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5. Long‐term safety of dietary salt: A 5‐year ProspEctive rAndomized bliNded and controlled stUdy in healThy aged cats (PEANUT study).

Author

Reynolds, Brice S., Chetboul, Valerie, Elliott, Jonathan, Laxalde, Jeremy, Nguyen, Patrick, Testault, Isabelle, Dorso, Laëticia, Abadie, Jérôme, Lefebvre, Hervé P., and Biourge, Vincent

Subjects
SALT-free diet, HIGH-salt diet, CATS, GLOMERULAR filtration rate, SPECIFIC gravity, CHRONIC kidney failure
Abstract

Background: High‐salt diets promote urine dilution and decrease urolithiasis risk. Objective: Prospectively evaluate the safety of chronic high dietary salt intake (randomized controlled trial). Animals: Twenty research colony neutered, healthy aged cats (11.5 years [10.0‐11.6], median [interquartile range]). Methods: Healthy cats were randomized to control or high‐salt dry diets (sodium: 1.02 ± 0.16 [mean, SD] and 3.26 ± 0.30 g/Mcal metabolizable energy [ME], respectively; chloride: 2.26 ± 0.33 and 5.71 ± 0.28 g/Mcal ME, respectively), fed for up to 60 months. Assessments included CBC, plasma biochemistry, urinalysis, glomerular filtration rate (GFR), blood pressure, renal and cardiac (conventional Doppler and 2‐dimensional color tissue Doppler) imaging, annually. Cats that died or were euthanized underwent necropsy. Diet effects over time were evaluated with linear mixed models. Results: Follow‐up duration (median [Interquartile range]) was similar between the control (38.7 months [28.6‐48.2]) and high‐salt group (51.4 months [45.7‐59.0]). Diet had no significant effect on changes in GFR, blood pressure, plasma creatinine concentration, end‐diastolic left ventricular (LV) wall thicknesses, LV internal diameters, LV systolic function, left atrial size, or systolic and diastolic Doppler variables. One control cat developed hypertension. One high‐salt group cat developed persistent azotemia. Serial plasma biochemistry and urine specific gravity suggested early chronic kidney disease in 4 nonazotemic cats (2 per group), consistent with necropsy findings. Conclusions and Clinical Importance: In healthy aged cats, a commercial veterinary diet containing 3.26 ± 0.30 g/Mcal ME sodium was safe with regard to renal and cardiac function for up to 5 years. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Evaluation of in vitro intrinsic radiosensitivity and characterization of five canine high-grade glioma cell lines.

Author

Cartiaux, Benjamin, Deviers, Alexandra, Delmas, Caroline, Abadie, Jérôme, Pumarola Battle, Martí, Moyal, Elizabeth Cohen-Jonathan, and Mogicato, Giovanni

Subjects
CELL lines, GLIOMAS, RADIATION tolerance, BRAIN tumors, DOGS, CELL morphology
Abstract

Glioma is the most common primary brain tumor in dogs and predominantly affects brachycephalic breeds. Diagnosis relies on CT or MRI imaging, and the proposed treatments include surgical resection, chemotherapy, and radiotherapy depending on the tumor's location. Canine glioma from domestic dogs could be used as a more powerful model to study radiotherapy for human glioma than the murine model. Indeed, (i) contrary to mice, immunocompetent dogs develop spontaneous glioma, (ii) the canine brain structure is closer to human than mice, and (iii) domestic dogs are exposed to the same environmental factors than humans. Moreover, imaging techniques and radiation therapy used in human medicine can be applied to dogs, facilitating the direct transposition of results. The objective of this study is to fully characterize 5 canine glioma cell lines and to evaluate their intrinsic radiosensitivity. Canine cell lines present numerous analogies between the data obtained during this study on different glioma cell lines in dogs. Cell morphology is identical, such as doubling time, clonality test and karyotype. Immunohistochemical study of surface proteins, directly on cell lines and after stereotaxic injection in mice also reveals close similarity. Radiosensitivity profile of canine glial cells present high profile of radioresistance. [ABSTRACT FROM AUTHOR]

Published
2023
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11. Canine Oral Melanoma Genomic and Transcriptomic Study Defines Two Molecular Subgroups with Different Therapeutical Targets

Author

Prouteau, Anais, primary, Mottier, Stephanie, additional, Primot, Aline, additional, Cadieu, Edouard, additional, Bachelot, Laura, additional, Botherel, Nadine, additional, Cabillic, Florian, additional, Houel, Armel, additional, Cornevin, Laurence, additional, Kergal, Camille, additional, Corre, Sébastien, additional, Abadie, Jérôme, additional, Hitte, Christophe, additional, Gilot, David, additional, Lindblad-Toh, Kerstin, additional, André, Catherine, additional, Derrien, Thomas, additional, and Hedan, Benoit, additional

Published
2022
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14. SPECT-CT Imaging of Dog Spontaneous Diffuse Large B-Cell Lymphoma Targeting CD22 for the Implementation of a Relevant Preclinical Model for Human

Author

Etienne, Floriane, Berthaud, Maxime, Nguyen, Frédérique, Bernardeau, Karine, Maurel, Catherine, Bodet-Milin, Caroline, Diab, Maya, Abadie, Jérôme, Gouilleux-Gruart, Valérie, Vidal, Aurélien, Bourgeois, Mickael, Chouin, Nicolas, Ibisch, Catherine, Davodeau, François, Oncologie nucléaire (CRCINA - Département NOHMAD - Equipe 13), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), 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)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-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)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Animaux Modèles pour la Recherche en Oncologie [Nantes] (AMaROC), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Stress Adaptation and Tumor Escape in breast cancer - SATE (CRCINA - Département ONCO - Equipe 8), Plateforme 'Production de protéines recombinantes' (P2R - INSERM UMS016/CNRS UMS3556/UN FED4203), Structure fédérative de recherche François Bonamy (SFR 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)-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), Service de Médecine Nucléaire [Nantes], Hôpital Laennec, Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours, Cyclotron ARRONAX [Saint-Herblain], ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain] (Institut de Recherche Public), This work was supported by the Institut Thématique MultiOrganismes (ITMO) Cancer of the Alliance pour les sciences de la vie et de la santé (AVIESAN) jointly with the Institut National du Cancer (INCA) under one grant entitled: Spontaneous tumor models in animals for translational research in oncology no. A11196NS (CANIMAB). Financial support was also provided by a Physics, Mathematics and Engineering sciences applied to the Cancer Research grant (DogPPK project) awarded by INSERM and INCa., Nuclear Oncology (CRCINA-ÉQUIPE 13), 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), Animaux modèles pour la recherche en oncologie comparée (AMaROC), Stress Adaptation and Tumor Escape in Breast Cancer (CRCINA-ÉQUIPE 8), Université de Tours (UT), 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), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth

Subjects
comparative oncology, diffuse large B-cell lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, SPECT-CT imaging, internalization, [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, immune system diseases, monoclonal antibody, hemic and lymphatic diseases, dog, internalization Etienne et al Radiolabeled Anti-canine CD22 Antibodies, CD22, Original Research
Abstract

International audience; Antibodies directed against CD22 have been used in radioimmunotherapy (RIT) clinical trials to treat patients with diffuse large B-cell lymphoma (DLBCL) with promising results. However, relevant preclinical models are needed to facilitate the evaluation and optimization of new protocols. Spontaneous DLBCL in dogs is a tumor model that may help accelerate the development of new methodologies and therapeutic strategies for RIT targeting CD22. Seven murine monoclonal antibodies specific for canine CD22 were produced by the hybridoma method and characterized. The antibodies' affinity and epitopic maps, their internalization capability and usefulness for diagnosis in immunohistochemistry were determined. Biodistribution and PET imaging on a mouse xenogeneic model of dog DLBCL was used to choose the most promising antibody for our purposes. PET-CT results confirmed biodistribution study observations and allowed tumor localization. The selected antibody, 10C6, was successfully used on a dog with spontaneous DLBCL for SPECT-CT imaging in the context of disease staging, validating its efficacy for diagnosis and the feasibility of future RIT assays. This first attempt at phenotypic imaging on dogs paves the way to implementing quantitative imaging methodologies that would be transposable to humans in a theranostic approach. Taking into account the feedback of existing human radioimmunotherapy clinical trials targeting CD22, animal trials are planned to investigate protocol improvements that are difficult to consider in humans due to ethical concerns.

Published
2020

19. Characterization of increasing stages of invasiveness identifies stromal/cancer cell crosstalk in rat models of mesothelioma

Author

Nader, Joëlle, Abadie, Jérôme, Deshayes, Sophie, Boissard, Alice, Blandin, Stéphanie, Blanquart, Christophe, Boisgerault, Nicolas, Coqueret, Olivier, Guette, Catherine, Grégoire, Marc, Pouliquen, Daniel, Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), 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), Senescence Escape and Soluble Markers of Cancer Progression (CRCINA-ÉQUIPE 12), ONIRIS [Nantes], Université de Nantes (UN), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Plateforme MicroPicell [Nantes], The research leading to these results has received funding from the National Health and Medical Research Institute (Inserm), the 'Ligue contre le Cancer' (Ligue Nationale and the Ligue inter-régionale du Grand Ouest, Comités 16, 44 et 72), the 'Fondation pour la Recherche Médicale' (FRM), the 'Région Pays de la Loire', the Institut de Recherche en Santé Respiratoire (IRSR) des Pays de la Loire, and the ARSMESO44 association., 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), and Bernardo, Elizabeth

Subjects
immune cells, [SDV.CAN] Life Sciences [q-bio]/Cancer, rat model, invasiveness, stroma, [SDV.CAN]Life Sciences [q-bio]/Cancer, sarcomatoid mesothelioma, Research Paper
Abstract

International audience; Sarcomatoid mesothelioma (SM) is a devastating cancer associated with one of the poorest outcome. Therefore, representative preclinical models reproducing different tumor microenvironments (TME) observed in patients would open up new prospects for the identification of markers and evaluation of innovative therapies. Histological analyses of four original models of rat SM revealed their increasing infiltrative and metastatic potential were associated with differences in Ki67 index, blood-vessel density, and T-lymphocyte and macrophage infiltration. In comparison with the noninvasive tumor M5-T2, proteomic analysis demonstrated the three invasive tumors F4-T2, F5-T1 and M5-T1 shared in common a very significant increase in the abundance of the multifunctional proteins galectin-3, prohibitin and annexin A5, and a decrease in proteins involved in cell adhesion, tumor suppression, or epithelial differentiation. The increased metastatic potential of the F5-T1 tumor, relative to F4-T2, was associated with an increased macrophage vs T-cell infiltrate, changes in the levels of expression of a panel of cytokine genes, an increased content of proteins involved in chromatin organization, ribosome structure, splicing, or presenting anti-adhesive properties, and a decreased content of proteins involved in protection against oxidative stress, normoxia and intracellular trafficking. The most invasive tumor, M5-T1, was characterized by a pattern of specific phenotypic and molecular features affecting the presentation of MHC class I-mediated antigens and immune cell infiltration, or involved in the reorganization of the cytoskeleton and composition of the extracellular matrix. These four preclinical models and data represent a new resource available to the cancer research community to catalyze further investigations on invasiveness.

Published
2018

21. Discovery of Human-Similar Gene Fusions in Canine Cancers

Author

Ulvé, Ronan, primary, Rault, Mélanie, additional, Bahin, Mathieu, additional, Lagoutte, Laetitia, additional, Abadie, Jérôme, additional, De Brito, Clotilde, additional, Coindre, Jean-Michel, additional, Botherel, Nadine, additional, Rousseau, Audrey, additional, Wucher, Valentin, additional, Cadieu, Edouard, additional, Thieblemont, Catherine, additional, Hitte, Christophe, additional, Cornevin, Laurence, additional, Cabillic, Florian, additional, Bachelot, Laura, additional, Gilot, David, additional, Hennuy, Benoit, additional, Guillaudeux, Thierry, additional, Le Goff, Arnaud, additional, Derrien, Thomas, additional, Hédan, Benoît, additional, and André, Catherine, additional

Published
2017
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22. Cartographie des forêts anciennes de France : objectifs, bilan et perspectives

Author

Dupouey, Jean-Luc, Amiaud, Bernard, Chauchard, Sandrine, Bergès, Laurent, Abadie, Jérôme, Archaux, Frédéric, Avon, Catherine, Bec, Raphaël, Bonnevialle, Marie, Burst, Maxime, Cordonnier, Thomas, Deconchat, Marc, Decocq, Guillaume, Delcourte, Marie, Fuhr, Marc, Grel, Audrey, Heintz, Wilfried, Janssen, Philippe, Landmann, Guy, LARRIEU, Laurent, LEROY, Nathalie, Montpied, Pierre, Panaïotis, Christophe, Renaux, Benoît, Rochel, Xavier, Thomas, Marie, Salvaudon, Aline, Vallauri, Daniel, Villemey, Anne, Institut National Polytechnique de Toulouse - INPT (FRANCE), Institut National de la Recherche Agronomique - INRA (FRANCE), Institut national de Recherche en Sciences et Technologies pour l'Environnement et l'Agriculture - IRSTEA (FRANCE), Université de Picardie Jules Verne (FRANCE), Université de Lorraine (FRANCE), Université de Valenciennes et du Hainaut-Cambrésis - UVHC (FRANCE), Ecologie et Ecophysiologie Forestières [devient SILVA en 2018] (EEF), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Ecosystèmes montagnards (UR EMGR), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Ecosystèmes méditerranéens et risques (UR EMAX), Ecosystèmes forestiers (UR EFNO), Parcs naturels du Massif central (IPAMAC), Parcs Nationaux de France, Dynamiques Forestières dans l'Espace Rural (DYNAFOR), Institut National de la Recherche Agronomique (INRA)-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Ecologie et Dynamique des Systèmes Anthropisés - UMR CNRS 7058 (EDYSAN), Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Cultures, Arts, Littératures, Histoire, Imaginaires, Sociétés, Territoires, Environnement - EA 4343 (CALHISTE), Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université Polytechnique Hauts-de-France (UPHF), WWF France Fondation, Groupement d’Intérêt Public 'Ecosystèmes Forestiers' (GIP ECOFOR), Centre Régional de la Propriété Forestière de Midi-Pyrénées (CRPF Midi-Pyrénées), Conservatoire Botanique National, Centre de Recherche en Géographie (LOTERR), Université de Lorraine (UL), Parc Naturel Régional du Luberon (PNRL), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Supérieure Agronomique de Toulouse-Institut National Polytechnique (Toulouse) (Toulouse INP), Ecologie et dynamique des systèmes anthropisés, Centre National de la Recherche Scientifique (CNRS), Université Polytechnique Hauts-de-France (UPHF)-Université Polytechnique Hauts-de-France (UPHF), and Centre d'Etude et de Recherche en Géographie de l'Aménagement des Paysages et de l'Environnement (CERGAPE - LOTERR)

Subjects
Forêt ancienne, Cartographie, [SDV]Life Sciences [q-bio], carte d'état-major, Synthèse, Carte d'état-major, forêt ancienne, biodiversité, synthèse, cartographie, France, Biodiversité, Environnement et Société, france, Géographie
Abstract

Session 7 b: Géohistoire des forêts; Il y a dix ans démarraient les premiers travaux de vectorisation, à l'échelle régionale, des forêts de la carte d'Etat-Major, en vue de l'établissement d'une carte nationale des forêts à longue continuité de l'état boisé. Où en est-on aujourd'hui ? Nous faisons le point de l'avancement des travaux et en tirons les premiers enseignements, en répondant aux questions suivantes : Quels sont les définitions et concepts sous-jacents à ces travaux ? Pourquoi cartographier les forêts dites "anciennes" ou "récentes" ? L'analyse des institutions ayant réalisé le travail montre que ce sont principalement les milieux de la conservation qui ont été moteurs dans ces travaux. Mais la production et la qualité des produits bois sont aussi concernés par cette cartographie. Le rôle actuel de puits de carbone des forêts françaises ne peut par exemple se comprendre qu'au travers de cette dynamique forestière ancienne. Pourquoi une focalisation sur la première moitié du XIXe siècle comme date de référence ? Que signifie la notion de minimum forestier ? Quelles en sont les limites ? Quels sont les supports de données les plus intéressantes pour cette cartographie ? Pourquoi la carte d'Etat-Major est une source particulière d'information, dans l'objectif de la cartographie des forêts anciennes, parmi la multitude de cartes ou statistiques disponibles à différentes dates et échelles ? Quelles sont les méthodes d'acquisition de la donnée ? Quelle est la précision spatiale des cartes d'occupation du sol obtenues ? Les principaux problèmes posés par l'utilisation de la carte d'Etat-Major seront présentés, ainsi que la façon dont différents projets y ont répondu. Quels résultats ont été obtenus ? Nous reviendrons entre autres sur l'estimation de la surface forestière française à la date de son minimum. Les cartes déjà réalisées, sur 33% du territoire, permettent de dessiner avec précision et de comparer les changements d'occupation du sol dans différentes régions de France, en termes de pourcentage de déboisement, reboisement et taux de forêt ancienne dans la forêt actuelle. Les évolutions du couvert forestier issues d'autres sources non cartographiques sont-elles confirmées ? Le lien avec le type de propriété foncière est particulièrement intéressant à analyser. Dans plusieurs zones de France (Pyrénées, Luberon, Alpes, Lorraine, Nord-Pas-de-Calais...) ont été réalisés des croisements entre ces cartes et les bases de données régionales de relevés floristiques (Inventaire forestier national, conservatoires botaniques). Ce nouveau type d'analyse permet d'identifier rapidement les espèces végétales liées à la continuité de l'état boisé, dites espèces de forêts anciennes, et les traits de vie qui leur sont associés. Nous présenterons une synthèse de ces résultats. Dans la moitié des zones déjà cartographiées, ce sont toutes les occupations du sol anciennes qui ont été numérisées et non seulement les forêts. Nous évoquerons l'intérêt de ce cadastre ancien, au-delà des seules questions forestières, pour le suivi de la dynamique à long terme des prairies, des milieux humides, des vignes ou des milieux urbanisés. Les techniques de vectorisation des occupations anciennes du sol évoluent vers une simplification et une accélération qui laisse présager une fin du travail plus rapide que prévue initialement, parfois au détriment de la qualité. L'extension à la France entière permettra une vision à la fois à petite échelle mais localement précise des mouvements des masses forestières. Nous discuterons les perspectives de recherche et les développements en cours, ouverts par ces progrès.

Published
2016

23. Neu5Gc and α1-3 GAL Xenoantigen Knockout Does Not Affect Glycemia Homeostasis and Insulin Secretion in Pigs

Author

Salama, Apolline, primary, Mosser, Mathilde, additional, Lévêque, Xavier, additional, Perota, Andrea, additional, Judor, Jean-Paul, additional, Danna, Corentin, additional, Pogu, Sylvie, additional, Mouré, Anne, additional, Jégou, Dominique, additional, Gaide, Nicolas, additional, Abadie, Jérôme, additional, Gauthier, Olivier, additional, Concordet, Jean-Paul, additional, Le Bas-Bernardet, Stéphanie, additional, Riochet, David, additional, Le Berre, Ludmilla, additional, Hervouet, Jérémy, additional, Minault, David, additional, Weiss, Pierre, additional, Guicheux, Jérôme, additional, Brouard, Sophie, additional, Bosch, Steffi, additional, Lagutina, Irina, additional, Duchi, Roberto, additional, Lazzari, Giovanna, additional, Cozzi, Emanuele, additional, Blancho, Gilles, additional, Conchon, Sophie, additional, Galli, Cesare, additional, Soulillou, Jean-Paul, additional, and Bach, Jean-Marie, additional

Published
2017
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24. Olive and grape seed extract prevents post-traumatic osteoarthritis damages and exhibits in vitro anti IL-1β activities before and after oral consumption

Author

Mével, Elsa, primary, Merceron, Christophe, additional, Vinatier, Claire, additional, Krisa, Stéphanie, additional, Richard, Tristan, additional, Masson, Martial, additional, Lesoeur, Julie, additional, Hivernaud, Vincent, additional, Gauthier, Olivier, additional, Abadie, Jérôme, additional, Nourissat, Geoffroy, additional, Houard, Xavier, additional, Wittrant, Yohann, additional, Urban, Nelly, additional, Beck, Laurent, additional, and Guicheux, Jérôme, additional

Published
2016
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26. Long-Term Toxicity of 213Bi-Labelled BSA in Mice

Author

Dorso, Laëtitia, primary, Bigot-Corbel, Edith, additional, Abadie, Jérôme, additional, Diab, Maya, additional, Gouard, Sébastien, additional, Bruchertseifer, Frank, additional, Morgenstern, Alfred, additional, Maurel, Catherine, additional, Chérel, Michel, additional, and Davodeau, François, additional

Published
2016
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27. The MTAP-CDKN2A Locus Confers Susceptibility to a Naturally Occurring Canine Cancer

Author

Shearin, Abigail, Hédan, Benoît, Cadieu, Edouard, Erich, Suzanne, Schmidt, Emmett, Faden, Daniel, Cullen, John, Abadie, Jérôme, Kwon, Erika, Gröne, Andrea, Devauchelle, Patrick, Rimbault, Maud, Karyadi, Danielle, Lynch, Mary, Galibert, Francis, Breen, Matthew, Rutteman, Gerard, André, Catherine, Parker, Heidi, Ostrander, Elaine, De Villemeur, Hervé, Cancer Genetics Branch, National Institute of Health (NIH)-National Human Genome Research Institute (NHGRI), Howard Hughes Medical Institute [Chevy Chase] (HHMI), Howard Hughes Medical Institute (HHMI), Department of Molecular Biomedical Sciences, North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC)-College of Veterinary Medicine Raleigh, Department of Population Health and Pathobiology, 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 ), Faculty of Veterinary Medicine, Utrecht University [Utrecht], Cancer Research Center, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Centre anti-cancereux, École nationale vétérinaire - Alfort (ENVA), Lineberger Comprehensive Cancer Center (UNC Lineberger), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Intramural Program of the National Human Genome Research Institute at NIH, AKC-Canine Health Foundation (grant 2667, 935), CNRS and French Association for Swiss dogs, NIH NCI (R01 CA69069, NIH U01 AI07033), Harvard Breast Cancer SPORE (P50 CA89393), Alberto Vittoni Award, Committee of Preventive Health Care of the Netherlands Royal Society of Veterinary Medicine, breed societies for Bernese mountain dogs in the Netherlands, breed societies for Bernese mountain dogs in the Germany, breed societies for Bernese mountain dogs in the Austria, and breed societies for Bernese mountain dogs in the Belgium

Subjects
Dogs, Histiocytic sarcoma, [SDV.CAN] Life Sciences [q-bio]/Cancer, p16, [SDV.CAN]Life Sciences [q-bio]/Cancer, Genome Wide Association Study, Cancer
Abstract

International audience; BACKGROUND: Advantages offered by canine population substructure, combined with clinical similarity to human disease makes the dog a particularly attractive system for finding genes associated with cancer. Cancers that have been difficult to study in human families or populations are of particular interest, especially those associated with one or a small number of breeds and a high level of occurrence. Histiocytic sarcoma (HS) is a rare and poorly understood neoplasm in humans, however it occurs in 15-25% of Bernese Mountain Dogs (BMD). METHODS: Genomic DNA was collected from affected and unaffected BMD in both North America and Europe. Both independent and combined genome wide association studies (GWAS) from the two geographic populations were used to identify cancer associated loci. Fine mapping and sequencing was used to narrow the primary locus.RESULTS: GWAS revealed a cancer-associated locus shared by both populations. The locus contains a single haplotype spanning MTAP and part of CDKN2A that is present in 96% of all affected BMD. The haplotype is within the region homologous to human chromosome 9p21, which has been implicated in numerous complex genetic diseases including several cancers. CONCLUSIONS: We present the first GWAS for HS in any species. The data identify an associated haplotype in the highly cited tumor suppressor locus near CDKN2A. These data demonstrate the power of studying distinctive malignancies in highly predisposed dog breeds. Impact: Here, we establish a naturally-occurring model of cancer susceptibility due to CDKN2 dysregulation, thus providing insight regarding this cancer-associated, complex, and poorly understood genomic region.

Published
2012

28. Non-ocular melanomas in cats: a retrospective study of 30 cases.

Author

Chamel, Gabriel, Abadie, Jérôme, Albaric, Olivier, Labrut, Sophie, Ponce, Frédérique, and Ibisch, Catherine

Abstract

Objectives The aim of the study was to describe the clinical outcome of 30 cats with non-ocular melanomas and to evaluate the association between clinical or pathological parameters and overall survival time. Methods The database of the animal histopathological laboratory of the National Veterinary School of Nantes (Oniris, Nantes, France) was retrospectively searched to identify cases of feline non-ocular melanomas between December 2009 and April 2014. For each case, clinical data, including signalment, location of the primary tumour, staging, treatment and outcome, were collected from the medical records or via interviews with referring veterinarians. Histological and immunohistochemical evaluation included mitotic index, cytonuclear atypias, junctional activity, Melan A and S100 immunostaining, and surgical margins. Univariate analysis to test the prognostic value of the different variables was performed by the Kaplan–Meier product limit method using the log-rank test of significance. Results Thirty cats were included in the study. Eleven had a cutaneous non-auricular melanoma, six had a tumour located on the pinna and 13 had a tumour in the oral cavity. Cats with auricular melanomas were significantly younger than cats with tumours in other locations. Location and presence of clinical signs were not of prognostic significance, but the achromic phenotype was significantly associated with a poorer prognosis. Twenty cats were treated with surgery and survived significantly longer than cats that received only medical treatment or that did not receive any treatment. According to our data, mitotic index, cytonuclear atypias, junctional activity, Melan A or S100 expression, and surgical margins were not associated with survival. Conclusions and relevance We show for the first time, in a large series, that the auricular form of melanoma affected significantly younger cats than other extraocular forms. Most feline non-ocular melanomas are malignant and achromic tumours are associated with a poorer prognosis. According to this study, surgery should be considered as a priority. [ABSTRACT FROM AUTHOR]

Published
2017
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29. Cardiovascular Effects of Dietary Salt Intake in Aged Healthy Cats: A 2-Year Prospective Randomized, Blinded, and Controlled Study

Author

Chetboul, Valérie, primary, Reynolds, Brice Stéphane, additional, Trehiou-Sechi, Emilie, additional, Nguyen, Patrick, additional, Concordet, Didier, additional, Sampedrano, Carolina Carlos, additional, Testault, Isabelle, additional, Elliott, Jonathan, additional, Abadie, Jérôme, additional, Biourge, Vincent, additional, and Lefebvre, Hervé Pierre, additional

Published
2014
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31. Thorough Investigation of a Canine Autoinflammatory Disease (AID) Confirms One Main Risk Locus and Suggests a Modifier Locus for Amyloidosis

Author

Olsson, Mia, primary, Tintle, Linda, additional, Kierczak, Marcin, additional, Perloski, Michele, additional, Tonomura, Noriko, additional, Lundquist, Andrew, additional, Murén, Eva, additional, Fels, Max, additional, Tengvall, Katarina, additional, Pielberg, Gerli, additional, Dufaure de Citres, Caroline, additional, Dorso, Laetitia, additional, Abadie, Jérôme, additional, Hanson, Jeanette, additional, Thomas, Anne, additional, Leegwater, Peter, additional, Hedhammar, Åke, additional, Lindblad-Toh, Kerstin, additional, and Meadows, Jennifer R. S., additional

Published
2013
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32. Long-Term Toxicity of 213Bi-Labelled BSA in Mice.

Author

Dorso, Laëtitia, Bigot-Corbel, Edith, Abadie, Jérôme, Diab, Maya, Gouard, Sébastien, Bruchertseifer, Frank, Morgenstern, Alfred, Maurel, Catherine, Chérel, Michel, and Davodeau, François

Subjects
SERUM albumin, TOXICITY testing, BISMUTH isotopes, RADIOLABELING, LABORATORY mice, RADIOIMMUNOTHERAPY
Abstract

Background: Short-term toxicological evaluations of alpha-radioimmunotherapy have been reported in preclinical assays, particularly using bismuth-213 (213Bi). Toxicity is greatly influenced not only by the pharmacokinetics and binding specificity of the vector but also by non-specific irradiation due to the circulating radiopharmaceutical in the blood. To assess this, an acute and chronic toxicity study was carried out in mice injected with 213Bi-labelled Bovine Serum Albumin (213Bi-BSA) as an example of a long-term circulating vector. Method: Biodistribution of 213Bi-BSA and 125I-BSA were compared in order to evaluate 213Bi uptake by healthy organs. The doses to organs for injected 213Bi-BSA were calculated. Groups of nude mice were injected with 3.7, 7.4 and 11.1 MBq of 213Bi-BSA and monitored for 385 days. Plasma parameters, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine, were measured and blood cell counts (white blood cells, platelets and red blood cells) were performed. Mouse organs were examined histologically at different time points. Results: Haematological toxicity was transient and non-limiting for all evaluated injected activities. At the highest injected activity (11.1 MBq), mice died from liver and kidney failure (median survival of 189 days). This liver toxicity was identified by an increase in both ALT and AST and by histological examination. Mice injected with 7.4 MBq of 213Bi-BSA (median survival of 324 days) had an increase in plasma BUN and creatinine due to impaired kidney function, confirmed by histological examination. Injection of 3.7 MBq of 213Bi-BSA was safe, with no plasma enzyme modifications or histological abnormalities. Conclusion: Haematological toxicity was not limiting in this study. Liver failure was observed at the highest injected activity (11.1 MBq), consistent with liver damage observed in human clinical trials. Intermediate injected activity (7.4 MBq) should be used with caution because of the risk of long-term toxicity to kidneys. [ABSTRACT FROM AUTHOR]

Published
2016
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35. A Nonionic Amphiphile Agent Promotes Gene Delivery In Vivo to Skeletal and Cardiac Muscles

Author

Pitard, Bruno, Pollard, Hélène, Agbulut, Onnik, Lambert, Olivier, Vilquin, Jean-Thomas, Cherel, Yan, Abadie, Jérôme, Samuel, Jane-Lise, Rigaud, Jean-Louis, Menoret, Severine, Anegon, Ignacio, and Escande, Denis

Abstract

Direct injection of naked DNA into skeletal or cardiac muscle induces detectable gene expression. Although this provides a practical system for transgene expression, the reported efficacy is too low to confer a therapeutic benefit. By following a rational strategy based on the supramolecular structures adopted by active complexes, we have discovered a novel nonionic amphiphile synthetic agent [poly(ethyleneoxide)13-poly(propyleneoxide)30-poly(ethyleneoxide)13 block copolymer; PE6400] that enables gene expression in up to 35% of muscle fibers from mouse tibial cranial muscle. PE6400 abolishes the ceiling effect on transgene expression of increasing amounts of naked DNA and permits long-term expression of the β-galactosidase reporter gene in immunologically tolerant transgenic rats. This improvement in gene expression over naked DNA was observed irrespective of the reporter gene, ranging from 0.7 to 3.4 kb, and of the animal model used. In skeletal muscle, the PE6400 formulation led to a level of transfection efficiency similar to that obtained by electrotransfer. PE6400 also promotes high transgene expression in cardiac muscle. In contrast, PE6400-DNA formulations were inefficient in vitro in established cell lines and in isolated cardiomyocytes. When microinjected into the cell cytoplasm, PE6400 promotes DNA trafficking into the nucleus and induces gene expression. PE6400 provides a simple gene delivery system for skeletal and myocardial gene transfer. We propose that the PE6400 formulation could serve for the treatment of diseases primarily affecting muscle or for the expression of therapeutic proteins for local or systemic benefit.

Published
2002
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36. SPECT-CT Imaging of Dog Spontaneous Diffuse Large B-Cell Lymphoma Targeting CD22 for the Implementation of a Relevant Preclinical Model for Human.

Author

Etienne F, Berthaud M, Nguyen F, Bernardeau K, Maurel C, Bodet-Milin C, Diab M, Abadie J, Gouilleux-Gruart V, Vidal A, Bourgeois M, Chouin N, Ibisch C, and Davodeau F

Abstract

Antibodies directed against CD22 have been used in radioimmunotherapy (RIT) clinical trials to treat patients with diffuse large B-cell lymphoma (DLBCL) with promising results. However, relevant preclinical models are needed to facilitate the evaluation and optimization of new protocols. Spontaneous DLBCL in dogs is a tumor model that may help accelerate the development of new methodologies and therapeutic strategies for RIT targeting CD22. Seven murine monoclonal antibodies specific for canine CD22 were produced by the hybridoma method and characterized. The antibodies' affinity and epitopic maps, their internalization capability and usefulness for diagnosis in immunohistochemistry were determined. Biodistribution and PET imaging on a mouse xenogeneic model of dog DLBCL was used to choose the most promising antibody for our purposes. PET-CT results confirmed biodistribution study observations and allowed tumor localization. The selected antibody, 10C6, was successfully used on a dog with spontaneous DLBCL for SPECT-CT imaging in the context of disease staging, validating its efficacy for diagnosis and the feasibility of future RIT assays. This first attempt at phenotypic imaging on dogs paves the way to implementing quantitative imaging methodologies that would be transposable to humans in a theranostic approach. Taking into account the feedback of existing human radioimmunotherapy clinical trials targeting CD22, animal trials are planned to investigate protocol improvements that are difficult to consider in humans due to ethical concerns., (Copyright © 2020 Etienne, Berthaud, Nguyen, Bernardeau, Maurel, Bodet-Milin, Diab, Abadie, Gouilleux-Gruart, Vidal, Bourgeois, Chouin, Ibisch and Davodeau.)

Published
2020
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37. Characterization of increasing stages of invasiveness identifies stromal/cancer cell crosstalk in rat models of mesothelioma.

Author

Nader JS, Abadie J, Deshayes S, Boissard A, Blandin S, Blanquart C, Boisgerault N, Coqueret O, Guette C, Grégoire M, and Pouliquen DL

Abstract

Sarcomatoid mesothelioma (SM) is a devastating cancer associated with one of the poorest outcome. Therefore, representative preclinical models reproducing different tumor microenvironments (TME) observed in patients would open up new prospects for the identification of markers and evaluation of innovative therapies. Histological analyses of four original models of rat SM revealed their increasing infiltrative and metastatic potential were associated with differences in Ki67 index, blood-vessel density, and T-lymphocyte and macrophage infiltration. In comparison with the noninvasive tumor M5-T2, proteomic analysis demonstrated the three invasive tumors F4-T2, F5-T1 and M5-T1 shared in common a very significant increase in the abundance of the multifunctional proteins galectin-3, prohibitin and annexin A5, and a decrease in proteins involved in cell adhesion, tumor suppression, or epithelial differentiation. The increased metastatic potential of the F5-T1 tumor, relative to F4-T2, was associated with an increased macrophage vs T-cell infiltrate, changes in the levels of expression of a panel of cytokine genes, an increased content of proteins involved in chromatin organization, ribosome structure, splicing, or presenting anti-adhesive properties, and a decreased content of proteins involved in protection against oxidative stress, normoxia and intracellular trafficking. The most invasive tumor, M5-T1, was characterized by a pattern of specific phenotypic and molecular features affecting the presentation of MHC class I-mediated antigens and immune cell infiltration, or involved in the reorganization of the cytoskeleton and composition of the extracellular matrix. These four preclinical models and data represent a new resource available to the cancer research community to catalyze further investigations on invasiveness., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Published
2018
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