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1. Heavy Chain Fibrillary Glomerulonephritis: A Case Report

Author: Angela Dispenzieri, Mariam P. Alexander, Frank Bridoux, Vincent Javaugue, Alexia Rinsant, Ellen D. McPhail, Sihem Kaaki, Jonathan J. Hogan, Sébastien Bender, Emilie Pinault, Surendra Dasari, Samar M. Said, Guy Touchard, Nelson Leung, Christophe Sirac, Samih H. Nasr, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Unité de Génétique Moléculaire Animale (UMR GMA), Université de Limoges (UNILIM)-Institut National de la Recherche Agronomique (INRA), Division of Biomedical Statistics and Informatics, Mayo Clinic, Division of Hematology, Mayo Clinic Rochester, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), and Unité de Génétique Moléculaire Animale (UGMA)
Subjects: Male, Pathology, medicine.medical_specialty, Paraproteinemias, 030232 urology & nephrology, Immunoglobulin light chain, Immunoglobulin G, 03 medical and health sciences, Fatal Outcome, Glomerulonephritis, 0302 clinical medicine, Biopsy, medicine, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Kidney, medicine.diagnostic_test, biology, business.industry, Amyloidosis, Fibrillary Glomerulonephritis, Middle Aged, medicine.disease, 3. Good health, medicine.anatomical_structure, Nephrology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunoglobulin heavy chain, Immunoglobulin Heavy Chains, business, Kidney disease
Abstract: Heavy chain amyloidosis and heavy chain deposition disease are the only known kidney diseases caused by the deposition of truncated immunoglobulin heavy chains. Fibrillary glomerulonephritis typically results from deposition of DNAJB9 (DnaJ heat shock protein family [Hsp40] member B9) and polytypic immunoglobulin G (IgG). We describe a patient with monoclonal gammopathy (IgG with λ light chain) who developed DNAJB9-negative fibrillary glomerulonephritis leading to end-stage kidney disease, with recurrence in 2 kidney allografts. Pre- and postmortem examination showed glomerular deposition of Congo red-negative fibrillar material that was determined to be immunoglobulin heavy chain. We propose the term "heavy chain fibrillary glomerulonephritis" to describe this lesion, which appears to be a rare kidney complication of monoclonal gammopathy. The diagnosis should be suspected when the kidney biopsy shows fibrillary glomerulonephritis with negative staining for immunoglobulin light chains and DNAJB9; the diagnosis can be confirmed using immunochemical and molecular studies.
Published: 2019

2. A Novel Calcium-Mediated EMT Pathway Controlled by Lipids: An Opportunity for Prostate Cancer Adjuvant Therapy

Author: Figiel, Sandy, Bery, Fanny, Chantôme, Aurélie, Fontaine, Delphine, Pasqualin, Côme, Maupoil, Véronique, Domingo, Isabelle, Guibon, Roseline, Bruyere, Franck, Potier-Cartereau, Marie, Vandier, Christophe, Fromont, Gaëlle, Mahéo, Karine, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Service d'urologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers, Université de Poitiers-Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: linoleic acid, eicosapentaenoic acid, calcium, [SDV.CAN]Life Sciences [q-bio]/Cancer, zeb1, prostate cancer, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Article, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The composition of periprostatic adipose tissue (PPAT) has been shown to play a role in prostate cancer (PCa) progression. We recently reported an inverse association between PCa aggressiveness and elevated PPAT linoleic acid (LA) and eicosapentaenoic acid (EPA) content. In the present study, we identified a new signaling pathway with a positive feedback loop between the epithelial-to-mesenchymal transition (EMT) transcription factor Zeb1 and the Ca2+-activated K+ channel SK3, which leads to an amplification of Ca2+ entry and cellular migration. Using in vitro experiments and ex vivo cultures of human PCa slices, we demonstrated that LA and EPA exert anticancer effects, by modulating Ca2+ entry, which was involved in Zeb1 regulation and cancer cellular migration. This functional approach using human prostate tumors highlights the clinical relevance of our observations, and may allow us to consider the possibility of targeting cancer spread by altering the lipid microenvironment.
Published: 2019

3. Vermamoeba vermiformis in hospital network: a benefit for Aeromonas hydrophila

Author: Vincent Delafont, Estelle Perraud, Sihem Kaaki, Marie-Hélène Rodier, Kévin Brunet, Elodie Maisonneuve, Ecologie et biologie des interactions (EBI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Biomatériaux et inflammation en site osseux - EA 4691 (BIOS), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), and Service d'Anatomie et de Cytologie Pathologiques [Poitiers]
Subjects: medicine.medical_specialty, Vermamoeba vermiformis, Microbiology, 03 medical and health sciences, Emerging pathogen, Medical microbiology, Antibiosis, medicine, Humans, Lobosea, Amoeba, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Hospital network, 0303 health sciences, General Veterinary, biology, 030306 microbiology, Adverse conditions, Water, General Medicine, biology.organism_classification, Hospitals, Aeromonas hydrophila, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Insect Science, Parasitology, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Water Microbiology, Bacteria
Abstract: Aeromonas hydrophila, considered as an emerging pathogen, is increasingly involved in opportunistic human infections. This bacterium, mainly present in aquatic environments, can therefore develop relationships with the free-living amoeba Vermamoeba vermiformis in hospital water networks. We showed in this study that the joint presence of V. vermiformis and A. hydrophila led to an increased bacterial growth in the first 48 h of contact and moreover to the protection of the bacteria in adverse conditions even after 28 days. These results highlight the fact that strategies should be implemented to control the development of FLA in hospital water systems.
Published: 2019

4. Transient Receptor Potential Channel Expression Signatures in Tumor-Derived Endothelial Cells: Functional Roles in Prostate Cancer Angiogenesis

Author: Bernardini, Michela, Brossa, Alessia, Chinigo, Giorgia, Grolez, Guillaume P., Trimaglio, Giulia, Allart, Laurent, Hulot, Audrey, Marot, Guillemette, Genova, Tullio, Joshi, Aditi, Mattot, Virginie, Fromont, Gaelle, Munaron, Luca, Bussolati, Benedetta, Prevarskaya, Natalia, Pla, Alessandra Fiorio, Gkika, Dimitra, Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 (PHYCELL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Molecular Biotechnology Center, Università degli studi di Torino = University of Turin (UNITO), Service de neurologie et pathologie du mouvement, Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), BILILLE, MOdel for Data Analysis and Learning (MODAL), Laboratoire Paul Painlevé (LPP), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-École polytechnique universitaire de Lille (Polytech Lille), Dipartimento di Scienze della Vita e Biologia dei Sistemi, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Molecular Biotechnology and Health Sciences, 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), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Università degli studi di Torino (UNITO), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Paul Painlevé - UMR 8524 (LPP), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-École polytechnique universitaire de Lille (Polytech Lille)-Université de Lille, Sciences et Technologies, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Turin, CHU Lille, CNRS, Inserm, Université de Lille, METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, Mécanismes de la Tumorigénèse et Thérapies Ciblées (M3T) - UMR 8161, Physiologie Cellulaire (PHYCEL) - U1003, Physiologie Cellulaire (PHYCELL) - U1003, Santé publique : épidémiologie et qualité des soins - EA 2694, Università degli studi di Torino = University of Turin [UNITO], Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 [PHYCELL], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 [M3T], Nutrition, croissance et cancer (U 1069) [N2C], Laboratoire Paul Painlevé - UMR 8524 (LPP), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-École polytechnique universitaire de Lille (Polytech Lille)
Subjects: [SDV]Life Sciences [q-bio], education, TRP, calcium channel, migration, prostate cancer, tumor angiogenesis, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Article
Abstract: Background: Transient receptor potential (TRP) channels control multiple processes involved in cancer progression by modulating cell proliferation, survival, invasion and intravasation, as well as, endothelial cell (EC) biology and tumor angiogenesis. Nonetheless, a complete TRP expression signature in tumor vessels, including in prostate cancer (PCa), is still lacking. Methods: In the present study, we profiled by qPCR the expression of all TRP channels in human prostate tumor-derived ECs (TECs) in comparison with TECs from breast and renal tumors. We further functionally characterized the role of the &lsquo, prostate-associated&rsquo, channels in proliferation, sprout formation and elongation, directed motility guiding, as well as in vitro and in vivo morphogenesis and angiogenesis. Results: We identified three &lsquo, genes whose expression is upregulated in prostate TECs: TRPV2 as a positive modulator of TEC proliferation, TRPC3 as an endothelial PCa cell attraction factor and TRPA1 as a critical TEC angiogenic factor in vitro and in vivo. Conclusions: We provide here the full TRP signature of PCa vascularization among which three play a profound effect on EC biology. These results contribute to explain the aggressive phenotype previously observed in PTEC and provide new putative therapeutic targets.
Published: 2019

5. Randall-type monoclonal immunoglobulin deposition disease: novel insights from a nationwide cohort study

Author: Bertrand Arnulf, Jean Michel Goujon, Dominique Nochy, Vincent Audard, Arnaud Jaccard, Camille Cohen, Mohamed Belmouaz, Jean Paul Fermand, Christophe Sirac, Mathilde Nouvier, François Provôt, Sébastien Bender, Bertrand Knebelmann, Guy Touchard, Florent Joly, Viviane Gnemmi, Frank Bridoux, Vincent Javaugue, Département de Néphrologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Chromatin Assembly, Nuclear Domains, Virus [Lyon], Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Néphrologie Transplantation, Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Département de Pathologie [AP-HP Hôpital Européen Georges Pompidou], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Service de néphrologie - hémodialyse et transplantation rénale, Service d'hématologie adulte [Hôpital de Saint Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie CHU Poitiers, Centre National de Référence Maladies Rares: Amylose al et Autres Maladies à Dépôts d'Immunoglobulines Monoclonales, Université de Poitiers, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Saint-Antoine [APHP], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5), CHU Saint Louis [APHP], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), and Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille
Subjects: Male, medicine.medical_specialty, Immunology, 030232 urology & nephrology, Paraproteinemias, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Immunoglobulin light chain, Biochemistry, Gastroenterology, Nephropathy, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Antineoplastic Combined Chemotherapy Protocols, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Medicine, Humans, Multiple myeloma, ComputingMilieux_MISCELLANEOUS, Aged, Kidney, business.industry, Acute kidney injury, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, Middle Aged, medicine.disease, Prognosis, 3. Good health, Survival Rate, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, 030220 oncology & carcinogenesis, Monoclonal, Female, Immunoglobulin Light Chains, Kidney Diseases, business, Immunoglobulin Heavy Chains, Monoclonal gammopathy of undetermined significance, Monoclonal Immunoglobulin Deposition Disease, Follow-Up Studies
Abstract: Monoclonal immunoglobulin deposition disease (MIDD) is a rare complication of B-cell clonal disorders, defined by Congo red negative–deposits of monoclonal light chain (LCDD), heavy chain (HCDD), or both (LHCDD). MIDD is a systemic disorder with prominent renal involvement, but little attention has been paid to the description of extrarenal manifestations. Moreover, mechanisms of pathogenic immunoglobulin deposition and factors associated with renal and patient survival are ill defined. We retrospectively studied a nationwide cohort of 255 patients, with biopsy-proven LCDD (n = 212) (including pure LCDD [n = 154], LCDD with cast nephropathy (CN) [n = 58]), HCDD (n = 23), or LHCDD (n = 20). Hematological diagnosis was monoclonal gammopathy of renal significance in 64% and symptomatic myeloma in 34%. Renal presentation was acute kidney injury in patients with LCCD and CN, and chronic glomerular disease in the other types, 35% of whom had symptomatic extrarenal (mostly hepatic and cardiac) involvement. Sequencing of 18 pathogenic LC showed high isoelectric point values of variable domain complementarity determining regions, possibly accounting for tissue deposition. Among 169 patients who received chemotherapy (bortezomib-based in 58%), 67% achieved serum free light chain (FLC) response, including very good partial response (VGPR) or above in 52%. Renal response occurred in 62 patients (36%), all of whom had achieved hematological response. FLC response ≥ VGPR and absence of severe interstitial fibrosis were independent predictors of renal response. This study highlights an unexpected frequency of extrarenal manifestations in MIDD. Rapid diagnosis and achievement of deep FLC response are key factors of prognosis.
Published: 2019

6. R-CHOP 14 with or without radiotherapy in non-bulky limited-stage diffuse large B-cell lymphoma (DLBCL)

Author: Gandhi Damaj, Katell Le Du, J. Fleury, Jean Pierre Marolleau, Vincent Delwail, Krimo Bouabdallah, Anne Devillers, Guillaume Cartron, Pierre Soubeyran, Valérie Costes, Olivier Tournilhac, Pascal Godmer, Emmanuel Gyan, Marie C. Béné, Steven Le Gouill, Marie-Pierre Moles, Jean Philippe Vuillez, Mohamed Benchalal, Philippe Colombat, Jérôme Cornillon, Thierry Fest, Hervé Maisonneuve, Eric Deconinck, Kamel Laribi, Vanessa Szablewski, Roch Houot, Bernard Branger, Thierry Lamy, Remy Gressin, Anne Banos, CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de référence des mastocytoses (CEREMAST), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Service d'hématologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], CHU Grenoble-Hôpital Michallon, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Hôpital de Bayonne, Centre Hospitalier de la Côte Basque (CHCB), Centre Eugène Marquis (CRLCC), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de médecine interne [CHU Bretagnes Atlantique], CHU Bretagnes Atlantique, Centre hospitalier La Roche-Sur-Yon, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'hématologie clinique, Université de Rennes (UR)-Hôpital Pontchaillou, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Réseau Sécurité Naissance - Naître Ensemble, Nantes, Département de médecine nucléaire [Rennes], CRLCC Eugène Marquis (CRLCC), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by Roche., Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), CHU Saint-Etienne, CH de la Côte Basque, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), BOUAKAZ, Amel, Centre de référence des mastocytoses, Institut Bergonié - CRLCC Bordeaux, Regulation of Bcl2 and p53 networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA - Département NOHMAD - Equipe 10), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne (CHELTER), Université Clermont Auvergne (UCA), and Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, genetic structures, Clinical Trials and Observations, [SDV]Life Sciences [q-bio], Kaplan-Meier Estimate, Biochemistry, Gastroenterology, law.invention, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, International Prognostic Index, Randomized controlled trial, law, immune system diseases, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, Child, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Hazard ratio, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, Chemotherapy regimen, Progression-Free Survival, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Vincristine, 030220 oncology & carcinogenesis, Female, Lymphoma, Large B-Cell, Diffuse, Rituximab, medicine.drug, Adult, medicine.medical_specialty, Randomization, Immunology, 03 medical and health sciences, Internal medicine, medicine, Humans, Progression-free survival, Cyclophosphamide, business.industry, Patient Selection, Cell Biology, medicine.disease, Surgery, Doxorubicin, Prednisone, business, Diffuse large B-cell lymphoma, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: International audience; The benefit of radiotherapy (RT) after chemotherapy in limited-stage diffuse large B-cell lymphoma (DLBCL) remains controversial. We conducted a randomized trial in patients with nonbulky limited-stage DLBCL to evaluate the benefit of RT after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Patients were stratified according to the modified International Prognostic Index, including lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, age, and disease stage. The patients received 4 or 6 consecutive cycles of R-CHOP delivered once every 2 weeks, followed or not by RT at 40 Gy delivered 4 weeks after the last R-CHOP cycle. All patients were evaluated by fluorodeoxyglucose-positron emission tomography scans performed at baseline, after 4 cycles of R-CHOP, and at the end of treatment. The primary objective of the trial was event-free survival (EFS) from randomization. The trial randomly assigned 165 patients in the R-CHOP arm and 169 in the R-CHOP plus RT arm. In an intent-to-treat analysis with a median follow-up of 64 months, 5-year EFS was not statistically significantly different between the 2 arms, with 89% ± 2.9% in the R-CHOP arm vs 92% ± 2.4% in the R-CHOP plus RT arm (hazard ratio, 0.61; 95% confidence interval [CI], 0.3-1.2; = .18). Overall survival was also not different at 92% (95% CI, 89.5%-94.5%) for patients assigned to R-CHOP alone and 96% (95% CI, 94.3%-97.7%) for those assigned to R-CHOP plus RT ( = not significant). R-CHOP alone is not inferior to R-CHOP followed by RT in patients with nonbulky limited-stage DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT00841945.
Published: 2018

7. Acanthamoeba castellanii is not be an adequate model to study human adenovirus interactions with macrophagic cells

Author: Maisonneuve, Elodie, Cateau, Estelle, Leveque, Nicolas, Kaaki, Sihem, Beby-Defaux, Agnès, Rodier, Marie-Hélène, Ulasov, Ilya, Ecologie et biologie des interactions (EBI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Microbiologie de l'Eau (MDE), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Université de Reims Champagne-Ardenne (URCA), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], and Centre hospitalier universitaire de Poitiers (CHU Poitiers)
Subjects: Adenoviruses, Immunofluorescence, lcsh:Medicine, Fluorescent Antibody Technique, Acanthamoeba, Pathology and Laboratory Medicine, White Blood Cells, Animal Cells, Medicine and Health Sciences, Amoebas, lcsh:Science, Protozoans, Acanthamoeba castellanii, Phagocytes, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Medical Microbiology, Viral Pathogens, Viruses, Cellular Types, Pathogens, Research Article, Cell Survival, Immune Cells, Immunology, Research and Analysis Methods, Microbiology, Cell Line, Virology, Parasite Groups, parasitic diseases, Humans, Trophozoites, Immunoassays, Microbial Pathogens, Blood Cells, Adenoviruses, Human, Macrophages, lcsh:R, Organisms, Biology and Life Sciences, Cell Biology, Coculture Techniques, Parasitic Protozoans, Viral Replication, DNA, Viral, Immunologic Techniques, lcsh:Q, Parasitology, DNA viruses, Apicomplexa
Abstract: International audience; Free living amoebae (FLA) including Acanthamoeba castellanii, are protozoa that feed on different microorganisms including viruses. These microorganisms show remarkable similarities with macrophages in cellular structures, physiology or ability to phagocyte preys, and some authors have therefore wondered whether Acanthamoeba and macrophages are evolutionary related. It has been considered that this amoeba may be an in vitro model to investigate relationships between pathogens and macrophagic cells. So, we intended in this study to compare the interactions between a human adenovirus strain and A. castellanii or THP-1 macrophagic cells. The results of molecular and microscopy techniques following co-cultures experiments have shown that the presence of the adenovirus decreased the viability of macrophages, while it has no effect on amoebic viability. On another hand, the viral replication occurred only in macrophages. These results showed that this amoebal model is not relevant to explore the relationships between adenoviruses and macrophages in in vitro experiments.
Published: 2017

8. Genomic and viral findings in two different primary Merkel cell carcinomas in a 76-year-old woman

Author: Marie-Laure Jullie, Eric Frouin, Thomas Jouary, Frédéric Chibon, L. Dousset, C. Dutriaux, A. Taieb, V. Foulongne, Service de dermatologie Hôpital Saint-André Bordeaux, CHU Bordeaux [Bordeaux], Validation et identification de nouvelles cibles en oncologie (VINCO), Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié - CRLCC Bordeaux-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie - CHRU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Haut-Lévêque [CHU Bordeaux], Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [CHRU Montpellier], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )
Subjects: Pathology, medicine.medical_specialty, Primary (chemistry), business.industry, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, Virology, 030207 dermatology & venereal diseases, 03 medical and health sciences, Nucleic acid thermodynamics, 0302 clinical medicine, Infectious Diseases, medicine.anatomical_structure, 030221 ophthalmology & optometry, Medicine, business, Merkel cell, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2017

9. Metabolic reprogramming in cancer cells, consequences on pH and tumour progression: Integrated therapeutic perspectives with dietary lipids as adjuvant to anticancer treatment

Author: Lucie Brisson, Pierre Besson, Driffa Moussata, Karine Mahéo, Gaëlle Fromont, Stephan Chevalier, Sébastien Roger, Jean-François Dumas, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Brisson, Lucie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Expression des gènes des phosphorylations oxydatives mitochondriales. Maintenance de l'ADN MT, Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm UMR1069, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hepato-Gastroenterology, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de résonance magnétique biologique et médicale (CRMBM), and Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Epithelial-Mesenchymal Transition, Bioenergetics, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Cachexia, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cancer cell metabolism, Neoplasms, Internal medicine, medicine, Humans, Cancer cell invasiveness, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS, pH, Autophagy, Cancer, N-3 polyunsaturated fatty acids, Hydrogen-Ion Concentration, medicine.disease, Dietary Fats, Mitochondria, 3. Good health, 030104 developmental biology, Endocrinology, Anaerobic glycolysis, Cancer cell, Disease Progression, Cancer research, Resistance to treatments, Adjuvant
Abstract: International audience; While tumours arise from acquired mutations in oncogenes or tumour-suppressor genes, it is clearly established that cancers are metabolic diseases characterized by metabolic alterations in tumour cells, and also non-tumour cells of the host organism resulting in tumour cachexia and patient weakness. In this review, we aimed at delineating details by which metabolic alterations in cancer cells, characterized by mitochondrial bioenergetics deregulations and the preference for aerobic glycolysis, are critical parameters controlling the aggressive progression of tumours. In particular, metabolic alteration in cancer cells are coupled to the modulation of intracellular and extracellular pH, epithelial-to-mesenchymal transition and associated increased invasiveness, autophagy, and the development of anticancer treatment resistance. Finally, based on mechanistic, pre-clinical and clinical studies, we proposed the adjuvant supplementation of dietary n-3 polyunsaturated fatty acids for a complementary holistic treatment of the cancer disease.
Published: 2017

10. Carcinoma-specific expression of P2Y11 receptor and its contribution in ATP-induced purinergic signalling and cell migration in human hepatocellular carcinoma cells

Author: Sobia Manzoor, Madiha Khalid, Lucie Brisson, Yunjie Hao, Sharifah Alawieyah Syed Mortadza, Roseline Guibon, Sébastien Roger, Menahil Tariq, Lin-Hua Jiang, Fatema Mousawi, Gaëlle Fromont, Brisson, Lucie, University of Leeds, National University of Sciences and Technology [Islamabad] (NUST), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Xinxiang Medical University, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institute of Molecular Physiology, and University of Sheffield [Sheffield]
Subjects: 0301 basic medicine, P2Y11 receptor, Carcinoma, Hepatocellular, cell migration, medicine.drug_class, Receptor expression, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, P2 receptor, HCC cells, 03 medical and health sciences, 0302 clinical medicine, Adenosine Triphosphate, Naphthalenesulfonates, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Movement, Purinergic Agents, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Extracellular, medicine, Humans, Calcium Signaling, Receptor, ComputingMilieux_MISCELLANEOUS, Diphosphonates, business.industry, Receptors, Purinergic P2, Liver Neoplasms, Cell migration, Transfection, Hep G2 Cells, Purinergic signalling, Receptor antagonist, P2Y 11 receptor, Molecular biology, 3. Good health, Up-Regulation, cytosolic Ca2+, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Oncology, Liver, 030220 oncology & carcinogenesis, Immunology, cytosolic Ca 2+, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], extracellular ATP, business, Research Paper
Abstract: // Madiha Khalid 1, 2, * , Lucie Brisson 3, * , Menahil Tariq 1 , Yunjie Hao 1 , Roseline Guibon 4 , Gaelle Fromont 4 , Sharifah Alawieyah Syed Mortadza 1 , Fatema Mousawi 1 , Sobia Manzoor 2 , Sebastien Roger 3, 5 and Lin-Hua Jiang 1, 3, 6, 7 1 School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK 2 Atta-ur-Rahman School of Applied Biosciences, National University of Science and Technology, Islamabad, Pakistan 3 Inserm UMR1069, Nutrition, Croissance et Cancer, Universite Francois-Rabelais de Tours, Tours, France 4 Centre Hospitalo-Universitaire de Tours, Tours, France 5 Institut Universitaire de France, Paris Cedex 05, France 6 Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang, P. R. China 7 Sino-UK Joint Laboratory of Brain Function and Injury, Xinxiang Medical University, Xinxiang, P. R. China * These authors have contributed equally to this work Correspondence to: Lin-Hua Jiang, email: l.h.jiang@leeds.ac.uk Sebastien Roger, email: sebastien.roger@univ-tours.fr Sobia Manzoor, email: dr.sobiamanzoor@asab.nust.edu.pk Keywords: HCC cells, extracellular ATP, P2Y 11 receptor, cytosolic Ca 2+ , cell migration Received: March 19, 2016 Accepted: February 15, 2017 Published: March 14, 2017 ABSTRACT Extracellular ATP-induced Ca 2+ signalling is critical in regulating diverse physiological and disease processes. Emerging evidence suggests high concentrations of extracellular ATP in tumour tissues. In this study, we examined the P2 receptor for ATP-induced Ca 2+ signalling in human hepatocellular carcinoma (HCC) cells. Fura-2-based measurements of the intracellular Ca 2+ concentration ([Ca 2+ ] i ) showed that extracellular ATP induced an increase in the [Ca 2+ ] i in human HCC Huh-7 and HepG2 cells. NF546, a P2Y 11 receptor agonist was equally effective in inducing an increase in the [Ca 2+ ] i . In contrast, agonists for the P2X receptors (αβmeATP and BzATP), P2Y 1 receptor (MRS2365) or P2Y 2 receptor (MRS2768) were ineffective. In addition, ATP/NF546-induced increases in the [Ca 2+ ] i were strongly inhibited by treatment with NF340, a P2Y 11 receptor antagonist. Immunofluorescent confocal imaging and western blotting analysis consistently demonstrated the P2Y 11 receptor expression in Huh-7 and HepG2 cells. Transfection with P2Y 11 -specific siRNA attenuated the P2Y 11 receptor protein expression level and also reduced NF546-induced increase in the [Ca 2+ ] i . Importantly, immunohistochemistry revealed that the P2Y 11 receptor was expressed at very high level in human HCC tissues and, by contrast, it was barely detected in normal liver tissues. Trans-well cell migration assay demonstrated that ATP and NF546 induced concentration-dependent stimulation of Huh-7 cell migration. Treatment with NF340 prevented ATP-induced stimulation of cell migration. Taken together, our results show carcinoma-specific expression of the P2Y 11 receptor and its critical role in mediating ATP-inducing Ca 2+ signalling and regulating cell migration in human HCC cells.
Published: 2017

11. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group

Author: Hervé Tilly, Bertrand Coiffier, Vincent Delwail, Olivier Fitoussi, Christophe Fermé, Bernadette Corront, Corinne Haioun, Jean-Marc Schiano, Hassan Farhat, Christophe Fruchart, Hervé Ghesquières, Serge Bologna, Frederic Peyrade, Richard Delarue, Jean-François Emile, Jean Gabarre, Bachra Choufi, Margaret Macro, Laurent Pascal, Fabrice Jardin, Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Université de Poitiers-CHU de Poitiers, Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement ( UMRESTTE UMR T9405 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux ( IFSTTAR ), Institut Gustave Roussy ( IGR ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre hospitalier d'Annecy, CH Annecy, Institut d'Electronique et de Télécommunications de Rennes ( IETR ), Université de Nantes ( UN ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Maison des Sciences de l'Homme et de l'Environnement Claude Nicolas Ledoux ( MSHE ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Hôpital Universitaire de Caen, Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire d'Immunologie ( EA 2686 ), Université de Lille, Droit et Santé, Service d'hématologie biologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Polyclinique Bordeaux Nord Aquitaine, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Laboratoire Chrono-environnement - UFC (UMR 6249) ( LCE ), Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Service d'immuno-hématologie pédiatrique [CHU Necker], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Poitiers - CHU de Poitiers, Institut de Physique de Rennes (IPR), Université de Rennes 1 (UR1) - Centre National de la Recherche Scientifique (CNRS), Hôpital Saint-Vincent de Paul, Département de médecine oncologique, Institut Gustave Roussy (IGR), Service de Radio-Oncologie [Lyon], Hospices Civils de Lyon - Centre Hospitalier Lyon Sud [Pierre Bénite], Institut d'Electronique et de Télécommunications de Rennes (IETR), Université de Rennes 1 (UR1) - Institut National des Sciences Appliquées - Rennes (INSA Rennes) - SUPELEC - Centre National de la Recherche Scientifique (CNRS), Maison des Sciences de l'Homme et de l'Environnement Claude Nicolas Ledoux (MSHE), Centre National de la Recherche Scientifique (CNRS) - Université de Franche-Comté (UFC), Centre Léon Bérard [Lyon], Laboratoire d'Immunologie (EA 2686), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5) - AP-HP Hôpital Necker - Enfants Malades [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Groupe d'étude des proliférations lymphoïdes, and Université de Rouen - Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, Vincristine, Sialic Acid Binding Ig-like Lectin 2, Population, CHOP, Neutropenia, Ofatumumab, Antibodies, Monoclonal, Humanized, Gastroenterology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, International Prognostic Index, Antineoplastic Agents, Immunological, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, education, Cyclophosphamide, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, education.field_of_study, business.industry, Antibodies, Monoclonal, Hematology, medicine.disease, Surgery, Regimen, Treatment Outcome, chemistry, Doxorubicin, 030220 oncology & carcinogenesis, Prednisone, Female, Lymphoma, Large B-Cell, Diffuse, business, Febrile neutropenia, 030215 immunology, medicine.drug
Abstract: Summary Background In 2011 we reported a rituximab plus miniCHOP (reduced-dose cyclophosphamide, doxorubicin, vincristine, and prednisone) combination for patients older than 80 years with diffuse large B-cell lymphoma (DLBCL). The 2-year overall survival was 59% (95% CI 49–67) with an excess of early toxicity. To improve those results we tested the same chemotherapy protocol in combination with ofatumumab and a pre-phase treatment. Methods For this open-label, multicentre, single-group, phase 2 trial, we recruited patients older than 80 years with untreated histologically-proven CD20-positive DLBCL, Ann Arbor stage I to IV, from 41 academic and hospital centres in France and Belgium. Patients received a pre-phase with oral vincristine (1 mg total dose 1 week before cycle 1 [day −7]) and oral prednisone (60 mg total dose starting 1 week before cycle 1, for 4 days [day −7 to day −4]) before the first cycle of the ofatumumab plus miniCHOP regimen. The regimen consisted of 1000 mg total dose of intravenous ofatumumab, 25 mg/m 2 of intravenous doxorubicin, 400 mg/m 2 of intravenous cyclophosphamide, and 1 mg of intravenous vincristine, on day 1 of each cycle; and 40 mg/m 2 of oral prednisone on days 1–5. Ofatumumab was administered with 1000 mg of paracetamol and 50 mg of diphenhydramine. The primary endpoint was overall survival in the intention-to-treat population. The statistical analysis has been done on an intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT01195714. Findings Between June 2, 2010, and Nov 4, 2011, we enrolled 120 patients. Age-adjusted International Prognostic Index was 2–3 in 68 (57%) of them. The median follow-up time was 26·8 months (IQR 24·5–30·1). The 2-year overall survival was 64·7% (95% CI 55·3–72·7) and median overall survival was not reached (95% CI 30·2–not reached). 45 patients died during the treatment, of whom 28 (62%) died due to lymphoma. The most common side-effect was haematological toxicity. Among the 120 patients, grade 3–4 neutropenia was reported in 24 (21%) patients and thrombocytopenia in two (2%), during the treatment period. Grade 3–4 anaemia was reported in six (5%) patients; seven (6%) patients had one episode of febrile neutropenia. 17 (15%) of 115 patients in the modified intention-to-treat population had red blood cell transfusions and three (3%) had platelet transfusions. Interpretation Our result suggest that, in patients older than 80 years with DLBCL, ofatumumab and pre-phase treatment seem to improve overall survival compared with the previously reported data. The combination of pre-phase treatment, a monoclonal antibody against CD20, and miniCHOP can be considered a new treatment platform for use in randomised clinical trial design for DLBCL treatment in patients older than 80 years. Funding The Lymphoma Study Association, GlaxoSmithKline.
Published: 2017

12. Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy–associated C3 glomerulopathy

Author: Stéphane Burtey, Laurence Vrigneaud, Moglie Le Quintrec, Véronique Frémeaux-Bacchi, Arnaud François, Vincent Javaugue, Laurent Daniel, Guy Touchard, Alexandre Karras, Frank Bridoux, Gabriel Choukroun, Yahsou Delmas, Pierre Ronco, Florent Petitprez, Bertrand Arnulf, David Ribes, Jean Michel Goujon, Sophie Chauvet, Dominique Guerrot, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Immunologie Biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Unité de Soins Intensifs Médicaux, CHU Amiens-Picardie-Département de Néphrologie, Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre National de Référence Maladies Rares: Amylose al et Autres Maladies à Dépôts d'Immunoglobulines Monoclonales, Université de Poitiers, Service de Néphrologie [Valenciennes], Centre Hospitalier de Valenciennes, Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Project: 305608,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,EURENOMICS(2012), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), DIGNAT-GEORGE, Françoise, European Consortium for High-Throughput Research in Rare Kidney Diseases - EURENOMICS - - EC:FP7:HEALTH2012-10-01 - 2017-09-30 - 305608 - VALID, Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), 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), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Service d'Anatomie et Cytologie Pathologique [Rouen], Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)
Subjects: Adult, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Databases, Factual, medicine.medical_treatment, Immunology, Kidney Glomerulus, 030232 urology & nephrology, Paraproteinemias, 030204 cardiovascular system & hematology, Biochemistry, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Drug Therapy, Glomerulopathy, Internal medicine, medicine, Humans, Molecular Targeted Therapy, Multiple myeloma, Aged, Retrospective Studies, Aged, 80 and over, Chemotherapy, Kidney, B-Lymphocytes, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, Complement C3, Middle Aged, medicine.disease, Chemotherapy regimen, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, medicine.anatomical_structure, Treatment Outcome, Kidney Diseases, France, business, Nephrotic syndrome, Monoclonal gammopathy of undetermined significance, Kidney disease
Abstract: International audience; The high frequency of monoclonal gammopathy in adult patients with C3 glomerulopathy (C3G) emphasizes the role of monoclonal immunoglobulin (MIg) in the occurrence of renal disease and raises the issue of the therapeutic management. The aim of the study was to evaluate the effect of chemotherapy in a large cohort of patients with MIg-associated C3G. Fifty adult patients with MIg and biopsy-proven C3G were extracted from the French national database of C3G. We retrospectively compared renal outcomes in patients who either received or did not receive chemotherapy targeting the underlying B-cell clone. At diagnosis, renal disease was severe, with nephrotic-range proteinuria in 20/46 (43%) patients and chronic kidney disease stage 3 or above in 42/49 (86%) patients. Monoclonal gammopathy was of IgG type in 47 (94%) patients. Hematological diagnosis was monoclonal gammopathy of renal significance in 30 (60%), multiple myeloma in 17 (34%), and chronic lymphocytic leukemia in 3 (6%) patients. Complement studies showed low C3 level in 22/50 (43%) and elevated soluble C5b-9 level in 27/34 (79%) patients. Twenty-nine patients received chemotherapy (including bortezomib in 22), whereas 8 and 13 patients received various immunosuppressive drugs or symptomatic measures alone, respectively. Patients who achieved hematological response after chemotherapy had higher renal response rates (P = .0001) and median renal survival (hazard ratio, 0.22; 95% confidence interval, 0.05-0.92; P = .009) than those receiving conservative/immunosuppressive therapy. In conclusion, our results suggest that chemotherapy adapted to the B-cell clone may constitute an efficient strategy for C3G in the setting of MIg, as rapid achievement of hematological response appears to result in improved renal survival.
Published: 2017

13. Shifting FcγRIIA-ITAM from activation to inhibitory configuration ameliorates arthritis

Author: Gilles Hayem, Erwan Boedec, Tarek Boussetta, Renato C. Monteiro, Jean-Michel Goujon, Pierre Launay, Pierre Bruhns, Sanae Ben Mkaddem, Marc Benhamou, Jamel El Benna, Friederike Jönsson, Elisabetta Rossato, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), LabEx Inflamex, Service de Rhumatologie, AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité-AP-HP, Anticorps en Thérapie et Pathologie, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), This work was supported by grants from Agence Nationale de la Recherche (ANR grants MIEN-2009 and BLANC International-2012) and by LabEx Inflamex. S.B. Mkaddem was supported by a grant from the French Foundation ARC (PDF20100601037)., ANR-11-IDEX-0005-02/10-LABX-0017,INFLAMEX,INSTITUTE OF INFLAMMATORY DISEASES(2011), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Signal Transduction, MESH: Mice, Transgenic, Fc receptor, Syk, Mice, Transgenic, Protein tyrosine phosphatase, MESH: Receptors, IgG, MESH: Protein-Tyrosine Kinases, Receptor tyrosine kinase, MESH: Syk Kinase, Arthritis, Rheumatoid, Mice, MESH: Mice, Inbred C57BL, MESH: Intracellular Signaling Peptides and Proteins, Immunoreceptor tyrosine-based activation motif, Animals, Syk Kinase, MESH: Animals, MESH: Immunoglobulins, Intravenous, Tyrosine, MESH: Mice, MESH: Arthritis, Rheumatoid, biology, MESH: Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Receptors, IgG, Intracellular Signaling Peptides and Proteins, Immunoglobulins, Intravenous, MESH: Reactive Oxygen Species, General Medicine, Protein-Tyrosine Kinases, Molecular biology, Mice, Inbred C57BL, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Signal transduction, Reactive Oxygen Species, MESH: Female, Tyrosine kinase, Signal Transduction, Research Article
Abstract: International audience; Rheumatoid arthritis-associated (RA-associated) inflammation is mediated through the interaction between RA IgG immune complexes and IgG Fc receptors on immune cells. Polymorphisms within the gene encoding the human IgG Fc receptor IIA (hFcγRIIA) are associated with an increased risk of developing RA. Within the hFcγRIIA intracytoplasmic domain, there are 2 conserved tyrosine residues arranged in a noncanonical immunoreceptor tyrosine-based activation motif (ITAM). Here, we reveal that inhibitory engagement of the hFcγRIIA ITAM either with anti-hFcγRII F(ab')2 fragments or intravenous hIgG (IVIg) ameliorates RA-associated inflammation, and this effect was characteristic of previously described inhibitory ITAM (ITAMi) signaling for hFcαRI and hFcγRIIIA, but only involves a single tyrosine. In hFcγRIIA-expressing mice, arthritis induction was inhibited following hFcγRIIA engagement. Moreover, hFcγRIIA ITAMi-signaling reduced ROS and inflammatory cytokine production through inhibition of guanine nucleotide exchange factor VAV-1 and IL-1 receptor-associated kinase 1 (IRAK-1), respectively. ITAMi signaling was mediated by tyrosine 304 (Y304) within the hFcγRIIA ITAM, which was required for recruitment of tyrosine kinase SYK and tyrosine phosphatase SHP-1. Anti-hFcγRII F(ab')2 treatment of inflammatory synovial cells from RA patients inhibited ROS production through induction of ITAMi signaling. These data suggest that shifting constitutive hFcγRIIA-mediated activation to ITAMi signaling could ameliorate RA-associated inflammation.
Published: 2014

14. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial

Author: Marek Trněný, Gregg Dueck, Pieternella J. Lugtenburg, Gilles Salles, John G. Gribben, Anne Lennard, Vincent Delwail, Bruce D. Cheson, Natalie Dimier, Elisabeth Wassner-Fritsch, Laurie H. Sehn, Jiri Mayer, Nathan Fowler, Oliver W. Press, Neil Chua, Günter Fingerle-Rowson, Kamal Bouabdallah, Hematology, BC Cancer Agency, Vancouver, Department of Internal Medicine, Hemato-Oncology, Medical Faculty of Masaryk University Brno, Charles University and General University Hospital, Université Mohamed Boudiaf de M'sila, Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Barts and the London Medical School, F. Hoffmann-La Roche [Basel], Faculty of Medicine [Brno] (MED / MUNI), Masaryk University [Brno] (MUNI)-Masaryk University [Brno] (MUNI), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Survival, Lymphoma, analysis, Follicular lymphoma, Phases of clinical research, chemistry.chemical_compound, 0302 clinical medicine, Obinutuzumab, London, Antineoplastic Combined Chemotherapy Protocols, Indolent Non-Hodgkin Lymphoma, Bendamustine Hydrochloride, Lymphoma, Non-Hodgkin, Middle Aged, Prognosis, 3. Good health, Europe, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Rituximab, Female, France, Switzerland, medicine.drug, Bendamustine, medicine.medical_specialty, Canada, Asia, Neutropenia, Patients, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antibodies, Monoclonal, Humanized, Antibodies, methods, Time, 03 medical and health sciences, Internal medicine, medicine, Humans, Survival rate, Aged, Neoplasm Staging, therapy, business.industry, toxicity, Interim analysis, medicine.disease, Thrombocytopenia, Surgery, chemistry, Drug Resistance, Neoplasm, Neoplasm Recurrence, Local, business, 030215 immunology, Follow-Up Studies
Abstract: International audience; BACKGROUND: Patients with indolent non-Hodgkin lymphoma who fail to achieve adequate disease control with rituximab-based treatment have few treatment options and a poor prognosis. We aimed to assess a combination of obinutuzumab (GA101), a novel glyco-engineered type II anti-CD20 monoclonal antibody, and bendamustine in this patient population. METHODS: In this open-label, randomised, phase 3 study (GADOLIN), patients aged 18 years or older with histologically documented, CD20-positive indolent non-Hodgkin lymphoma refractory to rituximab were enrolled at 83 hospital and community sites in 14 countries in Europe, Asia, and North and Central America. Patients were randomly assigned (1:1) using a hierarchical dynamic randomisation scheme stratified by indolent non-Hodgkin lymphoma subtype, rituximab-refractory type, number of previous therapies, and geographical region, to receive induction treatment (six 28-day cycles) with obinutuzumab plus bendamustine or bendamustine monotherapy, both given intravenously. Obinutuzumab plus bendamustine dosing was obinutuzumab 1000 mg (days 1, 8, and 15, cycle 1; day 1, cycles 2-6) plus bendamustine 90 mg/m(2) per day (days 1 and 2, cycles 1-6), and bendamustine monotherapy dosing was 120 mg/m(2) per day (days 1 and 2, all cycles). Non-progressing patients in the obinutuzumab plus bendamustine group received obinutuzumab maintenance (1000 mg every 2 months) for up to 2 years. The primary endpoint was progression-free survival in all randomised patients, as assessed by an independent review committee. Safety was assessed in all patients who received any amount of obinutuzumab or bendamustine. This study is registered with ClinicalTrials.gov, number NCT01059630, and has stopped recruiting patients. FINDINGS: Between April 15, 2010, and Sept 1, 2014, when the study was stopped after a pre-planned interim analysis, 396 patients were randomly assigned (194 to obinutuzumab plus bendamustine and 202 to bendamustine monotherapy). After a median follow-up time of 21.9 months (IQR 12.1-31.0) in the obinutuzumab plus bendamustine group and 20.3 months (9.5-29.7) in the bendamustine monotherapy group, progression-free survival was significantly longer with obinutuzumab plus bendamustine (median not reached [95% CI 22.5 months-not estimable]) than with bendamustine monotherapy (14.9 months [12.8-16.6]; hazard ratio 0.55 [95% CI 0.40-0.74]; p=0.0001). Grade 3-5 adverse events occurred in 132 (68%) of 194 patients in the obinutuzumab plus bendamustine group and in 123 (62%) of 198 patients in the bendamustine monotherapy group. The most frequent grade 3 or worse adverse events were neutropenia (64 [33%] in the obinutuzumab plus bendamustine group vs 52 [26%] in the bendamustine monotherapy group), thrombocytopenia (21 [11%] vs 32 [16%]), anaemia (15 [8%] vs 20 [10%]) and infusion-related reactions (21 [11%] vs 11 [6%]). Serious adverse events occurred in 74 patients (38%) in the obinutuzumab plus bendamustine group and in 65 patients (33%) in the bendamustine monotherapy group, and deaths due to adverse events occurred in 12 patients (6%) and 12 patients (6%), respectively. Three (25%) of 12 adverse event-related deaths in the obinutuzumab plus bendamustine group and five (42%) of 12 in the bendamustine monotherapy group were treatment related. INTERPRETATION: Obinutuzumab plus bendamustine followed by obinutuzumab maintenance has improved efficacy over bendamustine monotherapy in rituximab-refractory patients with indolent non-Hodgkin lymphoma, with manageable toxicity, and is a new treatment option for patients who have relapsed after or are no longer responding to rituximab-based therapy. FUNDING: F Hoffmann-La Roche Ltd
Published: 2016

15. Vermamoeba vermiformis-Aspergillus fumigatus relationships and comparison with other phagocytic cells

Author: Elodie Maisonneuve, Sihem Kaaki, Estelle Cateau, Marie-Hélène Rodier, Microbiologie de l'Eau (MDE), Ecologie et biologie des interactions (EBI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], and Centre hospitalier universitaire de Poitiers (CHU Poitiers)
Subjects: 0301 basic medicine, Cell type, 030106 microbiology, Cell, Fungus, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Cell Line, Microbiology, Aspergillus fumigatus, Conidium, 03 medical and health sciences, medicine, Humans, Phagocytic Cell, Amoeba, Incubation, ComputingMilieux_MISCELLANEOUS, Acanthamoeba castellanii, Phagocytes, General Veterinary, Macrophages, General Medicine, Spores, Fungal, biology.organism_classification, Infectious Diseases, medicine.anatomical_structure, Insect Science, Host-Pathogen Interactions, Parasitology, Water Microbiology
Abstract: Free living amoebae (FLA) are protists ubiquitously present in the environment. Aspergillus fumigatus is a mould responsible for severe deep-seated infections, and that can be recovered in the same habitats as the FLA. By conducting coculture experiments and fungal incubation with amoebal supernatants, we report herein that Vermamoeba vermiformis, a FLA present in hospital water systems, promotes filamentation and growth of A. fumigatus. This finding is of particular importance to institutions whose water systems might harbor FLA and could potentially be used by immunocompromised patients. Also, the relationships between V. vermiformis and A. fumigatus were compared to those between this fungus and two other phagocytic cells: Acanthamoeba castellanii, another FLA, and macrophage-like THP-1 cells. After 4 h of coincubation, the percentages of the three phagocytic cell types with adhered conidia were similar, even though the types of receptors between FLA and macrophagic cell seemed different. However, the percentage of THP-1 with internalized conidia was considerably lower (40 %) in comparison with the two other cell types (100 %). Thus, this study revealed that interactions between A. fumigatus and these three phagocytic cell types show similarities, even though it is premature to extrapolate these results to interpret relationships between A. fumigatus and macrophages.
Published: 2016

16. Dose-Ranging Study of the Performance of the Natural Oxygen Transporter HEMO 2 Life in Organ Preservation

Author: Mallet, Vanessa, Dutheil, Delphine, Polard, Valérie, Rousselot, Morgane, Leize, Elisabeth, Hauet, Thierry, Goujon, Jean Michel, Zal, Franck, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Adaptation et diversité en milieu marin (AD2M), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Agence Nationale de la Recherche through the Recherche et Innovation en Biotechnologie program [ANR-07-BIOT-007-01], Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Adaptation et diversité en milieu marin (ADMM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff [Roscoff] (SBR), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Oxygen transporter, [SDV]Life Sciences [q-bio], Organ Preservation Solutions, Ischemia-reperfusion injury, Organ Preservation, Kidney, Kidney preservation, Kidney Transplantation, Oxygen, HEMO2Life, Animals, Dose ranging, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The intensity of ischemia-reperfusion injury of the donor organ during the preservation phase and after anastomosis is acknowledged as being a key factor for long-term graft outcome. We previously showed that the addition of 5 g/L of the natural oxygen carrier HEMO(2)Life was beneficial for the cold static preservation of kidney grafts in both University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate solutions. Herein, we refined these findings by evaluating HEMO(2)Life at various dose levels in UW, both in vitro with endothelial cells and in vivo in a pig kidney autotransplantation preclinical model. We showed in vitro that cells were significantly better preserved with HEMO(2)Life in a dose-dependent manner, with benefits in terms of survival, metabolic activity, and cellular integrity. In vivo, serum creatinine measurements at reperfusion confirmed the important benefits of HEMO(2)Life treatment on function recovery at the dose levels of 1, 2, and 5 g/L. Likewise, histological analysis of kidney parenchyma biopsies from day 7 confirmed the superiority of HEMO(2)Life-supplemented UW over UW alone, and there was no difference between the doses. Three months' follow-up confirmed the trend of the first 2 weeks, with creatinine and fibrosis levels similar to those in pretransplant kidneys.
Published: 2014

17. Cell-of-Origin (COO) Classification, BCL2 and MYC Expression Associated Outcome in Younger Patients Treated By RCHOP Front-Line Therapy Versus Intensive Regimen Followed By Autologous Transplant for De Novo Advanced Diffuse Large B Cell Lymphoma (DLBCL) : Results of the French Prospective Multicenter Randomized Trial Goelams-075

Author: Laboure, Gaëlle, Parrens, Marie-Cecile, Tsaranazy, Anjarasoa, Bordier, Magali, Le Gouill, Steven, Delwail, Vincent, Gressin, Rémy, Cornillon, Jerome, Damaj, Gandhi, Foussard, Charles Yves, Maisonneuve, Hervé, Deconinck, Eric, Cartron, Guillaume, Dreyfus, François, Gyan, Emmanuel, Sutton, Laurent, Morineau, Nadine, Alexis, Magda, Banos, Anne, Damotte, Diane, Moreau, Anne, Kraeber-Bodéré, Françoise, Rossille, Delphine, Fest, Thierry, Lamy, Thierry, Milpied, Noel, CHU Bordeaux [Bordeaux], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie clinique, CHU Grenoble, CHU Saint-Etienne, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service d'hématologie, Centre hospitalier La Roche-Sur-Yon, Laboratoire d'Hématologie, Hôpital Jean Minjoz-Université de Franche-Comté (UFC), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CIC - Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital d'Argenteuil, Centre Catherine-de-Sienne [Nantes] (CCS), Centre Hospitalier Régional d'Orléans (CHR), Hôpital de Bayonne, CH de la Côte Basque, 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), Biologie Pharmacie Pathologie, Sorbonne Paris Cité-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Service de Médecine Nucléaire [Nantes], Hôpital Laennec, Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Service de médecine nucléaire, Institut de Cancérologie de l'Ouest- ICO Gauducheau, Laboratoire d'Hematologie, CHU Pontchaillou [Rennes], Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'Hématologie et Thérapie Cellulaire, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service d'Hématologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier de la Côte Basque (CHCB), Université Pierre et Marie Curie - Paris 6 (UPMC)-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 Paris Cité-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Angers, Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Dynamique des interactions membranaires normales et pathologiques ( DIMNP ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], CHRU Tours, CHRU Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Catherine de Sienne, Centre Hospitalier Régional d'Orléans ( CHR ), 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 ), Sorbonne Paris Cité-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, Microenvironnement et cancer ( MiCa ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)
Subjects: immune system diseases, hemic and lymphatic diseases, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, [ SDV.IMM.IMM ] Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, [ SDV.CAN ] Life Sciences [q-bio]/Cancer
Abstract: WOS:000368021800177; International audience; The prognostic value of COO classification by immunohistochemistry (IHC) for de novo untreated advanced DLBCL remains controversial after Rituximab-based frontline therapy. Other biomarkers such as BCL2 or MYC protein expression have been proposed to predict survival. IHCcharacteristics were investigated in a large multicenter randomized study.
Published: 2013

18. All anti-vascular endothelial growth factor drugs can induce 'pre-eclampsia-like syndrome': a RARe study

Author: Marc-Antoine Belaud-Rotureau, Gregory Verhoest, Cécile Vigneau, Brigitte Laguerre, Yannick Arlot-Bonnemains, Florence Jouan, Nolwenn Lorcy, Nathalie Rioux-Leclercq, Jean Michel Goujon, T. Dolley-Hitze, Cancer du rein : bases moléculaires de la tumorogenèse, Service de néphrologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]-Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes 1 (UR1), Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], CRLCC Eugène Marquis (CRLCC), Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Cytogénétique et de Biologie Cellulaire, This work was supported by Région Bretagne, Université de Rennes 1 (CoREC/Cs scientifique)., Service de néphrologie, Service d'anatomie et cytologie pathologiques [Rennes], Service d'urologie, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]-Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]-Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Male, Vascular Endothelial Growth Factor A, Pathology, Indoles, [SDV]Life Sciences [q-bio], Biopsy, Kidney Glomerulus, urologic and male genital diseases, chemistry.chemical_compound, drug side effects, Sunitinib, Registries, Aged, 80 and over, Kidney, Proteinuria, medicine.diagnostic_test, Syndrome, Middle Aged, Immunohistochemistry, Kidney Neoplasms, 3. Good health, medicine.anatomical_structure, Nephrology, anti-VEGF, Hypertension, Female, Renal biopsy, medicine.symptom, Adult, medicine.medical_specialty, Thrombotic microangiopathy, pre-eclampsia, kidney biopsy, Urology, Antineoplastic Agents, medicine, Humans, Pyrroles, Carcinoma, Renal Cell, Acute tubular necrosis, Aged, Retrospective Studies, Transplantation, Creatinine, business.industry, medicine.disease, chemistry, Kidney Failure, Chronic, Synaptopodin, business, Follow-Up Studies
Abstract: International audience; BACKGROUND: Specific therapies that target vascular endothelial growth factor (VEGF) and its receptors have improved the survival of patients with metastatic cancers, but can induce side effects. Renal side effects (proteinuria, hypertension and renal failure) are underestimated. METHODS: The French RARe (Reins sous traitement Anti-VEGF Registre) study collects data on patients with cancer who had a renal biopsy because of major renal side effects during treatment with anti-VEGF drugs. RESULTS: We collected 22 renal biopsies performed 16.2±10.6 months after the beginning of treatment; of which 21 had hypertension, mean proteinuria was 2.97±2.00 g/day and mean serum creatinine, 134±117 µmol/L. Thrombotic microangiopathy (TMA) was observed in 21 biopsy specimens, sometimes associated with acute tubular necrosis (ATN; n=4). TMA histological lesions were more important than the biological signs of TMA could suggest. Patients with ATN of >20% had higher serum creatinine levels than those with only TMA (231 versus 95 µmol/L). Nephrin, podocin and synaptopodin were variably down-regulated in all renal biopsies. VEGF was down-regulated in all glomeruli. CONCLUSION: This study underlines the importance of regular clinical and biological cardiovascular and renal checking during all anti-VEGF therapies for cancer for early detection of renal dysfunction. Collaboration between oncologists and nephrologists is essential. In such cases, renal biopsy might help in appreciating the severity of the renal lesions and after multidisciplinary discussion whether or not it is safe to continue the treatment.
Published: 2013

19. Pivotal Role of the Lipid Raft SK3-Orai1 Complex in Human Cancer Cell Migration and Bone Metastases

Author: Paul-Alain Jaffrès, Maxime Guéguinou, Christine Collin, Flavie Arbion, Thibauld Oullier, Pierre Besson, Gaëlle Fromont, Christophe Vandier, Jean-Pierre Haelters, Marie Potier-Cartereau, Séverine Marionneau-Lambot, Alban Girault, Jean-Christophe Pages, Virginie Joulin, Lucie Clarysse, Michelle Pinault, Philippe Bougnoux, Aurélie Chantôme, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers, Cancéropôle du Grand Ouest, Université de Nantes (UN), Virus, pseudo-virus: Morphogénèse et Antigénicité, Université de Tours-EA3856, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'Anatomopathologie [Tours], Chimie, Electrochimie Moléculaires et Chimie Analytique (CEMCA), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Hématopoïèse normale et pathologique, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm UMR1069, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-EA3856, Université de Brest (UBO)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Vandier, Christophe, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11)
Subjects: Cancer Research, Pathology, medicine.medical_specialty, Patch-Clamp Techniques, ORAI1 Protein, Small-Conductance Calcium-Activated Potassium Channels, Blotting, Western, Mice, Nude, Bone Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Metastasis, 03 medical and health sciences, Mice, 0302 clinical medicine, Membrane Microdomains, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Movement, Cell Line, Tumor, Medicine, Animals, Humans, Neoplasm Invasiveness, Lipid raft, 030304 developmental biology, 0303 health sciences, business.industry, ORAI1, Colocalization, Bone metastasis, Cell migration, Neoplasms, Experimental, medicine.disease, Immunohistochemistry, Potassium channel, Cell biology, Disease Models, Animal, Oncology, Cell culture, 030220 oncology & carcinogenesis, Female, lipids (amino acids, peptides, and proteins), Calcium Channels, business
Abstract: The SK3 channel, a potassium channel, was recently shown to control cancer cell migration, a critical step in metastasis outgrowth. Here, we report that expression of the SK3 channel was markedly associated with bone metastasis. The SK3 channel was shown to control constitutive Ca2+ entry and cancer cell migration through an interaction with the Ca2+ channel Orai1. We found that the SK3 channel triggers an association with the Orai1 channel within lipid rafts. This localization of an SK3–Orai1 complex seemed essential to control cancer cell migration. This suggests that the formation of this complex in lipid rafts is a gain-of-function, because we showed that none of the individual proteins were able to promote the complete phenotype. We identified the alkyl-lipid Ohmline as a disrupting agent for SK3–Orai1 lipid raft localization. Upon Ohmline treatment, the SK3–Orai1 complex moved away from lipid rafts, and SK3-dependent Ca2+ entry, migration, and bone metastases were subsequently impaired. The colocalization of SK3 and Orai1 in primary human tumors and bone metastases further emphasized the clinical relevance of our observations. Targeting SK3–Orai1 in lipid rafts may inaugurate innovative approaches to inhibit bone metastases. Cancer Res; 73(15); 4852–61. ©2013 AACR.
Published: 2013

20. Long-term follow up of the FL2000 study comparing CHVP-interferon to CHVP-interferon plus rituximab in follicular lymphoma

Author: Karim Belhadj, Gilles Salles, Steven Le Gouill, Sophie Lefort, Pauline Brice, Anne Sonet, Catherine Sebban, Bruno Audhuy, Emmanuel Bachy, Roch Houot, Guillaume Cartron, Pierre Feugier, F. Morschhauser, Nicole Brousse, Hervé Maisonneuve, Christophe Fermé, Charles Foussard, Vincent Delwail, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Microenvironnement et cancer (MiCa), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'hématologie, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Catholique de Louvain = Catholic University of Louvain (UCL), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie Biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie, Hospices civils Colmar, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Relations Hôte-Environnement (RHEM), Université Henri Poincaré - Nancy 1 (UHP), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Léon Bérard [Lyon], Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre hospitalier La Roche-Sur-Yon, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier de Brive-la-Gaillarde (CH Brive), Department of Pathology, Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-Assistance Publique-Hopitaux de Paris-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel Dieu, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Centre Hospitalier Brive-la-Gaillarde, Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance Publique-Hopitaux de Paris, Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Microenvironnement et cancer ( MiCa ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université Catholique de Louvain ( UCL ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Dynamique des interactions membranaires normales et pathologiques ( DIMNP ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Gustave Roussy ( IGR ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Relations Hôte-Environnement ( RHEM ), Université Henri Poincaré - Nancy 1 ( UHP ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, Université Paris Descartes - Paris 5 ( UPD5 ) -PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP]-Assistance Publique-Hopitaux de Paris, CHU Angers-Hôtel Dieu, Le Corre, Morgane, Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Catholique de Louvain (UCL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, and Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP]-Assistance Publique-Hopitaux de Paris
Subjects: Oncology, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Time Factors, medicine.medical_treatment, Follicular lymphoma, THERAPY, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Cohort Studies, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, International Prognostic Index, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, Prospective Studies, Lymphoma, Follicular, Etoposide, 0303 health sciences, IMPROVED SURVIVAL, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, CHEMOTHERAPY, Middle Aged, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Rituximab, Drug Therapy, Combination, Female, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.drug, Adult, medicine.medical_specialty, Cyclophosphamide, Adolescent, UNITED-STATES, [ SDV.IMM.IMM ] Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Median follow-up, Internal medicine, medicine, Humans, VINCRISTINE, 030304 developmental biology, Aged, Teniposide, Chemotherapy, business.industry, Interferon-alpha, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, PHASE-III, Surgery, Regimen, Doxorubicin, Prednisone, Original Articles and Brief Reports, business, Follow-Up Studies
Abstract: Anti-CD20-containing chemotherapy regimens have become the standard of care for patients with follicular lymphoma needing cytotoxic therapy. Four randomized trials demonstrated a clinical benefit for patients treated with rituximab. However, no long-term follow up (i.e. > 5 years) of these trials is yet available. Between May 2000 and May 2002, 358 newly diagnosed patients with high tumor burden follicular lymphoma were randomized to receive cyclophosphamide, adriamycin, etoposide and prednisolone plus interferon-α2a or a similar chemotherapy-based regimen plus rituximab, and outcome was up-dated. With a median follow up of 8.3 years, addition of rituximab remained significantly associated with prolonged event-free survival (primary end point) (P=0.0004) with a trend towards a benefit for overall survival (P=0.076). The Follicular Lymphoma International Prognostic Index score was strongly associated with outcome for both event-free and overall survival in univariate analysis and its prognostic value remained highly significant after adjusting for other significant covariates in multivariate models (P
Published: 2013

21. Expression of follicle-stimulating hormone receptor by the vascular endothelium in tumor metastases

Author: Aurelian Radu, Nicolae Ghinea, Philippe Camparo, Gaëlle Fromont, Martine Antoine, François Planeix, Julie Gonin, Christophe Pichon, Virginie Desestret, Michel Huerre, Ahsan Siraj, Marc Sanson, BMC, Ed., Département de Recherche Translationnelle, Institut Curie [Paris], Laboratoire de Neuropathologie Raymond Escourolle [CHU Pitié-Salpétriêre], Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Anatomie et cytologie pathologiques [CHU Tenon], CHU Tenon [AP-HP], Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Histotechnologie et Pathologie, Institut Pasteur [Paris] (IP), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UPMC - Département de neurologie 2 - Mazarin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de pathologie Amiens, Centre de pathologie Amiens - Picardie, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Département de recherche translationnelle, Institut Curie, Laboratoire de Neuropathologie Raymond Escourolle, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service d'anatomie pathologique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Institut Pasteur [Paris], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Leiomyosarcoma, Cancer Research, Pathology, Lung Neoplasms, Endothelial cells, Estrogen receptor, Metastasis, Prostate cancer, 0302 clinical medicine, Breast cancer, Neoplasms, Medicine, Neoplasm Metastasis, Lymph node, 0303 health sciences, Tumor blood vessels, Kidney cancer, Middle Aged, Kidney Neoplasms, Colon cancer, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Colonic Neoplasms, Uterine Neoplasms, Receptors, FSH, Female, Lung cancer, Research Article, Adult, medicine.medical_specialty, endocrine system, Endothelium, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, 03 medical and health sciences, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Genetics, Humans, 030304 developmental biology, Aged, Follicle-stimulating hormone receptor, business.industry, Cancer, Prostatic Neoplasms, medicine.disease, Microvessels, Endothelium, Vascular, business
Abstract: Background The Follicle Stimulating Hormone receptor (FSHR) is expressed by the vascular endothelium in a wide range of human tumors. It was not determined however if FSHR is present in metastases which are responsible for the terminal illness. Methods We used immunohistochemistry based on a highly FSHR-specific monoclonal antibody to detect FSHR in cancer metastases from 6 major tumor types (lung, breast, prostate, colon, kidney, and leiomyosarcoma ) to 6 frequent locations (bone, liver, lymph node, brain, lung, and pleura) of 209 patients. Results In 166 patients examined (79%), FSHR was expressed by blood vessels associated with metastatic tissue. FSHR-positive vessels were present in the interior of the tumors and some few millimeters outside, in the normally appearing tissue. In the interior of the metastases, the density of the FSHR-positive vessels was constant up to 7 mm, the maximum depth available in the analyzed sections. No significant differences were noticed between the density of FSHR-positive vessels inside vs. outside tumors for metastases from lung, breast, colon, and kidney cancers. In contrast, for prostate cancer metastases, the density of FSHR-positive vessels was about 3-fold higher at the exterior of the tumor compared to the interior. Among brain metastases, the density of FSHR-positive vessels was highest in lung and kidney cancer, and lowest in prostate and colon cancer. In metastases of breast cancer to the lung pleura, the percentage of blood vessels expressing FSHR was positively correlated with the progesterone receptor level, but not with either HER-2 or estrogen receptors. In normal tissues corresponding to the host organs for the analyzed metastases, obtained from patients not known to have cancer, FSHR staining was absent, with the exception of approx. 1% of the vessels in non tumoral temporal lobe epilepsy samples. Conclusion FSHR is expressed by the endothelium of blood vessels in the majority of metastatic tumors.
Published: 2012

22. Rituximab induction immunotherapy for first-line low-tumor-burden follicular lymphoma: survival analyses with 7-year follow-up

Author: Gilles Salles, Philippe Colombat, Charles Foussard, Franck Morschhauser, F. Lazreg, Pierre Soubeyran, Corinne Haioun, Vincent Delwail, Nicole Brousse, Catherine Sebban, Pauline Brice, Philippe Solal-Celigny, Hervé Tilly, Catherine Thieblemont, Loïc Bergougnoux, Eric Deconinck, Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service d'Hematologie, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'hématologie, Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié - CRLCC Bordeaux, Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel Dieu, Service d'Oncologie Médicale, Centre Léon Bérard [Lyon], Service d'oncologie, CRLCC Henri Becquerel, Service d'Hématologie, Roche, Onco-radiothérapie, hématologie, Centre Jean Bernard, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Bretonneau-CHRU Tours, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), CHU Angers-Hôtel Dieu, and Saas, Philippe
Subjects: Male, MESH : Immunization, Passive, MESH : Induction Chemotherapy, Follicular lymphoma, Kaplan-Meier Estimate, Gastroenterology, Antibodies, Monoclonal, Murine-Derived, MESH: Lymphoma, Follicular, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, Lymphoma, Follicular, MESH: Treatment Outcome, education.field_of_study, MESH: Middle Aged, MESH : Neoplasm Recurrence, Local, Induction Chemotherapy, Hematology, MESH: Follow-Up Studies, MESH : Adult, Middle Aged, MESH: Induction Chemotherapy, 3. Good health, MESH : Antineoplastic Agents, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, MESH : Disease-Free Survival, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Rituximab, MESH: Immunization, Passive, MESH: Neoplasm Recurrence, Local, medicine.drug, Adult, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Male, Population, Antineoplastic Agents, MESH : Treatment Outcome, Disease-Free Survival, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, Internal medicine, medicine, Humans, MESH : Middle Aged, Progression-free survival, education, MESH: Kaplan-Meier Estimate, MESH: Humans, business.industry, MESH : Lymphoma, Follicular, MESH : Humans, Immunization, Passive, Induction chemotherapy, MESH : Follow-Up Studies, MESH: Adult, medicine.disease, MESH: Male, MESH : Antibodies, Monoclonal, Murine-Derived, Lymphoma, Surgery, MESH: Antibodies, Monoclonal, Murine-Derived, MESH: Disease-Free Survival, MESH: Antineoplastic Agents, Neoplasm Recurrence, Local, business, Diffuse large B-cell lymphoma, MESH: Female, Progressive disease, Follow-Up Studies, 030215 immunology
Abstract: International audience; BACKGROUND: The purpose of this study was to report long-term results of rituximab induction monotherapy in patients with low-tumor-burden follicular lymphoma (LTBFL). PATIENTS AND METHODS: Of 49 first-line LTBFL patients who received weekly doses of rituximab (375 mg/m(2)), 46 have been followed with a long-term analysis of clinical and molecular responses. RESULTS: Best clinical response (at any staging within a year following treatment) was 80%, 24 (52%) patients had complete or unconfirmed complete response, 13 (28%) had partial response and 9 (20%) had stable or progressive disease. Of 31 patients having a positive bcl2-JH rearrangement, 15 (48%) became negative following treatment. After 83.9 months of follow-up (95% confidence interval 6.4-92.8 months), the median progression-free survival is 23.5 months and overall survival (OS) is 91.7%. Five patients died (one progression, one myelodysplasia, one diffuse large B-cell lymphoma and two solid tumors). Seven patients (15%) are progression-free including five who are bcl2 informative. No unexpected long-term adverse event has been observed. CONCLUSION: A significant proportion of patients remain progression-free 7 years after a single 4-dose rituximab treatment in first-line LTBFL. The 7-year overall survivalOS is very high in this selected population of patients.
Published: 2012

23. Altered expression of the gap junction protein connexin43 is associated with papillary thyroid carcinomas when compared with other noncancer pathologies of the thyroid

Author: Sophie Crespin, Lucie Karayan-Tapon, Gauthier Bouche, Anne Cantereau, Thibault Desurmont, Claudia Dominguez, Gaëlle Fromont, Marc Mesnil, Hélène Gibelin, Pierre Levillain, Jean-Louis Kraimps, Service de chirurgie viscérale et endocrinienne, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Cellules souches leucémiques et thérapeuthiques, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Laboratoire d'Anatomo-Pathologie, CHU de Poiters, Department of Public Health, Modèles de Cellules Souches Malignes et Thérapeutiques, and Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Carcinoma, Pathology, Thyroiditis, Goiter, endocrine system diseases, MESH: Thyroiditis, Endocrinology, Diabetes and Metabolism, Biopsy, [SDV]Life Sciences [q-bio], MESH: Gap Junctions, Thyroid Gland, MESH: Graves Disease, MESH: Down-Regulation, MESH: Biopsy, 0302 clinical medicine, Endocrinology, MESH: Microscopy, Confocal, Thyroid cancer, Tissue homeostasis, MESH: Goiter, Nodular, 0303 health sciences, Microscopy, Confocal, medicine.diagnostic_test, Thyroid, Gap Junctions, Graves Disease, 3. Good health, medicine.anatomical_structure, Thyroid Cancer, Papillary, MESH: Thyroid Neoplasms, 030220 oncology & carcinogenesis, cardiovascular system, Immunohistochemistry, biological phenomena, cell phenomena, and immunity, Goiter, Nodular, medicine.medical_specialty, endocrine system, Down-Regulation, Biology, Immunofluorescence, Thyroid carcinoma, 03 medical and health sciences, medicine, Biomarkers, Tumor, Humans, RNA, Messenger, Thyroid Neoplasms, 030304 developmental biology, Retrospective Studies, MESH: RNA, Messenger, MESH: Humans, Carcinoma, MESH: Retrospective Studies, medicine.disease, Carcinoma, Papillary, MESH: Connexin 43, MESH: Thyroid Gland, Connexin 43, MESH: Tumor Markers, Biological, sense organs
Abstract: International audience; BACKGROUND: Gap junctions are membrane structures composed of connexins (Cx) that allow diffusion of small molecules between cells. They are involved in tissue homeostasis, and various organ dysfunctions have been associated with gap junction defects. To verify their possible involvement in thyroid pathologies, the expression of connexin43 (Cx43), the major Cx in the human thyroid, was evaluated in a variety of diseases including cancer. METHODS: There were 122 samples from various thyroid pathologies that were collected to analyze the presence of Cx43 by immunofluorescence. Through confocal microscopy, different patterns of Cx43 localization were identified as normal (membrane) or abnormal (cytoplasmic or lack of detection). The analysis of Cx43 expression was further performed by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry in a subset of 25 papillary carcinomas and compared with nontumoral thyroid tissues. RESULTS: The presence of Cx43 was commonly altered in thyroid cancer, as abnormal Cx43 staining was detected in 94.1% of cancer, 47.4% of adenomas, 45.7% of multinodular goiter, 16.7% of Graves' disease, and 25% of thyroiditis. In papillary carcinoma samples, the deregulation of Cx43 expression was mostly the consequence of a decrease of Cx43 mRNA (68% of cases) when compared with normal tissue. When Cx43 mRNA was not downregulated (32% of cases), both loss of membrane staining and aberrant cytoplasmic distribution of the protein were observed. CONCLUSIONS: These results show that aberrations of Cx43 expression are associated with thyroid papillary carcinoma.
Published: 2011

24. Prevention of the β-amyloid peptide-induced inflammatory process by inhibition of double-stranded RNA-dependent protein kinase in primary murine mixed co-cultures

Author: Serge Milin, Milena Morel, Bernard Fauconneau, Julien Couturier, Guylène Page, Faraj Terro, Raymond Pontcharraud, Marc Paccalin, Cibles moléculaires et thérapeutiques de la maladie d'Alzheimer (CIMoTHeMA), Université de Poitiers, Service de gériatrie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Histologie, cytologie, cytogénétique, biologie cellulaire [CHU Limoges], CHU Limoges, Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], This study was supported by a grant from the Association France Alzheimer and by the French Ministry of Education and Research with a grant to the Research Unit GReViC, EA 3808 and by the Poitiers University Hospital., BMC, Ed., and Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-CHU Limoges
Subjects: MESH: Inflammation, MESH: Signal Transduction, Indoles, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Neurons, MESH: NF-kappa B, Apoptosis, lcsh:RC346-429, Mice, eIF-2 Kinase, 0302 clinical medicine, Annexin, MESH: Animals, Cells, Cultured, Neurons, MESH: Indoles, 0303 health sciences, MESH: Cytokines, Microglia, General Neuroscience, Imidazoles, NF-kappa B, Interleukin, MESH: Amyloid beta-Peptides, I-kappa B Kinase, MESH: Microglia, medicine.anatomical_structure, Neurology, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tumor necrosis factor alpha, MESH: Imidazoles, Signal Transduction, MESH: Cells, Cultured, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Microscopy, Electron, Scanning, Immunology, Biology, MESH: eIF-2 Kinase, MESH: Coculture Techniques, 03 medical and health sciences, Cellular and Molecular Neuroscience, Alzheimer Disease, MESH: Mice, Inbred C57BL, medicine, Animals, Humans, MESH: I-kappa B Kinase, Protein kinase A, MESH: Mice, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology, Inflammation, EIF-2 kinase, Amyloid beta-Peptides, MESH: Humans, Research, MESH: Apoptosis, I-Kappa-B Kinase, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Molecular biology, Protein kinase R, Coculture Techniques, Mice, Inbred C57BL, MESH: Astrocytes, Astrocytes, biology.protein, Microscopy, Electron, Scanning, 030217 neurology & neurosurgery, MESH: Alzheimer Disease
Abstract: Background Inflammation may be involved in the pathogenesis of Alzheimer's disease (AD). There has been little success with anti-inflammatory drugs in AD, while the promise of anti-inflammatory treatment is more evident in experimental models. A new anti-inflammatory strategy requires a better understanding of molecular mechanisms. Among the plethora of signaling pathways activated by β-amyloid (Aβ) peptides, the nuclear factor-kappa B (NF-κB) pathway could be an interesting target. In virus-infected cells, double-stranded RNA-dependent protein kinase (PKR) controls the NF-κB signaling pathway. It is well-known that PKR is activated in AD. This led us to study the effect of a specific inhibitor of PKR on the Aβ42-induced inflammatory response in primary mixed murine co-cultures, allowing interactions between neurons, astrocytes and microglia. Methods Primary mixed murine co-cultures were prepared in three steps: a primary culture of astrocytes and microglia for 14 days, then a primary culture of neurons and astrocytes which were cultured with microglia purified from the first culture. Before exposure to Aβ neurotoxicity (72 h), co-cultures were treated with compound C16, a specific inhibitor of PKR. Levels of tumor necrosis factor-α (TNFα), interleukin (IL)-1β, and IL-6 were assessed by ELISA. Levels of PT451-PKR and activation of IκB, NF-κB and caspase-3 were assessed by western blotting. Apoptosis was also followed using annexin V-FITC immunostaining kit. Subcellular distribution of PT451-PKR was assessed by confocal immunofluorescence and morphological structure of cells by scanning electron microscopy. Data were analysed using one-way ANOVA followed by a Newman-Keuls' post hoc test Results In these co-cultures, PKR inhibition prevented Aβ42-induced activation of IκB and NF-κB, strongly decreased production and release of tumor necrosis factor (TNFα) and interleukin (IL)-1β, and limited apoptosis. Conclusion In spite of the complexity of the innate immune response, PKR inhibition could be an interesting anti-inflammatory strategy in AD.
Published: 2011

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24 results on '"Service d'Anatomie et de Cytologie Pathologiques [Poitiers]"'

1. Heavy Chain Fibrillary Glomerulonephritis: A Case Report

2. A Novel Calcium-Mediated EMT Pathway Controlled by Lipids: An Opportunity for Prostate Cancer Adjuvant Therapy

3. Vermamoeba vermiformis in hospital network: a benefit for Aeromonas hydrophila

4. Transient Receptor Potential Channel Expression Signatures in Tumor-Derived Endothelial Cells: Functional Roles in Prostate Cancer Angiogenesis

5. Randall-type monoclonal immunoglobulin deposition disease: novel insights from a nationwide cohort study

6. R-CHOP 14 with or without radiotherapy in non-bulky limited-stage diffuse large B-cell lymphoma (DLBCL)

7. Acanthamoeba castellanii is not be an adequate model to study human adenovirus interactions with macrophagic cells

8. Genomic and viral findings in two different primary Merkel cell carcinomas in a 76-year-old woman

9. Metabolic reprogramming in cancer cells, consequences on pH and tumour progression: Integrated therapeutic perspectives with dietary lipids as adjuvant to anticancer treatment

10. Carcinoma-specific expression of P2Y11 receptor and its contribution in ATP-induced purinergic signalling and cell migration in human hepatocellular carcinoma cells

11. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group

12. Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy–associated C3 glomerulopathy

13. Shifting FcγRIIA-ITAM from activation to inhibitory configuration ameliorates arthritis

14. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial

15. Vermamoeba vermiformis-Aspergillus fumigatus relationships and comparison with other phagocytic cells

16. Dose-Ranging Study of the Performance of the Natural Oxygen Transporter HEMO 2 Life in Organ Preservation

18. All anti-vascular endothelial growth factor drugs can induce 'pre-eclampsia-like syndrome': a RARe study

19. Pivotal Role of the Lipid Raft SK3-Orai1 Complex in Human Cancer Cell Migration and Bone Metastases

20. Long-term follow up of the FL2000 study comparing CHVP-interferon to CHVP-interferon plus rituximab in follicular lymphoma

21. Expression of follicle-stimulating hormone receptor by the vascular endothelium in tumor metastases

22. Rituximab induction immunotherapy for first-line low-tumor-burden follicular lymphoma: survival analyses with 7-year follow-up

23. Altered expression of the gap junction protein connexin43 is associated with papillary thyroid carcinomas when compared with other noncancer pathologies of the thyroid

24. Prevention of the β-amyloid peptide-induced inflammatory process by inhibition of double-stranded RNA-dependent protein kinase in primary murine mixed co-cultures

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