Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary disease due to a mutation in the MENI tumor suppressor gene. The risk of the disease in first-degree relatives of MEN1 mutation carriers is 50%. MENI gene mutations are not identified in 10-30% of familiar MEN1 patients and in 60-80% of sporadic MEN1 cases, which can be explained by mutations in the noncoding regions of the MEN1 gene, large gene deletions or mutations in other yet unknown genes. Molecular genetic testing can exclude the diagnosis of MEN1 in patients who do not harbor the MEN1 mutation, thus revealing a MEN1 phenocopy. This obviates the need for annual screening for the early detection of other remaining components of the disease and its risk in progeny.

The role of the Epstein-Barr virus (EBV), a ubiquitous lymphotropic human herpesvirus type 4, in the etiology of nasopharyngeal carcinoma (NPC) is not fully understood. The mechanism of NPC carcinogenesis, associated with the virus, is also not clear. The objective of present investigation was to carry out comparative analysis of the structure of an LMP1 oncogene of EBV in viral isolates obtained from patients with two types of tumors of the oral cavity: (a) associated (i.e., NPC) and (b) not associated (other tumors of the same anatomical region, OTOC) with EBV. Comparative analysis of C-terminal regions of LMP1 variants that was based on a sequence analysis of LMP1 from tumor, blood and throat washing samples of NPC and OTOC patients showed that all structural characteristics of LMP1 in both groups of patients were genetically similar, and differences found between compared parameters were statistically insignificant. Thus, for the first time it has been revealed that in NPC and OTOC patients in Russia genetically related EBV strains with structurally similar LMP1 variants are persisting that are likely to reflect a polymorphism of the virus circulating in population. The findings allow us to suggest that in non-NPC-endemic regions of the world, which include Russia, the risk of NPC development does not depend on the EBVstrain and its variant of LMP1 so much, but mostly from the genetic predisposition of infected persons to the disease and the exposure to other, as yet unknown agents.

Neoplastic transformation of cells is characterized by karyotypic abnormalities involving aneuploidy, quantitative changes, as well as multiple clonal rearrangements of the number and structure of chromosomes. It is probable that chromosomes are one of the mechanisms of cells immortalization and transformation. Despite many years of study of chromosomal rearrangements, data on primary chromosomal rearrangements in early stages of transformation is still insufficient. We examined karyotypic abnormalities in embryonic rat fibroblasts in both the spontaneous transformation and transformation by oncogenes at different passages in vitro. Literature data and results of our cytogenetical analysis of rat cells lines established by different methods of transformation of cells of different tissue origin in vitro have shown that cell karyotype at early passages may either be normal or acquire diverse clonal chromosomal abnormalities. At later passages, other chromosomes of karyotype are involved in new rearrangements. Despite this, some of the lines do not acquire the malignant phenotype and remain to be immortalized. The role of instable chromosomes and their loci in immortalization and transformation of cells is discussed.

Uterine leiomyoma (UL) is a benign and most common tumor that affects 20-45% of women of fertile age. In this study, we analyzed the MED12 second exon nucleotide sequence from 15 DNA samples extracted from LM of 15 subjects with uterine leiomyoma and 15 DNA samples extracted from peripheral blood leukocytes of the same female subjects. It was shown that somatic mutations in the MED12 gene occur in 73% of cases with deletions of varying sizes and missense mutations being most common at codon 44. Mutations in the MED12 gene could play an indirect role in leiomyoma progression by modifying the activity of other genes that encode proteins involved in growth and tumor progression.

The aim of the research was to study the Epidermal Growth Factor Receptor (EGFR) expression, measure Epidermal Growth Factor (EGF) and melatonin concentrations in patients with endometrial carcinomas. In order to reveal EGFR expression, immunohistochemical examination of morphologic material (tumor of the uterine body, histopathological diagnosis: endometrial carcinoma) from 21 patients was performed. The EGF blood plasma levels were measured using the method of high performance liquid chromatography (HPLC).The blood serum levels of melatonin were measured by the method of immunoferment analysis ELISA(IBL International reagent). The resultant numerical data were processed statistically using the computer program SPSS-12-ANOVA. A statistical analysis was also performed using the system IBM SPSS Statistics, version 20. The investigation revealed: 1. In endometrial adenocarcinomas (high-grade, low-grade) the expression of EGFR is detected in 100%. 2. In endometrial adenocarcinomas a relatively weak positive correlation between EGFR expression and melatonin blood serum levels is observed. With that, there is a negative correlation between the blood levels of EGF and melatonin. 3. The average index of EGF blood plasma level in simple endometrial hyperplasia (atypia-free) is significantly lower than that of the patients with endometrial adenocarcinoma, while in complex endometrial hyperplasia (atypia-free) the average index of EGF blood plasma level is slightly lower than in endometrial carcinoma. With low-grade endometrial carcinomas, the average index of EGF blood plasma level is higher compared to that of the patients with high-grade endometrial adenocarcinomas. 4. The average level of blood plasma melatonin in patients with simple/complex endometrial hyperplasia (atypia-free) is significantly higher than in high-grade endometrial adenocarcinoma. 5. In endometrial adenocarcinoma (high-grade, low-grade),a drastic increase in average levels of blood plasma EGF is observed with a correspondingly sharp lowering in average blood serum melatonin levels. 6. Under about equal conditions (strong expression of EGFR in the timorous tissue and sharp/extremely sharp decrease in the levels of anti-proliferative/anti-neoplastic melatonin in blood serum) high values of proliferative EGF content in blood plasma are indicative of poor diagnosis.

The probability of development of the Ehrlich's ascites carcinoma in young August and Wistar rats was investigated. The Ehrlich's carcinoma strain was derived in mice in the N.N. Blokhin Russian Cancer Research Center. The tumor was transplanted into rats intraperitonially. It was shown that the transplanted murine carcinomas did not arouse tumors in rats, but caused pathologic effects: abrupt growth impairment and partial loss in the August rats while in the Wistar rats the growth impairment was slight and there was no loss. Thus, the first, there was no tumor growth in rats and the second, the indicated effects of the murine tumor transplantation were more dramatic in the August rats than thouse in the Wistar rats.

Myeloid sarcoma (MS) is a rare malignant solid tumor presented with myeloid blast cells showing varying degrees of maturation. MS may have an extramedullary site, precede, or develop simultaneously with the clinical manifestations of acute myeloid leukemia (AML); it may also occur as an AML relapse. Besides AML, MS may be a manifestation of chronic myeloid leukemia or other chronic myeloproliferative diseases. Due to the fact that this disease is rare, the bulk of the literature on MS is presented with single descriptions of retrospective studies and clinical cases. The paper describes 3 cases of MS with inversion of chromosome 16 and small bowel lesion.

To characterize the clinical and hematological variability of acute myeloid leukemia (AML) with t(8;21) and to identify the signs associated with the likelihood of its relapse.

To study the distribution of HLA-A*-B*-C*-DRB1 *-DQB1 * haplotypes in patients with blood system diseases, to establish the most common HLA haplotypes, and to compare the findings with the data on the frequency and distribution of the highest-frequency HLA haplotypes in donors of a number of leading registries.

To make a randomized comparison of 2 consolidation treatment options (two patient groups): 2 cycles of cytarabine in average (Ig/m2 in Group 2) and standard (100 mg/mi2 in Group 1) doses in combination with idarubicin (8-12 mg/m2) and mitoxantrone (10 mg/m2), after two 7+3 induction cycles of daunorubicin (60 mg/mi2) and subsequent 6 cycles of maintenance therapy.

The purpose of the paper is to present Russian experts' consolidated opinion about acute myeloid leukemia (AML) treatment in adult patients aged less than 60 years. The guidelines have been elaborated having regard to foreign publications and Russian experience, on the basis of global and Russian clinical trials to treat AML and to define indications for allogeneic bone marrow transplantation in patients during first complete remission.

During the peptides activity mechanism investigation it was shown that short peptides regulate gene expression and protein synthesis. These peptides stimulated cell proliferation, differentiation and decreased cell apoptosis. This effect is the reason of increasing of various organs function. The peptides injection decreased the frequency of cancerogenesis and increased physiological resource of cells, tissues and organism till 20-42%. Peptides increased vital resource and decreased the mortality rate of elderly people.

The overview represents the recent most conspicuous findings in aging studies. It includes new data on the whole genome association studies (GWAS) in big cohort of centenaries, recently found mutation protecting from Alzheimer disease, discovery of hypothalamus as a command center of human aging, very important data on the negative effect of common antioxidants in the treatment of lung cancer as well as new data concerning antiaging and anticancer effects of common drugs such as rapamycine and metformin. Substantial part of the review is devoted to the epigenetic problems of senescence and feasible impact of basic epigenetic mechanisms (methylation of DNA and histone proteins, DNA heterochromatization) in regulation of gene expression, long-term genome reprogramming during early childhood, and transgeneration transmission of epigenetic traits. The necessity of transition from molecular studies of dormant human genome (anatomy of human genome) to genome in action (dynamic genome) and thus with special emphasis to epigenetic medicine is stressed.

To study the effects of cytotoxic and targeted anti-VEGF drugs on some mechanisms of apoptosis.

To analyze breast cancer samples using the new technique multiplex ligation-dependent probe amplification (MLPA) assay. MATERIAL AND METHODS; Formalin-fixed paraffin-embedded breast carcinoma samples from 65 patients were examined. After manual microdissection, DNA was isolated using a commercial kit ("QIAGEN") and analyzed with SALSA MLPA KIT P078-B1 Breast Tumour ("MRC-Holland"). Capillary electrophoresis provided results.

To make an integrated assessment of the proliferative activity of gastric cancer (GC) (Ki-67 and mitotic index - MI) and the degree of tumor cell apoptosis (apoptotic index - AI), by calculating the cell regeneration coefficient (CRC) in relation to the histological variant and functional immunophenotype (IPT) of a tumor and to determine if there is a possible association of the above indicators with adjusted 4-year relapse-free survival rates.

This report presents the initial results of the first Russian molecular epidemiological study of melanoma. The investigation included 1035 patients with stage IIIB-IV melanoma residing in various regions of Russia. Sequencing of BRAF gene revealed mutation in 627 (60.6%) tumors; c.1799T > A (p.V600E) substitution was detected in 563 cases, and other mutations in 64 melanomas. Frequency of BRAF alterations was significantly higher in patients of younger age (< 50 years: 72.9%; > or = 50 years: 57.1%; p = 0.00003). 710 melanomas included in the study were located in sun non-exposed regions of the skin; this category of tumors was characterized by the highest occurrence of BRAF mutations (63.9%). In conclusion, more than a half of Russian patients with advanced melanoma are potential candidates for the treatment of kinase inhibitors of mutated BRAF.

The genetic polymorphism of enzymes of synthesis and metabolism of estrogens can input into predisposition to breast cancer. The purpose of actual study was to analyze the associations of polymorphic loci CYP17/B1rs10556836, CYP1A 1rs1048943, CYP1A2rs762551, CYP19A1rs2470152 and CYP17A1rs743572 with risk of development of breast cancer in Russian residents of the Western-Siberian region of Russia. The rates of alleles and genotypes of the given loci were determined in sampling of women suffering with breast cancer (n = 670 females) and in control group (480 females without oncological diseases). The sub-groups of patients with breast cancer in pre-menopause--and post-menopause were analyzed separately. The border-line association of locus CYP17A1rs743572 is demonstrated with increasing of risk of breast cancer during pre-menopause (allele C: p = 0.04). Among the rest of polymorphic loci no association was detected.

An overview of the results of studies on prolactin (PRL) is given. The molecular and genetic characteristics of PRL and its receptor (PRLR) are presented. The PRLR polymorphism in patients with tumors of the breast is described. Synthesized analogues of human PRL inhibited its peripheral effects. The vegetative nervous system modulate PRL secretion. PRL is a risk factor for breast and prostate cancer. The signaling mechanisms of PRL and its possible clinical use in therapy of breast cancer are characterized.

The review presents the main and additional features that distinguish tumor cells from normal tissue cells. They include sustained proliferative signaling, evasion from growth suppressors, resisting cell death, enabling replicative immortality, angiogenesis induction, and invasion and metastasis activation. Basis for the formation of these features is provided by tumor genome instability. Tumors are complex tissues that consist of different cell types interacting with each other as well as with normal cells. An important characteristic of tumor cells is the ability to interact with the tumor microenvironment and the formation of tumor stroma.