Vol 2, No 4 (2010)

The Russian government has begun creating a series of Technology Platforms (TPs). These platforms are meant to serve as a tool that should help close the gap between science and industry, encourage innovation at enterprises, and allow the government to focus its financial resources on the type of research and development that is of interest to business. The Ministry of Economic Development has issued a request for applications from initiators of TP development, and the government will determine the number of TPs based on the results of a selection process led by experts.

The idea of pharmaceutical clusters is being actively pursued in Russia. Several projects have already been implemented, while others are in the pipeline. There are optimistic reports about regions setting up manufacturing, improving the level of education, and creating jobs, and about pharmaceutical companies receiving infrastructure and tax incentives. Is there reason to expect innovation with pharmaceutical clusters as well? That issue, along with others, was taken up at the International Forum "Innovative Drug Research and Development in Russia" organized by the Adam Smith Institute on November 17-18, 2010, in Moscow.

Hereditary breast-ovarian cancer syndrome contributes to as much as 5-7% of breast cancer (BC) and 10-15% of ovarian cancer (OC) incidence. Mutations in the “canonical” genes BRCA1 and BRCA2 occur in 20-30% of affected pedigrees. In addition to BRCA1 and BRCA2 mutations, germ-line lesions in the CHEK2, NBS1, and PALB2 genes also contribute to familial BC clustering. The epidemiology of hereditary breast-ovarian cancer in Russia has some specific features. The impact of the “founder” effect is surprisingly remarkable: a single mutation, BRCA1 5382insC, accounts for the vast majority of BRCA1 defects across the country. In addition, there are two other recurrent BRCA1 alleles: BRCA1 4153delA and BRCA1 185delAG. Besides BRCA1, in Russia breast cancer is often caused by germ-line alterations in the CHEK2 and NBS1 genes. In contrast to BRCA1 and BRCA2, the CHEK2 and NBS1 heterozygosity does not significantly increase the OC risk. Several Russian breast cancer clinics recently started to investigate the efficacy of cisplatin in the therapy of BRCA1-related cancers; initial results show a unique sensitivity of BRCA1 -associated tumours to this compound.

P66shc is a gene that regulates the level of reactive oxygen species (ROS), apoptosis induction, and lifespan in mammals. Mice knocked out for p66shc have a lifespan ~30% longer and demonstrate an enhanced resistance to oxidative stress and age-related pathologies such as hypercholesterolemia, ischemia, and hyperglycemia. In this respect, p66shc is a promising pharmacological target for the treatment of age-related diseases. In this review, an attempt has been made to survey and put to a critical analysis data concerning the involvement of p66shc in the different signaling pathways that regulate oxidative stress and apoptosis.

This study presents the results of research on DNA polymorphism in children with malignant brain tumors (172 patients, 183 in the control group). Genotyping was performed using an allele-specific tetraprimer reaction for the genes of the first (CYP1A1 (2 sites)) and second phases of xenobiotic detoxication (GSTM1, GSTT1, GSTP1, GSTM3), DNA repair genes XRCC1, XPD (2 sites), OGG1, as well as NOS1 and MTHFR. The increased risk of disease is associated with a minor variant of CYP1A1 (606G) (p = 0.009; OR = 1.50) and a deletion variant of GSTT1, (p = 0.013, OR = 1.96). Maximum disease risk was observed in carriers of double deletions in GSTT1-GSTM1 (p = 0.017, OR = 2.42). The obtained results are discussed in reference to literary data on the risk of malignant brain tumor formation in children and adults.

The present work is devoted to the analysis of the G-quadruplex DNA structure using the bioinformatics method. The interest towards quadruplex DNAs is determined by their involvement in the functioning of telomeres and onco-promoters as well as by the possibility to create on their basis aptamers and nanostructures. Here, we present an algorithm for a general analysis of the polymorphism of the G-quadruplex structure from the data bank PDB using original parameters. 74 structures were grouped according to the following parameters: the number of DNA strands, the number of G-quartets, and the location and orientation of the connecting loops. Two quantitative parameters were used to describe the quadruplex structure: the twist angle between two adjacent quartets (analogous to that for the complementary pair in the duplex DNA) and the quartet planarity (an original parameter). The distribution patterns of these values are specific for each group of quadruplex structures and are dependent upon the type of connecting loops used (diagonal, lateral or propeller). The tetramolecular loopless parallel quadruplex was used as a comparison template. The lateral loops introduce the strongest distortion into the structure of quadruplexes: the values of the twist angles are the lowest and are not typical for the other quadruplex groups. The loops of the diagonal type introduce much weaker deformation into quadruplexes; the structures with propeller loops are characterized by the optimum geometry of G-quartets. Hence, the correlation between the twist angle and the tension in the structure of quadruplex DNA is revealed.

A database of Prostate Cancer Proteomics has been created by using the results of a proteomic study of human prostate carcinoma and benign hyperplasia tissues, and of some human-cultured cell lines (PCP, http://ef.inbi.ras.ru). PCP consists of 7 interrelated modules, each containing four levels of proteomic and biomedical data on the proteins in corresponding tissues or cells. The first data level, onto which each module is based, is a 2DE proteomic reference map where proteins separated by 2D electrophoresis, and subsequently identified by mass-spectrometry, are marked. The results of proteomic experiments form the second data level. The third level contains protein data from published articles and existing databases. The fourth level is formed with direct Internet links to the information on corresponding proteins in the NCBI and UniProt databases. PCP contains data on 359 proteins in total, including 17 potential biomarkers of prostate cancer, particularly AGR2, annexins, S100 proteins, PRO2675, and PRO2044. The database will be useful in a wide range of applications, including studies of molecular mechanisms of the aetiology and pathogenesis of prostate diseases, finding new diagnostic markers, etc.