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9 results on '"Axel, Lecesne"'

1. Doxorubicin alone versus doxorubicin with trabectedin followed by trabectedin alone as first-line therapy for metastatic or unresectable leiomyosarcoma (LMS-04): a randomised, multicentre, open-label phase 3 trial

Author

Patricia Pautier, Antoine Italiano, Sophie Piperno-Neumann, Christine Chevreau, Nicolas Penel, Nelly Firmin, Pascaline Boudou-Rouquette, François Bertucci, Corinne Balleyguier, Valérie Lebrun-Ly, Isabelle Ray-Coquard, Elsa Kalbacher, Aurélie Bardet, Emmanuelle Bompas, Olivier Collard, Nicolas Isambert, Cécile Guillemet, Maria Rios, Baptiste Archambaud, Florence Duffaud, Antoine ITALIANO, Patricia PAUTIER, Axel LECESNE, Sophie PIPERNO-NEUMANN, Christine CHEVREAU, Didier CUPISSOL, Nicolas PENEL, Jérôme ALEXANDRE, François BERTUCCI, Isabelle RAY-COQUARD, Valérie LEBRUN-LY, Elsa KALBACHER, Florence DUFFAUD, Corinne DELCAMBRE, Emmanuelle BOMPAS, Olivier COLLARD, Nicolas ISAMBERT, Cécile GUILLEMET, Patrick SOULIE, Maria RIOS, and Esma SAADA-BOUZID

Subjects
Oncology
Published
2022
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5. TNFR2/BIRC3-TRAF1 signaling pathway as a novel NK cell immune checkpoint in cancer

Author

Alexandre Ivagnès, Meriem Messaoudene, Gautier Stoll, Bertrand Routy, Aurélie Fluckiger, Takahiro Yamazaki, Kristina Iribarren, Connie P. M. Duong, Laetitia Fend, Anne Caignard, Isabelle Cremer, Axel LeCesne, Julien Adam, Charles Honoré, Olivier Mir, Loïc Chaigneau, Anne Berger, Pierre Validire, Christos Christidis, Valérie Le Brun-Ly, Mark J. Smyth, Xavier Mariette, Benoît L. Salomon, Guido Kroemer, Sylvie Rusakiewicz, and Laurence Zitvogel

Subjects
nk cells, cancer, immunity, immune checkpoint, tnfα, birc3, traf1, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Natural Killer (NK) cells control metastatic dissemination of murine tumors and are an important prognostic factor in several human malignancies. However, tumor cells hijack many of the NK cell functional features compromising their tumoricidal activity. Here, we show a deleterious role of the TNFα/TNFR2/BIRC3/TRAF1 signaling cascade in NK cells from the tumor microenvironment (TME). TNFα induces BIRC3/cIAP2 transcripts and reduces NKp46/NCR1 transcription and surface expression on NK cells, promoting metastases dissemination in mice and poor prognosis in GIST patients. NKp30 engagement, by promoting the release of TNFα, also contributes to BIRC3 upregulation, and more so in patients expressing predominantly NKp30C isoforms. These findings reveal that in the absence of IL-12 or a Th1-geared TME, TNFα can be considered as a negative regulatory cytokine for innate effectors.

Published
2018
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6. Attenuation of soft-tissue sarcomas resistance to the cytotoxic action of TNF-α by restoring p53 function.

Author

Jane Muret, Meriem Hasmim, Izabela Stasik, Abdelali Jalil, Aude Mallavialle, Arash Nanbakhsh, Ludovic Lacroix, Katy Billot, Véronique Baud, Jérome Thiery, Philippe Vielh, Philippe Terrier, Joelle Wiels, Lyubomir Vassilev, Axel Lecesne, Sylvie Bonvalot, and Salem Chouaib

Subjects
Medicine, Science
Abstract

BackgroundIsolated limb perfusion with TNF-α and melphalan is used with remarkable efficiency to treat unresectable limb sarcomas. Here we tested the ability of TNF-α to directly induce apoptosis of sarcoma cells. In addition, we investigated the impact of p53 in the regulation of such effect.Methodology/principal findingsWe first analysed the ability of TNF-α to induce apoptosis in freshly isolated tumour cells. For this purpose, sarcoma tumours (n = 8) treated ex vivo with TNF-α were processed for TUNEL staining. It revealed substantial endothelial cell apoptosis and levels of tumour cell apoptosis that varied from low to high. In order to investigate the role of p53 in TNF-α-induced cell death, human sarcoma cell lines (n = 9) with different TP53 and MDM2 status were studied for their sensitivity to TNF-α. TP53(Wt) cell lines were sensitive to TNF-α unless MDM2 was over-expressed. However, TP53(Mut) and TP53(Null) cell lines were resistant. TP53 suppression in TP53(Wt) cell lines abrogated TNF-α sensitivity and TP53 overexpression in TP53(Null) cell lines restored it. The use of small molecules that restore p53 activity, such as CP-31398 or Nutlin-3a, in association with TNF-α, potentiated the cell death of respectively TP53(Mut) and TP53(Wt)/MDM2(Ampl). In particular, CP-31398 was able to induce p53 as well as some of its apoptotic target genes in TP53(Mut) cells. In TP53(Wt)/MDM2(Ampl) cells, Nutlin-3a effects were associated with a decrease of TNF-α-induced NF-κB-DNA binding and correlated with a differential regulation of pro- and anti-apoptotic genes such as TP53BP2, GADD45, TGF-β1 and FAIM.Conclusion/significanceMore effective therapeutic approaches are critically needed for the treatment of unresectable limb sarcomas. Our results show that restoring p53 activity in sarcoma cells correlated with increased sensitivity to TNF-α, suggesting that this strategy may be an important determinant of TNF-α-based sarcomas treatment.

Published
2012
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7. Distal extremities soft tissue sarcomas: Are they so different from other limb localizations?

Author

Jean-Camille, Mattei, Véronique, Brouste, Philippe, Terrier, Sylvie, Bonvalot, Axel, Lecesne, Eberhard, Stoeckle, Antoine, Italiano, Dominique, Ranchere-Vince, Pierre, Meeus, Marick, Laé, Philippe, Rosset, Alexandre, Rochwerger, Jean Michel, Coindre, and Sébastien, Salas

Subjects
Adult, Male, Incidence, Humans, Extremities, Female, Sarcoma, Middle Aged, Neoplasm Metastasis, Neoplasm Recurrence, Local, Prognosis, Aged
Abstract

Soft tissue sarcoma localization in distal extremities (DESTS) of the limbs (hand/fingers, and foot/toes) is unusual. The literature is scarce about their behavior and this study was designed to assess their epidemiological characteristics, outcomes, and prognosis compared to other limb localizations (OLSTS).From 1980 to 2010, adult DESTS and OLSTS in 22 centers were included. Demographics, tumor type, treatment modalities, and latest follow-up status were collected. Primary endpoints were overall survival and local/metastatic recurrence incidences.Two hundred five DESTS and 3001 OLSTS were included. The patients were younger, with more female and smaller tumors in DESTS. There were more clear cell/epithelioid sarcomas, synovial sarcomas, and myxoid liposarcomas vs more dedifferentiated liposarcomas in OLSTS. DESTS tumors were less irradiated and more often amputated (24.3% vs 3.4%). The five-year survival rate was 78.2% compared to 68.6% in OLSTS and after multivariate analysis, STS localization did not impact survival or local/metastatic recurrence.Though rare and smaller than other limb localizations, DESTS are to be considered as aggressive. Despite a higher amputation rate, the prognosis remains the same as in OLSTS. Limb sparing vs amputation should be carefully assessed in DESTS, especially if grade 3 or of a poor prognosis histological subtype.

Published
2018

8. Germline

Author

Fanélie, Jouenne, Isaure, Chauvot de Beauchene, Emeline, Bollaert, Marie-Françoise, Avril, Olivier, Caron, Olivier, Ingster, Axel, Lecesne, Patrick, Benusiglio, Philippe, Terrier, Vincent, Caumette, Daniel, Pissaloux, Arnaud, de la Fouchardière, Odile, Cabaret, Birama, N'Diaye, Amélie, Velghe, Gaelle, Bougeard, Graham J, Mann, Serge, Koscielny, Jennifer H, Barrett, Mark, Harland, Julia, Newton-Bishop, Nelleke, Gruis, Remco, Van Doorn, Marion, Gauthier-Villars, Gaelle, Pierron, Dominique, Stoppa-Lyonnet, Isabelle, Coupier, Rosine, Guimbaud, Capucine, Delnatte, Jean-Yves, Scoazec, Alexander M, Eggermont, Jean, Feunteun, Luba, Tchertanov, Jean-Baptiste, Demoulin, Thierry, Frebourg, and Brigitte, Bressac-de Paillerets

Subjects
Male, Heterozygote, Receptor, Platelet-Derived Growth Factor alpha, Genes, p16, Sarcoma, Soft Tissue Neoplasms, Pedigree, Genetic Determinism, Exome Sequencing, Cyclin-Dependent Kinase Inhibitor p18, Humans, Female, Genetic Predisposition to Disease, Cyclin-Dependent Kinase Inhibitor p16, Germ-Line Mutation
Abstract

Sarcomas are rare mesenchymal malignancies whose pathogenesis is poorly understood; both environmental and genetic risk factors could contribute to their aetiology.We performed whole-exome sequencing (WES) in a familial aggregation of three individuals affected with soft-tissue sarcoma (STS) without TP53 mutation (Li-Fraumeni-like, LFL) and found a shared pathogenic mutation inGermline mutations in

Published
2016

9. Germline CDKN2A /P16INK4A mutations contribute to genetic determinism of sarcoma

Author

Gaëlle Pierron, Gaëlle Bougeard, Jean-Baptiste Demoulin, Axel Lecesne, Daniel Pissaloux, Emeline Bollaert, Thierry Frebourg, Brigitte Bressac-de Paillerets, Serge Koscielny, Capucine Delnatte, Jean-Yves Scoazec, Isaure Chauvot de Beauchêne, Jennifer H. Barrett, Philippe Terrier, Arnaud de la Fouchardière, Graham J. Mann, Isabelle Coupier, Nelleke A. Gruis, Jean Feunteun, Birama N’Diaye, Alexander M.M. Eggermont, Dominique Stoppa-Lyonnet, Olivier Ingster, Luba Tchertanov, Rosine Guimbaud, Patrick R. Benusiglio, Olivier Caron, Fanélie Jouenne, Marie-Françoise Avril, Marion Gauthier-Villars, Remco van Doorn, Julia Newton-Bishop, Vincent Caumette, Mark Harland, Amélie Velghe, Odile Cabaret, Immunologie intégrative des tumeurs (UMR 1186), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Technische Universität München [München] (TUM), De Duve Institute, Université Catholique de Louvain, Service de dermatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hematopoïèse et Cellules Souches (U362), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National du Cancer [Boulogne Billancourt] (INC), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Service de Pathologie [Centre Leon Berard], Centre Léon Bérard [Lyon], Service de génétique moléculaire, pharmacogénétique et hormonologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Inserm UMR837 Team 5, Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Centre for Atmospheric Science [Leeds] (NCAS), Natural Environment Research Council (NERC), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Leeds Institute of Cancer and Pathology [U.K.], Leiden University Medical Center (LUMC), Service de génétique, Institut Curie Paris, Unit of Somatic Genomics, Department of Genetics, Institut Curie, Paris Sciences et Lettres (PSL), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Gastro - Entérologie et Nutrition, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], CRLCC René Gauducheau, Tumeurs endocrines digestives : mécanismes de la tumorigenèse et de la progression tumorale, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hématopoïèse normale et pathologique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Centre de Mathématiques et de Leurs Applications (CMLA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Computational Algorithms for Protein Structures and Interactions (CAPSID), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Weastmead Institute for Medical Research and Melanoma Institute, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de Génétique Oncologique, Institut Curie [Paris], Unité d'Oncogénétique, CRLCC Val d'Aurelle - Paul Lamarque, Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Centre René Gauducheau, Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Institut Gustave Roussy ( IGR ), Immunologie intégrative des tumeurs ( UMR 1186 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Technical University of Munich ( TUM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Université d'Angers ( UA ) -CHU Angers, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de biostatistique et d'épidémiologie ( SBE ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), INSTITUT CURIE, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, Stabilité Génétique et Oncogenèse ( UMR 8200 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Mathématiques et de Leurs Applications ( CMLA ), École normale supérieure - Cachan ( ENS Cachan ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain = Catholic University of Louvain (UCL), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHAUVOT DE BEAUCHENE, Isaure, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Universiteit Leiden

Subjects
0301 basic medicine, medicine.medical_specialty, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV.CAN]Life Sciences [q-bio]/Cancer, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, PDGFRA, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Germline, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Loss of heterozygosity, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, [SDV.CAN] Life Sciences [q-bio]/Cancer, CDKN2A, Molecular genetics, Genetics, medicine, Genetic epidemiology, Hereditary Melanoma, neoplasms, Connective tissue disease, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, Cancer: dermatological, digestive system diseases, 3. Good health, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030220 oncology & carcinogenesis, Cancer research, Sarcoma, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract

International audience; BACKGROUND: Sarcomas are rare mesenchymal malignancies whose pathogenesis is poorly understood; both environmental and genetic risk factors could contribute to their aetiology.METHODS AND RESULTS: We performed whole-exome sequencing (WES) in a familial aggregation of three individuals affected with soft-tissue sarcoma (STS) without TP53 mutation (Li-Fraumeni-like, LFL) and found a shared pathogenic mutation in CDKN2A tumour suppressor gene. We searched for individuals with sarcoma among 474 melanoma-prone families with a CDKN2A-/+ genotype and for CDKN2A mutations in 190 TP53-negative LFL families where the index case was a sarcoma. Including the initial family, eight independent sarcoma cases carried a germline mutation in the CDKN2A/p16INK4A gene. In five out of seven formalin-fixed paraffin-embedded sarcomas, heterozygosity was lost at germline CDKN2A mutations sites demonstrating complete loss of function. As sarcomas are rare in CDKN2A/p16INK4A carriers, we searched in constitutional WES of nine carriers for potential modifying rare variants and identified three in platelet-derived growth factor receptor (PDGFRA) gene. Molecular modelling showed that two never-described variants could impact the PDGFRA extracellular domain structure.CONCLUSION: Germline mutations in CDKN2A/P16INK4A, a gene known to predispose to hereditary melanoma, pancreatic cancer and tobacco-related cancers, account also for a subset of hereditary sarcoma. In addition, we identified PDGFRA as a candidate modifier gene

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