normal embryonic development and organogenesis. Mice deficient for the fibulin-5 gene exhibit systemic elastic fiber defects with manifestation of loose skin, emphysematous lung and tortuous vessels. Additionally, fibulin-5 null mice exhibited increased angiogenesis after wound healing or PVA sponge implantation and matrigel implantation experiments show fibulin-5 inhibited vessel formation, suggesting fibulin-5 functions as an angiogenesis inhibitor. Fibulin-5 also plays critical roles in proliferation, migration and invasion of certain tumors, and the effect of fibulin-5 on tumorigenesis appears to be largely context-dependent. This effect might involve the inhibiting action of fibulin-5 on angiogenesis. This review focuses on recent advances in our understanding of the roles of fibulin-5 in tumorigenesis: both tumor promoting and suppressing activity of fibulin-5 are reviewed, and the emerging evidences of its promising potential as therapeutic options and/or targets in the treatment of cancer also highlighted.

To estimate the validity of the signs of metaplastic atrophic gastritis to elaborate a marker principle of its detection.

To determine the HER2 status of gastric adenocarcinomas, by using biopsy and intraoperative specimens.

Adenocarcinoma (ADC) and squamous cell carcinomas (SCC) are two subtypes of non-small cell lung carcinomas which are regarded as the leading cause of cancer-related malignancy worldwide. The aim of this study is to detect the differentially methylated loci (DMLs) and differentially methylated genes (DMGs) of these two tumor sets, and then to illustrate the different expression level of specific methylated genes. Using TCGA database and Illumina HumanMethylation 27 arrays, we first screened the DMGs and DMLs in tumor samples. Then, we explored the BiologicalProcess terms of hypermethylated and hypomethylated genes using Functional Gene Ontology (GO) catalogues. Hypermethylation intensively occurred in CpG-island, whereas hypomethylation was located in non-CpG-island. Most SCC and ADC hypermethylated genes involved GO function of DNA dependenit regulation of transcription, and hypomethylated genes mainly 'enriched in the term of immune responses. Additionally, the expression level of specific differentially methylated genesis distinctbetween ADC and SCC. It is concluded that ADC and SCC have different methylated status that might play an important role in carcinogenesis.

Association of rs1042522, rs17878362 and rs1625895 markers with non-Hodgkin's lymphoma risk is not well studied. Large number of non-Hodgkin's lymphoma entities, as well as a small effect of each of the polymorphisms on the lymphomas risk, leads to the analyses of these markers in each of histological subtypes of lymphoma and to study the polymorphisms in the haplotype groups. The goal of this work was to analyze the frequency, haplotypes and linkage disequilibrium of rs1042522, rs1625895 and rs17878362 in the patients with diffuse large B-cell lymphoma and in control group. The differences in the structure of LD between rs17878362, rs1042522 and rs1625895 TP53 gene in the population of the Siberian region were shown. Haplotype approach wasmore informative in the analyses of association of the gene TP53 polymorphisms and the diffuse large B-cell lymphomas risk in case-control study than the study of each polymorphism. The association of haplotype wArgG with diffuse large B-cell lymphoma risk, and the protective effect of haplotypes wProG or dupProG were identified. The difference in the effects of the haplotype TP53 was noted depending on the homozygous or heterozygous diplotype.

The purpose of the study was to determine the role of TP53 tumor suppressor gene polymorphisms in the occurrence of skin malignant neoplasms in glass fiber manufacturing workers. We carried out a comparative study of polymorphous loci Arg72Pro and dup16bp in TP53 gene in workers with skin cancer and hyperkeratosis (n = 68), occupied in continuous glass fiber manufacture, and in healthy workers (n = 52). The associations of both Pro and dup16 minor alleles of TP53 gene, and Arg/Pro-W/dup16 genotype combination with higher risks for skin oncologic diseases of occupational genesis have been revealed.

Currently, there is accumulated mass of data on the molecular-genetic disorders in prostate cancer (PCa), bladder cancer (BC) and renal cancer (RC). Tumor cells in these diseases are present in the urine sediment; their number is sufficient for molecular genetic analysis that makes possible the development of noninvasive diagnosis of oncourological diseases. A characteristic feature of PCa includes the overexpression of the PCA3 gene; assay kit Progensa™ to quantify such overexpression has been developed; approximately 50% of tumors express a TMPRSS2-ERG chimeric oncogene. Combined analysis of PCA3 and TMPRSS2-ERG allows to detect PCa with a diagnostic accuracy of 84%, which is significantly higher than that of prostate specific antigen test. As a potential markers of BC, there are somatic mutations in FGFR3, PIK3CA, TERT genes in urine sediment, which are found in this disease with a frequency of about 60, 30 and 50%, respectively. The basis of the test system for DNA diagnosis of BC in urine sediment may include a definition of a combination of mutations in these genes with microsatellite instability. Aberrant methylation of the 5'-regulatory regions of tumor suppressor genes, integrated in the panel, also is considered as a tool in the diagnosis of RC (VHL, RASSF1, RARB2, CDH1), PCa (GSTP1, PTGS2, LGALS3) and BC (RASSF1, APC, SFRP2) after standardization of panels of loci investigated, sample preparation methods, bisulfite conversion, and the design of primers and probes. Thus, a test systems for molecular genetic diagnosis of oncourological diseases in urine sediment are currently available or may be developed in the near future.

The epidemiological study in Vladivostok and Primorye Territory in period 1999 to 2013 was performed. In the structure of cancer incidence at the evaluated areas, renal cancer occupies fifth place among male population (5.7 and 5.3%, respectively), and 11th place (3.5%) among female population. The problem of renal cancer in this region and the administrative center is relevant due to the increasing incidence: a standardized measures in the period of 2009-2013 were 12.5 ± 0.3 and 11.7 ± 0.50/0000, respectively. The Increase of the incidence can be explained by the integrating influence of complex of changing demographics and health, social, hygienic and other factors. The questionnaire survey has become one of the main methods to identify risk factors for the development of the disease. Risk factors for renal cancer were identified by the case-control method. 231 patients with renal cancer (mean age 58.2 ± 1.7 years) and 354 healthy men and women (mean age 57.4 ± 2.2 years) underwent questionnaire survey. Specific risk factors for renal cancer were identified: migration (OR = 1.6, P = 0.0149); low socio-economic status (secondary-level education, income per family member less than 10,000 rubles, OR = 1.5, P = 0.0349); started smoking before 18 years of age (OR = 1.5, P = 0.0349); trade with physical activity and occupational hazards (car drivers, sailors, house-painters, OR = 2.0, P = 0.0000); occupational hazard: contact with oil products (OR = 1.6, P = 0.0262), contact with lead, asbestos, dyes (OR = 3.5, P = 0.0000); length of time worked with occupational hazard over 5 years (OR = 1.6, P = 0.0126); occupational hazard in the form of an underground work (OR = 8.0, P = 0.0000) and the presence of large amounts of dust (OR = 1.2, P = 0.0381); location of industrial enterprises within 2 kilometers from homesite (OR = 2.5, P = 0.0000). Based on the identified risk factors, predictive model for the assessment of individual risk and the formation of groups at risk for renal cancer was developed.

108 women diagnosed with leiomyoma and 84 women without this disease (control group) were examined during the research. Was conducted a comparative analysis of the genotypes distribution between women with cervical pathology of different complexity. The results of the research showed, that there is no connection between the С-1562Т polymorphism of the MMP-9 gene and the progression of leiomyoma the course of which is accompanied by false erosion of the cervix (ectopias epithelium) (p>0,521). There is also was not found any connection between the SNP in women with leiomyoma, who undergo conical electrocauterizing excision treatment because of the dysplastic epithelial changes that are considered to be precancerous (p>0,280).

An association between polymorphous (allelic) gene variants of phase II of enzymatic xenobiotic biotransformation (EXB) of multigene families of glutathione-S-transferase (GSTs) GSTM1*0, GSTT1*0, GSTP1*B Ile105Val, and N-acetyltransferase (NAT) NAT2*6 590G>A, NAT2*5 481C>T, as well as lung cancer in Mayak workers exposed occupationally to prolonged external γ-rays and internal α-radiation from incorporated 239Pu was studied. Analysis of the population frequency of genotypes and alleles of the studied genes in the cohort of Mayak workers revealed their compliance with the Hardy-Weinberg principle and with the corresponding frequency in the European population. The study was based on the case-control method. A case-group consisted of 49 Mayal workers with a verified diagnosis of lung cancer. The mean total absorbed dose from external γ-rays at the moment of diagnostics was 1.03 Gy; the mean total absorbed dose from internal α-radiation from incorporated 239Pu to lung was 0.35 Gy. Control consisted of 172 Mayak workers matched by the year of birth, gender, and age at the moment of employment at one of the main facilities with no lung cancer registered within the study period. No increase in the relative risk of lung cancer (odds ratio, OR) was revealed among the individuals with deletion variants of genes GSTM1*0 and GSTT1*0 (pp genotype, complete absence of gene products) as compared to the individuals with ww or wp genotype, which was determined in total for these genes (normal or partly decreased gene activity). An increase in OR of lung cancer in 1.849 times (p = 0.239) and in 2.439 times (p = 0.075) was found in the carriers with a complete absence of the product of genes GSTP1*B and NAT2*6 590G>A, correspondingly (pp genotype). A statistically significant decrease in OR of lung cancer was found in the wp genotype carriers of gene GSTP1*B (OR = 0.50, p = 0.041). Three variants of paired combinations of gene alleles were established in the carriers with a statistically significant increase in OR of lung cancer (ww GSTP1*B + pp GSTM1*0; ww GSTP1*B + pp NAT2*6 590G>A; pp GSTP1*B + pp NAT2*5 481C>T), and one combination in the carriers with a statistically significant decrease in OR of lung cancer (wp GSTP1*B and ww +wp GSTT1*0).

The cellular DNA repair systems sufficiently provide the resistance of tumors to ionizing radiation, and thus contribute to reducing the effectiveness of their radiotherapy. Therefore, suppression of the activity of critical DNA repair enzymes in tumor cells is considered one of the promising directions to overcome this resistance. As can be seen from the literature analysis, the use of many inhibitors of DNA repair enzymes have not yet yielded the results, which can be extrapolated to preclinical models or clinical trials. However, experimental studies show that the inhibitors of the enzyme family of poly(ADP-ribose) polymerases (PARP) are able to inhibit the growth of various human tumor cells. Pre-clinical and clinical trials of the PARP inhibitors also show promising results in terms of the possibility of their wide practical application. The effect of the PARP inhibitors consists in the blockage of the most important DNA repair systems. This leads to the accumulation of DNA single-strand breaks, the collapse of replication forks and to generation of lethal double-strand breaks (DSB). The PARP inhibitors can be used to suppress breast cancer and ovarian cancer with mutations in BRCA-1/2 genes ("BRCAness" cancer) without combination with radiotherapy or chemotherapy. In the tumor cells deficient in BRCA-1/2 genes DSB repair by homologous recombination pathway does not function. Therefore, the process of DNA DSB repair is switched to the non-homologous end-joining pathway, which operates with formation of the chromosomal rearrangements leading to cell death. Thus, the analysis results show that DNA repair inhibitors have the potential to improve the efficiency of cancer radiotherapy. Further research in this direction is very promising.

The total chymotrypsin-like activity of proteasornes, the activity of 20S- and 26S-proteasome pools and calpains, and the expression of metalloproteinase PAPP-A in primary tumors and metastasized tissues were studied in 13 patients with epithelial ovarian cancer. It was shown that initiation of the process of tumor dissemination occurs against the background of active proteolytic processes; A decrease in activity of 26S-proteasomes and total calpain activity and increased expression ofmetalloproteinase PAPP-A in the primary tu mors were found in patients with ascites as compared with patients without ascites. The disease progression after treatment and achieved stabilization were found in patients with decreased activity of intracellular proteases and a high content of PAPP-A in the primary tumors.

Applying the method of multiple parallel sequencing on the MiSeq platform (Illumina, United States), a comparative analysis of miRNA expression in tumor and normal colon tissuie cells was performed. Forty miRNAs aberrantly expressed in cancer were detected. Among them, 15 and 25 miRNAs showed increased arid decreased expression, respectively, for all or most of the cases. Sixteen miRNA clusters were identified, which showed a coordinated or incompletely coordinated aberrant expression in colorectal cancer cells. In two (miR-183/182 and miR-106b/25) and four (miR-143/145, miR-497/195, miR-30e/30c-1, and miR-30a/30c-2) miRNA clusters, respectively, a statistically significant coordinated increase or decrease in expression was iegistered for all miRNAs withini the corresponding cluster. Three aberrantly expressed well-known miRNAs (miR-100-5p, mil-30d-5p, and miR-204-5p) were identified, which, however, had never 'before been associated with coloreictal cancer. The obtained results demonstrate the potential and promising application of 6 miRNA clusters with' coordinated aberrant expression as markers for colorectal cancer.

It is found that after administration of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB,) which was hepatocarcinogenic to rats, in suckling mice, the number of neoplastic lesions in the liver of mice was 3 times higher than after analogous administration of equimolar dose of ortho-aminoazotoluene (OAT)). However, in the Ames test (TA-98 strain of Salmonella typhimurium) with activation by hepatic enzymes (S-9 fraction) of both intact and Aroclor-1254-induced mice and rats OAT contributed by an order of magnitude to revertant colonies compared to 3'-Me-DAB. In vivo inhibition of sulfotransferase activity, the enzyme which catalyzes the final stage of the mutagenic activation of aminoazo dyes, had no effect on carcinogenicity of 3'-Me-DAB but more than 4 times elevated that of OAT. It was concluded that the mechanism of carcinogenic action of aminoazo dyes studied is not genotoxic and that the carcinogenic potential of OAT is lost in the process of mutagenic activation.

We examined the correlations between the polymorphic alleles of the DNA repair genes XRCC1 (c.839G> A, rs25489; and c.1196A> G, rs25487), XPA (c.-4A> G, rs1800975), and XPD (c.2251A> C, rs13181) and the progression and severity of neoplasias in the bladder and kidney in patients of three distinct ethnic groups, Bashkir, Russians, and Tatar, residing in the Republic of Bashkorostan. The study enrolled 468 cancer patients and 351 healthy individuals. Genotyping for polymorphic alleles was carried out using the PCR-RFLP method. We identified a correlation between allele A of the c.839 G>A locus of the XRCC1 gene and the incidence of the bladder cancer (BC) and kidney cancer (KC) in the Tatar study group, using the additive genetic effects model (Odds Ratio (OR) = 5.23 and OR = 3.90). In turn, the heterozygous G/A genotype was present at a significantly higher frequency in the KC patients of Bashkir ethnic origin, compared with the control group (p = 0.0061, OR= 4.72). Additional analysis with consideration of participants' smoking status showed that the G/A genotype is significantly more frequent in smokers with BC (OR = 1.96, p = 0.05) then in healthy smokers. We also determined, using the recessive genetic model, that the genotype A/A of the c. 1196A>G locus of the XRCC1 gene was correlated with a higher risk of BC in the Russian cohort (OR = 2.29, p = 0.0082) and an increased incidence of KC in the Bashkir group (OR = 4.06, p = 0.05). A similar correlation was obtained for smokers. In contrast, the allele c.2251 A>C in the XPD gene correlated with a lower risk for BC and KC in the Tatars (p = 0.0003, OR = 0.48 and p < 0.0001, OR = 0.37) in the additive model and in the Bashkirs (p = 0.0083, OR = 0.12) and Russians (p = 0.0001, OR = 0.14) in the recessive model. Further, we uncovered that polymorphism c.839 G>A in the XRCC1 gene contributes to the progression of noninvasive and invasive BC and promotes KC at early and advanced stages of the disease. Thus, we identified similar correlations between DNA repair gene polymorphism and the incidence and progression of BC and KC. We propose that this result points to the involvement of common pathogenetic mechanisms in the initiation and progression of the urinary neoplasias.

Proof of the efficacy of cell therapy by numerous studies and clinical trials inevitably has raised the question of improving the regulatory framework that governs its use. Particular attention should be paid to the genetic safety of cell preparations. The immune, genetic, and pharmacological modification and expansion of cells in vitro can lead to an undesired effect, which not only has reduced the healing, recovery, and regulatory potential of cell therapy, but also increased the risk of accumulating genetically aberrant cells and the oncogenic transformation of cell preparations. The article has presented the estimation of the parameters of the genetic stability of cultured multipotent mesenchymal stromal cells (MSCs) derived from bone marrow and adipose tissue. The study was conducted using classic methods of genotoxicology, i.e., the individual cells gel-electrophoresis (DNA comets) and the micronucleus test. We described a basic level of DNA damage and the frequency of micronucleus, identified genetically instable cultures, and conducted the comparison of genetic variability of MSCs isolated from different tissues.

Both genetic and epigenetic changes underlite the mechanisms of tumor initiation and progression. In the present study we analyze sox2 gene expression and its epigenetic regulation in primary cultures of malignant gliomas. The sox2 expression was detected in the vast majority (74%) of the investigated gliomas and absent in morphologically normal brain tissue. This indicates the process of glioma malignant transformation. We have also shown that the association of different areas of the sox2 gene with important epigenetic markers, posttranslational modifications of H3 histone H3K4ac and H3K9met3, does not correlate with the sox2 expression. However, this may indicate the stochastic nature of the regulation of sox2 gene expression in malignant gliomas.

Membrane type 1 matrix metalloproteinase (MT1MMP) is one of matrix metalloproteinases (MMP), which play а key role in tumor invasion and metastasis. The aim of this study was to elucidate the peculiarities of expression of MT1MMP and endogenous regulators of its activity: the activator - furin and the inhibitor - TIMP-2, as invasive factors of squamous cell cervical carcinomas (SCC). The study was carried out using 11 specimens of SCC and 11 specimens of morphologically normal tissue adjacent to the tumor. It was shown that the increase of MT1-MMP and furin expression and low of TIMP-2 expression makes the main contribution to the destructive (invasive) potential of SCC. Moreover, substantial expression of MT1-MMP was registered in the specimens of morphologically normal adjoining to tumor tissue. This expression was found to make an additional contribution to the destructive potential of the cervical tumor.

Recent data on adult stem cells are reviewed. According to the present dominant paradigm, it is most probable that cancer predisposition arises or cancer is initiated in these cells.

Surgery results of II-III stage lung cancer remain unsatisfactory and the chemotherapy does not improve the survival. The main obstacle is the use of the standard clinical parameters for the treatment strategy and not sufficiently effective selection of regimens for the chemotherapy. Monoresistance genes defining the tumor cells sensitivity to the chemotherapeutic drugs play a significant role in development of the lung tumor resistance. The review examines the mechanisms of transport, activation and targets of the chemotherapeutic drugs, identifies the key markers for predicting their effectiveness and possible use in the clinical practice. Monoresistance genes, such as ABCC5, RRM1, ERCC1, TOP1, TOP2a, TUBB3 and TYMS are characteristic of lung cancer. Clinical trials demonstrating the efficiency of their use as predictive markers for the lung cancer chemotherapy are described. A prospective study with a personalized adjuvant chemotherapy for lung cancer patients will be performed.