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213 results on '"Institut de Recherche Pierre Fabre"'

1. Effect of Arginine Supplementation in the Metabolic Syndrome

Author: Institut de Recherche Pierre Fabre, Hospital Avicenne, Adeprina, and Robert Benamouzig, PU-PH in University Hospitals Paris-Seine-Saint-Denis-APHP-University Hospital Avicenne / Jean Verdier
Published: 2015

2. Characterization of the Metabolic Fate of an Oral Arginine Form

Author: Institut de Recherche Pierre Fabre, Hospital Avicenne, Adeprina, and Robert Benamouzig, PU-PH in University Hospitals Paris-Seine-Saint-Denis-APHP-University Hospital Avicenne / Jean Verdier
Published: 2015

3. Taxonomically informed metabolite annotation and data organization in natural products research

Author: B David, Jonathan Bisson, Miwa Dounoue-Kubo, Adriano Rutz, Joël Boustie, Simon Ollivier, D Olivier, LM Quiros Guerrero, J-L Wolfender, PM Allard, A Gaudry, Université de Lausanne (UNIL), Université de Genève (UNIGE), Institut des Sciences Chimiques de Rennes (ISCR), 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), University of Chicago, Institut de Recherche Pierre FABRE (INSTITUT DE RECHERCHE PIERRE FABRE), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Université de Lausanne = University of Lausanne (UNIL), Université de Genève = University of Geneva (UNIGE), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and 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)
Subjects: chemistry.chemical_compound, Annotation, chemistry, Metabolite, [CHIM]Chemical Sciences, Computational biology, Biology, Natural (archaeology), ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019
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4. Boosting γδ T cell-mediated antibody-dependent cellular cytotoxicity by PD-1 blockade in follicular lymphoma

Author: Renaud Morin, Don-Marc Franchini, Loic Ysebaert, Christine Bezombes, Cédric Rossi, J. M. Lagarde, Jean-Jacques Fournié, Christine Jean, Ariel Savina, Julie Bordenave, Mary Poupot, Patricia Pérez-Galán, Alba Matas Céspedes, Camille Laurent, Pauline Gravelle, Marie Tosolini, Emilie Decaup, Christian Klein, Laetitia Ligat, Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CERPER Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centre de Physiopathologie Toulouse Purpan (CPTP), Poupot, Mary, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et Cancérologie Intégrative, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Laboratoire Jacques-Louis Lions (LJLL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Pierre Fabre Dermo-Cosmétique, Pierre Fabre Applied Skin Research Centre, Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Surfaces Cellulaires et Signalisation chez les Végétaux (SCSV), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Institut de Mathématiques de Bourgogne [Dijon] (IMB), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Institut de Recherche Pierre Fabre, Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et Cancérologie Intégratives (CRC - Inserm U1138), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, lcsh:Immunologic diseases. Allergy, 3D model, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, [SDV]Life Sciences [q-bio], Immunology, Cell, Follicular lymphoma, chemical and pharmacologic phenomena, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, CD16, lcsh:RC254-282, γδ T cells, 03 medical and health sciences, 0302 clinical medicine, Immune system, follicular lymphoma, [SDV.CAN] Life Sciences [q-bio]/Cancer, PD-1, medicine, Immunology and Allergy, ComputingMilieux_MISCELLANEOUS, Original Research, Antibody-dependent cell-mediated cytotoxicity, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Lymphoma, Cytolysis, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cancer research, [SDV.IMM]Life Sciences [q-bio]/Immunology, anti-CD20 MAbs, lcsh:RC581-607
Abstract: International audience; Follicular lymphoma (FL) is a common non Hodgkin's lymphoma subtype in which immune escape mechanisms are implicated in resistance to chemo-immunotherapy. Although molecular studies point to qualitative and quantitative deregulation of immune checkpoints, in depth cellular analysis of FL immune escape is lacking. Here, by functional assays and in silico analyses we show that a subset of FL patients displays a 'high' immune escape phenotype. These FL cases are characterized by abundant infiltration of PD1+ CD16+ TCRVγ9Vδ2 γδ T lymphocytes. In a 3D co-culture assay (MALC), γδ T cells mediate both direct and indirect (ADCC in the presence of anti-CD20 mAbs) cytolytic activity against FL cell aggregates. Importantly, PD-1, which is expressed by most FL-infiltrating γδ T lymphocytes with ADCC capacity, impairs these functions. In conclusion, we identify a PD1-regulated γδ T cell cytolytic immune component in FL. Our data provide a treatment rational by PD-1 blockade aimed at boosting γδ T cell anti-tumor functions in FL.
Published: 2018
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5. Better characterization of vinflunine pharmacokinetics variability and exposure/toxicity relationship to improve its use: analyses from 18 trials

Author: Schmitt , A., Nguyen , L, Zorza , G, Ferré , P., Pétain , A., Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, CERPER Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Institut de Recherche Pierre Fabre
Subjects: Neutropenia, Clinical Trials, Phase I as Topic, Dose-Response Relationship, Drug, PK/PD, [ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Vinblastine, Antineoplastic Agents, Phytogenic, Models, Biological, modelling, Leukocyte Count, Clinical Trials, Phase II as Topic, Biological Variation, Population, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Humans, Administration, Intravenous, vinflunine, pharmacokinetics
Abstract: AIMS: Vinflunine is a novel tubulin‐targeted inhibitor indicated as a single agent for the treatment of bladder cancers after failure of prior platinum‐based therapy. Its pharmacokinetics (PK) and pharmacodynamics (PD) have been independently characterized through several phase I and phase II studies. However, no global pharmacometric analysis had been conducted as yet. METHODS: Vinflunine concentrations and safety data from 18 phase I and phase II studies were used to conduct population PK and PK/PD analysis, using Nonmem. A four‐compartment model was used to describe vinflunine PK and several covariates were tested to explain interindividual variability. In terms of PK/PD relationship, a semiphysiological population PK/PD model was applied to describe time course of absolute neutrophil counts (ANC) after vinflunine administration and logistic regression models were used to test the relationship between vinflunine exposure and toxicities. RESULTS: Vinflunine clearance is explained by creatinine clearance, body surface area and combination with PEGylated doxorubicin, leading to a decrease from 28.2 to 25.3% of the interindividual variability. When vinflunine dose is decreased, simulations of ANC time course (via a semiphysiological model) after vinflunine administration show a risk of neutropenia grade 3–4 at cycle 2 always lower than when dose is delayed. As an example, for moderate renal impaired patients, the risk is 42.1% when vinflunine is dosed at 320 mg m(–2) once every 4 weeks vs. 23.3% for 280 mg m(–2) once every 3 weeks. CONCLUSIONS: We propose for the first time a global comprehensive clinical pharmacological analysis for intravenous vinflunine that may help drive dose adjustment.
Published: 2018
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6. TRPV6 Is a Ca2+ Entry Channel Essential for Ca2+-induced Differentiation of Human Keratinocytes

Author: Benjamin Beck, Renata Polakowska, Natalia Prevarskaya, V’yacheslav Lehen’kyi, Maria Charveron, Roman Skryma, Pascal Bordat, Rôle des canaux ioniques membranaires et du calcium intracellulaire dans la physiopathologie de la prostate, Université de Lille, Sciences et Technologies-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut de Recherche Pierre FABRE (INSTITUT DE RECHERCHE PIERRE FABRE), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
Subjects: Keratinocytes, Time Factors, TRPV6, [SDV]Life Sciences [q-bio], Cellular differentiation, TRPV Cation Channels, Biology, Cell morphology, Biochemistry, Cell Line, Calcitriol, medicine, Humans, Gene silencing, RNA, Messenger, RNA, Small Interfering, Molecular Biology, Involucrin, Cells, Cultured, Dose-Response Relationship, Drug, Cell Differentiation, Cell Biology, Cell biology, Phenotype, medicine.anatomical_structure, Cell culture, Calcium, Calcium Channels, Keratinocyte, Intracellular
Abstract: International audience; Ca(2+) is an essential factor inducing keratinocyte differentiation due to the natural Ca(2+) gradient in the skin. However, the membrane mechanisms that mediate calcium entry and trigger keratinocyte differentiation had not previously been elucidated. In this study we demonstrate that Ca(2+)-induced differentiation up-regulates both mRNA and protein expression of a transient receptor potential highly Ca(2+)-selective channel, TRPV6. The latter mediates Ca(2+) uptake and accounts for the basal [Ca(2+)](i) in human keratinocytes. Our results show that TRPV6 is a prerequisite for keratinocyte entry into differentiation, because the silencing of TRPV6 in human primary keratinocytes led to the development of impaired differentiated phenotype triggered by Ca(2+). The expression of such differentiation markers as involucrin, transglutaminase-1, and cytokeratin-10 was significantly inhibited by small interfering RNA-TRPV6 as compared with differentiated control cells. TRPV6 silencing affected cell morphology and the development of intercellular contacts, as well as the ability of cells to stratify. 1,25-Dihydroxyvitamin D3, a cofactor of differentiation, dose-dependently increased TRPV6 mRNA and protein expression in human keratinocytes. This TRPV6 up-regulation led to a significant increase in Ca(2+) uptake in both undifferentiated and differentiated keratinocytes. We conclude that TRPV6 mediates, at least in part, the pro-differentiating effects of 1,25-dihydroxyvitamin D3 by increasing Ca(2+) entry, thereby promoting differentiation. Taken together, these data suggest that the TRPV6 channel is a key element in Ca(2+)/1,25-dihydroxyvitamin D3-induced differentiation of human keratinocytes.
Published: 2007
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7. L’arginine orale, particulièrement sous une forme à libération prolongée, est utilisée plus efficacement pour la synthèse de monoxyde d’azote quand les sujets présentent des facteurs de risque du syndrome métabolique

Author: DEVEAUX, Ambre, Fouillet, Hélène, Petzke, Klaus, HERMIER, Dominique, André, Etienne, Bunouf, Pierre, Lantoine-Adam, Frédérique, Benamouzig, Robert, Mathé, Véronique, Huneau, Jean-François, Mariotti, François, Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), AgroParisTech-Institut National de la Recherche Agronomique (INRA), German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Institut de Recherche Pierre FABRE (INSTITUT DE RECHERCHE PIERRE FABRE), Institut de Recherche Pierre Fabre, AgroParisTech, Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Centre de Recherche Pierre Fabre, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
Subjects: [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Introduction et but de l'étude: La supplémentation orale en arginine a un effet bénéfique sur des fonctions associées au monoxyde d'azote (NO) chez des sujets avec des facteurs de risque cardiovasculaires. Cet effet semble dépendre de la dose et de l'augmentation de l'arginine plasmatique qui en résulte, mais aussi de la situation physiopathologique. Aucune donnée ne permet cependant de lier la mise à disposition de l'arginine et la synthèse de NO, en situation normale ou de risque cardiométabolique. L'objectif de cette étude était de comparer la biodisponibilité de l'arginine ingérée et son utilisation pour la synthèse de NO (1) selon qu'elle est consommée sous une forme à libération immédiate (LI) ou sous une forme à libération prolongée (LP) mimant la mise à disposition naturellement lente de l'arginine alimentaire, et (2) selon la présence de facteurs de risque du syndrome métabolique. Matériel et méthodes: Dans une étude avec répartition au hasard, selon un protocole croisé, nous avons comparé la biodisponibilité et l'utilisation pour la synthèse de NO d'arginine LP et LI (1,5g, 3 fois par jour) consommée pendant une semaine chez 15 sujets sains témoins et 12 sujets sains présentant un « tour de taille hypertriglycéridémique » (TTH). Nous avons pour cela utilisé de l'arginine marquée ([ 15 N 2-(guanido)]-arginine) et des dosages isotopiques plasmatiques et urinaires pour suivre l'apparition de l'arginine ingérée dans la circulation systémique et sa conversion spécifique en NO. Résultats et Analyse statistique: Au niveau cinétique, comme attendu, les augmentations des concentrations plasmatiques en arginine ingérée, en arginine totale et en ornithine totale étaient moins brutales et plus étalées après arginine-LP que LI. Au bilan, concernant les aires sous courbe (AUCs) plasmatiques sur 24h, l'AUC de l'arginine ingérée était moins importante après la supplémentation en arginine-LP que LI, tandis que les AUCs de l'arginine et ornithine totales étaient peu variables selon la forme (LP ou LI) et la durée (premier ou dernier jour) de la supplémentation. Par ailleurs, l'utilisation de l'arginine ingérée pour la synthèse de NO était plus élevée chez les sujets TTH que chez les témoins, et elle était plus élevée avec la forme LP qu'avec la forme LI, en particulier chez les sujets TTH (Ps
Published: 2015

8. La supplémentation en L-arginine atténue la dysfonction endothéliale postprandiale lorsquel’argininémie basale est faible chez des sujets sains présentant des facteurs de risque dusyndrome métabolique

Author: Ambre Deveaux, Isabelle Pham, Sheila West, Etienne André, Frédérique Lantoine-Adam, Pierre Bunouf, Dominique Hermier, Véronique Mathé, Hélène Fouillet, Jean-François Huneau, Robert Benamouzig, François Mariotti, Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Departement de Physiologie et Explorations fonctionnelles, Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Departement of Nutritional Sciences, Pennsylvania State University (Penn State), Penn State System-Penn State System, Institut de Recherche Pierre FABRE (INSTITUT DE RECHERCHE PIERRE FABRE), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, AgroParisTech-Institut National de la Recherche Agronomique (INRA), Hôpital Jean Verdier, and Institut de Recherche Pierre Fabre
Subjects: [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; La supplémentation en L-arginine atténue la dysfonction endothéliale postprandiale lorsque l'argininémie basale est faible chez des sujets sains présentant des facteurs de risque du syndrome métabolique Veuillez choisir votre discipline: Clinique Présentation préférée: Communication orale Spécifiez votre âge
Published: 2015

9. Cytisine-like alkaloids from Ormosia hosiei Hemsl.E.H. Wilson

Author: Isabelle Pouny, Sirong Yi, Muriel Batut, Laure Vendier, François Sautel, Bruno David, Georges Massiot, Paola B. Arimondo, Pharmacochimie de la Régulation Epigénétique du Cancer (ETaC), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-PIERRE FABRE, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Pierre FABRE (INSTITUT DE RECHERCHE PIERRE FABRE), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Chongqing Institute of Medicinal Plant Cultivation, and China Academy of Chinese Medical Sciences
Subjects: Stereochemistry, Molecular Conformation, Plant Science, Horticulture, Ormosia hosiei, Receptors, Nicotinic, Crystallography, X-Ray, Biochemistry, Plant Roots, chemistry.chemical_compound, Cytisine, Alkaloids, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Molecular Biology, Nuclear Magnetic Resonance, Biomolecular, Octane, biology, Molecular Structure, Plant Stems, Chemistry, Absolute configuration, Fabaceae, General Medicine, biology.organism_classification, Azocines, Nicotinic agonist, Alpha-4 beta-2 nicotinic receptor, Quinolizines
Abstract: International audience; Four alkaloids named hosieines A–D were isolated from the root and stem of Ormosia hosiei. Their flat structures were established by mass spectrometry and by a combination of NMR experiments. These molecules probably share a common biosynthetic origin with the lupin alkaloids but they differ in the formation of the last ring, being here part of a rare 2-azabicyclo[3.2.1]octane system. Their absolute configuration was determined by X-ray crystallography using CuKα radiation. As has been described for cytisine, they display a remarkable affinity towards neuronal nicotinic acetylcholine α4β2 receptor.
Published: 2014
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10. F 16915 prevents heart failure-induced atrial fibrillation: a promising new drug as upstream therapy

Author: Frédérique Lantoine-Adam, Philippe Legrand, Elisabeth Dupont-Passelaigue, Frédéric Longo, Stanley Nattel, Stéphane N. Hatem, Robert Létienne, Georghia Michael, Bruno Le Grand, Kunihiro Nishida, Monique David-Dufilho, Daniel Catheline, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE, UMRS 956, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cardiologie, Laboratoire de Biochimie et Nutrition Humaine, AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut de Recherche Pierre Fabre, Institut de Recherche Pierre FABRE (INSTITUT DE RECHERCHE PIERRE FABRE), UMR_S 1166, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Laboratoire de biochimie, Institut National de la Recherche Agronomique (INRA), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), 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], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Department of Pharmacology and Therapeutics [Montréal], and McGill University = Université McGill [Montréal, Canada]
Subjects: Male, Drug, medicine.medical_specialty, Docosahexaenoic Acids, Pyridines, Heart Ventricles, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Nicotinyl Alcohol, Heart failure, Rats, Sprague-Dawley, Dogs, Internal medicine, Occlusion, medicine, Animals, Prodrugs, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Heart Atria, Ventricular remodeling, ComputingMilieux_MISCELLANEOUS, media_common, Pharmacology, Ventricular Remodeling, business.industry, Atrial fibrillation, Atrial Remodeling, General Medicine, medicine.disease, 3. Good health, medicine.anatomical_structure, Docosahexaenoic acid, Cardiology, F 16915, business, Complication, Anti-Arrhythmia Agents, Artery
Abstract: Atrial fibrillation (AF) is a common complication of heart failure. The aim of the present study was to investigate the effects of a new pure docosahexaenoic acid derivative called F 16915 in experimental models of heart failure-induced atria dysfunction. The atrial dysfunction-induced AF was investigated (1) in a dog model of tachypacing-induced congestive heart failure and (2) in a rat model of heart failure induced by occlusion of left descending coronary artery and 2 months reperfusion. F 16915 (5 g/day for 4 weeks) significantly reduced the mean duration of AF induced by burst pacing in the dog model (989 +/- 111 s in the vehicle group to 79 +/- 59 s with F 16915, P < 0.01). This dose of F 16915 also significantly reduced the incidence of sustained AF (5/5 dogs in the vehicle group versus 1/5 with F 16915, P < 0.05). In the rat model, the percentage of shortening fraction in the F 16915 group (100 mg/kg p.o. daily) was significantly restored after 2 months (32.6 +/- 7.4 %, n = 9 vs 17.6 +/- 3.4 %, n = 9 in the vehicle group, P < 0.01). F 16915 also reduced the de-phosphorylation of connexin43 from atria tissue. The present results show that treatment with F 16915 reduced the heart dilation, resynchronized the gap junction activity, and reduced the AF duration in models of heart failure. Thus, F 16915 constitutes a promising new drug as upstream therapy for the treatment of AF in patients with heart failure.
Published: 2014
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11. Comparative study between reconstructed and native human epidermis using nuclear microscopy

Author: M. Rosdy, Philippe Moretto, Etienne Gontier, M.D. Ynsa, Alain Mavon, Dirk E. Boerma, Aurelio Climent-Font and Miguel Ángel Respaldiza, Centre d'Etudes Nucléaires de Bordeaux Gradignan (CENBG), Université Sciences et Technologies - Bordeaux 1-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Pierre FABRE (INSTITUT DE RECHERCHE PIERRE FABRE), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, SkinEthic Laboratories (SKINETHIC LABORATORIES), and SkinEthic Laboratories
Subjects: Nuclear and High Energy Physics, Microprobe, Micro pixe, Analytical chemistry, Human skin, 01 natural sciences, Skin models, 03 medical and health sciences, 0302 clinical medicine, 29.30.−Kv, 87.64.−t, Native skin, Instrumentation, integumentary system, Chemistry, 010401 analytical chemistry, Nuclear microscopy, 0104 chemical sciences, Micro-PIXE, Micro-RBS, Ultrastructure, Biophysics, STIM, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Barrier effect, Epidermis, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, 030215 immunology
Abstract: International audience; The physiological status of native skin is suffering from large inter-individual variations, especially in terms of inorganic ions content. For this reason, together with the advent of ethic laws on animal experimentation, reconstructed skin or epidermis models are extensively employed nowadays in penetration studies for cosmetic or pharmacological applications. It has been already verified that reconstructed human epidermis (RHE) has similar physiological mechanisms to native human skin, but until now, there are few studies where the elemental concentrations of both skins, reconstructed and native, are compared. In this work, freeze-dried thin sections of human native skin obtained from surgery have been characterized using PIXE, RBS and STIM at the CENBG nuclear microprobe. RHE samples were treated and analyzed in the same conditions for comparison. The combination of the different imaging and analysis techniques made possible a clear delimitation and identification of skin ultrastructure. The elemental concentrations of P, S, Cl, K and Ca were measured in the different strata. For both skins, concentrations have been compared and significant differences in terms of elemental concentrations have been determined using statistical approaches. Similar physiological characteristics were pointed out in both skin models, in particular the Ca gradient presumably involved in the regulation of the barrier effect.
Published: 2006
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12. Bioactive flavonoids of Tanacetum parthenium revisited

Author: Christophe Long, Frédéric Ausseil, Bruno David, Georges Massiot, Catherine Lavaud, Pierre Sauleau, Valerie Cassabois, Institut de Recherche Pierre FABRE (INSTITUT DE RECHERCHE PIERRE FABRE), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Laboratoire de Pharmacognosie, Université de Reims Champagne-Ardenne (URCA), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: 0106 biological sciences, Jaceidin, Flavonols, Flavonoid, Mitosis, Antineoplastic Agents, Plant Science, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Horticulture, Biology, Chemical Fractionation, Tanacetum parthenium, 01 natural sciences, Biochemistry, chemistry.chemical_compound, Inhibitory Concentration 50, Botany, medicine, Inhibitory concentration 50, Animals, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Confusion, chemistry.chemical_classification, Flavonoids, Centaureidin, Traditional medicine, 010405 organic chemistry, Plant Extracts, General Medicine, 0104 chemical sciences, 3. Good health, 010404 medicinal & biomolecular chemistry, chemistry, medicine.symptom, 010606 plant biology & botany
Abstract: Bio-guided fractionation of an extract from Tanacetum parthenium showing activity as mitotic blocker allowed the isolation and identification of santin 3, jaceidin 2 and centaureidin 1. The latter two closely related flavonols, which, to the best of our knowledge, are isolated here together for the first time, form a mixture difficult to resolve and which is probably the reason for the confusion in the literature regarding their occurrence. Centaureidin 1 had an IC50 of 1 microM while jaceidin 2 and santin 3 were 200 times less active.
Published: 2003
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13. Avelumab Versus Docetaxel in Patients With Platinum-Treated Advanced NSCLC: 2-Year Follow-Up From the JAVELIN Lung 200 Phase 3 Trial

Author: Roisné-Hamelin, Florian, Pobiega, Sabrina, Jézéquel, Kévin, Miron, Simona, Dépagne, Jordane, Veaute, Xavier, Busso, Didier, Du, Marie-Hélène Le, Callebaut, Isabelle, Charbonnier, Jean-Baptiste, Cuniasse, Philippe, Zinn-Justin, Sophie, Marcand, Stéphane, Park, Keunchil, Özgüroğlu, Mustafa, Vansteenkiste, Johan, Spigel, David, Yang, James C.H., Ishii, Hidenobu, Garassino, Marina, de Marinis, Filippo, Szczesna, Aleksandra, Polychronis, Andreas, Uslu, Ruchan, Krzakowski, Maciej, Lee, Jong-Seok, Calabrò, Luana, Arén Frontera, Osvaldo, Xiong, Huiling, Bajars, Marcis, Ruisi, Mary, Barlesi, Fabrice, Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Samsung Medical Center Sungkyunkwan University School of Medicine, Institute Division of Hematology/Oncology, Istanbul University Cerrahpasa, Department of Pulmonology, University Hospitals Leuven [Leuven], Sarah Cannon Research Institute [Nashville, Tennessee], National Taiwan University Cancer Center [Taipei], IRCCS Istituto Nazionale dei Tumori [Milano], Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Seoul National University Bundang Hospital (SNUBH), Azienda Ospedaliera Universitaria Senese, EMD Serono Research & Development Institute, Institut Gustave Roussy (IGR), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and 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)
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, PD-L1, medicine.medical_specialty, Avelumab, Lung Neoplasms, Non–small cell lung cancer, Phase 3, Second-line, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Docetaxel, Antibodies, Monoclonal, Humanized, Gastroenterology, B7-H1 Antigen, NO, 03 medical and health sciences, 0302 clinical medicine, Non-small cell lung cancer, Internal medicine, medicine, Clinical endpoint, Humans, In patient, education, Multicenter, Lung, Platinum, Chemotherapy, education.field_of_study, business.industry, Confidence interval, 030104 developmental biology, medicine.anatomical_structure, Nivolumab, Oncology, 030220 oncology & carcinogenesis, Open-Label, Neoplasm Recurrence, Local, business, medicine.drug, Follow-Up Studies
Abstract: Introduction: In the JAVELIN Lung 200 trial, avelumab (anti-programmed death-ligand 1 [PD-L1] antibody) did not significantly prolong overall survival (OS) versus docetaxel in patients with platinum-treated PD-L1+ NSCLC. We report greater than 2-year follow-up data. Methods: Patients with stage IIIB or IV or recurrent NSCLC with disease progression after platinum-doublet chemotherapy were randomized 1:1 to avelumab 10 mg/kg every 2 weeks or docetaxel 75 mg/m(2) every 3 weeks. The primary end point was OS in patients with PD-L1+ tumors (greater than or equal to 1% tumor cell expression; IHC 73-10 pharmDx assay). Results: Of 792 patients, 529 had PD-L1+ tumors (264 versus 265 in the avelumab versus docetaxel arms, respectively). As of March 4, 2019, median duration of follow-up for OS in the PD L1+ population was 35.4 months in the avelumab arm and 34.7 months in the docetaxel arm; study treatment was ongoing in 25 (9.5%) versus 0 patients, respectively. In the PD-L1+ population, 2-year OS rates (95% confidence interval [CI]) with avelumab versus docetaxel were 29.9% (24.5%-35.5%) versus 20.5% (15.6%-25.8%); in greater than or equal to 50% PD L1+ subgroups, 2-year OS rates were 36.4% (29.1%-43.7%) versus 17.7% (11.8%-24.7%) and in the greater than or equal to 80% subgroup were 40.2% (31.3%-49.0%) versus 20.3% (12.9%-28.8%), respectively. Median duration of response (investigator assessed) was 19.1 months (95% CI: 10.8-34.8) versus 5.7 months (95% CI: 4.1-8.3). Safety profiles for both arms were consistent with the primary analysis. Conclusions: Although the JAVELIN Lung 200 primary analysis (reported previously) revealed that avelumab did not significantly prolong OS versus docetaxel in patients with platinum-treated PD-L1+ NSCLC, posthoc analyses at 2 years of follow-up revealed that 2-year OS rates were doubled with avelumab in subgroups with higher PD-L1 expression (greater than or equal to 50% and greater than or equal to 80%). (C) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc., EMD Serono Research & Development Institute, Inc., an affiliate of Merck KGaA, Darmstadt, Germany; Pfizer; Merck KGaA, LL This study was sponsored by EMD Serono Research & Development Institute, Inc., an affiliate of Merck KGaA, Darmstadt, Germany, as part of an alliance between Merck KGaA and Pfizer. Employees of the sponsor are coauthors of this manuscript and contributed to the design, execution, and interpretation of the analyses being reported, writing the report, and the decision to submit the article for publication, along with the other coauthors. The authors thank the patients and their families; the investigators, coinvestigators, and study teams at each participating center and at Merck KGaA, Darmstadt, Germany, and EMD Serono Research & Development Institute, Inc., Billerica, MA, an affiliate of Merck KGaA, Darmstadt, Germany, and Quintiles (Durham, NC) . Medical writing support was provided by Abhijith Thippeswamy of ClinicalThinking and funded by Merck KGaA and Pfizer.
Published: 2021
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14. The use of suction blisters to measure sunscreen protection against UVR- induced DNA damage

Author: Emmanuel Questel, Eléonore Gravier, Gwendal Josse, Thierry Douki, Jimmy Le Digabel, CERPER Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de Pharmacochimie Pierre Fabre Dermo-Cosmétique, Res Ctr, Institut Curie, Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, 0301 basic medicine, Suction (medicine), Ultraviolet Rays, DNA damage, education, Biophysics, Pyrimidine dimer, medicine.disease_cause, Young Adult, 030207 dermatology & venereal diseases, 03 medical and health sciences, Blister, 0302 clinical medicine, Tandem Mass Spectrometry, Healthy volunteers, medicine, Humans, Radiology, Nuclear Medicine and imaging, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Chromatography, High Pressure Liquid, ComputingMilieux_MISCELLANEOUS, Skin, Radiation, integumentary system, Radiological and Ultrasound Technology, Chemistry, food and beverages, Blisters, Molecular biology, Suction blister, Staining, 030104 developmental biology, Pyrimidine Dimers, Female, medicine.symptom, Sun Protection Factor, Sunscreening Agents, Genotoxicity, DNA Damage
Abstract: The formation of DNA photoproducts caused by solar UVR exposure needs to be investigated in-vivo and in particular in order to assess sunscreens' level of protection against solar genotoxicity. The study's purposes were: i) to evaluate if the roof of suction blisters is an appropriate sampling method for measuring photoproducts, and ii) to measure in-vivo sunscreen protection against cyclobutane pyrimidine dimers. Skin areas on the interior forearms of eight healthy volunteers were exposed in-vivo to 2 MED of simulated solar radiation (SSR) and to 15 MED on a sunscreen protected area. After irradiation, six suction blisters were induced and the blister roofs were collected. Analysis of SSR-induced CPDs was performed by two independent methods: a chromatography coupled to mass spectroscopy (HPLC-MS/MS) approach and a 3D-imaging of CPD immunostaining by multiphoton microscopy on floating epidermal sheets. HPLC-MS/MS analyses showed that SSR-unexposed skin presented no CPD dimers, whereas 2 MED SSR-exposed skin showed a significant number of TT-CPD. The sunscreen covered skin exposed to 15 MED appeared highly protected from DNA damage, as the amount of CPD-dimers remained below the detection limit. The multiphoton-immunostaining analysis consistently showed that no CPD staining was observed on the non-SSR-exposed skin. A significant increase of CPD staining intensity and number of CPD-positive cells were observed on the 2 MED SSR-exposed skin. Sunscreen protected skin presented a very low staining intensity and the number of CPD-positive cells remained very close to non-SSR-exposed skin. This study showed that suction blister samples are very appropriate for measuring CPD dimers in-vivo, and that sunscreens provide high protection against UVR-induced DNA damage.
Published: 2018
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15. Identification of epigenetic factors regulating the mesenchyme to epithelium transition by RNA interference screening in breast cancer cells

Author: Clara Salazar-Cardozo, Véronique Masson, Paola B. Arimondo, Frédéric Alby, Laurence Fleury, Jean-Marc Gregoire, Frédéric Ausseil, Pharmacochimie de la Régulation Epigénétique du Cancer (ETaC), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-PIERRE FABRE, This work was funded by the Institut de Recherche Pierre Fabre and the Centre national de la Recherche Scientifique., and PIERRE FABRE-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Cancer Research, Epithelial-Mesenchymal Transition, MESH: Cell Line, Tumor, [SDV]Life Sciences [q-bio], Mesenchyme, MESH: RNA Interference, Mesenchymal cell differentiation, Breast Neoplasms, Biology, Real-Time Polymerase Chain Reaction, Cell morphology, Epithelium, 03 medical and health sciences, RNA interference, Cell Line, Tumor, MESH: RNA, Small Interfering, KAT5/Tip60, Genetics, medicine, Humans, [CHIM]Chemical Sciences, Epigenetics, RNA, Small Interfering, Triple-negative breast cancer, MESH: Humans, MESH: Real-Time Polymerase Chain Reaction, DOT1L, MESH: Gene Knockdown Techniques, 3. Good health, Chromatin, MESH: Epithelial-Mesenchymal Transition, 030104 developmental biology, medicine.anatomical_structure, Oncology, Gene Knockdown Techniques, RNAi, Transition, Immunology, Screening, Cancer research, Female, RNA Interference, MESH: Female, MESH: Breast Neoplasms, Research Article
Abstract: Background In breast cancer, the epithelial to mesenchyme transition (EMT) is associated to tumour dissemination, drug resistance and high relapse risks. It is partly controlled by epigenetic modifications such as histone acetylation and methylation. The identification of genes involved in these reversible modifications represents an interesting therapeutic strategy to fight metastatic disease by inducing mesenchymal cell differentiation to an epithelial phenotype. Methods We designed a siRNA library based on chromatin modification-related to functional domains and screened it in the mesenchymal breast cancer cell line MDA-MB-231. The mesenchyme to epithelium transition (MET) activation was studied by following human E-CADHERIN (E-CAD) induction, a specific MET marker, and cell morphology. Candidate genes were validated by studying the expression of several differential marker genes and their impact on cell migration. Results The screen led to the identification of 70 gene candidates among which some are described to be, directly or indirectly, involved in EMT like ZEB1, G9a, SMAD5 and SMARCD3. We also identified the DOT1L as involved in EMT regulation in MDA-MB-231. Moreover, for the first time, KAT5 gene was linked to the maintenance of the mesenchymal phenotype. Conclusions A multi-parametric RNAi screening approach was developed to identify new EMT regulators such as KAT5 in the triple negative breast cancer cell line MDA-MB-231. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2683-5) contains supplementary material, which is available to authorized users.
Published: 2016
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16. EORTC-ROG expert opinion: Radiotherapy volume and treatment guidelines for neoadjuvant radiation of adenocarcinomas of the gastroesophageal junction and the stomach

Author: Karin Haustermans, Philip Poortmans, Akos Gulyban, Oscar Matzinger, Laurence Collette, Abraham Kuten, Philippe Maingon, Zvi Bernstein, Erich Gerber, Jean François Bosset, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Institut de Recherche Pierre Fabre, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
Subjects: Oncology, medicine.medical_specialty, medicine.medical_treatment, MESH: Neoadjuvant Therapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 030218 nuclear medicine & medical imaging, MESH : Adenocarcinoma, 03 medical and health sciences, 0302 clinical medicine, MESH: Practice Guidelines as Topic, Stomach Neoplasms, Internal medicine, medicine, Humans, MESH : Esophagogastric Junction, MESH : Stomach Neoplasms, Radiology, Nuclear Medicine and imaging, Lymph node, Neoadjuvant therapy, MESH: Humans, business.industry, Stomach, MESH: Adenocarcinoma, MESH : Humans, Cancer, MESH: Stomach Neoplasms, Hematology, Esophageal cancer, medicine.disease, Neoadjuvant Therapy, 3. Good health, Radiation therapy, Clinical trial, MESH : Practice Guidelines as Topic, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, MESH: Esophagogastric Junction, Esophagogastric Junction, business, MESH : Neoadjuvant Therapy
Abstract: International audience; PURPOSE: The Gastro-Intestinal Working Party of the EORTC Radiation Oncology Group (GIWP-ROG) developed guidelines for target volume definition in neoadjuvant radiation of adenocarcinomas of the gastroesophageal junction (GEJ) and the stomach. METHODS AND MATERIALS: Guidelines about the definition of the clinical target volume (CTV) are based on a systematic literature review of the location and frequency of local recurrences and lymph node involvement in adenocarcinomas of the GEJ and the stomach. Therefore, MEDLINE was searched up to August 2008. Guidelines concerning prescription, planning and treatment delivery are based on a consensus between the members of the GIWP-ROG. RESULTS: In order to support a curative resection of GEJ and gastric cancer, an individualized preoperative treatment volume based on tumour location has to include the primary tumour and the draining regional lymph nodes area. Therefore we recommend to use the 2nd English Edition of the Japanese Classification of Gastric Carcinoma of the Japanese Gastric Cancer Association which developed the concept of assigning tumours of the GEJ and the stomach to anatomically defined sub-sites corresponding respectively to a distinct lymphatic spread pattern. CONCLUSION: The GIWP-ROG defined guidelines for preoperative irradiation of adenocarcinomas of the GEJ and the stomach to reduce variability in the framework of future clinical trials.
Published: 2009
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17. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial

Author: Pirker, Robert, Pereira, Jose R, Szczesna, Aleksandra, Von Pawel, Joachim, Krzakowski, Maciej, Ramlau, Rodryg, Vynnychenko, Ihor, Park, Keunchil, Yu, Chih-Teng, Ganul, Valentyn, Roh, Jae-Kyung, Bajetta, Emilio, O'Byrne, Kenneth, De Marinis, Filippo, Eberhardt, Wilfried, Goddemeier, Thomas, Emig, Michael, Gatzemeier, Ulrich, Renseigné, Non, Chouaid, Christos, Department of Medicine I and Clinical Pathology, Universität Wien, Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), R Pirker, JR Pereira, Roh JK, E Bajetta, K O'Byrne, de Marinis F, W Eberhardt, Goddemeier T, M Emig, Gatzemeier U, équipe de l'étude FLEX ., Szczesna A, von Pawel J, M Krzakowski, R Ramlau, Vynnychenko I, K Park, CT Yu, and V Ganul
Subjects: Male, Lung Neoplasms, medicine.medical_treatment, Cetuximab, Gastroenterology, MESH: Antibodies, Monoclonal, MESH: Proportional Hazards Models, MESH: Aged, 80 and over, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, Medicine, MESH: Treatment Outcome, Aged, 80 and over, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Antibodies, Monoclonal, Vinorelbine, MESH: Neoplasm Staging, General Medicine, Middle Aged, 3. Good health, ErbB Receptors, Survival Rate, MESH: Antineoplastic Combined Chemotherapy Protocols, Treatment Outcome, MESH: Young Adult, MESH: Survival Analysis, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, medicine.medical_specialty, Adolescent, MESH: Survival Rate, MESH: Vinblastine, Antineoplastic Agents, MESH: Receptor, Epidermal Growth Factor, Antibodies, Monoclonal, Humanized, Vinblastine, Young Adult, 03 medical and health sciences, Internal medicine, Humans, Lung cancer, Survival rate, Aged, Neoplasm Staging, Proportional Hazards Models, 030304 developmental biology, Cancer staging, MESH: Adolescent, Chemotherapy, MESH: Humans, business.industry, Cancer, MESH: Adult, medicine.disease, Survival Analysis, MESH: Male, MESH: Lung Neoplasms, Surgery, MESH: Cisplatin, MESH: Antineoplastic Agents, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cisplatin, business, MESH: Female, MESH: Carcinoma, Non-Small-Cell Lung, Necitumumab
Abstract: International audience; BACKGROUND: Use of cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has the potential to increase survival in patients with advanced non-small-cell lung cancer. We therefore compared chemotherapy plus cetuximab with chemotherapy alone in patients with advanced EGFR-positive non-small-cell lung cancer. METHODS: In a multinational, multicentre, open-label, phase III trial, chemotherapy-naive patients (>or=18 years) with advanced EGFR-expressing histologically or cytologically proven stage wet IIIB or stage IV non-small-cell lung cancer were randomly assigned in a 1:1 ratio to chemotherapy plus cetuximab or just chemotherapy. Chemotherapy was cisplatin 80 mg/m(2) intravenous infusion on day 1, and vinorelbine 25 mg/m(2) intravenous infusion on days 1 and 8 of every 3-week cycle) for up to six cycles. Cetuximab-at a starting dose of 400 mg/m(2) intravenous infusion over 2 h on day 1, and from day 8 onwards at 250 mg/m(2) over 1 h per week-was continued after the end of chemotherapy until disease progression or unacceptable toxicity had occurred. The primary endpoint was overall survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00148798. FINDINGS: Between October, 2004, and January, 2006, 1125 patients were randomly assigned to chemotherapy plus cetuximab (n=557) or chemotherapy alone (n=568). Patients given chemotherapy plus cetuximab survived longer than those in the chemotherapy-alone group (median 11.3 months vs 10.1 months; hazard ratio for death 0.871 [95% CI 0.762-0.996]; p=0.044). The main cetuximab-related adverse event was acne-like rash (57 [10%] of 548, grade 3). INTERPRETATION: Addition of cetuximab to platinum-based chemotherapy represents a new treatment option for patients with advanced non-small-cell lung cancer. FUNDING: Merck KGaA.
Published: 2009
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18. A new hair follicle-derived human epidermal model for the evaluation of sunscreen genoprotection

Author: H. Dromigny, L. Duprat, Thierry Douki, H. Duplan, S. Bessou-Touya, Silvestre Rebelo-Moreira, D. Bacqueville, V. Perier, B. Guiraud, Institut de Recherche Pierre Fabre - Laboratoire de Pharmacocinétique Cutanée, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)
Subjects: DNA protection, Male, Erythema, DNA Repair, Solar-Simulated Radiation, Drug Evaluation, Preclinical, Human skin, Apoptosis, Bipyrimidine Photoproducts, medicine.disease_cause, Sunscreen, Skin, Irradiated Mammalian-Cells, [PHYS]Physics [physics], Radiation, Radiological and Ultrasound Technology, integumentary system, Protection Factor, Caspase 3, Middle Aged, Differential Repair, 3. Good health, Cell biology, medicine.anatomical_structure, Photoprotective Efficacy, Sunlight, Female, medicine.symptom, Induced DNA-Damage, Hair Follicle, Adult, DNA damage, Biophysics, Biology, Reconstructed Human Epidermis, Whole Human Skin, Botany, medicine, Humans, Radiology, Nuclear Medicine and imaging, Cyclobutane Pyrimidine Dimers, Epidermis (botany), Mutagenicity Tests, Reproducibility of Results, DNA, medicine.disease, Hair follicle, Skin Organ-Culture, Pyrimidine Dimers, In-Situ Repair, Skin cancer, Genotoxicity, Epidermis, Thymine Dimers, Sunscreening Agents
Abstract: International audience; Induction of skin cancer is the most deleterious effect of excessive exposure to sunlight. Accurate evaluation of sunscreens to protect the genome is thus of major importance. In particular, the ability. of suncare products to prevent the formation of DNA damage should be evaluated more directly since the Sun Protection Factor is only related to erythema induction. For this purpose, we developed an in vitro approach using a recently characterized reconstituted human epidermis (RHE) model engineered from hair follicle. The relevance of this skin substitute in terms of UV-induced genotoxicity was compared to ex vivo explants exposed to solar-simulated radiation (SSR). The yield of bipyrimidine photoproducts, their rate of repair, and the induction of apoptosis were very similar in both types of skin samples. In order to evaluate the protection afforded by sunscreen against DNA damage, bipyrimidine photoproducts were quantified in tissue models following SSR exposure in the presence or absence of a SPF50+ formula. A rather high DNA protection factor of approximately 20 was found in RHE, very similar to that determined for explants. Thus, RHE is a good surrogate to human skin, and also a convenient and useful tool for investigation of the genoprotection of sunscreens. (C) 2015 Elsevier B.V. All rights reserved.
Published: 2015
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19. The skin barrier function : a micro-PIXE study

Author: Marina Simon, Hervé Seznec, A. Mavon, Philippe Moretto, D. Bacqueville, Philippe Barberet, Le Noan, Ludovic, Centre d'Etudes Nucléaires de Bordeaux Gradignan (CENBG), Université Sciences et Technologies - Bordeaux 1-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Pierre FABRE (INSTITUT DE RECHERCHE PIERRE FABRE), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Université Sciences et Technologies - Bordeaux 1, and Institut de Recherche Pierre Fabre - Laboratoire de Pharmacocinétique Cutanée
Subjects: Micro pixe, Chemical compound, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Skin physiology, Analytical chemistry, Human skin, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, NUCLEAR MICROPROBE, PERCUTANEOUS-ABSORPTION, EPIDERMIS, IN-VIVO, Spectroscopy, Barrier function, Skin barrier function, 030304 developmental biology, DAMAGE, 0303 health sciences, [PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Chemistry, STRATUM-CORNEUM, Penetration (firestop), 3. Good health, MICROANALYSIS, Ion homeostasis, Biophysics
Abstract: Human body is perpetually subjected to environmental exposures as sun, natural, urban or industrial pollutions and societal exposures. Skin is the main physiological barrier facing to these different stresses; however its response mechanisms are still not well understood. Skin models are thus necessary to understand skin physiology and behavior in normal conditions or under stress. Because of the large natural interindividual variability and of some difficulties in obtaining human skin biopsies, we have been developing and characterizing different skin models such as reconstructed epidermis in vitro, native pigskin and human keratinocyte cells. These models allow us to study the mechanisms involved in ion homeostasis in correlation with structural organization and biological responses. In the present study, we have characterized the pig ear skin model using micro-particle induced x-ray emission (PIXE) analysis with the aim of evaluating the distribution of inorganic ions under normal or stress conditions together with the transepidermal penetration of external agents, such as aluminum oxides. The nuclear microprobe analysis allowed us to validate the culture conditions of the tissue and we have shown an alteration of the inorganic ion patterns after exposure to a chemical compound (sodium dodecyl sulfate) known for its deleterious effects on the barrier function. Finally, we have shown no transepidermal penetration of aluminum oxides after different exposures to cosmetic formulations. Copyright (C) 2009 John Wiley & Sons, Ltd.
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20. L-arginine supplementation alleviates post-prandial endothelial dysfunction when baseline fasting plasma arginine concentration is low: a randomized controlled trial in healthy subjects with risk factors for metabolic syndrome

Author: Deveaux, A., Pham, I., West, S. G., Andre, E., Lantoine-Adam, F., Bunouf, P., Sadi, S., Hermier, D., Mathe, V., Helene Fouillet, Huneau, J. F., Benamouzig, R., Mariotti, F., Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Paris Nord (Paris 13), Department of Nutritional Sciences, Pennsylvania State University (Penn State), Penn State System-Penn State System, Penn State System, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE, Centre de Recherche en Nutrition Humaine, Federation of European Physiological Societies., French Physiological Society., AgroParisTech-Institut National de la Recherche Agronomique (INRA), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), Université Paris 13 (UP13)-UFR SMBH, Institut de Recherche Pierre FABRE (INSTITUT DE RECHERCHE PIERRE FABRE), Institut de Recherche Pierre Fabre, and PIERRE FABRE-PIERRE FABRE
Subjects: [SDV]Life Sciences [q-bio], [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], ComputingMilieux_MISCELLANEOUS
Abstract: International audience

21. Développement de modèles de peau in vitro/ex vivo et caractérisation en réponse à des expositions physiques et chimiques. Application à l'étude de la fonction de barrière cutanée en relation avec la pénétration transcutanée d'oxydes métalliques et de nanoparticules

Author: Simon, M., Barberet, Ph., Moretto, Ph., Bacqueville, D., Mavon, A., Seznec, H., Centre d'Etudes Nucléaires de Bordeaux Gradignan (CENBG), Université Sciences et Technologies - Bordeaux 1-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Pierre FABRE (INSTITUT DE RECHERCHE PIERRE FABRE), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, and Le Noan, Ludovic
Subjects: [PHYS.PHYS.PHYS-MED-PH] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], [PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph]

22. High frequency ultrasonography but not 930nm-optical coherence tomography reliably evaluates melanoma thickness in vivo: a prospective validation study

Author: Nicolas Meyer, Valérie Lauwers-Cances, Laurence Lamant, S. Lourari, Hadj Batatia, B Krief, J. Laurent, J. M. Lagarde, Carle Paul, M.P. Konstantinou, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de Physique des Matériaux Divisés et des Interfaces (LPMDI), Université Paris-Est Marne-la-Vallée (UPEM)-Centre National de la Recherche Scientifique (CNRS), PIERRE FABRE, Magellium, Traitement et Compréhension d’Images (IRIT-TCI), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1), French Interministry Unified Fund (Fonds Interministériel Unifié), Midi-Pyrénées Region (Région Midi-Pyrénées), France, and Pierre Fabre Research Institute (Institut de Recherche Pierre Fabre), France
Subjects: Adult, Male, medicine.medical_specialty, Pathology, Skin Neoplasms, Intraclass correlation, Dermatology, Optical coherence tomography, In vivo, medicine, Humans, [INFO]Computer Science [cs], Prospective Studies, Melanoma, Early Detection of Cancer, Aged, Ultrasonography, Reproducibility, medicine.diagnostic_test, business.industry, Reproducibility of Results, Repeatability, Gold standard (test), Middle Aged, medicine.disease, 3. Good health, Female, Histopathology, Nuclear medicine, business, Tomography, Optical Coherence
Abstract: Summary Background Early diagnosis and rapid surgical excision are essential for improving the prognosis of patients with melanoma. Reflectance confocal microscopy has been validated as a feasible procedure for in vivo diagnosis of melanoma but cannot be used to measure tumour thickness. However, ultrasonography and optical coherence tomography may allow melanoma thickness to be measured in vivo. Objectives To validate the accuracy and reliability of high-frequency ultrasonography (HFUS) and optical coherence tomography for assessing melanoma thickness in vivo. Methods We conducted a prospective study on 131 patients with at least one equivocal melanocytic lesion. Each lesion underwent optical coherence tomography and HFUS assessment, followed by excision and pathological examination. Histopathology was considered to be the gold standard for assessing melanoma thickness. Repeatability, inter- and intrarater reproducibility and reliability were evaluated for each imaging procedure. Results Ultrasonography showed a good level of agreement with histology [intraclass correlation coefficient (ICC) 0·807; 95% confidence interval (CI) 0·703–0·877] and excellent inter-rater reproducibility (G = 0·97), resulting in reliable in vivo assessment of melanoma thickness. The 930-nm optical coherence tomography showed a poor level of agreement with histopathology (ICC 0·0; 95% CI −0·2–0·2) and the inter-rater reproducibility was null (G = 0·00). Conclusions HFUS is a reliable and reproducible noninvasive method for assessing melanoma thickness. Routine use of HFUS may allow single-step excision of equivocal melanocytic lesions, with surgical margins determined by in vivo assessment of tumour thickness.
Published: 2014
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23. Whole-brain radiation therapy plus concomitant temozolomide for the treatment of brain metastases from non-small-cell lung cancer: a randomized, open-label phase II study

Author: Jose I. Martinez, Maria G. Pallotta, Maciej Krzakowski, Nikolaos Throuvalas, Walter J. Curran, Christos Chouaid, Daniel Chua, Maya Gottfried, Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chua D , M Krzakowski, C Chouaid, Pallotta MG, Martinez JI, M Gottfried, W Curran, and N Throuvalas .
Subjects: Oncology, Male, Cancer Research, MESH: Combined Modality Therapy, Lung Neoplasms, medicine.medical_treatment, Phases of clinical research, Kaplan-Meier Estimate, MESH: Antineoplastic Agents, Alkylating, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, MESH: Treatment Outcome, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Brain Neoplasms, Middle Aged, Combined Modality Therapy, 3. Good health, Dacarbazine, Treatment Outcome, 030220 oncology & carcinogenesis, MESH: Brain Neoplasms, Female, medicine.drug, Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, MESH: Dacarbazine, 03 medical and health sciences, Internal medicine, medicine, Temozolomide, Humans, Lung cancer, Antineoplastic Agents, Alkylating, MESH: Kaplan-Meier Estimate, 030304 developmental biology, Aged, Chemotherapy, MESH: Humans, business.industry, MESH: Adult, medicine.disease, MESH: Male, Surgery, MESH: Lung Neoplasms, Radiation therapy, MESH: Cranial Irradiation, Regimen, Concomitant, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cranial Irradiation, business, MESH: Female, MESH: Carcinoma, Non-Small-Cell Lung, Brain metastasis
Abstract: International audience; BACKGROUND: A previously published study of temozolomide concurrent with whole-brain radiation therapy (WBRT) reported significant improvement in response rates and a nonsignificant trend toward improved overall survival compared with WBRT alone in patients with brain metastases primarily from lung cancer. This study sought to confirm the benefit of adding temozolomide to WBRT in patients with non-small-cell lung cancer (NSCLC) with brain metastases. PATIENTS AND METHODS: This planned phase III study (target = 380 events) was converted to a phase II study (target = 70 events) because of poor enrollment. Patients with NSCLC and > or = 1 newly diagnosed brain lesion were randomized to WBRT (30 Gy in 10 fractions) alone or combined with temozolomide (75 mg/m2/day) for 21 or 28 days. Endpoints included overall survival and time to central nervous system (CNS) progression. RESULTS: Median overall survival and median time to CNS progression was 4.4 and 3.1 months in the WBRT + temozolomide arm (n = 47) versus 5.7 and 3.8 months in the WBRT arm (n = 48). However, there were imbalances in the percentages of patients receiving previous chemotherapy and with synchronous brain metastases. Adding temozolomide to WBRT increased the frequency of nausea, vomiting, alopecia, fatigue, anorexia, and constipation. Most adverse events were mild to moderate. CONCLUSION: The benefit of adding temozolomide to WBRT was not confirmed; however, the accrual goal for the planned phase III trial was not reached, and the study regimen differed from regimens used previously. Therefore, the role of temozolomide in treating brain metastases remains unresolved.
Published: 2010
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24. Exposure equivalence between IV (0.8 mg/kg) and oral (1 mg/kg) busulfan in adult patients

Author: F. Léger, C. Puozzo, L. Nguyen, Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
Subjects: Adult, Male, medicine.medical_specialty, Actual body weight (ABW), Transplantation Conditioning, Administration, Oral, Biological Availability, Bioequivalence, Gastroenterology, Drug Administration Schedule, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Oral administration, Internal medicine, Humans, Medicine, Pharmacology (medical), Dosing, Haematopoietic stem cell transplantation (HSCT), Infusions, Intravenous, Antineoplastic Agents, Alkylating, Busulfan, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Pharmacology, Clinical Trials as Topic, Dose-Response Relationship, Drug, Adjusted ideal body weight (AIBW), business.industry, Hematopoietic Stem Cell Transplantation, Area under the curve, General Medicine, Middle Aged, 3. Good health, Bioavailability, Surgery, Transplantation, stomatognathic diseases, Area Under Curve, 030220 oncology & carcinogenesis, Female, business, 030215 immunology, medicine.drug
Abstract: This study was conducted to retrospectively compare the area under the curve (AUC) and the total clearance of busulfan (Bu) following oral and intravenous (IV) administrations and to determine which intravenous dose generated equivalent exposure to that of the oral form that has been marketed for decades. Patient pharmacokinetics were assessed at dose 9 during a conditioning regimen for stem-cell transplantation and included data from 277 patients for oral Bu (71 from fixed-dose studies and 206 from studies with dose adjustment allowed) and 120 patients for IV Bu (fixed dose). AUCs were compared between patients with fixed dose of oral Bu (n = 71, 1 mg/kg) and those of IV Bu (n = 120, 0.8 mg/kg). Total clearances were calculated for all 277 patients with oral Bu and compared to those with IV Bu, with the ratio of IV-to-oral clearance representing the absolute bioavailability of the oral form. Oral and IV populations differed on disease-type distribution but presented comparable demography parameters. IV Bu dosing was mostly based on the ideal body weight index while actual body weight or adjusted ideal body weight indexes were mostly used for oral. When normalised to comparable indexes, bioequivalent AUCs were achieved between oral and IV populations. Oral Bu bioavailability was about 80% when calculated from the ratio of IV-to-oral total clearances. This retrospective study carried out on a large set of data showed that similar plasma exposures were achieved with 1.0 mg/kg oral Bu or 0.8 mg/kg IV Bu.
Published: 2009
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25. Differential effect triggered by a heparan mimetic of the RGTA family preventing oral mucositis without tumor protection

Author: Xiaoli Yue, Eric Deutsch, Giampaolo Biti, M. Castaing, D. Violot, Monica Mangoni, Yungan Tao, Paule Opolon, Marie-Catherine Vozenin-Brotons, Christophe Morin, Jean Bourhis, Denis Barritault, Anne Auperin, V. Frascogna, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, OTR3 Sarl, OTR3, Radiosensibilité et radiocarcinogenèse humaines, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR), Département de radiothérapie [Gustave Roussy], Hématologie, and Département de médecine oncologique [Gustave Roussy]
Subjects: Cancer Research, Pathology, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Mice, Random Allocation, 0302 clinical medicine, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Glucans, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Radiation, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Amifostine, 3. Good health, Radiation Injuries, Experimental, Oncology, 030220 oncology & carcinogenesis, Drug Therapy, Combination, Female, HT29 Cells, medicine.drug, medicine.medical_specialty, Side effect, Mice, Nude, Radiation-Protective Agents, Radiation Dosage, Drug Administration Schedule, 03 medical and health sciences, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, In vivo, Cell Line, Tumor, medicine, Mucositis, Animals, Humans, Radiology, Nuclear Medicine and imaging, Radiosensitivity, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], 030304 developmental biology, Chemotherapy, Stomatitis, business.industry, Head and neck cancer, medicine.disease, Xenograft Model Antitumor Assays, Lip, Radiation therapy, Mice, Inbred C57BL, Cancer research, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business
Abstract: Purpose Oral mucositis is a common side effect induced by radio/chemotherapy in patients with head and neck cancer. Although it dramatically impairs patient quality of life, no efficient and safe therapeutic solution is available today. Therefore, we investigated the protective efficacy of a new heparan mimetic biopolymer, RGTA-OTR4131, used alone or in combination with amifostine, for oral mucositis and simultaneously evaluated its effect on tumor growth in vitro and in vivo . Methods and Materials A single dose of 16.5 Gy was selectively delivered to the snout of mice, and the effects of OTR4131 or amifostine-OTR4131 were analyzed by macroscopic scoring and histology. The effect of OTR4131 administration on tumor growth was then investigated in vitro and in xenograft models using two cell lines (HEP-2 and HT-29). Results Amifostine and OTR4131 significantly decreased the severity and duration of lip mucosal reactions. However, amifostine has to be administered before irradiation, whereas the most impressive protection was obtained when OTR4131 was injected 24 h after irradiation. In addition, OTR4131 was well tolerated, and the combination of amifostine and OTR4131 further enhanced mucosal protection. At the tumor level, OTR4131 did not modify HEP-2 cell line clonogenic survival in vitro or protect xenografted tumor cells from radiotherapy. Of interest, high doses of OTR4131 significantly decreased clonogenic survival of HT-29 cells. Conclusions RGTAs-OTR4131 is a well-tolerated, natural agent that effectively reduces radio-induced mucositis without affecting tumor sensitivity to irradiation. This suggests a possible transfer into the clinic for patients' benefit.
Published: 2009
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26. A new experimental method for measuring skin's natural tension

Author: Gwendal Josse, Camille Garcin, Emmanuelle Jacquet, Fouad Khatyr, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), CERPER Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
Subjects: medicine.medical_specialty, Materials science, Compressive Strength, medicine.medical_treatment, 0206 medical engineering, Posture, Human skin, 02 engineering and technology, Dermatology, Stress (mechanics), 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Skin Physiological Phenomena, medicine, Humans, ComputingMilieux_MISCELLANEOUS, integumentary system, Tension (physics), Equipment Design, Traction (orthopedics), [SPI.MECA]Engineering Sciences [physics]/Mechanics [physics.med-ph], Compression (physics), 020601 biomedical engineering, Finite element method, Surgery, Biomechanical Phenomena, Forearm, Elastomers, Stress, Mechanical, Biomedical engineering, Extensometer
Abstract: Purpose: The precise determination of skin's mechanical properties is still an open question. When performing an in vivo test, the piece of skin tested is not as well defined as it is in material testing. Moreover, the body zone and the body posture imply an initial stress on the skin. Consequently, a precise mechanical analysis needs a precise measurement of the natural skin tension. Methods: A new method and the relative device are presented. It is based on an extensiometry test. Skin is tested not only in traction but also in compression. The tested skin sample is well defined and protected from surrounding effects by follower tabs. The size and shape of the device have been optimised by a finite element modelisation. Results: The method was tested with elastomers pre-tensioned at different loads. It is shown that the initial tension can be retrieved with good precision. Tests were then performed in vivo on the forearm for different arm positions. It is shown that initial tension could be only clearly determined for the highest skin tension, although the skin presented very different traction behaviour with different arm positions. Conclusion: It is shown how body posture influences measurements. An innovative method for easily determining initial tension is presented. Nevertheless, further tests and device improvements are needed to apply this skin tension measurement for different body zones and body postures.
Published: 2008

27. Analyse in vivo du comportement mécanique de la peau

Author: Delalleau, Alexandre, Josse, Gwendal, Lagarde, Jean-Michel, Zahouani, Hassan, Bergheau, Jean-Michel, Pierre Fabre Dermo-Cosmétique, Pierre Fabre Applied Skin Research Centre, CERPER Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Laboratoire de Tribologie et Dynamique des Systèmes (LTDS), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Ecole Nationale d'Ingénieurs de Saint Etienne-Centre National de la Recherche Scientifique (CNRS), and CSMA
Subjects: inverse method, suction, méthode inverse, peau, finite elements, éléments finis, viscoélasticité, succion, [PHYS.MECA]Physics [physics]/Mechanics [physics], viscoelasticity, Skin, extensométrie
Abstract: International audience; The mechanical properties of the skin are of potential interest in the identification of certain diseases, for assessing therapeutic intervention, or for predicting the effect of trauma. Due to its unusual structure, the skin presents a nonlinear viscoelastic anisotropic quasi incompressible mechanical behaviour which has to be studied in vivo. In this paper, a new method to identify the viscoelastic parameters of the human skin in vivo is presented. It lies in an inverse approach which compares experimental and finite element numerical results. Current works generally propose different approaches and hypotheses which consequently give results difficult to analyze. In this paper, two types of experimental tests are performed on the same subjects so as to compare the results obtained and to underline the advantages of the proposed method.; L'analyse des composantes mécaniques de la peau est d'une importance primordiale pour divers domaines tels la dermatologie, la chirurgie et la cosmétique. En raison de sa structure particulière, le tissu cutané présente un comportement complexe viscoélastique non linéaire anisotrope et quasi-incompressible, qui doit de surcroît être étudié de manière in vivo. Nous proposons dans cet article une méthode innovante d'analyse des caractéristiques viscoélastiques de la peau. Cette dernière repose sur une approche inverse du problème, couplant résultats expérimentaux et simulations numériques par éléments finis. Deux essais mécaniques effectués sur un même individu sont considérés. Une comparaison des résultats obtenus est ainsi possible afin de mener une discussion relative, d'une part aux phénomènes induits par chacun de ces tests, et, d'autre part, à l'originalité de l'approche.
Published: 2007

28. UVA Induces Granzyme B in Human Keratinocytes through MIF

Author: Caroline Baudouin, Christine Jean, Marie Charveron, Anne Quillet-Mary, Alexandra Charruyer, Marie-José Haure, Hélène Hernandez-Pigeon, Guy Laurent, Centre de Physiopathologie de Toulouse-Purpan (INSERM U563 - CNRS UMR1037), Centre National de la Recherche Scientifique (CNRS)-Centre de lutte contre le cancer (CLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut Claudius Regaud, Laboratoires Expanscience, Laboratoires Expanscience, R&D, Laboratoire de Biologie Cellulaire Cutanée, Institut de Recherche Pierre Fabre, CHU Toulouse [Toulouse]-Institut Claudius Regaud-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de lutte contre le cancer (CLCC)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
Subjects: Photoaging, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Biochemistry, Extracellular matrix, 03 medical and health sciences, 0302 clinical medicine, medicine, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Cell migration, Cell Biology, medicine.disease, Cell biology, Fibronectin, Granzyme B, medicine.anatomical_structure, 030220 oncology & carcinogenesis, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Vitronectin, Keratinocyte, hormones, hormone substitutes, and hormone antagonists
Abstract: In a previous study, we have described that UVB induces granzyme B (GrB) in human keratinocyte cells, and that confers potent cellular cytotoxicity against various cellular models, including immune cells (Hernandez-Pigeon, H., Jean, C., Charruyer, A., Haure, M. J., Titeux, M., Tonasso, L., Quillet-Mary, A., Baudouin, C., Charveron, M., and Laurent, G. (2006) J. Biol. Chem. 281, 13525-13532). Herein, we have found that, in contrast to UVB, UVA failed to enhance keratinocyte cellular cytotoxicity but was still able to trigger GrB production. We show that GrB is accumulated through a p38 MAPK-dependent transcriptional mechanism stimulated by redox-dependent migration inhibitory factor release. Moreover, GrB purified from UVA-treated cellular extracts was found to degrade fibronectin in vitro. Treatment with antisense oligonucleotide directed against GrB resulted in the inhibition of UVA-induced cell detachment and cell death and facilitated cell migration through fibronectin and vitronectin matrix upon UVA exposure. Altogether, these results suggest another function for GrB in the context of the UV response. Indeed, combined with our previous study, it appears that, whereas this enzyme mediates keratinocyte cellular cytotoxicity following UVB irradiation, GrB supports the capacity of keratinocyte to degrade extracellular matrix components following UVA irradiation. UV-mediated GrB production may thus have important consequences in photoaging and photocarcinogenesis.
Published: 2007
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29. Ultrasonic wave propagation and mechanical properties of human skin stretched in vivo

Author: Prevorovsky, Zdenek, Jacquet, Emmanuelle, Placet, Vincent, Josse, Gwendal, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), CERPER Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
Subjects: [SPI.MECA]Engineering Sciences [physics]/Mechanics [physics.med-ph]
Abstract: December 9-13; International audience
Published: 2007

30. Sensitivity improvement of circular dichroism detection in HPLC by using a low-pass electronic noise filter: Application to the enantiomeric determination purity of a basic drug

Author: Jean-Paul Ribet, Marie Lorin, Philippe Morin, Raphaël Delépée, Jean-Claude Maurizot, Institut de Chimie Organique et Analytique (ICOA), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Orléans (UO)-Institut de Chimie du CNRS (INC), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
Subjects: Circular dichroism, enantiomeric purity, Resolution (mass spectrometry), Calibration curve, Analytical chemistry, 2-adrenoreceptor antagonist, 010501 environmental sciences, Sensitivity and Specificity, 01 natural sciences, High-performance liquid chromatography, Concentration ratio, Catalysis, Analytical Chemistry, Drug Discovery, Adrenergic alpha-Antagonists, Chromatography, High Pressure Liquid, Spectroscopy, Benzofurans, 0105 earth and related environmental sciences, Pharmacology, Detection limit, low-pass electronic noise filter, Chromatography, quantitation, Chemistry, 010401 analytical chemistry, Organic Chemistry, Imidazoles, Stereoisomerism, Repeatability, 0104 chemical sciences, circular dichroism, efaroxan, Enantiomer, HPLC, polysaccharide stationary phase
Abstract: The quality control of chiral drugs requires the determination of their enantiomeric purity. Nowadays, circular dichroism (CD) spectroscopy is gaining increasing importance in pharmaceutical analysis because of the commercially available CD detector in liquid chromatography. The separation of the two enantiomers of a basic drug (efaroxan) was achieved by high performance liquid chromatography using an amylose-derivated column with both UV and CD detections. A baseline-resolved separation (resolution: 5) was obtained after optimization of the mobile phase composition with hexane-ethanol-diethylamine (90:10:0.05; v/v/v). The use of a commercial low-pass electronic noise filter of the CD signal has improved the signal-to-noise ratio by a factor twelve and allowed the quantitation of each enantiomer in the 1.25-300 microg ml(-1) concentration range. The CD linear calibration curve, expressed in terms of stereoisomer height ratio versus concentration ratio, was plotted over the 0.4-6% range. A correlation coefficient greater than 0.999 was obtained by least-squares regression and the limit of detection for the distomer/eutomer ratio was estimated at 0.14%. Although the method validation showed good repeatability on the retention times (RSD0.9%), on the peak height ratios (RSD8.7%) of each enantiomer only up to 99.2% enantiomeric purity was achieved.
Published: 2007
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31. Antimalarial potential of xestoquinone, a protein kinase inhibitor isolated from a Vanuatu marine sponge Xestospongia sp

Author: Olivier Lozach, Laurent Meijer, Arnaud Parenty, Dominique Laurent, Frédéric Alby, Nicolas Lebouvier, Christian Doerig, Martine Knibiehler, Maryvonne Frostin, Séverine Maurel, Sophie Schmitt, Dominique Dorin, Valérie Jullian, Michel Sauvain, Institut Non Linéaire de Nice Sophia-Antipolis (INLN), 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)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physique de la matière condensée (LPMC), Pharmacochimie des substances naturelles et pharmacophores redox, Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), Laboratoire des Substances Naturelles, Synapse Développement, Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Insulaire du Vivant et de l'Environnement (LIVE), Université de la Nouvelle-Calédonie (UNC), UMS 2646 Pierre Fabre-CNRS, Institut de Sciences et Technologies du Médicament de Toulouse, 3, rue des satellites, 31400 Toulouse, France, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE-Centre National de la Recherche Scientifique (CNRS), Controle de la Proliferation Cellulaire Chez Plasmodium Falciparum, Institut National de la Santé et de la Recherche Médicale (INSERM), Recherches Epistémologiques et Historiques sur les Sciences Exactes et les Institutions Scientifiques (REHSEIS (UMR_7596)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Molécules et cibles thérapeutiques (MCT), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS), UMS 2646, PIERRE FABRE-Centre National de la Recherche Scientifique (CNRS), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Mer et santé (MS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Pierre Fabre-Centre National de la Recherche Scientifique (CNRS), faculte des sciences pharmaceutiques (umr 152 IRD), Faculte des Sciences Pharmaceutiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), and BUNC, Pole ID
Subjects: antiplasmodial drug, Plasmodium, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Pharmaceutical Science, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Pharmacognosy, 01 natural sciences, Biochemistry, Mice, chemistry.chemical_compound, Antimalarial drug, Drug Discovery, MESH: Protein Kinase Inhibitors, MESH: Animals, MESH: Plasmodium falciparum, MESH: Inhibitory Concentration 50, 0303 health sciences, biology, Kinase, Quinones, Biological activity, 3. Good health, Xestospongia, [SDV] Life Sciences [q-bio], Enzyme inhibitor, Molecular Medicine, Biological Assay, Antiplasmodial drug, antimalarial drug, Plasmodium falciparum, MESH: Biological Assay, MESH: Quinones, Antimalarials, Inhibitory Concentration 50, 03 medical and health sciences, parasitic diseases, Animals, Xestoquinone, Plasmodium berghei, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Protein kinase A, Protein Kinase Inhibitors, Molecular Biology, MESH: Mice, 030304 developmental biology, 010405 organic chemistry, Organic Chemistry, biology.organism_classification, MESH: Antimalarials, 0104 chemical sciences, MESH: Xestospongia, xestoquinone, chemistry, biology.protein
Abstract: As part of our search for new antimalarial drugs, we have screened for inhibitors of Pfnek-1, a protein kinase of Plasmodium falciparum, in south Pacific marine sponges. On the basis of a preliminary screening, the ethanolic crude extract of a new species of Xestospongia collected in Vanuatu was selected for its promising activity. A bioassay-guided fractionation led us to isolate xestoquinone which inhibits Pfnek-1 with an IC50 around 1 mu M. Among a small panel of plasmodial protein kinases, xestoquinone showed modest protein kinase inhibitory activity toward PfPK5 and no activity toward PfPK7 and PfGSK-3. Xestoquinone showed in vitro antiplasmodial activity against a FCB1 P. falciparum strain with an IC50 of 3 mu M and a weak selectivity index (SI 7). Xestoquinone exhibited a weak in vivo activity at 5 mg/kg in Plasmodium berghei NK65 infected mice and was toxic at higher doses. (c) 2006 Elsevier Ltd. All rights reserved.
Published: 2006
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32. Human Keratinocytes Acquire Cellular Cytotoxicity under UV-B Irradiation

Author: Christine Jean, Caroline Baudouin, Guy Laurent, Marie-José Haure, Matthias Titeux, Anne Quillet-Mary, Alexandra Charruyer, Hélène Hernandez-Pigeon, Marie Charveron, Laure Tonasso, Centre de Physiopathologie de Toulouse-Purpan (INSERM U563 - CNRS UMR1037), CHU Toulouse [Toulouse]-Institut Claudius Regaud-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de lutte contre le cancer (CLCC)-Centre National de la Recherche Scientifique (CNRS), Laboratoires Expanscience, Laboratoires Expanscience, R&D, Laboratoire de Biologie Cellulaire Cutanée, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Centre National de la Recherche Scientifique (CNRS)-Centre de lutte contre le cancer (CLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut Claudius Regaud, and Institut de Recherche Pierre Fabre
Subjects: Photoaging, Human skin, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, medicine, Cytotoxic T cell, Epidermal growth factor receptor, Cytotoxicity, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, integumentary system, biology, Cell Biology, medicine.disease, 3. Good health, Cell biology, Granzyme B, medicine.anatomical_structure, Perforin, 030220 oncology & carcinogenesis, Immunology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Keratinocyte, hormones, hormone substitutes, and hormone antagonists
Abstract: Ultraviolet (UV) radiation from the sun is widely considered as a major cause of human skin photoaging and skin cancer. Granzyme B (GrB) and perforin (PFN) are two proteins contained in granules and implicated in one of the mechanisms by which cytotoxic lymphocytes and natural killer cells exert their cytotoxicity against virus-infected, alloreactive, or transformed cells. The distribution of GrB and PFN in the skin has received little attention. However, Berthou and co-workers (Berthou, C., Michel, L., Soulie, A., Jean-Louis, F., Flageul, B., Dubertret, L., Sigaux, F., Zhang, Y., and Sasportes, M. (1997) J. Immunol. 159, 5293-5300) described that, whereas freshly isolated epidermal cells did not express GrB or PFN, keratinocyte growth to confluence was associated with GrB and PFN mRNA and protein synthesis. In this work, we have investigated the possible role of UV-B on GrB and PFN expression in keratinocytes. We found that UV-B induces GrB and PFN expression in these cells through redox-, epidermal growth factor receptor-, and mitogen-activated protein kinase-dependent signaling. Furthermore, under UV irradiation, keratinocytes acquire a significant cytotoxicity, which is GrB and PFN dependent, toward a variety of cellular targets including transformed T-lymphocytes, melanocytes, and keratinocytes. This phenomenon may have important functional consequences in the regulation of skin inflammatory response and in the emergence of cancer skin.
Published: 2006
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33. About in vivo mechanical tests on human skin

Author: Khatyr, Fouad, Jacquet, Emmanuelle, Varchon, Daniel, Josse, Gwendal, Imberdis, Claude, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), CERPER Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
Subjects: [PHYS.MECA.MEMA]Physics [physics]/Mechanics [physics]/Mechanics of materials [physics.class-ph], [SPI.MECA.MEMA]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Mechanics of materials [physics.class-ph], [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph]
Published: 2006

34. Modélisation du comportement viscoélastique de la peau in vivo

Author: Khatyr, Fouad, Imberdis, Claude, Varchon, Daniel, Josse, Gwendal, Lagarde, Jean-Michel, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), CERPER Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
Subjects: [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph]
Abstract: 18-21 avril
Published: 2005

35. Measure of the mechanical properties of skin with the test of suction. Comparison between 3 methods : geometric, Timoshenkos and finite elements

Author: Khatyr, Fouad, Imberdis, Claude, Varchon, Daniel, Lagarde, Jean-Michel, Josse, Gwendal, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), CERPER Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
Subjects: [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph]
Published: 2005

36. Modulation of multi-drug-resistance (MDR) in Staphylococcus aureus by Osha (Ligusticum porteri L., Apiaceae) essential oil compounds

Author: Cegiela-Carlioz, P., Bessiere, J.-M., David, B., Mariotte, A.-M., Gibbons, S., Dijoux-Franca, M.-G., Département de pharmacochimie moléculaire (DPM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de Phytochimie, Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Centre de Recherche sur les Substances Naturelles, Institut de Recherche Pierre Fabre, ISTMT, Centre for Pharmacognosy and Phytotherapy, and School of Pharmacy, University of London
Subjects: [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2005

37. Selective drug transport and P-glycoprotein activity in an in vitro blood-brain barrier model

Author: C. Puozzo, C. Chesné, André Guillouzo, Olivier Fardel, B. Joly, Roméo Cecchelli, Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), Université d'Artois (UA), Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Université de Rennes (UNIV-RENNES), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and Université de Rennes (UR)
Subjects: 0303 health sciences, medicine.drug_class, Drug delivery to the brain, General Medicine, Biology, Pharmacology, Toxicology, Blood–brain barrier, In vitro, 3. Good health, Vinblastine, Vinca alkaloid, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, In vivo, medicine, Verapamil, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Efflux, 030217 neurology & neurosurgery, 030304 developmental biology, medicine.drug
Abstract: International audience; To determine whether compounds are able to reach the neural microenvironment, a blood-brain barrier (BBB) co-culture model has been recently developed with bovine brain capillary endothelial cells and newborn rat astrocytes. In this study, the permeability of confluent endothelial cells to various compounds and the functional activity of P-glycoprotein (P-gp), an ATP-dependent pump known to efflux drugs from multidrug-resistant tumoral cells, was assessed. The permeability of the lipophilic compounds imipramine and sulpiride differed in relation to their structure. A good correlation was observed with in vivo brain extraction levels. P-gp activity was estimated by measuring the uptake of [3H]vinblastine by the endothelial cells, with or without verapamil, which is known to reverse drug resistance. Intracellular accumulation of the vinca alkaloid was strongly increased after addition of verapamil, suggesting that P-gp is active in these cells. These results provide further support for the use of the co-culture model of bovine brain endothelial cells and rat astrocytes to screen new centrally active drugs.
Published: 1995

38. Influence on Busilvex® pharmacokinetics of clonazepam compared to previous phenytoin historical data

Author: Carreras, E., Cahn, J. Y., Puozzo, C., Kröger, N., GUILLERMO SANZ, Buzyn, A., Bacigalupo, A., Vernant, J. P., TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Institut de Recherche Pierre Fabre, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Transplantation Conditioning, MESH: Busulfan, MESH: Drug Interactions, MESH : Transplantation Conditioning, MESH : Prospective Studies, MESH : Alkylating Agents, Clonazepam, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Clonazepam, Drug Interactions, MESH : Female, Prospective Studies, MESH : Busulfan, MESH : Immunosuppressive Agents, MESH : Cyclophosphamide, MESH: Transplantation Conditioning, MESH : Seizures, MESH: Middle Aged, Hematopoietic Stem Cell Transplantation, Middle Aged, MESH : Adult, MESH: Seizures, MESH: Alkylating Agents, MESH: Young Adult, Hematologic Neoplasms, Anticonvulsants, Female, MESH: Immunosuppressive Agents, MESH : Hematologic Neoplasms, Immunosuppressive Agents, Adult, MESH : Anticonvulsants, Alkylating Agents, Adolescent, MESH : Male, MESH : Young Adult, [SDV.CAN]Life Sciences [q-bio]/Cancer, Young Adult, MESH: Anticonvulsants, Seizures, MESH : Adolescent, MESH : Hematopoietic Stem Cell Transplantation, Humans, MESH : Middle Aged, Busulfan, Cyclophosphamide, MESH: Hematopoietic Stem Cell Transplantation, MESH: Adolescent, MESH: Humans, MESH : Humans, MESH: Cyclophosphamide, MESH: Adult, MESH: Male, MESH: Prospective Studies, MESH : Clonazepam, MESH : Drug Interactions, MESH: Phenytoin, Phenytoin, MESH: Female, MESH : Phenytoin, MESH: Hematologic Neoplasms
Abstract: International audience; This study investigated the effect of seizure prophylaxis on busulfan (Bu) plasma exposure. Twenty-four adult patients received an intravenous Bu-cyclophoshamide conditioning regimen prior to bone marrow transplantation. Busilvex (0.8 mg/kg) was administered every six hours during four consecutive days. Clonazepam (0.025 to 0.03 mg/kg/day as a continuous 12-h i.v. infusion) was administered at least 12 hours prior to i.v. Bu dosing and continued until 24 hours after the last dose. Pharmacokinetic (PK) data were compared with those previously collected in patients (n=127) treated with phenytoin for seizure prophylaxis. Through population PK analysis, a 10% average increase (coefficient of variation, RSE=5.35%) in total clearance of Bu was quantified when Bu was associated with clonazepam as compared to phenytoin, which was considered as not being clinically relevant. The suspected induction on Bu metabolism by phenytoin should have resulted in the opposite effect. The patient efficacy and safety profiles were comparable between the two cohorts.

39. plantMASST - Community-driven chemotaxonomic digitization of plants.

Author: Gomes PWP, Mannochio-Russo H, Schmid R, Zuffa S, Damiani T, Quiros-Guerrero LM, Caraballo-Rodríguez AM, Zhao HN, Yang H, Xing S, Charron-Lamoureux V, Chigumba DN, Sedio BE, Myers JA, Allard PM, Harwood TV, Tamayo-Castillo G, Kang KB, Defossez E, Koolen HHF, da Silva MN, E Silva CYY, Rasmann S, Walker TWN, Glauser G, Chaves-Fallas JM, David B, Kim H, Lee KH, Kim MJ, Choi WJ, Keum YS, de Lima EJSP, de Medeiros LS, Bataglion GA, Costa EV, da Silva FMA, Carvalho ARV, Reis JDE, Pamplona S, Jeong E, Lee K, Kim GJ, Kil YS, Nam JW, Choi H, Han YK, Park SY, Lee KY, Hu C, Dong Y, Sang S, Morrison CR, Borges RM, Teixeira AM, Lee SY, Lee BS, Jeong SY, Kim KH, Rutz A, Gaudry A, Bruelhart E, Kappers IF, Karlova R, Meisenburg M, Berdaguer R, Tello JS, Henderson D, Cayola L, Wright SJ, Allen DN, Anderson-Teixeira KJ, Baltzer JL, Lutz JA, McMahon SM, Parker GG, Parker JD, Northen TR, Bowen BP, Pluskal T, van der Hooft JJJ, Carver JJ, Bandeira N, Pullman BS, Wolfender JL, Kersten RD, Wang M, and Dorrestein PC
Abstract: Understanding the distribution of hundreds of thousands of plant metabolites across the plant kingdom presents a challenge. To address this, we curated publicly available LC-MS/MS data from 19,075 plant extracts and developed the plantMASST reference database encompassing 246 botanical families, 1,469 genera, and 2,793 species. This taxonomically focused database facilitates the exploration of plant-derived molecules using tandem mass spectrometry (MS/MS) spectra. This tool will aid in drug discovery, biosynthesis, (chemo)taxonomy, and the evolutionary ecology of herbivore interactions.
Published: 2024
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40. A Sample-Centric and Knowledge-Driven Computational Framework for Natural Products Drug Discovery.

Author: Gaudry A, Pagni M, Mehl F, Moretti S, Quiros-Guerrero LM, Cappelletti L, Rutz A, Kaiser M, Marcourt L, Queiroz EF, Ioset JR, Grondin A, David B, Wolfender JL, and Allard PM
Abstract: The ENPKG framework organizes large heterogeneous metabolomics data sets as a knowledge graph, offering exciting opportunities for drug discovery and chemodiversity characterization., Competing Interests: The authors declare no competing financial interest., (Published 2024 by American Chemical Society.)
Published: 2024
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41. The Patient-Oriented Scoring of Atopic Dermatitis and SCORAD in young children: New data on interpretability and clinical usefulness.

Author: Barbarot S, Aubert H, Stalder JF, Roye S, and Delarue A
Subjects: Child, Humans, Child, Preschool, Severity of Illness Index, Patient Acuity, Patient Reported Outcome Measures, Immunoglobulin A, Quality of Life, Dermatitis, Atopic diagnosis
Abstract: Background: There is limited data about the clinical meaningfulness of the Scoring of Atopic Dermatitis (SCORAD) and Patient-Oriented SCORAD (PO-SCORAD), particularly in children with mild-to-moderate AD. Regular use of patient-reported outcomes, may deliver more accurate information about the overall health status of AD patients than routine but sparse physician assessments., Objective: To confirm the correlation between SCORAD, PO-SCORAD, Patient-Oriented Eczema Measure (POEM) and Investigator's Global Assessment (IGA). To evaluate the interpretability and clinical usefulness of the SCORAD and PO-SCORAD scores in children., Methods: Data were drawn from a 12-week randomized controlled trial in 335 children, aged 2-6 years, with mainly mild-to-moderate AD. Investigators captured SCORAD and IGA at each study visit. Parents used PO-SCORAD twice-weekly, and POEM once-weekly., Results: There were strong correlations between PO-SCORAD and SCORAD (r = 0.874), PO-SCORAD and POEM (0.734) and PO-SCORAD and IGA (0.613). The best fit ('k' statistic: 0.68) between SCORAD and IGA classes was noted for the following SCORAD categories: <12 (clear/almost clear); 12-25 (mild); and ≥25 (moderate/severe). PO-SCORAD area under the curve over 8 weeks was significantly greater than that of SCORAD (p = 0.0002), giving a better estimate of disease severity between visits. Patients with a flare within the next 7 days had significantly higher PO-SCORAD scores 7 days before the flare (p < 0.0001). Moderate erythema was the most significant flare predictor (p < 0.0001)., Conclusion: PO-SCORAD is robust and reliable and appears to warrant far greater utility in routine clinical practice than other scores. PO-SCORAD, used twice-weekly, may improve the management of patients with AD., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)
Published: 2024
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42. Leaf metabolic traits reveal hidden dimensions of plant form and function.

Author: Walker TWN, Schrodt F, Allard PM, Defossez E, Jassey VEJ, Schuman MC, Alexander JM, Baines O, Baldy V, Bardgett RD, Capdevila P, Coley PD, van Dam NM, David B, Descombes P, Endara MJ, Fernandez C, Forrister D, Gargallo-Garriga A, Glauser G, Marr S, Neumann S, Pellissier L, Peters K, Rasmann S, Roessner U, Salguero-Gómez R, Sardans J, Weckwerth W, Wolfender JL, and Peñuelas J
Subjects: Phenotype, Plant Leaves, Metabolome, Longevity
Abstract: The metabolome is the biochemical basis of plant form and function, but we know little about its macroecological variation across the plant kingdom. Here, we used the plant functional trait concept to interpret leaf metabolome variation among 457 tropical and 339 temperate plant species. Distilling metabolite chemistry into five metabolic functional traits reveals that plants vary on two major axes of leaf metabolic specialization-a leaf chemical defense spectrum and an expression of leaf longevity. Axes are similar for tropical and temperate species, with many trait combinations being viable. However, metabolic traits vary orthogonally to life-history strategies described by widely used functional traits. The metabolome thus expands the functional trait concept by providing additional axes of metabolic specialization for examining plant form and function.
Published: 2023
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43. Antibody-drug conjugates come of age in oncology.

Author: Dumontet C, Reichert JM, Senter PD, Lambert JM, and Beck A
Subjects: Humans, Antibodies, Monoclonal therapeutic use, Tumor Microenvironment, Immunoconjugates pharmacology, Immunoconjugates therapeutic use, Antineoplastic Agents adverse effects, Neoplasms therapy
Abstract: Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the potency of highly cytotoxic agents, potentially reducing the severity of side effects by preferentially targeting their payload to the tumour site. ADCs are being increasingly used in combination with other agents, including as first-line cancer therapies. As the technology to produce these complex therapeutics has matured, many more ADCs have been approved or are in late-phase clinical trials. The diversification of antigenic targets as well as bioactive payloads is rapidly broadening the scope of tumour indications for ADCs. Moreover, novel vector protein formats as well as warheads targeting the tumour microenvironment are expected to improve the intratumour distribution or activation of ADCs, and consequently their anticancer activity for difficult-to-treat tumour types. However, toxicity remains a key issue in the development of these agents, and better understanding and management of ADC-related toxicities will be essential for further optimization. This Review provides a broad overview of the recent advances and challenges in ADC development for cancer treatment., (© 2023. Springer Nature Limited.)
Published: 2023
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44. The F-box protein UFO controls flower development by redirecting the master transcription factor LEAFY to new cis-elements.

Author: Rieu P, Turchi L, Thévenon E, Zarkadas E, Nanao M, Chahtane H, Tichtinsky G, Lucas J, Blanc-Mathieu R, Zubieta C, Schoehn G, and Parcy F
Subjects: Transcription Factors metabolism, Cryoelectron Microscopy, Gene Expression Regulation, Plant, Flowers genetics, Arabidopsis Proteins metabolism, Arabidopsis genetics, F-Box Proteins metabolism
Abstract: In angiosperms, flower development requires the combined action of the transcription factor LEAFY (LFY) and the ubiquitin ligase adaptor F-box protein, UNUSUAL FLORAL ORGANS (UFO), but the molecular mechanism underlying this synergy has remained unknown. Here we show in transient assays and stable transgenic plants that the connection to ubiquitination pathways suggested by the UFO F-box domain is mostly dispensable. On the basis of biochemical and genome-wide studies, we establish that UFO instead acts by forming an active transcriptional complex with LFY at newly discovered regulatory elements. Structural characterization of the LFY-UFO-DNA complex by cryo-electron microscopy further demonstrates that UFO performs this function by directly interacting with both LFY and DNA. Finally, we propose that this complex might have a deep evolutionary origin, largely predating flowering plants. This work reveals a unique mechanism of an F-box protein directly modulating the DNA binding specificity of a master transcription factor., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Published: 2023
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45. 10th antibody industrial symposium: new developments in antibody and adoptive cell therapies.

Author: Antunes A, Alvarez-Vallina L, Bertoglio F, Bouquin N, Cornen S, Duffieux F, Ferré P, Gillet R, Jorgensen C, Leick MB, Maillère B, Negre H, Pelegrin M, Poirier N, Reusch D, Robert B, Serre G, Vicari A, Villalba M, Volpers C, Vuddamalay G, Watier H, Wurch T, Zabeau L, Zielonka S, Zhang B, Beck A, and Martineau P
Subjects: France, Antibodies, Monoclonal therapeutic use, Immunotherapy, Adoptive
Abstract: The annual "Antibody Industrial Symposium", co-organized by LabEx MAbImprove and MabDesign, held its 10th anniversary edition in Montpellier, France, on June 28-29, 2022. The meeting focused on new results and concepts in antibody engineering (naked, mono- or multi-specific, conjugated to drugs or radioelements) and also on new cell-based therapies, such as chimeric antigenic receptor (CAR)-T cells. The symposium, which brought together scientists from academia and industry, also addressed issues concerning the production of these molecules and cells, and the necessary steps to ensure a strong intellectual property protection of these new molecules and approaches. These two days of exchanges allowed a rich discussion among the various actors in the field of therapeutic antibodies.
Published: 2023
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46. Flower Development in Arabidopsis.

Author: Chahtane H, Lai X, Tichtinsky G, Rieu P, Arnoux-Courseaux M, Cancé C, Marondedze C, and Parcy F
Subjects: Plant Leaves metabolism, Flowers, Meristem metabolism, Gene Expression Regulation, Plant, Arabidopsis metabolism, Arabidopsis Proteins genetics, Arabidopsis Proteins metabolism
Abstract: Like in other angiosperms, the development of flowers in Arabidopsis starts right after the floral transition, when the shoot apical meristem (SAM) stops producing leaves and makes flowers instead. On the flanks of the SAM emerge the flower meristems (FM) that will soon differentiate into the four main floral organs, sepals, petals, stamens, and pistil, stereotypically arranged in concentric whorls. Each phase of flower development-floral transition, floral bud initiation, and floral organ development-is under the control of specific gene networks. In this chapter, we describe these different phases and the gene regulatory networks involved, from the floral transition to the floral termination., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)
Published: 2023
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47. Open and reusable annotated mass spectrometry dataset of a chemodiverse collection of 1,600 plant extracts.

Author: Allard PM, Gaudry A, Quirós-Guerrero LM, Rutz A, Dounoue-Kubo M, Walker TWN, Defossez E, Long C, Grondin A, David B, and Wolfender JL
Subjects: Mass Spectrometry methods, Chromatography, Liquid methods, Plant Extracts chemistry, Drug Discovery methods
Abstract: As privileged structures, natural products often display potent biological activities. However, the discovery of novel bioactive scaffolds is often hampered by the chemical complexity of the biological matrices they are found in. Large natural extract collections are thus extremely valuable for their chemical novelty potential but also complicated to exploit in the frame of drug-discovery projects. In the end, it is the pure chemical substances that are desired for structural determination purposes and bioactivity evaluation. Researchers interested in the exploration of large and chemodiverse extract collections should thus establish strategies aiming to efficiently tackle such chemical complexity and access these structures. Establishing carefully crafted digital layers documenting the spectral and chemical complexity as well as bioactivity results of natural extracts collections can help prioritize time-consuming but mandatory isolation efforts. In this note, we report the results of our initial exploration of a collection of 1,600 plant extracts in the frame of a drug-discovery effort. After describing the taxonomic coverage of this collection, we present the results of its liquid chromatography high-resolution mass spectrometric profiling and the exploitation of these profiles using computational solutions. The resulting annotated mass spectral dataset and associated chemical and taxonomic metadata are made available to the community, and data reuse cases are proposed. We are currently continuing our exploration of this plant extract collection for drug-discovery purposes (notably looking for novel antitrypanosomatids, anti-infective and prometabolic compounds) and ecometabolomics insights. We believe that such a dataset can be exploited and reused by researchers interested in computational natural products exploration., (© The Author(s) 2023. Published by Oxford University Press GigaScience.)
Published: 2022
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48. Inventa : A computational tool to discover structural novelty in natural extracts libraries.

Author: Quiros-Guerrero LM, Nothias LF, Gaudry A, Marcourt L, Allard PM, Rutz A, David B, Queiroz EF, and Wolfender JL
Abstract: Collections of natural extracts hold potential for the discovery of novel natural products with original modes of action. The prioritization of extracts from collections remains challenging due to the lack of a workflow that combines multiple-source information to facilitate the data interpretation. Results from different analytical techniques and literature reports need to be organized, processed, and interpreted to enable optimal decision-making for extracts prioritization. Here, we introduce Inventa , a computational tool that highlights the structural novelty potential within extracts, considering untargeted mass spectrometry data, spectral annotation, and literature reports. Based on this information, Inventa calculates multiple scores that inform their structural potential. Thus, Inventa has the potential to accelerate new natural products discovery. Inventa was applied to a set of plants from the Celastraceae family as a proof of concept. The Pristimera indica (Willd.) A.C.Sm roots extract was highlighted as a promising source of potentially novel compounds. Its phytochemical investigation resulted in the isolation and de novo characterization of thirteen new dihydro- β -agarofuran sesquiterpenes, five of them presenting a new 9-oxodihydro- β -agarofuran base scaffold., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Quiros-Guerrero, Nothias, Gaudry, Marcourt, Allard, Rutz, David, Queiroz and Wolfender.)
Published: 2022
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49. Clinical Evidence of the Benefits of Phytonutrients in Human Healthcare.

Author: Monjotin N, Amiot MJ, Fleurentin J, Morel JM, and Raynal S
Subjects: Antioxidants pharmacology, Carotenoids pharmacology, Delivery of Health Care, Flavonoids pharmacology, Humans, Phytochemicals chemistry, Phytochemicals pharmacology, Polyphenols chemistry, Polyphenols pharmacology
Abstract: Phytonutrients comprise many different chemicals, including carotenoids, indoles, glucosinolates, organosulfur compounds, phytosterols, polyphenols, and saponins. This review focuses on the human healthcare benefits of seven phytochemical families and highlights the significant potential contribution of phytonutrients in the prevention and management of pathologies and symptoms in the field of family health. The structure and function of these phytochemical families and their dietary sources are presented, along with an overview of their potential activities across different health and therapeutic targets. This evaluation has enabled complementary effects of the different families of phytonutrients in the same area of health to be recognized.
Published: 2022
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50. (De)Activation (Ir)Reversibly or Degradation: Dynamics of Post-Translational Protein Modifications in Plants.

Author: Muleya V, Lois LM, Chahtane H, Thomas L, Chiapello M, and Marondedze C
Abstract: The increasing dynamic functions of post-translational modifications (PTMs) within protein molecules present outstanding challenges for plant biology even at this present day. Protein PTMs are among the first and fastest plant responses to changes in the environment, indicating that the mechanisms and dynamics of PTMs are an essential area of plant biology. Besides being key players in signaling, PTMs play vital roles in gene expression, gene, and protein localization, protein stability and interactions, as well as enzyme kinetics. In this review, we take a broader but concise approach to capture the current state of events in the field of plant PTMs. We discuss protein modifications including citrullination, glycosylation, phosphorylation, oxidation and disulfide bridges, N-terminal, SUMOylation, and ubiquitination. Further, we outline the complexity of studying PTMs in relation to compartmentalization and function. We conclude by challenging the proteomics community to engage in holistic approaches towards identification and characterizing multiple PTMs on the same protein, their interaction, and mechanism of regulation to bring a deeper understanding of protein function and regulation in plants.
Published: 2022
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