[Association of chromosome 8q24 variants with prostate cancer risk in the Siberian region of Russia and meta-analysis].

Compelling evidence demonstrates chromosome 8q24 as a prostate cancer susceptibility locus. In present work we studied whether the common variants of 8q24 region, rs6983267 and rs1447295, were associated with the sporadic prostate cancer risk in the Russian population. Polymorphisms were genotyped in 393 case and 384 control Russian Caucasian men from Siberia region. The A allele of rs1447295 was significantly associated with the risk of prostate cancer (OR[CI 95%] = 1.74 [1.26-2.4], p = 7.8 x 10(-4)). A common G-A haplotype for rs6983267 - rs1447295 also showed an association with prostate cancer risk in Russian population (OR[CI 95%] = 2.03 [1.1 - 3.75], p = 0.02). We performed a meta-analysis combining our results with previous studies to evaluate the association between studied SNPs and prostate cancer risk. Meta-analysis has strongly supported the association for these SNPs (p < 10(-6)). Accordingly our study confirms the association between chromosome 8q24 and prostate cancer risk.

[Prediction of a non-small cell lung cancer sensitivity to cisplatin and paclitaxel based on the marker genes expression].

The goal of the present study was to define gene expression signatures that predict a chemosensitivity of non-small cell lung cancer (NSCLC) to cisplatin and paclitaxel. To generate set of candidate genes likely to be predictive a current knowledge of the pathways involved in resistance and sensitivity to individual drugs was used. Forty four genes coding proteins belonging to following categories: ATP-dependent transport proteins, detoxification system proteins, reparation system proteins, tubulin and proteins responsible for its synthesis, cell cycle and apoptosis proteins were considered. Eight NSCLC cell lines (A549, Calul, H1299, H322, H358, H460, H292, and H23) were used in our study. For each NSCLC cell line a cisplatin and paclitaxel chemosensitivity as well as an expression level of 44 candidate genes were evaluated. To develop a chemosensitivity prediction model based on selected genes expression level a multiple regression analysis was performed. The model based on the expression level of 11 genes (TUBB3, TXR1, MRP5, MSH2, ERCC1, STMN, SMAC, FOLR1, PTPN14, HSPA2, GSTP1) allowed us to predict the paclitaxel cytotoxic concentration with high level of correlation (r = 0.91, p < 0.01). However, none model developed was able to reliably predict a sensitivity of the NSCLC cells to cisplatin.

[Polymorphic variants of folate metabolizing genes (C677T and A1298C MTHFR, C1420T SHMT1 and G1958A MTHFD) are not associated with the risk of breast cancer in West Siberian Region of Russia].

Breast cancer is the most incident cancer among women. We investigated the role of polymorphisms of folate metabolizing genes MTHFR (C677T and A1298C), SHMT1 (C1420T) and MTHFD (G1258A) in genetic susceptibility to this type of cancer. We determined allele and genotype frequencies in case (850 women with sporadic form of breast cancer) and control (810 women) groups. None of these polymorphisms was significantly associated with breast cancer risk. To increase statistical power of our study, we conducted a meta-analysis which included published genotype data and the results of our work. Meta-analysis also revealed no significant association of studied SNPs with breast cancer.

[Issues on evolution of CpG islands in genome of Marek's disease virus].

AIM: To study the hypothesis about influence of one form of epigenetic heredity--DNA metylation--on several criteria of pathogenicity of avian herpesviruses using Marek's disease virus (MDV) as a model. MATERIALS AND METHODS: Nucleotide sequences of genomic DNA of different serotypes of Marek's disease virus deposited in GenBank were used for the study. Analysis of distribution of CpG islands intra genome was performed with CPGPLOT program. RESULTS: Distribution and number of CpG islands differed markedly in pathogenic serotype 1 and apathogenic serotypes 2 and 3 of MDV. Diagrams of CpG islands distribution showed that serotypes 2 and 3 have significantly higher numbers of islands and they are evenly distributed across genomes. CONCLUSION: Lower numbers of CpG islands in MDV serotype 1 compared with serotypes 2 and 3 demonstrate presence of evolutionary pressure on pathogenic forms of MDV in order to escape from host cell's control of expression of viral proteins.

[Effect of point substitutions in the MnSOD, GPX1, and GSTP1 genes on the risk of familial and sporadic breast cancers in residents of the Altai region of the Russian Federation].

The frequencies of the polymorphic gene variants MnSOD Ala9Val, GPX1 Pro198Leu, and GSTP1 Ile105 Val were estimated in female residents of Altai krai with breast cancer. The frequency distributions of the genotypes for all genes studied in both patients and control subjects fit the Hardy-Weinberg equilibrium. The estimated frequencies of the genotypes for the studied genes in the control group did not differ from those earlier reported for Caucasoid women living in Europe. The T(rs1050450) allele of the GPX1 gene was demonstrated to protect against sporadic breast cancer (OR = 0.74 (95% CI = 0.58-0.94), p = 0.012). Carriers of the genotype combination MnSOD CC + GPX1 CC were found to have a 1.6 times higher risk of sporadic breast cancer compared to the control group (OR = 1.59 (1.05-2.41), p = 0.0258). The polymorphic loci GSTP1 (rs1695) and MnSOD (rs4880) were not found to be significantly associated with the risk of familial or sporadic breast cancer.

[The role of p53 and NF-kappaB transcription factors in redox-dependent dysregulation of mononuclear leukocyte apoptosis].

The aim of this work was to study programmed death of blood mononuclear leukocytes taken from healthy donors and patients with acute inflammatory diseases (acute appendicitis, community-acquired pneumonia). Cellular p53 and NF-kappaB transcription factors were detected by western blotting. Active form of NF-kappaB was shown to appear in mononuclear leukocytes undergoing oxidative stress in experiment and during acute inflammation, p53 was found only under oxidative stress conditions in vitro. Despite enhanced expression of target gene mRNA of these transcription factors in oxidative stress (proapoptotic protein Bax and antiapoptotic protein Bcl-XL), the resulting vector of p53 and NF-kappaB activation is stimulation of cell's apoptotic reaction.

[Cloning and expression of the gene of chymotrypsin-like protease of human kallikrein-7 in Escherichia coli and isolation of recombinant protein].

A sample of the human cDNA was used to amplify the segment encoding biosynthesis of chymotrypsin-like protease of kallikrein-7 and its cloning into the expressing plasmid pET23a(+). Biosynthesis of KLK-7 in transformed E. coil BL21(DE3) cells was accompanied by formation of insoluble inclusion bodies. The recombinant KLK-7 was extracted from the inclusion bodies using 7 M urea in the presence of 2-mercaptoethanol. The extracted recombinant KLK-7 was purified using methods of metal-chelate and ion-exchange chromatography, converted into a soluble form, and used for preparing monospecific antiserum.