Descriptor: "MESH : Neoplasm Proteins" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"MESH : Neoplasm Proteins"' showing total 13 results

Start Over Descriptor "MESH : Neoplasm Proteins"

13 results on '"MESH : Neoplasm Proteins"'

1. Sex differences in the GSK3β-mediated survival of adherent leukemic progenitors

Author: Jessica Bertrand, Bernard Payrastre, N Gallay, Nathalie Vergnolle, Véronique Maguer-Satta, Mathieu Despeaux, Cécile Demur, Ezzeddine Bourogaa, S Joly, P Bonnevialle, F Louache, Claire Racaud-Sultan, ANDRA, Laboratoire d'Hématologie [Purpan], Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Equipe 11, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Physiopathologie Toulouse Purpan, Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Departement /u563 : Oncogenèse, Signalisation et Innovation thérapeutique, Université Paul Sabatier - Toulouse 3 ( UPS ) -Institut Claudius Regaud-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Claudius Regaud
Subjects: Male, MESH : Aged, Antigens, CD34, MESH : Blotting, Western, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Glycogen Synthase Kinase 3, 0302 clinical medicine, MESH : Indoles, MESH : Tumor Cells, Cultured, GSK-3, Tumor Cells, Cultured, Protein Phosphatase 2, MESH : GTP-Binding Proteins, Cells, Cultured, MESH: Glycogen Synthase Kinase 3, MESH: Etoposide, Etoposide, MESH: Indoles, MESH : Maleimides, Aged, 80 and over, MESH : Cell Survival, 0303 health sciences, education.field_of_study, MESH: Middle Aged, MESH: Protein Phosphatase 2, Neoplasm Proteins, MESH: Cell Survival, MESH: Young Adult, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, RNA Interference, MESH: Cells, Cultured, MESH : Protein Phosphatase 2, MESH : Glycogen Synthase Kinase 3, MESH: Antineoplastic Agents, Phytogenic, Blotting, Western, MESH : Young Adult, Receptors, Cell Surface, MESH: Cell Adhesion, 03 medical and health sciences, MESH : Neoplasm Proteins, MESH: Sex Factors, Genetics, MESH: Blotting, Western, Humans, MESH : Middle Aged, MESH: Tumor Cells, Cultured, Progenitor cell, MESH : Aged, 80 and over, Clonogenic assay, education, Molecular Biology, Aged, MESH: Interleukin-3 Receptor alpha Subunit, MESH: Humans, Glycogen Synthase Kinase 3 beta, MESH : Hematopoietic Stem Cells, MESH : Humans, MESH : Leukemia, MESH: Adult, MESH: Antigens, CD34, Protein phosphatase 2, Hematopoietic Stem Cells, MESH: Neoplastic Stem Cells, Immunology, MESH: Female, MESH: Neoplasm Proteins, Cancer Research, Indoles, MESH : Receptors, Cell Surface, MESH : Interleukin-3 Receptor alpha Subunit, MESH : Antineoplastic Agents, Phytogenic, MESH: Hematopoietic Stem Cells, Maleimides, MESH: Aged, 80 and over, MESH : Female, MESH: Maleimides, MESH: Receptors, Cell Surface, MESH: Aged, Leukemia, Myeloid leukemia, MESH : Adult, Middle Aged, medicine.anatomical_structure, MESH : Antigens, CD34, Female, Stem cell, Adult, MESH: GTP-Binding Proteins, Cell Survival, MESH : Male, MESH : Sex Factors, MESH: RNA Interference, Population, Interleukin-3 Receptor alpha Subunit, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Etoposide, Biology, Receptors for Activated C Kinase, Young Adult, MESH : Neoplastic Stem Cells, Sex Factors, GTP-Binding Proteins, MESH: Leukemia, MESH : Cells, Cultured, Cell Adhesion, medicine, 030304 developmental biology, Antineoplastic Agents, Phytogenic, MESH: Male, MESH : Cell Adhesion, Cancer research, Bone marrow, MESH : RNA Interference
Abstract: International audience; Therapeutic resistance of acute myeloid leukemia stem cells, enriched in the CD34(+)38(-)123(+) progenitor population, is supported by extrinsic factors such as the bone marrow niche. Here, we report that when adherent onto fibronectin or osteoblast components, CD34(+)38(-)123(+) progenitors survive through an integrin-dependent activation of glycogen synthase kinase 3β (GSK3β) by serine 9-dephosphorylation. Strikingly, GSK3β-mediated survival was restricted to leukemic progenitors from female patients. GSK3β inhibition restored sensitivity to etoposide, and impaired the clonogenic capacities of adherent leukemic progenitors from female patients. In leukemic progenitors from female but not male patients, the scaffolding protein RACK1, activated downstream of α(5)β(1)-integrin engagement, was specifically upregulated and controlled GSK3β activation through the phosphatase protein phosphatase 2A (PP2A). In a mirrored manner, survival of adherent progenitors (CD34(+)38(-)) from male but not female healthy donors was partially dependent on this pathway. We conclude that the GSK3β-dependent survival pathway might be sex-specific in normal immature population and flip-flopped upon leukemogenesis. Taken together, our results strengthen GSK3β as a promising target for leukemic stem cell therapy and reveal gender differences as a new parameter in anti-leukemia therapy.
Published: 2011
Full Text: View/download PDF

2. A protocol to quantify mammary early common progenitors from long-term mammosphere culture

Author: Véronique Maguer-Satta, Emmanuel Delay, Elodie Bachelard-Cascales, Marion Chapellier, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH: Neoplasm Proteins, Time Factors, Cellular differentiation, Cell Culture Techniques, MESH : Aged, MESH : Receptors, Cell Surface, MESH : Blotting, Western, MESH : Interleukin-3 Receptor alpha Subunit, MESH : Antineoplastic Agents, Phytogenic, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Hematopoietic Stem Cells, Mice, 0302 clinical medicine, MESH: Aged, 80 and over, MESH : Indoles, MESH : Tumor Cells, Cultured, MESH : Female, MESH : GTP-Binding Proteins, MESH: Glycogen Synthase Kinase 3, MESH: Maleimides, MESH: Receptors, Cell Surface, MESH: Etoposide, MESH : Maleimides, MESH: Aged, MESH: Indoles, MESH : Cell Survival, 0303 health sciences, MESH: Middle Aged, Stem Cells, MESH: Protein Phosphatase 2, Cell Differentiation, General Medicine, MESH : Adult, Cell biology, MESH: Cell Survival, MESH: Young Adult, 030220 oncology & carcinogenesis, MESH : Antigens, CD34, Stem cell, MESH: Cells, Cultured, Adult, MESH: GTP-Binding Proteins, MESH : Protein Phosphatase 2, MESH : Glycogen Synthase Kinase 3, MESH : Male, MESH : Sex Factors, MESH: RNA Interference, MESH: Antineoplastic Agents, Phytogenic, MESH : Young Adult, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Etoposide, Biology, MESH: Cell Adhesion, Colony-Forming Units Assay, 03 medical and health sciences, MESH : Neoplasm Proteins, MESH : Neoplastic Stem Cells, MESH: Sex Factors, Spheroids, Cellular, MESH : Cells, Cultured, MESH: Leukemia, Animals, Humans, MESH: Blotting, Western, MESH : Middle Aged, MESH: Tumor Cells, Cultured, Progenitor cell, Mammary Glands, Human, MESH : Aged, 80 and over, 030304 developmental biology, Progenitor, MESH: Interleukin-3 Receptor alpha Subunit, MESH: Humans, MESH : Hematopoietic Stem Cells, Stem cell population, MESH : Humans, MESH : Leukemia, MESH: Adult, Cell Biology, MESH: Antigens, CD34, MESH: Neoplastic Stem Cells, MESH: Male, MESH : Cell Adhesion, Cell culture, Immunology, NIH 3T3 Cells, MESH : RNA Interference, MESH: Female, Developmental Biology
Abstract: International audience; Here we describe a protocol established in our laboratory to quantify early common progenitors/stem cells grown as spheres in non-adherent culture conditions. This protocol is based on the combination of two functional tests: the mammosphere assay to maintain and enrich early mammary progenitors/stem cells, and the epithelial colony-forming cells (E-CFC) assay to identify and quantify further differentiated epithelial progenitors. Primary spheres mainly contain progenitors and rare stem/early common progenitor cells while secondary and tertiary spheres contain progenitor cells derived from the early common progenitor/stem cell population maintained through passages and partially differentiated. Spheres are enzymatically and mechanically dissociated; the derived cells are subsequently plated on irradiated NIH-3T3 fibroblasts for further processing, as in the E-CFC assay. The principle of this assay is to quantify the number of epithelial colonies generated by cells present in the different sequential spheres. This assay has therefore been named ECP-DC, standing for Early Common Progenitor-Derived Colonies assay.
Published: 2012
Full Text: View/download PDF

3. Aberrant DNA methylation of cancer-associated genes in gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)

Author: Karen Balassiano, Jean-Yves Scoazec, Pierre Hainaut, Petra H.M. Peeters, Federico Canzian, Göran Hallmans, Sara Grioni, Domenico Palli, Bakary S. Sylla, Karina Meidtner, Marí a.José Sánchez, Carmen Navarro, Antonia Trichopoulou, J. Ramón Quirós, Ruth C. Travis, Kim Overvad, Roy Ehrnström, Eva Ardanaz, Eiliv Lund, Carlos A. González, Salvatore Panico, Pagona Laglou, H. Bas Bueno-de-Mesquita, G. Johan A. Offerhaus, Zdenko Herceg, Sheila Coelho Soares Lima, Mazda Jenab, Naomi E. Allen, Kay-Tee Khaw, Rudolf Kaaks, Sara Regnér, Anne Tjønneland, Roger Stenling, Françoise Clavel-Chapelon, Elio Riboli, Heiner Boeing, Núria Sala, M. E. Numans, Marie-Christine Boutron-Ruault, Miren Dorronsoro, Rosario Tumino, Paolo Vineis, Unit of Nutrition, Environment, and Cancer, Catalan Institute of Oncology, Department of Cardiology, Aalborg Hospital-Aarhus University Hospital, Danish Cancer Society, Institute of Cancer Epidemiology, Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Nutrition, hormones et cancer: épidémiologie et prévention ( E3N ), Epidémiologie, sciences sociales, santé publique ( IFR 69 ), Université Panthéon-Sorbonne ( UP1 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École des hautes études en sciences sociales ( EHESS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Panthéon-Sorbonne ( UP1 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École des hautes études en sciences sociales ( EHESS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of Cancer Epidemiology, German Cancer Research Center, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbrücke, Department of Epidemiology, German Institute of Human Nutrition, Department of Hygiene, Epidemiology and Medical Statistics, Centre for Environment and Health, Imperial College London-School of public health, Human Genetics Foundation ( HuGeF ), Università degli studi di Torino ( UNITO ), Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II-Medical School, Molecular and Nutritional Epidemiology Unit, ISPO-Cancer Research and Prevention Institute, Epidemiology, Cancer Registry, Azienda Ospedaliera 'Civile M.P.Arezzo', Institute of Community Medicine, University of Tromsø ( UiT ), National Institute for Public Health and the Environment [Bilthoven] ( RIVM ), Julius Centre for Health Sciences and Primary Care, University Medical Center, Julius Center for Health Sciences and Primary Care, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública ( CIBERESP ), Los Centros de Investigación Biomédica en Red (CIBER), Granada Cancer Registry, Andalusian School of Public Health, CIBERESP, CIBER Epidemiologia y Salud Pública, Epidemiology Department, Murcia Health Council, Navarra Public Health Institute, Leyre 15, Epidemiology and Health Information, Public Health Department of Gipuzkoa, Department of Public Health and Clinical Medicine/Nutritional Research, University of Umeå, Cancer Epidemiology Unit, University of Oxford [Oxford]-Cancer Epidemiology Unit, School of Clinical Medicine, University of Cambridge [UK] ( CAM ), Department of Epidemiology and Public Health, Imperial College London, International Agency for Cancer Research ( IACR ), International Agency for Cancer Research, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), General practice, EMGO - Mental health, Aarhus University Hospital, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, hormones et cancer: épidémiologie et prévention (E3N), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Human Genetics Foundation (HuGeF), Università degli studi di Torino = University of Turin (UNITO), Civile - M.P.Arezzo Hospital, University of Tromsø (UiT), National Institute for Public Health and the Environment [Bilthoven] (RIVM), VU University Medical Center [Amsterdam], Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Andalusian School of Public Health [Granada], Umeå University, University of Cambridge [UK] (CAM), International Agency for Cancer Research (IACR), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and Università degli studi di Torino (UNITO)
Subjects: MESH: Neoplasm Proteins, Male, Cancer Research, MESH : Aged, MESH : Prospective Studies, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: DNA Methylation, 0302 clinical medicine, MESH : Stomach Neoplasms, MESH : Female, Prospective Studies, MESH: Aged, Genetics, 0303 health sciences, Molecular Epidemiology, MESH: Middle Aged, MESH: Genetic Predisposition to Disease, MESH: Stomach Neoplasms, Methylation, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Neoplasm Proteins, Europe, Oncology, 030220 oncology & carcinogenesis, DNA methylation, Female, MESH : Male, MESH : Europe, MESH : Molecular Epidemiology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MLH1, 03 medical and health sciences, MESH : Neoplasm Proteins, p14arf, Stomach Neoplasms, medicine, MESH: Molecular Epidemiology, Humans, Genetic Predisposition to Disease, MESH : Middle Aged, Epigenetics, Gene, 030304 developmental biology, Aged, MESH: Humans, MESH : Humans, Cancer, DNA Methylation, medicine.disease, MESH: Prospective Studies, MESH: Male, MESH : Genetic Predisposition to Disease, MESH: Europe, MESH: Female, MESH : DNA Methylation
Abstract: Epigenetic events have emerged as key mechanisms in the regulation of critical biological processes and in the development of a wide variety of human malignancies, including gastric cancer (GC), however precise gene targets of aberrant DNA methylation in GC remain largely unknown. Here, we have combined pyrosequencing-based quantitative analysis of DNA methylation in 98 GC cases and 64 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and in cancer tissue and non-tumorigenic adjacent tissue of an independent series of GC samples. A panel of 10 cancer-associated genes (CHRNA3, DOK1, MGMT, RASSF1A, p14ARF, CDH1, MLH1, ALDH2, GNMT and MTHFR) and LINE-1 repetitive elements were included in the analysis and their association with clinicopathological characteristics (sex, age at diagnosis, anatomical sub-site, histological sub-type) was examined. Three out of the 10 genes analyzed exhibited a marked hypermethylation, whereas two genes (ALDH2 and MTHFR) showed significant hypomethylation, in gastric tumors. Among differentially methylated genes, we identified new genes (CHRNA3 and DOK1) as targets of aberrant hypermethylation in GC, suggesting that epigenetic deregulation of these genes and their corresponding cellular pathways may promote the development and progression of GC. We also found that global demethylation of tumor cell genomes occurs in GC, consistent with the notion that abnormal hypermethylation of specific genes occurs concomitantly with genome-wide hypomethylation. Age and gender had no significant influence on methylation states, but an association was observed between LINE-1 and MLH1 methylation levels with histological sub-type and anatomical sub-site. This study identifies aberrant methylation patters in specific genes in GC thus providing information that could be exploited as novel biomarkers in clinics and molecular epidemiology of GC. © 2011 Elsevier Ireland Ltd.
Published: 2011
Full Text: View/download PDF

4. Pediatric-inspired intensified therapy of adult T-ALL reveals the favorable outcome of NOTCH1/FBXW7 mutations, but not of low ERG/BAALC expression: a GRAALL study

Author: Ben Abdelali, Raouf, Asnafi, Vahid, Leguay, Thibaut, Boissel, Nicolas, Buzyn, Agnès, Chevallier, Patrice, Thomas, Xavier, Lepretre, Stephane, Huguet, Françoise, Vey, Norbert, Escoffre-Barbe, Martine, Tavernier, Emmanuelle, Reman, Oumedaly, Fegueux, Nathalie, Turlure, Pascal, Rousselot, Philippe, Cahn, Jean-Yves, Lheritier, Veronique, Chalandon, Yves, Béné, Marie-Christine, Macintyre, Elizabeth, Dombret, Hervé, Ifrah, Norbert, Renseigné, Non, Université Paris Descartes - Paris 5 (UPD5), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), equipe 14, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Hematology (IPC-Marseille), Service d'hématologie clinique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Hematology, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service d'Immunologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie clinique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Edouard Herriot [CHU - HCL], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Paris Descartes - Paris 5 ( UPD5 ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Toulouse III - Paul Sabatier ( UPS ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou, Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], IFR105-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Cytokines, hématopoïèse et réponse immune (CHRI), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Hôpital Pontchaillou, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Centre de Recherche en Cancérologie de Lyon (CRCL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)
Subjects: Oncology, Male, MESH : F-Box Proteins, MESH : Prospective Studies, Cell Cycle Proteins, MESH: Receptor, Notch1, Biochemistry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH : Cell Cycle Proteins, Neoplasm Proteins/genetics, MESH : Child, Clinical Protocols, MESH: Child, Mutational status, Favorable outcome, Prospective Studies, MESH: Leukemia-Lymphoma, Adult T-Cell, Receptor, Notch1, Child, ComputingMilieux_MISCELLANEOUS, MESH: Treatment Outcome, ddc:616, 0303 health sciences, Mutation, MESH : Trans-Activators, MESH: Middle Aged, Prognosis, Neoplasm Proteins, MESH: Young Adult, 030220 oncology & carcinogenesis, F-Box Proteins/genetics, Erg, medicine.medical_specialty, MESH: Gene Expression, Immunology, MESH : Young Adult, Disease-Free Survival, MESH: Prognosis, 03 medical and health sciences, MESH : Neoplasm Proteins, MESH: Cell Cycle Proteins, MESH : Adolescent, Humans, MESH : Middle Aged, Ubiquitin-Protein Ligases/genetics, MESH : Predictive Value of Tests, MESH : Clinical Protocols, MESH: Kaplan-Meier Estimate, Cell Cycle Proteins/genetics, MESH: Adolescent, Receptor, Notch1/genetics, MESH: Humans, F-Box Proteins, MESH : Humans, MESH: Adult, Leukemia-Lymphoma, Adult T-Cell/classification/drug therapy/genetics, MESH: Ubiquitin-Protein Ligases, MESH : Leukemia-Lymphoma, Adult T-Cell, MESH : Gene Expression, MESH: Disease-Free Survival, Adult Acute Lymphoblastic Leukemia, MESH : Ubiquitin-Protein Ligases, Carcinogenesis, MESH: Female, MESH: Neoplasm Proteins, Multivariate analysis, F-Box-WD Repeat-Containing Protein 7, Gene Expression, Kaplan-Meier Estimate, medicine.disease_cause, Bioinformatics, MESH: Clinical Protocols, Leukemia-Lymphoma, Adult T-Cell, MESH : Female, BAALC, MESH : Prognosis, MESH : Receptor, Notch1, Hematology, MESH : Adult, Middle Aged, MESH: Predictive Value of Tests, Treatment Outcome, MESH : Disease-Free Survival, Female, MESH : Mutation, Adult, MESH: Mutation, Adolescent, MESH: Trans-Activators, MESH : Male, Ubiquitin-Protein Ligases, MESH: F-Box Proteins, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Treatment Outcome, Trans-Activators/genetics, MESH : Kaplan-Meier Estimate, Young Adult, Transcriptional Regulator ERG, Predictive Value of Tests, Internal medicine, medicine, 030304 developmental biology, business.industry, Cell Biology, MESH: Male, MESH: Prospective Studies, Trans-Activators, business
Abstract: Despite recent progress in the understanding of acute lymphoblastic leukemia (T-ALL) oncogenesis, few markers are sufficiently frequent in large subgroups to allow their use in therapeutic stratification. Low ERG and BAALC expression (E/Blow) and NOTCH1/FBXW7 (N/F) mutations have been proposed as powerful prognostic markers in large cohorts of adult T-ALL. We therefore compared the predictive prognostic value of N/F mutations versus E/Blow in 232 adult T-ALLs enrolled in the LALA-94 and Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocols. The outcome of T-ALLs treated in the pediatric-inspired GRAALL trials was significantly superior to the LALA-94 trial. Overall, 43% and 69% of adult T-ALL patients were classified as E/Blow and N/F mutated, respectively. Strikingly, the good prognosis of N/F mutated patients was stronger in more intensively treated, pediatric-inspired GRAALL patients. The E/B expression level did not influence the prognosis in any subgroup. N/F mutation status and the GRAALL trial were the only 2 independent factors that correlated with longer overall survival by multivariate analysis. This study demonstrates that the N/F mutational status and treatment protocol are major outcome determinants for adults with T-ALL, the benefit of pediatric inspired protocols being essentially restricted to the N/F mutated subgroup.
Published: 2011
Full Text: View/download PDF

5. Prognostic value of phosphorylated STAT3 in advanced rectal cancer: a study from 104 French patients included in the EORTC 22921 trial

Author: Bernadette Kantelip, Harouna Zaki, Francine Arbez-Gindre, Mariette Mercier, Franck Monnien, Christophe Borg, Christiane Mougin, Jean-François Bosset, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Laboratoire d'anatomie pathologique [Besancon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Service d'Anatomie pathologique [CHRU Besançon], and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)
Subjects: Male, Oncology, MESH: Neoplasm Proteins, Pathology, MESH: Combined Modality Therapy, Colorectal cancer, medicine.medical_treatment, MESH : Aged, medicine.disease_cause, MESH: Epidemiologic Methods, law.invention, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH : Phosphorylation, 0302 clinical medicine, MESH: Aged, 80 and over, Randomized controlled trial, law, MESH : Tumor Markers, Biological, MESH : STAT3 Transcription Factor, MESH : Female, Phosphorylation, MESH : Rectal Neoplasms, MESH: Treatment Outcome, Aged, 80 and over, MESH: Aged, 0303 health sciences, MESH : Cell Nucleus, MESH: Middle Aged, MESH : Prognosis, MESH: STAT3 Transcription Factor, Anatomical pathology, MESH : Chemotherapy, Adjuvant, General Medicine, Middle Aged, MESH : Adult, Prognosis, Combined Modality Therapy, Neoplasm Proteins, 3. Good health, Treatment Outcome, Chemotherapy, Adjuvant, MESH: Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, France, Adult, STAT3 Transcription Factor, MESH: Cell Nucleus, medicine.medical_specialty, MESH : Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Treatment Outcome, MESH: Prognosis, MESH : Epidemiologic Methods, Pathology and Forensic Medicine, 03 medical and health sciences, MESH : Neoplasm Proteins, Internal medicine, Biomarkers, Tumor, medicine, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, MESH : France, Aged, 030304 developmental biology, Cell Nucleus, Chemotherapy, MESH: Humans, Oncogene, MESH: Phosphorylation, Rectal Neoplasms, business.industry, MESH : Humans, Cancer, MESH: Rectal Neoplasms, MESH: Adult, medicine.disease, MESH: Male, Clinical trial, MESH: France, MESH: Tumor Markers, Biological, Epidemiologic Methods, Carcinogenesis, business, MESH : Combined Modality Therapy, MESH: Female
Abstract: International audience; BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) has been implicated as an oncogene in several neoplastic diseases. However, the biological effects of STAT3 have not been extensively studied in rectal carcinogenesis. AIMS: To evaluate STAT3 activation in advanced rectal cancers and its association with clinicopathological variables and prognosis. METHODS: Nuclear immunohistochemical expression of phosphorylated STAT3 (p-STAT3) was studied in 104 advanced rectal cancers (T3-T4). All patients were participating in the EORTC 22921 trial to assess whether preoperative chemoradiotherapy followed by postoperative chemotherapy improved overall and progression-free survival. RESULTS: Nuclear p-STAT3 expression was detected in 37.5% of rectal cancer patients. No correlation was observed between p-STAT3 and any clinicopathological variables tested. However, patients with tumours positive for p-STAT3 had significantly improved overall survival. CONCLUSION: These results highlight an unexpected role for nuclear p-STAT3 expression in advanced rectal cancers and need further investigation to clarify this finding.
Published: 2010
Full Text: View/download PDF

6. 17q21 variants modify the association between early respiratory infections and asthma

Author: Smit, L.A., Bouzigon, E., Pin, V., Siroux, V., Monier, F., Aschard, H., Bousquet, J., Gormand, F., Just, J., le Moual, N., Nadif, R., Scheinmann, P., Vervloet, D., Lathrop, M., Demenais, F., Kauffmann, F., Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Faraldo, Beatrice, Programme Santé-environnement et Santé-travail - Facteurs environnementaux et interactions gène environnnement dans l'asthme et l'allergie - 2005 - ANR-05-SEST-0020 - SEST - VALID, Division of Environmental Epidemiology, Utrecht University [Utrecht]-Institute of Risk Assessment Sciences, Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Etude du Polymorphisme Humain (CEPH), Université Paris Diderot - Paris 7 (UPD7)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset, Variabilité Génétique et Maladies Humaines, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pédiatrie, CHU Grenoble-Hôpital Michallon, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pneumologie Allergologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pneumo-Allergologie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Supported by the French Ministry of Higher Education and Research, University Paris Diderot-Paris 7, grants from the French Agency for Environmental and Occupational Health Safety (grant AFSSET-APR-SE-2004), the French National Agency for Research (grants ANR 05-SEST-020-02/05-9-97 and ANR 06-CEBS), Merck Sharp & Dohme (MSD), Hospital program of clinical research (PHRC)-Paris, and GABRIEL, a multidisciplinary study to identify the genetic and environmental causes of asthma in the European Community (contract n° 01896 under the Integrated Programme LSH-2004-1.2.5-1 Post genomic approaches to understand the molecular bias of asthma aiming at a preventive or therapeutic control). Lidwien Smit is supported by a European Academy of Allergology and Clinical Immunology- Global Allergy and Asthma European Network (EAACI-GA2LEN) exchange fellowship award., ANR-05-SEST-0020,Facteurs environnementaux et interactions gène environnnement dans l'asthme et l'allergie(2005), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Etude du Polymorphisme Humain ( CEPH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Fondation Jean Dausset, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre de l'asthme et de l'allergologie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital Sainte-Marguerite [CHU - APHM] ( Hôpitaux Sud ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), ANR-06-CEBS,ANR-06-CEBS, Risk Assessment of Toxic and Immunomodulatory Agents, and Dep IRAS
Subjects: Male, MESH: Neoplasm Proteins, MESH : Retrospective Studies, MESH: Asthma, MESH : Respiratory Tract Infections, 0302 clinical medicine, MESH : Child, Risk Factors, immune system diseases, respiratory infection, MESH: Risk Factors, MESH: Child, Epidemiology, MESH : Female, Age of Onset, Young adult, Child, Respiratory Tract Infections, MESH: Genetic Association Studies, 0303 health sciences, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, Respiratory disease, ORMDL3, MESH: Genetic Predisposition to Disease, Respiratory infection, MESH : Chromosomes, Human, Pair 17, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Follow-Up Studies, MESH : Risk Factors, Neoplasm Proteins, MESH : Age of Onset, 3. Good health, MESH: Tobacco Smoke Pollution, Female, epidemiology, MESH: Membrane Proteins, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Adolescent, MESH : Male, MESH : Sex Factors, MESH: Age of Onset, Single-nucleotide polymorphism, MESH : Asthma, Polymorphism, Single Nucleotide, MESH : Tobacco Smoke Pollution, 03 medical and health sciences, Sex Factors, MESH : Neoplasm Proteins, MESH: Sex Factors, MESH : Adolescent, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Genetic Association Studies, Retrospective Studies, 030304 developmental biology, Asthma, Genetic association, MESH: Adolescent, MESH: Humans, business.industry, MESH : Humans, environmental tobacco smoke exposure, Membrane Proteins, MESH : Follow-Up Studies, MESH: Retrospective Studies, MESH : Genetic Association Studies, Odds ratio, medicine.disease, MESH: Male, respiratory tract diseases, gene-environment interaction, 030228 respiratory system, GSDML, MESH : Membrane Proteins, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Immunology, MESH: Respiratory Tract Infections, Tobacco Smoke Pollution, MESH : Genetic Predisposition to Disease, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Chromosomes, Human, Pair 17, MESH: Female, Chromosomes, Human, Pair 17, Follow-Up Studies
Abstract: Single nucleotide polymorphisms (SNPs) at chromosome 17q21 confer an increased risk of early-onset asthma. The objective was to study whether 17q21 SNPs modify associations between early respiratory infections and asthma. Association analysis was conducted in 499 children (268 with asthma, median age 11 yrs) from the Epidemiological Study on the Genetics and Environment of Asthma (EGEA). The 12-yr follow-up data were used to assess persistent or remittent asthma in young adulthood. Respiratory infection before 2 yrs of age was assessed retrospectively. For the 12 17q21 SNPs studied, the odds ratios (OR) for association between infection and early-onset asthma (age at onsetor=4 yrs) were higher in carriers of risk genotypes (OR 3.42-6.36) than in noncarriers (OR 1.84-2.44; p-value for interaction 0.02-0.04 for five SNPs). Risk genotypes also increased the association between infection and childhood asthma that remits in adulthood (OR 4.84-7.16 in carriers and 1.74-2.25 in noncarriers; p-value for interaction 0.008-0.05 for 10 SNPs). In children with 17q21 risk genotypes and early-life environmental tobacco smoke (ETS) exposure, associations between infection and asthma were further enhanced. 17q21 genetic variants and early ETS exposure enhance the association between early respiratory infections and early-onset asthma and childhood asthma that remits in adulthood.
Published: 2010
Full Text: View/download PDF

7. KBA.62: a useful marker for primary and metastatic melanomas

Author: Sophie Le Guellec, Philippe Rochaix, Paul Carle, Pierre Payoux, Séverine Valmary-Degano, Talal Al Saati, François Launay, Laurence Lamant, Serge Boulinguez, Frédéric Lauwers, Pierre Brousset, Cécile Pages, Laboratoire d'Anatomie Pathologique [Purpan], CHU Toulouse [Toulouse], Institut Claudius Regaud, CRLCC Institut Claudius Regaud, Plateau technique d'Histopathologie Expérimentale, Institut Claude de Préval (ICP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service de dermatologie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de chirurgie plastique et maxillo-faciale, CHU Purpan, Toulouse, Service de Médecine Nucléaire [Toulouse], CHU Toulouse [Toulouse]-Hôpital Rangueil, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Laboratoire d'anatomie pathologique [Besancon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Imagerie cérébrale et handicaps neurologiques, Université Paul Sabatier - Toulouse 3 ( UPS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'anatomie pathologique et histologie-cytologie [Rangueil], Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital de Rangueil, Université Sciences et Technologies - Bordeaux 1, Centre de Recherche en Cancérologie de Toulouse ( CRCT ), and Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: MESH: Neoplasm Proteins, Pathology, Skin Neoplasms, MESH : Immunohistochemistry, MESH: Lymphatic Metastasis, MESH : S100 Proteins, MESH: Antigens, Neoplasm, MESH: Lymph Nodes, MESH : Antigens, Neoplasm, Metastasis, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Antibodies, Monoclonal, 030207 dermatology & venereal diseases, 0302 clinical medicine, MESH : Tumor Markers, Biological, Lymph node, Melanoma, MESH : Lymph Nodes, Micrometastasis, S100 Proteins, Antibodies, Monoclonal, MESH : Lymphatic Metastasis, Immunohistochemistry, 3. Good health, Neoplasm Proteins, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH : Antibodies, Monoclonal, Lymphatic Metastasis, Lymph, MESH : Sensitivity and Specificity, MESH: S100 Proteins, Melanoma-Specific Antigens, medicine.medical_specialty, MESH: Melanoma, Sentinel lymph node, MESH : Melanoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Sensitivity and Specificity, Pathology and Forensic Medicine, 03 medical and health sciences, MESH : Neoplasm Proteins, Antigens, Neoplasm, medicine, Biomarkers, Tumor, Humans, Desmoplastic melanoma, MESH: Humans, business.industry, MESH: Skin Neoplasms, MESH : Skin Neoplasms, MESH : Humans, MESH : Melanoma-Specific Antigens, MESH: Immunohistochemistry, medicine.disease, MESH: Sensitivity and Specificity, MESH: Melanoma-Specific Antigens, MESH: Tumor Markers, Biological, Lymph Nodes, business
Abstract: International audience; We previously described a novel antimelanoma antibody, designated KBA.62. However, review of the literature showed that only a few studies have reported on this antibody. We report our experience in the diagnosis of melanoma using KBA.62 and its value in both primary and metastatic conditions. In addition to conventional melanomas, we included desmoplastic and spindle cell melanomas, whose diagnosis can be challenging. We also focus on identification of malignant cells in sentinel lymph node biopsies using KBA.62, by comparison with anti-S-100 protein and HMB-45 antibodies, because discrepancies in sensitivity and specificity of melanoma markers have given rise to numerous studies aiming to determine the best panel for the evaluation of sentinel lymph node from patients with melanoma. Overall, KBA.62 was positive in 93% of primary and metastatic melanomas. Interestingly, the 12 cases of desmoplastic and spindle cell melanomas had strongly positive results. In addition, the results of our study performed on a series of 215 sentinel lymph nodes showed that the sensitivity of anti-S-100 protein and KBA.62 antibodies in detecting occult metastasis was similar. Moreover, KBA.62 identified 6 patients (3%) who had confirmed sentinel lymph node metastasis but were negative for HMB-45. The resolution was higher with KBA.62 than that observed with anti-S-100 protein antibody, as the nonmelanocytic positive cells for KBA.62 in lymph nodes were only represented by endothelial cells, which therefore constituted an intrinsic positive control. We conclude that KBA.62 antibody is a useful additional marker for melanoma, specifically in desmoplastic/spindle cell cases and in the context of micrometastasis in sentinel lymph node.
Published: 2008
Full Text: View/download PDF

8. Analysis of the DND1 gene in men with sporadic and familial testicular germ cell tumors

Author: Gedske Daugaard, Sophie D. Fosså, Sergei Tjulandin, Walter P. Weber, Douglas F. Easton, Rachel Linger, Dominique Stoppa-Lyonnet, Peter Albers, David W. Hogg, Parry Guilford, Robert Huddart, Michael Friedlander, Peter A. Daly, Ketil Heimdal, Michael A.S. Jewett, Darshna Dudakia, Michael R. Stratton, Katherine L. Nathanson, Hans Stoll, Lajos Géczi, Mary L. McMaster, Catherine Bonaïti-Pellié, Stéphane Richard, Elizabeth A. Rapley, Lawrence H. Einhorn, Mark H. Greene, Victoria K. Cortessis, Edith Olah, Agnès Chompret, Axel Heidenreich, Radka Lohynska, Katherine M. Tucker, Kelly-Anne Phillips, D. Timothy Bishop, Larissa A. Korde, Ludmila Liubchenko, István Bodrogi, Section of Cancer Genetics, Institute of cancer research, Academic Radiotherapy Unit, Dept of Medical Oncology, Division of Medicine, University of New South Wales [Sydney] (UNSW)-Prince of Wales Hospital Randwick, Dept of Haematology and Medical Oncology, Peter MacCallum Cancer Center, Princess Margaret Hospital, University of Toronto, Dept of Radiotherapy and Oncology, University hospital of Prague, Dept of Oncology, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Génétique oncologique (GO - UMR 8125), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Service d'urologie, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Centre de Recherches Biologiques, CERB, Génomes et cancer (GC (FRE2939)), Département de Pédiatrie, Institut Gustave Roussy (IGR), Epidémiologie des cancers, Institut National de la Santé et de la Recherche Médicale (INSERM), Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de Génétique Oncologique, Institut Curie [Paris], Département de génétique, Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Génétique épidémiologique et structures des populations humaines (Inserm U535), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie génétique, Dept of Urological Oncology, Phillips university, Department of Urology, Klinikum Kassel GmbH, Department of Molecular Genetics and Department of Chemotherapy, National Institute of Oncology, Department of Medical Oncology, St James's hospital, Cancer Genetics Laboratory, University of Otago [Dunedin, Nouvelle-Zélande], Departments of Clinical Cancer Research and genetics, Rikshospitalet-Radiumhospitalet Trust, Laboratory of Clinical Genetics, Institute of Clinical Oncology, Medical Oncology, University Hospital Basel [Basel], Google Inc., Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Barts and The London Queen Mary's School of Medicine, Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Depts of Medicine and Biostatistics and Epidemology, Abramson Family Cancer Research Institute-Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Department of Preventive Medicine, Keck School of Medicine [Los Angeles], University of Southern California (USC)-University of Southern California (USC), Cancer Research U.K. Genetic Epidemiology Unit, Strangeways Research Laboratory, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Genetic Epidemiology Division, Cancer Research UK Clinical Centre, Saint James's University Hospital, University of New South Wales [Sydney] ( UNSW ) -Prince of Wales Hospital Randwick, Peter MacCallum Cancer Centre, University of Toronto-Princess Margaret Hospital, Génétique oncologique ( GO - UMR 8125 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Génomes et cancer ( GC (FRE2939) ), Institut Gustave Roussy ( IGR ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), INSTITUT CURIE, Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Génétique épidémiologique et structures des populations humaines ( Inserm U535 ), Epidémiologie, sciences sociales, santé publique ( IFR 69 ), Université Panthéon-Sorbonne ( UP1 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École des hautes études en sciences sociales ( EHESS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Panthéon-Sorbonne ( UP1 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École des hautes études en sciences sociales ( EHESS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of Otago, Institut de Physique et Chimie des Matériaux de Strasbourg ( IPCMS ), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Abramson Family Cancer Research Institute-University of Pennsylvania School of Medicine, University of Cambridge [UK] ( CAM ), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Institut Curie, Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, MESH: Neoplasm Proteins, Cancer Research, DNA Mutational Analysis, medicine.disease_cause, Polymerase Chain Reaction, law.invention, 0302 clinical medicine, law, Polymorphism (computer science), Family history, MESH: DNA Mutational Analysis, MESH : Polymerase Chain Reaction, Polymerase chain reaction, MESH: Testicular Neoplasms, Genetics, 0303 health sciences, Mutation, MESH: Genetic Predisposition to Disease, Neoplasms, Germ Cell and Embryonal, Neoplasm Proteins, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH: Neoplasms, Germ Cell and Embryonal, MESH : Mutation, Germ cell, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], MESH: Mutation, MESH : Male, MESH : DNA Mutational Analysis, Biology, MESH : Family Health, Article, 03 medical and health sciences, MESH : Neoplasm Proteins, MESH : Neoplasms, Germ Cell and Embryonal, Testicular Neoplasms, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, MESH : Testicular Neoplasms, [ SDV.OT ] Life Sciences [q-bio]/Other [q-bio.OT], Gene, 030304 developmental biology, Family Health, MESH: Humans, MESH : Humans, Cancer, MESH: Polymerase Chain Reaction, medicine.disease, MESH: Male, MESH: Family Health, MESH : Genetic Predisposition to Disease
Abstract: A base substitution in the mouse Dnd1 gene resulting in a truncated Dnd protein has been shown to be responsible for germ cell loss and the development of testicular germ cell tumors (TGCT) in the 129 strain of mice. We investigated the human orthologue of this gene in 263 patients (165 with a family history of TGCT and 98 without) and found a rare heterozygous variant, p. Glu86Ala, in a single case. This variant was not present in control chromosomes (0/4,132). Analysis of the variant in an additional 842 index TGCT cases (269 with a family history of TGCT and 573 without) did not reveal any additional instances. The variant, p. Glu86Ala, is within a known functional domain of DND1 and is highly conserved through evolution. Although the variant may be a rare polymorphism, a change at such a highly conserved residue is characteristic of a disease-causing variant. Whether it is disease-causing or not, mutations in DND1 make, at most, a very small contribution to TGCT susceptibility in adults and adolescents.
Published: 2008
Full Text: View/download PDF

9. Analysis of the fiber architecture of the heart by quantitative polarized light microscopy. Accuracy, limitations and contribution to the study of the fiber architecture of the ventricles during fetal and neonatal life

Author: Ayman Mourad, Gabrielle Michalowicz, Pierre-Simon Jouk, Annie Raoult, Yves Usson, Denis Caillerie, Vuk Milisic, RFMQ, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Equations aux Dérivées Partielles (EDP), Laboratoire Jean Kuntzmann (LJK), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Laboratoire sols, solides, structures - risques [Grenoble] (3SR), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Equations aux Dérivées Partielles ( EDP ), Laboratoire Jean Kuntzmann ( LJK ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Mathématiques Appliquées à Paris 5 ( MAP5 - UMR 8145 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National des Sciences Mathématiques et de leurs Interactions-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire sols, solides, structures - risques [Grenoble] ( 3S-R ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National Polytechnique de Grenoble ( INPG ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF)
Subjects: MESH: Neoplasm Proteins, MESH : Transcription Factors, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, MESH : DNA, Muscle Fibers, Skeletal, MESH : Models, Biological, 030204 cardiovascular system & hematology, Tracking (particle physics), 030218 nuclear medicine & medical imaging, Section (fiber bundle), MESH : Muscle Fibers, 0302 clinical medicine, Orientation (geometry), MESH : Myocardium, Medicine, MESH : G2 Phase, Fiber, MESH : Adaptation, Physiological, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, Polarized light microscopy, MESH : Tumor Suppressor Proteins, MESH: Infant, Newborn, MESH: Muscle Fibers, MESH: DNA, MESH : Protein Binding, General Medicine, MESH: Transcription Factors, Adaptation, Physiological, Azimuth, MESH: Reproducibility of Results, MESH: Heterochromatin, MESH: Microscopy, Polarization, Microscopy, Polarization, Cardiology and Cardiovascular Medicine, MESH : Chromosomal Proteins, Non-Histone, Pulmonary and Respiratory Medicine, MESH: Cell Line, Tumor, MESH: Myocardium, Heart Ventricles, MESH : Infant, Newborn, Models, Biological, 03 medical and health sciences, Optics, Fetal Heart, MESH : Neoplasm Proteins, MESH: Chromosomal Proteins, Non-Histone, Humans, MESH: Protein Binding, MESH: Tumor Suppressor Proteins, MESH : Microscopy, Polarization, MESH: Humans, Pixel, Plane (geometry), business.industry, MESH : Cell Line, Tumor, MESH : Heterochromatin, Myocardium, MESH : Reproducibility of Results, MESH : Humans, Infant, Newborn, MESH: Models, Biological, Reproducibility of Results, MESH : Nuclear Proteins, MESH : Fetal Heart, MESH: Adaptation, Physiological, MESH: G2 Phase, MESH: Fetal Heart, MESH : Heart Ventricles, Surgery, MESH: Heart Ventricles, business, MESH: Nuclear Proteins
Abstract: International audience; OBJECTIVE: To address the advantages and drawbacks of quantitative polarized light microscopy for the study of myocardial cell orientation and to identify its contribution in the field. METHODS: Quantitative polarized light microscopy allows to measure the orientation of myocardial fibers into the ventricular mass. For each pixel of a horizontal section, this orientation is the mean value of the directions of all myosin filaments contained in the thickness of the section for each pixel of the section and is accounted for by two angles, the azimuth angle, which is the angle of the fiber in the plane of the section, and the elevation angle, which measures the way the fiber escapes from the section. The azimuth is accurately measured, and its range of definition is complete from 0 degrees to 180 degrees . The elevation angle can be defined only in the range 0 degrees to 90 degrees . It is accurately measured between 20 degrees and 70 degrees . From 0 degrees to 20 degrees , there is a systematic bias raising the measured values, and from 70 degrees to 90 degrees , the angle is not accurately measured. RESULTS: With this method, we validated Streeter's conjecture concerning the architecture of the left ventricle. We formulated a pretzel conjecture about the fiber architecture of the whole ventricular mass during fetal period. In our model, elaborated by visual analysis of registered maps of orientation, the fibers run like geodesics on a nested set of 'pretzels'. Next, the validity of the helical ventricular myocardial band model of Torrent-Guasp has been examined. It appears that the band model does not account for the patterns observed in our data during the fetal period. However, after the major events of postnatal cardiovascular adaptation, our data can neither discard nor confirm Torrent-Guasp's model. CONCLUSIONS: Present limitations of quantitative polarized light analysis can neither confirm nor discard the existing models of fiber orientation in the whole ventricular mass after the neonatal period. However, the problems of mathematical and experimental validation of these two models have been posed in a rigorous manner. Non-ambiguous fiber tracking and demonstration of these models will require significant improvement of the definition range of the elevation angle that should be extended to 180 degrees .
Published: 2007
Full Text: View/download PDF

10. Spectrum of NPHP6/CEP290 mutations in Leber congenital amaurosis and delineation of the associated phenotype

Author: Josseline Kaplan, Jean-Louis Dufier, Hélène Dollfus, Elisa Fazzi, Arnold Munnich, Nathalie Delphin, Sylvie Gerber, Olivier Roche, Jean-Michel Rozet, Sylvain Hanein, Isabelle Perrault, Sabine Defoort-Dhellemmes, Virology Laboratory, Hôpital Rothchild, Neurologie et thérapeutique expérimentale, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR70-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of cell biology, Harvard Medical School [Boston] ( HMS ), Taplin Biological Mass Spectrometry Facility, Biogéosciences [Dijon] ( BGS ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Centre de recherche thérapeutique en ophtalmologie, Université Paris Descartes - Paris 5 ( UPD5 ) -EA2502, EA no 2502 du ministère de la Recherche, de l'Enseignement Supérieur et la Technologie, Université Paris Descartes - Paris 5 ( UPD5 ) -CERTO, Service d'ophtalmologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Laboratoire Magmas et Volcans ( LMV ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Neurosciences Fonctionnelles et Pathologies ( LNFP ), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Institut de génétique et biologie moléculaire et cellulaire ( IGBMC ), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service de génétique médicale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Necker - Enfants Malades [AP-HP], Handicaps génétiques de l'enfant ( Inserm U393 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Groupe de Physique des Solides ( GPS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Nanosciences de Paris ( INSP ), Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Harvard Medical School [Boston] (HMS), Biogéosciences [UMR 6282] [Dijon] (BGS), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Paris Descartes - Paris 5 (UPD5)-EA2502, Université Paris Descartes - Paris 5 (UPD5)-CERTO, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Neurosciences Fonctionnelles et Pathologies (LNFP), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Handicaps génétiques de l'enfant (Inserm U393), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Groupe de Physique des Solides (GPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut des Nanosciences de Paris (INSP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Biogéosciences [UMR 6282] (BGS), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR70-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Neoplasm Proteins, Retinal degeneration, Linkage disequilibrium, genetic structures, MESH: Introns, MESH: Antigens, Neoplasm, Cell Cycle Proteins, MESH : Child, Preschool, Linkage Disequilibrium, MESH : Antigens, Neoplasm, MESH : Frameshift Mutation, Exon, 0302 clinical medicine, MESH : Exons, MESH : Child, MESH: Child, Genotype, Child, Frameshift Mutation, Genetics (clinical), Genetics, 0303 health sciences, MESH : Linkage Disequilibrium, MESH : Optic Atrophy, Hereditary, Leber, MESH: Frameshift Mutation, MESH : Infant, Exons, MESH : Adult, MESH: Infant, Phenotype, Neoplasm Proteins, 3. Good health, MESH: Linkage Disequilibrium, Child, Preschool, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Adult, Optic Atrophy, Hereditary, Leber, Biology, MESH : Introns, Frameshift mutation, 03 medical and health sciences, MESH : Neoplasm Proteins, Antigens, Neoplasm, Intronic Mutation, medicine, Humans, Allele, Alleles, 030304 developmental biology, MESH: Humans, MESH: Alleles, MESH: Child, Preschool, MESH : Humans, Infant, MESH: Optic Atrophy, Hereditary, Leber, MESH: Adult, medicine.disease, Introns, eye diseases, Cytoskeletal Proteins, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030221 ophthalmology & optometry, sense organs, MESH: Exons, MESH : Alleles
Abstract: International audience; Leber congenital amaurosis (LCA) is the earliest and most severe retinal degeneration responsible for congenital blindness. Hitherto, 13 LCA genes have been mapped, nine of which have been identified. Recently, mutations in the NPHP6/CEP290 gene were shown to account for Joubert and Senior-Loken syndromes and to represent a frequent cause of isolated LCA. All LCA patients shared an intronic mutation resulting in an aberrantly spliced transcript and low levels of wild-type transcript that was believed to explain the absence of cerebellar and renal involvement in these patients. Here, we confirm the high frequency of NPHP6/CEP290 mutations in our series of LCA families hailing worldwide (22%). However, we show that conversely to other LCA genes, NPHP6 is involved in families of European descent only (38/38). A total of 24 different mutations were found, 23 of which are novel (one founder mutation in the North region of France). All mutations but two were either nonsense, frameshift, or splice-site changes. The common NPHP6/CEP290 intronic mutation accounted for 43% (33/76) of all disease alleles. Twelve families did not carry this common intronic mutation. At least 10 out of them harboured two mutations expected to truncate the protein questioning the relevance of the assumption according to which the retinal-restricted phenotype in LCA patient could be due to a residual NPHP6/CEP290 activity. Finally, we show that all patients were affected with the cone-rod subtype of the disease whatever their NPHP6/CEP290 genotype.
Published: 2007
Full Text: View/download PDF

11. STD and TRNOESY NMR studies for the epitope mapping of the phosphorylation motif of the oncogenic protein beta-catenin recognized by a selective monoclonal antibody

Author: Simon Megy, Gildas Bertho, Richard Benarous, Françoise Baleux, Josyane Gharbi-Benarous, Jean-Pierre Girault, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Chimie Organique, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques ( LCBPT - UMR 8601 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Chimie Organique ( UCO ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Chimie Organique (UCO), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)
Subjects: Models, Molecular, MESH: Neoplasm Proteins, Magnetic Resonance Spectroscopy, Amino Acid Motifs, MESH: beta Catenin, Peptide, Nuclear Overhauser effect, 01 natural sciences, Biochemistry, Epitope, MESH: Antibodies, Monoclonal, MESH : Phosphorylation, Epitopes, MESH: Amino Acid Motifs, MESH: Protein Structure, Tertiary, Structural Biology, Neoplasms, MESH: Nuclear Magnetic Resonance, Biomolecular, TRNOESY, MESH: Neoplasms, Phosphorylation, beta Catenin, MESH : Ubiquitin, chemistry.chemical_classification, 0303 health sciences, biology, Chemistry, MESH : Peptides, MESH: Peptides, Antibodies, Monoclonal, Nuclear magnetic resonance spectroscopy, P-β-Catenin/antibody complex, Ubiquitin ligase, Neoplasm Proteins, Restrained molecular dynamics, MESH : Antibodies, Monoclonal, MESH : SKP Cullin F-Box Protein Ligases, Two-dimensional nuclear magnetic resonance spectroscopy, MESH : Protein Structure, Tertiary, Binding fragment, MESH: Models, Molecular, MESH: SKP Cullin F-Box Protein Ligases, MESH : Amino Acid Motifs, MESH: Ubiquitin, MESH: Epitopes, MESH : Models, Molecular, Biophysics, MESH : Epitopes, MESH : Nuclear Magnetic Resonance, Biomolecular, Bound structure, 010402 general chemistry, 03 medical and health sciences, MESH : Neoplasm Proteins, P-β-Catenin phosphorylated peptide, Genetics, Humans, Molecular Biology, Nuclear Magnetic Resonance, Biomolecular, Antibody, 030304 developmental biology, MESH : Protein Processing, Post-Translational, MESH: Epitope Mapping, SKP Cullin F-Box Protein Ligases, MESH: Humans, MESH: Phosphorylation, Ubiquitin, MESH: Magnetic Resonance Spectroscopy, β-Catenin oncogenic protein, MESH : Humans, Cell Biology, MESH : beta Catenin, MESH : Neoplasms, 0104 chemical sciences, Protein Structure, Tertiary, STD NMR, Epitope mapping, MESH : Epitope Mapping, MESH: Protein Processing, Post-Translational, biology.protein, MESH : Magnetic Resonance Spectroscopy, Peptides, Protein Processing, Post-Translational, Epitope Mapping, Conformational epitope
Abstract: International audience; The interaction of the P-beta-Cat(19-44) peptide, a 26 amino acid peptide (K(19)AAVSHWQQQSYLDpSGIHpSGATTTAP(44)) that mimics the phosphorylated beta-Catenin antigen, has been studied with its monoclonal antibody BC-22, by transferred nuclear Overhauser effect NMR spectroscopy (TRNOESY) and saturation transfer difference NMR (STD NMR) spectroscopy. This antibody is specific to diphosphorylated beta-Catenin and does not react with the non-phosphorylated protein. Phosphorylation of beta-Catenin at sites Ser33 and Ser37 on the DSGXXS motif is required for the interaction of beta-Catenin with the ubiquitin ligase SCF(beta-TrCP). beta-TrCP is involved in the ubiquitination and proteasome targeting of the oncogenic protein beta-Catenin, the accumulation of which has been implicated in various human cancers. The three-dimensional structure of the P-beta-Cat(19-44) in the bound conformation was determined by TRNOESY NMR experiments; the peptide adopts a compact structure in the presence of mAb with formation of turns around Trp25 and Gln26, with a tight bend created by the DpS(33)GIHpS(37) motif; the peptide residues (D32-pS37) forming this bend are recognized by the antibody as demonstrated by STD NMR experiments. STD NMR studies provide evidence for the existence of a conformational epitope containing tandem repeats of phosphoserine motifs. The peptide's epitope is predominantly located in the large bend and in the N-terminal segment, implicating bidentate association. These findings are in excellent agreement with a recently published NMR structure required for the interaction of beta-Catenin with the SCF(beta-TrCP) protein.
Published: 2006
Full Text: View/download PDF

12. Cellular FLICE-inhibitory protein: an attractive therapeutic target?

Author: Olivier Micheau, Mort cellulaire et cancer, Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC-Institut National de la Santé et de la Recherche Médicale (INSERM), and Micheau, Olivier
Subjects: MESH: Neoplasm Proteins, MESH: Signal Transduction, MESH: CASP8 and FADD-Like Apoptosis Regulating Protein, MESH : Drug Design, MESH: Mice, Inbred NOD, apoptosis and human diseases, MESH : Multiple Sclerosis, Clinical Biochemistry, CASP8 and FADD-Like Apoptosis Regulating Protein, Arthritis, MESH : Alzheimer Disease, Apoptosis, MESH : Alternative Splicing, Disease, MESH : Models, Biological, MESH: Drug Design, Arthritis, Rheumatoid, MESH : Diabetes Mellitus, Type 1, Mice, 0302 clinical medicine, MESH: Lymphoproliferative Disorders, Mice, Inbred NOD, Neoplasms, MESH: Autoimmune Diseases, Drug Discovery, MESH: Neoplasms, MESH: Animals, MESH : Cardiovascular Diseases, 0303 health sciences, MESH: Arthritis, Rheumatoid, MESH : Gene Expression Regulation, MESH : Lymphoproliferative Disorders, MESH: Alternative Splicing, Intracellular Signaling Peptides and Proteins, MESH: Gene Expression Regulation, 3. Good health, Neoplasm Proteins, medicine.anatomical_structure, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Molecular Medicine, Signal transduction, Alzheimer's disease, MESH: Diabetes Mellitus, Type 1, Signal Transduction, Multiple Sclerosis, c-FLIP, T cell, Biology, Inhibitor of apoptosis, Models, Biological, Article, Autoimmune Diseases, 03 medical and health sciences, MESH : Neoplasm Proteins, MESH : Autoimmune Diseases, MESH : Intracellular Signaling Peptides and Proteins, Alzheimer Disease, MESH: Intracellular Signaling Peptides and Proteins, MESH : Mice, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Pharmacology, MESH : Signal Transduction, MESH: Humans, MESH : Mice, Inbred NOD, MESH: Apoptosis, MESH : Humans, MESH: Models, Biological, MESH: Cardiovascular Diseases, MESH: Multiple Sclerosis, MESH : CASP8 and FADD-Like Apoptosis Regulating Protein, medicine.disease, MESH : Neoplasms, Lymphoproliferative Disorders, Alternative Splicing, Diabetes Mellitus, Type 1, Gene Expression Regulation, Flip, Drug Design, Immunology, MESH : Arthritis, Rheumatoid, MESH : Animals, MESH: Alzheimer Disease, MESH : Apoptosis
Abstract: International audience; Cellular FLIP (c-FLIP), also known as FLICE-inhibitory protein, has been identified as an inhibitor of apoptosis triggered by engagement of death receptors (DRs) such as Fas or TRAIL (TNF-related apoptosis-inducing ligand). cFLIP is recruited to DR signalling complexes, where it prevents caspase activation. Animal models have indicated that c-FLIP plays an important role in T cell proliferation and heart development. Abnormal c-FLIP expression has been identified in various diseases such as multiple sclerosis (MS), Alzheimer's disease (AD), diabetes mellitus, rheumatoid arthritis (RA) and various cancers. This review focuses on recent insights into c-FLIP dysregulation associated with human diseases and addresses the possibilities of using c-FLIP as a therapeutic target.
Published: 2003
Full Text: View/download PDF

13. Analysis of prolactin-modulated gene expression profiles during the Nb2 cell cycle using differential screening techniques

Author: Bole-Feysot, Christine, Perret, Eric, Roustan, Paul, Bouchard, Brigitte, Kelly, Paul, Autard, Delphine, Endocrinologie moléculaire, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité de Biologie Moléculaire du Gène, and Sanofi Aventis Recherche
Subjects: MESH : Cell Survival, MESH : RNA, Messenger, MESH : Cloning, Molecular, MESH : Rats, MESH : Flow Cytometry, MESH : Gene Expression Regulation, Neoplastic, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH : Gene Expression Profiling, MESH : Eukaryotic Cells, MESH : Cell Division, MESH : Reprodu, MESH : Neoplasm Proteins, MESH : RNA, Neoplasm, MESH : Prolactin, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH : Mammals, MESH : Cell Cycle, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH : Animals, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract: BACKGROUND: Rat Nb2-11C lymphoma cells are dependent on prolactin for proliferation and are widely used to study prolactin signaling pathways. To investigate the role of this hormone in the transcriptional mechanisms that underlie prolactin-stimulated mitogenesis, five different techniques were used to isolate differentially expressed transcripts: mRNA differential display, representational difference analysis (RDA), subtractive suppressive hybridization (SSH), analysis of weakly expressed candidate genes, and differential screening of an organized library. RESULTS: About 70 transcripts were found to be modulated in Nb2 cells following prolactin treatment. Of these, approximately 20 represent unknown genes. All cDNAs were characterized by northern blot analysis and categorized on the basis of their expression profiles and the functions of the known genes. We compared our data with other cell-cycle-regulated transcripts and found several new potential signaling molecules that may be involved in Nb2 cell growth. In addition, abnormalities in the expression patterns of several transcripts were detected in Nb2 cells, including the constitutive expression of the immediate-early gene EGR-1. Finally, we compared the differential screening techniques in terms of sensitivity, efficiency and occurrence of false positives. CONCLUSIONS: Using these techniques to determine which genes are differentially expressed in Nb2 lymphoma cells, we have obtained valuable insight into the potential functions of some of these genes in the cell cycle. Although this information is preliminary, comparison with other eukaryotic models of cell-cycle progression enables identification of expression abnormalities and proteins potentially involved in signal transduction, which could indicate new directions for research.
Published: 2000

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources

Refine your results

13 results on '"MESH : Neoplasm Proteins"'

1. Sex differences in the GSK3β-mediated survival of adherent leukemic progenitors

2. A protocol to quantify mammary early common progenitors from long-term mammosphere culture

3. Aberrant DNA methylation of cancer-associated genes in gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)

4. Pediatric-inspired intensified therapy of adult T-ALL reveals the favorable outcome of NOTCH1/FBXW7 mutations, but not of low ERG/BAALC expression: a GRAALL study

5. Prognostic value of phosphorylated STAT3 in advanced rectal cancer: a study from 104 French patients included in the EORTC 22921 trial

6. 17q21 variants modify the association between early respiratory infections and asthma

7. KBA.62: a useful marker for primary and metastatic melanomas

8. Analysis of the DND1 gene in men with sporadic and familial testicular germ cell tumors

9. Analysis of the fiber architecture of the heart by quantitative polarized light microscopy. Accuracy, limitations and contribution to the study of the fiber architecture of the ventricles during fetal and neonatal life

10. Spectrum of NPHP6/CEP290 mutations in Leber congenital amaurosis and delineation of the associated phenotype

11. STD and TRNOESY NMR studies for the epitope mapping of the phosphorylation motif of the oncogenic protein beta-catenin recognized by a selective monoclonal antibody

12. Cellular FLICE-inhibitory protein: an attractive therapeutic target?

13. Analysis of prolactin-modulated gene expression profiles during the Nb2 cell cycle using differential screening techniques

Catalog

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

13 results on '"MESH : Neoplasm Proteins"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources