Frequencies of the 538insC mutation in the BRCA1 gene and the 1100delC mutation in the CHEK2 gene were compared in the group of breast cancer patients and the large-scale sample, consisting of 7920 DNA specimens from healthy residents of the city of Novosibirsk. Higher frequencies of these mutations in the patient group compared to the control sample (1.95 versus 0.25% for BRCA1 5382insC, and 1.78 versus 0.40% for CHEK2 1100delC) were observed, pointing to their association with susceptibility to breast cancer (OR = = 7.86, 95% CI 3.51-17.30 and OR =4.46, 95% C1 2.04-9.49, respectively).

H. pylori are etiological factor of human acute and chronic gastritis. Depending on pathogenic factors of microorganism and polymorphism of human genes, chronic gastritis can be a cause for ulcerative enteritis of the duodenum or stomach, gastric adenocarcinoma and MALT-lymphoma development. We revealed genetic features of bacteria, determined the intensity of inflammation, such as pathogenic factors--cag, plastic region of the genome and adhesin coding genes. Epigenetic changes, for example the methylation of E-cadherin gene associated with H pylori, are crucial for carcinogenesis. Thereby, predisposition of chronic gastritis associated with H. pylori to ulcerative enteritis of the duodenum, ulcerative stomach disease or gastric adenocarcinoma depends on topography, the intensity of inflammation and changes of acid production in the stomach.

The results of a immunomorphologic comprehensive study of epithelial-stromal relationships in the uterus hyperplasia and endometrial cancer suggest that the suppressor gene of cancer (PTEN) plays a key role in the process of neoplastic transformation of endometrial hyperplasia and adenocarcinoma development. For the first time the existence of two highly differentiated endometrial adenocarcinoma immunophenotype were detected The first one is a PTEN-negative endometrial aedenocarcinoma, characterized by an almost complete inhibition of tumor suppressor gene PTEN in the epithelium of the glands and stromal cell of the tumor The second type is a PTEN-positive endometrial adenocarcinoma, in which epithelial and stromal tumor suppressor gene PTEN activity has retained Based on these results we have formulated a hypothesis about the different types of endometrial hyperplasia morphogenesis and its possible transfer to cervical cancer associated with features of tumor suppressor gene PTEN.

Morphological and clinical characteristics of the urinary bladder cancers (UBC) are important diagnostics and prognostic criteria, however the possibilities of biopsy using/for prognosis of recidivation or efficiency of UBC treatment are limited. The most popular diagnostic and prognostic immunohistochemical markers are the regulators of cell cycle (P53, P21, Ki-67) and cytokeratins. In order to revealed immunohistochemical criteria, objectively reflected the malignancy of UBC, we studied the expression level of P53, proliferative index of Ki-67 and the malignant of UBC according to CK20 in the biopsy of 32 patients with superficial UBC. The immunohistochemical reaction with antibody to P53, CK20 and Ki-67 was carried out at paraffin slices. We detected differences of P53 expression levels at carcinomas with high and low malignancy rate. The expression levels of CK20 and the Ki-67 proliferative index were different between Ta and T1-T2 cancers (p = 0.006). Intensity of nuclear staining with P53 antibodies could be use for estimation of the UBC malignancy rate. Pathological type of CD20 expression and high percentage of Ki-67-positive staining nucleus are evidence of the invasive urothelial tumors. The using of P53, Ki-67 and CD20 could be recommended for pathohistological investigation of biopsy and surgical material of UBC to diagnostic objectification and prognosis of its clinical course.

Dynamics of development and morphology of hyperplastic skin lesions ("hoods") on the head of goldfish, which were bred using artificial selection for more than thousand years, were studied. During monitoring of hundred fishes, at the age of 6 months "hoods" were found in 39.5%, among 14 months-old fishes in 60,7%. Morphologic examination of "hoods" on various stages of development revealed epithelial hyperplasia with increased clear mucous cells number, dermis thickening and oedema. On later stages developed papillomatous outgrowth and areas of epithelial intrusion. The comparative oncology analysis allow to hypothesize these skin growth to be a genetically determined benign neoplasm. This is the first example of artificially selected neoplasm described in the literature. It supports our hypothesis of the possible evolutionary role of tumors.

High resolution melting analysis (HRMA) using special "saturating" fluorescent dyes is a new and very effective approach to genotyping and mutation scanning. HRMA, which is carried out usually just after PCR without any intermediate manipulations (the "closed tube" format), is simple and high-throughput method excluding sample cross-contaminations. The "closed tube" format makes, however, HRMA dependent on PCR mixes and, as such, limits its capability. The "open tube" format (post-PCR amplicon shortening and optimization of the ionic medium) proposed by us earlier, although somewhat more laborious, significantly increases sensitivity of the method and makes it possible to scan mutations in the short amplicons using conventional SYBR Green I dye and a standard (not adapted specifically for HRMA) real-time PCR instrument. Detection of mutant K-RAS in DNA of clinical specimens (tumor tissues, formalin-fixed paraffin-embedded samples) reveals equal, at least, sensitivity of this method as compared with the HRMA and much higher as compared with Sanger sequencing. The problem of false-negative results in mutation scanning of K-RAS, which is highly important in some forms of cancer, is discussed.

Insulin-like growth factors and the nuclear factor kappaB (NF-kappaB) are known to play an important role in pathogenesis of endometrial cancer. However, there is still uncertainty about their proteolytic regulation. We studied the correlation between chymotrypsin-like activity ofproteasomes and IGF-I, IGF-II and NF-kappaB levels in endometrial cancer tissues. The total activity of proteasomes and the 20S and 26S proteasome activities were shown to be significantly higher in malignant tumors than in unaltered endometrium. Negative correlations between the 26S proteasome activity and NF-kappaBp50 level as well as between the 26S and 20S proteasome activities and IGF-I level were found. The data obtained indicate a possible proteasome regulation of growth and transcription factors. As it is considered that the major pool of IGF-I is located in the extracellular space, it is likely that extracellular proteasomes also take part in the regulation of IGF-I content. The positive correlation between IGF-I level and PAPP-A metalloproteinase gives evidence that this proteolytic enzyme is another important regulator of growth factor level, which provides proteolysis of IGF-I binding proteins and increasing IGF-I concentration in tissues. The present data show possibility of proteolytic regulation of growth and nuclear factors that can play an important role in cancer pathogenesis.

Hepatocellular carcinoma (HCC) is among the most frequent malignancies in humans. HCC therapy is not efficient and the usual outcome is poor. In this regard, novel approaches to treat and prevent HCC are urgently needed. The Alpha-fetoprotein (AFP) is a serological marker of HCC. Recently it has been shown, that the DNA vaccines expressing AFP are capable in generating immune response against AFP. However, both, the immunization procedures and DNA vaccines used before were complex and not always very effective. We have shown that DNA vaccine encoding HIV-1 reverse transcriptase (RT) with fused ornithine decarboxylase (ODC) degradation signal induced a strong Th-1 immune response against RT in mice. Using this approach we designed a set of novel DNA vaccines bearing AFP and ODC degradation signal. Results obtained on transfected cells demonstrated efficient expression and fast proteasomal degradation of the recombinant AFP. The anti-tumor immune response stimulation was shown in immunized animals and most importantly a notable retardation of tumor growth was observed as a result of protective vaccination.

Casein kinase 2 (CK2), a highly conservative, multifunctional serine/threonine protein kinase, is critically important for the regulation of a plethora of processes in eukaryotes, such as cell proliferation, differentiation and death. CK2 is expressed in all tissues; in particular, its amount and activity are elevated in tumor cells. Unlike many regulatory proteins CK2 permanently adopts an active conformation. Of the utmost importance are the anti-apoptotic functions of CK2. This protein kinase is capable of regulating cell survival at multiple levels including DNA repair, NF-kappaB, Wnt, PI3K/Akt and JAK-STAT signaling cascades, chaperones, activation of anti-apoptotic proteins and down-regulation of pro-apoptotic counterparts, in particular, caspases. The versatility of CK2-mediated phosphorylation ensures the survival of tumor cells exposed to stimuli that differ in the origin and mechanisms of cytotoxicity. This manifold mode of CK2-dependent survival makes this enzyme an important target for antitumor therapy.

Papillary adenocarcinoma is an abundant form of renal cell carcinoma. At present any diagnostic and prognostic molecular markers of papillary adenocarcinoma are absent, however some cytogenetic and molecular-genetic features of disease are known. According to literary data, the 1q32 duplication is associated with progressive deterioration of primary tumor. We have done a genetic typing (D1S2142 and D1S3465 locus) of 39 papillary adenocarcinoma cases, used PCR and fragment analyses of the 1q32 area. Frequency of the allelic disbalance was 36.8%; the microsatellite instability was found out in 48.7% of cases. The association of genetic disturbances with clinic-morphological features of papillary adenocarcinoma wasn't revealed. In some cases genetic heterogeneity of tumor-adjacent renal parenchyma and primary tumors was found out at multifocal renal carcinoma. For the first time we ve demonstrated that the allelic disbalance in 1q32 area and the microsatellite instability are frequent molecular-genetic disturbances in sporadic papillary carcinomas at all stages of the disease. Probably, the microsatellite instability is connected with progressive deterioration of primary tumor at renal papillary adenocarcinoma.

Microbial ribonucleases possess a broad spectra of biological activities, demonstrating stimulating properties at low concentrations and cytotoxicity and genotoxicity at high concentrations. The mechanisms of their penetration into the cells are not clear so far. This research is aimed to the study of Bacillus intermedius RNase (binase) penetration in alveolar lung epithelial cells--pneumocytes of type II. Using immunofluorescence we have shown for the first time have internalization of binase by primary non-differentiated pneumocytes ATII. The enzyme did not penetrate in pneumocytes MLE-12, which also derived from type II cells. However, binase was cytotoxic towards tumor MLE-12 cells, but not ATII cells. The obtained results testified the higher sensitivity of tumor cells towards binase compared with normal cells, and also showed that penetration of the enzyme into alveolar cells did not directly correlated with the cell death.

The article presents results obtained in study of relationship between polymorph variants of CYP1A1 and CYP1A2 genes with reproductive and thyroid diseases risk in female workers of petrochemical industry, when compared with reference group females. Variants TD and DD of CYP1A2 gene appeared to be associated with nodes formation in uterus and breast in female workers and reference group females. Following liability markers are obtained: homozygous in rare allele genotype CC of CYP1A1 gene for reproductive and thyroid diseaes (fibrous cystic mastopathy and nodular goitre), heterozygous genotype AG of CYP1A1 gene in uterine myoma and fibrous cystic mastopathy, homozygous in deleted T genotype of CYP1A2 gene in autoimmune thyroiditis. Occupational hazards and long length of service at hazardous industries increase effects of rare alleles of the genes studied.

Multiple changes in the genome, transcriptome, and proteome are frequent in cancer cells. A search for molecular markers based on DNA, mRNA, or proteins is a main method to develop early specific diagnostics for cancer. While universal markers are still unavailable, similar trends are known for the expression patterns of particular genes in certain epithelial tumors. A bioinformatic screening of transcriptomic databases identified the NETO2 gene as a new potential promising marker of renal cancer. A substantial increase in NETO2 mRNA level was detected in 90% clear-cell renal cell carcinomas, 70% of non-small cell lung cancers, and 50% of papillary renal cancers by real-time PCR. The NETO2 mRNA level was increased to a lesser extent in cervical carcinoma and colon cancer and tended to decrease in cancer of the stomach. The NETO2 gene, which codes for a membrane glycoprotein with an unclear function, was assumed to provide a new promising marker for early diagnosis in renal cancer and non-small cell lung cancer.

A comparative morphological study of primary and relapsing desmoid tumors was carried out. Immunohistochemical analysis showed that the progress of desmoid tumors in the form of relapses was paralleled by an increase in the counts of immunopositive cells and intensity of β-catenin and cycloxygenase-2 expression.

Co-expression of colorectal adenocarcinoma cancer stem cells marker CD133 and a set of surface molecules described in published reports as possible cancer stem cell markers of other solid tumors was analyzed by flow cytometry. Minor cell populations expressing CD29, CD34, CD90, and CD117 against the background of CD133 expression were detected in cancer cells suspensions from the patients with colorectal adenocarcinoma. Our findings suggest that these markers can be used as additional markers of cancer stem cells of human colorectal adenocarcinoma.

Two groups of breast cancer patients (53±2 years) in clinical remission receiving no specific therapy were examined: group 1, with BRCA1 gene mutations (N=11) and group 2, without mutations of this kind (N=11). The two groups did not differ by insulinemia and glycemia, insulin resistance index, blood levels of thyrotropic hormone, sex hormone-binding globulin, insulin-like growth factor-1, triglycerides, or lipoproteins. In group 1, blood estradiol level was higher. Intensive glucose-induced generation of reactive oxygen species in these patients was associated with a decrease of cholesterolemia, of the C-peptide/insulin proportion, and a trend to higher urinary excretion of 4-hydroxyestrone, one of the most genotoxic catecholestrogens. BRCA1 gene mutations in breast cancer patients were associated with signs of estrogenization and a pro-genotoxic shift in the estrogen and glucose system, which could modulate the disease course and requires correction.

Allelic variants of folate cycle enzyme genes can contribute to predisposition to cancer. The impact of polymorphic loci A2756G of MTR gene and of C1420T of SHMT1 gene for the risk of prostatic cancer was studied in residents of West Siberia. The frequency of alleles of these loci in patients (N=371) and controls (N=285) was determined and the data were statistically processed. No statistically significant association with prostatic cancer was detected for any of the studied loci.

Introduction of recent achievements of molecular biology into clinical practice contributes significantly to both prevention and early detection of breast cancer in women and development of new approaches, including genotyping, to screening for breast cancer. Screening for genetic polymorphisms in genes TGFβ1 and TGFβR1 reveals carriers of sporadic breast cancer. This provides an opportunity to reassess the role and place of preventive measures, also including surgical method, in the fight against breast cancer.

Earlier we isolated and characterized human milk pro-apoptotic peptide - lactaptin and generated its engineered analog - RL2. It was shown that both lactaptin and RL2 are capable to induce apoptotic death of MCF-7 cells. In this report we have analyzed biochemical markers of RL2 induced MCF-7 apoptosis. The activation of initiator and effector caspases as well as mitochondrial membrane potential and cytoplasm membrane changes were analyzed using flow cytometry and Western-blot methods. We have found that RL2 induced apoptotic death of MCF-7 cells was accompanied by PS exposure on the plasma membrane surface. It also was shown that RL2 has induced dissipation of mitochondrial membrane potential and resulted in activation of initiator caspases 8, 9 and effector caspase 7.