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RESPONSABILE DELLA U. O. |
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Cognome e Nome |
Costelli Paola |
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Qualifica |
PA
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Dipartimento |
Scienze Cliniche e Biologiche |
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Settore Scientifico Disciplinare |
MED/04 |
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E-mail |
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tel |
011-6707062 |
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PERSONALE STRUTTURATO |
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Cognome e Nome |
Riccardo Autelli |
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Qualifica |
Ricercatore
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Dipartimento |
Scienze cliniche e Biologiche
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Ente di appartenenza |
Università di Torino |
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Cognome e Nome |
Fabio Penna |
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Qualifica |
Ricercatore |
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Dipartimento |
Scienze cliniche e Biologiche |
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Ente di appartenenza |
Università di Torino |
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Cognome e Nome |
De Stefanis Daniela
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Qualifica |
Tecnico |
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Dipartimento |
Scienze cliniche e Biologiche |
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Ente di appartenenza |
Università di Torino |
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PERSONALE NON STRUTTURATO |
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Cognome e Nome |
Fabrizio Pin |
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Qualifica |
Dottorando |
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Dipartimento |
Scienze cliniche e Biologiche
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Ente di appartenenza |
Università di Torino |
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Cognome e Nome |
Riccardo Ballarò
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Qualifica |
Dottorando
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Dipartimento |
Scienze cliniche e Biologiche
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Ente di appartenenza |
Università di Torino |
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Cognome e Nome |
Marc Beltrà Bach |
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Qualifica |
Dottorando
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Dipartimento |
Scienze cliniche e Biologiche
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Ente di appartenenza |
Università di Torino |
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LINEE DI RICERCA |
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Pathogenesis of cancer cachexia
Cancer cachexia, a complex syndrome that occurs in most of cancer patients, is characterized by body weight loss and marked skeletal muscle wasting. Cachexia negatively impacts on patient management, tolerance to antineoplastic treatments and quality of life. Recent data suggest that impaired myogenesis and tissue protein hypercatabolism contribute to the pathogenesis of cachexia. In addition, tumor-derived extracellular vescicles (EV) also seem to play a role.
The study is aimed to investigate the pathogenesis of cancer-induced muscle wasting by taking advantage of both in vivo and in vitro model systems, focusing on the following aspects: 1) mitochondrial biogenesis, dynamics, number and function; 2) effects of exercise and/or exercise mimetic drugs in modulating muscle wasting in tumor-bearing animals; 3) muscle-specific microRNAs as mediators and biomarkers of cachexia; 4) role of EVs in mediating the metabolic derangements that characterize cancer cachexia.
Autophagy in cell death and survival
Autophagy is the major intracellular catabolic pathway essential to living cells and represents the most effective mechanism for removal of damaged or unnecessary molecules/organelles. The role of autophagy, however, is not limited to substrate degradation; indeed, it was also suggested to participate to cell death. Autophagy is now recognized as a protective mechanism promoting cell survival in adverse or stress conditions, including hypoxia and redox imbalance.
The research project will mostly focus on liver and breast cancer-derived cell lines and will be aimed at: 1) understanding whether upregulated autophagy plays a key role in the resistance of neoplastic cells to anticancer drugs, 2) identifying the molecular mechanism(s) by which this occurs and 3) evaluating whether selectively targeting autophagy may represent a suitable strategy to overcome resistance of tumor cells to anticancer drugs.
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TECNOLOGIE IN POSSESSO DELL'U. O. |
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- Site-directed mutagenesis
- Eukaryotic transfection and gene expression analysis
- Induction and purification of recombinant proteins in bacteria
- Analysis of protein-protein interaction by two hybrid yeast system
- Muscle-specific in-vivo transfection
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STRUMENTAZIONE |
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Denominazione
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Struttura ove la strumentazione è allocata
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Responsabile della strumentazione
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Flow cytometer
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Dept. of Clinical and Biological Sciences
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Dr. Autelli
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Real Time PCR
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Dept. of Clinical and Biological Science
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Proff. Costelli, Parola
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Image analysis system
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Dept. of Clinical and Biological Science
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Prof. Canuto
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Fluorescence microscopy system
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Dept. of Clinical and Biological Science
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Proff. Costelli, Canuto
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| Gas-cromatograph |
Dept. of Clinical and Biological Science |
Prof. Canuto |
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PUBBLICAZIONI |
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Effect of the specific proteasome inhibitor bortezomib on cancer-related muscle wasting.Penna F, Bonetto A, Aversa Z, Minero VG, Rossi Fanelli F, Costelli P, Muscaritoli M.J Cachexia Sarcopenia Muscle, in press. doi: 10.1002/jcsm.12050
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Experimental cancer cachexia: Evolving strategies for getting closer to the human scenario.Penna F, Busquets S, Argilés JM. Semin Cell Dev Biol. 2015 Sep 3. pii: S1084-9521(15)00161-5. doi: 10.1016/j.semcdb.2015.09.002.
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A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Brandhorst S, Choi IY, Wei M, Cheng CW, Sedrakyan S, Navarrete G, Dubeau L, Yap LP, Park R, Vinciguerra M, Di Biase S, Mirzaei H, Mirisola MG, Childress P, Ji L, Groshen S, Penna F, Odetti P, Perin L, Conti PS, Ikeno Y, Kennedy BK, Cohen P, Morgan TE, Dorff TB, Longo VD.Cell Metab. 2015 Jul 7;22(1):86-99. doi: 10.1016/j.cmet.2015.05.012.
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Hypoxia up-regulates SERPINB3 through HIF-2α in human liver cancer cells.Cannito S, Turato C, Paternostro C, Biasiolo A, Colombatto S, Cambieri I, Quarta S, Novo E, Morello E, Villano G, Fasolato S, Musso T, David E, Tusa I, Rovida E, Autelli R, Smedile A, Cillo U, Pontisso P, Parola M.Oncotarget. 2015; Feb 10;6(4):2206-21.
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In vitro and in vivo conditional sensitization of hepatocellular carcinoma cells to TNF-induced apoptosis by taxol. Minero VG, De Stefanis D, Costelli P, Baccino FM, Bonelli G. Cell Cycle. 2015;14(7):1090-102. doi: 10.1080/15384101.2014.1000695.
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Coming back: autophagy in cachexia.Penna F, Baccino FM, Costelli P.Curr Opin Clin Nutr Metab Care. 2014 May;17(3):241-6. doi: 10.1097/MCO.0000000000000048.
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Autophagic degradation contributes to muscle wasting in cancer cachexia. Penna F, Costamagna D, Pin F, Camperi A, Fanzani A, Chiarpotto EM, Cavallini G, Bonelli G, Baccino FM, Costelli P. Am J Pathol. 2013 Apr;182(4):1367-78. doi: 10.1016/j.ajpath.2012.12.023.
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Sphingosine mediates TNFα-induced lysosomal membrane permeabilization and ensuing programmed cell death in hepatoma cells. Ullio C, Casas J, Brunk UT, Sala G, Fabriàs G, Ghidoni R, Bonelli G, Baccino FM, Autelli R. J Lipid Res. 2012 Jun;53(6):1134-43. doi: 10.1194/jlr.M022384.
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Muscle wasting and impaired myogenesis in tumor bearing mice are prevented by ERK inhibition. Penna F, Costamagna D, Fanzani A, Bonelli G, Baccino FM, Costelli P. PLoS One. 2010 Oct 27;5(10):e13604. doi: 10.1371/journal.pone.0013604.
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Muscle atrophy in experimental cancer cachexia: is the IGF-1 signaling pathway involved? Penna F, Bonetto A, Muscaritoli M, Costamagna D, Minero VG, Bonelli G, Rossi Fanelli F, Baccino FM, Costelli P. Int J Cancer. 2010 Oct 1;127(7):1706-17. doi: 10.1002/ijc.25146.
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DOTTORATI DI RICERCA |
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| Componente U.O. |
Dottorato di Ricerca |
Coordinatore |
Sede |
| Paola Costelli |
Medicina e Terapia Sperimentale |
Prof. Giuseppe Poli |
Torino |
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CONGRESSI C.I.B. |
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| Congressi |
Partecipazione |
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CNB4
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CNB5
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CNB6
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CNB7
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CNB8
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| CNB10 |
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Department of Experimental Medicine and Oncology
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Consorzio (sedi e unità operative) 