The work purpose was to reveal an existence of an associativity of the microRNA levels in blood serum to quantitative and functional indices of cells haemo - and lymphopoiesis at the experimental breast cancer induced by N -methyl - N- nitrosourea in the remote period after surgery and carrying out neoadjuvant polychemotherapy. At animals there were investigated levels of microRNA-21, microRNA-221, microRNA-222 and microRNA-429 in serum, also investigated quantitative and functional parameters of cells from bone marrow, from lymph of a chest channel and from spleen. Statistically significant distinctions on the microRNA level in blood serum and an existence of interrelations of microRNA levels with quantitative and functional indices of haemo- and lymphopoiesis cells were revealed.

In this work the effect of RHAMM (receptor hyaluronan-mediated motility)-target peptides was investigated on the viability, apoptosis and necrosis of prostate cancer cells (PC3m-LN4). It has been established that RHAMM-target peptides inhibited on 90 % cell viability of PC3m-LN4 cells at a concentration of 10 ug / ml (2х10-7 M) for 48 h. It has shown that RHAMM-target peptides induced apoptosis and inhibited necrosis of tumor cells. RHAMM-target peptide had no effect on fibroblasts (non-tumor cells) and fibroblasts (RHAMM-/-). The studies also revealed that RHAMM-target peptides enhanced activity of caspase-3/7 in cancer cells.

In this paper we have showed that evolutionary new genes DCD1(Dermicidin), LINC00309 (Long intergenic non-protein coding RNA 309) and CLLU1(Chronic lymphocytic leukemia up-regulated 1) have tumor-specific expression profile. Along with our previously published results this confirms the existence of the phenomenon of TSEEN (Tumor-Specifically Expressed, Evolutionarily Novel).

Activation of AKT signaling pathway and mTOR substrates of kidney tumor tissue occurs by improving AKT, its phosphorylated form, the serine / threonine proteinkinase m-TOR, the exchange regulator glycogen GSK-3-beta and also the inhibitor of 4E-BP1transcription. Increasing the size of primary tumor is followed by increasing the content of therein c-Raf and decreasing the content of phospho-m-TOR. The development of disseminated forms of the disease was associated with a reduction PTEN and phospho-AKT in tumor.

There was carried out a study to compare the frequency of spontaneous chromosomal aberrations (CA) in lymphocytes of peripheral blood between the group of cancer patients with different types of solid tumors and the group of healthy people of the same age. There was established a significant increase in the average frequency of CA in cancer patients. Analysis of the group of patients has revealed its heterogeneity: in the majority of patients the individual frequency of CA significantly exceeded the average frequency of CA in the control group, in some - did not differ from that. The first patients were described as the group with "generalized" genomic instability. Also this group differed by increased radiosensitivity of lymphocyte chromosomes during their irradiation in vivo.

There were studied distribution of polymorphic variants of gene of repair of DNA XPD A751C in lung cancer depending on histological type of tumor (small cell / non-small cell lung cancer) and the prevalence of tumor process (with foci / without foci of metastasis). It was found a significant increase in the incidence of minor allele C, CC and AC genotypes of the polymorphic site of gene XPD A751C in patients with lung cancer. We estimated relative risks of lung cancer development in carriers of polymorphic variants of gene XPD A751C. The heterozygous genotype AC polymorphism of gene XPD A751C is characterized by the greatest risk of developing lung cancer with small cell histological type. Homozygous CC genotype of the polymorphic site of gene XPD A751C is associated with non-small cell lung cancer development. Statistically significant differences in the distribution of polymorphic variants of gene A751C XPD depending on spread of cancer were not received.

Colorectal cancer is closely related to changes in the immune status at all stages of the disease. The main method of treatment for colorectal cancer is surgery. Surgical intervention as any pathological impact on the body from the outside is leading to suppression of both humoral and cellular immunity. Melatonin can be used to stimulate the immune system acting as a protective agent. Currently melatonin is used in oncology practice rather modest - as part of a complex postoperative therapy. Melatonin in pharmaceutical concentrations acts as differentiation factor reducing infiltrative and metastatic potential by restoring the links between signaling molecules and inhibiting existing cell-cell contacts, which can be used in the preoperative therapy.

It is necessary to maintain the safety of the cell proteome for the operation and adequate biological response of tumor cells to changing conditions, which is provided by chaperones and ATP-dependent proteases. Molecular chaperones, which include the small heat shock proteins, carry out folding, refolding and misfolding of proteins, support functional activity of intracellular proteins. Proteases, mainly proteasome, degrade abnormal, damaged and fulfilling its function proteins. The review presents modern data on the role of the proteasome and heat shock proteins in malignant tumors as well as the mechanism of interaction of these systems in the cell.

Secondary prevention of cervical cancer is the identification and treatment for preinvasive forms of the disease, which include cervical intraepithelial neoplasia (CIN). The traditional method of identification of CIN is cytological however the sensitivity and specificity of this method is limited. The efficacy of a test for human papillomavirus as well as new molecular-biological methods for assessing the prognosis of development of dysplasia and choice of appropriate treatment tactics are still in the process of discussion. The article contains information about different possibilities of using molecular-biological methods for assessing the prognosis of development of CIN and cervical cancer.

Molecular genetic analysis has become a mandatory component of cancer diagnostics. Preanalytical step for DNA and RNA analysis is a complex process requiring tight interaction between surgeons, pathologists and molecular geneticists. This article discusses key aspects of handling of the tissues before DNA- and RNA-testing.

Barrett’s esophagus is considered as a predictor of esophageal adenocarcinoma with multistage neoplastic progression at present time. The research assessed an expression of microRNA-21 in 25 patients with different degree of metaplasia and dysplasia of mucous coat of esophagus. The level of expression of microRNA depended on the presence and degree of expression of neoplastic changes of mucous coat of esophagus. The expression rising of microRNA was noted in patients with columnar-celled metaplasia and intraepithelial neoplasia and in case of esophageal adenocarcinoma. The treatment strategy could be determined by the method of estimation of the level of microRNA expression in biopsy material from mucous coat of esophagus in patients with gastroesophageal reflux disease and using other criteria.

Until recently the detection of carriers of mutations in hereditary cancer genes was aimed almost exclusively to the detection of subjects-at-risk, and consequently, personalized monitoring and preventive actions. However, it was revealed several years ago that some hereditary cancers are characterized by unique biological features and, therefore, unusual spectrum of drug sensitivity. For example, BRCA1/2-associated cancers usually demonstrate somatic loss of the remaining gene allele, and, hence, tumor-specific defects of DNA repair of double-strand breaks. This mechanism determines increased sensitivity of BRCA1/2-related cancers to cisplatin, mitomycin C and PARP inhibitors. Cancers arising as a part of Lynch syndrome can be effectively treated by the modulators of immune response. Tumors in patients with tuberous sclerosis often regress after administration of mTOR inhibitors. For the time being, there is already about a dozen of drugs demonstrating specific activity towards certain categories of hereditary cancers.

This manuscript includes an update on the latest developments in the biology of breast cancer as well as the most recent advances in prevention and multidisciplinary management of this disease: surgery after neoadjuvant chemotherapy and anti-HER2 therapy of HER2 positive breast cancer, neoadjuvant and adjuvant endocrine treatment of ER+ (Luminal A) breast cancer. Our task (as in the St. Gallen and ESMO consensus recommendations) is to assist physicians to improve both therapy impact in patients and their results.

Malignant glioma is the most frequently occurring primary brain tumor. Despite significant progress in the diagnostics and treatment of neoplastic diseases the prognosis for patients with III-IV grade gliomas, remains extremely unfavorable. Rapidly developing area in oncology is the employment of therapeutic viruses with natural or genetically engineered oncolytic activity. In the present study we demonstrated the oncolytic potential of a recombinant influenza A virus vector with impaired interferon antagonism function of NS1 protein in treatment of malignant glioma. Recombinant influenza A virus (HA-DS-GFP) expressing green fluorescent protein from the NS1 open reading frame was used as a model vector. HA-DS-GFP virus has shown infectivity towards glioma cells both in vitro, and in vivo (experimental glioma model in rats). Intratumoral inoculation of HA-DS-GFP resulted in a substantial inhibition or complete regression of tumor growth. Our data demonstrate that recombinant influenza vectors have promising potential in therapy of malignant gliomas.

In this study we established a HER2/neu expressing mouse tumor model using hepatoma MH-22a cell line tumorigenic in DBA mice. G10 clone with high level of HER2/neu expression was obtained by stable transfection and cloning. Solid tumors induced by subcutaneous injection of G10 cells into immunocompetent mice retain the expression of human receptor for at least three weeks. Treatment with trastuzumab results in statistically significant inhibition of tumor growth. This model can be used to evaluate in vivo efficiency of novel anti-HER2/neu antibodies and to test antibody-based conjugates for diagnostics.

Using the technology of DNA chips Infinium HumanMethylation 450 BeadChip it was analyzed quantitative DNA methylation status in 12 paired samples of prostate adenocarcinoma, and morphologically altered tissues. Analysis of differentially methylated regions of the genome showed an association with abnormal status for 21610 and 3852 hypomethylated hyper-methylated CpG sites. Dominance in the cancer genome hypermethylated sites and their predominant localization in the regulatory regions of genes indicate their possible role in the implementation of mechanisms of gene suppression in the pathogenesis of prostate cancer (PCa). For 14 genes studied were characterized array maximum values hypermethylation in promoter region (> 50% CpG sites) in combination with a high level of methylation differences between treatment groups (> 40%). Role of hypermethylation in some of them: AOX1, KLF8, ZNF154, TMEM106A in the pathogenesis of prostate cancer has been showed previously. Hypermethylation of genes ACSS3, TAC1, TUBA4B, ZSCAN12 not previously been shown for prostate cancer, but is characterized by the association with other cancers. In turn, the differences in the levels of methylation in genes GPRASP1, NKX2-6, ARX, CYBA, EPSTI1, RHCG been documented as a result of a number of genome-research oncology, but has not been studied in detail. To assess the diagnostic potential of epigenetic markers of prostate cancer there was carried out unbiased selection of individual CpG sites most reliably discriminate against tumor samples from a group of no tumor samples. In selected diagnostic model based on logistic regression included 9 CpG sites. Validation of the model was carried out on an independent dataset of methylation of 40 paired samples from the prostate cancer project Atlas of Cancer Genome (TCGA) analyzed on the same version of the DNA chip. Summarized rates of diagnostic informativeness of a model (specificity 95%, sensitivity of 97%, the area under the curve of the diagnostic test (ROC) - 0,96), obtained after validation, allow us to consider these CpG Sites as potential markers for molecular diagnosis of prostate cancer.

Aberrant methylation of regulation regions of tumorsuppressor genes is showed for many cancer diseases. In course of this modification an enzyme DNMT3 methylates RCGY sites in CpG-islands of regulation regions producing R(5mC)GY sites. Earlier we developed GLAD-PCR assay to determine R(5mC)GY site in a definite position of human genome. In this work we have applied GLAD-PCR assay to determine R(5mC)GY sites in regulation regions of ESR1 and ELMO1 tumor-suppressor genes. We have studied a fragment of first exon of ELMO1 gene and a part of ESR1 promoter region in DNA preparations from malignant cell line SW837 and colorectal tumor samples. We have checked four sites in each region and found two highly methylated sites: GCGC in first exon of ELMO1 gene and GCGT in promoter region of ESR1 gene. Site GCGT is weakly methylated in healthy tissues and more methylated in the most of colorectal samples. Site GCGC is not methylated in healthy tissues and significantly methylated in 60% of colorectal samples. A possibility to use GLAD-PCR assay for cancer diagnostics is discussed.

Peutz-Jeghers syndrome is a rare hereditary syndrome characterized by presence of hamartoma polyps in intestinal tract and usually by mucocutaneous pigmentation. Clinical-genetic characteristics of Russian patients with Peutz-Jeghers syndrome were studied for the first time. Four germline mutations in STK11gene were found in probands from six families and three of them had not been described previously. Clinical pattern of disease in Russian patients included: frequent polyposis of colon and stomach (62,5% and 75%, respectively) along with small bowel; frequent presence of malignant tumors (62,5%). These clinical aspects can help physicians to find out Peutz-Jeghers syndrome. Molecular-genetic testing of individuals should be recommended.

This review summarizes the clinical trials of the relationship of gene expression and protein ABC-transporters in breast cancer with the response to neoadjuvant chemotherapy (NAC) and survival of patients. In a large clinical material is considered the pre-treatment multidrug resistance (MDR) and adaptive MDR, that occurs in tumor cells during chemotherapy. Association pre-treatment MDR with NAC efficiency and survival is highly variable and not well-established. In all clinical trials, adaptive MDR showed a good association with NAC efficiency and survival of patients. The own results showed that 5-year distant metastasis-free survival was 73-78% and good response to NAC in patients with a decrease in ABC- expression. The up-regulation of these genes during NAC was related to a significant decrease (up to 50-55%) in metastasis-free survival and poor response to NAC. In the development of strategies to overcome MDR phenotype it is concluded based on the submitted clinical data.

Whole-genome expression analysis methods significantly clarified contemporary breast cancer classification. Besides today clinical practice lacks the use of expression methods due to complexity of conduction, analysis and lack of clinical application. Further studies of breast cancer expression characteristics and clinical trials with stratification based of phonotypical features may improve the results of existing anticancer agents. Creation of limited clinically applicable test system, which incorporates all the specific breast cancer subtypes is currently needed.