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Sala V.,University of Turin | Bergerone S.,Azienda Ospedaliera Citta Della Salute E Della Science Di Turin | Gatti S.,University of Turin | Gallo S.,University of Turin | And 4 more authors.
Cellular and Molecular Life Sciences | Year: 2014

MicroRNAs (miRNAs) are natural, single-stranded, small RNA molecules which subtly control gene expression. Several studies indicate that specific miRNAs can regulate heart function both in development and disease. Despite prevention programs and new therapeutic agents, cardiovascular disease remains the main cause of death in developed countries. The elevated number of heart failure episodes is mostly due to myocardial infarction (MI). An increasing number of studies have been carried out reporting changes in miRNAs gene expression and exploring their role in MI and heart failure. In this review, we furnish a critical analysis of where the frontier of knowledge has arrived in the fields of basic and translational research on miRNAs in cardiac ischemia. We first summarize the basal information on miRNA biology and regulation, especially concentrating on the feedback loops which control cardiac-enriched miRNAs. A focus on the role of miRNAs in the pathogenesis of myocardial ischemia and in the attenuation of injury is presented. Particular attention is given to cardiomyocyte death (apoptosis and necrosis), fibrosis, neovascularization, and heart failure. Then, we address the potential of miR-diagnosis (miRNAs as disease biomarkers) and miR-drugs (miRNAs as therapeutic targets) for cardiac ischemia and heart failure. Finally, we evaluate the use of miRNAs in the emerging field of regenerative medicine. © 2013 Springer.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-06-2014 | Award Amount: 3.00M | Year: 2015

Breast, colorectal and cervical cancer cause 250,000 deaths each year, representing 20% of EU-cancer mortality. Although important progress has been made in both detection and treatment, there is persisting inequity in progress to reduce its burden. Screening programmes vary substantially between countries and in most long-term effectiveness of screening has not yet been assessed. The objective of EU-TOPIA is to systematically evaluate and quantify the harms and benefits of the running programmes for breast, cervical, and colorectal cancer in all European countries, and identify ways to improve health outcomes and equity for citizens. We will first identify significant inequities in screening outcomes by assessing the key set of quality indicators for benefits and harms in each country. Using these indicators, outcomes and cost-effectiveness of existing cancer screening programmes in 2015 will be estimated. For this, state-of-the-art models of the natural history of the cancers will be constructed, using country-specific data with and from country-specific experts. Barriers hindering implementation of optimal screening programs will be assessed, leading to road maps for improved screening. These road maps contain feasible changes, e.g., to extend or reduce the program, to change the screen test used or change key quality indicators, to perform activities that reduce screen-related harm or incorporate new developments in screening, and provide policymakers with evidence for increased, decreased or optimized use of screening. Capacity for self-evaluation of screening will be built using three web-based tools (monitoring, model-quantification and barrier assessment) explained and trained in workshops with country representatives, also from the Associated Countries. The project will lead to reduced inequity, reduced number of cancer deaths and over-diagnosed cases, and increase in life years gained and better cost-effectiveness by 2025. That is why we call it EU-TOPIA.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.3.1-1 | Award Amount: 7.73M | Year: 2013

Important progress has been made in the field of HPV-disease prevention with the development and implementation of HPV vaccines and HPV DNA screening. In the CoheaHr project, the (cost-) effectiveness of different European preventive strategies will be compared. The goal is to build a reliable and comparable evidence base on the (cost-) effectiveness of these policies implemented under country-specific preventive services conditions. To achieve this goal, a set of specific tasks will be carried out. Three randomized trials will be performed in organised screening settings to determine: i) whether self-collection of specimens for HPV DNA testing is an effective and feasible alternative for physician-based sampling, ii) whether screening intervals can be extended in women vaccinated at young age, iii) whether vaccinating women two years before entering the screening programme will favour the use of HPV screening. The first and third randomized trials are multi-country trials whereas the second trial will be carried out in a cohort of Finnish women vaccinated in 2007. For unvaccinated, 25-45 year old women participating in screening, acceptability and general feasibility of HPV vaccination will be studied in a multi-country demonstration survey. Comparisons by transmission models are included to provide long-term projections for cancer incidence and mortality. Furthermore, the establishment of a standardised joint European data warehouse will be continued and extended for (continuous) evaluation of comparative effectiveness of screening and vaccination policies in Europe. Finally, there will be an ongoing effort for producing systematic reviews and meta-analyses which provide a sustainable resource for evidence. CoheaHr will provide a strong evidence base which enable policy and other decision makers to make informed decision-making on HPV prevention strategies, thereby contributing to strengthening health systems and health services interventions in Europe.

Agency: Cordis | Branch: FP7 | Program: CSA-SA | Phase: HEALTH.2013.4.1-4 | Award Amount: 554.66K | Year: 2013

Diabetes, Cardiovascular and Chronic kidney (DCC) -diseases are relentlessly increasing globally, causing enormous human suffering, premature deaths and unsustainable costs. Leading European research has indisputably pointed that the kidney filtration barrier and its epithelial cell, the podocyte, is a common denominator for the DCC-diseases. However, European excellence and expertise have remained uncoordinated in separate pockets and, consequently, underutilised for full societal benefits and capacity creation to combat the challenges of diabetic, hypertensive and primary kidney diseases. Notably, these diseases are of major healthcare interest and of key importance for discovery intensive biopharma industry. KidneyConnect brings together teams of excellence to underpin nationally funded programs under a) Discovery and Future Technologies b) New Research Platforms c) Translational and d) Clinical Podocyte Research to create connected capacities, access to well trained talents and to optimize strategies for industry-academia cowork. In addition to resource maps, KidneyConnect supports international congresses, training courses, talent coaching, special seminars and builds systematically relations to key stakeholders. Due to the limited funds available, main aims are to provide roadmaps for future efforts, outlines for shared data -and sample repositories, targeted training, societal outreach and, as a result, competitive European funded programs. Our events are arranged as satellites of established meetings and supported by in-kind contribution from partners. The goal is to establish faster translation from discovery to clinical practices by creating dynamic networks, sustainable capacities and outlines for improved kidney disease management. High cohesion and shared resources together with the most prominent European authorities included will guarantee optimized resource usage. Substantial benefits and competitiveness in the huge global markets are to be expected

Zinzani P.L.,S. Orsola Malpighi University Hospital | Viviani S.,Medical Oncology Unit 2 | Anastasia A.,Humanitas Cancer Center | Vitolo U.,Azienda Ospedaliera Citta Della Salute E Della Science Di Turin | And 11 more authors.
Haematologica | Year: 2013

Clinical trial results indicate that brentuximab vedotin brings considerable promise for the treatment of patients with relapsed or refractory Hodgkin's lymphoma. A retrospective multicenter study was conducted on 65 heavily pretreated patients who underwent therapy through a Named Patient Program in Italy (non trial-setting). The primary study endpoint was the objective response rate; secondary endpoints were safety, overall survival and progression- free survival. The best overall response rate (70.7%), including 21.5% complete responses, was observed at the first restaging after the third cycle of treatment. After a median follow up of 13.2 months, the overall survival rate at 20 months was 73.8% while the progression-free survival rate at 20 months was 24.2%. Globally nine patients are in continuous complete response with a median follow up of 14 months (range, 10-19 months). Four patients proceeded to autotransplantation and nine to allotransplantation. The most frequent extra-hematologic toxicity was peripheral neuropathy, observed in 21.5% of cases (9 patients with grade 1/2 and 5 patients with grade 3/4); neurological toxicity led to discontinuation of treatment in three patients and to dose reduction in four. In general the treatment was well tolerated and toxicities, both hematologic and extra-hematologic, were manageable. This report indicates and confirms that brentuximab vedotin as a single agent is effective and safe also when used in standard, everyday clinical practice outside a clinical trial. Best overall responses were recorded after three or four cycles and showed that brentuximab vedotin provides an effective bridge to further therapeutic interventions. © 2013 Ferrata Storti Foundation.

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