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Milano, Italy

Greco A.,Progression | Miranda C.,Progression | Pierotti M.A.,Scientific Directorate
Molecular and Cellular Endocrinology | Year: 2010

TRK oncogenes are observed in a consistent fraction of papillary thyroid carcinoma (PTC); they arise from the fusion of the 3′ terminal sequences of the NTRK1/. NGF receptor gene with 5′ terminal sequences of various activating genes, such as TPM3, TPR and TFG. TRK oncoproteins display constitutive tyrosine-kinase activity, leading to in vitro and in vivo transformation. In this review studies performed during the last 20 years will be summarized. The following topics will be illustrated: (a) frequency of TRK oncogenes and correlation with radiation and tumor histopathological features; (b) molecular mechanisms underlying NTRK1 oncogenic rearrangements; (c) molecular and biochemical characterization of TRK oncoproteins, and their mechanism of action; (d) role of activating sequences in the activation of TRK oncoproteins. © 2009 Elsevier Ireland Ltd. Source


Alisi A.,Unit of Metabolic and Autoimmune Liver Diseases | Locatelli M.,Scientific Directorate | Nobili V.,Unit of Metabolic and Autoimmune Liver Diseases
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2010

Purpose of review: The intent of this review is to provide a concise overview of all recent acquisitions in terms of therapies and early noninvasive diagnostic approaches for nonalcoholic fatty liver disease (NAFLD) in children. RECENT FINDINGS: NAFLD is increasingly being diagnosed in children. If undiscovered and if certain risks are present (i.e. obesity), nonalcoholic steatohepatitis, the most severe form of NAFLD, may silently progress to cirrhosis, hepatocarcinoma and liver-related death in adulthood. Current therapies include approaches for reducing the incidence of risk factors (i.e. weight reduction), drugs targeting the major molecular mechanisms thought essential in the pathogenesis of the disease (insulin resistance and oxidative stress) or both, but other novel treatments are under investigation. Summary: Although weight reduction, achieved through a combination of diet and exercise, makes it possible to modify the natural course of simple steatosis, the addition of adequate drugs might also provide a therapeutic action on nonalcoholic steatohepatitis. Moreover, preventive strategies and the design and translation into clinical practice of indices that integrate noninvasive diagnostic tools and serum biomarkers might be a winning approach for improving management of paediatric NAFLD/nonalcoholic steatohepatitis in the coming years. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source


Ranucci M.,Vascular Anesthesia and Intensive Care | Baryshnikova E.,Vascular Anesthesia and Intensive Care | Castelvecchio S.,Vascular Anesthesia and Intensive Care | Pelissero G.,Scientific Directorate
Annals of Thoracic Surgery | Year: 2013

Background: Postoperative bleeding is common after cardiac surgery. Major bleeding (MB) is a determinant of red blood cell (RBC) transfusion, especially in patients with preoperative anemia. Preoperative anemia and RBC transfusions are recognized risk factors for operative mortality. The present study investigates the role of MB as an independent determinant of operative mortality in cardiac surgery. Methods: A single-center retrospective study based on the institutional database of cardiac surgery in the period 2000-2012 was conducted. Sixteen thousand one hundred fifty-four (16,154) consecutive adult patients undergoing cardiac surgery were analyzed. The impact of postoperative bleeding and MB on operative (30 days) mortality was analyzed univariately and after correction for preoperative anemia, RBC transfusions, and other confounders. Results: Postoperative bleeding was significantly (p < 0.001) associated with operative mortality, both in univariate and multivariable models. The main complications associated with MB were thromboembolic complications, infections, and surgical reexploration. In a multivariable model, MB remained an independent predictor of operative mortality (odds ratio, 3.45; 95% confidence interval, 2.78 to 4.28). Preoperative anemia and RBC transfusions coexist in the model, acting with a multiplying effect when associated with MB. Conclusions: Major bleeding is per se a risk factor for operative mortality. However, its deleterious effects are strongly enhanced by RBC transfusions and, to a lesser extent, preoperative anemia. Major bleeding is a partially modifiable risk factor, and adequate preemptive and treatment strategies should be applied to limit this event. © 2013 The Society of Thoracic Surgeons. Source


Putignani L.,Unit of Parasitology | Del Chierico F.,Unit of Metagenomics | Petrucca A.,Unit of Metagenomics | Vernocchi P.,Unit of Metagenomics | And 2 more authors.
Pediatric Research | Year: 2014

The microbiota "organ" is the central bioreactor of the gastrointestinal tract, populated by a total of 10 14 bacteria and characterized by a genomic content (microbiome), which represents more than 100 times the human genome. The microbiota plays an important role in child health by acting as a barrier against pathogens and their invasion with a highly dynamic modality, exerting metabolic multistep functions and stimulating the development of the host immune system, through well-organized programming, which influences all of the growth and aging processes. The advent of "omics" technologies (genomics, proteomics, metabolomics), characterized by complex technological platforms and advanced analytical and computational procedures, has opened new avenues to the knowledge of the gut microbiota ecosystem, clarifying some aspects on the establishment of microbial communities that constitute it, their modulation and active interaction with external stimuli as well as food, within the host genetic variability. With a huge interdisciplinary effort and an interface work between basic, translational, and clinical research, microbiologists, specialists in "-omics" disciplines, and clinicians are now clarifying the role of the microbiota in the programming process of several gut-related diseases, from the physiological symbiosis to the microbial dysbiosis stage, through an integrated systems biology approach.Copyright © 2014 International Pediatric Research Foundation, Inc. Source


Pierotti M.A.,Scientific Directorate | Tamborini E.,Laboratory of Experimental Molecular Pathology | Negri T.,Laboratory of Experimental Molecular Pathology | Pricl S.,Laboratory of Experimental Molecular Pathology | Pilotti S.,University of Trieste
Nature Reviews Clinical Oncology | Year: 2011

Elucidation of the genetic processes leading to neoplastic transformation has identified cancer-promoting molecular alterations that can be selectively targeted by rationally designed therapeutic agents. Protein kinases are druggable targets and have been studied intensively. New methodologies-including crystallography and three-dimensional modeling-have allowed the rational design of potent and selective kinase inhibitors that have already reached the clinical stage. However, despite the clinical success of kinase-targeted therapies, most patients that respond eventually relapse as a result of acquired resistance. Darwinian-type selection of secondary mutations seems to have a major role in this resistance. The emergence and/or expansion of tumor clones containing new mutations in the target kinase and that are drug-insensitive have been observed after chronic treatment. The resistance mechanisms to tyrosine kinase inhibitors, in particular secondary resistant mutations as a consequence of treatment, will be discussed in detail. In particular, this Review will focus on KIT and PDGFRA mutations, which are involved in the pathogenesis of gastrointestinal stromal tumors. Harnessing the selection of mutated variants developed to overcome these resistance mechanisms is an ongoing goal of current research and new strategies to overcome drug resistance is being envisaged. © 2011 Macmillan Publishers Limited. All rights reserved. Source

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