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1. Neoadjuvant Nivolumab Plus Ipilimumab and Adjuvant Nivolumab in Localized Deficient Mismatch Repair/Microsatellite Instability–High Gastric or Esophagogastric Junction Adenocarcinoma: The GERCOR NEONIPIGA Phase II Study

Author: Thierry André, David Tougeron, Guillaume Piessen, Christelle de la Fouchardière, Christophe Louvet, Antoine Adenis, Marine Jary, Christophe Tournigand, Thomas Aparicio, Jérôme Desrame, Astrid Lièvre, Marie-Line Garcia-Larnicol, Thomas Pudlarz, Romain Cohen, Salomé Memmi, Dewi Vernerey, Julie Henriques, Jérémie H. Lefevre, Magali Svrcek, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Institut Mutualiste de Montsouris (IMM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), 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), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital privé Jean Mermoz [Lyon], Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Cooperator Multidisciplinary Oncology Group (GERCOR), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and We thank Bristol Myers Squibb for supplying nivolumab and ipilimumab and for the partial financial support and the ARCAD (Aide et Recherche en Cancérologie Digestive) Foundation for partial financial support.
Subjects: nivolumab, Cancer Research, clinical trial, gastroesophageal junction, [SDV.CAN]Life Sciences [q-bio]/Cancer, stomach tumor, Adenocarcinoma, tumor recurrence, DNA Mismatch Repair, phase 2 clinical trial, mismatch repair, Oncology, Stomach Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Humans, pathology, Microsatellite Instability, genetics, Esophagogastric Junction, human, neoadjuvant therapy, Neoplasm Recurrence, Local, ipilimumab, antineoplastic agent, Aged
Abstract: PURPOSE In patients with resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma, surgery plus perioperative platinum-based chemotherapy is the standard of care. Perioperative chemotherapy remains debatable for gastric/GEJ adenocarcinoma with deficient mismatch repair (dMMR)/microsatellite instability–high (MSI-H). PATIENTS AND METHODS NEONIPIGA (ClinicalTrials.gov identifier: NCT04006262 ) phase II study evaluated neoadjuvant nivolumab 240 mg once every two weeks ×6 and ipilimumab 1 mg/kg once every six weeks ×2, followed by surgery and adjuvant nivolumab 480 mg once every four weeks (nine injections) in patients with locally advanced resectable dMMR/MSI-H, clinical (c) tumor (T)2-T4 node (N)x metastasis (M)0 gastric/GEJ adenocarcinoma. The primary end point was a pathological complete response (pCR) rate. RESULTS Between October 2019 and June 2021, 32 patients with dMMR/MSI-H gastric/GEJ adenocarcinoma were enrolled. The median age was 65.5 years (range, 40-80). Clinical stages were cT2-T3N0 (n = 9), cT2-T3N1 (n = 22), and cT3N1M1 (n = 1, wrongly included). With a median follow-up of 14.9 months (95% CI, 10.6 to 17.6), 32 patients received neoadjuvant immunotherapy (27 patients completed all cycles). Neoadjuvant therapy-related grade 3/4 adverse events occurred in six patients (19%). Twenty-nine patients underwent surgery; three did not have surgery and had complete endoscopic response with tumor-free biopsies and a normal computed tomography scan (two refused surgery and one had metastasis at inclusion). The rate of surgical morbidity (Clavien-Dindo classification) was 55% (one postoperative death occurred). All 29 patients had an R0 resection, and 17 (58.6%; 90% CI, 41.8 to 74.1) had pCR (pathological T0N0). Becker tumor regression grades 1a, 1b, 2, and 3 were observed in 17 patients, three (including two pathological T0N1), two, and seven patients, respectively. Of the 29 patients with surgery, 23 received adjuvant nivolumab. At database lock, no patient had relapse and one died without relapse. CONCLUSION Nivolumab and ipilimumab-based neoadjuvant therapy is feasible and associated with no unexpected toxicity and a high pCR rate in patients with dMMR/MSI-H resectable gastric/GEJ adenocarcinoma.
Published: 2023
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2. Chemotherapy in advanced pancreatic adenosquamous carcinoma: A retrospective multicenter AGEO study

Author: Marie Auvray Kuentz, Vincent Hautefeuille, Louis de Mestier, Clélia Coutzac, Thierry Lecomte, Victor Nardon, Pascal Artru, Anthony Turpin, Antoine Drouillard, David Malka, My‐Linh Tran‐Minh, Isabelle Trouilloud, Astrid Lièvre, Nicolas Williet, Simon Pernot, Yann Touchefeu, Julien Taieb, Pascal Hammel, Aziz Zaanan, 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), CHU Amiens-Picardie, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Léon Bérard [Lyon], Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Strasbourg Europe (ICANS), Hôpital privé Jean Mermoz [Lyon], CHU Lille, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Gustave Roussy (IGR), Département de médecine oncologique, CRLCC Paul Strauss, Hopital Saint-Louis [AP-HP] (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pontchaillou [Rennes], Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut Bergonié [Bordeaux], UNICANCER, Centre hospitalier universitaire de Nantes (CHU Nantes), Cancer Research and Personalized Medicine - CARPEM [Paris], 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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], and None
Subjects: Cancer Research, Oncology, adenosquamous carcinoma, advanced disease, pancreatic cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, chemotherapy
Abstract: International audience; Pancreatic adenosquamous carcinoma (PASC) account for < 5% of pancreatic malignancies. The efficacy of modern chemotherapy regimens in patients with advanced PASC is unknown. Patients with advanced PASC from 2008 to 2021 were consecutively included in this retrospective multicenter study. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method. Ninety-four PASC from 16 French centers were included (median age, 67.3 years; males, 56.4%; metastatic disease, 85.1%). The first-line treatment was chemotherapy for 79 patients (84.0%) (37 FOLFIRINOX (FX), 7 Gemcitabine-nab paclitaxel (GN) and 35 for all other regimen) or best supportive care (BSC) alone for 15 patients (16.0%). No significant difference was observed between FX and GN in terms of PFS (P = .67) or OS (P = .5). Modern regimens pooled together (FX and GN) as compared to all others chemotherapy regimens showed an improvement of overall response rate (39.5% and 9.7%, P = .002), PFS (median, 7.8 vs 4.7 months, P = .02) and OS (median, 12.7 vs 9.2 months, P = .35). This large study evaluating first-line treatment regimens in advanced PASC suggests that modern regimens as FX or GN may be preferable to all other chemotherapy regimens. These results deserve confirmation in prospective studies.
Published: 2023
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3. Outcome of Patients With Resected Early-Stage Non-small Cell Lung Cancer and EGFR Mutations: Results From the IFCT Biomarkers France Study

Author: Pierre, Mordant, Solenn, Brosseau, Bernard, Milleron, Nicola, Santelmo, Séverine, Fraboulet-Moreau, Benjamin, Besse, Alexandra, Langlais, Dominique, Gossot, Pascal-Alexandre, Thomas, Jean-Louis, Pujol, Charles, Ricordel, Jeannick, Madelaine, Régine, Lamy, Clarisse, Audigier-Valette, Pascale, Missy, Hélène, Blons, Fabrice, Barlesi, Virginie, Westeel, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Institut Mutualiste de Montsouris (IMM), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and This work was supported by the IFCT. The funding sources had no role in the design, data collection, analysis, or interpretation of the study, or in the preparation of this manuscript
Subjects: Molecular profile, Pulmonary and Respiratory Medicine, Cancer Research, Lung Neoplasms, Stage I-II disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, NSCLC, Prognosis, Small Cell Lung Carcinoma, ErbB Receptors, Oncology, Carcinoma, Non-Small-Cell Lung, Mutation, Humans, Female, Surgery, Prospective Studies, Biomarkers, Neoplasm Staging
Abstract: International audience; INTRODUCTION: Molecular profile of resected stage I-II non-small cell lung cancer (NSCLC) would help refine prognosis and personalize induction or adjuvant strategies. We sought to report the molecular profile of resected stage I-II NSCLC and analyzed the impact of epidermal growth factor receptor (EGFR) mutations on outcomes in a Western population. PATIENTS AND METHODS: Surgical cases were identified from Biomarkers France study, a nationwide prospective study including NSCLC patients screened for EGFR, HER2, KRAS, BRAF, PIK3CA, ALK alterations from 2012 to 2013. Among surgical patients, clinical charts of the largest centers were reviewed in order to analyze the prognostic impact of EGFR mutations. RESULTS: In the BMF database (n = 17.636), surgical patients (n = 854) were characterized by a higher proportion of EGFR mutations than nonsurgical patients (12.9% vs. 10.2%, P = .025), while the other molecular alterations did not differ. The proportion of EGFR mutations was 27% in women undergoing surgery. In the study group (n = 293; EGFR wild type, n = 235; usual mutation, n = 50; rare mutation, n = 8), after a median follow-up of 67 months, 215 patients (74.4%) had not relapsed. No difference was found between EGFR-mutant and EGFR-wt tumors regarding recurrence site, disease-free survival, and overall survival. The 5-year disease-free survival and overall survival after surgical resection of stage I-II EGFR-mutated tumors were 65% and 75%, respectively. CONCLUSION: In resected stage I to II NSCLC, EGFR mutations were found in 12.9% of cases, associated with a 5-year overall survival of 75%, with no impact on recurrence site, disease-free survival, and overall survival.
Published: 2023
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4. The Appendix Orchestrates T-Cell Mediated Immunosurveillance in Colitis-Associated Cancer

Author: Tourneur-Marsille J, Nathalie Guedj, Mathieu Uzzan, M. Collard, Yves Panis, Jean-Pierre Hugot, Dumay A, Jean-Noël Freund, Maryline Roy, Xavier Treton, Eric Ogier-Denis, M. Albuquerque, Service de Chirurgie colorectale [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de Gastroentérologie [Hôpital Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Oncogenesis, Stress, Signaling (OSS), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Lymphocyte, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, Internal medicine, Laparotomy, medicine, Appendectomy, Ulcerative Colitis, Colitis, Hepatology, business.industry, Inflammatory Bowel Disease, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Appendicitis, Ulcerative colitis, Appendix, Immunosurveillance, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, business, CD8
Abstract: ObjectiveWhile appendectomy may reduce colorectal inflammation in patients with ulcerative colitis (UC), appendectomy has been suggested to be associated with an increased risk of colitis-associated cancer (CAC). The aim of this study was to explore the mechanism underlying the appendectomy-associated increased risk of CAC.DesignFive-week-old male BALB/c mice underwent appendectomy, appendicitis induction or sham laparotomy. They were then exposed to azoxymethane/dextran sodium sulfate (AOM/DSS) to induce CAC. Mice were sacrificed 12 weeks later, and colons were taken for pathological analysis and immunohistochemistry (CD3 and CD8 staining). Human colonic tumors from 21 UC patients who underwent surgical resection for CAC were immunophenotyped and stratified according to the appendectomy status.ResultsWhile appendectomy significantly reduced colitis severity and increased CAC number, appendicitis induction without appendectomy led to opposite results. Intra-tumor CD3+ and CD8+ T-cell densities were lower after appendectomy and higher after appendicitis induction compared to the sham laparotomy group. Blocking lymphocyte trafficking to the colon with the anti-α4β7 integrin antibody or a sphingosine-1-phosphate receptor agonist suppressed the inducing effect of the appendectomy on tumors’ number and on CD3+/CD8+ intra-tumoral density. CD8+ or CD3+ T cells isolated from inflammatory neo-appendix and intravenously injected into AOM/DSS-treated recipient mice increased CD3+/CD8+ T-cell tumor infiltration and decreased tumor number. In UC patients with a history of appendectomy, intra-tumor CD3+ and CD8+ T-cell densities were decreased compared to UC patients without history of appendectomy.ConclusionsIn UC, appendectomy could suppress a major site of T-cell priming resulting in a less efficient CAC immunosurveillance.Significance of this studyWhat is already known on this subject?The protective effect of preemptive appendectomy is currently investigated as a therapy for refractory ulcerative colitis (UC), with encouraging results.An increased risk of developing colitis-associated cancer (CAC) caused by this promising treatment has been identified.Since it is commonly accepted that CAC is related to colitis severity and extent, this finding is counterintuitive and the mechanisms of this paradoxical effect remain unknown.What are the new findings?In a mouse model of CAC, less extended colitis associated with an increased number of tumors was observed. Intra-tumor T-cell infiltration was significantly reduced after appendectomy. Blocking lymphocyte trafficking to the colon with current or experimental UC treatments mimicked the appendectomy-associated phenotype whereas neo-appendicitis or appendix-primed T-cell injection in recipient mice increased intra-tumor T-cell infiltration and strengthened protection against CAC.In UC patients with CAC, appendectomy was associated with a decreased intra-tumor T-cell infiltration.These findings suggest that, in UC, appendectomy could suppress a major site of T-cell priming in the colon, resulting in a reduced CAC immunosurveillance.How might it impact on clinical practice in the foreseeable future?This work emphasizes the fact that precautions will be necessary if appendectomy becomes an accepted therapeutic option for the treatment of refractory UC.Innovative cell-based therapies and immunotherapies, such as the administration of stimulated autologous appendicular T cells in patients with CAC are promising options.
Published: 2023
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5. LARS2 variants can present as premature ovarian insufficiency in the absence of overt hearing loss

Author: Anne Sophie Neyroud, Joëlle Rudinger-Thirion, Magali Frugier, Lisa G. Riley, Maud Bidet, Linda Akloul, Andrea Simpson, David Gilot, John Christodoulou, Célia Ravel, Andrew H. Sinclair, Marc-Antoine Belaud-Rotureau, Elena J. Tucker, Sylvie Jaillard, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), The University of Sydney, Clinique mutualiste La Sagesse, La Trobe University [Melbourne], Charles Darwin University [Australia], Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Melbourne, Murdoch Children's Research Institute (MCRI), and This work was supported by a CHU Rennes grant (Appel à Projets Innovations 2019 to SJ), an Australian NHMRC program grant (1074258 to AHS), NHMRC fellowships (1054432 to EJT, 1062854 to AHS) and an Australian Mito Foundation grant (EJT). Part of this work was performed under the Rare Diseases Functional Genomics program, supported by the Luminesce Alliance—Innovation for Children’s Health, a not for profit cooperative joint venture between the Sydney Children’s Hospitals Network, the Children’s Medical Research Institute, and the Children’s Cancer Institute. It has been established with the support of the NSW Government to coordinate and integrate pediatric research. Luminesce Alliance is also affiliated with the University of Sydney and the University of New South Wales Sydney (LGR). The research conducted at the Murdoch Children’s Research Institute was supported by the Victorian government’s operational infrastructure support program. The Chair in Genomic Medicine awarded to JC is generously supported by The Royal Children’s Hospital Foundation.
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, Genetics, Genetics (clinical)
Abstract: International audience; Premature ovarian insufficiency (POI) affects 1 in 100 women and is a leading cause of female infertility. There are over 80 genes in which variants can cause POI, with these explaining only a minority of cases. Whole exome sequencing (WES) can be a useful tool for POI patient management, allowing clinical care to be personalized to underlying cause. We performed WES to investigate two French sisters, whose only clinical complaint was POI. Surprisingly, they shared one known and one novel likely pathogenic variant in the Perrault syndrome gene, LARS2. Using amino-acylation studies, we established that the novel missense variant significantly impairs LARS2 function. Perrault syndrome is characterized by sensorineural hearing loss in addition to POI. This molecular diagnosis alerted the sisters to the significance of their difficulty in following conversation. Subsequent audiology assessment revealed a mild bilateral hearing loss. We describe the first cases presenting with perceived isolated POI and causative variants in a Perrault syndrome gene. Our study expands the phenotypic spectrum associated with LARS2 variants and highlights the clinical benefit of having a genetic diagnosis, with prediction of potential co-morbidity and prompt and appropriate medical care, in this case by an audiologist for early detection of hearing loss.
Published: 2022
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6. Lanreotide as maintenance therapy after first-line treatment in patients with non-resectable duodeno-pancreatic neuroendocrine tumours: An international double-blind, placebo-controlled randomised phase II trial – Prodige 31 REMINET: An FFCD study

Author: Côme Lepage, Jean-Marc Phelip, Astrid Lievre, Karine Le-Malicot, Laetitia Dahan, David Tougeron, Christos Toumpanakis, Frédéric Di-Fiore, Catherine Lombard-Bohas, Ivan Borbath, Romain Coriat, Thierry Lecomte, Rosine Guimbaud, Caroline Petorin, Jean-Louis Legoux, Pierre Michel, Jean-Yves Scoazec, Denis Smith, Thomas Walter, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Hôpital de la Timone [CHU - APHM] (TIMONE), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Royal Free Hospital [London, UK], Communications Cellulaires et Différenciation (CCD), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Cliniques Universitaires Saint-Luc [Bruxelles], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut Gustave Roussy (IGR), Département de biologie et pathologie médicales [Gustave Roussy], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Amgen, Bristol-Myers Squibb, BMS, Bayer, Merck, Novartis, Roche, Celgene, Sandoz, Advanced Accelerator Applications, AAA, Agence Nationale de la Recherche, ANR: ANR-11-LABX-0021, Ligue Contre le Cancer, Servier, Ipsen, and ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer(2011)
Subjects: Pancreatic Neoplasms, Clinical trial, Neuroendocrine Tumors, Cancer Research, Neuroendocrine tumours, Oncology, Duodeno-pancreatic, Maintenance, Non-resectable, Humans, [SDV.CAN]Life Sciences [q-bio]/Cancer, Somatostatin, Peptides, Cyclic
Abstract: International audience; Background: Following European guidelines, patients with aggressive metastatic or locally advanced, non-resectable, duodeno-pancreatic (DP) neuroendocrine tumours (NETs) should receive systemic combination chemotherapy until progression. Aggressive disease is defined as progressive and/or symptomatic metastases with or without significant hepatic invasion (>30–50%), and/or bone metastases. Methods: This academic randomised, double-blind, placebo-controlled phase II study aims to evaluate lanreotide autogel 120 mg (LAN) as maintenance treatment after at least 2 months of first-line treatment (L1) in aggressive G1-G2 DP-NET. Patients were randomly assigned in a 1:1 ratio to receive LAN or placebo (PBO), every 28 days, until progression or toxicity. The primary end-point was progression-free survival (PFS) at 6 months. Results: Among the 118 planned patients, 53 were included. Of these, 81.1% had a G2 tumour, and 90.6% had metastatic disease. L1 therapy consisted of chemotherapy (96.8%). Median duration of L1 was 4.6 months (range: 2.0–7.7). At the time of randomisation, 81.1% of patients had stable disease. Median follow-up was 27.0 months (95% CI: 19.5; 31.2). PFS at 6 months was 73.1% (90% CI: 55.3; 86.6) in LAN versus 54.2% (90% CI: 35.8; 71.8) in PBO. Median PFS was 19.4 months (95% CI: 7.6; 32.6) and 7.6 months (95% CI: 3.0; 9.0), respectively. Median overall survival was 41.9 months in PBO and was not reached in LAN. The toxicity profile was mainly grade 1–2 expected toxicities. Conclusions: The encouraging results of lanreotide autogel 120 mg as a maintenance treatment after L1 in aggressive G1/2 DP-NET should be confirmed. Trial registration: NCT02288377 (clinicaltrials.gov). © 2022 The Authors
Published: 2022
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7. Safety of Extended-Interval Dosing Strategy of Immune Checkpoint Inhibitors for Advanced NSCLC

Author: Clémence Pierre, Thomas Goter, Hervé Lena, Yannick Le Guen, Charles Ricordel, CHU Pontchaillou [Rennes], Oncogenesis, Stress, Signaling (OSS), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Pulmonary and Respiratory Medicine, Oncology, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience
Published: 2023
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8. Dominant TP63 missense variants lead to constitutive activation and premature ovarian insufficiency

Author: Elena J. Tucker, Niklas Gutfreund, Marc‐Antoine Belaud‐Rotureau, David Gilot, Tiffany Brun, Brianna L. Kline, Katrina M. Bell, Mathilde Domin‐Bernhard, Camille Théard, Philippe Touraine, Gorjana Robevska, Jocelyn van van den Bergen, Katie L. Ayers, Andrew H. Sinclair, Volker Dötsch, Sylvie Jaillard, University of Melbourne, Murdoch Children's Research Institute (MCRI), Institute of Biochemistry and Signal Transduction [Hamburg, Germany], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], CRLCC Eugène Marquis (CRLCC), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de référence Maladies Rares CLAD-Ouest [Rennes], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and This study was supported by a CHU Rennes grant (Appel à Projets Innovations 2019 to SJ), an Australian National Health and Medical Research Council (NHMRC) program grant (1074258 to AHS), NHMRC fellowships (1054432 to EJT, 1062854 to AHS), a Suzi Carp postdoctoral scholarship (to EJT) and the Deutsche Forschungsgemeinschaft (DO 545/18-1). The research conducted at the Murdoch Children's Research Institute was supported by the Victorian government's operational infrastructure support program. We thank the Bioinformatic department of Rennes University Hospital (Pr M. De Tayrac and Dr W. Carré) for technical assistance. Open access publishing facilitated by The University of Melbourne, as part of the Wiley - The University of Melbourne agreement via the Council of Australian University Librarians.
Subjects: premature ovarian insufficiency, [SDV]Life Sciences [q-bio], Tumor Suppressor Proteins, Mutation, Missense, Primary Ovarian Insufficiency, TAp63α, genomic diagnosis, Genetics, Humans, Female, TP63, infertility, p63 isoforms, Genetics (clinical), Transcription Factors
Abstract: International audience; Premature ovarian insufficiency (POI) is a leading form of female infertility, characterised by menstrual disturbance and elevated follicle-stimulating hormone before age 40. It is highly heterogeneous with variants in over 80 genes potentially causative, but the majority of cases having no known cause. One gene implicated in POI pathology is TP63. TP63 encodes multiple p63 isoforms, one of which has been shown to have a role in the surveillance of genetic quality in oocytes. TP63 C-terminal truncation variants and N-terminal duplication have been described in association with POI, however, functional validation has been lacking. Here we identify three novel TP63 missense variants in women with nonsyndromic POI, including one in the N-terminal activation domain, one in the C-terminal inhibition domain, and one affecting a unique and poorly understood p63 isoform, TA*p63. Via blue-native page and luciferase reporter assays we demonstrate that two of these variants disrupt p63 dimerization, leading to constitutively active p63 tetramer that significantly increases the transcription of downstream targets. This is the first evidence that TP63 missense variants can cause isolated POI and provides mechanistic insight that TP63 variants cause POI due to constitutive p63 activation and accelerated oocyte loss in the absence of DNA damage.
Published: 2022
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9. Prognostic impact of cytoreductive surgery conducted with primary intent, versus cytoreductive surgery after neoadjuvant chemotherapy, in the management of patients with advanced epithelial ovarian cancers: a multicentre, propensity score‐matched study from the <scp>FRANCOGYN</scp> group

Author: Henri Wohrer, Meriem Koual, Enrica Bentivegna, Louise Benoit, Marie Metairie, Pierre‐Adrien Bolze, Yohan Kerbage, Emilie Raimond, Cherif Akladios, Xavier Carcopino, Geoffroy Canlorbe, Jennifer Uzan, Vincent Lavoue, Camille Mimoun, Cyrille Huchon, Martin Koskas, Hélène Costaz, François Margueritte, Yohann Dabi, Cyril Touboul, Sofiane Bendifallah, Lobna Ouldamer, Nicolas Delanoy, Huyen‐Thu Nguyen‐Xuan, Anne‐Sophie Bats, Henri Azaïs, 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), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Cancer Research and Personalized Medicine - CARPEM [Paris], 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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and None
Subjects: epithelial ovarian cancer, interval cytoreductive surgery, Obstetrics and Gynecology, [SDV.CAN]Life Sciences [q-bio]/Cancer, primary cytoreductive surgery, propensity score, neoadjuvant chemotherapy
Abstract: International audience; Objective: To compare survival and morbidity rates between primary cytoreductive surgery (pCRS) and interval cytoreductive surgery (iCRS) for epithelial ovarian cancer (EOC), using a propensity score.Design: We conducted a propensity score-matched cohort study, using data from the FRANCOGYN cohort.Setting: Retrospective, multicentre study of data from patients followed in 15 French department specialized in the treatment of ovarian cancer.Sample: Patients included were those with International Federation of Gynaecology and Obstetrics (FIGO) stage III or IV EOC, with peritoneal carcinomatosis, having undergone CRS.Methods: The propensity score was designed using pre-therapeutic variables associated with both treatment allocation and overall survival (OS).Main outcome measures: The primary outcome was OS. Secondary outcomes included recurrence-free survival (RFS), quality of CRS and other variables related to surgical morbidity.Results: A total of 513 patients were included. Among these, 334 could be matched, forming 167 pairs. No difference in OS was found (hazard ratio, HR = 0.8, p = 0.32). There was also no difference in RFS (median = 26 months in both groups) nor in the rate of CRS leaving no macroscopic residual disease (pCRS 85%, iCRS 81.4%, p = 0.76). The rates of gastrointestinal tract resections, stoma, postoperative complications and hospital stay were significantly higher in the pCRS group.Conclusions: Analysis of groups of patients made comparable by propensity score matching showed no difference in survival, but lower postoperative morbidity in patients treated with iCRS.
Published: 2023
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10. Virtual Reality as a Hypnotic Tool in the Management of Anxiety During the Performance of the Axillary Block

Author: Lopes, Kelly, Dessieux, Thierry, Rousseau, Chloe, Beloeil, Hélène, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and None
Subjects: Anaesthesia, Perioperative anxiety, Health Information Management, [SDV]Life Sciences [q-bio], Axillary block, Medicine (miscellaneous), Hypnotic tool, Health Informatics, Virtual reality, Information Systems
Abstract: International audience; Regional anaesthesia is a gold standard in upper limb orthopaedic surgery. Carried out on an awake patient, it can be a source of anxiety. In recent years, hypnotic techniques have been proposed in the management of perioperative anxiety. Among them, virtual reality is increasingly used as a distraction tool during anxious or painful actions despite the scarcity of proof of its benefit in the literature. Before implementing the systematic use of virtual reality when performing regional anaesthesia in our institution, we designed a study hypothesizing that the use of a virtual reality headset when performing an axillary block would reduce patient's anxiety. The study is an investigator-initiated, prospective monocentric and observational trial comparing anxiety scores of patients who underwent upper limb surgery under an axillary block with or without virtual reality headset. The perioperative anxiety was assessed by a numerical range scale before and after the peripheral nerve block performance. Between June 2021 and June 2022, 99 patients were included: 53 wearing the virtual reality headset and 46 not. The difference in numerical range scale for anxiety before and after the axillary block performance did not differ in the virtual reality group compared to the group without headset (mean = -1.9 +/- 2.5 vs -1.5 +/- 2.0, (p = 0.2520)). Technical difficulties reported by the operators were similar in both groups. Despite the large number of patients included, the virtual reality headset did not reduce patient's anxiety during a peripheral nerve block. Perioperative anxiety was low in all patients.
Published: 2023
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11. Pulmonary manifestations induced by osimertinib

Author: Le Guen, Y, Lederlin, M, Triquet, L, Lesouhaitier, M, Le Tulzo, Y, Ricordel, C, CHU Pontchaillou [Rennes], Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and CRLCC Eugène Marquis (CRLCC)
Subjects: Pulmonary and Respiratory Medicine, 0303 health sciences, Pneumopathie interstitielle, Adverse drug reactions, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, respiratory tract diseases, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Effets secondaires indésirables des médicaments, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cancer bronchique, Lung cancer, Osimertinib, Interstitial pneumonia, 030304 developmental biology
Abstract: National audience; INTRODUCTION: The third-generation tyrosine kinase inhibitor (TKI) osimertinib is recommended as a first-line treatment in advanced non-small cell lung cancer harboring an activating mutation of Epidermal Growth Factor Receptor (EGFR). Adverse pulmonary events related to osimertinib exposure have been reported, primarily in Japanese patients. They rarely occur in the Caucasian population. OBSERVATION: Herein we report two clinical cases of osimertinib-induced lung toxicities in patients diagnosed with advanced lung adenocarcinoma harboring an EGFR mutation. In the first case, interstitial pneumonia was asymptomatic and evolved favorably after osimertinib discontinuation. The second patient presented a more extensive form of lung injuries and despite systemic corticosteroid therapy, the evolution was fatal. CONCLUSION: Osimertinib-related lung toxicities remain exceptional. While most forms are mild, consideration of TKI treatment discontinuation may be necessitated. Introduction of another TKI or rechallenge with osimertinib might be considered along with corticosteroid therapy if necessary. Diffuse alveolar damage is a pejorative prognostic factor.
Published: 2022
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12. Should we screen for colorectal cancer in people aged 75 and over? A systematic review - collaborative work of the French geriatric oncology society (SOFOG) and the French federation of digestive oncology (FFCD)

Author: Lydia, Guittet, Valérie, Quipourt, Thomas, Aparicio, Elisabeth, Carola, Jean-François, Seitz, Elena, Paillaud, Astrid, Lievre, Rabia, Boulahssass, Carole, Vitellius, Leila, Bengrine, Florence, Canoui-Poitrine, Sylvain, Manfredi, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Marseille, 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), Cancer Research and Personalized Medicine - CARPEM [Paris], 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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], IHFIH UPRES EA 3859, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CHU Henri Mondor [Créteil], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and None
Subjects: Aged, 80 and over, Cancer Research, Harms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Colonoscopy, Comorbidity, Cost effectiveness, Life Expectancy, Acceptability, Oncology, Genetics, Humans, Mass Screening, Colorectal Neoplasms, Early Detection of Cancer, Simulation, Aged
Abstract: Background We have done a systematic literature review about CRC Screening over 75 years old in order to update knowledge and make recommendations. Methods PUBMED database was searched in October 2021 for articles published on CRC screening in the elderly, and generated 249 articles. Further searches were made to find articles on the acceptability, efficacy, and harms of screening in this population, together with the state of international guidelines. Results Most benefit-risk data on CRC screening in the over 75 s derived from simulation studies. Most guidelines recommend stopping cancer screening at the age of 75. In private health systems, extension of screening up to 80–85 years is, based on the life expectancy and the history of screening. Screening remains effective in populations without comorbidity given their better life-expectancy. Serious adverse events of colonoscopy increase with age and can outweigh the benefit of screening. The great majority of reviews concluded that screening between 75 and 85 years must be decided case by case. Conclusion The current literature does not allow Evidence-Based Medicine propositions for mass screening above 75 years old. As some subjects over 75 years may benefit from CRC screening, we discussed ways to introduce CRC screening in France in the 75–80 age group. IRB An institutional review board composed of members of the 2 learned societies (SOFOG and FFCD) defined the issues of interest, followed the evolution of the work and reviewed and validated the report.
Published: 2023
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13. Immune checkpoint inhibitors in patients aged 80 or older with advanced non-small cell lung cancer or melanoma: a real-life multicentre study

Author: Soraya Benguerfi, Thierry Lesimple, Roch Houot, Charles Ricordel, Delphine Legoupil, Corinne Alleaume, Régine Lamy, Delphine Deniel Lagadec, Romain Corre, CHU Pontchaillou [Rennes], Centre Eugène Marquis (CRLCC), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU de Saint-Brieuc, Groupe Hospitalier Bretagne Sud (GHBS), and Centre Hospitalier Intercommunal de Cornouaille (CHIC)
Subjects: safety, Aged, 80 and over, Lung Neoplasms, efficacy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, General Medicine, elderly, Oncology, Carcinoma, Non-Small-Cell Lung, Humans, Radiology, Nuclear Medicine and imaging, Immune Checkpoint Inhibitors, Melanoma, non-small cell lung cancer, Aged, Retrospective Studies
Abstract: International audience; Background Data regarding characteristics, safety and survival outcomes of patients aged 80 or older treated with immune checkpoint inhibitors (ICI) in routine oncology practice are limited. Materials and methods We retrospectively collected data of patients aged 80 and older with advanced non-small cell lung cancer (NSCLC) or melanoma treated with anti-PD1, anti-PD-L1 or anti-CTLA-4 regardless of the treatment line, in 14 institutions, between January 2014 and June 2017. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan Meier method. Toxicity was assessed according to CTCAE 5.0. Multivariate analyses were performed with the Cox model. Results Eighty-two patients were included (36 with NSCLC, 45 with melanoma). Their median age was 82 years (range 80-93). Nivolumab and pembrolizumab were mainly used. In the NSCLC group, median PFS and OS were 2.3 months (95%CI 1.8-6.1) and 8.8 months (95%CI 5.5-18.1), respectively. In the melanoma group, median PFS and OS were 10.2 months (95%CI 4.5-20.0) and 24.5 months (95%CI 14.1-NR), respectively. The albumin level was found to be independently associated with a better OS in both groups. Grade 3-4 toxicities occurred in 15 patients (18.5%). One patient died from ICI-induced pulmonary toxicity. Conclusion Our study findings suggest that treatment with ICI in elderly patients with NSCLC and melanoma has a risk-benefit ratio that supports its use. However, we report in this cohort that one in five patients has a grade 3-4 IRAEs leading to treatment discontinuation. Geriatric assessment prior to initiation of therapy and during therapy should be routine in patients aged 80 years and older.
Published: 2022
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14. Practicalities accessing precision medicine in biliary tract cancer

Author: Julien Edeline, Angela Lamarca, Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Christie NHS Foundation Trust [Manchester, Royaume-Uni], and Fundacion Jimenez Diaz [Madrid] (FJD)
Subjects: Biliary Tract Neoplasms, Hepatology, Gastroenterology, Humans, [SDV.CAN]Life Sciences [q-bio]/Cancer, human, personalized medicine, biliary tract tumor, Precision Medicine
Abstract: International audience; [No abstract available]
Published: 2022
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15. Opioid-Sparing Techniques in Orthopedic Anesthesia-One Step to Opioid-Free Anesthesia?

Author: Helene Beloeil, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogenesis, Stress, Signaling (OSS), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Analgesics, Opioid, Pain, Postoperative, Anesthesiology and Pain Medicine, Opioid-free, [SDV]Life Sciences [q-bio], Humans, Anesthesia, General Medicine, Opioid sparing, Orthopedic anesthesia
Abstract: International audience; Opioid-free anesthesia is a multimodal anesthesia aimed at avoiding the negative impact of intraoperative opioid on patient’s postoperative outcomes. It is based on the physiology of pathways involved in intraoperative nociception. It has been shown to be feasible but the literature is still scarce on the clinically meaningful benefits as well as on the side effects and/or complications that might be associated with it. Moreover, most studies involved abdominal and/or bariatric surgery. Procedure-specific studies are lacking, especially in orthopedics.
Published: 2022
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16. Treatment, outcome, and prognostic factors in non-metastatic anal cancer: The French nationwide cohort study FFCD-ANABASE

Author: Vendrely, Véronique, Lemanski, Claire, Pommier, Pascal, Le Malicot, Karine, Saint, Angélique, Rivin del Campo, Eleonor, Regnault, Pauline, Baba-Hamed, Nabil, Ronchin, Philippe, Crehange, Gilles, Tougeron, David, Menager-Tabourel, Elodie, Diaz, Olivia, Hummelsberger, Michael, Minsat, Mathieu, Drouet, Franck, Larrouy, Anne, Peiffert, Didier, Lievre, Astrid, Zasadny, Xavier, Hautefeuille, Vincent, Mornex, Françoise, Lepage, Côme, Quero, Laurent, BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Institut du Cancer de Montpellier (ICM), Centre Léon Bérard [Lyon], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Clinique Tivoli Ducos [Bordeaux], Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Azuréen de Cancérologie [Mougins, France], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Institut Daniel Hollard [Grenoble], Centre de radiothérapie et d'oncologie médicale privée (Béziers), Institut Curie - Saint Cloud (ICSC), Clinique Mutualiste de l'Estuaire (Saint Nazaire), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Polyclinique de Limoges - site François Chénieux [Limoges], CHU Amiens-Picardie, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), and Fédération Francophone de Cancérologie Digestive.
Subjects: Oncology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Radiology, Nuclear Medicine and imaging, Chemoradiotherapy, Hematology, Anal cancer, IMRT, Observational cohort
Abstract: International audience; Introduction: International guidelines regarding the treatment of squamous cell carcinoma of the anus (SCCA) recommend intensity-modulated radiotherapy (IMRT) combined with mitomycin-based chemotherapy (CT). The French FFCD-ANABASE cohort aimed at evaluating clinical practices, treatment, and outcomes of SCCA patients.Methods: This prospective multicentric observational cohort included all non-metastatic SCCA patients treated in 60 French centers from January 2015 to April 2020. Patients and treatment characteristics, colostomy-free survival (CFS), disease-free survival (DFS), overall survival (OS), and prognostic factors were analyzed.Results: Among 1015 patients (male: 24.4 %; female: 75.6 %; median age: 65 years), 43.3 %presented with early-stage(T1-2, N0) and 56.7 % with locally advanced stage (T3-4 or N + ) tumors. IMRT was used for 815 patients (80.3 %) and a concurrent CT was administered in 781 patients, consisting of mitomycin-based CT for 80 %. The median follow-up was 35.5 months. DFS, CFS, and OS at 3 years were 84.3 %, 85.6 %, and 91.7 % respectively in the early-stage group compared to 64.4 %, 66.9 %, and 78.2 % in the locally-advanced group (p < 0.001). In multivariate analyses, male gender, locally-advanced stage, and ECOG PS ≥ 1 were associated with poorer DFS, CFS, and OS. IMRT was significantly associated with a better CFS in the whole cohort and almost reached significance in the locally-advanced group.Conclusion: Treatment of SCCA patients showed good respect for current guidelines. Significant differences in outcomes advocate for personalized strategies by either de-escalation for early-stage tumors or treatment intensification for locally-advanced tumors.
Published: 2023
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17. Non-canonical miRNA-RNA base-pairing impedes tumor suppressor activity of miR-16

Author: Anaïs M Quéméner, Laura Bachelot, Marc Aubry, Stéphane Avner, Delphine Leclerc, Gilles Salbert, Florian Cabillic, Didier Decaudin, Bernard Mari, Frédéric Mouriaux, Marie-Dominique Galibert, David Gilot, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Curie [Paris], Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Ligue Nationale Contre le Cancer, French Ministry of Research, Fondation ARC pour la Recherche, AVIESAN Plan Cancer, Région Bretagne, University of Rennes 1, CNRS, Ministère de la Recherche et de l’Enseignement Supérieur, Rennes Métropole, and Chard-Hutchinson, Xavier
Subjects: [SDV] Life Sciences [q-bio], Adult, Uveal Neoplasms, MicroRNAs, Ecology, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Humans, Plant Science, Cyclin D3, Biochemistry, Genetics and Molecular Biology (miscellaneous), Base Pairing, Melanoma
Abstract: Uveal melanoma (UM), the most common primary intraocular tumor in adults, has been extensively characterized by omics technologies during the last 5 yr. Despite the discovery of gene signatures, the molecular actors driving cancer aggressiveness are not fully understood, and UM is still associated with very poor overall survival (OS) at the metastatic stage. By defining the miR-16 interactome, we revealed that miR-16 mainly interacts via non-canonical base-pairing to a subset of RNAs, promoting their expression levels. Consequently, the canonical miR-16 activity, involved in the RNA decay of oncogenes, such ascyclin D3, is impaired. This non-canonical base-pairing can explain both the derepression of miR-16 targets and the promotion of oncogene expression observed in patients with poor OS in two cohorts. miR-16 activity, assessment using our RNA signature, discriminates the patient’s OS as effectively as current methods. To the best of our knowledge, this is the first time that a predictive signature has been composed of genes belonging to the same mechanism (miR-16) in UM. Altogether, our results strongly suggest that UM is a miR-16 disease.
Published: 2022
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18. A Preclinical Validation of Iron Oxide Nanoparticles for Treatment of Perianal Fistulizing Crohn's Disease

Author: Antoine Cazelles, Maxime K. Collard, Yoann Lalatonne, Sabrina Doblas, Magaly Zappa, Camélia Labiad, Dominique Cazals-Hatem, Léon Maggiori, Xavier Treton, Yves Panis, Ulrich Jarry, Thomas Desvallées, Pierre-Antoine Eliat, Raphaël Pineau, Laurence Motte, Didier Letourneur, Teresa Simon-Yarza, Eric Ogier-Denis, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Avicenne [AP-HP], Biotrial, Biosit : biologie, santé, innovation technologique (SFR UMS CNRS 3480 - INSERM 018), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Plate-forme Rennaise d'Imagerie et Spectroscopie Structurale et Métabolique (PRISM), Université de Rennes (UR)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), French National Institute of Health INSERM, Fondation pour la Recherche Medicale [M2R201906008873], INSERM-Transfert CoPoC, Idex Pre-maturation 'Universite Paris 2019', Conseil Regional de Bretagne (SAD 2021), Rennes Metropole (AIS 2021), and Jonchère, Laurent
Subjects: Male, [SDV]Life Sciences [q-bio], Crohn’s disease, perianal fistula, preclinical model, iron oxide nanoparticles, fistula treatment, Catalysis, Inorganic Chemistry, Rats, Sprague-Dawley, Crohn Disease, Animals, Rectal Fistula, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Organic Chemistry, General Medicine, Computer Science Applications, Rats, [SDV] Life Sciences [q-bio], Crohn's disease, Treatment Outcome, Quality of Life, Magnetic Iron Oxide Nanoparticles, Neoplasm Recurrence, Local
Abstract: International audience; Fistulizing anoperineal lesions are severe complications of Crohn's disease (CD) that affect quality of life with a long-term risk of anal sphincter destruction, incontinence, permanent stoma, and anal cancer. Despite several surgical procedures, they relapse in about two-thirds of patients, mandating innovative treatments. Ultrasmall particles of iron oxide (USPIO) have been described to achieve in vivo rapid healing of deep wounds in the skin and liver of rats thanks to their nanobridging capability that could be adapted to fistula treatment. Our main purpose was to highlight preclinical data with USPIO for the treatment of perianal fistulizing CD. Twenty male Sprague Dawley rats with severe 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced proctitis were operated to generate two perianal fistulas per rat. At day 35, two inflammatory fistulas were obtained per rat and perineal magnetic resonance imaging (MRI) was performed. After a baseline MRI, a fistula tract was randomly drawn and topically treated either with saline or with USPIO for 1 min (n = 17 for each). The rats underwent a perineal MRI on postoperative days (POD) 1, 4, and 7 and were sacrificed for pathological examination. The primary outcome was the filling or closure of the fistula tract, including the external or internal openings. USPIO treatment allowed the closure and/or filling of all the treated fistulas from its application until POD 7 in comparison with the control fistulas (23%). The treatment with USPIO was safe, permanently closed the fistula along its entire length, including internal and external orifices, and paved new avenues for the treatment of perianal fistulizing Crohn's disease.
Published: 2022
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19. Defining Benchmark Outcomes for Distal Pancreatectomy: Results of a French Multicentric Study

Author: Thibault Durin, Ugo Marchese, Alain Sauvanet, Safi Dokmak, Zineb Cherkaoui, David Fuks, Christophe Laurent, Marie André, Ahmet Ayav, Cloe Magallon, Olivier Turrini, Laurent Sulpice, Fabien Robin, Philippe Bachellier, Piettro Addeo, François-Régis Souche, Thomas Bardol, Julie Perinel, Mustapha Adham, Stylianos Tzedakis, David Jérémie Birnbaum, Olivier Facy, Johan Gagniere, Sébastien Gaujoux, Ecoline Tribillon, Edouard Roussel, Lilian Schwarz, Louise Barbier, Alexandre Doussot, Nicolas Regenet, Antonio Iannelli, Jean-Marc Regimbeau, Guillaume Piessen, Xavier Lenne, Stéphanie Truant, Mehdi El Amrani, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service de chirurgie hepato-pancreato-biliaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, Université Paris Cité (UPCité), Institut des Sciences de la Terre (ISTerre), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de recherche pour le développement [IRD] : UR219-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel-Université Grenoble Alpes (UGA), Unité de Recherche Œnologie [Villenave d'Ornon] (OENO), Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut des Sciences de la Vigne et du Vin [Villenave d'Ornon] (ISVV), Université de Bordeaux (UB), Moët Hennessy Champagne Services (MHCS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Faculté de Médecine [Nancy], Université de Lorraine (UL), Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Oncogenesis, Stress, Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], CHU Saint-Eloi-Université de Montpellier (UM), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Charles Nicolle [Rouen], Service de chirurgie digestive [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), 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), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Hôpital l'Archet, Chirurgie digestive [CHU Amiens], CHU Amiens-Picardie, Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Normandie Université (NU)-Normandie Université (NU)
Subjects: Surgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; OBJECTIVE: Defining robust and standardized outcome references for distal pancreatectomy (DP) by using Benchmark analysis. BACKGROUND: Outcomes after DP are recorded in medium or small-sized studies without standardized analysis. Therefore, the best results remain uncertain. METHODS: This multicenter study included all patients undergoing DP for resectable benign or malignant tumors in 21 French expert centers in pancreas surgery from 2014 to 2018. A low-risk cohort defined by no significant comorbidities was analyzed to establish 18 outcome benchmarks for DP. These values were tested in high-risk, minimally invasive and benign tumor cohorts. RESULTS: 1188 patients were identified and 749 low-risk patients were screened to establish Benchmark cut-offs. Therefore, Benchmark rate for mini-invasive approach was ≥q36.8%. Benchmark cut-offs for postoperative mortality, major morbidity grade ≥q3a and clinically significant pancreatic fistula rates were 0%, ≤q27% and ≤q28%, respectively. The benchmark rate for readmission was ≤q 16%. For patients with pancreatic adenocarcinoma, cut-offs were ≥q75%, ≥q69.5% and ≥q66% for free resection margins (R0), 1-year disease free-survival and 3-year overall survival, respectively. The rate of mini-invasive approach in high-risk cohort was lower than the Benchmark cut-off (34.1% vs. ≥q36.8%). All Benchmark cut-offs were respected for benign tumor group. The proportion of benchmark cases was correlated to outcomes of DP. Centers with a majority of low-risk patients had worse results than those operating complex cases. CONCLUSION: This large-scale study is the first benchmark analysis of DP outcomes and provides robust and standardized data. This may allow for comparisons between surgeons, centers, studies, and surgical techniques.
Published: 2022
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20. Robot-assisted laparoscopy repair of uterine isthmocele: A two-center observational study

Author: Cardaillac, Claire, Salmon, Caroline, Vaucel, Edouard, Gueudry, Pauline, Lavoue, Vincent, Nyangoh Timoh, Krystel, Thubert, Thibault, Centre hospitalier universitaire de Nantes (CHU Nantes), CH Cholet, CHU Pontchaillou [Rennes], Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Motricité, interactions, performance UR 4334 / Movement - Interactions - Performance (MIP), Le Mans Université (UM)-Nantes Université - UFR des Sciences et Techniques des Activités Physiques et Sportives (Nantes Univ - UFR STAPS), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)
Subjects: cesarean scar, laparoscopic niche resection, Obstetrics and Gynecology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, General Medicine, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, surgical management, uterine scar defect, uterine niches
Abstract: International audience; Objective: To analyze outcomes and postoperative complications in patients undergoing robot-assisted isthmocele repair.Method: This retrospective cohort study included 33 patients who had robot-assisted laparoscopic surgical management of an isthmocele between September 2013 and August 2020 in two French university hospitals. All charts were reviewed to identify patient characteristics, preoperative and postoperative anatomical findings, complications, and postoperative fertility and symptoms. Patients who had undergone this procedure were asked to complete a telephone questionnaire about their treatment satisfaction and symptoms.Results: The isthmocele was discovered most often as a result of subfertility (57.6%), but also ectopic pregnancy (18.2%), pelvic pain (15.2%), and postmenstrual bleeding (9.1%). Robot-assisted repair of the isthmocele significantly improved myometrial thickness (from 1.55 mm before surgery to 4.26 mm after surgery [mean difference 2.71; 95% confidence interval, 1.91-3.51], P = 0.0005). Among 20 patients who still desired a child after surgery, 15 became pregnant and 14 had full-term live births. Among the nine patients who had surgery for disabling symptoms, five had no persistent symptoms, three reported global improvement, and one had the same gynecologic discomfort. Seventeen patients agreed to complete the questionnaires (51.5%), and all stated that they would choose to have this surgery again.Conclusion: Robot-assisted repair of an isthmocele is a viable minimally invasive procedure.
Published: 2022
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21. Editor Profile: Eric Chevet

Author: Chevet, Eric, Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), and Jonchère, Laurent
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; In this special interview series, we profile members of The FEBS Journal Editorial Board to highlight their research focus, perspectives on the journal and future directions in their field. Eric Chevet is Research Director at the French National Institute of Health (INSERM) and Director of the INSERM Unit U1242 'Oncogenesis, Stress, Signaling' in the Comprehensive Cancer Centre Eugene Marquis at the University of Rennes. He has served as Editorial Board Member of The FEBS Journal since 2019.
Published: 2022
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22. Characterization of the Peri-Membrane Fluorescence Phenomenon Allowing the Detection of Urothelial Tumor Cells in Urine

Author: Charly Gutierrez, Xavier Pinson, Kathleen Jarnouen, Marine Charpentier, Raphael Pineau, Laëtitia Lallement, Rémy Pedeux, Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Microscopie de Rennes (MRic), Université de Rennes (UR)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), VitaDX International (VitaDX), Region Bretagne, European Regional Development Fund, Rennes Metropole, VitaDX, University Rennes 1, INSERM, ANR (ERAAT), ANR-17-RAR3-0003,ERAAT,Enhancing Endoplasmic Reticulum Proteostasis to Rescue Alpha1 Antitrypsin Deficiency(2017), Jonchère, Laurent, and Enhancing Endoplasmic Reticulum Proteostasis to Rescue Alpha1 Antitrypsin Deficiency - - ERAAT2017 - ANR-17-RAR3-0003 - E-RARE - VALID
Subjects: Cancer Research, [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, liquid biopsy, diagnostic test, urinary cytology, non-invasive, bladder cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, fluorescence, urine, peri-membrane fluorescence
Abstract: International audience; Urine cytology is non-invasive, easy to collect, with medium sensitivity and a high specificity. It is an effective way to detect high-grade bladder cancer (BC), but it is less effective on low-grade BC because the rate of equivocal results is much higher. Recently, the fluorescent properties of plasma membranes of urothelial tumor cells (UTC) found in urine cytology have been shown to be useful in improving the early detection of BC. This phenomenon is called peri-membrane fluorescence (PMF). Based on previous studies that have identified the PMF on UTCs, the main objective was to characterize this phenomenon. For this study, a software was specially created to quantify the PMF of all tested cells and different treatments performed. PMF was not found to be a morphological and discriminating feature of UTCs, all cells in shape and not from urine show PMF. We were able to highlight the crucial role of plasma membrane integrity in the maintenance of PMF. Finally, it was found that the induction of a strong cellular stress induced a decrease in PMF, mimicking what was observed in non-tumor cells collected from urine. These results suggest that PMF is found in cells able to resist this stress, such as tumor cells.
Published: 2022
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23. pBFK, a new thermosensitive shuttle vector for Streptococcus pyogenes gene deletion by homologous recombination

Author: S. Boukthir, P. Gaudu, A. Faili, S. Kayal, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes - Faculté des sciences pharmaceutiques et biologiques (UR Pharmacie), Université de Rennes (UR), and This work was supported by the University Rennes Medical School, and by University Hospital Center of Rennes-France and did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Subjects: Multidisciplinary, Gene deletion, Streptococcus pyogenes, [SDV]Life Sciences [q-bio], Group A Streptococcus, Isogenic mutant, Homologous recombination
Abstract: International audience; Streptococcus pyogenes, or Group A Streptococcus (GAS), is a major human pathogen for which genetic manipulation remains an ongoing challenge. We created a new temperature-sensitive plasmid pBFK expressing spectinomycin resistance adapted to homologous recombination procedure to perform a complete gene deletion in GAS. Herein the mutagenesis strategy with pBFK was performed in a highly virulent GAS emm3 genotype.
Published: 2023
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24. Development of sensitive and robust multiplex digital PCR assays for the detection of ESR1 mutations in the plasma of metastatic breast cancer patients

Author: Julien Corné, Véronique Quillien, Céline Callens, Pascal Portois, François-Clément Bidard, Emmanuelle Jeannot, Florence Godey, Fanny Le Du, Lucie Robert, Héloïse Bourien, Angélique Brunot, Laurence Crouzet, Christophe Perrin, Claudia Lefeuvre-Plesse, Véronique Diéras, Thibault De la Motte Rouge, CRLCC Eugène Marquis (CRLCC), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], and This work was supported by 'La Vannetaise', a French association dedicated to the prevention and awareness of cancer in women.
Subjects: Plasma, Liquid biopsy, ESR1, Biochemistry (medical), Clinical Biochemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, Multiplex digital PCR, General Medicine, cfDNA, Metastatic breast cancer, Biochemistry
Abstract: International audience; BACKGROUND: Early detection of ESR1 mutations is a key element for better personalization of the management of patients with HR+/HER2- Metastatic Breast Cancer (MBC). Analysis of circulating tumor DNA from liquid biopsies is a particularly well-suited strategy for longitudinal monitoring of such patients. MATERIALS AND METHODS: Using the naica® three-color digital PCR platform, we developed a screening assay allowing the detection of 11 ESR1 mutations and designed a sequential strategy for precise mutation identification. We then applied this strategy in the analysis of plasma circulating cell-free DNA from 109 HR+/HER2- MBC patients and performed a double-blind comparison study on a subset of patients with the multiplex assay used at the Institut Curie (IC) for the PADA-1 study. RESULTS: Thirty-one patients (28.4%) harboured at least one ESR1 mutation, with the following frequencies: D538G (41.03%), Y537S (25.64%), E380Q (10.26%), Y537N (10.26%), "(536-540)" (7.69%), Y537C (2.56%), and L536R (2.56%). The presence of ESR1 mutation(s) was significantly associated with liver metastases (p = 0.0091). A very good agreement (91%) was observed with the IC assay. CONCLUSION: Our assays have proven to be robust and highly sensitive and are very well-suited for monitoring ESR1 mutations in the plasma of MBC patients.
Published: 2023
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25. TACE and conformal radiotherapy vs. TACE alone for hepatocellular carcinoma: A randomised controlled trial

Author: Cyrille Féray, Loic Campion, Philippe Mathurin, Isabelle Archambreaud, Xavier Mirabel, Jean Pierre Bronowicki, Emmanuel Rio, Christophe Perret, Laurent Mineur, Frédéric Oberti, Yann Touchefeu, Jérôme Gournay, Hélène Regnault, Julien Edeline, Agnès Rode, Patrick Hillion, Jean Frédéric Blanc, Eric Nguyen Khac, Daniel Azoulay, Alain Luciani, Athena Galetto Preglisasco, Elodie Faurel-Paul, Hélène Auble, Françoise Mornex, Philippe Merle, Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôtel-Dieu de Nantes, Institut Sainte Catherine [Avignon], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiologie [Mondor], Centre pour l'innovation en cancérologie de Lyon (CICLY), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), 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), Service d'Hépatologie et de Gastroentérologie [Lyon], and Hospices Civils de Lyon (HCL)
Subjects: RILD, TTP, Hepatocellular carcinoma, ITT, overall survival, adverse event, time to tumour progression, PS, ALBI, mRECIST, ECOG, PFS, Barcelona Clinic Liver Cancer, hazard ratio, albumin–bilirubin, HR, Internal Medicine, radio-induced liver disease, Immunology and Allergy, HCC, 3-DCRT, propensity score, TACE, SBRT, Conformal external radiotherapy, Hepatology, Gastroenterology, AE, OS, computed tomography, transcatheter arterial chemoembolisation, three-dimensional conformal radiotherapy, intention-to-treat, BCLC, clinical tumour volume, stereotaxic body radiation therapy, Eastern Cooperative Oncology Group, CRT, CTV, conformal radiotherapy, progression-free survival, modified Response Evaluation Criteria in Solid Tumour, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, CT
Abstract: International audience; Background & aims: Transcatheter arterial chemoembolisation (TACE) is recommended for patients with hepatocellular carcinoma devoid of macrovascular invasion or extrahepatic spread but not eligible for curative therapies. We compared the efficacy and safety of the combination of a single TACE and external conformal radiotherapy (CRT) vs. classical TACE.Methods: TACERTE was an open-labelled, randomised controlled trial with a 1:1 allocation rate to two or three TACE (arm A) or one TACE + CRT (arm B). Participants had a mean age of 70 years, and 86% were male. The aetiology was alcohol in 85%. The primary endpoint was liver progression-free survival (PFS) in the intention-to-treat population. The typical CRT schedule was 54 Gy in 18 sessions of 3 Gy.Results: Of the 120 participants randomised, 64 were in arm A and 56 in arm B; 100 participants underwent the planned schedule and defined the 'per-protocol' group. In intention-to-treat participants, the liver PFS at 12 and 18 months were 59% and 19% in arm A and 61% and 36% in arm B (hazard ratio [HR] 0.69; 95% CI 0.40-1.18; p = 0.17), respectively. In the per-protocol population, treated liver PFS tended to be better in arm B (HR 0.61; 95% CI 0.34-1.06; p = 0.081) than in arm A. Liver-related grade III-IV adverse events were more frequent in arm B than in arm A. Median overall survival reached 30 months (95% CI 23-35) in arm A and 22 months (95% CI 15.7-26.2) in arm B.Conclusions: Although TACE + CRT tended to improve local control, this first Western randomised controlled trial showed that the combined strategy failed to increase PFS or overall survival and led more frequently to liver-related adverse effects.Impact and implications: Hepatocellular carcinoma is frequently treated by arterial embolisation of the tumour and more recently by external radiotherapy. We tried to determine whether combination of the two treatments (irradiation after embolisation) might produce interesting results. Our results in this prospective randomised study were not able to demonstrate a beneficial effect of combining embolisation and irradiation in these patients. On the contrary, we observed more adverse effects with the combined treatment.
Published: 2023
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26. SOCRATE-PRODIGE 55 trial: A randomized phase II study to evaluate second-line ramucirumab alone or with paclitaxel in older patients with advanced gastric cancer

Author: Emeric Boisteau, Eric François, Thomas Aparicio, Karine Le Malicot, Rabia Boulahssass, Thierry Lecomte, Pierre Laurent-Puig, Boris Guiu, Elena Paillaud, Marie-Pierre Galais, Daniel Lopez-Trabada Ataz, David Tougeron, Louis-Marie Dourthe, Rosine Guimbaud, Emmanuelle Samalin, Marie Moreau, Christophe Louvet, Côme Lepage, Astrid Lièvre, Jonchère, Laurent, Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre Hospitalier Universitaire de Nice (CHU Nice), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulation de la transcription et maladies génétiques (RTMG), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Cancer Research and Personalized Medicine - CARPEM [Paris], 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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Clinique Sainte Anne [Strasbourg], Fédération Francophone de Cancérologie Digestive (FFCD), Institut Mutualiste de Montsouris (IMM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Pontchaillou [Rennes], The study was financially supported by Lilly. The Fédération Francophone de Cancérologie Digestive is funding the bio-bank and molecular analysis., IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Advanced gastric cancer, Hepatology, Paclitaxel, Gastroenterology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antibodies, Monoclonal, Humanized, Ramucirumab, [SDV.CAN] Life Sciences [q-bio]/Cancer, Stomach Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Quality of Life, Humans, Prospective Studies, Geriatric, Aged
Abstract: International audience; INTRODUCTION: Patients ≥ 70 years old constitute 40% of patients with advanced gastric cancer (GC). Ramucirumab plus Paclitaxel is a therapeutic option validated in the second-line treatment of advanced GC, but as older patients are at higher risk of severe toxicity, due to comorbidities and/or frailty, we aimed to evaluate second-line Ramucirumab alone or combined with Paclitaxel in terms of overall survival (OS) and quality of life (QoL) in patients ≥ 70 years-old with advanced GC. METHODS: In this multicenter, randomized, open-label, non-comparative, prospective phase II clinical trial, the main inclusion criteria are: patients ≥ 70 years old, with advanced GC having progressed after first-line chemotherapy or in the six months following the last administration of adjuvant chemotherapy, with WHO performance status
Published: 2022
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27. Angiopoietin-like 4-Induced 3D Capillary Morphogenesis Correlates to Stabilization of Endothelial Adherens Junctions and Restriction of VEGF-Induced Sprouting

Author: Athanasia Liabotis, Corinne Ardidie-Robouant, Philippe Mailly, Samaher Besbes, Charly Gutierrez, Yoann Atlas, Laurent Muller, Stéphane Germain, Catherine Monnot, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Carcinose Angiogenèse et Recherche Translationnelle, Angiogenese et recherche translationnelle (CART U965), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Angiogénèse embryonnaire et pathologique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre interdisciplinaire de recherche en biologie (CIRB), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Labex MemoLife, Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologie vasculaire et endocrinologie rénale - Chaire de médecine expérimentale (INSERM U36), and Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: angiopoietin-like 4, vascular endothelial growth factor, angiogenesis, adherens junction, in vitro 3D model, vascularization, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), C angiopoietin-like 4, General Biochemistry, Genetics and Molecular Biology
Abstract: Angiopoietin-like 4 (ANGPTL4) is a target of hypoxia that accumulates in the endothelial extracellular matrix. While ANGPTL4 is known to regulate angiogenesis and vascular permeability, its context-dependent role related to vascular endothelial growth factor (VEGF) has been suggested in capillary morphogenesis. We here thus develop in vitro 3D models coupled to imaging and morphometric analysis of capillaries to decipher ANGPTL4 functions either alone or in the presence of VEGF. ANGPTL4 induces the formation of barely branched and thin endothelial capillaries that display linear adherens junctions. However, ANGPTL4 counteracts VEGF-induced formation of abundant ramified capillaries presenting cell–cell junctions characterized by VE-cadherin containing reticular plaques and serrated structures. We further deciphered the early angiogenesis steps regulated by ANGPTL4. During the initial activation of endothelial cells, ANGPTL4 alone induces cell shape changes but limits the VEGF-induced cell elongation and unjamming. In the growing sprout, ANGPTL4 maintains cohesive VE-cadherin pattern and sustains moderate 3D cell migration but restricts VEGF-induced endothelium remodeling and cell migration. This effect is mediated by differential short- and long-term regulation of P-Y1175-VEGFR2 and ERK1-2 signaling by ANGPTL4. Our in vitro 3D models thus provide the first evidence that ANGPTL4 induces a specific capillary morphogenesis but also overcomes VEGF effect.
Published: 2021
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28. Newly identified tumor suppressor functions of ING proteins

Author: Léane Heliez, Charles Ricordel, Philippe Becuwe, Rémy Pedeux, Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Faculté des Sciences et Technologies [Université de Lorraine] (FST ), Université de Lorraine (UL), and Institut National de la Santé et de la Recherche Médicale, Inserm
Subjects: Pharmacology, Drug Discovery, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; The INhibitor of Growth (ING) proteins (ING1, ING2, ING3, ING4 and ING5) are a family of epigenetic regulators. Their decreased expression in numerous cancers led to identifying the ING proteins as gatekeeper tumor suppressors as they regulate cell cycle progression, apoptosis and senescence. Subsequently, they were also described as caretaker tumor suppressors through their involvement in DNA replication and the DNA damage response (DDR). Recent studies have identified new interactions of the ING proteins with proteins or pathways implicated in cell proliferation, the maintenance of stem cells pluripotency or the DDR. Furthermore, the ING proteins have been identified as regulators of ribosomal RNA synthesis and of mRNA stability and as regulators of mitochondrial DNA transcription resulting in the regulation of metabolism. These new findings highlight new antitumorigenic activities of the ING proteins that are potential targets for cancer treatment. © 2022 The Authors
Published: 2023
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29. AGR2 protein expression in colorectal tumour epithelialcompartment

Author: Eric Chevet, F Bassal, Stéphanie Beq, Benjamin Bonhomme, Emeric Boisteau, Julien Calloch, Dominique Cazals-Hatem, Frederic Delom, Delphine Fessart, Serge Evrard, Roman Hrstka, ted hupp, Astrid Lièvre, Edouard Louis, Jeremie Mariau, Marie-Alice Meuwis, Eric Ogier-Denis, Valerie Paradis, Simon Pernot, R Pineau, Xavier Treton, Valerie Velasco, Sophie Vieujean, CRLCC Eugène Marquis (CRLCC), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Thabor Therapeutics, Institut Bergonié [Bordeaux], UNICANCER, CHU Pontchaillou [Rennes], BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Edinburgh, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA-Research), Université de Liège, Centre Hospitalier Universitaire de Liège (CHU-Liège), GIGA [Université Liège], and PLBIO, Institut National Du Cancer
Subjects: COLORECTAL CANCER, SIGNAL TRANSDUCTION, Gastroenterology, [SDV.CAN]Life Sciences [q-bio]/Cancer
Published: 2022
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30. Prevalence and risk factors of asthma in dairy farmers: Ancillary analysis of AIRBAg

Author: Stéphane Jouneau, Anthony Chapron, Cécile Ropars, Solenne Marette, Ange-Marie Robert, Thomas Gouyet, Chantal Belleguic, Cécile Rochefort-Morel, Stéphanie Guillot, Carole Mailloux, Benoît Desrues, Jean-François Viel, Jean Barakat, Anne-Laure Barel, Henri-Pierre Baron, Rachel Bassen, Florence Behaghel-Baruteau, Cyril Bernier, Séverine Beyer, Romain Boissel, Vanessa Brault, Graziella Brinchault, Dominique Bureau, Odile Castel, Anne-France Cazuguel, Catherine Decelle-Trochet, Marcel Delaunay, Isabelle Delaunay-Lelièvre, Bruno Eveno, Krisztina Fekete, Lisa Fourmont, Amandine Guervin, Tiphaine Guy, Guillaume Héry, Pauline Hardouin, Anne Hespel, Nathalie Jeffray, Yves Koskas, Virginie de Lauzun, Antoine Lebossé, Sandrine Lecot, David Marquette, Virginie Martin, Ahmed Merzoug, Hugues Morel, Jean Morer, Patrick Morisseau, Aurélie Oksenhendler, Elisabeth Orhant, Dominique Peron, Mauricette Piguel-Royer, Marie Pinault, Jean-Paul Pousset, Jean-Claude Presle, Patrick Raillard, Bernard Regnault, Antoine Séguineau, Anne Sevin, Fanny Thépault, Christian Verger, Jonchère, Laurent, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Mutualité sociale agricole des Portes de Bretagne, CRLCC Eugène Marquis (CRLCC), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and This AIRBAg study was supported financially by Rennes University Hospital, France (COREC 2011 funding), the Association for the respiratory insufficiency of Brittany (‘Association pour les insuffisants respiratoires de Bretagne’ (AIRB)), the French Ministry of Labour (DIRECCTE), and Novartis Pharma, France.
Subjects: [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Farmers, Allergy, Wheezing, [SDV]Life Sciences [q-bio], Bronchial obstruction, Biochemistry, Asthma, Chronic respiratory disease, Agricultural Workers' Diseases, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Risk Factors, Hypersensitivity, Prevalence, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, General Environmental Science
Abstract: International audience; BACKGROUND: Prolonged occupational agricultural exposure is associated with an increase in asthma diagnosis. This study aimed to identify the prevalence and risk factors for asthma in dairy farmers. METHODS: AIRBAg was a cross-sectional study including 1203 representative dairy farmers. They completed a self-administered questionnaire and underwent a health respiratory check-up. Referral to a pulmonologist was made for any participant with wheezing, dyspnoea, chronic bronchitis, a chronic cough or a FEV(1)/FEV(6) ratio
Published: 2021
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31. MiR-31-3p do not predict anti-EGFR efficacy in first-line therapy of RAS wild-type metastatic right-sided colon cancer

Author: Emeric Boisteau, Alexandra Lespagnol, Marie De Tayrac, Sébastien Corre, Anthony Perrot, Nathalie Rioux-Leclercq, Séverine Martin-Lannerée, Pascal Artru, Philippe Chalabreysse, Pierre-Guillaume Poureau, Laurent Doucet, Dahna Coupez, Jaafar Bennouna, Céline Bossard, Romain Coriat, Frédéric Beuvon, Lucile Bauguion, François Leclair, Romain Chautard, Thierry Lecomte, Serge Guyetant, Romain Desgrippes, Denis Grasset, Hélène Lhostis, Karine Bouhier-Leporrier, Frédéric Bibeau, Julien Edeline, Marie-Dominique Galibert, Astrid Lièvre, CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), IntegraGen, Hôpital privé Jean Mermoz [Lyon], Cypath : siège social [Villeurbanne], University Hospital Gasthuisberg, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Départemental Vendée (CHDV), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CH de Saint-Malo [Broussais], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire [Rennes], CRLCC Eugène Marquis (CRLCC), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogenesis, Stress, Signaling (OSS), This research received no external funding. We thank the Rennes University Hospital and the Centre d'Etude des Maladies Digestives de Rennes (CEMDR) for their financial support. Anthony Perrot was financially supported by the Rennes University Hospital., Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University Hospital Gasthuisberg [Leuven], and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Hepatology, [SDV]Life Sciences [q-bio], Gastroenterology, colorectal cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.CAN]Life Sciences [q-bio]/Cancer, miR-31-3p, anti-EGFR mAb, Bevacizumab, ErbB Receptors, MicroRNAs, Antineoplastic Combined Chemotherapy Protocols, Colonic Neoplasms, biomarker, metastasis, Humans, Colorectal Neoplasms, Retrospective Studies
Abstract: International audience; BACKGROUND: Low miR-31-3p expression was identified as predictive of anti-EGFR efficacy in RAS-wt mCRC. Primary tumor side was also proposed as a predictive factor of anti-EGFR benefit. This retrospective multicentric study evaluated the predictive role of miR-31-3p in right-sided RAS-wt mCRC patients treated with first-line CT+anti-EGFR or CT+bevacizumab (Beva). METHODS: Seventy-two right-sided RAS-wt mCRC patients treated in first-line with CT+anti-EGFR (n=43) or Beva (n=29) were included. Overall survival (OS), progression-free survival (PFS) and response rate (RR) were analyzed and stratified according to tumor miR-31-3p expression level and targeted therapy (TT). RESULTS: BRAF V600E mutation was more frequent in high vs low miR-31-3p expressers (60.6% vs 15.4%, P < 0.001). PFS was significantly longer with CT+Beva than with CT+anti-EGFR (13 vs 7 months; P = 0.024). Among low miR-31-3p expressers, PFS, OS and RR were not significantly different between the two groups, while in high miR-31-3p expressers, only PFS was longer in the CT+Beva group (11 vs 6 months; P = 0.03). In patients treated with CT+anti-EGFR, low miR-31-3p expressers had a significantly longer OS (20 vs 13 months; P = 0.02) than high miR-31-3p expressers. ORR was not significantly different between the two groups of treatment, in both low and high miR-31-3p expressers. MiR-31-3p expression status was statistically correlated between primary tumors and corresponding metastases. CONCLUSION: In this study, miR-31-3p couldn’t identify a subgroup of patients with right-sided RAS-wt mCRC who might benefit from anti-EGFR and suggest that Beva is the TT of choice in first-line treatment of these patients.
Published: 2021
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32. Analysis of international publication trends in artificial intelligence in ophthalmology

Author: Christophe Boudry, Hassan Al Hajj, Louis Arnould, Frederic Mouriaux, Université de Caen Normandie (UNICAEN), Normandie Université (NU), Unité Régionale de Formation à l'Information Scientifique et Technique de Paris (URFIST Paris), École nationale des chartes (ENC), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Laboratoire de Traitement de l'Information Medicale (LaTIM), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Mines-Télécom [Paris] (IMT), Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Ophtalmologie [Rennes] = Ophtalmology [Rennes], CHU Pontchaillou [Rennes], Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Boudry, Christophe, Université européenne de Bretagne - European University of Brittany (UEB)-Université de Brest (UBO)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Optimisation Continue des Actions Thérapeutiques par l'Intégration d'Informations Multimodales, Université de Brest (UBO)-Télécom Bretagne-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and CRLCC Eugène Marquis (CRLCC)
Subjects: China, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SHS.INFO]Humanities and Social Sciences/Library and information sciences, education, Glaucoma, Retinal diseases, [SHS.INFO] Humanities and Social Sciences/Library and information sciences, Sensory Systems, Cellular and Molecular Neuroscience, Ophthalmology, Artificial Intelligence, Bibliometrics, Humans, Journals, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Purpose: Artificial intelligence (AI) has entered the field of medicine, and ophthalmology is no exception. The objective of this study was to report on scientific production and publication trends, to identify journals, countries, international collaborations, and major MeSH terms involved in AI in ophthalmology research.Methods: Scientometric methods were used to evaluate global scientific production and development trends in AI in ophthalmology using PubMed and the Web of Science Core Collection.Results: A total of 1356 articles were retrieved over the period 1966-2019. The yearly growth of AI in ophthalmology publications has been 18.89% over the last ten years, indicating that AI in ophthalmology is a very attractive topic in science. Analysis of the most productive journals showed that most were specialized in computer and medical systems. No journal was found to specialize in AI in ophthalmology. The USA, China, and the UK were the three most productive countries. The study of international collaboration showed that, besides the USA, researchers tended to collaborate with peers from neighboring countries. Among the twenty most frequent MeSH terms retrieved, there were only four related to clinical topics, revealing the retina and glaucoma as the most frequently encountered subjects of interest in AI in ophthalmology. Analysis of the top ten Journal Citation Reports categories of journals and MeSH terms for articles confirmed that AI in ophthalmology research is mainly focused on engineering and computing and is mainly technical research related to computer methods.Conclusions: This study provides a broad view of the current status and trends in AI in ophthalmology research and shows that AI in ophthalmology research is an attractive topic focusing on retinal diseases and glaucoma. This study may be useful for researchers in AI in ophthalmology such as clinicians, but also for scientists to better understand this research topic, know the main actors in this field (including journals and countries), and have a general overview of this research theme.
Published: 2021
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33. Impact of severe obesity in the management of patients with high-risk endometrial cancer: A FRANCOGYN study

Author: Ombline Simon, Ludivine Dion, Krystel Nyangoh Timoh, Pierre François Dupré, Henri Azaïs, Sofiane Bendifallah, Cyril Touboul, Yohan Dabi, Olivier Graesslin, Emilie Raimond, Hélène Costaz, Yohan Kerbage, Cyrille Huchon, Camille Mimoun, Martin Koskas, Cherif Akladios, Lise Lecointre, Geoffroy Canlorbe, Pauline Chauvet, Lobna Ouldamer, Jean Levêque, Vincent Lavoué, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), 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), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CHU Lille, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Strasbourg, CHU Pitié-Salpêtrière [AP-HP], CHU Clermont-Ferrand, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: MESH: Humans, Clinical management, MESH: Lymph Node Excision, [SDV]Life Sciences [q-bio], Obstetrics and Gynecology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, MESH: Obesity, Morbid, Endometrial Neoplasms, Obesity, Morbid, [SDV] Life Sciences [q-bio], [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, [SDV.CAN] Life Sciences [q-bio]/Cancer, Endometrial cancer, Reproductive Medicine, Humans, Lymph Node Excision, MESH: Obesity, Female, Surgery, Obesity, MESH: Endometrial Neoplasms, Neoplasm Recurrence, Local, MESH: Female, MESH: Neoplasm Recurrence, Local
Abstract: International audience; Objective: To assess the surgical management and survival of severely obese patients with high-risk endometrial cancer.Materials and methods: Data from 269 patients with high-risk endometrial cancer who were treated between 2001 and 2018 were collected from a multicenter database (11 centers). We classified the patients according to their BMI and compared outcomes in two groups: a normal weight group of women with a BMI < 25 kg/m2, and a severe obesity group of women with a BMI ≥ 35 kg/m2. The groups were compared for epidemiologic, pathologic, management, relapse-free survival (RFS) and overall survival (OS) elements.Results: Patients in the severe obesity group were younger (64 years vs. 68 years, p < 0.05) and had more comorbidities (hypertension, diabetes). They also had more locally advanced tumors and pelvic lymph node involvement (47% vs 24%, p < 0.05). The severely obese patients were less likely to undergo recommended surgical staging, with fewer lumbar aortic dissections than women of normal weight (23% vs 36%, p < 0.05) and fewer pelvic sentinel lymph node biopsies (26.5% vs 12.1%, p < 0.05). No difference in RFS or OS were observed between the two groups.Conclusion: Patients with severe obesity and high-risk endometrial cancer have more locally advanced tumors, and are less likely to be managed according to surgical recommendations. However, RFS and OS do not seem to be affected.
Published: 2022
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34. The protease-inhibitor SerpinB3 as a critical modulator of the stem-like subset in human cholangiocarcinoma

Author: Matteo Parri, Cédric Coulouarn, Stefania Recalcati, Giuliana Cavalloni, Matteo Fassan, Claudia Campani, Luca Di Tommaso, Guido Torzilli, Andrea Cappon, Alessandra Biasiolo, Fabio Marra, Jesper B. Andersen, Chiara Raggi, B. Piombanti, Matteo Ramazzotti, Giulia Lori, Patricia Munoz-Garrido, Pietro Invernizzi, Laurent Sulpice, Santina Quarta, M. Correnti, Patrizia Pontisso, Caterina Peraldo Neia, Mirella Pastore, Monika Lewinska, Douglas Vnp Oliveira, Correnti, M, Cappon, A, Pastore, M, Piombanti, B, Lori, G, Oliveira, D, Munoz-Garrido, P, Lewinska, M, Andersen, J, Coulouarn, C, Sulpice, L, Peraldo Neia, C, Cavalloni, G, Quarta, S, Biasiolo, A, Fassan, M, Ramazzotti, M, Parri, M, Recalcati, S, di Tommaso, L, Campani, C, Invernizzi, P, Torzilli, G, Marra, F, Pontisso, P, Raggi, C, Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Università degli Studi di Milano = University of Milan (UNIMI), Università degli Studi di Padova = University of Padua (Unipd), Università degli Studi di Firenze = University of Florence (UniFI), University of Copenhagen = Københavns Universitet (UCPH), CHU Pontchaillou [Rennes], Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Cancer Genomics Laboratory, Fondazione 'Edo ed Elvo Tempia Valenta', Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Candiolo Cancer Institute [Candiolo, Italie], Università degli studi di Torino = University of Turin (UNITO), Humanitas University [Milan] (Hunimed), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), San Gerardo Hospital [Monza, Italy] (SGH), and Funding for this work was partially provided by the Italian Foundation of Cancer Research award (MFGA17588, IG23117) to Dr Raggi and (IG17786) to Prof. Marra, and in part by the University of Padua (Project: CPDA110795) to Prof. Pontisso. Dr Coulouarn was supported by Inserm, University of Rennes 1, and ITMO Cancer AVIESAN dans le cadre du Plan cancer (Non-coding RNA in cancerology: fundamental to translational). Dr Andersen, Dr Coulouarn, Dr Sulpice, Prof. Recalcati, Prof. Invernizzi and Dr Raggi are members of the European Network for the Study of Cholangiocarcinoma (ENSCCA) and participate in the initiative COST Action EURO-CHOLANGIO-NET granted by the COST Association (CA18122). Prof. Invernizzi is a member of the European Reference Network on Hepatological Diseases (ERN RARE LIVER). This study was partly supported by Italian Ministry of Health grants (PE-2016-02363915 and GR-2018-12367794). The authors thank AMAF Monza ONLUS and AIRCS for the unrestricted research funding.
Subjects: Homeobox protein NANOG, cancer stem cells, cancer stem cell, Epithelial-Mesenchymal Transition, [SDV.CAN]Life Sciences [q-bio]/Cancer, Mice, SCID, Cholangiocarcinoma, Mice, SOX2, Cancer stem cell, Antigens, Neoplasm, Mice, Inbred NOD, Cell Line, Tumor, Animals, Humans, Protease Inhibitors, Progenitor cell, Serpins, Hepatology, biology, SerpinB3, CD44, Liver Neoplasms, Membrane Proteins, Transfection, invasion, ADAM Proteins, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, KLF4, Cell culture, Cancer research, biology.protein, Neoplastic Stem Cells, cholangiocarcinoma, Peptide Hydrolases
Abstract: Background and aims: Cholangiocarcinoma (CCA) is a form of primary liver cancer with limited therapeutic options. Recently, cancer stem cells (CSCs) have been proposed as a driving force of tumour initiation and dissemination, thus representing a crucial therapeutic target. The protease inhibitor SerpinB3 (SB3) has been identified in several malignancies including hepatocellular carcinoma. SB3 has been involved in the early events of hepatocarcinogenesis and is highly expressed in hepatic progenitor cells and in a mouse model of liver progenitor cell activation. However, only limited information on the possible role of SB3 in CCA stem-like compartment is available. Methods: Enrichment of CCA stem-like subset was performed by sphere culture (SPH) in CCA cell lines (CCLP1, HUCCT1, MTCHC01 and SG231). Quantitative RT-PCR and Western blotting were used to detect SB3 in both SPH and parental monolayer (MON) cells. Acquired CSC-like features were analysed using an endogenous and a paracrine in vitro model, with transfection of SB3 gene or addition of recombinant SB3 to cell medium respectively. SB3 tumorigenic role was explored in an in vivo mouse model of CCA by subcutaneous injection of SB3-transfected MON (MONSB3+) cells in immune-deficient NOD-SCID/IL2Rgnull (NSG) mice. SB3 expression in human CCA sections was investigated by immunohistochemistry. Overall survival (OS) and time to recurrence (TTR) analyses were carried out from a transcriptome database of 104 CCA patients. Results: SB3, barely detected in parental MON cells, was overexpressed in the same CCA cells grown as 3D SPH. Notably, MONSB3+ showed significant overexpression of genes associated with stemness (CD24, CD44, CD133), pluripotency (c-MYC, NOTCH1, STAT3, YAP, NANOG, BMI1, KLF4, OCT4, SOX2), epithelial mesenchymal transition (β-catenin, SLUG) and extracellular matrix remodelling (MMP1, MMP7, MMP9, ADAM9, ADAM10, ADAM17, ITGB3). SB3-overexpressing cells showed superior spherogenic capacity and invasion ability compared to control. Importantly, MONSB3+ exhibited activation of MAP kinases (ERK1/2, p38, JNK) as well as phosphorylation of NFκB (p65) in addition to up-regulation of the proto-oncogene β-catenin. All these effects were reversed after transient silencing of SB3. According to the in vitro finding, MONSB3+ cells retained high tumorigenic potential in NSG mice. SB3 overexpression was observed in human CCA tissues and analysis of OS as well as TTR indicated a worse prognosis in SB3+ CCA patients. Conclusion: These findings indicate a SB3 role in mediating malignant phenotype of CCA and identify a new therapeutic target.
Published: 2021
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35. The seismicity of Mars

Author: Simon Stähler, Anna Horleston, Sharon Kedar, John-Robert Scholz, L. Luno, J. B. McClean, Henri Samuel, Fabian Euchner, S. Barkaoui, Tristram Warren, Mélanie Drilleau, Martin Schimmel, Maren Böse, M. Nonon, M. van Driel, Nicholas A Teanby, Alexander E. Stott, Savas Ceylan, Ludovic Margerin, A. Jacob, Brigitte Knapmeyer-Endrun, William B. Banerdt, Guenole Mainsant, Tamara Gudkova, Antoine Lucas, T. Gabsi, Renee Weber, Taichi Kawamura, Vincent Conejero, Eléonore Stutzmann, Daniele Antonangeli, C. Agard, Constantinos Charalambous, C. Ferrier, P. Combes, K. Hurst, Philippe Lognonné, Don Banfield, Aymeric Spiga, William T. Pike, Constanza Pardo, J. A Rodriguez Manfredi, Martin Knapmeyer, Attilio Rivoldini, Francis Nimmo, U. R. Christensen, Sue Smrekar, Ingrid Daubar, R. Llorca-Cejudo, Mark P. Panning, Scott D. King, Eric Beucler, Foivos Karakostas, Amir Khan, E. Barrett, Mark A. Wieczorek, Raphaël F. Garcia, Clément Perrin, Naomi Murdoch, David Mimoun, C. Yana, John Clinton, Domenico Giardini, Swiss National Supercomputing Centre, Swiss National Science Foundation, Agence Nationale de la Recherche (France), State Secretariat for Education, Research and Innovation (Switzerland), UK Space Agency, California Institute of Technology, German Centre for Air and Space Travel, Schimmel, Martin, Centre National de la Recherche Scientifique (CNRS), Institut de Physique du Globe de Paris (IPGP), Centre National de la Recherche Scientifique (CNRS)-Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-IPG PARIS-Institut national des sciences de l'Univers (INSU - CNRS), Institute of Geophysics [ETH Zürich], Department of Earth Sciences [Swiss Federal Institute of Technology - ETH Zürich] (D-ERDW), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Institut de Physique du Globe de Paris, Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Department of Mechanical Engineering [Imperial College London], Imperial College London, Max-Planck-Institut für Sonnensystemforschung (MPS), Max-Planck-Gesellschaft, INSTITUT OF GEOPHYSICS ETHZ, Swiss Seismological Service, Department of Earth and Environmental Sciences [München], Ludwig-Maximilians-Universität München (LMU), Department of Geological Sciences [Gainesville] (UF|Geological), University of Florida [Gainesville] (UF), Cornell University [New York], Laboratoire de Planétologie et Géodynamique [UMR 6112] (LPG), Université d'Angers (UA)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), European Academy-EURAC, Institute for Applied Remote Sensing, Kyoto University [Kyoto], Departments of Anesthesiology and Physiology and Biophysics, University of Alabama at Birmingham [ Birmingham] (UAB), Laboratoire de Météorologie Dynamique (UMR 8539) (LMD), Département des Géosciences - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École des Ponts ParisTech (ENPC)-École polytechnique (X)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), De la Préhistoire à l'Actuel : Culture, Environnement et Anthropologie (PACEA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), Schmidt United Institute of Physics of the Earth [Moscow] (IPE), Russian Academy of Sciences [Moscow] (RAS), NASA, Deutsches Zentrum für Luft- und Raumfahrt (DLR), Centre National d'Études Spatiales [Toulouse] (CNES), Laboratoire d'Ingénierie des Matériaux (LIM), Institut de recherche en astrophysique et planétologie (IRAP), Institut national des sciences de l'Univers (INSU - CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Institut Supérieur de l'Aéronautique et de l'Espace (ISAE-SUPAERO), UNS-CNRS-Observatoire de la Côte d'Azur, Department of Earth and Planetary Sciences [Santa Cruz], University of California [Santa Cruz] (UCSC), University of California-University of California, School of Earth Sciences [Bristol], University of Bristol [Bristol], Joseph Louis LAGRANGE (LAGRANGE), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Supérieur de l'Aéronautique et de l'Espace - ISAE-SUPAERO (FRANCE), Department of Earth Sciences [ETH Zürich] (D-ERDW), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), California Institute of Technology (CALTECH)-NASA, Department of Geological Sciences, University of Florida [Gainesville], Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Cornell University, Université d'Angers (UA)-Université de Nantes - Faculté des Sciences et des Techniques, Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Département des Géosciences - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Université Fédérale Toulouse Midi-Pyrénées-Centre National d'Études Spatiales [Toulouse] (CNES)-Météo France-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Université Fédérale Toulouse Midi-Pyrénées-Centre National d'Études Spatiales [Toulouse] (CNES)-Météo France-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS), Centre National de la Recherche Scientifique (CNRS)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), Schimmel, Martin [0000-0003-2601-4462], Department of Earth and Environmental Sciences [Munich], Laboratoire de Planétologie et Géodynamique UMR6112 (LPG), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA), Laboratoire de Géophysique Interne et Tectonophysique (LGIT), Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Laboratoire Central des Ponts et Chaussées (LCPC)-Institut des Sciences de la Terre (ISTerre), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-PRES Université de Grenoble-Institut de recherche pour le développement [IRD] : UR219-Institut national des sciences de l'Univers (INSU - CNRS)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-PRES Université de Grenoble-Institut de recherche pour le développement [IRD] : UR219-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique du Globe de Paris (IPG Paris), Max-Planck-Institut für Sonnensystemforschung = Max Planck Institute for Solar System Research (MPS), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Unité de recherche de l'institut du thorax (ITX-lab), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), University of California [Santa Cruz] (UC Santa Cruz), University of California (UC)-University of California (UC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), and ANR-14-CE36-0012,SEISMARS,Seismology on Mars(2014)
Subjects: Seismometer, 010504 meteorology & atmospheric sciences, [PHYS.ASTR.EP]Physics [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], Mars, Induced seismicity, InSight Mars Marsbeben Seismizität, 010502 geochemistry & geophysics, seismology, 01 natural sciences, Mantle (geology), Elysium, [SDU.STU.PL]Sciences of the Universe [physics]/Earth Sciences/Planetology, Autre, Planet, inner planets, ComputingMilieux_MISCELLANEOUS, Seismology, InSight, 0105 earth and related environmental sciences, Seismicity, Crust, Geology, Mars Exploration Program, [SDU]Sciences of the Universe [physics], 13. Climate action, General Earth and Planetary Sciences
Abstract: The InSight (Interior Exploration using Seismic Investigations, Geodesy and Heat Transport) mission landed in Elysium Planitia on Mars on 26 November 2018 and fully deployed its seismometer by the end of February 2019. The mission aims to detect, characterize and locate seismic activity on Mars, and to further constrain the internal structure, composition and dynamics of the planet. Here, we present seismometer data recorded until 30 September 2019, which reveal that Mars is seismically active. We identify 174 marsquakes, comprising two distinct populations: 150 small-magnitude, high-frequency events with waves propagating at crustal depths and 24 low-frequency, subcrustal events of magnitude Mw 3–4 with waves propagating at various depths in the mantle. These marsquakes have spectral characteristics similar to the seismicity observed on the Earth and Moon. We determine that two of the largest detected marsquakes were located near the Cerberus Fossae fracture system. From the recorded seismicity, we constrain attenuation in the crust and mantle, and find indications of a potential low-S-wave-velocity layer in the upper mantle. © 2020, The Author(s), under exclusive licence to Springer Nature Limited., We acknowledge NASA, CNES and its partner agencies and institutions (UKSA, SSO, DLR, JPL, IPGP-CNRS, ETHZ, IC and MPS-MPG) and the flight operations team at JPL, SISMOC, MSDS, IRIS-DMC and PDS for providing SEIS data. The Swiss co-authors were jointly funded by (1) the Swiss National Science Foundation and French Agence Nationale de la Recherche (SNF-ANR project 157133 ‘Seismology on Mars’), (2) the Swiss National Science Foundation (SNF project 172508 ‘Mapping the internal structure of Mars’), (3) the Swiss State Secretariat for Education, Research and Innovation (SEFRI project ‘MarsQuake Service-Preparatory Phase’) and (4) ETH Research grant no. ETH-06 17-02. Additional support came from the Swiss National Supercomputing Centre (CSCS) under project ID s922. The Swiss contribution in the implementation of the SEIS electronics was made possible by funding from the federal Swiss Space Office (SSO) and contractual and technical support from the ESA-PRODEX office. The French Team acknowledge the French Space Agency CNES, which has supported and funded all SEIS-related contracts and CNES employees, as well as CNRS and the French team universities for personal and infrastructure support. Additional support was provided by ANR (ANR-14-CE36-0012-02 and ANR-19-CE31-0008-08) and, for the IPGP team, by the UnivEarthS Labex programme (ANR-10-LABX-0023), IDEX Sorbonne Paris Cité (ANR-11-IDEX-0005-0). SEIS-SP development and delivery were funded by the UK Space Agency. A portion of the work was carried out at the InSight Project at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration. The MPS SEIS team acknowledges funding for development of the SEIS leveling system by the DLR German Space Agency. We thank gempa GmbH for software development related to the MQS tools. This paper is InSight contribution number 102.
Published: 2020
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36. Role of the unfolded protein response in tumor cell characteristics and cancer outcome

Author: Antoine Galmiche, Eric Chevet, Olivier Pluquet, Chloé Sauzay, CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), CRLCC Eugène Marquis (CRLCC), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé, and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
Subjects: 0301 basic medicine, Oncology, endocrine system, endoplasmic-reticulum stress, Cancer Research, medicine.medical_specialty, MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, Tumor cells, er stress, digestive system, in-vivo, Outcome (game theory), alpha-fetoprotein, 03 medical and health sciences, 0302 clinical medicine, Text mining, Neoplasms, Internal medicine, medicine, Humans, up-regulation, breast-cancer, mechanisms, business.industry, Cancer, Prognosis, advanced-hepatocellular-carcinoma, medicine.disease, 3. Good health, 030104 developmental biology, multiple-myeloma, 030220 oncology & carcinogenesis, biological sciences, Unfolded Protein Response, Unfolded protein response, resistant prostate-cancer, business
Abstract: International audience; Purpose of reviewIn the present review, we discuss the possible role of the unfolded protein response (UPR) in the acquisition of tumor cell characteristics and in the prognosis of cancer outcome, which could assist and contribute to the development of more promising therapeutic strategies.Recent findingsAccumulating evidence supports the idea that alteration of endoplasmic reticulum proteostasis is a key player in cancer development and aggressiveness. Some UPR components were reported as independent prognostic biomarker. Recent evidence supports a relationship between the UPR activation status and prognosis of tumors. This may represent an interesting avenue for better characterization of carcinogenesis and tumor type.SummaryThe contribution of the UPR to the characteristics of malignant tumors is complex and dependent on both intrinsic (e.g. oncogene addiction) and extrinsic (e.g. hypoxia) contexts. Through adaptation to severe microenvironmental conditions, UPR branches are generally a survival strategy for cancer cells, which are able to cope with this challenging context. We address the question of whether the activation status of the UPR is related to tumor properties and discuss the role of the UPR in the clinical context.
Published: 2017
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37. Selective Catalytic Electroreduction of CO2 at Silicon Nanowires (SiNWs) Photocathodes Using Non-Noble Metal-Based Manganese Carbonyl Bipyridyl Molecular Catalysts in Solution and Grafted onto SiNWs

Author: Mollereau, B., Rzechorzek, N. M., Roussel, B. D., Sedru, M., Brink, D., Bailly-Maitre, B., Palladino, F., Medinas, D. B., Domingos, P. M., Hunot, S., Chandran, S., Birman, S., Baron, T., Vivien, D., Duarte, C. B., Ryoo, H. D., Steller, H., Urano, F., Chevet, E., Kroemer, G., Ciechanover, A., Calabrese, E. J., Kaufman, R. J., Hetz, C, Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Département de Chimie Moléculaire (DCM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Joseph Fourier - Grenoble 1 (UJF), ANR-11-LABX-0003-01, Agence Nationale de la Recherche, Institut de Chimie Moléculaire de Grenoble, ANR-11-LABX-0003,ARCANE,Grenoble, une chimie bio-motivée(2011), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Laboratory of Apoptosis and Cancer Biology, Rockefeller University [New York], Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme de métabolomique, Direction de la recherche [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Pôle de biologie, 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), Apoptose, cancer et immunité (Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Photocurrent, Materials science, Silicon, 010405 organic chemistry, Inorganic chemistry, chemistry.chemical_element, General Chemistry, Manganese, Glassy carbon, 010402 general chemistry, 01 natural sciences, 7. Clean energy, Catalysis, 0104 chemical sciences, chemistry, Electrode, [CHIM]Chemical Sciences, Cyclic voltammetry, Silicon nanowires
Abstract: International audience; The electrocatalytic redn. of CO2 to CO in hydroorg. medium has been investigated at illuminated (λ \textgreater 600 nm; 20 mW cm-2) hydrogen-terminated silicon nanowires (SiNWs-H) photocathodes using three Mn-based carbonyl bipyridyl complexes as homogeneous mol. catalysts ([Mn(L) (CO)3(CH3CN)](PF6) and [Mn(bpy) (CO)3Br] with L = bpy = 2,2'-bipyridine and dmbpy = 4,4'-dimethyl-2,2'-bipyridine). Systematic comparison of their cyclic voltammetry characteristics with those obtained at flat hydrogen-terminated silicon and traditional glassy carbon electrodes (GCE) enabled us to demonstrate the superior catalytic efficiency of SiNWs-H in terms of cathodic photocurrent densities and overpotentials. For example, the photocurrent densities measured at -1.0 V vs SCE for [Mn(bpy) (CO)3(CH3CN)](PF6) at SiNWs-H exceeded 1.0 mA cm-2 in CO2-satd. CH3CN + 5% vol./vol. H2O, whereas almost zero current was measured at this potential at GCE. Such characteristics have been supported by the energetic diagrams built for the different SiNWs\textbarMn-based catalyst interfaces. The fill factor FF and energy conversion efficiency η calcd. under catalytic conditions were higher for [Mn(bpy or dmbpy) (CO)3(CH3CN)](PF6) (FF = 0.35 and 0.34; η = 3.0 and 2.0%, resp.). Further preparative-scale electrolysis at SiNWs-H photocathode with Mn-based complex catalysts in electrolytic soln. evidenced the quant. conversion of CO2 to CO with a higher stability of the [Mn(dmbpy) (CO)3(CH3CN)](PF6) complex. Finally, in order to develop technol. viable electrocatalytic devices, the elaboration of SiNWs-H photoelectrodes modified with a Mn-based complex has been successfully achieved from an electropolymerizable catalyst, and it was shown that the electrocatalytic activity of the complex was retained after immobilization.
Published: 2015
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38. Controlling the unfolded protein response-mediated life and death decisions in cancer

Author: Eoghan P. McGrath, Katarzyna Mnich, Sandra Healy, Marion Maurel, Eric Chevet, Afshin Samali, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), 06/RFP/BIC002, Science Foundation Ireland, Ligue Contre le Cancer, IAP 7/32, Interuniversity Attraction Poles, Institut National du Cancer, and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
Subjects: Cell death, Cancer Research, Programmed cell death, Cell Survival, [SDV.CAN]Life Sciences [q-bio]/Cancer, Apoptosis, UPR, Protein Serine-Threonine Kinases, Biology, Endoplasmic Reticulum, Malignant transformation, Adenosine Triphosphate, Neoplasms, Endoribonucleases, medicine, Animals, Homeostasis, Humans, Cell Lineage, Cancer, Oncogene, Endoplasmic reticulum, Endoplasmic Reticulum Stress, medicine.disease, Activating Transcription Factor 6, Cell biology, Cell Transformation, Neoplastic, Cancer cell, Unfolded Protein Response, Unfolded protein response, ER stress, Signal Transduction
Abstract: International audience; Cancer cells are exposed to intrinsic (oncogene) or extrinsic (microenvironmental) challenges, leading to activation of stress response pathways. The unfolded protein response (UPR) is the cellular response to endoplasmic reticulum (ER) stress and plays a pivotal role in tumor development. Depending on ER stress intensity and duration, the UPR is either pro-survival to preserve ER homeostasis or pro-death if the stress cannot be resolved. On one hand, the adaptive arm of the UPR is essential for cancer cells to survive the harsh conditions they are facing, and on the other hand, cancer cells have evolved mechanisms to bypass ER stress-induced cell death, thereby conferring them with a selective advantage for malignant transformation. Therefore, the mechanisms involved in the balance between survival and death outcomes of the UPR may be exploited as therapeutic tools to treat cancer
Published: 2015
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39. Proteostasis control by the unfolded protein response

Author: Scott A. Oakes, Eric Chevet, Claudio Hetz, Biomedical Neuroscience Institute, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
Subjects: [SDV]Life Sciences [q-bio], Cell fate determination, Biology, Models, Biological, Article, 03 medical and health sciences, 0302 clinical medicine, Animals, Homeostasis, Humans, Glucose homeostasis, Kinase activity, 030304 developmental biology, 0303 health sciences, Endoplasmic reticulum, Proteins, Cell Biology, Endoplasmic Reticulum Stress, Cell biology, Proteostasis, Unfolded Protein Response, Unfolded protein response, Protein folding, Signal transduction, 030217 neurology & neurosurgery, Signal Transduction
Abstract: International audience; Stress induced by accumulation of misfolded proteins in the endoplasmic reticulum is observed in many physiological and pathological conditions. To cope with endoplasmic reticulum stress, cells activate the unfolded protein response, a dynamic signalling network that orchestrates the recovery of homeostasis or triggers apoptosis, depending on the level of damage. Here we provide an overview of recent insights into the mechanisms that cells employ to maintain proteostasis and how the unfolded protein response determines cell fate under endoplasmic reticulum stress
Published: 2015
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40. Correction to: Surgery in reference centers improves survival of sarcoma patients: a nationwide study

Author: M. Karanian-Philippe, Isabelle Ray-Coquard, A. Di Marco, J.-M. Guilloit, C. Perrin, M. Toulmonde, J.-P. Spano, G. Ferron, C. Le Pechoux, O. Collard, M. Rios, François Sirveaux, J. Guiramand, A. Dufresne, L. Chaigneau, C. Chevreau, S. Causeret, P. Gimbergues, L.R. Le Nail, M. Jafari, J.-C. Ruzic, O. Marco, F. Gouin, G. Vaz, A. Dupré, P. Anract, E. Stoeckle, A. Michot, F. Dujardin, Jean-Yves Blay, Emmanuelle Bompas, F. Guillemin, C. Honore, F. Duffaud, P. Meeus, A. Rochwerger, Nicolas Penel, F. Fiorenza, F. Le Loarer, S. Bonvalot, Mickaël Ropars, A. Le Cesne, F. Ducimetière, D. Pérol, A. Italiano, F. Marchal, P. Soibinet, Sébastien Carrère, J.-C. Machiavello, A. Giraud, François Bertucci, N. Firmin, M. Brahmi, AIRPARIF - Surveillance de la qualité de l'air en Île-de-France, Institut Bergonié - CRLCC Bordeaux, Centre Léon Bérard [Lyon], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], 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), Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique (LHEEA), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Centre chirurgical Émile-Gallé, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Department of Surgical Oncology, Jean Perrin Comprehensive Cancer Centre, Service de Chirurgie orthopédique et traumatologique [CHU Limoges], CHU Limoges, Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes (LCP-A2MC), CHU Pitié-Salpêtrière [APHP], Institut Claudius Regaud, CRLCC Institut Claudius Regaud, Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR), Centre de Recherches sur les Macromolécules Végétales (CERMAV), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire Interdisciplinaire de Recherche Impliquant la Géologie et la Mécanique, Université Joseph Fourier - Grenoble 1 (UJF), Centre Oscar Lambret, Laboratoire des Mécanismes et Transfert en Géologie (LMTG), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, medicine.medical_specialty, Multivariate analysis, [SDV]Life Sciences [q-bio], medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Relapse free survival, 03 medical and health sciences, 0302 clinical medicine, medicine, Neurofibromatosis, Pathological, ComputingMilieux_MISCELLANEOUS, business.industry, Hazard ratio, Cancer, Hematology, medicine.disease, 3. Good health, Surgery, Radiation therapy, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Sarcoma, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background NETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry. Patients and methods Patients’ characteristics and follow-up are prospectively collected and data monitored. Descriptive, uni- and multivariate analysis of prognostic factors were conducted in the entire series (N = 35 784) and in the subgroup of incident patient population (N = 29 497). Results Among the 35 784 patients, 155 different histological subtypes were reported. 4310 (11.6%) patients were metastatic at diagnosis. Previous cancer, previous radiotherapy, neurofibromatosis type 1 (NF1), and Li–Fraumeni syndrome were reported in 12.5%, 3.6%, 0.7%, and 0.1% of patients respectively. Among the 29 497 incident patients, 25 851 (87.6%) patients had surgical removal of the sarcoma, including 9949 (33.7%) operated in a NETSARC center. Location, grade, age, size, depth, histotypes, gender, NF1, and surgery outside a NETSARC center all correlated to overall survival (OS), local relapse free survival (LRFS), and event-free survival (EFS) in the incident patient population. NF1 history was one of the strongest adverse prognostic factors for LRFS, EFS, and OS. Presentation to an MDTB was associated with an improved LRFS and EFS, but was an adverse prognostic factor for OS if surgery was not carried out in a reference center. In multivariate analysis, surgery in a NETSARC center was positively correlated with LRFS, EFS, and OS [P
Published: 2019
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41. Integrated and Quantitative Proteomics of Human Tumors

Author: Yakkioui, Y., Temel, Y., Chevet, E., Negroni, L., Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Phosphopeptides, Proteomics, Proteome, Glycopeptides, [SDV.CAN]Life Sciences [q-bio]/Cancer, hepatocellular carcinoma, Mass Spectrometry, Neoplasm Proteins, iTRAQ, Sequence Analysis, Protein, Tandem Mass Spectrometry, Neoplasms, Solid tumors, Chordoma, Animals, Humans, Protein Processing, Post-Translational, Chromatography, High Pressure Liquid
Abstract: International audience; Quantitative proteomics represents a powerful approach for the comprehensive analysis of proteins expressed under defined conditions. These properties have been used to investigate the proteome of disease states, including cancer. It has become a major subject of studies to apply proteomics for biomarker and therapeutic target identification. In the last decades, technical advances in mass spectrometry have increased the capacity of protein identification and quantification. Moreover, the analysis of posttranslational modification (PTM), especially phosphorylation, has allowed large-scale identification of biological mechanisms. Even so, increasing evidence indicates that global protein quantification is often insufficient for the explanation of biology and has shown to pose challenges in identifying new and robust biomarkers. As a consequence, to improve the accuracy of the discoveries made using proteomics in human tumors, it is necessary to combine (i) robust and reproducible methods for sample preparation allowing statistical comparison, (ii) PTM analyses in addition to global proteomics for additional levels of knowledge, and (iii) use of bioinformatics for decrypting protein list. Herein, we present technical specificities for samples preparation involving isobaric tag labeling, TiO2-based phosphopeptides enrichment and hydrazyde-based glycopeptides purification as well as the key points for the quantitative analysis and interpretation of the protein lists. The method is based on our experience with tumors analysis derived from hepatocellular carcinoma, chondrosarcoma, human embryonic intervertebral disk, and chordoma experiments.
Published: 2017
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42. CD95-Mediated Proton Regulation

Author: Auréa Cophignon, Mallorie Poët, Laurent Counillon, Michael Monet, Michel Tauc, Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Laboratoire SYstèmes et Matériaux pour la MEcatronique (SYMME), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Laboratoire de PhysioMédecine Moléculaire (LP2M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Laboratoire CNRS 3093, Université de Nice-Sophia Antipolis, Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Université de Rennes (UR), and Université Nice Sophia Antipolis (1965 - 2019) (UNS)
Subjects: 0301 basic medicine, chemistry.chemical_classification, Chemistry, [SDV]Life Sciences [q-bio], Intracellular pH, Kinetic measurements, Kinetics, Transporter, Intracellular acidification, Ligand (biochemistry), 03 medical and health sciences, 030104 developmental biology, Enzyme, Yield (chemistry), Biophysics, CD95 signaling, ComputingMilieux_MISCELLANEOUS, Ion transporter, Intracellular, Ion transport
Abstract: The Na+/H+ exchanger NHE1 is at the crossroads of a large diversity of signaling pathways, whose activation modifies the cooperative response of the transporter to intracellular H+ ions. Here we show how the activation of the Na+/H+ exchanger NHE1 by the cleaved ligand of CD95 can be measured. We demonstrate two different methods designed to set intracellular pH at precise values. Then we show how these can be coupled to fast kinetics of lithium transport, which will enable to measure the NHE1 activity like for an enzyme, because they will yield rates of transport.
Published: 2017
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43. Atypical epithelial hyperplasia of the breast: state of the art

Author: Susie Brousse, Aurélie Cauchois, Charles Coutant, Jean Levêque, Adelaïde Racin, Ludivine Dion, Vincent Lavoué, Françoise Beltjens, CHU Pontchaillou [Rennes], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)
Subjects: Risk, Pathology, medicine.medical_specialty, surgical excision, Biopsy, Lobular carcinoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Atypical ductal hyperplasia, core needle biopsy, 030218 nuclear medicine & medical imaging, atypical lobular hyperplasia, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, breast cancer, Atypia, Medicine, Humans, Pharmacology (medical), Epithelial hyperplasia, Breast, skin and connective tissue diseases, lobular carcinoma in situ, Hyperplasia, medicine.diagnostic_test, business.industry, medicine.disease, Immunohistochemistry, 3. Good health, Oncology, columnar cell lesions with atypia, 030220 oncology & carcinogenesis, Female, business, lobular neoplasia, Precancerous Conditions, Lobular Neoplasia
Abstract: International audience; Introduction: Atypical epithelial hyperplasia (AEH) of the breast is considered benign histological lesions with breast cancer risk. This review focuses on clinical signification and management of AEH that remains controversial. Areas covered: A review of published studies was performed using medline database. In this review, we fully describe the current evidence available. In particular, we describe 1) data from immunohistochemistry and molecular studies that suggest AEH is a precursor of breast cancer; 2) epidemiological studies demonstrate low rate of breast cancer in women with AEH; 3) surgical excision is necessary after diagnosis of AEH, such as lobular carcinoma in situ or atypical ductal hyperplasia, on core needle biopsy; 4) although current recommendations are evolving to fewer (if not no) excisions for flat epithelial with atypia and classic lobular neoplasia found on percutaneous biopsy (without radiologic indications for excision). Expert commentary: HEA management steel need prospective evidences, but recent retrospective data give some clue for less invasive management for some of HEA. © 2016 Informa UK Limited, trading as Taylor & Francis Group.
Published: 2016
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44. Role of the tumor microenvironment in regulating apoptosis and cancer progression

Author: Karin Tarte, Rémy Pedeux, Katherine Yaacoub, Thierry Guillaudeux, Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Oncogenesis Stress Signaling (OSS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Service d’immunologie, de thérapie cellulaire et d’hématopoïèse, Hôpital Pontchaillou, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), and Jonchère, Laurent
Subjects: 0301 basic medicine, reed-sternberg cells, Cancer Research, chemotherapy resistance, Stromal cell, epstein-barr-virus, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, Apoptosis, Tumor initiation, Biology, Metastasis, peripheral-blood, 03 medical and health sciences, 0302 clinical medicine, drug-resistance, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neoplasms, medicine, Tumor Expansion, Tumor Microenvironment, Animals, Humans, Molecular Targeted Therapy, Receptors, Immunologic, b-cells, stromal cells, Cell Proliferation, Tumor microenvironment, ligand expression, classical hodgkins lymphoma, chemokine expression, Suicide gene, medicine.disease, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer cell, Immunology, Cancer research, Interleukin 12, Disease Progression, Tumor Escape, Inflammation Mediators, Apoptosis Regulatory Proteins, Signal Transduction
Abstract: International audience; Apoptosis is a gene-directed program that is engaged to efficiently eliminate dysfunctional cells. Evasion of apoptosis may be an important gate to tumor initiation and therapy resistance. Like any other developmental program, apoptosis can be disrupted, by several genetic aberrations driving malignant cells into an uncontrolled progression and survival. For its sustained growth, cancer develops in a complex environment, which provides survival signals and rescues malignant cells from apoptosis. Recent studies have clearly shown a wide interaction between tumor cells and their microenvironment, confirming the influence of the surrounding cells on tumor expansion and invasion. These non-malignant cells not only intensify tumor cells growth but also upgrade the process of metastasis. The strong crosstalk between malignant cells and a reactive microenvironment is mediated by soluble chemokines and cytokines, which act on tumor cells through surface receptors. Disturbing the microenvironment signaling might be an encouraging approach for patient's treatment. Therefore, the ultimate knowledge of "tumormicroenvironment" interactions facilitates the identification of novel therapeutic procedures that mobilize cancer cells from their supportive cells. This review focuses on cancer progression mediated by the dysfunction of apoptosis and by the fundamental relationship between tumor and reactive cells. New insights and valuable targets for cancer prevention and therapy are also presented.
Published: 2016
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45. Signaling the Unfolded Protein Response in primary brain cancers

Author: Véronique Quillien, Tony Avril, Pierre-Jean Le Reste, Xavier Morandi, Eric Chevet, CHU Pontchaillou [Rennes], Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), CRLCC Eugène Marquis (CRLCC), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), We apologize to colleagues whose work was not cited in this article due to space limitation. This work was supported by grants from Institut National du Cancer (INCa) and La Ligue Contre le Cancer to EC., Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: 0301 basic medicine, Choroid Plexus Neoplasms, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, UPR, Stress, Pineal Gland, Brain cancer, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Glioma, Meningeal Neoplasms, Medicine, Animals, Humans, education, Cerebellar Neoplasms, Molecular Biology, brain cancer, Chemotherapy, education.field_of_study, business.industry, Brain Neoplasms, General Neuroscience, Endoplasmic reticulum, Limiting nutrient, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease, Endoplasmic Reticulum Stress, 3. Good health, 030104 developmental biology, Immunology, Cancer cell, Cancer research, Unfolded protein response, Unfolded Protein Response, Neurology (clinical), business, Glioblastoma, Meningioma, Pinealoma, Developmental Biology, Medulloblastoma, Signal Transduction
Abstract: International audience; The Unfolded Protein Response (UPR) is an adaptive cellular program used by eukaryotic cells to cope with protein misfolding stress in the Endoplasmic Reticulum (ER). During tumor development, cancer cells are facing intrinsic (oncogene activation) and extrinsic (limiting nutrient or oxygen supply; exposure to chemotherapies) challenges, with which they must cope to survive. Primary brain tumors are relatively rare but deadly and present a significant challenge in the determination of risk factors in the population. These tumors are inherently difficult to cure because of their protected location in the brain. As such surgery, radiation and chemotherapy options carry potentially lasting patient morbidity and incomplete tumor cure. Some of these tumors, such as glioblastoma, were reported to present features of ER stress and to depend on UPR activation to sustain growth, but to date there is no clear general representation of the ER stress status in primary brain tumors. In this review, we describe the key molecular mechanisms controlling the UPR and their implication in cancers. Then we extensively review the literature reporting the status of ER stress in various primary brain tumors and discuss the potential impact of such observation on patient stratification and on the possibility of developing appropriate targeted therapies using the UPR as therapeutic target
Published: 2016
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46. Using AlphaScreen® to Identify Small-Molecule Inhibitors Targeting a Conserved Host–Pathogen Interaction

Author: Said Taouji, Sisley Austin, Fabienne Rayne, Harald Wodrich, Eric Chevet, Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Microbiologie Fondamentale et Pathogénicité (MFP), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
Subjects: 0301 basic medicine, Host–pathogen interaction, [LP]PxY motif, High-throughput, [SDV.CAN]Life Sciences [q-bio]/Cancer, NEDD4, Peptide, 384-Well plate, law.invention, Protein–protein interaction, 03 medical and health sciences, Ubiquitin, law, Ubiquitin ligase Nedd4, Adenovirus, AlphaScreen®, Antiviral, chemistry.chemical_classification, biology, Protein-Protein interactions, Small molecule, Molecular biology, Small-molecule inhibitors, 030104 developmental biology, Capsid, Biochemistry, chemistry, Recombinant DNA, biology.protein
Abstract: International audience; AlphaScreen ® is a technology particularly suitable for bi-molecular inhibitor screening assays, e.g. using protein–protein interactions with purifi ed recombinant proteins. Each binding partner of the bi-molecular interaction is coupled either to donor or to acceptor beads. The technology is based on the quantifi able transfer of oxygen singlets from donor to acceptor microbeads brought together by a specifi c interaction between the partners. We identifi ed the conserved interaction between WW domains of cellular ubiquitin ligases of the Nedd4 family and a short peptide motif (PPxY) present in several structural and nonstructural viral proteins as a potential drug target. Using an AlphaScreen assay recapitulating the interaction between Nedd4.2 and the PPxY motif of the adenoviral capsid protein VI, we screened a library of small molecules and identifi ed specifi c inhibitors of this interaction. © Springer Science+Business Media New York 2016.
Published: 2016
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47. Proteostasis trumps YAP in colon cancer

Author: Eric Chevet, Tony Avril, Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), CRLCC Eugène Marquis (CRLCC), Institut National Du Cancer, Ligue Contre le Cancer, and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
Subjects: Colorectal cancer, [SDV]Life Sciences [q-bio], Cell Biology, Biology, Bioinformatics, medicine.disease, Biochemistry, Verteporfin, 3. Good health, Proteostasis, Proteotoxicity, Cancer cell, medicine, Cancer research, Molecular Biology, medicine.drug
Abstract: International audience; In this issue of Science Signaling, Zhang et al. find a new role for verteporfin in the control of colorectal cancer progression through the selective induction of proteotoxicity rather than through inhibition of the transcription cofactor YAP. The study further documents the potential strategy of targeting proteostasis to kill cancer cells
Published: 2015
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48. Endometrial cancer in elderly women: Which disease, which surgical management? A systematic review of the literature

Author: Marine Saidani, Clotilde Poupon, Jean Levêque, Aurélie Cauchois, F. Foucher, C. Bourgin, Vincent Lavoué, CHU Pontchaillou [Rennes], Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)
Subjects: Carcinogenesis, health care facilities, manpower, and services, [SDV]Life Sciences [q-bio], Disease, 0302 clinical medicine, Postoperative Complications, Robotic Surgical Procedures, oncogeriatric scores, elderly women, Laparoscopy, Aged, 80 and over, education.field_of_study, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, General Medicine, Prognosis, humanities, 3. Good health, Survival Rate, Oncology, 030220 oncology & carcinogenesis, endometrial cancer, Female, medicine.medical_specialty, Population, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 03 medical and health sciences, medicine, Humans, Intensive care medicine, education, Survival rate, Geriatric Assessment, Aged, Neoplasm Staging, surgical approach, business.industry, Endometrial cancer, Carcinoma, Cancer, social sciences, Length of Stay, medicine.disease, Surgery, Endometrial Neoplasms, Concomitant, business
Abstract: International audience; Objective: Endometrial cancer primarily affects elderly women. The aim of the present literature review is to define the population of elderly women with this disease and to define the characteristics of this cancer in elderly people as well as its surgical treatment. Materials and Methods: A systematic review of the English-language literature of the last 20 years indexed in the PubMed database. Results Endometrial cancer is more aggressive in elderly women. However, surgical staging performed in elderly patients is often not concomitant with the disease’s aggressiveness in this group. Mini-invasive surgery is performed less often, for no obvious reason. Of note, oncogeriatric evaluation was not usually ruled out to determine the most appropriate surgical modality. Conclusion: Studies are needed to evaluate surgical management of endometrial cancer in elderly women, notably with the aid of oncogeriatric scores to predict surgical morbidity.
Published: 2015
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49. A Novel Covalent mTOR Inhibitor, DHM25, Shows in Vivo Antitumor Activity against Triple-Negative Breast Cancer Cells

Author: Yves Collette, Kenji F. Shoji, Olivier Delalande, Rémy Castellano, Mac Dinh Hung, Patrick Legembre, Marine Malleter, Mickael Jean, Emmanuelle Josselin, Pierre van de Weghe, Hariniaina Rampanarivo, Amélie Fouqué, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Oncogenesis Stress Signaling (OSS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Institut National Du Cancer, Ministère de l'Enseignement Supérieur et de la Recherche, Fondation ARC pour la Recherche sur le Cancer, Comité du Morbihan, Ligue Nationale Contre le Cancer, Comité de Maine-et-Loire, Ligue Nationale Contre le Cancer, Comité des Côtes-d'Armor, Ligue Nationale Contre le Cancer, Comité du Finistère, Ligue Nationale Contre le Cancer, Comité d’Ille-et-Vilaine, Ligue Nationale Contre le Cancer, Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
Subjects: Models, Molecular, [SDV]Life Sciences [q-bio], Antineoplastic Agents, Breast Neoplasms, Metastasis, Mice, Structure-Activity Relationship, Mice, Inbred NOD, Cell Line, Tumor, Drug Discovery, medicine, Animals, Humans, Kinome, Benzopyrans, Kinase activity, Phosphorylation, PI3K/AKT/mTOR pathway, Triple-negative breast cancer, Phosphoinositide-3 Kinase Inhibitors, Kinase, Chemistry, TOR Serine-Threonine Kinases, RPTOR, medicine.disease, Molecular biology, 3. Good health, Oncogene Protein v-akt, Cancer cell, Cancer research, Molecular Medicine, Female, Drug Screening Assays, Antitumor, Signal Transduction
Abstract: International audience; Constitutive activation of the PI3K/mTOR signaling pathway contributes to carcinogenesis and metastasis in most, if not all, breast cancers. From a chromene backbone reported to inhibit class I PI3K catalytic subunits, several rounds of chemical syntheses led to the generation of a new collection of chromologues that showed enhanced ability to kill PI3K-addicted cancer cells and to inhibit Akt phosphorylation at serine 473, a hallmark of PI3K/mTOR activation. This initial screen uncovered a chromene designated DHM25 that exerted potent antitumor activity against breast tumor cell lines. Strikingly, DHM25 was shown to be a selective and covalent inhibitor of mTOR using biochemical and cellular analyses, modeling, and a large panel of kinase activity assays spanning the human kinome (243 kinases). Finally, in vivo, this novel drug was an efficient inhibitor of growth and metastasis of triple-negative breast cancer cells, paving the way for its clinical application in oncology
Published: 2015
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50. Novel roles of the unfolded protein response in the control of tumor development and aggressiveness

Author: Eric Chevet, Martin E. Fernandez-Zapico, Afshin Samali, Kim Barroso, Nicolas Dejeans, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Schulze Center for Novel Therapeutics, Division of Oncology Research [Rochester], Mayo Clinic [Rochester], Apoptosis Research Centre (ARC), National University of Ireland [Galway] (NUI Galway), This work was funded by grants from Institut National du Cancer (INCa) and Ligue Contre le Cancer to EC. ND was supported by a post-doctoral fellowship from Fondation de France., and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
Subjects: cellular physiology, Cancer Research, tumor, endoplasmic-reticulum stress, Epithelial-Mesenchymal Transition, [SDV]Life Sciences [q-bio], Cell, emt, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, heme oxygenase-1 gene, Biology, er stress, in-vivo, Mice, stress, Neoplasms, medicine, Animals, Homeostasis, Humans, cancer, to-mesenchymal transition, Secretory pathway, transcription factor, Gastrointestinal Neoplasms, glioblastoma-multiforme, Endoplasmic reticulum, Cell Membrane, malignant progression, Phenotype, Cell biology, endoplasmic reticulum, medicine.anatomical_structure, Cell Transformation, Neoplastic, Drug Resistance, Neoplasm, Cancer cell, Unfolded protein response, Disease Progression, Unfolded Protein Response, negative breast-cancer, Signal transduction, Biogenesis, Signal Transduction
Abstract: International audience; The hallmarks of cancer currently define the molecular mechanisms responsible for conferring specific tumor phenotypes. Recently, these characteristics were also connected to the status of the secretory pathway, thereby linking the functionality of this cellular machinery to the acquisition of cancer cell features. The secretory pathway ensures the biogenesis of proteins that are membrane-bound or secreted into the extracellular milieu and can control its own homeostasis through an adaptive signaling pathway named the Unfolded Protein Response (UPR). In the present review, we discuss the specific features of the UPR in various tumor types and the impact of the selective activation of this pathway on cell transformation, tumor development and aggressiveness.
Published: 2015
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