Descriptor: "MESH: Lymphoma, Large B-Cell, Diffuse" - Searchworks@Jio Institute Digital Library Search Results

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27 results on '"MESH: Lymphoma, Large B-Cell, Diffuse"'

1. Health-related quality of life and utility outcomes with selinexor in relapsed/refractory diffuse large B-cell lymphoma

Author: Agnes Nagy, Rene-Olivier Casasnovas, Sameer Bakhshi, Sharon Shacham, Juan-Manuel Sancho, Ronit Gurion, Josée M. Zijlstra, Jatin P. Shah, Miklos Egyed, Brian T. Hill, Krzysztof Warzocha, Gabriel Tremblay, Michael W. Schuster, Fritz Offner, Reda Bouabdallah, Dimitrios Tomaras, Paolo Caimi, Andre Goy, Priyanka Samal, Catherine Thieblemont, Joost S.P. Vermaat, Matthew Ku, Ulrich Jäger, John Kuruvilla, Nagesh Kalakonda, George A Follows, Eric Van Den Neste, Miguel Ángel Canales Albendea, Michael Kauffman, Nada Hamad, Fatima De la Cruz, Patrick Daniele, Marie Maerevoet, Theodoros Vasilakopoulos, Federica Cavallo, Sylvain Choquet, Karyopharm Therapeutics Inc., Newton, MA, U918, Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Amsterdam UMC, Addenbrooke's Hospital, Cambridge University NHS Trust, Leiden University Medical Center (LUMC), Institute of Translational Medicine, University of Liverpool, Hackensack University Medical Center [Hackensack], Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Catholique de Louvain = Catholic University of Louvain (UCL), Cleveland Clinic, Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Turin, Hospital Universitario Virgen del Rocío [Sevilla], University Health Network, St Vincent's Hospital Melbourne [Australia], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Medizinische Universität Wien = Medical University of Vienna, University Hospitals Case Medical Center, Tel Aviv University [Tel Aviv], Institute of Hematology and Transfusion Medicine[Warsaw, Poland] (IHTM), Germans Trias i Pujol Hospital, Barcelona Autonomous University, Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Ghent University Hospital, National and Kapodistrian University of Athens (NKUA), Semmelweis University [Budapest], Hospital Universitario La Paz, UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, and UCL - (SLuc) Service d'hématologie
Subjects: Male, Oncology, Cancer Research, Health utility, FACT-Lym, patient reported outcomes, MESH: Patient Reported Outcome Measures, MESH: Aged, 80 and over, 0302 clinical medicine, Quality of life, Recurrence, Medicine and Health Sciences, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, health, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, Middle Aged, MESH: Drug Resistance, Neoplasm, 3. Good health, health-related quality of life, Hydrazines, EQ-5D-5L, patient-reported outcomes, 030220 oncology & carcinogenesis, Female, health utility, Lymphoma, Large B-Cell, Diffuse, MESH: Hydrazines, Adult, disutility of adverse events, medicine.medical_specialty, diffuse large B-cell lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Refractory, Internal medicine, medicine, Humans, health state utility, selinexor, Patient Reported Outcome Measures, Aged, Health related quality of life, MESH: Humans, business.industry, MESH: Quality of Life, MESH: Adult, Triazoles, medicine.disease, MESH: Male, MESH: Recurrence, Lymphoma, MESH: Triazoles, utility, Drug Resistance, Neoplasm, Relapsed refractory, Quality of Life, MESH: Lymphoma, Large B-Cell, Diffuse, business, MESH: Female, Diffuse large B-cell lymphoma, Progressive disease, 030215 immunology
Abstract: Aim: Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Functional Assessment of Cancer Therapy (FACT) - Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Results: Treatment responders maintained higher FACT - Lymphoma (p = 3 adverse events and serious adverse events were not associated with clinically meaningful negative QoL impacts.
Published: 2021
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2. The immune contexture of primary central nervous system diffuse large B cell lymphoma associates with patient survival and specific cell signaling

Author: Emmanuel Cornillot, Vanessa Lacheretz-Szablewski, Valérie Costes-Martineau, Valérie Rigau, Valère Cacheux, Melissa Alame, Jacques Colinge, Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, and Hôpital Gui de Chauliac [CHU Montpellier]
Subjects: 0301 basic medicine, MESH: Signal Transduction, Male, medicine.medical_treatment, Medicine (miscellaneous), Kaplan-Meier Estimate, MESH: Down-Regulation, MESH: Central Nervous System Neoplasms, Central Nervous System Neoplasms, Cohort Studies, 0302 clinical medicine, MESH: Aged, 80 and over, HLA Antigens, MESH: Tumor Microenvironment, Tumor Microenvironment, cellular interactions, Precision Medicine, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), MESH: Cohort Studies, MESH: HLA Antigens, MESH: Aged, Aged, 80 and over, MESH: Middle Aged, immune contexture, Wnt signaling pathway, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, bioinformatics, Middle Aged, Prognosis, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, immunotherapy, Lymphoma, Large B-Cell, Diffuse, Research Paper, Signal Transduction, Adult, Notch signaling pathway, Down-Regulation, [SDV.CAN]Life Sciences [q-bio]/Cancer, chemical and pharmacologic phenomena, Human leukocyte antigen, Biology, MESH: Precision Medicine, MESH: Prognosis, 03 medical and health sciences, MESH: Gene Expression Profiling, Immune system, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, MESH: Kaplan-Meier Estimate, PCNSL, Aged, Tumor microenvironment, MESH: Humans, Gene Expression Profiling, MESH: Adult, Immunotherapy, medicine.disease, Immune checkpoint, MESH: Male, 030104 developmental biology, Cancer research, MESH: Lymphoma, Large B-Cell, Diffuse, Diffuse large B-cell lymphoma, MESH: Female
Abstract: International audience; Rationale: Primary central nervous system diffuse large B-cell lymphoma (PCNSL) is a rare and aggressive entity that resides in an immune-privileged site. The tumor microenvironment (TME) and the disruption of the immune surveillance influence lymphoma pathogenesis and immunotherapy resistance. Despite growing knowledge on heterogeneous therapeutic responses, no comprehensive description of the PCNSL TME is available. We hence investigated the immune subtypes of PCNSL and their association with molecular signaling and survival. Methods: Analysis of PCNSL transcriptomes (sequencing, n = 20; microarrays, n = 34). Integrated correlation analysis and signaling pathway topology enabled us to infer intercellular interactions. Immunohistopathology and digital imaging were used to validate bioinformatic results. Results: Transcriptomics revealed three immune subtypes: immune-rich, poor, and intermediate. The immune-rich subtype was associated to better survival and characterized by hyper-activation of STAT3 signaling and inflammatory signaling, e.g., IFNγ and TNF-α, resembling the hot subtype described in primary testicular lymphoma and solid cancer. WNT/β-catenin, HIPPO, and NOTCH signaling were hyper-activated in the immune-poor subtype. HLA down-modulation was clearly associated with a low or intermediate immune infiltration and the absence of T-cell activation. Moreover, HLA class I down-regulation was also correlated with worse survival with implications on immune-intermediate PCNSL that frequently feature reduced HLA expression. A ligand-receptor intercellular network revealed high expression of two immune checkpoints, i.e., CTLA-4/CD86 and TIM-3/LAGLS9. TIM-3 and galectin-9 proteins were clearly upregulated in PCNSL. Conclusion: Altogether, our study reveals that patient stratification according to immune subtypes, HLA status, and immune checkpoint molecule quantification should be considered prior to immune checkpoint inhibitor therapy. Moreover, TIM-3 protein should be considered an axis for future therapeutic development.
Published: 2020
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3. Common origin of sequential cutaneous CD30+ lymphoproliferations with nodal involvement evidenced by genome-wide clonal evolution

Author: José Adélaïde, Max Chaffanet, Nadine Carbuccia, Anne Murati, Reda Bouabdallah, Lénaïg Mescam, Morgan Avenin, Daniel Birnbaum, Luc Xerri, Diane Coso, Sebastien Taix, François Bertucci, Séverine Garnier, N. Bonnet, Arnaud Guille, Département de Biopathologie, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hématologie, Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Histology, CD30, [SDV]Life Sciences [q-bio], diffuse large B-cell lymphoma, Context (language use), MESH: Lymph Nodes, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Somatic evolution in cancer, MESH: Clonal Evolution, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, cutaneous anaplastic large-cell lymphoma, immune system diseases, hemic and lymphatic diseases, medicine, Lymphomatoid papulosis, Gene, Lymph node, MESH: Humans, MESH: Middle Aged, MESH: Skin Neoplasms, MESH: Lymphomatoid Papulosis, General Medicine, medicine.disease, lymphomatoid papulosis, MESH: Male, Lymphoma, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, MESH: Lymphoma, Large B-Cell, Diffuse, MESH: Disease Progression, MESH: Lymphoma, Large-Cell, Anaplastic, Diffuse large B-cell lymphoma, MESH: Neoplasm Recurrence, Local
Abstract: AIMS This study sought to clarify the molecular pathways underlying the putative evolution from lymphomatoid papulosis (LyP) to cutaneous anaplastic large-cell lymphoma (c-ALCL) and lymph node invasion (LNI). METHODS AND RESULTS We analysed nine sequential tumours from the same patient presenting with parallel evolution of LyP (n = 3) and c-ALCL (n = 1) with LNI (n = 1), combined with systemic diffuse large B-cell lymphoma (DLBCL) (n = 4). Clonality analysis showed a common clonal T-cell origin in the five CD30+ lesions, and a common clonal B-cell origin in the four DLBCL relapses. Array-comparative genomic hybridisation and targeted next-generation sequencing analysis demonstrated relative genomic stability of LyP lesions as compared with clonally related anaplastic large-cell lymphoma (ALCL) tumours, which showed 4q and 22q13 deletions involving the PRDM8 and TIMP3 tumour suppressor genes, respectively. The three analysed CD30+ lesions showed mostly private (specific to each sample) genetic alterations, suggesting early divergence from a common precursor. In contrast, DLBCL tumours showed progressive accumulation of private alterations, indicating late divergence. CONCLUSIONS Sequential cutaneous and nodal CD30+ tumours were clonally related. This suggests that LyP, c-ALCL and LNI represent a continuous spectrum of clonal evolution emerging from a common precursor of cutaneous CD30+ lymphoproliferations. Therefore, nodal ALCL tumours in the context of LyP should be considered as a form of transformation rather than composite lymphoma.
Published: 2019
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4. Factors related to the relative survival of patients with diffuse large B-cell lymphoma in a population-based study in France: does socio-economic status have a role?

Author: Alain Monnereau, Sébastien Orazio, Olivier Dejardin, Sandra Le Guyader-Peyrou, Marc Maynadié, Xavier Troussard, Registre des hémopathies malignes de la Gironde, Institut Bergonié - CRLCC Bordeaux, Cancer environnement ( EPICENE ), Bordeaux population health ( BPH ), Université de Bordeaux ( UB ) -Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bordeaux ( UB ) -Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Cancers et préventions, Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Registre des hémopathies malignes de Côte d'Or, Registre des hémopathies malignes de Basse-Normandie, CHU Caen, Laboratoire d'hématologie biologique [Caen], Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Caen, Cancer environnement (EPICENE ), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Registre des hémopathies malignes de Basse-Normandie [CHU Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), université de Bourgogne, LNC, and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, 0301 basic medicine, Pediatrics, Multivariate analysis, MESH: Registries, MESH : Aged, MESH: Comorbidity, Comorbidity, MESH : Lymphoma, Large B-Cell, Diffuse, MESH: Aged, 80 and over, 0302 clinical medicine, International Prognostic Index, MESH : Child, MESH: Child, MESH : Population Surveillance, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, MESH : Female, Registries, Young adult, Child, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, MESH : Prognosis, Relative survival, MESH: Patient Outcome Assessment, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Articles, Hematology, Middle Aged, MESH : Adult, Prognosis, MESH : Patient Outcome Assessment, 3. Good health, MESH: Young Adult, Population Surveillance, MESH: Survival Analysis, 030220 oncology & carcinogenesis, MESH : Comorbidity, Marital status, Female, France, Lymphoma, Large B-Cell, Diffuse, Non-Hodgkin Leukemia, Adult, medicine.medical_specialty, Adolescent, MESH : Male, MESH: Factor Analysis, Statistical, MESH : Young Adult, MESH : Factor Analysis, Statistical, MESH: Prognosis, MESH: Population Surveillance, MESH: Social Class, Young Adult, 03 medical and health sciences, MESH : Adolescent, Internal medicine, MESH : Social Class, medicine, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, MESH : France, Survival analysis, Aged, MESH: Adolescent, MESH: Humans, business.industry, MESH : Humans, MESH: Adult, medicine.disease, Survival Analysis, MESH: Male, Patient Outcome Assessment, MESH: France, 030104 developmental biology, Social Class, MESH: Lymphoma, Large B-Cell, Diffuse, MESH : Survival Analysis, Factor Analysis, Statistical, business, MESH: Female, Diffuse large B-cell lymphoma, MESH : Registries
Abstract: IF 7.702; International audience; The survival of patients with diffuse large B-cell lymphoma has increased during the last decade as a result of addition of anti-CD20 to anthracycline-based chemotherapy. Although the trend is encouraging, there are persistent differences in survival within and between the USA and European countries suggesting that non-biological factors play a role. Our aim was to investigate the influence of such factors on relative survival of patients with diffuse large B-cell lymphoma. We conducted a retrospective, multicenter, registry-based study in France on 1165 incident cases of diffuse large B-cell lymphoma between 2002 and 2008. Relative survival analyses were performed and missing data were controlled with the multiple imputation method. In a multivariate analysis, adjusted for age, sex and International Prognostic Index, we confirmed that time period was associated with a better 5-year relative survival. The registry area, the medical specialty of the care department (onco-hematology versus other), the time to travel to the nearest teaching hospital, the place of treatment (teaching versus not-teaching hospital -borderline significance), a comorbidity burden and marital status were independently associated with the 5-year relative survival. Adjusted for first-course treatment, inclusion in a clinical trial and treatment discussion in a multidisciplinary meeting were strongly associated with a better survival outcome. In contrast, socio-economic status (determined using the European Deprivation Index) was not associated with outcome. Despite therapeutic advances, various non-biological factors affected the relative survival of patients with diffuse large B-cell lymphoma. The notion of lymphoma-specific expertise seems to be essential to achieve optimal care management and reopens the debate regarding centralization of these patients' care in hematology/oncology departments.
Published: 2016
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5. Identification of novel recurrent ETV6-IgH fusions in primary central nervous system lymphoma

Author: Dominique Figarella-Branger, Franck Bielle, Clovis Adam, Louis Royer-Perron, Guillaume Gauchotte, David Meyronet, Aurélie Bruno, Chiara Villa, Amithys Rahimian, Blandine Boisselier, Carole Soussain, Fabrice Chrétien, Khê Hoang-Xuan, Caroline Houillier, Sandrine Eimer, Mailys Daniau, Frederic Davi, Karima Mokhtari, Karim Labreche, Justine Guegan, Pierre de la Grange, Agusti Alentorn, Marc Polivka, Audrey Rousseau, Frédéric Lemoine, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), OncoNeuroTek [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], GenoSplice, Ltd, GenoSplice technology, GenoSplice [Paris], iCONICS, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d’Anatomopathologie [Le Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hospices civils de Lyon, hôpital neurologique Pierre-Wertheimer, Laboratoire d'Anatomie Pathologique-Neuropathologique [AP-HM Hôpital La Timone], Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Pathologie [Hôpital Foch], Hôpital Foch [Suresnes], Centre Hospitalier Sainte Anne [Paris], Centre Hospitalier Universitaire de Bordeaux (CHU de Bordeaux), Département de Pathologie Cellulaire et Tissulaire [CHU Angers] (Laboratoire d’Histopathologie-Cytopathologie), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hôpital René HUGUENIN (Saint-Cloud), This work is part of the national program Cartes d’Identité des Tumeurs (CIT) funded and developed by the Ligue nationale contre le cancer, the Institut National du Cancer, Association pour la recherche sur les tumeurs cérébrales (ARTC), Cancéropôle Île-de-France 'Emergence 2015-1' (2015-1-EMERG-05-INSERM 6-1), Ligue nationale contre le cancer (Comité du Val d’Oise, R14044DD), Ligue Nationale contre le cancer 'Recherche épidemiologique' (N° PRE2015.LNCC), Fondation pour la Recherche Médicale (FDT20140930968), and the program 'Investissements d’avenir' ANR-10-IAIHU-06, and the Institut National du Cancer (INCa) (Réseau Expert National LOC, Lymphomes Oculo-Cérébraux). This study was supported by the Lymphomes Oculo-Cérébraux (LOC) study group network (Réseau national de centres experts des lymphomes primitifs du système nerveux central), We would like to thank the French LOC Network investigators. Specimens from Marseille were retrieved from the AP-HM tumor bank AC 2013-1786, ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Incubateur et Pépinière d'Entreprises Paris-Salpêtrière (iPEPS-ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Male, Cancer Research, Oncogene Proteins, Fusion, MESH: Central Nervous System Neoplasms, Fusion gene, Central Nervous System Neoplasms, 0302 clinical medicine, hemic and lymphatic diseases, MESH: Middle Aged, medicine.diagnostic_test, Primary central nervous system lymphoma, RNA sequencing, ETV6-IgH, MESH: Follow-Up Studies, Middle Aged, Prognosis, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Survival Rate, Oncology, fusion gene, MESH: Repressor Proteins, 030220 oncology & carcinogenesis, Basic and Translational Investigations, Female, Lymphoma, Large B-Cell, Diffuse, MESH: Biomarkers, Tumor, Haploinsufficiency, Immunoglobulin Heavy Chains, MESH: Immunoglobulin Heavy Chains, MESH: Proto-Oncogene Proteins c-ets, MESH: Survival Rate, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MESH: Prognosis, 03 medical and health sciences, primary CNS lymphoma, medicine, Biomarkers, Tumor, Humans, Survival rate, MESH: Humans, Proto-Oncogene Proteins c-ets, medicine.disease, MESH: Male, Lymphoma, haploinsufficiency, Repressor Proteins, ETV6, 030104 developmental biology, Cancer research, Immunoglobulin heavy chain, MESH: Lymphoma, Large B-Cell, Diffuse, Neurology (clinical), MESH: Female, Fluorescence in situ hybridization, Follow-Up Studies, MESH: Oncogene Proteins, Fusion
Abstract: International audience; Background: Primary central nervous system lymphoma (PCNSL) represents a particular entity within non-Hodgkin lymphomas and is associated with poor outcome. The present study addresses the potential clinical relevance of chimeric transcripts in PCNSL discovered by using RNA sequencing (RNA-seq).Methods: Seventy-two immunocompetent and newly diagnosed PCNSL cases were included in the present study. Among them, 6 were analyzed by RNA-seq to detect new potential fusion transcripts. We confirmed the results in the remaining 66 PCNSL. The gene fusion was validated by fluorescence in situ hybridization (FISH) using formalin-fixed paraffin-embedded (FFPE) samples. We assessed the biological and clinical impact of one new gene fusion.Results: We identified a novel recurrent gene fusion, E26 transformation-specific translocation variant 6-immunoglobulin heavy chain (ETV6-IgH). Overall, ETV6-IgH was found in 13 out of 72 PCNSL (18%). No fusion conserved an intact functional domain of ETV6, and ETV6 was significantly underexpressed at gene level, suggesting an ETV6 haploinsufficiency mechanism. The presence of the gene fusion was also validated by FISH in FFPE samples. Finally, PCNSL samples harboring ETV6-IgH showed a better prognosis in multivariate analysis, P = 0.03, hazard ratio = 0.33, 95% CI = 0.12-0.88. The overall survival at 5 years was 69% for PCNSL harboring ETV6-IgH versus 29% for samples without this gene fusion.Conclusions: ETV6-IgH is a new potential surrogate marker of PCNSL with favorable prognosis with ETV6 haploinsufficiency as a possible mechanism. The potential clinical impact of ETV6-IgH should be validated in larger prospective studies.
Published: 2018
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6. IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions

Author: Bianca Balbino, George Delidakis, Tae Hyun Kang, Makiko Watanabe, Kendra Triplett, Anja Lux, Navin Varadarajan, Odile Richard-Le Goff, Oana I. Lungu, Pierre Bruhns, George Georgiou, Corrine Alford, Gabrielle Romain, Margaret A. Lindorfer, Wissam Charab, Falk Nimmerjahn, Yan Jessie Zhang, Hidetaka Tanno, Wupeng Yan, Nicholas M. Marshall, Moses Donkor, Chang-Han Lee, Jiwon Lee, Ronald P. Taylor, Biliana Todorova, University of Texas at Austin [Austin], University of Houston, Anticorps en Thérapie et Pathologie, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Erlangen-Nürnberg [Germany], University of Virginia School of Medicine [US], Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), University of Virginia, Department of Biochemistry and Molecular Genetics (xxx), University of Virginia [Charlottesville], We thank Y. Tanno for assistance with protein expression, A. Bui for assistance with liquid chromatography–tandem mass spectrometry, P. Tucker (University of Texas at Austin) for cancer cell lines, D. Lee (MD Anderson Cancer Center) for patient-derived primary acute lymphocytic leukemia cells, the Macromolecular Crystallography Facility of the University of Texas at Austin, the Berkeley Center for Structural Biology, the Advanced Light Source (supported by the Director, Office of Science, Office of Basic Energy Sciences, of the US Department of Energy under contract DE-AC02-05CH11231), the Proteomics Facility at the University of Texas at Austin (supported by grant RP110782 from the Cancer Prevention Research Training Program), and A. Nicola and the Plate-Forme d'Imagerie Dynamique (Institut Pasteur, Paris) for help with the bioluminescence experiments. Supported by the Clayton Foundation, the Institut Pasteur (P.B. laboratory), the Institut National de la Santé et de la Recherche Médicale (P.B. laboratory), the European Research Council Seventh Frame-work Program (ERC-2013-CoG 616050 for the P.B. laboratory), the Pasteur–Paris University International PhD program (B.B.), the Cancer Prevention Research Training Program (RP140108 to M.D., RP160015 to H.T., and RP130570 to N.V.), the American Cancer Society (123506-PF-13-354-01-CDD to N.M.), Uehara Memorial Foundation (H.T.), Japan Society for the Promotion of Science (H.T.), Deutsche Forschungsgemeinschaft (CRC1181-A07 to F.N.), the US National Institutes of Health (R01CA174385 to N.V., and R01 GM104896 to Y.J.Z.) and the Welch Foundation (F-1778 to Y.J.Z.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Cancer Prevention and Research Institute of Texas., European Project: 616050,EC:FP7:ERC,ERC-2013-CoG,MYELOSHOCK(2014), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Virginia, Martin, Marie, and Role of myeloid cells, their mediators and their antibody receptors in allergic shock (anaphylaxis) using humanized mouse models and clinical samples - MYELOSHOCK - - EC:FP7:ERC2014-09-01 - 2019-08-31 - 616050 - VALID
Subjects: Cytotoxicity, Immunologic, 0301 basic medicine, Cellular immunity, MESH: Complement C1q, MESH: Immunotherapy, Crystallography, X-Ray, Mass Spectrometry, MESH: Antibodies, Monoclonal, Mice, Tandem Mass Spectrometry, Neoplasms, Immunology and Allergy, MESH: Animals, MESH: Neoplasms, Cytotoxicity, Receptor, MESH: Phagocytosis, MESH: Crystallization, MESH: Immunoglobulin G, biology, Effector, Antibodies, Monoclonal, MESH: Enzyme-Linked Immunosorbent Assay, MESH: Chromatography, Gel, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma, 3. Good health, Cell biology, MESH: Surface Plasmon Resonance, Chromatography, Gel, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunotherapy, Lymphoma, Large B-Cell, Diffuse, Antibody, Crystallization, Lymphoma, B-Cell, MESH: Cell Line, Tumor, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Enzyme-Linked Immunosorbent Assay, In Vitro Techniques, MESH: Receptors, IgG, MESH: Immunoglobulin Fc Fragments, 03 medical and health sciences, Classical complement pathway, Immune system, Phagocytosis, Cell Line, Tumor, Animals, Humans, MESH: Cytotoxicity, Immunologic, MESH: Mice, MESH: Lymphoma, B-Cell, MESH: In Vitro Techniques, MESH: Mass Spectrometry, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Humans, Complement C1q, Receptors, IgG, MESH: Tandem Mass Spectrometry, Surface Plasmon Resonance, MESH: Crystallography, X-Ray, Immunoglobulin Fc Fragments, Complement system, MESH: Burkitt Lymphoma, 030104 developmental biology, Immunoglobulin G, biology.protein, MESH: Lymphoma, Large B-Cell, Diffuse, MESH: Chromatography, Liquid, Chromatography, Liquid
Abstract: International audience; Engineered crystallizable fragment (Fc) regions of antibody domains, which assume a unique and unprecedented asymmetric structure within the homodimeric Fc polypeptide, enable completely selective binding to the complement component C1q and activation of complement via the classical pathway without any concomitant engagement of the Fcγ receptor (FcγR). We used the engineered Fc domains to demonstrate in vitro and in mouse models that for therapeutic antibodies, complement-dependent cell-mediated cytotoxicity (CDCC) and complement-dependent cell-mediated phagocytosis (CDCP) by immunological effector molecules mediated the clearance of target cells with kinetics and efficacy comparable to those of the FcγR-dependent effector functions that are much better studied, while they circumvented certain adverse reactions associated with FcγR engagement. Collectively, our data highlight the importance of CDCC and CDCP in monoclonal-antibody function and provide an experimental approach for delineating the effect of complement-dependent effector-cell engagement in various therapeutic settings.
Published: 2017
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7. Prognostic impact of fat tissue loss and cachexia assessed by computed tomography scan in elderly patients with diffuse large B-cell lymphoma treated with immunochemotherapy

Author: Hervé Tilly, Stéphane Leprêtre, Jerome Kraut, Fabrice Jardin, Marie-Laure Fontoura, Romain Modzelewski, Aspasia Stamatoullas, Jean Michel Picquenot, Oana Brehar, Carole Fronville, Vincent Camus, Ali N. Chamseddine, Luminata Groza, Pascal Lenain, Hélène Lanic, Nathalie Cardinael, Emilie Lemasle, Nathalie Contentin, Florian Clatot, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique Psychiatrique Universitaire [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Groupe d'étude des proliférations lymphoïdes (GPL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Breton, Céline, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU), Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, MESH: Combined Modality Therapy, Cachexia, MESH: Immunotherapy, [SDV]Life Sciences [q-bio], Gastroenterology, MESH: Aged, 80 and over, 0302 clinical medicine, International Prognostic Index, Medicine, MESH: Aged, 2. Zero hunger, Aged, 80 and over, 0303 health sciences, Hazard ratio, Hematology, General Medicine, Prognosis, Combined Modality Therapy, 3. Good health, [SDV] Life Sciences [q-bio], Adipose Tissue, 030220 oncology & carcinogenesis, Rituximab, Female, Immunotherapy, Lymphoma, Large B-Cell, Diffuse, MESH: Tomography, X-Ray Computed, MESH: Adipose Tissue, medicine.drug, medicine.medical_specialty, MESH: Prognosis, 03 medical and health sciences, Internal medicine, Humans, 030304 developmental biology, Aged, Retrospective Studies, MESH: Humans, business.industry, MESH: Retrospective Studies, medicine.disease, MESH: Male, Confidence interval, Surgery, MESH: Cachexia, Sarcopenia, MESH: Lymphoma, Large B-Cell, Diffuse, business, Tomography, X-Ray Computed, MESH: Female, Body mass index, Diffuse large B-cell lymphoma
Abstract: Objectives Approximately 30% of DLBCL patients are older than 70 yr. This study evaluated the prognostic impact of a cachexia score (CS) including fat tissue loss (adipopenia) and sarcopenia as assessed by computed tomography (CT scan) in elderly DLBCL patients treated with chemotherapy and rituximab (R). Methods This retrospective analysis included 80 DLBCL patients older than 70 yr treated with R-CHOP or R-miniCHOP. Skeletal muscle (SM) and visceral (V) and subcutaneous (S) adipose (A) tissues were measured by analysing CT images at the third lumbar (L3) level. Results The median age of the patients was 78 yr. Forty-four and 46 patients were considered sarcopenic and adipopenic, respectively. The median progression-free survival (PFS) was 13.6 months in the adipopenic group and 49.4 months in the non-adipopenic group [hazard ratio (HR) = 2.27; 95% confidence interval (CI): 1.3–4; P = 0.0042]. The median overall survival (OS) was 25.7 months in the adipopenic group and 57.1 months in the non-adipopenic group (HR = 1.93; 95% CI: 1.05–3.55; P = 0.0342). A two-point CS including adipopenia and sarcopenia was created and defined two distinct risk groups with differences in outcomes that were highly significant. The CS was predictive of the prognosis in a multivariate analysis including body mass index (BMI) (< or ≥25 kg/m2), age (< or ≥80 yr), international prognostic index (IPI) and albuminaemia (HR = 3.67; 95% CI = 1.93–6.97; P
Published: 2014

8. Reply: Prognostic implications of imaging-based bone marrow assessment in lymphoma: 18F-FDG PET, MR imaging, or 18F-FDG PET/MR imaging?

Author: Alexandre Cochet, Louis Berthet, Olivier Humbert, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Laboratoire Electronique, Informatique et Image ( Le2i ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, and HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, MESH : Bone Marrow, Multimodal Imaging, MESH : Lymphoma, Large B-Cell, Diffuse, 030218 nuclear medicine & medical imaging, [ SDV.IB.MN ] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 0302 clinical medicine, MESH: Fluorodeoxyglucose F18, Bone Marrow, MESH : Tomography, X-Ray Computed, Medicine, MESH : Female, ComputingMilieux_MISCELLANEOUS, education.field_of_study, MESH: Multimodal Imaging, MESH: Positron-Emission Tomography, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH: Bone Marrow, Female, Radiology, Lymphoma, Large B-Cell, Diffuse, MESH: Tomography, X-Ray Computed, medicine.medical_specialty, MESH : Male, MESH : Multimodal Imaging, Population, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 18f fdg pet, 03 medical and health sciences, Fluorodeoxyglucose F18, Humans, Radiology, Nuclear Medicine and imaging, education, MESH: Humans, business.industry, MESH : Humans, MESH : Positron-Emission Tomography, MESH : Fluorodeoxyglucose F18, medicine.disease, Mr imaging, MESH: Male, Lymphoma, carbohydrates (lipids), Positron-Emission Tomography, MESH: Lymphoma, Large B-Cell, Diffuse, Bone marrow, Nuclear medicine, business, Tomography, X-Ray Computed, MESH: Female
Abstract: REPLY: We thank Adams et al. for their comments on our article ([1][1]). Their recent paper cited in their letter provides interesting results about the comparable performance of whole-body MR imaging and 18F-FDG PET/CT for detection of bone marrow involvement in a mixed population of patients with
Published: 2013
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9. Sarcopenia is an independent prognostic factor in elderly patients with diffuse large B-cell lymphoma treated with immunochemotherapy

Author: Hervé Tilly, Hélène Lanic, Romain Modzelewski, Florian Clatot, Jean Michel Picquenot, Sylvain Mareschal, Jerôme Kraut-Tauzia, Fabrice Jardin, Aspasia Stamatoullas, Stéphane Leprêtre, Service d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Normandie Université (NU), 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), Breton, Céline, Service d'Oncologie Médicale, CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), service d'anatomo-pathologie, CRLCC Henri Becquerel, Equipe Quantification en Imagerie Fonctionnelle ( QuantIF-LITIS ), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes ( LITIS ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ) -Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Institut national des sciences appliquées Rouen Normandie ( INSA Rouen Normandie ), Normandie Université ( NU ) -Université Le Havre Normandie ( ULH ), Normandie Université ( NU ), 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 ), and CRLCC Haute Normandie-CRLCC Henri Becquerel
Subjects: Male, Sarcopenia, MESH : Retrospective Studies, MESH : Antineoplastic Combined Chemotherapy Protocols, Body Surface Area, MESH : Aged, Gastroenterology, Body Mass Index, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, MESH : Muscle, Skeletal, MESH: Sarcopenia, ComputingMilieux_MISCELLANEOUS, MESH: Treatment Outcome, Aged, 80 and over, 0303 health sciences, education.field_of_study, Prognosis, 3. Good health, [SDV] Life Sciences [q-bio], MESH: Antineoplastic Combined Chemotherapy Protocols, Oncology, Vincristine, 030220 oncology & carcinogenesis, Rituximab, MESH : Vincristine, medicine.medical_specialty, Tomography Scanners, X-Ray Computed, MESH : Tomography Scanners, X-Ray Computed, MESH: Prognosis, MESH: Body Mass Index, MESH: Doxorubicin, 03 medical and health sciences, Humans, MESH : Aged, 80 and over, education, Cyclophosphamide, Aged, Retrospective Studies, MESH: Age Factors, MESH: Humans, [ SDV ] Life Sciences [q-bio], MESH : Humans, MESH : Prednisone, MESH: Cyclophosphamide, MESH: Retrospective Studies, MESH : Organ Size, medicine.disease, MESH : Body Mass Index, MESH : Sarcopenia, MESH: Antibodies, Monoclonal, Murine-Derived, MESH: Prednisone, MESH: Female, Body mass index, Diffuse large B-cell lymphoma, Cancer Research, MESH: Organ Size, [SDV]Life Sciences [q-bio], MESH : Lymphoma, Large B-Cell, Diffuse, Antibodies, Monoclonal, Murine-Derived, MESH: Aged, 80 and over, MESH: Body Surface Area, International Prognostic Index, Prednisone, hemic and lymphatic diseases, MESH : Female, MESH : Cyclophosphamide, MESH: Aged, Body surface area, MESH: Muscle, Skeletal, MESH : Prognosis, Age Factors, Hematology, Organ Size, Treatment Outcome, Female, Lymphoma, Large B-Cell, Diffuse, medicine.drug, MESH : Body Surface Area, MESH : Male, Population, MESH: Vincristine, MESH : Treatment Outcome, Internal medicine, medicine, MESH : Doxorubicin, Muscle, Skeletal, 030304 developmental biology, MESH: Tomography Scanners, X-Ray Computed, business.industry, MESH: Male, MESH : Antibodies, Monoclonal, Murine-Derived, Surgery, Doxorubicin, MESH: Lymphoma, Large B-Cell, Diffuse, MESH : Age Factors, business
Abstract: International audience; Approximately 25-35% of patients with diffuse large B-cell lymphoma (DLBCL) are older than 70 years. The aim of this study was to investigate the prognostic impact of depletion of skeletal muscle (sarcopenia) in elderly patients with DLBCL. This retrospective analysis included 82 patients with DLBCL older than 70 years and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, Oncovin, prednisone) or R-miniCHOP. Sarcopenia was measured by the analysis of stored computed tomography (CT) images at the L3 level at baseline. The surface of the muscular tissues was selected according to the CT Hounsfield unit. This value was normalized for stature in order to calculate the lumbar L3 skeletal muscle index (LSMI, in cm(2)/m(2)). The mean age of the population was 78 years. According to the defined cut-offs for LSMI, 45 patients with DLBCL were considered sarcopenic. Sarcopenic patients displayed a higher revised International Prognostic Index (R-IPI) compared with patients without sarcopenia, and were older, with a mean age of 80 years and 77 years, respectively (p = 0.006). With a median follow-up of 39 months, the 2-year overall survival in the sarcopenic population was 46% compared with 84% in the non-sarcopenic group (HR = 3.22; 95% CI = 1.73-5.98; p = 0.0002). In a multivariate analysis, sarcopenia remained predictive of outcome (p = 0.005). Sarcopenia is a relevant and predictive factor in elderly patients with DLBCL treated with rituximab plus chemotherapy.
Published: 2013

10. In newly diagnosed diffuse large B-cell lymphoma, determination of bone marrow involvement with 18F-FDG PET/CT provides better diagnostic performance and prognostic stratification than does biopsy

Author: Olivier Humbert, Alexandre Cochet, Salim Kanoun, Caroline Legouge, François Brunotte, Olivier Casasnovas, Inna Dygai-Cochet, Alina Berriolo-Riedinger, Michel Toubeau, Louis Berthet, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Service de Médecine Nucléaire, UNICANCER-UNICANCER, Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Laboratoire Electronique, Informatique et Image ( Le2i ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon )
Subjects: MESH : Bone Marrow, Male, MESH : Retrospective Studies, Biopsy, MESH : Aged, Iliac crest, MESH : Lymphoma, Large B-Cell, Diffuse, Multimodal Imaging, 030218 nuclear medicine & medical imaging, [ SDV.IB.MN ] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, MESH: Biopsy, 0302 clinical medicine, International Prognostic Index, MESH: Aged, 80 and over, MESH: Fluorodeoxyglucose F18, Bone Marrow, MESH : Tomography, X-Ray Computed, MESH : Neoplasm Staging, MESH : Female, MESH: Aged, Aged, 80 and over, MESH : Prognosis, MESH: Middle Aged, medicine.diagnostic_test, MESH: Multimodal Imaging, MESH: Neoplasm Staging, MESH : Adult, Middle Aged, Prognosis, MESH: Positron-Emission Tomography, 3. Good health, medicine.anatomical_structure, MESH: Young Adult, 030220 oncology & carcinogenesis, MESH: Survival Analysis, MESH: Bone Marrow, Female, Radiology, Lymphoma, Large B-Cell, Diffuse, MESH: Tomography, X-Ray Computed, Adult, medicine.medical_specialty, Adolescent, MESH : Male, MESH : Multimodal Imaging, MESH : Young Adult, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, MESH: Prognosis, 03 medical and health sciences, Young Adult, Fluorodeoxyglucose F18, MESH : Adolescent, medicine, Humans, Radiology, Nuclear Medicine and imaging, MESH : Middle Aged, MESH : Aged, 80 and over, Aged, Neoplasm Staging, Retrospective Studies, MESH: Adolescent, PET-CT, MESH: Humans, business.industry, MESH : Humans, MESH : Positron-Emission Tomography, MESH: Adult, MESH: Retrospective Studies, MESH : Fluorodeoxyglucose F18, medicine.disease, Survival Analysis, MESH: Male, Lymphoma, Concomitant, MESH : Biopsy, Positron-Emission Tomography, MESH: Lymphoma, Large B-Cell, Diffuse, Bone marrow, MESH : Survival Analysis, business, Nuclear medicine, Tomography, X-Ray Computed, Diffuse large B-cell lymphoma, MESH: Female
Abstract: International audience; UNLABELLED: In newly diagnosed diffuse large B-cell lymphoma (DLBCL), the sensitivity of bone marrow biopsy (BMB) for the detection of bone marrow involvement (BMI) can be low because of sampling error if the BMI is focal and not diffuse. Although (18)F-FDG PET/CT is now recommended for initial staging of DLBCL, its role regarding BMI is not well defined. This study evaluated whether (18)F-FDG PET/CT, in comparison with BMB, is useful for the detection of BMI and predictive of outcome. METHODS: From the 142 patients who were referred to our institution for newly diagnosed DLBCL from June 2006 to October 2011, 133 were retrospectively enrolled in our study. All patients underwent whole-body (18)F-FDG PET/CT and a BMB from the iliac crest before any treatment. (18)F-FDG PET/CT was considered positive for BMI in cases of uni- or multifocal bone marrow (18)F-FDG uptake that could not be explained by benign findings on the underlying CT image or history. A final diagnosis of BMI was considered if the BMB was positive or if the positive (18)F-FDG PET/CT was confirmed by guided biopsy or targeted MR imaging or in cases of disappearance of focal bone marrow uptake concomitant with the disappearance of uptake in other lymphoma lesions on (18)F-FDG PET/CT monitoring. Progression-free survival and overall survival were analyzed using the Cox proportional hazards regression model. RESULTS: Thirty-three patients were considered to have BMI. Of these, 8 were positive according to the BMB and 32 were positive according to (18)F-FDG PET/CT. (18)F-FDG PET/CT was more sensitive (94% vs. 24%; P < 0.001), showed a higher negative predictive value (98% vs. 80%), and was more accurate (98% vs. 81%) than BMB. Median follow-up was 24 mo (range, 1-67 mo). Twenty-nine patients (22%) experienced recurrence or disease progression during follow-up, and 20 patients died (15%). In multivariate analysis, only the International Prognostic Index and the (18)F-FDG PET/CT bone marrow status were independent predictors of progression-free survival (P = 0.005 and 0.02, respectively), whereas only the International Prognostic Index remained an independent predictor of overall survival (P = 0.004). CONCLUSION: Assessment of BMI with (18)F-FDG PET/CT provides better diagnostic performance and prognostic stratification in newly diagnosed DLBCL than does BMB.
Published: 2013
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11. Endogenous neurotrophins and Trk signaling in diffuse large B cell lymphoma cell lines are involved in sensitivity to rituximab-induced apoptosis

Author: Anne-Laure Fauchais, Dominique Bordessoule, Marie-Odile Jauberteau, Marie-Claude Lise, Cynthia Bellanger, Lydie Dubanet, D. Troutaud, Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service de Médecine interne A et polyclinique médicale [CHU Limoges], CHU Limoges, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], Service d'Immunologie et immunogénétique [CHU Limoges], and Université de Limoges (UNILIM)
Subjects: Cancer Treatment, lcsh:Medicine, Fluorescent Antibody Technique, MESH: Flow Cytometry, Tropomyosin receptor kinase A, MESH: Brain-Derived Neurotrophic Factor, Receptor, Nerve Growth Factor, Immunoenzyme Techniques, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, Neurotrophic factors, immune system diseases, hemic and lymphatic diseases, Nerve Growth Factor, Molecular Cell Biology, Tumor Cells, Cultured, lcsh:Science, MESH: Fluorescent Antibody Technique, MESH: Nerve Growth Factor, Apoptotic Signaling Cascade, Non-Hodgkin lymphoma, 0303 health sciences, Multidisciplinary, biology, Cell Death, MESH: Real-Time Polymerase Chain Reaction, MESH: Receptor, trkC, MESH: Receptor, trkB, MESH: Receptor, trkA, MESH: Enzyme-Linked Immunosorbent Assay, Hematology, Signaling in Selected Disciplines, Flow Cytometry, MESH: Drug Resistance, Neoplasm, Signaling Cascades, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Medicine, Rituximab, Lymphomas, Lymphoma, Large B-Cell, Diffuse, Immunotherapy, Neurotrophin, medicine.drug, Research Article, Signal Transduction, Lymphoma, B-Cell, Blotting, Western, Immunology, Antineoplastic Agents, Enzyme-Linked Immunosorbent Assay, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Real-Time Polymerase Chain Reaction, 03 medical and health sciences, medicine, MESH: Blotting, Western, Humans, Receptor, trkB, Receptor, trkC, MESH: Tumor Cells, Cultured, Nerve Growth Factors, RNA, Messenger, Receptor, trkA, Autocrine signalling, MESH: Immunoenzyme Techniques, Biology, 030304 developmental biology, MESH: Lymphoma, B-Cell, MESH: RNA, Messenger, Brain-derived neurotrophic factor, Oncogenic Signaling, MESH: Humans, MESH: Nerve Growth Factors, Brain-Derived Neurotrophic Factor, lcsh:R, MESH: Receptor, Nerve Growth Factor, medicine.disease, nervous system, MESH: Antibodies, Monoclonal, Murine-Derived, Drug Resistance, Neoplasm, Trk receptor, Hematologic cancers and related disorders, Cancer research, biology.protein, MESH: Antineoplastic Agents, MESH: Lymphoma, Large B-Cell, Diffuse, lcsh:Q, Diffuse large B-cell lymphoma
Abstract: International audience; BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a common and often fatal malignancy. Immunochemotherapy, a combination of rituximab to standard chemotherapy, has resulted in improved survival. However a substantial proportion of patients still fail to reach sustained remission. We have previously demonstrated that autocrine brain-derived neurotrophic factor (BDNF) production plays a function in human B cell survival, at least partly via sortilin expression. As neurotrophin receptor (Trks) signaling involved activation of survival pathways that are inhibited by rituximab, we speculated that neurotrophins may provide additional support for tumour cell survival and therapeutic resistance in DLBCL. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we used two DLBCL cell lines, SUDHL4 and SUDHL6, known to be respectively less and more sensitive to rituximab. We found by RT-PCR, western blotting, cytometry and confocal microscopy that both cell lines expressed, in normal culture conditions, BDNF and to a lesser extent NGF, as well as truncated TrkB and p75(NTR)/sortilin death neurotrophin receptors. Furthermore, BDNF secretion was detected in cell supernatants. NGF and BDNF production and Trk receptor expression, including TrkA, are regulated by apoptotic conditions (serum deprivation or rituximab exposure). Indeed, we show for the first time that rituximab exposure of DLBCL cell lines induces NGF secretion and that differences in rituximab sensitivity are associated with differential expression patterns of neurotrophins and their receptors (TrkA). Finally, these cells are sensitive to the Trk-inhibitor, K252a, as shown by the induction of apoptosis. Furthermore, K252a exhibits additive cytotoxic effects with rituximab. CONCLUSIONS/SIGNIFICANCE: Collectively, these data strongly suggest that a neurotrophin axis, such NGF/TrkA pathway, may contribute to malignant cell survival and rituximab resistance in DLBCL.
Published: 2011
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12. Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment

Author: Ash A. Alizadeh, Ronald Levy, Chih Long Liu, Ranjana H. Advani, Yasodha Natkunam, Shuchun Zhao, Andrew J. Gentles, Sylvia K. Plevritis, Izidore S. Lossos, Randy D. Gascoyne, Alvaro J. Alencar, Javier Briones, Holbrook E Kohrt, Roch Houot, June Helen Myklebust, Matthew J. Goldstein, Robert Tibshirani, Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Department of Pathology [Stanford], Stanford Medicine, Stanford University-Stanford University, and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: LMO2, Pathology, Clinical Trials and Observations, MESH: Metalloproteins, Biochemistry, Cohort Studies, 0302 clinical medicine, International Prognostic Index, MESH: Aged, 80 and over, MESH: Tumor Microenvironment, MESH: Child, hemic and lymphatic diseases, Neoplasms, Tumor Microenvironment, MESH: Neoplasms, Child, MESH: Cohort Studies, Regulation of gene expression, MESH: Aged, Aged, 80 and over, 0303 health sciences, MESH: Middle Aged, MESH: Genetic Testing, MESH: Genetic Predisposition to Disease, Hematology, MESH: Gene Expression Regulation, Neoplastic, LIM Domain Proteins, Middle Aged, Prognosis, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, MESH: Young Adult, 030220 oncology & carcinogenesis, MESH: Survival Analysis, Lymphoma, Large B-Cell, Diffuse, MESH: LIM Domain Proteins, Adult, medicine.medical_specialty, Adolescent, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MESH: Prognosis, 03 medical and health sciences, MESH: Gene Expression Profiling, Tumor Necrosis Factor Receptor Superfamily, Member 9, Young Adult, Proto-Oncogene Proteins, Metalloproteins, medicine, Biomarkers, Tumor, Humans, Genetic Predisposition to Disease, Genetic Testing, Survival analysis, MESH: Genes, Neoplasm, 030304 developmental biology, MESH: Adaptor Proteins, Signal Transducing, Adaptor Proteins, Signal Transducing, Aged, MESH: Adolescent, Tumor microenvironment, MESH: Humans, Gene Expression Profiling, Germinal center, MESH: Adult, Cell Biology, medicine.disease, Survival Analysis, Gene expression profiling, MESH: Proto-Oncogene Proteins, MESH: Antigens, CD137, MESH: Tumor Markers, Biological, Cancer research, MESH: Lymphoma, Large B-Cell, Diffuse, Diffuse large B-cell lymphoma, MESH: DNA-Binding Proteins, Genes, Neoplasm
Abstract: Several gene-expression signatures predict survival in diffuse large B-cell lymphoma (DLBCL), but the lack of practical methods for genome-scale analysis has limited translation to clinical practice. We built and validated a simple model using one gene expressed by tumor cells and another expressed by host immune cells, assessing added prognostic value to the clinical International Prognostic Index (IPI). LIM domain only 2 (LMO2) was validated as an independent predictor of survival and the “germinal center B cell–like” subtype. Expression of tumor necrosis factor receptor superfamily member 9 (TNFRSF9) from the DLBCL microenvironment was the best gene in bivariate combination with LMO2. Study of TNFRSF9 tissue expression in 95 patients with DLBCL showed expression limited to infiltrating T cells. A model integrating these 2 genes was independent of “cell-of-origin” classification, “stromal signatures,” IPI, and added to the predictive power of the IPI. A composite score integrating these genes with IPI performed well in 3 independent cohorts of 545 DLBCL patients, as well as in a simple assay of routine formalin-fixed specimens from a new validation cohort of 147 patients with DLBCL. We conclude that the measurement of a single gene expressed by tumor cells (LMO2) and a single gene expressed by the immune microenvironment (TNFRSF9) powerfully predicts overall survival in patients with DLBCL.
Published: 2011
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13. microRNA profiling in Epstein-Barr virus-associated B-cell lymphoma

Author: Jochen Imig, Jia Yun Zhu, Christoph Renner, Natalie Motsch, Friedrich A. Grässer, Alberto Faggioni, Tanja Reineke, Michal J. Okoniewski, Gunter Meister, Marianne Tinguely, Stephanie Barth, Pankaj Trivedi, Institute of Virology, Universität des Saarlandes [Saarbrücken], Center for Integrated Protein Sciences Munich (CIPSM), Max Planck Institute of Biochemistry (MPIB), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Functional Genomics Center Zurich, Institute of Surgical Pathology, University hospital of Zurich [Zurich], Department of Experimental Medicine [Roma], Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Regensburg University, Biochemistry I, Division of Oncology, Department of Internal Medicine-Oncology, Deutsche Krebshilfe (grant 107166 to G.M. and F.G.), German Bundesministerium fur Bildung und Forschung (grant NGFN to S.B. and #01GS0801/4 to F.G.), Max-Planck-Society (to Meister lab, partial), German Bundesministerium fur Bildung und Forschung (grant NGFN-Plus #01GS0801/5 to G.M.), Bavarian Ministry for Education and Science (BayGene to G.M.), MIUR, AIRC, Progetto strategico (ISS9ACF/1) and FISM (2007/R/17) (to A.F. and P.T.). Funding for open access charge: Grant 107166 from the Deutsche Krebshilfe (to G.M. and F.G.) Grant NGFN-Plus #01GS0801/4 from the German Ministry of Education (to F.G.)., and University of Zurich
Subjects: Epstein-Barr Virus Infections, Herpesvirus 4, Human, MESH: beta Catenin, medicine.disease_cause, 0302 clinical medicine, hemic and lymphatic diseases, MESH: Reverse Transcriptase Polymerase Chain Reaction, Nuclear protein, B-cell lymphoma, beta Catenin, 0303 health sciences, MESH: Epstein-Barr Virus Infections, Reverse Transcriptase Polymerase Chain Reaction, Nuclear Proteins, MESH: Gene Expression Regulation, Neoplastic, MESH: RNA, Small Untranslated, 3. Good health, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, MESH: Wnt Proteins, 030220 oncology & carcinogenesis, Lymphoma, Large B-Cell, Diffuse, Ubiquitin-Protein Ligases, 610 Medicine & health, 10071 Functional Genomics Center Zurich, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Molecular Sequence Annotation, Biology, Cell Line, MESH: Proto-Oncogene Proteins c-myb, Proto-Oncogene Proteins c-myb, 03 medical and health sciences, MESH: Gene Expression Profiling, 1311 Genetics, Downregulation and upregulation, 10049 Institute of Pathology and Molecular Pathology, Proto-Oncogene Proteins, microRNA, MESH: Gene Library, Genetics, medicine, Humans, Epstein–Barr virus infection, Gene Library, 030304 developmental biology, Binding Sites, MESH: Humans, Gene Expression Profiling, Molecular Sequence Annotation, MESH: Herpesvirus 4, Human, medicine.disease, Epstein–Barr virus, Molecular biology, MESH: Ubiquitin-Protein Ligases, MESH: Cell Line, Wnt Proteins, MESH: Proto-Oncogene Proteins, MicroRNAs, MESH: Binding Sites, 10032 Clinic for Oncology and Hematology, Cancer research, 570 Life sciences, biology, RNA, Small Untranslated, RNA, MESH: Lymphoma, Large B-Cell, Diffuse, Carcinogenesis, Diffuse large B-cell lymphoma, MESH: MicroRNAs, MESH: Nuclear Proteins, MESH: DNA-Binding Proteins
Abstract: The Epstein–Barr virus (EBV) is an oncogenic human Herpes virus found in ∼15% of diffuse large B-cell lymphoma (DLBCL). EBV encodes miRNAs and induces changes in the cellular miRNA profile of infected cells. MiRNAs are small, non-coding RNAs of ∼19–26 nt which suppress protein synthesis by inducing translational arrest or mRNA degradation. Here, we report a comprehensive miRNA-profiling study and show that hsa-miR-424, -223, -199a-3p, -199a-5p, -27b, -378, -26b, -23a, -23b were upregulated and hsa-miR-155, -20b, -221, -151-3p, -222, -29b/c, -106a were downregulated more than 2-fold due to EBV-infection of DLBCL. All known EBV miRNAs with the exception of the BHRF1 cluster as well as EBV-miR-BART15 and -20 were present. A computational analysis indicated potential targets such as c-MYB, LATS2, c-SKI and SIAH1. We show that c-MYB is targeted by miR-155 and miR-424, that the tumor suppressor SIAH1 is targeted by miR-424, and that c-SKI is potentially regulated by miR-155. Downregulation of SIAH1 protein in DLBCL was demonstrated by immunohistochemistry. The inhibition of SIAH1 is in line with the notion that EBV impedes various pro-apoptotic pathways during tumorigenesis. The down-modulation of the oncogenic c-MYB protein, although counter-intuitive, might be explained by its tight regulation in developmental processes. ISSN:1362-4962 ISSN:0301-5610
Published: 2011
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14. Age-related Epstein-Barr virus-associated B-cell lymphoproliferative disorders in elderly white patients

Author: Nimubona, Stanislas, Bernard, Marc, De Guibert, Sophie, Duval, Hélène, Caulet-Maugendre, Sylvie, Tass, Patrick, Lamy, Thierry, Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], Service d'hématologie clinique, Université de Rennes (UR)-Hôpital Pontchaillou, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institute of Neuroscience and Medicine [Jülich] (INM-1), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: MESH: Aged, MESH: France, MESH: Aged, 80 and over, MESH: Humans, MESH: Epstein-Barr Virus Infections, [SDV]Life Sciences [q-bio], MESH: Lymphoma, Large B-Cell, Diffuse, MESH: Herpesvirus 4, Human, MESH: Female, ComputingMilieux_MISCELLANEOUS, MESH: Male
Abstract: International audience
Published: 2010
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15. Prognostic significance of BAD and AIF apoptotic pathways in diffuse large B-cell lymphoma

Author: Daniel Petit, D. Troutaud, Agnès Olivrie, Barbara Petit, Marie-Odile Jauberteau, Marie-Pierre Gourin-Chaury, Benoît Marin, Cynthia Bellanger, Jean Feuillard, Dominique Bordessoule, Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Université de Limoges (UNILIM), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'Anatomie Pathologique [CHU Limoges], CHU Limoges, Unité Fonctionnelle Registre Général des Cancers du Limousin (UFRGC), Service de l'Information Médicale et de l'Évaluation [CHU Limoges] (SIME), Neuroépidémiologie Tropicale et Comparée (NETEC), Université de Limoges (UNILIM)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], Unité de Génétique Moléculaire Animale (UGMA), Université de Limoges (UNILIM)-Institut National de la Recherche Agronomique (INRA), Service de Médecine interne A et polyclinique médicale [CHU Limoges], Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Université de Limoges (UNILIM), Unité de Génétique Moléculaire Animale (UMR GMA), Institut National de la Recherche Agronomique (INRA)-Université de Limoges (UNILIM), This work and C.B. were supported by Ligue Nationale Contre le Cancer (Comité Départemental de La Haute-Vienne) and CORC (Comité d'Orientation Recherche Cancer en Limousin)., and Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-CHU Limoges
Subjects: Male, Cancer Research, Pathology, bcl-2, Apoptosis, CHOP, MESH: Antibodies, Monoclonal, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, International Prognostic Index, clinical stage, MESH: Stilbenes, Antineoplastic Combined Chemotherapy Protocols, Stilbenes, Medicine, 0303 health sciences, B-Lymphocytes, MESH: Middle Aged, medicine.diagnostic_test, Antibodies, Monoclonal, Apoptosis Inducing Factor, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, Prognosis, 3. Good health, pp1α, MESH: Antineoplastic Combined Chemotherapy Protocols, Oncology, Vincristine, 030220 oncology & carcinogenesis, Immunohistochemistry, Rituximab, Female, Lymphoma, Large B-Cell, Diffuse, medicine.drug, medicine.medical_specialty, Lymphoma, B-Cell, non-hodgkin lymphoma, MESH: Vincristine, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH: Prognosis, chop, 03 medical and health sciences, MESH: Doxorubicin, MESH: B-Lymphocytes, Biopsy, Humans, Cyclophosphamide, 030304 developmental biology, MESH: Lymphoma, B-Cell, MESH: Humans, business.industry, MESH: Apoptosis, MESH: Cyclophosphamide, medicine.disease, MESH: Male, Lymphoma, MESH: Apoptosis Inducing Factor, Doxorubicin, MESH: Antibodies, Monoclonal, Murine-Derived, Cancer research, Prednisone, MESH: Lymphoma, Large B-Cell, Diffuse, business, Diffuse large B-cell lymphoma, MESH: Prednisone, MESH: Female
Abstract: Chantier qualité GA; International audience; BACKGROUND: To determine whether proapoptotic proteins were associated with clinicopathologic heterogeneity and influenced survival in patients with diffuse large B-cell lymphoma (DLBCL), we evaluated patterns of expression of the BCL-2 family member BAD, PP1alpha (the catalytic subunit of PP1 involved in activation of BAD), and apoptosis-inducing factor (AIF). PATIENTS AND METHODS: We retrospectively analyzed 46 patients all treated with standard chemotherapy ([CHOP] cyclophosphamide/doxorubicin/vincristine/prednisone-like); of these, 16 received rituximab. Immunohistochemical analyses were performed from biopsy samples of nodal DLBCL that were performed at initial diagnosis. Normal reactive lymph nodes were used as controls. RESULTS: BAD expression was found in 38 of 46 DLBCL cases and, though variable, was often strong. PP1alpha and AIF were detected in all tumors tested with a relative strong expression. Lower BAD expression was shown to be significantly associated with advanced clinical stages (Ann Arbor stage III + IV and International Prognostic Index intermediate-high to high; P = .006 and P = .0008, respectively). Moreover, BAD staining was positively correlated with BCL-2 (P = .022) and PP1alpha (P = .013) staining. Finally, high AIF expression proved to be predictive of a longer overall survival in non-rituximab-treated patients. CONCLUSION: Our study shows for the first time in DLBCL that differential BAD expression might play a role in the development of the disease, possibly reflecting its function as a tumor suppressor. Furthermore, our data highlight the interest in targeting BAD phosphatases and AIF-mediated mitochondrial apoptosis for new therapeutic strategies.
Published: 2010
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16. Immuno-fluorescence in situ hybridization index predicts survival in patients with diffuse large B-cell lymphoma treated with R-CHOP: a GELA study

Author: Copie-Bergman, Christiane, Gaulard, Philippe, Leroy, Karen, Briere, Josette, Baia, Maryse, Jais, Jean-Philippe, Salles, Gilles, Berger, Françoise, Haioun, Corinne, Tilly, Herve, Emile, Jean-François, Banham, Alison, Mounier, Nicolas, Gisselbrecht, Christian, Feugier, Pierre, Coiffier, Bertrand, Molina, Thierry, Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Département de pathologie, Hospices Civils de Lyon ( HCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'Hématologie, CRLCC Henri Becquerel, Service d'anatomie pathologique, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Laboratoire épidémiologie et oncogénèse des tumeurs digestives, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Nuffield Department of Clinical Laboratory Sciences, University of Oxford [Oxford], Service d'onco-hématologie, CHU Nice-Hôpital l'Archet, Service d'hématologie-oncologie adultes, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Département de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 ( UPD5 ), This study was supported by a grant from the Programme Hospitalier de Recherche Clinique AP-HP (AOM 03060), Dako A/S and ARTGIL (Association pour la Recherche Thérapeutique, Génétique et Immunologique dans les lymphomes). AHB was supported by Leukaemia Research, UK., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service d'anatomie pathologique [CHU Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP]
Subjects: MESH : Antineoplastic Combined Chemotherapy Protocols, MESH : Aged, MESH : Dose-Response Relationship, Drug, MESH: Risk Assessment, MESH : Lymphoma, Large B-Cell, Diffuse, MESH: Antibodies, Monoclonal, MESH: Dose-Response Relationship, Drug, MESH : Proto-Oncogene Proteins c-bcl-2, MESH: Proportional Hazards Models, MESH: Aged, 80 and over, immune system diseases, hemic and lymphatic diseases, MESH : Female, MESH: In Situ Hybridization, Fluorescence, MESH : Risk Assessment, MESH : Cyclophosphamide, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, MESH : Prognosis, MESH: Enzyme-Linked Immunosorbent Assay, MESH : Enzyme-Linked Immunosorbent Assay, MESH: Predictive Value of Tests, MESH : In Situ Hybridization, Fluorescence, MESH: Antineoplastic Combined Chemotherapy Protocols, MESH : Genes, myc, MESH: Survival Analysis, MESH : Antibodies, Monoclonal, MESH : Severity of Illness Index, MESH : Vincristine, MESH: Probability, MESH : Probability, MESH : Male, MESH : Drug Administration Schedule, MESH: Vincristine, MESH : Treatment Outcome, MESH: Drug Administration Schedule, MESH: Multivariate Analysis, MESH: Prognosis, MESH: Doxorubicin, MESH: Severity of Illness Index, MESH : Doxorubicin, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Middle Aged, MESH : Predictive Value of Tests, MESH : Aged, 80 and over, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Genes, myc, MESH: Humans, MESH : Humans, MESH: Biological Markers, MESH: Cyclophosphamide, MESH : Multivariate Analysis, MESH : Prednisone, MESH : Proportional Hazards Models, MESH: Male, MESH : Antibodies, Monoclonal, Murine-Derived, MESH : Biological Markers, MESH: Proto-Oncogene Proteins c-bcl-2, MESH: Antibodies, Monoclonal, Murine-Derived, MESH: Lymphoma, Large B-Cell, Diffuse, MESH : Survival Analysis, MESH: Prednisone, MESH: Female
Abstract: International audience; PURPOSE: To evaluate the prognostic value of cell of origin immunohistochemical markers and BCL2, BCL6, and c-MYC translocations in a homogeneous cohort of patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). PATIENTS AND METHODS: Patients with CD20+ DLBCL were enrolled in the randomized LNH98-5 and 01-5B Groupe d'Etude des Lymphomes de l'Adulte trials. Paraffin-embedded tumor samples of 119 patients treated with R-CHOP were analyzed by immunohistochemistry for CD10, BCL6, MUM1/IRF4, LMO2, and forkhead box protein P1 (FOXP1) expression and for BCL2, BCL6, and c-MYC breakpoints by fluorescence in situ hybridization (FISH) on tissue microarray. RESULTS: LMO2 expression and BCL2 breakpoint were associated with the germinal center (GC) subtype defined by Hans' algorithm, respectively (P < .0001; P = .0002) whereas FOXP1 expression and BCL6 breakpoint were associated with the non-germinal center (non-GC) subtype (P = .008 and P = .0001, respectively). The immunohistochemical markers analyzed independently, GC/non-GC phenotype and BCL2 breakpoint did not predict overall survival (OS). BCL6 breakpoint was significantly associated with an unfavorable impact on OS (P = .04). Interestingly, an immunoFISH index, defined by positivity for at least two of three non-GC markers (FOXP1, MUM1/IRF4, BCL6 breakpoint) was significantly associated with a shorter 5-year OS rate (44%; 95% CI, 28 to 60 v 78%; 95% CI, 59 to 89; P = .01) which was independent (P = .04) of the age-adjusted International Prognostic Index (P = .04) in multivariate analysis. CONCLUSION: Our study demonstrates that combining immunohistochemistry with FISH allows construction of an immunoFISH index that significantly predicts survival in elderly DLBCL patients treated with R-CHOP.
Published: 2009
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17. Immuno-fluorescence in situ hybridization index predicts survival in patients with diffuse large B-cell lymphoma treated with R-CHOP: a GELA study.: ImmunoFISH index in DLBCL patients treated with R-CHOP

Author: Copie-Bergman, Christiane, Gaulard, Philippe, Leroy, Karen, Briere, Josette, Baia, Maryse, Jais, Jean-Philippe, Salles, Gilles, Berger, Françoise, Haioun, Corinne, Tilly, Herve, Emile, Jean-François, Banham, Alison, Mounier, Nicolas, Gisselbrecht, Christian, Feugier, Pierre, Coiffier, Bertrand, Molina, Thierry, Guellaen, Georges, Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Département de pathologie, Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service d'anatomie pathologique [CHU Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Service d'onco-hématologie, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Service d'hématologie-oncologie adultes, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5), and This study was supported by a grant from the Programme Hospitalier de Recherche Clinique AP-HP (AOM 03060), Dako A/S and ARTGIL (Association pour la Recherche Thérapeutique, Génétique et Immunologique dans les lymphomes). AHB was supported by Leukaemia Research, UK.
Subjects: MESH: Probability, MESH: Vincristine, MESH: Drug Administration Schedule, MESH: Risk Assessment, MESH: Multivariate Analysis, MESH: Prognosis, MESH: Antibodies, Monoclonal, MESH: Dose-Response Relationship, Drug, MESH: Proportional Hazards Models, MESH: Doxorubicin, MESH: Aged, 80 and over, immune system diseases, hemic and lymphatic diseases, MESH: Severity of Illness Index, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: In Situ Hybridization, Fluorescence, MESH: Genes, myc, MESH: Treatment Outcome, MESH: Aged, MESH: Humans, MESH: Middle Aged, MESH: Biological Markers, MESH: Enzyme-Linked Immunosorbent Assay, MESH: Cyclophosphamide, MESH: Predictive Value of Tests, MESH: Male, MESH: Antineoplastic Combined Chemotherapy Protocols, MESH: Proto-Oncogene Proteins c-bcl-2, MESH: Antibodies, Monoclonal, Murine-Derived, MESH: Survival Analysis, MESH: Lymphoma, Large B-Cell, Diffuse, MESH: Prednisone, MESH: Female
Abstract: International audience; PURPOSE: To evaluate the prognostic value of cell of origin immunohistochemical markers and BCL2, BCL6, and c-MYC translocations in a homogeneous cohort of patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). PATIENTS AND METHODS: Patients with CD20+ DLBCL were enrolled in the randomized LNH98-5 and 01-5B Groupe d'Etude des Lymphomes de l'Adulte trials. Paraffin-embedded tumor samples of 119 patients treated with R-CHOP were analyzed by immunohistochemistry for CD10, BCL6, MUM1/IRF4, LMO2, and forkhead box protein P1 (FOXP1) expression and for BCL2, BCL6, and c-MYC breakpoints by fluorescence in situ hybridization (FISH) on tissue microarray. RESULTS: LMO2 expression and BCL2 breakpoint were associated with the germinal center (GC) subtype defined by Hans' algorithm, respectively (P < .0001; P = .0002) whereas FOXP1 expression and BCL6 breakpoint were associated with the non-germinal center (non-GC) subtype (P = .008 and P = .0001, respectively). The immunohistochemical markers analyzed independently, GC/non-GC phenotype and BCL2 breakpoint did not predict overall survival (OS). BCL6 breakpoint was significantly associated with an unfavorable impact on OS (P = .04). Interestingly, an immunoFISH index, defined by positivity for at least two of three non-GC markers (FOXP1, MUM1/IRF4, BCL6 breakpoint) was significantly associated with a shorter 5-year OS rate (44%; 95% CI, 28 to 60 v 78%; 95% CI, 59 to 89; P = .01) which was independent (P = .04) of the age-adjusted International Prognostic Index (P = .04) in multivariate analysis. CONCLUSION: Our study demonstrates that combining immunohistochemistry with FISH allows construction of an immunoFISH index that significantly predicts survival in elderly DLBCL patients treated with R-CHOP.
Published: 2009
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18. The expression of 16 genes related to the cell of origin and immune response predicts survival in elderly patients with diffuse large B-cell lymphoma treated with CHOP and rituximab

Author: Pierre Feugier, Eric Labouyrie, Hervé Tilly, Felix Reyes, A. de Reyniès, David S. Rickman, Françoise Berger, Corinne Haioun, Gilles Salles, Karen Leroy, Christian Gisselbrecht, Thierry Jo Molina, Christian Bastard, Bertrand Coiffier, J-P Jais, Josette Brière, P. Gaulard, Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Département de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 ( UPD5 ), Programme CIT, Ligue Nationale Contre le Cancer, Service d'Anatomo-Pathologie, Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Hospices Civils de Lyon ( HCL ), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'anatomo-pathologie [Paris], Institut Mondor de recherche biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Département de pathologie [Mondor], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service d'Anatomie et Cytologie Pathologiques, Service d'Hématologie, CRLCC Henri Becquerel, Service de génétique oncologique, Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS 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 ), Guellaen, Georges, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5), Ligue Nationale Contre le Cancer (LNCC), Hospices Civils de Lyon (HCL), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure - Lyon (ENS 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 Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service d'hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Subjects: Oncology, Male, Cellular immunity, MESH: Cytoskeletal Proteins, MESH : Antineoplastic Combined Chemotherapy Protocols, MESH: Metalloproteins, MESH : Aged, MESH: Antibodies, Monoclonal, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, 80 and over, MESH : Cytidine Deaminase, Aged, 80 and over, 0303 health sciences, Hematology, MESH: Middle Aged, MESH : Reverse Transcriptase Polymerase Chain Reaction, Antibodies, Monoclonal, LIM Domain Proteins, Diffuse, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, Vincristine, MESH: Repressor Proteins, 030220 oncology & carcinogenesis, Rituximab, MESH : DNA-Binding Proteins, MESH : Vincristine, medicine.medical_specialty, Article, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Doxorubicin, MESH: Forkhead Transcription Factors, Large B-Cell, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, Cyclophosphamide, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Aged, MESH: Humans, MESH : Gene Expression Profiling, MESH : Humans, MESH: Cyclophosphamide, MESH : Prednisone, MESH : Cytoskeletal Proteins, medicine.disease, Lymphoma, Cytoskeletal Proteins, rab GTP-Binding Proteins, Immunology, Diffuse large B-cell lymphoma, MESH: Female, MESH: Prednisone, Cancer Research, MESH : rab GTP-Binding Proteins, APOBEC-3G Deaminase, CHOP, MESH : Lymphoma, Large B-Cell, Diffuse, Antibodies, Monoclonal, Murine-Derived, International Prognostic Index, MESH: Aged, 80 and over, MESH : Metalloproteins, immune system diseases, MESH: Reverse Transcriptase Polymerase Chain Reaction, hemic and lymphatic diseases, Monoclonal, MESH : Female, MESH : Cyclophosphamide, MESH: Aged, Reverse Transcriptase Polymerase Chain Reaction, Forkhead Transcription Factors, Middle Aged, DNA-Binding Proteins, MESH : Forkhead Transcription Factors, MESH : Antibodies, Monoclonal, Female, Lymphoma, Large B-Cell, Diffuse, MESH : Repressor Proteins, medicine.drug, MESH : Male, MESH: Vincristine, Biology, Antibodies, MESH: Multivariate Analysis, Proto-Oncogene Proteins, Internal medicine, Cytidine Deaminase, Metalloproteins, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Doxorubicin, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Adaptor Proteins, Signal Transducing, 030304 developmental biology, MESH: Cytidine Deaminase, Gene Expression Profiling, MESH : Multivariate Analysis, MESH: Male, Repressor Proteins, MESH: rab GTP-Binding Proteins, Doxorubicin, Multivariate Analysis, Prednisone, MESH: Lymphoma, Large B-Cell, Diffuse, MESH: DNA-Binding Proteins
Abstract: International audience; Gene expression profiles have been associated with clinical outcome in patients with diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-containing chemotherapy. Using Affymetrix HU133A microarrays, we analyzed the lymphoma transcriptional profile of 30 patients treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and 23 patients treated with rituximab (R)-CHOP in the Groupe d'Etude des Lymphomes de l'Adulte clinical centers. We used this data set to select transcripts showing an association with progression-free survival in all patients or showing a differential effect in the two treatment groups. We performed real-time quantitative reverse transcription-PCR in the 23 R-CHOP samples of the screening set and an additional 44 R-CHOP samples set to evaluate the prognostic significance of these transcripts. In these 67 patients, the level of expression of 16 genes and the cell-of-origin classification were significantly associated with overall survival, independently of the International Prognostic Index. A multivariate model comprising four genes of the cell-of-origin signature (LMO2, MME, LPP and FOXP1) and two genes related to immune response, identified for their differential effects in R-CHOP patients (APOBEC3G and RAB33A), demonstrated a high predictive efficiency in this set of patients, suggesting that both features affect outcome in DLBCL patients receiving immunochemotherapy.
Published: 2008
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19. [Primary non-Hodgkin lymphoma of the uterine corpus. Case report and review of the literature]

Author: Leung , F., Ramanah , R., Arbez Gindre , F., Kantelip , B., Maillet , R., Riethmuller , D., 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 ), Immunologie et Chimie Thérapeutiques (ICT), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)
Subjects: MESH : Uterine Hemorrhage, MESH: Humans, MESH: Middle Aged, MESH: Uterine Neoplasms, MESH : Humans, [SDV.CAN]Life Sciences [q-bio]/Cancer, Middle Aged, MESH : Lymphoma, Large B-Cell, Diffuse, MESH : Uterine Neoplasms, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, immune system diseases, hemic and lymphatic diseases, Uterine Neoplasms, MESH: Uterine Hemorrhage, Humans, MESH: Lymphoma, Large B-Cell, Diffuse, Female, MESH : Female, MESH : Middle Aged, Lymphoma, Large B-Cell, Diffuse, Uterine Hemorrhage, MESH: Female
Abstract: International audience; We report a case of primary nonHodgkin lymphoma (NHL) of the uterine corpus, diagnosed by endometrial biopsy, in a 60-year-old patient suffering from uterine bleeding. Pathological analysis had concluded to diffuse large B-cell lymphoma. Further staging had not revealed other nodal or extranodal localization (Ann Arbor stage IE) and there were no signs of recurrence during follow-up. Therefore, the diagnostic criteria for true primary NHL of the uterine corpus were met. This localization is extremely rare since only six cases have previously been published. The patient was successfully treated by an immunochemotherapy combining rituximab-CHOP and rituximab-VCAP. After 28 months of follow-up, she is free from the disease. A review of the literature regarding these exceptional tumors is undertaken.
Published: 2008
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20. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire

Author: Soussain, Carole, Hoang-Xuan, Khê, Taillandier, Luc, Fourme, Emmanuelle, Choquet, Sylvain, Witz, Francis, Casasnovas, Olivier, Dupriez, Brigitte, Souleau, Bertrand, Taksin, Anne-Laure, Gisselbrecht, Christian, Jaccard, Arnaud, Omuro, Antonio, Sanson, Marc, Janvier, Maud, Kolb, Brigitte, Zini, Jean-Marc, Leblond, Véronique, Renseigné, Non, Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Réseau d'Etude des Gliomes, REG, Service de Neuro-Oncologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, UPMC - Département de neurologie 2 - Mazarin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Oncology, Cancer Research, MESH: Combined Modality Therapy, MESH: Busulfan, medicine.medical_treatment, Salvage therapy, Hematopoietic stem cell transplantation, MESH: Eye Neoplasms, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, MESH: Cytarabine, Prospective Studies, Etoposide, MESH: Etoposide, MESH: Aged, MESH: Middle Aged, Brain Neoplasms, MESH: Thiotepa, Cytarabine, Hematopoietic Stem Cell Transplantation, Middle Aged, Combined Modality Therapy, 3. Good health, MESH: Salvage Therapy, Survival Rate, MESH: Antineoplastic Combined Chemotherapy Protocols, 030220 oncology & carcinogenesis, MESH: Brain Neoplasms, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Lymphoma, Large B-Cell, Diffuse, Intraocular lymphoma, Stem cell, MESH: Neoplasm Recurrence, Local, medicine.drug, Adult, medicine.medical_specialty, MESH: Survival Rate, 03 medical and health sciences, Multicenter trial, Internal medicine, medicine, Humans, Busulfan, Cyclophosphamide, MESH: Hematopoietic Stem Cell Transplantation, Aged, Salvage Therapy, Chemotherapy, MESH: Humans, business.industry, Eye Neoplasms, MESH: Cyclophosphamide, MESH: Adult, medicine.disease, MESH: Male, MESH: Prospective Studies, Surgery, Lymphoma, MESH: Lymphoma, Large B-Cell, Diffuse, Methotrexate, Neoplasm Recurrence, Local, business, human activities, MESH: Female, Thiotepa, 030217 neurology & neurosurgery
Abstract: Purpose The prognosis of relapsing primary CNS lymphoma (PCNSL) is poor. We report the results of a prospective multicenter trial of intensive chemotherapy followed by autologous hematopoietic stem-cell rescue (IC + HCR) in immunocompetent adult patients with PCNSL or intraocular lymphoma (IOL) after failure of high-dose methotrexate-based treatment. Patients and Methods Salvage treatment consisted of two cycles of high-dose cytarabine and etoposide (CYVE). Intensive chemotherapy combined thiotepa, busulfan, and cyclophosphamide. Forty-three patients (median age, 52 years; range, 23 to 65 years) were included, with relapse (n = 22), refractory disease (n = 17), or a partial response to first-line treatment (n = 4). The response to CYVE was not assessable in three cases because of treatment-related death. Twenty patients (47%) were chemosensitive to CYVE: 15 of them proceeded to IC + HCR. IC + HCR was also administered to 12 patients who did not respond to CYVE. All but one of the 27 patients who underwent IC + HCR entered complete remission. Results With a median follow-up of 36 months, the median overall survival was 18.3 months in the overall population, and 58.6 months among patients who completed IC + HCR. The respective median progression-free survival (PFS) times after IC + HCR were 11.6 and 41.1 months. The 2-year overall survival probability was 45% in the whole population and 69% among the 27 patients who received IC + HCR. The 2-year PFS probability was 43% among all the patients and 58% in the IC + HCR subpopulation. Conclusion IC + HCR is an effective treatment for refractory and recurrent PCNSL.
Published: 2008
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21. Integrating clinical, gene expression, protein expression and preanalytical data for in silico cancer research

Author: Rossille, D., Burgun, A., Celine PANGAULT, Fest, T., Laboratoire d'Informatique Médicale (LIM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Modélisation Conceptuelle des Connaissances Biomédicales, Microenvironnement et cancer (MiCa), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Le Corre, Morgane
Subjects: Proteomics, Genetic Research, Lymphoma, Medical Records Systems, Computerized, MESH: Clinical Trials as Topic, MESH: Medical Informatics Applications, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Medical Records Systems, Computerized, MESH: Prognosis, Cohort Studies, Databases, MESH: Software, [SDV.CAN] Life Sciences [q-bio]/Cancer, Genetic, Computer Systems, Databases, Genetic, Biomarkers, Tumor, Humans, Medical Informatics Applications, MESH: Cohort Studies, MESH: Databases, Genetic, Cancer, Clinical Trials as Topic, MESH: Humans, MESH: Proteomics, Information storage and retrieval, MESH: Computer Systems, MESH: Information Storage and Retrieval, MESH: Gene Expression Regulation, Neoplastic, Prognosis, Gene Expression Regulation, Neoplastic, MESH: France, MESH: Genetic Research, MESH: Tumor Markers, Biological, Database Management Systems, MESH: Lymphoma, Large B-Cell, Diffuse, France, Lymphoma, Large B-Cell, Diffuse, Systems integration, MESH: Lymphoma, Software, MESH: Database Management Systems
Abstract: International audience; We present the phase I development of an integrative platform for the analysis of clinical, gene expression, protein expression and pre-analytical data. The platform is aimed at providing transparent access and analysis tools to researchers investigating new biomarkers and prognosis factors in the particular field of lymphoma diseases. In this article, we report on the data integration phase. The platform's principal advantage is its completeness as it integrates in a single environment clinical, genomic and proteomic data, allowing for their combined analysis. The architecture consists in a data warehouse including data on patients, clinical trials and array platforms and a DeMilitarized Zone for data exchange. A secure web-based platform allows any collaborative team to request the data warehouse and access basic statistics on integrated data. The presented system is currently in use.
Published: 2008

22. Les enjeux du préanalytique dans l’analyse du transcriptome et du proteome sanguins Application à la recherche clinique: l’expérience du GOELAMS [Stakes of pre-analytical parameters in blood transcriptomic and proteomic analysis. Application to clinical research: the GOELAMS trial]

Author: Pangault, Céline, Arlotto, Marie, Berger, François, de Vos, John, Béné, Marie-Christine, Fest, Thierry, Goelams, Groupe Ouest-Est Des Leucémies Aiguës Et Autres Maladies Du Sang, Microenvironnement cellulaire et moléculaire des tumeurs, Université de Rennes (UR), Neurosciences précliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service d'Immunologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Issartel, Jean-Paul, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: MESH: Neoplasm Proteins, MESH: Humans, MESH: Proteomics, MESH: Transcription, Genetic, MESH: Research Design, MESH: Blood Preservation, MESH: Blood Specimen Collection, MESH: Reproducibility of Results, MESH: Lymphoma, Non-Hodgkin, MESH: Tumor Markers, Biological, MESH: Cryopreservation, MESH: Lymphoma, Large B-Cell, Diffuse, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Specimen Handling, MESH: Cohort Studies
Abstract: International audience; Numerous parameters related to the patients and the conditions of the sample collection can affect the properties of a biological sample. The pre-analytical parameters are especially important to deal with in the setting of multicenter clinical trials. Here, we report the preliminary results of a trial conducted by the cooperative group GOELAMS (Groupe Ouest-Est des Leucémies aiguës et Autres Maladies du Sang) to define the pre-analytical parameters that affect the proteomic analysis of serum samples in patients with B-cell non Hodgkin lymphoma included in clinical trials.
Published: 2007
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23. Human γδ T lymphocytes strip and kill tumor cells simultaneously

Author: Aurélie Wiedemann, Mary Poupot, Jean-Jacques Fournié, Julie Gertner, Poupot, Mary, Centre de Physiopathologie Toulouse Purpan (CPTP), 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)
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, MESH: Cell Death, Programmed cell death, Immunology, Cell, MESH: Flow Cytometry, Biology, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Live cell imaging, medicine, Immunology and Allergy, Secretion, MESH: Animals, 030304 developmental biology, 0303 health sciences, MESH: Humans, medicine.diagnostic_test, hemic and immune systems, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.disease, Lymphoma, Cell biology, Cytolysis, medicine.anatomical_structure, MESH: T-Lymphocytes, Lytic cycle, MESH: Lymphoma, Large B-Cell, Diffuse, 030215 immunology, MESH: Cell Membrane, MESH: Cells, Cultured
Abstract: International audience; When human gammadelta lymphocytes bind to tumor cells for killing, they also strip their membrane for unknown reasons. Here we investigated this topic using the model of human gammadelta lymphocytes co-incubated with anaplastic large cell lymphomas, a group of tumors with cytolytic T or null lineage. By using flow cytometry and live cell imaging, we show that as soon as both cells were in contact, the TCR-mediated activation of gammadelta lymphocytes simultaneously triggered their secretion of lytic granules and stripping of lymphoma cell membranes, and both activities continued even after their cell death. However reciprocally in such conjugates, resistant lymphoma failed to strip gammadelta cells and to kill them by untargeted secretion of their own lytic granules. This indicated that secretion of lytic granules and target membrane stripping are associated in lytic cell conjugates, and that gammadelta T lymphocytes strip and kill their targets simultaneously.
Published: 2007
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24. High expression of calcium-binding proteins, S100A10, S100A11 and CALM2 in anaplastic large cell lymphoma

Author: Jean C Deloulme, Sibrand Poppema, Tjasso Blokzijl, Lydia Visser, Willem Kamps, Renata Rust, Klaas Kok, Geert Harms, Pieter van der Vlies, Judith van der Leij, Anke van den Berg, Megan S. Lim, Research and Evaluation of Educational Effectiveness, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Department of Pathology and Laboratory, University of Grningen, Department of Paediatric Oncology, University of Groningen [Groningen], Mécanismes d'expression cellulaire des effecteurs humoraux, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Departement of medical genetics, Department of Pathology, University of Utah, and Andrieux, Annie
Subjects: CD4-Positive T-Lymphocytes, MESH: Annexin A2, Galectin 1, LINES, medicine.disease_cause, MESH: Down-Regulation, 0302 clinical medicine, MESH: Reverse Transcriptase Polymerase Chain Reaction, hemic and lymphatic diseases, Anaplastic lymphoma kinase, Serial analysis of gene expression, Anaplastic large-cell lymphoma, 1q12–21 amplicon, Annexin A2, Cells, Cultured, Oligonucleotide Array Sequence Analysis, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, S100 Proteins, Large-cell lymphoma, MESH: CD4-Positive T-Lymphocytes, Hematology, MESH: Gene Expression Regulation, Neoplastic, Amplicon, MESH: Calmodulin, ALCL, CANCER, Immunohistochemistry, 3. Good health, Reverse transcription polymerase chain reaction, IMMUNOPHENOTYPIC ANALYSIS, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, GROWTH, MESH: Membrane Proteins, Lymphoma, Large B-Cell, Diffuse, MESH: S100 Proteins, MESH: Cells, Cultured, MESH: Cell Line, Tumor, Down-Regulation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MESH: Calcium Signaling, 03 medical and health sciences, MESH: Gene Expression Profiling, [SDV.CAN] Life Sciences [q-bio]/Cancer, Calmodulin, Cell Line, Tumor, medicine, Humans, Calcium Signaling, S100A11, 1q12-21 amplicon, CLUSTERIN, Gene, 030304 developmental biology, MESH: Galectin 1, MESH: Humans, Gene Expression Profiling, Membrane Proteins, MESH: Immunohistochemistry, KI-1 LYMPHOMA, medicine.disease, GENE, GENOTYPIC ANALYSIS, TISSUE, MESH: Oligonucleotide Array Sequence Analysis, S100A10, Cancer research, CALM2, T-CELLS, MESH: Lymphoma, Large B-Cell, Diffuse, Carcinogenesis
Abstract: International audience; Anaplastic large cell lymphomas (ALCL) are characterised by the presence of CD30-positive large cells, which usually are of T-cell type. Based on the presence or absence of translocations involving the anaplastic lymphoma kinase (ALK) locus, ALCL cases can be divided into two groups. To gain more insight in the biology of ALCL, we applied serial analysis of gene expression (SAGE) on the Karpas299 cell line and identified 25 up- and 19 downregulated genes. Comparison of the differentially expressed genes with DNA copy number changes in Karpas299 revealed that two overexpressed genes, S100A10 and S100A11, were located in an amplicon suggesting that the increased mRNA levels were caused by DNA amplification. Quantitative reverse transcription polymerase chain reaction on 5 ALCL cell lines and 12 ALCL tissues confirmed the SAGE data for 13 out of 14 up- and one out of four downregulated genes. Immunohistochemical staining confirmed the presence of S100A10, a calcium-binding protein, in three out of five ALK+ and all 7 ALK- ALCL cases. S100A11 staining was confirmed in all ALK+ and six of seven ALK- ALCL cases. Three of the upregulated genes represented calcium-binding proteins, which suggest that altered intracellular signaling might be associated with the oncogenesis of ALCL.
Published: 2005
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25. Profiling Blood Lymphocyte Interactions with Cancer Cells Uncovers the Innate Reactivity of Human γδ T Cells to Anaplastic Large Cell Lymphoma

Author: Frédéric Pont, Mary Poupot, Jean-Jacques Fournié, Centre de Physiopathologie de Toulouse-Purpan (INSERM U563 - CNRS UMR1037), Centre National de la Recherche Scientifique (CNRS)-Centre de lutte contre le cancer (CLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut Claudius Regaud, Poupot, Mary, and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut Claudius Regaud-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de lutte contre le cancer (CLCC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, T-Lymphocytes, MESH: HT29 Cells, Cell Communication, Jurkat cells, Jurkat Cells, 0302 clinical medicine, MESH: Jurkat Cells, Immunology and Allergy, Anaplastic large-cell lymphoma, Cell Line, Transformed, B-Lymphocytes, 0303 health sciences, Receptors, Antigen, T-Cell, gamma-delta, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, U937 Cells, 3. Good health, Immunosurveillance, MESH: Leukocytes, Mononuclear, medicine.anatomical_structure, MESH: Immunity, Innate, Lymphoma, Large B-Cell, Diffuse, HT29 Cells, Adult, Trogocytosis, T cell, Immunology, MESH: Lymphocyte Subsets, Biology, MESH: U937 Cells, MESH: Coculture Techniques, 03 medical and health sciences, Antigen, MESH: Receptors, Antigen, T-Cell, gamma-delta, MESH: B-Lymphocytes, MESH: Cell Communication, medicine, Humans, MESH: Cell Line, Transformed, 030304 developmental biology, MESH: K562 Cells, MESH: Humans, MESH: Adult, medicine.disease, Coculture Techniques, Immunity, Innate, Lymphocyte Subsets, MESH: T-Lymphocytes, Cancer cell, Leukocytes, Mononuclear, MESH: Lymphoma, Large B-Cell, Diffuse, K562 Cells, CD8, 030215 immunology
Abstract: Quantifying the contacts that circulating lymphocytes have with cancer cells is useful, because their deficit favors malignancy progression. All normal lymphocytes contact, scan, and acquire membrane fragments (trogocytosis) from foreign cells for their immunosurveillance. So in this study, we used the in vitro trogocytosis of PKH67-stained cancer cell lines as a measure of their interactions with bulks of PBMC freshly isolated from healthy donors. Allogeneic PBMC mixed and coincubated in vitro for 1 h did not trogocytosis, whereas in the same conditions CD20+, CD4+, CD8+, γδ T, and CD16+ PBMC interacted strongly with the cancer cells. Although most unprimed lymphoid effectors of innate (NK) and adaptive (B and T) immunity from healthy donors spontaneously trogocytosed different tumoral cell lines, some carcinoma cell lines could escape them in the coculture. This also uncovered the strong interactions of circulating Vγ9/Vδ2+ central memory γδ T cells with anaplastic large cell lymphoma. These interaction profiles were stable upon time for healthy blood donors but were different with other tumors and blood donors. This profiling provides interaction signatures for the immunomonitoring of cancer.
Published: 2005
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26. Nitric oxide production in human macrophagic cells phagocytizing opsonized zymosan: direct characterization by measurement of the luminol dependent chemiluminescence

Author: Sandra Spiesser, C Damais, Ioanis Vouldoukis, J P Kolb, Bernard Dugas, Nathalie Dugas, Jacques Dornand, Antoine Gross, Microbiologie et Pathologie Cellulaire Infectieuse, and Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Xanthine, MESH: Leukemia, Monocytic, Acute, Nitric Oxide Synthase Type II, MESH: Superoxides, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Biochemistry, Guanidines, MESH: omega-N-Methylarginine, chemistry.chemical_compound, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Superoxides, MESH: Cell-Free System, Tumor Cells, Cultured, MESH: Phagocytosis, MESH: Opsonin Proteins, MESH: Superoxide Dismutase, MESH: Immunoglobulin G, NADPH oxidase, biology, Superoxide, MESH: Immunoglobulin E, MESH: Macrophage Activation, Cell Differentiation, General Medicine, Free Radical Scavengers, Opsonin Proteins, MESH: Guanidines, Nitric oxide synthase, MESH: Nitrates, Leukemia, Monocytic, Acute, Neoplastic Stem Cells, MESH: Nitric Oxide Synthase, MESH: Nitric Oxide Synthase Type II, Luminol, Lymphoma, Large B-Cell, Diffuse, Peroxynitrite, MESH: Zymosan, MESH: Cell Differentiation, Xanthine Oxidase, MESH: Chemiluminescent Measurements, Phagocytosis, Tretinoin, MESH: Xanthine Oxidase, Nitric Oxide, Xanthine, Nitric oxide, Superoxide dismutase, Calcitriol, Humans, MESH: Tumor Cells, Cultured, MESH: Tretinoin, MESH: Humans, Nitrates, omega-N-Methylarginine, Cell-Free System, Superoxide Dismutase, MESH: Luminol, Macrophages, Zymosan, MESH: Macrophages, Immunoglobulin E, Macrophage Activation, MESH: Neoplastic Stem Cells, chemistry, MESH: Calcitriol, MESH: Nitric Oxide, Immunoglobulin G, Luminescent Measurements, MESH: Free Radical Scavengers, biology.protein, MESH: Lymphoma, Large B-Cell, Diffuse, Nitric Oxide Synthase
Abstract: When differentiated into mature macrophages by the combination of all-trans retinoic acid and 1,25-dihydroxyvitamin D3, the human promonocytic cell lines U937 and THP-1 expressed inducible nitric oxide synthase (iNOS) transcripts. During their differentiation, the cells acquired the capacity to produce not only superoxide anion (O2.-) but also nitric oxide (.NO) in response to IgG (or IgE)-opsonized zymosan. The inhibitors of the iNOS pathway, aminoguanidine and NG-monomethyl-L-arginine (L-NMMA), suppressed the production of .NO and enhanced the steady-state concentration of O2.- determined. Conversely, superoxide dismutase (SOD) scavenged the O2.- released and increased the .NO-derived nitrite concentration detected. These data suggested a possible interaction between O2.- and .NO. In differentiated U937 (or THP-1) cells, IgG or IgE-opsonized zymosan induced a strong time-dependent luminol-dependent chemiluminescence (LDCL), which was abrogated by SOD and partially inhibited by aminoguanidine or L-NMMA. Since the iNOS inhibitors did not directly scavenge O2.-, LDCL determination in the presence or absence of SOD and/or iNOS inhibitors demonstrated a concomitant production of O2.- and .NO. These radicals induced the formation of a .NO-derived product(s), probably peroxynitrite (ONOO-), which was required to elicit maximal LDCL. Finally, LDCL measurement provided a convenient tool to characterize iNOS triggering and demonstrated an interaction between NADPH oxidase and iNOS products in human macrophagic cells phagocytizing opsonized-zymosan. These findings show that in activated macrophages, iNOS activity can be involved in LDCL and support the debated hypothesis of iNOS participation to the microbicidal activity of human macrophages.
Published: 1998

27. Primary lymphoma of the lacrimal sac: an EORTC ophthalmic oncology task force study

Author: Elisabeth Ralfkiaer, Birgitte R Juhl, Franck Bacin, Peter Meyer, Tero Kivelä, B. Kantelip, Claudia Auw-Haedrich, Steffen Heegaard, Nicolas Ducrey, Marta Carrera, Sarah E. Coupland, Jan Ulrik Prause, Nicolai Christian Sjö, Lene Dissing Sjö, Jean Louis Kemeny, Bernard Delbosc, Eye Pathology Institute, University of Copenhagen ( KU ), Department of Pathology, Rigshospitalet [Copenhagen], Department of Ophthalmology, Helsinki University Central Hospital, University Hospital in Freiburg, Service d'ophtalmologie [Clermont-Ferrand], CHU Clermont-Ferrand, Department of Ophthalmic Pathology, Hospital of Bellvitge-University of Barcelona, Department of Cellular and Molecular Pathology, University of Liverpool, Service d'ophtalmologie [Besançon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, 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 ), Jules Gonin Hospital, Laboratoire d'anatomie pathologique [Besancon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), 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 de pathologie, University of Basle, European Organization for Research and Treatment of Cancer, University of Copenhagen = Københavns Universitet (KU), Copenhagen University Hospital-Copenhagen University Hospital, Service d'ophtalmologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service d'Anatomie pathologique [CHRU Besançon], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), University of Copenhagen = Københavns Universitet (UCPH), 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), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), and Saas, Philippe
Subjects: Oncology, Pathology, MESH : Retrospective Studies, MESH : Aged, MESH: Antigens, Neoplasm, MESH : Lymphoma, Large B-Cell, Diffuse, MESH : Antigens, Neoplasm, MESH: Aged, 80 and over, MESH : Lymphoma, B-Cell, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, MESH: Lymphoma, B-Cell, Marginal Zone, MESH: Antigens, CD, MESH: Aged, MESH: Middle Aged, MALT lymphoma, Sensory Systems, Lacrimal sac, 3. Good health, MESH : Lymphoma, B-Cell, Marginal Zone, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Male, MESH: Lacrimal Apparatus Diseases, Lacrimal gland, Ophthalmic pathology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Internal medicine, MESH : Antigens, CD, medicine, MESH : Middle Aged, MESH : Aged, 80 and over, MESH: Lymphoma, B-Cell, MESH : Lacrimal Apparatus Diseases, MESH: Humans, business.industry, Clinical Science - Extended Report, MESH : Humans, Cancer, MESH: Retrospective Studies, medicine.disease, MESH: Male, Dacryocystitis, Lymphoma, Ophthalmology, 030221 ophthalmology & optometry, MESH: Lymphoma, Large B-Cell, Diffuse, Tears, business, MESH: Female, Diffuse large B-cell lymphoma, Mucosa-associated lymphoid tissue
Abstract: International audience; AIM: To define the clinical and histopathological characteristics of primary lacrimal sac lymphoma in a predominantly white population. METHODS: Specimens of lacrimal sac lymphoma and follow up data were solicited from members of the Ophthalmic Oncology Task Force of the European Organization for Research and Treatment of Cancer (EORTC) and the European Ophthalmic Pathology Society (EOPS). Specimens were stained with haematoxylin and eosin and an immunohistochemical panel against leucocyte antigens was applied. Diagnosis was reached by consensus of five experienced pathologists according to the World Health Organization classification system. The histopathological findings were correlated with the clinical data. RESULTS: Of 15 primary lacrimal sac lymphomas, five (33%) were diffuse large B cell lymphoma (DLBCL), five (33%) were extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT lymphoma), three were classified as "transitional MALT lymphoma," being in transition from MALT lymphoma to DLBCL, and two were unclassified B cell lymphomas. Nine of the patients were female, and the median age at the time of diagnosis was 71 years (range 45-95 years). The most frequent presenting symptoms were epiphora (85%), swelling in the region of the lacrimal sac (79%), and dacryocystitis (21%). All but one patient presented in stage I. Systemic spread occurred in three of nine patients (33%). The 5 year overall survival was 65%. CONCLUSIONS: DLBCL and MALT lymphoma are equally common in the lacrimal sac in contrast with the remaining periorbital and/or orbital region where MALT lymphoma predominates.
Published: 2006
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27. Primary lymphoma of the lacrimal sac: an EORTC ophthalmic oncology task force study

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