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155 results on '"Physiopathologie du cancer du foie"'

1. Guidelines for the use and interpretation of assays for monitoring autophagy.

Author: Molecular and Cellular Biology ; University of Leuven, Laboratoire d'Epigénétique et Cancer ; CNRS - Université Paris XI - Paris Sud, Department of Pharmacology ; Department of Pharmacology, Immunobiologie des Cellules Dendritiques ; INSERM - Institut Pasteur de Paris, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (FEMTO-ST) ; CNRS - Université de Franche-Comté - Université de Technologie de Belfort-Montbeliard - Ecole Nationale Supérieure de Mécanique et des Microtechniques, Telethon Institute for Genetics and Medicine ; Telethon Institute, Medical Genetics ; Federico II University, Department of Molecular and Human Genetics ; Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute ; Texas Children's Hospital, Signalisation et physiopathologie des cellules épithéliales ; INSERM - Université Paris XI - Paris Sud, Dynamique des interactions membranaires normales et pathologiques (DIMNP) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Institut de biochimie et génétique cellulaires (IBGC) ; CNRS - Université Victor Segalen - Bordeaux II, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Celullar and Molecular Medicine ; Celullar and Molecular Medicine, Estrogène, Expression génique et pathologies du Système Nerveux Central (E2SNC) ; Université de Franche-Comté - IFR133, Infection bactérienne, inflammation, et carcinogenèse digestive ; INSERM - IFR50 - Université Nice Sophia Antipolis (UNS), Université Nice Sophia Antipolis (UNS) ; Université Nice Sophia Antipolis (UNS) - PRES Euro-Méditerranéen, Department of Computer Science [Tsukuba] ; University of Tsukuba, Gunma University ; Institute for Molecular & Cellular Regulation, Cell Biology, Physiology and Immunology ; Cell Biology, Physiology and Immunology, Dulbecco Telethon Institute/Department of Biology ; Dulbecco Telethon Institute/Department of Biology, Department of Chemistry and HKU-CAS Joint Laboratory ; University of Hong-Kong, Laboratoire Bordelais de Recherche en Informatique (LaBRI) ; CNRS - Université Sciences et Technologies - Bordeaux I - Université Victor Segalen - Bordeaux II - École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Learning Sciences Lab ; National Institute of Education, Nanyang Technological University, University of California ; University of California, Physiopathologie du cancer du foie ; INSERM - Université Victor Segalen - Bordeaux II, Emory University School of Medicine ; Emory University School of Medicine, Cytokines et Immunologie des Tumeurs Humaines ; INSERM - Institut Gustave Roussy - Université Paris XI - Paris Sud, Biology ; University of Rome"Tor Vergata", Oxford University ; Oxford University, Strathclyde Institute of Pharmacy and Biomedical Sciences ; University of Strathclyde, Interactions Bactéries-Cellules (UIBC) ; Institut national de la recherche agronomique (INRA) - INSERM - Institut Pasteur de Paris, Department of Experimental Medicine and Oncology ; University of Turin, Institut de génomique fonctionnelle (IGF) ; CNRS - INSERM - Université Montpellier I - Université Montpellier II - Sciences et techniques, CNV ; University of Valparaiso, Section of Haemato-oncology ; Institute of cancer research, Régulation de l'expression génétique (REG) ; CNRS - École normale supérieure [ENS] - Paris, Brunel University ; Brunel University, University of New-Mexico ; University of New-Mexico, Facultad de Ciencias Químicas y Farmacéuticas ; Centro de Estudios Moleculares de la Célula, Biochemistry and Molecular Biology ; Biochemistry and Molecular Biology, Dpt. of Cancer & Cell Biology ; University of Cincinnati, Institut Jacques Monod (IJM) ; CNRS - Université Paris VII - Paris Diderot, Virologie humaine ; INSERM - IFR128 - École Normale Supérieure (ENS) - Lyon, Instituto de Investigaciones Biotecnológicas, (IIB-INTECH) ; Universidad Nacional de San Martin, MRC Centre for Developmental Neurobiology ; MRC Centre for Developmental Neurobiology, University of Brescia ; University of Brescia, Immunité infection vaccination ; INSERM - Université Claude Bernard - Lyon I (UCBL) - IFR128, Dept of City and Regional Planning ; Peiking University, Montreal Neurological Institute ; McGill University, Department of Developmental Biology and Neurosciences ; Tohoku University - Graduate School of Life Sciences, Biologie Cellulaire du Noyau (BCN) ; CNRS - Institut Pasteur de Paris, Faculty of Medicine ; University of Ottawa, Institut de recherche en cancérologie de Montpellier (IRCM) ; INSERM - CRLCC Val d'Aurelle - Paul Lamarque - Université Montpellier I, Immunologie et chimie thérapeutiques (ICT) ; CNRS - Cancéropôle du Grand Est, Université de Strasbourg (UNISTRA) ; Université de Strasbourg, Département Digestif ; CHU Nice - Hôpital de l'Archet, Centre méditérannéen de médecine moléculaire (C3M) ; INSERM - Université Nice Sophia Antipolis (UNS), National Institute of Advanced Industrial Science and Technology [Tsukuba] (AIST) ; National Institute for Advanced Industrial Science and Technology - AIST (JAPAN), Department of Oncology ; John Radcliffe Hospital, School of Biochemistry and Immunology ; School of Biochemistry and Immunology, Department of Cellular and Structural Biology, University of Texas Health Science Center ; University of Texas, Laboratoire de Pathologie Clinique et Expérimentale ; CHU Nice, Department of Biochemistry ; University of Hong Kong, Danish Cancer Society ; Institute of Cancer Biology, Institut de biologie et chimie des protéines [Lyon] (IBCP) ; CNRS - Université Claude Bernard - Lyon I (UCBL), Department of Gastroenterology, Hepatology and Endocrinology (MHH) ; Hannover medical school, Cancer Research UK London Research Institute ; Cancer Research UK London Research Institute, Cell Biology, section Radiation & Stress Cell Biology ; UMCG, Univ. of Groningen, Department of Molecular Genetics ; Weizmann Institute of Science, Institute of Immunology ; University Hospital Schleswig-Holstein, Institute for Immunology ; Institute for Immunology, Department of Neuroscience ; University of Texas Southwestern Medical Center at Dallas, Centre de génétique et de physiologie moléculaire et cellulaire (CGphiMC) ; CNRS - Université Claude Bernard - Lyon I (UCBL), Centre de Recherche des Cordeliers ; INSERM - Université Paris V - Paris Descartes - Université Pierre et Marie Curie (UPMC) - Paris VI, Apoptose, cancer et immunité ; INSERM - Institut Gustave Roussy - Université Paris XI - Paris Sud, metabolomics platform ; Institut Gustave Roussy, Pôle de biologie ; Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital européen Georges Pompidou, Université Paris Descartes - Faculté de Médecine (UP5) ; Université Paris V - Paris Descartes - PRES Sorbonne Paris Cité, Department of Molecular Neuroscience ; Department of Molecular Neuroscience, European Organization for Nuclear Research (CERN) ; CERN, Center for Visual Information Technology (CVIT) ; International Institute of Information Technology, Massachusetts Institute of technology [Cambridge] (MIT) ; Massachusetts Institute of Technology (MIT), Department of Biochemistry and Molecular Biology ; University of Washington, Centre for Cancer Biology ; Hanson Institute, Adelaide, Jeune Equipe JE 2526 ; Université d'Auvergne - Clermont-Ferrand I, Institut de Recherche Agronomique (Unité sous contrat USC-2018) ; Institut national de la recherche agronomique (INRA), Facultad de Medicina ; Universidad de Chile, Institut de génétique moléculaire de Montpellier (IGMM) ; CNRS - Université Montpellier II - Sciences et techniques, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC) ; IFR140 - Université de Rennes 1 - IRSET, Centre de génétique moléculaire (CGM) ; CNRS - Université Paris XI - Paris Sud - Université Pierre et Marie Curie (UPMC) - Paris VI, National Cheng Kung University [Taiwan] (NCKU) ; Institute of Basic Medical Sciences, Microenvironnement et Physiopathologie de la Differenciation ; INSERM - Université Paris XI - Paris Sud, Howard Hughes Medical Institute ; Howard Hugues Medical Institute, Southwestern Medical Center ; University of Texas, School of Information science and engineering ; Lanzhou University, School of computer and information ; Hefei University, National Neuroscience Institute ; National Neuroscience Institute, National University of Singapore (NUS) ; NUS, Institut de Mécanique des Fluides et des Solides (IMFS) ; CNRS - Université de Strasbourg - ENGEES, Institut Armand Frappier (IAF) ; Réseau International des Instituts Pasteur - Institut National de la Recherche Scientifique, Central China Normal University ; Central China Normal University, Center for International Blood and Marrow Transplant Research (CIBMTR) ; Medical College Of Wisconsin - Emory University School of Medicine, Departamento de Bioquímica y Biología Molecular ; Universidad de Oviedo - Instituto Universitario de Oncología, Laboratoire d'analyse et d'architecture des systèmes [Toulouse] (LAAS) ; CNRS - Université Paul Sabatier (UPS) - Toulouse III - Institut National Polytechnique de Toulouse - INPT - Institut National des Sciences Appliquées [INSA] - Toulouse, Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Equipe Labellisée par la Ligue Nationale contre le Cancer ; LNCC, Johns Hopkins University (JHU) ; Johns Hopkins University, Institute of Molecular Biosciences, Karl-Franzens University Graz, (IMB) ; Karl-Franzens University Graz, Department of Pediatrics ; Università degli studi di Napoli Federico II, Department of Experimental Pharmacology ; Università degli Study di Napoli Federico II, Drug Research and Evaluation ; Istituto Superiore di Sanita‘, Albert Einstein College of Medicine (ALBERT EINSTEIN COLLEGE OF MEDICINE) ; Albert Einstein College of Medicine, Institute of Molecular Biology and Biotechnology ; Foundation for Research and Technology - Hellas, Institut des Sciences de l'Evolution - Montpellier (ISEM) ; CNRS - Institut de recherche pour le développement [IRD] - Université Montpellier II - Sciences et techniques, Institut de signalisation, biologie du développement et cancer (ISBDC) ; CNRS - Université Nice Sophia Antipolis (UNS), Departments of Neurology ; Departments of Neurology, Vanderbilt University [Nashville] ; Vanderbilt University of Nashville, Departments of Pharmacology ; Departments of Pharmacology, Department of Cell Biology [New Haven] ; Yale University School of Medicine - Howard Hugues Medical Institute, Anatomic Pathology Section, Department of Human Pathology and Oncology ; University of Siena, Harvard Medical School (HMS) ; Harvard University, Depts of Radiation Oncology and Pathology ; Wayne State University - Karmanos Cancer Institute, USC Neuromuscular Center, Department of Neurology ; University of Southern California, Department of Biology ; University of Copenhagen, Department of Cell Biology and Biophysics ; University of Athens, Department of Pathology ; Case Western Reserve University, University of Texas at San Antonio ; University of Texas at San Antonio, Institute of Translational Medicine ; Institute of Translational Medicine, Institute of Biochemistry (IBC) ; Swiss Federal Institute of Technology Zurich - Eidgenössische Technische Hochschule Zürich (ETH), Department of Biology ; University of Rome Tor Vergata, Génétique, physiopathologie et ingénierie du tissu osseux (GéPITOS) ; CNRS - Université Nice Sophia Antipolis (UNS), Innovation Thérapeutique : du Fondamental au Médicament ; CNRS - Institut national de la recherche agronomique (INRA) - INSERM - MEDICEN - Université Paris XI - Paris Sud, Hôpital Antoine Béclère ; Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris XI - Paris Sud, Señalización Celular 4 ; Señalización Celular 4, Department of Molecular Biology ; University of Tuebingen, Department of Neurology Columbia University 650 West 168th Street ; Department of Neurology Columbia University 650 West 168th Street, Department of Pathology and Cell Biology Columbia University 650 West 168th Street ; Department of Pathology and Cell Biology Columbia University 650 West 168th Street, Center for Motor Neuron Biology and Disease Columbia University 650 West 168th Street ; Center for Motor Neuron Biology and Disease Columbia University 650 West 168th Street, Department of Cell Biology and Morphology ; Université de Lausanne, CC 101 ; Université Montpellier II - Sciences et techniques, Department of Cell Biology, Institute of Biomembranes, University Medical Center Utrecht ; Institute of Biomembranes, University Medical Center Utrecht, Service de dermatologie ; CHU Nice, Vieillissement, stress, inflammation ; Université Pierre et Marie Curie (UPMC) - Paris VI, University of Cambridge (UK) (CAM) ; University of Cambridge (UK), The Department of Chemical and Environmental Sciences ; University of Limerick, Fondazione IRCCS Istituto Nazionale dei Tumori ; Fondazione IRCCS Istituto Nazionale dei Tumori, Neurogenetics laboratory ; Neurogenetics laboratory, Department of Pathology ; Otto-von-Guericke University, Experimental Tumor Pathology ; University of Erlangen, Unit of Oculogenomics ; Institute for Research in Ophthalmology", Swiss Federal Institute of Technology ; University of Lausanne, Eye Hospital, Department of Ophthalmology, Jules-Gonin , ; Eye Hospital", Division of regenerative Medicine ; San Raffaele Scientific Institute, ICBM ; Faculty of Medicine - University of Chile, Department of pathology ; Harvard Medical School, Department of Endocrine and Oncology Surgery ; Royal North Shore Hospital, Department of Surgery, Bankstown Hospital and South Western Sydney Clinical School ; University of New South Wales, Medical Research Council Human Immunology Unit ; John Radcliffe Hospital - Weatherall Institute of Molecular Medicine, Department of Pharmacology and Molecular Sciences ; University of Bern, Université de Genève ; Université de Genève, Kimmel Cancer Center, and the Stem Cell Biology and Regenerative Medicine Center ; Thomas Jefferson University, Muscular and Neurodegenerative Disease Unit ; University of Genoa and G. Gaslini Pediatric Institute, Department of Clinical and Experimental Medicine ; Division of Cell Biology; and Linköping Diabetes Research Centre, Cancer Institute ; University College London, Department of Biochemistry and Biophysics ; University of California, San Francisco, Department of Experimental and Diagnostic Medicine and Interdisciplinary Center for Study of inflammation and ER-GenTech ; University of Ferrara, Laboratory of Molecular and Cellular Parasitology - Department of Microbiology ; Yong Loo Lin School of Medicine, National University of Singapore, Center of Microbial and Plant Genetics (CMPG) ; Katholieke Universiteit Leuven, Abramson Cancer Institute and Department of Cancer Biology ; University of Pennsylvania, Instituto de Microbiologia Paulo de Goes ; Universidade Federal do Rio de Janeiro, Immunité Innée et Signalisation ; Institut Pasteur de Paris, Istituto CSS Mendel ; Istituto CSS Mendel, Department of Medical and Surgical Pediatrics ; University Hospital, Messina, Department of Intensive care Medicine ; Katholieke Universiteit Leuven, Department of Cell Biology ; Vrije Universiteit Brussel, Department for Molecular Biomedical Research ; Department for Molecular Biomedical Research, Department of Pediatrics ; University of Padova, Department of Chemistry ; Peking University, Department of Mathematics ; Shanghai University, Sch Mat Sci & Engn ; Aucune, Institut de Recherche Interdisciplinaire (IRI) ; CNRS - Université Lille II - Droit et santé - Université Lille I - Sciences et technologies, Institut d'électronique, de microélectronique et de nanotechnologie (IEMN) ; CNRS - Institut supérieur de l'électronique et du nunérique (ISEN) - Université de Valenciennes et du Hainaut-Cambresis - Université Lille I - Sciences et technologies, Nankai University ; Nankai University, Division of Endocrinology and Diabetes ; University of Oklahoma Health Science Center, Department of Pharmacology and Cancer Biology ; Duke University, Modélisation, Information & Systèmes (MIS) ; Université de Picardie Jules Verne, Department of Experimental Oncology and Molecular Medicine ; Fondazione IRCCS Istituto Nazionale dei Tumori, Institute of Modern Physics ; Chinese Academy of Science (CAS), Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; ganzu Province, Institute of Computing Technology [Biejing] (ICT) ; Chinese Academy of Science (CAS), European Synchrotron Radiation Facility (ESRF) ; ESRF, Plant Physiology Laboratory ; Chinese Academy of Sciences - Botanical Institute of South china, Division of Biopharmaceutics ; Leiden University, The Institute of Environmental Medicine [Stockholm] (IMM) ; Karolinska Institutet, Institut de biochimie et biophysique moléculaire et cellulaire (IBBMC) ; CNRS - Université Paris XI - Paris Sud, Center for Brain Repair and Rehabilitation ; University of Gothenburg - Institute of Neuroscience and Physiology, department of genetics - Institute of biochemistry and biophysics ; institute of biochemistry an biophysics - polish academic of sciences, Departament de Bioquímica i Biologia Molecular ; Universitat de Barcelona - Facultat de Biologia - Institute for Research in Biomedicine - CIBERDEM, Chaperones Research Group ; Chaperones Research Group, Klionsky, Daniel J, Abdalla, Fabio C, Abeliovich, Hagai, Abraham, Robert T, Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A, Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M, Al-Zeer, Munir A, Albert, Matthew L, Albin, Roger L, Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O, Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K, Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Auberger, Patrick, Baba, Misuzu, Backues, Steven K, Baehrecke, Eric H, Bahr, Ben A, Bai, Xue-Yuan, Bailly, Yannick, Baiocchi, Robert, Baldini, Giulia, Balduini, Walter, Ballabio, Andrea, Bamber, Bruce A, Bampton, Edward T W, Bánhegyi, Gábor, Bartholomew, Clinton R, Bassham, Diane C, Bast, Robert C, Batoko, Henri, Bay, Boon-Huat, Beau, Isabelle, Béchet, Daniel M, Begley, Thomas J, Behl, Christian, Behrends, Christian, Bekri, Soumeya, Bellaire, Bryan, Bendall, Linda J, Benetti, Luca, Berliocchi, Laura, Bernardi, Henri, Bernassola, Francesca, Besteiro, Sébastien, Bhatia-Kissova, Ingrid, Bi, Xiaoning, Biard-Piechaczyk, Martine, Blum, Janice S, Boise, Lawrence H, Bonaldo, Paolo, Boone, David L, Bornhauser, Beat C, Bortoluci, Karina R, Bossis, Ioannis, Bost, Frédéric, Bourquin, Jean-Pierre, Boya, Patricia, Boyer-Guittaut, Michaël, Bozhkov, Peter V, Brady, Nathan R, Brancolini, Claudio, Brech, Andreas, Brenman, Jay E, Brennand, Ana, Bresnick, Emery H, Brest, Patrick, Bridges, Dave, Bristol, Molly L, Brookes, Paul S, Brown, Eric J, Brumell, John H, Brunetti-Pierri, Nicola, Brunk, Ulf T, Bulman, Dennis E, Bultman, Scott J, Bultynck, Geert, Burbulla, Lena F, Bursch, Wilfried, Butchar, Jonathan P, Buzgariu, Wanda, Bydlowski, Sergio P, Cadwell, Ken, Cahová, Monika, Cai, Dongsheng, Cai, Jiyang, Cai, Qian, Calabretta, Bruno, Calvo-Garrido, Javier, Camougrand, Nadine, Campanella, Michelangelo, Campos-Salinas, Jenny, Candi, Eleonora, Cao, Lizhi, Caplan, Allan B, Carding, Simon R, Cardoso, Sandra M, Carew, Jennifer S, Carlin, Cathleen R, Carmignac, Virginie, Carneiro, Leticia A M, Carra, Serena, Caruso, Rosario A, Casari, Giorgio, Casas, Caty, Castino, Roberta, Cebollero, Eduardo, Cecconi, Francesco, Celli, Jean, Chaachouay, Hassan, Chae, Han-Jung, Chai, Chee-Yin, Chan, David C, Chan, Edmond Y, Chang, Raymond Chuen-Chung, Che, Chi-Ming, Chen, Ching-Chow, Chen, Guang-Chao, Chen, Guo-Qiang, Chen, Min, Chen, Quan, Chen, Steve S-L, Chen, Wenli, Chen, Xi, Chen, Xiangmei, Chen, Xiequn, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Zhixiang, Cheng, Alan, Cheng, Christopher H K, Cheng, Yan, Cheong, Heesun, Cheong, Jae-Ho, Cherry, Sara, Chess-Williams, Russ, Cheung, Zelda H, Chevet, Eric, Chiang, Hui-Ling, Chiarelli, Roberto, Chiba, Tomoki, Chin, Lih-Shen, Chiou, Shih-Hwa, Chisari, Francis V, Cho, Chi Hin, Cho, Dong-Hyung, Choi, Augustine M K, Choi, Dooseok, Choi, Kyeong Sook, Choi, Mary E, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chu, Charleen T, Chuang, Tsung-Hsien, Chueh, Sheau-Huei, Chun, Taehoon, Chwae, Yong-Joon, Chye, Mee-Len, Ciarcia, Roberto, Ciriolo, Maria R, Clague, Michael J, Clark, Robert S B, Clarke, Peter G H, Clarke, Robert, Codogno, Patrice, Coller, Hilary A, Colombo, María I, Comincini, Sergio, Condello, Maria, Condorelli, Fabrizio, Cookson, Mark R, Coombs, Graham H, Coppens, Isabelle, Corbalan, Ramon, Cossart, Pascale, Costelli, Paola, Costes, Safia, Coto-Montes, Ana, Couve, Eduardo, Coxon, Fraser P, Cregg, James M, Crespo, José L, Cronjé, Marianne J, Cuervo, Ana Maria, Cullen, Joseph J, Czaja, Mark J, D'Amelio, Marcello, Darfeuille-Michaud, Arlette, Davids, Lester M, Davies, Faith E, De Felici, Massimo, De Groot, John F, De Haan, Cornelis A M, De Martino, Luisa, De Milito, Angelo, De Tata, Vincenzo, Debnath, Jayanta, Degterev, Alexei, Dehay, Benjamin, Delbridge, Lea M D, Demarchi, Francesca, Deng, Yi Zhen, Dengjel, Jörn, Dent, Paul, Denton, Donna, Deretic, Vojo, Desai, Shyamal D, Devenish, Rodney J, Di Gioacchino, Mario, Di Paolo, Gilbert, Di Pietro, Chiara, Díaz-Araya, Guillermo, Díaz-Laviada, Inés, Diaz-Meco, Maria T, Diaz-Nido, Javier, Dikic, Ivan, Dinesh-Kumar, Savithramma P, Ding, Wen-Xing, Distelhorst, Clark W, Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dokudovskaya, Svetlana, Dong, Zheng, Dorsey, Frank C, Dosenko, Victor, Dowling, James J, Doxsey, Stephen, Dreux, Marlène, Drew, Mark E, Duan, Qiuhong, Duchosal, Michel A, Duff, Karen, Dugail, Isabelle, Durbeej, Madeleine, Duszenko, Michael, Edelstein, Charles L, Edinger, Aimee L, Egea, Gustavo, Eichinger, Ludwig, Eissa, N Tony, Ekmekcioglu, Suhendan, El-Deiry, Wafik S, Elazar, Zvulun, Elgendy, Mohamed, Ellerby, Lisa M, Eng, Kai Er, Engelbrecht, Anna-Mart, Engelender, Simone, Erenpreisa, Jekaterina, Escalante, Ricardo, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Espert, Lucile, Espina, Virginia, Fan, Huizhou, Fan, Jia, Fan, Qi-Wen, Fan, Zhen, Fang, Shengyun, Fang, Yongqi, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Farré, Jean-Claude, Faure, Mathias, Fechheimer, Marcus, Feng, Carl G, Feng, Jian, Feng, Qili, Feng, Youji, Fésüs, László, Feuer, Ralph, Figueiredo-Pereira, Maria E, Fimia, Gian Maria, Fingar, Diane C, Finkbeiner, Steven, Finkel, Toren, Finley, Kim D, Fiorito, Filomena, Fisher, Edward A, Fisher, Paul B, Flajolet, Marc, Florez-Mcclure, Maria L, Florio, Salvatore, Fon, Edward A, Fornai, Francesco, Fortunato, Franco, Fotedar, Rati, Fowler, Daniel H, Fox, Howard S, Franco, Rodrigo, Frankel, Lisa B, Fransen, Marc, Fuentes, José M, Fueyo, Juan, Fujii, Jun, Fujisaki, Kozo, Fujita, Eriko, Fukuda, Mitsunori, Furukawa, Ruth H, Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galliot, Brigitte, Galy, Vincent, Ganesh, Subramaniam, Ganetzky, Barry, Ganley, Ian G, Gao, Fen-Biao, Gao, George F, Gao, Jinming, Garcia, Lorena, Garcia-Manero, Guillermo, Garcia-Marcos, Mikel, Garmyn, Marjan, Gartel, Andrei L, Gatti, Evelina, Gautel, Mathias, Gawriluk, Thomas R, Gegg, Matthew E, Geng, Jiefei, Germain, Marc, Gestwicki, Jason E, Gewirtz, David A, Ghavami, Saeid, Ghosh, Pradipta, Giammarioli, Anna M, Giatromanolaki, Alexandra N, Gibson, Spencer B, Gilkerson, Robert W, Ginger, Michael L, Goncu, Ebru, Gongora, Céline, Gonzalez, Claudio D, Gonzalez, Ramon, González-Estévez, Cristina, González-Polo, Rosa Ana, Gonzalez-Rey, Elena, Gorbunov, Nikolai V, Gorski, Sharon, Goruppi, Sandro, Gottlieb, Roberta A, Gozuacik, Devrim, Granato, Giovanna Elvira, Grant, Gary D, Green, Kim N, Gregorc, Aleš, Gros, Frédéric, Grose, Charles, Grunt, Thomas W, Gual, Philippe, Guan, Jun-Lin, Guan, Kun-Liang, Guichard, Sylvie M, Gukovskaya, Anna S, Gukovsky, Ilya, Gunst, Jan, Gustafsson, Asa B, Halayko, Andrew J, Hale, Amber N, Halonen, Sandra K, Hamasaki, Maho, Han, Feng, Han, Ting, Hancock, Michael K, Hansen, Malene, Harada, Hisashi, Harada, Masaru, Hardt, Stefan E, Harper, J Wade, Harris, Adrian L, Harris, James, Harris, Steven D, Hébert, Marie-Joseé, Heidenreich, Kim A, Helfrich, Miep H, Helgason, Gudmundur V, Henske, Elizabeth P, Herman, Brian, Herman, Paul K, Hetz, Claudio, Hilfiker, Sabine, Hill, Joseph A, Hocking, Lynne J, Hofman, Paul, Hofmann, Thomas G, Höhfeld, Jörg, Holyoake, Tessa L, Hong, Ming-Huang, Hood, David A, Hotamisligil, Gökhan S, Houwerzijl, Ewout J, Høyer-Hansen, Maria, Hu, Bingren, Hu, Chien-An A, Hu, Hong-Ming, Hua, Ya, Huang, Canhua, Huang, Ju, Huang, Shengbing, Huang, Wei-Pang, Huber, Tobias B, Huh, Won-Ki, Hung, Tai-Ho, Hupp, Ted R, Hur, Gang Min, Hurley, James B, Hussain, Sabah N A, Hussey, Patrick J, Hwang, Jung Jin, Hwang, Seungmin, Ichihara, Atsuhiro, Ilkhanizadeh, Shirin, Inoki, Ken, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L, Ip, Nancy Y, Isaka, Yoshitaka, Ishida, Hiroyuki, Isidoro, Ciro, Isobe, Ken-Ichi, Iwasaki, Akiko, Izquierdo, Marta, Izumi, Yotaro, Jaakkola, Panu M, Jäättelä, Marja, Jackson, George R, Jackson, William T, Janji, Bassam, Jendrach, Marina, Jeon, Ju-Hong, Jeung, Eui-Bae, Jiang, Hong, Jiang, Hongchi, Jiang, Jean X, Jiang, Ming, Jiang, Qing, Jiang, Xuejun, Jiménez, Alberto, Jin, Meiyan, Jin, Shengkan, Joe, Cheol O, Johansen, Terje, Johnson, Daniel E, Johnson, Gail V W, Jones, Nicola L, Joseph, Bertrand, Joseph, Suresh K, Joubert, Annie M, Juhász, Gábor, Juillerat-Jeanneret, Lucienne, Jung, Chang Hwa, Jung, Yong-Keun, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kadowaki, Motoni, Kagedal, Katarina, Kamada, Yoshiaki, Kaminskyy, Vitaliy O, Kampinga, Harm H, Kanamori, Hiromitsu, Kang, Chanhee, Kang, Khong Bee, Kang, Kwang Il, Kang, Rui, Kang, Yoon-A, Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanno, Haruo, Kanthasamy, Anumantha G, Kanthasamy, Arthi, Karantza, Vassiliki, Kaushal, Gur P, Kaushik, Susmita, Kawazoe, Yoshinori, Ke, Po-Yuan, Kehrl, John H, Kelekar, Ameeta, Kerkhoff, Claus, Kessel, David H, Khalil, Hany, Kiel, Jan A K W, Kiger, Amy A, Kihara, Akio, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Hou, Kim, Eun-Kyoung, Kim, Hyung-Ryong, Kim, Jae-Sung, Kim, Jeong Hun, Kim, Jin Cheon, Kim, John K, Kim, Peter K, Kim, Seong Who, Kim, Yong-Sun, Kim, Yonghyun, Kimchi, Adi, Kimmelman, Alec C, King, Jason S, Kinsella, Timothy J, Kirkin, Vladimir, Kirshenbaum, Lorrie A, Kitamoto, Katsuhiko, Kitazato, Kaio, Klein, Ludger, Klimecki, Walter T, Klucken, Jochen, Knecht, Erwin, Ko, Ben C B, Koch, Jan C, Koga, Hiroshi, Koh, Jae-Young, Koh, Young Ho, Koike, Masato, Komatsu, Masaaki, Kominami, Eiki, Kong, Hee Jeong, Kong, Wei-Jia, Korolchuk, Viktor I, Kotake, Yaichiro, Koukourakis, Michael I, Kouri Flores, Juan B, Kovács, Attila L, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Kretz-Remy, Carole, Krichevsky, Anna M, Kroemer, Guido, Krüger, Rejko, Krut, Oleg, Ktistakis, Nicholas T, Kuan, Chia-Yi, Kucharczyk, Roza, Kumar, Ashok, Kumar, Raj, Kumar, Sharad, Kundu, Mondira, Kung, Hsing-Jien, Kurz, Tino, Kwon, Ho Jeong, La Spada, Albert R, Lafont, Frank, Lamark, Trond, Landry, Jacques, Lane, Jon D, Lapaquette, Pierre, Laporte, Jocelyn F, László, Lajos, Lavandero, Sergio, Lavoie, Josée N, Layfield, Robert, Lazo, Pedro A, Le, Weidong, Le Cam, Laurent, Ledbetter, Daniel J, Lee, Alvin J X, Lee, Byung-Wan, Lee, Gyun Min, Lee, Jongdae, Lee, Ju-Hyun, Lee, Michael, Lee, Myung-Shik, Lee, Sug Hyung, Leeuwenburgh, Christiaan, Legembre, Patrick, Legouis, Renaud, Lehmann, Michael, Lei, Huan-Yao, Lei, Qun-Ying, Leib, David A, Leiro, José, Lemasters, John J, Lemoine, Antoinette, Lesniak, Maciej S, Lev, Dina, Levenson, Victor V, Levine, Beth, Levy, Efrat, Li, Faqiang, Li, Jun-Lin, Li, Lian, Li, Sheng, Li, Weijie, Li, Xue-Jun, Li, Yan-Bo, Li, Yi-Ping, Liang, Chengyu, Liang, Qiangrong, Liao, Yung-Feng, Liberski, Pawel P, Lieberman, Andrew, Lim, Hyunjung J, Lim, Kah-Leong, Lim, Kyu, Lin, Chiou-Feng, Lin, Fu-Cheng, Lin, Jian, Lin, Jiandie D, Lin, Kui, Lin, Wan-Wan, Lin, Weei-Chin, Lin, Yi-Ling, Linden, Rafael, Lingor, Paul, Lippincott-Schwartz, Jennifer, Lisanti, Michael P, Liton, Paloma B, Liu, Bo, Liu, Chun-Feng, Liu, Kaiyu, Liu, Leyuan, Liu, Qiong A, Liu, Wei, Liu, Young-Chau, Liu, Yule, Lockshin, Richard A, Lok, Chun-Nam, Lonial, Sagar, Loos, Benjamin, Lopez-Berestein, Gabriel, López-Otín, Carlos, Lossi, Laura, Lotze, Michael T, Lőw, Peter, Lu, Binfeng, Lu, Bingwei, Lu, Bo, Lu, Zhen, Luciano, Frédéric, Lukacs, Nicholas W, Lund, Anders H, Lynch-Day, Melinda A, Ma, Yong, Macian, Fernando, Mackeigan, Jeff P, Macleod, Kay F, Madeo, Frank, Maiuri, Luigi, Maiuri, Maria Chiara, Malagoli, Davide, Malicdan, May Christine V, Malorni, Walter, Man, Na, Mandelkow, Eva-Maria, Manon, Stéphen, Manov, Irena, Mao, Kai, Mao, Xiang, Mao, Zixu, Marambaud, Philippe, Marazziti, Daniela, Marcel, Yves L, Marchbank, Katie, Marchetti, Piero, Marciniak, Stefan J, Marcondes, Mateus, Mardi, Mohsen, Marfe, Gabriella, Mariño, Guillermo, Markaki, Maria, Marten, Mark R, Martin, Seamus J, Martinand-Mari, Camille, Martinet, Wim, Martinez-Vicente, Marta, Masini, Matilde, Matarrese, Paola, Matsuo, Saburo, Matteoni, Raffaele, Mayer, Andreas, Mazure, Nathalie M, Mcconkey, David J, Mcconnell, Melanie J, Mcdermott, Catherine, Mcdonald, Christine, Mcinerney, Gerald M, Mckenna, Sharon L, Mclaughlin, Bethann, Mclean, Pamela J, Mcmaster, Christopher R, Mcquibban, G Angus, Meijer, Alfred J, Meisler, Miriam H, Meléndez, Alicia, Melia, Thomas J, Melino, Gerry, Mena, Maria A, Menendez, Javier A, Menna-Barreto, Rubem F S, Menon, Manoj B, Menzies, Fiona M, Mercer, Carol A, Merighi, Adalberto, Merry, Diane E, Meschini, Stefania, Meyer, Christian G, Meyer, Thomas F, Miao, Chao-Yu, Miao, Jun-Ying, 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Nezis, Ioannis P, Nguyen, Huu Phuc, Nie, Daotai, Nishino, Ichizo, Nislow, Corey, Nixon, Ralph A, Noda, Takeshi, Noegel, Angelika A, Nogalska, Anna, Noguchi, Satoru, Notterpek, Lucia, Novak, Ivana, Nozaki, Tomoyoshi, Nukina, Nobuyuki, Nürnberger, Thorsten, Nyfeler, Beat, Obara, Keisuke, Oberley, Terry D, Oddo, Salvatore, Ogawa, Michinaga, Ohashi, Toya, Okamoto, Koji, Oleinick, Nancy L, Oliver, F Javier, Olsen, Laura J, Olsson, Stefan, Opota, Onya, Osborne, Timothy F, Ostrander, Gary K, Otsu, Kinya, Ou, Jing-Hsiung James, Ouimet, Mireille, Overholtzer, Michael, Ozpolat, Bulent, Paganetti, Paolo, Pagnini, Ugo, Pallet, Nicolas, Palmer, Glen E, Palumbo, Camilla, Pan, Tianhong, Panaretakis, Theocharis, Pandey, Udai Bhan, Papackova, Zuzana, Papassideri, Issidora, Paris, Irmgard, Park, Junsoo, Park, Ohkmae K, Parys, Jan B, Parzych, Katherine R, Patschan, Susann, Patterson, Cam, Pattingre, Sophie, Pawelek, John M, Peng, Jianxin, Perlmutter, David H, Perrotta, Ida, Perry, George, Pervaiz, 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Chile, Institut de génétique moléculaire de Montpellier (IGMM) ; CNRS - Université Montpellier II - Sciences et techniques, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC) ; IFR140 - Université de Rennes 1 - IRSET, Centre de génétique moléculaire (CGM) ; CNRS - Université Paris XI - Paris Sud - Université Pierre et Marie Curie (UPMC) - Paris VI, National Cheng Kung University [Taiwan] (NCKU) ; Institute of Basic Medical Sciences, Microenvironnement et Physiopathologie de la Differenciation ; INSERM - Université Paris XI - Paris Sud, Howard Hughes Medical Institute ; Howard Hugues Medical Institute, Southwestern Medical Center ; University of Texas, School of Information science and engineering ; Lanzhou University, School of computer and information ; Hefei University, National Neuroscience Institute ; National Neuroscience Institute, National University of Singapore (NUS) ; NUS, Institut de Mécanique des Fluides et des Solides (IMFS) ; CNRS - Université de Strasbourg - ENGEES, Institut Armand Frappier (IAF) ; Réseau International des Instituts Pasteur - Institut National de la Recherche Scientifique, Central China Normal University ; Central China Normal University, Center for International Blood and Marrow Transplant Research (CIBMTR) ; Medical College Of Wisconsin - Emory University School of Medicine, Departamento de Bioquímica y Biología Molecular ; Universidad de Oviedo - Instituto Universitario de Oncología, Laboratoire d'analyse et d'architecture des systèmes [Toulouse] (LAAS) ; CNRS - Université Paul Sabatier (UPS) - Toulouse III - Institut National Polytechnique de Toulouse - INPT - Institut National des Sciences Appliquées [INSA] - Toulouse, Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Equipe Labellisée par la Ligue Nationale contre le Cancer ; LNCC, Johns Hopkins University (JHU) ; Johns Hopkins University, Institute of Molecular Biosciences, Karl-Franzens University Graz, (IMB) ; Karl-Franzens University Graz, Department of Pediatrics ; Università degli studi di Napoli Federico II, Department of Experimental Pharmacology ; Università degli Study di Napoli Federico II, Drug Research and Evaluation ; Istituto Superiore di Sanita‘, Albert Einstein College of Medicine (ALBERT EINSTEIN COLLEGE OF MEDICINE) ; Albert Einstein College of Medicine, Institute of Molecular Biology and Biotechnology ; Foundation for Research and Technology - Hellas, Institut des Sciences de l'Evolution - Montpellier (ISEM) ; CNRS - Institut de recherche pour le développement [IRD] - Université Montpellier II - Sciences et techniques, Institut de signalisation, biologie du développement et cancer (ISBDC) ; CNRS - Université Nice Sophia Antipolis (UNS), Departments of Neurology ; Departments of Neurology, Vanderbilt University [Nashville] ; Vanderbilt University of Nashville, Departments of Pharmacology ; Departments of Pharmacology, Department of Cell Biology [New Haven] ; Yale University School of Medicine - Howard Hugues Medical Institute, Anatomic Pathology Section, Department of Human Pathology and Oncology ; University of Siena, Harvard Medical School (HMS) ; Harvard University, Depts of Radiation Oncology and Pathology ; Wayne State University - Karmanos Cancer Institute, USC Neuromuscular Center, Department of Neurology ; University of Southern California, Department of Biology ; University of Copenhagen, Department of Cell Biology and Biophysics ; University of Athens, Department of Pathology ; Case Western Reserve University, University of Texas at San Antonio ; University of Texas at San Antonio, Institute of Translational Medicine ; Institute of Translational Medicine, Institute of Biochemistry (IBC) ; Swiss Federal Institute of Technology Zurich - Eidgenössische Technische Hochschule Zürich (ETH), Department of Biology ; University of Rome Tor Vergata, Génétique, physiopathologie et ingénierie du tissu osseux (GéPITOS) ; CNRS - Université Nice Sophia Antipolis (UNS), Innovation Thérapeutique : du Fondamental au Médicament ; CNRS - Institut national de la recherche agronomique (INRA) - INSERM - MEDICEN - Université Paris XI - Paris Sud, Hôpital Antoine Béclère ; Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris XI - Paris Sud, Señalización Celular 4 ; Señalización Celular 4, Department of Molecular Biology ; University of Tuebingen, Department of Neurology Columbia University 650 West 168th Street ; Department of Neurology Columbia University 650 West 168th Street, Department of Pathology and Cell Biology Columbia University 650 West 168th Street ; Department of Pathology and Cell Biology Columbia University 650 West 168th Street, Center for Motor Neuron Biology and Disease Columbia University 650 West 168th Street ; Center for Motor Neuron Biology and Disease Columbia University 650 West 168th Street, Department of Cell Biology and Morphology ; Université de Lausanne, CC 101 ; Université Montpellier II - Sciences et techniques, Department of Cell Biology, Institute of Biomembranes, University Medical Center Utrecht ; Institute of Biomembranes, University Medical Center Utrecht, Service de dermatologie ; CHU Nice, Vieillissement, stress, inflammation ; Université Pierre et Marie Curie (UPMC) - Paris VI, University of Cambridge (UK) (CAM) ; University of Cambridge (UK), The Department of Chemical and Environmental Sciences ; University of Limerick, Fondazione IRCCS Istituto Nazionale dei Tumori ; Fondazione IRCCS Istituto Nazionale dei Tumori, Neurogenetics laboratory ; Neurogenetics laboratory, Department of Pathology ; Otto-von-Guericke University, Experimental Tumor Pathology ; University of Erlangen, Unit of Oculogenomics ; Institute for Research in Ophthalmology", Swiss Federal Institute of Technology ; University of Lausanne, Eye Hospital, Department of Ophthalmology, Jules-Gonin , ; Eye Hospital", Division of regenerative Medicine ; San Raffaele Scientific Institute, ICBM ; Faculty of Medicine - University of Chile, Department of pathology ; Harvard Medical School, Department of Endocrine and Oncology Surgery ; Royal North Shore Hospital, Department of Surgery, Bankstown Hospital and South Western Sydney Clinical School ; University of New South Wales, Medical Research Council Human Immunology Unit ; John Radcliffe Hospital - Weatherall Institute of Molecular Medicine, Department of Pharmacology and Molecular Sciences ; University of Bern, Université de Genève ; Université de Genève, Kimmel Cancer Center, and the Stem Cell Biology and Regenerative Medicine Center ; Thomas Jefferson University, Muscular and Neurodegenerative Disease Unit ; University of Genoa and G. Gaslini Pediatric Institute, Department of Clinical and Experimental Medicine ; Division of Cell Biology; and Linköping Diabetes Research Centre, Cancer Institute ; University College London, Department of Biochemistry and Biophysics ; University of California, San Francisco, Department of Experimental and Diagnostic Medicine and Interdisciplinary Center for Study of inflammation and ER-GenTech ; University of Ferrara, Laboratory of Molecular and Cellular Parasitology - Department of Microbiology ; Yong Loo Lin School of Medicine, National University of Singapore, Center of Microbial and Plant Genetics (CMPG) ; Katholieke Universiteit Leuven, Abramson Cancer Institute and Department of Cancer Biology ; University of Pennsylvania, Instituto de Microbiologia Paulo de Goes ; Universidade Federal do Rio de Janeiro, Immunité Innée et Signalisation ; Institut Pasteur de Paris, Istituto CSS Mendel ; Istituto CSS Mendel, Department of Medical and Surgical Pediatrics ; University Hospital, Messina, Department of Intensive care Medicine ; Katholieke Universiteit Leuven, Department of Cell Biology ; Vrije Universiteit Brussel, Department for Molecular Biomedical Research ; Department for Molecular Biomedical Research, Department of Pediatrics ; University of Padova, Department of Chemistry ; Peking University, Department of Mathematics ; Shanghai University, Sch Mat Sci & Engn ; Aucune, Institut de Recherche Interdisciplinaire (IRI) ; CNRS - Université Lille II - Droit et santé - Université Lille I - Sciences et technologies, Institut d'électronique, de microélectronique et de nanotechnologie (IEMN) ; CNRS - Institut supérieur de l'électronique et du nunérique (ISEN) - Université de Valenciennes et du Hainaut-Cambresis - Université Lille I - Sciences et technologies, Nankai University ; Nankai University, Division of Endocrinology and Diabetes ; University of Oklahoma Health Science Center, Department of Pharmacology and Cancer Biology ; Duke University, Modélisation, Information & Systèmes (MIS) ; Université de Picardie Jules Verne, Department of Experimental Oncology and Molecular Medicine ; Fondazione IRCCS Istituto Nazionale dei Tumori, Institute of Modern Physics ; Chinese Academy of Science (CAS), Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; ganzu Province, Institute of Computing Technology [Biejing] (ICT) ; Chinese Academy of Science (CAS), European Synchrotron Radiation Facility (ESRF) ; ESRF, Plant Physiology Laboratory ; Chinese Academy of Sciences - Botanical Institute of South china, Division of Biopharmaceutics ; Leiden University, The Institute of Environmental Medicine [Stockholm] (IMM) ; Karolinska Institutet, Institut de biochimie et biophysique moléculaire et cellulaire (IBBMC) ; CNRS - Université Paris XI - Paris Sud, Center for Brain Repair and Rehabilitation ; University of Gothenburg - Institute of Neuroscience and Physiology, department of genetics - Institute of biochemistry and biophysics ; institute of biochemistry an biophysics - polish academic of sciences, Departament de Bioquímica i Biologia Molecular ; Universitat de Barcelona - Facultat de Biologia - Institute for Research in Biomedicine - CIBERDEM, Chaperones Research Group ; Chaperones Research Group, Klionsky, Daniel J, Abdalla, Fabio C, Abeliovich, Hagai, Abraham, Robert T, Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A, Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M, Al-Zeer, Munir A, Albert, Matthew L, Albin, Roger L, Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O, Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K, Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Auberger, Patrick, Baba, Misuzu, Backues, Steven K, Baehrecke, Eric H, Bahr, Ben A, Bai, Xue-Yuan, Bailly, Yannick, Baiocchi, Robert, Baldini, Giulia, Balduini, Walter, Ballabio, Andrea, Bamber, Bruce A, Bampton, Edward T W, Bánhegyi, Gábor, Bartholomew, Clinton R, Bassham, Diane C, Bast, Robert C, Batoko, Henri, Bay, Boon-Huat, Beau, Isabelle, Béchet, Daniel M, Begley, Thomas J, Behl, Christian, Behrends, Christian, Bekri, Soumeya, Bellaire, Bryan, Bendall, Linda J, Benetti, Luca, Berliocchi, Laura, Bernardi, Henri, Bernassola, Francesca, Besteiro, Sébastien, Bhatia-Kissova, Ingrid, Bi, Xiaoning, Biard-Piechaczyk, Martine, Blum, Janice S, Boise, Lawrence H, Bonaldo, Paolo, Boone, David L, Bornhauser, Beat C, Bortoluci, Karina R, Bossis, Ioannis, Bost, Frédéric, Bourquin, Jean-Pierre, Boya, Patricia, Boyer-Guittaut, Michaël, Bozhkov, Peter V, Brady, Nathan R, Brancolini, Claudio, Brech, Andreas, Brenman, Jay E, Brennand, Ana, Bresnick, Emery H, Brest, Patrick, Bridges, Dave, Bristol, Molly L, Brookes, Paul S, Brown, Eric J, Brumell, John H, Brunetti-Pierri, Nicola, Brunk, Ulf T, Bulman, Dennis E, Bultman, Scott J, Bultynck, Geert, Burbulla, Lena F, Bursch, Wilfried, Butchar, Jonathan P, Buzgariu, Wanda, Bydlowski, Sergio P, Cadwell, Ken, Cahová, Monika, Cai, Dongsheng, Cai, Jiyang, Cai, Qian, Calabretta, Bruno, Calvo-Garrido, Javier, Camougrand, Nadine, Campanella, Michelangelo, Campos-Salinas, Jenny, Candi, Eleonora, Cao, Lizhi, Caplan, Allan B, Carding, Simon R, Cardoso, Sandra M, Carew, Jennifer S, Carlin, Cathleen R, Carmignac, Virginie, Carneiro, Leticia A M, Carra, Serena, Caruso, Rosario A, Casari, Giorgio, Casas, Caty, Castino, Roberta, Cebollero, Eduardo, Cecconi, Francesco, Celli, Jean, Chaachouay, Hassan, Chae, Han-Jung, Chai, Chee-Yin, Chan, David C, Chan, Edmond Y, Chang, Raymond Chuen-Chung, Che, Chi-Ming, Chen, Ching-Chow, Chen, Guang-Chao, Chen, Guo-Qiang, Chen, Min, Chen, Quan, Chen, Steve S-L, Chen, Wenli, Chen, Xi, Chen, Xiangmei, Chen, Xiequn, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Zhixiang, Cheng, Alan, Cheng, Christopher H K, Cheng, Yan, Cheong, Heesun, Cheong, Jae-Ho, Cherry, Sara, Chess-Williams, Russ, Cheung, Zelda H, Chevet, Eric, Chiang, Hui-Ling, Chiarelli, Roberto, Chiba, Tomoki, Chin, Lih-Shen, Chiou, Shih-Hwa, Chisari, Francis V, Cho, Chi Hin, Cho, Dong-Hyung, Choi, Augustine M K, Choi, Dooseok, Choi, Kyeong Sook, Choi, Mary E, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chu, Charleen T, Chuang, Tsung-Hsien, Chueh, Sheau-Huei, Chun, Taehoon, Chwae, Yong-Joon, Chye, Mee-Len, Ciarcia, Roberto, Ciriolo, Maria R, Clague, Michael J, Clark, Robert S B, Clarke, Peter G H, Clarke, Robert, Codogno, Patrice, Coller, Hilary A, Colombo, María I, Comincini, Sergio, Condello, Maria, Condorelli, Fabrizio, Cookson, Mark R, Coombs, Graham H, Coppens, Isabelle, Corbalan, Ramon, Cossart, Pascale, Costelli, Paola, Costes, Safia, Coto-Montes, Ana, Couve, Eduardo, Coxon, Fraser P, Cregg, James M, Crespo, José L, Cronjé, Marianne J, Cuervo, Ana Maria, Cullen, Joseph J, Czaja, Mark J, D'Amelio, Marcello, Darfeuille-Michaud, Arlette, Davids, Lester M, Davies, Faith E, De Felici, Massimo, De Groot, John F, De Haan, Cornelis A M, De Martino, Luisa, De Milito, Angelo, De Tata, Vincenzo, Debnath, Jayanta, Degterev, Alexei, Dehay, Benjamin, Delbridge, Lea M D, Demarchi, Francesca, Deng, Yi Zhen, Dengjel, Jörn, Dent, Paul, Denton, Donna, Deretic, Vojo, Desai, Shyamal D, Devenish, Rodney J, Di Gioacchino, Mario, Di Paolo, Gilbert, Di Pietro, Chiara, Díaz-Araya, Guillermo, Díaz-Laviada, Inés, Diaz-Meco, Maria T, Diaz-Nido, Javier, Dikic, Ivan, Dinesh-Kumar, Savithramma P, Ding, Wen-Xing, Distelhorst, Clark W, Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dokudovskaya, Svetlana, Dong, Zheng, Dorsey, Frank C, Dosenko, Victor, Dowling, James J, Doxsey, Stephen, Dreux, Marlène, Drew, Mark E, Duan, Qiuhong, Duchosal, Michel A, Duff, Karen, Dugail, Isabelle, Durbeej, Madeleine, Duszenko, Michael, Edelstein, Charles L, Edinger, Aimee L, Egea, Gustavo, Eichinger, Ludwig, Eissa, N Tony, Ekmekcioglu, Suhendan, El-Deiry, Wafik S, Elazar, Zvulun, Elgendy, Mohamed, Ellerby, Lisa M, Eng, Kai Er, Engelbrecht, Anna-Mart, Engelender, Simone, Erenpreisa, Jekaterina, Escalante, Ricardo, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Espert, Lucile, Espina, Virginia, Fan, Huizhou, Fan, Jia, Fan, Qi-Wen, Fan, Zhen, Fang, Shengyun, Fang, Yongqi, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Farré, Jean-Claude, Faure, Mathias, Fechheimer, Marcus, Feng, Carl G, Feng, Jian, Feng, Qili, Feng, Youji, Fésüs, László, Feuer, Ralph, Figueiredo-Pereira, Maria E, Fimia, Gian Maria, Fingar, Diane C, Finkbeiner, Steven, Finkel, Toren, Finley, Kim D, Fiorito, Filomena, Fisher, Edward A, Fisher, Paul B, Flajolet, Marc, Florez-Mcclure, Maria L, Florio, Salvatore, Fon, Edward A, Fornai, Francesco, Fortunato, Franco, Fotedar, Rati, Fowler, Daniel H, Fox, Howard S, Franco, Rodrigo, Frankel, Lisa B, Fransen, Marc, Fuentes, José M, Fueyo, Juan, Fujii, Jun, Fujisaki, Kozo, Fujita, Eriko, Fukuda, Mitsunori, Furukawa, Ruth H, Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galliot, Brigitte, Galy, Vincent, Ganesh, Subramaniam, Ganetzky, Barry, Ganley, Ian G, Gao, Fen-Biao, Gao, George F, Gao, Jinming, Garcia, Lorena, Garcia-Manero, Guillermo, Garcia-Marcos, Mikel, Garmyn, Marjan, Gartel, Andrei L, Gatti, Evelina, Gautel, Mathias, Gawriluk, Thomas R, Gegg, Matthew E, Geng, Jiefei, Germain, Marc, Gestwicki, Jason E, Gewirtz, David A, Ghavami, Saeid, Ghosh, Pradipta, Giammarioli, Anna M, Giatromanolaki, Alexandra N, Gibson, Spencer B, Gilkerson, Robert W, Ginger, Michael L, Goncu, Ebru, Gongora, Céline, Gonzalez, Claudio D, Gonzalez, Ramon, González-Estévez, Cristina, González-Polo, Rosa Ana, Gonzalez-Rey, Elena, Gorbunov, Nikolai V, Gorski, Sharon, Goruppi, Sandro, Gottlieb, Roberta A, Gozuacik, Devrim, Granato, Giovanna Elvira, Grant, Gary D, Green, Kim N, Gregorc, Aleš, Gros, Frédéric, Grose, Charles, Grunt, Thomas W, Gual, Philippe, Guan, Jun-Lin, Guan, Kun-Liang, Guichard, Sylvie M, Gukovskaya, Anna S, Gukovsky, Ilya, Gunst, Jan, Gustafsson, Asa B, Halayko, Andrew J, Hale, Amber N, Halonen, Sandra K, Hamasaki, Maho, Han, Feng, Han, Ting, Hancock, Michael K, Hansen, Malene, Harada, Hisashi, Harada, Masaru, Hardt, Stefan E, Harper, J Wade, Harris, Adrian L, Harris, James, Harris, Steven D, Hébert, Marie-Joseé, Heidenreich, Kim A, Helfrich, Miep H, Helgason, Gudmundur V, Henske, Elizabeth P, Herman, Brian, Herman, Paul K, Hetz, Claudio, Hilfiker, Sabine, Hill, Joseph A, Hocking, Lynne J, Hofman, Paul, Hofmann, Thomas G, Höhfeld, Jörg, Holyoake, Tessa L, Hong, Ming-Huang, Hood, David A, Hotamisligil, Gökhan S, Houwerzijl, Ewout J, Høyer-Hansen, Maria, Hu, Bingren, Hu, Chien-An A, Hu, Hong-Ming, Hua, Ya, Huang, Canhua, Huang, Ju, Huang, Shengbing, Huang, Wei-Pang, Huber, Tobias B, Huh, Won-Ki, Hung, Tai-Ho, Hupp, Ted R, Hur, Gang Min, Hurley, James B, Hussain, Sabah N A, Hussey, Patrick J, Hwang, Jung Jin, Hwang, Seungmin, Ichihara, Atsuhiro, Ilkhanizadeh, Shirin, Inoki, Ken, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L, Ip, Nancy Y, Isaka, Yoshitaka, Ishida, Hiroyuki, Isidoro, Ciro, Isobe, Ken-Ichi, Iwasaki, Akiko, Izquierdo, Marta, Izumi, Yotaro, Jaakkola, Panu M, Jäättelä, Marja, Jackson, George R, Jackson, William T, Janji, Bassam, Jendrach, Marina, Jeon, Ju-Hong, Jeung, Eui-Bae, Jiang, Hong, Jiang, Hongchi, Jiang, Jean X, Jiang, Ming, Jiang, Qing, Jiang, Xuejun, Jiménez, Alberto, Jin, Meiyan, Jin, Shengkan, Joe, Cheol O, Johansen, Terje, Johnson, Daniel E, Johnson, Gail V W, Jones, Nicola L, Joseph, Bertrand, Joseph, Suresh K, Joubert, Annie M, Juhász, Gábor, Juillerat-Jeanneret, Lucienne, Jung, Chang Hwa, Jung, Yong-Keun, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kadowaki, Motoni, Kagedal, Katarina, Kamada, Yoshiaki, Kaminskyy, Vitaliy O, Kampinga, Harm H, Kanamori, Hiromitsu, Kang, Chanhee, Kang, Khong Bee, Kang, Kwang Il, Kang, Rui, Kang, Yoon-A, Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanno, Haruo, Kanthasamy, Anumantha G, Kanthasamy, Arthi, Karantza, Vassiliki, Kaushal, Gur P, Kaushik, Susmita, Kawazoe, Yoshinori, Ke, Po-Yuan, Kehrl, John H, Kelekar, Ameeta, Kerkhoff, Claus, Kessel, David H, Khalil, Hany, Kiel, Jan A K W, Kiger, Amy A, Kihara, Akio, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Hou, Kim, Eun-Kyoung, Kim, Hyung-Ryong, Kim, Jae-Sung, Kim, Jeong Hun, Kim, Jin Cheon, Kim, John K, Kim, Peter K, Kim, Seong Who, Kim, Yong-Sun, Kim, Yonghyun, Kimchi, Adi, Kimmelman, Alec C, King, Jason S, Kinsella, Timothy J, Kirkin, Vladimir, Kirshenbaum, Lorrie A, Kitamoto, Katsuhiko, Kitazato, Kaio, Klein, Ludger, Klimecki, Walter T, Klucken, Jochen, Knecht, Erwin, Ko, Ben C B, Koch, Jan C, Koga, Hiroshi, Koh, Jae-Young, Koh, Young Ho, Koike, Masato, Komatsu, Masaaki, Kominami, Eiki, Kong, Hee Jeong, Kong, Wei-Jia, Korolchuk, Viktor I, Kotake, Yaichiro, Koukourakis, Michael I, Kouri Flores, Juan B, Kovács, Attila L, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Kretz-Remy, Carole, Krichevsky, Anna M, Kroemer, Guido, Krüger, Rejko, Krut, Oleg, Ktistakis, Nicholas T, Kuan, Chia-Yi, Kucharczyk, Roza, Kumar, Ashok, Kumar, Raj, Kumar, Sharad, Kundu, Mondira, Kung, Hsing-Jien, Kurz, Tino, Kwon, Ho Jeong, La Spada, Albert R, Lafont, Frank, Lamark, Trond, Landry, Jacques, Lane, Jon D, Lapaquette, Pierre, Laporte, Jocelyn F, László, Lajos, Lavandero, Sergio, Lavoie, Josée N, Layfield, Robert, Lazo, Pedro A, Le, Weidong, Le Cam, Laurent, Ledbetter, Daniel J, Lee, Alvin J X, Lee, Byung-Wan, Lee, Gyun Min, Lee, Jongdae, Lee, Ju-Hyun, Lee, Michael, Lee, Myung-Shik, Lee, Sug Hyung, Leeuwenburgh, Christiaan, Legembre, Patrick, Legouis, Renaud, Lehmann, Michael, Lei, Huan-Yao, Lei, Qun-Ying, Leib, David A, Leiro, José, Lemasters, John J, Lemoine, Antoinette, Lesniak, Maciej S, Lev, Dina, Levenson, Victor V, Levine, Beth, Levy, Efrat, Li, Faqiang, Li, Jun-Lin, Li, Lian, Li, Sheng, Li, Weijie, Li, Xue-Jun, Li, Yan-Bo, Li, Yi-Ping, Liang, Chengyu, Liang, Qiangrong, Liao, Yung-Feng, Liberski, Pawel P, Lieberman, Andrew, Lim, Hyunjung J, Lim, Kah-Leong, Lim, Kyu, Lin, Chiou-Feng, Lin, Fu-Cheng, Lin, Jian, Lin, Jiandie D, Lin, Kui, Lin, Wan-Wan, Lin, Weei-Chin, Lin, Yi-Ling, Linden, Rafael, Lingor, Paul, Lippincott-Schwartz, Jennifer, Lisanti, Michael P, Liton, Paloma B, Liu, Bo, Liu, Chun-Feng, Liu, Kaiyu, Liu, Leyuan, Liu, Qiong A, Liu, Wei, Liu, Young-Chau, Liu, Yule, Lockshin, Richard A, Lok, Chun-Nam, Lonial, Sagar, Loos, Benjamin, Lopez-Berestein, Gabriel, López-Otín, Carlos, Lossi, Laura, Lotze, Michael T, Lőw, Peter, Lu, Binfeng, Lu, Bingwei, Lu, Bo, Lu, Zhen, Luciano, Frédéric, Lukacs, Nicholas W, Lund, Anders H, Lynch-Day, Melinda A, Ma, Yong, Macian, Fernando, Mackeigan, Jeff P, Macleod, Kay F, Madeo, Frank, Maiuri, Luigi, Maiuri, Maria Chiara, Malagoli, Davide, Malicdan, May Christine V, Malorni, Walter, Man, Na, Mandelkow, Eva-Maria, Manon, Stéphen, Manov, Irena, Mao, Kai, Mao, Xiang, Mao, Zixu, Marambaud, Philippe, Marazziti, Daniela, Marcel, Yves L, Marchbank, Katie, Marchetti, Piero, Marciniak, Stefan J, Marcondes, Mateus, Mardi, Mohsen, Marfe, Gabriella, Mariño, Guillermo, Markaki, Maria, Marten, Mark R, Martin, Seamus J, Martinand-Mari, Camille, Martinet, Wim, Martinez-Vicente, Marta, Masini, Matilde, Matarrese, Paola, Matsuo, Saburo, Matteoni, Raffaele, Mayer, Andreas, Mazure, Nathalie M, Mcconkey, David J, Mcconnell, Melanie J, Mcdermott, Catherine, Mcdonald, Christine, Mcinerney, Gerald M, Mckenna, Sharon L, Mclaughlin, Bethann, Mclean, Pamela J, Mcmaster, Christopher R, Mcquibban, G Angus, Meijer, Alfred J, Meisler, Miriam H, Meléndez, Alicia, Melia, Thomas J, Melino, Gerry, Mena, Maria A, Menendez, Javier A, Menna-Barreto, Rubem F S, Menon, Manoj B, Menzies, Fiona M, Mercer, Carol A, Merighi, Adalberto, Merry, Diane E, Meschini, Stefania, Meyer, Christian G, Meyer, Thomas F, Miao, Chao-Yu, Miao, Jun-Ying, Michels, Paul A M, Michiels, Carine, Mijaljica, Dalibor, Milojkovic, Ana, Minucci, Saverio, Miracco, Clelia, Miranti, Cindy K, Mitroulis, Ioannis, Miyazawa, Keisuke, Mizushima, Noboru, Mograbi, Baharia, Mohseni, Simin, Molero, Xavier, Mollereau, Bertrand, Mollinedo, Faustino, Momoi, Takashi, Monastyrska, Iryna, Monick, Martha M, Monteiro, Mervyn J, Moore, Michael N, Mora, Rodrigo, Moreau, Kevin, Moreira, Paula I, Moriyasu, Yuji, Moscat, Jorge, Mostowy, Serge, Mottram, Jeremy C, Motyl, Tomasz, Moussa, Charbel E-H, Müller, Sylke, Muller, Sylviane, Münger, Karl, Münz, Christian, Murphy, Leon O, Murphy, Maureen E, Musarò, Antonio, Mysorekar, Indira, Nagata, Eiichiro, Nagata, Kazuhiro, Nahimana, Aimable, Nair, Usha, Nakagawa, Toshiyuki, Nakahira, Kiichi, Nakano, Hiroyasu, Nakatogawa, Hitoshi, Nanjundan, Meera, Naqvi, Naweed I, Narendra, Derek P, Narita, Masashi, Navarro, Miguel, Nawrocki, Steffan T, Nazarko, Taras Y, Nemchenko, Andriy, Netea, Mihai G, Neufeld, Thomas P, Ney, Paul A, Nezis, Ioannis P, Nguyen, Huu Phuc, Nie, Daotai, Nishino, Ichizo, Nislow, Corey, Nixon, Ralph A, Noda, Takeshi, Noegel, Angelika A, Nogalska, Anna, Noguchi, Satoru, Notterpek, Lucia, Novak, Ivana, Nozaki, Tomoyoshi, Nukina, Nobuyuki, Nürnberger, Thorsten, Nyfeler, Beat, Obara, Keisuke, Oberley, Terry D, Oddo, Salvatore, Ogawa, Michinaga, Ohashi, Toya, Okamoto, Koji, Oleinick, Nancy L, Oliver, F Javier, Olsen, Laura J, Olsson, Stefan, Opota, Onya, Osborne, Timothy F, Ostrander, Gary K, Otsu, Kinya, Ou, Jing-Hsiung James, Ouimet, Mireille, Overholtzer, Michael, Ozpolat, Bulent, Paganetti, Paolo, Pagnini, Ugo, Pallet, Nicolas, Palmer, Glen E, Palumbo, Camilla, Pan, Tianhong, Panaretakis, Theocharis, Pandey, Udai Bhan, Papackova, Zuzana, Papassideri, Issidora, Paris, Irmgard, Park, Junsoo, Park, Ohkmae K, Parys, Jan B, Parzych, Katherine R, Patschan, Susann, Patterson, Cam, Pattingre, Sophie, Pawelek, John M, Peng, Jianxin, Perlmutter, David H, Perrotta, Ida, Perry, George, Pervaiz, Shazib, Peter, Matthias, Peters, Godefridus J, Petersen, Morten, Petrovski, Goran, Phang, James M, Piacentini, Mauro, Pierre, Philippe, Pierrefite-Carle, Valérie, Pierron, Gérard, Pinkas-Kramarski, Ronit, Piras, Antonio, Piri, Natik, Platanias, Leonidas C, Pöggeler, Stefanie, Poirot, Marc, Poletti, Angelo, Poüs, Christian, Pozuelo-Rubio, Mercedes, Prætorius-Ibba, Mette, Prasad, Anil, Prescott, Mark, Priault, Muriel, Produit-Zengaffinen, Nathalie, Progulske-Fox, Ann, Proikas-Cezanne, Tassula, Przedborski, Serge, Przyklenk, Karin, Puertollano, Rosa, Puyal, Julien, Qian, Shu-Bing, Qin, Liang, Qin, Zheng-Hong, Quaggin, Susan E, Raben, Nina, Rabinowich, Hannah, Rabkin, Simon W, Rahman, Irfan, Rami, Abdelhaq, Ramm, Georg, Randall, Glenn, Randow, Felix, Rao, V Ashutosh, Rathmell, Jeffrey C, Ravikumar, Brinda, Ray, Swapan K, Reed, Bruce H, Reed, John C, Reggiori, Fulvio, Régnier-Vigouroux, Anne, Reichert, Andreas S, Reiners, John J, Reiter, Russel J, Ren, Jun, Revuelta, José L, Rhodes, Christopher J, Ritis, Konstantinos, Rizzo, Elizete, Robbins, Jeffrey, Roberge, Michel, Roca, Hernan, Roccheri, Maria C, Rocchi, Stephane, Rodemann, H Peter, Rodríguez De Córdoba, Santiago, Rohrer, Bärbel, Roninson, Igor B, Rosen, Kirill, Rost-Roszkowska, Magdalena M, Rouis, Mustapha, Rouschop, Kasper M A, Rovetta, Francesca, Rubin, Brian P, Rubinsztein, David C, Ruckdeschel, Klaus, Rucker, Edmund B, Rudich, Assaf, Rudolf, Emil, Ruiz-Opazo, Nelson, Russo, Rossella, Rusten, Tor Erik, Ryan, Kevin M, Ryter, Stefan W, Sabatini, David M, Sadoshima, Junichi, Saha, Tapas, Saitoh, Tatsuya, Sakagami, Hiroshi, Sakai, Yasuyoshi, Salekdeh, Ghasem Hoseini, Salomoni, Paolo, Salvaterra, Paul M, Salvesen, Guy, Salvioli, Rosa, Sanchez, Anthony M J, Sánchez-Alcázar, José A, Sánchez-Prieto, Ricardo, Sandri, Marco, Sankar, Uma, Sansanwal, Poonam, Santambrogio, Laura, Saran, Shweta, Sarkar, Sovan, Sarwal, Minnie, Sasakawa, Chihiro, Sasnauskiene, Ausra, Sass, Miklós, Sato, Ken, Sato, Miyuki, 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Sinha, Debasish, Sinicrope, Frank A, Sirko, Agnieszka, Siu, Parco M, Sivridis, Efthimios, Skop, Vojtech, Skulachev, Vladimir P, Slack, Ruth S, Smaili, Soraya S, Smith, Duncan R, Soengas, Maria S, Soldati, Thierry, Song, Xueqin, Sood, Anil K, Soong, Tuck Wah, Sotgia, Federica, Spector, Stephen A, Spies, Claudia D, Springer, Wolfdieter, Srinivasula, Srinivasa M, Stefanis, Leonidas, Steffan, Joan S, Stendel, Ruediger, Stenmark, Harald, Stephanou, Anastasis, Stern, Stephan T, Sternberg, Cinthya, Stork, Björn, Strålfors, Peter, Subauste, Carlos S, Sui, Xinbing, Sulzer, David, Sun, Jiaren, Sun, Shi-Yong, Sun, Zhi-Jun, Sung, Joseph J Y, Suzuki, Kuninori, Suzuki, Toshihiko, Swanson, Michele S, Swanton, Charles, Sweeney, Sean T, Sy, Lai-King, Szabadkai, Gyorgy, Tabas, Ira, Taegtmeyer, Heinrich, Tafani, Marco, Takács-Vellai, Krisztina, Takano, Yoshitaka, Takegawa, Kaoru, Takemura, Genzou, Takeshita, Fumihiko, Talbot, Nicholas J, Tan, Kevin S W, Tanaka, Keiji, Tanaka, Kozo, Tang, Daolin, Tang, 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Abstract: International audience, In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused o

2. Guidelines for the use and interpretation of assays for monitoring autophagy.

Author: Molecular and Cellular Biology ; University of Leuven, Laboratoire d'Epigénétique et Cancer ; CNRS - Université Paris XI - Paris Sud, Department of Pharmacology ; Department of Pharmacology, Immunobiologie des Cellules Dendritiques ; INSERM - Institut Pasteur de Paris, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (FEMTO-ST) ; CNRS - Université de Franche-Comté - Université de Technologie de Belfort-Montbeliard - Ecole Nationale Supérieure de Mécanique et des Microtechniques, Telethon Institute for Genetics and Medicine ; Telethon Institute, Medical Genetics ; Federico II University, Department of Molecular and Human Genetics ; Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute ; Texas Children's Hospital, Signalisation et physiopathologie des cellules épithéliales ; INSERM - Université Paris XI - Paris Sud, Dynamique des interactions membranaires normales et pathologiques (DIMNP) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Institut de biochimie et génétique cellulaires (IBGC) ; CNRS - Université Victor Segalen - Bordeaux II, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Celullar and Molecular Medicine ; Celullar and Molecular Medicine, Estrogène, Expression génique et pathologies du Système Nerveux Central (E2SNC) ; Université de Franche-Comté - IFR133, Infection bactérienne, inflammation, et carcinogenèse digestive ; INSERM - IFR50 - Université Nice Sophia Antipolis (UNS), Université Nice Sophia Antipolis (UNS) ; Université Nice Sophia Antipolis (UNS) - PRES Euro-Méditerranéen, Department of Computer Science [Tsukuba] ; University of Tsukuba, Gunma University ; Institute for Molecular & Cellular Regulation, Cell Biology, Physiology and Immunology ; Cell Biology, Physiology and Immunology, Dulbecco Telethon Institute/Department of Biology ; Dulbecco Telethon Institute/Department of Biology, Department of Chemistry and HKU-CAS Joint Laboratory ; University of Hong-Kong, Laboratoire Bordelais de Recherche en Informatique (LaBRI) ; CNRS - Université Sciences et Technologies - Bordeaux I - Université Victor Segalen - Bordeaux II - École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Learning Sciences Lab ; National Institute of Education, Nanyang Technological University, University of California ; University of California, Physiopathologie du cancer du foie ; INSERM - Université Victor Segalen - Bordeaux II, Emory University School of Medicine ; Emory University School of Medicine, Cytokines et Immunologie des Tumeurs Humaines ; INSERM - Institut Gustave Roussy - Université Paris XI - Paris Sud, Biology ; University of Rome"Tor Vergata", Oxford University ; Oxford University, Strathclyde Institute of Pharmacy and Biomedical Sciences ; University of Strathclyde, Interactions Bactéries-Cellules (UIBC) ; Institut national de la recherche agronomique (INRA) - INSERM - Institut Pasteur de Paris, Department of Experimental Medicine and Oncology ; University of Turin, Institut de génomique fonctionnelle (IGF) ; CNRS - INSERM - Université Montpellier I - Université Montpellier II - Sciences et techniques, CNV ; University of Valparaiso, Section of Haemato-oncology ; Institute of cancer research, Régulation de l'expression génétique (REG) ; CNRS - École normale supérieure [ENS] - Paris, Brunel University ; Brunel University, University of New-Mexico ; University of New-Mexico, Facultad de Ciencias Químicas y Farmacéuticas ; Centro de Estudios Moleculares de la Célula, Biochemistry and Molecular Biology ; Biochemistry and Molecular Biology, Dpt. of Cancer & Cell Biology ; University of Cincinnati, Institut Jacques Monod (IJM) ; CNRS - Université Paris VII - Paris Diderot, Virologie humaine ; INSERM - IFR128 - École Normale Supérieure (ENS) - Lyon, Instituto de Investigaciones Biotecnológicas, (IIB-INTECH) ; Universidad Nacional de San Martin, MRC Centre for Developmental Neurobiology ; MRC Centre for Developmental Neurobiology, University of Brescia ; University of Brescia, Immunité infection vaccination ; INSERM - Université Claude Bernard - Lyon I (UCBL) - IFR128, Dept of City and Regional Planning ; Peiking University, Montreal Neurological Institute ; McGill University, Department of Developmental Biology and Neurosciences ; Tohoku University - Graduate School of Life Sciences, Biologie Cellulaire du Noyau (BCN) ; CNRS - Institut Pasteur de Paris, Faculty of Medicine ; University of Ottawa, Institut de recherche en cancérologie de Montpellier (IRCM) ; INSERM - CRLCC Val d'Aurelle - Paul Lamarque - Université Montpellier I, Immunologie et chimie thérapeutiques (ICT) ; CNRS - Cancéropôle du Grand Est, Université de Strasbourg (UNISTRA) ; Université de Strasbourg, Département Digestif ; CHU Nice - Hôpital de l'Archet, Centre méditérannéen de médecine moléculaire (C3M) ; INSERM - Université Nice Sophia Antipolis (UNS), National Institute of Advanced Industrial Science and Technology [Tsukuba] (AIST) ; National Institute for Advanced Industrial Science and Technology - AIST (JAPAN), Department of Oncology ; John Radcliffe Hospital, School of Biochemistry and Immunology ; School of Biochemistry and Immunology, Department of Cellular and Structural Biology, University of Texas Health Science Center ; University of Texas, Laboratoire de Pathologie Clinique et Expérimentale ; CHU Nice, Department of Biochemistry ; University of Hong Kong, Danish Cancer Society ; Institute of Cancer Biology, Institut de biologie et chimie des protéines [Lyon] (IBCP) ; CNRS - Université Claude Bernard - Lyon I (UCBL), Department of Gastroenterology, Hepatology and Endocrinology (MHH) ; Hannover medical school, Cancer Research UK London Research Institute ; Cancer Research UK London Research Institute, Cell Biology, section Radiation & Stress Cell Biology ; UMCG, Univ. of Groningen, Department of Molecular Genetics ; Weizmann Institute of Science, Institute of Immunology ; University Hospital Schleswig-Holstein, Institute for Immunology ; Institute for Immunology, Department of Neuroscience ; University of Texas Southwestern Medical Center at Dallas, Centre de génétique et de physiologie moléculaire et cellulaire (CGphiMC) ; CNRS - Université Claude Bernard - Lyon I (UCBL), Centre de Recherche des Cordeliers ; INSERM - Université Paris V - Paris Descartes - Université Pierre et Marie Curie (UPMC) - Paris VI, Apoptose, cancer et immunité ; INSERM - Institut Gustave Roussy - Université Paris XI - Paris Sud, metabolomics platform ; Institut Gustave Roussy, Pôle de biologie ; Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital européen Georges Pompidou, Université Paris Descartes - Faculté de Médecine (UP5) ; Université Paris V - Paris Descartes - PRES Sorbonne Paris Cité, Department of Molecular Neuroscience ; Department of Molecular Neuroscience, European Organization for Nuclear Research (CERN) ; CERN, Center for Visual Information Technology (CVIT) ; International Institute of Information Technology, Massachusetts Institute of technology [Cambridge] (MIT) ; Massachusetts Institute of Technology (MIT), Department of Biochemistry and Molecular Biology ; University of Washington, Centre for Cancer Biology ; Hanson Institute, Adelaide, Jeune Equipe JE 2526 ; Université d'Auvergne - Clermont-Ferrand I, Institut de Recherche Agronomique (Unité sous contrat USC-2018) ; Institut national de la recherche agronomique (INRA), Facultad de Medicina ; Universidad de Chile, Institut de génétique moléculaire de Montpellier (IGMM) ; CNRS - Université Montpellier II - Sciences et techniques, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC) ; IFR140 - Université de Rennes 1 - IRSET, Centre de génétique moléculaire (CGM) ; CNRS - Université Paris XI - Paris Sud - Université Pierre et Marie Curie (UPMC) - Paris VI, National Cheng Kung University [Taiwan] (NCKU) ; Institute of Basic Medical Sciences, Microenvironnement et Physiopathologie de la Differenciation ; INSERM - Université Paris XI - Paris Sud, Howard Hughes Medical Institute ; Howard Hugues Medical Institute, Southwestern Medical Center ; University of Texas, School of Information science and engineering ; Lanzhou University, School of computer and information ; Hefei University, National Neuroscience Institute ; National Neuroscience Institute, National University of Singapore (NUS) ; NUS, Institut de Mécanique des Fluides et des Solides (IMFS) ; CNRS - Université de Strasbourg - ENGEES, Institut Armand Frappier (IAF) ; Réseau International des Instituts Pasteur - Institut National de la Recherche Scientifique, Central China Normal University ; Central China Normal University, Center for International Blood and Marrow Transplant Research (CIBMTR) ; Medical College Of Wisconsin - Emory University School of Medicine, Departamento de Bioquímica y Biología Molecular ; Universidad de Oviedo - Instituto Universitario de Oncología, Laboratoire d'analyse et d'architecture des systèmes [Toulouse] (LAAS) ; CNRS - Université Paul Sabatier (UPS) - Toulouse III - Institut National Polytechnique de Toulouse - INPT - Institut National des Sciences Appliquées [INSA] - Toulouse, Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Equipe Labellisée par la Ligue Nationale contre le Cancer ; LNCC, Johns Hopkins University (JHU) ; Johns Hopkins University, Institute of Molecular Biosciences, Karl-Franzens University Graz, (IMB) ; Karl-Franzens University Graz, Department of Pediatrics ; Università degli studi di Napoli Federico II, Department of Experimental Pharmacology ; Università degli Study di Napoli Federico II, Drug Research and Evaluation ; Istituto Superiore di Sanita‘, Albert Einstein College of Medicine (ALBERT EINSTEIN COLLEGE OF MEDICINE) ; Albert Einstein College of Medicine, Institute of Molecular Biology and Biotechnology ; Foundation for Research and Technology - Hellas, Institut des Sciences de l'Evolution - Montpellier (ISEM) ; CNRS - Institut de recherche pour le développement [IRD] - Université Montpellier II - Sciences et techniques, Institut de signalisation, biologie du développement et cancer (ISBDC) ; CNRS - Université Nice Sophia Antipolis (UNS), Departments of Neurology ; Departments of Neurology, Vanderbilt University [Nashville] ; Vanderbilt University of Nashville, Departments of Pharmacology ; Departments of Pharmacology, Department of Cell Biology [New Haven] ; Yale University School of Medicine - Howard Hugues Medical Institute, Anatomic Pathology Section, Department of Human Pathology and Oncology ; University of Siena, Harvard Medical School (HMS) ; Harvard University, Depts of Radiation Oncology and Pathology ; Wayne State University - Karmanos Cancer Institute, USC Neuromuscular Center, Department of Neurology ; University of Southern California, Department of Biology ; University of Copenhagen, Department of Cell Biology and Biophysics ; University of Athens, Department of Pathology ; Case Western Reserve University, University of Texas at San Antonio ; University of Texas at San Antonio, Institute of Translational Medicine ; Institute of Translational Medicine, Institute of Biochemistry (IBC) ; Swiss Federal Institute of Technology Zurich - Eidgenössische Technische Hochschule Zürich (ETH), Department of Biology ; University of Rome Tor Vergata, Génétique, physiopathologie et ingénierie du tissu osseux (GéPITOS) ; CNRS - Université Nice Sophia Antipolis (UNS), Innovation Thérapeutique : du Fondamental au Médicament ; CNRS - Institut national de la recherche agronomique (INRA) - INSERM - MEDICEN - Université Paris XI - Paris Sud, Hôpital Antoine Béclère ; Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris XI - Paris Sud, Señalización Celular 4 ; Señalización Celular 4, Department of Molecular Biology ; University of Tuebingen, Department of Neurology Columbia University 650 West 168th Street ; Department of Neurology Columbia University 650 West 168th Street, Department of Pathology and Cell Biology Columbia University 650 West 168th Street ; Department of Pathology and Cell Biology Columbia University 650 West 168th Street, Center for Motor Neuron Biology and Disease Columbia University 650 West 168th Street ; Center for Motor Neuron Biology and Disease Columbia University 650 West 168th Street, Department of Cell Biology and Morphology ; Université de Lausanne, CC 101 ; Université Montpellier II - Sciences et techniques, Department of Cell Biology, Institute of Biomembranes, University Medical Center Utrecht ; Institute of Biomembranes, University Medical Center Utrecht, Service de dermatologie ; CHU Nice, Vieillissement, stress, inflammation ; Université Pierre et Marie Curie (UPMC) - Paris VI, University of Cambridge (UK) (CAM) ; University of Cambridge (UK), The Department of Chemical and Environmental Sciences ; University of Limerick, Fondazione IRCCS Istituto Nazionale dei Tumori ; Fondazione IRCCS Istituto Nazionale dei Tumori, Neurogenetics laboratory ; Neurogenetics laboratory, Department of Pathology ; Otto-von-Guericke University, Experimental Tumor Pathology ; University of Erlangen, Unit of Oculogenomics ; Institute for Research in Ophthalmology", Swiss Federal Institute of Technology ; University of Lausanne, Eye Hospital, Department of Ophthalmology, Jules-Gonin , ; Eye Hospital", Division of regenerative Medicine ; San Raffaele Scientific Institute, ICBM ; Faculty of Medicine - University of Chile, Department of pathology ; Harvard Medical School, Department of Endocrine and Oncology Surgery ; Royal North Shore Hospital, Department of Surgery, Bankstown Hospital and South Western Sydney Clinical School ; University of New South Wales, Medical Research Council Human Immunology Unit ; John Radcliffe Hospital - Weatherall Institute of Molecular Medicine, Department of Pharmacology and Molecular Sciences ; University of Bern, Université de Genève ; Université de Genève, Kimmel Cancer Center, and the Stem Cell Biology and Regenerative Medicine Center ; Thomas Jefferson University, Muscular and Neurodegenerative Disease Unit ; University of Genoa and G. Gaslini Pediatric Institute, Department of Clinical and Experimental Medicine ; Division of Cell Biology; and Linköping Diabetes Research Centre, Cancer Institute ; University College London, Department of Biochemistry and Biophysics ; University of California, San Francisco, Department of Experimental and Diagnostic Medicine and Interdisciplinary Center for Study of inflammation and ER-GenTech ; University of Ferrara, Laboratory of Molecular and Cellular Parasitology - Department of Microbiology ; Yong Loo Lin School of Medicine, National University of Singapore, Center of Microbial and Plant Genetics (CMPG) ; Katholieke Universiteit Leuven, Abramson Cancer Institute and Department of Cancer Biology ; University of Pennsylvania, Instituto de Microbiologia Paulo de Goes ; Universidade Federal do Rio de Janeiro, Immunité Innée et Signalisation ; Institut Pasteur de Paris, Istituto CSS Mendel ; Istituto CSS Mendel, Department of Medical and Surgical Pediatrics ; University Hospital, Messina, Department of Intensive care Medicine ; Katholieke Universiteit Leuven, Department of Cell Biology ; Vrije Universiteit Brussel, Department for Molecular Biomedical Research ; Department for Molecular Biomedical Research, Department of Pediatrics ; University of Padova, Department of Chemistry ; Peking University, Department of Mathematics ; Shanghai University, Sch Mat Sci & Engn ; Aucune, Institut de Recherche Interdisciplinaire (IRI) ; CNRS - Université Lille II - Droit et santé - Université Lille I - Sciences et technologies, Institut d'électronique, de microélectronique et de nanotechnologie (IEMN) ; CNRS - Institut supérieur de l'électronique et du nunérique (ISEN) - Université de Valenciennes et du Hainaut-Cambresis - Université Lille I - Sciences et technologies, Nankai University ; Nankai University, Division of Endocrinology and Diabetes ; University of Oklahoma Health Science Center, Department of Pharmacology and Cancer Biology ; Duke University, Modélisation, Information & Systèmes (MIS) ; Université de Picardie Jules Verne, Department of Experimental Oncology and Molecular Medicine ; Fondazione IRCCS Istituto Nazionale dei Tumori, Institute of Modern Physics ; Chinese Academy of Science (CAS), Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; ganzu Province, Institute of Computing Technology [Biejing] (ICT) ; Chinese Academy of Science (CAS), European Synchrotron Radiation Facility (ESRF) ; ESRF, Plant Physiology Laboratory ; Chinese Academy of Sciences - Botanical Institute of South china, Division of Biopharmaceutics ; Leiden University, The Institute of Environmental Medicine [Stockholm] (IMM) ; Karolinska Institutet, Institut de biochimie et biophysique moléculaire et cellulaire (IBBMC) ; CNRS - Université Paris XI - Paris Sud, Center for Brain Repair and Rehabilitation ; University of Gothenburg - Institute of Neuroscience and Physiology, department of genetics - Institute of biochemistry and biophysics ; institute of biochemistry an biophysics - polish academic of sciences, Departament de Bioquímica i Biologia Molecular ; Universitat de Barcelona - Facultat de Biologia - Institute for Research in Biomedicine - CIBERDEM, Chaperones Research Group ; Chaperones Research Group, Klionsky, Daniel J, Abdalla, Fabio C, Abeliovich, Hagai, Abraham, Robert T, Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A, Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M, Al-Zeer, Munir A, Albert, Matthew L, Albin, Roger L, Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O, Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K, Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Auberger, Patrick, Baba, Misuzu, Backues, Steven K, Baehrecke, Eric H, Bahr, Ben A, Bai, Xue-Yuan, Bailly, Yannick, Baiocchi, Robert, Baldini, Giulia, Balduini, Walter, Ballabio, Andrea, Bamber, Bruce A, Bampton, Edward T W, Bánhegyi, Gábor, Bartholomew, Clinton R, Bassham, Diane C, Bast, Robert C, Batoko, Henri, Bay, Boon-Huat, Beau, Isabelle, Béchet, Daniel M, Begley, Thomas J, Behl, Christian, Behrends, Christian, Bekri, Soumeya, Bellaire, Bryan, Bendall, Linda J, Benetti, Luca, Berliocchi, Laura, Bernardi, Henri, Bernassola, Francesca, Besteiro, Sébastien, Bhatia-Kissova, Ingrid, Bi, Xiaoning, Biard-Piechaczyk, Martine, Blum, Janice S, Boise, Lawrence H, Bonaldo, Paolo, Boone, David L, Bornhauser, Beat C, Bortoluci, Karina R, Bossis, Ioannis, Bost, Frédéric, Bourquin, Jean-Pierre, Boya, Patricia, Boyer-Guittaut, Michaël, Bozhkov, Peter V, Brady, Nathan R, Brancolini, Claudio, Brech, Andreas, Brenman, Jay E, Brennand, Ana, Bresnick, Emery H, Brest, Patrick, Bridges, Dave, Bristol, Molly L, Brookes, Paul S, Brown, Eric J, Brumell, John H, Brunetti-Pierri, Nicola, Brunk, Ulf T, Bulman, Dennis E, Bultman, Scott J, Bultynck, Geert, Burbulla, Lena F, Bursch, Wilfried, Butchar, Jonathan P, Buzgariu, Wanda, Bydlowski, Sergio P, Cadwell, Ken, Cahová, Monika, Cai, Dongsheng, Cai, Jiyang, Cai, Qian, Calabretta, Bruno, Calvo-Garrido, Javier, Camougrand, Nadine, Campanella, Michelangelo, Campos-Salinas, Jenny, Candi, Eleonora, Cao, Lizhi, Caplan, Allan B, Carding, Simon R, Cardoso, Sandra M, Carew, Jennifer S, Carlin, Cathleen R, Carmignac, Virginie, Carneiro, Leticia A M, Carra, Serena, Caruso, Rosario A, Casari, Giorgio, Casas, Caty, Castino, Roberta, Cebollero, Eduardo, Cecconi, Francesco, Celli, Jean, Chaachouay, Hassan, Chae, Han-Jung, Chai, Chee-Yin, Chan, David C, Chan, Edmond Y, Chang, Raymond Chuen-Chung, Che, Chi-Ming, Chen, Ching-Chow, Chen, Guang-Chao, Chen, Guo-Qiang, Chen, Min, Chen, Quan, Chen, Steve S-L, Chen, Wenli, Chen, Xi, Chen, Xiangmei, Chen, Xiequn, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Zhixiang, Cheng, Alan, Cheng, Christopher H K, Cheng, Yan, Cheong, Heesun, Cheong, Jae-Ho, Cherry, Sara, Chess-Williams, Russ, Cheung, Zelda H, Chevet, Eric, Chiang, Hui-Ling, Chiarelli, Roberto, Chiba, Tomoki, Chin, Lih-Shen, Chiou, Shih-Hwa, Chisari, Francis V, Cho, Chi Hin, Cho, Dong-Hyung, Choi, Augustine M K, Choi, Dooseok, Choi, Kyeong Sook, Choi, Mary E, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chu, Charleen T, Chuang, Tsung-Hsien, Chueh, Sheau-Huei, Chun, Taehoon, Chwae, Yong-Joon, Chye, Mee-Len, Ciarcia, Roberto, Ciriolo, Maria R, Clague, Michael J, Clark, Robert S B, Clarke, Peter G H, Clarke, Robert, Codogno, Patrice, Coller, Hilary A, Colombo, María I, Comincini, Sergio, Condello, Maria, Condorelli, Fabrizio, Cookson, Mark R, Coombs, Graham H, Coppens, Isabelle, Corbalan, Ramon, Cossart, Pascale, Costelli, Paola, Costes, Safia, Coto-Montes, Ana, Couve, Eduardo, Coxon, Fraser P, Cregg, James M, Crespo, José L, Cronjé, Marianne J, Cuervo, Ana Maria, Cullen, Joseph J, Czaja, Mark J, D'Amelio, Marcello, Darfeuille-Michaud, Arlette, Davids, Lester M, Davies, Faith E, De Felici, Massimo, De Groot, John F, De Haan, Cornelis A M, De Martino, Luisa, De Milito, Angelo, De Tata, Vincenzo, Debnath, Jayanta, Degterev, Alexei, Dehay, Benjamin, Delbridge, Lea M D, Demarchi, Francesca, Deng, Yi Zhen, Dengjel, Jörn, Dent, Paul, Denton, Donna, Deretic, Vojo, Desai, Shyamal D, Devenish, Rodney J, Di Gioacchino, Mario, Di Paolo, Gilbert, Di Pietro, Chiara, Díaz-Araya, Guillermo, Díaz-Laviada, Inés, Diaz-Meco, Maria T, Diaz-Nido, Javier, Dikic, Ivan, Dinesh-Kumar, Savithramma P, Ding, Wen-Xing, Distelhorst, Clark W, Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dokudovskaya, Svetlana, Dong, Zheng, Dorsey, Frank C, Dosenko, Victor, Dowling, James J, Doxsey, Stephen, Dreux, Marlène, Drew, Mark E, Duan, Qiuhong, Duchosal, Michel A, Duff, Karen, Dugail, Isabelle, Durbeej, Madeleine, Duszenko, Michael, Edelstein, Charles L, Edinger, Aimee L, Egea, Gustavo, Eichinger, Ludwig, Eissa, N Tony, Ekmekcioglu, Suhendan, El-Deiry, Wafik S, Elazar, Zvulun, Elgendy, Mohamed, Ellerby, Lisa M, Eng, Kai Er, Engelbrecht, Anna-Mart, Engelender, Simone, Erenpreisa, Jekaterina, Escalante, Ricardo, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Espert, Lucile, Espina, Virginia, Fan, Huizhou, Fan, Jia, Fan, Qi-Wen, Fan, Zhen, Fang, Shengyun, Fang, Yongqi, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Farré, Jean-Claude, Faure, Mathias, Fechheimer, Marcus, Feng, Carl G, Feng, Jian, Feng, Qili, Feng, Youji, Fésüs, László, Feuer, Ralph, Figueiredo-Pereira, Maria E, Fimia, Gian Maria, Fingar, Diane C, Finkbeiner, Steven, Finkel, Toren, Finley, Kim D, Fiorito, Filomena, Fisher, Edward A, Fisher, Paul B, Flajolet, Marc, Florez-Mcclure, Maria L, Florio, Salvatore, Fon, Edward A, Fornai, Francesco, Fortunato, Franco, Fotedar, Rati, Fowler, Daniel H, Fox, Howard S, Franco, Rodrigo, Frankel, Lisa B, Fransen, Marc, Fuentes, José M, Fueyo, Juan, Fujii, Jun, Fujisaki, Kozo, Fujita, Eriko, Fukuda, Mitsunori, Furukawa, Ruth H, Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galliot, Brigitte, Galy, Vincent, Ganesh, Subramaniam, Ganetzky, Barry, Ganley, Ian G, Gao, Fen-Biao, Gao, George F, Gao, Jinming, Garcia, Lorena, Garcia-Manero, Guillermo, Garcia-Marcos, Mikel, Garmyn, Marjan, Gartel, Andrei L, Gatti, Evelina, Gautel, Mathias, Gawriluk, Thomas R, Gegg, Matthew E, Geng, Jiefei, Germain, Marc, Gestwicki, Jason E, Gewirtz, David A, Ghavami, Saeid, Ghosh, Pradipta, Giammarioli, Anna M, Giatromanolaki, Alexandra N, Gibson, Spencer B, Gilkerson, Robert W, Ginger, Michael L, Goncu, Ebru, Gongora, Céline, Gonzalez, Claudio D, Gonzalez, Ramon, González-Estévez, Cristina, González-Polo, Rosa Ana, Gonzalez-Rey, Elena, Gorbunov, Nikolai V, Gorski, Sharon, Goruppi, Sandro, Gottlieb, Roberta A, Gozuacik, Devrim, Granato, Giovanna Elvira, Grant, Gary D, Green, Kim N, Gregorc, Aleš, Gros, Frédéric, Grose, Charles, Grunt, Thomas W, Gual, Philippe, Guan, Jun-Lin, Guan, Kun-Liang, Guichard, Sylvie M, Gukovskaya, Anna S, Gukovsky, Ilya, Gunst, Jan, Gustafsson, Asa B, Halayko, Andrew J, Hale, Amber N, Halonen, Sandra K, Hamasaki, Maho, Han, Feng, Han, Ting, Hancock, Michael K, Hansen, Malene, Harada, Hisashi, Harada, Masaru, Hardt, Stefan E, Harper, J Wade, Harris, Adrian L, Harris, James, Harris, Steven D, Hébert, Marie-Joseé, Heidenreich, Kim A, Helfrich, Miep H, Helgason, Gudmundur V, Henske, Elizabeth P, Herman, Brian, Herman, Paul K, Hetz, Claudio, Hilfiker, Sabine, Hill, Joseph A, Hocking, Lynne J, Hofman, Paul, Hofmann, Thomas G, Höhfeld, Jörg, Holyoake, Tessa L, Hong, Ming-Huang, Hood, David A, Hotamisligil, Gökhan S, Houwerzijl, Ewout J, Høyer-Hansen, Maria, Hu, Bingren, Hu, Chien-An A, Hu, Hong-Ming, Hua, Ya, Huang, Canhua, Huang, Ju, Huang, Shengbing, Huang, Wei-Pang, Huber, Tobias B, Huh, Won-Ki, Hung, Tai-Ho, Hupp, Ted R, Hur, Gang Min, Hurley, James B, Hussain, Sabah N A, Hussey, Patrick J, Hwang, Jung Jin, Hwang, Seungmin, Ichihara, Atsuhiro, Ilkhanizadeh, Shirin, Inoki, Ken, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L, Ip, Nancy Y, Isaka, Yoshitaka, Ishida, Hiroyuki, Isidoro, Ciro, Isobe, Ken-Ichi, Iwasaki, Akiko, Izquierdo, Marta, Izumi, Yotaro, Jaakkola, Panu M, Jäättelä, Marja, Jackson, George R, Jackson, William T, Janji, Bassam, Jendrach, Marina, Jeon, Ju-Hong, Jeung, Eui-Bae, Jiang, Hong, Jiang, Hongchi, Jiang, Jean X, Jiang, Ming, Jiang, Qing, Jiang, Xuejun, Jiménez, Alberto, Jin, Meiyan, Jin, Shengkan, Joe, Cheol O, Johansen, Terje, Johnson, Daniel E, Johnson, Gail V W, Jones, Nicola L, Joseph, Bertrand, Joseph, Suresh K, Joubert, Annie M, Juhász, Gábor, Juillerat-Jeanneret, Lucienne, Jung, Chang Hwa, Jung, Yong-Keun, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kadowaki, Motoni, Kagedal, Katarina, Kamada, Yoshiaki, Kaminskyy, Vitaliy O, Kampinga, Harm H, Kanamori, Hiromitsu, Kang, Chanhee, Kang, Khong Bee, Kang, Kwang Il, Kang, Rui, Kang, Yoon-A, Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanno, Haruo, Kanthasamy, Anumantha G, Kanthasamy, Arthi, Karantza, Vassiliki, Kaushal, Gur P, Kaushik, Susmita, Kawazoe, Yoshinori, Ke, Po-Yuan, Kehrl, John H, Kelekar, Ameeta, Kerkhoff, Claus, Kessel, David H, Khalil, Hany, Kiel, Jan A K W, Kiger, Amy A, Kihara, Akio, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Hou, Kim, Eun-Kyoung, Kim, Hyung-Ryong, Kim, Jae-Sung, Kim, Jeong Hun, Kim, Jin Cheon, Kim, John K, Kim, Peter K, Kim, Seong Who, Kim, Yong-Sun, Kim, Yonghyun, Kimchi, Adi, Kimmelman, Alec C, King, Jason S, Kinsella, Timothy J, Kirkin, Vladimir, Kirshenbaum, Lorrie A, Kitamoto, Katsuhiko, Kitazato, Kaio, Klein, Ludger, Klimecki, Walter T, Klucken, Jochen, Knecht, Erwin, Ko, Ben C B, Koch, Jan C, Koga, Hiroshi, Koh, Jae-Young, Koh, Young Ho, Koike, Masato, Komatsu, Masaaki, Kominami, Eiki, Kong, Hee Jeong, Kong, Wei-Jia, Korolchuk, Viktor I, Kotake, Yaichiro, Koukourakis, Michael I, Kouri Flores, Juan B, Kovács, Attila L, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Kretz-Remy, Carole, Krichevsky, Anna M, Kroemer, Guido, Krüger, Rejko, Krut, Oleg, Ktistakis, Nicholas T, Kuan, Chia-Yi, Kucharczyk, Roza, Kumar, Ashok, Kumar, Raj, Kumar, Sharad, Kundu, Mondira, Kung, Hsing-Jien, Kurz, Tino, Kwon, Ho Jeong, La Spada, Albert R, Lafont, Frank, Lamark, Trond, Landry, Jacques, Lane, Jon D, Lapaquette, Pierre, Laporte, Jocelyn F, László, Lajos, Lavandero, Sergio, Lavoie, Josée N, Layfield, Robert, Lazo, Pedro A, Le, Weidong, Le Cam, Laurent, Ledbetter, Daniel J, Lee, Alvin J X, Lee, Byung-Wan, Lee, Gyun Min, Lee, Jongdae, Lee, Ju-Hyun, Lee, Michael, Lee, Myung-Shik, Lee, Sug Hyung, Leeuwenburgh, Christiaan, Legembre, Patrick, Legouis, Renaud, Lehmann, Michael, Lei, Huan-Yao, Lei, Qun-Ying, Leib, David A, Leiro, José, Lemasters, John J, Lemoine, Antoinette, Lesniak, Maciej S, Lev, Dina, Levenson, Victor V, Levine, Beth, Levy, Efrat, Li, Faqiang, Li, Jun-Lin, Li, Lian, Li, Sheng, Li, Weijie, Li, Xue-Jun, Li, Yan-Bo, Li, Yi-Ping, Liang, Chengyu, Liang, Qiangrong, Liao, Yung-Feng, Liberski, Pawel P, Lieberman, Andrew, Lim, Hyunjung J, Lim, Kah-Leong, Lim, Kyu, Lin, Chiou-Feng, Lin, Fu-Cheng, Lin, Jian, Lin, Jiandie D, Lin, Kui, Lin, Wan-Wan, Lin, Weei-Chin, Lin, Yi-Ling, Linden, Rafael, Lingor, Paul, Lippincott-Schwartz, Jennifer, Lisanti, Michael P, Liton, Paloma B, Liu, Bo, Liu, Chun-Feng, Liu, Kaiyu, Liu, Leyuan, Liu, Qiong A, Liu, Wei, Liu, Young-Chau, Liu, Yule, Lockshin, Richard A, Lok, Chun-Nam, Lonial, Sagar, Loos, Benjamin, Lopez-Berestein, Gabriel, López-Otín, Carlos, Lossi, Laura, Lotze, Michael T, Lőw, Peter, Lu, Binfeng, Lu, Bingwei, Lu, Bo, Lu, Zhen, Luciano, Frédéric, Lukacs, Nicholas W, Lund, Anders H, Lynch-Day, Melinda A, Ma, Yong, Macian, Fernando, Mackeigan, Jeff P, Macleod, Kay F, Madeo, Frank, Maiuri, Luigi, Maiuri, Maria Chiara, Malagoli, Davide, Malicdan, May Christine V, Malorni, Walter, Man, Na, Mandelkow, Eva-Maria, Manon, Stéphen, Manov, Irena, Mao, Kai, Mao, Xiang, Mao, Zixu, Marambaud, Philippe, Marazziti, Daniela, Marcel, Yves L, Marchbank, Katie, Marchetti, Piero, Marciniak, Stefan J, Marcondes, Mateus, Mardi, Mohsen, Marfe, Gabriella, Mariño, Guillermo, Markaki, Maria, Marten, Mark R, Martin, Seamus J, Martinand-Mari, Camille, Martinet, Wim, Martinez-Vicente, Marta, Masini, Matilde, Matarrese, Paola, Matsuo, Saburo, Matteoni, Raffaele, Mayer, Andreas, Mazure, Nathalie M, Mcconkey, David J, Mcconnell, Melanie J, Mcdermott, Catherine, Mcdonald, Christine, Mcinerney, Gerald M, Mckenna, Sharon L, Mclaughlin, Bethann, Mclean, Pamela J, Mcmaster, Christopher R, Mcquibban, G Angus, Meijer, Alfred J, Meisler, Miriam H, Meléndez, Alicia, Melia, Thomas J, Melino, Gerry, Mena, Maria A, Menendez, Javier A, Menna-Barreto, Rubem F S, Menon, Manoj B, Menzies, Fiona M, Mercer, Carol A, Merighi, Adalberto, Merry, Diane E, Meschini, Stefania, Meyer, Christian G, Meyer, Thomas F, Miao, Chao-Yu, Miao, Jun-Ying, Michels, Paul A M, Michiels, Carine, Mijaljica, Dalibor, Milojkovic, Ana, Minucci, Saverio, Miracco, Clelia, Miranti, Cindy K, Mitroulis, Ioannis, Miyazawa, Keisuke, Mizushima, Noboru, Mograbi, Baharia, Mohseni, Simin, Molero, Xavier, Mollereau, Bertrand, Mollinedo, Faustino, Momoi, Takashi, Monastyrska, Iryna, Monick, Martha M, Monteiro, Mervyn J, Moore, Michael N, Mora, Rodrigo, Moreau, Kevin, Moreira, Paula I, Moriyasu, Yuji, Moscat, Jorge, Mostowy, Serge, Mottram, Jeremy C, Motyl, Tomasz, Moussa, Charbel E-H, Müller, Sylke, Muller, Sylviane, Münger, Karl, Münz, Christian, Murphy, Leon O, Murphy, Maureen E, Musarò, Antonio, Mysorekar, Indira, Nagata, Eiichiro, Nagata, Kazuhiro, Nahimana, Aimable, Nair, Usha, Nakagawa, Toshiyuki, Nakahira, Kiichi, Nakano, Hiroyasu, Nakatogawa, Hitoshi, Nanjundan, Meera, Naqvi, Naweed I, Narendra, Derek P, Narita, Masashi, Navarro, Miguel, Nawrocki, Steffan T, Nazarko, Taras Y, Nemchenko, Andriy, Netea, Mihai G, Neufeld, Thomas P, Ney, Paul A, Nezis, Ioannis P, Nguyen, Huu Phuc, Nie, Daotai, Nishino, Ichizo, Nislow, Corey, Nixon, Ralph A, Noda, Takeshi, Noegel, Angelika A, Nogalska, Anna, Noguchi, Satoru, Notterpek, Lucia, Novak, Ivana, Nozaki, Tomoyoshi, Nukina, Nobuyuki, Nürnberger, Thorsten, Nyfeler, Beat, Obara, Keisuke, Oberley, Terry D, Oddo, Salvatore, Ogawa, Michinaga, Ohashi, Toya, Okamoto, Koji, Oleinick, Nancy L, Oliver, F Javier, Olsen, Laura J, Olsson, Stefan, Opota, Onya, Osborne, Timothy F, Ostrander, Gary K, Otsu, Kinya, Ou, Jing-Hsiung James, Ouimet, Mireille, Overholtzer, Michael, Ozpolat, Bulent, Paganetti, Paolo, Pagnini, Ugo, Pallet, Nicolas, Palmer, Glen E, Palumbo, Camilla, Pan, Tianhong, Panaretakis, Theocharis, Pandey, Udai Bhan, Papackova, Zuzana, Papassideri, Issidora, Paris, Irmgard, Park, Junsoo, Park, Ohkmae K, Parys, Jan B, Parzych, Katherine R, Patschan, Susann, Patterson, Cam, Pattingre, Sophie, Pawelek, John M, Peng, Jianxin, Perlmutter, David H, Perrotta, Ida, Perry, George, Pervaiz, Shazib, Peter, Matthias, Peters, Godefridus J, Petersen, Morten, Petrovski, Goran, Phang, James M, Piacentini, Mauro, Pierre, Philippe, Pierrefite-Carle, Valérie, Pierron, Gérard, Pinkas-Kramarski, Ronit, Piras, Antonio, Piri, Natik, Platanias, Leonidas C, Pöggeler, Stefanie, Poirot, Marc, Poletti, Angelo, Poüs, Christian, Pozuelo-Rubio, Mercedes, Prætorius-Ibba, Mette, Prasad, Anil, Prescott, Mark, Priault, Muriel, Produit-Zengaffinen, Nathalie, Progulske-Fox, Ann, Proikas-Cezanne, Tassula, Przedborski, Serge, Przyklenk, Karin, Puertollano, Rosa, Puyal, Julien, Qian, Shu-Bing, Qin, Liang, Qin, Zheng-Hong, Quaggin, Susan E, Raben, Nina, Rabinowich, Hannah, Rabkin, Simon W, Rahman, Irfan, Rami, Abdelhaq, Ramm, Georg, Randall, Glenn, Randow, Felix, Rao, V Ashutosh, Rathmell, Jeffrey C, Ravikumar, Brinda, Ray, Swapan K, Reed, Bruce H, Reed, John C, Reggiori, Fulvio, Régnier-Vigouroux, Anne, Reichert, Andreas S, Reiners, John J, Reiter, Russel J, Ren, Jun, Revuelta, José L, Rhodes, 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Modélisation, Information & Systèmes (MIS) ; Université de Picardie Jules Verne, Department of Experimental Oncology and Molecular Medicine ; Fondazione IRCCS Istituto Nazionale dei Tumori, Institute of Modern Physics ; Chinese Academy of Science (CAS), Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; ganzu Province, Institute of Computing Technology [Biejing] (ICT) ; Chinese Academy of Science (CAS), European Synchrotron Radiation Facility (ESRF) ; ESRF, Plant Physiology Laboratory ; Chinese Academy of Sciences - Botanical Institute of South china, Division of Biopharmaceutics ; Leiden University, The Institute of Environmental Medicine [Stockholm] (IMM) ; Karolinska Institutet, Institut de biochimie et biophysique moléculaire et cellulaire (IBBMC) ; CNRS - Université Paris XI - Paris Sud, Center for Brain Repair and Rehabilitation ; University of Gothenburg - Institute of Neuroscience and Physiology, department of genetics - Institute of biochemistry and biophysics ; institute of biochemistry an biophysics - polish academic of sciences, Departament de Bioquímica i Biologia Molecular ; Universitat de Barcelona - Facultat de Biologia - Institute for Research in Biomedicine - CIBERDEM, Chaperones Research Group ; Chaperones Research Group, Klionsky, Daniel J, Abdalla, Fabio C, Abeliovich, Hagai, Abraham, Robert T, Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A, Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M, Al-Zeer, Munir A, Albert, Matthew L, Albin, Roger L, Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O, Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K, Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Auberger, Patrick, Baba, Misuzu, Backues, Steven K, Baehrecke, Eric H, Bahr, Ben A, Bai, Xue-Yuan, Bailly, Yannick, Baiocchi, Robert, Baldini, Giulia, Balduini, Walter, Ballabio, Andrea, Bamber, Bruce A, Bampton, Edward T W, Bánhegyi, Gábor, Bartholomew, Clinton R, Bassham, Diane C, Bast, Robert C, Batoko, Henri, Bay, Boon-Huat, Beau, Isabelle, Béchet, Daniel M, Begley, Thomas J, Behl, Christian, Behrends, Christian, Bekri, Soumeya, Bellaire, Bryan, Bendall, Linda J, Benetti, Luca, Berliocchi, Laura, Bernardi, Henri, Bernassola, Francesca, Besteiro, Sébastien, Bhatia-Kissova, Ingrid, Bi, Xiaoning, Biard-Piechaczyk, Martine, Blum, Janice S, Boise, Lawrence H, Bonaldo, Paolo, Boone, David L, Bornhauser, Beat C, Bortoluci, Karina R, Bossis, Ioannis, Bost, Frédéric, Bourquin, Jean-Pierre, Boya, Patricia, Boyer-Guittaut, Michaël, Bozhkov, Peter V, Brady, Nathan R, Brancolini, Claudio, Brech, Andreas, Brenman, Jay E, Brennand, Ana, Bresnick, Emery H, Brest, Patrick, Bridges, Dave, Bristol, Molly L, Brookes, Paul S, Brown, Eric J, Brumell, John H, Brunetti-Pierri, Nicola, Brunk, Ulf T, Bulman, Dennis E, Bultman, Scott J, Bultynck, Geert, Burbulla, Lena F, Bursch, Wilfried, Butchar, Jonathan P, Buzgariu, Wanda, Bydlowski, Sergio P, Cadwell, Ken, Cahová, Monika, Cai, Dongsheng, Cai, Jiyang, Cai, Qian, Calabretta, Bruno, Calvo-Garrido, Javier, Camougrand, Nadine, Campanella, Michelangelo, Campos-Salinas, Jenny, Candi, Eleonora, Cao, Lizhi, Caplan, Allan B, Carding, Simon R, Cardoso, Sandra M, Carew, Jennifer S, Carlin, Cathleen R, Carmignac, Virginie, Carneiro, Leticia A M, Carra, Serena, Caruso, Rosario A, Casari, Giorgio, Casas, Caty, Castino, Roberta, Cebollero, Eduardo, Cecconi, Francesco, Celli, Jean, Chaachouay, Hassan, Chae, Han-Jung, Chai, Chee-Yin, Chan, David C, Chan, Edmond Y, Chang, Raymond Chuen-Chung, Che, Chi-Ming, Chen, Ching-Chow, Chen, Guang-Chao, Chen, Guo-Qiang, Chen, Min, Chen, Quan, Chen, Steve S-L, Chen, Wenli, Chen, Xi, Chen, Xiangmei, Chen, Xiequn, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Zhixiang, Cheng, Alan, Cheng, Christopher H K, Cheng, Yan, Cheong, Heesun, Cheong, Jae-Ho, Cherry, Sara, Chess-Williams, Russ, Cheung, Zelda H, Chevet, Eric, Chiang, Hui-Ling, Chiarelli, Roberto, Chiba, Tomoki, Chin, Lih-Shen, Chiou, Shih-Hwa, Chisari, Francis V, Cho, Chi Hin, Cho, Dong-Hyung, Choi, Augustine M K, Choi, Dooseok, Choi, Kyeong Sook, Choi, Mary E, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chu, Charleen T, Chuang, Tsung-Hsien, Chueh, Sheau-Huei, Chun, Taehoon, Chwae, Yong-Joon, Chye, Mee-Len, Ciarcia, Roberto, Ciriolo, Maria R, Clague, Michael J, Clark, Robert S B, Clarke, Peter G H, Clarke, Robert, Codogno, Patrice, Coller, Hilary A, Colombo, María I, Comincini, Sergio, Condello, Maria, Condorelli, Fabrizio, Cookson, Mark R, Coombs, Graham H, Coppens, Isabelle, Corbalan, Ramon, Cossart, Pascale, Costelli, Paola, Costes, Safia, Coto-Montes, Ana, Couve, Eduardo, Coxon, Fraser P, Cregg, James M, Crespo, José L, Cronjé, Marianne J, Cuervo, Ana Maria, Cullen, Joseph J, Czaja, Mark J, D'Amelio, Marcello, Darfeuille-Michaud, Arlette, Davids, Lester M, Davies, Faith E, De Felici, Massimo, De Groot, John F, De Haan, Cornelis A M, De Martino, Luisa, De Milito, Angelo, De Tata, Vincenzo, Debnath, Jayanta, Degterev, Alexei, Dehay, Benjamin, Delbridge, Lea M D, Demarchi, Francesca, Deng, Yi Zhen, Dengjel, Jörn, Dent, Paul, Denton, Donna, Deretic, Vojo, Desai, Shyamal D, Devenish, Rodney J, Di Gioacchino, Mario, Di Paolo, Gilbert, Di Pietro, Chiara, Díaz-Araya, Guillermo, Díaz-Laviada, Inés, Diaz-Meco, Maria T, Diaz-Nido, Javier, Dikic, Ivan, Dinesh-Kumar, Savithramma P, Ding, Wen-Xing, Distelhorst, Clark W, Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dokudovskaya, Svetlana, Dong, Zheng, Dorsey, Frank C, Dosenko, Victor, Dowling, James J, Doxsey, Stephen, Dreux, Marlène, Drew, Mark E, Duan, Qiuhong, Duchosal, Michel A, Duff, Karen, Dugail, Isabelle, Durbeej, Madeleine, Duszenko, Michael, Edelstein, Charles L, Edinger, Aimee L, Egea, Gustavo, Eichinger, Ludwig, Eissa, N Tony, Ekmekcioglu, Suhendan, El-Deiry, Wafik S, Elazar, Zvulun, Elgendy, Mohamed, Ellerby, Lisa M, Eng, Kai Er, Engelbrecht, Anna-Mart, Engelender, Simone, Erenpreisa, Jekaterina, Escalante, Ricardo, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Espert, Lucile, Espina, Virginia, Fan, Huizhou, Fan, Jia, Fan, Qi-Wen, Fan, Zhen, Fang, Shengyun, Fang, Yongqi, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Farré, Jean-Claude, Faure, Mathias, Fechheimer, Marcus, Feng, Carl G, Feng, Jian, Feng, Qili, Feng, Youji, Fésüs, László, Feuer, Ralph, Figueiredo-Pereira, Maria E, Fimia, Gian Maria, Fingar, Diane C, Finkbeiner, Steven, Finkel, Toren, Finley, Kim D, Fiorito, Filomena, Fisher, Edward A, Fisher, Paul B, Flajolet, Marc, Florez-Mcclure, Maria L, Florio, Salvatore, Fon, Edward A, Fornai, Francesco, Fortunato, Franco, Fotedar, Rati, Fowler, Daniel H, Fox, Howard S, Franco, Rodrigo, Frankel, Lisa B, Fransen, Marc, Fuentes, José M, Fueyo, Juan, Fujii, Jun, Fujisaki, Kozo, Fujita, Eriko, Fukuda, Mitsunori, Furukawa, Ruth H, Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galliot, Brigitte, Galy, Vincent, Ganesh, Subramaniam, Ganetzky, Barry, Ganley, Ian G, Gao, Fen-Biao, Gao, George F, Gao, Jinming, Garcia, Lorena, Garcia-Manero, Guillermo, Garcia-Marcos, Mikel, Garmyn, Marjan, Gartel, Andrei L, Gatti, Evelina, Gautel, Mathias, Gawriluk, Thomas R, Gegg, Matthew E, Geng, Jiefei, Germain, Marc, Gestwicki, Jason E, Gewirtz, David A, Ghavami, Saeid, Ghosh, Pradipta, Giammarioli, Anna M, Giatromanolaki, Alexandra N, Gibson, Spencer B, Gilkerson, Robert W, Ginger, Michael L, Goncu, Ebru, Gongora, Céline, Gonzalez, Claudio D, Gonzalez, Ramon, González-Estévez, Cristina, González-Polo, Rosa Ana, Gonzalez-Rey, Elena, Gorbunov, Nikolai V, Gorski, Sharon, Goruppi, Sandro, Gottlieb, Roberta A, Gozuacik, Devrim, Granato, Giovanna Elvira, Grant, Gary D, Green, Kim N, Gregorc, Aleš, Gros, Frédéric, Grose, Charles, Grunt, Thomas W, Gual, Philippe, Guan, Jun-Lin, Guan, Kun-Liang, Guichard, Sylvie M, Gukovskaya, Anna S, Gukovsky, Ilya, Gunst, Jan, Gustafsson, Asa B, Halayko, Andrew J, Hale, Amber N, Halonen, Sandra K, Hamasaki, Maho, Han, Feng, Han, Ting, Hancock, Michael K, Hansen, Malene, Harada, Hisashi, Harada, Masaru, Hardt, Stefan E, Harper, J Wade, Harris, Adrian L, Harris, James, Harris, Steven D, Hébert, Marie-Joseé, Heidenreich, Kim A, Helfrich, Miep H, Helgason, Gudmundur V, Henske, Elizabeth P, Herman, Brian, Herman, Paul K, Hetz, Claudio, Hilfiker, Sabine, Hill, Joseph A, Hocking, Lynne J, Hofman, Paul, Hofmann, Thomas G, Höhfeld, Jörg, Holyoake, Tessa L, Hong, Ming-Huang, Hood, David A, Hotamisligil, Gökhan S, Houwerzijl, Ewout J, Høyer-Hansen, Maria, Hu, Bingren, Hu, Chien-An A, Hu, Hong-Ming, Hua, Ya, Huang, Canhua, Huang, Ju, Huang, Shengbing, Huang, Wei-Pang, Huber, Tobias B, Huh, Won-Ki, Hung, Tai-Ho, Hupp, Ted R, Hur, Gang Min, Hurley, James B, Hussain, Sabah N A, Hussey, Patrick J, Hwang, Jung Jin, Hwang, Seungmin, Ichihara, Atsuhiro, Ilkhanizadeh, Shirin, Inoki, Ken, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L, Ip, Nancy Y, Isaka, Yoshitaka, Ishida, Hiroyuki, Isidoro, Ciro, Isobe, Ken-Ichi, Iwasaki, Akiko, Izquierdo, Marta, Izumi, Yotaro, Jaakkola, Panu M, Jäättelä, Marja, Jackson, George R, Jackson, William T, Janji, Bassam, Jendrach, Marina, Jeon, Ju-Hong, Jeung, Eui-Bae, Jiang, Hong, Jiang, Hongchi, Jiang, Jean X, Jiang, Ming, Jiang, Qing, Jiang, Xuejun, Jiménez, Alberto, Jin, Meiyan, Jin, Shengkan, Joe, Cheol O, Johansen, Terje, Johnson, Daniel E, Johnson, Gail V W, Jones, Nicola L, Joseph, Bertrand, Joseph, Suresh K, Joubert, Annie M, Juhász, Gábor, Juillerat-Jeanneret, Lucienne, Jung, Chang Hwa, Jung, Yong-Keun, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kadowaki, Motoni, Kagedal, Katarina, Kamada, Yoshiaki, Kaminskyy, Vitaliy O, Kampinga, Harm H, Kanamori, Hiromitsu, Kang, Chanhee, Kang, Khong Bee, Kang, Kwang Il, Kang, Rui, Kang, Yoon-A, Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanno, Haruo, Kanthasamy, Anumantha G, Kanthasamy, Arthi, Karantza, Vassiliki, Kaushal, Gur P, Kaushik, Susmita, Kawazoe, Yoshinori, Ke, Po-Yuan, Kehrl, John H, Kelekar, Ameeta, Kerkhoff, Claus, Kessel, David H, Khalil, Hany, Kiel, Jan A K W, Kiger, Amy A, Kihara, Akio, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Hou, Kim, Eun-Kyoung, Kim, Hyung-Ryong, Kim, Jae-Sung, Kim, Jeong Hun, Kim, Jin Cheon, Kim, John K, Kim, Peter K, Kim, Seong Who, Kim, Yong-Sun, Kim, Yonghyun, Kimchi, Adi, Kimmelman, Alec C, King, Jason S, Kinsella, Timothy J, Kirkin, Vladimir, Kirshenbaum, Lorrie A, Kitamoto, Katsuhiko, Kitazato, Kaio, Klein, Ludger, Klimecki, Walter T, Klucken, Jochen, Knecht, Erwin, Ko, Ben C B, Koch, Jan C, Koga, Hiroshi, Koh, Jae-Young, Koh, Young Ho, Koike, Masato, Komatsu, Masaaki, Kominami, Eiki, Kong, Hee Jeong, Kong, Wei-Jia, Korolchuk, Viktor I, Kotake, Yaichiro, Koukourakis, Michael I, Kouri Flores, Juan B, Kovács, Attila L, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Kretz-Remy, Carole, Krichevsky, Anna M, Kroemer, Guido, Krüger, Rejko, Krut, Oleg, Ktistakis, Nicholas T, Kuan, Chia-Yi, Kucharczyk, Roza, Kumar, Ashok, Kumar, Raj, Kumar, Sharad, Kundu, Mondira, Kung, Hsing-Jien, Kurz, Tino, Kwon, Ho Jeong, La Spada, Albert R, Lafont, Frank, Lamark, Trond, Landry, Jacques, Lane, Jon D, Lapaquette, Pierre, Laporte, Jocelyn F, László, Lajos, Lavandero, Sergio, Lavoie, Josée N, Layfield, Robert, Lazo, Pedro A, Le, Weidong, Le Cam, Laurent, Ledbetter, Daniel J, Lee, Alvin J X, Lee, Byung-Wan, Lee, Gyun Min, Lee, Jongdae, Lee, Ju-Hyun, Lee, Michael, Lee, Myung-Shik, Lee, Sug Hyung, Leeuwenburgh, Christiaan, Legembre, Patrick, Legouis, Renaud, Lehmann, Michael, Lei, Huan-Yao, Lei, Qun-Ying, Leib, David A, Leiro, José, Lemasters, John J, Lemoine, Antoinette, Lesniak, Maciej S, Lev, Dina, Levenson, Victor V, Levine, Beth, Levy, Efrat, Li, Faqiang, Li, Jun-Lin, Li, Lian, Li, Sheng, Li, Weijie, Li, Xue-Jun, Li, Yan-Bo, Li, Yi-Ping, Liang, Chengyu, Liang, Qiangrong, Liao, Yung-Feng, Liberski, Pawel P, Lieberman, Andrew, Lim, Hyunjung J, Lim, Kah-Leong, Lim, Kyu, Lin, Chiou-Feng, Lin, Fu-Cheng, Lin, Jian, Lin, Jiandie D, Lin, Kui, Lin, Wan-Wan, Lin, Weei-Chin, Lin, Yi-Ling, Linden, Rafael, Lingor, Paul, Lippincott-Schwartz, Jennifer, Lisanti, Michael P, Liton, Paloma B, Liu, Bo, Liu, Chun-Feng, Liu, Kaiyu, Liu, Leyuan, Liu, Qiong A, Liu, Wei, Liu, Young-Chau, Liu, Yule, Lockshin, Richard A, Lok, Chun-Nam, Lonial, Sagar, Loos, Benjamin, Lopez-Berestein, Gabriel, López-Otín, Carlos, Lossi, Laura, Lotze, Michael T, Lőw, Peter, Lu, Binfeng, Lu, Bingwei, Lu, Bo, Lu, Zhen, Luciano, Frédéric, Lukacs, Nicholas W, Lund, Anders H, Lynch-Day, Melinda A, Ma, Yong, Macian, Fernando, Mackeigan, Jeff P, Macleod, Kay F, Madeo, Frank, Maiuri, Luigi, Maiuri, Maria Chiara, Malagoli, Davide, Malicdan, May Christine V, Malorni, Walter, Man, Na, Mandelkow, Eva-Maria, Manon, Stéphen, Manov, Irena, Mao, Kai, Mao, Xiang, Mao, Zixu, Marambaud, Philippe, Marazziti, Daniela, Marcel, Yves L, Marchbank, Katie, Marchetti, Piero, Marciniak, Stefan J, Marcondes, Mateus, Mardi, Mohsen, Marfe, Gabriella, Mariño, Guillermo, Markaki, Maria, Marten, Mark R, Martin, Seamus J, Martinand-Mari, Camille, Martinet, Wim, Martinez-Vicente, Marta, Masini, Matilde, Matarrese, Paola, Matsuo, Saburo, Matteoni, Raffaele, Mayer, Andreas, Mazure, Nathalie M, Mcconkey, David J, Mcconnell, Melanie J, Mcdermott, Catherine, Mcdonald, Christine, Mcinerney, Gerald M, Mckenna, Sharon L, Mclaughlin, Bethann, Mclean, Pamela J, Mcmaster, Christopher R, Mcquibban, G Angus, Meijer, Alfred J, Meisler, Miriam H, Meléndez, Alicia, Melia, Thomas J, Melino, Gerry, Mena, Maria A, Menendez, Javier A, Menna-Barreto, Rubem F S, Menon, Manoj B, Menzies, Fiona M, Mercer, Carol A, Merighi, Adalberto, Merry, Diane E, Meschini, Stefania, Meyer, Christian G, Meyer, Thomas F, Miao, Chao-Yu, Miao, Jun-Ying, Michels, Paul A M, Michiels, Carine, Mijaljica, Dalibor, Milojkovic, Ana, Minucci, Saverio, Miracco, Clelia, Miranti, Cindy K, Mitroulis, Ioannis, Miyazawa, Keisuke, Mizushima, Noboru, Mograbi, Baharia, Mohseni, Simin, Molero, Xavier, Mollereau, Bertrand, Mollinedo, Faustino, Momoi, Takashi, Monastyrska, Iryna, Monick, Martha M, Monteiro, Mervyn J, Moore, Michael N, Mora, Rodrigo, Moreau, Kevin, Moreira, Paula I, Moriyasu, Yuji, Moscat, Jorge, Mostowy, Serge, Mottram, Jeremy C, Motyl, Tomasz, Moussa, Charbel E-H, Müller, Sylke, Muller, Sylviane, Münger, Karl, Münz, Christian, Murphy, Leon O, Murphy, Maureen E, Musarò, Antonio, Mysorekar, Indira, Nagata, Eiichiro, Nagata, Kazuhiro, Nahimana, Aimable, Nair, Usha, Nakagawa, Toshiyuki, Nakahira, Kiichi, Nakano, Hiroyasu, Nakatogawa, Hitoshi, Nanjundan, Meera, Naqvi, Naweed I, Narendra, Derek P, Narita, Masashi, Navarro, Miguel, Nawrocki, Steffan T, Nazarko, Taras Y, Nemchenko, Andriy, Netea, Mihai G, Neufeld, Thomas P, Ney, Paul A, Nezis, Ioannis P, Nguyen, Huu Phuc, Nie, Daotai, Nishino, Ichizo, Nislow, Corey, Nixon, Ralph A, Noda, Takeshi, Noegel, Angelika A, Nogalska, Anna, Noguchi, Satoru, Notterpek, Lucia, Novak, Ivana, Nozaki, Tomoyoshi, Nukina, Nobuyuki, Nürnberger, Thorsten, Nyfeler, Beat, Obara, Keisuke, Oberley, Terry D, Oddo, Salvatore, Ogawa, Michinaga, Ohashi, Toya, Okamoto, Koji, Oleinick, Nancy L, Oliver, F Javier, Olsen, Laura J, Olsson, Stefan, Opota, Onya, Osborne, Timothy F, Ostrander, Gary K, Otsu, Kinya, Ou, Jing-Hsiung James, Ouimet, Mireille, Overholtzer, Michael, Ozpolat, Bulent, Paganetti, Paolo, Pagnini, Ugo, Pallet, Nicolas, Palmer, Glen E, Palumbo, Camilla, Pan, Tianhong, Panaretakis, Theocharis, Pandey, Udai Bhan, Papackova, Zuzana, Papassideri, Issidora, Paris, Irmgard, Park, Junsoo, Park, Ohkmae K, Parys, Jan B, Parzych, Katherine R, Patschan, Susann, Patterson, Cam, Pattingre, Sophie, Pawelek, John M, Peng, Jianxin, Perlmutter, David H, Perrotta, Ida, Perry, George, Pervaiz, Shazib, Peter, Matthias, Peters, Godefridus J, Petersen, Morten, Petrovski, Goran, Phang, James M, Piacentini, Mauro, Pierre, Philippe, Pierrefite-Carle, Valérie, Pierron, Gérard, Pinkas-Kramarski, Ronit, Piras, Antonio, Piri, Natik, Platanias, Leonidas C, Pöggeler, Stefanie, Poirot, Marc, Poletti, Angelo, Poüs, Christian, Pozuelo-Rubio, Mercedes, Prætorius-Ibba, Mette, Prasad, Anil, Prescott, Mark, Priault, Muriel, Produit-Zengaffinen, Nathalie, Progulske-Fox, Ann, Proikas-Cezanne, Tassula, Przedborski, Serge, Przyklenk, Karin, Puertollano, Rosa, Puyal, Julien, Qian, Shu-Bing, Qin, Liang, Qin, Zheng-Hong, Quaggin, Susan E, Raben, Nina, Rabinowich, Hannah, Rabkin, Simon W, Rahman, Irfan, Rami, Abdelhaq, Ramm, Georg, Randall, Glenn, Randow, Felix, Rao, V Ashutosh, Rathmell, Jeffrey C, Ravikumar, Brinda, Ray, Swapan K, Reed, Bruce H, Reed, John C, Reggiori, Fulvio, Régnier-Vigouroux, Anne, Reichert, Andreas S, Reiners, John J, Reiter, Russel J, Ren, Jun, Revuelta, José L, Rhodes, Christopher J, Ritis, Konstantinos, Rizzo, Elizete, Robbins, Jeffrey, Roberge, Michel, Roca, Hernan, Roccheri, Maria C, Rocchi, Stephane, Rodemann, H Peter, Rodríguez De Córdoba, Santiago, Rohrer, Bärbel, Roninson, Igor B, Rosen, Kirill, Rost-Roszkowska, Magdalena M, Rouis, Mustapha, Rouschop, Kasper M A, Rovetta, Francesca, Rubin, Brian P, Rubinsztein, David C, Ruckdeschel, Klaus, Rucker, Edmund B, Rudich, Assaf, Rudolf, Emil, Ruiz-Opazo, Nelson, Russo, Rossella, Rusten, Tor Erik, Ryan, Kevin M, Ryter, Stefan W, Sabatini, David M, Sadoshima, Junichi, Saha, Tapas, Saitoh, Tatsuya, Sakagami, Hiroshi, Sakai, Yasuyoshi, Salekdeh, Ghasem Hoseini, Salomoni, Paolo, Salvaterra, Paul M, Salvesen, Guy, Salvioli, Rosa, Sanchez, Anthony M J, Sánchez-Alcázar, José A, Sánchez-Prieto, Ricardo, Sandri, Marco, Sankar, Uma, Sansanwal, Poonam, Santambrogio, Laura, Saran, Shweta, Sarkar, Sovan, Sarwal, Minnie, Sasakawa, Chihiro, Sasnauskiene, Ausra, Sass, Miklós, Sato, Ken, Sato, Miyuki, Schapira, Anthony H V, Scharl, Michael, Schätzl, Hermann M, Scheper, Wiep, Schiaffino, Stefano, Schneider, Claudio, Schneider, Marion E, Schneider-Stock, Regine, Schoenlein, Patricia V, Schorderet, Daniel F, Schüller, Christoph, Schwartz, Gary K, Scorrano, Luca, Sealy, Linda, Seglen, Per O, Segura-Aguilar, Juan, Seiliez, Iban, Seleverstov, Oleksandr, Sell, Christian, Seo, Jong Bok, Separovic, Duska, Setaluri, Vijayasaradhi, Setoguchi, Takao, Settembre, Carmine, Shacka, John J, Shanmugam, Mala, Shapiro, Irving M, Shaulian, Eitan, Shaw, Reuben J, Shelhamer, James H, Shen, Han-Ming, Shen, Wei-Chiang, Sheng, Zu-Hang, Shi, Yang, Shibuya, Kenichi, Shidoji, Yoshihiro, Shieh, Jeng-Jer, Shih, Chwen-Ming, Shimada, Yohta, Shimizu, Shigeomi, Shintani, Takahiro, Shirihai, Orian S, Shore, Gordon C, Sibirny, Andriy A, Sidhu, Stan B, Sikorska, Beata, Silva-Zacarin, Elaine C M, Simmons, Alison, Simon, Anna Katharina, Simon, Hans-Uwe, Simone, Cristiano, Simonsen, Anne, Sinclair, David A, Singh, Rajat, Sinha, Debasish, Sinicrope, Frank A, Sirko, Agnieszka, Siu, Parco M, Sivridis, Efthimios, Skop, Vojtech, Skulachev, Vladimir P, Slack, Ruth S, Smaili, Soraya S, Smith, Duncan R, Soengas, Maria S, Soldati, Thierry, Song, Xueqin, Sood, Anil K, Soong, Tuck Wah, Sotgia, Federica, Spector, Stephen A, Spies, Claudia D, Springer, Wolfdieter, Srinivasula, Srinivasa M, Stefanis, Leonidas, Steffan, Joan S, Stendel, Ruediger, Stenmark, Harald, Stephanou, Anastasis, Stern, Stephan T, Sternberg, Cinthya, Stork, Björn, Strålfors, Peter, Subauste, Carlos S, Sui, Xinbing, Sulzer, David, Sun, Jiaren, Sun, Shi-Yong, Sun, Zhi-Jun, Sung, Joseph J Y, Suzuki, Kuninori, Suzuki, Toshihiko, Swanson, Michele S, Swanton, Charles, Sweeney, Sean T, Sy, Lai-King, Szabadkai, Gyorgy, Tabas, Ira, Taegtmeyer, Heinrich, Tafani, Marco, Takács-Vellai, Krisztina, Takano, Yoshitaka, Takegawa, Kaoru, Takemura, Genzou, Takeshita, Fumihiko, Talbot, Nicholas J, Tan, Kevin S W, Tanaka, Keiji, Tanaka, Kozo, Tang, Daolin, Tang, Dingzhong, Tanida, Isei, Tannous, Bakhos A, Tavernarakis, Nektarios, Taylor, Graham S, Taylor, Gregory A, Taylor, J Paul, Terada, Lance S, Terman, Alexei, Tettamanti, Gianluca, Thevissen, Karin, Thompson, Craig B, Thorburn, Andrew, Thumm, Michael, Tian, Fengfeng, Tian, Yuan, Tocchini-Valentini, Glauco, Tolkovsky, Aviva M, Tomino, Yasuhiko, Tönges, Lars, Tooze, Sharon A, Tournier, Cathy, Tower, John, Towns, Roberto, Trajkovic, Vladimir, Travassos, Leonardo H, Tsai, Ting-Fen, Tschan, Mario P, Tsubata, Takeshi, Tsung, Allan, Turk, Boris, Turner, Lorianne S, Tyagi, Suresh C, Uchiyama, Yasuo, Ueno, Takashi, Umekawa, Midori, Umemiya-Shirafuji, Rika, Unni, Vivek K, Vaccaro, Maria I, Valente, Enza Maria, Van Den Berghe, Greet, Van Der Klei, Ida J, Van Doorn, Wouter, Van Dyk, Linda F, Van Egmond, Marjolein, Van Grunsven, Leo A, Vandenabeele, Peter, Vandenberghe, Wim P, Vanhorebeek, Ilse, Vaquero, Eva C, Velasco, Guillermo, Vellai, Tibor, Vicencio, Jose Miguel, Vierstra, Richard D, Vila, Miquel, Vindis, Cécile, Viola, Giampietro, Viscomi, Maria Teresa, Voitsekhovskaja, Olga V, Von Haefen, Clarissa, Votruba, Marcela, Wada, Keiji, Wade-Martins, Richard, Walker, Cheryl L, Walsh, Craig M, Walter, Jochen, Wan, Xiang-Bo, Wang, Aimin, Wang, Chenguang, Wang, Dawei, Wang, Fan, Wang, Fen, Wang, Guanghui, Wang, Haichao, Wang, Hong-Gang, Wang, Horng-Dar, Wang, Jin, Wang, Ke, Wang, Mei, Wang, Richard C, Wang, Xinglong, Wang, Xuejun, Wang, Ying-Jan, Wang, Yipeng, Wang, Zhen, Wang, Zhigang Charles, Wang, Zhinong, Wansink, Derick G, Ward, Diane M, Watada, Hirotaka, Waters, Sarah L, Webster, Paul, Wei, Lixin, Weihl, Conrad C, Weiss, William A, Welford, Scott M, Wen, Long-Ping, Whitehouse, Caroline A, Whitton, J Lindsay, Whitworth, Alexander J, Wileman, Tom, Wiley, John W, Wilkinson, Simon, Willbold, Dieter, Williams, Roger L, Williamson, Peter R, Wouters, Bradly G, Wu, Chenghan, Wu, Dao-Cheng, Wu, William K K, Wyttenbach, Andreas, Xavier, Ramnik J, Xi, Zhijun, Xia, Pu, Xiao, Gengfu, 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Zheng, Xiaoxiang, Zhivotovsky, Boris, Zhong, Qing, Zhou, Cong-Zhao, Zhu, Changlian, Zhu, Wei-Guo, Zhu, Xiao-Feng, Zhu, Xiongwei, Zhu, Yuangang, Zoladek, Teresa, Zong, Wei-Xing, Zorzano, Antonio, Zschocke, Jürgen, and Zuckerbraun, Brian
Abstract: International audience, In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused o

3. Guidelines for the use and interpretation of assays for monitoring autophagy.

Author: Molecular and Cellular Biology ; University of Leuven, Laboratoire d'Epigénétique et Cancer ; CNRS - Université Paris XI - Paris Sud, Department of Pharmacology ; Department of Pharmacology, Immunobiologie des Cellules Dendritiques ; INSERM - Institut Pasteur de Paris, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (FEMTO-ST) ; CNRS - Université de Franche-Comté - Université de Technologie de Belfort-Montbeliard - Ecole Nationale Supérieure de Mécanique et des Microtechniques, Telethon Institute for Genetics and Medicine ; Telethon Institute, Medical Genetics ; Federico II University, Department of Molecular and Human Genetics ; Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute ; Texas Children's Hospital, Signalisation et physiopathologie des cellules épithéliales ; INSERM - Université Paris XI - Paris Sud, Dynamique des interactions membranaires normales et pathologiques (DIMNP) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Institut de biochimie et génétique cellulaires (IBGC) ; CNRS - Université Victor Segalen - Bordeaux II, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Celullar and Molecular Medicine ; Celullar and Molecular Medicine, Estrogène, Expression génique et pathologies du Système Nerveux Central (E2SNC) ; Université de Franche-Comté - IFR133, Infection bactérienne, inflammation, et carcinogenèse digestive ; INSERM - IFR50 - Université Nice Sophia Antipolis (UNS), Université Nice Sophia Antipolis (UNS) ; Université Nice Sophia Antipolis (UNS) - PRES Euro-Méditerranéen, Department of Computer Science [Tsukuba] ; University of Tsukuba, Gunma University ; Institute for Molecular & Cellular Regulation, Cell Biology, Physiology and Immunology ; Cell Biology, Physiology and Immunology, Dulbecco Telethon Institute/Department of Biology ; Dulbecco Telethon Institute/Department of Biology, Department of Chemistry and HKU-CAS Joint Laboratory ; 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LNCC, Johns Hopkins University (JHU) ; Johns Hopkins University, Institute of Molecular Biosciences, Karl-Franzens University Graz, (IMB) ; Karl-Franzens University Graz, Department of Pediatrics ; Università degli studi di Napoli Federico II, Department of Experimental Pharmacology ; Università degli Study di Napoli Federico II, Drug Research and Evaluation ; Istituto Superiore di Sanita‘, Albert Einstein College of Medicine (ALBERT EINSTEIN COLLEGE OF MEDICINE) ; Albert Einstein College of Medicine, Institute of Molecular Biology and Biotechnology ; Foundation for Research and Technology - Hellas, Institut des Sciences de l'Evolution - Montpellier (ISEM) ; CNRS - Institut de recherche pour le développement [IRD] - Université Montpellier II - Sciences et techniques, Institut de signalisation, biologie du développement et cancer (ISBDC) ; CNRS - Université Nice Sophia Antipolis (UNS), Departments of Neurology ; Departments of Neurology, Vanderbilt University [Nashville] ; Vanderbilt University of Nashville, Departments of Pharmacology ; 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biophysics ; institute of biochemistry an biophysics - polish academic of sciences, Departament de Bioquímica i Biologia Molecular ; Universitat de Barcelona - Facultat de Biologia - Institute for Research in Biomedicine - CIBERDEM, Chaperones Research Group ; Chaperones Research Group, Klionsky, Daniel J, Abdalla, Fabio C, Abeliovich, Hagai, Abraham, Robert T, Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A, Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M, Al-Zeer, Munir A, Albert, Matthew L, Albin, Roger L, Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O, Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K, Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Auberger, Patrick, Baba, Misuzu, 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Brown, Eric J, Brumell, John H, Brunetti-Pierri, Nicola, Brunk, Ulf T, Bulman, Dennis E, Bultman, Scott J, Bultynck, Geert, Burbulla, Lena F, Bursch, Wilfried, Butchar, Jonathan P, Buzgariu, Wanda, Bydlowski, Sergio P, Cadwell, Ken, Cahová, Monika, Cai, Dongsheng, Cai, Jiyang, Cai, Qian, Calabretta, Bruno, Calvo-Garrido, Javier, Camougrand, Nadine, Campanella, Michelangelo, Campos-Salinas, Jenny, Candi, Eleonora, Cao, Lizhi, Caplan, Allan B, Carding, Simon R, Cardoso, Sandra M, Carew, Jennifer S, Carlin, Cathleen R, Carmignac, Virginie, Carneiro, Leticia A M, Carra, Serena, Caruso, Rosario A, Casari, Giorgio, Casas, Caty, Castino, Roberta, Cebollero, Eduardo, Cecconi, Francesco, Celli, Jean, Chaachouay, Hassan, Chae, Han-Jung, Chai, Chee-Yin, Chan, David C, Chan, Edmond Y, Chang, Raymond Chuen-Chung, Che, Chi-Ming, Chen, Ching-Chow, Chen, Guang-Chao, Chen, Guo-Qiang, Chen, Min, Chen, Quan, Chen, Steve S-L, Chen, Wenli, Chen, Xi, Chen, Xiangmei, Chen, Xiequn, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Zhixiang, Cheng, Alan, Cheng, Christopher H K, Cheng, Yan, Cheong, Heesun, Cheong, Jae-Ho, Cherry, Sara, Chess-Williams, Russ, Cheung, Zelda H, Chevet, Eric, Chiang, Hui-Ling, Chiarelli, Roberto, Chiba, Tomoki, Chin, Lih-Shen, Chiou, Shih-Hwa, Chisari, Francis V, Cho, Chi Hin, Cho, Dong-Hyung, Choi, Augustine M K, Choi, Dooseok, Choi, Kyeong Sook, Choi, Mary E, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chu, Charleen T, Chuang, Tsung-Hsien, Chueh, Sheau-Huei, Chun, Taehoon, Chwae, Yong-Joon, Chye, Mee-Len, Ciarcia, Roberto, Ciriolo, Maria R, Clague, Michael J, Clark, Robert S B, Clarke, Peter G H, Clarke, Robert, Codogno, Patrice, Coller, Hilary A, Colombo, María I, Comincini, Sergio, Condello, Maria, Condorelli, Fabrizio, Cookson, Mark R, Coombs, Graham H, Coppens, Isabelle, Corbalan, Ramon, Cossart, Pascale, Costelli, Paola, Costes, Safia, Coto-Montes, Ana, Couve, Eduardo, Coxon, Fraser P, Cregg, James M, Crespo, José L, Cronjé, 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Miquel, Vindis, Cécile, Viola, Giampietro, Viscomi, Maria Teresa, Voitsekhovskaja, Olga V, Von Haefen, Clarissa, Votruba, Marcela, Wada, Keiji, Wade-Martins, Richard, Walker, Cheryl L, Walsh, Craig M, Walter, Jochen, Wan, Xiang-Bo, Wang, Aimin, Wang, Chenguang, Wang, Dawei, Wang, Fan, Wang, Fen, Wang, Guanghui, Wang, Haichao, Wang, Hong-Gang, Wang, Horng-Dar, Wang, Jin, Wang, Ke, Wang, Mei, Wang, Richard C, Wang, Xinglong, Wang, Xuejun, Wang, Ying-Jan, Wang, Yipeng, Wang, Zhen, Wang, Zhigang Charles, Wang, Zhinong, Wansink, Derick G, Ward, Diane M, Watada, Hirotaka, Waters, Sarah L, Webster, Paul, Wei, Lixin, Weihl, Conrad C, Weiss, William A, Welford, Scott M, Wen, Long-Ping, Whitehouse, Caroline A, Whitton, J Lindsay, Whitworth, Alexander J, Wileman, Tom, Wiley, John W, Wilkinson, Simon, Willbold, Dieter, Williams, Roger L, Williamson, Peter R, Wouters, Bradly G, Wu, Chenghan, Wu, Dao-Cheng, Wu, William K K, Wyttenbach, Andreas, Xavier, Ramnik J, Xi, Zhijun, Xia, Pu, Xiao, Gengfu, Xie, Zhiping, Xie, Zhonglin, Xu, Da-Zhi, Xu, Jianzhen, Xu, Liang, Xu, Xiaolei, Yamamoto, Ai, Yamamoto, Akitsugu, Yamashina, Shunhei, Yamashita, Michiaki, Yan, Xianghua, Yanagida, Mitsuhiro, Yang, Dun-Sheng, Yang, Elizabeth, Yang, Jin-Ming, Yang, Shi Yu, Yang, Wannian, Yang, Wei Yuan, Yang, Zhifen, Yao, Meng-Chao, Yao, Tso-Pang, Yeganeh, Behzad, Yen, Wei-Lien, Yin, Jia-Jing, Yin, Xiao-Ming, Yoo, Ook-Joon, Yoon, Gyesoon, Yoon, Seung-Yong, Yorimitsu, Tomohiro, Yoshikawa, Yuko, Yoshimori, Tamotsu, Yoshimoto, Kohki, You, Ho Jin, Youle, Richard J, Younes, Anas, Yu, Li, Yu, Long, Yu, Seong-Woon, Yu, Wai Haung, Yuan, Zhi-Min, Yue, Zhenyu, Yun, Cheol-Heui, Yuzaki, Michisuke, Zabirnyk, Olga, Silva-Zacarin, Elaine, Zacks, David, Zacksenhaus, Eldad, Zaffaroni, Nadia, Zakeri, Zahra, Zeh, Herbert J, Zeitlin, Scott O, Zhang, Hong, Zhang, Hui-Ling, Zhang, Jianhua, Zhang, Jing-Pu, Zhang, Lin, Zhang, Long, Zhang, Ming-Yong, Zhang, Xu Dong, Zhao, Mantong, Zhao, Yi-Fang, Zhao, Ying, Zhao, Zhizhuang J, 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biophysics ; institute of biochemistry an biophysics - polish academic of sciences, Departament de Bioquímica i Biologia Molecular ; Universitat de Barcelona - Facultat de Biologia - Institute for Research in Biomedicine - CIBERDEM, Chaperones Research Group ; Chaperones Research Group, Klionsky, Daniel J, Abdalla, Fabio C, Abeliovich, Hagai, Abraham, Robert T, Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A, Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M, Al-Zeer, Munir A, Albert, Matthew L, Albin, Roger L, Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O, Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K, Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Auberger, Patrick, Baba, Misuzu, 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L, Edinger, Aimee L, Egea, Gustavo, Eichinger, Ludwig, Eissa, N Tony, Ekmekcioglu, Suhendan, El-Deiry, Wafik S, Elazar, Zvulun, Elgendy, Mohamed, Ellerby, Lisa M, Eng, Kai Er, Engelbrecht, Anna-Mart, Engelender, Simone, Erenpreisa, Jekaterina, Escalante, Ricardo, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Espert, Lucile, Espina, Virginia, Fan, Huizhou, Fan, Jia, Fan, Qi-Wen, Fan, Zhen, Fang, Shengyun, Fang, Yongqi, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Farré, Jean-Claude, Faure, Mathias, Fechheimer, Marcus, Feng, Carl G, Feng, Jian, Feng, Qili, Feng, Youji, Fésüs, László, Feuer, Ralph, Figueiredo-Pereira, Maria E, Fimia, Gian Maria, Fingar, Diane C, Finkbeiner, Steven, Finkel, Toren, Finley, Kim D, Fiorito, Filomena, Fisher, Edward A, Fisher, Paul B, Flajolet, Marc, Florez-Mcclure, Maria L, Florio, Salvatore, Fon, Edward A, Fornai, Francesco, Fortunato, Franco, Fotedar, Rati, Fowler, Daniel H, Fox, Howard S, Franco, Rodrigo, Frankel, Lisa B, Fransen, Marc, Fuentes, José M, Fueyo, Juan, Fujii, Jun, Fujisaki, Kozo, Fujita, Eriko, Fukuda, Mitsunori, Furukawa, Ruth H, Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galliot, Brigitte, Galy, Vincent, Ganesh, Subramaniam, Ganetzky, Barry, Ganley, Ian G, Gao, Fen-Biao, Gao, George F, Gao, Jinming, Garcia, Lorena, Garcia-Manero, Guillermo, Garcia-Marcos, Mikel, Garmyn, Marjan, Gartel, Andrei L, Gatti, Evelina, Gautel, Mathias, Gawriluk, Thomas R, Gegg, Matthew E, Geng, Jiefei, Germain, Marc, Gestwicki, Jason E, Gewirtz, David A, Ghavami, Saeid, Ghosh, Pradipta, Giammarioli, Anna M, Giatromanolaki, Alexandra N, Gibson, Spencer B, Gilkerson, Robert W, Ginger, Michael L, Goncu, Ebru, Gongora, Céline, Gonzalez, Claudio D, Gonzalez, Ramon, González-Estévez, Cristina, González-Polo, Rosa Ana, Gonzalez-Rey, Elena, Gorbunov, Nikolai V, Gorski, Sharon, Goruppi, Sandro, Gottlieb, Roberta A, Gozuacik, Devrim, Granato, Giovanna Elvira, Grant, Gary D, Green, Kim N, Gregorc, Aleš, Gros, Frédéric, 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Abstract: International audience, In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused o

4. Non-invasive diagnosis and follow-up of chronic infection with hepatitis B virus

Author: Vincent Leroy, Stéphane Chevaliez, Marie Decraecker, Dominique Roulot, Jean Nana, Tarik Asselah, Xavier Causse, David Durantel, Vincent Thibaut, Nathalie Ganne-Carrié, Christophe Bureau, Victor de Lédinghen, Marc Bourlière, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Grenoble Alpes (UGA), CHU Grenoble, Hôpital Beaujon [AP-HP], Centre Hospitalier Régional d'Orléans (CHRO), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Saint-Joseph [Marseille], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Humans, Hepatology, MESH: Hepatitis B, Chronic, [SDV]Life Sciences [q-bio], Gastroenterology, MESH: Follow-Up Studies, ab, MESH: DNA, Viral, MESH: Hepatitis B Surface Antigens, MESH: Hepatitis B virus, MESH: RNA, MESH: Liver Neoplasms, MESH: Persistent Infection, MESH: Liver Cirrhosis, MESH: Carcinoma, Hepatocellular, MESH: Hepatitis B e Antigens
Abstract: Diagnosis of chronic hepatitis B virus (HBV) infection, initial staging of infection and monitoring of treated and untreated patients are mainly based on clinical, biological and imaging criteria allowing a complete non-invasive management for the majority of patients. Along to the conventional virological tools, rapid diagnostic tests and blotting paper tests for HBV DNA are validated alternatives. After diagnosis, the initial work-up should include HIV, HCV and HDV serologies, HBeAg status, and HBsAg and HBV DNA quantification. Assessment of severity (inflammation and fibrosis) is based on ALT serum levels and non-invasive evaluation of liver fibrosis by elastography or blood tests, which must be interpreted cautiously using specific cutoffs and taking into account ALT levels. Taken together, these parameters allow disease classification and treatment decision. Decision of hepatocellular carcinoma screening by ultra-sound every six months may be difficult in non-cirrhotic patients and the use of risk-scores such as PAGE-B is encouraged. Chronic HBV infection often has a dynamic and often unpredictable profile and regular monitoring is mandatory. In untreated patients, regular (3-12 months) follow-up should include ALT and HBV DNA serum levels. Periodical HBsAg quantification and non-invasive evaluation of liver fibrosis may refine disease outcome and prognosis. In treated patients, checking efficacy is mainly based on HBV DNA negativity. In patients with advanced fibrosis, evolution of liver stiffness can be useful for portal hypertension evaluation, but its improvement should not be considered to stop hepatocellular carcinoma screening. Finally, new parameters (HBV RNA, HBcrAg) are promising but their use is still restricted for research.
Published: 2022

5. Non-invasive diagnosis and follow-up of portal hypertension

Author: Victor de Lédinghen, Thomas Sersté, Christophe Bureau, Marika Rudler, Dominique Thabut, Nathalie Ganne-Carrié, Delphine Weil, Charlotte Bouzbib, Laurent Castera, Christophe Cassinotto, Frédéric Oberti, M. Bourlière, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département radiologie diagnostique et interventionnelle Saint Eloi [CHRU Montpellier], Pôle Digestif [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Pierre, Service d’Hépato-Gastroentérologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Joseph [Marseille], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: medicine.medical_specialty, Cirrhosis, Portal venous pressure, [SDV]Life Sciences [q-bio], MESH: Elasticity Imaging Techniques, Chronic liver disease, Gastroenterology, Asymptomatic, MESH: Esophageal and Gastric Varices, Internal medicine, Medicine, In patient, MESH: Hypertension, Portal, MESH: Humans, Hepatology, medicine.diagnostic_test, business.industry, Non invasive, MESH: Follow-Up Studies, medicine.disease, Endoscopy, MESH: Endoscopy, Gastrointestinal, Portal hypertension, medicine.symptom, MESH: Liver Cirrhosis, business
Abstract: Compensated advanced chronic liver disease (cACLD) describes the spectrum of advanced fibrosis/cirrhosis in asymptomatic patients at risk of developing clinically significant portal hypertension (CSPH, defined by a hepatic venous pressure gradient (HVPG) 10 mmHg). Patients with cACLD are at high risk of liver-related morbidity and mortality. In patients at risk of chronic liver disease, cACLD is strongly suggested by a liver stiffness (LSM) value >15 kPa or clinical/biological/radiological signs of portal hypertension, and ruled out by LSM 150 G/L (favourable Baveno VI criteria) at the time of diagnosis. There is no non-invasive method alternative for oeso-gastroduodenal endoscopy in patients with unfavourable Baveno criteria (liver stiffness 20 kPa or platelet count 50 G/l). Platelet count and liver stiffness measurements must be performed once a year in patients with cACLD with favourable Baveno VI criteria at the time of diagnosis. A screening oeso-gastroduodenal endoscopy is recommended if Baveno VI criteria become unfavourable.
Published: 2022

6. French hepatitis C care cascade: substantial impact of direct-acting antivirals, but the road to elimination is still long

Author: Josiane Pillonel, A Rachas, Elisabeth Delarocque-Astagneau, Cécile Brouard, Nathalie Lydié, Christine Silvain, Marjorie Boussac, Corinne Pioche, Florence Lot, Julien Durand, Victor de Ledinghen, Stéphane Chevaliez, Direction des maladies infectieuses - Infectious Diseases Division [Saint-Maurice], Santé publique France - French National Public Health Agency [Saint-Maurice, France], Caisse Nationale de l'Assurance Maladie [Paris] (CNAM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre National de Référence Virus des hépatites B, C et Delta, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Raymond Poincaré [AP-HP], To all the people who contributed to producing the estimates used in this work: JC. Desenclos, A. Gautier, M. Jauffret-Roustide, C. Larsen, Y. Le Strat, C. Pelat, D. Rahib, JB. Richard, L. Saboni, C. Sommen (Sant? publique France), and F. Barin (National Reference Centre for HIV), C. Gastaldi-M?nager, T. Lesuffleur (Cnam) and the infectious work-group of the ReDSIAM. To Jude Sweeney for the English revision of the manuscript.
Subjects: Adult, Male, Health Knowledge, Attitudes, Practice, medicine.medical_specialty, Adolescent, Cascade of care, Elimination, Hepatitis C virus, Population, medicine.disease_cause, Direct-acting antivirals, Antiviral Agents, lcsh:Infectious and parasitic diseases, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Medical microbiology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Diagnosis, Credible interval, medicine, Prevalence, Humans, lcsh:RC109-216, 030212 general & internal medicine, education, Aged, Aged, 80 and over, education.field_of_study, business.industry, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, Confidence interval, Management, 3. Good health, Treatment, Chronic infection, Cross-Sectional Studies, Infectious Diseases, Tropical medicine, Female, 030211 gastroenterology & hepatology, France, business, Research Article
Abstract: Background Hepatitis C virus (HCV) elimination by 2030, as targeted by the World Health Organization (WHO), requires that 90% of people with chronic infection be diagnosed and 80% treated. We estimated the cascade of care (CoC) for chronic HCV infection in mainland France in 2011 and 2016, before and after the introduction of direct-acting antivirals (DAAs). Methods The numbers of people (1) with chronic HCV infection, (2) aware of their infection, (3) receiving care for HCV and (4) on antiviral treatment, were estimated for 2011 and 2016. Estimates for 1) and 2) were based on modelling studies for 2011 and on a virological sub-study nested in a national cross-sectional survey among the general population for 2016. Estimates for 3) and 4) were made using the National Health Data System. Results Between 2011 and 2016, the number of people with chronic HCV infection decreased by 31%, from 192,700 (95% Credibility interval: 150,900-246,100) to 133,500 (95% Confidence interval: 56,900-312,600). The proportion of people aware of their infection rose from 57.7 to 80.6%. The number of people receiving care for HCV increased by 22.5% (representing 25.7% of those infected in 2016), while the number of people on treatment increased by 24.6% (representing 12.1% of those infected in 2016). Conclusions This study suggests that DAAs substantially impact CoC. However, access to care and treatment for infected people remained insufficient in 2016. Updating CoC estimates will help to assess the impact of new measures implemented since 2016 as part of the goal to eliminate HCV.
Published: 2020

7. A single early-in-life antibiotic course increases susceptibility to DSS-induced colitis

Author: Guillermo I. Perez-Perez, Martin J. Blaser, Victoria E. Ruiz, Ceren Özkul, Thomas Battaglia, Claire Roubaud-Baudron, Joseph Xu, Ken Cadwell, Hacettepe University = Hacettepe Üniversitesi, New York University School of Medicine, NYU System (NYU), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle de Gérontologie Clinique [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Xavier Arnozan, Skirball Institute of Biomolecular Medicine, New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU), New York University Langone Medical Center (NYU Langone Medical Center), WINLAB Rutgers University, Rutgers, The State University of New Jersey [New Brunswick] (RU), Rutgers University System (Rutgers)-Rutgers University System (Rutgers), and Roubaud-Baudron, Claire
Subjects: 0301 basic medicine, Pulsed antibiotic treatment, Antibiotics, lcsh:Medicine, Disease, Childhood antibiotic use, Inflammatory bowel disease, chemistry.chemical_compound, Mice, 0302 clinical medicine, Intestinal Mucosa, Genetics (clinical), DSS-induced colitis, medicine.diagnostic_test, Dextran Sulfate, Age Factors, Biodiversity, T-Lymphocytes, Helper-Inducer, Colitis, 3. Good health, Anti-Bacterial Agents, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Molecular Medicine, Disease Susceptibility, Macrolide, medicine.drug, lcsh:QH426-470, medicine.drug_class, Tylosin, digestive system, Permeability, Flow cytometry, 03 medical and health sciences, Immune system, Genetics, medicine, Animals, Molecular Biology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Gastrointestinal microbiota, business.industry, Research, lcsh:R, Amoxicillin, medicine.disease, Gastrointestinal Microbiome, Disease Models, Animal, stomatognathic diseases, lcsh:Genetics, 030104 developmental biology, chemistry, Immunology, Dysbiosis, business, 030217 neurology & neurosurgery
Abstract: Background There is increasing evidence that the intestinal microbiota plays a crucial role in the maturation of the immune system and the prevention of diseases during childhood. Early-life short-course antibiotic use may affect the progression of subsequent disease conditions by changing both host microbiota and immunologic development. Epidemiologic studies provide evidence that early-life antibiotic exposures predispose to inflammatory bowel disease (IBD). Methods By using a murine model of dextran sodium sulfate (DSS)-induced colitis, we evaluated the effect on disease outcomes of early-life pulsed antibiotic treatment (PAT) using tylosin, a macrolide and amoxicillin, a beta-lactam. We evaluated microbiota effects at the 16S rRNA gene level, and intestinal T cells by flow cytometry. Antibiotic-perturbed or control microbiota were transferred to pups that then were challenged with DSS. Results A single PAT course early-in-life exacerbated later DSS-induced colitis by both perturbing the microbial community and altering mucosal immune cell composition. By conventionalizing germ-free mice with either antibiotic-perturbed or control microbiota obtained 40 days after the challenge ended, we showed the transferrable and direct effect of the still-perturbed microbiota on colitis severity in the DSS model. Conclusions The findings in this experimental model provide evidence that early-life microbiota perturbation may increase risk of colitis later in life.
Published: 2020

8. Targeted gene therapy in human-induced pluripotent stem cells from a patient with primary hyperoxaluria type 1 using CRISPR/Cas9 technology

Author: Jean-Marc Blouin, Pierre Dubus, J.P. Esteve, Audrey Bidet, Lamia Azzi-Martin, Aurélie Bedel, Brigitte Llanas, Emmanuel Richard, François Moreau-Gaudry, Jérôme Harambat, Magalie Lalanne, Isabelle Moranvillier, Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), and Physiopathologie du cancer du foie
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Genetic enhancement, Genetic Vectors, Induced Pluripotent Stem Cells, Biophysics, Biochemistry, Primary hyperoxaluria, Mice, 03 medical and health sciences, 0302 clinical medicine, CRISPR-Associated Protein 9, Animals, Humans, CRISPR, Medicine, Induced pluripotent stem cell, Molecular Biology, Base Sequence, business.industry, Cas9, Gene targeting, Genetic Therapy, Cell Biology, medicine.disease, 3. Good health, Transplantation, 030104 developmental biology, Genetic Loci, 030220 oncology & carcinogenesis, Hyperoxaluria, Primary, Hepatocytes, Cancer research, CRISPR-Cas Systems, business, Minigene
Abstract: Primary hyperoxaluria type 1 (PH1) is an inherited metabolic disorder caused by a deficiency of the peroxisomal enzyme alanine-glyoxylate aminotransferase (AGT), which leads to overproduction of oxalate by the liver and results in urolithiasis, nephrocalcinosis and renal failure. The only curative treatment for PH1 is combined liver and kidney transplantation, which is limited by the lack of suitable organs, significant complications, and the life-long requirement for immunosuppressive agents to maintain organ tolerance. Hepatocyte-like cells (HLCs) generated from CRISPR/Cas9 genome-edited human-induced pluripotent stem cells would offer an attractive unlimited source of autologous gene-corrected liver cells as an alternative to orthotopic liver transplantation (OLT). Here we report the CRISPR/Cas9 nuclease-mediated gene targeting of a single-copy AGXT therapeutic minigene into the safe harbour AAVS1 locus in PH1-induced pluripotent stem cells (PH1-iPSCs) without off-target inserts. We obtained a robust expression of a codon-optimized AGT in HLCs derived from AAVS1 locus-edited PH1-iPSCs. Our study provides the proof of concept that CRISPR/Cas9-mediated integration of an AGXT minigene into the AAVS1 safe harbour locus in patient-specific iPSCs is an efficient strategy to generate functionally corrected hepatocytes, which in the future may serve as a source for an autologous cell-based gene therapy for the treatment of PH1.
Published: 2019

9. Analysis of Liver Cancer Cell Lines Identifies Agents With Likely Efficacy Against Hepatocellular Carcinoma and Markers of Response

Author: Quentin Bayard, Eric Letouzé, Jill Pilet, Jean-Charles Nault, Léa Meunier, Bettina Grasl-Kraupp, Camille Péneau, Nataliya Rohr-Udilova, Tiziana La Bella, Gabrielle Couchy, J. Calderaro, Stefano Caruso, Leanne de Koning, Jessica Zucman-Rossi, Sandrine Imbeaud, Bérengère Ouine, Anna-Line Calatayud, Sandra Rebouissou, Samia Rekik, Paulette Bioulac-Sage, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Sorbonne Paris Cité (USPC), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Medizinische Universität Wien = Medical University of Vienna, Institut Curie [Paris], Université Paris sciences et lettres (PSL), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, chemistry.chemical_compound, 0302 clinical medicine, MEK Inhibitor, Antineoplastic Combined Chemotherapy Protocols, Gene expression, Gene Regulatory Networks, Protein Interaction Maps, Precision Medicine, Response to Therapy, Hepatocyte differentiation, MEK inhibitor, Liver Neoplasms, Gastroenterology, 3. Good health, Gene Expression Regulation, Neoplastic, Phenotype, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Liver Tumor, 030211 gastroenterology & hepatology, Signal transduction, Signal Transduction, medicine.drug, Sorafenib, Carcinoma, Hepatocellular, Tumor suppressor gene, Cell Survival, Clinical Decision-Making, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], microRNA, Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, Hepatology, Patient Selection, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Biomarker, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 030104 developmental biology, chemistry, Alisertib, Cancer research, Drug Screening Assays, Antitumor, Transcriptome
Abstract: International audience; BACKGROUND AND AIMS: Hepatocellular carcinomas (HCCs) are heterogeneous aggressive tumors with low rates of response to treatment at advanced stages. We screened a large panel of liver cancer cell lines (LCCLs) to identify agents that might be effective against HCC and markers of therapeutic response.METHODS: We performed whole-exome RNA and microRNA sequencing and quantification of 126 proteins in 34 LCCLs. We screened 31 anticancer agents for their ability to decrease cell viability. We compared genetic, RNA, and protein profiles of LCCLs with those of primary HCC samples and searched for markers of response.RESULTS: The protein, RNA and mutational signatures of the LCCLs were similar to those of the proliferation class of HCC, which is the most aggressive tumor type. Cell lines with alterations in genes encoding members of the Ras-MAPK signaling pathway and that required fibroblast growth factor (FGF)19 signaling via FGF receptor 4 for survival were more sensitive to trametinib than to FGF receptor 4 inhibitors. Amplification of FGF19 resulted in increased activity of FGF19 only in tumor cells that kept a gene expression pattern of hepatocyte differentiation. We identified single agents and combinations of agents that reduced viability of cells with features of the progenitor subclass of HCC. LCCLs with inactivating mutations in TSC1 and TSC2 were sensitive to the mammalian target of rapamycin inhibitor rapamycin, and cells with inactivating mutations in TP53 were sensitive to the Aurora kinase A inhibitor alisertib. Amplification of MET was associated with hypersensitivity to cabozantinib and the combination of sorafenib and inhibitors of MAP kinase 1 and MAP kinase2 had a synergistic antiproliferative effect.CONCLUSION: LCCLs can be screened for drugs and agents that might be effective for treatment of HCC. We identified genetic alterations and gene expression patterns associated with response to these agents. This information might be used to select patients for clinical trials.
Published: 2019

10. Repeat surgery in HNF1alpha-inactivated adenomatosis

Author: Nora Frulio, Laurence Chiche, Laurent Possenti, Paulette Bioulac-Sage, Charles Balabaud, Christophe Laurent, Saint Paul Marie Christine, Jean-Frédéric Blanc, Brigitte Le Bail, Physiopathologie du cancer du foie, and Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, Reoperation, Liver surgery, Nodule detection, medicine.medical_specialty, Time Factors, [SDV]Life Sciences [q-bio], Repeat Surgery, Adenoma, Liver Cell, Resection, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Hepatocyte Nuclear Factor 1-alpha, Favorable outcome, Hepatology, business.industry, Liver Neoplasms, Gastroenterology, Middle Aged, Hepatocellular adenoma, medicine.disease, Neoplasm Proteins, 3. Good health, Surgery, 030220 oncology & carcinogenesis, Disease Progression, Female, 030211 gastroenterology & hepatology, business
Abstract: Summary Background and aims Stopping oral contraceptives following nodule detection usually prevents further hepatocellular growth (HCA); rare cases of growth have been reported after surgery. The aim of the study was to review our resected HCA cases and their outcomes and more specifically, growth. Methods We retrieved all HCA cases that required a second intervention and HCA growth cases of none resected HCA after resection of one or several HCAs. Results Out of the 210 resected classified HCA cases, a second resection was performed in 5 cases, 4 of which were in women with HNF1alpha-inactivated adenomatosis (H-adenomatosis) and had a favorable outcome. The fifth case was the occurrence of an inflammatory HCA, 3 years after resection of a previous one. Of the 65 resected HNF1-inactivated HCAs (H-HCAs), the nodules that remained continued to increase very slowly in 3 adenomatosis cases. After surgery, the liver became dysmorphic years later in one case, and the nodules grew but not significantly in another case. After the diagnosis of adenomatosis, progressive growth leads to surgery 12 years later in the last case. Conclusion These results confirm that, in rare H-adenomatosis, size of nodules may increase very slowly, probably in part through coalescence of micro H-HCAs and leading occasionally to a second resection.
Published: 2019

11. Histopathological factors help to predict lymph node metastases more efficiently than extra-nodal recurrences in submucosa invading pT1 colorectal cancer

Author: J Jezequel, Mélanie Cariou, Bogdan Badic, Michel Robaszkiewicz, Laura Samaison, Pascale Marcorelles, Tiphaine Kermarrec, Jean-Pierre Bail, Arnaud Uguen, Jean-Baptiste Nousbaum, Laurent Doucet, Philippe Saliou, Franck Cholet, Fanny Barel, Amélie Bourhis, Anaïs Auffret, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Soins Primaires, Santé Publique, Registre des cancers de Bretagne Occidentale (SPURBO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Laboratoire d'Anatomo-Pathologie (CHU - AnaPath), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), and Michel, Geneviève
Subjects: Male, 0301 basic medicine, Databases, Factual, Colorectal cancer, High grade tumor, lcsh:Medicine, PT1 Colorectal Cancer, 0302 clinical medicine, Risk Factors, Submucosa, Tissue Distribution, Registries, lcsh:Science, Lymph node, Aged, 80 and over, Multidisciplinary, Colonoscopy, Middle Aged, 3. Good health, medicine.anatomical_structure, Lymphatic Metastasis, Adenocarcinoma, Female, France, Radiology, Colorectal Neoplasms, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Extra nodal, Aged, Neoplasm Staging, Retrospective Studies, business.industry, lcsh:R, Cancer, Endoscopy, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 030104 developmental biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, lcsh:Q, Lymph Nodes, Neoplasm Recurrence, Local, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: The therapeutic management of patients with endoscopic resection of colorectal cancer invading the submucosa (i.e. pT1 CRC) depends on the balance between the risk of cancer relapse and the risk of surgery-related morbidity and mortality. The aim of our study was to report on the histopathological risk factors predicting lymph node metastases and recurrences in an exhaustive case series comprising every pT1 CRC (of adenocarcinoma subtype only) diagnosed in Finistère (France) during 5-years. For 312 patients with at least 46 months follow-up included in the digestive cancers registry database, histopathological factors required for risk stratification in pT1 CRC were reviewed. Patients were treated by endoscopic resection only (51 cases), surgery only (138 cases), endoscopic resection followed by surgery (102 cases) or transanal resection (21 cases). Lymph node metastases were diagnosed in 19 patients whereas 15 patients had an extra-nodal recurrence (7 local recurrences only, 4 distant metastases only and 4 combining local and distant recurrences). Four patients with distant metastases died of their cancer. Poor tumor differentiation, vascular invasion and high grade tumor budding on HES slides were notably identified as strong risk-factors of lymph node metastases but the prediction of extra-nodal recurrences (local, distant and sometimes fatal) was less obvious, albeit it was more frequent in patients treated by transanal resection than with other treatment strategies. Beyond good performances in predicting lymph node metastases and guiding therapeutic decision in patients with pT1 CRC, our study points that extra-nodal recurrence of cancer is more difficult to predict and requires further investigations.
Published: 2019

12. Snapshot summary of diagnosis and management of hepatocellular adenoma subtypes

Author: Hervé Trillaud, P. Bioulac-Sage, Laurence Chiche, Nora Frulio, Brigitte Le Bail, Jean-Frédéric Blanc, Charles Balabaud, Christophe Laurent, Claire Castain, Christine Sempoux, Physiopathologie du cancer du foie, and Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Severe bleeding, Oncology, medicine.medical_specialty, Adenoma, [SDV]Life Sciences [q-bio], Disease, Adenoma, Liver Cell, Malignant transformation, 03 medical and health sciences, 0302 clinical medicine, Molecular classification, Internal medicine, medicine, Humans, Major complication, Pathological, Hepatology, business.industry, Liver Neoplasms, Gastroenterology, Hepatocellular adenoma, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business
Abstract: Hepatocellular adenomas (HCA) are rare benign hepatocellular tumors occurring mainly in women taking oral contraceptives with 2 major complications: severe bleeding and malignant transformation that can be avoided if nodules exceeding 5 cm are resected. This simple attitude has been challenged in the recent years with HCA in men, in young adolescent, in aged persons, and complications in hepatocellular adenomas below 5 cm. The discovery of specific mutations leading to specific phenotypes has modified the clinical spectrum of the disease. The phenotypic immune classification of HCA based on the molecular classification is being widely used in liver referral centers. The aim of this snapshot is to briefly present for each subtype the clinical, pathological, immuno-pathological criteria as well as the risk of complications and guidelines for treatment and management.
Published: 2019

13. Genome-wide identification of host-segregating SNPs for source attribution of clinical Campylobacter coli isolates

Author: Lehours, Philippe, Jehanne, Quentin, Pascoe, Ben, Benejat, Lucie, Ducournau, Astrid, Mourkas, Evangelos, Mégraud, Francis, Bessède, Emilie, Sheppard, Samuel, Centre National de Référence des Campylobacters et des Hélicobacters [Bordeaux] (CNRCH), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biology and Biochemistry [Bath, Royaume-Uni], Milner Centre for Evolution [Bath, Royaume-Uni], University of Bath [Bath]-University of Bath [Bath], Biochemistry and Molecular Biology Unit, Department of Basic Sciences, School of Medicine, University of Kinshasa (UNIKIN), LEHOURS, PHILIPPE, and University of Bath [Bath]
Subjects: [SDV] Life Sciences [q-bio], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV]Life Sciences [q-bio], [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology
Abstract: International audience; Campylobacter is among the most common causes of gastroenteritis worldwide. Campylobacter jejuni and Campylobacter coli are the most common species causing human-disease. DNA-sequence-based methods for strain characterization have focussed largely on C. jejuni, responsible for 80-90% of infections, meaning that C. coli epidemiology has lagged behind. Here we have analyzed the genome of 450 C. coli isolates to determine genetic markers that can discriminate isolates sampled from 3 major reservoir hosts (chickens, cattle and pigs). These markers were then applied to identify the source of infection of 147 C. coli from French clinical cases. Using STRUCTURE software, 259 potential host-segregating markers were revealed by probabilistic characterization of SNP frequency variation in strain collections from three different hosts. These SNPs were found in 41 genes or intergenic regions, mostly coding for proteins involved in motility and membrane functions. Source attribution of clinical isolates based on the differential presence of these markers confirmed chicken as the most common source of C. coli infection in France.IMPORTANCE Genome-wide and source attribution studies based on Campylobacter species have shown their importance for the understanding of foodborne infections. Although the use of MLST based on 7 genes from C. jejuni is a powerful method to structure populations, when applied to C. coli results have not clearly demonstrated their robustness. Therefore, we aim here to provide more accurate data based on the identification of single-nucleotide polymorphisms. Results from this study reveal an important number of host-segregating SNPs, found in proteins implied in motility, membrane functions or DNA repair systems. These findings offer new interesting opportunities for further study on C. coli adaptation to its environment. Additionally, the results demonstrate that poultry is potentially the main reservoir of C. coli in France.
Published: 2020

14. Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus

Author: Deng-Chyang Wu, Francis K.L. Chan, Chieh Chang Chen, Wei Lun Chang, David Y. Graham, Jyh-Ming Liou, Khay Guan Yeoh, Bor Shyang Sheu, Tsung-Hsien Chiang, Alex Hwong Ruey Leow, Joseph J.Y. Sung, Varocha Mahachai, Khean-Lee Goh, Francis Mégraud, Ming-Shiang Wu, Yi-Chia Lee, Kentaro Sugano, Tzu Chan Hong, Emad M. El-Omar, Takuji Gotoda, Peter Malfertheiner, Ping-I. Hsu, Mei Jyh Chen, Yoshio Yamaoka, Chun Ying Wu, Hong Lu, Jaw-Town Lin, Jeng Yih Wu, Hsiu Chi Cheng, National Taiwan University Hospital [Taipei], National Taiwan University College of Medicine [Taipei], National Taiwan University Cancer Center [Taipei], Otto-von-Guericke University [Magdeburg] (OVGU), Ludwig Maximilian University [Munich] (LMU), National Cheng Kung University Hospital [Tainan], Kaohsiung Medical University Hospital, Jichi Medical School [Tochigi], Tainan Hospital [Tainan], National University of Singapore (NUS), China Medical University [Tainan], University of Malaya [Kuala Lumpur, Malaisie], Chulalongkorn University [Bangkok], King Chulalongkorn Memorial Hospital [Bangkok], Nihon University School of Medicine [Tokyo, Japan], National Yang Ming University (NYMU), Taipei Veterans General Hospital [Taiwan], National Taiwan University Hospital Bei-Hu Branch [Taipei], Shanghai Jiao Tong University [Shanghai], Oita University Faculty of Medicine [Oita, Japon], Michael E. DeBakey Veterans Affairs Medical Center [Houston] (MEDVAMC), Baylor College of Medicine (BCM), Baylor University, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), French National Reference Centre for Helicobacters, CHU de Bordeaux Pellegrin [Bordeaux], The Chinese University of Hong Kong [Hong Kong], China Medical University Hospital [Taichung], University of New South Wales [Sydney] (UNSW), Asian Pacific Alliance on Helicobacter and Microbiota (APAHAM), Megraud, Francis, Otto-von-Guericke-Universität Magdeburg = Otto-von-Guericke University [Magdeburg] (OVGU), Jichi Medical University [Tochigi-Ken, Japan], and University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM)
Subjects: medicine.medical_specialty, Atrophic gastritis, Asymptomatic, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Health care, medicine, Young adult, Mass screening, 030304 developmental biology, 0303 health sciences, Cancer prevention, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, cancer prevention, business.industry, gastric cancer, screening, Gastroenterology, Intestinal metaplasia, helicobacter pylori - treatment, Helicobacter pylori, biology.organism_classification, medicine.disease, 3. Good health, helicobacter pylori, 030211 gastroenterology & hepatology, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: ObjectiveA global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for prevention of gastric cancer (GC).Methods28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed.ResultsConsensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of ‘the point of no return’. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori.ConclusionEvidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori. Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC.
Published: 2020

15. Classification system for Helicobacter pylori therapies: Compared and contrasted to traditional infectious disease therapy

Author: Francis Mégraud, David Y. Graham, Michael E. DeBakey Veterans Affairs Medical Center [Houston] (MEDVAMC), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), and Megraud, Francis
Subjects: MEDLINE, Microbial Sensitivity Tests, Communicable Diseases, Helicobacter Infections, 03 medical and health sciences, 0302 clinical medicine, Drug Resistance, Bacterial, Antimicrobial stewardship, Medicine, Humans, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Helicobacter pylori, business.industry, Gastroenterology, Amoxicillin, General Medicine, biology.organism_classification, 3. Good health, Anti-Bacterial Agents, Infectious Diseases, Infectious disease (medical specialty), Immunology, 030211 gastroenterology & hepatology, Drug Therapy, Combination, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; No abstract available
Published: 2020

16. European Registry on Helicobacter pylori management (Hp-EuReg): patterns and trends in first-line empirical eradication prescription and outcomes of 5 years and 21 533 patients

Author: Nyssen OP, Bordin D, Tepes B, Pérez-Aisa Á, Vaira D, Caldas M, Bujanda L, Castro-Fernandez M, Lerang F, Leja M, Rodrigo L, Rokkas T, Kupcinskas L, Pérez- Lasala J, Jonaitis L, Shvets O, Gasbarrini A, Simsek H, Axon ATR, Buzás G, Machado JC, Niv Y, Boyanova L, Goldis A, Lamy V, Tonkic A, Przytulski K, Beglinger C, Venerito M, Bytzer P, Capelle L, Milosavljević T, Milivojevic V, Veijola L, Molina-Infante J, Vologzhanina L, Fadeenko G, Ariño I, Fiorini G, Garre A, Garrido J, F Pérez C, Puig I, Heluwaert F, Megraud F, O'Morain C, Gisbert JP, Romano M, Universidad Autónoma de Madrid (UAM), AS Loginov Moscow Clinical Scientific Center [Moscow, Russian Federation], A.I. Yevdokimov Moscow State University of Medicine and Dentistry [Moscow, Russian Federation], AM DC Rogaska [Rogaska Slatina, Slovenia], Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), University of Bologna/Università di Bologna, Universidad del Pais Vasco / Euskal Herriko Unibertsitatea [Espagne] (UPV/EHU), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Østfold Hospital, University of Latvia (LU), Universidad de Oviedo [Oviedo], Henry Dunant Hospital [Athens, Greece], Lithuanian University of Health Sciences [Kaunas, Lithuania], Hospital Universitario HM Sanchinarro [Madrid, Spain], Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, Leeds General Infirmary (LGI), Leeds Teaching Hospitals NHS Trust, Ferencváros Health Centre [Budapest, Hungary], Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Tel Aviv University (TAU), Medical University of Sofia [Bulgarie], Timisoara Hospital [Timisoara, Romania], Centre Hospitalier Universitaire de Charleroi, University of Split, Medical Centre for Postgraduate Education [Warsaw, Poland], University Hospital Basel [Basel], Otto-von-Guericke-Universität Magdeburg = Otto-von-Guericke University [Magdeburg] (OVGU), Copenhagen University Hospital, Meander Medical Center [Amersfoort, Netherlands], University of Belgrade [Belgrade], Herttoniemi Hospital [Helsinki, Finland], San Pedro de Alcantara Hospital [Cáceres, Espagne], Gastrocentr [Perm, Russian Federation], Digestive Ukrainian Academy of Medical Sciences [Kyiv, Ukraine], Hospital Clínico Universitario 'Lozano Blesa' [Zaragoza, Spain], Althaia Xarxa Assistencial Universitària de Manresa [Manresa, Spain], Universitat de Vic-Universitat Central de Catalunya [Manresa, Spain] (UVicUCC), Complejo Hospitalario Universitario de Santiago de Compostela [Saint-Jacques-de-Compostelle, Espagne] (CHUS), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Trinity College Dublin, Hp-EuReg Investigators: Jen Hinojosa, Inmaculada Santaella, Nuria Fernandez Moreno, Ilaria Maria Saracino, Horacio Alonso Galán, Almudena Durán, Jennifer Fernandez Pacheco, Miroslav Vujasinovic, Rinaldo Pellicano Molinette, Zdenko Kikec, Pedro-Luis Gonzalez Cordero, Maia Donday, Polona Lampic, Vid Leban, Aleksander Gruncic Krajnc, Natasa Brglez Jurecic, Galyna Dmytrivna Fadieienko, Lorena Lee, Irene V Barbado, Alfredo José Lucendo, Alfredo José Lucendo, Jesus Barrio RIo Hortega, Tatiana Alekseevna Ilchishina, Irina Voynovan, Luis Ignacio Fernández-Salazar, Jose María Huguet, Pilar Canelles, Aiman Silkanovna Sarsenbaeva, Ines Modolell Consorci, Pedro Almela, Marina Roldán Lafuente, Josep Maria Botargues, Miguel Areia, Luís Elvas, Susana Isabel Alves, Daniel Brito, Ana Teresa Cadime, Sandra Lúcia Madeira Saraiva, Charalampos Tzathas, Vassiliki Ntouli, Alicia C Marin, Cem Simsek, Alba Rocco, Juan Antonio Ortuño, Tommaso Di Maira, Sotirios D Georgopoulos, Stephan Brackmann, Vendel Kristensen Lovisenberg, Blas Jose Gomez-Rodriguez, Perminder Singh Phull, Sergey Alekseyevich, Monica Perona, Rustam Abdulkhakov, Deirdre McNamara, Sinead M Smith, Denise Elizabeth Brennan, Marina Fedorovna Osipenko, Cristobal de la Coba, Pilar Varela, Maria Anatolyevna Livzan, Oleg V Zaytsev, Vladislav Vladimirovich Tsukanov, Alexander Viktorovich Vasyutin, Olga Sergeevna Amelchugova, Spiros Michopoulus, Sergey Gennadievich Burkov, Dan Dumitrascu, Bogdan Ianosi, Ingrid Prytz Berset, Rafael Ruiz-Zorrilla Lopez, Charo Antón, Anne Courillon-Mallet, Natasa Brglez Jurecic, Judith Gomez-Camarero, Manuel Jimenez-Moreno, Ahmet Uygun, Ian Leonard Phillip Beales, Alain Huerta-Madrigal, Javier Alcedo, Mercè Barenys, Francesco Franceschi, Jean-Charles Delchier, Liliana Silvia Pozzati, Monika Augustyn, Maja Seruga, Miriam Hiestand, Patric Mosler, Zaza Beniashvili, Doron Boltin, Hubert Louis, Ramon Pajares, Natalia Valerievna Zakharova, Natalia Nikolaevna Dekhnich, Victor Asparuhov Kamburov, Maria Pina Dore, Lorena Sancho, Oscar Núñez, Katrine Dvergsnes Sørlandet, Peter Malfertheiner, Ana Campillo, Miguel Fernandez-Bermejo, Manuel Domínguez-Cajal, José Luis Domínguez Jiménez, Alicia Algaba, Fernando Bermejo, Borislav Vladimirov, László Czakó, Teresa Angueira, Eduardo Iyo, Ekaterina Yuryevna, Larissa Tarasova, Ludmila Grigorieva, Judith Millastre, Aldis Pukitis, Valeriy Kryvy, Roald Torp, Albert Tomàs, Edurne Amorena, Fermin Estremera, Rossen Nikolov, Asghar Quasim, Yury Aleksandrovich Kucheryavyy, Natalia Baryshnikova, Xavier Calvet, Ariadna Figuerola, Marco Romano, Antonietta Gerarda Gravina, Oscar Núñez, Fazia Mana, Pilar Sánchez-Pobre, Zoya Spassova, Jesús M González-Santiago, Ricardo Marcos-Pinto, F Wolfhagen, Svetlana Cui, Ivonne Leeuwenburgh, Driffa Moussata, Adi Lahat-Zok, Sergii Hryhorovych, Rasmus Goll, Tatyana Vasilyevna, Juris Pokrotnieks, Philippe Émile, Nadiya Byelyayeva, Marta Lozano, Mette Wildner-Christensen, Bengt Odman, Yana Valerieva, Alenka Forte, Antonio Cuadrado, Patrice Pienkowski, Ilze Kikuste, Dag Arne Lihaug Hoff, Jane Moeller Hansen, Konrads Funka, Alla Kononova, Sergey Kolbasnikov, Michael Selgrad, Jolanta Sumskiene, Jonathan Hirsch, Francisco Javier Zozaya Larequi, Alain C Burette, Nora Dancs Petz-Aladar, Janne Rajala Herttoniemi, Christina Reimer, Diogo Libanio, Pedro Pimentel-Nunes, Ivailo Evstatiev, Juozas Kupcinskas, Mikhail Butov, Peter Mensink, T Tang, Andrey Yurevich Baranovsky, Natalya Marchenko, Boris Bastens, Lyudmila Mateva, Dominique Lamarque, Leonardo Henry, Mario Ribeiro, M Ter Borg, Alexander C Ford, Enrique Medina, Manuel Rodriguez-Tellez, Francisco José Rancel, Elisa Martin, Carolina Torres Gonzalez, Lissa Maria Franco, Angel Lanas, Pilar Canelles, Noelia Alcaide, Bruno Richard-Molard, Megraud, Francis, Nyssen O.P., Bordin D., Tepes B., Perez-Aisa A., Vaira D., Caldas M., Bujanda L., Castro-Fernandez M., Lerang F., Leja M., Rodrigo L., Rokkas T., Kupcinskas L., Perez-Lasala J., Jonaitis L., Shvets O., Gasbarrini A., Simsek H., Axon A.T.R., Buzas G., Machado J.C., Niv Y., Boyanova L., Goldis A., Lamy V., Tonkic A., Przytulski K., Beglinger C., Venerito M., Bytzer P., Capelle L., Milosavljevic T., Milivojevic V., Veijola L., Molina-Infante J., Vologzhanina L., Fadeenko G., Arino I., Fiorini G., Garre A., Garrido J., F Perez C., Puig I., Heluwaert F., Megraud F., O'Morain C., Gisbert J.P., Universidad Autonoma de Madrid (UAM), University of Bologna, Università cattolica del Sacro Cuore [Roma] (Unicatt), Universidade do Porto, Tel Aviv University [Tel Aviv], Otto-von-Guericke University [Magdeburg] (OVGU), Nyssen, Op, Bordin, D, Tepes, B, Pérez-Aisa, Á, Vaira, D, Caldas, M, Bujanda, L, Castro-Fernandez, M, Lerang, F, Leja, M, Rodrigo, L, Rokkas, T, Kupcinskas, L, Pérez- Lasala, J, Jonaitis, L, Shvets, O, Gasbarrini, A, Simsek, H, Axon, Atr, Buzás, G, Machado, Jc, Niv, Y, Boyanova, L, Goldis, A, Lamy, V, Tonkic, A, Przytulski, K, Beglinger, C, Venerito, M, Bytzer, P, Capelle, L, Milosavljević, T, Milivojevic, V, Veijola, L, Molina-Infante, J, Vologzhanina, L, Fadeenko, G, Ariño, I, Fiorini, G, Garre, A, Garrido, J, F Pérez, C, Puig, I, Heluwaert, F, Megraud, F, O'Morain, C, Gisbert, Jp, and Romano, M
Subjects: Male, Registrie, Proton Pump Inhibitor, Practice Patterns, 0302 clinical medicine, Clarithromycin, Prospective Studies, Registries, Practice Patterns, Physicians', [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Gastroenterology, Middle Aged, Anti-Bacterial Agents, 3. Good health, Europe, 030220 oncology & carcinogenesis, Combination, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, medicine.drug, Human, Adult, medicine.medical_specialty, TRIPLE THERAPY, QUADRUPLE THERAPY, CONSENSUS, INFECTION, METAANALYSIS, CLARITHROMYCIN, GUIDELINES, RESISTANCE, ARTICLE, Settore MED/12 - GASTROENTEROLOGIA, First line, Helicobacter Infections, 03 medical and health sciences, Drug Therapy, Internal medicine, Anti-Bacterial Agent, medicine, Humans, Medical prescription, Adverse effect, Aged, Physicians', Helicobacter pylori, business.industry, helicobacter pylori - treatment, Proton Pump Inhibitors, Amoxicillin, biology.organism_classification, Metronidazole, Prospective Studie, Concomitant, helicobacter pylori, business, Helicobacter Infection, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: ObjectiveThe best approach for Helicobacter pylori management remains unclear. An audit process is essential to ensure clinical practice is aligned with best standards of care.DesignInternational multicentre prospective non-interventional registry starting in 2013 aimed to evaluate the decisions and outcomes in H. pylori management by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables included demographics, previous eradication attempts, prescribed treatment, adverse events and outcomes. Data monitoring was performed to ensure data quality. Time-trend and geographical analyses were performed.Results30 394 patients from 27 European countries were evaluated and 21 533 (78%) first-line empirical H. pylori treatments were included for analysis. Pretreatment resistance rates were 23% to clarithromycin, 32% to metronidazole and 13% to both. Triple therapy with amoxicillin and clarithromycin was most commonly prescribed (39%), achieving 81.5% modified intention-to-treat eradication rate. Over 90% eradication was obtained only with 10-day bismuth quadruple or 14-day concomitant treatments. Longer treatment duration, higher acid inhibition and compliance were associated with higher eradication rates. Time-trend analysis showed a region-dependent shift in prescriptions including abandoning triple therapies, using higher acid-inhibition and longer treatments, which was associated with an overall effectiveness increase (84%–90%).ConclusionManagement of H. pylori infection by European gastroenterologists is heterogeneous, suboptimal and discrepant with current recommendations. Only quadruple therapies lasting at least 10 days are able to achieve over 90% eradication rates. European recommendations are being slowly and heterogeneously incorporated into routine clinical practice, which was associated with a corresponding increase in effectiveness.
Published: 2020

17. Review: Other Helicobacter species

Author: Annemieke Smet, Armelle Menard, University of Antwerp (UA), Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence des Campylobacters et Hélicobacters [CHU Bordeaux] (CNR Campylobacters et Hélicobacters), CHU Bordeaux [Bordeaux], and Menard, Armelle
Subjects: Gastrointestinal Diseases, [SDV]Life Sciences [q-bio], Virulence, Disease, Gut flora, Genome, Animal Diseases, Meningitis, Bacterial, Helicobacter Infections, Microbiology, 03 medical and health sciences, Helicobacter cinaedi, 0302 clinical medicine, Sepsis, Helicobacter, Animals, Humans, Biology, 030304 developmental biology, Comparative genomics, non-Helicobacter pylori Helicobacter, 0303 health sciences, biology, 030306 microbiology, Gastroenterology, human disease, General Medicine, pathogenesis, Helicobacter pylori, biology.organism_classification, animal models, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, genomics and evolution, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Human medicine, animal disease
Abstract: This article is a review of the most important, accessible, and relevant literature published between April 2018 and April 2019 in the field of Helicobacter species other than Helicobacter pylori. The initial part of the review covers new insights regarding the presence of gastric and enterohepatic non-H. pylori Helicobacter species (NHPH) in humans and animals, while the subsequent section focuses on the progress in our understanding of the pathogenicity and evolution of these species. Over the last year, relatively few cases of gastric NHPH infections in humans were published, with most NHPH infections being attributed to enterohepatic Helicobacters. A novel species, designated "Helicobacter caesarodunensis," was isolated from the blood of a febrile patient and numerous cases of human Helicobacter cinaedi infections underlined this species as a true emerging pathogen. With regard to NHPH in animals, canine/feline gastric NHPH cause little or no harm in their natural host; however they can become opportunistic when translocated to the hepatobiliary tract. The role of enterohepatic Helicobacter species in colorectal tumors in pets has also been highlighted. Several studies in rodent models have further elucidated the mechanisms underlying the development of NHPH-related disease, and the extra-gastric effects of a Helicobacter suis infection on brain homeostasis was also studied. Comparative genomics facilitated a breakthrough in the evolutionary history of Helicobacter in general and NHPH in particular. Investigation of the genome of Helicobacter apodemus revealed particular traits with regard to its virulence factors. A range of compounds including mulberries, dietary fiber, ginseng, and avian eggs which target the gut microbiota have also been shown to affect Helicobacter growth, with a potential therapeutic utilization and increase in survival.
Published: 2020

18. Review ‐ Helicobacter, inflammation, immunology and vaccines

Author: Karen Robinson, Philippe Lehours, Centre National de Référence des Campylobacters et des Hélicobacters [Bordeaux] (CNRCH), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), National Institute of Water and Atmospheric Research [Christchurch] (NIWA), and LEHOURS, PHILIPPE
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Helicobacter Infections, 03 medical and health sciences, 0302 clinical medicine, Animals, Humans, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, innate immunity, 030304 developmental biology, 0303 health sciences, Helicobacter pylori, vaccines, Gastroenterology, adaptive immunity, General Medicine, Immunity, Innate, cytokines, 3. Good health, [SDV] Life Sciences [q-bio], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Gastric Mucosa, inflammation, 030220 oncology & carcinogenesis, Bacterial Vaccines, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract: International audience; Understanding the mechanisms involved in induction and regulation of the immune and inflammatory response to Helicobacter pylori is extremely important in determining disease outcomes. H pylori expresses a plethora of factors that influence the host response. Vaccines against H pylori are desperately needed for the prevention of gastric carcinogenesis, especially with the increasing trends in antimicrobial resistance. This review summarizes some important findings, published between 1 April 2019 and 31 March 2020, in the areas of H pylori-mediated inflammation, immunity and vaccines.
Published: 2020

19. Review: Diagnosis of Helicobacter pylori infection

Author: Gauri, Godbole, Francis, Mégraud, Emilie, Bessède, Public Health England [London, UK], Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), and Megraud, Francis
Subjects: Antigens, Bacterial, Helicobacter pylori, Biopsy, Gastroenterology, General Medicine, Helicobacter Infections, 3. Good health, Feces, 03 medical and health sciences, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 0302 clinical medicine, Infectious Diseases, Breath Tests, 030220 oncology & carcinogenesis, Humans, Urea, 030211 gastroenterology & hepatology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology
Abstract: International audience; New imaging techniques are still the topic of many evaluations for both the diagnosis of Helicobacter pylori gastritis and the detection of early gastric cancer. Concerning invasive tests, there were studies on the reuse of the rapid urease test material for other tests, and a novel fluorescent method to be used for histology but with limited sensitivity. Progress occurred essentially in the molecular methods area, especially next‐generation sequencing which is applied to detect both H pylori and the mutations associated with antibiotic resistance. For non‐invasive tests, a few studies have been published on the validity of breath collection bags, the shortening of the testing time, the performance of different analysers or the added value of citric acid in the protocol. The accuracy of serological immunochromatographic tests is also improving. Multiplex serology detecting antibodies to certain proteins allows confirmation of a current infection. Dried blood spots can be used to collect and store blood without a loss of accuracy. Finally, the serum antibody titer can be useful in predicting the risk of gastric cancer. Several stool antigen tests were evaluated with good results, and a novel test using immunomagnetic beads coated with monoclonal antibodies is potentially interesting. PCR detection in stools can also be effective but needs an efficient DNA extraction method. The use of easyMAG® (bioMérieux) combined with Amplidiag® H pylori + ClariR (Mobidiag) appears to be powerful.
Published: 2020

20. The Reply

Author: Caroline Hyernard, Claire Roubaud Baudron, Pôle de Gérontologie Clinique [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Xavier Arnozan, Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), and Roubaud-Baudron, Claire
Subjects: 030203 arthritis & rheumatology, 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Risk Factors, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Humans, Bacteremia, General Medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Aged
Abstract: International audience; No abstract available
Published: 2020

21. Survey of the antimicrobial resistance of Helicobacter pylori in France in 2018 and evolution during the previous 5 years

Author: Astrid Ducournau, Paul Charron, Emilie Bessède, Philippe Lehours, Francis Mégraud, Chloé Alix, Lucie Bénéjat, Centre National de Référence des Campylobacters et des Hélicobacters [Bordeaux] (CNRCH), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), and LEHOURS, PHILIPPE
Subjects: Male, [SDV]Life Sciences [q-bio], Antibiotics, Gastroenterology, 0302 clinical medicine, Levofloxacin, Clarithromycin, biology, General Medicine, Middle Aged, 3. Good health, Anti-Bacterial Agents, [SDV] Life Sciences [q-bio], Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, France, Rifampin, real-time PCR, medicine.drug, Adult, medicine.medical_specialty, medicine.drug_class, Microbial Sensitivity Tests, Helicobacter Infections, 03 medical and health sciences, Antibiotic resistance, Internal medicine, Metronidazole, Drug Resistance, Bacterial, medicine, Humans, primary resistance, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Aged, levofloxacin, Helicobacter pylori, business.industry, Amoxicillin, biology.organism_classification, culture, business, Rifampicin
Abstract: International audience; Background and objectives: Surveillance of Helicobacter pylori resistance to antibiotics was carried out in France in 2014, 2016, and 2018. We report here the results of the 2018 survey as well as the evolution over the 5-year period.Materials and methods: In this observational study, gastric biopsies were obtained by 62 gastroenterologists randomly selected in 5 regions of France and sent to a central laboratory where culture, antimicrobial susceptibility testing, and a real-time PCR were performed in order to detect H pylori and its mutations associated with clarithromycin resistance.Results and conclusion: During the year 2018, 951 patients were included: 55.3% women, mean age: 52.4 years ± 15.7, 71.6% born in France. Among them, 359 patients were H pylori positive by both culture and real-time PCR, and 7 more by PCR only. There were 244 naive patients, 110 previously treated patients, and unknown for 5. Primary resistance to clarithromycin was 20.9% [16.3-26.4], to levofloxacin 17.6% [13.4-22.9], and to metronidazole 58.6% [52.3%-64.6%]. Secondary resistance for these antibiotics was 56.4%, 22.7%, and 87.3%, respectively. There was no resistance to amoxicillin and tetracycline and very low resistance to rifampicin (1.2%) in both naive and treated patients. Primary resistance to clarithromycin decreased from 22.2% to 20.3% between 2014 and 2016, and appears to be stable since then. This can be linked to a stable consumption of macrolides over the 3-year time period. Primary levofloxacin resistance was relatively stable while metronidazole resistance increased. Interestingly, in both naive and treated patients, amoxicillin and rifampicin resistance were rare.
Published: 2020

22. Characteristics of MGUS and Multiple Myeloma According to the Target of Monoclonal Immunoglobulins, Glucosylsphingosine, or Epstein-Barr Virus EBNA-1

Author: Bosseboeuf, Adrien, Mennesson, Nicolas, Allain-Maillet, Sophie, Tallet, Anne, Piver, Eric, Decaux, Olivier, Moreau, Caroline, Moreau, Philippe, Lehours, Philippe, Mégraud, Francis, Salle, Valéry, Bigot-Corbel, Edith, Harb, Jean, Hermouet, Sylvie, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Molecular Mechanisms of Chronic Inflammation in Hematological Diseases (CRCINA-ÉQUIPE 16), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Laboratoire de Biochimie [CHU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service de Médecine Interne [CHU Pontchaillou, Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes], Laboratoire de Biochimie [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Département d'Hématologie Clinique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Bactériologie [Bordeaux], Centre National de Référence des Campylobacters et des Hélicobacters [Bordeaux] (CNRCH), Médecine Interne et Maladies Systémiques [CHU Amiens-Picardie], CHU Amiens-Picardie, Laboratoire de Biochimie [Nantes], Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire d'Hematologie [CHU Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Le Bihan, Sylvie, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: monoclonal immunoglobulin, [SDV]Life Sciences [q-bio], interleukin-13 (IL-13), monoclonal gammopathy of undetermined significance (MGUS), auto-antigen, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, interleukin-26 (IL-26), glucosylsphingosine (GlcSph), lcsh:RC254-282, Article, [SDV] Life Sciences [q-bio], multiple myeloma, sialylation, inflammation, hemic and lymphatic diseases, interleukin-17 (IL-17), cytokine, antigen specificity, lysoglucosyl-ceramide (LGL1)
Abstract: International audience; Chronic stimulation by infectious or self-antigens initiates subsets of monoclonal gammopathies of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or multiple myeloma (MM). Recently, glucosylsphingosine (GlcSph) was reported to be the target of one third of monoclonal immunoglobulins (Igs). In this study of 233 patients (137 MGUS, 6 SMM, 90 MM), we analyzed the GlcSph-reactivity of monoclonal Igs and non-clonal Igs. The presence of GlcSph-reactive Igs in serum was unexpectedly frequent, detected for 103/233 (44.2%) patients. However, GlcSph was targeted by the patient’s monoclonal Ig for only 37 patients (15.9%); for other patients (44 MGUS, 22 MM), the GlcSph-reactive Igs were non-clonal. Then, the characteristics of patients were examined: compared to MM with an Epstein-Barr virus EBNA-1-reactive monoclonal Ig, MM patients with a GlcSph-reactive monoclonal Ig had a mild presentation. The inflammation profiles of patients were similar except for moderately elevated levels of 4 cytokines for patients with GlcSph-reactive Igs. In summary, our study highlights the importance of analyzing clonal Igs separately from non-clonal Igs and shows that, if autoimmune responses to GlcSph are frequent in MGUS/SMM and MM, GlcSph presumably represents the initial pathogenic event for ~16% cases. Importantly, GlcSph-initiated MM appears to be a mild form of MM disease.
Published: 2020

23. Analysis of the Targets and Glycosylation of Monoclonal IgAs From MGUS and Myeloma Patients

Author: Adrien Bosseboeuf, Célia Seillier, Nicolas Mennesson, Sophie Allain-Maillet, Maeva Fourny, Anne Tallet, Eric Piver, Philippe Lehours, Francis Mégraud, Laureline Berthelot, Jean Harb, Edith Bigot-Corbel, Sylvie Hermouet, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Laboratoire de Biochimie [CHU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du cancer du foie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Laboratoire de Bactériologie, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire de Biochimie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'Hématologie [CHU Nantes], The Ligue Nationale contre le Cancer, the Cancéropôle Grand Ouest and Région Pays de la Loire and Région Centre (2015–2016), and Janssen USA., Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Le Bihan, Sylvie, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: 0301 basic medicine, Male, hepatitis C virus, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Glycosylation, lysoglucosylceramide (LGL-1), [SDV]Life Sciences [q-bio], Hepacivirus, medicine.disease_cause, Monoclonal Gammopathy of Undetermined Significance, Cohort Studies, Epstein–Barr virus, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Immunology and Allergy, Antigens, Viral, Multiple myeloma, Original Research, Aged, 80 and over, Viral Core Proteins, Antibodies, Monoclonal, Middle Aged, Hepatitis C, 3. Good health, [SDV] Life Sciences [q-bio], multiple myeloma, Monoclonal, Female, Epstein–Barr virus nuclear antigen 1, lcsh:Immunologic diseases. Allergy, Hepatitis C virus, Immunology, infectious antigens, monoclonal gammopathy of undetermined significance (MGUS), Glucosylceramides, Virus, 03 medical and health sciences, sialylation, Antigen, medicine, monoclonal immunoglobulin A (IgA), Humans, Aged, business.industry, medicine.disease, Immunoglobulin A, 030104 developmental biology, Epstein-Barr Virus Nuclear Antigens, business, lcsh:RC581-607, Monoclonal gammopathy of undetermined significance, 030215 immunology
Abstract: International audience; Previous studies showed that monoclonal immunoglobulins G (IgGs) of “monoclonal gammopathy of undetermined significance” (MGUS) and myeloma were hyposialylated, thus presumably pro-inflammatory, and for about half of patients, the target of the monoclonal IgG was either a virus—Epstein–Barr virus (EBV), other herpes viruses, hepatitis C virus (HCV)—or a glucolipid, lysoglucosylceramide (LGL1), suggesting antigen-driven disease in these patients. In the present study, we show that monoclonal IgAs share these characteristics. We collected 35 sera of patients with a monoclonal IgA (6 MGUS, 29 myeloma), and we were able to purify 25 of the 35 monoclonal IgAs (6 MGUS, 19 myeloma). Monoclonal IgAs from MGUS and myeloma patients were significantly less sialylated than IgAs from healthy volunteers. When purified monoclonal IgAs were tested against infectious pathogens and LGL1, five myeloma patients had a monoclonal IgA that specifically recognized viral proteins: the core protein of HCV in one case, EBV nuclear antigen 1 (EBNA-1) in four cases (21.1%of IgA myeloma). Monoclonal IgAs from three myeloma patients reacted against LGL1. In summary, monoclonal IgAs are hyposialylated and as described for IgG myeloma, significant subsets (8/19, or 42%) of patients with IgA myeloma may have viral or self (LGL1) antigen-driven disease.
Published: 2020

24. HAVCR2 mutations are associated with severe hemophagocytic syndrome in subcutaneous panniculitis-like T-cell lymphoma

Author: Sonigo, Gabrielle, Battistella, Maxime, Beylot-Barry, Marie, Ingen-Housz-Oro, Saskia, Franck, Nathalie, Barète, Stéphane, Boulinguez, Serge, Dereure, Olivier, Bonnet, Nathalie, Brice, Pauline, Boccara, Olivia, Bodemer, Christine, Adamski, Henri, D'Incan, Michel, Ortonne, Nicolas, Fraitag, Sylvie, Brunet-Possenti, Florence, Dalle, Stéphane, Suarez, Felipe, Skowron, François, Haidar, Dima, Maubec, Eve, Bohelay, Gerome, Laroche, Liliane, Mahé, Antoine, Birckel, Elodie, Bouaziz, Jean-David, Brocheriou, Isabelle, Dubois, Romain, Faiz, Sarah, Fadlallah, Jehane, Ram-Wolff, Caroline, Carlotti, Agnès, Bens, Guido, Balme, Brigitte, Vergier, Béatrice, Laurent-Roussel, Sara, Deschamps, Lydia, Carpentier, Olivier, Moguelet, Philippe, Herve, Genevieve, Comoz, Francois, Le Gall, François, Leverger, Guy, Finon, Antoine, Augereau, Olivier, Blechet, Claire, Kerdraon, Rémy, Lamant, Laurence, Tournier, Emilie, Franck, Frédéric, Costes-Martineau, Valérie, Szablewski, Vanessa, Taix, Sebastien, Beschet, Isabelle, Guérin, Frédéric, Sepulveda Garrido, Fernando, Bagot, Martine, De Saint Basile, Geneviève, Michonneau, David, de Masson, Adèle, Socié, Gérard, Bodemer, Shristine ChB, Marçais, Ambroise, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], CHU Henri Mondor, Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Toulouse [Toulouse], Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Hôpital Nord [CHU - APHM], Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Service de dermatologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CHU Pontchaillou [Rennes], CHU Clermont-Ferrand, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'immuno-hématologie pédiatrique [CHU Necker], Centre Hospitalier de Valence (CH DE VALENCE), Centre hospitalier de Valence, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Avicenne [AP-HP], Hôpital pasteur [Colmar], Service de Dermatologie [AP-HP Hôpital Saint-Louis], Service d'Anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière] (ACP), Mouvement, Équilibre, Performance, Santé (MEPS), Université de Pau et des Pays de l'Adour (UPPA), Service de Dermatologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de dermatologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiopathologie du cancer du foie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Service de pathologie [CHU Bichat], Service d’Anatomie et cytologie pathologiques [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Service d'anatomie et cytologie pathologiques [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Laboratoire d'aérologie (LAERO), Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Unité d'hématologie et de transplantation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service d’anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomie et cytologie pathologiques [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Centre Hospitalier Régional d'Orléans (CHR), Laboratoire d'aérologie (LA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Immunologie humaine, physiopathologie & immunithérapie (HIPI (UMR_S_976 / U976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'Anatomie et cytologie pathologiques [CHU Tenon], CHU Tenon [AP-HP], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), COLO, Mouniati, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor [Créteil], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Pathology, medicine.medical_specialty, Panniculitis, [SDV]Life Sciences [q-bio], Immunology, 2 supplemental tables, [SDV.CAN]Life Sciences [q-bio]/Cancer, Lymphoma, T-Cell, HAVCR2, Biochemistry, Lymphohistiocytosis, Hemophagocytic, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Subcutaneous Panniculitis-Like T-Cell Lymphoma, 9 references Article type: Letter Scientific category: Lymphoma, Humans, Medicine, Genetic Predisposition to Disease, Hepatitis A Virus Cellular Receptor 2, Genetic Association Studies, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Hemophagocytic lymphohistiocytosis, business.industry, Cell Biology, Hematology, medicine.disease, 3. Good health, Lymphoma, [SDV] Life Sciences [q-bio], 1 supplemental figure, 030220 oncology & carcinogenesis, Mutation, Mutation (genetic algorithm), 2 tables, Female, business, Biomarkers
Abstract: International audience
Published: 2020

25. APRIL-producing eosinophils are involved in gastric MALT lymphomagenesis induced by Helicobacter sp infection

Author: Pierre Dubus, Sara Peru, Alban Giese, Pauline Floch, Alice Blosse, Bertrand Huard, Francis Mégraud, Christiane Copie Bergman, Lamia Azzi Martin, Agnès Ruskone Fournestraux, Benoit S. Marteyn, Michael Levy, Philippe Lehours, Bettina Fabiani, Martine Prochazkova-Carlotti, Elodie Sifré, Cyrielle Robe, Michael Hahne, Centre National de Référence des Campylobacters et des Hélicobacters [Bordeaux] (CNRCH), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU de Bordeaux Pellegrin [Bordeaux], London Health Sciences Center (LHSC), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, and LEHOURS, PHILIPPE
Subjects: 0301 basic medicine, Male, [SDV]Life Sciences [q-bio], medicine.medical_treatment, T-Lymphocytes, lcsh:Medicine, Mice, 0302 clinical medicine, Helicobacter, lcsh:Science, B-Lymphocytes, Multidisciplinary, biology, GATA3, FOXP3, Middle Aged, [SDV] Life Sciences [q-bio], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, medicine.anatomical_structure, Lymphatic system, Cytokine, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Adult, [SDV.IMM] Life Sciences [q-bio]/Immunology, Regulatory T cell, Tumor Necrosis Factor Ligand Superfamily Member 13, [SDV.CAN]Life Sciences [q-bio]/Cancer, Mice, Transgenic, Article, Helicobacter Infections, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Animals, Humans, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, B cell, lcsh:R, Lymphoma, B-Cell, Marginal Zone, Bacterial pathogenesis, medicine.disease, biology.organism_classification, Lymphoma, Eosinophils, Mice, Inbred C57BL, 030104 developmental biology, Gastric Mucosa, Immunology, lcsh:Q, Gastric cancer
Abstract: The roles of the inflammatory response and production of a proliferation-inducing ligand (APRIL) cytokine in gastric mucosa-associated lymphoid tissue (MALT) lymphomagenesis induced by Helicobacter species infection are not clearly understood. We characterized the gastric mucosal inflammatory response associated with gastric MALT lymphoma (GML) and identified APRIL-producing cells in two model systems: an APRIL transgenic mouse model of GML induced by Helicobacter infection (Tg-hAPRIL) and human gastric biopsy samples from Helicobacter pylori-infected GML patients. In the mouse model, polarization of T helper 1 (tbet), T helper 2 (gata3), and regulatory T cell (foxp3) responses was evaluated by quantitative PCR. In humans, a significant increase in april gene expression was observed in GML compared to gastritis. APRIL-producing cells were eosinophilic polynuclear cells located within lymphoid infiltrates, and tumoral B lymphocytes were targeted by APRIL. Together, the results of this study demonstrate that the Treg-balanced inflammatory environment is important for gastric lymphomagenesis induced by Helicobacter species, and suggest the pro-tumorigenic potential of APRIL-producing eosinophils.
Published: 2020

26. The Nuclear Remodeling Induced by Helicobacter Cytolethal Distending Toxin Involves MAFB Oncoprotein

Author: Lamia Azzi-Martin, Christophe Grosset, Valérie Prouzet-Mauléon, Wencan He, Alice Buissonnière, Christelle Péré-Védrenne, Bruno Cardinaud, Armelle Ménard, Philippe Lehours, Francis Mégraud, Grosset, Christophe, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), TBM-Core [Bordeaux] (CNRS UMS 3427 - INSERM US 005), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence des Campylobacters et Hélicobacters (CNR Campylobacters et Hélicobacters), CHU Bordeaux [Bordeaux], Biothérapies des maladies génétiques et cancers, This research was funded in part by the ‘Ligue Contre le Cancer Gironde’, and the Federative Research Structure ‘Biology: from basics to Medicine’ (‘TransBioMed’) at the University of Bordeaux., and Flow Cytometry Facility / TransBioMed Core [Bordeaux] (INSERM US005 - CNRS UMS 3427 - UB)
Subjects: Cytolethal distending toxin, Health, Toxicology and Mutagenesis, Cell, Bacterial Toxins, MafB Transcription Factor, lcsh:Medicine, Toxicology, Article, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Helicobacter, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene silencing, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, CdtB subunit, 030304 developmental biology, Cell Nucleus, Oncogene Proteins, 0303 health sciences, helicobacter hepaticus, MAFB oncoprotein, biology, lcsh:R, biology.organism_classification, Actin cytoskeleton, 3. Good health, Cell biology, medicine.anatomical_structure, Gene Expression Regulation, MAFB, 030220 oncology & carcinogenesis, Ectopic expression, helicobacter pullorum, Helicobacter hepaticus, cytolethal distending toxin, Helicobacter pullorum
Abstract: Enterohepatic Helicobacters, such as Helicobacter hepaticus and Helicobacter pullorum, are associated with several intestinal and hepatic diseases. Their main virulence factor is the cytolethal distending toxin (CDT). In the present study, whole genome microarray-based identification of differentially expressed genes was performed in vitro in HT-29 intestinal cells while following the ectopic expression of the active CdtB subunit of H. hepaticus CDT. A CdtB-dependent upregulation of the V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) gene encoding the MAFB oncoprotein was found, as well as the CdtB-dependent regulation of several MAFB target genes. The transduction and coculture experiments confirmed MAFB mRNA and protein induction in response to CDT and its CdtB subunit in intestinal and hepatic cell lines. An analysis of MAFB protein subcellular localization revealed a strong nuclear and perinuclear localization in the CdtB-distended nuclei in intestinal and hepatic cells. MAFB was also detected at the cell periphery of the CdtB-induced lamellipodia in some cells. The silencing of MAFB changed the cellular response to CDT with the formation of narrower lamellipodia, a reduction of the increase in nucleus size, and the formation of less γH2AX foci, the biomarker for DNA double-strand breaks. Taken together, these data show that the CDT of enterohepatic Helicobacters modulates the expression of the MAFB oncoprotein, which is translocated in the nucleus and is associated with the remodeling of the nuclei and actin cytoskeleton.
Published: 2020

27. A standardised model for stool banking for faecal microbiota transplantation: a consensus report from a multidisciplinary UEG working group

Author: Zain Kassam, Alexander Link, Eero Mattila, Chris J. J. Mulder, Josbert J. Keller, Christoph Högenauer, Ed J. Kuijper, Maurizio Sanguinetti, Gianluca Laniro, Maria J G T Vehreschild, Elisabeth M. Terveer, Ajit Sood, Patrizia Kump, Simon D. Goldenberg, Oleksiy Gridnyev, Simon Mark Dahl Baunwall, Olena Gubska, Giovanni Cammarota, Simone C. Lieberknecht, Cyriel Y. Ponsioen, Francis Mégraud, Andrey Dorofeev, Shiv Kumar Sarin, Antonio Gasbarrini, Reetta Satokari, Herbert Tilg, Christian Lodberg Hvas, Horace R T Williams, Rogier E. Ooijevaar, Laurent Alric, Radislav Nakov, Hein W. Verspaget, Abraham Goorhuis, Ramesh P. Arasaradnam, Georgina L. Hold, Lorenza Putignani, Perttu Arkkila, Sergiy Tkatch, Juozas Kupcinskas, Harry Sokol, Megraud, Francis, Haaglanden Medical Center [La Haye, Pays-Bas] (HMC), Leiden University Medical Center (LUMC), University of Amsterdam [Amsterdam] (UvA), Aarhus University Hospital, Frankfurt University Hospital, Medical University Graz, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French Group of Fecal Microbiota Transplantation [Paris] (GFTF), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Tsaritsa Yoanna University Hospital = Queen Giovanna University Hospital [Sofia], King‘s College London, Guy's and St Thomas NHS Foundation Trust [London], Ukranian Scientific and Practical Center of Endocrine Surgery [Kyiv], Fondazione Policlinico Universitario Agostino Gemelli IRCCS, National Medical Academy of Postgraduate Education n.a. P.L. Shupic [Kiev], Bogomolets national medical university, University Hospital Coventry Warwickshire (UHCW), University Hospital Coventry, Institute of Liver and Biliary Sciences [New Delhi], Dayanand Medical College and Hospital [Ludhiana], IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), VU University Medical Center [Amsterdam], Lithuanian University of health Sciences [Kaunas], Otto-von-Guericke-Universität Magdeburg = Otto-von-Guericke University [Magdeburg] (OVGU), Leids Universitair Medisch Centrum [Leiden], University of New South Wales [Sydney] (UNSW), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Finch Therapeutics Group, ESCMID Study Group for Host and Microbiota Interaction [Basel] (ESGHAMI), Imperial College London, University of Cologne, German Centre for Infection Research (DZIF), University of Helsinki, Tsaritsa Yoanna University Hospital [Sofia], Fondazione Policlinico Universitario Agostino Gemelli IRCCS [Rome], Fondazione Policlinico Universitario Agostino Gemelli [Rome], CHU Toulouse [Toulouse], Otto-von-Guericke University [Magdeburg] (OVGU), Innsbruck Medical University [Austria] (IMU), Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, APH - Global Health, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, HUS Abdominal Center, Department of Medicine, Clinicum, Gastroenterologian yksikkö, Reetta Maria Satokari / Principal Investigator, HUMI - Human Microbiome Research, Research Programs Unit, Faculty of Medicine, and HUS Internal Medicine and Rehabilitation
Subjects: Quality Assurance, Health Care, Small Bowel, Fecal microbiota transplantation, Feces, 0302 clinical medicine, fluids and secretions, Recurrence, Procedure, Multidisciplinary approach, stool bank, Medicine, 030212 general & internal medicine, faecal microbiota transplantation, Biological Specimen Banks, Informed Consent, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Microbiota, Clostridium infections, microbiology, therapy, Clostridium difficile, isolation&purification, Donor selection, Consensus, digestive, oral, and skin physiology, Age Factors, Gastroenterology, 3. Good health, Oncology, Original Article, 030211 gastroenterology & hepatology, medicine.medical_specialty, Settore MED/12 - GASTROENTEROLOGIA, legislation, Faecal microbiota transplantation, Donor Selection, Specimen Handling, Contraindications, Procedure, Immunocompromised Host, 03 medical and health sciences, Internal medicine, Humans, business.industry, Clostridioides difficile, Contraindications, Settore MED/09 - MEDICINA INTERNA, Fecal bacteriotherapy, Health Care, Transplantation, 3121 General medicine, internal medicine and other clinical medicine, Clostridium Infections, 616.9-022.363. [udc], Quality Assurance, business, Clostridioides, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: BACKGROUND: Fecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of feces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council.OBJECTIVE: Several European and international consensus statements concerning fecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document.METHODS: Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about fecal microbiota transplantation.RESULTS: A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening.CONCLUSION: The implementation of fecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor feces preparations for patients.
Published: 2020

28. Leukaemia Inhibitory Factor (LIF) Inhibits Cancer Stem Cells Tumorigenic Properties through Hippo Kinases Activation in Gastric Cancer

Author: Océane C B Martin, Cathy Staedel, Philippe Lehours, Julie Giraud, Silvia Molina-Castro, Camille Tiffon, Elodie Sifré, Clémentine Beauvoit, Lornella Seeneevassen, Hélène Boeuf, Francis Mégraud, Pierre Dubus, Christine Varon, Boeuf, Hélène, Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidad de Costa Rica (UCR), Acides Nucléiques : Régulations Naturelle et Artificielle (ARNA), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Cancer Research, endocrine system, [SDV]Life Sciences [q-bio], ALDH, Leukemia inhibitory factor receptor, lcsh:RC254-282, Article, 03 medical and health sciences, 0302 clinical medicine, Cancer stem cell, JAK1 Inhibitor, medicine, gastric carcinoma, CD44, Hippo signaling pathway, biology, Chemistry, Kinase, Gastric carcinoma, JAK-STAT signaling pathway, Cancer, LATS1/2, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, GP190, 3. Good health, JAK, [SDV] Life Sciences [q-bio], 030104 developmental biology, Ruxolitinib, Oncology, 030220 oncology & carcinogenesis, Cancer research, biology.protein, YAP, XMU-MP-1
Abstract: Cancer stem cells (CSCs) present chemo-resistance mechanisms contributing to tumour maintenance and recurrence, making their targeting of utmost importance in gastric cancer (GC) therapy. The Hippo pathway has been implicated in gastric CSC properties and was shown to be regulated by leukaemia inhibitory factor receptor (LIFR) and its ligand LIF in breast cancer. This study aimed to determine LIF&rsquo, s effect on CSC properties in GC cell lines and patient-derived xenograft (PDX) cells, which remains unexplored. LIF&rsquo, s treatment effect on CSC markers expression and tumoursphere formation was evaluated. The Hippo kinase inhibitor XMU-MP-1 and/or the JAK1 inhibitor Ruxolitinib were used to determine Hippo and canonical JAK/STAT pathway involvement in gastric CSCs&rsquo, response to LIF. Results indicate that LIF decreased tumorigenic and chemo-resistant CSCs, in both GC cell lines and PDX cells. In addition, LIF increased activation of LATS1/2 Hippo kinases, thereby decreasing downstream YAP/TAZ nuclear accumulation and TEAD transcriptional activity. LIF&rsquo, s anti-CSC effect was reversed by XMU-MP-1 but not by Ruxolitinib treatment, highlighting the opposite effects of these two pathways downstream LIFR. In conclusion, LIF displays anti-CSC properties in GC, through Hippo kinases activation, and could in fine constitute a new CSCs-targeting strategy to help decrease relapse cases and bad prognosis in GC.
Published: 2020

29. Regional variations in Helicobacter pylori infection, gastric atrophy and gastric cancer risk: The ENIGMA study in Chile

Author: Rolando Herrero, Katy Heise, Johanna Acevedo, Paz Cook, Claudia Gonzalez, Jocelyne Gahona, Raimundo Cortés, Luis Collado, María Enriqueta Beltrán, Marcos Cikutovic, Paula Gonzalez, Raul Murillo, Marcis Leja, Francis Megraud, Maria de la Luz Hernandez, Sylvaine Barbier, Jin Young Park, Catterina Ferreccio, ENIGMA Chile study group, International Agency for Research on Cancer [Lyon, France], Agencia Costarricense de Investigaciones Biomédicas [Costa Rica] (Fundación INCIENSA), Hospital Base Valdivia [ Valdivia, Chile], Health Ministry [Santiago, Chile], Pontificia Universidad Católica de Chile (UC), Advanced Center for Chronic Diseases, ACCDis [Santiago, Chile], Secretaría Regional Ministerial de Salud [Antofagasta Region, Chile], Universidad de Antofagasta, Universidad Austral de Chile, University of Latvia (LU), Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Megraud, Francis, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2
Subjects: Male, Epidemiology, Pathology and Laboratory Medicine, Gastroenterology, Geographical locations, 0302 clinical medicine, Risk Factors, Helicobacter, Epidemiology of cancer, Prevalence, Medicine and Health Sciences, Medicine, Chile, Enzyme-Linked Immunoassays, Young adult, Child, education.field_of_study, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Cancer Risk Factors, Stomach, Middle Aged, Bacterial Pathogens, 3. Good health, Oncology, Medical Microbiology, Child, Preschool, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Pathogens, Cancer Epidemiology, Research Article, Adult, medicine.medical_specialty, Adolescent, Science, Population, Research and Analysis Methods, Microbiology, Helicobacter Infections, Young Adult, 03 medical and health sciences, Signs and Symptoms, Atrophy, Stomach Neoplasms, Internal medicine, Gastrointestinal Tumors, Humans, CagA, Seroprevalence, Immunoassays, education, Microbial Pathogens, Aged, Chile (Country), Bacteria, business.industry, Organisms, Infant, Biology and Life Sciences, Cancers and Neoplasms, Cancer, South America, Helicobacter pylori, medicine.disease, biology.organism_classification, Helicobacter Pylori, digestive system diseases, Gastric Cancer, Age Groups, Medical Risk Factors, People and Places, Immunologic Techniques, Population Groupings, Clinical Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: Regional variations in gastric cancer incidence are not explained by prevalence of Helicobacter pylori, the main cause of the disease, with several areas presenting high H. pylori prevalence but low gastric cancer incidence. The IARC worldwide H. pylori prevalence surveys (ENIGMA) aim at systematically describing age and sex-specific prevalence of H. pylori infection around the world and generating hypotheses to explain regional variations in gastric cancer risk.Methods: We selected age- and sex-stratified population samples in two areas with different gastric cancer incidence and mortality in Chile: Antofagasta (lower rate) and Valdivia (higher rate). Participants were 1-69 years old and provided interviews and blood for anti-H. pylori antibodies (IgG, VacA, CagA, others) and atrophy biomarkers (pepsinogens).Results: H. pylori seroprevalence (Age-standardized to world population) and antibodies against CagA and VacA were similar in both sites. H. pylori seroprevalence was 20% among children
Published: 2020

30. Primary Cutaneous CD4+ Small/Medium T-Cell Lymphoproliferative Disorders

Author: Beltzung, Fanny, Ortonne, Nicolas, Pelletier, Laura, Beylot-Barry, Marie, Ingen-Housz-Oro, Saskia, Franck, Frédéric, Pereira, Bruno, Godfraind, Catherine, Delfau, Marie-Hélène, D'Incan, Michel, Vergier, Béatrice, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Henri Mondor, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Bordeaux [Bordeaux], CHU Clermont-Ferrand, service de Biostatistiques, DRCI, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), and CHU Henri Mondor [Créteil]
Subjects: skin, follicular helper T cells, primary cutaneous T-cell lymphoma, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, primary cutaneous CD4(+) small/medium T-cell lymphoproliferative disorder
Abstract: International audience; Primary cutaneous CD4 small/medium T-cell lymphoproliferative disorder (PCSMLPD) is a recently recognized entity in the 2017 World Health Organization (WHO) classification. It belongs to the T-follicular helper (TFH) lymphoproliferations. The clinical, pathologic, and molecular features of this localized disease are underresearched. We conducted a retrospective multicentric study of 60 patients with a PCSMLPD that presented as a single cutaneous lesion. Clinical, pathologic, and targeted molecular analyses were performed. PCSMLPD presented mostly as a nodule (45%), located on the head and neck area (50%) in adults (mean age: 59 y [43.3 to 75.2]). All patients had an indolent disease course, either at initial staging or during follow-up (mean: 16.6 mo [1.3 to 31.9]). Spontaneous regression was reported in 31.9% of cases. The infiltrates were most often nodular and/or diffuse, expanding in the whole dermis (78%, Pattern 1), rather than subepidermal band-like in the superficial dermis (22%, Pattern 2). Epidermotropism, folliculotropism, and capillary hyperplasia were common. The expression of TFH lineage markers was more extensive in lesions with Pattern 2, but a substantial B-cell infiltrate was seen in both types of lesions. A clonal rearrangement of the TCR genes was identified in 68% of cases. One sample of the 13 tested revealed a mutation in the DNMT3A gene among the 9 genes studied (TET2, DNMT3A, IDH2, RHOA, SETD2, PLCG1, STAT3, STAT5B, and CD28). PCSMLPD follows a benign clinical course and can spontaneously regress after biopsy. Although PCSMLPD expresses TFH lineage markers, mutations usually found in angioimmunoblastic T-cell lymphomas are uncommon.
Published: 2020

31. Long-Term Effects of Early-Life Antibiotic Exposure on Resistance to Subsequent Bacterial Infection

Author: Zhiheng Pei, Bruce A. Vallance, Thomas Battaglia, Claire Roubaud-Baudron, Guillermo I. Perez-Perez, Jackie Li, Alexander M. Swan, Martin J. Blaser, Victoria E. Ruiz, Ceren Özkul, Pôle de Gérontologie Clinique [CHU Bordeaux], Hôpital Xavier Arnozan-CHU Bordeaux [Bordeaux], Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU), Saint Francis College [Brooklyn, New York City], University of British Columbia (UBC), Hacettepe University = Hacettepe Üniversitesi, WINLAB Rutgers University, Rutgers, The State University of New Jersey [New Brunswick] (RU), Rutgers University System (Rutgers)-Rutgers University System (Rutgers), and Roubaud-Baudron, Claire
Subjects: Antibiotics, Long Term Adverse Effects, Gut flora, pathogen-induced colitis, host resistance, antibiotics, murine model, chemistry.chemical_compound, fluids and secretions, Citrobacter rodentium, Medicine, Pathogen, 2. Zero hunger, Citrobacter, 0303 health sciences, gastrointestinal microbiota, biology, Age Factors, Enterobacteriaceae Infections, Colitis, bioluminescence, QR1-502, 3. Good health, Anti-Bacterial Agents, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Female, Disease Susceptibility, medicine.drug, Research Article, medicine.drug_class, Colon, Tylosin, Microbiology, digestive system, Host-Microbe Biology, colonic inflammation, 03 medical and health sciences, Virology, Animals, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, 030306 microbiology, business.industry, Amoxicillin, biology.organism_classification, medicine.disease, Gastrointestinal Microbiome, Mice, Inbred C57BL, stomatognathic diseases, chemistry, business
Abstract: The gastrointestinal microbiota protects hosts from enteric infections; while antibiotics, by altering the microbiota, may diminish this protection. We show that after early-life exposure to antibiotics host susceptibility to enhanced Citrobacter rodentium-induced colitis is persistent and that this enhanced disease susceptibility is transferable by the antibiotic-altered microbiota. These results strongly suggest that early-life antibiotics have long-term consequences on the gut microbiota and enteropathogen infection susceptibility., Early-life antibiotic exposure may provoke long-lasting microbiota perturbation. Since a healthy gut microbiota confers resistance to enteric pathogens, we hypothesized that early-life antibiotic exposure would worsen the effects of a bacterial infection encountered as an adult. To test this hypothesis, C57BL/6 mice received a 5-day course of tylosin (macrolide), amoxicillin (β-lactam), or neither (control) early in life and were challenged with Citrobacter rodentium up to 80 days thereafter. The early-life antibiotic course led to persistent alterations in the intestinal microbiota and even with pathogen challenge 80 days later worsened the subsequent colitis. Compared to exposure to amoxicillin, exposure to tylosin led to greater disease severity and microbiota perturbation. Transferring the antibiotic-perturbed microbiota to germfree animals led to worsened colitis, indicating that the perturbed microbiota was sufficient for the increased disease susceptibility. These experiments highlight the long-term effects of early-life antibiotic exposure on susceptibility to acquired pathogens.
Published: 2019

32. Comparison of extracellular and hepatobiliary MR contrast agents for the diagnosis of small HCCs

Author: Onorina Bruno, Olivier Sutter, Jérémie Riou, Agnès Rodes, Frédéric Oberti, Christophe Aubé, I. Bricault, Valérie Vilgrain, Hervé Trillaud, Anita Paisant, Valérie Laurent, Maxime Ronot, Christophe Cassinotto, Boris Guiu, Sophie Michalak, Département de Radiologie [CHU de Rennes], Université de Rennes (UR), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Paris 13 (UP13), Hôpital Jean Verdier [AP-HP], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de Bactériologie de l'Hôpital de la Croix-Rousse, Hospices Civils de Lyon (HCL), Département radiologie diagnostique et interventionnelle Saint Eloi [CHRU Montpellier], Pôle Digestif [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle d'imagerie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Pathologie [Clichy], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: 0301 basic medicine, Cirrhosis, Hepatocellular carcinoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Liver neoplasm, 03 medical and health sciences, 0302 clinical medicine, Magnetic resonance imaging, medicine, Hepatology, medicine.diagnostic_test, business.industry, Washout, Nodule (medicine), Gold standard (test), HCCS, medicine.disease, 3. Good health, 030104 developmental biology, Contrast agent, 030211 gastroenterology & hepatology, medicine.symptom, Nuclear medicine, business
Abstract: Background & Aims The aim of this study was to use a head-to-head nodule comparison to compare the performance of extracellular contrast agent MRI (ECA-MRI) with that of hepatobiliary contrast agent MRI (HBA-MRI) for the non-invasive diagnosis of small hepatocellular carcinomas (HCCs). Methods Between August 2014 and October 2017, 171 patients with cirrhosis, each with 1 to 3 nodules measuring 1–3 cm, were enrolled across 8 centers. All patients underwent both an ECA-MRI and an HBA-MRI within a month. A non-invasive diagnosis of HCC was made when a nodule exhibited arterial phase hyper-enhancement (APHE) with washout at the portal venous phase (PVP) and/or delayed phase (DP) for ECA-MRI, or the PVP and/or HB phase (HBP) for HBA-MRI. The gold standard was defined by using a previously published composite algorithm. Results A total of 225 nodules, of which 153 were HCCs and 72 were not, were included. The sensitivites of both MRI techniques were similar. Specificity was 83.3% (95% CI 72.7–91.1) for ECA-MRI and 68.1% (95% CI 56.0–78.6) for HBA-MRI. In terms of HCC diagnosis on ECA-MRI, 138 nodules had APHE, 84 had washout at PVP, and 104 at DP; on HBA-MRI, 128 nodules had APHE, 71 had washout at PVP, and 99 at HBP. For nodules 2–3 cm in size, sensitivity and specificity were similar between the 2 approaches. For nodules 1–2 cm in size, specificity dropped to 66.1% (95% CI 52.2–78.2) for HBA-MRI vs. 85.7% (95% CI 73.8–93.6) for ECA-MRI. Conclusions HBA-MRI specificity is lower than that of ECA-MRI for diagnosing small HCCs in patients with cirrhosis. These results raise the question of the proper use of HBA-MRI in algorithms for the non-invasive diagnosis of small HCCs. Lay summary There are 2 magnetic resonance imaging (MRI)-based approaches available for the non-invasive diagnosis of hepatocellular carcinoma (HCC), using either extracellular or hepatobiliary contrast agents. The current results showed that the sensitivity of MRI with hepatobiliary contrast agents was similar to that with extracellular contrast agents, but the specificity was lower. Thus, hepatobiliary contrast agent-based MRI, although detailed in international guidelines, should be used with caution for the non-invasive diagnosis of HCC. Clinical trial number NCT00848952 .
Published: 2019

33. PEPOP 2.0: new approaches to mimic non-continuous epitopes

Author: Liza Felicori, Franck Molina, Benedicte Jardin, Alexandre G. de Brevern, Violaine Moreau, Lionel Valera, Géraldine Lavigne, Vincent Demolombe, Ricardo Andrez Machado De Ávila, Aurélien Lebreton, Christophe Nguyen, Biochimie et Physiologie Moléculaire des Plantes (BPMP), Université de Montpellier (UM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Plateforme de Spectrométrie de Masse Protéomique - Mass Spectrometry Proteomics Platform (MSPP), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA), Sys2Diag-Modélisation et Ingénierie des Systèmes Complexes Biologiques pour le Diagnostic (Sys2Diag), Centre National de la Recherche Scientifique (CNRS)-Alcediag, Laboratoire Agronomie et Environnement (LAE), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Sysdag, Sysdiag CNRS Bio-Rad UMR 3145, Cap Delta/Parc Euromédecine, Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CNRS/Bio-Rad, Centre National de la Recherche Scientifique (CNRS), Lab-STICC_UBS_CACS_IAS, Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), GRICH, Hichem, Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), and Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Protein surface, Computer science, IPP, [SDV]Life Sciences [q-bio], Peptide, medicine.disease_cause, Biochemistry, Epitope, Structural bioinformatics, Epitopes, Mice, 0302 clinical medicine, Structural Biology, Peptide design, [SDV.BV] Life Sciences [q-bio]/Vegetal Biology, lcsh:QH301-705.5, chemistry.chemical_classification, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], biology, Applied Mathematics, Immunogenicity, Methodology Article, A protein, Antibodies, Monoclonal, Antigenicity, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Computer Science Applications, [SDV] Life Sciences [q-bio], Molecular mimicry, 030220 oncology & carcinogenesis, lcsh:R858-859.7, Discontinuous epitope, DNA microarray, Antibody, Surface protein, Discontinuous and continuous epitope, Computational biology, lcsh:Computer applications to medicine. Medical informatics, 03 medical and health sciences, Protein Domains, medicine, Molecule, Animals, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Amino Acid Sequence, Binding site, Molecular Biology, 030304 developmental biology, Internet, Immune Sera, Computational Biology, Proteins, B-cell epitope, Ag-ab interaction, lcsh:Biology (General), chemistry, biology.protein, Peptides, Software
Abstract: Background Bioinformatics methods are helpful to identify new molecules for diagnostic or therapeutic applications. For example, the use of peptides capable of mimicking binding sites has several benefits in replacing a protein which is difficult to produce, or toxic. Using peptides is less expensive. Peptides are easier to manipulate, and can be used as drugs. Continuous epitopes predicted by bioinformatics tools are commonly used and these sequential epitopes are used as is in further experiments. Numerous discontinuous epitope predictors have been developed but only two bioinformatics tools have been proposed so far to predict peptide sequences: Superficial and PEPOP 2.0. PEPOP 2.0 can generate series of peptide sequences that can replace continuous or discontinuous epitopes in their interaction with their cognate antibody. Results We have developed an improved version of PEPOP (PEPOP 2.0) dedicated to answer to experimentalists’ need for a tool able to handle proteins and to turn them into peptides. The PEPOP 2.0 web site has been reorganized by peptide prediction category and is therefore better formulated to experimental designs. Since the first version of PEPOP, 32 new methods of peptide design were developed. In total, PEPOP 2.0 proposes 35 methods in which 34 deal specifically with discontinuous epitopes, the most represented epitope type in nature. Conclusion Through the presentation of its user-friendly, well-structured new web site conceived in close proximity to experimentalists, we report original methods that show how PEPOP 2.0 can assist biologists in dealing with discontinuous epitopes. Electronic supplementary material The online version of this article (10.1186/s12859-019-2867-5) contains supplementary material, which is available to authorized users.
Published: 2019

34. Double-hit or dual expression of MYC and BCL2 in primary cutaneous large B-cell lymphomas

Author: Laurence Verneuil, Stéphane Dalle, Jean-Philippe Merlio, Serge Boulinguez, Sarah Menguy, Audrey Gros, Marie Beylot-Barry, Eric Frison, Anne Pham-Ledard, Olivier Dereure, Béatrice Vergier, Caroline Ram-Wolff, Laurent Machet, Sophie Dalac, Martina Prochazkova-Carlotti, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, CHU Bordeaux [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), CHU Toulouse [Toulouse], Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Dermatologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Skin Neoplasms, Dual expression, Pathology and Forensic Medicine, Proto-Oncogene Proteins c-myc, 03 medical and health sciences, 0302 clinical medicine, Dermis, immune system diseases, hemic and lymphatic diseases, medicine, Humans, B cell, Aged, Aged, 80 and over, Gene Rearrangement, business.industry, Large cell, Gene rearrangement, Middle Aged, medicine.disease, BCL6, 3. Good health, Lymphoma, 030104 developmental biology, medicine.anatomical_structure, Proto-Oncogene Proteins c-bcl-2, 030220 oncology & carcinogenesis, Female, Lymphoma, Large B-Cell, Diffuse, Differential diagnosis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; In nodal diffuse large B-cell lymphoma, the search for double-hit with MYC and BCL2 and/or BCL6 rearrangements or for dual expression of BCL2 and MYC defines subgroups of patients with altered prognosis that has not been evaluated in primary cutaneous large B-cell lymphoma. Our objectives were to assess the double-hit and dual expressor status in a cohort of 44 patients with primary cutaneous large B-cell lymphoma according to the histological subtype and to evaluate their prognosis relevance. The 44 cases defined by the presence of more than 80% of large B-cells in the dermis corresponded to 21 primary cutaneous follicle centre lymphoma with large cell morphology and 23 primary cutaneous diffuse large B-cell lymphoma, leg type. Thirty-one cases (70%) expressed BCL2 and 29 (66%) expressed MYC. Dual expressor profile was observed in 25 cases (57%) of either subtypes (n = 6 or n = 19, respectively). Only one primary cutaneous follicle centre lymphoma, large-cell case had a double-hit status (2%). Specific survival was significantly worse in primary cutaneous diffuse large B-cell lymphoma, leg type than in primary cutaneous follicle centre lymphoma, large cell (p = 0.021) and for the dual expressor primary cutaneous large B-cell lymphoma group (p = 0.030). Both overall survival and specific survival were worse for patients belonging to the dual expressor primary cutaneous diffuse large B-cell lymphoma, leg type subgroup (p = 0.001 and p = 0.046, respectively). Expression of either MYC and/or BCL2 negatively impacted overall survival (p = 0.017 and p = 0.018 respectively). As the differential diagnosis between primary cutaneous follicle centre lymphoma, large cell and primary cutaneous diffuse large B-cell lymphoma, leg type has a major impact on prognosis, dual-expression of BCL2 and MYC may represent a new diagnostic criterion for primary cutaneous diffuse large B-cell lymphoma, leg type subtype and further identifies patients with impaired survival. Finally, the double-hit assessment does not appear clinically relevant in primary cutaneous large B-cell lymphoma.
Published: 2018

35. Extrahepatic cancers are the leading cause of death in patients achieving hepatitis B virus control or hepatitis C virus eradication

Author: Thong Dao, Pierre Nahon, Christos Christidis, Jean-Pierre Zarski, Pierre Attali, Valérie Bourcier, Ghassan Riachi, Victor de Ledinghen, Laurent Alric, Dominique Thabut, Claire Wartelle, Eric Nguyen-Khac, Patrick Marcellin, Carole Cagnot, Dominique Roulot, Christophe Pilette, Armand Abergel, Fabien Zoulim, Vincent Di Martino, Eric Letouzé, Richard Layese, Jean-Pierre Bronowicki, Jean-Frédéric Blanc, Christine Silvain, Ariane Mallat, Stanislas Pol, Denis Ouzan, Jean-Didier Grangé, Angela Sutton, Jean-Marie Péron, Brigitte Bernard-Chabert, Dominique Larrey, Albert Tran, David Zucman, Marc Bourlière, Etienne Audureau, Lawrence Serfaty, Manon Allaire, Paul Calès, Yannick Bacq, Dominique Guyader, Philippe Mathurin, Françoise Roudot-Thoraval, Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ANRS France Recherche Nord & sud Sida-hiv hépatites, Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut Arnault Tzanck, Hospices Civils de Lyon (HCL), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Hôpital Claude Huriez [Lille], CHU Lille, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Tenon [AP-HP], Onxeo S.A., Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Le Mans (CH Le Mans), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hellenic Open University [Patras], Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Foch [Suresnes], Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS (France Recherche Nord & sud Sida‐HIV Hépatites‐FRENCH)HECAM (Hepatocellular Carcinoma Multi‐Technological) Consortium, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], CHU Saint-Eloi, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre d'investigation de la fibrose hépatique [CHU de Bordeaux] (Hôpital Haut-Lévêque ), Hôpital Haut-Lévêque [CHU de Bordeaux], Université Nice Sophia Antipolis (... - 2019) (UNS), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), SIGMA Clermont, Hépatologie Gastro-Entérologie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service d'hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UMR INSERM U955, École nationale vétérinaire d'Alfort (ENVA), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-gastroentérologie [CHU Amiens-Picardie], Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes (UGA)-CHU Grenoble, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], CHU Trousseau [APHP], and Univ Angers, Okina
Subjects: Liver Cirrhosis, Male, Cirrhosis, Databases, Factual, [SDV]Life Sciences [q-bio], medicine.disease_cause, Gastroenterology, Cohort Studies, 0302 clinical medicine, Neoplasms, Prospective Studies, education.field_of_study, Hepatocellular / virology, Liver Neoplasms, Liver Neoplasms / epidemiology, Hepatitis C, Middle Aged, Hepatitis B, Prognosis, 3. Good health, 030220 oncology & carcinogenesis, Disease Progression, Female, Liver Cirrhosis / epidemiology, 030211 gastroenterology & hepatology, France, Databases Factual, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Hepatitis C virus, Antiviral Agents / therapeutic use, Population, Liver Neoplasms / pathology, Chronic / complications, Antiviral Agents, Risk Assessment, Article, Liver Cirrhosis / virology, 03 medical and health sciences, Hepatitis B, Chronic, Liver Cirrhosis / physiopathology, Internal medicine, medicine, Humans, education, Aged, Hepatitis B virus, Chronic / drug therapy, Neoplasms / pathology, Hepatology, business.industry, Carcinoma, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Chronic, medicine.disease, Chronic / pathology, Survival Analysis, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatocellular / epidemiology, Liver Neoplasms / virology, Neoplasms / virology Prognosis, Carcinom, Standardized mortality ratio, Hepatocellular / pathology, Male Middle Aged Neoplasms / mortality, business
Abstract: Comment in Does cirrhosis associated with well controlled viral hepatitis confer a risk for extrahepatic cancer? Yang JD, Gores GJ. Hepatology. 2018 Oct;68(4):1217-1219. doi: 10.1002/hep.30063. Epub 2018 Jul 10.; International audience; Data on extrahepatic cancers (EHCs) in compensated viral cirrhosis are limited. The objective of the prospective multicenter Agence Nationale de Recherche sur le SIDA et les Hépatites virales CO12 CirVir cohort was to assess the occurrence of all clinical events in patients with compensated viral cirrhosis, including all types of cancer. Patients with the following inclusion criteria were enrolled in 35 French centers: (1) biopsy-proven hepatitis B virus (HBV) or hepatitis C virus (HCV) cirrhosis, (2) Child-Pugh A, or (3) absence of previous liver complications including primary liver cancer (PLC). Patients were followed up prospectively every 6 months. The standardized mortality ratio (SMR) was calculated according to age and gender using 5-year periods. The impact of sustained viral response (SVR) in HCV patients and maintained viral suppression in HBV patients were assessed using time-dependent analysis. A total of 1,671 patients were enrolled between 2006 and 2012 (median age, 54.9 years; men, 67.3%; HCV, 1,323; HBV, 317; HCV-HBV, 31). Metabolic features and excessive alcohol and tobacco consumption were recorded in 15.2%, 36.4%, and 56.4% of cases, respectively. After a median follow-up of 59.7 months, 227 PLCs were diagnosed (5-year cumulative incidence [CumI] 13.4%) and 93 patients developed EHC (14 patients with lymphoid or related tissue cancer and 79 with solid tissue cancer; 5-year EHC CumI, 5.9%). Compared to the general French population, patients were younger at cancer diagnosis, with significantly higher risk of EHC in HCV patients (SMR, 1.31; 95 confidence interval [CI], 1.04-1.64; P = 0.017) and after SVR (SMR = 1.57; 95% CI, 1.08-2.22; P = 0.013). EHC was the fourth leading cause of death in the whole cohort and the first in patients with viral control/eradication.CONCLUSION: Compared to the general French population, HCV cirrhosis is associated with a higher risk of EHC and the first cause of death in patients with viral cirrhosis who achieve virological control/eradication. (Hepatology 2018).
Published: 2018

36. [Guide to university hospital careers in dermatology. The GRENT (Graines Engrais Tuteurs - Seed Fertilizer Plant stick) Program]

Author: Christine Bodemer, Olivier Chosidow, Marie Beylot-Barry, Selim Aractingi, Caroline Gaudy-Marqueste, Mahtab Samimi, Angèle Soria, Michel Richard, Carle Paul, Bernard Cribier, Brigitte Dréno, J.-P. Lacour, Assistance Publique - Hôpitaux de Marseille (APHM), Institut National de la Santé et de la Recherche Médicale (INSERM), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Service de dermatologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Henri Mondor, Université Paris Est Créteil, Hôpitaux Universitaires de Strasbourg, Service de Dermatologie, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, CHU Toulouse [Toulouse], CHU Grenoble-Hôpital Michallon, Physiopathologie du cancer du foie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 030203 arthritis & rheumatology, business.industry, Fertilizer plant, Dermatology, University hospital, 3. Good health, Toxicology, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Medicine, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: National audience
Published: 2018

37. A histopathological classification system of Tyr::NRASQ61Kmurine melanocytic lesions: A reproducible simplified classification

Author: Léa Legrand, Pierre Sohier, Zackie Aktary, Christine Grill, Véronique Delmas, Lionel Larue, B. Vergier, Edouard Reyes-Gomez, Florence Bernex, Signalisation normale et pathologique de l'embryon aux thérapies innovante des cancers, Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Génétique fonctionnelle et médicale (GFM - ENVA), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), ANR-10-IDEX-0001-02/11-LABX-0038,CelTisPhyBio,Des cellules aux tissus: au croisement de la Physique et de la Biologie(2010), Signalisation normale et pathologique de l'embryon aux thérapies innovantes des cancers, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National Du Cancer, Ligue Contre le Cancer - comite de l'Oise, ITMO Cancer, ANR Labex CelTisPhyBio [ANR-11-LBX-0038, ANR-10-IDEX-0001-02 PSL], INCa, and ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010)
Subjects: 0301 basic medicine, melanocyte, MESH: Melanoma, MESH: Mice, Transgenic, Computer science, education, melanoma model, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Monomeric GTP-Binding Proteins, Dermatology, Computational biology, transgenic mice, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Cohen's kappa, melanoma, MESH: Animals, MESH: Mice, MESH: Mutation, Missense, β-catenin, Mouse Melanoma, Ink4a, MESH: Amino Acid Substitution, Pten, 030104 developmental biology, Oncology, Homogeneous, 030220 oncology & carcinogenesis, Genetically Engineered Mouse, histopathology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Ras
Abstract: International audience; Genetically engineered mouse models offer essential opportunities to investigate the mechanisms of initiation and progression in melanoma. Here, we report a new simplified histopathology classification of mouse melanocytic lesions in Tyr::NRASQ61K derived models, using an interactive decision tree that produces homogeneous categories. Reproducibility for this classification system was evaluated on a panel of representative cases of murine melanocytic lesions by pathologists and basic scientists. Reproducibility, measured as inter-rater agreement between evaluators using a modified Fleiss' kappa statistic, revealed a very good agreement between observers. Should this new simplified classification be adopted, it would create a robust system of communication between researchers in the field of mouse melanoma models.
Published: 2017

38. Direct-acting antiviral agent–based regimen for HCV recurrence after combined liver-kidney transplantation: Results from the ANRS CO23 CUPILT study

Author: Jérôme Dumortier, A. Rohel, Jean-Charles Duclos-Vallée, Christophe Duvoux, Vincent Di Martino, Christine Silvain, Sébastien Dharancy, Danielle Botta-Fridlund, Sylvie Radenne, Maryline Debette-Gratien, Nassim Kamar, Audrey Coilly, Vincent Leroy, Georges-Philippe Pageaux, Armand Abergel, Louis d’Alteroche, Emilie Rossignol, Claire Francoz, Pauline Houssel-Debry, P. Perré, Filomena Conti, Claire Fougerou-Leurent, François Habersetzer, Camille Besch, Christophe Moreno, H. Montialoux, Valérie Canva, Albert Tran, Didier Samuel, Victor de Lédinghen, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Paul Brousse, Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Service d'Hépatologie, Hôpital Henri Mondor, AP-HP, Créteil, France., Hôpital Henri Mondor, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastro-entérologie, Hôpital Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Département d'hépatologie, Service d'hépatologie, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital de la Croix-Rousse [CHU - HCL], Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Chirurgie Digestive, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Chirurgie digestive et hépatobiliaire, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, ANRS France Recherche Nord & sud Sida-hiv hépatites, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Graft Rejection, Male, Sofosbuvir, [SDV]Life Sciences [q-bio], medicine.medical_treatment, kidney transplantation/nephrology, Hepacivirus, 030230 surgery, Liver transplantation, medicine.disease_cause, 0302 clinical medicine, Recurrence, Risk Factors, Immunology and Allergy, liver disease: infectious, Pharmacology (medical), Prospective Studies, Prospective cohort study, education.field_of_study, Graft Survival, Middle Aged, Prognosis, Hepatitis C, 3. Good health, [SDV] Life Sciences [q-bio], kidney failure/injury, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, medicine.drug, Adult, medicine.medical_specialty, infectious disease, Hepatitis C virus, Population, clinical research/practice, Antiviral Agents, 03 medical and health sciences, Internal medicine, medicine, Humans, Adverse effect, education, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Transplantation, business.industry, Kidney Transplantation, Liver Transplantation, Regimen, Immunology, infection and infectious agents - viral: hepatitis C, business, liver transplantation/hepatology, Follow-Up Studies
Abstract: International audience; Hepatitis C virus (HCV) infection is associated with reduced patient survival following combined liver-kidney transplantation (LKT). The aim of this study was to assess the efficacy and safety of second-generation direct-acting antivirals (DAAs) in this difficult-to-treat population. The ANRS CO23 "Compassionate use of Protease Inhibitors in Viral C Liver Transplantation" (CUPILT) study is a prospective cohort including transplant recipients with recurrent HCV infection treated with DAAs. The present work focused on recipients with recurrent infection following LKT. The study population included 23 patients. All patients received at least one NS5B inhibitor (sofosbuvir) in their antiviral regimen an average of 90 months after LKT. Ninety-six percent of recipients achieved a sustained virological response (SVR) at week 12 (SVR12). In terms of tolerance, 39% of recipients presented with at least one serious adverse event. None of the patients experienced acute rejection during therapy and there were no deaths during follow-up. The glomerular filtration rate (GFR) decreased significantly from baseline to the end of therapy. However, this study did not show that the decline in GFR persisted over time or that it was directly related to DAAs. The DAA-based regimen is well tolerated with excellent results in terms of efficacy. It will become the gold standard for the treatment of recurrent HCV following LKT.
Published: 2017

39. Baseline and Post-Treatment Hepatitis C NS5A Resistance in Relapsed Patients from a Multicentric Real-Life Cohort

Author: Philippe Halfon, Jacques Izopet, Pascale Trimoulet, Caroline Scholtes, Sofiane Mohamed, Denis Ouzan, Laurent Chiche, Victor de Ledinghen, Hacène Khiri, Marc Bourlière, M.A. Thelu, Sophie Metivier, Guillaume Penaranda, Anne Plauzolles, Laurent Alric, Vincent Leroy, Fabien Zoulim, Sylvie Larrat, Florence Abravanel, ALPHABIO - Laboratoire de biologie médicale, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gastro-entérologie - Hépatologie [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Hôpital Michallon, Institut Arnault Tzanck, Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen [Fondation Ambroise Paré - Marseille], Centre Hospitalier Universitaire de Lyon (CHU Lyon), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Bordeaux [Bordeaux], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Hôpital Haut-Lévêque [CHU Bordeaux], Hôpital Saint-Joseph [Marseille], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de Virologie [CHU Purpan, Toulouse], Institut Fédératif de Biologie (IFB) - Hôpital Purpan, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT)
Subjects: Male, 0301 basic medicine, DNA Mutational Analysis, Viral Nonstructural Proteins / genetics, Drug Resistance, Hepacivirus, Drug resistance, Viral Nonstructural Proteins, Virological response, Viral Nonstructural Proteins / antagonists & inhibitors, 0302 clinical medicine, Medicine, Pharmacology (medical), Viral, Treatment Failure, Hepatitis C, Viral Load, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Treatment Outcome, Infectious Diseases, Antiviral Agents / pharmacology, Cohort, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Viral load, Hepacivirus / genetics, medicine.medical_specialty, Genotype, Antiviral Agents / therapeutic use, Antiviral Agents, 03 medical and health sciences, Pharmacotherapy, Drug Therapy, Internal medicine, Drug Resistance, Viral, Humans, NS5A, Pharmacology, business.industry, medicine.disease, 030104 developmental biology, Hepatitis C / virology, Hepacivirus / drug effects, Post treatment, Hepatitis C / drug therapy, business
Abstract: Background Recent data have suggested that failure to achieve sustained virological response with direct-acting antiviral therapy is usually due to relapse and is primarily associated with the emergence of resistance-associated substitutions. The aim of this study was to investigate the prevalence and characterization of non-structural-5A resistance-associated substitutions in patients infected with HCV genotypes 1, 3 and 4 treated by direct-acting antiviral therapy, including anti-non-structural-5A, and to characterize the pre-existing resistance-associated substitutions in subjects treated with anti-non-structural-5A inhibitors. Methods From January 2014 to March 2016, 2,995 patients infected with HCV genotypes 1, 3 and 4 were exposed to non-structural-5A inhibitors. Sequencing results at the time of virological failure were available for 61 patients; sequencing at baseline was available for 35 of these patients. Results Among the 35 patients with sequencing results available at baseline, 15 had no resistance-associated substitution, 16 had only one resistance-associated substitution, and 4 had more than one resistance-associated substitution. Resistance-associated substitutions were harbored in 57% of the sequences in the non-structural-5A region. Among the 61 patients sequenced at virological failure, 50 (82%) patients presented at least one resistance-associated substitutions inducing a high level of resistance to non-structural-5A inhibitors (>10-fold resistance). Conclusions This pooled analysis suggests that non-structural-5A resistance-associated substitutions screening should be recommended when considering retreatment with a non-structural-5A inhibitor regimen in patients who have previously experienced failed non-structural-5A treatment.
Published: 2017

40. New tumor suppressor microRNAs target glypican-3 in human liver cancer

Author: Nathalie Dugot-Senant, Flora Cartier, Sarah Lesjean, Justine Charpentier, Amani Ghousein, Emilie Indersie, Martin Hagedorn, Angélique Desplat, Véronique Trézéguet, Christophe Grosset, Katarzyna B. Hooks, Francis Sagliocco, Grosset, Christophe, Initiative d'excellence de l'Université de Bordeaux - - IDEX BORDEAUX2010 - ANR-10-IDEX-0003 - IDEX - VALID, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Biothérapies des maladies génétiques et cancers, TBM-Core [Bordeaux] (CNRS UMS 3427 - INSERM US 005), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from the French National Cancer Institute (grants INCa_5828/INCa_ PLBIO_2012_110 and INCa_TRANSLA_2013_209) to CFG and VT, the French Ministry of Health (grant n°DGOS/PF4/0013/105) to CFG, the Fondation pour la Recherche Médicale (FRM, grant n°DBI20131228566) to CFG, the Ligue Nationale contre le Cancer (LNCC) to CFG and VT, the Cancéropôle Grand Sud-Ouest to CFG and VT, the French State in the frame of the 'Investments for the future' Programme IdEx Bordeaux (grant ANR10-IDEX-03-02) to KBH and the charity associations Eva Pour La Vie, Aidons Marina, Fondation Flavien and E.S.CA.PE to MH and CFG., ANR-10-IDEX-0003,IDEX BORDEAUX,Initiative d'excellence de l'Université de Bordeaux(2010), Flow Cytometry Facility / TransBioMed Core [Bordeaux] (INSERM US005 - CNRS UMS 3427 - UB), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), and ANR-10-IDEX-0003-02/10-IDEX-0003,IDEX BORDEAUX,IdEx Bordeaux(2010)
Subjects: Adult, Male, 0301 basic medicine, Hepatoblastoma, Pathology, medicine.medical_specialty, Carcinoma, Hepatocellular, Adolescent, [SDV]Life Sciences [q-bio], Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, liver, Glypican 3, Young Adult, 03 medical and health sciences, Glypicans, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, microRNA, medicine, Humans, cancer, Genes, Tumor Suppressor, Aged, Cell Proliferation, Oncogene, Liver Neoplasms, Wnt signaling pathway, Cancer, hepatocellular carcinoma, Middle Aged, medicine.disease, glypican-3, 3. Good health, Gene Expression Regulation, Neoplastic, MicroRNAs, 030104 developmental biology, Oncology, Cancer research, Female, Signal transduction, Liver cancer, Research Paper
Abstract: International audience; Glypican-3 (GPC3) is an oncogene, frequently upregulated in liver malignancies such as hepatocellular carcinoma (HCC) and hepatoblastoma and constitutes a potential molecular target for therapy in liver cancer. Using a functional screening system, we identified 10 new microRNAs controlling GPC3 expression in malignant liver cells, five of them e.g. miR-4510, miR-203a-3p, miR-548aa, miR-376b-3p and miR-548v reduce GPC3 expression. These 5 microRNAs were significantly downregulated in tumoral compared to non-tumoral liver and inhibited tumor cell proliferation. Interestingly, miR-4510 inversely correlated with GPC3 mRNA and protein in HCC samples. This microRNA also induced apoptosis of hepatoma cells and blocked tumor growth in vivo in the chick chorioallantoic membrane model. We further show that the tumor suppressive effect of miR-4510 is mediated through direct targeting of GPC3 mRNA and inactivation of Wnt/β-catenin transcriptional activity and signaling pathway. Moreover, miR-4510 up-regulated the expression of several tumor suppressor genes while reducing the expression of other pro-oncogenes. In summary, we uncovered several new microRNAs targeting the oncogenic functions of GPC3. We provided strong molecular, cellular and in vivo evidences for the tumor suppressive activities of miR-4510 bringing to the fore the potential value of this microRNA in HCC therapy.
Published: 2017

41. MicroRNA therapy inhibits hepatoblastoma growth in vivo by targeting β‐catenin and Wnt signaling

Author: Indersie, Emilie, Lesjean, Sarah, Hooks, Katarzyna B., Sagliocco, Francis, Ernault, Tony, Cairo, Stefano, Merched‐Sauvage, Maria, Rullier, Anne, Le Bail, Brigitte, Taque, Sophie, Grotzer, Michael, Branchereau, Sophie, Guettier, Catherine, Fabre, Monique, Brugières, Laurence, Hagedorn, Martin, Buendia, Marie‐Annick, Grosset, Christophe F., Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du cancer du foie, Physiopathologie et traitement des maladies du foie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), CHU Bordeaux [Bordeaux], Laboratoire d'anatomie pathologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Department of Oncology, Universität Zürich [Zürich] = University of Zurich (UZH), Département de chirurgie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Virus Hépatotropes et Cancers, Université Paris-Sud - Paris 11 (UP11)-IFR89-EA 3541, Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), XenTech [Evry], Department of Morphology, Surgery and Experimental Medicine [Ferrara Italy] (School of Medicine), Università degli Studi di Ferrara (UniFE), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service d'Hématologie et d'Oncologie pédiatrique, CHU Pontchaillou [Rennes], University hospital of Zurich [Zurich], Departement de Pathologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Supported by grants from the French National Cancer Institute (grant INCa_TRANSLA_2013_209) to C.F.G, E.I., and M.A.B., French Ministry of Health (grant DGOS/PF4/0013/105) to L.B., Fondation pour la Recherche Medicale (grant DBI20131228566) to C.F.G., Ligue Nationale contre le Cancer to C.F.G., Canceropole Grand Sud-Ouest to C.F.G., the French State in the framework of the ' Investments for the Future' Program IdEx Bordeaux (grant ANR-10-IDEX-03-02) to K.B.H., and the charity associations Eva Pour La Vie, Aidons Marina, Fondation Flavien, and E.S.CA.P.E. to M.H., E.I., and C.F.G., ANR-10-IDEX-0003,IDEX BORDEAUX,Initiative d'excellence de l'Université de Bordeaux(2010), Università degli Studi di Ferrara = University of Ferrara (UniFE), Grosset, Christophe, and Initiative d'excellence de l'Université de Bordeaux - - IDEX BORDEAUX2010 - ANR-10-IDEX-0003 - IDEX - VALID
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Original Article, Original Articles
Abstract: International audience; Hepatoblastoma (HBL) is the most common pediatric liver cancer. In this malignant neoplasm, beta-catenin protein accumulates and increases Wnt signaling due to recurrent activating mutations in the catenin-beta 1 (CTNNB1) gene. Therefore, beta-catenin is a key therapeutic target in HBL. However, controlling beta-catenin production with therapeutic molecules has been challenging. New biological studies could provide alternative therapeutic solutions for the treatment of HBL, especially for advanced tumors and metastatic disease. In this study, we identified microRNAs (miRNAs) that target beta-catenin and block HBL cell proliferation in vitro and tumor growth in vivo. Using our dual-fluorescence-FunREG system, we screened a library of 1,712 miRNA mimics and selected candidates inhibiting CTNNB1 expression through interaction with its untranslated regions. After validating the regulatory effect of nine miRNAs on beta-catenin in HBL cells, we measured their expression in patient samples. Let-7i-3p, miR-449b-3p, miR-624-5p, and miR-885-5p were decreased in tumors compared to normal livers. Moreover, they inhibited HBL cell growth and Wnt signaling activity in vitro partly through beta-catenin down-regulation. Additionally, miR-624-5p induced cell senescence in vitro, blocked experimental HBL growth in vivo, and directly targeted the beta-catenin 3'-untranslated region. Conclusion: Our results shed light on how beta-catenin-regulating miRNAs control HBL progression through Wnt signaling inactivation. In particular, miR-624-5p may constitute a promising candidate for miRNA replacement therapy for HBL patients. (Hepatology Communications 2017;1:168-183).
Published: 2017

42. miR‐4510 blocks hepatocellular carcinoma development through RAF1 targeting and RAS/RAF/MEK/ERK signalling inactivation

Author: Anne-Aurélie Raymond, Justine Charpentier, Jean-William Dupuy, Flora Cartier, Paulette Bioulac-Sage, Amani Ghousein, Christophe Grosset, Nicola Mosca, Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Génomique Fonctionnelle Bordeaux [Bordeaux] (CGFB), Institut Polytechnique de Bordeaux-Université de Bordeaux Ségalen [Bordeaux 2], Physiopathologie du cancer du foie, BaRITOn - Bordeaux Research in Translational Oncology, Université de Bordeaux Ségalen [Bordeaux 2], This study was supported by grants from L’Association pour le Développement du Liban to AG, La Ligue Régionale Contre le Cancer (Comités Dordogne, Comité Gironde) to AG and CFG, the French State in the framework of the ‘Investments for the future’ Programme IdEx Bordeaux (grant ANR‐10‐IDEX‐03‐02) to NM and La region Nouvelle‐Aquitaine to NM., ANR-10-IDEX-0003-02/10-IDEX-0003,IDEX BORDEAUX,IdEx Bordeaux(2010), Ghousein, Amani, Mosca, Nicola, Cartier, Flora, Charpentier, Justine, Dupuy, Jean-William, Raymond, Anne-Aurélie, Bioulac-Sage, Paulette, Grosset, Christophe F, Grosset, Christophe, Initiative d'excellence de l'Université de Bordeaux - - IDEX BORDEAUX2010 - ANR-10-IDEX-0003 - IDEX - VALID, and ANR-10-IDEX-0003,IDEX BORDEAUX,Initiative d'excellence de l'Université de Bordeaux(2010)
Subjects: Sorafenib, MAPK/ERK pathway, Carcinoma, Hepatocellular, MAP Kinase Signaling System, Down-Regulation, [SDV.CAN]Life Sciences [q-bio]/Cancer, liver, Proto-Oncogene Mas, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Glypicans, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Regorafenib, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RAF1, Extracellular Signal-Regulated MAP Kinases, Protein kinase A, Wnt Signaling Pathway, Cell Proliferation, miR-4510, Messenger RNA, Hepatology, Oncogene, Chemistry, Cell growth, Liver Neoplasms, Wnt signaling pathway, hepatocellular carcinoma, RAS/RAF/MEK/ERK signalling, Xenograft Model Antitumor Assays, digestive system diseases, 3. Good health, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins c-raf, MicroRNAs, 030220 oncology & carcinogenesis, Cancer research, 030211 gastroenterology & hepatology, Chickens, Signal Transduction, medicine.drug
Abstract: International audience; BACKGROUND:Therapeutic outcomes using the multikinase inhibitors, sorafenib and regorafenib, remain unsatisfactory for patients with advanced hepatocellular carcinoma (HCC). Thus, new drug modalities are needed. We recently reported the remarkable capacity of miR-4510 to impede the growth of HCC and hepatoblastoma through Glypican-3 (GPC3) targeting and Wnt pathway inactivation.METHODS:To identify new targets of miR-4510, we used a label-free proteomic approach and reported down-regulation of RAF proto-oncogene serine/threonine-protein kinase (RAF1) by miR-4510. Because the tumourigenic role of RAF1 in HCC is controversial, we further studied RAF1:miR-4510 interactions using cellular, molecular as well as functional approaches and a chicken chorioallantoic membrane (CAM) xenograft model.RESULTS:We found an increase in RAF1 protein in 59.3% of HCC patients and a specific up-regulation of its transcript in proliferative tumours. We showed that miR-4510 inactivates the RAS/RAF/MEK/ERK pathway and reduces the expression of downstream targets (ie c-Fos proto-oncogene [FOS]) through RAF1 direct targeting. At a cellular level, miR-4510 inhibited HCC cell proliferation and migration and induced senescence in part by lowering RAF1 messenger RNA (mRNA) and protein expression. Finally, we confirmed the pro-tumoural function of RAF1 protein in HCC cells and its ability to sustain HCC tumour progression in vitro and in vivo.CONCLUSIONS:In this work, we confirm that RAF1 acts as an oncogene in HCC and further demonstrate that miR-4510 acts as a strong tumour suppressor in the liver by targeting many proto-oncogenes, including GPC3 and RAF1, and subsequently controlling key biological and signalling pathways among which Wnt and RAS/RAF/MEK/ERK signals.
Published: 2019

43. Radiation Exposure During Transarterial Chemoembolization: Angio-CT Versus Cone-Beam CT

Author: Julien Le Roy, Nicolas Molinari, Lauranne Piron, Jean-Paul Beregi, Ali Belgour, Julien Delicque, Joël Greffier, Carole Allimant, Christophe Cassinotto, Boris Guiu, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Département radiologie diagnostique et interventionnelle Saint Eloi [CHRU Montpellier], Pôle Digestif [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Institut Montpelliérain Alexander Grothendieck (IMAG), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), and CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Male, Cone beam computed tomography, Carcinoma, Hepatocellular, Computed Tomography Angiography, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Radiology, Interventional, Effective dose (radiation), 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Chemoembolization, Therapeutic, Cone beam ct, Aged, Interventional radiology, medicine.diagnostic_test, business.industry, Angio ct, Radiation exposure, Liver Neoplasms, Ultrasound, Significant difference, Cone-beam computed tomography, Reproducibility of Results, Middle Aged, Liver, Female, Chemoembolization, Therapeutic, Cardiology and Cardiovascular Medicine, business, Nuclear medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Introduction: Cone-beam computed tomography (CBCT) has been developed to improve reliability of many interventional radiology (IR) procedures performed with Angio system, such as transarterial chemoembolization (TACE). Angio-CT has emerged as a new imaging technology that combines a CT scanner with an Angio system in the same IR suite. The purpose of our study was to compare Angio system with CBCT capability and Angio-CT in terms of patient radiation exposure during TACE procedures.Materials and methods: Consecutive TACE procedures performed between January 2016 and September 2017 with the two imaging modalities (Artis Zeego defining the CBCT group and Infinix-i 4D-CT defining the Angio-CT group) were reviewed. TACE and patient's characteristics and patient radiation exposure parameters were collected. Dose-area products (DAP) and dose-length products (DLP) were converted into effective doses (ED) using conversion factors. Accuracy of tumor targeting and response was retrospectively assessed.Results: A total of 114 TACE procedures in 96 patients were included with 57 procedures in each group. The total ED in the Angio-CT group was 2.5 times lower than that in the CBCT group (median 15.4 vs. 39.2 mSv, p < 0.001). Both 2D ED and 3D ED were lower in the Angio-CT group than in the CBCT group (5.1 vs. 20 mSv, p < 0.001, and 7.4 vs. 17.9 mSv, p < 0.001, respectively). There was no significant difference neither in terms of classes of tumor targeting (p = 0.509) nor in terms of classes of tumor response (p = 0.070) between both groups.Conclusion: Angio-CT provides significant decrease in patient effective dose during TACE procedures compared to Angio system with CBCT.
Published: 2019

44. Cytolethal distending toxin induces the formation of transient messenger-rich ribonucleoprotein nuclear invaginations in surviving cells

Author: Jean-Luc Morel, Victoria Korolik, Christelle Péré-Védrenne, Mojgan Djavaheri-Mergny, Philippe Lehours, Christophe Grosset, Pierre Dubus, Wencan He, Chloé Alix, Lamia Azzi-Martin, Martina Prochazkova-Carlotti, Emilie Le Roux-Goglin, Armelle Ménard, Christine Varon, Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Griffith University [Brisbane], Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Campylobacters et des Hélicobacters [Bordeaux] (CNRCH), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Glycomics, Centre National de Référence des Campylobacters et Hélicobacters (CNR Campylobacters et Hélicobacters), CHU Bordeaux [Bordeaux], Signalisation et physiopathologie des cellules épithéliales, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Christelle Péré-Védrenne was the recipient of a predoctoral fellowship from the Ligue Nationale Contre le Cancer. This work was supported in part by the Ligue Nationale Contre le Cancer INSERM, the University of Bordeaux and the Federative Research Structure ‘Biology: from basics to Medicine’ (‘TransBioMed’) at the, Gestionnaire, Hal Sorbonne Université, Physiopathologie du cancer du foie, Université de Bordeaux (UB), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER, Varon, Christine, insitute for glycomics, Infection à helicobacter, inflammation et cancer, Histologie et Pathologie Moléculaire, Université Bordeaux Segalen - Bordeaux 2, and Grosset, Christophe
Subjects: Cytoplasm, [SDV.BA] Life Sciences [q-bio]/Animal biology, Cytolethal distending toxin, [SDV]Life Sciences [q-bio], Cell, Biochemistry, Ribosome, Mice, Helicobacter, Biology (General), ComputingMilieux_MISCELLANEOUS, Ribonucleoprotein, Staining, 0303 health sciences, Chemistry, [SDV.BA]Life Sciences [q-bio]/Animal biology, Messenger RNA, Cell Staining, Translation (biology), [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Specimen preparation and treatment, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Nucleic acids, medicine.anatomical_structure, Ribonucleoproteins, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cellular Structures and Organelles, Research Article, QH301-705.5, Cell Survival, Imaging Techniques, Bacterial Toxins, Immunology, Nucleoplasmic reticulum, [SDV.CAN]Life Sciences [q-bio]/Cancer, Microbiology, Cell Line, Helicobacter Infections, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Microscopy, Electron, Transmission, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Virology, Fluorescence Imaging, Genetics, medicine, Animals, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], RNA, Messenger, Cytoplasmic Staining, Molecular Biology, 030304 developmental biology, Cell Nucleus, Biology and life sciences, 030306 microbiology, [SCCO.NEUR]Cognitive science/Neuroscience, DAPI staining, Cell Biology, DNA, RC581-607, Mice, Inbred C57BL, Research and analysis methods, Polyketides, Nuclear staining, Hepatocytes, RNA, DNA damage, Parasitology, Immunologic diseases. Allergy, Peptides, Mutagens
Abstract: Humans are frequently exposed to bacterial genotoxins involved in digestive cancers, colibactin and Cytolethal Distending Toxin (CDT), the latter being secreted by many pathogenic bacteria. Our aim was to evaluate the effects induced by these genotoxins on nuclear remodeling in the context of cell survival. Helicobacter infected mice, coculture experiments with CDT- and colibactin-secreting bacteria and hepatic, intestinal and gastric cells, and xenograft mouse-derived models were used to assess the nuclear remodeling in vitro and in vivo. Our results showed that CDT and colibactin induced-nuclear remodeling can be associated with the formation of deep cytoplasmic invaginations in the nucleus of giant cells. These structures, observed both in vivo and in vitro, correspond to nucleoplasmic reticulum (NR). The core of the NR was found to concentrate ribosomes, proteins involved in mRNA translation, polyadenylated RNA and the main components of the complex mCRD involved in mRNA turnover. These structures are active sites of mRNA translation, correlated with a high degree of ploidy, and involve MAPK and calcium signaling. Additional data showed that insulation and concentration of these adaptive ribonucleoprotein particles within the nucleus are dynamic, transient and protect the cell until the genotoxic stress is relieved. Bacterial genotoxins-induced NR would be a privileged gateway for selected mRNA to be preferably transported therein for local translation. These findings offer new insights into the context of NR formation, a common feature of many cancers, which not only appears in response to therapies-induced DNA damage but also earlier in response to genotoxic bacteria., Author summary Humans are frequently exposed to bacterial genotoxins linked to cancers, colibactin and Cytolethal Distending Toxin (CDT). These genotoxins induce DNA damage and can promote formation of nucleoplasmic reticulum (NR), deeply invaginated in the nucleoplasm of giant nuclei both in vivo and in vitro. Our cellular models showed that these structures can be observed together with profound nuclear reorganization corresponding to remodeling of nuclear material. The core of the genotoxin-induced NRs concentrates protein production machinery of the cell as well as controlling elements of protein turnover. These genotoxin-induced dynamic structures may also be signaling hubs controlling mRNA turnover and translation of selected mRNAs and thus correspond to a privileged gateway for the synthesis of selected mRNA which are preferentially transported from the nucleus through pores and translated therein. These transient and reversible hubs allow the cell to pause and repair the DNA damage caused by bacterial genotoxins in order to maintain cell survival. As NR formation is a common feature of many cancers, similar mechanism could occur and contribute to the resistance of cancer cells to radiotherapies and some chemotherapies aimed at inducing DNA damage.
Published: 2019

45. Long-term clinical outcome and HAVCR2 mutations in 70 patients with subcutaneous panniculitis-like T-cell lymphoma: a study from the French Cutaneous Lymphoma Group

Author: M. Bagot, Stéphane Barete, François Skowron, Pauline Brice, Gwenaël Hervé, David Michonneau, Béatrice Vergier, A. Finon, Caroline Ram-Wolff, Marie Beylot-Barry, A. Març Ais, Stéphane Dalle, Serge Boulinguez, F. Brunet-Possenti, Vanessa Szablewski, S. Laurent-Roussel, Eve Maubec, O. Carpentier, F. Sepulveda Garrido, G. Sonigo, E. Birckel, Olivier Dereure, V. Costes Martineau, Henri Adamski, R. Kerdraon, A. de Masson, I. Brocheriou, S. Oro, Agnès Carlotti, Fabien Guérin, F. Franck, O. Augereau, C. Bléchet, N. Bonnet, P. Moguelet, Jd. Bouaziz, Olivia Boccara, Gérard Socié, R. Dubois, F. Le Gall, F. Suarez, Marisa Battistella, L. Deschamps, Nicolas Ortonne, Nicolas Franck, B. Balme, G. Bens, G. de Saint-Basile, F. Comoz, D. Haidar, S. Taix, Sylvie Fraitag, Christine Bodemer, Jehane Fadlallah, E. Tournier, A. Mahe, Laurence Lamant, Guy Leverger, G. Bohelay, Michel D'Incan, S. Faiz, I. Beschet, Liliane Laroche, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Sciences Cognitives (ISC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Nord [CHU - APHM], CRLCC Henri Becquerel, CHU Necker - Enfants Malades [AP-HP], Service de dermatologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service de Dermatologie [Rennes], CHU Pontchaillou [Rennes], Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Service de Dermatologie, Hôpital Bichat, AP-HP, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Pontificia Universidad Católica de Chile (UC), Département de dermatologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique (LHEEA), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Service d'anatomie pathologique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Centre Hospitalier Régional d'Orléans (CHR), Laboratoire Hippolyte Fizeau (FIZEAU), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Service d’Anatomie et cytologie pathologiques [CHU Tenon], Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Laboratoire des symbioses tropicales et méditerranéennes (UMR LSTM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Laboratoire d'aérologie (LA), Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, L'Oréal Recherche France (L'Oréal Recherche), L'OREAL, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Dermatologie [Rennes] = Dermatology [Rennes], Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Hôpital Saint-Jacques-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional d'Orléans (CHRO), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Laboratoire d'aérologie (LAERO), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Nice Sophia Antipolis (1965 - 2019) (UNS), CHU Trousseau [APHP], Université de Toulouse (UT)-Université de Toulouse (UT)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)
Subjects: Cancer Research, medicine.medical_specialty, business.industry, HAVCR2, medicine.disease, Dermatology, Cutaneous lymphoma, 3. Good health, Oncology, Subcutaneous Panniculitis-Like T-Cell Lymphoma, Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

46. Re: Tumor Targeting and Three-Dimensional Voxel-Based Dosimetry to Predict Tumor Response, Toxicity, and Survival after Yttrium-90 Resin Microsphere Radioembolization in Hepatocellular Carcinoma

Author: Georges-Philippe Pageaux, Christophe Cassinotto, Carole Allimant, Boris Guiu, José Ursic-Bedoya, Marilyne Kafrouni, Eric Assenat, D. Ilonca, Julien Delicque, Denis Mariano-Goulart, Serge Aho, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Médico-Chirurgical des Maladies de l'Appareil Digestif et de Transplantation Hépatique, CHU Saint-Eloi, Epidemiology, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Radiology & Nuclear Medicine, and UCL - (SLuc) Service de médecine nucléaire
Subjects: Male, Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], computer.software_genre, 030218 nuclear medicine & medical imaging, Liver disease, 0302 clinical medicine, Risk Factors, Voxel, Positron Emission Tomography Computed Tomography, Medicine, Yttrium Radioisotopes, Embolization, ComputingMilieux_MISCELLANEOUS, Randomized Controlled Trials as Topic, Liver Neoplasms, Radiotherapy Dosage, Middle Aged, Embolization, Therapeutic, Progression-Free Survival, Microspheres, 3. Good health, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Toxicity, Female, Cardiology and Cardiovascular Medicine, Carcinoma, Hepatocellular, chemistry.chemical_element, 03 medical and health sciences, Carcinoma, Dosimetry, Humans, Radiology, Nuclear Medicine and imaging, Progression-free survival, Aged, Neoplasm Staging, Retrospective Studies, business.industry, Yttrium, medicine.disease, Clinical Trials, Phase III as Topic, chemistry, Radiopharmaceuticals, business, Nuclear medicine, computer
Abstract: Purpose To identify predictive factors of tumor response, progression-free survival (PFS), overall survival (OS), and toxicity using three-dimensional (3D) voxel-based dosimetry in patients with intermediate and advanced stage hepatocellular carcinoma (HCC) treated by yttrium-90 (90Y) resin microspheres radioembolization (RE). Materials and Methods From February 2012 to December 2015, 45 90Y resin microspheres RE procedures were performed for HCC (Barcelona Clinic Liver Cancer stage B/C; n = 15/30). Area under the dose-volume histograms (AUDVHs) were calculated from 3D voxel-based dosimetry to measure 90Y dose deposition. Factors associated with tumor control (ie, complete/partial response or stable disease on Modified Response Evaluation Criteria in Solid Tumors) at 6 months were investigated. PFS and OS analyses were performed (Kaplan-Meier). Toxicity was assessed by occurrence of radioembolization-induced liver disease (REILD). Results Tumor control rate was 40.5% (17/42). Complete tumor targeting (odds ratio = 36.97; 95% confidence interval, 1.83–747; P 61 Gy, complete tumor targeting and AUDVHtumor 61 Gy had median PFS of 2.7, 1.8, 6.3, and 12.1 months (P Conclusions Complete tumor targeting and 90Y dose to tumor are independent factors associated with tumor control and clinical outcomes.
Published: 2019

47. An In Vitro Evaluation of Four Types of Drug-Eluting Embolics Loaded with Idarubicin

Author: Christophe Cassinotto, Boris Guiu, Luis Thompson, Gloria Hincapie, Mathieu Boulin, Gregory M. Cruise, Yue Wu, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Ambry Genetics [Aliso Viejo, CA, USA], Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Physiopathologie du cancer du foie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), and Salvy-Córdoba, Nathalie
Subjects: [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Drug Storage, [SDV.CAN]Life Sciences [q-bio]/Cancer, Bead, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Drug Stability, Drug-eluting embolic beads (DEBs), Medicine, Idarubicin, Radiology, Nuclear Medicine and imaging, Chemoembolization, Therapeutic, Particle Size, Suspension (vehicle), Drug Carriers, Antibiotics, Antineoplastic, Chromatography, Average diameter, Elution, business.industry, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Microspheres, In vitro, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Drug Liberation, Kinetics, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, 030220 oncology & carcinogenesis, visual_art, visual_art.visual_art_medium, Particle size, Cardiology and Cardiovascular Medicine, business, Drug carrier, medicine.drug
Abstract: Purpose This study compared loading, elution, and stability of drug-eluting embolic beads (DEBs) loaded with idarubicin. Materials and Methods DC Bead (100–300 μm), HepaSphere (30–60 μm), LifePearl (200 μm), and Tandem (100 μm) DEBs were loaded with 5 mg/mL idarubicin. Loading, elution, diameter changes, loading stability over 2 weeks in storage, and time in suspension were determined for each of the DEBs. Results Loading of more than 99% of idarubicin was achieved within 15 minutes for LifePearl, DC Bead, and Tandem beads. LifePearl, DC Bead, HepaSphere, and Tandem beads eluted 75% of the total idarubicin released in 13, 24, 42, and 91 minutes, respectively. In vitro elution was completed in 2 hours with 73% ± 3%, 74% ± 3%, 65% ± 6%, and 7% ± 0% of the loaded idarubicin eluted for LifePearl, DC Bead, HepaSphere, and Tandem, respectively. Statistically significant differences were observed at every time point between at least 2 of the products. Overall, in vitro idarubicin elution was rapid and nearly complete for LifePearl, DC Bead, and HepaSphere beads but was minimal and slow from Tandem beads. The average diameter of DEBs after loading was reduced by 5% for LifePearl, whereas it was increased by 9% and 1% for DC Bead and Tandem, respectively. After loading, time in suspension was 11 ± 4 and 10 ± 2 minutes for LifePearl and HepaSphere, respectively, whereas DC Bead and Tandem beads were held in suspension for greater than 20 minutes. Conclusions Although all 4 DEBs loaded idarubicin within 15 minutes with minimal changes in diameter, the elution amounts, rates of release, and time in suspension varied.
Published: 2019

48. A novel spleen-dedicated stiffness measurement by FibroScan® improves the screening of high-risk oesophageal varices

Author: Federico Ravaioli, M. Rosselli, Giuseppe Mazzella, Mirella Fraquelli, Antonio Colecchia, Corina Rusu, Nathalie Ganne-Carrié, Giovanni Marasco, Paul Calès, Davide Festi, Horia Stefanescu, Victor de Ledinghen, Pietro Andreone, Stefanescu H., Marasco G., Cales P., Fraquelli M., Rosselli M., Ganne-Carrie N., de Ledinghen V., Ravaioli F., Colecchia A., Rusu C., Andreone P., Mazzella G., Festi D., Regional Institute of Gastroenterology and Hepatology [Cluj-Napoca], Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), II Gastroenterology Unit, Department of Medicine, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Physiopathologie du cancer du foie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, and Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Baveno VI criteria, liver stiffness measurement, portal hypertension, spleen stiffness measurement, Chronic liver disease, Esophageal and Gastric Varices, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Liver stiffness, Predictive Value of Tests, Internal medicine, medicine, Humans, Prospective Studies, ComputingMilieux_MISCELLANEOUS, Aged, Hepatology, medicine.diagnostic_test, business.industry, Platelet Count, Liver Diseases, Reproducibility of Results, Middle Aged, medicine.disease, 3. Good health, Endoscopy, Logistic Models, 030220 oncology & carcinogenesis, Multivariate Analysis, Portal hypertension, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, Female, business, Varices, Spleen
Abstract: Background & Aims Several non-invasive tests (NITs) have been developed to diagnose oesophageal varices (EV), including the recent Baveno VI criteria to rule out high-risk varices (HRV). Spleen stiffness measurement (SSM) with the standard FibroScan (R) (SSM@50Hz) has been evaluated. However, the EV grading could be underestimated because of a ceiling threshold (75 kPa) of the SSM@50Hz. The aims were to evaluate SSM by a novel spleen-dedicated FibroScan (R) (SSM@100Hz) for EV diagnosis compared with SSM@50Hz, other validated NITs and Baveno VI criteria. Methods This prospective multicentre study consecutively enrolled patients with chronic liver disease; blood data, endoscopy, liver stiffness measurement (LSM), SSM@50Hz and SSM@100Hz were collected. Results Two hundred and sixty patients met inclusion criteria. SSM@100Hz success rate was significantly higher than that of SSM@50Hz (92.5% vs 76.0%, P < .001). SSM@100Hz accuracy for the presence of EV (AUC = 0.728) and HRV (AUC = 0.756) was higher than in other NITs. SSM@100Hz AUC for large EV (0.782) was higher than SSM@50Hz (0.720, P = .027). AUC for HRV with SSM@100Hz (0.780) was higher than with LSM (0.615, P < .001). The spared endoscopy rate of Baveno VI criteria (8.1%) was significantly increased by the combination to SSM@50Hz (26.5%) or SSM@100Hz (38.9%, P < .001 vs others). The missed HRV rate was, respectively, 0% and 4.7% for combinations. Conclusions SSM@100Hz is a new performant non-invasive marker for EV and HRV providing a higher accuracy than SSM@50Hz and other NITs. The combination of Baveno VI criteria and SSM@100Hz significantly increased the spared endoscopy rate compared to Baveno VI criteria alone or combined with SSM@50Hz. Clinical trial number: NCT02180113.
Published: 2019

49. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment a prospective cohort study

Author: Albert Tran, Victor de Ledinghen, Armand Abergel, Céline Dorival, Olivier Chazouillères, Louis d’Alteroche, Isabelle Rosa, Didier Samuel, Moana Gelu-Simeon, Laurent Alric, Vincent Leroy, Jérôme Gournay, François Habersetzer, Dominique Guyader, Stanislas Pol, Véronique Loustaud-Ratti, Ghassan Riachi, Jean-Pierre Bronowicki, Hélène Fontaine, Anne Minello, Christophe Hézode, Philippe Mathurin, Claire Geist, Nathalie Ganne, Mélanie Simony, Dominique Thabut, François Raffi, Xavier Causse, Patrick Marcellin, Sophie Metivier, Paul Calès, Isabelle Portal, Marc Bourlière, Dominique Larrey, Fabien Zoulim, Fabrice Carrat, Alpha Diallo, Georges Haour, Tarik Asselah, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANRS France Recherche Nord & sud Sida-hiv hépatites, Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire de Nice (CHU Nice), Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Rouen, Normandie Université (NU), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Image Science for Interventional Techniques (ISIT), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Centre National de la Recherche Scientifique (CNRS), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional d'Orléans (CHRO), Service d'Hépato-gastro-entérologie [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Equipe EPICAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Intercommunal de Créteil (CHIC), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Aix Marseille Université (AMU), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Toulouse [Toulouse], Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], CCSD, Accord Elsevier, Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Liver transplantation, Antiviral Agents, Gastroenterology, 03 medical and health sciences, Liver disease, Viewpoint, 0302 clinical medicine, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Aged, Proportional Hazards Models, business.industry, Incidence, Liver Neoplasms, Hazard ratio, General Medicine, Hepatitis C, Hepatitis C, Chronic, Middle Aged, Hepatology, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Hepatocellular carcinoma, Female, France, business
Abstract: Although direct-acting antivirals have been used extensively to treat patients with chronic hepatitis C virus (HCV) infection, their clinical effectiveness has not been well reported. We compared the incidence of death, hepatocellular carcinoma, and decompensated cirrhosis between patients treated with direct-acting antivirals and those untreated, in the French ANRS CO22 Hepather cohort.We did a prospective study in adult patients with chronic HCV infection enrolled from 32 expert hepatology centres in France. We excluded patients with chronic hepatitis B, those with a history of decompensated cirrhosis, hepatocellular carcinoma, or liver transplantation, and patients who were treated with interferon-ribavirin with or without first-generation protease inhibitors. Co-primary study outcomes were incidence of all-cause mortality, hepatocellular carcinoma, and decompensated cirrhosis. The association between direct-acting antivirals and these outcomes was quantified using time-dependent Cox proportional hazards models. This study is registered with ClinicalTrials.gov, number NCT01953458.Between Aug 6, 2012, and Dec 31, 2015, 10 166 patients were eligible for the study. 9895 (97%) patients had available follow-up information and were included in analyses. Median follow-up was 33·4 months (IQR 24·0-40·7). Treatment with direct-acting antivirals was initiated during follow-up in 7344 patients, and 2551 patients remained untreated at the final follow-up visit. During follow-up, 218 patients died (129 treated, 89 untreated), 258 reported hepatocellular carcinoma (187 treated, 71 untreated), and 106 had decompensated cirrhosis (74 treated, 32 untreated). Exposure to direct-acting antivirals was associated with increased risk for hepatocellular carcinoma (unadjusted hazard ratio [HR] 2·77, 95% CI 2·07-3·71) and decompensated cirrhosis (3·83, 2·29-6·42). After adjustment for variables (age, sex, body-mass index, geographical origin, infection route, fibrosis score, HCV treatment-naive, HCV genotype, alcohol consumption, diabetes, arterial hypertension, biological variables, and model for end-stage liver disease score in patients with cirrhosis), exposure to direct-acting antivirals was associated with a decrease in all-cause mortality (adjusted HR 0·48, 95% CI 0·33-0·70) and hepatocellular carcinoma (0·66, 0·46-0·93), and was not associated with decompensated cirrhosis (1·14, 0·57-2·27).Treatment with direct-acting antivirals is associated with reduced risk for mortality and hepatocellular carcinoma and should be considered in all patients with chronic HCV infection.INSERM-ANRS (France Recherche NordSud Sida-HIV Hépatites), ANR (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, and Roche.
Published: 2019

50. Antigenic Mimicry in Paraneoplastic Immune Thrombocytopenia

Author: Guillaume Vial, Etienne Rivière, Anne-Aurélie Raymond, Chloé James, Sylvaine Di-Tommaso, Nathalie Dugot-Senant, Jean-William Dupuy, Mokrane Yacoub, Marie Parrens, Fréderic Saltel, Jean-François Viallard, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Flow Cytometry Facility / TransBioMed Core [Bordeaux] (INSERM US005 - CNRS UMS 3427 - UB), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Génomique Fonctionnelle Bordeaux [Bordeaux] (CGFB), Institut Polytechnique de Bordeaux-Université de Bordeaux Ségalen [Bordeaux 2], Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, TBM-Core [Bordeaux] (CNRS UMS 3427 - INSERM US 005), and Boullé, Christelle
Subjects: lcsh:Immunologic diseases. Allergy, 0301 basic medicine, medicine.medical_treatment, Immunology, Case Report, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Immune system, proteomics, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Refractory, immune system diseases, hemic and lymphatic diseases, Article CLINIQUE, medicine, Immunology and Allergy, antigenic mimicry, Kidney, business.industry, Autoantibody, Cancer, solid tumors, medicine.disease, Nephrectomy, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, tumor antigens, immune thrombocytopenia, Immunohistochemistry, lcsh:RC581-607, business, 030215 immunology
Abstract: International audience; The association of immune thrombocytopenia (ITP) with cancer has been reported, but the causality of tumor cells in paraneoplastic ITP pathogenesis and maintenance has never been established. We analyzed the unusual case of refractory ITP and coincident urothelial tumor of the kidney with circulating high titer anti-GPIIBIIIA autoantibodies. Intriguingly, after nephrectomy, the patient recovered fully and her anti-GPIIBIIIA autoantibodies disappeared. Proteomic and immunohistochemistry analyses revealed erratic GPIIB expression by the tumor cells, suggesting possible antigenic mimicry chronically stimulating the immune system and leading to this patient's refractory ITP. Such previously unreported findings provide proof-of-concept that requires further confirmation with the prospective study of a larger number of patients.
Published: 2019

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