381 results on '"Nicole Brousse"'
Search Results
2. Gastrointestinal Disorder Associated with Olmesartan Mimics Autoimmune Enteropathy.
- Author
-
Sophie Scialom, Georgia Malamut, Bertrand Meresse, Nicolas Guegan, Nicole Brousse, Virginie Verkarre, Coralie Derrieux, Elizabeth Macintyre, Philippe Seksik, Guillaume Savoye, Guillaume Cadiot, Lucine Vuitton, Lysiane Marthey, Franck Carbonnel, Nadine Cerf-Bensussan, and Christophe Cellier
- Subjects
Medicine ,Science - Abstract
Background and objectivesAnti-hypertensive treatment with the angiotensin II receptor antagonist olmesartan is a rare cause of severe Sprue-like enteropathy. To substantiate the hypothesis that olmesartan interferes with gut immune homeostasis, clinical, histopathological and immune features were compared in olmesartan-induced-enteropathy (OIE) and in autoimmune enteropathy (AIE).MethodsMedical files of seven patients with OIE and 4 patients with AIE enrolled during the same period were retrospectively reviewed. Intestinal biopsies were collected for central histopathological review, T cell Receptor clonality and flow cytometric analysis of isolated intestinal lymphocytes.ResultsAmong seven olmesartan-treated patients who developed villous atrophy refractory to a gluten free diet, three had extra-intestinal autoimmune diseases, two had antibodies reacting with the 75 kilodalton antigen characteristic of AIE and one had serum anti-goblet cell antibodies. Small intestinal lesions and signs of intestinal lymphocyte activation were thus reminiscent of the four cases of AIE diagnosed during the same period. Before olmesartan discontinuation, remission was induced in all patients (7/7) by immunosuppressive drugs. After interruption of both olmesartan and immunosuppressive drugs in six patients, remission was maintained in 4 but anti-TNF-α therapy was needed in two.ConclusionThis case-series shows that olmesartan can induce intestinal damage mimicking AIE. OIE usually resolved after olmesartan interruption but immunosuppressive drugs may be necessary to achieve remission. Our data sustain the hypothesis that olmesartan interferes with intestinal immuno regulation in predisposed individuals.
- Published
- 2015
- Full Text
- View/download PDF
3. Long-term follow up of the FL2000 study comparing CHVP-interferon to CHVP-interferon plus rituximab in follicular lymphoma
- Author
-
Emmanuel Bachy, Roch Houot, Franck Morschhauser, Anne Sonet, Pauline Brice, Karim Belhadj, Guillaume Cartron, Bruno Audhuy, Christophe Fermé, Pierre Feugier, Catherine Sebban, Vincent Delwail, Hervé Maisonneuve, Steven Le Gouill, Sophie Lefort, Nicole Brousse, Charles Foussard, and Gilles Salles
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Anti-CD20-containing chemotherapy regimens have become the standard of care for patients with follicular lymphoma needing cytotoxic therapy. Four randomized trials demonstrated a clinical benefit for patients treated with rituximab. However, no long-term follow up (i.e. > 5 years) of these trials is yet available. Between May 2000 and May 2002, 358 newly diagnosed patients with high tumor burden follicular lymphoma were randomized to receive cyclophosphamide, adriamycin, etoposide and prednisolone plus interferon-α2a or a similar chemotherapy-based regimen plus rituximab, and outcome was up-dated. With a median follow up of 8.3 years, addition of rituximab remained significantly associated with prolonged event-free survival (primary end point) (P=0.0004) with a trend towards a benefit for overall survival (P=0.076). The Follicular Lymphoma International Prognostic Index score was strongly associated with outcome for both event-free and overall survival in univariate analysis and its prognostic value remained highly significant after adjusting for other significant covariates in multivariate models (P
- Published
- 2013
- Full Text
- View/download PDF
4. Epstein-Barr virus-induced gene 3 (EBI3): a novel diagnosis marker in Burkitt lymphoma and diffuse large B-cell lymphoma.
- Author
-
Julie Gonin, Frédérique Larousserie, Christian Bastard, Jean-Michel Picquenot, Jérôme Couturier, Isabelle Radford-Weiss, Céline Dietrich, Nicole Brousse, Marie-Cécile Vacher-Lavenu, and Odile Devergne
- Subjects
Medicine ,Science - Abstract
The distinction between Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), two types of mature aggressive B-cell lymphomas that require distinct treatments, can be difficult because of forms showing features intermediate between DLBCL and BL (here called BL/DLBCL). They can be discriminated by the presence of c-myc translocations characteristic of BL. However, these are not exclusive of BL and when present in DLBCL are associated with lower survival. In this study, we show that Epstein-Barr virus-induced gene 3 (EBI3) is differentially expressed among BL and DLBCL. Analysis of gene expression data from 502 cases of aggressive mature B-cell lymphomas available on Gene Expression Omnibus and immunohistochemical analysis of 184 cases of BL, BL/DLBCL or DLBCL, showed that EBI3 was not expressed in EBV-positive or -negative BL cases, whereas it was expressed by over 30% of tumoral cells in nearly 80% of DLBCL cases, independently of their subtypes. In addition, we show that c-myc overexpression represses EBI3 expression, and that DLBCL or BL/DLBCL cases with c-myc translocations have lower expression of EBI3. Thus, EBI3 immunohistochemistry could be useful to discriminate BL from DLBCL, and to identify cases of BL/DLBCL or DLBCL with potential c-myc translocations.
- Published
- 2011
- Full Text
- View/download PDF
5. Prognostic significance of new immunohistochemical markers in refractory classical Hodgkin lymphoma: a study of 59 cases.
- Author
-
Danielle Canioni, Bénédicte Deau-Fischer, Pierre Taupin, Vincent Ribrag, Richard Delarue, Jacques Bosq, Marie-Thérèse Rubio, Damien Roux, Viorel Vasiliu, Bruno Varet, Nicole Brousse, and Olivier Hermine
- Subjects
Medicine ,Science - Abstract
Although most classical Hodgkin lymphoma patients are cured, a significant minority fail after primary therapy and may die as result of their disease. To date, there is no consensus on biological markers that add value to usual parameters (which comprise the International Prognostic Score) used at diagnosis to predict outcome. We evaluated 59 patients (18 with primary refractory or early relapse disease and 41 responders) for bcl2, Ki67, CD20, TiA1 and c-kit expression by semi-quantitative immunohistochemical study and correlated the results with the response to treatment.The results showed that expression of bcl2 and CD20 in Hodgkin and Reed Sternberg cells, and expression of TiA1 in micro-environmental lymphocytes, and c-kit positive mast cells in microenvironment, were independent prognostic markers. These novel cHL markers could be used in association with clinical parameters to identify newly diagnosed patients with favorable or unfavorable prognosis and to better tailor treatment for different risk groups.
- Published
- 2009
- Full Text
- View/download PDF
6. NKp46 is a diagnostic biomarker and may be a therapeutic target in gastrointestinal T-cell lymphoproliferative diseases: A CELAC study
- Author
-
Nicolas Guegan, Florence Lhospice, Sascha Cording, Amélie Trinquand, Julie Bruneau, Olivier Hermine, Virginie Verkarre, Nicole Brousse, Christophe Cellier, Georgia Malamut, Elizabeth Macintyre, Felipe Suarez, Laurent Frenzel, Vahid Asnafi, Morgane Cheminant, Sherine Khater, Bertrand Meresse, Ambroise Marçais, Nadine Cerf-Bensussan, Tom van Gils, Chris J. J. Mulder, Thierry Jo Molina, Ludovic Lhermitte, C. cile Bonnafous, David Sibon, Anne-Sophie Jannot, Richard Delarue, Laurent Pouyet, Gastroenterology and hepatology, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Département de Pathologie [CHU Necker], Université Sorbonne Paris Cité (USPC)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), VU University Medical Center [Amsterdam], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris, Mi-mAbs (C/O CIML), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Innate Pharma, Service de gastroenterologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Mécanismes cellulaires et moléculaires des désordres hématologiques et implications thérapeutiques = Molecular mechanisms of hematological disorders and therapeutic implications (ERL 8254), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,Male ,MESH: Biopsy / methods ,Enteropathy-Associated T-Cell Lymphoma / diagnosis ,Entropathy-Associated T-Cell Lymphoma / etiology ,Enteropathy-Associated T-Cell Lymphoma / immunology ,T cell ,Biopsy ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Coeliac Disease ,Coeliac disease ,03 medical and health sciences ,0302 clinical medicine ,Enteropathy-Associated T-Cell Lymphoma ,Intestinal mucosa ,Intestine, Small ,medicine ,Cytotoxic T cell ,Humans ,Intestinal Mucosa ,MESH: Enteropathy-Associated T-Cell Lymphoma / pathology ,Intestinal Mucosa / immunology ,Intestinal Mucosa / pathology ,Killer Cells, Natural / immunology ,Antibody Targeted Therapy ,Cells, Cultured ,business.industry ,Natural Cytotoxicity Triggering Receptor 1 ,Gastroenterology ,MESH: Natural Cytotoxicity Triggering Receptor 1 / immunology ,Antibodies, Monoclonal ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Middle Aged ,medicine.disease ,NKG2D ,Prognosis ,3. Good health ,Killer Cells, Natural ,Celiac Disease ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer research ,Intraepithelial lymphocyte ,Enteropathy-associated T-cell lymphoma ,Female ,France ,Gastrointestinal Lymphoma ,business ,Ex vivo ,Biomarkers ,Tumour markers - Abstract
ObjectivesPrimary GI T-cell lymphoproliferative diseases (T-LPD) are heterogeneous entities, which raise difficult diagnosis and therapeutic challenges. We have recently provided evidences that lymphomas complicating coeliac disease (CD) arise from innate-like lymphocytes, which may carry NK receptors (NKRs).DesignNKRs expression was compared by flow cytometry in intraepithelial lymphocytes (IEL) from CD, type I or type II refractory CD (RCD). NKp46 was next assessed by immunohistochemistry in paraffin-embedded biopsies from 204 patients with CD, RCDI, RCDII or GI T-cell lymphomas and from a validation cohort of 61 patients. The cytotoxic properties of an anti-NKp46 monoclonal antibody conjugated to pyrrolobenzodiazepine (PBD) was tested ex vivo in human primary tumour cells isolated from fresh duodenal biopsies.ResultsNKp46 (but not CD94, NKG2A, NKG2C, NKG2D) was significantly more expressed by malignant RCDII IEL than by normal IEL in CD and RCDI. In paraffin biopsies, detection of >25 NKp46+ IEL per 100 epithelial cells discriminated RCDII from CD and RCDI. NKp46 was also detected in enteropathy-associated T-cell lymphomas (EATL, 24/29) and in monomorphic epitheliotropic intestinal T-cell lymphomas (MEITL, 4/4) but not in indolent T-LPD (0/15). Treatment with anti-NKp46-PBD could efficiently and selectively kill human NKp46+ primary IEL ex vivo.ConclusionNKp46 is a novel biomarker useful for diagnosis and therapeutic stratification of GI T-LPD. Strong preclinical rationale identifies anti-NKp46-PBD as a promising therapy for RCDII, EATL and MEITL.
- Published
- 2019
7. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network
- Author
-
Georg Maschmeyer, Bernd Metzner, Corinne Haioun, Richard Delarue, Thomas Fischer, Ulrich Dührsen, Michal Szymczyk, Jan Walewski, Mathias Hänel, Michael Unterhalt, Catherine Thieblemont, Norma Peter, Kamal Bouabdallah, Christiane Pott, Michael Hallek, Vincent Ribrag, Stephan Stilgenbauer, André Bosly, Catherine Sebban, Josef Birkmann, Christian Schmidt, Marie-Hélène Delfau-Larue, Jürgen Finke, Wolfgang Hiddemann, Nicole Brousse, Elizabeth Macintyre, Gilles Salles, Pierre Feugier, Wolfram Klapper, Roswitha Forstpointner, Eva Hoster, Michael Kneba, Rene-Olivier Casasnovas, Martin Dreyling, Lothar Kanz, Reda Bouabdallah, Olivier Hermine, Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Department of Internal Medicine III, University of Munich, Institute of Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology ( MCMCC ), CHU Dinant-Godinne UCL Namur, Internal Medicine III, Universität Ulm, APHP Hôpital Saint Louis, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier ( ICGM ICMMM ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Département d'Hematologie, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Second Medical Department, University Hospital Schleswig-Holstein, University of Cologne, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Hématologie, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Paracelsus Medical University, Ludwig-Maximilians University Hospital, 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 ), Klinikum Chemnitz, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), University Hospital Freiburg, Carl Thiem Hospital Cottbus, Université Mohamed Boudiaf de M'sila, Centre Léon Bérard [Lyon], Agence départementale d’architecture et d’urbanisme du Haut-Rhin ( ADAUHR ), University Hospital Essen, Medizinische Klinik, Hämatologie und Onkologie, Klinikum Ernst von Bergmann, Department of Internal Medicine II (Oncology, Hematology, Immunology, Rheumatology, Pulmonology), University Hospital Tuebingen, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Laboratoire d'anatomie pathologique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Department of Pathology, Hematopathology Section and Lymph Node Registry, Universityhospital Schleswig-Holstein, Campus Kiel, 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'immunologie biologique, University Hospital Schleswig–Holstein, III. Medizinische Klinik, Technische Universität München [München] ( TUM ), Institut Imagine (UMR 1163), Laboratory of Cellular and Molecular Mechanisms of Hemathological Disorders and Therapeutic Implication, Maria Sklodowska-Curie Memorial Cancer Center, Institut Charles Gerhardt - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICG ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM) - Université Montpellier 2 - Sciences et Techniques (UM2) - Université Montpellier 1 (UM1) - Centre National de la Recherche Scientifique (CNRS), Institut Paoli Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC) - Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service de Radio-Oncologie [Lyon], Hospices Civils de Lyon - Centre Hospitalier Lyon Sud [Pierre Bénite], Hôpital Edouard Herriot, Hospices Civils de Lyon - Hôpital Edouard Herriot, Institut Gustave Roussy (IGR), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), University Medical Centre Freiburg, Centre Hospitalier Universitaire de Bordeaux, Agence départementale d’architecture et d’urbanisme du Haut-Rhin (ADAUHR), Laboratoire d'Informatique de l'Université du Maine (LIUM), Université du Maine (UM), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5) - AP-HP Hôpital Necker - Enfants Malades [Paris], AP-HP Hôpital Necker - Enfants Malades [Paris], Service hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) - Groupe Hospitalier Necker-Enfants Malades, 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), and Technische Universität München [München] (TUM)
- Subjects
Adult ,Male ,medicine.medical_specialty ,Vincristine ,Transplantation Conditioning ,Medizin ,Lymphoma, Mantle-Cell ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,0302 clinical medicine ,Autologous stem-cell transplantation ,International Prognostic Index ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Treatment Failure ,Cyclophosphamide ,ComputingMilieux_MISCELLANEOUS ,business.industry ,Cytarabine ,Hematopoietic Stem Cell Transplantation ,General Medicine ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Surgery ,Transplantation ,Doxorubicin ,030220 oncology & carcinogenesis ,Prednisone ,Female ,Rituximab ,Mantle cell lymphoma ,Immunotherapy ,business ,Immunosuppressive Agents ,Febrile neutropenia ,030215 immunology ,medicine.drug - Abstract
Summary Background Mantle cell lymphoma is characterised by a poor long-term prognosis. The European Mantle Cell Lymphoma Network aimed to investigate whether the introduction of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation (ASCT) improves outcome. Methods This randomised, open-label, parallel-group, phase 3 trial was done in 128 haemato-oncological hospital departments or private practices in Germany, France, Belgium, and Poland. Patients aged 65 years or younger with untreated stage II–IV mantle cell lymphoma were centrally randomised (1:1), with computer-assisted random block selection, to receive either six courses of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by myeloablative radiochemotherapy and ASCT (control group), or six courses of alternating R-CHOP or R-DHAP (rituximab plus dexamethasone, high-dose cytarabine, and cisplatin) followed by a high-dose cytarabine-containing conditioning regimen and ASCT (cytarabine group). Patients were stratified by study group and international prognostic index. The primary outcome was time to treatment failure from randomisation to stable disease after at least four induction cycles, progression, or death from any cause. Patients with stage II–IV mantle cell lymphoma were included in the primary analysis if treatment was started according to randomisation. For safety analyses, patients were assessed according to the treatment actually started. This study is registered with ClinicalTrials.gov, number NCT00209222. Findings Of 497 patients (median age 55 years [IQR 49–60]) randomised from July 20, 2004, to March 18, 2010, 234 of 249 in the control group and 232 of 248 in the cytarabine group were included in the primary analysis. After a median follow-up of 6·1 years (95% CI 5·4–6·4), time to treatment failure was significantly longer in the cytarabine group (median 9·1 years [95% CI 6·3–not reached], 5 year rate 65% [95% CI 57–71]) than in the control group (3·9 years [3·2–4·4], 40% [33–46]; hazard ratio 0·56; p=0·038). During induction immunochemotherapy, patients who received high-dose cytarabine had increased grade 3 or 4 haematological toxicity (haemoglobin 71 [29%] of 241m vs 19 [8%] of 227 controls; platelets 176 [73%] of 240 vs 21 [9%] of 225), grade 3 or 4 febrile neutropenia (39 [17%] of 230 vs 19 [8%] of 224), and grade 1 or 2 renal toxicity (creatinine 102 [43%] of 236 vs 22 [10%] of 224). The number of ASCT-related deaths was similar (eight [3·4%]) in both groups. Interpretation Immunochemotherapy containing high-dose cytarabine followed by ASCT should be considered standard of care in patients aged 65 years or younger with mantle cell lymphoma. Funding European Commission, Lymphoma Research Foundation, and Roche.
- Published
- 2016
8. The localisation of the apical Par/Cdc42 polarity module is specifically affected in microvillus inclusion disease
- Author
-
André Le Bivic, Ophélie Nicolle, Marion Rabant, Dominique Massey-Harroche, Nicole Brousse, Olivier Goulet, Grégoire Michaux, and Frank M. Ruemmele
- Subjects
0301 basic medicine ,Enterocyte ,Polarity (physics) ,Cell Biology ,General Medicine ,Anatomy ,Apical membrane ,Biology ,Microvillus ,Intestinal absorption ,Syntaxin 3 ,3. Good health ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,Cell polarity ,medicine ,Epithelial polarity - Abstract
BACKGROUND INFORMATION: . Microvillus inclusion disease (MVID) is a genetic disorder affecting intestinal absorption. It is caused by mutations in MYO5B or syntaxin 3 (STX3) affecting apical membrane trafficking. Morphologically MVID is characterised by a depletion of apical microvilli and the formation of microvillus inclusions inside the cells, suggesting a loss of polarity. To investigate this hypothesis we examined the location of essential apical polarity determinants in five MVID patients. RESULTS: We found that the polarity determinants Cdc42, Par6B, PKCζ/ι and the structural proteins ezrin and phospho-ezrin were lost from the apical membrane and accumulated either in the cytoplasm or on the basal side of enterocytes in patients which suggests an inversion of cell polarity. Moreover microvilli-like structures were observed at the basal side in electron microscopy. We next performed Myo5B depletion in 3D-grown human Caco2 cells forming cysts and we found a direct link between the loss of Myo5B and the mislocalisation of the same apical proteins; furthermore we observed that a majority of cyst displayed an inverted polarity phenotype as seen in some patients. Finally we found that this loss of polarity was specific for MVID: tissue samples of patients with Myo5B independent absorption disorders showed normal polarity but we identified Cdc42 as a potentially essential biomarker for tricho-hepato-enteric syndrome. CONCLUSION: Our findings indicate that the loss of Myo5B induces a strong loss of enterocyte polarity, potentially leading to polarity inversion. SIGNIFICANCE: Our results show that polarity determinants could be useful markers to help establishing a diagnosis in patients. Furthermore they could be used to characterise other rare intestinal absorption diseases.
- Published
- 2015
9. A Single-Tube, EuroClonality-Inspired, TRG Clonality Multiplex PCR Aids Management of Patients with Enteropathic Diseases, including from Formaldehyde-Fixed, Paraffin-Embedded Tissues
- Author
-
Olivier Hermine, Nadine Cerf-Bensussan, Virginie Verkarre, Bertrand Meresse, Thierry Jo Molina, Nicole Brousse, Amélie Trinquand, Coralie Derrieux, Julie Bruneau, Georgia Malamut, Christophe Cellier, Elizabeth Macintyre, Patrick Villarese, David Sibon, Marion Alcantara, and Ludovic Lhermitte
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Tissue Fixation ,Lymphoproliferative disorders ,Lymphoma, T-Cell ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Immunophenotyping ,Formaldehyde ,Multiplex polymerase chain reaction ,medicine ,Humans ,Multiplex ,Prospective Studies ,Gene Rearrangement ,Paraffin Embedding ,business.industry ,Gene rearrangement ,medicine.disease ,Lymphoma ,Celiac Disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Molecular Medicine ,Immunohistochemistry ,Intraepithelial lymphocyte ,business ,Multiplex Polymerase Chain Reaction - Abstract
Celiac disease is a chronic inflammation of the small intestine with villous atrophy that can become refractory to a gluten-free diet. Two categories of refractory celiac disease can be distinguished by the phenotype of intraepithelial lymphocytes and the status of TRG genes. Their distinction is important because 30% to 50% of type II but only 0% to 14% of type I evolve to an aggressive enteropathy-associated T-cell lymphoma and therefore require intensive treatment. Currently, differential diagnosis integrates immunohistochemistry, immunophenotyping, and TRG clonality analyses, but each has limitations. A single-tube multiplex TRG PCR (ECN) was prospectively compared to an in-house two-tube TRG PCR (N2T) in 73 samples, including 67 cryopreserved intestine tissues. Thirteen formalin-fixed, paraffin-embedded (FFPE) samples were also analyzed retrospectively. The ECN PCR had comparable efficiency to detect major clonal rearrangements in highly infiltrated tissues from T-cell lymphoproliferative disorders and type II refractory celiac disease and to detect the persistence of minor clones in type II refractory celiac disease follow-up samples. The ECN PCR abolished the risk of amplification of false-positive weak clonal rearrangements in cryopreserved specimens and allowed improved detection of clonal rearrangements in DNA from FFPE samples. The ECN PCR allows robust assessment of cryopreserved and FFPE digestive tissues at diagnosis and follow-up of enteropathies with villous atrophy, thus guiding therapeutic management.
- Published
- 2018
10. Incidence, Presentation, and Prognosis of Malignancies in Ataxia-Telangiectasia: A Report From the French National Registry of Primary Immune Deficiencies
- Author
-
Nicole Brousse, Felipe Suarez, Alain Fischer, Danielle Canioni, Jean-Philippe Jais, Olivier Hermine, Nizar Mahlaoui, Catherine Dubois d'Enghien, Chantal Andriamanga, and Dominique Stoppa-Lyonnet
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lymphoma ,Population ,Ataxia Telangiectasia ,Neoplasms ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Carcinoma ,Humans ,Registries ,Prolymphocytic leukemia ,education ,Aged ,Retrospective Studies ,education.field_of_study ,Leukemia ,business.industry ,Incidence ,Lymphoma, Non-Hodgkin ,Incidence (epidemiology) ,Age Factors ,Immunologic Deficiency Syndromes ,Cancer ,Retrospective cohort study ,Middle Aged ,Prognosis ,medicine.disease ,Hodgkin Disease ,Acute Disease ,Mutation ,Ataxia-telangiectasia ,Immunology ,Female ,France ,business - Abstract
Purpose Biallelic mutations in ATM cause ataxia-telangiectasia (AT), a rare inherited disease with a high incidence of cancer. Precise estimates of the risk, presentation, and outcomes of cancer in patients with AT need to be addressed in large series. Patients and Methods In this large retrospective cohort, 69 patients with cancers (24.5%) were identified among 279 patients with AT. Centralized review was performed on 60% of the lymphomas. Incidence rates were compared with the French population, and risk factors were analyzed. Results Eight patients developed acute leukemias (including four T-cell acute lymphoblastic leukemias), 12 developed Hodgkin lymphoma (HL), 38 developed non-Hodgkin lymphoma (NHL), three developed T-cell prolymphocytic leukemia (T-PLL), and eight developed carcinoma at a median age of 8.3, 10.6, 9.7, 24.2, and 31.4 years, respectively (P < .001). The majority of NHLs were aggressive B-cell NHL. Epstein-Barr virus was associated with all of the HLs and 50% of the NHLs. Overall survival was shorter in patients with AT who developed cancer compared with those who did not develop cancer (15 v 24 years, respectively; P < .001). Survival was improved in patients who achieved a major response to treatment (3.46 v 0.87 years for major v minor responses, respectively; P = .011). Immunodeficiency was associated with increased risk of cancer. ATM mutation type was associated with a difference in survival in the entire cohort but not with cancer incidence or cancer survival. Conclusion B-cell NHL, HL, and acute lymphoblastic leukemia occur at a high rate and earlier age than carcinomas in AT. T-PLLs are rarer than initially reported. Prognosis is poor, but patients may benefit from treatment with an improved survival.
- Published
- 2015
11. Actinomyces in Chronic Granulomatous Disease: An Emerging and Unanticipated Pathogen
- Author
-
Nizar Mahlaoui, Steven M. Holland, Uri Lopatin, Ulrich Siler, Nicole Brousse, Bojana Beović, Reinhard Zbinden, Janine Reichenbach, Louise Galmiche, Tayfun Güngör, Stéphane Blanche, Samer Kayal, Reinhard Seger, University of Zurich, and Reichenbach, J
- Subjects
Male ,Sulfamethoxazole ,Antibiotics ,Disease ,Azithromycin ,Granulomatous Disease, Chronic ,Actinomycosis ,Communicable Diseases, Emerging ,Polymerase Chain Reaction ,2726 Microbiology (medical) ,Trimethoprim ,Chronic granulomatous disease ,Child ,Bone Marrow Transplantation ,biology ,10179 Institute of Medical Microbiology ,Clindamycin ,Ceftriaxone ,Penicillin G ,Anti-Bacterial Agents ,Infectious Diseases ,Penicillin V ,Female ,medicine.drug ,Adult ,Microbiology (medical) ,Adolescent ,medicine.drug_class ,610 Medicine & health ,DNA, Ribosomal ,Article ,Microbiology ,Young Adult ,medicine ,Actinomyces ,Humans ,business.industry ,Amoxicillin ,2725 Infectious Diseases ,Meropenem ,medicine.disease ,biology.organism_classification ,10036 Medical Clinic ,Immunology ,570 Life sciences ,Thienamycins ,business - Abstract
Background. Chronic granulomatous disease (CGD) is a rare inherited disease of the phagocyte NADPH oxidase system that causes defective production of toxic oxygen metabolites, impaired bacterial and fungal killing, and recurrent life-threatening infections, mostly by catalase-producing organisms. We report for the first time, to our knowledge, chronic infections with Actinomyces species in 10 patients with CGD. Actinomycosis is a chronic granulomatous condition that commonly manifests as cervicofacial, pulmonary, or abdominal disease, caused by slowly progressive infection with oral and gastrointestinal commensal Actinomyces species. Treatment of actinomycosis is usually simple in immunocompetent individuals, requiring long-term, high-dose intravenous penicillin, but is more complicated in those with CGD because of delayed diagnosis and an increased risk of chronic invasive or debilitating disease. Methods. Actinomyces was identified by culture, staining, 16S ribosomal DNA polymerase chain reaction, and/ or a complement fixation test in 10 patients with CGD. Results. All 10 patients presented with a history of fever and elevated inflammatory signs without evident focus. Diagnosis was delayed and clinical course severe and protracted despite high-dose intravenous antibiotic therapy and/or surgery. These results suggest an unrecognized and unanticipated susceptibility to weakly pathogenic Actinomyces species in patients with CGD because these are catalase-negative organisms previously thought to be nonpathogenic in CGD. Conclusions. Actinomycosis should be vigorously sought and promptly treated in patients with CGD presenting with uncommon and prolonged clinical signs of infection. Actinomycosis is a catalase-negative infection important to consider in CGD.
- Published
- 2017
12. Impact of Expert Pathologic Review of Lymphoma Diagnosis: Study of Patients From the French Lymphopath Network
- Author
-
Mylène Dandoit, Catherine Chassagne-Clément, Alexandra Traverse-Glehen, Gilles Salles, Marie Parrens, Peggy Dartigues, Marie-Pierre Chenard-Neu, Marc Maynadié, B. Fabiani, Pierre Brousset, Françoise Berger, Laurent Martin, Jean-François Michiels, Claire Bastien, Josette Brière, Michel Peoc'h, Patrick Tas, Diane Damotte, Philippe Gaulard, Martine Patey, Nadia Amara, Manuela Delage, Anne Moreau, Isabelle Quintin-Roue, Céline Bossard, Antoine de Mascarel, Marie-Christine Copin, Pierre Déchelotte, Henri Sevestre, Isabelle Soubeyran, Sylvie Thiebault, Luc Xerri, Camille Laurent, Jean-Michel Picquenot, Christiane Copie-Bergman, Antoine Martin, Frédéric Charlotte, Blandine Fabre, Béatrice Vergier, Georges Delsol, Flavie Arbion, Corinne Haioun, Tony Petrella, Marine Baron, Marie-Christine Rousselet, Thomas Filleron, Cécile Le Naoures, Thérèse Rousset, Nicole Brousse, and Thierry Jo Molina
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Myeloid ,Lymphoma ,Newly diagnosed ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Medicine ,Humans ,Lymphoid neoplasms ,Prospective Studies ,Prospective cohort study ,Referral and Consultation ,Neoplasm Grading ,Potential impact ,Pathology, Clinical ,business.industry ,Lymphoma diagnosis ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Clinical Competence ,France ,business ,Who classification ,030215 immunology - Abstract
Purpose To prospectively assess the clinical impact of expert review of lymphoma diagnosis in France. Materials and Methods From January 2010 to December 2013, 42,145 samples from patients with newly diagnosed or suspected lymphomas were reviewed, according to the 2008 WHO classification, in real time by experts through the Lymphopath Network. Changes in diagnosis between referral and expert review were classified as major or minor according to their potential impact on patient care. Results The 42,145 reviewed samples comprised 36,920 newly diagnosed mature lymphomas, 321 precursor lymphoid neoplasms, 314 myeloid disorders, and 200 nonhematopoietic neoplasms, with 4,390 benign lesions. There were 4,352 cutaneous and 32,568 noncutaneous lymphomas. The most common mature noncutaneous lymphomas were diffuse large B-cell lymphomas (32.4%), follicular lymphomas (15.3%), classic Hodgkin lymphomas (13%), peripheral T-cell lymphomas (6.3%) of which angioimmunoblastic T-cell lymphomas (2.3%) were the most frequent, and mucosa-associated lymphoid tissue lymphomas (5.8%). A diagnostic change between referral and expert review occurred in 19.7% of patients, with an estimated impact on patient care for 17.4% of patients. This rate was significantly higher for patients sent with a provisional diagnosis seeking expert second opinion (37.8%) than for patients sent with a formal diagnosis (3.7%). The most frequent discrepancies were misclassifications in lymphoma subtype (41.3%), with 12.3% being misclassifications among small B-cell lymphoma entities. Fewer than 2% of changes were between benign and malignant lymphoid conditions. Minor changes (2.3%) mostly consisted of follicular lymphoma misgrading and diffuse large B-cell lymphoma subtype misclassification. Conclusion To our knowledge, this study provides the largest ever description of the distribution of lymphoma entities in a western country and highlights how expert review significantly contributes to a precise lymphoma diagnosis and optimal clinical management in a proportion of patients.
- Published
- 2017
13. Subcutaneous Panniculitis-like T-cell Lymphoma: Immunosuppressive Drugs Induce Better Response than Polychemotherapy
- Author
-
Christine Bodemer, Saskia Ingen-Housz-Oro, Tony Petrella, Olivier Hermine, Nathalie Franck, Sylvie Fraitag, Martine Bagot, David Michonneau, Maxime Battistella, Marie Beylot-Barry, Béatrice Vergier, Stéphane Barete, Nicole Brousse, Nicolas Ortonne, Marc Maynadié, Laboratoire d'anatomie pathologique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maisonneuve-Rosemont Hospital Research Center, University of Montreal, CHU Henri Mondor [Créteil], Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Anatomie pathologique [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Dpt anatomie pathologique [CHU Bordeaux], Université de Bourgogne (UB), Service de dermatologie [CHU Necker], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie [Saint-Louis], Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Clinique Adulte [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Dpt Dermatologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université de Bourgogne ( UB ), Service de dermatologie [CHU Necker-Enfants malades], Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Oncodermatologie, immunologie et cellules souches cutanées ( DIO U976 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Male ,Panniculitis ,Time Factors ,Biopsy ,medicine.medical_treatment ,Gastroenterology ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,030207 dermatology & venereal diseases ,0302 clinical medicine ,Subcutaneous Panniculitis-Like T-Cell Lymphoma ,Antineoplastic Combined Chemotherapy Protocols ,Child ,medicine.diagnostic_test ,Remission Induction ,General Medicine ,Middle Aged ,3. Good health ,Treatment Outcome ,Immunosuppressive drug ,Child, Preschool ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,France ,Immunosuppressive Agents ,Adult ,medicine.medical_specialty ,Adolescent ,[ SDV.IMM.IMM ] Life Sciences [q-bio]/Immunology/Immunotherapy ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Dermatology ,Lymphoma, T-Cell ,Young Adult ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Medical history ,Pathological ,Proportional Hazards Models ,Retrospective Studies ,business.industry ,Autoantibody ,Infant ,[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy ,medicine.disease ,Lymphoma ,business ,[ SDV.MHEP.DERM ] Life Sciences [q-bio]/Human health and pathology/Dermatology ,[SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology - Abstract
International audience; Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare condition usually considered to have a favourable prognosis. However, it is not known whether polychemotherapy or immunosuppressive-based therapy is the best approach for treating SPTCL. Using data collected between 2000 and 2012 in France, we analysed clinical, biological and pathological data of 27 patients with SPTCL. Medical history revealed that 40% of patients had been previously diagnosed with an autoimmune disorder and 22% with inflammatory panniculitis. Haemophagocytic syndrome was present in 37% of cases. Autoantibodies were positive in 65% of cases. Complete remission (CR) was reached in 74% of cases. Immunosuppressive drug treatment was given in 69.5% of patients (group 1) and polychemotherapy in 30.5% (group 2). CR was 81.2% and 28.5% (p?=?0.025), respectively. Progression rate was 6.2% and 42.8% (p?=?0.067), respectively. This study suggests that immunosuppressive drugs should be considered as the first-line treatment for SPTCL.
- Published
- 2017
14. Subcutaneous Panniculitis-like T-Cell Clonal Proliferation in an Infant. Lymphoma or Reactive Lymphoproliferation?
- Author
-
Christine Bodemer, Nicole Brousse, Brigitte Bader-Meunier, and Sylvie Fraitag
- Subjects
Pathology ,medicine.medical_specialty ,medicine.anatomical_structure ,business.industry ,T cell ,Immunology ,medicine ,Panniculitis ,medicine.disease ,business ,Pathology and Forensic Medicine ,Lymphoma - Published
- 2014
15. CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d'Etude des Lymphomes de l'Adulte
- Author
-
Pauline Brice, François Lefrère, Vincent Ribrag, Gilles Salles, Nicole Brousse, Achiel Van Hoof, Olivier Hermine, Hervé Tilly, Corinne Haioun, Olivier Casasnovas, Richard Delarue, and Alain Delmer
- Subjects
Male ,Transplantation Conditioning ,Kaplan-Meier Estimate ,Lymphoma, Mantle-Cell ,CHOP ,Biochemistry ,Gastroenterology ,Dexamethasone ,Antibodies, Monoclonal, Murine-Derived ,International Prognostic Index ,Autologous stem-cell transplantation ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Melphalan ,Cytarabine ,Neoplasms, Second Primary ,Hematology ,Middle Aged ,Treatment Outcome ,Vincristine ,Female ,Kidney Diseases ,Rituximab ,Whole-Body Irradiation ,medicine.drug ,Adult ,medicine.medical_specialty ,Immunology ,Transplantation, Autologous ,Disease-Free Survival ,Internal medicine ,DHAP ,medicine ,Humans ,Cyclophosphamide ,Aged ,Peripheral Blood Stem Cell Transplantation ,business.industry ,Cell Biology ,medicine.disease ,Hematologic Diseases ,Surgery ,Transplantation ,Regimen ,Doxorubicin ,Prednisone ,Mantle cell lymphoma ,Cisplatin ,business - Abstract
Treatment of mantle cell lymphoma (MCL) in younger patients remains a challenge. We report results of a phase 2 trial using cytarabine and rituximab as induction regimen before autologous stem cell transplantation. Patients younger than 66 years with stage 3 or 4 MCL were included. Treatment consisted of 3 courses of CHOP21 with rituximab at the third one and 3 of R-DHAP. Responding patients were eligible for autologous stem cell transplantation with TAM6 or BEAM. Sixty patients were included. Median age was 57 years. Characteristics of patients were: BM involvement 85%, leukemic disease 48%, gastrointestinal involvement 52%, Performance Status > 16%, lactate dehydrogenase > 1N 38%, Mantle Cell Lymphoma International Prognostic Index (low 55%, intermediate 38%, high 13%). The overall response rate was 93% after (R)-CHOP and 95% after R-DHAP. Although uncommon after (R)-CHOP (12%), 57% of patients were in complete response after R-DHAP. With median follow-up of 67 months, median event-free survival is 83 months, and median overall survival is not reached. Five-year overall survival is 75%. Comparison with a previous study without rituximab shows improvement of outcome (median event-free survival, 51 vs 83 months). No toxic death or unexpected toxicities were observed. This study confirms that induction with rituximab and cytarabine-based regimens is safe and effective in MCL patients. This regimen is currently compared with R-CHOP21 induction in a multicentric European protocol.
- Published
- 2013
16. Severe cutaneous bacillus Calmette-Guérin infection in immunocompromised children: the relevance of skin biopsy
- Author
-
Amélie Gantzer, Capucine Picard, Sylvie Fraitag, Alain Fischer, Olivier Lortholary, Bénédicte Neven, Christine Bodemer, and Nicole Brousse
- Subjects
medicine.medical_specialty ,Severe combined immunodeficiency ,Pathology ,Histology ,medicine.diagnostic_test ,business.industry ,Dermatology ,medicine.disease ,Pathology and Forensic Medicine ,Transplantation ,Graft-versus-host disease ,Immune reconstitution inflammatory syndrome ,Skin biopsy ,medicine ,Primary immunodeficiency ,Histopathology ,business ,Immunodeficiency - Abstract
Disseminated bacillus Calmette-Guerin infection (BCGitis) is an uncommon condition which is usually associated with primary immunodeficiency. Skin histopathology findings have been described in rare cases only. A retrospective clinicopathological study was performed to assess the potential utility of skin biopsies in the diagnosis, prognosis and follow-up of these patients. Four cases of disseminated BCGitis in children with Severe Combined ImmunoDeficiency were biopsied before and after Haematopoietic Stem Cell Transplantation (HSCT). The results were compared to the clinical and immunological status of the children. Early skin biopsies revealed either dense dermal infiltration by foamy macrophages filled with acid fast bacilli (AFB) or mycobacterial spindle-cell pseudotumors rich in AFB. There were no granulomas. These patterns led to the diagnosis of disseminated BCGitis potentially caused by severe immunodeficiency. After HSCT, repeated skin biopsies were performed on persistent or new cutaneous lesions to rule out immune reconstitution inflammatory syndrome and to check for tuberculoid granulomas. One patient died of BCGitis combined with graft versus host disease. The 3 others presented with progressive-onset well differentiated granulomas over a long period and recovered. Skin biopsy is a useful part of the diagnostic workup for disseminated BCGitis, directing the clinician toward severe immunodeficiency. Moreover, skin biopsy may be a useful means of monitoring immune restoration for prognostic purposes.
- Published
- 2012
17. Late-onset post-transplantation lymphoproliferative disorders after kidney transplantation: a monocentric study over three decades
- Author
-
Olivier Hermine, Renaud Snanoudj, Frank Martinez, Felipe Suarez, Dany Anglicheau, Julien Adam, Christophe Legendre, David Michonneau, Marie-France Mamzer-Bruneel, Danielle Canioni, Nicole Brousse, and Jérôme Lambert
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Lymphoproliferative disorders ,Renal function ,Antineoplastic Agents ,Gastroenterology ,Antibodies, Monoclonal, Murine-Derived ,Internal medicine ,medicine ,Humans ,Longitudinal Studies ,Kidney transplantation ,Retrospective Studies ,Transplantation ,Chemotherapy ,Kidney ,business.industry ,Disease Management ,Middle Aged ,Prognosis ,medicine.disease ,Kidney Transplantation ,Chemotherapy regimen ,Lymphoproliferative Disorders ,Surgery ,Survival Rate ,medicine.anatomical_structure ,Nephrology ,Drug Therapy, Combination ,Female ,Rituximab ,business ,medicine.drug - Abstract
BACKGROUND Late-onset post-transplantation lymphoproliferative disorders (PTLDs) occur 1 year after transplantation and are associated with poor prognosis. Initial treatment usually involves a reduction in immunosuppressive treatment. While early-onset PTLDs have a good prognosis following RI, this approach is generally inadequate for late-onset PTLDs. We assessed the specific outcome of late-onset PTLDs after kidney transplantation during the past three decades. METHODS We reviewed the clinical and biological data of 52 kidney transplant recipients who developed late-onset PTLDs at our centre between 1980 and 2010. We compared clinical features, long-term outcome and renal prognosis of late-onset PTLDs both before and after the era of rituximab. RESULTS Before 2000, 38% of the patients underwent surgery and 76% received chemotherapy either immediately or after surgery. After 2000, rituximab was administrated to 70% of the patients either alone (23%) or in combination with chemotherapy (77%). Chemotherapy alone was administrated in 26% of the cases. Before and after 2000, complete remission was achieved in 38 and 87% of the cases, respectively (P = 0.0005). The 5-year overall survival (OS) was 33.3 and 69% (P = 0.003), and 5-year disease-free survival was 37.5 and 80%, respectively (P = 0.19). Renal function was preserved in 70% of the cases at the end of the follow-up. CONCLUSIONS This study shows an increase in OS and low graft loss for patients with late-onset PTLDs during the last decade, which may be attributed to multiple changes in clinical practice, including a more standardized treatment and the use of rituximab in combination with chemotherapy.
- Published
- 2012
18. Prognostic Value of Ki-67 Index, Cytology, and Growth Pattern in Mantle-Cell Lymphoma: Results From Randomized Trials of the European Mantle Cell Lymphoma Network
- Author
-
Stephan Stilgenbauer, Andreas Rosenwald, Christoph Loddenkemper, Olivier Hermine, Bertrand Coiffier, Catherine Thieblemont, Johanna Kluin-Nelemans, Wolfgang Hiddemann, Christian Schmidt, Michael Hallek, Michael Pfreundschuh, Françoise Berger, Heinz-Wolfram Bernd, Roswitha Forstpointner, Reda Bouabdallah, Wolfram Klapper, Eva Hoster, Roman Kodet, Lothar Kanz, Nicole Brousse, Martin Dreyling, Thomas F. E. Barth, Sylvia Hartmann, Ursula Vehling-Kaiser, Michael Unterhalt, Vincent Ribrag, Stefano Pileri, Grzegorz Rymkiewicz, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Stem Cell Aging Leukemia and Lymphoma (SALL)
- Subjects
Oncology ,Male ,Cancer Research ,Pathology ,Time Factors ,Biopsy ,Kaplan-Meier Estimate ,Lymphoma, Mantle-Cell ,IMPROVES RESPONSE ,0302 clinical medicine ,International Prognostic Index ,Risk Factors ,Cytology ,CYCLOPHOSPHAMIDE ,Medicine ,Randomized Controlled Trials as Topic ,Aged, 80 and over ,biology ,PROLIFERATION ,Discriminant Analysis ,Middle Aged ,Prognosis ,Immunohistochemistry ,Tumor Burden ,Europe ,030220 oncology & carcinogenesis ,Ki-67 ,SURVIVAL ,Female ,Adult ,medicine.medical_specialty ,DOXORUBICIN ,MCL-NETWORK ,Malignancy ,IMMUNOCHEMOTHERAPY ,Risk Assessment ,VALIDATION ,03 medical and health sciences ,Predictive Value of Tests ,Internal medicine ,Humans ,VINCRISTINE ,Aged ,Cell Proliferation ,Proportional Hazards Models ,Retrospective Studies ,business.industry ,Proportional hazards model ,MIPI ,Retrospective cohort study ,medicine.disease ,Lymphoma ,Ki-67 Antigen ,Multivariate Analysis ,biology.protein ,Mantle cell lymphoma ,business ,030215 immunology - Abstract
Purpose Mantle-cell lymphoma (MCL) is a rather aggressive B-cell malignancy whose considerable variability of individual outcome is associated with clinical characteristics (Mantle Cell Lymphoma International Prognostic Index [MIPI]). The Ki-67 index is a strong independent prognostic factor; however, the biologic MIPI (MIPI-b) distinguishes only two groups, which does not appropriately depict the clinical heterogeneity. By using the cohort from the European MCL Younger and MCL Elderly trials, we aimed to evaluate the additional prognostic impact of cytology and growth pattern and to improve risk stratification with the Ki-67 index and MIPI. Patients and Methods Diagnostic tumor biopsies were reviewed by the European Mantle Cell Lymphoma Pathology Panel to determine Ki-67 index by using published guidelines, cytology, and growth pattern. We evaluated prognostic effects for overall survival (OS) by Cox regression. For the cohort used for MIPI-b development (German Low-Grade Lymphoma Study Group [GLSG] 1996 and GLSG2000), we checked whether the equally weighted combination of Ki-67 index (dichotomized at the validated 30% cutoff) and MIPI risk groups was adequate and compared the prognostic power of this modified combination to MIPI and MIPI-b for the MCL Younger/MCL Elderly cohort. Results The Ki-67 index was assessed in 508 of 832 patients (median age, 62 years). Blastoid cytology was associated with inferior OS independently of MIPI but not independently of the Ki-67 index. Growth pattern was not independently prognostic. The modified combination of the Ki-67 index and MIPI separated four groups with 5-year OS: 85%, 72%, 43%, and 17% (P < .001) and was more discriminative than MIPI and MIPI-b. Conclusion Using the Ki-67 index is superior to using cytology and growth pattern as prognostic factors in MCL. The modified combination of the Ki-67 index and MIPI showed a refined risk stratification, reflecting their strong complementary prognostic effects while integrating the most relevant prognostic factors available in clinical routine.
- Published
- 2016
19. Physiopathologie du greffon intestinal
- Author
-
Nadine Cerf-Bensussan, Nicole Brousse, Sabine Sarnacki, and Olivier Goulet
- Subjects
Graft rejection ,business.industry ,medicine.medical_treatment ,Immunosuppression ,General Medicine ,Pathophysiology ,Tacrolimus ,Immune tolerance ,Transplantation ,surgical procedures, operative ,Non specific ,Immunity ,Immunology ,Medicine ,business - Abstract
Following the introduction of tacrolimus, intestinal transplantation is now a valid option for patients with chronic intestinalfailure. However, its outcome is undermined by the abundant lymphoid component of the graft and the septic nature of the procedure. The heavy immunosuppression necessitated by this transplant, and its non specific nature, creates a risk of infectious and tumoral complications. Several approaches are being tested to improve the immune tolerance of intestinal grafts, both in animals models and in the clinic. The most promising seek to induce specific tolerance while sparing antimicrobial and antitumoral immunity.
- Published
- 2012
20. The histopathological spectrum of cutaneous meningeal heterotopias: clues and pitfalls
- Author
-
Christine Bodemer, Sylvie Fraitag, Maxime Battistella, Nicole Brousse, Catherine Fallet-Bianco, and Nathalie Guedj
- Subjects
CD31 ,Pathology ,medicine.medical_specialty ,Histology ,business.industry ,Enolase ,Meninges ,General Medicine ,Anatomy ,medicine.disease ,S100 protein ,Pathology and Forensic Medicine ,Lesion ,medicine.anatomical_structure ,Scalp ,Lymphangioma ,medicine ,Immunohistochemistry ,medicine.symptom ,business - Abstract
Battistella M, Guedj N, Fallet-Bianco C, Bodemer C, Brousse N & Fraitag S (2011) Histopathology59, 407–420 The histopathological spectrum of cutaneous meningeal heterotopias: clues and pitfalls Aims: To describe the histopathological features of heterotopic cutaneous meningeal tissue. Methods and results: Nineteen cases were collected between 1993 and 2010. Immunohistochemistry for epithelial membrane antigen (EMA), neuron specific enolase (NSE), S100, glial fibrillary acid protein (GFAP), progesterone receptor (PR), CD31, glucose transporter-1 (Glut-1), podoplanin and NKI-C3 was performed. Lesions were congenital (100%) and presented as aplasia cutis with alopecia (63%) or lumps (37%), on the scalp (18 of 19) and sacral region. Resonance magnetic imaging revealed four underlying anomalies of the neuraxis. Histopathological analysis showed meningeal tissue arranged in four variably associated architectural patterns: fibrous (100%), pseudovascular (100%), cellular (68%) and pseudomyxoid (32%). Other features included collagen bodies (58%), calcifications (26%) and dermal melanocytes (32%). Heterotopic brain tissue or heterotopic ependymal cyst was associated in two cases. Arachnoidal cells expressed EMA and NSE, but not S100 protein, CD31 or GFAP. They expressed podoplanin (93%), especially in pseudovascular areas, NKI-C3 (79%), and less frequently Glut-1 (46%) and PR (30%). Conclusions: Histopathological features of cutaneous meningeal heterotopias are various and sometimes misleading. Fibrous lesions should not be misdiagnosed as aplasia cutis. Podoplanin-positive pseudovascular spaces represent the main pitfall and should not be diagnosed as lymphangioma. Correct diagnosis is confirmed by EMA and NSE coexpression within the lesion.
- Published
- 2011
21. Loss of p19Arf in a Rag1−/− B-cell precursor population initiates acute B-lymphoblastic leukemia
- Author
-
Serge Romana, Charles G. Mullighan, Nicole Brousse, Sven Kracker, Arndt Borkhardt, Amine Boudil, Marina Cavazzana-Calvo, Julie Bruneau, Julia Hauer, Estelle Morillon, Salima Hacein-Bey-Abina, Daniela Tiedau, Frederick D Bushmann, Marc Lelorc'h, Gary P. Wang, and Alain Fischer
- Subjects
Hematopoiesis and Stem Cells ,Antigens, CD19 ,Immunology ,Population ,Antigens, CD34 ,Apoptosis ,Bone Marrow Cells ,chemical and pharmacologic phenomena ,Biochemistry ,CD19 ,Recombination-activating gene ,Mice ,immune system diseases ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,hemic and lymphatic diseases ,Precursor cell ,medicine ,Animals ,Antigens, Ly ,Humans ,Receptor, Notch1 ,education ,Cells, Cultured ,Cyclin-Dependent Kinase Inhibitor p16 ,B cell ,Homeodomain Proteins ,Regulation of gene expression ,B-Lymphocytes ,education.field_of_study ,biology ,Gene Expression Regulation, Leukemic ,Membrane Proteins ,hemic and immune systems ,Cell Biology ,Hematology ,Hematopoietic Stem Cells ,medicine.disease ,Mice, Mutant Strains ,Proto-Oncogene Proteins c-kit ,Leukemia ,Phenotype ,medicine.anatomical_structure ,biology.protein ,Cancer research ,Stromal Cells ,tissues ,Neoplasm Transplantation ,Signal Transduction - Abstract
In human B-acute lymphoblastic leukemia (B-ALL), RAG1-induced genomic alterations are important for disease progression. However, given that biallelic loss of the RAG1 locus is observed in a subset of cases, RAG1's role in the development of B-ALL remains unclear. We chose a p19Arf−/−Rag1−/− mouse model to confirm the previously published results concerning the contribution of CDKN2A (p19ARF /INK4a) and RAG1 copy number alterations in precursor B cells to the initiation and/or progression to B-acute lymphoblastic leukemia (B-ALL). In this murine model, we identified a new, Rag1-independent leukemia-initiating mechanism originating from a Sca1+CD19+ precursor cell population and showed that Notch1 expression accelerates the cells' self-renewal capacity in vitro. In human RAG1-deficient BM, a similar CD34+CD19+ population expressed p19ARF. These findings suggest that combined loss of p19Arf and Rag1 results in B-cell precursor leukemia in mice and may contribute to the progression of precursor B-ALL in humans.
- Published
- 2011
22. Cutaneous hematologic disorders in children
- Author
-
Sylvie Fraitag, Yves de Prost, Nicole Brousse, Olivia Boccara, Christine Bodemer, and Stéphane Blanche
- Subjects
medicine.medical_specialty ,Mycosis fungoides ,business.industry ,Lymphoblastic lymphoma ,Pityriasis lichenoides ,Lymphoproliferative disorders ,Hematology ,medicine.disease ,Dermatology ,Cutaneous lymphoma ,Lymphoma ,Oncology ,Pityriasis lichenoides chronica ,hemic and lymphatic diseases ,Pediatrics, Perinatology and Child Health ,medicine ,Lymphomatoid papulosis ,business - Abstract
Background To determine and list the clinical and pathological features of cutaneous hematologic diseases in childhood. Procedure We retrospectively analyzed the data for 51 patients up to 15 years of age, who presented with primary cutaneous hematologic disorders according to the WHO-EORTC classification, at Necker-Enfants Malades Hospital, Paris, France, over a 17-year period. The cases were classified into the following diagnostic categories: CD30+ T-cell lymphoproliferative disorders (24) all consisting of lymphomatoid papulosis (LyP, 24), lymphoblastic lymphoma (LL, 7), acute leukemias (AL, 7), mycosis fungoides (MF, 5), Epstein–Barr virus-related lymphoproliferative disorders (EBV-related LPD, 5), T/NK-cell lymphoma, nasal type (1), γ/δ T-cell lymphoma (1), and panniculitis-like T-cell lymphoma (1). Results We encountered a majority of LyP. No secondary lymphoma was found in LyP patients with a median follow-up of 8 years. 29% and 80% of LyP and MF patients, respectively, presented with pityriasis lichenoides chronica (PLC) before onset of disease. Owing to a frequently misleading clinicopathological presentation, MF patients were first underdiagnosed. Clinicopathological features of LL and AL were highly stereotypical, leading to the diagnosis being suspected and confirmed more promptly. In the latter patients and in EBV-related LPD patients, skin lesions usually led to the discovery of systemic disease. Conclusion Distribution of cutaneous hematologic diseases seems to be different in adults and in children aged
- Published
- 2011
23. Plexiform Fibrohistiocytic Tumor with Molecular and Cytogenetic Analysis
- Author
-
Nicole Brousse, Stéphanie Leclerc-Mercier, Christophe Glorion, Thibault Fabas, Sylvie Fraitag, and Florence Pedeutour
- Subjects
Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Plexiform fibrohistiocytic tumor ,Karyotype ,Superficial biopsy ,Dermatology ,medicine.disease ,3. Good health ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Granuloma ,Pediatrics, Perinatology and Child Health ,medicine ,%22">Fish ,business ,Fluorescence in situ hybridization - Abstract
A child with plexiform fibrohistiocytic tumor is presented, in whom a superficial biopsy was misdiagnosed as an inflammatory granuloma. Cytogenetic analysis revealed a 46,X,del(X)(q13)[3]/46,XX[23] karyotype. However, fluorescence in situ hybridization (FISH) and array-comparative genomic hybridization (CGH) analysis failed to detect any numerical or quantitative genomic anomaly. Because of lack of specific chromosomal hallmarks, a molecular diagnosis of plexiform fibrohistiocytic tumor with the currently available tools is not reliable.
- Published
- 2011
24. Enteropathy-associated T-cell lymphoma: A review on clinical presentation, diagnosis, therapeutic strategies and perspectives
- Author
-
Georgia Malamut, Richard Delarue, B. Deau-Fischer, Marie-Olivia Chandesris, Nadine Cerf-Bensussan, Olivier Hermine, Christophe Cellier, Elisabeth Macintyre, Virginie Verkarre, Felipe Suarez, Bertrand Meresse, Nicole Brousse, and Marie-Thérèse Rubio
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Disease ,Lymphoma, T-Cell ,Risk Assessment ,Transplantation, Autologous ,Risk Factors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Not evaluated ,Chemotherapy ,business.industry ,Gastroenterology ,General Medicine ,Prognosis ,medicine.disease ,Lymphoma ,Surgery ,Transplantation ,Celiac Disease ,Malnutrition ,Enteropathy-associated T-cell lymphoma ,business ,Complication - Abstract
Summary Introduction Enteropathy-associated T-cell lymphoma (EATL) is a rare complication of celiac disease ( Methods International literature review with PubMed search (up to January 2009) of pathophysiological, clinical and therapeutic data. Results EATL is found in patients with a mean age of 59 years, often with a complication that signals its diagnosis. Refractory celiac disease (RCD), equivalent to low-grade intraepithelial T-cell lymphoma, could be an intermediary between celiac disease and high-grade invasive T-cell lymphoma. The median survival is 7 months, with no significant difference between stages; the cumulative 5-year survival is less than 20%. The poor prognosis is determined by disease that has often spread before it is diagnosed (50%), multifocal involvement of the small bowel (50%), poor general health status and undernutrition, and recurrence of complications (infections, perforations, gastrointestinal haemorrhages, occlusions), thus delaying the chemotherapy and contributing to frequent chemotherapy resistance. There is currently no effective and consensual treatment: preventive surgery for complications is controversial, and the results of chemotherapy are disappointing. The classic CHOP protocol (combination of doxorubicin–cyclophosphamide–vincristine–prednisone) does not have satisfactory results and survival remains poor, especially in patients with underlying RCD. High-dose chemotherapy with autotransplantion seems to only improve the prognosis in localised forms. Allogeneic bone marrow transplantation was not evaluated. In all, 1/3 of patients, being unfit for treatment, die before 3 months and half of treated patients stop chemotherapy prematurely due to inefficacy, intolerance and/or complications. Conclusion Improvement of the prognosis requires collaboration in order to compose a national cohort, to evaluate new diagnostic and therapeutic strategies and to define prognostic factors.
- Published
- 2010
25. Regulatory T-Cell Depletion in Angioimmunoblastic T-Cell Lymphoma
- Author
-
Marie-Helene Delfau, Nicole Brousse, Elizabeth Macintyre, Danielle Canioni, Teresa Marafioti, Amédée Renand, Julie Bruneau, Olivier Hermine, Jennifer C. Paterson, Nadine Martin-Garcia, Philippe Gaulard, and Vahid Asnafi
- Subjects
Angioimmunoblastic T-cell lymphoma ,Regulatory T cell ,T cell ,Short Communications ,Follicular lymphoma ,chemical and pharmacologic phenomena ,Lymphoma, T-Cell ,T-Lymphocytes, Regulatory ,Lymphocyte Depletion ,Pathology and Forensic Medicine ,Biomarkers, Tumor ,medicine ,Humans ,Lymph node ,business.industry ,FOXP3 ,hemic and immune systems ,medicine.disease ,Lymphoma ,Phenotype ,medicine.anatomical_structure ,Immunoblastic Lymphadenopathy ,Immunology ,Lymph Nodes ,Lymph ,business - Abstract
Angioimmunoblastic T-cell lymphoma (AITL) is the most frequent nodal T-cell lymphoma and is characterized by a polymorphic lymph node infiltrate, various dysimmune disorders, and a poor prognosis. Regulatory T-cells (Treg) play an emerging role in the prognosis of non-Hodgkin B-cell lymphoma and mediate significant autoreactive T-cell suppression. In this report, we demonstrate that numbers of Treg are significantly decreased in AITL lymph nodes [n = 30, 91 (40-195) per high power fields] compared with follicular lymphoma [n = 19, 179 (86-355)] and reactive lymph nodes [n = 8, 186 (140-265)]. Moreover, the few Treg in lymph nodes of AITL are resting Treg (rTreg) and have a naive CD45RA+, PD1-, and ICOS- phenotype [n = 5, 57% of Treg are CD45RA+ (16-96)], in contrast to the Treg in follicular lymphomas [n = 5, 7.4% (1-13)] or reactive lymph nodes [n = 7, 18.6% (6-48)]. Interestingly, Treg depletion was not observed in AITL peripheral blood at diagnosis. Altogether, these data suggest that Treg depletion could contribute to the nodal neoplastic T(FH) expansion and dysimmune symptoms in AITL.
- Published
- 2010
26. Ocular adnexal lymphoma and Helicobacter pylori gastric infection
- Author
-
Claire Mathiot, J. Girodet, Nicole Brousse, Jean-Luc Beretti, Frédéric Mal, Corine Plancher, Bernard Asselain, Pierre Validire, Agnès Ferroni, Livia Lumbroso-Le Rouic, Kheira Beldjord, Patricia Validire, Patricia de Cremoux, Rémi Dendale, Anne Vincent-Salomon, E Macintyre, Marc Lecuit, Didier Decaudin, Olivier Hermine, Institut Curie [Paris], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Institut Mutualiste de Montsouris (IMM), Microorganismes et Barrières de l'Hôte (Equipe avenir), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie, and Equipe avenir Microorganismes et Barrières de l'Hôte
- Subjects
Male ,Pathology ,MESH: Eye Neoplasms ,Gastroenterology ,Cohort Studies ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,MESH: Lymphoma, B-Cell, Marginal Zone ,Stomach cancer ,MESH: Cohort Studies ,[SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology ,MESH: Aged ,MESH: Middle Aged ,Hematology ,biology ,Stomach ,digestive, oral, and skin physiology ,Middle Aged ,3. Good health ,medicine.anatomical_structure ,Gastritis ,030220 oncology & carcinogenesis ,Medicine ,Female ,MESH: Gastritis ,medicine.symptom ,Adult ,medicine.medical_specialty ,Helicobacter Infections ,03 medical and health sciences ,Ocular Adnexal Lymphoma ,Internal medicine ,medicine ,Humans ,Aged ,Gastric Infection ,MESH: Humans ,Helicobacter pylori ,business.industry ,Eye Neoplasms ,MESH: Helicobacter Infections ,MESH: Adult ,Lymphoma, B-Cell, Marginal Zone ,biology.organism_classification ,medicine.disease ,digestive system diseases ,MESH: Male ,Lymphoma ,030221 ophthalmology & optometry ,MESH: Helicobacter pylori ,business ,MESH: Female - Abstract
There is a causal association between Helicobacter pylori (Hp) gastric infection and the development of gastric MALT lymphoma. In contrast, the link between Hp gastric infection and the development of extragastric lymphoma has not been thoroughly investigated. We, therefore, studied the prevalence of gastric Hp infection at initial diagnosis of ophthalmologic and nonophthalmologic extragastric lymphoma patients. Three cohorts of patients were studied: a first one of 83 patients with OAL, a second one of 101 patients with extraophthalmologic extragastric lymphoma, and a third one of 156 control individuals (control) without malignant lymphoma. Gastric Hp infection was investigated by histopathological analysis and Hp-specific PCR assay on gastric biopsy tissue samples. We found gastric Hp infection in 37 OAL patients (45%), in 25 extraophthalmologic extragastric lymphoma cases (25%), and in 18 controls individuals (12%) (P < 0.0001 OAL/C and P < 0.01 OAL/extra-OAL cases). Gastritis was found in 51% and 9% of Hp-positive and Hp-negative lymphoma patients, respectively (P < 10−4). Gastric Hp infection only correlated with MALT/LPL lymphoma (P = 0.03). There is a significant association between gastric Hp infection and MALT/LPL OAL. This suggests a novel mechanism of indirect infection-associated lymphomagenesis whereby chronic local antigen stimulation would lead to the emergence of ectopic B-cell lymphoma. © 2010 Wiley-Liss, Inc. Am. J. Hematol.
- Published
- 2010
27. Loss-of-function of MYO5B is the main cause of microvillus inclusion disease: 15 novel mutations and a CaCo-2 RNAi cell model
- Author
-
Thomas Müller, Virginie Colomb, Olivier Goulet, Kristian Pfaller, Frédérique Sauvat, Lukas A. Huber, Juliette Lefebvre, Silvia Lechner, Natalia Schiefermeier, Axel Enninger, Yann Revillon, Danielle Canioni, Hannes L. Ebner, Genevieve de Saint-Basile, Jacques Schmitz, Gerd Utermann, Frank M. Ruemmele, Michael W. Hess, Peter Heinz-Erian, Cornelia E. Thöni, Andreas R. Janecke, Florence Lacaille, and Nicole Brousse
- Subjects
Male ,Adolescent ,Brush border ,Blotting, Western ,DNA Mutational Analysis ,Myosin Type V ,Mutation, Missense ,Microvillous inclusion disease ,Vacuole ,Biology ,medicine.disease_cause ,digestive system ,Malabsorption Syndromes ,Myosin ,Genetics ,medicine ,Humans ,Endomembrane system ,Child ,Genetics (clinical) ,Mutation ,Microvilli ,Myosin Heavy Chains ,Infant ,medicine.disease ,Microvillus ,Cell biology ,medicine.anatomical_structure ,Biochemistry ,Codon, Nonsense ,Caco-2 ,Child, Preschool ,Diarrhea, Infantile ,Female ,RNA Interference ,Caco-2 Cells ,Digestive System Abnormalities - Abstract
Autosomal recessive microvillus inclusion disease (MVID) is characterized by an intractable diarrhea starting within the first few weeks of life. The hallmarks of MVID are a lack of microvilli on the surface of villous enterocytes, occurrence of intracellular vacuoles lined by microvilli (microvillus inclusions), and the cytoplasmic accumulation of periodic acid-Schiff (PAS)-positive vesicles in enterocytes. Recently, we identified mutations in MYO5B, encoding the unconventional type Vb myosin motor protein, in a first cohort of nine MVID patients. In this study, we identified 15 novel nonsense and missense mutations in MYO5B in 11 unrelated MVID patients. Fluorescence microscopy, Western blotting, and electron microscopy were applied to analyze the effects of MYO5B siRNA knock-down in polarized, brush border possessing CaCo-2 cells. Loss of surface microvilli, increased formation of microvillus inclusions, and subapical enrichment of PAS-positive endomembrane compartments were induced in polarized, filter-grown CaCo-2 cells, following MYO5B knock-down. Our data indicate that MYO5B mutations are a major cause of microvillus inclusion disease and that MYO5B knock-down recapitulates most of the cellular phenotype in vitro, thus independently showing loss of MYO5B function as the cause of microvillus inclusion disease.
- Published
- 2010
28. Presentation and Long-Term Follow-up of Refractory Celiac Disease: Comparison of Type I With Type II
- Author
-
Georgia Malamut, Olivier Hermine, Diane Damotte, Bertrand Meresse, Christophe Cellier, Virginie Verkarre, Aurelien Amiot, Thierry Lecomte, Elizabeth Macintyre, Nicole Brousse, Jacques Cosnes, Isabelle Radford-Weiss, Anne Lavergne-Slove, Yoram Bouhnik, Jean-Frederic Colombel, Pauline Afchain, Ludovic Trinquart, Nadine Cerf-Bensussan, Matthieu Allez, and Jean-Charles Delchier
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Multivariate analysis ,CD3 Complex ,CD8 Antigens ,Disease ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,Adrenal Cortex Hormones ,Internal medicine ,Humans ,Medicine ,Survival rate ,2. Zero hunger ,Hepatology ,business.industry ,Middle Aged ,medicine.disease ,Immunohistochemistry ,3. Good health ,Lymphoma ,Survival Rate ,Celiac Disease ,030220 oncology & carcinogenesis ,Intraepithelial lymphocyte ,Enteropathy-associated T-cell lymphoma ,Female ,030211 gastroenterology & hepatology ,business ,Follow-Up Studies - Abstract
Refractory celiac disease (RCD) was recently subdivided into 2 subtypes (RCD I and II) based on a normal or abnormal phenotype of intraepithelial lymphocytes (IELs), respectively. It is not clear, however, if these 2 entities differ in their presentation at diagnosis or long-term outcome. We compared the clinical and biological characteristics of RCD I and RCD II at diagnosis, the risk of developing an overt lymphoma, and the predictive factors of survival.Medical files of 14 patients with RCD I and 43 with RCD II were analyzed retrospectively. Predictive factors of overt lymphoma and survival were studied in univariate and multivariate analyses.At diagnosis, malnutrition, ulcerative jejunitis, and lymphocytic gastritis were more common in patients with RCD II than RCD I (P.05). Overt lymphomas occurred in 2 patients with RCD I and 16 with RCD II. In the univariate analysis, abnormal IEL phenotype and increased age at diagnosis of RCD were predictive factors for overt lymphoma. Abnormal IEL phenotype (P.01), clonality (P= .01), and overt lymphoma (P= .001) predicted short survival time. Only abnormal IEL phenotype (P= .03) and overt lymphoma (P= .04) were predictive in the multivariate analysis. The 5-year survival rate was 93% in patients with RCD I and 44% with RCD II.RCD II has a much more severe presentation and prognosis than patients with RCD I;44% of patients with RCD II survive 5 years after diagnosis. Abnormal IEL phenotype is a predictive factor but not a necessary condition for the development of overt lymphoma.
- Published
- 2009
29. Étude anatomoclinique de dix cas de fasciite nodulaire de l’enfant
- Author
-
Sylvie Fraitag, Nicole Brousse, J.-N. Dauendorffer, Nicolas Ortonne, and Christine Bodemer
- Subjects
Gynecology ,medicine.medical_specialty ,business.industry ,Sex factors ,medicine ,Follow up studies ,Dermatology ,business - Abstract
Resume Introduction La fasciite nodulaire est rare chez l’enfant. En dehors de cas isoles, l’analyse de la litterature ne revele que deux series pediatriques anciennes portant respectivement sur 15 et six cas. Malades et methodes Etude retrospective des caracteristiques anatomocliniques de dix cas de fasciite nodulaire diagnostiques a l’hopital Necker–Enfants-Malades entre 1992 et 2006, chez des enfants âges de moins de 15 ans. Resultats Cette etude met en evidence quatre elements nouveaux : (1) une topographie preferentielle des lesions au niveau du tronc, qui s’oppose a la localisation la plus frequente decrite jusqu’alors, a savoir le membre superieur ; (2) une predominance feminine, alors qu’une predominance masculine est habituellement rapportee ; (3) un taux de recidive apres exerese initiale de 22 %, superieur a ce qui est indique dans la litterature ; (4) une positivite de l’immunomarquage p53 superieure a ce qui est rapporte chez l’adulte, difference qui pourrait s’expliquer par notre recrutement uniquement pediatrique. Discussion La forte positivite de l’immunomarquage p53 semble conforter l’hypothese de la nature preneoplasique et non pas reactionnelle de la fasciite nodulaire de l’enfant.
- Published
- 2008
30. Impact of Rituximab and/or High-Dose Therapy With Autotransplant at Time of Relapse in Patients With Follicular Lymphoma: A GELA Study
- Author
-
Philippe Solal-Celigny, Nicolas Mounier, Corinne Haioun, Catherine Sebban, Nicole Brousse, Bertrand Coiffier, Pierre Feugier, Bertrand Souleau, Richard Delarue, Hervé Tilly, and Pauline Brice
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Population ,Follicular lymphoma ,Salvage therapy ,Kaplan-Meier Estimate ,Transplantation, Autologous ,Disease-Free Survival ,Antibodies, Monoclonal, Murine-Derived ,Recurrence ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Combined Modality Therapy ,education ,Lymphoma, Follicular ,Aged ,Randomized Controlled Trials as Topic ,Retrospective Studies ,Salvage Therapy ,Chemotherapy ,education.field_of_study ,business.industry ,Hematopoietic Stem Cell Transplantation ,Antibodies, Monoclonal ,Middle Aged ,medicine.disease ,Surgery ,Prednisolone ,Female ,Rituximab ,Neoplasm Recurrence, Local ,business ,medicine.drug ,Teniposide - Abstract
Purpose The treatment of patients with follicular lymphoma has changed with the introduction of high-dose therapy (HDT) with autologous stem-cell transplant then with rituximab. The effect of these two strategies on the outcome of relapsing patients with follicular lymphoma has never been compared. Patients and Methods We analyzed two cohorts of patients treated in two successive randomized studies with the same treatment, cyclophosphamide, doxorubicin, teniposide, and prednisolone plus interferon, to evaluate the role of rituximab and HDT in salvage therapy after first disease progression or relapse. Results Of the 364 patients included in these two studies, 254 progressed or relapsed and constitute the population of this analysis. Among them, 98 had been treated with HDT, including 33 of them after rituximab-containing salvage regimen, and 69 with rituximab alone or combined with chemotherapy but without HDT. Patients’ characteristics at diagnosis were similar in all subgroups. If event-free survival was identical for patients treated within Groupe d'Etude des Lymphomes Folliculaires (GELF) -86 or GELF-94 studies, overall survival was longer in GELF-94 study. HDT was associated with a statistically significant benefit in terms of event-free survival from relapse and survival after relapse (SAR). Rituximab was associated with a greater benefit than HDT for these two end points. When both treatments were combined, patients treated with rituximab-containing salvage regimen followed by HDT had 5-year SAR more than 90%. Conclusion In follicular lymphoma, for patients treated with first-line chemotherapy the combination of a salvage regimen containing rituximab with or without HDT leads to a dramatic improvement of long-term outcome.
- Published
- 2008
31. Immune disorders in agnogenic myeloid metaplasia: relations to myelofibrosis
- Author
-
Nicole Brousse, E. Rondeau, Pierre Boivin, Dhermy D, Jérôme Bernard, M Vroclans, and Philippe Solal-Celigny
- Subjects
Adult ,Male ,Polycythaemia ,Immunoglobulin levels ,Immunoglobulins ,Pathogenesis ,Immune system ,Rheumatoid Factor ,medicine ,Rheumatoid factor ,Humans ,Agnogenic myeloid metaplasia ,Myelofibrosis ,Polycythemia Vera ,Aged ,Autoantibodies ,business.industry ,Autoantibody ,Hematology ,Middle Aged ,medicine.disease ,Coombs Test ,Primary Myelofibrosis ,Immunology ,Female ,business - Abstract
Summary. Tests for a dysimmune state were done in an unselected group of 67 patients with agnogenic myeloid metaplasia (AMM). The results were compared to those of 56 patients with polycythaemia vera (PV). 75% of AMM patients versus 32% of PV patients had various abnormalities. The most frequent disorders among AMM patients were serum antinuclear and anti smooth muscle autoantibodies (10 3% each), a positive test for rheumatoid factor (21 7%), a polyclonal increase in serum immunoglobulin levels (46 8%) or a serum monoclonal component (9 7%), a positive direct Coombs’test (19%), an anti I autoantibody (30%). In AMM patients there was no relationship between age, sex, importance of splenic enlargement, time from diagnosis or treatment and the present of a dysimmunity. Furthermore, in AMM patients, but also in PV patients, it seems that the more frequent and numerous these abnormalities the more severe is the myelofibrosis. Like other previous studies, these results suggest a lymphoid cell involvement in AMM and a role for these immune disorders in the pathogenesis of myelofibrosis.
- Published
- 2008
32. Evaluation of C4d Deposition and Circulating Antibody in Small Bowel Transplantation
- Author
-
Danielle Canioni, O. Goulet, Florence Lacaille, N Patey-Mariaud de Serre, D. Dion, Nicole Brousse, and Cécile Talbotec
- Subjects
Graft Rejection ,Male ,medicine.medical_specialty ,Pathology ,Adolescent ,medicine.medical_treatment ,Gastroenterology ,Antibodies ,Internal medicine ,Intestine, Small ,medicine ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,Clinical significance ,Prospective Studies ,Child ,Grading (tumors) ,Heart transplantation ,Transplantation ,Kidney ,biology ,business.industry ,Standard treatment ,Infant ,Complement C4 ,Organ Transplantation ,medicine.anatomical_structure ,Child, Preschool ,biology.protein ,Abdomen ,Female ,Antibody ,business - Abstract
Antibody-mediated rejection (AMR) consensus criteria are defined in kidney and heart transplantation by histological changes, circulating donor-specific antibody (DSA), and C4d deposition in affected tissue. AMR consensus criteria are not yet identified in small bowel transplantation (SBTx). We investigated those three criteria in 12 children undergoing SBTx, including one retransplantation and four combined liver-SBTx (SBTx), with a follow-up of 12 days to 2 years. All biopsies (91) were evaluated with a standardized grading scheme for acute rejection (AR), vascular lesions and C4d expression. Sera were obtained at day 0 and during the follow-up. C4d was expressed in 37% of biopsies with or without AR, but in 50% of biopsies with severe vascular lesions. In addition, vascular lesions were always associated with AR and a poor outcome. All children with AR (grade 2 or 3) observed before the third month died or lost the graft. DSA were never found in any studied sera. We found no evidence that C4d deposition was of any clinical relevance to the outcome of SBTx. However, the grading of vascular lesions may constitute a useful marker to identify AR that is potentially resistant to standard treatment, and for which an alternative therapy should be considered.
- Published
- 2008
33. High Numbers of Tumor-Associated Macrophages Have an Adverse Prognostic Value That Can Be Circumvented by Rituximab in Patients With Follicular Lymphoma Enrolled Onto the GELA-GOELAMS FL-2000 Trial
- Author
-
Charles Foussard, Nicole Brousse, Luc Xerri, Anne Sonet, Marie-Christine Rousselet, Danielle Canioni, Frank Morchhauser, Gilles Salles, Marie Keuppens, Thierry Lamy, and Nicolas Mounier
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Pathology ,Cyclophosphamide ,Follicular lymphoma ,Antigens, Differentiation, Myelomonocytic ,Tumor-associated macrophage ,Gastroenterology ,Antibodies, Monoclonal, Murine-Derived ,Antigens, CD ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Prospective Studies ,Lymphoma, Follicular ,Survival rate ,Etoposide ,Aged ,Teniposide ,business.industry ,CD68 ,Macrophages ,Antibodies, Monoclonal ,Interferon-alpha ,Middle Aged ,Prognosis ,medicine.disease ,Lymphoma ,Survival Rate ,Treatment Outcome ,Oncology ,Doxorubicin ,Prednisone ,Female ,Rituximab ,business ,medicine.drug - Abstract
PurposeHigh amounts of intratumoral macrophages have been shown to correlate with poor prognosis in patients with follicular lymphoma (FL) treated with chemotherapy without rituximab. We tried to establish whether intratumoral macrophage count (MC) definitely is able to predict the outcome of FL patients in the rituximab era.Patients and MethodsWe analyzed immunohistochemical CD68 expression in 194 FL patients from the FL-2000 trial, randomly assigned to receive cyclophosphamide, doxorubicin, etoposide, prednisolone, and interferon (CHVP-I) or rituximab plus CHVP-I. Immunohistochemistry was performed on paraffin sections using anti-CD68 KP1 antibody, and stained macrophages were scored on high-power field (hpf) in either intrafollicular (IF) or extrafollicular (EF) areas.ResultsFor IF MC, the best cutoff point was estimated at 10 macrophages/hpf. Low IF MC was significantly associated with a better event-free survival (EFS; P = .011). However, this effect was observed only in the CHVP-I arm (P = .012) and not in the rituximab plus CHVP-I arm. Using a cutoff of 15 IF MC, we found no significant association with EFS. For EF MC, fewer than 22 macrophages/hpf were associated with better EFS in the CHVP-I arm (P = .02) but not in the rituximab plus CHVP-I arm.ConclusionThese results show that MC can predict outcome of FL patients and that rituximab is able to circumvent the unfavorable outcome associated with high MC.
- Published
- 2008
34. Diagnostic d’adénome métanéphrique rénal : Intérêt de l’immunohistochimie et apport de la biopsie
- Author
-
Nicole Brousse, Viorel Vasiliu, Olivier Hélénon, Louise Galmiche, Jean-Michel Casanova, and Sylvain Poirée
- Subjects
Pathology and Forensic Medicine - Abstract
Resume La majorite des tumeurs renales de l’adulte sont des carcinomes. Ils sont traites de facon chirurgicale par une excision limitee ou par une nephrectomie. En cas de tumeur renale decouverte fortuitement et de petite taille, une biopsie est proposee afin d’adapter le traitement. Nous rapportons le cas d’une femme de 45 ans presentant une masse renale. Une biopsie de cette masse mettait en evidence un adenome metanephrique. Cette tumeur etant benigne, aucune exerese chirurgicale n’a ete realisee. Nous abordons d’une part l’interet de l’immunohistochimie dans le diagnostic differentiel des tumeurs « a petites cellules basophiles » du rein. D’autre part, cette observation souligne la place croissante de la biopsie dans la prise en charge optimale des tumeurs renales.
- Published
- 2007
35. Manifestations gastro-intestinales des déficits immunitaires primitifs
- Author
-
Virginie Verkarre, Georgia Malamut, Nicole Brousse, and Christophe Cellier
- Subjects
Gynecology ,medicine.medical_specialty ,business.industry ,Gastroenterology ,Medicine ,General Medicine ,business - Abstract
Resume Les manifestations gastro-intestinales des deficits immunitaires primitifs (DIP) sont frequentes et souvent revelatrices du deficit immunitaire. Si elles miment, pour la plupart, les maladies digestives de l’immunocompetant, elles comportent des specificites diagnostiques et therapeutiques qui doivent etre connues pour la prise en charge adaptee de ces patients. Cette revue etablit la description des atteintes digestives des DIP en proposant notamment une demarche diagnostique et fait etat des therapeutiques disponibles.
- Published
- 2007
36. Gastrointestinal Disorder Associated with Olmesartan Mimics Autoimmune Enteropathy
- Author
-
Nicolas Guegan, Sophie Scialom, Nadine Cerf-Bensussan, Coralie Derrieux, Lysiane Marthey, Nicole Brousse, Georgia Malamut, Lucine Vuitton, Philippe Seksik, Virginie Verkarre, Guillaume Cadiot, Franck Carbonnel, Christophe Cellier, Bertrand Meresse, Elizabeth Macintyre, Guillaume Savoye, Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'hépato-gastro-entérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Interactions de l'épithelium intestinal et du système immunitaire (UMR_S 793), Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP], Service d'Anatomie et de Cytologie Pathologiques, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], PremUp Foundation, Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Sorbonne Universités-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'immuno-hématologie pédiatrique [CHU Necker], Service hématologie, French group of faecal microbotia transplantation (FGFT), CHU Saint-Antoine [APHP], Service d'Hépato-Gastroentérologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Hépatogastroentérologie, CHU de Bicêtre, Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Interactions de l'épithelium intestinal et du système immunitaire ( UMR_S 793 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Recherche Agronomique ( INRA ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -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)-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Sorbonne Universités-Université Paris Descartes - Paris 5 ( UPD5 ) -CHI Créteil-Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ), French group of faecal microbotia transplantation ( FGFT ), Gastroenterology and nutrition department, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -CHU Saint-Antoine [APHP], Département des maladies de l'appareil digestif, CHU Rouen, Université de Reims Champagne-Ardenne ( URCA ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and HAL-UPMC, Gestionnaire
- Subjects
Adult ,Male ,Adolescent ,Gastrointestinal Diseases ,Science ,Tetrazoles ,Angiotensin II receptor antagonist ,Autoimmune enteropathy ,Diagnosis, Differential ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Antigen ,medicine ,Humans ,Enteropathy ,Polyendocrinopathies, Autoimmune ,Aged ,Multidisciplinary ,business.industry ,[ SDV.SP.MED ] Life Sciences [q-bio]/Pharmaceutical sciences/Medication ,Imidazoles ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Middle Aged ,medicine.disease ,[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,3. Good health ,Gastrointestinal disorder ,030220 oncology & carcinogenesis ,Immunology ,Medicine ,Female ,[ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,030211 gastroenterology & hepatology ,Gluten free ,Olmesartan ,business ,Angiotensin II Type 1 Receptor Blockers ,Research Article ,medicine.drug - Abstract
International audience; Background and Objectives : Anti-hypertensive treatment with the angiotensin II receptor antagonist olmesartan is a rare cause of severe Sprue-like enteropathy. To substantiate the hypothesis that olmesartan interferes with gut immune homeostasis, clinical, histopathological and immune features were compared in olmesartan-induced-enteropathy (OIE) and in autoimmune enteropathy (AIE).Methods : Medical files of seven patients with OIE and 4 patients with AIE enrolled during the same period were retrospectively reviewed. Intestinal biopsies were collected for central histopathological review, T cell Receptor clonality and flow cytometric analysis of isolated intestinal lymphocytes. Results : Among seven olmesartan-treated patients who developed villous atrophy refractory to a gluten free diet, three had extra-intestinal autoimmune diseases, two had antibodies reacting with the 75 kilodalton antigen characteristic of AIE and one had serum anti-goblet cell antibodies. Small intestinal lesions and signs of intestinal lymphocyte activation were thus reminiscent of the four cases of AIE diagnosed during the same period. Before olmesartan discontinuation, remission was induced in all patients (7/7) by immunosuppressive drugs. After interruption of both olmesartan and immunosuppressive drugs in six patients, remission was maintained in 4 but anti-TNF-α therapy was needed in two.Conclusion : This case-series shows that olmesartan can induce intestinal damage mimicking AIE. OIE usually resolved after olmesartan interruption but immunosuppressive drugs may be necessary to achieve remission. Our data sustain the hypothesis that olmesartan interferes with intestinal immuno regulation in predisposed individuals.
- Published
- 2015
37. Cells Associated with the Malignant Clone in Non-Hodgkin�s Lymphomas
- Author
-
Nicole Brousse, L. Nonnenmacher, Georges Delsol, Françoise Rigal-Huguet, T. Al Saati, E. Kuhlein, and P. Caveriviere
- Subjects
Hodgkin s ,Clone (cell biology) ,Biology ,Virology - Published
- 2015
38. Azathioprine induction of tumors with microsatellite instability: risk evaluation using a mouse model
- Author
-
Sahra, Bodo, Magali, Svrcek, Isabelle, Sourrouille, Peggy, Cuillières-Dartigues, Tatiana, Ledent, Sylvie, Dumont, Laetitia, Dinard, Philippe, Lafitte, Camille, Capel, Ada, Collura, Olivier, Buhard, Kristell, Wanherdrick, Alexandra, Chalastanis, Virginie, Penard-Lacronique, Bettina, Fabiani, Jean-François, Fléjou, Nicole, Brousse, Laurent, Beaugerie, Alex, Duval, and Martine, Muleris
- Subjects
Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Time Factors ,Lymphoma ,Kaplan-Meier Estimate ,DNA Mismatch Repair ,Risk Assessment ,Young Adult ,thiopurine tolerance ,Risk Factors ,Azathioprine ,Animals ,Humans ,neoplasms ,Aged ,pharmacogenetics ,Mice, Knockout ,Dose-Response Relationship, Drug ,Middle Aged ,Inflammatory Bowel Diseases ,iatrogenic cancer ,Immunohistochemistry ,digestive system diseases ,Disease Models, Animal ,MutS Homolog 2 Protein ,Phenotype ,Female ,microsatellite instability ,Immunosuppressive Agents ,Research Paper - Abstract
Mismatch-repair (MMR)-deficient cells show increased in vitro tolerance to thiopurines because they escape apoptosis resulting from MMR-dependent signaling of drug-induced DNA damage. Prolonged treatment with immunosuppressants including azathioprine (Aza), a thiopurine prodrug, has been suggested as a risk factor for the development of late onset leukemias/lymphomas displaying a microsatellite instability (MSI) phenotype, the hallmark of a defective MMR system. We performed a dose effect study in mice to investigate the development of MSI lymphomas associated with long term Aza treatment. Over two years, Aza was administered to mice that were wild type, null or heterozygous for the MMR gene Msh2. Ciclosporin A, an immunosuppressant with an MMR-independent signaling, was also administered to Msh2(wt) mice as controls. Survival, lymphoma incidence and MSI tumor phenotype were investigated. Msh2(+/-) mice were found more tolerant than Msh2(wt) mice to the cytotoxicity of Aza. In Msh2(+/-) mice, Aza induced a high incidence of MSI lymphomas in a dose-dependent manner. In Msh2(wt) mice, a substantial lifespan was only observed at the lowest Aza dose. It was associated with the development of lymphomas, one of which displayed the MSI phenotype, unlike the CsA-induced lymphomas. Our findings define Aza as a risk factor for an MSI-driven lymphomagenesis process.
- Published
- 2015
39. Implication of the folate-methionine metabolism pathways in susceptibility to follicular lymphomas
- Author
-
Sidonie Niclot, Paul Landais, Elisabeth Macintyre, Claudine Junien, Bruno Varet, Pierre Taupin, Nicole Brousse, D Savoy, Gilles Salles, Dominique Baudry-Bluteau, Quentin Pruvot, and Caroline Besson
- Subjects
Adult ,Male ,Methyltransferase ,Genotype ,Immunology ,Follicular lymphoma ,Biology ,5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ,Biochemistry ,Thymidylate synthase ,chemistry.chemical_compound ,Folic Acid ,Methionine ,Risk Factors ,medicine ,Humans ,Genetic Predisposition to Disease ,Methionine synthase ,Allele ,Lymphoma, Follicular ,Alleles ,Methylenetetrahydrofolate Reductase (NADPH2) ,Glycine Hydroxymethyltransferase ,Polymorphism, Genetic ,DNA ,Thymidylate Synthase ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Enzymes ,chemistry ,Methylenetetrahydrofolate reductase ,Mutation ,Cancer research ,biology.protein ,Female - Abstract
The incidence of follicular lymphoma (FL) in industrialized countries has been increasing since the 1950s. Polymorphisms in genes encoding key enzymes controlling folate-methionine metabolism, including methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MS or MTR), serine hydroxymethyltransferase (SHMT), and thymidylate synthase (TS or TYMS), modify the risk of various cancers and possibly FL. This study specifically looks for an association between MTHFR, MTR, TYMS, and SHMT polymorphisms and the risk of FL. We carried out a case-control study with 172 patients diagnosed with FL and 206 control subjects. We report that the risk of FL was doubled by the association of one mutant allele at both MTHFR polymorphisms. Individuals with MTR 2756AA had 2-fold higher risk of FL, and subjects not having at least one TYMS 2R allele showed a 2-fold higher risk of FL. The MTR 2756AA genotype conferred a greater multivariate-adjusted relative risk of FL, and the risk was multiplied by almost 5 in the TYMS2R(-)/MTR 2756AA combination. In conclusion, common polymorphisms in key enzymes of the folate-methionine metabolism pathway result in an increased risk of FL and suggest that inadequate intake of dietary folate and other methyl donor nutrients may contribute to the development of this malignancy. (Blood. 2006;108:278-285)
- Published
- 2006
40. Minimal change nephrotic syndrome and classical Hodgkin's lymphoma: Report of 21 cases and review of the literature
- Author
-
Richard Delarue, Olivier Hermine, Dominique Nochy, F. Boue, Vincent Audard, Pierre Ronco, M. Abtahi, Nicole Brousse, J.-J. Sotto, P. Remy, Djillali Sahali, F. Larousserie, Alain Delmer, Philippe Grimbert, and Peter Lang
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Time Factors ,Adolescent ,T-Lymphocytes ,Nephrosis ,Comorbidity ,Gastroenterology ,Cohort Studies ,Nodular sclerosis ,Risk Factors ,Glomerulopathy ,minimal change nephrotic syndrome ,Internal medicine ,steroid-resistant nephrotic syndrome ,medicine ,Humans ,Clinical significance ,Aged ,Retrospective Studies ,business.industry ,Nephrosis, Lipoid ,NF-kappa B ,Glomerulonephritis ,Middle Aged ,medicine.disease ,Hodgkin Disease ,Lymphoma ,Steroid-resistant nephrotic syndrome ,Nephrology ,classical Hodgkin's lymphoma ,Cytokines ,Female ,Th2 cytokines ,business ,Nephrotic syndrome - Abstract
Minimal change nephrotic syndrome (MCNS) is described as a paraneoplastic manifestation of classical Hodgkin's lymphoma (cHL). We reassessed the pathophysiological and clinical significance of this association. A retrospective study was performed to evaluate a cohort of adult patients who developed MCNS and cHL. Twenty-one patients recruited in 15 French centers were analyzed. cHL was associated with inflammatory and general symptoms in most cases. The morphological subtype was predominantly nodular sclerosis (71.4%). MCNS appeared before the diagnosis of lymphoma in eight patients (38.1%) and in this case, it was characterized by a nephrotic syndrome (NS) frequently resistant (50%) or dependent (12.5%) to steroid treatment. Interestingly, diagnosis (3–120 months after MCNS) and effective treatment of the hemopathy were associated with the disappearance of the MCNS. cHL was diagnosed before MCNS in nine patients (42.9%), and in this case, glomerulopathy was associated with cHL relapse in 55.5% of cases. In four patients (19%), the two diseases occurred simultaneously. Extensive immunohistochemical study of lymph nodes was performed in eight patients and did not reveal particular features. In conclusion, MCNS associated with cHL is frequently dependent or resistant to steroid regimen, but remission of NS is obtained with the cure of lymphoma.
- Published
- 2006
- Full Text
- View/download PDF
41. Langerhans cells express matrix metalloproteinases 9 and 2 and tissue inhibitors of metalloproteinases 1 and 2 in healthy human gingival tissue and in periodontitis
- Author
-
Nicole Brousse, G. Godeau, B. Pellat, Sylvie Séguier, M. Folliguet, and Agnès Bodineau
- Subjects
Microbiology (medical) ,Pathology ,medicine.medical_specialty ,Langerhans cell ,Immunology ,Gingiva ,Connective tissue ,Matrix metalloproteinase ,Biology ,Matrix (biology) ,Microbiology ,Immunoenzyme Techniques ,Immunolabeling ,Cell Movement ,medicine ,Humans ,Protease Inhibitors ,Periodontitis ,General Dentistry ,Basement membrane ,Tissue Inhibitor of Metalloproteinase-2 ,Microscopy, Confocal ,Tissue Inhibitor of Metalloproteinase-1 ,Tissue Inhibitor of Metalloproteinases ,medicine.disease ,Matrix Metalloproteinases ,medicine.anatomical_structure ,Matrix Metalloproteinase 9 ,Langerhans Cells ,Matrix Metalloproteinase 2 ,Immunohistochemistry - Abstract
Background: As antigen-presenting cells, Langerhans cells may play an important role in the initiation and maintenance of periodontal disease. This study is the first report that extends our knowledge of the expression of matrix metalloproteinases and their endogenous tissue inhibitors by Langerhans cells in healthy and diseased gingival tissues. Methods: Single and double immunolabeling procedures were carried out using monoclonal antibodies against CD1a, matrix metalloproteinases 2 and 9, and tissue inhibitors of matrix metalloproteinases 1 and 2, and analyzed by conventional and confocal microscopes. Results: Langerhans cells expressed matrix metalloproteinases 2 and 9, and tissue inhibitors of matrix metalloproteinases 1 and 2 in healthy and diseased gingival tissues. The tissue inhibitors of matrix metalloproteinase-positive Langerhans cells were mainly observed in the upper epithelial layers. Matrix metalloproteinase 9-positive Langerhans cells were observed especially during periodontitis and in the basal epithelial layer or crossing the basement membrane. Conclusion: During periodontal disease, changes in the expression of matrix metalloproteinases and their tissue inhibitors by gingival Langerhans cells could be implicated in the migration of the cells towards the connective tissue.
- Published
- 2006
42. Implication of TNF-Related Apoptosis-Inducing Ligand in Inflammatory Intestinal Epithelial Lesions
- Author
-
Bernadette Bègue, Harald Wajant, Nadine Cerf-Bensussan, Frank M. Ruemmele, Jean-François Beaulieu, Dominique Berrebi, Nicole Brousse, Pierre Desreumaux, Daniela Siegmund, Danielle Canioni, Michael J. Lentze, Laurent Dubuquoy, Jacques Schmitz, Jean-Christophe Bambou, and O. Goulet
- Subjects
Male ,Blotting, Western ,Molecular Sequence Data ,Apoptosis ,Sensitivity and Specificity ,digestive system ,Inflammatory bowel disease ,Sampling Studies ,Statistics, Nonparametric ,TNF-Related Apoptosis-Inducing Ligand ,Mice ,Paracrine signalling ,Reference Values ,medicine ,Animals ,Humans ,Electrophoretic mobility shift assay ,Interleukin 8 ,Cells, Cultured ,Caspase ,Mice, Inbred BALB C ,Membrane Glycoproteins ,Base Sequence ,Hepatology ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Tumor Necrosis Factor-alpha ,Interleukin-8 ,Gastroenterology ,Epithelial Cells ,Flow Cytometry ,Inflammatory Bowel Diseases ,medicine.disease ,Molecular biology ,Blot ,Disease Models, Animal ,Gene Expression Regulation ,biology.protein ,Female ,Tumor necrosis factor alpha ,Inflammation Mediators ,Apoptosis Regulatory Proteins - Abstract
Background & Aims: Few data exist on the molecular events causing intestinal epithelial destruction during inflammatory processes, such as inflammatory bowel disease (IBD). In this work, we analyzed the potential implication of tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) in these inflammatory lesions. Methods: TRAIL and TRAIL-receptor expression were analyzed in normal, inflammatory ileum/colon and human intestinal epithelial cell (IEC) lines (HIEC), Caco-2, and HT-29 using RNase protection assay, real-time and reverse-transcription polymerase chain reaction (RT-PCR), immunohistochemistry, and Western blot analysis. TRAIL-induced activation of NF-κB was determined by electrophoretic mobility shift assay. Caspase-recruitment domain (CARD)15 expression and interleukin-(IL)8 production were studied by RT-PCR and enzyme-linked immunosorbent assay. Apoptosis was monitored using Annexin-V/caspase-3 assays. Results: Normal mature IEC expressed low TRAIL levels, whereas, in inflammatory lesions, TRAIL messenger RNA and protein were markedly up-regulated in IEC and lamina propria lymphocytes at levels comparable with trinitrobenzene sulfonic acid-induced colitis. Interferon-γ and TNF-α potently induced TRAIL in IEC. In vitro analyses revealed a dual biologic effect of TRAIL on HIEC: Under noninflammatory conditions, TRAIL up-regulated via nuclear factor-κB CARD15 and IL-8, whereas, under inflammatory conditions, TRAIL became a potent inducer of apoptosis in HIEC, which was confirmed ex vivo using ileal organ cultures. TNF-α markedly increased the expression of the proapoptotic receptor TRAIL-R2. TRAIL-induced IEC apoptosis required a functional caspase cascade. Conclusions: TRAIL is a new inflammatory mediator implicated in the homeostasis of intestinal epithelial barrier functions. TRAIL is highly up-regulated in IEC in inflammatory ileum and colon. It may augment in an auto-/paracrine fashion the elimination of IEC via apoptosis.
- Published
- 2006
43. Study of the Impact of Liver Transplantation on the Outcome of Intestinal Grafts in Children
- Author
-
F. Lacaille, Christine Le Bihan, Nicole Brousse, Olivier Goulet, Sabine Sarnacki, Myriam Jugie, Yann Revillon, Danielle Canioni, Nadine Cerf-Bensussan, Dominique Jan, and Diane Damotte
- Subjects
Graft Rejection ,Male ,medicine.medical_specialty ,Biopsy ,medicine.medical_treatment ,Liver transplantation ,Single Center ,Gastroenterology ,Tacrolimus ,Intestinal mucosa ,Internal medicine ,Intestine, Small ,medicine ,Humans ,Child ,Retrospective Studies ,Transplantation ,business.industry ,Graft Survival ,Apoptotic body ,medicine.disease ,Immunohistochemistry ,Appendicitis ,Small intestine ,Liver Transplantation ,Treatment Outcome ,medicine.anatomical_structure ,Child, Preschool ,Female ,business ,Biomarkers ,Immunosuppressive Agents ,Immunostaining - Abstract
BACKGROUND Successful small bowel transplantation remains a challenge due to the septic and immune content of the gut. The possible beneficial role of the liver was assessed in pediatric recipients of isolated intestinal and liver intestinal combined transplantation, receiving the same immunosuppressive therapy. METHODS Fifteen children who underwent small bowel transplantation (seven SbTx) or combined liver-small bowel transplantation (eight LSbTx) at a single center between 1994 and 1998 were retrospectively reviewed and compared with fifteen controls (eight normal and seven appendicitis as inflammatory control). Transplant and patient survival, acute rejection episodes were analyzed and compared. Epithelial apoptotic body counts (ABC) and NF-kB (p65), Caspase-3 and Bax intestinal immunostaining from days 0 to 20 after transplantation were assessed. RESULTS Graft and patient survivals at 5 years were respectively 75% and 75% in LSbTx; 43% and 57% in SbTx (NS). Histological analysis showed higher ABC in LSbTx intestinal mucosa (P = 0.05 on day 5, P < 0.01 thereafter). Immunostaining of biopsies on day 0 after reperfusion showed different expression of NF-kB, Caspase-3 and Bax on endothelial (P < 0.05 for NF-kB and Bax), mononuclear (P < 0.05 for Bax) and epithelial cells in LSbTx and SbTx. CONCLUSIONS Our results suggest a protective role of the liver toward intestinal transplantation even in absence of significative difference, probably due to the small number of children. Early changes in NF-kB immunostaining in the biopsies sampled on day 0, pointed to a possible beneficial effect of the liver in the very early phase following transplantation, perhaps through the differential control of ischemia-reperfusion.
- Published
- 2006
44. Characteristics and Outcome of Diffuse Large B-Cell Lymphoma in Hepatitis C Virus–Positive Patients in LNH 93 and LNH 98 Groupe d'Etude des Lymphomes de l'Adulte Programs
- Author
-
Eric Lepage, Felix Reyes, Bertrand Coiffier, Caroline Besson, Nicole Brousse, Stanislas Pol, Danielle Canioni, Olivier Hermine, Philippe Gaulard, Pierre Morel, Pierre Lederlin, Achiel Van Hoof, Hervé Tilly, and Christian Gisselbrecht
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Pathology ,Lymphoma, B-Cell ,Hepatitis C virus ,Hepacivirus ,medicine.disease_cause ,Antiviral Agents ,Severity of Illness Index ,Gastroenterology ,Disease-Free Survival ,Seroepidemiologic Studies ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Survival analysis ,Aged ,biology ,business.industry ,Incidence ,Incidence (epidemiology) ,Hepatitis C ,Middle Aged ,medicine.disease ,biology.organism_classification ,Immunohistochemistry ,Survival Analysis ,Lymphoma ,Treatment Outcome ,Liver ,Oncology ,Hepatitis C Virus Positive ,Female ,Lymphoma, Large B-Cell, Diffuse ,Hepatitis C Antigens ,business ,Diffuse large B-cell lymphoma ,Spleen - Abstract
Purpose Epidemiologic studies show an association between hepatitis C virus (HCV) and B-cell non-Hodgkin's lymphoma (NHL). Treatment and outcome of patients with diffuse large-cell lymphoma (DLCL) and HCV infection are still a matter of debate. Patients and Methods We studied the HCV-positive patients with B-cell DLCL included in the Groupe d'Etude des Lymphomes de l'Adulte (GELA) programs LNH 93 and LNH 98. They were compared with the other patients with DLCL included in these programs. HCV infection prevalence was 0.5% (26 of 5,586 patients). Results Histologic types of HCV-positive DLCL were more frequently transformed from low-grade lymphoma than DLCL in HCV-negative patients (32% v 6%, P = .02). This is also supported by more frequent spleen involvement in HCV-positive patients (46% v 17%, P < .001). HCV-positive patients had more frequently elevated lactate dehydrogenase levels than other patients (77% v 55%, P = .02). Outcome of HCV-positive patients was poorer for overall survival (P = .02) but not for event-free survival (P = .13). After matching on age and prognosis factors, at 2 years of follow-up, the overall survival was 56% (95% CI, 33% to 76%) among HCV-positive patients, versus 80% (70% to 89%), and the event-free survival was 53% (33% to 72%) versus 74% (64% to 84%). The short-term hepatic toxicity of chemotherapy was strongly increased among HCV-positive patients. After exclusion of the two subjects with chronic hepatitis B virus infection, the overall proportion of subjects undergoing hepatic toxicity was 65% (15 of 23 patients). Conclusion HCV-positive patients with DLCL differ from other patients both at presentation and during chemotherapy. Specific protocols evaluating antiviral therapy should be designed for these patients.
- Published
- 2006
45. Analysis of Interleukin-27 (EBI3/p28) Expression in Epstein-Barr Virus- and Human T-Cell Leukemia Virus Type 1-Associated Lymphomas
- Author
-
Olivier Hermine, Frédérique Larousserie, Nicole Brousse, Emilie Bardel, Monique Perennec, Odile Devergne, Stefan Pflanz, Bertrand Arnulf, Laurence Brégeaud, Carmen Lome-Maldonado, and R.A. Kastelein
- Subjects
medicine.medical_treatment ,Interleukin ,EBI3 ,Biology ,medicine.disease ,medicine.disease_cause ,Epstein–Barr virus ,Jurkat cells ,Pathology and Forensic Medicine ,Lymphoma ,Leukemia ,Cytokine ,hemic and lymphatic diseases ,medicine ,Cancer research ,Interleukin 27 - Abstract
Interleukin (IL)-27 is a novel heterodimeric cytokine of the IL-12 family that is composed of two subunits, Epstein-Barr virus (EBV)-induced gene 3 (EBI3) and p28. EBI3 is expressed at high levels in EBV-transformed B-cell lines and is induced in vitro by the EBV oncogene LMP1 in a nuclear factor (NF)-κB-dependent manner. We show here that EBI3 expression is up-regulated in human T-cell leukemia virus type 1 (HTLV-1)-infected cell lines and IL-2-dependent leukemic cells from adult T-cell leukemia/lymphoma (ATL) patients, compared to normal activated T cells. EBI3 expression was decreased in HTLV-1-transformed cells after treatment with the NF-κB inhibitor BAY11-7082 and was induced in Jurkat cells by expression of HTLV-1 wild-type Tax oncoprotein, but not by the Tax mutant M22, which is defective for NF-κB activation. In situ analysis of EBI3 and p28 expression in Hodgkin's lymphomas (HLs), in various EBV-associated lymphoproliferative disorders (LPDs) (including post-transplant LPDs and nasal-type NK/T-cell lymphomas), and in ATL showed that EBI3 was expressed by neoplastic cells in all cases of HL and of LMP1-positive EBV-associated LPD, at variable levels in ATL cases, but rarely in control T-cell lymphomas. In contrast, in all lymphomas tested, no or few tumoral cells expressed p28. Consistent with these data, no significant p28 or IL-27 expression was detected in HL-derived cell lines, or in EBV- or HTLV-1-transformed cell lines. This selective overexpression of EBI3 by transformed cells suggests that EBI3 may play a role, independently from its association to p28, in regulating anti-viral or anti-tumoral immune responses.
- Published
- 2005
46. Plasmocytome cutané EBV+ isolé chez une malade transplantée rénale : efficacité d’un traitement par rituximab
- Author
-
Emmanuel Mahé, Nicole Brousse, Sylvie Fraitag, Henri Kreis, Bruno Varet, A. Carbonnelle, and Emmanuel Morelon
- Subjects
hemic and lymphatic diseases ,Dermatology - Abstract
Resume Introduction Les syndromes lymphoproliferatifs post-transplantation sont des complications bien connues de la transplantation d’organe habituellement associees au virus Epstein-Barr (EBV). Observation Une femme de 25 ans, transplantee renale, avait deux nodules sous-cutanes sur le mollet apparus 3 ans apres une seconde greffe renale. La biopsie d’un nodule revelait un plasmocytome associe a l’EBV localise dans l’hypoderme. Le bilan d’extension ne montrait pas de localisation extra cutanee. Un traitement par rituximab etait debute et permettait une remission complete. Commentaires Les localisations extra-ganglionnaires des syndromes lymphoproliferatifs post-transplantation sont regulierement rapportees, mais les localisations cutanees isolees restent exceptionnelles. Les presentations histologiques sont tres variees, mais la forme a type de plasmocytome est rare. Le traitement initial des syndromes lymphoproliferatifs post-transplantation cutanes, lies a l’EBV, sans atteinte extracutanee associee, consiste le plus souvent en une reduction de l’immunosuppression et/ou un traitement antiviral et d’une surveillance prolongee. L’utilisation d’anticorps monoclonaux anti-CD20 (rituximab) est actuellement proposee.
- Published
- 2004
47. Lymphomes non hodgkiniens de l’enfant
- Author
-
Nicole Brousse, Viorel Vasiliu, Jean Michon, and Danielle Canioni
- Subjects
Pathology and Forensic Medicine - Abstract
Resume Les lymphomes non hodgkiniens representent environ 5 % des cancers de l’enfant et sont la 3 e cause de cancer apres les tumeurs cerebrales et les leucemies. Ils different des lymphomes de l’adulte car ils sont presque tous de haut grade histologique de malignite, ont une architecture diffuse et une atteinte frequente extra-ganglionnaire. Trois groupes histologiques predominent, le lymphome de Burkitt, de topographie essentiellement abdominale, le lymphome lymphoblastique de localisation mediastinale predominante et le lymphome anaplasique a grandes cellules. Ces tumeurs progressent vite. Le traitement est different pour les 3 groupes histologiques et necessite un diagnostic rapide et de certitude.
- Published
- 2004
48. Autoimmune enteropathy: molecular concepts
- Author
-
Nicole Brousse, Frank M. Ruemmele, and Olivier Goulet
- Subjects
business.industry ,Intestinal failure ,Immunology ,Gastroenterology ,medicine ,Autoimmune enteropathy ,medicine.disease ,business - Abstract
Enteropathies causing temporary or permanent intestinal failure are a big diagnostic and therapeutic challenge for pediatric gastroenterologists. A now well-recognized and distinct entity is in the form of "autoimmune enteropathy (AIE)". Recent advances in the molecular workup of AIE gave first insight into the pathophysiology of AIE. In this review, we discuss new molecular concepts of AIE resulting in new diagnostic and therapeutic possibilities.The identification of disease-causing mutations in the FOXP3 gene as a basic defect resulting in AIE points to a defect in regulatory T-cell homeostasis. FOXP3, primarily expressed by CD4+CD25+regulatory T cells, is a potent transcriptional suppressor and key modulator of T-cell functions. Nonfunctional FOXP3 leads to a tremendous hyperactivation of T cells, resulting in autoimmune aggression, such as seen in patients with immune dysregulation, polyendocrinopathy autoimmune enteropathy X-linked (IPEX) syndrome, a subgroup of AIE. There is recent evidence suggesting that a defect of regulatory factors other than FOXP3 might cause AIE. Anti-enterocyte autoantibodies, another main characteristic of AIE, seem to be of a secondary nature and can no more be considered as directly disease causing.Based on the profound immune dysregulation, new treatment strategies emerged for AIE. The use of T-cell immunosuppressive drugs, such as tacrolimus combined to steroids, seems to be beneficial in some patients; however, long-term remission is not always possible. Bone marrow transplantation might be the treatment of choice in those patients who do not respond to immunosuppression; however, the first encouraging results remain to be confirmed since to date long-term outcome remains mixed.
- Published
- 2004
49. Maladie de Hodgkin classique : biologie et formes frontières
- Author
-
Philippe Gaulard and Nicole Brousse
- Subjects
immune system diseases ,hemic and lymphatic diseases ,Pathology and Forensic Medicine - Abstract
Resume Les progres dans la biologie de la maladie de Hodgkin ont abouti a l’individualisation de deux entites, la maladie de Hodgkin « classique », et la maladie de Hodgkin nodulaire a predominance lymphocytaire, anterieurement appelee « paragranulome de Poppema et Lennert », dont les comportements cliniques different. Ils ont egalement permis d’affiner les criteres diagnostiques permettant de distinguer la maladie de Hodgkin de certains lymphomes non hodgkiniens pouvant lui ressembler comme le lymphome a grandes cellules anaplasiques, le lymphome a grandes cellules B riche en lymphocytes T et certains lymphomes T peripheriques, de type angioimmunoblastique (LAI). La cellule de Reed-Sternberg, cellule tumorale de la maladie de Hodgkin « classique », n’a pas encore revele tous ses secrets. Cependant, ces dernieres annees, les arguments en faveur de son origine lymphoide B se sont accumules. L’implication du virus d’Epstein-Barr, de la secretion de cytokines et d’une deregulation de l’expression d’oncogenes, dans la pathogenie de la maladie de Hodgkin peut etre avancee. En particulier, l’activation de la voie NF-kB et le role autocrine de l’interleukine 13 semblent jouer un role determinant.
- Published
- 2004
50. Bone marrow histological patterns can predict survival of patients with grade 1 or 2 follicular lymphoma: a study from the Groupe d‘Etude des Lymphomes Folliculaires
- Author
-
Luc Xerri, Michel Peuchmaur, Philippe Rousselot, Pauline Brice, Bruno Salles, Philippe Solal-Celigny, Véronique Meignin, Nicole Brousse, Myrna Chababi, Pierre-Yves Peaud, Eric Lepage, and Danielle Canioni
- Subjects
medicine.medical_specialty ,Pathology ,Hematology ,medicine.diagnostic_test ,Medullary cavity ,business.industry ,Follicular lymphoma ,Anatomical pathology ,Histology ,medicine.disease ,Gastroenterology ,medicine.anatomical_structure ,Internal medicine ,Biopsy ,Medicine ,Bone marrow ,business ,Grading (tumors) - Abstract
Summary The influence of bone marrow biopsy (BMB) histology on prognosis and management of follicular lymphomas (FL) remains controversial. A total of 390 patients with grade 1 or 2 FL were prospectively included in the multicentric Groupe d’Etude des Lymphomes Folliculaires trial and their BMB reviewed in order (i) to quantify the ratio of lymphomatous foci (LFo) area to that of BMB size (LFo/BMB), (ii) to determine the BMB patterns for a practical grading of marrow infiltration, (iii) to assess the intra- and interobserver reproducibility of this grading and (iv) to analyse this grading on event-free (EFS) and overall survival (OS), using univariate and multivariate analyses. A total of 267 patients (68%) had BMB involvement, with inter- and intra-observer reproducibility for classifying the patterns of involvement of 91 and 96%, respectively. Uni- and multivariate analyses demonstrated the adverse influence of (i) a ratio of LFo/BMB ‡0AE1, i.e. three or four nodules/ medullary space or ‡1 nodule + foci of diffuse involvement on EFS (P ¼ 0AE03) and (ii) two different histological patterns in the same BMB on EFS (P ¼ 0AE004) and OS (P ¼ 0AE001). This latter finding was only significant in patients with a high tumour burden and remained significant in multivariate analysis. These results indicate that BMB histology can predict survival of FL patients with a high tumour burden, and may help in defining their treatment.
- Published
- 2004
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.