Driving Precision Medicine through Proteomics and Metabolomics - 12th Central and Eastern European Proteomic Conference (CEEPC), Bucharest,Romania

As Romanians prepared to celebrate 100 years of the '‘Great Unification of 1918?' which united all provinces into one Romania, the 12^th Central and Eastern European Proteomic Conference (CEEPC) jointly with the 39^th Anniversary of the Institute of Cellular Biology and Pathology '‘N. Simionescu’' (ICBP-NS), held their inaugural meeting at the Romanian Academy in Bucharest – a national forum of highest scientific recognition. With an exciting theme entitled, ‘Advances in Proteomics and Progress in Precision Medicine’, delegates gathered to debate Precision medicine’s revolution in diagnosis and treatment, which now accounts for predictive, preventative, and targeted treatment strategies with informed decisions according to individual’s unique clinical, molecular and genetic profile. Proteomics has a pivotal role to play in furthering precision health and medicine for the benefit of mankind. To this end, CEEPC continues to drive advances in proteomics, metabolomics, and diseases as well as raising awareness of pressing global humanitarian and health-care issues including mental health diseases, aging, chronic diseases, global epidemics and environmental issues. Today, CEEPC is a well-recognized major annual conference with a focused vision and a highly valued ideology as it continues to propagate scientific, medical and proteomic collaborations whilst expanding as more Eastern European countries prepare to join.     

Cancer drug-resistance and a look at specific proteins: Rho GDP-dissociation inhibitor 2, Y-box binding protein 1, and HSP70/90 organizing protein in proteomics clinical application

Resistance to anti-cancer drugs is a well recognized problem and very often it is responsible for failure of the cancer treatment. In this study, the proteome alterations associated with the development of acquired resistance to cyclin-depedent kinases inhibitor bohemine, a promising anti-cancer drug, were analyzed with the primary aim of identifying potential targets of resistance within the cell that could pave a way to selective elimination of specific resistant cell types. A model of parental susceptible CEM T-lymphoblastic leukemia cells and its resistant counterpart CEM-BOH was used and advanced 2-D liquid chromatography was applied to fractionate cellular proteins. Differentially expressed identified proteins were further verified using immunoblotting and immunohistochemistry. Our study has revealed that Rho GDP-dissociation inhibitor 2, Y-box binding protein 1, and the HSP70/90 organizing protein have a critical role to play in resistance to cyclin-depedent kinases inhibitor. The results indicated not only that quantitative protein changes play an important role in drug-resistance, but also that there are various other parameters such as truncation, post-translational modification(s), and subcellular localization of selected proteins. Furthermore, these proteins were validated for their roles in drug resistance using different cell lines resistant to diverse representatives of anti-cancer drugs such as vincristine and daunorubicin.     

Mapping of the secretome of primary isolates of mammalian cells, stem cells and derived cell lines

Within a mammalian organism, the interaction among cells both at short and long distances is mediated by soluble factors released by cells into the extracellular environment. The secreted proteins may involve extracellular matrix proteins, proteinases, growth factors, protein hormones, immunoregulatory cytokines, chemokines or other bioactive molecules that have a direct impact on target cell phenotype. Stem cells of mesenchymal, adipose, neural and embryonic origin, fibroblast feeder cells as well as primary isolates of astrocytes, endothelial and muscle cells have recently become targets of intensive secretome profiling with the search for proteins regulating cell survival, proliferation, differentiation or inflammatory response. Recent advances and challenges of the stem cell and primary cell secretome analysis together with the most relevant results are discussed in this review.     

Proteomics of neural stem cells

The isolation of neural stem cells from fetal and adult mammalian CNS and the demonstration of functional neurogenesis in adult CNS have offered perspectives for treatment of many devastating hereditary and acquired neurological diseases. Due to this enormous potential, neural stem cells are a subject of extensive molecular profiling studies with a search for new markers and regulatory pathways governing their self-renewal as opposed to differentiation. Several in-depth proteomic studies have been conducted on primary or immortalized cultures of neural stem cells and neural progenitor cells, and yet more remains to be done. Additionally, neurons and glial cells have been obtained from embryonic stem cells and mesenchymal stem cells, and proteins associated with the differentiation process have been characterized to a certain degree with a view to further investigations. This review summarizes recent findings relevant to the proteomics of neural stem cells and discusses major proteins significantly regulated during neural stem cell differentiation with a view to their future use in cell-based regenerative and reparative therapy.     

Prevalence of HIV,Hepatitis B and C Infections and an Assessment of HCV-Genotypes and Two IL28B SNPs among People Who Inject Drugs in Three Regions of Nepal

As part of a comprehensive health care programme for people who use drugs in Nepal, HIV and viral hepatitis B and C status—including risk factors, HCV-genotypes and co-infections—as well as two IL28B Single-nucleotide polymorphisms (SNPs) were assessed for a random sample of 401 people who inject drugs in three regions of Nepal: mid-western Terrai (Nepalgunj), the eastern region (Dharan, Biratnagar) and the central region (Kathmandu, Lalitpur and Chitwan). Individuals were included who showed at least a minimum of health care seeking behaviour. This latter criterion was defined by being registered with any organisation offering health services. The average age of the participants was 30.5 yrs, and the average length of intravenous drug use was 8.5 yrs. The prevalence rates of HBsAg, anti-HIV antibodies and HCV-RNA were 3.5%, 13.8% and 41.9%, respectively. Spontaneous HCV clearance was evident in 16% of all of those who tested positive for anti-HCV antibodies. Independent risk factors for HCV-RNA positivity were age, gender, geographical region, duration of injecting drug use, history of imprisonment and HIV co-infection. In the age group ≤24 yrs, the rate of spontaneous HCV clearance was 43.5%. Overall, 59.8% of HCV infections were caused by HCV genotype 3 and 40.2% by HCV genotype 1. No other HCV genotypes were identified in this study. The IL28B SNP rs12979860 and rs8099917 were identified in 122 patients, and 75.4% of all participants had both favourable genotypes rs12979860 C/C and rs8099917 T/T.     

1st Central and Eastern European Proteomic Conference and 3rd Czech Proteomic Conference

The 1st Central and Eastern European Proteomic Conference was organized together with the 3rd Czech Proteomic Conference in the TOP Hotel, Prague in the Czech Republic from the 29th to the 31st October, 2007. The aim was to strengthen links with scientists from Central and Eastern Europe including Russia, which until now have been weak or nonexistent, and to highlight the emergence of excellent proteomic studies from various countries, which until now were not visible.