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290 results on '"Ligue Nationale Contre le Cancer (LNCC)"'

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, 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 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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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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

4. Are Sleep Complaints Related to Cognitive Functioning in Non-Central Nervous System Cancer? A Systematic Review

Author: Bénédicte Giffard, Joy Perrier, Mylène Duivon, Béatrice Desgranges, Neuropsychologie et imagerie de la mémoire humaine (NIMH), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-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), Plateforme Cancer et Cognition, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest, Perrier, Joy, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Cancéropole Nord-Ouest-Ligue Nationale Contre le Cancer (LNCC)
Subjects: Adult, Sleep Wake Disorders, Perceived sleep quality, medicine.medical_specialty, Insomnia, Neurology, Non-central nervous system cancer, 03 medical and health sciences, Cognition, 0302 clinical medicine, Neoplasms, medicine, Humans, Perceived cognitive functioning, Effects of sleep deprivation on cognitive performance, Cognitive skill, Cognitive performance, Sleep disorder, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Neuropsychology, Cancer, medicine.disease, 3. Good health, Neuropsychology and Physiological Psychology, 030220 oncology & carcinogenesis, [SCCO.PSYC]Cognitive science/Psychology, [SCCO.PSYC] Cognitive science/Psychology, Quality of Life, medicine.symptom, Sleep, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract: International audience; Patients with non-central nervous system (CNS) cancer frequently report cognitive complaints, that are recurrent and affect their quality of life. In order to improve supportive care of these cognitive difficulties, it is important to identify associated factors. Sleep disturbance is a good candidate to study, as patients with non-CNS cancer frequently report sleep disorders, and sleep plays a key role in cognitive functioning. The objective of the present systematic review was to summarize the results of studies evaluating the relationship between cognition and sleep in non-CNS cancer, and to highlight the need for further studies. PubMed [Medline] and Scopus databases were screened from April to November 2020 for studies published in English evaluating the association between cognition and sleep in adults with non-CNS cancer. The characteristics and risk of bias for each of the 30 included studies have been reported. Greater cognitive complaints in patients with non-CNS cancer were related to poorer self-reported sleep quality in almost all studies (n = 22/24). By contrast, around half of the studies reported a significant association between poorer neuropsychological performances and sleep complaints (n = 5/11). The studies were found to have several limitations, such as the lack of a control group, which would have shed the light on the period of occurrence of this association (e.g. after cancer diagnosis or after cancer treatments). Our review also identified factors that may influence the relationship between cognition and sleep. Recommendations are given for improving the methodology of future studies and extending the impact of their results.
Published: 2021

5. Returning to work by thyroid cancer survivors 5 years after diagnosis: the VICAN survey

Author: G. Creff, Marc-Karim Bendiane, Idlir Licaj, F. Jegoux, Emmanuel Babin, CHU Pontchaillou [Rennes], 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), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Plateforme Cancer et Cognition, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), The Arctic University of Norway [Tromsø, Norway] (UiT), Malbec, Odile, and Ligue Nationale Contre le Cancer (LNCC)
Subjects: Adult, Male, Employment, medicine.medical_specialty, Multivariate analysis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Weight Gain, Logistic regression, Thyroid cancer, Cancer Survivors, Quality of life, medicine, Humans, Thyroid Neoplasms, Survivors, Fatigue, Oncology (nursing), business.industry, Incidence (epidemiology), Public health, Thyroidectomy, [SDV] Life Sciences [q-bio], Oncology, Incomes, Quality of Life, Female, medicine.symptom, business, Cohort study, Weight gain, Demography
Abstract: International audience; Purpose: Return to work (RTW) following cancer diagnosis is a challenge for both the patient and society. As thyroid cancer (TC) incidence is increasing, this study aims to assess difficulties in returning to work and income changes in TC survivors 5 years post-diagnosis.Methods: This study belongs to the national VICAN survey conducted in France among TC patients diagnosed between January and June 2010. Data were collected through phone interviews, medical surveys and from the national medico-administrative register in 2012 and 2015. We used multivariate logistic regressions to investigate TC impact on employment and income changes.Results: Of 146 patients, 121(82.9%) were women; the mean age was 42 years (SD = 8.34), 119 (81.3%) were diagnosed at an early stage, and 142(97.6%) underwent thyroidectomy. At 5 years post-diagnosis, 116 (79.7%) of the TC survivors were professionally active, 22 (15.4%) were unemployed and 8 (4.90%) were receiving disability. Among the patients employed at the time of diagnosis (n = 122), 15 (12.3%) had not returned to work 5 years post-diagnosis. Between 2 and 5 years post-diagnosis, there was no significant improvement in rates of RTW. At 5 years post-diagnosis, 90 (61.6%) reported an income decline. All TC survivors who have not returned to work were women and declared higher fatigue. Moreover, in multivariate analyses, not returning to work was associated with weight gain (OR = 8.41 (1.21; 58.23)) and working arrangements (6.90 (1.18-38.48)), while income decline was associated with comorbidities (OR = 2.28 (1.07; 4.86)) and to be engaged in manual work (OR = 2.28 (1.07; 4.88)).Conclusion: This study highlights that, despite a good prognostic, up to 12.3% of TC survivors had not returned to work and 61.6% reported an income decline, 5 years post-diagnosis. Weight gain, fatigue, to be a woman and working-type arrangement were associated with higher probability of not returning to work.Implications for cancer survivors: TC affects a young working population. Our study identified potentially vulnerable TC survivors and important modifiable factors which may help TC survivors to be professionally active and, therefore, increase their overall quality of life.
Published: 2022

6. Immunothérapies du cancer : quel impact sur les fonctions cognitives ?

Author: Florence Joly, Hélène Castel, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme Cancer et Cognition, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Cancéropole Nord-Ouest-Ligue Nationale Contre le Cancer (LNCC), Sciences, EDP, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest
Subjects: Oncology, 0303 health sciences, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], MEDLINE, Cancer, Cognition, General Medicine, medicine.disease, General Biochemistry, Genetics and Molecular Biology, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: International audience
Published: 2020

7. Intratumor CMS Heterogeneity Impacts Patient Prognosis in Localized Colon Cancer

Author: Valérie Taly, Hélène Blons, Karine Le Malicot, David Gentien, Alex Duval, Julien Taieb, Laetitia Marisa, Jean-François Emile, Aurélien de Reyniès, Ramon Salazar, Mira Ayadi, Daniela Aust, Valérie Boige, Camilla Pilati, Sophie Mouillet-Richard, Janick Selves, Yuna Blum, Audrey Rapinat, Côme Lepage, Pierre Laurent-Puig, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ligue Nationale Contre le Cancer - Paris, Ligue Nationale Contre le Cancer (LNCC), 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), 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), Fédération Francophone de la Cancérologie Digestive, FFCD, Université de Bourgogne (UB), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), 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), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Institut Curie [Paris], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], This study was supported by the program 'Cartes d'Identité des Tumeurs' (CIT) from the Ligue Nationale Contre le Cancer (LNCC), by the Institut National du Cancer (INCa) with the program Heterogeneity of tumors and ecosystem (HTE program) within the sub program 'deciphering the heterogeneous genome-microenvironment interplay in colon and hepatocellular carcinomas (HETCOLI)', by the ITMO CANCER through the program single cell COCAHEMISCLE, by the integrated site of cancer research 'cancer research for personalized medicine' (SIRIC CARPEM, INCa-DGOS-Inserm_12561) and the Fédération Francophone de Cancérologie Digestive (FFCD). We thank the biological resource center EPIGENETEC (BB-0033-00055) for their support., Jonchère, Laurent, Ligue Nationnale Contre le Cancer, 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 de Paris (UP), 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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), Cancer Research and Personalized Medicine - CARPEM [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Fédération Francophone de Cancérologie Digestive (FFCD), CHU Dijon, Universitat de Barcelona (UB), Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Ambroise Paré [AP-HP], and Laurent-Puig, Pierre
Subjects: Oncology, Male, Cancer Research, medicine.medical_specialty, Multivariate analysis, Colorectal cancer, [SDV]Life Sciences [q-bio], Cell, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Transcriptome, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Cell Line, Tumor, medicine, Tumor Microenvironment, Humans, Treatment resistance, health care economics and organizations, Aged, business.industry, Gene Expression Profiling, Hazard ratio, medicine.disease, Prognosis, Survival Rate, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Colonic Neoplasms, Female, Personalized medicine, business
Abstract: Purpose: The consensus molecular subtypes (CMS) represent a significant advance in the understanding of intertumor heterogeneity in colon cancer. Intratumor heterogeneity (ITH) is the new frontier for refining prognostication and understanding treatment resistance. This study aims at deciphering the transcriptomic ITH of colon cancer and understanding its potential prognostic implications. Experimental Design: We deconvoluted the transcriptomic profiles of 1,779 tumors from the PETACC8 trial and 155 colon cancer cell lines as weighted sums of the four CMSs, using the Weighted In Silico Pathology (WISP) algorithm. We assigned to each tumor and cell line a combination of up to three CMS subtypes with a threshold above 20%. Results: Over 55% of tumors corresponded to mixtures of at least two CMSs, demonstrating pervasive ITH in colon cancer. Of note, ITH was associated with shorter disease-free survival (DFS) and overall survival, [HR, 1.34; 95% confidence interval (CI; 1.12–1.59), 1.40, 95% CI (1.14–1.71), respectively]. Moreover, we uncovered specific combinations of CMS associated with dismal prognosis. In multivariate analysis, ITH represents the third parameter explaining DFS variance, after T and N stages. At a cellular level, combined WISP and single-cell transcriptomic analysis revealed that most colon cancer cell lines are a mixture of cells falling into different CMSs, indicating that ITH may correspond to distinct functional statuses of colon cancer cells. Conclusions: This study shows that CMS-based transcriptomic ITH is frequent in colon cancer and impacts its prognosis. CMS-based transcriptomic ITH may correspond to distinct functional statuses of colon cancer cells, suggesting plasticity between CMS-related cell populations. Transcriptomic ITH deserves further assessment in the context of personalized medicine.
Published: 2021

8. Potential Effect of Immunotherapy Agents on Cognitive Function in Cancer Patients

Author: Marie Lange, Laure Tron, Hélène Castel, Janette L. Vardy, Florence Joly, Centre de recherche clinique [CHU Caen] (CRC), 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 Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme Cancer et Cognition, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Cancéropole Nord-Ouest-Ligue Nationale Contre le Cancer (LNCC), University of New South Wales [Sydney] (UNSW), Normandie Université (NU)-Normandie Université (NU)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest, CASTEL, Hélène, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)
Subjects: Cancer Research, Drug-Related Side Effects and Adverse Reactions, [SDV]Life Sciences [q-bio], medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, Bioinformatics, Immunotherapy, Adoptive, Targeted therapy, 03 medical and health sciences, Antineoplastic Agents, Immunological, Cognition, 0302 clinical medicine, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neoplasms, medicine, Humans, Cognitive Dysfunction, Adverse effect, 030304 developmental biology, 0303 health sciences, business.industry, Cancer, Immunotherapy, medicine.disease, Chimeric antigen receptor, 3. Good health, [SDV] Life Sciences [q-bio], Clinical trial, Oncology, 030220 oncology & carcinogenesis, Chimeric Antigen Receptor T-Cell Therapy, Disease Susceptibility, business, Biomarkers
Abstract: A paradigm shift is occurring in cancer therapy, where instead of targeting tumor cells, immunotherapy agents (IA) target the immune system to overcome cancer tolerance and to stimulate an antitumor immune response. IA using immune checkpoint inhibitors (CPI) or chimeric antigen receptor T-cells have emerged as the most encouraging approaches to treat cancer patients. CPI are reported to induce moderate-to-severe neurologic immune-related adverse events in less than 1% of patients, whereas chimeric antigen receptor T-cell therapy is associated with frequent neurological toxicities that can be severe or even fatal. Cognitive difficulties have been described following chemotherapy and targeted therapy, but not specifically explored in patients receiving IA. The aim of this review is to establish a picture of the first published studies suggesting some biological and physiopathological effects of IA on cognitive functions among cancer patients. The first results originate from a preclinical study evaluating the role of CPI associated with peripheral radiation on cognitive dysfunction and the recent discovery of the central nervous lymphatic system allowing leukocytes to penetrate the central nervous system. Evaluating possible side effects of IA on cognitive function will be an important challenge for future clinical trials and for better understanding the underlying mechanisms through preclinical animal models.
Published: 2019

9. CRISPR screens identify tumor-promoting genes conferring melanoma cell plasticity and resistance

Author: Anais M. Quemener, Florian Rambow, Arthur Gautron, Delphine Leclerc, Héloïse M Leclair, Marc Aubry, Cédric Coulouarn, Anaïs Paris, Marie-Dominique Galibert, Laura Bachelot, Jean-Christophe Marine, Nina Tardif, Sébastien Corre, Oskar Marín-Béjar, David Gilot, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Biosit : biologie, santé, innovation technologique (SFR UMS CNRS 3480 - INSERM 018), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Génomique Environnementale et Humaine (GEH), Université de Rennes (UR), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), This study received financial support from the following: Fondation ARC pour la Recherche (ARC labellized team), Ligue Nationale Contre le Cancer (LNCC), Départements du Grand‐Ouest, Région Bretagne, University of Rennes 1, CNRS, SFR Biosit, Association Vaincre le Cancer. Further support was provided by a 'Ligue Nationale Contre le Cancer' (LNCC) Grand Ouest fellowship (AG) and from the Région Bretagne (AG), and Fondation ARC pour la Recherche (AG) and the LNCC (AQ) and from French Ministry of Research (NT and DL) and from Institut National contre le Cancer (INCa) (AP)., Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), 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)-Centre National de la Recherche Scientifique (CNRS)-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)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), and HAL UR1, Admin
Subjects: 0301 basic medicine, Medicine (General), CRISPR-SAM, medicine.medical_treatment, Cell Plasticity, Druggability, QH426-470, Research & Experimental Medicine, SMAD3, Targeted therapy, 0302 clinical medicine, CRISPR, Clustered Regularly Interspaced Short Palindromic Repeats, Cancer, Skin, Melanoma, Articles, Phenotype, SAM, Medicine, Research & Experimental, Molecular Medicine, Life Sciences & Biomedicine, Proto-Oncogene Proteins B-raf, CRISPR‐SAM, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, CRISPR&#8208, Article, 03 medical and health sciences, R5-920, [SDV.CAN] Life Sciences [q-bio]/Cancer, Downregulation and upregulation, Cell Line, Tumor, Aryl hydrocarbon Receptor, Genetics, medicine, melanoma, Humans, Protein Kinase Inhibitors, Transcription factor, Science & Technology, targeted therapy resistance, medicine.disease, Aryl hydrocarbon receptor, 030104 developmental biology, Drug Resistance, Neoplasm, Cancer research, biology.protein, Neoplasm Recurrence, Local, 030217 neurology & neurosurgery
Abstract: Most genetic alterations that drive melanoma development and resistance to targeted therapy have been uncovered. In contrast, and despite their increasingly recognized contribution, little is known about the non‐genetic mechanisms that drive these processes. Here, we performed in vivo gain‐of‐function CRISPR screens and identified SMAD3, BIRC3, and SLC9A5 as key actors of BRAFi resistance. We show that their expression levels increase during acquisition of BRAFi resistance and remain high in persister cells and during relapse. The upregulation of the SMAD3 transcriptional activity (SMAD3‐signature) promotes a mesenchymal‐like phenotype and BRAFi resistance by acting as an upstream transcriptional regulator of potent BRAFi‐resistance genes such as EGFR and AXL. This SMAD3‐signature predicts resistance to both current melanoma therapies in different cohorts. Critically, chemical inhibition of SMAD3 may constitute amenable target for melanoma since it efficiently abrogates persister cells survival. Interestingly, decrease of SMAD3 activity can also be reached by inhibiting the Aryl hydrocarbon Receptor (AhR), another druggable transcription factor governing SMAD3 expression level. Our work highlights novel drug vulnerabilities that can be exploited to develop long‐lasting antimelanoma therapies., Using a CRISPR activation screening, we identified genes involved in BRAF inhibitor (BRAFi) resistance in cutaneous melanoma. Their upregulation promoted tumour growth of therapy‐naïve melanoma cells and BRAFi‐resistance. Inhibition of these genes (not mutated) may be useful for therapy.
Published: 2021

10. The urotensin II receptor relays key neurobiological mechanisms in subarachnoid hemorrhage: Efficacy of pathway-targeted drugs on long-term brain deficits

Author: Pedard, Martin, Dubois, Martine, Gruel, Roxane, Desrues, Laurence, Godefroy, David, Wurtz, Olivier, Castel, Hélène, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme Cancer et Cognition, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Cancéropole Nord-Ouest-Ligue Nationale Contre le Cancer (LNCC)
Subjects: [SDV]Life Sciences [q-bio], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

11. How to assess and manage cognitive impairment induced by treatments of non-central nervous system cancer

Author: Johan Le Fel, Laure Tron, Omar Touzani, Idlir Licaj, Marie Lange, Olivier Rigal, Rozenn Le Gal, Damien Ricard, Thomas Durand, Martine Dubois, Isabelle Hardy-Léger, Hélène Castel, Florence Joly, Catherine Belin, Didier Maillet, Myriam Bernaudin, Véronique Pancré, Bénédicte Giffard, Mathieu Boone, Joy Perrier, CCSD, Accord Elsevier, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), 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 Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme Cancer et Cognition, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest, Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Psychologie : Interactions, Temps, Emotions, Cognition (PSITEC) - ULR 4072 (PSITEC), Université de Lille, Hôpital Côte de Nacre [CHU Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Neuropsychologie et imagerie de la mémoire humaine (NIMH), Normandie Université (NU)-Normandie Université (NU)-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), CHU Amiens-Picardie, Cognition and Action Group (COGNAC-G - UMR 8257), École normale supérieure - Cachan (ENS Cachan)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cancéropole Nord-Ouest, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service d'Oncologie médicale [CHU Caen], UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Cancéropole Nord-Ouest-Ligue Nationale Contre le Cancer (LNCC), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), and Normandie Université (NU)-Normandie Université (NU)-École Pratique des Hautes Études (EPHE)
Subjects: Electronic cognitive tests, Cognitive Neuroscience, [SDV]Life Sciences [q-bio], 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Cognition, Neoplasms, Management of cognitive impairment, Humans, 0501 psychology and cognitive sciences, Animal model, Cognitive Dysfunction, 050102 behavioral science & comparative psychology, Cognitive rehabilitation therapy, Cognitive impairment, Research question, Cancer treatments, Behavior, 05 social sciences, Neuropsychology, Cancer patients, Expert group, 3. Good health, Comprehension, [SDV] Life Sciences [q-bio], Neuropsychology and Physiological Psychology, Central nervous system cancer, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract: CERVOXY COLL; International audience; A number of neurotoxicity associated with oncological treatments has been reported in non-central nervous system cancers.An expert group presents the state of the art and a guide to help the choice of appropriated tools to assess patient cognition in studies on oncology and neurobehavior in animal models. In addition, current cognitive rehabilitation programs currently under evaluation are also discussed.Cognitive assessments in oncology depend on the research question, study design, cognitive domains, patients’ characteristics, psychometric properties of the tests, and whether the tests are supervised or not by a neuropsychologist. Batteries of electronic tests can be proposed, but several of them are characterized by weak psychometric developments. In order to improve the comprehension on the impact of cancer treatments on cognition, new animal models are in development, and would in the future include non-human primate models.By bringing together the skills and practices of oncologists, neurologists, neuropsychologists, neuroscientists, we propose a series of specific tools and tests that accompany the cognitive management of non-CNS cancer patients.
Published: 2019

12. The role of metamemory on cognitive complaints in cancer patients

Author: Bénédicte Giffard, Audrey Perrotin, Philippe Allain, Jacques Dayan, Francis Eustache, Jean‐Michel Grellard, Audrey Faveyrial, Florence Joly, Marie Lange, Plateforme Cancer et Cognition, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Cancéropole Nord-Ouest-Ligue Nationale Contre le Cancer (LNCC), Neuropsychologie et imagerie de la mémoire humaine (NIMH), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Laboratoire de Psychologie des Pays de la Loire (LPPL), Université d'Angers (UA)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Guillaume Régnier [Rennes], Centre de recherche clinique [CHU Caen] (CRC), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oncologie médicale [CHU Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Eustache, Francis, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest, Normandie Université (NU)-Normandie Université (NU)-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), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, cognition, metamemory, neuropsychology, Neuropsychological Tests, lcsh:RC321-571, memory, Executive Function, Judgment, Neoplasms, Surveys and Questionnaires, Humans, Learning, Cognitive Dysfunction, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Aged, Original Research, Middle Aged, Memory, Short-Term, Mental Recall, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Metacognition, cancer patients, metacognitive monitoring
Abstract: Objective Although cancer patients frequently report cognitive disturbances, it is commonly asserted a lack of association between cognitive complaints and neuropsychological test performances. Our goal was to better understand the relationships between subjective and objective cognitive scores through a metamemory monitoring assessment. Methods Sixty cancer patients currently treated by chemotherapy and/or targeted therapy, and 30 healthy controls (HC) were included. Cognitive complaint was assessed by FACT‐cog, QAM and DEX questionnaires. One or more z‐scores ≤−1.65 among these three questionnaires defined the presence of cognitive complaints. Objective cognitive performances assessed episodic memory, processing speed and executive functions/working memory (ESR paradigm, TMT, Stroop, n‐back). Metamemory was assessed with a Judgment of Learning (JOL) task. Results Patients with cognitive complaints had significantly more depressive and anxiety symptoms (ps, Cancer patients do not underestimate their memory performance. Cancer patients make less overestimation than healthy controls.
Published: 2019

13. Cancer du sein et exosomes tumoraux circulants dans les troubles cognitifs associés au cancer : Etude preuve de concept

Author: Castel, Hélène, Parment, Renaud, Dubois, Martine, Desrues, Laurence, Delhem, N., Morales, O, Joly, Florence, Morin, Fabrice, Gandolfo, Pierrick, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme Cancer et Cognition, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CASTEL, Hélène, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Cancéropole Nord-Ouest-Ligue Nationale Contre le Cancer (LNCC), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: [SDV] Life Sciences [q-bio], TheoryofComputation_MISCELLANEOUS, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV]Life Sciences [q-bio], ComputingMilieux_COMPUTERSANDEDUCATION, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, GeneralLiterature_MISCELLANEOUS, ComputingMilieux_MISCELLANEOUS
Abstract: Invited lecture; National audience
Published: 2019

14. Cognitive Changes After Adjuvant Treatment in Older Adults with Early‐Stage Breast Cancer

Author: Bénédicte Giffard, Nadine Longato, Johan Lefel, Francis Eustache, Alexandra Leconte, Jean-Emmanuel Kurtz, Florence Joly, Bénédicte Clarisse, Olivier Rigal, Corinne Veyret, Christelle Levy, Hélène Castel, Philippe Barthélémy, Natacha Heutte, Laure Tron, D. Allouache, Marie Lange, Chantal Rieux, Sabine Noal, Bodescot, Myriam, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), 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 Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme Cancer et Cognition, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychologie et imagerie de la mémoire humaine (NIMH), Normandie Université (NU)-Normandie Université (NU)-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), This work was supported by a national grant (Programme Hospitalier de Recherche Clinique, grant APN 2008 no 06–08) and Sanofi. The Northwest Data Center (CTD-CNO) is acknowledged for managing the data. It is supported by grants from the French National League Against Cancer (LNC) and the French National Cancer Institute (INCa)., Centre de recherche clinique [CHU Caen] (CRC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Centre d’études des transformations des activités physiques et sportives (CETAPS), Normandie Université (NU)-Normandie Université (NU)-Institut de Recherche Interdisciplinaire Homme et Société (IRIHS), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Comité Sein [Caen], UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Service d'Oncologie médicale [CHU Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de Recherche clinique [Caen], Service d'Oncologie médicale [Rouen], ChemBioPharm, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Neuropsychologie cognitive et neuroanatomie fonctionnelles de la mémoire humaine, École nationale supérieure des sciences de l'information et des bibliothèques (ENSSIB), Université de Lyon, Normandie Université (NU)-Normandie Université (NU)-Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Cancéropole Nord-Ouest-Ligue Nationale Contre le Cancer (LNCC), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)
Subjects: Cancer Research, medicine.medical_specialty, Aging, Cognition disorders, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Systemic therapy, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Adjuvant therapy, Humans, Chemotherapy, 030212 general & internal medicine, Cognitive skill, Cognitive decline, ComputingMilieux_MISCELLANEOUS, Aged, business.industry, Cancer, Cognition, medicine.disease, 3. Good health, Geriatric Oncology, Oncology, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cognitive changes, Female, Breast neoplasms, business
Abstract: Background Group-based trajectory modeling is particularly important to identify subgroups of patients with pathological cognitive changes after cancer treatment. To date, only one study has explored cognitive trajectories in older patients with cancer. The present article describes objective cognitive changes before to after adjuvant treatment in older adults with early-stage breast cancer (EBC) after adjuvant treatment compared with healthy controls. Patients and Methods Participants were patients ≥65 years of age with newly diagnosed EBC and healthy controls (age-, sex-, and education-matched). The pretreatment assessment was conducted before adjuvant therapy, and the post-treatment assessment after the end of the first adjuvant treatment. Objective cognitive changes before to after treatment were evaluated based on the Reliable Change Index for cognitive decline accounting for cognitive impairment status. Results The sample consisted of women newly diagnosed with EBC (n = 118) and healthy controls (n = 62). Five patterns of changes before to after treatment were identified based on the presence of cognitive decline and cognitive impairment. The distribution of these five change patterns was statistically significant (p = .0001). Thirty-six percent of patients had phase shift changes, 31% without initial objective cognitive impairment developed impairment, 15% had a normal aging, 12% had a nonpathological decline, and 6% experienced accelerated cognitive decline. Conclusion This study described for the first time objective cognitive changes before to after treatment of older adults with EBC immediately after the end of adjuvant treatment. A longer-term remote follow-up of adjuvant treatment is needed to better understand the cognitive trajectories of older patients with EBC. Implications for Practice After the end of adjuvant treatment, 31% of older adults with early-stage breast cancer without initial objective cognitive impairment developed impairment, and 6% experienced accelerated cognitive decline. Initial cognitive functioning should be included in the balance of benefits and harms of systemic therapy for patients who are likely to be at highest risk for cognitive decline after cancer treatments. Regular cognitive follow-up of patients who had cognitive impairment before cancer treatment should monitor symptoms suggestive of neurodegenerative disease and avert the effect of cognitive disorders on patients’ autonomy.
Published: 2019

15. Longitudinal investigation of cognitive deficits in breast cancer patients and their gray matter correlates: impact of education level

Author: Francis Eustache, Nastassja Morel, Bénédicte Giffard, Joy Perrier, Sabine Noal, Armelle Viard, D. Allouache, Christelle Levy, Florence Joly, Neuropsychologie et imagerie de la mémoire humaine (NIMH), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-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), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de recherche clinique [CHU Caen] (CRC), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Service d'Oncologie médicale [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme Cancer et Cognition, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest, This work was supported by the ARC foundation – for cancer research (2017–2020), the association 'Ligue contre la cancer' (both national and Calvados department), the association 'Cancer du sein, parlons en' (2011), and the Cancéropôle Nord-Ouest., Bodescot, Myriam, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Normandie Université (NU)-Normandie Université (NU)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Cancéropole Nord-Ouest-Ligue Nationale Contre le Cancer (LNCC)
Subjects: Oncology, Neuropsychological Tests, Anxiety, Behavioral Neuroscience, 0302 clinical medicine, Breast cancer, Cognition, Medicine, Attention, Longitudinal Studies, Cognitive decline, Gray Matter, Education level, Cognitive reserve, Academic Success, 05 social sciences, Neuropsychology, Brain, Middle Aged, Executive functions, 3. Good health, Psychiatry and Mental health, Neurology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Adult, medicine.medical_specialty, Cognitive Neuroscience, Memory, Episodic, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, 050105 experimental psychology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Atrophy, Magnetic resonance imaging, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Cognitive Dysfunction, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aged, business.industry, medicine.disease, Quality of Life, Neurology (clinical), business, Cognition Disorders, 030217 neurology & neurosurgery
Abstract: International audience; Cognitive deficits are a major complaint in breast cancer patients, even before chemotherapy. Comprehension of the cerebral mechanisms related to cognitive impairment in breast cancer patients remains difficult due to the scarcity of studies investigating both cognitive and anatomical imaging changes. Furthermore, only some of the patients experienced cognitive decline following chemotherapy, yet few studies have identified risk factors for cognitive deficits in these patients. It has been shown that education level could impact cognitive abilities during the recovery phase following chemotherapy. Our main aim was to longitudinally evaluate cognitive and anatomical changes associated with cancer and chemotherapy in breast cancer patients. Our secondary aim was to assess the impact of education level on cognitive performances and gray matter (GM) atrophy in these patients. Twenty patients were included before chemotherapy (T1), 1 month (T2) and 1 year (T3) after chemotherapy. Twenty-seven controls without a history of cancer were assessed at T1 and T3 only. Cluster groups based on education level were defined for both groups and were further compared. Comparison between patients and controls revealed deficits in patients on verbal episodic memory retrieval at T1 and T3 and on executive functions at T3. After chemotherapy, breast cancer patients had GM atrophy that persisted or recovered 1 year after chemotherapy depending on the cortical areas. Increase in GM volumes from T1 to T3 were also found in both groups. At T2, patients with a higher level of education compared to lower level exhibited higher episodic memory retrieval and state anxiety scores, both correlating with cerebellar volume. This higher level of education group exhibited hippocampal atrophy. Our results suggest that, before chemotherapy, cancer-related processes impact cognitive functioning and that this impact seems exacerbated by the effect of chemotherapy on certain brain regions. Increase in GM volumes after chemotherapy were unexpected and warrant further investigations. Higher education level was associated, 1 month after the end of chemotherapy, with greater anxiety and hippocampal atrophy despite a lack of cognitive deficits. These results suggest, for the first time, the occurrence of compensation mechanisms that may be linked to cognitive reserve in relationship to state anxiety. This identification of factors, which may compensate cognitive impairment following chemotherapy, is critical for patient care and quality of life.
Published: 2018

16. Cancer treatments on cognition: Building translational research to optimize design of preclinical animal studies

Author: Dubois, Martine, Campart, Cynthia, Al Sagheer, Tareq, Tonon, Marie-Christine, Perzo, Nicolas, Gandolfo, Pierrick, Lange, Marie, Joly, Florence, Castel, Hélène, Différenciation et communication neuronale et neuroendocrine (DC2N), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme Cancer et Cognition, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest, Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Centre de recherche clinique [CHU Caen] (CRC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Cancéropole Nord-Ouest-Ligue Nationale Contre le Cancer (LNCC)
Subjects: [SCCO]Cognitive science, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2018

17. Prospective comparison of the Montreal Cognitive Assessment (MoCA) and the Mini Mental State Examination (MMSE) in geriatric oncology

Author: Idlir Licaj, Heidi Laviec, Nicole Frenkiel, Priscille Le Bon, Claire Chatel, Julie Denhaerynck, Alexandra Leconte, Audrey Rambeau, Florence Joly, Marie Lange, Bénédicte Clarisse, Bérengère Beauplet, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Département Filière Gériatrique [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), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Centre de recherche clinique [CHU Caen] (CRC), Normandie Université (NU)-Normandie Université (NU)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Plateforme Cancer et Cognition, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Cancéropole Nord-Ouest-Ligue Nationale Contre le Cancer (LNCC), Laboratoire d'Hématologie Biologique [CHU Caen], Institut d'Hématologie de Basse-Normandie (IHBN), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), The Northwest Data Center (CTD-CNO) is acknowledged for managing the data. It is supported by grants from the French National League Against Cancer (LNC) and the French National Cancer Institute (INCa). This study was supported by a grant from the Cancéropole Nord-Ouest., CCSD, Accord Elsevier, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC)
Subjects: Male, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Comorbidity, Medical Oncology, 0302 clinical medicine, Older patients, Risk Factors, Neoplasms, Activities of Daily Living, Mass Screening, 030212 general & internal medicine, Prospective Studies, Cognitive impairment, Prospective cohort study, Aged, 80 and over, medicine.diagnostic_test, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Age Factors, Montreal Cognitive Assessment, Cognition, Mental Status and Dementia Tests, 3. Good health, Oncology, Geriatric oncology, 030220 oncology & carcinogenesis, Educational Status, Female, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Sensitivity and Specificity, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, mental disorders, medicine, Dementia, Humans, Cognitive Dysfunction, Geriatric Assessment, Aged, Psychotropic Drugs, Mini–Mental State Examination, business.industry, medicine.disease, Geriatrics, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Polypharmacy, Geriatrics and Gerontology, business
Abstract: International audience; INTRODUCTION:Among the various instruments recommended by the International Society of Geriatric Oncology, the Mini Mental State Examination (MMSE) is the most commonly used cognitive screening test before oncological treatment. Although the Montreal Cognitive Assessment (MoCA) has been shown to be more sensitive than the MMSE in several pathologies, no specific data exist for older patients with cancer. We aimed to compare the proportions of older patients with cancer who had screened positive for cognitive impairment according to the MMSE and MoCA scores obtained during a pretherapeutic geriatric assessment (GA) in oncology.PATIENTS AND METHODS:This prospective study was conducted among 66 patients older than 70 years who were candidates for a first-line treatment for either a solid tumor or hematological malignancy. Patients with brain tumor or previously known dementia were ineligible. During GA, cognitive function was assessed using both the MoCA and the MMSE tests administered in a random order.RESULTS:Median age was 78 years. Most patients (n = 43, 65.2%) had a solid tumor. The median scores were 26 [11-30] for MMSE and 24 [8-30] for MoCA. Thirteen (19.7%) and 44 (66.7%) patients were screened positive for cognitive impairment according to MMSE and MoCA scores, respectively. Overall, 55 (66.7%) patients were screened positive: 12 (21.8%) on both scores, 32 (70.5%) with the MoCA only, and one patient with MMSE only (p
Published: 2018

18. GPCR-induced repression of autophagy in glioblastoma cells: impact on lamellipodium expansion and chemotactic migration

Author: Campisi, Daniele, Coly, Pierre-Michaël, Castel, Hélène, Gandolfo, Pierrick, Morin, Fabrice, CASTEL, Hélène, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer and Cognition Platform, Ligue Nationale contre le cancer,14000Caen, France, Plateforme Cancer et Cognition, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Cancéropole Nord-Ouest-Ligue Nationale Contre le Cancer (LNCC), Neuroendocrinologie cellulaire et moléculaire, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest
Subjects: TheoryofComputation_MISCELLANEOUS, GeneralLiterature_INTRODUCTORYANDSURVEY, [SDV]Life Sciences [q-bio], TheoryofComputation_GENERAL, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV] Life Sciences [q-bio], [SDV.CAN] Life Sciences [q-bio]/Cancer, ComputingMilieux_COMPUTERSANDEDUCATION, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMethodologies_GENERAL, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS
Abstract: Price for the best oral presentation; National audience
Published: 2018

19. Chemokine GPCR signalling is controlled by Filamin A: implication in high-grade glioma development

Author: Mutel, Alexandre, Lecointre, Céline, Dembele Kleouforo, Paul, Guichet, Pierre-Olivier, Mouchard, Laurent, Desrues, Laurence, Langlois, Olivier, Laquérriere, Annie, Marguet, Florent, Gandolfo, Pierrick, Morin, Fabrice, Castel, Hélène, CASTEL, Hélène, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Equipe Traitement de l'information en Biologie Santé (TIBS - LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Service de neurochirurgie [CHU Rouen], CHU Rouen, Normandie Université (NU), Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Department of Pathology, Rouen University Hospital, Plateforme Cancer et Cognition, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Cancéropole Nord-Ouest-Ligue Nationale Contre le Cancer (LNCC), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest
Subjects: [SDV] Life Sciences [q-bio], [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV]Life Sciences [q-bio], [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

20. FGFR3 Mutational Activation Can Induce Luminal-like Papillary Bladder Tumor Formation and Favors a Male Sex Bias

Author: Ming-Jun Shi, Jacqueline Fontugne, Aura Moreno-Vega, Xiang-Yu Meng, Clarice Groeneveld, Florent Dufour, Aurélie Kamoun, Sia Viborg Lindskrog, Luc Cabel, Clémentine Krucker, Audrey Rapinat, Claire Dunois-Larde, May-Linda Lepage, Elodie Chapeaublanc, Olivier Levrel, Victoria Dixon, Thierry Lebret, Anna Almeida, Aurélien De Reynies, Natacha Rochel, Lars Dyrskjøt, Yves Allory, François Radvanyi, Isabelle Bernard-Pierrot, Bernard-Pierrot, Isabelle, Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Ligue Nationale Contre le Cancer (LNCC), Institut Curie [Paris], Hôpital Foch [Suresnes], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: Male, Urology, Urinary Bladder, Sexism, Fibroblast growth factor, Tyrosine kinase receptor, Mice, Transgenic, [SDV.CAN]Life Sciences [q-bio]/Cancer, Luminal tumors, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Mouse model, Mice, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], receptor 3, Humans, Animals, Receptor, Fibroblast Growth Factor, Type 3, Estrogen receptor, Sex bias, Bladder cancer, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Fibroblast growth factor receptor 3, Androgen receptor, Urinary Bladder Neoplasms, Tumor microenvironment, Mutation, Androgens, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female
Abstract: Background: Bladder cancer (BCa) is more common in men and presents differences in molecular subtypes based on sex. Fibroblast growth factor receptor 3 (FGFR3) mutations are enriched in the luminal papillary muscle-invasive BCa (MIBC) and non-MIBC subtypes. Objective: To determine whether FGFR3 mutations initiate BCa and impact BCa male sex bias. Design, setting, and participants: We developed a transgenic mouse model expressing the most frequent FGFR3 mutation, FGFR3-S249C, in urothelial cells. Bladder tumorigenesis was monitored in transgenic mice, with and without carcinogen exposure. Mouse and human BCa transcriptomic data were compared. Intervention: Mutant FGFR3 overexpression in mouse urothelium and siRNA knockdown in cell lines, and N-butyl-N(4-hydroxybutyl)-nitrosamine (BBN) exposure. Outcome measurements and statistical analysis: Impact of transgene dosage on tumor frequency, synergy with BBN treatment, and FGFR3 pathway activation were analyzed. The sex-specific incidence of FGFR3-mutated tumors was evaluated in mice and humans. FGFR3 expression in FGFR3-S249C mouse urothelium and in various human epithelia was measured. Mutant FGFR3 regulation of androgen (AR) and estrogen (ESR1) receptor activity was evaluated, through target gene expression (regulon) and reporter assays. Results and limitations: FGFR3-S249C expression in mice induced low-grade papillary BCa resembling human luminal counterpart at histological, genomic, and transcriptomic levels, and promoted BBN-induced basal BCa formation. Mutant FGFR3 expression levels impacted tumor incidence in mice, and mutant FGFR3–driven human tumors were restricted to epithelia presenting high normal FGFR3 expression levels. BCa male sex bias, also found in our model, was even higher in human FGFR3-mutated tumors compared with wild-type tumors and was associated with higher AR and lower ESR1 regulon activity. Mutant FGFR3 expression inhibited both ESR1 and AR activity in mouse tumors and human cell lines, demonstrating causation only between FGFR3 activation and low ESR1 activity in tumors. Conclusions: Mutant FGFR3 initiates luminal papillary BCa formation and favors BCa male sex bias, potentially through FGFR3-dependent ESR1 downregulation. Patients with premalignant lesions or early-stage BCa could thus potentially benefit from FGFR3 targeting. FGFR3 expression level in epithelia could account for FGFR3-driven carcinoma tissue specificity. Patient summary: By developing a transgenic mouse model, we showed that gain-of-function mutations of FGFR3 receptor, among the most frequent genetic alterations in bladder cancer (BCa), initiate BCa formation. Our results could support noninvasive detection of FGFR3 mutations and FGFR3 targeting in early-stage bladder lesions.
Published: 2023

21. A structural determinant in TM2 of chemokine and vasoactive peptide GPCRs plays a key role in cell chemotactic migration

Author: Desrues, Laurence, Joubert Jane, Eilen, Coly, Pierre-Mickaël, Mutel, Alexandre, Perzo, Nicolas., Guilhaudis, Laure, Milazzo, Isabelle, Morin, Fabrice, Gandolfo, Pierrick, Prézeau, Laurent, Chabbert, Marie, Castel, Hélène, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Equipe de Chimie Organique et Biologie Structurale (ECOBS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Plateforme Cancer et Cognition, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Cancéropole Nord-Ouest-Ligue Nationale Contre le Cancer (LNCC), and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest
Subjects: [SDV]Life Sciences [q-bio], [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

22. Transcriptomic response of intestine to low fish meal diet and dietary marine hydrolysates in european seabass (dicentrarchus labrax)

Author: Leduc, Alexandre, Zatylny-Gaudin, Céline, Corre, Erwan, Lefevre-Scelles, Antoine, Castel, Hélène, Fournier, Vincent, Gisbert, Enric, Henry, Joël, Biologie des Organismes et Ecosystèmes Aquatiques (BOREA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Adaptation et diversité en milieu marin (AD2M), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Différenciation et communication neuronale et neuroendocrine (DC2N), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme Cancer et Cognition, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Cancéropole Nord-Ouest-Ligue Nationale Contre le Cancer (LNCC), AQUATIV, IRTA, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest, and Institut de Recerca i Tecnologia Agroalimentàries = Institute of Agrifood Research and Technology (IRTA)
Subjects: [SDV]Life Sciences [q-bio], [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

23. Proline in 2.58 of chemokine and vasoactive peptide G-protein coupled receptors: A structural determinant in chemotaxis?

Author: Desrues, Laurence, Joubert Jane, Eilen, Perzo, Nicolas, Guilhaudis, Laure, Milazzo, Isabelle, Chabbert, Marie, Prézeau, Laurent, Morin, Fabrice, Gandolfo, Pierrick, Castel, Hélène, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Equipe de Chimie Organique et Biologie Structurale (ECOBS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Plateforme Cancer et Cognition, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Cancéropole Nord-Ouest-Ligue Nationale Contre le Cancer (LNCC), and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest
Subjects: [SDV]Life Sciences [q-bio], [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

24. Living Labs and other participatory approaches applied to research on multiple environnemental exposures and chronic risks

Author: LAURENT, Olivier, Yara Carrejo, Gironza, Ancelet, Sophie, Armant, Olivier, Denis, Bard, Katia, Baumgartner, Sylvie, Bortoli, Boudet, Céline, Chamaret, Philippe, Chartier, Michel, Cormier, Stéphanie, Arthur, David, Desqueyroux, Hélène, Gerber, Mariette, Gilbin, Rodolphe, Grimbuhler, Sonia, Grison, Stephane, Larqué, Lionel, Laurier, Dominique, Mougin, Christian, Gamet-Payrastre, Laurence, Rannou, Alain, Scanff, Pascale, Vanzemberg, Arnaud, Schraub, Simon, Supervil, Sylvie, Thybaud, Eric, Trousse, Brigitte, Charron, Sylvie, Laboratoire d épidémiologie des rayonnements ionisants (IRSN/PSE-SANTE/SESANE/LEPID), Service de recherche sur les effets biologiques et Sanitaires des rayonnements ionisants (IRSN/PSE-SANTE/SESANE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), 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 ), Laboratoire d'écotoxicologie des radionucléides (IRSN/PSE-ENV/SRTE/LECO), Service de recherche sur les transferts et les effets des radionucléides sur les écosystèmes (IRSN/PSE-ENV/SRTE), Société francophone de santé environnement (SFSE), France Nature Environnement (FNE), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de l'Environnement Industriel et des Risques (INERIS), Institut Ecocitoyen pour la Connaissance des Pollutions [Fos-sur-Mer], Centre Permanent d'Initiatives pour l'Environnement des Pays de l'Aisne (CPIE des Pays de l'Aisne), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département des sciences en santé environnementale (DEESSE), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Association nationale des comités et commissions locales d'information [Teteghem] (ANCCLI), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Technologies et Méthodes pour les Agricultures de demain (UMR ITAP), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, 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 de radiotoxicologie et radiobiologie expérimentale (IRSN/PSE-SANTE/SESANE/LRTOX), ALLISS Sciences Sociétés [Paris], Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pôle Santé Environnement - Direction Santé (IRSN/PSE-SANTE), Cellule Valorisation des données (IRSN/DTR/D3NSI/SVDDA/CVD), Direction Déléguée Développement numérique et aux systèmes d’information (IRSN/DTR/D3NSI), Ligue Nationale Contre le Cancer (LNCC), Direction des Risques et de la Performance (IRSN/DRP), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria), Service des politiques d’ouverture à la société (IRSN/DST/SPOS), Direction de la Stratégie (IRSN/DST), IRSN 2030, IS Global, and Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN)
Subjects: [SDE.ES]Environmental Sciences/Environmental and Society
Abstract: International audience; The objectives of environmental health research are diverse (e.g.: identifying situations at potential risk, estimating exposures and effects, testing the effectiveness of preventive actions) and related methods are diverse as well. Opportunities for greater implication of the civil society and related challenges differ at each step of research activities. These aspects need to be better known and shared collectively.
Published: 2023

25. RAS activation induces synthetic lethality of MEK inhibition with mitochondrial oxidative metabolism in acute myeloid leukemia

Author: Justine Decroocq, Rudy Birsen, Camille Montersino, Prasad Chaskar, Jordi Mano, Laury Poulain, Chloe Friedrich, Anne-Sophie Alary, Helene Guermouche, Ambrine Sahal, Guillemette Fouquet, Mathilde Gotanègre, Federico Simonetta, Sarah Mouche, Pierre Gestraud, Auriane Lescure, Elaine Del Nery, Claudie Bosc, Adrien Grenier, Fetta Mazed, Johanna Mondesir, Nicolas Chapuis, Liza Ho, Aicha Boughalem, Marc Lelorc’h, Camille Gobeaux, Michaela Fontenay, Christian Recher, Norbert Vey, Arnaud Guillé, Daniel Birnbaum, Olivier Hermine, Isabelle Radford-Weiss, Petros Tsantoulis, Yves Collette, Rémy Castellano, Jean-Emmanuel Sarry, Eric Pasmant, Didier Bouscary, Olivier Kosmider, Jerome Tamburini, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Université Paris Cité (UPCité), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Sud Francilien, Laboratorio d'Informatica Musicale (LIM), Università degli Studi di Milano = University of Milan (UNIMI), Institut Curie [Paris], Centre de Bioinformatique (CBIO), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Translational Research Department, Institut Curie, BioImaging Cell and Tissue Core Facility (PICT-IBiSA), Université de Genève = University of Geneva (UNIGE), Ligue Nationale Contre le Cancer - Paris, Ligue Nationale Contre le Cancer (LNCC), Laboratoire CERBA [Saint Ouen l'Aumône], Département d’Oncologie Médicale [IPC, Marseille], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Cancer Research and Personalized Medicine - CARPEM [Paris], 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP]
Subjects: Mitogen-Activated Protein Kinase Kinases, Cancer Research, [SDV]Life Sciences [q-bio], Hematology, Proto-Oncogene Proteins p21(ras), Leukemia, Myeloid, Acute, Mice, Oxidative Stress, fms-Like Tyrosine Kinase 3, Oncology, hemic and lymphatic diseases, Mutation, Animals, Humans, Synthetic Lethal Mutations, neoplasms
Abstract: Despite recent advances in acute myeloid leukemia (AML) molecular characterization and targeted therapies, a majority of AML cases still lack therapeutically actionable targets. In 127 AML cases with unmet therapeutic needs, as defined by the exclusion of ELN favorable cases and of FLT3-ITD mutations, we identified 51 (40%) cases with alterations in RAS pathway genes (RAS+, mostly NF1, NRAS, KRAS, and PTPN11 genes). In 79 homogeneously treated AML patients from this cohort, RAS+ status were associated with higher white blood cell count, higher LDH, and reduced survival. In AML models of oncogenic addiction to RAS-MEK signaling, the MEK inhibitor trametinib demonstrated antileukemic activity in vitro and in vivo. However, the efficacy of trametinib was heterogeneous in ex vivo cultures of primary RAS+ AML patient specimens. From repurposing drug screens in RAS-activated AML cells, we identified pyrvinium pamoate, an anti-helminthic agent efficiently inhibiting the growth of RAS+ primary AML cells ex vivo, preferentially in trametinib-resistant PTPN11- or KRAS-mutated samples. Metabolic and genetic complementarity between trametinib and pyrvinium pamoate translated into anti-AML synergy in vitro. Moreover, this combination inhibited the propagation of RA+ AML cells in vivo in mice, indicating a potential for future clinical development of this strategy in AML.
Published: 2022

26. Cancer-related cognitive impairment in non-CNS cancer patients: Targeted review and future action plans in Europe

Author: European Cancer and Cognition Consortium (ECCC), Sleurs, Charlotte, Amidi, Ali, Wu, Lisa M, Kiesl, David, Zimmer, Philipp, Lange, Marie, Rogiers, Anne, Giffard, Benedicte, Binarelli, Giulia, Borghgraef, Cindy, Deprez, Sabine, Duivon, Mylène, De Ruiter, Michiel, Schagen, Sanne, Ahmed-Lecheheb, Djihane, Castel, Hélène, Buskbjerg, Cecilie R, Dos Santos, Mélanie, Joly, Florence, Perrier, Joy, Brussels Heritage Lab, Laboratory for Medical and Molecular Oncology, Clinical sciences, Medical Oncology, Tilburg University [Tilburg], Netspar, FUTURE HEALTH DEPARTMENT [KU Leuven] (KU-IBBT), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Aarhus University [Aarhus], Northwestern University Feinberg School of Medicine, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Kepler University Hospital, Technische Universität Dortmund [Dortmund] (TU), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), 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 Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Ligue Nationale Contre le Cancer (LNCC), Centre Hospitalier Universitaire Brugmann [Bruxelles] (CHU), Neuropsychologie et imagerie de la mémoire humaine (NIMH), Normandie Université (NU)-Normandie Université (NU)-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), Université libre de Bruxelles (ULB), Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, University of Amsterdam [Amsterdam] (UvA), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), GIP Cyceron (Cyceron), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Cancer and Cognition Consortium (ECCC) - Department of Cognitive Neuropsychology, Tilburg University, Tilburg, the Netherlands, Eustache, Francis, and Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE)
Subjects: Cognitive Dysfunction/diagnosis, Neuroimaging, clinical, rehabilitation, immune checkpoint inhibitors, Clinical, Neoplasms, preclinical, Humans, Neoplasms/therapy, Cognitive Dysfunction, risk factors, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], European consortium, neuroimaging, Rehabilitation, Hematology, Symptomatic immune-related adverse events, Preclinical, Europe, Delphi consensus, Risk factors, PRO-CTCAE™, PATIENT-REPORTED OUTCOMES, oncology, Quality of Life, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cancer-related cognitive impairment (CRCI), Biomarkers
Abstract: International audience; Cancer-related cognitive impairment (CRCI) has increasingly been identified over the last two decades in non-CNS system cancer patients. Across Europe, researchers have contributed to this effort by developing preclinical models, exploring underlying mechanisms and assessing cognitive and quality of life changes. The ultimate goal is to develop interventions to treat patients experiencing CRCI. To do so, new challenges need to be addressed requiring the implementation of multidisciplinary research groups. In this consensus paper, we summarize the state of the art in the field of CRCI combined with the future challenges and action plans in Europe. These challenges include data sharing/pooling, standardization of assessments as well as assessing additional biomarkers and neuroimaging investigations, notably through translational studies. We conclude this position paper with specific actions for Europe based on shared scientific expert opinion and stakeholders involved in the Innovative Partnership for Action Against Cancer, with a particular focus on cognitive intervention programs.
Published: 2022

27. The LILAS project: analysis of applying participatory approaches such as Living Labs to research on multiple environmental exposures to ionizing radiation, other stressors and chronic risks

Author: LAURENT, Olivier, Yara Carrejo, Gironza, Ancelet, Sophie, Armant, Olivier, Denis, Bard, Katia, Baumgartner, Sylvie, Bortoli, Boudet, Céline, Chamaret, Philippe, Chartier, Michel, Cormier, Stéphanie, Arthur, David, Desqueyroux, Hélène, Gerber, Mariette, Gilbin, Rodolphe, Grimbuhler, Sonia, Larqué, Lionel, Laurier, Dominique, Mougin, Christian, Gamet-Payrastre, Laurence, Rannou, Alain, Reaud, Cynthia, Scanff, Pascale, Vanzemberg, Arnaud, Schraub, Simon, Supervil, Sylvie, Eric, Thybaud, Trousse, Brigitte, Charron, Sylvie, Laboratoire d épidémiologie des rayonnements ionisants (IRSN/PSE-SANTE/SESANE/LEPID), Service de recherche sur les effets biologiques et Sanitaires des rayonnements ionisants (IRSN/PSE-SANTE/SESANE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), 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 ), Laboratoire d'écotoxicologie des radionucléides (IRSN/PSE-ENV/SRTE/LECO), Service de recherche sur les transferts et les effets des radionucléides sur les écosystèmes (IRSN/PSE-ENV/SRTE), Société francophone de santé environnement (SFSE), France Nature Environnement (FNE), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de l'Environnement Industriel et des Risques (INERIS), Institut Ecocitoyen pour la Connaissance des Pollutions [Fos-sur-Mer], Centre Permanent d'Initiatives pour l'Environnement des Pays de l'Aisne (CPIE des Pays de l'Aisne), École des Hautes Études en Santé Publique [EHESP] (EHESP), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Association nationale des comités et commissions locales d'information [Teteghem] (ANCCLI), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Technologies et Méthodes pour les Agricultures de demain (UMR ITAP), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, 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), ALLISS Sciences Sociétés [Paris], Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pôle Santé Environnement - Direction Santé (IRSN/PSE-SANTE), Service des politiques d’ouverture à la société (IRSN/DST/SPOS), Direction de la Stratégie (IRSN/DST), Cellule Valorisation des données (IRSN/DTR/D3NSI/SVDDA/CVD), Direction Déléguée Développement numérique et aux systèmes d’information (IRSN/DTR/D3NSI), Service de la programmation, des partenariats, de la prospective et de l’appui à l’innovation (IRSN/DST/SP3IN), Ligue Nationale Contre le Cancer (LNCC), Direction des Risques et de la Performance (IRSN/DRP), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria), IRSN2030, ICRP - International Commission on Radiation Protection, Université de Rennes (UR), Département des sciences en santé environnementale (DEESSE), Laboratoire d'étude et de recherche en environnement et santé (LERES), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Protection et Sûreté Nucléaire (IPSN), Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PRP-HOM/SRBE/LRTOX), Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PSE-SANTE/SESANE/LRTOX), IRSN via appel à projets interne IRSN2030, TECNICO LISBOA, and Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan)
Subjects: [SDE]Environmental Sciences, [SDE.ES]Environmental Sciences/Environmental and Society
Abstract: International audience; Participatory research approaches in environmental health are still rarely applied to radiation research. Opportunities for greater implication of the civil society and related challenges differ at each step of such research activities. The LILAS project aimed, as a preparatory step toward the development of participatory research projects on multiple environmental exposures to ionizing radiation and other stressors
Published: 2022

28. A gene subset requires CTCF bookmarking during the fast post‐mitotic reactivation of mouse ES cells

Author: Almira Chervova, Nicola Festuccia, Luis Altamirano‐Pacheco, Agnès Dubois, Pablo Navarro, Epigénomique, Prolifération et Identité Cellulaire - Epigenomics, Proliferation and the Identity of Cells (EPIC), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Collège Doctoral, Sorbonne Université (SU), PN acknowledges the Institut Pasteur, the CNRS and Revive (Investissement d'Avenir, ANR-10-LABX-73) for recurrent funding and the Ligue Nationale Contre le Cancer (LNCC EL2018 NAVARRO) and the European Research Council (ERC-CoG-2017 BIND) for financial support., The authors also acknowledge the Biomics and Flow Cytometry platforms of Institut Pasteur., and ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010)
Subjects: Genetics, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Molecular Biology, Biochemistry
Abstract: International audience; Mitosis leads to global downregulation of transcription that then needs to be efficiently resumed. In somatic cells, this is mediated by a transient hyper-active state that first reactivates housekeeping and then cell identity genes. Here, we show that mouse embryonic stem cells, which display rapid cell cycles and spend little time in G1, also display accelerated reactivation dynamics. This uniquely fast global reactivation lacks specificity towards functional gene families, enabling the restoration of all regulatory functions before DNA replication. Genes displaying the fastest reactivation are bound by CTCF, a mitotic bookmarking transcription factor. In spite of this, the post-mitotic global burst is robust and largely insensitive to CTCF depletion. There are, however, around 350 genes that respond to CTCF depletion rapidly after mitotic exit. Remarkably, these are characterised by promoter-proximal mitotic bookmarking by CTCF. We propose that the structure of the cell cycle imposes distinct constrains to post-mitotic gene reactivation dynamics in different cell types, via mechanisms that are yet to be identified but that can be modulated by mitotic bookmarking factors.
Published: 2022

29. ATM-dependent formation of a novel chromatin compartment regulates the Response to DNA Double Strand Breaks and the biogenesis of translocations

Author: Nadine Puget, Daan Noordermeer, Thomas Clouaire, Vincent Rocher, Coline Arnould, Gaëlle Legube, Aldo S. Bader, Martin Bushell, Raphaël Mourad, Emma Lesage, Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Cancer Research UK Beatson Institute [Glasgow], Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Ligue Nationale contre le Cancer (LNCC), ANR-18-CE12-0015,REPAIRCHROM,Analyse multi-échelle des mécanismes précoces de remodelage de la chromatine au niveau des dommages dans l'ADN(2018), and European Project: 647344,H2020,ERC-2014-CoG,DIvA(2015)
Subjects: Genome instability, chemistry.chemical_compound, Cohesin, DNA damage, Chemistry, Chromosome, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Gene, DNA, Chromatin, Cell biology, Genomic organization
Abstract: This article is a preprint and has not been certified by peer review; DNA Double-Strand Breaks (DSBs) repair is essential to safeguard genome integrity but the contribution of chromosome folding into this process remains elusive. Here we unveiled basic principles of chromosome dynamics upon DSBs in mammalian cells, controlled by key kinases from the DNA Damage Response. We report that ATM is responsible for the reinforcement of topologically associating domains (TAD) that experience a DSB. ATM further drives the formation of a new chromatin sub-compartment (“D” compartment) upon clustering of damaged TADs decorated with γH2AX and 53BP1. “D” compartment formation mostly occurs in G1, is independent of cohesin and is enhanced upon DNA-PK pharmacological inhibition. Importantly, a subset of DNA damage responsive genes that are upregulated following DSBs also physically localize in the D sub-compartment and this ensures their optimal activation, providing a function for DSB clustering in activating the DNA Damage Response. However, these DSB-induced changes in genome organization also come at the expense of an increased translocations rate, which we could also detect on cancer genomes. Overall, our work provides a function for DSB-induced compartmentalization in orchestrating the DNA Damage Response and highlights the critical impact of chromosome architecture in genomic instability.
Published: 2022

30. Priming therapy by targeting enhancer-initiated pathways in patient-derived pancreatic cancer cells

Author: Nicolas A. Fraunhoffer, Aura I. Moreno Vega, Analía Meilerman Abuelafia, Marie Morvan, Emilie Lebarbier, Tristan Mary-Huard, Michael Zimmermann, Gwen Lomberk, Raul Urrutia, Nelson Dusetti, Yuna Blum, Remy Nicolle, Juan Iovanna, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad de Buenos Aires [Buenos Aires] (UBA), Ligue Nationale Contre le Cancer (LNCC), Modélisation aléatoire de Paris X (MODAL'X), Université Paris Nanterre (UPN), AgroParisTech Innovation, Medical College of Wisconsin [Milwaukee] (MCW), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), (le programme) Cartes d'identité des tumeurs (CIT), and Ligue Nationales Contre le Cancer (LNCC)
Subjects: Epidrugs, [SDV]Life Sciences [q-bio], PDAC, General Medicine, Priming chemotherapies, Transcriptome, General Biochemistry, Genetics and Molecular Biology
Abstract: International audience; BACKGROUND: Systems biology leveraging multi-OMICs technologies, is rapidly advancing development of precision therapies and matching patients to targeted therapies, leading to improved responses. A new pillar of precision oncology lies in the power of chemogenomics to discover drugs that sensitizes malignant cells to other therapies. Here, we test a chemogenomic approach using epigenomic inhibitors (epidrugs) to reset patterns of gene expression driving the malignant behavior of pancreatic tumors. METHODS: We tested a targeted library of ten epidrugs targeting regulators of enhancers and super-enhancers on reprogramming gene expression networks in seventeen patient-derived primary pancreatic cancer cell cultures (PDPCCs), of both basal and classical subtypes. We subsequently evaluated the ability of these epidrugs to sensitize pancreatic cancer cells to five chemotherapeutic drugs that are clinically used for this malignancy. FINDINGS: To comprehend the impact of epidrug priming at the molecular level, we evaluated the effect of each epidrugs at the transcriptomic level of PDPCCs. The activating epidrugs showed a higher number of upregulated genes than the repressive epidrugs (χ(2) test p-value
Published: 2023

31. Le sommeil dans les cancers non cérébraux : revue de la littérature, mécanismes potentiels et perspectives pour mieux comprendre les troubles cognitifs associés

Author: Mylène Duivon, Géraldine Rauchs, Joy Perrier, Bénédicte Giffard, Perrier, Joy, Neuropsychologie et imagerie de la mémoire humaine (NIMH), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-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), Plateforme Cancer et Cognition, CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest
Subjects: Polysomnographie, Polysomnography, Cognitive Neuroscience, 05 social sciences, [SCCO] Cognitive science, Actigraphy, 050105 experimental psychology, 3. Good health, [SCCO]Cognitive science, 03 medical and health sciences, Behavioral Neuroscience, Cognition, Breast cancer, 0302 clinical medicine, Neuropsychology and Physiological Psychology, Cancer du sein Actimétrie, Neurology, Sommeil, 0501 psychology and cognitive sciences, Neurology (clinical), Sleep, Fatigue, 030217 neurology & neurosurgery
Abstract: Breast cancer patients have frequent complaints of sleep disturbances. Sleep plays a major role in cognitive functioning, especially in executive functions, such as planning or flexibility, and also in memory consolidation. These cognitive functions are among the most frequently impaired in breast cancer. However, the influence of sleep on cognitive performance in patients treated for breast cancer has been little investigated. In addition, the physio-pathological mechanisms associated with sleep disturbances in breast cancer patients are not clear for now. The objective of this non-exhaustive review is to describe sleep alterations encountered in breast cancer, their potential mechanisms and to link these alterations with cognitive difficulties of patients. The studies conducted until now revealed the existence of a sleep complaint, with mainly insomnia symptoms, in breast cancer patients. These results are in accordance with those of studies using actigraphy after chemotherapy. Polysomnography (PSG) studies also suggest alterations in sleep architecture, but these studies are scarce and suffer from several limitations. Sleep alterations have mainly been studied in the context of chemotherapy. However, sleep alterations are little studied in case of other treatments, such as hormonal therapy, or even in the absence of treatment. Recent studies have highlighted the potential role of sleep–wake cycle alterations and sleep apnea in breast cancer occurrence and survival; however, this association still needs to be more deeply evaluated. Finally, the links between objective sleep alterations and cognition are still little explored. A better understanding of sleep disorders in breast cancer will allow adapting the treatment in order to improve patients’ quality of life., Les patientes atteintes d’un cancer du sein se plaignent fréquemment d’une altération de leur sommeil. Ce dernier joue un rôle crucial dans le fonctionnement cognitif, notamment dans les fonctions exécutives telles que la planification ou la flexibilité, ou encore dans la consolidation des souvenirs en mémoire à long terme. Ces fonctions cognitives sont fréquemment altérées dans le cancer du sein. Cependant, l’influence du sommeil sur les performances cognitives reste peu documentée dans cette pathologie. En outre, les mécanismes physiopathologiques associés aux troubles du sommeil dans le cancer du sein sont, actuellement, mal compris. L’objectif de cette mise au point est de faire un état de l’art des altérations du sommeil rencontrées dans le cancer du sein, de décrire les potentiels mécanismes impliqués et de mettre en lien ces altérations avec les troubles cognitifs. Les études réalisées jusqu’ici auprès de patientes atteintes d’un cancer du sein révèlent l’existence d’une plainte de sommeil, avec principalement des symptômes évocateurs d’insomnie. Ces résultats sont en accord avec les données obtenues en actimétrie après chimiothérapie. Les études en polysomnographie (PSG) suggèrent également des altérations de l’architecture du sommeil, mais ces études sont encore peu nombreuses et souffrent de plusieurs limites. Les altérations du sommeil ont été majoritairement décrites chez des patientes traitées par chimiothérapie. En revanche, elles sont peu étudiées dans le cadre d’autres traitements, tels que l’hormonothérapie, ou même en dehors des traitements. Des études récentes mettent en avant les effets potentiellement carcinogènes des altérations du rythme activité–repos et des apnées, mais la causalité de ces effets doit être confirmée. Enfin, les liens existant entre les altérations du sommeil et la cognition sont encore peu explorés, notamment à l’aide de mesures objectives du sommeil. Une meilleure compréhension des troubles du sommeil dans le cancer du sein permettra d’adapter la prise en charge afin d’améliorer, à terme, la qualité de vie des patientes.
Published: 2021

32. Impact of creative art therapy on fatigue and quality of life in patients treated for localized breast cancer: A randomized study

Author: Florence Joly, David Pasquier, Christelle Levy, Mireille Mousseau, Marie‐Christine D’Almeida, Sabine Noal, Florence Le Tinier, Julien Geffrelot, Catherine Ciais, Viviane Szymczak, Catherine Leon, Marie Pierre Rousselot, Stephanie Darbas, Chantal Hanzen, Natacha Heutte, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), 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 Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Ligue Nationale Contre le Cancer (LNCC), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Service d'oncologie médicale, CHU Grenoble-Hôpital Michallon, Biologie et Pharmacologie des Plaquettes sanguines : hémostase, thrombose, transfusion (BPP), Université de Strasbourg (UNISTRA)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement Français du Sang - Grand Est (EFS - alsace strasbourg), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre d’études des transformations des activités physiques et sportives (CETAPS), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut de Recherche Interdisciplinaire Homme et Société (IRIHS), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)
Subjects: Psychiatry and Mental health, Oncology, Depression, [SDV]Life Sciences [q-bio], Quality of Life, Art Therapy, Humans, Experimental and Cognitive Psychology, Breast Neoplasms, Female, Anxiety
Abstract: Art therapy (AT) as supportive care may help patients cope with cancer treatments. This non-blinded randomized trial assessed the impact of creative AT on severe fatigue and quality of life (QoL) in localized breast cancer patients undergoing irradiation.320 patients were randomized to an AT group (ATG; 8 weekly sessions starting during irradiation) or to a standard group (SG). The primary endpoint was severe global fatigue (Functional Assessment of Chronic Therapy Fatigue subscale score37) at 1 month post-irradiation. Quality of life (Fact-B), anxiety/depression (Hospital Anxiety and Depression Scale (HADS)) and different dimensions of fatigue 20-item Multidimensional Fatigue Inventory (MFI-20) were assessed at 1, 6 and 12 months post-irradiation. The secondary endpoints, fatigue among patients treated with chemotherapy, QoL (Fact-B), anxiety/depression (HADS) and different dimensions of fatigue (MFI-20) at 1, 6 and 12 months post-irradiation (with post hoc analysis in patients with treated with chemotherapy) were also assessed.82% of patients completed ≥8 sessions. Severe initial global fatigue was observed in 43% of patients in each group, and among in 64% of patients whose treatment protocol contained chemotherapy. At 1 month post-irradiation, 45% in the ATG and 57% of patients in the SG reported severe global fatigue (p = 0.37); among patients with initial severe mental fatigue (MFF), 79% and 44% had improved MFF (p = 0.007) respectively; similarly 79% and 44% with initial poor motivation had better mental motivation (p = 0.03). At 6 and 12 months, social well-being scores in the ATG were higher (21.3 and 21.4 vs. 19.8 and 19.2, p = 0.05 and p 0.01) with a significant improvement for patients who had chemotherapy (41% vs. 18%, p = 0.017). A positive association was observed between the number of AT sessions, fatigue and QoL (p 0.01).AT did not significantly improve global severe fatigue among all cancer participants 1 month after radiation therapy, however it had a positive impact on social well-being and may improve MFF and motivation.
Published: 2022

33. Multilayer spectrum of intratumoral heterogeneity in basal bladder cancer

Author: François Radvanyi, Xavier Paoletti, Dimitri Vordos, Thierry Lebret, Emilie Henry, Cécile Reyes, David Gentien, Romain Pelletier, Damien Drubay, Tatiana Popova, Pascale Soyeux-Porte, Yves Allory, Nanor Sirab, Aurélien de Reyniès, Damien Pouessel, Anissa Moktefi, Carine Ngo, Pascale Maillé, Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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 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), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Institut Curie [Paris], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Foch [Suresnes], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Ligue Nationale Contre le Cancer - Paris, Ligue Nationale Contre le Cancer (LNCC), Institut National Du Cancer, INCa, and This work was supported by the French Institut National du Cancer INCa (PRT‐K 2013, Programme de Recherche Translationnelle en Cancérologie, ‘DIATRIBBE’
Subjects: DNA Copy Number Variations, [SDV]Life Sciences [q-bio], intratumor heterogeneity, Biology, Pathology and Forensic Medicine, basal/squamous subtype, Basal (phylogenetics), Molecular classification, Intratumor heterogeneity, medicine, Biomarkers, Tumor, Humans, Precision Medicine, molecular classifier, Bladder cancer, business.industry, Gene Expression Profiling, GATA3, medicine.disease, Immunohistochemistry, Urinary Bladder Neoplasms, muscle-invasive bladder cancer, Mutation, Cancer research, histological variant, Personalized medicine, business, Immunostaining
Abstract: Basal/squamous (Ba/Sq) subtype represents an intrinsic and robust group in the consensus molecular classification of muscle-invasive bladder cancer (MIBC), with poor outcome and controversial chemosensitivity. We aimed to investigate the spectrum of intratumor heterogeneity (ITH) in the Ba/Sq subtype. First, we validated a 29-gene NanoString CodeSet to predict the Ba/Sq subtype for FFPE samples. We identified heterogeneous Ba/Sq tumors in a series of 331 MIBC FFPE samples using dual GATA3/KRT5/6 immunohistochemistry (IHC). Heterogeneous regions with distinct immunostaining patterns were studied separately for gene expression using the 29-gene CodeSet, for mutations by targeted next-generation sequencing, and for copy number alteration (CNA) by microarray hybridization. Among 83 Ba/Sq tumors identified by GATA3/KRT5/6 dual staining, 19 tumors showed heterogeneity at the IHC level. In one third of the 19 cases, regions from the same tumor were classified in different distinct molecular subtypes. The mutational and CNA profiles confirmed the same clonal origin for IHC heterogeneous regions with possible subclonal evolution. Overall, two patterns of intratumoral heterogeneity (ITH) were observed in Ba/Sq tumors: low ITH (regions with distinct immunostaining, but common molecular subtype and shared CNA) or high ITH (regions with distinct immunostaining, molecular subtype, and CNA). These results showed multilayer heterogeneity in Ba/Sq MIBC. In view of personalized medicine, this heterogeneity adds complexity and should be taken into account for sampling procedures used for diagnosis and treatment choice. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Published: 2022

34. Autophagy Contributes to Metabolic Reprogramming and Therapeutic Resistance in Pancreatic Tumors

Author: Gabriela Reyes-Castellanos, Nadine Abdel Hadi, Alice Carrier, CARRIER, Alice, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, and Fondation ARC pour la Recherche sur le Cancer (PJA 20151203544 and PJA 20181208207). NAH was supported by Association AZM et Saade (Lebanon) and Fondation pour la Recherche Médicale (FRM), and GR-C by the CONACYT (Mexico, grant 339091/471717) and la Ligue Nationale Contre le Cancer (LNCC).
Subjects: therapeutic resistance, autophagy, mitochondrial metabolism, QH301-705.5, [SDV]Life Sciences [q-bio], pancreatic ductal adenocarcinoma, cancer metabolism, General Medicine, A pancreatic ductal adenocarcinoma, Pancreatic Neoplasms, [SDV] Life Sciences [q-bio], Drug Resistance, Neoplasm, Tumor Microenvironment, Humans, Biology (General), Carcinoma, Pancreatic Ductal
Abstract: International audience; Metabolic reprogramming is a feature of cancers for which recent research has been particularly active, providing numerous insights into the mechanisms involved. It occurs across the entire cancer process, from development to resistance to therapies. Established tumors exhibit dependencies for metabolic pathways, constituting vulnerabilities that can be targeted in the clinic. This knowledge is of particular importance for cancers that are refractory to any therapeutic approach, such as Pancreatic Ductal Adenocarcinoma (PDAC). One of the metabolic pathways dysregulated in PDAC is autophagy, a survival process that feeds the tumor with recycled intracellular components, through both cell-autonomous (in tumor cells) and nonautonomous (from the local and distant environment) mechanisms. Autophagy is elevated in established PDAC tumors, contributing to aberrant proliferation and growth even in a nutrient-poor context. Critical elements link autophagy to PDAC including genetic alterations, mitochondrial metabolism, the tumor microenvironment (TME), and the immune system. Moreover, high autophagic activity in PDAC is markedly related to resistance to current therapies. In this context, combining autophagy inhibition with standard chemotherapy, and/or drugs targeting other vulnerabilities such as metabolic pathways or the immune response, is an ongoing clinical strategy for which there is still much to do through translational and multidisciplinary research.
Published: 2022

35. Relevance of biopsy-derived pancreatic organoids in the development of efficient transcriptomic signatures to predict adjuvant chemosensitivity in pancreatic cancer

Author: R. Nicolle, O. Gayet, M. Bigonnet, J. Roques, B. Chanez, F. Puleo, J. Augustin, J.F. Emile, M. Svrcek, T. Arsenijevic, P. Hammel, V. Rebours, M. Giovannini, P. Grandval, L. Dahan, V. Moutardier, E. Mitry, J.L. Van Laethem, J.B. Bachet, J. Cros, J. Iovanna, N.J. Dusetti, Institut Curie [Paris], Ligue Nationale Contre le Cancer (LNCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Université libre de Bruxelles (ULB), Hôpital Henri Mondor, Hôpital Ambroise Paré [AP-HP], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Paul Brousse, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pitié-Salpêtrière [AP-HP], Institut de biologie systémique et synthétique (ISSB), Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), INSTITUTE OF LANDSCAPE MATTER DYNAMICS LEIBNIZ CENTRE FOR AGRICULTURAL LANDSCAPE AND LAND USE RESEARCH ZALF MUNCHEBERG DEU, Partenaires IRSTEA, Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Service de Pathologie [Clichy], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Pneumologia Ospedale San Paolo, Università degli Studi di Milano = University of Milan (UNIMI), Assistance Publique - Hôpitaux de Marseille (APHM), Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Stress Cellulaire, and Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Cancer Research, Oncology, [SDV]Life Sciences [q-bio], Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Original Research
Abstract: Highlights • Most patient with pancreatic cancer are treated by chemotherapy. • Treatments selection are not personalized on the tumor characteristics. • Signatures predicting chemotherapy efficiency are essential for personalizing treatments. • An RNA signature of gemcitabine-sensitivity is developed leveraged on the dissimilarities between 2D and 3D in vitro models. • Combining different in vitro models can help in defining clinically efficient transcriptomic signatures., Pancreatic ductal adenocarcinoma (PDAC) patients are frequently treated by chemotherapy. Even if personalized therapy based on molecular analysis can be performed for some tumors, PDAC regimens selection is still mainly based on patients' performance status and expected efficacy. Therefore, the establishment of molecular predictors of chemotherapeutic efficacy could potentially improve prognosis by tailoring treatments. We have recently developed an RNA-based signature that predicts the efficacy of adjuvant gemcitabine using 38 PDAC primary cell cultures. While demonstrated its efficiency, a significant association with the classical/basal-like PDAC spectrum was observed. We hypothesized that this flaw was due to the basal-like biased phenotype of cellular models used in our strategy. To overcome this limitation, we generated a prospective cohort of 27 consecutive biopsied derived pancreatic organoids (BDPO) and include them in the signature identification strategy. As BDPO's do not have the same biased phenotype as primary cell cultures we expect they can compensate one with each other and cover a broader range of molecular phenotypes. We then obtained an improved signature predicting gemcitabine sensibility that was validated in a cohort of 300 resected PDAC patients that have or have not received adjuvant gemcitabine. We demonstrated a significant association between the improved signature and the overall and disease-free survival in patients predicted as sensitive and treated with adjuvant gemcitabine. We propose then that including BDPO along primary cell cultures represent a powerful strategy that helps to overcome primary cell cultures limitations producing unbiased RNA-based signatures predictive of adjuvant treatments in PDAC.
Published: 2022

36. Le projet LILAS : analyse de l’application des approches participatives sur les multi-expositions environnementales et les risques chroniques

Author: Laurent, Olivier, Carrejo Gironza, Yara, Ancelet, Sophie, Armant, Olivier, Bard, Denis, Baumgartner, Katia, Bortoli, Sylvie, Boudet, Céline, Chamaret, Philippe, Chartier, Michel, Cormier, Stéphanie, David, Arthur, Desqueyroux, Hélène, Gerber, Mariette, Gilbin, Rodolphe, Grimbuhler, Sonia, Grison, Stephane, Larqué, Lionel, Laurier, Dominique, Mougin, Christian, Gamet-Payrastre, Laurence, Rannou, Alain, Vanzemberg, Arnaud, Schraub, Simon, Supervil, Sylvie, Thybaud, Eric, Trousse, Brigitte, Charron, Sylvie, Laboratoire d épidémiologie des rayonnements ionisants (IRSN/PSE-SANTE/SESANE/LEPID), Service de recherche sur les effets biologiques et Sanitaires des rayonnements ionisants (IRSN/PSE-SANTE/SESANE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire d'écotoxicologie des radionucléides (IRSN/PSE-ENV/SRTE/LECO), Service de recherche sur les transferts et les effets des radionucléides sur les écosystèmes (IRSN/PSE-ENV/SRTE), Société francophone de santé environnement (SFSE), France Nature Environnement (FNE), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de l'Environnement Industriel et des Risques (INERIS), Institut Ecocitoyen pour la Connaissance des Pollutions [Fos-sur-Mer], Service d'expertise et d'étude en radioprotection des populations et de la radioactivité dans l'environnement (IRSN/PSE-ENV/SEREN), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Centre Permanent d'Initiatives pour l'Environnement des Pays de l'Aisne (CPIE des Pays de l'Aisne), EHESP-Irset (EHESP-Irset), École des Hautes Études en Santé Publique [EHESP] (EHESP), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Association nationale des comités et commissions locales d'information [Teteghem] (ANCCLI), Technologies et Méthodes pour les Agricultures de demain (UMR ITAP), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, 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), Alliance Sciences-Société, Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pôle Santé Environnement - Direction Santé (IRSN/PSE-SANTE), Service des politiques d’ouverture à la société (IRSN/DST/SPOS), Direction de la Stratégie (IRSN/DST), Service de la programmation, des partenariats, de la prospective et de l’appui à l’innovation (IRSN/DST/SP3IN), Ligue Nationale Contre le Cancer (LNCC), Direction des Risques et de la Performance (IRSN/DRP), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria), IRSN2030, Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Laboratoire d'écotoxicologie des radionucléides (IRSN/PRP-ENV/SERIS/LECO), Service de Recherche et d'Expertise sur les Risques environnementaux (IRSN/PRP-ENV/SERIS), Institut National de la Santé et de la Recherche Médicale (INSERM), 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 ), Département des sciences en santé environnementale (DEESSE), Information – Technologies – Analyse Environnementale – Procédés Agricoles (UMR ITAP), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PSE-SANTE/SESANE/LRTOX), ALLISS Sciences Sociétés [Paris], and Ligue Nationale Contre le Cancer - Paris
Subjects: méthodes en santé-environ- multiple exposure, Laboratoire viavant, Méthodes en santé-environnement, multi-expositions, Methods in environmental health research, Analysis tools, co-construction, Multiple exposures, analysis tool, [SDE]Environmental Sciences, participatory research, Living Lab, Grille d'analyse, methods in environmental health, recherches participatives
Abstract: International audience; Context: Participatory research in environmental health remains rare in France. The objectives of environmental health research projects can, like their methods, be very diverse. Opportunities for greater involvement of civil society, as well as its challenges, differ at each step of such research activities. All these aspects need to be widely shared. As a preparatory step toward the development of concrete new participatory research projects on multiple environmental exposures, the LILAS project aimed to (1) favor the mutual understanding of the main issues and research methods in environmental health and their stakes for different participants, but also the requirements, strengths, and limitations of these methods, and (2) identify the expected benefits and points to watch out for related to stronger civic participation in these projects.Methods: The LILAS project identified and gathered together institutional researchers, academics and civil society participants (mainly from nongovernmental organizations) interested in multiple exposures (chemical and radiological). The relevant literature was searched to learn from previous participatory research projects in this broad field. Several meetings enabled the group to collectively identify different types of studies and analyze the benefits, limitations and methods related to the introduction of such participation. An analysis matrix was co-constructed and completed by study participants, as in a Living Lab approach.Results: The matrix lists for different types of studies (assessment of environmental exposures, identification of their determinants, interventions on these exposures, quantitative risk assessment, epidemiological studies, experimental research, ecosystem health, etc.) the expected benefits for several categories of stakeholders, the fundamental principles of research methods, and their related practical constraints, advantages and limitations related to the use of participatory or more standard approaches.Conclusion: The LILAS project enabled the development of a solid basis for the co-construction of participatory research projects to study multiple environmental exposures.; Contexte : Les recherches participatives en santé-environnement restent encore peu développées en France. Les objectifs poursuivis par les recherches en santé-environnement (par exemple : estimer des expositions et/ou des effets, tester des actions préventives) et les méthodes employées à ces fins sont variées. Les opportunités d’une plus grande implication de la société civile et les défis associés diffèrent à chaque étape de ces recherches. Ces aspects demandent à être mieux appréhendés collectivement. Le projet LILAS visait, en amont du développement de futurs projets concrets de recherches participatives sur les multi-expositions environnementales, à (1) favoriser une bonne compréhension commune des principales problématiques et méthodes de recherche en santé-environnement, de leurs enjeux, prérequis, forces et limites, et à (2) identifier les bénéfices et points de vigilance liés à l’introduction de plus fortes dimensions participatives dans ces recherches.Méthode adoptée : Le projet LILAS a identifié et rassemblé des chercheurs institutionnels, académiques et acteurs de la société civile (associations loi 1901) intéressés par les multi-expositions (chimiques, radiologiques). Cinq réunions ont permis d’identifier collectivement différents types d’études et de réfléchir sur les apports, limites et prérequis méthodologiques relatifs à l’introduction de différents degrés de participation dans celles-ci. Une matrice résumant ces aspects a été co-construite puis alimentée par les participants, en s’inspirant des approches Living Lab (soit laboratoire vivant).Résultats : Pour différents types d’études (études d’estimations d’expositions, d’interventions sur celles-ci, évaluations de risques sanitaires, études épidémiologiques, expérimentales, études sur la santé des écosystèmes, etc.), la matrice élaborée en commun liste les bénéfices attendus pour différentes parties prenantes, les principes fondamentaux des méthodes employées et contraintes pratiques associées, les avantages et limites relatifs à l’emploi d’approches participatives (notamment les Living Labs) ou plus « classiques ».Conclusion : Le projet LILAS a permis de poser des bases consolidées pour la co-construction de projets de recherches participatives sur les multi-expositions environnementales.
Published: 2022

37. Clinico-biological features of T-cell acute lymphoblastic leukemia with fusion proteins

Author: Thomas Steimlé, Marie-Emilie Dourthe, Marion Alcantara, Aurore Touzart, Mathieu Simonin, Johanna Mondesir, Ludovic Lhermitte, Jonathan Bond, Carlos Graux, Nathalie Grardel, Jean-Michel Cayuela, Isabelle Arnoux, Virginie Gandemer, Marie Balsat, Norbert Vey, Elizabeth Macintyre, Norbert Ifrah, Hervé Dombret, Arnaud Petit, André Baruchel, Philippe Ruminy, Nicolas Boissel, Vahid Asnafi, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Ligue Nationale Contre le Cancer - Paris, Ligue Nationale Contre le Cancer (LNCC), CHU UCL Namur, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Recherche clinique appliquée à l'hématologie (URP_3518), Université Paris Cité (UPCité), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pontchaillou [Rennes], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), and Gestionnaire, HAL Sorbonne Université 5
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Adult, Male, Acute lymphocytic leukaemia, Adolescent, Oncogene Proteins, Fusion, T-Lymphocytes, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Infant, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, Article, Young Adult, Oncology, Child, Preschool, Humans, Female, Child, Cancer genetics, RC254-282
Abstract: T-cell acute lymphoblastic leukemias (T-ALL) represent 15% of pediatric and 25% of adult ALL. Since they have a particularly poor outcome in relapsed/refractory cases, identifying prognosis factors at diagnosis is crucial to adapting treatment for high-risk patients. Unlike acute myeloid leukemia and BCP ALL, chromosomal rearrangements leading to chimeric fusion-proteins with strong prognosis impact are sparsely reported in T-ALL. To address this issue an RT-MPLA assay was applied to a consecutive series of 522 adult and pediatric T-ALLs and identified a fusion transcript in 20% of cases. PICALM-MLLT10 (4%, n = 23), NUP214-ABL1 (3%, n = 19) and SET-NUP214 (3%, n = 18) were the most frequent. The clinico-biological characteristics linked to fusion transcripts in a subset of 235 patients (138 adults in the GRAALL2003/05 trials and 97 children from the FRALLE2000 trial) were analyzed to identify their prognosis impact. Patients with HOXA trans-deregulated T-ALLs with MLLT10, KMT2A and SET fusion transcripts (17%, 39/235) had a worse prognosis with a 5-year EFS of 35.7% vs 63.7% (HR = 1.63; p = 0.04) and a trend for a higher cumulative incidence of relapse (5-year CIR = 45.7% vs 25.2%, HR = 1.6; p = 0.11). Fusion transcripts status in T-ALL can be robustly identified by RT-MLPA, facilitating risk adapted treatment strategies for high-risk patients.
Published: 2022

38. Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division

Author: Laurent Gagnoux, Serena Petracchini, Benoit Ladoux, Amel Mettouchi, Martial Balland, Mads Daugaard, Mukund Gupta, Emmanuel Lemichez, Francis Impens, Poul H. Sorensen, Sébastien Janel, Elisa Vitiello, Anne Doye, Frank Lafont, Florian Fage, Atef Asnacios, Teresa Mendes Maia, Daniel Hamaoui, Jerome Gilleron, 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), Equipe labellisée Ligue contre le Cancer, Matière et Systèmes Complexes (MSC), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Cellular Microbiology and Physics of Infection Group [Lille] (CMPI), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Universiteit Gent = Ghent University (UGENT), Institut de Biologie Valrose (IBV), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Vancouver Prostate Centre [Vancouver General Hospital] (VPC), Vancouver General Hospital, University of British Columbia (UBC), Toxines bactériennes - Bacterial Toxins, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This study was supported by institutional INSERM and Institut Pasteur fundings, 'Investments for the Future' LabEx SIGNALIFE ANR-11-LABX-0028-01 and grants from the Ligue Nationale contre le Cancer (LNCC labellisation and RS20/75-63), Association pour la Recherche contre le Cancer (ARC PJA20191209650), EPIC-XS, project number 823839, funded by the Horizon 2020 programme of the European Union (PRC-5074) and FRM-Piraud prize to E.L., Bio-SPC 'Contrat Doctoral' PhD fellowship to S.P., LNCC PhD fellowship to D.H., the Vancouver Prostate Centre to M.D., and Team Finn and The Ride to Concur Cancer to P.H.S., Fundings from ANR to A.A. ('ImmunoMeca' ANR-12-BSV5-0007-01, 'Initiatives d’excellence' Idex ANR-11-IDEX-0005-02, and 'Labex Who Am I?' ANR-11-LABX-0071)and to F.L. (ANR-10-EQPX-04-01), and from FEDER (12001407) to F.L. B.L. acknowledges financial supports from the Mechanobiology Institute, the European Research Council under the European Union's 7th Framework Programme (FP7/2007-2013) / ERC n° 617233 and NUS-USPC collaborative program., ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), ANR-12-BSV5-0007,ImmunoMeca,Caractérisation du rôle de la mécanique dans l'immunité: vers un modèle intégré de l'activation des cellules T(2012), ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), ANR-11-LABX-0071,WHO AM I,Determinants de l'Identité : de la molécule à l'individu(2011), ANR-10-EQPX-0004,Imaginex BioMed,Plateau de microscopie de criblage à haut débit et d'analyse à très haute résolution(2010), European Project: 617233,EC:FP7:ERC,ERC-2013-CoG,DURACELL(2014), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université Nice Sophia Antipolis (... - 2019) (UNS), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), National University of Singapore (NUS), Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University [Belgium] (UGENT), 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 National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: rac1 GTP-Binding Protein, Integrins, Cell division, Mechanotransduction, Ubiquitin-Protein Ligases, [SDV]Life Sciences [q-bio], Integrin, General Physics and Astronomy, RAC1, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Mechanotransduction, Cellular, General Biochemistry, Genetics and Molecular Biology, Extracellular matrix, Focal adhesion, Integrin signalling, 03 medical and health sciences, 0302 clinical medicine, Medicine and Health Sciences, Cyclin D1, 030304 developmental biology, Optineurin, 0303 health sciences, CNF1 toxin, Multidisciplinary, biology, Chemistry, Ubiquitination, Biology and Life Sciences, Cell migration, General Chemistry, Hostpathogen interaction, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Cell biology, E3 ubiquitin ligase, biology.protein, Rac1 GTPase, Cell Division, 030217 neurology & neurosurgery, Tumour suppressor
Abstract: Extracellular matrix (ECM) elasticity is perceived by cells via focal adhesion structures, which transduce mechanical cues into chemical signalling to conform cell behavior. Although the contribution of ECM compliance to the control of cell migration or division is extensively studied, little is reported regarding infectious processes. We study this phenomenon with the extraintestinal Escherichia coli pathogen UTI89. We show that UTI89 takes advantage, via its CNF1 toxin, of integrin mechanoactivation to trigger its invasion into cells. We identify the HACE1 E3 ligase-interacting protein Optineurin (OPTN) as a protein regulated by ECM stiffness. Functional analysis establishes a role of OPTN in bacterial invasion and integrin mechanical coupling and for stimulation of HACE1 E3 ligase activity towards the Rac1 GTPase. Consistent with a role of OPTN in cell mechanics, OPTN knockdown cells display defective integrin-mediated traction force buildup, associated with limited cellular invasion by UTI89. Nevertheless, OPTN knockdown cells display strong mechanochemical adhesion signalling, enhanced Rac1 activation and increased cyclin D1 translation, together with enhanced cell proliferation independent of ECM stiffness. Together, our data ascribe a new function to OPTN in mechanobiology. Uropathogenic strains of Escherichia coli (UPEC) are a leading cause of urinary tract infections (UTIs) and invasion involves Rho GTPase members, notably Rac1, to drive actin cytoskeleton rearrangement leading to engulfment. Here, Petracchini et al. provide evidence of an ECM stiffnessmodulated role of Optineurin (OPTN), which regulates HACE1-dependant Rac1 activity and thus controls integrinmediated mechanotransduction and bacterial invasion.
Published: 2022
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39. Sumoylation of Human Argonaute 2 at Lysine-402 Regulates Its Stability

Author: Pierre Lapaquette, Anne Dejean, Umut Sahin, Alexandra Andrieux, Guilhem Faure, Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ligue Nationale Contre le Cancer - Paris, Ligue Nationale Contre le Cancer (LNCC), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from Ligue Nationale Contre le Cancer (LNCC, Equipe Labellisée), Odyssey-RE, Institut National du Cancer, L’Agence Nationale de la Recherche and European Research Council., CECILIO, Catherine, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Ligue Nationnale Contre le Cancer
Subjects: Protein Folding, Small RNA, Small interfering RNA, Hydrolases, [SDV]Life Sciences [q-bio], SUMO protein, lcsh:Medicine, Gene Expression, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Biochemistry, Mice, RNA interference, 0302 clinical medicine, Nucleic Acids, Phosphorylation, RNA, Small Interfering, lcsh:Science, 0303 health sciences, Multidisciplinary, Conjugated Proteins, Argonaute, Enzymes, Cell biology, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Argonaute Proteins, Small Ubiquitin-Related Modifier Proteins, Epigenetics, Research Article, Protein Structure, Nucleases, Ubiquitin-Protein Ligases, SUMO-1 Protein, Biophysics, Piwi-interacting RNA, SUMO2, Biology, Protein Chemistry, 03 medical and health sciences, Cell Line, Tumor, Genetics, Animals, Humans, Gene Silencing, 030304 developmental biology, Biology and life sciences, Lysine, lcsh:R, Proteins, Sumoylation, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Molecular biology, Nuclear Pore Complex Proteins, Ubiquitin-Conjugating Enzymes, Enzymology, RNA, lcsh:Q, RANBP2, Protein Processing, Post-Translational, HeLa Cells, Molecular Chaperones
Abstract: International audience; Gene silencing by small RNAs has emerged as a powerful post-transcriptional regulator of gene expression, however processes underlying regulation of the small RNA pathway in vivo are still largely elusive. Here, we identified sumoylation as a novel post-translational modification acting on Ago2, the main effector of small RNA-mediated gene silencing. We demonstrate that Ago2 can be modified by SUMO1 and SUMO2/3 and identified Lys402 as the major Ago2 sumoylation site in vivo. Ago2 physically interacts with the SUMO E2 conjugating enzyme Ubc9 and the E3 ligase RanBP2 facilitates Ago2 sumoylation in vitro. Mutation of Lys402 enhances the stability of Ago2 protein and impairment of cellular sumoylation by siRNA- or shRNA-mediated extinction of Ubc9 or in Ubc9 knockout mouse tissues results in increased steady-state levels and enhanced stability of Ago2. Similarly, knockdown of RanBP2 or of the SAE2 E1 enzyme enhances Ago2 protein levels. Lys402 is located in the L2g1 loop linking the PAZ and PIWI domains of Ago2, in the immediate vicinity of Tyr393 which can be phosphorylated, implying that the L2g1 linker represents an easily accessible hot spot for post-translational modifications. Altogether, our results show that sumoylation of Ago2 at Lys402 negatively regulates its stability, thereby establishing a first link between SUMO and the small RNA machinery.
Published: 2014

40. A Truncated NRIP1 Mutant Amplifies Microsatellite Instability of Colorectal Cancer by Regulating MSH2/MSH6 Expression, and Is a Prognostic Marker of Stage III Tumors

Author: Palassin, Pascale, Lapierre, Marion, Pyrdziak, Samuel, Wagner, Antoine, Stehle, Régine, Corsini, Carole, Duffour, Jacqueline, Bonnet, Sandrine, Boulahtouf, Abdelhay, Rodriguez, Carmen, Ho-Puncheun, Alexandre, Lopez-Crapez, Evelyne, Boissière-Michot, Florence, Bibeau, Frédéric, Thezenas, Simon, Elarouci, Nabila, Selves, Janick, Hoffmann, Jean-Sébastien, Roepman, Paul, Mazard, Thibault, Buhard, Olivier, Duval, Alex, Jalaguier, Stéphan, Cavaillès, Vincent, Castet-Nicolas, Audrey, 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), Institut du Cancer de Montpellier (ICM), Ligue Nationale Contre le Cancer - Paris, Ligue Nationnale Contre le Cancer, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Agendia NV, Agendia NV, Amsterdam, Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], 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)-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 Régional Universitaire [Montpellier] (CHRU Montpellier), Unité de Formation et de Recherche des Sciences Pharmaceutiques et Biologiques, Ligue Nationale Contre le Cancer (LNCC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologies biliaires, fibrose et cancer du foie [CRSA], 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Gibier, François
Subjects: congenital, hereditary, and neonatal diseases and abnormalities, [SDV]Life Sciences [q-bio], nutritional and metabolic diseases, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, colorectal cancer, Article, digestive system diseases, [SDV] Life Sciences [q-bio], patient prognosis, mismatch repair, microsatellite instability, neoplasms, RIP140/NRIP1, RC254-282
Abstract: Simple Summary The alteration of mismatch repair (MMR) genes leads to microsatellite instability and plays a key role in colorectal cancer (CRC) pathogenesis and prognosis. The transcription factor NRIP1 is involved in intestinal tumorigenesis and is a good prognostic marker in CRC. In this study, we demonstrate that NRIP1 induces MSH2 and MSH6 MMR gene transcription and reduces microsatellite instability. A dominant-negative truncated NRIP1 mutant amplifies the MMR-deficient phenotype and appears as a key player in MSI-driven tumorigenesis since it significantly correlates with a short overall survival of patients with advanced CRC, especially MLH1-deficient ones. Abstract Microsatellite instability (MSI) is related to the alteration of mismatch repair (MMR) genes and plays a key role in colorectal cancer (CRC) pathogenesis. We previously reported that the transcription factor Nuclear Receptor Interacting Protein 1 (NRIP1) is involved in sporadic intestinal tumorigenesis. The aim of this study was to decipher its role in MSI CRC. By using different mouse models and engineered cell lines, we demonstrated that NRIP1 increased MSH2 and MSH6 MMR gene transcription and mRNA/protein levels. In human CRC cells, NRIP1 expression was associated with decreased MSI and the hypermutator phenotype, and with resistance to chemotherapy drugs. Using a cohort of 194 CRC patients, we detected in 22% of the cases a MSI-induced frameshift mutation in the NRIP1 coding sequence. This genetic alteration generates a truncated protein with a dominant negative activity that increased human CRC cell proliferation and impaired the regulation of MSH2 and MSH6 gene expression. Moreover, the NRIP1 mutant correlated with a decreased overall survival of patients with advanced CRC, especially when MLH1-deficient. By decreasing the expression of MSH2 and MSH6 gene expression, the NRIP1 variant may amplify MLH1-dependent CRC progression and behave as a new prognostic marker of advanced MSI CRC.
Published: 2021

41. Living Labs and other participatory approaches applied to research on multiple environnemental exposures and chronic risks

Author: Mariette Gerber, Yara Carrejo Gironza, Brigitte Trousse, Christian Mougin, Olivier Armant, Sylvie Bortoli, Sylvie Platel, Arthur David, Stéphanie Cormier, Sylvie Charron, Denis Bard, Simon Schraub, Alain Rannou, Olivier Laurent, Sonia Grimbuhler, Hélène Desqueyroux, Philippe Chamaret, Arnaud Vanzemberg, Sophie Ancelet, Lionel Larqué, Céline Boudet, Laurence Payrastre, Rodolphe Gilbin, Katia Baumgartner, Stéphane Grison, Laboratoire d épidémiologie des rayonnements ionisants (IRSN/PSE-SANTE/SESANE/LEPID), Service de recherche sur les effets biologiques et Sanitaires des rayonnements ionisants (IRSN/PSE-SANTE/SESANE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire d'écotoxicologie des radionucléides (IRSN/PRP-ENV/SERIS/LECO), Service de Recherche et d'Expertise sur les Risques environnementaux (IRSN/PRP-ENV/SERIS), Société francophone de santé environnement (SFSE), France Nature Environnement (FNE), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de l'Environnement Industriel et des Risques (INERIS), Institut Ecocitoyen pour la Connaissance des Pollutions [Fos-sur-Mer], Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria), 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 ), Laboratoire d'étude et de recherche en environnement et santé (LERES), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Santé Environnement Travail et Génie Sanitaire (DSETGS), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Association nationale des comités et commissions locales d'information [Teteghem] (ANCCLI), Information – Technologies – Analyse Environnementale – Procédés Agricoles (UMR ITAP), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - 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), Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PSE-SANTE/SESANE/LRTOX), ALLISS Sciences Sociétés [Paris], Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Service de la programmation, des partenariats, de la prospective et de l’appui à l’innovation (IRSN/DST/SP3IN), Direction de la Stratégie (IRSN/DST), Ligue Nationale Contre le Cancer - Paris, Ligue Nationale Contre le Cancer (LNCC), Centre Permanent d'Initiatives pour l'Environnement des Pays de l'Aisne (CPIE des Pays de l'Aisne), Service des politiques d’ouverture à la société (IRSN/DST/SPOS), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Laboratoire d'épidémiologie des rayonnements ionisants (LEPID), Laboratoire d'écotoxicologie des radionucléides (PRP-ENV/SERIS/LECO), Institut Ecocitoyen [Fos-sur-Mer] (IECP), 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 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Ligue Nationnale Contre le Cancer
Subjects: Multiple exposures, methods in environmental health research, [SDE]Environmental Sciences, General Earth and Planetary Sciences, Citizen journalism, Sociology, Living Lab, Environmental planning, co-creation, General Environmental Science
Abstract: International audience; BACKGROUND AND AIM: Participatory research in environmental health is still rare in France. The objectives of environmental health research, in general, can be very diverse (e.g.: identifying situations associated with risks estimating exposures and effects, testing the effectiveness of preventive actions) and related methods are diverse as well. Opportunities for greater implication of the civil society and related challenges differ at each step of research activities. These aspects need to be better known and shared collectively. The LILAS project aimed to 1) co-construct, among institutional researchers, academics and civil society representatives, a mutual understanding of the main problematics and research methods in environmental health, their stakes for different actors, but also the requirements, strengths and limitations of these methods 2) identify expected benefits and points of vigilance related to stronger degrees of participation as part of such environmental health research projects. METHODS: LILAS gathered institutional researchers, academics and civil society representatives interested in multiple exposures (chemical, radiological). Several meetings allowed to collectively identify different types of study (including environmental epidemiological studies) and reflect about the added value, limitations, and methodological principles related to the introduction of growing participation as part of such studies. An analysis matrix was co-created and filled by participants. RESULTS:For different types of studies (studies for assessment of environmental exposures, identification of their determinants, interventions on these exposures, development of sensors, quantitative risk assessment, environmental epidemiological studies, experimental research, studies on the health of ecosystems…), the matrix lists expected benefits for several categories of stakeholders, fundamental methodological principles and practical constraints, advantages and limitations related to the use of participatory approaches (such as the living lab one) or more “classical” approaches. CONCLUSIONS:LILAS has allowed, through a cross-acculturation process, to develop consolidated grounds for the co-construction of future participatory research projects on multiple environmental exposures.
Published: 2021

42. Transcription/Replication Conflicts in Tumorigenesis and Their Potential Role as Novel Therapeutic Targets in Multiple Myeloma

Author: Raphaël Rodriguez, Jérôme Moreaux, Yea-Lih Lin, Philippe Pasero, Malik Lutzmann, Laure Dutrieux, Michel Cogné, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Chimie biologique des membranes et ciblage thérapeutique (CBMCT - UMR 3666 / U1143), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), 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)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Lapeyronie [Montpellier] (CHU), Université Paul-Valéry - Montpellier 3 (UPVM), INCa (Institut National du Cancer)Institut National du Cancer (INCA) France [PLBIO18-362 PIT-MM, PLBIO19-098 INCA_13832], ANR (the French National Research Agency) under the \'Investissements d'avenir\' program [ANR-16-IDEX-0006], ANR French National Research Agency (ANR) [2017-CE15-002401, ANR-18-CE15-0010-01], SIRIC Montpellier Cancer [INCaDGOS-Inserm_12553], Labex EpiGenMed, Institut Universitaire de France, Ligue Nationale Contre le Cancer LNCC, Centre de recherche de l'Institut Curie [Paris], Institut Curie [Paris], Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Rennes (UR)-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 ), ANR-16-IDEX-0006,MUSE,MUSE(2016), ANR-18-CE15-0010,PLASMADIFF-3D,Rôle de l'organisation tridimensionnelle et de la dynamique de la chromatine au cours de la différenciation plasmocytaire(2018), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC), Rodriguez, Raphaël, MUSE - - MUSE2016 - ANR-16-IDEX-0006 - IDEX - VALID, and APPEL À PROJETS GÉNÉRIQUE 2018 - Rôle de l'organisation tridimensionnelle et de la dynamique de la chromatine au cours de la différenciation plasmocytaire - - PLASMADIFF-3D2018 - ANR-18-CE15-0010 - AAPG2018 - VALID
Subjects: 0301 basic medicine, Genome instability, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Cancer Research, transcription replication conflicts, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, medicine.disease_cause, plasma cells, 03 medical and health sciences, 0302 clinical medicine, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, stomatognathic system, Transcription (biology), [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Secretion, Gene, Multiple myeloma, RC254-282, biology, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, R-loops, medicine.disease, genomic instability, G-quadruplexes, 3. Good health, Cell biology, multiple myeloma, tumorigenesis, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, biology.protein, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Antibody, Carcinogenesis
Abstract: Simple Summary Multiple myeloma is a hematologic cancer characterized by the accumulation of malignant plasma cells in the bone marrow. It remains a mostly incurable disease due to the inability to overcome refractory disease and drug-resistant relapse. Oncogenic transformation of PC in multiple myeloma is thought to occur within the secondary lymphoid organs. However, the precise molecular events leading to myelomagenesis remain obscure. Here, we identified genes involved in the prevention and the resolution of conflicts between the replication and transcription significantly overexpressed during the plasma cell differentiation process and in multiple myeloma cells. We discussed the potential role of these factors in myelomagenesis and myeloma biology. The specific targeting of these factors might constitute a new therapeutic strategy in multiple myeloma. Abstract Plasma cells (PCs) have an essential role in humoral immune response by secretion of antibodies, and represent the final stage of B lymphocytes differentiation. During this differentiation, the pre-plasmablastic stage is characterized by highly proliferative cells that start to secrete immunoglobulins (Igs). Thus, replication and transcription must be tightly regulated in these cells to avoid transcription/replication conflicts (TRCs), which could increase replication stress and lead to genomic instability. In this review, we analyzed expression of genes involved in TRCs resolution during B to PC differentiation and identified 41 genes significantly overexpressed in the pre-plasmablastic stage. This illustrates the importance of mechanisms required for adequate processing of TRCs during PCs differentiation. Furthermore, we identified that several of these factors were also found overexpressed in purified PCs from patients with multiple myeloma (MM) compared to normal PCs. Malignant PCs produce high levels of Igs concomitantly with cell cycle deregulation. Therefore, increasing the TRCs occurring in MM cells could represent a potent therapeutic strategy for MM patients. Here, we describe the potential roles of TRCs resolution factors in myelomagenesis and discuss the therapeutic interest of targeting the TRCs resolution machinery in MM.
Published: 2021

43. Role of DNA Repair Variants and Diagnostic Radiology Exams in Differentiated Thyroid Cancer Risk: A Pooled Analysis of Two Case–Control Studies

Author: Carole Rubino, Pascal Guénel, Emilie Cordina-Duverger, Françoise Borson-Chazot, Vincent Souchard, Pierre Laurent-Puig, Florent de Vathaire, Thérèse Truong, Julie Guibon, Anne-Valérie Guizard, Mojgan Karimi, Elizabeth Adjadj, Catherine Ory, Hélène Blanché, Jean-Baptiste Cazier, Sylvie Chevillard, Martin Schlumberger, Constance Xhaard, Claire Schvartz, Yan Ren, Fabienne Lesueur, Jean-François Deleuze, Anne Boland, Mohammed Zakarya Zemmache, Sandra Canale, Eugènia Mariné Barjoan, Claire Mulot, Monia Zidane, Université Paris-Sud - Paris 11 (UP11), Institut Gustave Roussy (IGR), 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, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Université Paris-Saclay, Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Fondation Jean Dausset - Centre d’Etudes du Polymorphisme Humain [Paris] (CEPH), Laboratory of Excellence GENMED (Medical Genomics), Laboratoire de Cancérologie Expérimentale (LCE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut de Biologie François JACOB (JACOB), 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), Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), Service de Radobiologie Expérimentale et Innovation Technologique (SREIT), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), 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)), 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), Institut Jean Godinot [Reims], UNICANCER, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), 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 Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Epigenetec, Centre de Ressources Biologiques (CRB), Université Sorbonne Paris Cité (USPC), Université Paris Descartes - Paris 5 (UPD5), University of Birmingham [Birmingham], FDV received the following grants as principal investigator of Young-Thyr study: Fondation de France (Grant number 65391), L'Alliance pour les sciences de la vie et de la santé, « AVIESAN » (Grants number ENV201416 and 2007005070), the Ligue Nationale Contre le Cancer (LNCC) (Grants number EPDAC6036, EPDTP6004, R10127LL).TT received the following grants for CATHY 470 and Young-Thyr studies genotyping Institut National du Cancer (Grant number 9533), the ARC foundation (Grant number PGA120150202302) MZ performed this work during her PhD funded by Ecole des Hautes Etudes en Santé Publique (EHESP) and the ARC Foundation (Grant number ARCDOC42020070002532)., Université Paris Sud Orsay, Inserm, U900, Institut Curie, Université PSL, Mines ParisTech, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, and BOZEC, Erwan
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Neoplasms, Radiation-Induced, Adolescent, DNA Repair, Epidemiology, DNA repair, Thyroid Gland, Single-nucleotide polymorphism, Logistic regression, Polymorphism, Single Nucleotide, Risk Assessment, 03 medical and health sciences, Young Adult, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, Genetic predisposition, Biomarkers, Tumor, Humans, Genetic Predisposition to Disease, Thyroid Neoplasms, Child, Thyroid cancer, Aged, Aged, 80 and over, business.industry, Thyroid, Case-control study, Dose-Response Relationship, Radiation, Middle Aged, medicine.disease, Confidence interval, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Case-Control Studies, Female, Radiology, France, business
Abstract: Background: Given the increased use and diversity of diagnostic procedures, it is important to understand genetic susceptibility to radiation-induced thyroid cancer. Methods: On the basis of self-declared diagnostic radiology examination records in addition to existing literature, we estimated the radiation dose delivered to the thyroid gland from diagnostic procedures during childhood and adulthood in two case–control studies conducted in France. A total of 1,071 differentiated thyroid cancer (DTC) cases and 1,188 controls from the combined studies were genotyped using a custom-made Illumina OncoArray DNA chip. We focused our analysis on variants in genes involved in DNA damage response and repair pathways, representing a total of 5,817 SNPs in 571 genes. We estimated the OR per milli-Gray (OR/mGy) of the radiation dose delivered to the thyroid gland using conditional logistic regression. We then used an unconditional logistic regression model to assess the association between DNA repair gene variants and DTC risk. We performed a meta-analysis of the two studies. Results: The OR/mGy was 1.02 (95% confidence interval, 1.00–1.03). We found significant associations between DTC and rs7164173 in CHD2 (P = 5.79 × 10−5), rs6067822 in NFATc2 (P = 9.26 × 10−5), rs1059394 and rs699517 both in ENOSF1/THYS, rs12702628 in RPA3, and an interaction between rs7068306 in MGMT and thyroid radiation doses (P = 3.40 × 10−4). Conclusions: Our results suggest a role for variants in CDH2, NFATc2, ENOSF1/THYS, RPA3, and MGMT in DTC risk. Impact: CDH2, NFATc2, ENOSF1/THYS, and RPA3 have not previously been shown to be associated with DTC risk.
Published: 2021

44. A Recurrent Activating Missense Mutation in Waldenström Macroglobulinemia Affects the DNA Binding of the ETS Transcription Factor SPI1 and Enhances Proliferation

Author: Nathalie Droin, Philippe Rameau, Philippe Dessen, Florence Nguyen-Khac, Bilyana Stoilova, Elena Mylonas, Marine Armand, Damien Roos-Weil, Olivier Bernard, Els Verhoeyen, Paresh Vyas, Said Aoufouchi, Marlen Metzner, Françoise Pflumio, Frédéric Charlotte, Vincent Ribrag, Diane Lara, Olivier Elemento, Pierre Morel, Eric Durot, Cécile Hérate, Pascale Cornillet-Lefebvre, Véronique Della-Valle, Hussein Ghamlouch, Virginie Ropars, Frederik Damm, Nabih Azar, Christel Guillouf, François-Loïc Cosset, Camille Decaudin, Valérie Camara-Clayette, M'Boyba Diop, Veronique Leblond, Thomas Mercher, Jean-Baptiste Charbonnier, Rima Haddad, Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Enveloppe Nucléaire, Télomères et Réparation de l’ADN (INTGEN), Département Biochimie, Biophysique et Biologie Structurale (B3S), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation (MHH), Hannover Medical School [Hannover] (MHH), CEA Direction des Sciences du Vivant (CEA/DSV), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), The Weatherall Institute of Molecular Medicine, University of Oxford [Oxford], Weill Medical College of Cornell University [New York], Institut Gustave Roussy (IGR), Plateforme de Bioinformatique [Gustave Roussy], Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de recherche translationnelle (Labo RT), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS 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 Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Département d'hématologie [Gustave Roussy], Laboratoire d'hématologie, Centre Hospitalier Universitaire de Reims (CHU Reims), Plateforme imagerie et cytométrie (PFIC), Ligue Nationale Contre le Cancer - Paris, Ligue Nationale Contre le Cancer (LNCC), Brigham and Women's Hospital [Boston], Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], 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), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (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)-Sorbonne Université (SU), Ligue Nationnale Contre le Cancer, Centre de Recherche et d'Etude en Droit et Science Politique (CREDESPO), Université de Bourgogne (UB), University of Oxford, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and École Pratique des Hautes Études (EPHE)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Mutation, Missense, lymphoma, Biology, Cell Line, Mice, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Mutant protein, Proto-Oncogene Proteins, spi-1/pu.1, pu.1, Animals, Humans, somatic mutation, Nucleotide Motifs, Lenalidomide, Transcription factor, mouse, Cell Proliferation, cll, B-Lymphocytes, Binding Sites, SPI1, Base Sequence, Proto-Oncogene Proteins c-ets, Point mutation, ETS transcription factor family, Promoter, Azepines, Triazoles, Cell biology, cell differentiation, 030104 developmental biology, Gene Expression Regulation, Oncology, 030220 oncology & carcinogenesis, Myeloid Differentiation Factor 88, Trans-Activators, acute myeloid-leukemia, Waldenstrom Macroglobulinemia, Transcription Factor Gene, Protein Binding, Transcription Factors
Abstract: The ETS-domain transcription factors divide into subfamilies based on protein similarities, DNA-binding sequences, and interaction with cofactors. They are regulated by extracellular clues and contribute to cellular processes, including proliferation and transformation. ETS genes are targeted through genomic rearrangements in oncogenesis. The PU.1/SPI1 gene is inactivated by point mutations in human myeloid malignancies. We identified a recurrent somatic mutation (Q226E) in PU.1/SPI1 in Waldenström macroglobulinemia, a B-cell lymphoproliferative disorder. It affects the DNA-binding affinity of the protein and allows the mutant protein to more frequently bind and activate promoter regions with respect to wild-type protein. Mutant SPI1 binding at promoters activates gene sets typically promoted by other ETS factors, resulting in enhanced proliferation and decreased terminal B-cell differentiation in model cell lines and primary samples. In summary, we describe oncogenic subversion of transcription factor function through subtle alteration of DNA binding leading to cellular proliferation and differentiation arrest. Significance: The demonstration that a somatic point mutation tips the balance of genome-binding pattern provides a mechanistic paradigm for how missense mutations in transcription factor genes may be oncogenic in human tumors. This article is highlighted in the In This Issue feature, p. 681
Published: 2019

45. HPV-circulating tumoural DNA by droplet-based digital polymerase chain reaction, a new molecular tool for early detection of HPV metastatic anal cancer? A case report

Author: Laure Gibault, David Veyer, Marie-Laure Lucas, Hélène Péré, Laurence Weiss, Valérie Taly, Sonia Garrigou, Marion Mandavit, Juliette Pavie, Simon Pernot, Laboratoire de Virologie [Hôpital Européen Georges Pompidou - APHP], 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'Immunologie Clinique [Hôpital Européen Georges Pompidou - APHP], Unité Fonctionnelle de Pharmacogénétique et Oncologie Moléculaire [AP-HP Hôpital Européen Georges Pompidou] (Service de Biochimie), 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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Sorbonne Université (SU), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe labellisée Ligue contre le Cancer, Service d'Anatomo-cytopathologie [Hôpital Européen Georges Pompidou - APHP], Université Paris Descartes - Paris 5 (UPD5), This work was supported by the Assistance Publique Hopitaux de Paris (AP-HP), Ministère de l’Enseignement Supérieur et de la Recherche, the Université Paris-Descartes, the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Santé et de la Recherche Médicale (INSERM), the SIRIC CARPEM and the ligue nationale contre le cancer (LNCC, Program 'Equipe labelise´e LIGUE', no. EL2016.LNCC/VaT)., and TALY, Valerie
Subjects: Cancer Research, [SDV]Life Sciences [q-bio], HPV ctDNA, Early detection, [SDV.CAN]Life Sciences [q-bio]/Cancer, Metastasis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, HGAIN, Medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Digital polymerase chain reaction, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, business.industry, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Oncology, chemistry, 030220 oncology & carcinogenesis, Cancer research, Droplet-based digital PCR, business, Metastatic anal cancer, DNA
Abstract: International audience; no abstract
Published: 2019

46. Apport de la génomique dans la médecine de demain, applications cliniques et enjeux

Author: Lionel Perrier, Guillaume Grenet, Bruno Laviolle, Florence Gaillard-Bigot, Pascal Bilbault, Olivier Perche, Hélène Espérou, Jean-François Guérin, Julia Morere, Julien Thevenon, Caroline Guillot, Élodie Bégué, François Gueyffier, Damien Sanlaville, Pierre-Henry Longeray, Nathalie Varoqueaux, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine Laennec, Université de Lyon, Lyon, France., Ligue Nationale Contre le Cancer - Paris, Ligue Nationale Contre le Cancer (LNCC), The Lymphoma Academic Research Organisation [Lyon] (LYSARC), Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire (HP2 ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hospices Civils de Lyon, Departement de Neurologie (HCL), Pfizer Oncology, Fédération française des diabétiques, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Groupe d'Analyse et de Théorie Economique Lyon - Saint-Etienne (GATE Lyon Saint-Étienne), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Centre hospitalier universitaire de Grenoble (CHU de Grenoble), CHU Grenoble, Roche SAS, Neuilly-sur-Seine, France, Laboratoire Roche SAS, AstraZeneca, 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), Ligue Nationnale Contre le Cancer, Hypoxie et physiopathologies cardiovasculaire et respiratoire, Groupe d'analyse et de théorie économique (GATE Lyon Saint-Étienne), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), and Dao, Taï
Subjects: Thérapeutique, [QFIN]Quantitative Finance [q-fin], [SDV]Life Sciences [q-bio], Questions éthiques, Médecine personnalisée, 030226 pharmacology & pharmacy, [QFIN] Quantitative Finance [q-fin], Séquençage du génome entier, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Pronostic, Pharmacology (medical), Diagnostic
Abstract: International audience; Le séquençage du génome est aujourd’hui accessible à la population mais il n’existe que peu de preuves de son utilité comme outil diagnostique, thérapeutique et pronostique. En France, le plan France médecine génomique 2025 a été lancé en 2015 avec pour objectif d’intégrer les analyses génomiques dans la pratique clinique pour des indications validées et de développer une filière nationale de la médecine génomique incluant des partenariats industriels. Une réflexion sur les applications scientifiques et les enjeux opérationnels et sociétaux est nécessaire afin de formuler des recommandations pour permettre de mieux associer la génomique et la médecine de demain. Dans la perspective d’une médecine factuelle personnalisée, il convient de promouvoir des études avec un niveau d’exigence méthodologique approprié et d’approfondir la définition du niveau de preuve. Les nombreux enjeux opérationnels nécessitent de mettre en place des organisations et des moyens afin de fluidifier le circuit de rendu des résultats ainsi que des adaptations réglementaires sur les statuts des professions impliquées, la gestion des données générées et le consentement des patients. En parallèle des actions de formation en génétique à destination des professionnels de santé et des actions de sensibilisation sur les tests génétiques vis-à-vis du grand public doivent être envisagées. Les enjeux éthiques doivent également être pris en compte, notamment sur la participation du patient aux décisions le concernant en fonction de ses attentes et en intégrant la notion d’incertitude dans l’information délivrée. Les effets sociologiques sur le vécu et les attentes des patients et de la population générale vis-à-vis de la médecine génomique doivent également être évalués pour améliorer l’information, la prévention et l’accompagnement des personnes. Enfin, des études médicoéconomiques doivent être conduites pour éclairer les décideurs sur le caractère coût-efficace du séquençage complet du génome pour la santé des populations.
Published: 2019

47. Telomerase Activation and ATRX Mutations Are Independent Risk Factors for Metastatic Pheochromocytoma and Paraganglioma

Author: Charles Lépine, Annabelle Venisse, Sylvie Job, Mathilde Sibony, Tchao Meatchi, Estelle Robidel, Jérôme Cros, Alexandre Buffet, Judith Favier, Nelly Burnichon, Luis Jaime Castro-Vega, Virginie Verkarre, Anne-Paule Gimenez-Roqueplo, Laurence Amar, Aurélien de Reyniès, Arturo Londoño-Vallejo, Irena Draskovic, Jérôme Bertherat, Ligue Nationale Contre le Cancer - Paris, Ligue Nationnale Contre le Cancer, Université Pierre et Marie Curie - Paris 6 (UPMC), Service Genetique, 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire électrotechnique et électronique industrielle (LEEI), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire de Recherche en Imagerie : Méthodes d'imagerie des Échanges transcapillaires (LRI - EA4062), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], 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), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Faculté de Médecine, Université de Ngozi, Ligue Nationale Contre le Cancer (LNCC), Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, X-linked Nuclear Protein, Cancer Research, Telomerase, SDHB, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pheochromocytoma, Neuroendocrine tumors, medicine.disease_cause, Paraganglioma, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Promoter Regions, Genetic, ComputingMilieux_MISCELLANEOUS, ATRX, Neoplasm Staging, Mutation, Whole Genome Sequencing, business.industry, DNA Methylation, Prognosis, medicine.disease, Telomere, Enzyme Activation, Cell Transformation, Neoplastic, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, DNA methylation, Cancer research, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Purpose: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors. Whereas most PPGLs are benign, up to 20% may become metastatic with SDHB- and FH-mutated tumors showing the higher risk. We aimed at determining the contribution of immortalization mechanisms to metastatic progression. Experimental Design: Immortalization mechanisms were investigated in 200 tumors. To identify telomerase (+) tumors, we analyzed genomic alterations leading to transcriptional activation of TERT comprising promoter mutations, hypermethylation and gain copy number. To identify tumors that activated the alternative lengthening of telomere (ALT) mechanism, we combined analyses of telomere length by slot blot, telomere heterogeneity by telomere FISH, and ATRX mutations by next-generation sequencing. Univariate/multivariate and metastasis-free survival (MFS) and overall survival (OS) analyses were carried out for assessment of risk factors and clinical outcomes. Results: Only 37 of 200 (18.5%) tumors achieved immortalization. Telomerase activation occurred in 12 metastatic tumors and was prevalent in SDHB-mutated paragangliomas (P = 2.42e−09). ALT features were present in 25 tumors, mostly pheochromocytomas, regardless of metastatic status or molecular group (P = 0.169), yet ATRX mutations were found preferentially in SDHB/FH-mutated metastatic tumors (P = 0.0014). Telomerase activation and ATRX mutations were independent factors of poor prognosis: MFS (hazard ratio, 48.2 and 33.1; P = 6.50E−07 and 1.90E−07, respectively); OS (hazard ratio, 97.4 and 44.1; P = 4.30E−03 and 2.00E−03, respectively) and were associated with worse MFS and OS (log-rank tests P < 0.0001). Conclusions: Assessment of telomerase activation and ATRX mutations could be used to identify metastatic PPGLs, particularly in tumors at high risk of progression.
Published: 2019

48. Multifaceted modes of action of the anticancer probiotic Enterococcus hirae

Author: Marion Leduc, Didier Raoult, Laura Mondragón, Kristina Iribarren, Anne-Gaëlle Goubet, Diane Derrien, Satoru Yonekura, Noélie Bossut, Valerio Iebba, Nicola Segata, Guo Chen, Ivo G. Boneca, Lisa Derosa, Adrien Joseph, Fabrice Andre, Sylvère Durand, Aurélie Fluckiger, Maryam Tidjani Alou, Fanny Aprahamian, Richard J. Wheeler, Maryse Moya-Nilges, Eugenie Pizzato, Bo Qu, Guido Kroemer, Oliver Kepp, Nicolas Pons, Romain Daillère, Fabien Lemaitre, Laurence Zitvogel, Department of Radiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France, Faculté de Médecine Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Shanghai Jiao Tong University [Shanghai], Institut Gustave Roussy (IGR), 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 de Paris (UP), Ligue Nationale Contre le Cancer - Paris, Ligue Nationnale Contre le Cancer, UMR 1015 Immunologie des tumeurs et immunothérapie contre le cancer (ITIC), Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform (UTechS UBI), Institut Pasteur [Paris], MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Trento [Trento], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), 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), Karolinska University Hospital [Stockholm], Fondation pour la Recherche Médicale, Ligue contre le Cancer (équipes labellisées), Leducq Foundation, Seerave Foundation, SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), SIRIC Cancer Research and Personalized Medicine (CARPEM), Fondation ARC pour la Recherche sur le Cancer, Région Ile-de-France, Chancellerie des universités de Paris (Legs Poix), FRM, European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR), Gustave Roussy Odyssea, Fondation Carrefour, High-end Foreign Expert Program in China: GDW20171100085 and GDW20181100051, Institut National du Cancer (INCA) France, Inserm (HTE), Institut Universitaire de France, ANR-10-COHO-0004,CANTO,Etude des toxicités chroniques des traitements anticancéreux chez les patientes porteuses cancer(2010), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), European Project: 680969,H2020,H2020-HCO-2015,ERA-CVD(2015), European Project: 825410, H2020-EU.3.1., H2020-EU.3.1.2.,ONCOBIOME (2019), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), 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), Ligue Nationale Contre le Cancer (LNCC), Institut Pasteur [Paris] (IP), Université Paris Cité (UPCité), Goubet, A. -G., Wheeler, R., Fluckiger, A., Qu, B., Lemaitre, F., Iribarren, K., Mondragon, L., Tidjani Alou, M., Pizzato, E., Durand, S., Derosa, L., Aprahamian, F., Bossut, N., Moya-Nilges, M., Derrien, D., Chen, G., Leduc, M., Joseph, A., Pons, N., Le Chatelier, E., Segata, N., Yonekura, S., Iebba, V., Kepp, O., Raoult, D., Andre, F., Kroemer, G., Boneca, I. G., Zitvogel, L., Daillere, R., 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 (UPC), Université Paris Cité (UPC), Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Université Paris-Saclay, Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), and European Project: 825410,ONCOBIOME
Subjects: 0301 basic medicine, medicine.medical_treatment, [SDV]Life Sciences [q-bio], microbiome, law.invention, Probiotic, Mice, 0302 clinical medicine, Cancer immunotherapy, Enterococcus hirae, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Neoplasms, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, CD137, 3. Good health, Bifidobacterium animalis, Anti-Bacterial Agents, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, immunotherapy, Immunotherapy, microbiota, cancer, tumor, probiotic, intratumoral IFNγ, Biology, Article, Microbiology, 03 medical and health sciences, Memory T Cells, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, Animals, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Microbiome, Molecular Biology, Probiotics, Autophagy, Cell Biology, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Gastrointestinal Microbiome, Mice, Inbred C57BL, 030104 developmental biology, Dysbiosis
Abstract: International audience; A deviated repertoire of the gut microbiome predicts resistance to cancer immunotherapy. Enterococcus hirae compensated cancer-associated dysbiosis in various tumor models. However, the mechanisms by which E. hirae restored the efficacy of cyclophosphamide administered with concomitant antibiotics remain ill defined. Here, we analyzed the multifaceted modes of action of this anticancer probiotic. Firstly, E. hirae elicited emigration of thymocytes and triggered systemic and intratumoral IFN gamma-producing and CD137-expressing effector memory T cell responses. Secondly, E. hirae activated the autophagy machinery in enterocytes and mediated ATG4B-dependent anticancer effects, likely as a consequence of its ability to increase local delivery of polyamines. Thirdly, E. hirae shifted the host microbiome toward a Bifidobacteria-enriched ecosystem. In contrast to the live bacterium, its pasteurized cells or membrane vesicles were devoid of anticancer properties. These pleiotropic functions allow the design of optimal immunotherapies combining E. hirae with CD137 agonistic antibodies, spermidine, or Bifidobacterium animalis. We surmise that immunological, metabolic, epithelial, and microbial modes of action of the live E. hirae cooperate to circumvent primary resistance to therapy.
Published: 2021

49. Living Labs et autres approches participatives appliquées à la recherche sur les multi-expositions environnementales et les risques chroniques

Author: Olivier Laurent, Yara Carrejo Gironza, Sophie Ancelet, Olivier Armant, Denis Bard, Katia Baumgartner, Sylvie Bortoli, Céline Boudet, Philippe Chamaret, Michel Chartier, Stéphanie Cormier, Arthur David, Hélène Desqueyroux, Mariette Gerber, Rodolphe Gilbin, Sonia Grimbuhler, Stéphane Grison, Lionel Larqué, Dominique Laurier, Christian Mougin, Laurence Gamet-Payrastre, Sylvie Platel, Alain Rannou, Pascale Scanff, Arnaud Vanzemberg, Simon Schraub, Sylvie Supervil, Eric Thybaud, Brigitte Trousse, Sylvie Charron, Laboratoire d'épidémiologie des rayonnements ionisants (LEPID), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire d'écotoxicologie des radionucléides (PRP-ENV/SERIS/LECO), Société francophone de santé environnement (SFSE), France Nature Environnement (FNE), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de l'Environnement Industriel et des Risques (INERIS), Institut Ecocitoyen pour la Connaissance des Pollutions [Fos-sur-Mer], Laboratoire d'étude et d'expertise sur la radioactivité de l'environnement [Saint-Paul-Lez-Durance] (PSE-ENV/SEREN/LEREN), Centre Permanent d'Initiatives pour l'Environnement des Pays de l'Aisne (CPIE des Pays de l'Aisne), Institut de recherche en santé, environnement et travail (Irset), 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 ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Association nationale des comités et commissions locales d'information [Teteghem] (ANCCLI), Information – Technologies – Analyse Environnementale – Procédés Agricoles (UMR ITAP), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de radiotoxicologie et radiobiologie expérimentale (LRTOX), ALLISS Sciences Sociétés [Paris], Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-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-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ligue Nationale Contre le Cancer - Paris, Ligue Nationnale Contre le Cancer, Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria), France Living Labs, IRSN2030, Institut de Radioprotection et de Sûreté Nucléaire, Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-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 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 d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire d épidémiologie des rayonnements ionisants (IRSN/PSE-SANTE/SESANE/LEPID), Service de recherche sur les effets biologiques et Sanitaires des rayonnements ionisants (IRSN/PSE-SANTE/SESANE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire d'écotoxicologie des radionucléides (IRSN/PSE-ENV/SRTE/LECO), Service de recherche sur les transferts et les effets des radionucléides sur les écosystèmes (IRSN/PSE-ENV/SRTE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire d'étude et d'expertise sur la radioactivité de l'environnement (IRSN/PSE-ENV/SEREN/LEREN), Service d'expertise et d'étude en radioprotection des populations et de la radioactivité dans l'environnement (IRSN/PSE-ENV/SEREN), 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 ), Laboratoire d'étude et de recherche en environnement et santé (LERES), Département Santé Environnement Travail et Génie Sanitaire (DSETGS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - 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), Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PSE-SANTE/SESANE/LRTOX), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pôle Santé Environnement - Direction Santé (IRSN/PSE-SANTE), Direction Déléguée Développement numérique et aux systèmes d’information (IRSN/DTR/D3NSI), Service de la programmation, des partenariats, de la prospective et de l’appui à l’innovation (IRSN/DST/SP3IN), Direction de la Stratégie (IRSN/DST), Ligue Nationale Contre le Cancer (LNCC), Direction des Risques et de la Performance (IRSN/DRP), Service des politiques d’ouverture à la société (IRSN/DST/SPOS), and Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN)
Subjects: Recherches participatives, Méthodes en santé-environnement, [SHS.ENVIR]Humanities and Social Sciences/Environmental studies, [SDV]Life Sciences [q-bio], Grille d’analyse, Multi-expositions, Living Lab, Co-construction, [SHS]Humanities and Social Sciences
Abstract: Contexte Les recherches participatives en santé-environnement restent peu développées en France. Les objectifs poursuivis de manière générale par les recherches en santé-environnement (ex : identifier des situations potentiellement à risque, estimer des expositions, évaluer des effets, tester des actions préventives) et les méthodes employées à ces fins sont variés. Les opportunités d’une plus grande implication de la société civile et défis associés diffèrent à chaque étape de ces recherches. Ces aspects demandent à être mieux appréhendés collectivement. Le projet LILAS vise, en amont du développement de futurs projets de recherches participatives sur les multi-expositions environnementales, à 1) co-construire, entre chercheurs institutionnels, académiques et représentants de la société civile, une bonne compréhension commune des principales problématiques et méthodes de recherche en santé-environnement, de leurs enjeux, prérequis, forces et limites 2) identifier les bénéfices et points de vigilance liés à l’introduction de plus fortes dimensions participatives dans ces recherches. Méthode adoptéeLe projet LILAS a rassemblé des chercheurs institutionnels, académiques et représentants de la société civile intéressés par les multi-expositions (chimiques, radiologiques). Une recherche bibliographique a été initiée pour tirer le retour d’expérience de projets de recherches participatives en santé-environnement. Plusieurs réunions ont permis d’identifier collectivement différents types d’études et de réfléchir sur les apports, limites et principes méthodologiques relatifs à l’introduction de différents degrés de participation dans celles-ci. Une matrice d’analyse a été co-construite puis alimentée par les participants, en s’inspirant des approches « Living Lab ».Résultats Pour différents types d’études (études d’évaluations d’expositions, d’identification de leurs déterminants, tests d’interventions sur ceux-ci, développement de capteurs, évaluations de risques sanitaires, études épidémiologiques, recherches expérimentales, études sur la santé des écosystèmes…), la matrice liste les bénéfices attendus pour plusieurs catégories de parties prenantes, les principes méthodologiques fondamentaux et contraintes pratiques, les avantages et limites relatifs à l’emploi d’approches participatives (comme l’approche Living Lab) ou plus “classiques”, mais également les besoins d’accompagnements institutionnels et les effets structurants nécessaires à leur déploiement et leur amélioration qualitative.Conclusion LILAS a permis, par acculturation croisée, de poser des bases consolidées pour la co-construction de futurs projets de recherches participatives sur les multi-expositions environnementales.
Published: 2021

50. Integrative study of diet-induced mouse models of NAFLD identifies PPARα as a sexually dimorphic drug target

Author: Françoise Lenfant, Anne Fougerat, Cheng Zhang, Laurence Gamet-Payrastre, Marion Régnier, Maeva Guillaume, Lorraine Smith, Thierry Levade, Arnaud Polizzi, Yannick Lippi, Caroline Sommer, Marine Huillet, Talal Al Saati, Hervé Guillou, Sandrine Lagarrigue, Sarra Smati, Nicolas Loiseau, Jinghong Wan, Catherine Postic, Yuna Blum, Alain Marrot, Adil Mardinoglu, Tiffany Fougeray, Muhammad Arif, Walter Wahli, Blandine Tramunt, Christophe Bureau, Patricia Dubot, Pierre Gourdy, Sandrine Ellero-Simatos, Céline Lukowicz, Alexandra Montagner, Frédéric Lasserre, Rémy Burcelin, Aurélie Batut, Claire Naylies, Jean-François Arnal, Alexia Laroyenne, Nathalie Hennuyer, Sophie Lotersztajn, Justine Bertrand-Michel, Bart Staels, Jean-Philippe Pradère, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-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-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Transcriptomic impact of Xenobiotics (E23 TRiX), Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Royal Institute of Technology [Stockholm] (KTH ), ANEXPLO, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Lab Excellence Inflamex (CRI INSERM U1149 - Bichat Medical Faculty), Université Paris Diderot - Paris 7 (UPD7), Plateforme Ezop (Ezop), Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, 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), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Lee Kong Chian School of Medicine, Nanyang Technological University [Singapour], Université de Lausanne (UNIL), CHU Toulouse [Toulouse], ANR-20-CE14-0035-04, Agence Nationale de la Recherche, FATMAL, Joint Programming Initiative A healthy diet for a healthy life, N/A, Institut National de la Santé et de la Recherche Médicale, N/A, Société Française de Nutrition, N/A, Société Francophone du Diabète, N/A, Société Nationale Française de Gastro-Entérologie, N/A, Association Française pour l'Etude du Foie, N/A, Région Occitanie, N/A, Agreenskills, ANR-17-CE14-0035,PUSHUPS,Etude de la dysfonction des cellules souches musculaires au cours du sepsis(2017), LESUR, Hélène, Etude de la dysfonction des cellules souches musculaires au cours du sepsis - - PUSHUPS2017 - ANR-17-CE14-0035 - AAPG2017 - VALID, Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Ligue Nationale Contre le Cancer (LNCC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Rennes Angers, Université de Lausanne = University of Lausanne (UNIL), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-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 des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), AGROCAMPUS OUEST, 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Nanyang Technological University (NTU), Hôpital de Rangueil, Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), and Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Peroxisome proliferator-activated receptor, Biology, Diet, High-Fat, Transcriptome, Mice, 03 medical and health sciences, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Fibrosis, Internal medicine, lipid metabolism, medicine, Metabolome, Animals, Humans, PPAR alpha, nonalcoholic steatohepatitis, liver metabolism, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Fatty liver, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Lipid metabolism, Lipidome, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Mice, Inbred C57BL, [SDV] Life Sciences [q-bio], Gene expression profiling, Disease Models, Animal, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, Liver, chemistry, gene expression, Female, 030211 gastroenterology & hepatology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: ObjectiveWe evaluated the influence of sex on the pathophysiology of non-alcoholic fatty liver disease (NAFLD). We investigated diet-induced phenotypic responses to define sex-specific regulation between healthy liver and NAFLD to identify influential pathways in different preclinical murine models and their relevance in humans.DesignDifferent models of diet-induced NAFLD (high-fat diet, choline-deficient high-fat diet, Western diet or Western diet supplemented with fructose and glucose in drinking water) were compared with a control diet in male and female mice. We performed metabolic phenotyping, including plasma biochemistry and liver histology, untargeted large-scale approaches (liver metabolome, lipidome and transcriptome), gene expression profiling and network analysis to identify sex-specific pathways in the mouse liver.ResultsThe different diets induced sex-specific responses that illustrated an increased susceptibility to NAFLD in male mice. The most severe lipid accumulation and inflammation/fibrosis occurred in males receiving the high-fat diet and Western diet, respectively. Sex-biased hepatic gene signatures were identified for these different dietary challenges. The peroxisome proliferator-activated receptor α (PPARα) co-expression network was identified as sexually dimorphic, and in vivo experiments in mice demonstrated that hepatocyte PPARα determines a sex-specific response to fasting and treatment with pemafibrate, a selective PPARα agonist. Liver molecular signatures in humans also provided evidence of sexually dimorphic gene expression profiles and the sex-specific co-expression network for PPARα.ConclusionsThese findings underscore the sex specificity of NAFLD pathophysiology in preclinical studies and identify PPARα as a pivotal, sexually dimorphic, pharmacological target.Trial registration numberNCT02390232.
Published: 2021

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