136 results on '"Cambefort, Jeanne"'
Search Results
2. Physical properties of DNA components affecting the transposition efficiency of the mariner Mos1 element
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Casteret, Sophie, Chbab, Najat, Cambefort, Jeanne, Augé-Gouillou, Corinne, Bigot, Yves, and Rouleux-Bonnin, Florence
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- 2009
- Full Text
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3. Genome and metabolic network of 'Candidatus Phaeomarinobacter ectocarpi' Ec32, a new candidate genus of Alphaproteobacteria frequently associated with brown algae
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Dittami, Simon M., Barbeyron, Tristan, Boyen, Catherine, Cambefort, Jeanne, Collet, Guillaume, Delage, Ludovic, Gobet, Angelique, Groisillier, Agnes, Leblanc, Catherine, Michel, Gurvan, Scornet, Delphine, Siegel, Anne, Tapia, Javier E., Tonon, Thierry, Dittami, Simon M., Barbeyron, Tristan, Boyen, Catherine, Cambefort, Jeanne, Collet, Guillaume, Delage, Ludovic, Gobet, Angelique, Groisillier, Agnes, Leblanc, Catherine, Michel, Gurvan, Scornet, Delphine, Siegel, Anne, Tapia, Javier E., and Tonon, Thierry
- Abstract
Rhizobiales and related orders of Alphaproteobacteria comprise several genera of nodule-inducing symbiotic bacteria associated with plant roots. Here we describe the genome and the metabolic network of "Candidatus Phaeomarinobacter ectocarpi" Ec32, a member of a new candidate genus closely related to Rhizobiales and found in association with cultures of the filamentous brown algal model Ectocarpus. The "Ca. P. ectocarpi" genome encodes numerous metabolic pathways that may be relevant for this bacterium to interact with algae. Notably, it possesses a large set of glycoside hydrolases and transporters, which may serve to process and assimilate algal metabolites. It also harbors several proteins likely to be involved in the synthesis of algal hormones such as auxins and cytokinins, as well as the vitamins pyridoxine, biotin, and thiamine. As of today, "Ca. P. ectocarpi" has not been successfully cultured, and identical 16S rDNA sequences have been found exclusively associated with Ectocarpus. However, related sequences (>= 97% identity) have also been detected free-living and in a Fucus vesiculosus microbiome barcoding project, indicating that the candidate genus "Phaeomarinobacter" may comprise several species, which may colonize different niches.
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- 2014
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4. Genome and metabolic network of “Candidatus Phaeomarinobacter ectocarpi†Ec32, a new candidate genus of Alphaproteobacteria frequently associated with brown algae
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Dittami, Simon M., primary, Barbeyron, Tristan, additional, Boyen, Catherine, additional, Cambefort, Jeanne, additional, Collet, Guillaume, additional, Delage, Ludovic, additional, Gobet, Angélique, additional, Groisillier, Agnès, additional, Leblanc, Catherine, additional, Michel, Gurvan, additional, Scornet, Delphine, additional, Siegel, Anne, additional, Tapia, Javier E., additional, and Tonon, Thierry, additional
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- 2014
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5. Regulation of Mariner Transposition: The Peculiar Case of Mos1
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Jaillet, Jérôme, primary, Genty, Murielle, additional, Cambefort, Jeanne, additional, Rouault, Jacques-Deric, additional, and Augé-Gouillou, Corinne, additional
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- 2012
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6. Nuclear Importation of Mariner Transposases among Eukaryotes: Motif Requirements and Homo-Protein Interactions
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Demattei, Marie-Véronique, primary, Hedhili, Sabah, additional, Sinzelle, Ludivine, additional, Bressac, Christophe, additional, Casteret, Sophie, additional, Moiré, Nathalie, additional, Cambefort, Jeanne, additional, Thomas, Xavier, additional, Pollet, Nicolas, additional, Gantet, Pascal, additional, and Bigot, Yves, additional
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- 2011
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7. The genome-scale metabolic network of Ectocarpus siliculosus (Ecto GEM): a resource to study brown algal physiology and beyond.
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Prigent, Sylvain, Collet, Guillaume, Dittami, Simon M., Delage, Ludovic, Ethis de Corny, Floriane, Dameron, Olivier, Eveillard, Damien, Thiele, Sven, Cambefort, Jeanne, Boyen, Catherine, Siegel, Anne, and Tonon, Thierry
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BROWN algae ,METABOLISM ,ALGAL genomes ,HETEROKONTOPHYTA ,ECOSYSTEMS ,BIOMASS ,PHYSIOLOGY ,ALGAE - Abstract
Brown algae (stramenopiles) are key players in intertidal ecosystems, and represent a source of biomass with several industrial applications. Ectocarpus siliculosus is a model to study the biology of these organisms. Its genome has been sequenced and a number of post-genomic tools have been implemented. Based on this knowledge, we report the reconstruction and analysis of a genome-scale metabolic network for E. siliculosus, Ecto GEM (). This atlas of metabolic pathways consists of 1866 reactions and 2020 metabolites, and its construction was performed by means of an integrative computational approach for identifying metabolic pathways, gap filling and manual refinement. The capability of the network to produce biomass was validated by flux balance analysis. Ecto GEM enabled the reannotation of 56 genes within the E. siliculosus genome, and shed light on the evolution of metabolic processes. For example, E. siliculosus has the potential to produce phenylalanine and tyrosine from prephenate and arogenate, but does not possess a phenylalanine hydroxylase, as is found in other stramenopiles. It also possesses the complete eukaryote molybdenum co-factor biosynthesis pathway, as well as a second molybdopterin synthase that was most likely acquired via horizontal gene transfer from cyanobacteria by a common ancestor of stramenopiles. Ecto GEM represents an evolving community resource to gain deeper understanding of the biology of brown algae and the diversification of physiological processes. The integrative computational method applied for its reconstruction will be valuable to set up similar approaches for other organisms distant from biological benchmark models. [ABSTRACT FROM AUTHOR]
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- 2014
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8. Induction chemotherapy in head and neck cancer
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Yoann Pointreau, Gilles Calais, Jérôme Fayette, Ibrahim Atean, Jean-Louis Lefebvre, Cambefort, Jeanne, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Université Lille Nord de France (COMUE)-UNICANCER, and Université de Tours-Centre National de la Recherche Scientifique (CNRS)
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Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Antineoplastic Agents ,Disease ,Targeted therapy ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Stage (cooking) ,induction chemotherapy ,Neoplasm Staging ,Pharmacology ,Chemotherapy ,Performance status ,business.industry ,Head and neck cancer ,Induction chemotherapy ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Neoadjuvant Therapy ,taxanes ,Radiation therapy ,Chemotherapy, Adjuvant ,Head and Neck Neoplasms ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Carcinoma, Squamous Cell ,head and neck cancer ,organ preservation ,business - Abstract
International audience; Five hundred and fifty thousand new head and neck cancer cases are diagnosed each year worldwide. They are mostly locally advanced squamous cell carcinoma with a poor prognosis in terms of locoregional and distant failure. A major challenge for patients with locally advanced squamous cell carcinoma is to achieve a high cure rate while preserving functions. Treatment strategies are designed according to the disease stage, primary site, operable status, patient age, and performance status. Surgery, radiation therapy, chemotherapy, and more recently molecular-targeted therapies are part of these strategies, but their sequence remains to be defined. Over the last 30 years, induction chemotherapy has attained an important position in the management of patients with locally advanced squamous cell carcinoma, particularly since the introduction of taxanes. The decision to deliver induction chemotherapy (and its intensification) must be considered in the light of other treatments aiming at better locoregional control (normofractioned radiotherapy, accelerated or hyperfractionated radiotherapy, addition of concurrent chemotherapy, or of targeted therapy) with or without adjuvant treatment. This review summarizes the rationale, these data, and perspectives on induction chemotherapy-based strategies. Anti-Cancer Drugs 22: 613-620 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
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- 2011
9. Landscape of chromatin control element patents: positioning effects in pharmaceutical bioproduction
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Fabien Palazzoli, Yves Bigot, Florence Bonnin-Rouleux, Solenne Bire, Cambefort, Jeanne, Centre National de la Recherche Scientifique (CNRS), Université Francois Rabelais [Tours], Université François Rabelais de Tours, Ministère de l'Education Nationale, de la Recherche et de la Technologie, Association Française conte la Myopathie, Groupement de Recherche CNRS 2157, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
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0106 biological sciences ,[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT] ,[SDV.BIO]Life Sciences [q-bio]/Biotechnology ,Knowledge management ,Biomedical Engineering ,Bioengineering ,Intellectual property ,01 natural sciences ,Applied Microbiology and Biotechnology ,Patents as Topic ,03 medical and health sciences ,010608 biotechnology ,Technology, Pharmaceutical ,[INFO.INFO-BT]Computer Science [cs]/Biotechnology ,Control (linguistics) ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0303 health sciences ,business.industry ,Gene Transfer Techniques ,Bioproduction ,Chromatin ,United States ,[SDV.BIO] Life Sciences [q-bio]/Biotechnology ,Biotechnology ,Genetic Enhancement ,[INFO.INFO-BT] Computer Science [cs]/Biotechnology ,Molecular Medicine ,Element (criminal law) ,business - Abstract
Characteristics of the current patent landscape on chromatin control elements indicate the intellectual property strategies of technological leaders.
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- 2011
10. Direct Cost-Modeling of Rheumatoid Arthritis According to Disease Activity Categories in France
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Ariel Beresniak, Laure Gossec, Alain Saraux, Danielle Dupont, Marion Bamberger, Bruno Bregman, Philippe Goupille, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Cambefort, Jeanne
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medicine.medical_specialty ,Cost estimate ,[SDV]Life Sciences [q-bio] ,Immunology ,MEDLINE ,Arthritis ,Severity of Illness Index ,Arthritis, Rheumatoid ,Disease activity ,DISEASE ACTIVITY SCORE ,03 medical and health sciences ,0302 clinical medicine ,MODELING ,Cost of Illness ,Rheumatology ,Internal medicine ,Severity of illness ,medicine ,Humans ,Immunology and Allergy ,030212 general & internal medicine ,RHEUMATOID ARTHRITIS ,health care economics and organizations ,030203 arthritis & rheumatology ,business.industry ,Remission Induction ,Health Care Costs ,Direct cost ,medicine.disease ,3. Good health ,[SDV] Life Sciences [q-bio] ,Models, Economic ,Rheumatoid arthritis ,Physical therapy ,France ,business ,Monte Carlo Method - Abstract
Objective.The objective of this cost-of-illness study was to assess the use of direct medical resources, excluding drug costs, by patients with rheumatoid arthritis (RA) in France, and to construct cost estimates according to level of disease activity.Methods.Three categories of RA disease activity were defined according to Disease Activity Score 28-joint count (DAS28) thresholds: remission (DAS28 < 2.6), low disease activity state (LDAS; i.e., DAS28 ≤ 3.2), and moderate to high disease activity (MHDAS; i.e., DAS28 > 3.2). Eight resource utilization items were defined: medical visits, laboratory tests, hospitalization, imaging, physiotherapy, nursing, adaptive aids, and transportation. Resource utilization and unit costs from the national-payer perspective were estimated through expert opinion and simulated using distribution ranges for each item. Cost distributions were computed by Monte-Carlo simulations estimating overall costs per 6 months over a 2-year period.Results.For patients achieving remission, costs were estimated at a mean of €771 (SD 199) for the first 6 months and at €511 (SD 162) for each subsequent 6-month period. For patients achieving LDAS, costs were estimated at €905 (SD 263) for the first 6 months and €696 (SD 240) for each subsequent 6-month period. For patients in MHDAS, costs were estimated at €1215 per 6 months (SD 405).Conclusion.This cost-of-illness assessment provided current estimates of direct medical costs for RA according to disease activity in France. The findings suggest that achieving remission or LDAS is associated with substantially lower medical costs for RA versus being in MHDAS.
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- 2010
11. An Enzyme-Linked Immunosorbent Assay to Study Bevacizumab Pharmacokinetics
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Etienne Dorval, Anne-Claire Duveau, David Ternant, Thierry Lecomte, Danielle Degenne, Hervé Watier, Nicolas Ceze, Gilles Paintaud, Cambefort, Jeanne, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
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Bevacizumab ,Angiogenesis ,medicine.drug_class ,therapeutic drug monitoring ,medicine.medical_treatment ,Angiogenesis Inhibitors ,bevacizumab ,Pharmacology ,Antibodies, Monoclonal, Humanized ,Monoclonal antibody ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Humans ,Medicine ,Pharmacology (medical) ,030304 developmental biology ,0303 health sciences ,biology ,business.industry ,Growth factor ,Antibodies, Monoclonal ,Cancer ,medicine.disease ,3. Good health ,Area Under Curve ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,030220 oncology & carcinogenesis ,Monoclonal ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,biology.protein ,enzyme-linked immunosorbent assay ,Drug Monitoring ,Antibody ,Colorectal Neoplasms ,business ,pharmacokinetics ,medicine.drug - Abstract
International audience; Introduction: Bevacizumab is an antivascular endothelial growth factor humanized monoclonal antibody used to inhibit angiogenesis in cancer. It displays an important interindividual pharmacokinetic variability, which could explain part of the interindividual differences in clinical response. Therefore, an assay to measure bevacizumab serum concentrations is needed. Methods: An enzyme-linked immunosorbent assay was developed using microtiter plates sensitised with vascular endothelial growth factor(165), a recombinant form of vascular endothelial growth factor. Lower and upper limits of quantitation as well as limit of detection were determined. Eight calibrators and three quality controls, with concentrations of 5 mg/L, 30 mg/L, and 75 mg/L, were tested on five occasions initially and on five subsequent occasions. Trough and peak serum concentrations of bevacizumab were measured in patients with metastatic colorectal cancer. Bevacizumab concentrations were described using a two-compartment population pharmacokinetic model with first-order constants. Results: Imprecision and accuracy of calibrators and quality controls were 20% or less, except for the zero calibrator. The limit of detection was 0.033 mg/L. Lower and upper limits of quantitation were 5 and 75 mg/L, respectively. A total of 175 blood samples was available for analysis from 16 patients. Median (range) trough and peak concentrations during the treatment were 47.2 (9.6-106.9) mg/L and 159.3 (33.0-327.3) mg/L, respectively. Conclusion: This method is rapid, accurate, reproducible, and may be useful for pharmacokinetic and pharmacokinetic-pharmacodynamic studies as well as in therapeutic drug monitoring of bevacizumab.
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- 2010
12. Prognosis and follow-up of psoriatic arthritis with peripheral joint involvement: Development of recommendations for clinical practice based on published evidence and expert opinion
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Alain Cantagrel, Alain Saraux, Thierry Schaeverbeke, Jacques Tebib, Bernard Combe, Carle Paul, Philippe Gaudin, Philippe Goupille, F. Lavie, Daniel Wendling, Emmanuelle Dernis, Carine Salliot, Jean-Francis Maillefert, René-Marc Flipo, Pascal Claudepierre, Xavier Le Loët, CHU Cochin [APHP], Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Lariboisière - Université Paris Diderot - Paris 7 (UP7), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Pellegrin, CHU Bordeaux [Bordeaux] - Groupe hospitalier Pellegrin, Génétique, Immunothérapie, Chimie et Cancer (GICC), Université François Rabelais - Tours - Centre National de la Recherche Scientifique (CNRS), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF) - CHU Grenoble, CHU Dijon, Centre Hospitalier Universitaire de Dijon (CHU Dijon), Hôpital Lapeyronie, Université Montpellier 1 (UM1) - Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier) - Hôpital Lapeyronie, Service de rhumatologie, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Service de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, CHU Bordeaux [Bordeaux], Service d'immunologie et rhumatologie, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Rhumatologie, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Lapeyronie [Montpellier] (CHU), CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Cambefort, Jeanne
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MESH: Inflammation ,[SDV]Life Sciences [q-bio] ,Delphi method ,Alternative medicine ,MESH: Monitoring, Physiologic ,Arthritis ,Recommendations ,0302 clinical medicine ,MESH: Arthritis, Psoriatic ,030212 general & internal medicine ,Practice Patterns, Physicians' ,MESH: Publishing ,Evidence-Based Medicine ,Follow-up ,MESH: Follow-Up Studies ,Prognosis ,MESH: Predictive Value of Tests ,3. Good health ,[SDV] Life Sciences [q-bio] ,MESH: Joints ,[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,Psoriatic arthritis ,Radiological weapon ,Predictive value of tests ,MESH: Expert Testimony ,medicine.medical_specialty ,MEDLINE ,MESH: Prognosis ,03 medical and health sciences ,Rheumatology ,Predictive Value of Tests ,medicine ,Humans ,MESH: Physician's Practice Patterns ,Expert Testimony ,Monitoring, Physiologic ,Inflammation ,Publishing ,030203 arthritis & rheumatology ,MESH: Humans ,business.industry ,Arthritis, Psoriatic ,Everyday clinical practice ,Evidence-based medicine ,medicine.disease ,Radiography ,Physical therapy ,Joints ,business ,MESH: Evidence-Based Medicine ,Follow-Up Studies - Abstract
International audience; Objectives: To develop recommendations about prognosis and follow-up of psoriatic arthritis (PsA) with peripheral joint involvement in everyday clinical practice. Methods: The strategy was as following: (a) The choice of five questions, by the scientific committee according to the Delphi method, considered as a basis for the recommendations; (b) the Systematic Literature Research based on Medline, Cochrane and abstracts from the annual meetings of SFR, EULAR and ACR. An expert committee composed with 68 rheumatologists elaborated and validated the recommendations, specifying the strength and the degree of agreement for each of them. Results: The questions selected were: (1) How can articular and cutaneous disease activity of PsA be assessed in usual clinical practice? (2) Which parameters are predictive for functional, radiological and fatal outcome in PsA? (3) Which clinical and biological parameters are useful for the follow-up of PsA? At which frequency? (4) Which X-rays are useful for the follow-up of PsA? At which frequency? (5) How can the response to treatments be assessed in PsA? The literature search identified 1181 abstracts and 123 articles were included and analyzed. Seven recommendations, whose strength ranged from B to D, were drafted and validated by a final vote of the expert committee. Conclusion: Seven recommendations about follow-up of patients with PsA for daily practice were developed. They can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of patients with PsA. (C) 2009 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
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- 2009
13. Evaluation of two strategies (initial methotrexate monotherapy vs its combination with adalimumab) in management of early active rheumatoid arthritis: data from the GUEPARD trial
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Charles Zarnitsky, Olivier Meyer, Xavier Puéchal, Denis Mulleman, René Marc Flipo, Xavier Mariette, Thierry Schaeverbeke, Patrice Fardellone, Martin Soubrier, Jean Sibilia, Maxime Dougados, Bernarde Combe, Francis Berenbaum, Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Hôpital Bichat - Claude Bernard, Hôpital Lapeyronie [Montpellier] (CHU), Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bichat - Claude Bernard - Université Paris Diderot - Paris 7 (UP7), Hôpital Lapeyronie, Université Montpellier 1 (UM1) - Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier) - Hôpital Lapeyronie, Génétique, Immunothérapie, Chimie et Cancer (GICC), Université François Rabelais - Tours - Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux] - Groupe hospitalier Pellegrin, CHU Cochin [APHP], and Cambefort, Jeanne
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Male ,[SDV]Life Sciences [q-bio] ,Severity of Illness Index ,Arthritis, Rheumatoid ,Anti-TNF ,0302 clinical medicine ,immune system diseases ,Immunopathology ,Medicine ,Pharmacology (medical) ,Prospective Studies ,030212 general & internal medicine ,skin and connective tissue diseases ,Area under the curve ,Antibodies, Monoclonal ,Tight contol ,Middle Aged ,3. Good health ,[SDV] Life Sciences [q-bio] ,Treatment Outcome ,Antirheumatic Agents ,Rheumatoid arthritis ,Disease Progression ,Drug Therapy, Combination ,Female ,medicine.drug ,Adult ,musculoskeletal diseases ,medicine.medical_specialty ,Combination therapy ,Antibodies, Monoclonal, Humanized ,03 medical and health sciences ,Rheumatology ,Internal medicine ,Adalimumab ,Humans ,Aged ,030203 arthritis & rheumatology ,Tumor Necrosis Factor-alpha ,business.industry ,Recovery of Function ,medicine.disease ,Surgery ,Radiography ,Regimen ,Methotrexate ,business - Abstract
International audience; Objectives. In early and active RA despite MTX, continuous treatment with TNF blockers in combination with MTX is recommended. To compare this strategy with an initial combination of MTX and adalimumab (ADA) given for 3 months and then adjusted based on the disease activity status. Methods. Prospective unblinded randomized multicentre controlled 1-year trial in which 65 patients with early (5.1] RA were assigned to Group 1 (32 patients): MTX (0.3mg/kg/week, maximum of 20mg/week, without escalating dose regimen) or to Group 2 (33 patients): initial combination therapy with MTX (as in Group 1) and ADA (40 mg eow). In both groups, treatment was adjusted every 3 months. The aim was to achieve a low DAS (DAS28(ESR)
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- 2009
14. Primary neuroendocrine tumor of the sacrum: case report and review of the literature
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Pauline Beaussart, Fanny Dujardin, Denis Mulleman, Gonzague de Pinieux, Anne de Muret, Eric Waynberger, Philippe Rosset, Cambefort, Jeanne, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), and Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
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Male ,musculoskeletal diseases ,Sacrum ,medicine.medical_specialty ,medicine.medical_treatment ,Primary carcinoid ,[SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine ,Neuroendocrine tumors ,[SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Neuroendocrine tumor ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Aged ,Spinal Neoplasms ,business.industry ,medicine.disease ,Magnetic Resonance Imaging ,Low back pain ,Primary tumor ,3. Good health ,Surgery ,body regions ,Radiation therapy ,Neuroendocrine Tumors ,030220 oncology & carcinogenesis ,Orthopedic surgery ,Radiology ,medicine.symptom ,Tomography, X-Ray Computed ,business ,Sacrococcygeal teratoma ,030217 neurology & neurosurgery ,MRI - Abstract
International audience; Primary carcinoid tumor (well-differentiated neuroendocrine tumor) of the bone involving the sacrum is extremely rare. We report the case of a 72-year-old man who presented with a 20-year history of intermittent low back pain and was found to have an intraosseous sacral mass on imaging. A needle biopsy revealed that this lesion was a well-differentiated neuroendocrine tumor. Workup did not show any primary tumor or other metastatic disease. There was no associated tailgut cyst or sacrococcygeal teratoma. The lesion was treated with radiation therapy because a surgical approach was rejected. The patient is free of metastatic disease after 28 years evolution of the lesion, retrospectively seen to be present on a conventional radiography performed in 1980. A review of the literature revealed 20 case reports of neuroendocrine tumors arising from the presacral region (with or without associated tailgut cyst or sacrococcygeal teratoma) and sometimes extending to the sacrum. One additional case was located within the neural canal and involved the sacrum, the presacral region, and the rectal wall. Our case is the only tumor arising primarily from the sacrum. The long evolution of this lesion without any other location makes metastatic disease very improbable and this case appears to be a unique example of primary intraosseous sacral carcinoid tumor.
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- 2009
15. A plea for reason in using magnetic resonance imaging for the diagnostic and therapeutic management of spondyloarthropathies
- Author
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Thao Pham, Pascal Claudepierre, Daniel Wendling, Philippe Goupille, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Service de rhumatologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Rhumatologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Cambefort, Jeanne, and Université de Tours-Centre National de la Recherche Scientifique (CNRS)
- Subjects
MESH: Antirheumatic Agents ,medicine.medical_specialty ,[SDV]Life Sciences [q-bio] ,MEDLINE ,MESH: Magnetic Resonance Imaging ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Magnetic resonance imaging ,0302 clinical medicine ,Plea ,Rheumatology ,X ray computed ,Diagnosis ,medicine ,Humans ,Spondyloarthropathies ,MESH: Sacroiliac Joint ,MESH: Case Management ,ComputingMilieux_MISCELLANEOUS ,030203 arthritis & rheumatology ,MESH: Humans ,medicine.diagnostic_test ,Tumor Necrosis Factor-alpha ,business.industry ,Sacroiliac Joint ,Case management ,Spine ,3. Good health ,[SDV] Life Sciences [q-bio] ,Treatment ,[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,Antirheumatic Agents ,MESH: Tumor Necrosis Factor-alpha ,Spondylarthropathies ,Radiology ,Tomography, X-Ray Computed ,MESH: Tomography, X-Ray Computed ,Nuclear medicine ,business ,Case Management ,MESH: Spine ,MESH: Spondylarthropathies ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience
- Published
- 2009
16. Cetuximab Pharmacokinetics Influences Progression-Free Survival of Metastatic Colorectal Cancer Patients
- Author
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Hervé Watier, M. Boisdron-Celle, Thierry Lecomte, Gilles Paintaud, Erick Gamelin, Friedrich Piller, Nicolas Azzopardi, Alain Morel, Valérie Gouilleux-Gruart, David Ternant, Céline Vignault-Desvignes, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), UPR1934, Parc Naturel Régional des Boucles de la Seine Normande, 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 de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Développement normal et pathologique des lymphocytes et signalisation, Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Immunologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Cytokines : structure, signalisation et prolifération tumorale, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cambefort, Jeanne, Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Population ,Urology ,Phases of clinical research ,Cetuximab ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Pharmacology ,Adenocarcinoma ,Antibodies, Monoclonal, Humanized ,030226 pharmacology & pharmacy ,Disease-Free Survival ,Drug Administration Schedule ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication ,medicine ,Humans ,Progression-free survival ,Neoplasm Metastasis ,education ,neoplasms ,ComputingMilieux_MISCELLANEOUS ,Aged ,Volume of distribution ,Aged, 80 and over ,education.field_of_study ,Cumulative dose ,business.industry ,Antibodies, Monoclonal ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Middle Aged ,digestive system diseases ,3. Good health ,Irinotecan ,Oncology ,030220 oncology & carcinogenesis ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Female ,Fluorouracil ,business ,Colorectal Neoplasms ,medicine.drug - Abstract
Purpose: An ancillary phase II study was conducted to study interindividual variability in cetuximab pharmacokinetics and its influence on progression-free survival (PFS) in metastatic colorectal cancer patients cotreated with irinotecan and 5-fluorouracil. Experimental Design: Ninety-six patients received cetuximab as an infusion loading dose of 400 mg/m2 followed by weekly infusions of 250 mg/m2. Doses of irinotecan and 5-fluorouracil were adjusted individually. Cetuximab concentrations were measured by ELISA. Compartmental pharmacokinetic parameters were estimated by a population approach, and PFS was analyzed using a Cox model. Results: Cetuximab pharmacokinetics was best described using a two-compartment model with both first-order and saturable (zero-order) elimination. Estimated pharmacokinetic parameters (% standard error) were as follows: central volume of distribution V1 = 2.96 L (4%), peripheral volume of distribution V2 = 4.65 L (6%), elimination clearance CL = 0.497 L/d (4%), distribution clearance Q = 0.836 L/d (8%), and zero-order elimination rate k0 = 8.71 mg/d (10%). Body surface area influenced V1, V2, and k0. Pretreatment serum albumin influenced CL. Risk of disease progression decreased with cetuximab global clearance (cumulative dose/cumulative area under the concentration versus time curve; P = 0.00016). Median PFS of patients with a cetuximab residual concentration on day 14 below median value was 3.3 months as compared with 7.8 months for the other patients (P = 0.004). Conclusions: Cetuximab pharmacokinetics in colorectal cancer patients can be described using a model combining linear and nonlinear elimination rates. PFS is influenced by global clearance of cetuximab, a parameter that can be estimated using cetuximab residual concentration on day 14. Clin Cancer Res; 17(19); 6329–37. ©2011 AACR.
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- 2011
17. Therapeutic Drug Monitoring of Infliximab in Spondyloarthritis: An Observational Open-Label Study
- Author
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Jean-Camille Méric, F. Lauféron, Delphine Chu Miow Lin, Emilie Ducourau, Philippe Goupille, Gilles Paintaud, Hervé Watier, Denis Mulleman, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Cambefort, Jeanne
- Subjects
Adult ,Male ,musculoskeletal diseases ,medicine.medical_specialty ,medicine.drug_class ,Decision Making ,Anti-Inflammatory Agents ,Monoclonal antibody ,dose-response relationship ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,Internal medicine ,Spondylarthritis ,ankylosing spondylitis ,medicine ,Humans ,Pharmacology (medical) ,Trough Concentration ,030212 general & internal medicine ,skin and connective tissue diseases ,BASDAI ,Aged ,030203 arthritis & rheumatology ,Pharmacology ,drug monitoring ,Ankylosing spondylitis ,medicine.diagnostic_test ,business.industry ,Antibodies, Monoclonal ,Middle Aged ,medicine.disease ,Infliximab ,3. Good health ,stomatognathic diseases ,Treatment Outcome ,Therapeutic drug monitoring ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Female ,Observational study ,business ,infliximab ,medicine.drug - Abstract
International audience; Background: Infliximab is a chimeric monoclonal antibody that binds to human tumor necrosis factor alpha and which is approved for refractory spondyloarthritis (SpA). Individual adjustment of infliximab dosage may help to improve the therapeutic response in SpA. We investigated whether a knowledge of infliximab serum concentration modifies physician decision and improves the control of disease activity in SpA. Methods: Thirty-two patients routinely treated with infliximab were included in an observational open-label study. On visit 1 (V1), according to disease activity, a preliminary therapeutic decision was selected among 4 therapeutic options (ie, decrease, increase, maintain the dosage of infliximab, or switch over for another treatment), and a blood sample was collected to measure infliximab trough serum concentration. The final therapeutic decision, based on both disease activity and infliximab serum concentration assessed at V1, was applied at the following infusion (V2). Clinical and biological evaluations were performed at V3 and V4 and compared with those at V1. Results: The measurement of infliximab trough concentration modified the therapeutic decision for 10 patients (31%). For both patients with increased or decreased infliximab dosage at V2, median Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was similar at V3 or V4 as compared with that at V1. However, a trend for an inverse relationship between infliximab serum concentrations and BASDAI was observed. Conclusions: Knowledge of infliximab trough concentration modified the therapeutic decision for SpA patients with predominantly axial symptoms but did not improve the control of disease activity as estimated by the BASDAI.
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- 2011
18. PSORIATIC ARTHRITIS: A MULTIDISCIPLINARY APPROACH Strategic recommendations on the therapeutic management of psoriatic arthritis
- Author
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Passeron, Th., Goupille, Philippe, Boulinguez, S., Centre méditérannéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Cambefort, Jeanne
- Subjects
[SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology ,ComputingMilieux_MISCELLANEOUS ,[SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology - Abstract
National audience
- Published
- 2011
19. Successful autologous stem cell transplantation in Gaucher disease patient with multiple myeloma
- Author
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François Maillot, Philippe Goupille, Laurence Picon, Lotfi Benboubker, Alexandre Aubourg, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Cambefort, Jeanne
- Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,Oncology ,medicine.medical_specialty ,business.industry ,Disease patient ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Hematology ,medicine.disease ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Autologous stem-cell transplantation ,Text mining ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,business ,Multiple myeloma ,ComputingMilieux_MISCELLANEOUS ,030215 immunology - Abstract
International audience
- Published
- 2011
20. Regulation of IGF-1-dependent cyclin D1 and E expression by hEag1 channels in MCF-7 cells: The critical role of hEag1 channels in G1 phase progression
- Author
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Valérie Gouilleux-Gruart, Halima Ouadid-Ahidouch, Anne-Sophie Borowiec, Kaiss Lassoued, Frédéric Hague, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Développement normal et pathologique des lymphocytes et signalisation, Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cambefort, Jeanne, Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Time Factors ,Cyclin E ,Cyclin D ,Cyclin A ,Cyclin B ,G1/S transition ,Cell cycle ,S Phase ,Cyclin expression regulation ,03 medical and health sciences ,0302 clinical medicine ,Cyclin D1 ,Cell Line, Tumor ,Potassium Channel Blockers ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Insulin-Like Growth Factor I ,Molecular Biology ,030304 developmental biology ,Cyclin ,Oncogene Proteins ,0303 health sciences ,biology ,G1 Phase ,Cell Biology ,Astemizole ,hEag1 ,Ether-A-Go-Go Potassium Channels ,Up-Regulation ,Cell biology ,030220 oncology & carcinogenesis ,biology.protein ,IGF-1 ,Ion Channel Gating ,Cyclin A2 - Abstract
Insulin-like Growth Factor-1 (IGF-1) plays a key role in breast cancer development and cell cycle regulation. It has been demonstrated that IGF-1 stimulates cyclin expression, thus regulating the G1 to S phase transition of the cell cycle. Potassium (K(+)) channels are involved in the G1 phase progression of the cell cycle induced by growth factors. However, mechanisms that allow growth factors to cooperate with K(+) channels in order to modulate the G1 phase progression and cyclin expression remain unknown. Here, we focused on hEag1 K(+) channels which are over-expressed in breast cancer and are involved in the G1 phase progression of breast cancer cells (MCF-7). As expected, IGF-1 increased cyclin D1 and E expression of MCF-7 cells in a cyclic manner, whereas the increase of CDK4 and 2 levels was sustained. IGF-1 stimulated p21(WAF1/Cip1) expression with a kinetic similar to that of cyclin D1, however p27(Kip1) expression was insensitive to IGF-1. Interestingly, astemizole, a blocker of hEag1 channels, but not E4031, a blocker of HERG channels, inhibited the expression of both cyclins after 6-8h of co-stimulation with IGF-1. However, astemizole failed to modulate CDK4, CDK2, p21(WAF1/Cip1) and p27(Kip1) expression. The down-regulation of hEag1 by siRNA provoked a decrease in cyclin expression. This study is the first to demonstrate that K(+) channels such as hEag1 are directly involved in the IGF-1-induced up-regulation of cyclin D1 and E expression in MCF-7 cells. By identifying more specifically the temporal position of the arrest site induced by the inhibition of hEag1 channels, we confirmed that hEag1 activity is predominantly upstream of the arrest site induced by serum-deprivation, prior to the up-regulation of both cyclins D1 and E. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
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- 2011
21. TNF ALPHA ANTAGONIST THERAPY and safety monitoring
- Author
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Séverine Guillaume-Czitrom, Olivier Vittecoq, Jacques Morel, Manuelle Viguier, Jean-Marie Berthelot, Eric Hachulla, Jean Sibilia, Anne Sudre, Vincent Goëb, Laure Gossec, Philippe Goupille, Bruno Fautrel, Alain Saraux, Valérie Martinez, Yoram Bouhnik, Tu-Anh Tran, Xavier Puéchal, Jean-Francis Maillefert, Pascal Claudepierre, Isabelle Huet, Thao Pham, Pascal Richette, Jean-Pierre Marolleau, Daniel Wendling, Philippe Gaudin, Martin Soubrier, Denis Jullien, Thierry Schaeverbeke, Luc Mouthon, Marc Lémann, Hervé Bachelez, Jacques Blacher, Arnaud Constantin, Odile Launay, Xavier Mariette, Stanislas Pol, Charles Masson, Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Université Paris Descartes - Paris 5 (UPD5), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Lapeyronie [Montpellier] (CHU), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université Paris Diderot - Paris 7 (UPD7)-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), CHU Pitié-Salpêtrière [APHP], CHU Cochin [AP-HP], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Cambefort, Jeanne, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Génétique, Immunothérapie, Chimie et Cancer ( GICC ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hospices Civils de Lyon ( HCL ), Université Paris Descartes - Paris 5 ( UPD5 ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Hôpital Lapeyronie [Montpellier] ( CHU ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 ( UPD7 )
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Adult ,Male ,medicine.medical_specialty ,Fact sheet ,[SDV]Life Sciences [q-bio] ,MEDLINE ,Antibodies, Monoclonal, Humanized ,Receptors, Tumor Necrosis Factor ,Etanercept ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Pregnancy ,Internal medicine ,medicine ,Adalimumab ,Humans ,Spondylitis, Ankylosing ,030212 general & internal medicine ,Intensive care medicine ,Adverse effect ,Randomized Controlled Trials as Topic ,030203 arthritis & rheumatology ,Evidence-Based Medicine ,Tumor Necrosis Factor-alpha ,business.industry ,Antibodies, Monoclonal ,Evidence-based medicine ,Middle Aged ,Infliximab ,3. Good health ,Surgery ,[SDV] Life Sciences [q-bio] ,Immunoglobulin G ,Practice Guidelines as Topic ,Female ,business ,medicine.drug - Abstract
Objectives To develop and/or update fact sheets about TNFα antagonists treatments, in order to assist physicians in the management of patients with inflammatory joint disease. Methods 1. selection by a committee of rheumatology experts of the main topics of interest for which fact sheets were desirable; 2. identification and review of publications relevant to each topic; 3. development and/or update of fact sheets based on three levels of evidence: evidence-based medicine, official recommendations, and expert opinion. The experts were rheumatologists and invited specialists in other fields, and they had extensive experience with the management of chronic inflammatory diseases, such as rheumatoid. They were members of the CRI (Club Rhumatismes et Inflammation), a section of the Societe Francaise de Rhumatologie. Each fact sheet was revised by several experts and the overall process was coordinated by three experts. Results Several topics of major interest were selected: contraindications of TNFα antagonists treatments, the management of adverse effects and concomitant diseases that may develop during these therapies, and the management of everyday situations such as pregnancy, surgery, and immunizations. After a review of the literature and discussions among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: 1. in RA and SpA, initiation and monitoring of TNFα antagonists treatments, management of patients with specific past histories, and specific clinical situations such as pregnancy; 2. diseases other than RA, such as juvenile idiopathic arthritis; 3. models of letters for informing the rheumatologist and general practitioner; 4. and patient information. Conclusion These TNFα antagonists treatments fact sheets built on evidence-based medicine and expert opinion will serve as a practical tool for assisting physicians who manage patients on these therapies. They will be available continuously at www.cri-net.com and updated at appropriate intervals.
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- 2011
22. Persistant Lymphopenia after Thymoglobulin (R) in Kidney Transplantation Is Associated with Clinical and Genetic Factors
- Author
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Longuet, H., Jean-Michel. Halimi, Gilles Thibault, Jocelyne Marliere, Velge, F., Christelle Barbet, Yvon Lebranchu, claude baron, Matthias Buchler, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Cambefort, Jeanne
- Subjects
[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2011
23. Model-based design of rituximab dosing optimization in follicular non-hodgkin lymphoma
- Author
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Ternant, David, Cartron, Guillaume, Henin, E., Tod, Michel, Girard, Pascal, Paintaud, Gilles, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Cambefort, Jeanne, and Université de Tours-Centre National de la Recherche Scientifique (CNRS)
- Subjects
[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2011
24. SFRO 2010: congress highlights
- Author
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Pointreau, Y., Hennequin, C., Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Cambefort, Jeanne
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[SDV] Life Sciences [q-bio] ,Prostate cancer ,Radiotherapy ,2010 SFRO Congress ,[SDV]Life Sciences [q-bio] ,Quality ,Technical in novations - Abstract
National audience; The 21(st) SFRO Congress during October 2010 focused on three main topics: prostate, radiotherapy technical innovations (including reirradiation) and quality of life. The pitfalls of IMRT (treatment time, number of monitor unit, low doses) are in competition with arctherapy dynamic techniques that offer reduction treatment time for an equivalent ballistic. These techniques with high dose gradient should be coupled with the better imagery of repositioning (IGRT) to ensure benefice. A prospective evaluation of toxicity, clinical benefit on tumor control but also on quality of life of patients is necessary. In many current and future clinical trials, quality of life related to health will be a relevant outcome measurement to secure the importance of treatment for the patient and the health system. (C) 2011 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.
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- 2011
25. Development of an ion-pairing reversed-phase liquid chromatography method using a double detection analysis (UV and evaporative light scattering detection) to monitor the stability of Alimta (R)-pemetrexed preparations: Identification and quantification of L-glutamic acid as a potential degradation product
- Author
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Respaud, Renaud, Tournamille, Jean-Francois, Croix, Cecile, Laborie, Helene, Elfakir, Claire, Viaud-Massuard, Marie-Claude, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Organique et Analytique (ICOA), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Orléans (UO)-Institut de Chimie du CNRS (INC), Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Cambefort, Jeanne
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Ion-pairing agents ,ELSD ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Pemetrexed ,HPLC ,L-Glutamic acid - Abstract
International audience; A new method based on high-performance liquid chromatography coupled to ultraviolet and evaporative light scattering detection (HPLC-UV-ELSD) was developed for the determination of L-glutamic acid, a potential degradation product of pemetrexed, and for the quantification of pemetrexed itself. This is an ion-pairing, reversed-phase method. The column was a Synergi MAX-RP C12 4 mu m (150 mm x 4.6 mm). The mobile phase was 1 mM tridecafluorolteptanoic acid in aqueous solution and acetonitrile under gradient elution mode. L-Glutamic acid was detected by ELSD, and pemetrexed by UV at 254 nm. Good resolution was achieved between pemetrexed and L-glutamic acid. The HPLC method was validated according to SFSTP and ICH guidelines, and applied the accuracy profile procedure with a five-level validation experimental design. For pemetrexed, the decision criteria selected consisted of the acceptability limits (+/- 3%) and the proportion of results within the calculated tolerance intervals (95%). In conclusion, the proposed analytical procedures were validated over the selected validation domains for L-glutamic acid (0.005-0.025 mg/mL) and pemetrexed (0.4-0.6 mg/mL) and shown to provide a very effective method. (C) 2010 Elsevier B.V. All rights reserved.
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- 2011
26. Optimizing TNF alpha antagonist therapy in patients with spondyloarthritis: Why and how?
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Wendling, Daniel, Prati, Clement, Goupille, Philippe, Mulleman, Denis, Cambefort, Jeanne, Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Université de Tours-Centre National de la Recherche Scientifique (CNRS)
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Treatment ,[SDV] Life Sciences [q-bio] ,TNF alpha antagonists ,[SDV]Life Sciences [q-bio] ,Spondyloarthritis ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
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- 2011
27. Menin controls the concentration of retinoblastoma protein
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Patrick Gaudray, Laura Desbourdes, Laetitia Corset, Günther Weber, Dina Ivo, Cambefort, Jeanne, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), and Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
[SDV]Life Sciences [q-bio] ,Biology ,Retinoblastoma Protein ,Retinoblastoma-like protein 1 ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Proto-Oncogene Proteins ,E2F1 ,Animals ,Humans ,MEN1 ,Molecular Biology ,Gene ,030304 developmental biology ,0303 health sciences ,Cell Cycle ,Retinoblastoma protein ,Cell Biology ,Cell cycle ,eye diseases ,Chromatin ,[SDV] Life Sciences [q-bio] ,Knockout mouse ,Cancer research ,biology.protein ,030211 gastroenterology & hepatology ,Developmental Biology - Abstract
International audience; Menin, the protein encoded by the Multiple Endocrine Neoplasia type 1 gene, is involved in the cell cycle control through its participation in functional dynamics of chromatin and regulation of transcription. RB, the protein of the retinoblastoma gene RB1, controls the progression of the cell cycle and is regulated in its activity by means of a feedback by phosphorylation. Studies in double heterozygous knockout mice for Men1 and the Retinoblastoma gene Rb1 have recently indicated that both genes may be implicated in the same pathways. In the course of our studies on Menin, we found that after suppression or in absence of Menin, RB1 expression was strongly reduced in a posttranscriptional manner. Under conditions of growth arrest, the hyperphosphorylated form of RB was most strongly affected, whereas its hypophosphorylated form was less or not at all reduced. Our findings confirm the hypothesis that the pathways of two tumor suppressor genes are connected.
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- 2011
28. Cost-Effectiveness of UGT1A1*28 Genotyping in Preventing Severe Neutropenia Following FOLFIRI Therapy in Colorectal Cancer
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Hélène Bourgoin, Thierry Lecomte, Hélène Blasco, Chantal Le Guellec, Solen Pichereau, Anne Le Louarn, Cambefort, Jeanne, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), and Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
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Oncology ,medicine.medical_specialty ,Neutropenia ,Genotype ,Cost effectiveness ,Cost-Benefit Analysis ,Population ,Leucovorin ,Pharmaceutical Science ,lcsh:RS1-441 ,030226 pharmacology & pharmacy ,Severity of Illness Index ,lcsh:Pharmacy and materia medica ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Granulocyte Colony-Stimulating Factor ,Medicine ,Humans ,Genetic Testing ,Glucuronosyltransferase ,education ,Genotyping ,Pharmacology ,education.field_of_study ,Polymorphism, Genetic ,business.industry ,Decision Trees ,lcsh:RM1-950 ,medicine.disease ,3. Good health ,Surgery ,Irinotecan ,Models, Economic ,lcsh:Therapeutics. Pharmacology ,Bone marrow suppression ,030220 oncology & carcinogenesis ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,FOLFIRI ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Camptothecin ,Fluorouracil ,business ,Colorectal Neoplasms ,Febrile neutropenia ,medicine.drug - Abstract
International audience; Purpose. Functional polymorphisms of the UGT1A1 gene, particularly the UGT1A1*28 variant, are associated with the severity of the bone marrow suppression in patients with metastatic colorectal cancer receiving irinotecan. This study assesses the cost-effectiveness of screening for UGT1A1*28 polymorphism associated with primary prophylactic Granulocytes Colony Stimulating Factor in patients homozygous for the *28 allele. The effectiveness was estimated based on the number of neutropenia avoided. Methods. This study was conducted from a hospital perspective. Relevant literature was analysed from 2000 to 2009 in order to select data and model parameters. We modelled a theoretical population treated with combined 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) for metastatic colorectal cancer. A decision tree simulated the health outcomes, measured by the prevalence of neutropenic events for two strategies, with or without UGT1A1 genotype screening. The model incorporated direct hospital costs in 2006 and was validated with a sensitivity analysis. We calculated the cost-effectiveness ratio: CE=Delta C / Delta E = "genotyping" cost - "no genotyping" cost / number of febrile neutropenia avoided. Results. In the "genotyping strategy", the cost to avoid one febrile neutropenia event per 1000 patients treated was (sic) 942.8 to (sic) 1090.1. The sensitivity analysis showed a better CE ratio of (sic) 733.4 to (sic) 726.6 per febrile neutropenic event avoided. Conclusions. UGT1A1 genotype screening before irinotecan treatment is a cost-efficient strategy for the hospital. Systematic genotyping prior to chemotherapy, and administration of CSF in patients homozygotes for the *28 allele allow to avoid 91 febrile neutropenias at an acceptable cost.
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- 2011
29. Transposase-Transposase Interactions in MOS1 Complexes: A Biochemical Approach
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Carpentier, Guillaume, Jaillet, Jerome, Pflieger, Aude, Adet, Jeremy, Renault, Sylvaine, Auge-Gouillou, Corinne, Cambefort, Jeanne, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
transposase dimerization ,genetic structures ,transposase/DNA complexes ,transposition regulation ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,mariner transposition - Abstract
International audience; Transposases are proteins that have assumed the mobility of class II transposable elements. In order to map the interfaces involved in transposase transposase interactions, we have taken advantage of 12 transposase mutants that impair mariner transposase-transposase interactions taking place during transposition. Our data indicate that transposase transposase interactions regulating Mos1 transposition are sophisticated and result from (i) active MOS1 dimerization through the first HTH of the N-terminal domain, which leads to inverted terminal repeat (ITR) binding; (ii) inactive dimerization carried by part of the C-terminal domain, which prevents ITR binding; and (iii) oligomerization. Inactive dimers are nonpermissive in organizing complexes that produce ITR binding, but the interfaces (or interactions) supplied in this state could play a role in the various rearrangements needed during transposition. Oligomerization is probably not due to a specific MOS1 domain, but rather the result of nonspecific interactions resulting from incorrect folding of the protein. Our data also suggest that the MOS1 catalytic domain is a main actor in the overall organization of MOS1, thus playing a role in MOS1 oligomerization. Finally, we propose that MOS1 behaves as predicted by the pre-equilibrium existing model, whereby proteins are found to exist simultaneously in populations with diverse conformations, monomers and active and inactive dimers for MOS1. We were able to identify several MOS1 mutants that modify this pre-existing equilibrium. According to their properties, some of these mutants will be useful tools to break down the remaining gaps in our understanding of mariner transposition. (C) 2010 Elsevier Ltd. All rights reserved.
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- 2011
30. Influence of Fc gamma rIIIA genetic polymorphism on lymphocyte depletion in kidney transplanted patients
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Ternant, David, Buchler, Matthias, Thibault, Gilles, Al Najjar, Azmi, Watier, Herve, Lebranchu, Yvon, Paintaud, Gilles, Cambefort, Jeanne, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
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[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
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- 2011
31. Bacteria and HIT: a close connection?
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Yves Gruel, Hervé Watier, Cambefort, Jeanne, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), and Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
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[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,0303 health sciences ,Immunology ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Cell Biology ,Hematology ,Heparin ,Biology ,biology.organism_classification ,Biochemistry ,3. Good health ,Connection (mathematics) ,Microbiology ,03 medical and health sciences ,0302 clinical medicine ,biology.protein ,medicine ,Antibody ,Bacteria ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,030215 immunology ,medicine.drug - Abstract
HIT is caused by antibodies specific to PF4/heparin complexes. In this issue of Blood, Krauel et al report novel findings supporting the hypothesis that primary synthesis of these antibodies results from bacterial infections. HIT, therefore, appears to be a misdirected antibacterial host defense response. 1 .
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- 2011
32. Long-Term Effects of In Vivo Administration of An Anti-VLA-4 Antibody (natalizumab) on Mobilization of Committed and Primitive Hematopoietic Progenitor Cells In Humans
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Gilles Thibault, Anne-Marie Guennoc, Jorge Domenech, Michel Degenne, Zakia Bekhechi, Christian Binet, Olivier Herault, Maud Pallix, Elfi Ducrocq, Julien Goustille, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Cambefort, Jeanne
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[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,Myeloid ,Immunology ,CD34 ,Biology ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Natalizumab ,medicine ,Progenitor cell ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0303 health sciences ,Mesenchymal stem cell ,VLA-4 ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Cell Biology ,Hematology ,3. Good health ,Haematopoiesis ,medicine.anatomical_structure ,Stem cell ,030215 immunology ,medicine.drug - Abstract
Abstract 2264 The alpha4 beta1 integrin (VLA-4) exert a critical role on hematopoiesis by confining hematopoietic stem cells (HSC) and progenitor cells (HPC) within the niche. Previous preclinical studies have pointed out this role showing that HPCs can be mobilized by in vivo administration of a blocking anti-VLA-4 antibody (Ab) (Papayannopoulou et al, 1993). Very recently, two papers (Bonig et al, 2008; Zohren et al, 2008) have shown that such Ab exhibits a similar effect in humans for one month after treatment by natalizumab. In the present study, we have investigated long-term hematopoietic effects (up to 23 months) of repeated infusions of natalizumab in patients treated for multiple sclerosis (n=22). Seven patients have been explored sequentially (every month for one year) and 15 have been studied punctually (6 before and 9 after one year of treatment). We found that peripheral blood leukocytosis was consistently increased for one year in relation to lymphocytes, particularly to B lineage (by 3-fold). In parallel, an increase of circulating HPCs (CD34+ cells and total CFU) was observed and appeared more pronounced with levels above baseline values in all the patients studied (by 6-fold) while no increase of circulating mesenchymal stromal cells (CFU-F) was found. The increase was noted for both lymphoid (T and B lineages) and myeloid (granulo-monocyte, erythroid, and megakaryocyte) committed progenitor cells but also for primitive HPC (CD34+CD38- cells and CAFC). This effect was still found at long-term (up to two years of treatment) for both committed and primitive HPC. In conclusion, the HPC mobilizing effect of chronic administration of anti-VLA-4 Ab in humans involves all types of HPCs (lymphoid and myeloid, committed and primitive ones) and is not exhausted with time. Disclosures: No relevant conflicts of interest to declare.
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- 2010
33. EFFECTS OF INTRA-ARTICULAR INJECTIONS OF HYLAN GF-20 ON SERUM AND URINE BIOMARKERS IN PATIENTS WITH KNEE OSTEOARTHRITIS: THE BIOVISCO STUDY
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Conrozier, T., Chevalier, X., Balblanc, J.-C., Richette, P., Rannou, François, Mulleman, D., Maillet, B., Maillefert, J.-F., Mathieu, P., Henrotin, Y., Vignon, E., Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Lariboisière - Université Paris Diderot - Paris 7 (UP7), CHU Cochin [APHP], Génétique, Immunothérapie, Chimie et Cancer (GICC), Université François Rabelais - Tours - Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Dijon (CHU Dijon), Cambefort, Jeanne, Université de Tours-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), and CHU Cochin [AP-HP]
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[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
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- 2010
34. VEGF Polymorphisms are Associated With an Increasing Risk of Developing Renal Cell Carcinoma
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Bruyere, Franck, Hovens, Christopher M., Marson, Marie-Noelle, d'Arcier, Benjamin Faivre, Costello, Anthony J., Watier, Herve, Linassier, Claude, Ohresser, Marc, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Cambefort, Jeanne
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genotype ,risk factors ,genetic ,carcinoma ,vascular endothelial growth factors ,[SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology ,[SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology ,polymorphism ,renal cell - Abstract
International audience; Purpose: Vascular endothelial cell growth factor is studied in different malignant tumors as a key endothelial cell mitogen. Many single nucleotide polymorphisms in the VEGF gene have been described. We compared VEGF gene polymorphisms between a control group and a renal cancer group. Materials and Methods: This study was performed in 202 control, white, healthy blood donors (control group) and in 51 consecutive patients with renal cell carcinoma. We studied VEGF genotype polymorphisms at positions -2549, -460, -1154, -405 and -936 using polymerase chain restriction fragment length polymorphism, and looked for correlations with clinical data. Results: No association was found between VEGF gene polymorphism and renal cell carcinoma prognostic parameters. However, in contrast as observed for controls and other polymorphisms the patient group displayed a heterozygote excess (p = 0.0179, 35.9% more than that expected) at the -460 polymorphism. Comparing the control group and the renal cell carcinoma group we detected a significantly increased risk of renal cell carcinoma in subjects with the C-460T polymorphism. T carrier genotypes and the T allele increased the risk of renal cell carcinoma with an OR of 14.15 (95% CI 1.900-105.41, p = 0.0017) and 2.14 (95% CI 1.34-3.419, p = 0.0018), respectively. The genotype at the -2549 polymorphism exhibited a nonsignificant trend for increased risk but the D allele was significantly associated with increased risk (p = 0.0305). Conclusions: Our results suggest that the -460 polymorphism is a risk factor for renal cancer. An individual screening test could be proposed for high risk populations.
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- 2010
35. Normal tissue tolerance to external beam radiation therapy: Larynx and pharynx
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Debelleix, C., Pointreau, Y., Lafond, C., Denis, F., Calais, G., Bourhis, J.-H., Hôpital Saint-André, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), and Cambefort, Jeanne
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Ionizing radiation ,Organ at risk ,otorhinolaryngologic diseases ,Pharynx ,[SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine ,Larynx ,Tolerability ,[SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine - Abstract
National audience; For head and neck cancers, the radiation dose usually needed to sterilize a macroscopic tumour is at least 70 Gy in conventional fractionation. In the larynx, this dose level enables optimal tumour control while exposing the patient to a limited risk of severe complications. For oropharynx and nasopharynx tumors, it is sometimes possible to limit the dose received by the larynx according to the extent of the primary lesion. Thus, if the tumour constraints permit, the maximum dose to the larynx must be less than 63 to 66 Gy. To reduce the risk of laryngeal edema, it is recommended if possible to limit the mean non-involved larynx dose to 40 to 45 Gy. In the pharynx, literature's data suggested to minimize the volume of the pharyngeal constrictor muscles receiving a dose greater than or equal to 60 Gy. Limiting the volume receiving a dose greater than or equal to 50 Gy reduces the risk of dysphagia. These dose constraints should be tailored to each patient taking into account the extent of the initial primary lesion, the possible addition of chemotherapy or a modified fractionation radiotherapy. (C) 2010 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.
- Published
- 2010
36. Selection of regulator peptides of STAT5 activity
- Author
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Stephan-Queffeulou, E., Tian, L., Padiolleau, S., Yahiaoui, S., Gouilleux, F., Friboulet, A., Bihan-Avalle, B., Génie Enzymatique et Cellulaire (GEC), Université de Technologie de Compiègne (UTC)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Cambefort, Jeanne
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[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2010
37. Tocilizumab therapy and safety management
- Author
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Eric Bruckert, Thao Pham, Stanislas Pol, Daniel Wendling, Alain Saraux, Séverine Guillaume, Michel De Bandt, Jacques Morel, Bruno Fautrel, Charles Masson, Philippe Goupille, Xavier Mariette, Arnaud Constantin, Jacques-Eric Gottenberg, Pascal Claudepierre, Eric Hachulla, Laure Gossec, Thierry Schaeverbeke, Jean Sibilia, Xavier Puéchal, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Lapeyronie [Montpellier] (CHU), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pitié-Salpêtrière [APHP], CHU Cochin [APHP], Génétique, Immunothérapie, Chimie et Cancer (GICC), Université François Rabelais - Tours - Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bicêtre, Hôpital Claude Huriez, Université de Lille, Droit et Santé - Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Lapeyronie, Université Montpellier 1 (UM1) - Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier) - Hôpital Lapeyronie, CHU Bordeaux [Bordeaux] - Groupe hospitalier Pellegrin, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Cambefort, Jeanne
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musculoskeletal diseases ,medicine.medical_specialty ,Safety Management ,Fact sheet ,[SDV]Life Sciences [q-bio] ,Antibodies, Monoclonal, Humanized ,Tocilizumab therapy ,Arthritis, Rheumatoid ,03 medical and health sciences ,chemistry.chemical_compound ,Joint disease ,0302 clinical medicine ,Tocilizumab ,Rheumatology ,Patient Education as Topic ,Risk Factors ,Patient information ,Medicine ,Humans ,030304 developmental biology ,030203 arthritis & rheumatology ,0303 health sciences ,Evidence-Based Medicine ,business.industry ,Contraindications ,Antibodies, Monoclonal ,Evidence-based medicine ,3. Good health ,[SDV] Life Sciences [q-bio] ,chemistry ,Expert opinion ,Family medicine ,Physical therapy ,business - Abstract
To develop fact sheets about tocilizumab, in order to assist physicians in the management of patients with inflammatory joint disease.1. selection by a committee of rheumatology experts of the main topics of interest for which fact sheets were desirable; 2. identification and review of publications relevant to each topic; 3. development of fact sheets based on three levels of evidence: evidence-based medicine, official recommendations, and expert opinion. The 20 experts were rheumatologists and invited specialists in other fields, and they had extensive experience with the management of RA. They were members of the CRI (Club Rhumatismes et Inflammation), a section of the Société Francaise de Rhumatologie. Each fact sheet was revised by several. experts and the overall process was coordinated by three experts.Several topics of major interest were selected: contraindications of tocilizumab; the management of adverse effects and concomitant diseases that may develop during tocilizumab therapy; and the management of everyday situations such as pregnancy, surgery, and immunizations. After a review of the literature and discussions among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: Several topics of major interest were selected: contraindications of tocilizumab; the management of adverse effects and concomitant diseases that may develop during tocilizumab therapy; and the management of everyday situations such as pregnancy, surgery, and immunizations. After a review of the literature and discussions among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: 1. in RA, initiation and monitoring of tocilizumab therapy, management of patients with specific past histories, and specific clinical situations such as pregnancy; 2. diseases other than RA, such as juvenile idiopathic arthritis; 3. models of letters for informing the rheumatologist and general practitioner; 4. and patient information.These tocilizumab fact sheets built on evidence-based medicine and expert opinion will serve as a practical tool for assisting physicians who manage patients on tocilizumab therapy. They will be available continuously at www.cri-net.com and updated at appropriate intervals.
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- 2010
38. In Vitro Recombination and Inverted Terminal Repeat Binding Activities of the Mcmar1 Transposase
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Marie-Véronique Demattei, Corinne Augé-Gouillou, Yves Bigot, Sylvaine Renault, Hichem Lahouassa, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Cambefort, Jeanne
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Molecular Sequence Data ,DNA Footprinting ,Transposases ,Electrophoretic Mobility Shift Assay ,Biology ,Biochemistry ,Transposition (music) ,chemistry.chemical_compound ,Plasmid ,Sequence Homology, Nucleic Acid ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Direct repeat ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Insertion sequence ,Binding site ,Transposase ,Recombination, Genetic ,Genetics ,Base Sequence ,Terminal Repeat Sequences ,Molecular biology ,DNA-Binding Proteins ,chemistry ,DNA Transposable Elements ,In vitro recombination ,DNA - Abstract
International audience; The Mcmar1 mariner element (MLE) presents some intriguing features with two large, perfectly conserved, 355 bp inverted terminal repeats (ITRs) containing two 28 bp direct repeats (DRs). The presence of a complete ORF in Mcmar1 makes it possible to explore the transposition of this unusual M LE. Mcmar1 transposase (MCMAR1) was purified, and in vitro transposition assays showed that it is able to promote ITR-dependent DNA cleavages and recombination events, which correspond to plasmid fusions and transpositions with imprecise ends. Further analyses indicated that MCMAR1 is able to interact with the 355 bp ITR through two DRs: the EDR (external DR) is a high-affinity binding site for MCMAR1, whereas the IDR (internal DR) is a low-affinity binding site. The main complex detected within the EDR contained a transposase dimer and only one DNA molecule. We hypothesize that the inability of MCMAR1 to promote precise in vitro transposition events could be due to mutations in its ORF sequence or to the specific features of transposase binding to the ITR. Indeed, the ITR region spanning from EDR to IDR resembles a MITE and could be bent by specific host factors. This suggests that the assembly of the transposition complex is more complex than that of those involved in the mobility of the Mos1 and Hintar1 mariner elements.
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- 2010
39. Implication of the calcium sensing receptor and the Phosphoinositide 3-kinase/Akt pathway in the extracellular calcium-mediated migration of RAW 264.7 osteoclast precursor cells
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Laurent Petit, Said Kamel, Ziad A. Massy, Cédric Boudot, Fabrice Gouilleux, Zuzana Saidak, Abdel Krim Boulanouar, Romuald Mentaverri, Michel Brazier, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), MECANISMES PHYSIOPATHOLOGIQUES ET CONSEQUENSES DES CALCIFICATIONS CARDIOVASCULAIRES, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours, Université de Tours-Centre National de la Recherche Scientifique (CNRS), Cambefort, Jeanne, Université de Tours (UT), and Gouilleux, Fabrice
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MAPK/ERK pathway ,Histology ,Physiology ,Endocrinology, Diabetes and Metabolism ,p38 mitogen-activated protein kinases ,[SDV]Life Sciences [q-bio] ,Osteoclasts ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Akt phosphorylation ,Phosphoinositide 3-kinase ,Bone remodeling ,Cell Line ,03 medical and health sciences ,Mice ,Osteoclast ,Cell Movement ,medicine ,Animals ,Osteoclast precursors ,Phosphorylation ,10. No inequality ,Protein kinase B ,1-Phosphatidylinositol 4-Kinase ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,PI3K/AKT/mTOR pathway ,Migration ,Extracellular Ca(2+) ,030304 developmental biology ,0303 health sciences ,biology ,Calcium sensing receptor ,030302 biochemistry & molecular biology ,Extracellular Ca2+ ,Molecular biology ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,biology.protein ,Calcium ,Calcium-sensing receptor ,Proto-Oncogene Proteins c-akt ,Receptors, Calcium-Sensing ,Signal Transduction - Abstract
International audience; While the processes involved in the formation, maturation and apoptosis of osteoclasts have been investigated extensively in previous studies, little is known about the mechanisms responsible for the localization and homing of osteoclast precursor cells to the bone environment in order to initiate the bone remodeling process. Recent studies have suggested that the extracellular Ca(2+) (Ca(o)(2+)) concentration gradient present near the bone environment may be one of the participating factors, producing a chemoattractant effect on osteoclast precursors. Using the murine osteoclast precursor cells of the monocyte-macrophage lineage, the RAW 264.7 cell line, we have shown that Ca(o)(2+) increases the migration of these cells in a directional manner. The participation of the calcium sensing receptor (CaR) in this effect was tested by knocking down its expression through RNA interference, which resulted in an abolition of the migratory response. By the use of specific pathway inhibitors and western blot analysis, the phosphoinositide 3-kinase (PI3K)/Akt and phospholipase C beta pathways were shown to be implicated in the migratory effect. The implication of the Akt pathway in the Ca(o)(2+)-induced chemoattraction of RAW 264.7 cells was also confirmed by transducing the cells with the fusion protein TAT-dominant negative-Akt, which decreased the migratory effect. In contrast, the MAPK pathways (ERK1/2, p38 and JNK) were not involved in the production of the migratory effect. We conclude that through the activation of the CaR and subsequent signaling via the PI3K/Akt pathway, Ca(o)(2+) produces a chemoattractant effect on the osteoclast precursor RAW 264.7 cells. These results suggest that the Ca(o)(2+) gradient present near the bone may be one of the initiating factors for the homing of osteoclast precursors to bone, thus possibly playing a role in the initiation of bone remodeling. (C) 2010 Elsevier Inc. All rights reserved.
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- 2010
40. Site-directed integration of transgenes: transposons revisited using DNA-binding-domain technologies
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Demattei, Marie-Veronique, Thomas, Xavier, Carnus, Elodie, Auge-Gouillou, Corinne, Renault, Sylvaine, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Cambefort, Jeanne
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[SDV.GEN]Life Sciences [q-bio]/Genetics ,Targeted transposition ,Transgenesis ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,DNA binding domain ,Transposase - Abstract
International audience; In the last 20 years, tools derived from DNA transposons have made major contributions to genetic studies from gene delivery to gene discovery. Various complementary and fairly ubiquitous DNA vehicles have been developed. Although many transposons are efficient DNA vehicles, they appear to have limited ability to target specific sequences, since all that is required at the integration locus is the presence of a short 2- to 4-bp sequence. Consequently, insertions mediated by transposon-based vectors occur somewhat randomly. In the past 5 years, strategies have emerged to enhance the site-specificity of transposon-based vectors, and to avoid random integrations. The first proposes that new target site specificity could be grafted onto a transposase by adding a new DNA-binding domain. Alternative strategies consist of indirectly targeting either the transposase or the transposon to a chosen genomic locus. The most important information available about each strategy are presented, and limitations and future prospects are discussed.
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- 2010
41. Target site selection by the mariner-like element, Mos1
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Crenes, Gwenaelle, Moundras, Corinne, Demattei, Marie-Veronique, Bigot, Yves, Petit, Agnes, Renault, Sylvaine, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Cambefort, Jeanne
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Target ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,genetic structures ,Insertion site ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Transposase ,Mos1 - Abstract
International audience; The eukaryotic transposon Mos1 is a class-II transposable element that moves using a "cut-and-paste" mechanism in which the transposase is the only protein factor required. The formation of the excision complex is well documented, but the integration step has so far received less investigation. Like all mariner-like elements, Mos1 was thought to integrate into a TA dinucleotide without displaying any other target selection preferences. We set out to synthesize what is currently known about Mos1 insertion sites, and to define the characteristics of Mos1 insertion sequences in vitro and in vivo. Statistical analysis can be used to identify the TA dinucleotides that are non-randomly targeted for transposon integration. In vitro, no specific feature determining target choice other than the requirement for a TA dinucleotide has been identified. In vivo, data were obtained from two previously reported integration hotspots: the bacterial cat gene and the Caenorhabditis elegans rDNA locus. Analysis of these insertion sites revealed a preference for TA dinucleotides that are included in TATA or TA x TA motifs, or located within AT-rich regions. Analysis of the physical properties of sequences obtained in vitro and in vivo do not help to explain Mos1 integration preferences, suggesting that other characteristics must be involved in Mos1 target choice.
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- 2010
42. Trough Infliximab Concentrations Predict Efficacy and Sustained Control of Disease Activity in Rheumatoid Arthritis
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Jean-Pierre Valat, Gilles Paintaud, Denis Mulleman, David Ternant, Philippe Goupille, Charlotte Magdelaine-Beuzelin, Patrick Emond, Delphine Chu Miow Lin, Emilie Ducourau, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Cambefort, Jeanne, and Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
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Adult ,Male ,musculoskeletal diseases ,rheumatoid arthritis ,medicine.medical_specialty ,therapeutic drug monitoring ,030226 pharmacology & pharmacy ,Gastroenterology ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Predictive Value of Tests ,immune system diseases ,Internal medicine ,Immunopathology ,Medicine ,Humans ,Pharmacology (medical) ,skin and connective tissue diseases ,Aged ,030203 arthritis & rheumatology ,Pharmacology ,Autoimmune disease ,Biologic marker ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,Antibodies, Monoclonal ,Middle Aged ,medicine.disease ,Infliximab ,3. Good health ,Surgery ,Regimen ,stomatognathic diseases ,Cross-Sectional Studies ,Treatment Outcome ,Therapeutic drug monitoring ,Rheumatoid arthritis ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Delayed-Action Preparations ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Female ,business ,infliximab ,pharmacokinetics ,medicine.drug ,Follow-Up Studies - Abstract
International audience; Infliximab is a chimeric monoclonal antibody that binds to human tumor necrosis factor alpha and is approved for refractory rheumatoid arthritis. We studied the association between infliximab concentration and long-term control of disease activity in patients with rheumatoid arthritis treated on a routine basis both in cross-sectional analysis and over the long term. Trough serum infliximab concentrations were measured in patients with rheumatoid arthritis receiving infliximab infusions during the period August to October 2006. Disease activity was assessed by the Disease Activity Score for 28 Joints (DAS28) and usual biologic markers. During a 42-week follow-up period, patients were classified into two groups: those continuing with the same or lower doses of infliximab (Group A = treatment success) and those who switched to another bio-pharmaceutical or required an increase in infliximab dose (Group B = treatment failure). Treatment maintenance for Group A was analyzed by categories of infliximab concentration at baseline and compared by the log rank test. In 28 patients, C-reactive protein and infliximab concentrations were inversely related. Infliximab concentration in patients with low disease activity (DAS28 3.2 or less) was higher than in those with persistent active disease (DAS28 greater than 3.2); median values were 3.26 and 0.16 mg/L, respectively (P < 0.01). Analysis after 42 weeks showed that patients in Group A had higher infliximab concentrations at baseline than those with treatment failure (P < 0.01). In rheumatoid arthritis, infliximab concentration is predictive of sustained efficacy with the same infliximab regimen and should be considered on a routine basis.
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- 2010
43. A New and Efficient Ring Contraction of Dihydrobenzopyran to Dihydrobenzofuran Derivatives
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Chasset-Boye, Sophie, Viaud-Massuard, Marie-Claude, Suzenet, Franck, Guillaumet, Gerald, Institut de Chimie Organique et Analytique (ICOA), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Orléans (UO)-Institut de Chimie du CNRS (INC), Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Cambefort, Jeanne
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[SDV] Life Sciences [q-bio] ,benzopyran ,[SDV]Life Sciences [q-bio] ,benzofuran ,ring contraction ,Lewis acid - Abstract
International audience; A simple and efficient synthesis of benzofuran from benzopyran is described. The ring contraction takes place in the presence of Lewis acid. BBr3 in dichloromethane have proven to be the best conditions. A, mechanism Via an aziridinium intermediate is proposed.
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- 2010
44. Body surface area, erythrocyte sedimentation rate, methotrexate and antibodies to infliximab influence the pharmacokinetics of infliximab in rheumatoid arthritis
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Paintaud, Gilles, Ducourau, Emilie, Ternant, David, Gorondan, A., Legoff, B., Perdriger, A., Devauchelle, V., Solau-Gervais, E., Goupille, Philippe, Mulleman, Denis, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire [Rennes], Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Cambefort, Jeanne
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[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
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- 2010
45. Trough infliximab concentration may predict long-term maintenance of infliximab in ankylosing spondylitis
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I. Griffoul-Espitalier, Philippe Goupille, Nicolas Azzopardi, Gilles Paintaud, D. Chu Miow Lin, Denis Mulleman, Jean-Pierre Valat, Cambefort, Jeanne, Azzopardi, Nicolas, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Tours-Centre National de la Recherche Scientifique (CNRS)
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Male ,Time Factors ,[SDV]Life Sciences [q-bio] ,030226 pharmacology & pharmacy ,Severity of Illness Index ,Cohort Studies ,0302 clinical medicine ,Immunology and Allergy ,Infusions, Intravenous ,ComputingMilieux_MISCELLANEOUS ,[SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,Antibodies, Monoclonal ,Long term maintenance ,General Medicine ,Middle Aged ,Response to treatment ,3. Good health ,Predictive factor ,[SDV] Life Sciences [q-bio] ,Treatment Outcome ,[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,Antirheumatic Agents ,Female ,[SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy ,medicine.drug ,musculoskeletal diseases ,Adult ,medicine.medical_specialty ,Immunology ,Trough (economics) ,Risk Assessment ,Drug Administration Schedule ,03 medical and health sciences ,[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication ,Rheumatology ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Spondylitis, Ankylosing ,Aged ,Monitoring, Physiologic ,030203 arthritis & rheumatology ,Ankylosing spondylitis ,Dose-Response Relationship, Drug ,business.industry ,[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy ,medicine.disease ,Long-Term Care ,Infliximab ,Surgery ,business ,Follow-Up Studies - Abstract
Infliximab is approved for refractory ankylosing spondylitis (AS) but 39% of patients experience no response to treatment after 24 weeks [1]. de Vries et al reported that the clinical response was ...
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- 2010
46. Effectiveness of adalimumab in treating patients with active psoriatic arthritis and predictors of good clinical responses for arthritis, skin and nail lesions
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H. Kupper, M. Frank, Neil McHugh, E. Rodevand, P. Holck, Marjatta Leirisalo-Repo, B. Manger, R. van Vollenhoven, Martina Kron, Oliver FitzGerald, Philippe Goupille, F. Van den Bosch, Sonja Kary, Cambefort, Jeanne, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Karolinska Institutet [Stockholm]
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Male ,[SDV]Life Sciences [q-bio] ,Arthritis ,Severity of Illness Index ,030207 dermatology & venereal diseases ,0302 clinical medicine ,Medicine and Health Sciences ,CRITERIA ,Immunology and Allergy ,Prospective Studies ,Clinical and epidemiological research ,INDEX ,PLACEBO ,Antibodies, Monoclonal ,Middle Aged ,Prognosis ,COLLEGE-OF-RHEUMATOLOGY ,3. Good health ,CONTROLLED TRIAL ,[SDV] Life Sciences [q-bio] ,Treatment Outcome ,SAFETY ,Antirheumatic Agents ,Female ,Polyarthritis ,medicine.drug ,Adult ,musculoskeletal diseases ,medicine.medical_specialty ,Immunology ,Antibodies, Monoclonal, Humanized ,VALIDATION ,General Biochemistry, Genetics and Molecular Biology ,Nail Diseases ,03 medical and health sciences ,Psoriatic arthritis ,Rheumatology ,Internal medicine ,Psoriasis ,INFLIXIMAB ,medicine ,Adalimumab ,Humans ,030203 arthritis & rheumatology ,business.industry ,Arthritis, Psoriatic ,PERFORMANCE ,medicine.disease ,Infliximab ,Physical therapy ,Dermatologic Agents ,business ,Rheumatism - Abstract
Objectives:To evaluate the effectiveness of adalimumab in patients with psoriatic arthritis (PsA) and identify predictors of good clinical response for joint and skin lesions.Methods:Patients received adalimumab 40 mg every other week in addition to standard therapy in this prospective, 12-week, open-label, uncontrolled study. Four definitions of good clinical response were used: ⩾50% improvement in American College of Rheumatology response criteria (ACR50), good response according to European League Against Rheumatism (EULAR) guidelines, a ⩾3-grade improvement in Physician Global Assessment of psoriasis (PGA) and a ⩾50% improvement in the Nail Psoriasis Severity Index (NAPSI). Response predictors were determined by logistic regression with backward elimination (selection level was 5%).Results:Of 442 patients, 94% completed 12 weeks of treatment. At week 12, 74%, 51% and 32% of the patients had achieved ACR20, 50 and 70, respectively; 87% and 61% experienced moderate and good responses according to EULAR criteria, respectively. The percentage of patients with PGA results of “clear/almost clear” increased from 34% (baseline) to 68%. The mean NAPSI score was reduced by 44%. No new safety signals were detected. A lower Health Assessment Questionnaire Disability Index (HAQ-DI) score, greater pain assessment, male sex and absence of systemic glucocorticoid therapy were strongly associated with achievement of ACR50 and good response according to EULAR criteria. In addition, greater C-reactive protein concentration and polyarthritis predicted ACR50, and non-involvement of large joints predicted a good response according to EULAR criteria.Conclusions:Adalimumab was effective in patients with PsA. Lower impairment of physical function, greater pain, male sex and no systemic treatment with glucocorticoids were factors that increased the chance of achieving a good clinical response.
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- 2010
47. Stat5a serine 725 and 779 phosphorylation is a prerequisite for hematopoietic transformation
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Andrea Hoelbl, Geqiang Li, Boris Kovacic, Sabine Fajmann, Richard Moriggl, Marc A. Kerenyi, Katrin Friedbichler, Peter Valent, Sabine Cerny-Reiterer, Fabrice Gouilleux, Veronika Sexl, Ernst W. Müllner, Hartmut Beug, Saliha Yahiaoui, Kevin D. Bunting, Cambefort, Jeanne, Medizinische Universität Wien = Medical University of Vienna, Développement normal et pathologique des lymphocytes et signalisation, Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Ludwig Boltzmann Institute for Cancer Research [Vienna, Austria], Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours, and Université de Tours (UT)
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Male ,[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,Myeloid ,T-Lymphocytes ,Biochemistry ,Immunoenzyme Techniques ,Serine ,Mice ,0302 clinical medicine ,STAT5 Transcription Factor ,Mast Cells ,Phosphorylation ,Cells, Cultured ,STAT5 ,Bone Marrow Transplantation ,0303 health sciences ,Leukemia ,Myeloid Neoplasia ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,food and beverages ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Hematology ,Middle Aged ,Flow Cytometry ,Cell biology ,Haematopoiesis ,Cell Transformation, Neoplastic ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Tyrosine kinase ,Adult ,Blotting, Western ,Immunology ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,Fetus ,medicine ,Animals ,Humans ,Cell Lineage ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,RNA, Messenger ,Transcription factor ,Aged ,Cell Proliferation ,030304 developmental biology ,Precursor Cells, B-Lymphoid ,Tumor Suppressor Proteins ,Cell Biology ,medicine.disease ,Molecular biology ,Hematopoiesis ,Liver Transplantation ,Mice, Inbred C57BL ,biology.protein - Abstract
International audience; Stat5 transcription factors are essential gene regulators promoting proliferation, survival, and differentiation of all hematopoietic cell types. Mutations or fusions of oncogenic tyrosine kinases often result in constitutive Stat5 activation. We have modeled persistent Stat5 activity by using an oncogenic Stat5a variant (cS5). To analyze the hitherto unrecognized role of Stat5 serine phosphorylation in this context, we have generated cS5 constructs with mutated C-terminal serines 725 and 779, either alone or in combination. Genetic complementation assays in primary Stat5(null/null) mast cells and Stat5(Delta N) T cells demonstrated reconstitution of proliferation with these mutants. Similarly, an in vivo reconstitution experiment of transduced Stat5(null/null) fetal liver cells transplanted into irradiated wild-type recipients revealed that these mutants exhibit biologic activity in lineage differentiation. By contrast, the leukemogenic potential of cS5 in bone marrow transplants de-creased dramatically in cS5 single-serine mutants or was completely absent upon loss of both serine phosphorylation sites. Our data suggest that Stat5a serine phosphorylation is a prerequisite for cS5-mediated leukemogenesis. Hence, interference with Stat5a serine phosphorylation might provide a new therapeutic option for leukemia and myeloid dysplasias without affecting major functions of Stat5 in normal hematopoiesis. (Blood. 2010;116(9):1548-1558)
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- 2010
48. Chemotherapy of advanced small-bowel adenocarcinoma: a multicenter AGEO study
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Thomas Aparicio, Iradj Sobhani, David Tougeron, Laurent Costes, Julien Taieb, Mélanie Gauthier, Thierry Lecomte, Pauline Afchain, J.-M. Gornet, Valérie Moulin, Aziz Zaanan, Christophe Locher, Franck Bonnetain, David Malka, Emmanuel Mitry, Cambefort, Jeanne, Institut Gustave Roussy (IGR), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Hôpital Ambroise Paré [AP-HP], CHU Rouen, Normandie Université (NU), Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), Institut Gustave Roussy ( IGR ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Hôpital Ambroise Paré, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP), Génétique, Immunothérapie, Chimie et Cancer ( GICC ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Diderot - Paris 7 (UPD7)-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), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
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Male ,Lung Neoplasms ,Organoplatinum Compounds ,[SDV]Life Sciences [q-bio] ,Leucovorin ,chemotherapy ,Gastroenterology ,0302 clinical medicine ,Carcinoembryonic antigen ,FOLFOX ,Duodenal Neoplasms ,Antineoplastic Combined Chemotherapy Protocols ,Intestine, Small ,Medicine ,prognostic factor ,Peritoneal Neoplasms ,Aged, 80 and over ,small-bowel adenocarcinoma ,biology ,Liver Neoplasms ,Hematology ,Middle Aged ,Prognosis ,Chemotherapy regimen ,3. Good health ,Oxaliplatin ,Survival Rate ,[SDV] Life Sciences [q-bio] ,Oncology ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,FOLFIRI ,Female ,030211 gastroenterology & hepatology ,Fluorouracil ,medicine.drug ,Adult ,medicine.medical_specialty ,Irinotecan ,03 medical and health sciences ,Internal medicine ,Humans ,Progression-free survival ,Survival rate ,Aged ,Neoplasm Staging ,Retrospective Studies ,Jejunal Neoplasms ,Performance status ,business.industry ,Surgery ,Ileal Neoplasms ,biology.protein ,Camptothecin ,Cisplatin ,business ,Follow-Up Studies - Abstract
International audience; Background: Small-bowel adenocarcinoma (SBA) is a rare tumor of poor prognosis. Data on the efficacy of chemotherapy for advanced SBA are scarce. Patients and methods: All patients with advanced SBA who received frontline chemotherapy from 1996 to 2008 were eligible for this retrospective multicenter study. Results: Ninety-three consecutive patients were included. In the entire population, the median progression-free survival (PFS) and overall survival (OS) times were 6.6 and 15.1 months, respectively. Median PFS times among patients treated with LV5FU2 (n = 10), FOLFOX (n = 48) FOLFIRI (n = 19) and LV5FU2-cisplatin (n = 16) were 7.7, 6.9, 6.0 and 4.8 months, respectively, while median OS times were 13.5, 17.8, 10.6 and 9.3 months, respectively. In multivariate analysis, World Health Organization performance status (PS) (P < 0.0001) and elevated serum levels of carcinoembryonic antigen (CEA) (P = 0.02) and carbohydrate antigen 19-9 (CA 19-9) (P = 0.03) were the only variables significantly associated with poor OS. In the subgroup of patients treated with platinum-based chemotherapy, multivariate analysis showed that LV5FU2-cisplatin was associated with poorer PFS (P < 0.0001) and OS (P = 0.02) compared with FOLFOX. Conclusions: This is the largest study of chemotherapy in advanced SBA. Baseline PS and CEA and CA 19-9 levels were the main prognostic factors. FOLFOX seems to be the most effective platinum-based chemotherapy regimen.
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- 2010
49. Desulfonylation of Indoles and 7-Azaindoles Using Sodium tert-Butoxide
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Charlotte Chaulet, Marie-Claude Viaud-Massuard, Joan Basset, Maria-Dolores Pujol, Cécile Croix, Cambefort, Jeanne, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Quimica Farmaceutica Lab
- Subjects
Indole test ,3-b]pyridine ,[CHIM.ORGA]Chemical Sciences/Organic chemistry ,010405 organic chemistry ,Chemistry ,Sodium ,Organic Chemistry ,chemistry.chemical_element ,sodium tert-butoxide ,010402 general chemistry ,Sodium tert-butoxide ,[CHIM.ORGA] Chemical Sciences/Organic chemistry ,01 natural sciences ,0104 chemical sciences ,N-desulfonylation ,chemistry.chemical_compound ,indole ,sealed tube ,Organic chemistry ,1H-pyrrolo[2 - Abstract
International audience; A mild method for the desulfonylation of N-indoles and N-azaindoles is described. Deprotection is carried out under basic conditions, using sodium tert-butoxide in dioxane. Several functionalized indoles and 7-azaindoles were efficiently deprotected by this method, which is mild enough to be used to deprotect compounds including functions that are known to be sensitive to acidic or basic conditions.
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- 2010
50. Methotrexate does not influence infliximab pharmacokinetics and concentration-effect relationship in ankylosing spondylitis patients
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Ternant, David, Lauferon, F., Mulleman, Denis, Wendling, D., Ducourau, Emilie, Valat, Jean-Pierre, Goupille, Philippe, Paintaud, Gilles, Cambefort, Jeanne, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Université de Tours-Centre National de la Recherche Scientifique (CNRS)
- Subjects
[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2010
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