Search

Your search keyword '"Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)"' showing total 3,600 results
Start Over Author "Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)"
3,600 results on '"Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)"'

1. Oncolytic attenuated measles virus encoding NY-ESO-1 induces HLA I and II presentation of this tumor antigen by melanoma and dendritic cells

Author

Grard, Marion, Idjellidaine, Mohamed, Arbabian, Atousa, Chatelain, Camille, Berland, Laurine, Combredet, Chantal, Dutoit, Soizic, Deshayes, Sophie, Dehame, Virginie, Labarrière, Nathalie, Fradin, Delphine, Boisgerault, Nicolas, Blanquart, Christophe, Tangy, Frédéric, Fonteneau, Jean-François, LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Laboratoire d’innovation : vaccins – Innovation lab : vaccines, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), This work was supported by 'La Ligue Régionale Grand Ouest contre le Cancer' (CD16, CD22, CD44, CD49, CD72, CD79 and CD85), 'l’association ARSMESO44', 'la Fondation ARC (PJA 20191209661)', 'l’Agence Nationale pour la Recherche (ANR-16-CE18-0016)', and 'LabEX IGO' program supported by the National Research Agency via the investment of the future program ANR-11-LABX-0016–01'., ANR-16-CE18-0016,OncoMeVax,Un virus de la rougeole modifié pour traiter le cancer(2016), and ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011)

Subjects
[SDV]Life Sciences [q-bio], [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology
Abstract

International audience; Antitumor virotherapy stimulates the antitumor immune response during tumor cell lysis induced by oncolytic viruses (OVs). OV can be modified to express additional transgenes that enhance their therapeutic potential. In this study, we armed the spontaneously oncolytic Schwarz strain of measles viruses (MVs) with the gene encoding the cancer/testis antigen NY-ESO-1 to obtain MVny. We compared MV and MVny oncolytic activity and ability to induce NY-ESO-1 expression in six human melanoma cell lines. After MVny infection, we measured the capacity of melanoma cells to present NY-ESO-1 peptides to CD4 + and CD8 + T cell clones specific for this antigen. We assessed the ability of MVny to induce NY-ESO-1 expression and presentation in monocyte-derived dendritic cells (DCs). Our results show that MVny and MV oncolytic activity are similar with a faster cell lysis induced by MVny. We also observed that melanoma cell lines and DC expressed the NY-ESO-1 protein after MVny infection. In addition, MVny-infected melanoma cells and DCs were able to stimulate NY-ESO-1-specific CD4 + and CD8 + T cells. Finally, MVny was able to induce DC maturation. Altogether, these results show that MVny could be an interesting candidate to stimulate NY-ESO-1-specific T cells in melanoma patients with NY-ESO-1-expressing tumor cells.

Published
2023

2. Bi-allelic variants in DOHH, catalyzing the last step of hypusine biosynthesis, are associated with a neurodevelopmental disorder

Author

Ziegler, Alban, Steindl, Katharina, Hanner, Ashleigh S, Kumar Kar, Rajesh, Prouteau, Clément, Boland, Anne, Deleuze, Jean Francois, Coubes, Christine, Bézieau, Stéphane, Küry, Sébastien, Maystadt, Isabelle, Le Mao, Morgane, Lenaers, Guy, Navet, Benjamin, Faivre, Laurence, Tran Mau-Them, Frédéric, Zanoni, Paolo, Chung, Wendy K, Rauch, Anita, Bonneau, Dominique, Park, Myung Hee, University of Zurich, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - 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), Universität Zürich [Zürich] = University of Zurich (UZH), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de Génotypage (CNG), Institut de Génomique d'Evry (IG), 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)-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), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Génétique Humaine [Charleroi, Belgium] (Institut de Pathologie et de Génétique), Institut de Pathologie et de Génétique, Charleroi, Immunomodulation of the Tumor Microenvironment and Immunotherapy of Thoracic Cancers (CRCI2NA / Eq 1), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Unité fonctionnelle d' Innovation en Diagnostic Génomique des Maladies Rares (CHU Dijon) (UF6254), University hospital of Zurich [Zurich], Columbia University Medical Center (CUMC), and Columbia University [New York]

Subjects
DHPS, 10039 Institute of Medical Genetics, Lysine, [SDV]Life Sciences [q-bio], deoxyhypusine hydroxylase, DOHH, Gene Expression, translation, 610 Medicine & health, neurodevelopmental disorder, hypusine, Mixed Function Oxygenases, post, translational modification, Neurodevelopmental Disorders, Report, EIF5A1, Genetics, Humans, 570 Life sciences, biology, eIF5A, microcephaly, Alleles, Genetics (clinical)
Abstract

Deoxyhypusine hydroxylase (DOHH) is the enzyme catalyzing the second step in the post-translational synthesis of hypusine [N(ε)-(4-amino-2-hydroxybutyl)lysine] in the eukaryotic initiation factor 5A (eIF5A). Hypusine is formed exclusively in eIF5A by two sequential enzymatic steps catalyzed by deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). Hypusinated eIF5A is essential for translation and cell proliferation in eukaryotes, and all three genes encoding eIF5A, DHPS, and DOHH are highly conserved throughout eukaryotes. Pathogenic variants affecting either DHPS or EIF5A have been previously associated with neurodevelopmental disorders. Using trio exome sequencing, we identified rare bi-allelic pathogenic missense and truncating DOHH variants segregating with disease in five affected individuals from four unrelated families. The DOHH variants are associated with a neurodevelopmental phenotype that is similar to phenotypes caused by DHPS or EIF5A variants and includes global developmental delay, intellectual disability, facial dysmorphism, and microcephaly. A two-dimensional gel analyses revealed the accumulation of deoxyhypusine-containing eIF5A [eIF5A(Dhp)] and a reduction in the hypusinated eIF5A in fibroblasts derived from affected individuals, providing biochemical evidence for deficiency of DOHH activity in cells carrying the bi-allelic DOHH variants. Our data suggest that rare bi-allelic variants in DOHH result in reduced enzyme activity, limit the hypusination of eIF5A, and thereby lead to a neurodevelopmental disorder.

Published
2022

3. SARS-CoV-2 E and 3a Proteins Are Inducers of Pannexin Currents

Author

Barbara B. R. Oliveira-Mendes, Malak Alameh, Béatrice Ollivier, Jérôme Montnach, Nicolas Bidère, Frédérique Souazé, Nicolas Escriou, Flavien Charpentier, Isabelle Baró, Michel De Waard, Gildas Loussouarn, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), LabEx Ion Channels Science and Therapeutics [France], Signaling in Oncogenesis, Angiogenesis and Permeability - SOAP (CRCI2NA / Eq 6), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Département de Santé Globale - Department Global Health, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), We thank the Agence Nationale de la Recherche for its financial support to the Région Pays de la Loire (ANR FLASH Covid-19 - CoV2-E-TARGET) and the laboratory of excellence ‘Ion Channels, Science and Therapeutics’ (grant No. ANR-11-LABX-0015)., ANR-20-COVI-0058,CoV2-E-TARGET,Criblage d'inhibiteurs de la protéine E du SARS-CoV-2(2020), ANR-11-LABX-0015,ICST,Canaux ioniques d'intérêt thérapeutique(2011), Loussouarn, Gildas, Criblage d'inhibiteurs de la protéine E du SARS-CoV-2 - - CoV2-E-TARGET2020 - ANR-20-COVI-0058 - COVID-19 - VALID, Laboratoires d'excellence - Canaux ioniques d'intérêt thérapeutique - - ICST2011 - ANR-11-LABX-0015 - LABX - VALID, Signaling in Oncogenesis, Angiogenesis and Permeability (CRCINA-ÉQUIPE 15), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)

Subjects
[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, COVID-19, SARS-CoV-2, viroporins, E protein, 3a protein, pannexin currents, cell death, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, General Medicine
Abstract

Controversial reports have suggested that SARS-CoV E and 3a proteins may be viroporins that conduct currents through the plasma membrane of the infected cells. If true, these proteins would represent accessible targets for the development of new antiviral drugs by using high-throughput patch-clamp techniques. Here we aimed at better characterizing the cell responses induced by E or 3a protein with a particular focus on the ion conductances measured at the cell surface. First, we show that expression of SARS-CoV-2 E or 3a protein in CHO cells gives rise to cells with newly-acquired round shape, tending to detach from the Petri dish. This suggests that cell death is induced upon expression of E or 3a protein. We confirmed this hypothesis by using flow cytometry, in agreement with earlier reports on other cell types. In adhering cells expressing E or 3a protein, whole-cell currents were in fact not different from the control condition indicating that E and 3a proteins are not plasma membrane viroporins. In contrast, recording currents on detached cells uncovered outwardly-rectifying currents, much larger than those observed in control. The current characteristics are reminiscent of what was previously observed in cells expressing SARS-CoV-1 E or 3a proteins. Herein, we illustrate for the first time that carbenoxolone blocks these outward currents suggesting that they are conducted by pannexin channels, mostly likely activated by cell morphology change and/or cell death. Alongside we also demonstrate that truncation of the C-terminal PDZ binding motifs reduces the proportion of dying cells but does not prevent pannexin currents suggesting distinct pathways for cell death and pannexin currents induced by E and 3a proteins. We conclude that SARS-CoV-2 E and 3a proteins are not acting as viroporins expressed at the plasma membrane.Author SummaryA viroporin (or viral porin) is a class of proteins that is encoded by a virus genome. It is named porin because its biological role is to conduct ions through a pore that it created in a lipid membrane such as the one surrounding a human cell. if such viroporin is present at the external membrane of a human cell infected by a virus, it can be an easy target of an antiviral agent which thus does not have to enter the cell to be active. One example of viroporin is the flu M2 protein that is the target of amantadine, an antiviral agent used against flu. In previous studies, two proteins of SARS-CoV viruses, named E protein and 3a protein, have been suggested to be viroporins at the surface of infected human cells, potentially opening a new research avenue against SARS. Here we demonstrate that both proteins are not viroporins at the external membrane but they rather trigger changes in the cell shape and promote cell death. They only indirectly induce the activity of a porin that is encoded by the cell genome, named pannexin.

Published
2023
Full Text
View/download PDF

4. Rare germline heterozygous missense variants in BRCA1-associated protein 1, BAP1, cause a syndromic neurodevelopmental disorder

Author

Sébastien Küry, Frédéric Ebstein, Alice Mollé, Thomas Besnard, Ming-Kang Lee, Virginie Vignard, Tiphaine Hery, Mathilde Nizon, Grazia M.S. Mancini, Jacques C. Giltay, Benjamin Cogné, Kirsty McWalter, Wallid Deb, Hagar Mor-Shaked, Hong Li, Rhonda E. Schnur, Ingrid M. Wentzensen, Anne-Sophie Denommé-Pichon, Cynthia Fourgeux, Frans W. Verheijen, Eva Faurie, Rachel Schot, Cathy A. Stevens, Daphne J. Smits, Eileen Barr, Ruth Sheffer, Jonathan A. Bernstein, Chandler L. Stimach, Eliana Kovitch, Vandana Shashi, Kelly Schoch, Whitney Smith, Richard H. van Jaarsveld, Anna C.E. Hurst, Kirstin Smith, Evan H. Baugh, Suzanne G. Bohm, Emílie Vyhnálková, Lukáš Ryba, Capucine Delnatte, Juanita Neira, Dominique Bonneau, Annick Toutain, Jill A. Rosenfeld, Séverine Audebert-Bellanger, Brigitte Gilbert-Dussardier, Sylvie Odent, Frédéric Laumonnier, Seth I. Berger, Ann C.M. Smith, Franck Bourdeaut, Marc-Henri Stern, Richard Redon, Elke Krüger, Raphaël Margueron, Stéphane Bézieau, Jeremie Poschmann, Bertrand Isidor, Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Universität Greifswald - University of Greifswald, Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University Medical Center [Utrecht], GeneDx [Gaithersburg, MD, USA], Hadassah Hebrew University Medical Center [Jerusalem], Emory University School of Medicine, Emory University [Atlanta, GA], Laboratoire de Biologie Neurovasculaire Intégrée [Angers] (CNRS UMR6214 - INSERM U771), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers, MitoVasc - 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), University of Tennessee System, Stanford University, Duke University Medical Center, University of Alabama at Birmingham [ Birmingham] (UAB), Columbia University [New York], Charles University [Prague] (CU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Baylor College of Medicine (BCM), Baylor University, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Unité neurovasculaire et troubles cognitifs (Neuvacod), Université de Poitiers, CHU Pontchaillou [Rennes], 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 référence Maladies Rares CLAD-Ouest [Rennes], Children's National Medical Center, National Human Genome Research Institute (NHGRI), Institut Curie [Paris], Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Greifswald University Hospital, Research reported in this manuscript was supported by the NIH Common Fund through the Office of Strategic Coordination/Office of the NIH Director under award number U01HG007672 to V.S. Further support was obtained by funding from the German Research Foundation (SFBTR 167 A4, GRK2719 B4) to E.K, and Clinical Genetics

Subjects
Male, Heterozygote, Proteasome Endopeptidase Complex, tumor, Adolescent, T-Lymphocytes, Ubiquitin-Protein Ligases, [SDV]Life Sciences [q-bio], Mutation, Missense, UPS, ubiquitin-proteasome system, chromatin remodeling, Histones, SDG 3 - Good Health and Well-being, Loss of Function Mutation, Report, ubiquitin, Genetics, Humans, cancer, Family, BAP1, Child, deubiquitination, Germ-Line Mutation, Genetics (clinical), [SDV.GEN]Life Sciences [q-bio]/Genetics, neurodevelopment, BRCA1 Protein, Tumor Suppressor Proteins, Ubiquitination, Infant, Chromatin Assembly and Disassembly, BRCA1, Chromatin, Gene Expression Regulation, Neurodevelopmental Disorders, intellectual disability, Child, Preschool, histone 2A, Female, Host Cell Factor C1, Ubiquitin Thiolesterase
Abstract

International audience; Nuclear deubiquitinase BAP1 (BRCA1-associated protein 1) is a core component of multiprotein complexes that promote transcription by reversing the ubiquitination of histone 2A (H2A). BAP1 is a tumor suppressor whose germline loss-of-function variants predispose to cancer. To our knowledge, there are very rare examples of different germline variants in the same gene causing either a neurodevelopmental disorder (NDD) or a tumor predisposition syndrome. Here, we report a series of 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic NDD. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. In T cells isolated from two affected children, H2A deubiquitination was impaired. In matching peripheral blood mononuclear cells, histone H3 K27 acetylation ChIP-seq indicated that these BAP1 variants induced genome-wide chromatin state alterations, with enrichment for regulatory regions surrounding genes of the ubiquitin-proteasome system (UPS). Altogether, these results define a clinical syndrome caused by rare germline missense BAP1 variants that alter chromatin remodeling through abnormal histone ubiquitination and lead to transcriptional dysregulation of developmental genes.

Published
2022

5. Serum phosphate level and its kinetic as an early marker of acute kidney injury in tumor lysis syndrome

Author

Lemerle, Marie, Schmidt, Aline, Thepot-Seegers, Valérie, Kouatchet, Achille, Moal, Valérie, Raimbault, Melina, Orvain, Corentin, Augusto, Jean-François, Demiselle, Julien, Département de Néphrologie-Dialyse-Transplantation [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Stress Adaptation and Tumor Escape - SATE (CRCI2NA / Eq 7), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), PRES Université Nantes Angers Le Mans (UNAM), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), CHU Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Regenerative NanoMedicine [Strasbourg] (RNM), and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
ROC Curve, Nephrology, [SDV]Life Sciences [q-bio], Humans, Acute Kidney Injury, Tumor Lysis Syndrome, Biomarkers, Phosphates, Retrospective Studies
Abstract

Acute kidney injury (AKI) is a major cause of mortality in tumor lysis syndrome. The biochemical parameters and kinetics of tumor lysis syndrome remain poorly described. Particularly, whether blood serum phosphate variations may help in the identification and management of patients who will eventually develop AKI remains to be studied.In this retrospective study, we included patients with tumor lysis syndrome episodes without AKI at diagnosis, and analyzed serum phosphate kinetic, clinical and tumor lysis syndrome biochemical variables to identify factors associated with AKI onset, and determine threshold values of phosphatemia associated with AKI development.One hundred thirty tumor lysis syndrome episodes occurred in 120 patients during an 11-year period at the University Hospital of Angers. AKI developed in 56 tumor lysis syndrome episodes. In multivariable analysis, among the analyzed factors, only an increase in serum phosphate levels (before AKI diagnosis), exposure to platinum salts and an increase in LDH levels were associated with AKI development. Before AKI onset, a serum phosphate cut-off of 2.1 mmol/L was not effective in predicting AKI development (sensitivity 48%, specificity 84%, area under the receiver operating characteristic curve (AUC) 0.63 [0.52-0.74]). No other biochemical parameters were effective to better predict AKI occurrence.This work suggests that increases in serum phosphate and LDH appear to be early and reliable biomarkers of AKI in tumor lysis syndrome. No valuable threshold value of serum phosphate was found to effectively predict AKI. This work is the basis for further prospective controlled studies on phosphate monitoring and phosphate lowering therapies to prevent AKI during tumor lysis syndrome.

Published
2022

6. Frequency and Genomic Aspects of Intrinsic Resistance to Vismodegib in Locally Advanced Basal Cell Carcinoma

Author

Andrey A. Yurchenko, Oltin T. Pop, Meriem Ighilahriz, Ismael Padioleau, Fatemeh Rajabi, Hayley J. Sharpe, Nicolas Poulalhon, Brigitte Dreno, Amir Khammari, Marc Delord, Antonio Alberti, Nadem Soufir, Maxime Battistella, Samia Mourah, Fanny Bouquet, Ariel Savina, Andrej Besse, Max Mendez-Lopez, Florent Grange, Sandrine Monestier, Laurent Mortier, Nicolas Meyer, Caroline Dutriaux, Caroline Robert, Philippe Saiag, Florian Herms, Jerome Lambert, Frederic J. de Sauvage, Nicolas Dumaz, Lukas Flatz, Nicole Basset-Seguin, Sergey I. Nikolaev, Pecqueret, Valérie, Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Brustzentrum Kantonsspital St. Gallen, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), The Babraham Institute [Cambridge, UK], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Centre hospitalier universitaire de Nantes (CHU Nantes), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut ROCHE [Boulogne-Billancourt], Roche S.A.S, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital de la Timone [CHU - APHM] (TIMONE), Equipe 3 - Facteurs de persistance des cellules leucémique - (INSERM U837), Institut pour la Recherche sur le Cancer de Lille (U837 INSERM - IRCL), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux [Bordeaux], Institut Gustave Roussy (IGR), Oncologie dermatologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpital Ambroise Paré [AP-HP], Service de Dermatologie [AP-HP Hôpital Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Genentech, Inc., and Genentech, Inc. [San Francisco]

Subjects
Cancer Research, Skin Neoplasms, animal structures, integumentary system, Pyridines, [SDV]Life Sciences [q-bio], fungi, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV] Life Sciences [q-bio], [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, Carcinoma, Basal Cell, Humans, Anilides, Hedgehog Proteins, Cerebellar Neoplasms
Abstract

Purpose: Vismodegib is approved for the treatment of locally advanced basal cell carcinoma (laBCC), but some cases demonstrate intrinsic resistance (IR) to the drug. We sought to assess the frequency of IR to vismodegib in laBCC and its underlying genomic mechanisms. Experimental Design: Response to vismodegib was evaluated in a cohort of 148 laBCC patients. Comprehensive genomic and transcriptomic profiling was performed in a subset of five intrinsically resistant BCC (IR-BCC). Results: We identified that IR-BCC represents 6.1% of laBCC in the studied cohort. Prior treatment with chemotherapy was associated with IR. Genetic events that were previously associated with acquired resistance (AR) in BCC or medulloblastoma were observed in three out of five IR-BCC. However, IR-BCCs were distinct by highly rearranged polyploid genomes. Functional analyses identified hyperactivation of the HIPPO-YAP and WNT pathways at RNA and protein levels in IR-BCC. In vitro assay on the BCC cell line further confirmed that YAP1 overexpression increases the cell proliferation rate. Conclusions: IR to vismodegib is a rare event in laBCC. IR-BCCs frequently harbor resistance mutations in the Hh pathway, but also are characterized by hyperactivation of the HIPPO-YAP and WNT pathways.

Published
2022

7. Point-of-care ultrasonography for risk stratification of non-critical suspected COVID-19 patients on admission (POCUSCO): A prospective binational study

Author

François Morin, Delphine Douillet, Jean François Hamel, Dominique Savary, Christophe Aubé, Karim Tazarourte, Kamélia Marouf, Florence Dupriez, Phillipe Le Conte, Thomas Flament, Thomas Delomas, Mehdi Taalba, Nicolas Marjanovic, Francis Couturaud, Nicolas Peschanski, Thomas Boishardy, Jérémie Riou, Vincent Dubée, Pierre-Marie Roy, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - 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 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 ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Research on Healthcare Performance (RESHAPE - Inserm U1290 - UCBL1), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Cliniques Universitaires Saint-Luc [Bruxelles], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Mémorial France États-Unis de Saint-Lô (CH Saint-Lô), CHU Rouen, Normandie Université (NU), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), CHU Pontchaillou [Rennes], Micro et Nanomédecines Translationnelles (MINT), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Multidisciplinary, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Abstract

Background Lung point-of-care ultrasonography (L-POCUS) is highly effective in detecting pulmonary peripheral patterns and may allow early identification of patients who are likely to develop an acute respiratory distress syndrome (ARDS). We hypothesized that L-POCUS performed within the first 48 hours of non-critical patients with suspected COVID-19 would identify those with a high-risk of worsening. Methods POCUSCO was a prospective, multicenter study. Non-critical adult patients who presented to the emergency department (ED) for suspected or confirmed COVID-19 were included and had L-POCUS performed within 48 hours following ED presentation. The lung damage severity was assessed using a previously developed score reflecting both the extension and the intensity of lung damage. The primary outcome was the rate of patients requiring intubation or who died within 14 days following inclusion. Results Among 296 patients, 8 (2.7%) met the primary outcome. The area under the curve (AUC) of L-POCUS was 0.80 [95%CI:0.60–0.94]. The score values which achieved a sensibility >95% in defining low-risk patients and a specificity >95% in defining high-risk patients were Conclusion L-POCUS performed within the first 48 hours following ED presentation allows risk-stratification of patients with non-severe COVID-19.

Published
2023

8. <scp>DNA</scp> damage repair kinase <scp>DNA‐PK</scp> and <scp>cGAS</scp> synergize to induce cancer‐related inflammation in glioblastoma

Author

Clara Taffoni, Johanna Marines, Hanane Chamma, Soumyabrata Guha, Mathilde Saccas, Amel Bouzid, Ana‐Luiza Chaves Valadao, Clément Maghe, Jane Jardine, Mi Kyung Park, Katarzyna Polak, Mara De Martino, Claire Vanpouille‐Box, Maguy Del Rio, Celine Gongora, Julie Gavard, Nicolas Bidère, Min Sup Song, Donovan Pineau, Jean‐Philippe Hugnot, Karima Kissa, Laura Fontenille, Fabien P Blanchet, Isabelle K Vila, Nadine Laguette, Institut de génétique humaine (IGH), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), AZELEAD, Signaling in Oncogenesis, Angiogenesis and Permeability - SOAP (CRCI2NA / Eq 6), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), The University of Texas M.D. Anderson Cancer Center [Houston], Weill Cornell Medicine [Cornell University], Cornell University [New York], 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 de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Laboratory of Pathogen and Host Immunity [Montpellier] (LPHI), Institut de Recherche en Infectiologie de Montpellier (IRIM), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), European Project: 637763,H2020,ERC-2014-STG,CrIC(2015), and European Project: 893772,DIM-CrIC

Subjects
DNA-PK, General Immunology and Microbiology, inflammation, [SDV]Life Sciences [q-bio], General Neuroscience, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Molecular Biology, tumor immunogenicity, General Biochemistry, Genetics and Molecular Biology, cGAS
Abstract

International audience; Cytosolic DNA promotes inflammatory responses upon detection by the cyclic GMP-AMP (cGAMP) synthase (cGAS). It has been suggested that cGAS downregulation is an immune escape strategy harnessed by tumor cells. Here, we used glioblastoma cells that show undetectable cGAS levels to address if alternative DNA detection pathways can promote pro-inflammatory signaling. We show that the DNA-PK DNA repair complex (i) drives cGAS-independent IRF3-mediated type I Interferon responses and (ii) that its catalytic activity is required for cGAS-dependent cGAMP production and optimal downstream signaling. We further show that the cooperation between DNA-PK and cGAS favors the expression of chemokines that promote macrophage recruitment in the tumor microenvironment in a glioblastoma model, a process that impairs early tumorigenesis but correlates with poor outcome in glioblastoma patients. Thus, our study supports that cGAS-dependent signaling is acquired during tumorigenesis and that cGAS and DNA-PK activities should be analyzed concertedly to predict the impact of strategies aiming to boost tumor immunogenicity.

Published
2022

9. Biological differences between two commercial anti-CD19 CAR T cells products and impact on outcomes in lymphoma patients

Author

Tessoulin, Benoit, Grain, Audrey, Ollier, Jocelyn, Gastinne, Thomas, Dubruille, Viviane, Mahé, Béatrice, Blin, Nicolas, Lok, Anne, Vantyghem, Sophie, Sortais, Clara, Touzeau, Cyrille, Moreau, Philippe, Le Gouill, Steven, Chevallier, Patrice, Clémenceau, Béatrice, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Manipulation of Lymphocytes for Immunotherapy (CRCI2NA / Eq 12), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie Clinique [CHU Nantes] (Unité d'Investigation Clinique), Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Département d'Hématologie Clinique [CHU Nantes], Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), university hospital, University Hospital, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), and Ollier, Jocelyn

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Abstract

International audience

Published
2022

10. Heterogeneous RNA editing and influence of ADAR2 on mesothelioma chemoresistance and the tumor microenvironment

Author

Hariharan, Ananya, Qi, Weihong, Rehrauer, Hubert, Wu, Licun, Ronner, Manuel, Wipplinger, Martin, Kresoja-Rakic, Jelena, Sun, Suna, Oton-Gonzalez, Lucia, Sculco, Marika, Serre-Beinier, Véronique, Meiller, Clément, Blanquart, Christophe, Fonteneau, Jean-François, Vrugt, Bart, Rüschoff, Jan Hendrik, Opitz, Isabelle, Jean, Didier, de Perrot, Marc, Felley-Bosco, Emanuela, University of Zurich, University hospital of Zurich [Zurich], Functional Genomics Center Zurich, Universität Zürich [Zürich] = University of Zurich (UZH)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), University Health Network, Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), 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)-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), Immunomodulation of the Tumor Microenvironment and Immunotherapy of Thoracic Cancers (CRCI2NA / Eq 1), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Institute of Pathology and Molecular Pathology [Zurich], and Blanquart, Christophe

Subjects
Mesothelioma, 10255 Clinic for Thoracic Surgery, Adenosine Deaminase, Mesothelioma, Malignant, RNA-Binding Proteins, [SDV.CAN]Life Sciences [q-bio]/Cancer, 610 Medicine & health, BRCA-associated protein 1, antifolate therapy, mesothelioma, RNA editing, tumor microenvironment, type-1 interferon, Mice, [SDV.CAN] Life Sciences [q-bio]/Cancer, Drug Resistance, Neoplasm, 10049 Institute of Pathology and Molecular Pathology, Tumor Microenvironment, Animals, RNA Editing
Abstract

We previously observed increased levels of adenosine-deaminase-acting-on-dsRNA (Adar)-dependent RNA editing during mesothelioma development in mice exposed to asbestos. The aim of this study was to characterize and assess the role of ADAR-dependent RNA editing in mesothelioma. We found that tumors and mesothelioma primary cultures have higher ADAR-mediated RNA editing compared to mesothelial cells. Unsupervised clustering of editing in different genomic regions revealed heterogeneity between tumor samples as well as mesothelioma primary cultures. ADAR2 expression levels are higher in BRCA1-associated protein 1 wild-type tumors, with corresponding changes in RNA editing in transcripts and 3'UTR. ADAR2 knockdown and rescue models indicated a role in cell proliferation, altered cell cycle, increased sensitivity to antifolate treatment, and type-1 interferon signaling upregulation, leading to changes in the microenvironment in vivo. Our data indicate that RNA editing contributes to mesothelioma heterogeneity and highlights an important role of ADAR2 not only in growth regulation in mesothelioma but also in chemotherapy response, in addition to regulating inflammatory response downstream of sensing nucleic acid structures., Molecular Oncology, 16 (22), ISSN:1574-7891

Published
2022

11. Sleep apnea and incident unprovoked venous thromboembolism: Data from the French Pays de la Loire Sleep Cohort

Author

Trzepizur, W., Gerves-Pinquie, C., Heude, B., Blanchard, M., Meslier, N, Jouvenot, M., Kerbat, S., Le Mao, R., Magois, E., Racineux, J., Sabi, A., Théreaux, J., Couturaud, F., Gagnadoux, F, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), MitoVasc - Équipe CarME (Cardiovascular Pathophysiology) (MITOVASC-CARME), MitoVasc - 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)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Recherche en Santé Respiratoire des Pays de la Loire ( IRSRPL), École supérieure d'électronique de l'ouest [Angers] (ESEO), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Cloud Sleep Lab, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience

Published
2022

12. Hyaluronic Acid Scaffolds for Loco-Regional Therapy in Nervous System Related Disorders

Author

Amel Djoudi, Rodolfo Molina-Peña, Natalia Ferreira, Ilaria Ottonelli, Giovanni Tosi, Emmanuel Garcion, Frank Boury, Molina Pena, Rodolfo, EuroNanoMed III (project GLIOSILK) - AN33.32R - INCOMING, Design and application of innovative loco-regional Treatments in Gliobastoma (CRCI2NA / Eq 5), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), La Ligue Contre le Cancer (grant number TARC21174 to A.D.), Region Pays-de-la-Loire programs to F.B.: Bioimplants for Bone Regeneration (BILBO) part of the BIOREGATE Research-Training-Innovation consortium (RFI) and NanoFar + (International Strategy), French National Research Agency (AN33.32R) under the frame of EuroNanoMed III (project GLIOSILK), LabEx IRON (Innovative Radiopharmaceuticals in Oncology and Neurology) as part of the French government Investissements d’Avenir program (ANR-11-LABX-0018 to E.G.), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Angers (Angers, France), and European Project: AN33.32R

Subjects
[CHIM.POLY] Chemical Sciences/Polymers, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV]Life Sciences [q-bio], Hyaluronic acid scaffolds, [SDV.CAN]Life Sciences [q-bio]/Cancer, loco-regional treatment, Disaccharides, Nervous System, Catalysis, Acetylglucosamine, Inorganic Chemistry, hyaluronic acid, hydrogels, nervous system, scaffolds, Humans, Polyelectrolytes, Hydrogels, Glycosaminoglycans, Glucuronic Acid, Tissue Scaffolds, Tissue Engineering, Hyaluronic Acid, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Physical and Theoretical Chemistry, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, Molecular Biology, Spectroscopy, Organic Chemistry, glioblastoma, General Medicine, Computer Science Applications, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, [SDV] Life Sciences [q-bio], [SDV.IB.BIO] Life Sciences [q-bio]/Bioengineering/Biomaterials, [CHIM.POLY]Chemical Sciences/Polymers
Abstract

International audience; Hyaluronic acid (HA) is a Glycosaminoglycan made of disaccharide units containing Nacetyl-D-glucosamine and glucuronic acid. Its molecular mass can reach 10 MDa and its physiological properties depend on its polymeric property, polyelectrolyte feature and viscous nature. HA is a ubiquitous compound found in almost all biological tissues and fluids. So far, HA grades are produced by biotechnology processes, while in the human organism it is a major component of the extracellular matrix (ECM) in brain tissue, synovial fluid, vitreous humor, cartilage and skin. Indeed, HA is capable of forming hydrogels, polymer crosslinked networks that are very hygroscopic. Based on these considerations, we propose an overview of HA-based scaffolds developed for brain cancer treatment, central and peripheral nervous systems, discuss their relevance and identify the most successful developed systems.

Published
2022

13. IL-7 is expressed in malignant mesothelioma and has a prognostic value

Author

Hoa‐Le Mai, Sophie Deshayes, Thi‐Van‐Ha Nguyen, Virginie Dehame, Anne‐Laure Chéné, Sophie Brouard, Christophe Blanquart, Team 4 : Deciphering organ immune regulation in inflammation and transplantation (DORI-t) (U1064 Inserm - CR2TI), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), Immunomodulation of the Tumor Microenvironment and Immunotherapy of Thoracic Cancers (CRCI2NA / Eq 1), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Service de pneumologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut du Thorax [Nantes], Hôpital Guillaume-et-René-Laennec [Saint-Herblain], and Blanquart, Christophe

Subjects
Mesothelioma, Cancer Research, IL-7, Lung Neoplasms, Receptors, Interleukin-7, Pleural Neoplasms, Interleukin-7, Mesothelioma, Malignant, [SDV.CAN]Life Sciences [q-bio]/Cancer, Asbestos, General Medicine, IL-7R, Prognosis, Oncology, [SDV.CAN] Life Sciences [q-bio]/Cancer, Genetics, Molecular Medicine, biomarker, Humans, pleural fluids, Biomarkers
Abstract

International audience; Malignant pleural mesothelioma (MPM) is an aggressive cancer mainly related to asbestos exposure. Despite recent therapeutic advances, notably immunotherapies, the benefit remains limited and restricted to a small percentage of patients. Thus, a better understanding of the disease is needed to identify new therapeutic strategies. Recently, interleukin 7 receptor (IL-7R) has been described as being expressed by MPM cells and associated with poorer patient survival. Thus, the aim of this work was to study the IL-7R/IL-7 pathway in MPM using patient samples. We found that, although more than 40% of MPM cells expressed IL-7R, IL-7 had no effect on their intracellular signaling. Accordingly, the addition of IL-7 to the culture medium did not affect MPM cell growth. Using The Cancer Genome Atlas (TCGA) database, we showed that high IL7 gene expression in MPM tumors was associated with a higher overall patient survival and an induction of genes involved in the immune response. In pleural effusions (PEs), we found that IL-7 concentration was not a good diagnostic biomarker. However, we observed that high IL-7 levels in PEs were associated with shorter survival of MPM patients, but not of lung cancer patients. The prognostic value of IL-7 was also conserved when only patients with epithelioid mesothelioma, the most common histological type of MPM, were analyzed. Taken together, our study suggests that, although the IL-7R/IL-7 signaling pathway is not functional in MPM cells, IL-7 expression in PEs may have prognostic value in MPM patients.

Published
2022

14. MELAS syndrome causes glutamate and tricarboxylic acid cycle dysfunctions alleviated by ketone body treatment

Author

Belal, Sophie, Goudenège, David, Bocca, Cinzia, Dumont, Florent, Chao de la Barca, Juan Manuel, Desquiret-Dumas, Valérie, Gueguen, Naïg, Geffroy, Guillaume, Benyahia, Rayane, Kane, Selma, Khiati, Salim, Bris, Céline, Aranyi, Tamas, Stockholm, Daniel, Inisan, Aurore, Renaud, Aurélie, Barth, Magalie, Simard, Gilles, Reynier, Pascal, Letournel, Franck, Lenaers, Guy, Bonneau, Dominique, Chevrollier, Arnaud, Procaccio, Vincent, MitoVasc - 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), Unité de Physiologie Fonctionnelle des Organismes Marins, Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Laboratoire de Biologie Intégrative des Modèles Marins (LBI2M), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Ingénierie et Plateformes au Service de l'Innovation Thérapeutique (IPSIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Institute of Enzymology [Budapest], Research Centre for Natural Sciences, Hungarian Academy of Sciences (MTA)-Hungarian Academy of Sciences (MTA), Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, Stress Oxydant et Pathologies Métaboliques (SOPAM), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Multi-omics, mtDNA, [SDV]Life Sciences [q-bio], Mitochondrial diseases, Glutamate, MELAS syndrome
Abstract

International audience; (1) Background: The development of mitochondrial medicine has been severely impeded by a lack of effective therapies. (2) Methods: To better understand Mitochondrial Encephalopathy Lactic Acidosis Syndrome Stroke-like episodes (MELAS) syndrome, neuronal cybrid cells carrying different mutation loads of the m.3243A > G mitochondrial DNA variant were analysed using a multi-omic approach. (3) Results: Specific metabolomic signatures revealed that the glutamate pathway was significantly increased in MELAS cells with a direct correlation between glutamate concentration and the m.3243A > G heteroplasmy level. Transcriptomic analysis in mutant cells further revealed alterations in specific gene clusters, including those of the glutamate, gamma-aminobutyric acid pathways, and tricarboxylic acid (TCA) cycle. These results were supported by post-mortem brain tissue analysis from a MELAS patient, confirming the glutamate dysregulation. Exposure of MELAS cells to ketone bodies significantly reduced the glutamate level and improved mitochondrial functions, reducing the accumulation of several intermediate metabolites of the TCA cycle and alleviating the NADH-redox imbalance. (4) Conclusions: Thus, a multi-omic integrated approach to MELAS cells revealed glutamate as a promising disease biomarker, while also indicating that a ketogenic diet should be tested in MELAS patients.

Published
2022

15. Editorial: Extracellular Vesicles in CNS Diseases

Author

Raffaella Soleti, Maria Antonietta Panaro, Tarek Benameur, Giovanni Messina, Chiara Porro, Innate Immunity and Immunotherapy (CRCI2NA / Eq 4), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), King Faisal University (KFU), Università degli Studi di Foggia = University of Foggia (Unifg), and Blanchard, Simon

Subjects
[SDV] Life Sciences [q-bio], amyotrophic lateral sclerosis, CNS diseases, miRNA - microRNA, [SDV]Life Sciences [q-bio], exosomes, extracellular vesicles, Biochemistry, Genetics and Molecular Biology (miscellaneous), Molecular Biology, Biochemistry
Abstract

International audience; No abstract available

Published
2022

16. Emotional processes in partners’ quality of life at various stages of breast cancer pathway: a longitudinal study

Author

Anne-Sophie Baudry, Laurence Vanlemmens, Anne Congard, Aurélie Untas, Carine Segura-Djezzar, Claudia Lefeuvre-Plesse, Florence Coussy, Séverine Guiu, Jean-Sébastien Frenel, Baptiste Sauterey, Sonya Yakimova, Véronique Christophe, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Laboratoire de Psychologie des Pays de la Loire (LPPL), Université d'Angers (UA)-Nantes Université - UFR Lettres et Langages (Nantes Univ - UFR LL), Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Laboratoire de Psychopathologie et Processus de Santé (LPPS (URP_4057)), Université Paris Cité (UPCité), Department of Medical Oncology, CRLCC Eugène Marquis (CRLCC), Residual Tumor & Response to Treatment Laboratory [Paris] (RT2Lab), Translational Research Department [Paris], Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Oncologie Médicale [Institut Curie, Paris], Institut Curie [Paris], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, 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), Integrative Cancer Genomics (CRCI2NA / Eq 8), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre de Recherche en Psychologie de la Connaissance, du Langage et de l'Émotion (PsyCLÉ), Aix Marseille Université (AMU), Unité de Recherche en Sciences Cognitives et Affectives (URECA), and Université de Lille, Sciences Humaines et Sociales-PRES Université Lille Nord de France

Subjects
[SCCO.PSYC]Cognitive science/Psychology, Public Health, Environmental and Occupational Health
Abstract

Several studies have shown that emotional competence (EC) impacts cancer adjustment via anxiety and depression symptoms. The objective was to test this model for the quality of life (QoL) of partners: first, the direct effect of partners' EC on their QoL, anxiety and depression symptoms after cancer diagnosis (T1), after chemotherapy (T2) and after radiotherapy (T3); Second, the indirect effects of partners' EC at T1 on their QoL at T2 and T3 through anxiety and depression symptoms.192 partners of women with breast cancer completed a questionnaire at T1, T2 and T3 to assess their EC (PEC), anxiety and depression symptoms (HADS) and QoL (Partner-YW-BCI). Partial correlations and regression analyses were performed to test direct and indirect effects of EC on issues.EC at T1 predicted fewer anxiety and depression symptoms at each time and all dimensions of QoL, except for career management and financial difficulties. EC showed different significant indirect effects (i.e. via anxiety or depression symptoms) on all sub-dimensions of QoL, except for financial difficulties, according to the step of care pathway (T2 and T3). Anxiety and depression played a different role in the psychological processes that influence QoL.Findings confirm the importance of taking emotional processes into account in the adjustment of partners, especially regarding their QoL and the support they may provide to patients. It, thus, seems important to integrate EC in future health models and psychosocial interventions focused on partners or caregivers.

Published
2022

17. Sars-Cov-2 T-Cell Responses after One or Two COVID-19 Vaccine Boosters in Allogeneic Transplant Recipients

Author

Clémenceau, Béatrice, Le Bourgeois, Amandine, Guillaume, Thierry, Coste-Burel, Marianne, Peterlin, Pierre, Garnier, Alice, Jullien, Maxime, Ollier, Jocelyn, Béné, Marie C, Chevallier, Patrice, Manipulation of Lymphocytes for Immunotherapy (CRCI2NA / Eq 12), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Laboratoire d'Hematologie [CHU Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), and Ollier, Jocelyn

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, Biochemistry, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience

Published
2022

18. O-66 - Preparation of 211At-labeled aromatic compounds from thioarylprecursors

Author

Maingueneau, Clémence, Eychenne, Romain, Gestin, Jean-François, Guérard, François, Nuclear Oncology (CRCI2NA / Eq 2), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), GIP ARRONAX [Nantes], Université de Nantes (UN), and Guérard, François

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

International audience

Published
2022

19. P-230 - Aryliodonium ylides as efficient precursors for astatine-211 labeling

Author

Maingueneau, Clémence, Berdal, Marion, Eychenne, Romain, Gaschet, Joëlle, Chérel, Michel, Gestin, Jean-Francois, Guérard, Francois, Nuclear Oncology (CRCI2NA / Eq 2), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), GIP ARRONAX [Nantes], Université de Nantes (UN), and Guérard, François

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

International audience

Published
2022

20. Aerosol-mediated non-viral lung gene therapy: The potential of aminoglycoside-based cationic liposomes

Author

Le Gall, T, Berchel, M, Davies, L, Mottais, A, Ghanem, R, Fautrel, A, Gill, D, Hyde, S, Lehn, P, Lehn, J-M, Lemiègre, L, Benvegnu, T, Jaffrès, P-A, Pitard, B, Montier, T, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Chimie, Electrochimie Moléculaires et Chimie Analytique (CEMCA), Université de Brest (UBO)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Brestois Santé Agro Matière (IBSAM), John Radcliffe Hospital [Oxford University Hospital], University of Oxford, 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 ), H2P2 - Histo Pathologie Hight Precision (H2P2), Université de Rennes (UR)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de Science et d'ingénierie supramoléculaires (ISIS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Collège de France (CdF (institution)), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Agence Nationale de la Recherche, ANR: ANR-17-CE18-0015-03, Bundesministerium für Bildung und Forschung, BMBF: 16GW0342, ANR-20-AMRB-0009, ANR-17-CE18-0015,VINP,monopDNA-Nanoparticules Virus-Inspirées pour transfert de gènes.(2017), ANR-20-AMRB-0009,TARGET-THERAPY,Spatially targeted eradication of antimicrobial-resistant bacteria: Novel polymer-based photodynamic therapy following aerosol lung delivery(2020), Jonchère, Laurent, monopDNA-Nanoparticules Virus-Inspirées pour transfert de gènes. - - VINP2017 - ANR-17-CE18-0015 - AAPG2017 - VALID, Spatially targeted eradication of antimicrobial-resistant bacteria: Novel polymer-based photodynamic therapy following aerosol lung delivery - - TARGET-THERAPY2020 - ANR-20-AMRB-0009 - FR-DE AMR Bilateral call - VALID, Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oxford [Oxford], 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 ), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)

Subjects
Aminoglycoside-based cationic lipids, 0303 health sciences, Structure-activity, Pharmaceutical Science, respiratory system, Article, Cystic fibrosis, Lipidic formulations, 3. Good health, RS1-441, Lung gene therapy, Nebulization, 03 medical and health sciences, Pharmacy and materia medica, aminoglycoside-based cationic lipids, cystic fibrosis, lipidic formulations, lung gene therapy, nebulization, structure-activity, 0302 clinical medicine, 030220 oncology & carcinogenesis, [CHIM] Chemical Sciences, [CHIM]Chemical Sciences, 030304 developmental biology
Abstract

International audience; Aerosol lung gene therapy using non-viral delivery systems represents a credible therapeutic strategy for chronic respiratory diseases, such as cystic fibrosis (CF). Progress in CF clinical setting using the lipidic formulation GL67A has demonstrated the relevance of such a strategy while emphasizing the need for more potent gene transfer agents. In recent years, many novel non-viral gene delivery vehicles were proposed as potential alternatives to GL67 cationic lipid. However, they were usually evaluated using procedures difficult or even impossible to implement in clinical practice. In this study, a clinically-relevant administration protocol via aerosol in murine lungs was used to conduct a comparative study with GL67A. Diverse lipidic compounds were used to prepare a series of formulations inspired by the composition of GL67A. While some of these formulations were ineffective at transfecting murine lungs, others demonstrated modest-to-very-efficient activities and a series of structure-activity relationships were unveiled. Lipidic aminoglycoside derivative-based formulations were found to be at least as efficient as GL67A following aerosol delivery of a luciferase-encoding plasmid DNA. A single aerosol treatment with one such formulation was found to mediate long-term lung transgene expression, exceeding half the animal’s lifetime. This study clearly supports the potential of aminoglycoside-based cationic lipids as potent GL67-alternative scaffolds for further enhanced aerosol non-viral lung gene therapy for diseases such as CF. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Published
2022

21. The DCMU Herbicide Shapes T-cell Functions By Modulating Micro-RNA Expression Profiles

Author

Pierre Autin, Sophie Deshayes, Juliette Lea, Nicolas Boisgerault, Emilie Dupré, Nathalie Labarrière, Rémy Leguevel, Jean-François Fonteneau, Christophe Blanquart, Delphine Fradin, Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Immunomodulation of the Tumor Microenvironment and Immunotherapy of Thoracic Cancers (CRCI2NA / Eq 1), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), 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 ), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), and Pecqueret, Valérie

Subjects
Herbicides, [SDV]Life Sciences [q-bio], micro-RNA, Immunology, CD8-Positive T-Lymphocytes, CD8+ T cells, [SDV] Life Sciences [q-bio], MicroRNAs, herbicide, Diuron, cancer, Immunology and Allergy, Animals, Humans, Zebrafish
Abstract

DCMU [N-(3,4-dichlorophenyl)-N-dimethylurea] or diuron is a widely used herbicide, which can cause adverse effects on human, especially on immune cells, due to their intrinsic properties and wide distribution. These cells are important for fighting not only against virus or bacteria but also against neoplastic cell development. We developed an approach that combines functional studies and miRNA and RNA sequencing data to evaluate the effects of DCMU on the human immune response against cancer, particularly the one carried out by CD8+ T cells. We found that DCMU modulates the expression of miRNA in a dose-dependent manner, leading to a specific pattern of gene expression and consequently to a diminished cytokine and granzyme B secretions. Using mimics or anti-miRs, we identified several miRNA, such as hsa-miR-3135b and hsa-miR-21-5p, that regulate these secretions. All these changes reduce the CD8+ T cells’ cytotoxic activity directed against cancer cells, in vitro and in vivo in a zebrafish model. To conclude, our study suggests that DCMU reduces T-cell abilities, participating thus to the establishment of an environment conducive to cancer development.

Published
2022

22. Amélioration de la quantification des images TEP à l'yttrium 90

Author

Millardet, Maël, Signal, IMage et Son (LS2N - équipe SIMS ), Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Nantes Université (Nantes Univ), Nuclear Oncology (CRCI2NA / Eq 2), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), École Centrale de Nantes (Nantes Univ - ECN), MILCOM, École Centrale de Nantes, Saïd Moussaoui, Thomas Carlier (co-directeur), École centrale de Nantes, Thomas Carlier, and Diana Carolina Mateus Lamus

Subjects
optimisation linéaire, PET, TEP, analyse multi-objectifs, algorithmes de reconstruction tomographique, [INFO.INFO-DS]Computer Science [cs]/Data Structures and Algorithms [cs.DS], yttrium-90, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, multi-objective analysis, linear programmation, yttrium 90, Multiobjective analysis, tomographic reconstruction algorithms
Abstract

Yttrium-90 PET imaging is becoming increasingly popular. However, the probability that decay of a yttrium-90 nucleus will lead to the emission of a positron is only 3.2 × 10−5, and the reconstructed images are therefore characterised by a high level of noise, as well as a positive bias in low activity regions. To correct these problems, classical methods use penalised algorithms or allow negative values in the image. However, a study comparing and combining these different methods in the specific context of yttrium-90 was still missing at the beginning of this thesis. This thesis, therefore, aims to fill this gap. Unfortunately, the methods allowing negative values cannot be used directly in a dosimetric study. Therefore, this thesis starts by proposing a new method of post-processing the images, aiming to remove the negative values while keeping the average values as locally as possible. A complete multi-objective analysis of these different methods is then proposed. This thesis ends by laying the foundations of what could become an algorithm providing a set of adequate reconstruction hyper-parameters from sinograms alone.; La popularité de l'imagerie TEP à l'yttrium 90 va grandissante. Cependant, la probabilité qu'une désintégration d'un noyau d'yttrium 90 mène à l'émission d'un positon n'est que de 3,2 × 10−5, et les images reconstruites sont par conséquent caractérisées par un niveau de bruit élevé, ainsi que par un biais positif dans les régions de faible activité. Pour corriger ces problèmes, les méthodes classiques consistent à utiliser des algorithmes pénalisés, ou autorisant des valeurs négatives dans l'image. Cependant, une étude comparant et combinant ces différentes méthodes dans le contexte spécifique de l'yttrium 90 manquait encore à l'appel au début de cette thèse. Cette dernière vise donc à combler ce manque. Malheureusement, les méthodes autorisant les valeurs négatives ne peuvent pas être utilisées directement dans le cadre d'une étude dosimétrique, et cette thèse commence donc par proposer une nouvelle méthode de post-traitement des images, visant à en supprimer les valeurs négatives en en conservant les valeurs moyennes le plus localement possible. Une analyse complète multi-objectifs de ces différentes méthodes est ensuite proposée. Cette thèse se termine en posant les prémices de ce qui pourra devenir un algorithme permettant de proposer un jeu d'hyper-paramètres de reconstruction adéquats, à partir des seuls sinogrammes.

Published
2022

23. Improvement of the quantification of yttrium-90 PET images

Author

Millardet, Maël, Signal, IMage et Son (LS2N - équipe SIMS ), Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Nantes Université - École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Nantes Université (Nantes Univ), Nuclear Oncology (CRCI2NA / Eq 2), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Nantes Université - École Centrale de Nantes (Nantes Univ - ECN), MILCOM, École Centrale de Nantes, Saïd Moussaoui, Thomas Carlier (co-directeur), and Millardet, Maël

Subjects
optimisation linéaire, PET, TEP, analyse multi-objectifs, algorithmes de reconstruction tomographique, yttrium-90, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, multi-objective analysis, linear programmation, yttrium 90, tomographic reconstruction algorithms
Abstract

Yttrium-90 PET imaging is becoming increasingly popular. However, the probability that decay of a yttrium-90 nucleus will lead to the emission of a positron is only 3.2 × 10−5, and the reconstructed images are therefore characterised by a high level of noise, as well as a positive bias in low activity regions. To correct these problems, classical methods use penalised algorithms or allow negative values in the image. However, a study comparing and combining these different methods in the specific context of yttrium-90 was still missing at the beginning of this thesis. This thesis, therefore, aims to fill this gap. Unfortunately, the methods allowing negative values cannot be used directly in a dosimetric study. Therefore, this thesis starts by proposing a new method of post-processing the images, aiming to remove the negative values while keeping the average values as locally as possible. A complete multi-objective analysis of these different methods is then proposed. This thesis ends by laying the foundations of what could become an algorithm providing a set of adequate reconstruction hyper-parameters from sinograms alone., La popularité de l'imagerie TEP à l'yttrium 90 va grandissante. Cependant, la probabilité qu'une désintégration d'un noyau d'yttrium 90 mène à l'émission d'un positon n'est que de 3,2 × 10−5, et les images reconstruites sont par conséquent caractérisées par un niveau de bruit élevé, ainsi que par un biais positif dans les régions de faible activité. Pour corriger ces problèmes, les méthodes classiques consistent à utiliser des algorithmes pénalisés, ou autorisant des valeurs négatives dans l'image. Cependant, une étude comparant et combinant ces différentes méthodes dans le contexte spécifique de l'yttrium 90 manquait encore à l'appel au début de cette thèse. Cette dernière vise donc à combler ce manque. Malheureusement, les méthodes autorisant les valeurs négatives ne peuvent pas être utilisées directement dans le cadre d'une étude dosimétrique, et cette thèse commence donc par proposer une nouvelle méthode de post-traitement des images, visant à en supprimer les valeurs négatives en en conservant les valeurs moyennes le plus localement possible. Une analyse complète multi-objectifs de ces différentes méthodes est ensuite proposée. Cette thèse se termine en posant les prémices de ce qui pourra devenir un algorithme permettant de proposer un jeu d'hyper-paramètres de reconstruction adéquats, à partir des seuls sinogrammes.

Published
2022

24. Impact of RAFT chain transfer agents on the polymeric shell density of magneto-fluorescent nanoparticles and their cellular uptake

Author

Thibaut Blondy, Julien Poly, Camille Linot, Joanna Boucard, Emilie Allard-Vannier, Steven Nedellec, Phillipe Hulin, Céline Hénoumont, Lionel Larbanoix, Robert N. Muller, Sophie Laurent, Eléna Ishow, Christophe Blanquart, Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Immunomodulation of the Tumor Microenvironment and Immunotherapy of Thoracic Cancers (CRCI2NA / Eq 1), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Institut de Science des Matériaux de Mulhouse (IS2M), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nanomédicaments et Nanosondes, EA 6295 (NMNS), Université de Tours (UT), Santé - François Bonamy, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Mons-Hainaut, Center for Microscopy and Molecular Imaging (IBMM - CMMI), Université libre de Bruxelles (ULB), and Blanquart, Christophe

Subjects
Polymers, Tumor Microenvironment, Nanoparticles, lipids (amino acids, peptides, and proteins), General Materials Science, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Coloring Agents, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Polyethylene Glycols, Polymerization
Abstract

International audience; The impact of nanoparticle surface chemistry on cell interactions and especially cell uptake has become evident over the last few years in nanomedicine. Since PEG polymers have proved to be ideal tools for attaining stealthiness and favor escape from the in vivo mononuclear phagocytotic system, the accurate control of their geometry is of primary importance and can be achieved through reversible addition-fragmentation transfer (RAFT) polymerization. In this study, we demonstrate that the residual groups of the chain transfer agents (CTAs) introduced in the main chain exert a significant impact on the cellular internalization of functionalized nanoparticles. High-resolution magic angle spinning 1 H NMR spectroscopy and fluorescence spectroscopy permitted by the magneto-fluorescence properties of nanoassemblies (NAs) revealed the compaction of the PEG comb-like shell incorporating CTAs with a long alkyl chain, without changing the overall surface potential. As a consequence of the capability of alkyl units to self-assemble at the NA surface while hardly contributing more than 0.5% to the total polyelectrolyte weight, denser PEGylated NAs showed notably less internalization in all cells of the tumor microenvironment (tumor cells, macrophages and healthy cells). Interestingly, such differentiated uptake is also observed between pro-inflammatory M1-like and immunosuppressive M2-like macrophages, with the latter more efficiently phagocytizing NAs coated with a less compact PEGylated shell. In contrast, the NA diffusion inside multicellular spheroids, used to mimic solid tumors, appeared to be independent of the NA coating. These results provide a novel effort-saving approach where the sole variation of the chemical nature of CTAs in RAFT PEGylated polymers strikingly modulate the cell uptake of nanoparticles upon the organization of their surface coating and open the pathway toward selectively addressing macrophage populations for cancer immunotherapy.

Published
2022

25. Targeting NKG2A to boost anti-tumor CD8 T-cell responses in human colorectal cancer

Author

Kathleen Ducoin, Romain Oger, Linda Bilonda Mutala, Cécile Deleine, Nicolas Jouand, Juliette Desfrançois, Juliette Podevin, Emilie Duchalais, Jonathan Cruard, Houssem Benlalam, Nathalie Labarrière, Céline Bossard, Anne Jarry, Nadine Gervois-Segain, Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), Signaling in Oncogenesis, Angiogenesis and Permeability - SOAP (CRCI2NA / Eq 6), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), INSTITUT Roche, Santé - François Bonamy, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), and Pecqueret, Valérie

Subjects
[SDV] Life Sciences [q-bio], Killer Cells, Natural, Lymphocytes, Tumor-Infiltrating, Oncology, [SDV]Life Sciences [q-bio], Immunology, Immunology and Allergy, Humans, CD8-Positive T-Lymphocytes, Colorectal Neoplasms, NK Cell Lectin-Like Receptor Subfamily C
Abstract

International audience; Recently, the inhibitory CD94/NKG2A receptor has joined the group of immune checkpoints (ICs) and its expression has been documented in NK cells and CD8+ T lymphocytes in several cancers and some infectious diseases. In colorectal cancer (CRC), we previously reported that NKG2A+ tumor-infiltrating lymphocytes (TILs) are predominantly CD8+ αβ T cells and that CD94 overexpression and/or its ligand HLA-E were associated with a poor prognosis. This study aimed to thoroughly characterize the NKG2A+ CD8+ TIL subpopulation and document the impact of NKG2A on anti-tumor responses in CRC. Our findings highlight new features of this subpopulation: (i) enrichment in colorectal tumors compared to paired normal colonic mucosa, (ii) their character as tissue-resident T cells and their majority terminal exhaustion status, (iii) co-expression of other ICs delineating two subgroups differing mainly in the level of NKG2A expression and the presence of PD-1, (iv) high functional avidity despite reduced proliferative capacity and finally (v) inhibition of anti-tumor reactivity that is overcome by blocking NKG2A. From a clinical point of view, these results open a promising alternative for immunotherapies based on NKG2A blockade in CRC, which could be performed alone or in combination with other IC inhibitors, adoptive cell transfer or therapeutic vaccination.

Published
2022

26. Inhibition of the pseudokinase MLKL alters extracellular vesicle release and reduces tumor growth in glioblastoma

Author

Gwennan André-Grégoire, Clément Maghe, Tiphaine Douanne, Sara Rosińska, Fiorella Spinelli, An Thys, Kilian Trillet, Kathryn A. Jacobs, Cyndie Ballu, Aurélien Dupont, Anne-Marie Lyne, Florence M.G. Cavalli, Ignacio Busnelli, Vincent Hyenne, Jacky G. Goetz, Nicolas Bidère, Julie Gavard, Signaling in Oncogenesis, Angiogenesis and Permeability - SOAP (CRCI2NA / Eq 6), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Equipe Labellisée Ligue Contre le Cancer [Nantes] (ELLCC), 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 ), Institut Curie - PSL Research University [Paris] (IC-PSLRU), 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), Centre de Bioinformatique (CBIO), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), and Gavard, Julie

Subjects
PROGRAMMED NECROSIS, Science & Technology, Multidisciplinary, [SDV]Life Sciences [q-bio], TEMOZOLOMIDE, MICROENVIRONMENT, Multidisciplinary Sciences, [SDV] Life Sciences [q-bio], MIXED LINEAGE KINASE, DOMAIN-LIKE, Science & Technology - Other Topics, PROMOTE, TRAFFICKING, DOWNSTREAM, STEM-CELLS, MEDIATES NECROPTOSIS
Abstract

Extracellular vesicles (EVs) are lipid-based nanosized particles that convey biological material from donor to recipient cells. EVs play key roles in glioblastoma progression because glioblastoma stem-like cells (GSCs) release pro-oncogenic, pro-angiogenic, and pro-inflammatory EVs. However, the molecular basis of EV release remains poorly understood. Here, we report the identification of the pseudokinase MLKL, a crucial effector of cell death by necroptosis, as a regulator of the constitutive secretion of EVs in GSCs. We find that genetic, protein, and pharmacological targeting of MLKL alters intracellular trafficking and EV release, and reduces GSC expansion. Nevertheless, this function ascribed to MLKL appears independent of its role during necroptosis. In vivo, pharmacological inhibition of MLKL reduces the tumor burden and the level of plasmatic EVs. This work highlights the necroptosis-independent role of MLKL in vesicle release and suggests that interfering with EVs is a promising therapeutic option to sensitize glioblastoma cells. ispartof: ISCIENCE vol:25 issue:10 ispartof: location:United States status: published

Published
2022

27. HRAS Q61L Mutation as a Possible Target for Non-Small Cell Lung Cancer: Case Series and Review of Literature

Author

Laurent Mathiot, Guillaume Herbreteau, Siméon Robin, Charlotte Fenat, Jaafar Bennouna, Christophe Blanquart, Marc Denis, Elvire Pons-Tostivint, Blanquart, Christophe, Immunomodulation of the Tumor Microenvironment and Immunotherapy of Thoracic Cancers (CRCI2NA / Eq 1), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ), and Hôpital Foch [Suresnes]

Subjects
Proto-Oncogene Proteins p21(ras), Lung Neoplasms, [SDV.CAN] Life Sciences [q-bio]/Cancer, Carcinoma, Non-Small-Cell Lung, Mutation, tipifarnib, Humans, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, HRAS Gln61Leu, oncogenic driver, Lung cancer NSCLC
Abstract

International audience; Introduction: Assessment of actionable gene mutations and oncogene fusions have made a paradigm shift in treatment strategies of non-small cell lung cancer (NSCLC). HRAS mutations involved around 0.2-0.8% of NSCLC patients, mostly on codon 61. For these patients, few data are available regarding clinical characteristics and response to therapies.Methods: Next-Generation Sequencing (NGS) done routinely at Nantes University Hospital was used to identify HRAS molecular alterations in NSCLC patients. We identified and described four HRAS p.GlnQ61Leu mutated patients. Literature of previously HRAS-mutant NSCLC cases was reviewed, and available data in solid tumour with the most advanced H-Ras specific inhibitor, tipifarnib, were presented.Results: Of 1614 patients diagnosed with advanced NSCLC from January 2018 to December 2020, four (0.25%) had HRAS p.Gln61Leu mutation. Three of them died during the first-line systemic therapy. Furthermore, three additional cases were identified in literature. All cases were current or former smokers, most of them had pleural or pericardial effusion at diagnosis.Conclusions: The clinical course of patients with HRAS-mutant NSCLC remains unclear. Furthers cases should be identified in order to clarify prognosis and response to therapies. Tipifarnib, a farnesyl transferase inhibitor, is a promising candidate to target HRAS-mutant tumours and should be explored in NSCLC patients.

Published
2022

28. Slower degradation rate of cytarabine in blood samples from acute myeloid leukemia by comparison with control samples

Author

Philippe Guardiola, Sarah Ghamrawi, Séverine Férec, Mathilde Hunault-Berger, Simon Souchet, Chadi Abbara, Guillaume Drevin, Marie Briet, Jean-Baptiste Robin, Aline Schmidt, Département de Pharmacologie-Toxicologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Université d'Angers (UA), Service de Génomique Onco-Hématologique [CHU Angers], Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service des maladies du sang [CHU Angers], Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), 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), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), and Bernardo, Elizabeth

Subjects
Male, 0301 basic medicine, Cancer Research, Time Factors, medicine.medical_treatment, Toxicology, Gastroenterology, 0302 clinical medicine, Drug Stability, AML, Tandem Mass Spectrometry, hemic and lymphatic diseases, Pharmacology (medical), Chromatography, High Pressure Liquid, Randomized Controlled Trials as Topic, Cytarabine, In vitro degradation, Area under the curve, Myeloid leukemia, Middle Aged, 3. Good health, Leukemia, Myeloid, Acute, Oncology, Deamination, 030220 oncology & carcinogenesis, Female, Multiple linear regression analysis, Stability, Half-Life, medicine.drug, Adult, Antimetabolites, Antineoplastic, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, Clinical pharmacokinetic, Specimen Handling, Young Adult, 03 medical and health sciences, Clinical Trials, Phase II as Topic, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cytidine Deaminase, Internal medicine, medicine, Humans, Clinical significance, Pharmacology, Chemotherapy, business.industry, 030104 developmental biology, Clinical Trials, Phase III as Topic, Case-Control Studies, business
Abstract

International audience; Purpose: Cytarabine, a key chemotherapy agent for acute myeloid leukemia (AML) treatment, is deaminated into inactive uracil-arabinoside by cytidine deaminase. This deamination leads to samples stability issues with respect to clinical pharmacokinetic trials. The aim of our study was to study in vitro cytarabine stability in blood samples obtained from AML patients.Methods: Cytarabine quantification was performed using a fully validated LC/MS/MS method. In vitro cytarabine stability was assessed at room temperature over 24 h in samples coming from 14 AML patients and 7 control patients (CTRL) with no hematological malignancy. In vitro concentrations versus time data were analyzed using a noncompartmental approach.Results: Cytarabine in vitro area under the curve (AUCIVlast) was 22-fold higher in AML samples as compared to CTRL samples (AML mean (standard deviation (SD)), 51,829 (27,004) h ng/mL; CTRL mean (SD), 2356 (1250) h ng/mL, p = 0.00019). This increase was associated with a prolonged in vitro degradation half-life (t1/2IVdeg AML mean (SD), 15 (11.8) h; CTRL mean (SD), 0.36 (0.37) h, p = 0.0033). Multiple linear regression analysis showed that AML diagnosis significantly influenced t1/2IVdeg and AUCIVlas relationship.Conclusion: Cytarabine stability is higher in AML than in CTRL samples. The absence of correlation between t1/2IVdeg and AUCIVlast in AML samples suggests that in vitro cytarabine degradation in AML is complex. These results open perspectives including the evaluation of the clinical relevance and the involved molecular mechanisms.

Published
2020

29. Anti‐SARS‐CoV‐2 vaccines in recipient and/or donor before allotransplant

Author

Maxime Jullien, Marianne Coste‐Burel, Beatrice Clemenceau, Valentin Letailleur, Thierry Guillaume, Pierre Peterlin, Alice Garnier, Amandine Le Bourgeois, Berthe‐Marie Imbert, Jocelyn Ollier, Audrey Grain, Cyrille Touzeau, Philippe Moreau, Marie C Béné, Henri Vié, Patrice Chevallier, Département d'Hématologie Clinique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de virologie [CHU Nantes], Manipulation of Lymphocytes for Immunotherapy (CRCI2NA / Eq 12), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Service d'hématologie biologique [Nantes] (Cytologie Hématologique), Hôtel-Dieu de Nantes-Centre hospitalier universitaire de Nantes (CHU Nantes), and Ollier, Jocelyn

Subjects
allogeneic, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.IMM] Life Sciences [q-bio]/Immunology, viruses, fungi, virus diseases, COVID-19, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, SARS-CoV-2 mRNA, cellular response, surgical procedures, operative, vaccine, [SDV.IMM]Life Sciences [q-bio]/Immunology, hematological, skin and connective tissue diseases, humoral response, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; The impact of pre-transplant anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine in 20 recipients of allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and/or their donors is reported here, showing that the persistence of anti-SARS-CoV-2 antibodies can be detected in almost all patients, whatever the type of vaccine used, and up to 9 months post transplant. Also, an anti-SARS-CoV-2 spike glycoprotein CD3+ T-cell response could be detected in six (35%) of 17 evaluable patients. This study provides a rationale to consider anti-SARS-CoV-2 vaccination of both recipients and donors before Allo-HSCT.

Published
2022

30. Mitochondrial DNA copy number as a prognostic marker is age-dependent in adult glioblastoma

Author

Baptiste Sourty, Laure-Marie Dardaud, Céline Bris, Valérie Desquiret-Dumas, Blandine Boisselier, Laëtitia Basset, Dominique Figarella-Branger, Alain Morel, Marc Sanson, Vincent Procaccio, Audrey Rousseau, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - 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), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Onco-neurologie = Département de neurologie 2 [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [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), and HAL-SU, Gestionnaire

Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Basic and Translational Investigations, glioblastoma, AcademicSubjects/MED00300, AcademicSubjects/MED00310, methylation, mitochondrial DNA, prognosis, metabolism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background Glioblastoma (GBM) is the most common and aggressive form of glioma. GBM frequently displays chromosome (chr) 7 gain, chr 10 loss and/or EGFR amplification (chr7+/chr10-/EGFRamp). Overall survival (OS) is 15 months after treatment. In young adults, IDH1/2 mutations are associated with longer survival. In children, histone H3 mutations portend a dismal prognosis. Novel reliable prognostic markers are needed in GBM. We assessed the prognostic value of mitochondrial DNA (mtDNA) copy number in adult GBM. Methods mtDNA copy number was assessed using real-time quantitative PCR in 232 primary GBM. Methylation of POLG and TFAM genes, involved in mtDNA replication, was assessed by bisulfite-pyrosequencing in 44 and 51 cases, respectively. Results Median age at diagnosis was 56.6 years-old and median OS, 13.3 months. 153/232 GBM (66 %) displayed chr7+/chr10-/EGFRamp, 23 (9.9 %) IDH1/2 mutation, 3 (1.3 %) H3 mutation and 53 (22.8 %) no key genetic alterations. GBM were divided into two groups, “Low” (n = 116) and “High” (n = 116), according to the median mtDNA/nuclear DNA ratio (237.7). There was no significant difference in OS between the two groups. By dividing the whole cohort according to the median age at diagnosis, OS was longer in the “High” vs “Low” subgroup (27.3 vs 15 months, P = .0203) in young adult GBM (n = 117) and longer in the “Low” vs “High” subgroup (14.5 vs 10.2 months, P = .0116) in older adult GBM (n = 115). POLG was highly methylated, whereas TFAM remained unmethylated. Conclusion mtDNA copy number may be a novel prognostic biomarker in GBM, its impact depending on age.

Published
2022

31. Prognostic Value of Metabolic, Volumetric and Textural Parameters of Baseline [18F]FDG PET/CT in Early Triple-Negative Breast Cancer

Author

Clément Bouron, Clara Mathie, Valérie Seegers, Olivier Morel, Pascal Jézéquel, Hamza Lasla, Camille Guillerminet, Sylvie Girault, Marie Lacombe, Avigaelle Sher, Franck Lacoeuille, Anne Patsouris, Aude Testard, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Design and application of innovative loco-regional Treatments in Gliobastoma (CRCI2NA / Eq 5), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), and LACOEUILLE, FRANCK

Subjects
[18F]FDG PET/CT, [SDV] Life Sciences [q-bio], Cancer Research, Oncology, [SDV]Life Sciences [q-bio], textural features, TNBC, prognosis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

(1) Background: triple-negative breast cancer (TNBC) remains a clinical and therapeutic challenge primarily affecting young women with poor prognosis. TNBC is currently treated as a single entity but presents a very diverse profile in terms of prognosis and response to treatment. Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose ([18F]FDG) is gaining importance for the staging of breast cancers. TNBCs often show high [18F]FDG uptake and some studies have suggested a prognostic value for metabolic and volumetric parameters, but no study to our knowledge has examined textural features in TNBC. The objective of this study was to evaluate the association between metabolic, volumetric and textural parameters measured at the initial [18F]FDG PET/CT and disease-free survival (DFS) and overall survival (OS) in patients with nonmetastatic TBNC. (2) Methods: all consecutive nonmetastatic TNBC patients who underwent a [18F]FDG PET/CT examination upon diagnosis between 2012 and 2018 were retrospectively included. The metabolic and volumetric parameters (SUVmax, SUVmean, SUVpeak, MTV, and TLG) and the textural features (entropy, homogeneity, SRE, LRE, LGZE, and HGZE) of the primary tumor were collected. (3) Results: 111 patients were enrolled (median follow-up: 53.6 months). In the univariate analysis, high TLG, MTV and entropy values of the primary tumor were associated with lower DFS (p = 0.008, p = 0.006 and p = 0.025, respectively) and lower OS (p = 0.002, p = 0.001 and p = 0.046, respectively). The discriminating thresholds for two-year DFS were calculated as 7.5 for MTV, 55.8 for TLG and 2.6 for entropy. The discriminating thresholds for two-year OS were calculated as 9.3 for MTV, 57.4 for TLG and 2.67 for entropy. In the multivariate analysis, lymph node involvement in PET/CT was associated with lower DFS (p = 0.036), and the high MTV of the primary tumor was correlated with lower OS (p = 0.014). (4) Conclusions: textural features associated with metabolic and volumetric parameters of baseline [18F]FDG PET/CT have a prognostic value for identifying high-relapse-risk groups in early TNBC patients.

Published
2022

32. P-169 - Influence of radiolysis on astatine-211 chemistry

Author

Ghalei, Mohammad, Mahdi Khoshouei, Parastoo, Vandenborre, Johan, Guérard, François, Blain, Guillaume, Zarei, Mojtaba, Haddad, Ferid, Fattahi, Massoud, Guérard, François, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), GIP ARRONAX [Nantes], Université de Nantes (UN), Nuclear Oncology (CRCI2NA / Eq 2), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

International audience

Published
2022

33. A Randomised Phase II Study of Azacitidine (AZA) Alone or with Lenalidomide (LEN), Valproic Acid (VPA) or Idarubicin (IDA) in Higher-Risk MDS or Low Blast AML: GFM's 'Pick a Winner' Trial, with the Impact of Somatic Mutations

Author

Lionel, Adès, Nicolas, Duployez, Agnes, Guerci-Bresler, Kamel, Laribi, Pierre, Peterlin, Norbert, Vey, Sylvain, Thepot, Stefan, Wickenhauser, Hacene, Zerazhi, Aspassia, Stamatoullas, Eric, Wattel, Christian, Recher, Andrea, Toma, Sophie, Dimicoli-Salazar, Thorsten, Braun, Odile, Beyne-Rauzy, Jean-Pierre, Marolleau, Stéphane, Cheze, Sophie, Park, Thomas, Cluzeau, Stanislas, Nimubona, Dominique, Bordessoule, Riad, Benramdane, Bruno, Quesnel, Shanti, Amé, Stéphane, de Botton, Fathia, Chermat, Claude, Preudhomme, Sylvie, Chevret, Pierre, Fenaux, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), 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), Centre Hospitalier Universitaire de Nancy (CHU Nancy), Centre Hospitalier Le Mans (CH Le Mans), Centre hospitalier universitaire de Nantes (CHU Nantes), Nantes Université (Nantes Univ), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Aix Marseille Université (AMU), 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), Stress Adaptation and Tumor Escape - SATE (CRCI2NA / Eq 7), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Henri Duffaut (Avignon), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure de Lyon (ENS de 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), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Henri Mondor, Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Grenoble, XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre Hospitalier René Dubos [Pontoise], Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Institut Gustave Roussy (IGR), Département d'hématologie [Gustave Roussy], Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
Leukemia, Myeloid, Acute, Treatment Outcome, Valproic Acid, Antineoplastic Combined Chemotherapy Protocols, Mutation, Azacitidine, Humans, Idarubicin, Lenalidomide, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; In order to improve the outcome observed with azacitidine (AZA) in higher-risk Myelodysplastic syndrome (MDS), its combination with other drugs in MDS must be evaluated. So far, no combination has not been shown to be more effective than AZA alone. AZA-PLUS was a phase II trial that, in a "pick a winner" approach, randomly assigned patients with higher-risk MDS, CMML and low blast count AML to: AZA; AZA plus lenalidomide; AZA plus Valproic Acid or AZA plus Idarubicin. 322 patients were included. After six\,cycles, 69 (21.4%) CR\,+\,PR were observed with no benefit from any combination. Median EFS and OS were 17.2 and 19.7\,months in the whole cohort, respectively, with no difference across randomised arms. Infection and rates of hospitalisation during the first six\,cycles were higher in the AZA-LEN And AZA-IDA arm, related to increased myelosuppression. Factors associated with better response were IPSS, favourable or intermediate karyotype, haemoglobin, lower circulating blast count, fibrinogen level and lower LDH, while poorer survival was seen in therapy-related MDS and, in the case of TP53, PTPN11 or CSF3R mutation. The combinations used did not improve the outcome obtained with AZA alone. However, our "pick a winner" randomised strategy may remain useful with potentially more active drugs to be tested in combination with AZA.

Published
2022

34. ALL relapse after anti-CD19 CAR-T cells therapy in a young adult: which therapeutic options?

Author

Grain, Audrey, Ollier, Jocelyn, Guillaume, Thierry, Chevallier, Patrice, Le Calvez, Baptiste, Eveillard, Marion, Clémenceau, Béatrice, Ollier, Jocelyn, Manipulation of Lymphocytes for Immunotherapy (CRCI2NA / Eq 12), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Service d'Hématologie et Oncologie pédiatriques [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'Hématologie [CHU Nantes], and Service d'Hématologie Biologique [CHU Nantes]

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy
Abstract

International audience; T-cells expressing a Chimeric Antigen Receptor (CAR) recognizing the CD19 antigen allowed high early response rates in high-risk B acute lymphoblastic leukemias (B-ALL). Nevertheless, 35% to 44% of patients relapse. Among the mechanisms of immune evasion in CD19+ relapses of ALL, expression and secretion of molecules inhibiting cytotoxic T-lymphocytes, or lack of expression of co-stimulatory molecules, have been described. Expansion, persistence and cytotoxic activity of CAR-T cells could also be deficient.Here, we present the case of a young adult who presented successive relapses of ALL after chemotherapy, hematopoietic stem cell transplant (HSCT) and anti-CD19 CAR-T cells. An extended immunophenotype of leukemic cells and sensitivity to anti-CD19 CAR-T cells mediated lysis are analysed.

Published
2022

35. A combined field study of Buruli ulcer disease in southeast Benin proposing preventive strategies based on epidemiological, geographic, behavioural and environmental analyses

Author

Alexandra Boccarossa, Horace Degnonvi, Télesphore Yao Brou, Marie Robbe-Saule, Lucille Esnault, Yan Boucaud, Matthieu Eveillard, Ronald Gnimavo, Saturnin Hounsou, Armel Djenontin, Christian Roch Johnson, Sébastien Fleuret, Estelle Marion, Dupuis, Christine, Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Espaces et Sociétés (ESO), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Le Mans Université (UM)-Université d'Angers (UA)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Géographie et d'Aménagement Régional de l'Université de Nantes (NantesUniv – IGARUN), Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Agro Rennes Angers, 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), Université d’Abomey-Calavi = University of Abomey Calavi (UAC), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Centre de Dépistage et de Traitement de la Lèpre et de l’Ulcère de Buruli [Pobe, Benin] (CDTLUB), and Fondation Raoul Follereau [Pobe, Benin]

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

Buruli ulcer is a neglected tropical disease caused by M. ulcerans, an environmental mycobacterium. This cutaneous infectious disease affects populations with poor access to sanitation, safe water and healthcare living in rural areas of West and Central Africa. Stagnant open bodies of surface water and slow-running streams are the only risk factor identified in Africa, and there is no human-to-human transmission. Appropriate and effective prevention strategies are required for populations living in endemic areas. Based on a multidisciplinary approach in an area in which Buruli ulcer is endemic in South Benin, we investigated the link between all human-environment interactions relating to unprotected water and behaviors associated with Buruli ulcer risk likely to affect incidence rates. We characterised the sources of water as well as water bodies and streams used by communities, by conducting a prospective case-control study directly coupled with geographic field observations, spatial analysis, and the detection of M. ulcerans in the environment. A full list of the free surface waters used for domestic activities was generated for a set of 34 villages, and several types of human behaviour associated with a higher risk of transmission were identified: (i) prolonged walking in water to reach cultivated fields, (ii) collecting water, (iii) and swimming. Combining the results of the different analyses identified the risk factor most strongly associated with Buruli ulcer was the frequency of contact with unprotected and natural water, particularly in regularly flooded or irrigated lowlands. We confirm that the use of clean water from drilled wells confers protection against Buruli ulcer. These specific and refined results provide a broader scope for the design of an appropriate preventive strategy including certain practices or infrastructures observed during our field investigations. This strategy could be improved by the addition of knowledge about irrigation practices and agricultural work in low-lying areas.

Published
2022

36. How radiolysis impacts astatine speciation?

Author

Mohammad Ghalei, Parastoo Mahdi Khoshouei, Johan Vandenborre, François Guerard, Guillaume Blain, Mojtaba Zarei, Ferid Haddad, Massoud Fattahi, Guérard, François, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nuclear Oncology (CRCI2NA / Eq 2), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), GIP ARRONAX [Nantes], and Université de Nantes (UN)

Subjects
Radiation, Hydrogen Chloride, [SDV.CAN] Life Sciences [q-bio]/Cancer, Radiolysis, Astatine Chemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, Chloroform, G-yield
Abstract

International audience; This work deals with the impact of chloroform radiolysis on astatine chemistry. Astatine-211 is a promising radionuclide for the targeted alpha therapy of cancers. Yet, the production of 211 At based radiopharmaceuticals is often complicated by radiolysis due to its own decay, leading to solvent degradation and then impacting astatine chemical state and radiolabeling efficiency. A better understanding of the radiolysis phenomenon is thus necessary. Two experiments are performed: (1) pH measurement during the At extraction in chloroform medium, (2) pH determination calculated from the HCl chemical yield which is obtained during the radiolysis of chloroform medium by γ-ray. In both cases, the pH values are determined at 2.0 ± 0.5. Then, it is possible to predict the acidic conditions during the 211 At production by HCl radiolytic yield determination. This work demonstrated that the radiolysis induced by At during its production in CHCl3 medium should be taken into account as it has a significant effect on acid-basic conditions. The work helps understanding the mechanisms of production of a major impurity generated from 211 At radiolysis in chloroform which alters its radiochemistry, allowing for the identification of solutions to counteract these unwanted effects.

Published
2022

37. Neuropilin-1 modulates the 3D invasive properties of glioblastoma stem-like cells

Author

Mathilde Kerhervé, Sara Rosińska, Kilian Trillet, Alya Zeinaty, Magalie Feyeux, Steven Nedellec, Julie Gavard, Gavard, Julie, Signaling in Oncogenesis, Angiogenesis and Permeability - SOAP (CRCI2NA / Eq 6), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Equipe Labellisée Ligue Contre le Cancer [Nantes] (ELLCC), Santé - François Bonamy, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Cell Biology, Developmental Biology
Abstract

Glioblastoma multiforme (GBM) is a rare, yet devastating, primary brain tumor in adults. Current treatments remain generally ineffective and GBM almost invariably recurs, resulting in median survival of 15 months. This high malignancy sources notably from the resilience and invasive capabilities of tumor cells. Within GBM, exists a population of self-sustaining transformed cells with stem-like properties (GSCs), which are thought to be responsible for tumor initiation, growth, and invasion, as well as recurrence. In the tumor microenvironment, GSCs might be found in the vicinity of brain endothelial cells, which provide a protective habitat. Likewise, these resistant, quiescent GSCs may accumulate in hypoxic zones, away from the perivascular niche, or travel towards the healthy brain parenchyma, by eminently co-opting neuro-vascular tracks. Herein, we established an ex vivo model to explore GSC invasive behavior. We found that patient-derived cells massively invade the collagen matrix. In addition, we described that the glycoprotein Neuropilin-1 (NRP1) contributes to GSC spreading and invasion. Indeed, both RNA interference-mediated silencing and CRISPR-mediated gene editing deletion of NRP1 strongly impaired the 3D invasive properties of patient-derived GSCs and their close localization to the brain blood vessels. Of note, other typical features of GSCs, such as expansion and self-renewal were maintained. From a mechanistic standpoint, this biological effect might rely on the expression of the β3 subunit integrin cell-extracellular matrix adhesive receptor. Our data, therefore, propose a reliable approach to explore invasive properties of patient glioma cells ex vivo and identify NRP1 as a mediator in this malignant process.

Published
2022

38. Enhancement of the Anti-Angiogenic Effects of Delphinidin When Encapsulated within Small Extracellular Vesicles

Author

Merwan Barkallah, Judith Nzoughet-Kouassi, Gilles Simard, Loric Thoulouze, Sébastien Marze, Marie-Hélène Ropers, Ramaroson Andriantsitohaina, Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), MitoVasc - 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), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and DUPRE, Olivier

Subjects
viruses, Angiogenesis Inhibitors, [SDV.CAN]Life Sciences [q-bio]/Cancer, small extracellular vesicles, Nitric Oxide, Article, Anthocyanins, Extracellular Vesicles, angiogenesis, Drug Delivery Systems, Drug Stability, [SDV.CAN] Life Sciences [q-bio]/Cancer, Humans, cancer, TX341-641, Aorta, Cells, Cultured, [CHIM.MATE] Chemical Sciences/Material chemistry, Nutrition and Dietetics, Neovascularization, Pathologic, delphinidin, Nutrition. Foods and food supply, virus diseases, food and beverages, Dendritic Cells, [CHIM.MATE]Chemical Sciences/Material chemistry, respiratory system, endothelial cells, cardiovascular diseases, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract

International audience; (1) Background: The anthocyanin delphinidin exhibits anti-angiogenic properties both in in vitro and in vivo angiogenesis models. However, in vivo delphinidin is poorly absorbed, thus its modest bioavailability and stability reduce its anti-angiogenic effects. The present work takes advantage of small extracellular vesicle (sEV) properties to enhance both the stability and efficacy of delphinidin. When encapsulated in sEVs, delphinidin inhibits the different stages of angiogenesis on human aortic endothelial cells (HAoECs). (2) Methods: sEVs from immature dendritic cells were produced and loaded with delphinidin. A method based on UHPLC-HRMS was implemented to assess delphinidin metabolites within sEVs. Proliferation assay, nitric oxide (NO) production and Matrigel assay were evaluated in HAoECs. (3) Results: Delphinidine, 3-O-β-rutinoside and Peonidin-3-galactoside were found both in delphinidin and delphinidin-loaded sEVs. sEV-loaded delphinidin increased the potency of free delphinidin 2-fold for endothelial proliferation, 10-fold for endothelial NO production and 100-fold for capillary-like formation. Thus, sEV-loaded delphinidin exerts effects on the different steps of angiogenesis. (4) Conclusions: sEVs may be considered as a promising approach to deliver delphinidin to target angiogenesis-related diseases, including cancer and pathologies associated with excess vascularization.

Published
2021
Full Text
View/download PDF

39. TRASS: a global approach to assess the severity of truncal acne

Author

N. Auffret, J.M. Nguyen, M.‐T. Leccia, J.P. Claudel, B. Dréno, Private Practice [Paris], Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Département de dermatologie, allergologie et photobiologie [Hôpital Michallon du CHU Grenoble Alpes], Centre Hospitalier Universitaire [Grenoble] (CHU)-Hôpital Michallon, Private Practice [Tours], Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), CIC biothérapies CBT 0503 [Nantes], Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Département de Dermato-Cancerologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), and Pecqueret, Valérie

Subjects
Male, truncal acne, trunk, [SDV]Life Sciences [q-bio], Torso, Dermatology, Administration, Cutaneous, Severity of Illness Index, scale, [SDV] Life Sciences [q-bio], Cicatrix, Infectious Diseases, scoring tool, Acne Vulgaris, Quality of Life, Humans, Female, acne severity, acne
Abstract

International audience; Introduction: Only a small amount of published data regarding truncal acne is available and no proper tool to assess its severity exists.Aim: to provide dermatologists with an easy-to-use tool to assess truncal acne (TRASS, truncal acne severity scale) using a global approach.Methods: A scoring tool that assesses the severity of acne (based on GEA and ECLA scales) on the trunk using a global approach was built, including three subscores: family history, clinical signs and quality of life (QoL). In order to test TRASS, the experts used photos of 47 patients attending their clinics with truncal acne. The ROP (Regression OPtimized) model was applied to assess the diagnosis performance of TRASS and to identify items contributing to the classification of the patients. Internal testing was made to demonstrate the robustness of the model. Correlation analyses between the different items were performed to evaluate the interaction between the different items and their impact on the severity grading of truncal acne.Results: Patients with the most severe acne were identified by TRASS. The error level was 6.6% after internal validation and 10.4% when using the median value or the centile 75th (6.6% and 10.4%). Correlation was significant between systemic treatment and scars (p=0.0025) and nodules (p=0.01988) and between location and QoL (p=0.0095).Conclusion: TRASS is the first global, patient-centred approach to evaluate truncal acne by scoring the importance of each factor independently from its clinical severity. TRASS may allow the practitioner to choose and validate the most suitable therapy together with the patient in order to treat his or her truncal acne successfully and to limit treatment failure.

Published
2021

40. Antiangiogenic Compound Axitinib Demonstrates Low Toxicity and Antitumoral Effects against Medulloblastoma

Author

Marina Pagnuzzi-Boncompagni, Vincent Picco, Valérie Vial, Victor Planas-Bielsa, Ashaina Vandenberghe, Thomas Daubon, Marie-Alix Derieppe, Christopher Montemagno, Jérôme Durivault, Renaud Grépin, Sonia Martial, Jérôme Doyen, Julie Gavard, Gilles Pagès, Centre Scientifique de Monaco (CSM), Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA), Signaling in Oncogenesis, Angiogenesis and Permeability - SOAP (CRCI2NA / Eq 6), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), and Bernardo, Elizabeth

Subjects
Cancer Research, angiogenesis, pediatric brain cancer, medulloblastoma, targeted therapy, [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV.CAN]Life Sciences [q-bio]/Cancer, RC254-282, Article
Abstract

Simple Summary Medulloblastoma is the most frequent pediatric brain cancer. Despite great improvements in the treatment of this disease over the last decades, survivors are subject to debilitating adverse effects that strongly impair their quality of life. There is an urgent need to find efficient anticancer therapies with fewer toxic effects. In this study, we suggest that an FDA- and EMA-approved antiangiogenic compound named axitinib may display effective antitumoral effects and low toxicity towards children as compared to a reference treatment currently used in clinical protocols. We also show that this compound can enter the brain compartment and exert antitumoral effects in vivo. Our study paves the way towards a clinical trial of repurposing axitinib to a pediatric brain cancer indication. Abstract Background: Despite the improvement of medulloblastoma (MB) treatments, survivors face severe long-term adverse effects and associated morbidity following multimodal treatments. Moreover, relapses are fatal within a few months. Therefore, chemotherapies inducing fewer adverse effects and/or improving survival at relapse are key for MB patients. Our purpose was to evaluate the last-generation antiangiogenic drugs for their relevance in the therapeutic arsenal of MB. Methods: We screened three EMA- and FDA-approved antiangiogenic compounds (axitinib, cabozantinib and sunitinib) for their ability to reduce cell viability of five MB cell lines and their low toxicity towards two normal cell lines in vitro. Based on this screening, single-agent and combination therapies were designed for in vivo validation. Results: Axitinib, cabozantinib and sunitinib decreased viability of all the tested tumor cells. Although sunitinib was the most efficient in tumor cells, it also impacted normal cells. Therefore, axitinib showed the highest selectivity index for MB cells as compared to normal cells. The compound did not lead to acute toxicity in juvenile rats and crossed the blood–brain barrier. Moreover, axitinib efficiently reduced the growth rate of experimental brain tumors. Analysis of public databases showed that high expression of axitinib targets correlates with poor prognosis. Conclusion: Our results suggest that axitinib is a compelling candidate for MB treatment.

Published
2021

41. Turning up the Green Light

Author

U. Valentin Nägerl, Julien Cassereau, Vincent Courdavault, CCSD, Accord Elsevier, MitoVasc - Équipe MitoLab (Mitochondrial Pathophysiology) (MITOVASC-MITOLAB), MitoVasc - 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)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biomolécules et biotechnologies végétales (BBV EA 2106), Université de Tours (UT), Interdisciplinary Institute for Neuroscience [Bordeaux] (IINS), Université de Bordeaux (UB)-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), and Université de Tours

Subjects
0303 health sciences, animal structures, fluorescent proteins, Super-resolution microscopy, [SDV]Life Sciences [q-bio], Green Fluorescent Proteins, brain imaging, protein engineering, Cell Biology, Protein engineering, Biology, Green-light, Biochemical Activity, Fluorescence, Green fluorescent protein, [SDV] Life Sciences [q-bio], Folding (chemistry), 03 medical and health sciences, 0302 clinical medicine, super-resolution microscopy, Mutation, Biophysics, ComputingMilieux_MISCELLANEOUS, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

International audience; Fluorescent proteins (FPs) have become indispensable tools in biological research for labeling cells and proteins and sensing their biochemical activity. By introducing 'folding mutations', Campbell et al. engineered a new GFP variant with dramatically enhanced cellular brightness and stability, facilitating advanced cellular bioimaging applications in neuroscience and beyond.

Published
2021

42. The von Willebrand Factor stamps Plasmatic Extracellular Vesicles from Glioblastoma Patients

Author

Emmanuel Jouglar, Gwennan André-Grégoire, Quentin Sabbagh, Jean-Sebastien Frenel, Nicolas Bidère, Carolina Alves-Nicolau, Aurélien Dupont, Laetitia Guevel, Julie Gavard, Signaling in Oncogenesis, Angiogenesis and Permeability (CRCINA-ÉQUIPE 15), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, 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 ), Signaling in Oncogenesis, Angiogenesis and Permeability - SOAP (CRCI2NA / Eq 6), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), 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 ), Gavard, Julie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)

Subjects
Male, Cell biology, Proteome, Science, [SDV]Life Sciences [q-bio], Tumor burden, Extracellular vesicles, Article, Extracellular Vesicles, 03 medical and health sciences, 0302 clinical medicine, Individual health, Von Willebrand factor, von Willebrand Factor, Biomarkers, Tumor, Tumor Microenvironment, Humans, Medicine, Aged, Cancer, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, Tumor microenvironment, Multidisciplinary, biology, Brain Neoplasms, business.industry, Extracellular vesicle, Middle Aged, Prognosis, medicine.disease, [SDV] Life Sciences [q-bio], Case-Control Studies, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Female, Glioblastoma, business, Homeostasis, Follow-Up Studies
Abstract

Glioblastoma is a devastating tumor of the central nervous system characterized by a poor survival and an extremely dark prognosis, making its diagnosis, treatment and monitoring highly challenging. Numerous studies have highlighted extracellular vesicles (EVs) as key players of tumor growth, invasiveness and resistance, as they carry and disseminate oncogenic material in the local tumor microenvironment and at distance. However, whether their quality and quantity reflect individual health status and changes in homeostasis is still not fully elucidated. Here, we separated EVs from plasma collected at different time points alongside with the clinical management of GBM patients. Our findings confirm that plasmatic EVs could be separated and characterized with standardized protocols, thereby ensuring the reliability of measuring vesiclemia, i.e. extracellular vesicle concentration in plasma. This unveils that vesiclemia is a dynamic parameter, which could be reflecting tumor burden and/or response to treatments. Further label-free liquid chromatography tandem mass spectrometry unmasks the von Willebrand Factor (VWF) as a selective protein hallmark for GBM-patient EVs. Our data thus support the notion that EVs from GBM patients showed differential protein cargos that can be further surveyed in circulating EVs, together with vesiclemia.

Published
2021

43. Deciphering Tumor Niches: Lessons From Solid and Hematological Malignancies

Author

Stéphane J.C. Mancini, Karl Balabanian, Isabelle Corre, Julie Gavard, Gwendal Lazennec, Marie-Caroline Le Bousse-Kerdilès, Fawzia Louache, Véronique Maguer-Satta, Nathalie M. Mazure, Fatima Mechta-Grigoriou, Jean-François Peyron, Valérie Trichet, Olivier Herault, Microenvironnement des niches tumorales [UNIV Tours] (CNRS GDR 3697 MicroNiT), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang Bretagne, EFS, Cancéropôle Grand-Ouest [Bretagne-Centre-Pays de Loire], 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 ), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Carnot, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre Intégré d'Oncologie Nantes/Angers, Sys2Diag-Modélisation et Ingénierie des Systèmes Complexes Biologiques pour le Diagnostic (Sys2Diag), Centre National de la Recherche Scientifique (CNRS)-Alcediag, Interactions cellules souches-niches : physiologie, tumeurs et réparation tissulaire, Service de Santé des Armées-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, 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-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Sarcomes osseux et remodelage des tissus calcifiés - Phy-Os [Nantes - INSERM U1238] (Phy-Os), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT)-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)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université Bretagne Loire (UBL), Université de Tours (UT)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CNRS GDR 3697 MicroNiT, Centre National de la Recherche Scientifique (CNRS), CNRS UMR9005, 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 ), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Signaling in Oncogenesis, Angiogenesis and Permeability - SOAP (CRCI2NA / Eq 6), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Université de Tours (UT), Lazennec, Gwendal, Signaling in Oncogenesis, Angiogenesis and Permeability (CRCINA-ÉQUIPE 15), Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes (UN)-Université d'Angers (UA)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes (UN)-Université d'Angers (UA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes (UN)-Université d'Angers (UA), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), and Université de Tours (UT)-Université de Tours (UT)

Subjects
Stromal cell, endothelial plasticity, Angiogenesis, Mini Review, [SDV]Life Sciences [q-bio], Niche, Immunology, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Communication, cytokines and chemokines, Biology, cancer-associated fibroblasts (CAFs), 03 medical and health sciences, angiogenesis, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cancer-Associated Fibroblasts, Cancer stem cell, Neoplasms, medicine, Tumor Microenvironment, Immunology and Allergy, Animals, Humans, 030304 developmental biology, 0303 health sciences, Neovascularization, Pathologic, energy/oxidative metabolism, Mesenchymal stem cell, mitochondrial transfer, Mesenchymal Stem Cells, RC581-607, microenvironment, 3. Good health, Haematopoiesis, medicine.anatomical_structure, mesenchymal stem/stromal cells (MSCs), 030220 oncology & carcinogenesis, Cancer research, Cytokines, Bone marrow, Endothelium, Vascular, Immunologic diseases. Allergy
Abstract

International audience; Knowledge about the hematopoietic niche has evolved considerably in recent years, in particular through in vitro analyzes, mouse models and the use of xenografts. Its complexity in the human bone marrow, in particular in a context of hematological malignancy, is more difficult to decipher by these strategies and could benefit from the knowledge acquired on the niches of solid tumors. Indeed, some common features can be suspected, since the bone marrow is a frequent site of solid tumor metastases. Recent research on solid tumors has provided very interesting information on the interactions between tumoral cells and their microenvironment, composed notably of mesenchymal, endothelial and immune cells. This review thus focuses on recent discoveries on tumor niches that could help in understanding hematopoietic niches, with special attention to 4 particular points: i) the heterogeneity of carcinoma/cancer-associated fibroblasts (CAFs) and mesenchymal stem/stromal cells (MSCs), ii) niche cytokines and chemokines, iii) the energy/oxidative metabolism and communication, especially mitochondrial transfer, and iv) the vascular niche through angiogenesis and endothelial plasticity. The elements highlighted in this review identify actors and/or pathways of the microenvironment that are broadly and often involved in cancer processes. This would open avenues for innovative therapeutic opportunities targeting not only cancer stem cells but also their regulatory tumor niche(s), in order to improve current antitumor therapies.

Published
2021

44. Efficacy of Antiviral Treatment in Hepatitis C Virus (HCV)-Driven Monoclonal Gammopathies Including Myeloma

Author

Alba Rodríguez-García, María Linares, María Luz Morales, Sophie Allain-Maillet, Nicolas Mennesson, Ricardo Sanchez, Rafael Alonso, Alejandra Leivas, Alfredo Pérez-Rivilla, Edith Bigot-Corbel, Sylvie Hermouet, Joaquín Martínez-López, Instituto de Investigación Sanitaria Hospital 12 de Octubre [Madrid, Spain] (I2SH), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Hospital Universitario 12 de Octubre [Madrid], Laboratoire de Biochimie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'Hématologie [CHU Nantes], and Dupuis, Christine

Subjects
Male, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Immunology, Paraproteinemias, Hepacivirus, Antibodies, Viral, Antiviral Agents, Monoclonal Gammopathy of Undetermined Significance, hepatitis (C) virus, Immunology and Allergy, Humans, Aged, Original Research, monoclonal gammopathies, Antibodies, Monoclonal, RC581-607, Middle Aged, Viral Load, Hepatitis C, antiviral, infection, [SDV] Life Sciences [q-bio], multiple myeloma, Treatment Outcome, Disease Progression, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Disease Susceptibility, Immunologic diseases. Allergy, Biomarkers
Abstract

International audience; Multiple myeloma (MM) remains an incurable plasma cell malignancy. While its origin is enigmatic, an association with infectious pathogens including hepatitis C virus (HCV) has been suggested. Here we report nine patients with monoclonal gammopathy of undetermined significance (MGUS) or MM with previous HCV infection, six of whom received antiviral treatment. We studied the evolution of the gammopathy disease, according to anti-HCV treatment and antigen specificity of purified monoclonal immunoglobulin, determined using the INNO LIA™ HCV Score assay, dot-blot assays, and a multiplex infectious antigen microarray. The monoclonal immunoglobulin from 6/9 patients reacted against HCV. Four of these patients received antiviral treatment and had a better evolution than untreated patients. Following antiviral treatment, one patient with MM in third relapse achieved complete remission with minimal residual disease negativity. For two patients who did not receive antiviral treatment, disease progressed. For the two patients whose monoclonal immunoglobulin did not react against HCV, antiviral treatment was not effective for MGUS or MM disease. Our results suggest a causal relationship between HCV infection and MGUS and MM progression. When HCV was eliminated, chronic antigen-stimulation disappeared, allowing control of clonal plasma cells. This opens new possibilities of treatment for MGUS and myeloma.

Published
2021

45. Strong SARS-CoV-2 T-Cell Responses after One or Two COVID-19 Vaccine Boosters in Allogeneic Hematopoietic Stem Cell Recipients

Author

Béatrice Clémenceau, Amandine Le Bourgeois, Thierry Guillaume, Marianne Coste-Burel, Pierre Peterlin, Alice Garnier, Maxime Jullien, Jocelyn Ollier, Audrey Grain, Marie C. Béné, Patrice Chevallier, Ollier, Jocelyn, Manipulation of Lymphocytes for Immunotherapy (CRCI2NA / Eq 12), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), and Centre hospitalier universitaire de Nantes (CHU Nantes)

Subjects
Vaccines, Vaccines, Synthetic, COVID-19 Vaccines, [SDV.IMM] Life Sciences [q-bio]/Immunology, SARS-CoV-2, T-Lymphocytes, Hematopoietic Stem Cell Transplantation, Immunization, Secondary, COVID-19, [SDV.CAN]Life Sciences [q-bio]/Cancer, cellular immunity, General Medicine, Hematopoietic Stem Cells, [SDV.CAN] Life Sciences [q-bio]/Cancer, anti-SARS-CoV-2 vaccines, humoral immunity, booster, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, mRNA Vaccines, allogeneic hematopoietic stem cell transplantation, BNT162 Vaccine
Abstract

International audience; A full exploration of immune responses is deserved after anti-SARS-CoV-2 vaccination and boosters, especially in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although several reports indicate successful humoral responses in such patients, the literature is scarce on cellular specific immunity. Here, both B- (antibodies) and T-cell responses were explored after one (V3 n = 40) or two (V4 n = 12) BNT162b2 mRNA vaccine boosters in 52 allo-HSCT recipients at a median of 755 days post-transplant (250 BAU/mL) and anti-spike T-cell responses. Similarly, 81% of the patients developed protective antibody levels, without difference between V3 and V4 (82.5% vs. 75%, p = 0.63), and 85% displayed T-cell responses. The median frequency of anti-spike T cells did not differ either between controls or the whole cohort of patients, although it was significantly lower for V3 (but not V4) patients. COVID-19 infections were solely observed in individuals having received only one booster. These results indicate that four vaccine injections help to achieve a satisfactory level of both humoral and cellular immune protection in allo-HSCT patients.

Published
2022

46. Efficacy and tolerability of Janus kinase inhibitors in myelofibrosis: a systematic review and network meta-analysis

Author

Jérémie Riou, Jean-Jacques Kiladjian, Damien Luque Paz, Corentin Orvain, Léa Sureau, Jean-Christophe Ianotto, Valérie Ugo, Bernardo, Elizabeth, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'Hématologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), Service des maladies du sang [CHU Angers], Service d'hématologie clinique [CHRU de Brest], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CIC Saint Louis (CIC-1427), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Délégation à la recherche clinique et l'innovation [CHU Angers] (DRCI), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)

Subjects
Bridged-Ring Compounds, Oncology, medicine.medical_specialty, Ruxolitinib, Pyrrolidines, Anemia, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, law.invention, 03 medical and health sciences, Targeted therapies, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Randomized controlled trial, law, Internal medicine, Nitriles, medicine, Humans, Janus Kinase Inhibitors, Myelofibrosis, RC254-282, Myeloproliferative neoplasm, Sulfonamides, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Hematology, medicine.disease, 3. Good health, Pyrimidines, Treatment Outcome, Pacritinib, Tolerability, Molecularly targeted therapy, Primary Myelofibrosis, 030220 oncology & carcinogenesis, Splenomegaly, Pyrazoles, Janus kinase, business, 030215 immunology, medicine.drug
Abstract

Myelofibrosis is a myeloproliferative neoplasm associated with constitutional symptoms, increasing splenomegaly, and worsening cytopenias. Janus kinase (JAK) inhibitors have been used for the treatment of myelofibrosis for several years, but there is a lack of comparative information between those treatments. A systematic review and network meta-analysis was performed on randomized controlled trials in patients with myelofibrosis receiving JAK inhibitor or placebo or control. Primary outcomes were efficacy on spleen volume reduction and total symptom score reduction. Additional analyses were conducted on anemia and thrombopenia events. Seven studies were included in the network meta-analysis including 1953 patients randomly assigned to four JAK inhibitors—ruxolitinib, fedratinib, pacritinib, momelotinib—or control. In first-line therapy, momelotinib and fedratinib were associated with comparable efficacy to ruxolitinib, and with less toxicity on erythrocytes and platelets, respectively. Pacritinib was less effective on splenomegaly than ruxolitinib as a first-line treatment but seemed effective in second line, after ruxolitinib exposure. Fedratinib and ruxolitinib that are FDA approved in myelofibrosis have both confirmed being valuable option to treat splenomegaly and constitutional symptoms, and their slightly different tolerance-profiles can guide therapeutic choice for first-line treatment, according to patient profile. Momelotinib could be another option especially due to its positive effect on anemia.

Published
2021

47. Risk of infection according to the gamma globulin level in the 100 days following allogeneic stem cell transplantations

Author

Aline Schmidt, Aurelien Giltat, Jean-Baptiste Robin, Jérémie Riou, Valentin Lacombe, Mathilde Hunault, Valérie Ugo, Pierre Abgueguen, Christopher Nunes Gomes, Sylvie François, Sylvain Thepot, Valérie Daniel, Corentin Orvain, Xavier Dieu, Laurane Cottin, Service des maladies du sang [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département de Biochimie et Génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), Service d'hématologie [Angers], Service des maladies infectieuses et tropicales [CHU Angers], Département de Pharmacie [CHU d'Angers], Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Bernardo, Elizabeth, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)

Subjects
Male, Transplantation Conditioning, Lymphoma, medicine.medical_treatment, Graft vs Host Disease, gamma-globulins, Hematopoietic stem cell transplantation, Gastroenterology, Hypogammaglobulinemia, 0302 clinical medicine, Leukemia, biology, Risk of infection, Immunoglobulins, Intravenous, Gamma globulin, Bacterial Infections, Hematology, General Medicine, Middle Aged, Prognosis, 3. Good health, 030220 oncology & carcinogenesis, hematopoietic stem cell transplantation, Cyclosporine, Female, Antibody, Stem cell, Immunosuppressive Agents, allografts, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Opportunistic Infections, 03 medical and health sciences, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, Transplantation, Homologous, Aged, business.industry, infections, Immunologic Deficiency Syndromes, Mycophenolic Acid, Myeloablative Agonists, medicine.disease, Increased risk, Mycoses, ROC Curve, Myelodysplastic Syndromes, biology.protein, Virus Activation, business, 030215 immunology
Abstract

International audience; Background: Immunoglobulin replacement therapy is recommended in case of severe hypogammaglobulinemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the supposed increased risk of infection in case of hypogammaglobulinemia has not been confirmed in allo-HSCT. In this study, we assessed the relationship between the gamma globulin level and the risk of infection during the 100 days following the allo-HSCT.Methods: We gathered the weekly laboratory tests from day 7 to day 100 of 76 allograft patients, giving a total of 1 044 tests. 130 infections were documented clinically, by imaging, or microbiologically.Results: Average gamma globulin levels between D-7 and D100 did not differ between patients with or without infection (642 ± 232 and 671 ± 246 mg/dL, respectively, P = .65). Gamma globulin level

Published
2021

48. Teaching bacterial infections in pharmaceutical studies: why not ‘with students’ instead of ‘to students’?

Author

Matthieu Eveillard, Samuel Legeay, Isabelle Baglin, ATOMycA (CRCINA-ÉQUIPE 6), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Micro et Nanomédecines Translationnelles (MINT), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Cooperative learning, Adult, Male, media_common.quotation_subject, [SDV]Life Sciences [q-bio], education, Outcome (game theory), Microbiology, Young Adult, [SCCO]Cognitive science, Perception, Surveys and Questionnaires, 0502 economics and business, Genetics, Co-creation, ComputingMilieux_COMPUTERSANDEDUCATION, Humans, Learning, Students, Molecular Biology, media_common, Medical education, Hierarchy, 4. Education, Teaching, 05 social sciences, 050301 education, Collaborative learning, Focus group, Self Concept, 3. Good health, Schools, Pharmacy, Active learning, Female, School Teachers, Psychology, 0503 education, 050203 business & management
Abstract

In pharmaceutical studies, a course of bacteriology based on case studies provided by the teacher was transformed in a course based on a combination of student/teacher co-creation of cases and peer reviewing. Our objectives were to describe the perception of students about the new format and to assess the impact of changing on the learning outcomes. For teaching evaluation, we used a questionnaire and focus groups. The assessment of learning outcome was performed by comparing the students’ scores in final tests with the previous and the revised course formats. The students embraced the creation of cases in small groups with the teacher. In addition, they reported a perception of weakened hierarchy between the teacher and themselves, an increase of their self-confidence and a better ability to transfer their learning to their professional activities in community pharmacies. Lastly, their opinion about the transferability of this format in other disciplines were divided.

Published
2021

49. Assessment of physicians’ resilience level during the COVID-19 pandemic

Author

E Riquin, P.-M. Roy, Delphine Douillet, Olivier Hugli, P Miroux, Francois Morin, Thomas Moumneh, Rafael Mahieu, Maxime Léger, M Noizet, F Javaudin, M Oberlin, Dominique Savary, E Thibaud, Jérémie Riou, A Caillaud, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - 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), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Hôpital pasteur [Colmar], Centre Hospitalier de Mulhouse, site du Hasenrain (Mulhouse), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), 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 ), Lausanne University Hospital, Chard-Hutchinson, Xavier, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université d'Angers (UA)-Université de Rennes 1 (UR1), and 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 )

Subjects
Adult, Male, medicine.medical_specialty, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Specialty, Neurosciences. Biological psychiatry. Neuropsychiatry, Anxiety, Molecular neuroscience, Article, law.invention, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, law, Intensive care, Anesthesiology, Physicians, Genetics, Medicine, Humans, 030212 general & internal medicine, Resilience (network), Pandemics, Biological Psychiatry, Depression (differential diagnoses), business.industry, SARS-CoV-2, COVID-19, Emergency department, Middle Aged, Resilience, Psychological, Intensive care unit, 3. Good health, Psychiatry and Mental health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Family medicine, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business, 030217 neurology & neurosurgery, RC321-571
Abstract

We aim to assess physicians’ level of resilience and define factors that improve or decrease the resilience level during the COVID-19 pandemic. Physicians from hospitals located in areas with different COVID-19 caseload levels, were invited to participate in a national e-survey between April and May 2020. Study participants were mainly emergency physicians, and anaesthesiologists, infectious disease consultants, and intensive care. The survey assessed participant’s characteristics, factors potentially associated with resilience, and resilience using the Connor-Davidson Resilience Scale (RISC-25), with higher scores indicative of greater resilience. Factors associated with the resilience score were assessed using a multivariable linear regression. Of 451 responding physicians involved in the care of COVID-19 patients, 442 were included (98%). Age was 36.1 ± 10.3 years and 51.8% were male; 63% worked in the emergency department (n = 282), 10.4% in anesthesiology (n = 46), 9.9% in infectious disease department (n = 44), 4.8% in intensive care unit (n = 21) or other specialties (n = 49). The median RISC-25 score was at 69 (IQR 62–75). Factors associated with higher RISC scores were anesthesia as a specialty, parenthood, no previous history of anxiety or depression and nor increased anxiety. To conclude, this study is the first to characterize levels of resilience among physicians involved in COVID-19 unit. Our data points to certain protective characteristics and some detrimental factors, such as anxiety or depression, that could be amenable to remediating or preventing strategies to promote resilience and support caregivers in a pandemic.

Published
2021

50. Warburg-like effect is a hallmark of complex I assembly defects

Author

Naïg Gueguen, Anaïs Lebert, Guy Lenaers, Patrizia Amati-Bonneau, Magalie Barth, Mariame Selma Kane, Cédric Gadras, Pascal Reynier, David Goudenège, Dominique Bonneau, Valérie Desquiret-Dumas, Stéphanie Leruez, Stéphanie Chupin, Daniel Henrion, Morgane Le Mao, Céline Wetterwald, Vincent Procaccio, Salim Khiati, Géraldine Leman, Guillaume Geffroy, Lydie Tessier, Arnaud Chevrollier, 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), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA), ARN : régulations naturelle et artificielle, Université Bordeaux Segalen - Bordeaux 2-Institut Européen de Chimie et de Biologie-Institut National de la Santé et de la Recherche Médicale (INSERM), Mitochondrie : Régulations et Pathologie, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Biochimie et Génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Réseau Maladies Métaboliques, Hôpitaux Universitaires du Grand Ouest, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Physiopathologie et thérapie des déficits sensoriels et moteurs, and Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Mitochondrial Diseases, [SDV]Life Sciences [q-bio], Citric Acid Cycle, Regulator, 03 medical and health sciences, 0302 clinical medicine, Humans, Glycolysis, RNA, Small Interfering, Overproduction, Molecular Biology, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, Principal Component Analysis, Reactive oxygen species, Electron Transport Complex I, ATP synthase, biology, Catabolism, NADH Dehydrogenase, Fibroblasts, Pyruvate dehydrogenase complex, Warburg effect, Mitochondria, Cell biology, 030104 developmental biology, Metabolic Engineering, chemistry, 030220 oncology & carcinogenesis, biology.protein, Molecular Medicine, RNA Interference, Reactive Oxygen Species
Abstract

Due to its pivotal role in NADH oxidation and ATP synthesis, mitochondrial complex I (CI) emerged as a crucial regulator of cellular metabolism. A functional CI relies on the sequential assembly of nuclear- and mtDNA-encoded subunits; however, whether CI assembly status is involved in the metabolic adaptations in CI deficiency still remains largely unknown. Here, we investigated the relationship between CI functions, its structure and the cellular metabolism in 29 patient fibroblasts representative of most CI mitochondrial diseases. Our results show that, contrary to the generally accepted view, a complex I deficiency does not necessarily lead to a glycolytic switch, i.e. the so-called Warburg effect, but that this particular metabolic adaptation is a feature of CI assembly defect. By contrast, a CI functional defect without disassembly induces a higher catabolism to sustain the oxidative metabolism. Mechanistically, we demonstrate that reactive oxygen species overproduction by CI assembly intermediates and subsequent AMPK-dependent Pyruvate Dehydrogenase inactivation are key players of this metabolic reprogramming. Thus, this study provides a two-way-model of metabolic responses to CI deficiencies that are central not only in defining therapeutic strategies for mitochondrial diseases, but also in all pathophysiological conditions involving a CI deficiency.

Published
2019

Catalog

Books, media, physical & digital resources
See catalog results