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Rossi A.,S.G. Moscati Hospital | Torri V.,Laboratory of Methodology for Biomedical Research | Garassino M.C.,Fondazione IRCCS | Porcu L.,Laboratory of Methodology for Biomedical Research | Galetta D.,National Cancer Research Center Giovanni Paolo
Cancer Treatment Reviews | Year: 2014

Breast, colorectal and lung cancers represent the three most incident forms of cancer worldwide. Among these three "big killers", lung cancer is considered the one with the worst prognosis due to its high mortality even in early stages. Due to their more favorable prognosis, breast and colorectal cancers might appear to have benefited from major advances. Most oncologists who are faced with metastatic non-small cell lung cancer (NSCLC) find the reported results very frustrating when compared with those for metastatic breast (MBC) and colorectal cancers (MCRC). The aim of this analysis was to quantify and compare the relative magnitude of overall survival (OS) improvements in the first-line approaches in metastatic NSCLC, MBC and MCRC through the analysis of the main landmark meta-analyses and randomized clinical trials (RCTs) of commercially available drugs. Five items were considered and analyzed for each cancer. Moreover we evaluated the real clinical impact of the results reported by each item on the entire population; for each "big killer" an overall hazard ratio (HR) was estimated: 0.88 (95%+ CI: 0.72-1.07) for MBC, 0.94 (95%+ CI: 0.82-1.07) for MCRC, and about 0.80 (95%+ CI: 0.73-0.90) for advanced NSCLC. We showed that, in the last decades, these three tumors had important and constant OS improvements reached step by step. The relative magnitude of OS improvement seems higher in metastatic NSCLC than MBC and MCRC. © 2013 Elsevier Ltd.

Zuccotti M.,University of Parma | Merico V.,Centro Of Ricerca Interdipartimentale Of Ingegneria Tissutale | Redi C.A.,Fondazione IRCCS | Garagna S.,Centro Of Ricerca Interdipartimentale Of Ingegneria Tissutale
Human Reproduction Update | Year: 2011

Background: A limitation to our ability to distinguish between developmentally competent and incompetent eggs is our still only partial knowledge of the critical features that are needed to make a good egg and when during oogenesis these specific characteristics are acquired. The main objective of this review is to summarize the results of areas of investigation that are contributing to our still inadequate understanding of the molecular aspects of making developmentally competent eggs. Methods: For each area discussed, a systematic search was made using PubMed. The search was without temporal limits but mainly yielded publications between 1982-1999 (23%) and 2000-2011 (77%). Results: Taking an oocyte-centred view, we describe throughout folliculogenesis: (i) the factors that regulate oocyte growth; (ii) the role of oocyte-cumulus cell dialogue; (iii) the epigenetic organization of the oocyte genome and (iv) the storage and regulation of maternal RNAs. Conclusions: The multifaceted complex of factors involved in oocyte growth constitutes the backbone on which oocyte developmental competence is built up. Operating behind the expression of these factors is a specific epigenetic signature established during oogenesis, but our knowledge is only approximate and major efforts will be required for more accurate analyses at specific gene loci. The growing research on small silencing RNAs during oogenesis and early oocyte development is revealing these molecules' critical role in mRNA degra-dation. Our next challenge will be to dissect the complex interactions among the different molecular players identified and to establish the presence of functional links among these factors. © The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

Cordenonsi M.,University of Padua | Zanconato F.,University of Padua | Azzolin L.,University of Padua | Forcato M.,University of Modena and Reggio Emilia | And 11 more authors.
Cell | Year: 2011

Cancer stem cells (CSCs) are proposed to drive tumor initiation and progression. Yet, our understanding of the cellular and molecular mechanisms that underlie CSC properties is limited. Here we show that the activity of TAZ, a transducer of the Hippo pathway, is required to sustain self-renewal and tumor-initiation capacities in breast CSCs. TAZ protein levels and activity are elevated in prospective CSCs and in poorly differentiated human tumors and have prognostic value. Gain of TAZ endows self-renewal capacity to non-CSCs. In epithelial cells, TAZ forms a complex with the cell-polarity determinant Scribble, and loss of Scribble - or induction of the epithelial-mesenchymal transition (EMT) - disrupts the inhibitory association of TAZ with the core Hippo kinases MST and LATS. This study links the CSC concept to the Hippo pathway in breast cancer and reveals a mechanistic basis of the control of Hippo kinases by cell polarity. © 2011 Elsevier Inc.

Iorio M.V.,Fondazione IRCCS | Croce C.M.,Ohio State University
Methods in Molecular Biology | Year: 2013

The evaluation of microRNA profiles has represented one of the first approaches to investigate the aberrant microRNA expression in different human cancers, providing the first experimental evidence of the involvement of these small noncoding RNAs in the tumorigenic process. Currently, these and other methods have been applied to the search of new molecular biomarkers of diagnosis, prognosis, and response to therapy prediction. Here, we described the approach we used for the determination of a miRNA signature unique for human ovarian cancer, first performing a large-scale screening using a custom-made microarray platform, and then validating the obtained data by Northern blot or real-time PCR. © Springer Science+Business Media, New York 2013.

Skirton H.,University of Plymouth | Lewis C.,University of Plymouth | Lewis C.,Genetic Interest Group | Kent A.,Genetic Interest Group | Coviello D.A.,Fondazione IRCCS
European Journal of Human Genetics | Year: 2010

The use of genetics and genomics within a wide range of health-care settings requires health professionals to develop expertise to practise appropriately. There is a need for a common minimum standard of competence in genetics for health professionals in Europe but because of differences in professional education and regulation between European countries, setting curricula may not be practical. Core competences are used as a basis for health professional education in many fields and settings. An Expert Group working under the auspices of the EuroGentest project and European Society of Human Genetics Education Committee agreed that a pragmatic solution to the need to establish common standards for education and practice in genetic health care was to agree to a set of core competences that could apply across Europe. These were agreed through an exhaustive process of consultation with relevant health professionals and patient groups. Sets of competences for practitioners working in primary, secondary and tertiary care have been agreed and were approved by the European Society of Human Genetics. The competences provide an appropriate framework for genetics education of health professionals across national boundaries, and the suggested learning outcomes are available to guide development of curricula that are appropriate to the national context, educational system and health-care setting of the professional involved. Collaboration between individuals from many European countries and professions has resulted in an adaptable framework for both pre-registration and continuing professional education. This competence framework has the potential to improve the quality of genetic health care for patients globally. © 2010 Macmillan Publishers Limited All rights reserved.

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