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      EPMA position paper in cancer: current overview and future perspectives

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          Abstract

          At present, a radical shift in cancer treatment is occurring in terms of predictive, preventive, and personalized medicine (PPPM). Individual patients will participate in more aspects of their healthcare. During the development of PPPM, many rapid, specific, and sensitive new methods for earlier detection of cancer will result in more efficient management of the patient and hence a better quality of life. Coordination of the various activities among different healthcare professionals in primary, secondary, and tertiary care requires well-defined competencies, implementation of training and educational programs, sharing of data, and harmonized guidelines. In this position paper, the current knowledge to understand cancer predisposition and risk factors, the cellular biology of cancer, predictive markers and treatment outcome, the improvement in technologies in screening and diagnosis, and provision of better drug development solutions are discussed in the context of a better implementation of personalized medicine. Recognition of the major risk factors for cancer initiation is the key for preventive strategies (EPMA J. 4(1):6, 2013). Of interest, cancer predisposing syndromes in particular the monogenic subtypes that lead to cancer progression are well defined and one should focus on implementation strategies to identify individuals at risk to allow preventive measures and early screening/diagnosis. Implementation of such measures is disturbed by improper use of the data, with breach of data protection as one of the risks to be heavily controlled. Population screening requires in depth cost-benefit analysis to justify healthcare costs, and the parameters screened should provide information that allow an actionable and deliverable solution, for better healthcare provision.

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          Most cited references310

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          Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs.

          MicroRNAs (miRNAs) are a class of noncoding RNAs that post-transcriptionally regulate gene expression in plants and animals. To investigate the influence of miRNAs on transcript levels, we transfected miRNAs into human cells and used microarrays to examine changes in the messenger RNA profile. Here we show that delivering miR-124 causes the expression profile to shift towards that of brain, the organ in which miR-124 is preferentially expressed, whereas delivering miR-1 shifts the profile towards that of muscle, where miR-1 is preferentially expressed. In each case, about 100 messages were downregulated after 12 h. The 3' untranslated regions of these messages had a significant propensity to pair to the 5' region of the miRNA, as expected if many of these messages are the direct targets of the miRNAs. Our results suggest that metazoan miRNAs can reduce the levels of many of their target transcripts, not just the amount of protein deriving from these transcripts. Moreover, miR-1 and miR-124, and presumably other tissue-specific miRNAs, seem to downregulate a far greater number of targets than previously appreciated, thereby helping to define tissue-specific gene expression in humans.
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            Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study.

            Prevention and control of disease and injury require information about the leading medical causes of illness and exposures or risk factors. The assessment of the public-health importance of these has been hampered by the lack of common methods to investigate the overall, worldwide burden. The Global Burden of Disease Study (GBD) provides a standardised approach to epidemiological assessment and uses a standard unit, the disability-adjusted life year (DALY), to aid comparisons. DALYs for each age-sex group in each GBD region for 107 disorders were calculated, based on the estimates of mortality by cause, incidence, average age of onset, duration, and disability severity. Estimates of the burden and prevalence of exposure in different regions of disorders attributable to malnutrition, poor water supply, sanitation and personal and domestic hygiene, unsafe sex, tobacco use, alcohol, occupation, hypertension, physical inactivity, use of illicit drugs, and air pollution were developed. Developed regions account for 11.6% of the worldwide burden from all causes of death and disability, and account for 90.2% of health expenditure worldwide. Communicable, maternal, perinatal, and nutritional disorders explain 43.9%; non-communicable causes 40.9%; injuries 15.1%; malignant neoplasms 5.1%; neuropsychiatric conditions 10.5%; and cardiovascular conditions 9.7% of DALYs worldwide. The ten leading specific causes of global DALYs are, in descending order, lower respiratory infections, diarrhoeal diseases, perinatal disorders, unipolar major depression, ischaemic heart disease, cerebrovascular disease, tuberculosis, measles, road-traffic accidents, and congenital anomalies. 15.9% of DALYs worldwide are attributable to childhood malnutrition and 6.8% to poor water, and sanitation and personal and domestic hygiene. The three leading contributors to the burden of disease are communicable and perinatal disorders affecting children. The substantial burdens of neuropsychiatric disorders and injuries are under-recognised. The epidemiological transition in terms of DALYs has progressed substantially in China, Latin America and the Caribbean, other Asia and islands, and the middle eastern crescent. If the burdens of disability and death are taken into account, our list differs substantially from other lists of the leading causes of death. DALYs provide a common metric to aid meaningful comparison of the burden of risk factors, diseases, and injuries.
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              MicroRNA biogenesis: coordinated cropping and dicing.

              V Kim (2005)
              The recent discovery of microRNAs (miRNAs) took many by surprise because of their unorthodox features and widespread functions. These tiny, approximately 22-nucleotide, RNAs control several pathways including developmental timing, haematopoiesis, organogenesis, apoptosis, cell proliferation and possibly even tumorigenesis. Among the most pressing questions regarding this unusual class of regulatory miRNA-encoding genes is how miRNAs are produced in cells and how the genes themselves are controlled by various regulatory networks.
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                Author and article information

                Contributors
                godfrey.grech@um.edu.mt
                yjzhan2011@gmail.com
                yoo_akh@ncc.re.kr
                rostbubnov@gmail.com
                Suzanne.Hagan@gcu.ac.uk
                romano.danesi@unipi.it
                Giorgio.Vittadini@bracco.com
                ddesider@uthsc.edu
                Journal
                EPMA J
                EPMA J
                The EPMA Journal
                BioMed Central (London )
                1878-5077
                1878-5085
                15 April 2015
                15 April 2015
                2015
                : 6
                : 1
                : 9
                Affiliations
                [ ]Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
                [ ]Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, China
                [ ]Colorectal Cancer Branch, Division of Translational and Clinical Research I, Research Institute, National Cancer Center, Gyeonggi, 410-769 Republic of Korea
                [ ]Clinical Hospital ‘Pheophania’ of State Management of Affairs Department, Kyiv, Ukraine
                [ ]Zabolotny Institute of Microbiology and Virology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
                [ ]Dept of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
                [ ]Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
                [ ]Bracco Imaging, Centro Ricerche Bracco, San Donato Milanese, Italy
                [ ]Department of Neurology, University of Tennessee Center for Health Science, Memphis, USA
                Article
                30
                10.1186/s13167-015-0030-6
                4407842
                25908947
                86a3d351-56d3-43ba-aae6-74888438e1bf
                © Grech et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 8 February 2015
                : 26 February 2015
                Categories
                Position Article and Guidelines
                Custom metadata
                © The Author(s) 2015

                Molecular medicine
                predictive preventive personalized medicine,risk assessment,expert recommendation,standardization,individual profile,disease modeling,multimodal diagnostics,screening,biomarker,biobank

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