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323 results on '"Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)"'

1. 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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2. 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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3. 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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4. Panitumumab in combination with chemoradiotherapy for the treatment of locally-advanced anal canal carcinoma: Results of the FFCD 0904 phase II trial

Author: Vendrely, Véronique, Ronchin, Philippe, Minsat, Mathieu, Le Malicot, Karine, Lemanski, Claire, Mirabel, Xavier, Etienne, Pierre-Luc, Lièvre, Astrid, Darut-Jouve, Ariane, de la Fouchardière, Christelle, Giraud, Nicolas, Breysacher, Gilles, Argo-Leignel, Delphine, Thimonnier, Elsa, Magné, Nicolas, Abdelghani, Meher Ben, Lepage, Côme, Aparicio, Thomas, BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Institut du Cancer de Montpellier (ICM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Bourgogne, Centre Léon Bérard [Lyon], Institut de Cancérologie Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CRLCC Paul Strauss, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hopital Saint-Louis [AP-HP] (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Epidermal growth factor receptor, Panitumumab, Squamous cell carcinoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Chemoradiotherapy, Immunotherapy, Anal cancer
Abstract: Background and purpose: Standard treatment of squamous cell carcinoma of the anus (SCCA)is 5-fluorouracil (5FU) and mitomycin C (MMC) based chemoradiotherapy (CRT). This phase II study (EudraCT: 2011-005436-26) assessed the tolerance and complete response (CR) rate at 8 weeks of panitumumab (Pmab) combined with MMC-5FU-based CRT.Methods: Patients with locally advanced tumors without metastases (T2 > 3 cm, T3-T4, or N + whatever T stage) were treated with IMRT up to 65 Gy and concomitant CT according to the doses defined by a previous phase I study (MMC: 10 mg/m2; 5FU: 400 mg/m2; Pmab: 3 mg/kg). The expected CR rate was 80%.Results: Forty-five patients (male: 9, female: 36; median age: 60.1 [41.5-81]) were enrolled in 15 French centers. The most common related grade 3-4 toxicities observed were digestive (51.1%), hematologic (lymphopenia: 73.4%; neutropenia: 11.1%), radiation dermatitis (13.3%), and asthenia (11.1%) with RT interruption in 14 patients. One patient died because of mesenteric ischemia during the CRT, possibly related to treatment. In ITT analysis, the CR rate at 8 weeks after CRT was 66.7% [90%CI: 53.4-78.2]. Median follow-up was 43.6 months [IC 95%: 38.61-47.01]. Overall survival, recurrence-free and colostomy-free survival at 3 years were 80% [95%CI: 65.1-89], 62.2% [IC95%: 46.5-74.6] and 68.8 % [IC95%: 53.1-80.2] respectively.Conclusion: Panitumumab in combination with CRT for locally advanced SCCA failed to meet the expected CR rate and exhibited a poor tolerance. Furthermore, late RFS, CFS, and OS did not suggest any outcome improvement to justify further clinical trials.Clinicaltrials: gov identifier: NCT01581840.
Published: 2023
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5. 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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6. 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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7. 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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8. A novel IRE1 kinase inhibitor for adjuvant glioblastoma treatment

Author: Diana Pelizzari-Raymundo, Dimitrios Doultsinos, Raphael Pineau, Chloé Sauzay, Thodoris Koutsandreas, Timothy Langlais, Antonio Carlesso, Elena Gkotsi, Luc Negroni, Tony Avril, Aristotelis Chatziioannou, Eric Chevet, Leif A. Eriksson, Xavier Guillory, Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biomedical Research Foundation of the Academy of Athens (BRFAA), Institut des Sciences Chimiques de Rennes (ISCR), 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), University of Gothenburg (GU), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), We thank Dr Frédéric Delom, Dr Delphine Fessart, Pr Reynald Gillet, Dr David Gillot, Dr Élodie Lafont, Dr Eric Ogier-Denis, and Pr Afshin Samali for the critical reading of the manuscript. Part of this work was carried out using the Spectroscopies-CDTP core facility, the animal facility ARCHE, and the immunohistochemistry platform H2P2 (UMS Biosit, Université de Rennes 1- Campus de Villejean - 35043 RENNES Cedex, FRANCE). This work was supported by grants from Institut National du Cancer (INCa, PLBIO), Agence Nationale de la Recherche (ANR, ERAAT), Fondation pour la Recherche Médicale (FRM, DEQ20180339169), the EU COST action 861952 \'Proteocure\' and Cancéropôle Grand-Ouest (Gliotreat) to E.C., EU H2020 MSCA ITN-675448 (TRAINERS) and MSCA RISE-734749 (INSPIRED) grants to E.C., A.C., and L.A.E., INSERM (International Research Project – TUPRIC) to A.C. and E.C., La Ligue contre le Cancer (comités 22, 35, 36, 56 et 85), INSERM, Région Bretagne and from the institut des Neurosciences Cliniques de Rennes (INCR) to T.A. The Swedish Research Council (VR, grant no 2019-3684)), the Swedish Cancer Foundation (grant no 21-1447 Pj) and the Swedish National Infrastructure for Computing (SNIC, funded in part through VR grant agreement 2018-05973) are gratefully acknowledged for funding and allocations of computing time, respectively (L.A.E.). D.P.R. was funded by grants from INSERM (LA VANNETAISE) and the Brittany Region, D.D. was funded by EU H2020 MSCA ITN-675448, C.S. was funded by a Plan Cancer post-doctoral fellowship, X.G. was funded by the Fondation ARC pour la recherche sur le cancer, grant PDF20191209830, C.S. was funded by a post-doctoral fellowship from INSERM-plan cancer., and ANR-17-RAR3-0003,ERAAT,Enhancing Endoplasmic Reticulum Proteostasis to Rescue Alpha1 Antitrypsin Deficiency(2017)
Subjects: Biological sciences, Multidisciplinary, Medicine, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Molecular neuroscience, Neuroscience
Abstract: International audience; Inositol-requiring enzyme 1 (IRE1) is a major mediator of the unfolded protein response (UPR), which is activated upon endoplasmic reticulum (ER) stress. Tumor cells experience ER stress due to adverse microenvironmental cues, a stress overcome by relying on IRE1 signaling as an adaptive mechanism. Herein, we report the discovery of structurally new IRE1 inhibitors identified through the structural exploration of its kinase domain. Characterization in in vitro and in cellular models showed that they inhibit IRE1 signaling and sensitize glioblastoma (GB) cells to the standard chemotherapeutic, temozolomide (TMZ). Finally, we demonstrate that one of these inhibitors, Z4P, permeates the blood-brain barrier (BBB), inhibits GB growth, and prevents relapse in vivo when administered together with TMZ. The hit compound disclosed herein satisfies an unmet need for targeted, non-toxic IRE1 inhibitors and our results support the attractiveness of IRE1 as an adjuvant therapeutic target in GB.
Published: 2023
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9. Transcriptomic evidence for tumor-specific beneficial or adverse effects of TGFβ pathway inhibition on the prognosis of patients with liver cancer

Author: Matthis Desoteux, Betty Maillot, Kevin Bévant, Tanguy Ferlier, Raffaële Leroux, Gaëlle Angenard, Corentin Louis, Laurent Sulpice, Karim Boudjema, Cédric Coulouarn, 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), CHU Pontchaillou [Rennes], 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), and The authors are supported by Inserm, Université de Rennes 1, Région Bretagne, Ministère de l'Enseignement Supérieur de la Recherche et de l'Innovation, Ligue Nationale Contre le Cancer, Ligue Contre le Cancer (CD22, CD35, CD44, CD85) (R22026NN), Fondation ARC (R21043NN), INCa and ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé) dans le cadre du Plan cancer (Noncoding RNA in cancerology: fundamental to translational) (C20014NS). This work was supported by a grant from the French Ministry of Health and the French National Cancer Institute, PRT-K20-136, CHU Rennes, CLCC Eugène Marquis, Rennes (R21095NN). BM was supported from a fellowship from Association de Chirurgie Hépato-Bilio-Pancréatique et Transplantation Hépatique (ACHBT) and CHU Rennes.
Subjects: TGFβ, galunisertib, [SDV]Life Sciences [q-bio], hepatocellular carcinoma, gene signature, survival, General Biochemistry, Genetics and Molecular Biology
Abstract: International audience; Therapeutic targeting of the transforming growth factor beta (TGFβ) pathway in cancer represents a clinical challenge since TGFβ exhibits either tumor suppressive or tumor promoting properties, depending on the tumor stage. Thus, treatment with galunisertib, a small molecule inhibitor of TGFβ receptor type 1, demonstrated clinical benefits only in subsets of patients. Due to the functional duality of TGFβ in cancer, one can hypothesize that inhibiting this pathway could result in beneficial or adverse effects depending on tumor subtypes. Here, we report distinct gene expression signatures in response to galunisertib in PLC/PRF/5 and SNU-449, two cell lines that recapitulate human hepatocellular carcinoma (HCC) with good and poor prognosis, respectively. More importantly, integrative transcriptomics using independent cohorts of patients with HCC demonstrates that galunisertib-induced transcriptional reprogramming in SNU-449 is associated with human HCC with a better clinical outcome (i.e., increased overall survival), while galunisertib-induced transcriptional reprogramming in PLC/PRF/5 is associated with human HCC with a worse clinical outcome (i.e., reduced overall survival), demonstrating that galunisertib could indeed be beneficial or detrimental depending on HCC subtypes. Collectively, our study highlights the importance of patient selection to demonstrate a clinical benefit of TGFβ pathway inhibition and identifies Serpin Family F Member 2 (SERPINF2) as a putative companion biomarker for galunisertib in HCC.
Published: 2023
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10. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial

Author: Robin Kate Kelley, Makoto Ueno, Changhoon Yoo, Richard S Finn, Junji Furuse, Zhenggang Ren, Thomas Yau, Heinz-Josef Klümpen, Stephen L Chan, Masato Ozaka, Chris Verslype, Mohamed Bouattour, Joon Oh Park, Olga Barajas, Uwe Pelzer, Juan W Valle, Li Yu, Usha Malhotra, Abby B Siegel, Julien Edeline, Arndt Vogel, Mehmet Akce, Immaculada Ales Diaz, Gustavo Alves, Sumitra Anand, Cagatay Arslan, Jamil Asselah, Eric Assenat, Francine Aubin, Li-Yuan Bai, Yuxian Bai, Susan Bates, Stephen Begbie, Irit Ben-Aharon, Nina Beri, Marie-Luise Berres, Jean-Frederic Blanc, Ivan Borbath, Robert Bordonaro, Giovanni Brandi, Adam Burgoyne, Kritiya Butthongkomvong, Ke Cao, Marcela Carballido, Marcos Camandaroba, Stephan Lam Chang, Jen-Shi Chen, Ming-Huang Chen, Xiaoming Chen, Ashley Cheng, Tai-Jan Chiu, Hye Jin Choi, Hong Jae Chon, Joelle Collignon, Antonio Cubillo Gracian, Sarah Davis, Ricardo Saraiva de Carvalho, D.J.A. de Groot, Anne Demols, Judith De Vos, Maria Diab, Jacob Easaw, Martin Eatock, Rawad Elias, Fredericus Eskens, Alfredo Falcone, Plinio Fernandez, Richard Finn, Fabio Franke, Masayuki Furukawa, Olumide Gbolahan, Karen Geboes, Keri-Lee Geneser, Zhimin Geng, Ravit Geva, Roopinder Gillmore, Thorsten Goetze, Hongfeng Gou, Julieta Grasselli, Shanzhi Gu, Mahmut Gumus, Nadia Haj Mohammad, Chunyi Hao, Hakan Harputluoglu, Hassan Hatoum, Volker Heinemann, Wang Kwong Ho, Chiun Hsu, Ayala Hubert, Juneul Hwang, Mevlude Inanc, Soledad Iseas, Vaishnavi Jeyasingam, Paula Jimenez Fonseca, Warren Joubert, Jitlada Juengsamarn, Diego Kaen, Masahi Kanai, Stefan Kasper-Virchow, Ghazaleh Kazemi, Fergal Kelleher, Robin Kelley, Jin Won Kim, Jong Gwang Kim, Ana Beatriz Kinupe Abrahao, Heinz Klumpen, Mark Kochenderfer, Fatih Kose, Ho Ching Lam, Choong-kun Lee, Hyun Woo Lee, Margaret Lee, Myung Ah Lee, Wai Man Sarah Lee, Samuel Le Sourd, Dongliang Li, Wei Li, Houjie Liang, Tingbo Liang, Chun Sen Lim, Brian Lingerfelt, Charles Lopez, John Low, Teresa Macarulla Mercade, David Malka, Yimin Mao, Gianluca Masi, Steven McCune, Ray McDermott, Elaine McWhirter, Guillermo Mendez, Michele Milella, Tomonori Mizutani, Camila Moniz, Luisa Morales, Andres Jesús Munoz Martin, Bruno Nervi, Nuttapong Ngamphaiboon, Sang Cheul Oh, Berna Oksuzoglu, Darryl Outlaw, Mustafa Ozguroglu, Ozgur Ozyilkan, Claudio Painemeal, Yueyin Pan, Chuang Peng, Caroline Petorin, Denis Pezet, Derek Power, Shukui Qin, Aflah Roohullah, Hyewon Ryu, Pamela Salman, Rita Sasidharan, Taroh Satho, Kornelius Schulze, Martin Scott-Brown, Ruben Segovia, Thomas Seufferlin, Salvatore Siena, Isabelle Sinapi, Cristina Smolenschi, Tianqiang Song, Aumkhae Sookprasert, Nopadol Soparattanapaisarn, Naureen Starling, Stacey Stein, Salomon Stemmer, Haichuan Su, Rie Sugimoto, Thatthan Suksombooncharoen, Vincent Tam, Ai Lian Tan, Chih Kiang Tan, Suebpong Tanasanvimon, Giuseppe Tonini, Giampaolo Tortora, Akihito Tsuji, Rodrigo Uribe, Marino Venerito, Helena Verdaguer Mata, Ana Paula Victorino, James Wade, Dirk Thomas Waldschmidt, Lu Wang, Wan Zamaniah Wan Isahk, Harpeet Wasan, Rui Weschenfelder, Chun Yin Wong, Yoke Fui Wong, Suayib Yalcin, Patricio Yanez Weber, Xuezhong Yang, Hisateru Yasui, Ozan Yazici, Chia-Jui Yen, Jieer Ying, Wenchang Yu, Haitao Zhao, Helen Diller Family Comprehensive Cancer Center [San Francisco], David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Kyorin University School of Medicine [Tokyo, Japan], Kyorin University [Tokyo, Japan], The University of Hong Kong (HKU), The Chinese University of Hong Kong [Hong Kong], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The Christie NHS Foundation Trust [Manchester, Royaume-Uni], University of Manchester [Manchester], 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), Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA., and Internal medicine
Subjects: [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine
Abstract: Background: Biliary tract cancers, which arise from the intrahepatic or extrahepatic bile ducts and the gallbladder, generally have a poor prognosis and are rising in incidence worldwide. The standard-of-care treatment for advanced biliary tract cancer is chemotherapy with gemcitabine and cisplatin. Because most biliary tract cancers have an immune-suppressed microenvironment, immune checkpoint inhibitor monotherapy is associated with a low objective response rate. We aimed to assess whether adding the immune checkpoint inhibitor pembrolizumab to gemcitabine and cisplatin would improve outcomes compared with gemcitabine and cisplatin alone in patients with advanced biliary tract cancer. Methods: KEYNOTE-966 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 175 medical centres globally. Eligible participants were aged 18 years or older; had previously untreated, unresectable, locally advanced or metastatic biliary tract cancer; had disease measurable per Response Evaluation Criteria in Solid Tumours version 1.1; and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible participants were randomly assigned (1:1) to pembrolizumab 200 mg or placebo, both administered intravenously every 3 weeks (maximum 35 cycles), in combination with gemcitabine (1000 mg/m2 intravenously on days 1 and 8 every 3 weeks; no maximum duration) and cisplatin (25 mg/m2 intravenously on days 1 and 8 every 3 weeks; maximum 8 cycles). Randomisation was done using a central interactive voice-response system and stratified by geographical region, disease stage, and site of origin in block sizes of four. The primary endpoint of overall survival was evaluated in the intention-to-treat population. The secondary endpoint of safety was evaluated in the as-treated population. This study is registered at ClinicalTrials.gov, NCT04003636. Findings: Between Oct 4, 2019, and June 8, 2021, 1564 patients were screened for eligibility, 1069 of whom were randomly assigned to pembrolizumab plus gemcitabine and cisplatin (pembrolizumab group; n=533) or placebo plus gemcitabine and cisplatin (placebo group; n=536). Median study follow-up at final analysis was 25·6 months (IQR 21·7–30·4). Median overall survival was 12·7 months (95% CI 11·5–13·6) in the pembrolizumab group versus 10·9 months (9·9–11·6) in the placebo group (hazard ratio 0·83 [95% CI 0·72–0·95]; one-sided p=0·0034 [significance threshold, p=0·0200]). In the as-treated population, the maximum adverse event grade was 3 to 4 in 420 (79%) of 529 participants in the pembrolizumab group and 400 (75%) of 534 in the placebo group; 369 (70%) participants in the pembrolizumab group and 367 (69%) in the placebo group had treatment-related adverse events with a maximum grade of 3 to 4. 31 (6%) participants in the pembrolizumab group and 49 (9%) in the placebo group died due to adverse events, including eight (2%) in the pembrolizumab group and three (1%) in the placebo group who died due to treatment-related adverse events. Interpretation: Based on a statistically significant, clinically meaningful improvement in overall survival compared with gemcitabine and cisplatin without any new safety signals, pembrolizumab plus gemcitabine and cisplatin could be a new treatment option for patients with previously untreated metastatic or unresectable biliary tract cancer. Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.
Published: 2023
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11. 188Re-SSS Lipiodol Radioembolization in HCC Patients: Results of a Phase 1 Trial (Lip-Re-01 Study)

Author: Etienne Garin, Xavier Palard, Yan Rolland, Samuel Le Sourd, Nicolas Lepareur, Valérie Ardisson, Christelle Bouvry, Sophie Laffont, Boris Campillo-Gimenez, Eric Bellissant, Julien Edeline, 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), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 This study was sponsored and funded by the Cancer Institute Eugène Marquis of Rennes, France.
Subjects: Y-90-loaded microspheres, radioembolization, Cancer Research, hepatocellular carcinoma (HCC), Oncology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 90Y-loaded microspheres, 188Re-SSS lipiodol, radiation therapy, Re-188-SSS lipiodol
Abstract: International audience; Simple Summary Radioembolization is a kind of internal radiation therapy which is currently used in non-operable HCC. Several radiolabeled product can be used as Y-90-loaded microspheres or less frequently radiolabeled lipiodol either with iodine 131 (in the past) or currently with rhenium 188 (Re-188). Currently used Re-188-labeled compounds are limited by in vivo instability. This study sought to evaluate the safety, bio-distribution, and response to Re-188-SSS lipiodol, a new and more stable compound. Method: Lip-Re-01 was an activity-escalation Phase 1 study involving HCC patients progressing after sorafenib. The primary endpoint was safety. Secondary endpoints included bio-distribution and response evaluation. Results: Fourteen heavily pre-treated HCC patients were treated in Level 1 (n = 6), Level 2 (n = 6), and Level 3 (n = 2). Safety was acceptable with only 1/6 of Level 1 and 1/6 of Level 2 patients experiencing limiting toxicity. The study was prematurely discontinued unrelated to clinical outcomes. Cumulative urinary elimination and fecal eliminations at 72 h were very low, confirming high in vivo stability. Partial response occurred in 37.5% of the patients receiving 3.6 GBq of Re-188-SSS lipiodol or more. Conclusion: As the 3.6 GBq activity proved to be safe, it will be used in an ongoing Phase 2 study. Background: Despite the wide development of Y-90-loaded microspheres, Re-188-labeled lipiodol is still being used for radioembolization of hepatocellular carcinoma (HCC). However, the use of this latter compound is limited by in vivo instability. This study sought to evaluate the safety, bio-distribution, and response to Re-188-SSS lipiodol, a new and more stable compound. Method: Lip-Re-01 was an activity-escalation Phase 1 study involving HCC patients progressing after sorafenib. The primary endpoint was safety based on Common Terminology Criteria for Adverse Events (AEs) of Grade >= 3 within 2 months. Secondary endpoints included bio-distribution assessed by scintigraphy quantification from 1 to 72 h, tumor to non-tumor uptake ratio (T/NT), as well as blood, urine and feces collection over 72 h, dosimetry, and response evaluation (mRECIST). Results: Overall, 14 heavily pre-treated HCC patients were treated using a whole liver approach. The mean injected activity was 1.5 +/- 0.4 GBq for activity Level 1 (n = 6), 3.6 +/- 0.3 GBq for Level 2 (n = 6), and 5.0 +/- 0.4 GBq for Level 3 (n = 2). Safety was acceptable with only 1/6 of Level 1 and 1/6 of Level 2 patients experiencing limiting toxicity (one liver failure; one lung disease). The study was prematurely discontinued unrelated to clinical outcomes. Uptake occurred in the tumor, liver, and lungs, and only sometimes in the bladder. The T/NT ratio was high with a mean of 24.9 +/- 23.4. Cumulative urinary elimination and fecal eliminations at 72 h were very low, 4.8 +/- 3.2% and 0.7 +/- 0.8%, respectively. Partial response occurred in 21% of patients (0% in the first activity level; 37.5% in the others). Conclusion: The high in vivo stability of Re-188-SSS lipiodol was confirmed, resulting in encouraging responses for a Phase 1 study. As the 3.6 GBq activity proved to be safe, it will be used in a future Phase 2 study.
Published: 2023
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12. Cefotaxime resistance in bile samples is an independent predictor of deep infectious complications after pancreaticoduodenectomy in patients with endoprosthesis

Author: Fabien Robin, Marie Livin, Damien Bergeat, Haitham Triki, Elodie Gaignard, Marine Cailleaux, Vincent Cattoir, Karim Boudjema, Pierre Tattevin, Laurent Sulpice, 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), ARN régulateurs bactériens et médecine (BRM), 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 ), Chemistry, Oncogenesis, Stress and Signaling (COSS), and Jonchère, Laurent
Subjects: [SDV] Life Sciences [q-bio], pancreatoduodenectomy, bacteriobilia, Hepatology, complications, [SDV]Life Sciences [q-bio], Surgery, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, endoprosthesis, infection
Abstract: International audience; Background Bacteriobilia may increase the rate of deep infectious complications (DIC) after pancreaticoduodenectomy. To better adjust prophylactic and empirical antibacterial treatment, we aimed to characterize bacteriobilia in patients with preoperative endoprosthesis, and its association with postoperative DIC. Methods All patients who underwent pancreaticoduodenectomy in our center between 2010 and 2019 were included. The association between microbiological findings from bile samples, and postoperative DIC was analyzed, and we compared microbiology data between 2010-2014 and 2015-2019 periods. Results We enrolled 578 patients (median age 67 years [59-72], 58.7% males), of whom 220 (38.1%) had preoperative biliary endoprosthesis, with 197 (89.5%) positive preoperative bile samples pathogens were Enterobacterales, enterococci, and Candida albicans. The incidence of DIC was similar in patients with or without endoprosthesis (20.4% vs 17.8%, P = .352). Bacterial isolates collected during 2015-2019 were more resistant to cefotaxime than those recovered from 2010-2014 (45.5% vs 25.5%, P = .009). The only independent risk factor for DIC in patients with endoprosthesis was cefotaxime resistance in bile (hazard ratio 3.027 [1.115-8.216], P = .03). Conclusions The incidence of DIC is high after pancreaticoduodenectomy, with or without endoprosthesis, despite routine postoperative treatment. Cefotaxime resistance, the only independent predictor of DIC in patients with endoprosthesis, has increased over time. Hence, cefotaxime may no longer be an appropriate empirical treatment.
Published: 2023
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13. A novel optinEuRin stress connection in glaucoma

Author: Elodie Lafont, Tony Avril, 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), Institut National de la Santé et de la Recherche Médicale, Ligue Contre le Cancer, Région Bretagne, and Université de Rennes 1
Subjects: autophagy, cell death, glaucoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Biology, ER stress, Molecular Biology, Biochemistry, optineurin
Abstract: International audience; The endoplasmic reticulum (ER) is the organelle where the production and shaping of most secreted and transmembrane proteins happens. ER function is finely regulated to prevent accumulation of misfolded proteins generating ER stress. ER stress is common in both healthy and pathological situations due to multiple intrinsic and extrinsic factors including acute demand in protein synthesis, hypoxia or impaired protein folding caused by gene mutations. Sayyad et al. found that the M98K mutation of optineurin sensitizes glaucoma retinal ganglion cells to ER stress-induced cell death. This is associated with an autophagy-dependent elevation of ER stress sensor expression.
Published: 2023
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14. Incidence and Characteristics of Pseudoprogression in IDH-mutant High-Grade Gliomas: A POLA Network Study

Author: Antoine Seyve, Caroline Dehais, Olivier Chinot, Apolline Djelad, Elisabeth Cohen-Moyal, Charlotte Bronnimann, Carole Gourmelon, Evelyne Emery, Philippe Colin, Mathieu Boone, Elodie Vauléon, Olivier Langlois, Anna-Luisa di Stefano, Romuald Seizeur, François Ghiringhelli, Anne D’Hombres, Loic Feuvret, Jacques Guyotat, Laurent Capelle, Catherine Carpentier, Louis Garnier, Jérôme Honnorat, David Meyronet, Karima Mokhtari, Dominique Figarella-Branger, François Ducray, Hospices Civils de Lyon, Departement de Neurologie (HCL), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Bordeaux [Bordeaux], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service de Neurochirurgie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Culture et Environnements, Préhistoire, Antiquité, Moyen-Age (CEPAM), 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), Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Hospices Civils de Lyon (HCL), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Référence Maladie Rare 'Syndromes neurologiques Paranéoplasiques', Hospices Civils de Lyon (HCL)-Hopital Neurologique, and Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
Subjects: Cancer Research, High-grade glioma, Oncology, pseudoprogression, Neurology (clinical), IDH-mutant, chemotherapy, radiotherapy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Incidence and characteristics of pseudoprogression in isocitrate dehydrogenase-mutant high-grade gliomas (IDHmt HGG) remain to be specifically described. Methods We analyzed pseudoprogression characteristics and explored the possibility of pseudoprogression misdiagnosis in IDHmt HGG patients, treated with radiotherapy (RT) (with or without chemotherapy [CT]), included in the French POLA network. Pseudoprogression was analyzed in patients with MRI available for review (reference cohort, n = 200). Pseudoprogression misdiagnosis was estimated in this cohort and in an independent cohort (control cohort, n = 543) based on progression-free survival before and after first progression. Results In the reference cohort, 38 patients (19%) presented a pseudoprogression after a median time of 10.5 months after RT. Pseudoprogression characteristics were similar across IDHmt HGG subtypes. In most patients, it consisted of the appearance of one or several infracentimetric, asymptomatic, contrast-enhanced lesions occurring within 2 years after RT. The only factor associated with pseudoprogression occurrence was adjuvant PCV CT. Among patients considered as having a first true progression, 7 out of 41 (17%) in the reference cohort and 35 out of 203 (17%) in the control cohort were retrospectively suspected to have a misdiagnosed pseudoprogression. Patients with a misdiagnosed pseudoprogression were characterized by a time to event and an outcome similar to that of patients with a pseudoprogression but presented with larger and more symptomatic lesions. Conclusion In patients with an IDHmt HGG, pseudoprogression occurs later than in IDH-wildtype glioblastomas and seems not only frequent but also frequently misdiagnosed. Within the first 2 years after RT, the possibility of a pseudoprogression should be carefully considered.
Published: 2023
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15. Genomic characteristics and clinical significance of CD56+ circulating tumor cells in small cell lung cancer

Author: Charles Ricordel, L. Chaillot, E. I. Vlachavas, M. Logotheti, A. Jouannic, T. Desvallees, G. Lecuyer, M. Aubry, G. Kontogianni, C. Mastrokalou, F. Jouan, U. Jarry, R. Corre, Y. Le Guen, T. Guillaudeux, H. Lena, A. Chatziioannou, Rémy Pedeux, Service de pneumologie [Rennes] = Pneumology [Rennes], 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), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), 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 ), Biomedical Research Foundation of the Academy of Athens (BRFAA), Région Bretagne (MOPCAP), La Ligue Contre le Cancer (Grand Ouest), Association pour la Recherche sur le Cancer (ARC), ANR through the Labcom Oncotrial projet 2014–2019 (Université de Rennes 1—UAR Biosit—BIOTRIAL, Rennes, France) and JOTGO 2015 grant from Roche® company., and ANR-17-LCCO-0005,OncoTrial2,Développement de Modèles Cellulaires, Tissulaires et Animaux en Cancérologie(2017)
Subjects: Multidisciplinary, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: IntroductionCirculating Tumor Cells (CTC) have been studied in various solid tumors but clinical utility of CTC in Small Cell Lung Cancer (SCLC) remains unclear. The aim of the CTC-CPC study was to develop an EpCAM-independent CTC isolation method allowing isolation of a broader range of living CTC from SCLC and decipher their genomic and biological characteristics.Patients and methodsCTC-CPC is a monocentric prospective non-interventional study including treatment-naïve newly diagnosed SCLC. CD56+CTC were isolated from whole blood samples, at diagnosis and relapse after first-line treatment and submitted to Whole-exome-sequencing (WES).ResultsPhenotypic study confirms tumor lineage and tumorigenic properties of isolated cells for the 4 patients analyzed with WES. WES of CD56+CTC and matched tumor biopsy reveal genomic alteration frequently impaired in SCLC. At diagnosis CD56+CTC were characterized by a high mutation load, a distinct mutational profile and a unique genomic, compared to match tumors biopsies. In addition to classical pathways altered in SCLC, we found new biological processes specifically affected in CD56+CTC at diagnosis. High numeration of CD56+CTC (>7/ml) at diagnosis was associated with ES-SCLC. Comparing CD56+CTC isolated at diagnosis and relapse, we identify differentially altered oncogenic pathways (e.g. DLL3 or MAPK pathway).ConclusionsWe report a versatile method of CD56+CTC detection in SCLC. Numeration of CD56+CTC at diagnosis is correlated with disease extension. Isolated CD56+CTC are tumorigenic and a distinct mutational profile. We report a minimal gene set as a unique signature of CD56+CTC and identify new affected biological pathways enriched in EpCAM-independent isolated CTC in SCLC.
Published: 2023
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16. GLI1, a novel target of the ER stress regulator p97/VCP, promotes ATF6f-mediated activation of XBP1

Author: Almada, Luciana L., Barroso, Kim, Sen, Sandhya, Törüner, Murat, Sigafoos, Ashley N, Raja Arul, Glancis L, Pease, David R, Vera, Renzo E., Olson, Rachel L O, Auner, Holger W, Pedeux, Rémy, Iovanna, Juan L, Chevet, Eric, Fernandez-Zapico, Martin E, Mayo Clinic [Rochester], 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), Imperial College London, 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), This work was funded by grants from INSERM, Institut National du Cancer (INCa, PLBio 2017, 2019, 2020), Région Bretagne, Rennes Métropole, Fondation pour la recherche Médicale (FRM, DEQ20180339169), EU H2020 MSCA ITN-675448 (TRAINERS), la Ligue Contre le Cancer Comités d'Ille-et-Vilaine, des Côtes d'Armor et du Morbihan and MSCA RISE-734749 (INSPIRED) to EC and MEFZ was supported by NCI CA136526. KB was funded by a grant from la Ligue Contre le Cancer., and European Project: 675448,H2020,H2020-MSCA-ITN-2015,TRAIN-ERS(2015)
Subjects: Structural Biology, p97/VCP, GLI1, Genetics, Biophysics, [SDV.CAN]Life Sciences [q-bio]/Cancer, UPR, USF2, ER stress, Molecular Biology, Biochemistry, HDAC1, Hedgehog
Abstract: International audience; Upon accumulation of improperly folded proteins in the Endoplasmic Reticulum (ER), the Unfolded Protein Response (UPR) is triggered to restore ER homeostasis. The induction of stress genes is a sine qua non condition for effective adaptive UPR. Although this requirement has been extensively described, the mechanisms underlying this process remain in part uncharacterized. Here, we show that p97/VCP, an AAA+ ATPase known to contribute to ER stress-induced gene expression, regulates the transcription factor GLI1, a primary effector of Hedgehog (Hh) signaling. Under basal (non-ER stress) conditions, GLI1 is repressed by a p97/VCP-HDAC1 complex while upon ER stress GLI1 is induced through a mechanism requiring both USF2 binding and increase histone acetylation at its promoter. Interestingly, the induction of GLI1 was independent of ligand-regulated Hh signaling. Further analysis showed that GLI1 cooperates with ATF6f to induce promoter activity and expression of XBP1, a key transcription factor driving UPR. Overall, our work demonstrates a novel role for GLI1 in the regulation of ER stress gene expression and defines the interplay between p97/VCP, HDAC1 and USF2 as essential players in this process.
Published: 2023
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17. Criteria for preclinical models of cholangiocarcinoma:scientific and medical relevance

Author: Calvisi, Diego, Boulter, Luke, Vaquero, Javier, Saborowski, Anna, Fabris, Luca, Rodrigues, Pedro, Coulouarn, Cédric, Castro, Rui, Segatto, Oreste, Raggi, Chiara, van der Laan, Luc, Carpino, Guido, Goeppert, Benjamin, Roessler, Stephanie, Kendall, Timothy, Evert, Matthias, Gonzalez-Sanchez, Ester, Valle, Juan, Vogel, Arndt, Bridgewater, John, Borad, Mitesh, Gores, Gregory, Roberts, Lewis, Marin, Jose, Andersen, Jesper, Alvaro, Domenico, Forner, Alejandro, Banales, Jesus, Cardinale, Vincenzo, Macias, Rocio, Vicent, Silve, Chen, Xin, Braconi, Chiara, Verstegen, Monique, Fouassier, Laura, Scheiter, Alexander, Selaru, Florin, Evert, Katja, Utpatel, Kirsten, Broutier, Laura, Cadamuro, Massimiliano, Huch, Meritxell, Goldin, Robert, Gradilone, Sergio, Saito, Yoshimasa, University of Regensburg, University of Edinburgh, Instituto de Salud Carlos III [Madrid] (ISC), Hannover Medical School [Hannover] (MHH), Yale School of Medicine [New Haven, Connecticut] (YSM), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), 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), Universidade de Lisboa, Università degli Studi di Firenze = University of Florence (UniFI), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Università degli Studi di Roma 'Foro Italico', Heidelberg University Hospital [Heidelberg], University of Barcelona, Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), The Christie NHS Foundation Trust [Manchester, Royaume-Uni], University of Manchester [Manchester], University College of London [London] (UCL), Mayo Clinic, Mayo Clinic [Rochester], Universidad de Salamanca, University of Copenhagen = Københavns Universitet (UCPH), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA), University of California [San Francisco] (UC San Francisco), University of California (UC), University of Glasgow, 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), The authors thank the European Network for the Study of Cholangiocarcinoma (ENS-CCA) and the European H2020 COST Action CA18122. The authors also acknowledge the valuable contributions of the external advisory panel. C.C. is supported by Inserm, Université de Rennes 1 and by a grant from the French Ministry of Health and the French National Cancer Institute (PRT-K20-136), CHU Rennes, CLCC Eugène Marquis, Rennes. M.M.A.V. and L.J.W.v.d.L. are supported by Medical Delta Regenerative Medicine 4D (Generating complex tissues with stem cells and printing technology) and TKI-LSH grant EMC-LSH19002. S.R. is supported by the German Research Foundation (DFG, project no. 314905040 and no. 493697503) and by German Cancer Aid (Deutsche Krebshilfe, project no. 70113922). S.V. is supported by Ministerio de Ciencia, Innovación y Universidades, Convocatoria 2019 para incentivar la Incorporación Estable de Doctores (IED2019-001007-I), by FEDER/Ministerio de Ciencia, Innovación y Universidades – Agencia Estatal de Investigación (PID2020‐116344‐RB‐100) and by the Government of Navarra-Health Research Department (58, and 2018). J.V. is funded by Ministerio de Ciencia e Innovación, part of Agencia Estatal de Investigación (AEI), through the Retos Investigación grant number PID2019-108651RJ-I00/DOI 10.13039/501100011033. The authors thank CERCA Programme/Generalitat de Catalunya for institutional support. R.I.R.M. and J.J.G.M. are supported by Instituto de Salud Carlos III, Spain (PI20/00189, PI19/00819) co-funded by the European Union. L. Fouassier belongs to a team supported by the Fondation pour la Recherche Médicale (Equipe FRM 2020 no. EQU202003010517) and is supported by Inserm and Sorbonne Université, INCa and ITMO Cancer of Aviesan within the framework of the 2021–2030 Cancer Control Strategy, on funds administered by Inserm.
Subjects: Hepatology, [SDV]Life Sciences [q-bio], Gastroenterology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Abstract: International audience; Cholangiocarcinoma (CCA) is a rare malignancy that develops at any point along the biliary tree. CCA has a poor prognosis, its clinical management remains challenging, and effective treatments are lacking. Therefore, preclinical research is of pivotal importance and necessary to acquire a deeper understanding of CCA and improve therapeutic outcomes. Preclinical research involves developing and managing complementary experimental models, from in vitro assays using primary cells or cell lines cultured in 2D or 3D to in vivo models with engrafted material, chemically induced CCA or genetically engineered models. All are valuable tools with well-defined advantages and limitations. The choice of a preclinical model is guided by the question(s) to be addressed; ideally, results should be recapitulated in independent approaches. In this Consensus Statement, a task force of 45 experts in CCA molecular and cellular biology and clinicians, including pathologists, from ten countries provides recommendations on the minimal criteria for preclinical models to provide a uniform approach. These recommendations are based on two rounds of questionnaires completed by 35 (first round) and 45 (second round) experts to reach a consensus with 13 statements. An agreement was defined when at least 90% of the participants voting anonymously agreed with a statement. The ultimate goal was to transfer basic laboratory research to the clinics through increased disease understanding and to develop clinical biomarkers and innovative therapies for patients with CCA.
Published: 2023
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18. Metalloprotease-mediated cleavage of CD95 Ligand

Author: Vesna Risso, Mélissa Thomas, Blandine Guével, Regis Lavigne, Emmanuelle Com, Sophie Martin, Manon Nivet, Charles Pineau, Luc Negroni, Élodie Lafont, Éric Chevet, Leif A. Eriksson, Matthieu Le Gallo, 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 Gothenburg (GU), 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), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CRLCC Eugène Marquis (CRLCC), Infrastructures en Biologie Santé et Agronomie, PLBIO2019, Institut National Du Cancer, Région Bretagne, and 2018‐05973, Vetenskapsrådet
Subjects: soluble CD95L, [SDV]Life Sciences [q-bio], proteolytic cleavage, CD95L, Cell Biology, CD95 Ligand, metalloproteases, Molecular Biology, Biochemistry
Abstract: International audience; CD95 is a member of the TNF receptor superfamily that is ubiquitously expressed in healthy and pathological tissues. Stimulation of CD95 by its physiological ligand CD95L induces its oligomerization leading in turn to the transduction of either apoptotic or non-apoptotic signals. CD95L can exist as both membrane-anchored and soluble forms (sCD95L), the latter resulting from the proteolytic cleavage of the former. Candidate proteases able to achieve CD95L cleavage were identified as matrix metalloproteases (MMP) due to their demonstrated ability to cleave other TNF superfamily ligands. The main goal of this study was to systematically identify the MMP family members capable of cleaving CD95L and subsequently determine the corresponding cleavage sites. By using different orthogonal biochemical approaches and combining them with molecular modeling, we confirmed data from the literature regarding CD95L cleavage by MMP-3 and MMP-7. Moreover, we found that MMP-2 and MMP-12 can cleave CD95L and characterized their resulting cleavage sites. This study provides a systematic approach to analyze the cleavage of CD95L, which until now had only been poorly described.
Published: 2023
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19. Functional Assessment of a New PBX1 Variant in a 46,XY Fetus with Severe Syndromic Difference of Sexual Development through CRISPR-Cas9 Gene Editing

Author: Laura Mary, Delphine Leclerc, Audrey Labalme, Pascale Bellaud, Séverine Mazaud-Guittot, Stéphane Dréano, Bertrand Evrard, Antoine Bigand, Aurélie Cauchoix, Philippe Loget, Anna Lokchine, Laurence Cluzeau, David Gilot, Marc-Antoine Belaud-Rotureau, 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], 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), Hospices Civils de Lyon (HCL), 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 ), H2P2 - Histo Pathologie Hight Precision (H2P2), Université de Rennes (UR)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), 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 ), This study received financial support from AVIESAN Plan Cancer, Région Bretagne, Agence Nationale de Recherche, University of Rennes 1 and Ministère de la Recherche et de l’Enseignement Supérieur (MESRI, PhD Scholarship)., and Jonchère, Laurent
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, sexual development, Genetics, DSD, genome editing, [SDV.GEN] Life Sciences [q-bio]/Genetics, RNA-seq, CRISPR-Cas9, Genetics (clinical)
Abstract: International audience; Sexual development is a complex process relying on numerous genes. Disruptions in some of these genes are known to cause differences of sexual development (DSDs). Advances in genome sequencing allowed the discovery of new genes implicated in sexual development, such as PBX1. We present here a fetus with a new PBX1 NM_002585.3: c.320G>A,p.(Arg107Gln) variant, presenting with severe DSD along with renal and lung malformations. Using CRISPR-Cas9 gene editing on HEK293T cells, we generated a KD cell line for PBX1. The KD cell line showed reduced proliferation and adhesion properties compared with HEK293T cells. HEK293T and KD cells were then transfected plasmids coding either PBX1 WT or PBX1-320G>A (mutant). WT or mutant PBX1 overexpression rescued cell proliferation in both cell lines. RNA-seq analyses showed less than 30 differentially expressed genes, in ectopic mutant-PBX1-expressing cells compared with WT-PBX1. Among them, U2AF1, encoding a splicing factor subunit, is an interesting candidate. Overall, mutant PBX1 seems to have modest effects compared with WT PBX1 in our model. However, the recurrence of PBX1 Arg107 substitution in patients with closely related phenotypes calls for its impact in human diseases. Further functional studies are needed to explore its effects on cellular metabolism.
Published: 2023
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20. Gene Editing Corrects In Vitro a G > A GLB1 Transition from a GM1 Gangliosidosis Patient

Author: Delphine Leclerc, Louise Goujon, Sylvie Jaillard, Bénédicte Nouyou, Laurence Cluzeau, Léna Damaj, Christèle Dubourg, Amandine Etcheverry, Thierry Levade, Roseline Froissart, Stéphane Dréano, Xavier Guillory, Leif A Eriksson, Erika Launay, Frédéric Mouriaux, Marc-Antoine Belaud-Rotureau, Sylvie Odent, David Gilot, 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], École des Hautes Études en Santé Publique [EHESP] (EHESP), 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 ), 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 ), Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hospices Civils de Lyon (HCL), Institut des Sciences Chimiques de Rennes (ISCR), 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 University of Gothenburg (GU)
Subjects: [SDV]Life Sciences [q-bio], Genetics, Original Research, Biotechnology
Abstract: International audience; Ganglioside-monosialic acid (GM1) gangliosidosis, a rare autosomal recessive disorder, is frequently caused by deleterious single nucleotide variants (SNVs) in GLB1 gene. These variants result in reduced β-galactosidase (β-gal) activity, leading to neurodegeneration associated with premature death. Currently, no effective therapy for GM1 gangliosidosis is available. Three ongoing clinical trials aim to deliver a functional copy of the GLB1 gene to stop disease progression. In this study, we show that 41% of GLB1 pathogenic SNVs can be replaced by adenine base editors (ABEs). Our results demonstrate that ABE efficiently corrects the pathogenic allele in patient-derived fibroblasts, restoring therapeutic levels of β-gal activity. Off-target DNA analysis did not detect off-target editing activity in treated patient’s cells, except a bystander edit without consequences on β-gal activity based on 3D structure bioinformatics predictions. Altogether, our results suggest that gene editing might be an alternative strategy to cure GM1 gangliosidosis.
Published: 2023
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21. 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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22. A TRAFFIC themed series - Host membrane trafficking subversion by pathogens

Author: Chevet, Eric, de Matteis, Maria Antonietta, Eskelinen, Eeva-Liisa, Farhan, Hesso, Chevet, Eric, De Matteis, Maria Antonietta, Eskelinen, Eeva-Liisa, Farhan, Hesso, Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Telethon Institute of Genetics and Medicine = Istituto Telethon di Genetica e Medicina (TIGEM), University of Naples Federico II = Università degli studi di Napoli Federico II, University of Turku, Universität Innsbruck [Innsbruck], and None
Subjects: Structural Biology, Genetics, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Biology, Molecular Biology, Biochemistry
Abstract: International audience
Published: 2023
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23. IRE1α overexpression in malignant cells limits tumor progression by inducing an anti-cancer immune response

Author: Adriana Martinez-Turtos, Rachel Paul, Manuel Grima-Reyes, Hussein Issaoui, Adrien Krug, Rana Mhaidly, Jozef P. Bossowski, Johanna Chiche, Sandrine Marchetti, Els Verhoeyen, Eric Chevet, Jean-Ehrland Ricci, 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), Equipe Labellisée LIGUE Contre le Cancer [Nice] (EL/LCC), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), la Ligue Nationale Contre le Cancer 'Equipe Labellisée, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Ricci, Jean-Ehrland
Subjects: X-Box Binding Protein 1, [SDV]Life Sciences [q-bio], Immunology, Immunity, apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, IRE1α, UPR, Protein Serine-Threonine Kinases, [SDV] Life Sciences [q-bio], Mice, [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, Neoplasms, Endoribonucleases, Animals, Immunology and Allergy, RIDD, anti-cancer immunosurveillance, XBP1s, Neoplastic Processes, Signal Transduction, Cancer
Abstract: International audience; IRE1α is one of the three ER transmembrane transducers of the Unfolded Protein Response (UPR) activated under endoplasmic reticulum (ER) stress. IRE1α activation has a dual role in cancer as it may be either pro- or anti-tumoral depending on the studied models. Here, we describe the discovery that exogenous expression of IRE1α, resulting in IRE1α auto-activation, did not affect cancer cell proliferation in but resulted in a tumor-suppressive phenotype in syngeneic immunocompetent mice. We found that exogenous expression of IRE1α in murine colorectal and Lewis lung carcinoma cells impaired tumor growth when syngeneic tumor cells were subcutaneously implanted in immunocompetent mice but not in immunodeficient mice. Mechanistically, the in vivo tumor-suppressive effect of overexpressing IRE1α in tumor cells was associated with IRE1α RNAse activity driving both XBP1 mRNA splicing and regulated IRE1-dependent decay of RNA (RIDD). We showed that the tumor-suppressive phenotype upon IRE1α overexpression was characterized by the induction of apoptosis in tumor cells along with an enhanced adaptive anti-cancer immunosurveillance. Hence, our work indicates that IRE1α overexpression and/or activation in tumor cells can limit tumor growth in immunocompetent mice. This finding might point toward the need of adjusting the use of IRE1α inhibitors in cancer treatments based on the predominant outcome of the RNAse activity of IRE1α.
Published: 2022
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24. LncRNAs in domesticated animals: from dog to livestock species

Author: Sandrine Lagarrigue, Matthias Lorthiois, Thomas Derrien, David Gilot, Fabien Degalez, Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), AGROCAMPUS OUEST, 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), Chemistry, Oncogenesis, Stress and Signaling (COSS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, 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), 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)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Livestock, Genome-wide association study, Computational biology, Biology, Genome, Transcriptome, Mice, 03 medical and health sciences, Dogs, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Animals, Epigenetics, Phylogeny, 030304 developmental biology, Comparative genomics, 0303 health sciences, Phylogenetic tree, RNA, Human genetics, Animals, Domestic, 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], RNA, Long Noncoding
Abstract: Animal genomes are pervasively transcribed into multiple RNA molecules, of which many will not be translated into proteins. One major component of this transcribed non-coding genome is the long non-coding RNAs (lncRNAs), which are defined as transcripts longer than 200 nucleotides with low coding-potential capabilities. Domestic animals constitute a unique resource for studying the genetic and epigenetic basis of phenotypic variations involving protein-coding and non-coding RNAs, such as lncRNAs. This review presents the current knowledge regarding transcriptome-based catalogues of lncRNAs in major domesticated animals (pets and livestock species), covering a broad phylogenetic scale (from dogs to chicken), and in comparison with human and mouse lncRNA catalogues. Furthermore, we describe different methods to extract known or discover novel lncRNAs and explore comparative genomics approaches to strengthen the annotation of lncRNAs. We then detail different strategies contributing to a better understanding of lncRNA functions, from genetic studies such as GWAS to molecular biology experiments and give some case examples in domestic animals. Finally, we discuss the limitations of current lncRNA annotations and suggest research directions to improve them and their functional characterisation.
Published: 2021
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25. Selective Internal Radiation Combined with Chemotherapy Maintains the Quality of Life in Intrahepatic Cholangiocarcinomas

Author: Etienne Garin, Yan Rolland, Luc Beuzit, Camille Goislard de Monsabert, Eveline Boucher, Astrid Lièvre, Yann Touchefeu, Samuel Le Sourd, David Tougeron, Karim Boudjema, Boris Campillo-Gimenez, Isabelle Baumgaertner, Olivier Farges, Ahmet Ayav, Marc Pracht, Julien Edeline, Boris Guiu, CRLCC Eugène Marquis (CRLCC), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire Traitement du Signal et de l'Image (LTSI), 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), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CRHU Nancy, CHU Pontchaillou [Rennes], Chemistry, Oncogenesis, Stress and Signaling (COSS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), BTG, Ligue Contre le Cancer, Université de Montpellier (UM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Jonchère, Laurent, and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: vomiting, Yttrium-90, medicine.medical_treatment, insomnia, Brachytherapy, diarrhea, cisplatin, thrombocytopenia, chemotherapy, Gastroenterology, 030218 nuclear medicine & medical imaging, chemoradiotherapy, Cholangiocarcinoma, 0302 clinical medicine, Quality of life, dose response, pain, Embolization, RC254-282, clinical article, adult, gemcitabine, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, yttrium 90, nausea, humanities, 3. Good health, sirtuin, aged, female, anorexia, patient-reported outcomes, 030220 oncology & carcinogenesis, liver resection, [SDV.IB]Life Sciences [q-bio]/Bioengineering, medicine.symptom, medicine.drug, radioembolization, medicine.medical_specialty, Nausea, patient-reported outcome, Article, multiple cycle treatment, 03 medical and health sciences, male, Internal medicine, biliary tract cancer, medicine, follow up, neutropenia, Humans, human, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Cisplatin, loss of appetite, Chemotherapy, business.industry, questionnaire, constipation, dyspnea, Gemcitabine, Radiation therapy, phase 2 clinical trial, multicenter study, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, Concomitant, microsphere, Quality of Life, fatigue, asthenia, bile duct carcinoma, business
Abstract: Background: In the Yttrium-90 Microspheres in Cholangiocarcinoma (MISPHEC) single-arm phase 2 trial, concomitant chemotherapy and selective internal radiotherapy (SIRT) showed antitumor activity as a first-line treatment of unresectable intrahepatic cholangiocarcinomas (ICCs). In this sub-analysis, we aimed to evaluate one of the secondary endpoints, the health-related quality of life (QoL), evaluated with an EORTC QLQ-C30 instrument at the baseline and during treatment. Methods: The MISPHEC trial included treatment-naïve patients with an unresectable ICC between November 2013 and June 2016. Patients received concomitant first-line chemotherapy with cisplatin and gemcitabine for 8 cycles, SIRT was administered during cycle 1 (for patients with unilobar disease) or cycles 1 and 3 (for patients with bilobar disease) using glass Yttrium-90 microspheres. We evaluated the QoL—measured by the QLQ-C30 questionnaire—at the baseline, every 8 weeks during chemotherapy and follow-up, between 12 and 15 weeks after embolization and every 12 weeks after a liver resection if applicable. Results: A total of 41 patients were included, of which 34 completed questionnaires at the baseline. No clinically significant changes in the global health score or the sub-scales of the QLQ-C30 were observed during follow-up. The physical, social and role function mean score worsened during treatment and fatigue, nausea and pain scores increased although the differences were not clinically significant. In patients undergoing subsequent surgery, the QoL was not impaired. Conclusions: A combination of SIRT and chemotherapy with gemcitabine and cisplatin as the first-line treatment of unresectable ICCs was found to maintain the QoL.
Published: 2021
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26. Human iPSC-derived neurons reveal early developmental alteration of neurite outgrowth in the late-occurring neurodegenerative Wolfram syndrome

Author: Jérôme Polentes, Hélène Polvèche, Cécile Martinat, Axel Sciauvaud, Maria-Gabriela Boza-Moran, Laetitia Aubry, Marc Peschanski, Margot Jarrige, Sandra Pourtoy-Brasselet, Michel Cailleret, Eric Chevet, Institut des cellules souches pour le traitement et l'étude des maladies monogéniques (I-STEM), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, CRLCC Eugène Marquis (CRLCC), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), I-Stem is part of the Biotherapies Institute for Rare Diseases (BIRD) supported by the Association Française contre les Myopathies (AFM-Téléthon). This project was also supported by grants from Association syndrome de Wolfram, Association Nationale de la Recherche et de la Technologie and Agence Nationale pour la Recherche : NeurATRIS ANR-11-INBS-0011 and Labex REVIVE ANR-10-LABX-73. M.-G.B.-M. was supported by the programme 'investissement d’avenir' INGESTEM. We thank Yolande Masson and Lina El Kassar for karyotyping the cell lines and Alexandre Carteron for the technical support with the ampliseq experiments. We thank Dr Cécile Delettre and the late Pr Christian Hamel (Institut des neurosciences de Montpellier) for the gift of the WS5 fibroblasts, and the New York Stem Cell Foundation for WS1 and WS2 iPSC lines. We thank Pr Ole Isacson (Harvard Medical School) for advice and reading the manuscript and Pr Nathalie Holic for advice with genome editing. We gratefully acknowledge support from the PSMN (Pôle Scientifique de Modélisation Numérique) of the ENS de Lyon for computing resource, ANR-11-INBS-0011,NeurATRIS,Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences(2011), ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Aubry, Laetitia, Infrastructures - Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences - - NeurATRIS2011 - ANR-11-INBS-0011 - INBS - VALID, and Laboratoires d'excellence - Stem Cells in Regenerative Biology and Medicine - - REVIVE2010 - ANR-10-LABX-0073 - LABX - VALID
Subjects: neurite outgrowth, Neurite, induced pluripotent stem cells, Wolfram syndrome, [SDV]Life Sciences [q-bio], neurons, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Article, 03 medical and health sciences, neurodegenerative disease, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neurites, Genetics, medicine, Humans, Age of Onset, Induced pluripotent stem cell, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Valproic Acid, axon guidance, Endoplasmic reticulum, medicine.disease, Phenotype, [SDV] Life Sciences [q-bio], neurodevelopmental disease, Gene Expression Regulation, Case-Control Studies, endoplasmic reticulum stress, Unfolded protein response, Axon guidance, CRISPR-Cas Systems, Neuroscience, 030217 neurology & neurosurgery, medicine.drug
Abstract: International audience; Recent studies indicate that neurodegenerative processes that appear during childhood and adolescence in individuals with Wolfram syndrome (WS) occur in addition to early brain development alteration, which is clinically silent. Underlying pathological mechanisms are still unknown. We have used induced pluripotent stem cell-derived neural cells from individuals affected by WS in order to reveal their phenotypic and molecular correlates. We have observed that a subpopulation of Wolfram neurons displayed aberrant neurite outgrowth associated with altered expression of axon guidance genes. Selective inhibition of the ATF6α arm of the unfolded protein response prevented the altered phenotype, although acute endoplasmic reticulum stress response—which is activated in late Wolfram degenerative processes—was not detected. Among the drugs currently tried in individuals with WS, valproic acid was the one that prevented the pathological phenotypes. These results suggest that early defects in axon guidance may contribute to the loss of neurons in individuals with WS.
Published: 2021
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27. ETV6-RUNX1 and RUNX1 directly regulate RAG1 expression: one more step in the understanding of childhood B-cell acute lymphoblastic leukemia leukemogenesis

Author: Anne-Gaëlle Rio, Zi-Ling Liu, Virginie Gandemer, Aurélien A. Sérandour, Benoit Soubise, Marie-Dominique Galibert, Hana Raslova, Jason S. Carroll, Laurent Corcos, Jocelyne Demengeot, Nathalie Douet-Guilbert, Lydie Debaize, Jérémie Rouger-Gaudichon, Marie-Bérengère Troadec, Gilles Salbert, Yan Jiang, David Gilot, Hélène Jakobczyk, Stéphane Avner, 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), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Jilin University (JLU), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Cancer Research UK Cambridge Institute [Cambridge, Royaume-Uni] (CRUK), University of Cambridge [UK] (CAM), Ecophysiologie et Génomique Fonctionnelle de la Vigne (UMR EGFV), Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV)-Ecole Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine (Bordeaux Sciences Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Chemistry, Oncogenesis, Stress and Signaling (COSS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Instituto Gulbenkian de Ciência [Oeiras] (IGC), Fundação Calouste Gulbenkian, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Pontchaillou [Rennes], Ligue Regionale contre le cancerLigue nationale contre le cancer [22, 29, 35, 56, 79, 41], Region Bretagne Region Bretagne, Societe Francaise d'Hematologie, Rennes Metropole Region Bretagne, societe francaise de lutte contre les cancers et les leucemies de l'enfant et de l'adolescent, Federation Enfants et Sante, AVIESAN Plan Cancer, Halte au Cancer, Association Gaetan Saleun, Mrs. M-Dominique Blanc-Bert, Canceropole Grand Ouest, Societe Francaise de Biochimie et Biologie Moleculaire, People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme [291851], European Project: 291851,EC:FP7:PEOPLE,FP7-PEOPLE-2011-CIG,ALLRUN(2012), 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 ), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chard-Hutchinson, Xavier, and Modeling TEL/AML1 childhood lymphoblastic leukemia in zebrafish - ALLRUN - - EC:FP7:PEOPLE2012-02-01 - 2016-01-31 - 291851 - VALID
Subjects: Cancer Research, Letter, Oncogene Proteins, Fusion, [SDV]Life Sciences [q-bio], Recombination-activating gene, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Etv6 runx1, Tumor Cells, Cultured, Humans, Leukaemia, Medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Homeodomain Proteins, 0303 health sciences, Gene Expression Regulation, Leukemic, business.industry, Hematology, B-cell acute lymphoblastic leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma, [SDV] Life Sciences [q-bio], Cell Transformation, Neoplastic, Oncology, RUNX1, chemistry, 030220 oncology & carcinogenesis, Core Binding Factor Alpha 2 Subunit, Cancer research, business, Haematological diseases
Abstract: Funder: Société Française de Biochimie et Biologie Moléculaire ; French Research Ministry, Funder: Cancéropole Grand Ouest ; Région Bretagne ; Société Française d’Hématologie, Funder: Ligue Régionale contre le cancer, ETV6-RUNX1 and RUNX1 directly promote RAG1 expression. ETV6-RUNX1 and RUNX1 preferentially bind to the −1200 bp enhancer of RAG1 and the −80 bp promoter of RAG1 gene respectively, and compete for these bindings. ETV6-RUNX1 and RUNX1 induce an excessive RAG recombinase activity. ETV6-RUNX1 participates directly in two events of the multi-hit ALL leukemogenesis: as an initiating event and as an activator of RAG1 expression.
Published: 2021
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28. Role of Pro-oncogenic Protein Disulfide Isomerase (PDI) Family Member Anterior Gradient 2 (AGR2) in the Control of Endoplasmic Reticulum Homeostasis

Author: Marion Bouchecareilh, Duc Thang Nguyên, Eric Chevet, Audrey Mulot, Daniel Boismenu, Frédéric Delom, Michael J. Wise, Arisa Higa, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], UNICANCER, Mécanismes moléculaires de l'angiogénèse, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Astrophysical Sciences [Princeton], Princeton University, Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), 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 Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)
Subjects: [SDV]Life Sciences [q-bio], AGR2, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, Endoplasmic Reticulum, Biochemistry, Ribosome, 03 medical and health sciences, Mice, 0302 clinical medicine, Dogs, Mucoproteins, Proto-Oncogene Proteins, Chlorocebus aethiops, Animals, Homeostasis, Humans, Protein disulfide-isomerase, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Oncogene Proteins, 0303 health sciences, Endoplasmic reticulum, Proteins, STIM1, Cell Biology, Translocon, Endoplasmic Reticulum Stress, Cell biology, Secretory protein, HEK293 Cells, Gene Expression Regulation, 030220 oncology & carcinogenesis, COS Cells, Unfolded protein response, Unfolded Protein Response
Abstract: The protein-disulfide isomerase (PDI) family member anterior gradient 2 (AGR2) is reportedly overexpressed in numerous cancers and plays a role in cancer development. However, to date the molecular functions of AGR2 remain to be characterized. Herein we have identified AGR2 as bound to newly synthesized cargo proteins using a proteomics analysis of endoplasmic reticulum (ER) membrane-bound ribosomes. Nascent protein chains that translocate into the ER associate with specific ER luminal proteins, which in turn ensures proper folding and posttranslational modifications. Using both imaging and biochemical approaches, we confirmed that AGR2 localizes to the lumen of the ER and indirectly associates with ER membrane-bound ribosomes through nascent protein chains. We showed that AGR2 expression is controlled by the unfolded protein response and is in turn is involved in the maintenance of ER homeostasis. Remarkably, we have demonstrated that siRNA-mediated knockdown of AGR2 significantly alters the expression of components of the ER-associated degradation machinery and reduces the ability of cells to cope with acute ER stress, properties that might be relevant to the role of AGR2 in cancer development.
Published: 2011
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29. New Challenges Facing Systemic Therapies of Advanced HCC in the Era of Different First-Line Immunotherapy-Based Combinations

Author: Julien Edeline, Tim Meyer, Jean-Frédéric Blanc, Jean-Luc Raoul, Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), University College of London [London] (UCL), CHU Bordeaux [Bordeaux], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, and None
Subjects: Cancer Research, Oncology, systemic therapies, anti-PD-1, [SDV.CAN]Life Sciences [q-bio]/Cancer, hepatocellular carcinoma, immunotherapy
Abstract: International audience; The standard of care of first-line systemic therapy for advanced hepatocellular carcinoma (HCC) is currently changing with the results of the IMbrave150 trial which are demonstrating superiority of the atezolizumab-bevacizumab combination over sorafenib, modifying this line of treatment for the first time in over 10 years. Recently, other immunotherapy-based combinations (durvalumab-tremelimumab, lenvatinib-pembrolizumab, cabozantinib-atezolizumab, and camrelizumab-rivoceranib) reported results in phase III studies, and might challenge this new standard of care. This revolution will lead to a considerable change in practice, and highlight challenges for future drug development. In this review, we will, firstly, describe results of the different combinations, and discuss the difficulties in selecting the first-line treatment. We will then present the different recommendations about second-line treatment following the first-line immunotherapy-based combination, discussing the rationale for the differences in existing recommendations. We will finally discuss the challenges for future drug development in advanced HCC.
Published: 2022
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30. Characteristics, Patterns of Care and Predictive Geriatric Factors in Elderly Patients Treated for High-Grade IDH-Mutant Gliomas: A French POLA Network Study

Author: Coline Montégut, Jean-Sébastien Guillamo, François Ducray, Caroline Dehais, Elisabeth Cohen-Jonathan Moyal, Christine Desenclos, Antoine Petit, Romuald Seizeur, Lien Bekaert, Claude Gaultier, Marie Jeannette Motuo Fotso, Marie Blonski, Jean-Sébastien Frenel, Elodie Vauléon, Olivier Langlois, Georges Noel, Antoine F. Carpentier, Anna Luisa Di Stefano, Charlotte Bronnimann, Dominique Figarella-Branger, Olivier Chinot, Emeline Tabouret, 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), Hôpital de la Timone [CHU - APHM] (TIMONE), 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), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Claudius Regaud, CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service de Neurochirurgie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Institut de Cancérologie de Strasbourg Europe (ICANS), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Foch [Suresnes], CHU Bordeaux [Bordeaux], Service d'Anatomie Pathologique et de Neuropathologie [Hôpital de la Timone - CHU - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Rôle et mécanismes d'action de l'adrenomedulline dans la croissance tumorale : Application au modèle des gliomes, Université de la Méditerranée - Aix-Marseille 2-IFR11-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Onco-neurologie = Département de neurologie 2 [CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 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), Centre d'Études Préhistoire, Antiquité, Moyen-Age (CEPAM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and 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)
Subjects: Cancer Research, high grade glioma, Oncology, geriatric assessment, IDH mutation, elderly, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: Describe the characteristics, patterns of care, and predictive geriatric factors of elderly patients with IDHm high-grade glioma (HGG) included in the French POLA network. Material and Methods: The characteristics of elderly (≥70 years) patients IDHm HGG were compared to those of younger patients IDHm HGG (
Published: 2022
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31. Presentation and Prognosis of Primary Expansile and Infiltrative Mucinous Carcinomas of the Ovary

Author: Marine Huin, Jerome Lorenzini, Flavie Arbion, Xavier Carcopino, Cyril Touboul, Yohann Dabi, Yohan Kerbage, Hélène Costaz, Lise Lecointre, Vincent Lavoué, Pierre-Adrien Bolze, Cyrille Huchon, Alexandre Bricou, Geoffroy Canlorbe, Camille Mimoun, Sofiane Bendifallah, Tristan Gauthier, Gilles Body, Lobna Ouldamer, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU), Centre Hospitalier Intercommunal de Créteil (CHIC), CHU Lille, Hôpital Jeanne de Flandre [Lille], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CHU Strasbourg, 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 Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Risques cliniques et sécurité en santé des femmes et en santé périnatale (RISCQ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHI Poissy-Saint-Germain, Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Tenon [AP-HP], CHU Limoges, None, and Jonchère, Laurent
Subjects: expansile mucinous carcinomas, [SDV.CAN] Life Sciences [q-bio]/Cancer, lymphadenectomy, mucinous ovarian carcinoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, prognosis
Abstract: International audience; Objective: The aim of the present study was to evaluate evolution and prognosis of mucinous ovarian carcinomas (mOC), with respect to the two invasive patterns: expansile and infiltrative invasion. Methods: This was a descriptive, retrospective, multicenter study conducted in 13 French centres from 1 January 2001 to 31 December 2019. All patients operated on for epithelial ovarian neoplasia of the mucinous type (infiltrative/ expansile) were included, whether the surgery was performed immediately or after neoadjuvant chemotherapy. Results: A total of 94 women with mucinous carcinomas were included in the present study. Mucinous tumours were divided into 35 expansile (37%) and 59 infiltrative (63%) mOC. There was a statistically significant difference in early and late stages at initial diagnosis between expansile and infiltrative mOC. None of the expansile mOC showed metastatic lymph nodes, whereas almost a quarter of the infiltrative mOC were metastatic to the pelvic /para-aortic region. There was a clear difference in RFS, in favour of expansile mOC, with 90% survival at 5 years, compared with 60% for infiltrative mOC. Conclusions: Although infiltrative and expansile mOC belong to the same histological family, they present many distinctions in clinical presentation, histological invasion, and disease course.
Published: 2022
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32. QM/MM Well-Tempered Metadynamics Study of the Mechanism of XBP1 mRNA Cleavage by Inositol Requiring Enzyme 1 alpha RNase

Author: Sayyed Jalil Mahdizadeh, Emil Pålsson, Antonio Carlesso, Eric Chevet, Leif A. Eriksson, University of Gothenburg (GU), 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), Vinnova Seal-of-Excellence program [2019-02205], Alfred Ahlqvists Foundation, Faculty of Science at the University of Gothenburg, Swedish Science Research Council [2019-3684], Swedish Cancer Foundation [21-1447-Pj], and Swedish Research Council [2018-05973]
Subjects: Molecular Docking Simulation, Ribonucleases, General Chemical Engineering, Endoribonucleases, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Chemistry, RNA, Messenger, Library and Information Sciences, Protein Serine-Threonine Kinases, Inositol, Computer Science Applications
Abstract: International audience; A range of methodologies were herein employed to study the unconventional XBP1 mRNA cleavage mechanism performed by the unfolded protein response (UPR) mediator Inositol Requiring Enzyme 1α (IRE1). Using Protein-RNA molecular docking along with a series of extensive restrained/unrestrained atomistic molecular dynamics (MD) simulations, the dynamical behavior of the system was evaluated and a reliable model of the IRE1/XBP1 mRNA complex was constructed. From a series of well-converged quantum mechanics molecular mechanics well-tempered metadynamics (QM/MM WT-MetaD) simulations using the Grimme dispersion interaction corrected semiempirical parametrization method 6 level of theory (PM6-D3) and the AMBER14SB-OL3 force field, the free energy profile of the cleavage mechanism was determined, along with intermediates and transition state structures. The results show two distinct reaction paths based on general acid-general base type mechanisms, with different activation energies that perfectly match observations from experimental mutagenesis data. The study brings unique atomistic insights into the cleavage mechanism of XBP1 mRNA by IRE1 and clarifies the roles of the catalytic residues H910 and Y892. Increased understanding of the details in UPR signaling can assist in the development of new therapeutic agents for its modulation.
Published: 2022
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33. Quality of life at diagnosis for unresectable stage III NSCLC: Initial results from the national prospective study OBSTINATE (GFPC 06-2019)

Author: Ricordel, C, Anota, A., Bernardi, M., Falchero, L, Auliac, J. B., Greillier, L, Bylicki, O., de Chabot, G., Demaegdt, A., Vergnenegre, A, Decroisette, C, Martel-Lafay, I., Chouaid, C, Guisier, F., Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), and AstraZeneca
Subjects: [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience
Published: 2022
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34. Clinical Significance and Genomic Characteristics of CD56+Circulating Tumor Cells in Small Cell Lung Carcinoma

Author: Ricordel, C, Chaillot, L., Vlachavas, E. -I., Logotheti, M., Desvallees, T., Aubry, M., Kontogianni, G., Mastrokalou, C., Jouan, F., Jarry, U., Guillaudeux, T., Léna, H., Chatziioannou, A, Pedeux, R, 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), 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 ), and Biomedical Research Foundation of the Academy of Athens (BRFAA)
Subjects: [SDV.CAN]Life Sciences [q-bio]/Cancer, small cell lung cancer, CD56, circulating tumor cell
Abstract: International audience
Published: 2022
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35. The cecal appendix is correlated with greater maximal longevity in mammals

Author: Eric Ogier-Denis, Jérémie Bardin, M. Collard, Michel Laurin, 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), Centre de Recherche en Paléontologie - Paris (CR2P), Muséum national d'Histoire naturelle (MNHN)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chemistry, Oncogenesis, Stress and Signaling (COSS), 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 Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), HAL-SU, Gestionnaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: 0106 biological sciences, Senescence, Aging, senescence, Histology, phylogenetic generalized least squares, media_common.quotation_subject, Longevity, diarrhea, Zoology, Appendix, Biology, Evolution of ageing, digestive system, 010603 evolutionary biology, 01 natural sciences, Social life, 03 medical and health sciences, Cecum, [SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, [SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], medicine, Selective advantage, Animals, gastrointestinal anatomy, convergent evolution, Life history, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, media_common, Mammals, Original Paper, 0303 health sciences, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], vermiform appendix, Cell Biology, bacterial infections and mycoses, Biological Evolution, Original Papers, medicine.anatomical_structure, [SDV.BA.ZV] Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, Anatomy, lifespan, extrinsic mortality, Developmental Biology
Abstract: The cecal appendix had been considered as a useless vestige since Darwin's work, but recent research questioned this idea demonstrating that the cecal appendix appeared among the mammals at least 80 million years ago and has made multiple and independent appearances without any obvious correlation with diet, social life, ecology, or size of the cecum. However, functions and probable selective advantage conferred by this anatomical structure still remain enigmatic. We found, through analyses of data on 258 mammalian species, that cecal appendix presence is correlated with increased maximal observed longevity. This is the first demonstration of a correlation between cecal appendix presence and life history. Interestingly, the classical evolutionary theory of aging that predicts an increased longevity when the extrinsic mortality is reduced has been questioned several times, but recent comparative studies asserted its validity in the taxa, which experience age‐dependent and density‐dependent mortality, as in mammals. Thus, the cecal appendix may contribute to the increase in longevity through a reduction of extrinsic mortality. A lower risk of fatal infectious diarrhea is one of the most plausible hypotheses that could explain it. However, several hypotheses coexist about the possible functions of the cecal appendix, and our results provide new insights about this much‐disputed question. In addition, we show that the cecal appendix arose at least 16 times and was lost only once during the evolutionary history of the considered mammals, an asymmetry that supports the existence of a positive selective of this structure., Most people think about the appendix as a useless and even harmful structure that is removed on emergency in case of appendicitis. This belief harks as far back as Darwin, but it has been questioned by recent works that suggests that the cecal appendix does have a function. In this study, we found that the presence of an appendix is correlated with greater longevity in mammals, even when controlling for the strong positive size effects and for the phylogeny.
Published: 2021
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36. Severe acute respiratory syndrome coronavirus 2 vaccination for patients with solid cancer: Review and point of view of a French oncology intergroup (GCO, TNCD, UNICANCER)

Author: Jean-Yves Blay, Virgine Westeel, Khê Hoang-Xuan, Philippe Gorphe, Thomas Aparicio, Thierry Lecomte, David Tougeron, Astrid Lièvre, Pierre Michel, Sébastien Gaujoux, Amélie Servettaz, Pascale Mariani, Maxime Hentzien, Michel Ducreux, Léon Maggiori, Firouzé Bani-Sadr, Laura Mansi, Jean Bourhis, Olivier Bouché, Boris Guiu, Christophe Louvet, Florence Huguet, Barbara Seitz-Polski, Juliette Thariat, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Universitaire de Cancérologie [Sorbonne Université] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cooperator Multidisciplinary Oncology Group (GERCOR), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Institut Curie [Paris], 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), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Léon Bérard [Lyon], None, University Hospital of Montpellier, Institut Universitaire de Cancérologie [Paris] (IUC), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Jonchère, Laurent, CHU Trousseau [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: 0301 basic medicine, Cancer Research, Pediatrics, medicine.medical_specialty, COVID-19 Vaccines, medicine.medical_treatment, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Neutropenia, medicine.disease_cause, Current Perspective, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neoplasms, Pandemic, medicine, Humans, Chemotherapy, education, Coronavirus, education.field_of_study, Radiotherapy, SARS-CoV-2, business.industry, Vaccination, COVID-19, Cancer, medicine.disease, 3. Good health, Radiation therapy, Solid cancers, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, business
Abstract: International audience; The impacts of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on cancer care are multiple, entailing a high risk of death from coronavirus disease 2019 (COVID-19) in patients with cancer treated by chemotherapy. SARS-CoV-2 vaccines represent an opportunity to decrease the rate of severe COVID-19 cases in patients with cancer and also to restore normal cancer care. Patients with cancer to be targeted for vaccination are difficult to define owing to the limited contribution of these patients in the phase III trials testing the different vaccines. It seems appropriate to vaccinate not only patients with cancer with ongoing treatment or with a treatment having been completed less than 3 years ago but also household and close contacts. High-risk patients with cancer who are candidates for priority access to vaccination are those treated by chemotherapy. The very high-priority population includes patients with curative treatment and palliative first- or second-line chemotherapy, as well as patients requiring surgery or radiotherapy involving a large volume of lung, lymph node and/or haematopoietic tissue. When possible, vaccination should be carried out before cancer treatment begins. SARS-CoV-2 vaccination can be performed during chemotherapy while avoiding periods of neutropenia and lymphopenia. For organisational reasons, vaccination should be performed in cancer care centres with messenger RNA vaccines (or non-replicating adenoviral vaccines in non-immunocompromised patients). Considering the current state of knowledge, the benefit-risk ratio strongly favours SARS-CoV-2 vaccination of all patients with cancer. To obtain more data concerning the safety and effectiveness of vaccines, it is necessary to implement cohorts of vaccinated patients with cancer.
Published: 2021
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37. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer

Author: Kelly, Ronan J, Ajani, Jaffer A, Kuzdzal, Jaroslaw, Zander, Thomas, Van Cutsem, Eric, Piessen, Guillaume, Mendez, Guillermo, Feliciano, Josephine, Motoyama, Satoru, Lièvre, Astrid, Uronis, Hope, Elimova, Elena, Grootscholten, Cecile, Geboes, Karen, Zafar, Syed, Snow, Stephanie, Ko, Andrew H, Feeney, Kynan, Schenker, Michael, Kocon, Piotr, Zhang, Jenny, Zhu, Lili, Lei, Ming, Singh, Prianka, Kondo, Kaoru, Cleary, James M, Moehler, Markus, CheckMate 577 Investigators, Van den Eynde, Marc, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Service d'hépato-gastro-entérologie, UCL - (SLuc) Service d'hématologie, Baylor University, MD Anderson Cancer Center [Houston], The University of Texas Health Science Center at Houston (UTHealth), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Universitätsklinikum Köln (Uniklinik Köln), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), CHU Lille, Favaloro Foundation, Johns Hopkins University (JHU), Akita University, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Duke Cancer Institute Durham, Duke University Medical Center, Princess Margaret Hospital, University of Toronto, Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Ghent University Hospital, Florida Hospital Cancer Institute, University of California [San Francisco] (UC San Francisco), University of California (UC), Bristol-Myers Squibb Company, Dana-Farber Cancer Institute [Boston], Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Bristol Myers Squibb Bristol-Myers Squibb, Ono Pharmaceutical, 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), University of California [San Francisco] (UCSF), University of California, and Johannes Gutenberg - Universität Mainz (JGU)
Subjects: Adult, Male, medicine.medical_specialty, Esophageal Neoplasms, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, Adenocarcinoma, 030204 cardiovascular system & hematology, Gastroenterology, B7-H1 Antigen, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Stomach Neoplasms, Internal medicine, Medicine and Health Sciences, medicine, Carcinoma, Humans, 030212 general & internal medicine, Esophagus, Immune Checkpoint Inhibitors, Neoadjuvant therapy, Aged, Aged, 80 and over, Chemotherapy, business.industry, Cancer, Chemoradiotherapy, Adjuvant, General Medicine, Middle Aged, medicine.disease, Neoadjuvant Therapy, Intention to Treat Analysis, 3. Good health, Nivolumab, medicine.anatomical_structure, Chemotherapy, Adjuvant, Carcinoma, Squamous Cell, Female, Esophagogastric Junction, business, Adjuvant, Chemoradiotherapy
Abstract: BackgroundNo adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer. MethodsWe conducted CheckMate 577, a global, randomized, double-blind, placebo-controlled phase 3 trial to evaluate a checkpoint inhibitor as adjuvant therapy in patients with esophageal or gastroesophageal junction cancer. Adults with resected (R0) stage II or III esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy and had residual pathological disease were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by nivolumab at a dose of 480 mg every 4 weeks) or matching placebo. The maximum duration of the trial intervention period was 1 year. The primary end point was disease-free survival. ResultsThe median follow-up was 24.4 months. Among the 532 patients who received nivolumab, the median disease-free survival was 22.4 months (95% confidence interval [CI], 16.6 to 34.0), as compared with 11.0 months (95% CI, 8.3 to 14.3) among the 262 patients who received placebo (hazard ratio for disease recurrence or death, 0.69; 96.4% CI, 0.56 to 0.86; P
Published: 2021
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38. 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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39. 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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40. Prophylactic and Therapeutic Effect of Kynurenine for Experimental Autoimmune Encephalomyelitis (EAE) Disease

Author: Gayathri Sundaram, Alban Bessede, David Gilot, Ananda Staats Pires, Larry S Sherman, Bruce J Brew, Gilles J Guillemin, Jonchère, Laurent, University of New South Wales [Sydney] (UNSW), ImmuSmol, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Macquarie University, Universidade Federal de Santa Catarina = Federal University of Santa Catarina [Florianópolis] (UFSC), Oregon Health and Science University [Portland] (OHSU), The University of Notre Dame [Sydney], ImmuSmol France, Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), International Cotutelle Macquarie University Research Exellence Scholarship (Cotutelle 'iMQRES'), and National Health and Medical Research Council (NHMRC)
Subjects: pro-ligand, immunosuppression, [SDV.CAN] Life Sciences [q-bio]/Cancer, aryl-hydrocarbon receptor, Tryptophan, [SDV.CAN]Life Sciences [q-bio]/Cancer, ligand, multiple sclerosis, Molecular Biology, Biochemistry, kynurenine, kynurenine pathway
Abstract: Background: The essential amino acid, tryptophan, is predominantly metabolised through the kynurenine pathway (KP) to generate kynurenine, an aryl-hydrocarbon receptor (AhR) pro-ligand that exerts its effects in a ligand-dependent manner. Interaction between kynurenine and the AhR is an effector mechanism of immunosuppression. We previously found that the KP is involved in multiple sclerosis (MS) disease progression. We postulated that AhR activation by kynurenine might be neuroprotective by encouraging differentiation of Tregs. In this study, we assess both the prophylactic and therapeutic efficiency of kynurenine on disease severity and progression in mice with experimental autoimmune encephalomyelitis (EAE), an MS model. Methods: Myelin oligodendrocyte glycoprotein induced EAE mice (n = 6 per group) were treated with 200 mg/kg L-kynurenine once daily for 10 days beginning on either day 1 of EAE induction (prophylactic) or once they demonstrated motor weakness (therapeutic). Clinical disease severity measured by disease score, time on rotarod, and body weight. Results: The prophylactic kynurenine treatment significantly ( P < .0001) prevented the development of a more severe disease course with mice demonstrating diminished relapse rate and improved clinical and behavioural outcomes. However, therapeutic kynurenine did not significantly ( P = .4463) decrease the clinical signs until 36 days following induction of disease; after 36 days, it also significantly ( P = .0479) reduced disease relapse. Mean body weight measurements only correlated with time on rotarod ( r = −.6410; P = .0007) but not clinical scores ( r = .1925; P = .3674). Conclusions: Kynurenine ameliorates EAE disease progression prophylactically and reduces relapses therapeutically. Further investigations are needed to elucidate the molecular mechanism explaining the therapeutic role of kynurenine for MS.
Published: 2022
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41. Integrative analysis of genomic and transcriptomic alterations of AGR2 and AGR3 in cancer

Author: Delphine Fessart, Ines Villamor, Eric Chevet, Frederic Delom, Jacques Robert, BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-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), CRLCC Eugène Marquis (CRLCC), N/A, Agence Nationale de la Recherche, N/A, Conseil Régional Aquitaine, DEQ20180339169, Fondation pour la Recherche Médicale, N/A, Institut National Du Cancer, N/A, Site de recherche intégrée sur le cancer de Bordeau, N/A, Ligue contre le cancer Gironde, and PJA 20181207750, Fondation ARC pour la Recherche sur le Cancer
Subjects: AGR3, genomic, General Neuroscience, Immunology, cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, transcriptomic, General Biochemistry, Genetics and Molecular Biology, AGR2
Abstract: The AGR2 and AGR3 genes have been shown by numerous groups to be functionally associated with adenocarcinoma progression and metastasis. In this paper, we explore the data available in databases concerning genomic and transcriptomic features of these two genes: the NCBI dbSNP database was used to explore the presence and roles of constitutional SNPs, and the NCI, Cancer Cell Line Encyclopedia (CCLE) and TCGA databases were used to explore somatic mutations and copy number variations (CNVs), as well as mRNA expression of these genes in human cancer cell lines and tumours. Relationships of AGR2 / 3 expression with whole-genome mRNA expression and cancer features (i.e. mutations and CNVs of oncogenes and tumour suppressor genes (TSG)) were established using the CCLE and TCGA databases. In addition, the CCLE data concerning CRISPR gene extinction screens (Achilles project) of these two genes and a panel of oncogenes and TSG were explored. We observed that no functional polymorphism or recurrent mutation could be detected in AGR2 or AGR3 . The expression of these genes was positively correlated with the expression of epithelial genes and inversely correlated with that of mesenchymal genes. It was also significantly associated with several cancer features, such as TP53 or SMAD4 mutations, depending on the gene and the cancer type. In addition, the CRISPR screens revealed the absence of cell fitness modification upon gene extinction, in contrast with oncogenes (cell fitness decrease) and TSG (cell fitness increase). Overall, these explorations revealed that AGR2 and AGR3 proteins appear as common non-genetic evolutionary factors in the process of human tumorigenesis.
Published: 2022
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42. The hexosamine pathway and coat complex II promote malignant adaptation to nutrient scarcity

Author: Helena Dragic, Audrey Barthelaix, Cédric Duret, Simon Le Goupil, Hadrien Laprade, Sophie Martin, Sabine Brugière, Yohann Couté, Christelle Machon, Jerome Guitton, Justine Rudewicz, Paul Hofman, Serge Lebecque, Cedric Chaveroux, Carole Ferraro-Peyret, Toufic Renno, Serge N Manié, 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), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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), BioSanté (UMR BioSanté), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Centre de Bioinformatique de Bordeaux (CBIB), CGFB, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), This work was supported by the Institut National du Cancer (7981), la Ligue Nationale Contre le Cancer (R18159CC), and Rennes Métropole (R20167NN). The proteomic experiments were partially supported by Agence Nationale de la Recherche under projects ProFI (Proteomics French Infrastructure, ANR-10-INBS-08) and GRAL, a program from the Chemistry Biology Health Graduate School of University Grenoble Alpes (ANR-17-EURE-0003)., ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), and Jonchère, Laurent
Subjects: ErbB Receptors, Glucose, Glycosylation, Ecology, [SDV.CAN] Life Sciences [q-bio]/Cancer, Health, Toxicology and Mutagenesis, Humans, Hexosamines, [SDV.CAN]Life Sciences [q-bio]/Cancer, Plant Science, Nutrients, Biochemistry, Genetics and Molecular Biology (miscellaneous)
Abstract: The glucose-requiring hexosamine biosynthetic pathway (HBP), which produces UDP-N-acetylglucosamine for glycosylation reactions, promotes lung adenocarcinoma (LUAD) progression. However, lung tumor cells often reside in low-nutrient microenvironments, and whether the HBP is involved in the adaptation of LUAD to nutrient stress is unknown. Here, we show that the HBP and the coat complex II (COPII) play a key role in cell survival during glucose shortage. HBP up-regulation withstood low glucose-induced production of proteins bearing truncated N-glycans, in the endoplasmic reticulum. This function for the HBP, alongside COPII up-regulation, rescued cell surface expression of a subset of glycoproteins. Those included the epidermal growth factor receptor (EGFR), allowing an EGFR-dependent cell survival under low glucose in anchorage-independent growth. Accordingly, high expression of the HBP rate-limiting enzyme GFAT1 was associated with wild-type EGFR activation in LUAD patient samples. Notably, HBP and COPII up-regulation distinguished LUAD from the lung squamous-cell carcinoma subtype, thus uncovering adaptive mechanisms of LUAD to their harsh microenvironment.
Published: 2022
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43. Trachelectomy: How is it actually done? A review from FRANCOGYN group

Author: Lefebvre, A, Raimond, Emilie, Chauvet, Pauline, Touboul, Cyril, Canlorbe, Geoffroy, Lavoué, Vincent, Ouldamer, Lobna, Collinet, Pierre, Bendifallah, Sofiane, Carcopino, Xavier, Lecointre, Lise, Kerbage, Yohan, CHU Lille, Department of Obstetrics and Gynaecology, Institute Alix de Champagne University Hospital, Reims, France., CHU Clermont-Ferrand, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], CHU Pontchaillou [Rennes], Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, and Jonchère, Laurent
Subjects: [SDV] Life Sciences [q-bio], [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Fertility, [SDV.CAN] Life Sciences [q-bio]/Cancer, Trachelectomy, [SDV]Life Sciences [q-bio], Cervical cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Cerclage
Abstract: International audience; Because of the peak incidence of cervical cancer between the ages of 35 and 44 and the increasing age of first pregnancy, the issue of fertility preservation in cases of early-stage cervical cancer in women in this reproductive age category arises. Early-stage cervical cancer patients have a good prognosis and are surgically treated in cases of mildly aggressive human papillomavirus-related histological type (squamous cell carcinoma, adenocarcinoma), FIGO stage IA to IB1 (i.e.
Published: 2022
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44. Long Noncoding RNAs in Cholangiocarcinoma

Author: Cédric Coulouarn, Panagiotis Papoutsoglou, Aude Merdrignac, CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), 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), This work was supported by Inserm, Université de Rennes 1, and ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé) dans le cadre du Plan cancer (Non-coding RNA in cancerology: fundamental to translational, [Grant C18007NS to CC]). CC is a member of the European Network for the Study of Cholangiocarcinoma (ENSCCA) and participates in the initiative COST Action EURO-CHOLANGIO-NET granted by the COST Association (CA18122)., 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), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: signaling pathway, 0301 basic medicine, Angiogenesis, Cell, information science, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Epigenesis, Genetic, liver cancer, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, parasitic diseases, medicine, Animals, Humans, cardiovascular diseases, Epigenetics, Epithelial–mesenchymal transition, Hepatology, fungi, RNA, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Long non-coding RNA, 030104 developmental biology, medicine.anatomical_structure, Bile Duct Neoplasms, Tumor progression, long non coding RNA, cardiovascular system, Cancer research, biomarker, Biomarker (medicine), RNA, Long Noncoding, 030211 gastroenterology & hepatology, cholangiocarcinoma
Abstract: International audience; Cholangiocarcinoma (CCA) is the second primary hepatic malignancy after hepatocellular carcinoma. CCA is characterized by its aggressiveness and poor prognosis associated with limited therapeutic options. Thus, a better understanding of molecular pathogenesis of CCA together with the identification of robust biomarkers and therapeutic targets is still necessary to improve the management of patients with CCA. In this review, we discuss the role of long non coding RNAs (lncRNAs) in CCA onset and progression. LncRNAs represent a heterogeneous class of RNA molecules with various genomic location and organization acting at both transcriptional and post-transcriptional levels. Notably, we provide an overview of the functions of lncRNAs in epigenetic modulation and regulation of signaling pathways and cell behaviors leading to tumor progression (e.g. apoptosis, survival, epithelial to mesenchymal transition, migration, invasion, angiogenesis). Moreover, we depict the clinical relevance of lncRNAs as biomarkers and emerging therapeutic targets in CCA.
Published: 2021
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45. Pharmacological Targeting of IRE1 in Cancer

Author: Dimitrios Doultsinos, Eric Chevet, Antonio Carlesso, Diana Pelizzari Raymundo, Xavier Guillory, Leif A. Eriksson, Jonchère, Laurent, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Sciences Chimiques de Rennes (ISCR), 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), University of Gothenburg (GU), This work was funded by grants from Institut National du Cancer (INCa PLBIO), Fondation pour la Recherche Médicale (FRM, équipe labellisée 2018), ERANET , and Agence Nationale de la Recherche (ERAAT) to E.C., EU H2020 MSCA ITN-675448 (TRAINERS), and MSCA RISE-734749 (INSPIRED) provided grants to L.A.E. and E.C. D.P.R. was funded by INSERM (LA VANNETAISE). X.G. was funded by a post-doctoral fellowship from Fondation ARC , and D.D. and A.C. were MSCA ITN fellows (TRAINERS)., Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), 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), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)
Subjects: 0301 basic medicine, Cancer Research, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), IRE1, Protein Serine-Threonine Kinases, Inositol-requiring enzyme 1, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, Allosteric Regulation, Protein Domains, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Endoribonucleases, inhibitors, Humans, Medicine, Mode of action, Protein Kinase Inhibitors, activators, business.industry, Cancer, unfolded protein response, Endoplasmic Reticulum Stress, medicine.disease, 3. Good health, Gene Expression Regulation, Neoplastic, endoplasmic reticulum, 030104 developmental biology, Oncology, Protein kinase domain, 030220 oncology & carcinogenesis, Proteostasis, Unfolded protein response, business, Signal Transduction
Abstract: International audience; IRE1α (inositol requiring enzyme 1 alpha) is one of the main transducers of the unfolded protein response (UPR). IRE1α plays instrumental protumoral roles in several cancers, and high IRE1α activity has been associated with poorer prognoses. In this context, IRE1α has been identified as a potentially relevant therapeutic target. Pharmacological inhibition of IRE1α activity can be achieved by targeting either the kinase domain or the RNase domain. Herein, the recent advances in IRE1α pharmacological targeting is summarized. We describe the identification and optimization of IRE1α inhibitors as well as their mode of action and limitations as anticancer drugs. The potential pitfalls and challenges that could be faced in the clinic, and the opportunities that IRE1α modulating strategies may present are discussed.
Published: 2020
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46. Nutrition and physical activity: French intergroup clinical practice guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, AFC, SFP-APA, SFNCM, AFSOS)

Author: Didier Quilliot, Bruno Raynard, Francisca Joly, Damien Vansteene, Société Nationale Française de Gastroentérologie, Didier Barnoud, Frédérique Peschaud, Valérie Garabige, Fédération Francophone de Cancérologie Digestive, Société française de radiothérapie oncologique, Société française de chirurgie digestive, Groupe Coopérateur multidisciplinaire en Oncologie, Astrid Lièvre, Vanessa Cottet, Eric Fontaine, Société Française des Professionnels en Activité Physique Adaptée, Xavier Hébuterne, Thomas Mouillot, Frédéric Chorin, Aude-Marie Foucaut, Florence Huguet, Cindy Neuzillet, Amélie Anota, Olivier Bouché, Anne-Laure Védie, Florian Scotté, Timothée Marchal, Société Française d’Endoscopie Digestive, Pascale Mariani, Stéphane M. Schneider, Fédération nationale des centres de lutte contre le cancer, Carole Bouleuc, Sami Antoun, Institut Curie [Paris], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 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), Unité de Biostatistique et d'Evaluation des Thérapeutiques (UBET), Centre Léon Bérard [Lyon], Laboratoire éducations et promotion de la santé (LEPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Gustave Roussy (IGR), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Pasteur [Nice] (CHU), Laboratoire Motricité Humaine Expertise Sport Santé (LAMHESS), 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)-Université de Toulon (UTLN)-Université Côte d'Azur (UCA), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de chirurgie générale, digestive et oncologique [CHU Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], 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'Endocrinologie - Diabète - Nutrition [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département interdisciplinaire d’organisation des parcours patients (DIOPP), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Hospitalier Universitaire de Reims (CHU Reims), Jonchère, Laurent, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Laboratoire Educations et Pratiques de Santé (LEPS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: medicine.medical_specialty, Medicine (miscellaneous), [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), symptoms and symptom management, Disease, gastrointestinal (lower), 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), [SDV.CAN] Life Sciences [q-bio]/Cancer, Endopeptidases, medicine, Humans, 030212 general & internal medicine, Stage (cooking), Intensive care medicine, Exercise, Societies, Medical, Oncology (nursing), business.industry, Cancer, General Medicine, Perioperative, Evidence-based medicine, medicine.disease, gastrointestinal (upper), 3. Good health, supportive care, Medical–Surgical Nursing, Malnutrition, pancreatic, 030220 oncology & carcinogenesis, Quality of Life, business, education and training, Follow-Up Studies
Abstract: International audience; This document is a summary of the French intergroup guidelines regarding the nutrition and physical activity (PA) management in digestive oncology. This collaborative work was produced under the auspices of all French medical and surgical societies involved in digestive oncology, nutrition and supportive care. It is based on published guidelines, recent literature review and expert opinions. Recommendations are graded according to the level of evidence. Malnutrition affects more than half of patients with digestive cancers and is often underdiagnosed. It has multiple negative consequences on survival, quality of life and risk of treatment complications. Consequently, in addition to anticancer treatments, supportive care including nutritional support and PA plays a central role in the management of digestive cancers. It is crucial to detect malnutrition (diagnostic criteria updated in 2019) early, to prevent it and to act against it at all stages of the cancer and at all times of the care pathway. In this context, we proposed recommendations for the evaluation and management in nutrition and PA in digestive oncology for each stage of the disease (perioperative setting, during radiation therapy, during systemic treatments, at the palliative phase, after cancer). Guidelines for nutrition and PA management aim at increasing awareness about malnutrition in oncology. They are continuously evolving and need to be regularly updated.
Published: 2020
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47. Immune-related Encephalitis in Two Patients Treated With Immune Checkpoint Inhibitor

Author: Lucie Robert, Fanny Thepault, Sophie Langner-Lemercier, A. Salé, Charles Ricordel, Alexis Angibaud, Hervé Lena, Romain Corre, CHU Pontchaillou [Rennes], CH de Saint-Malo [Broussais], 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), Roche, AstraZeneca, Pfizer, MSD, BMS, Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Pulmonary and Respiratory Medicine, Cancer Research, Immune checkpoint inhibitors, Immune encephalitis, [SDV.CAN]Life Sciences [q-bio]/Cancer, NSCLC, 03 medical and health sciences, 0302 clinical medicine, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Immune-related adverse events, Atezolizumab, medicine, Lung cancer, ComputingMilieux_MISCELLANEOUS, business.industry, medicine.disease, 3. Good health, Nivolumab, Oncology, 030220 oncology & carcinogenesis, Immunology, business, 030217 neurology & neurosurgery, Encephalitis
Abstract: International audience
Published: 2020
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48. COVID-19 epidemic: Proposed alternatives in the management of digestive cancers: A French intergroup clinical point of view (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SFR)

Author: Sylvain Manfredi, Astrid Lièvre, Société Nationale Française de Gastroentérologie, Jean Jacques Tuech, Camille Boulagnon-Rombi, Fédération Francophone de Cancérologie Digestive, Frédéric Di Fiore, L. Schwarz, Alice Gangloff, Pierre Michel, Jean-Marc Phelip, Société Française d’Endoscopie Digestive, Groupe Coopérateur multidisciplinaire en Oncologie, Côme Lepage, Thierry Lecomte, Olivier Bouché, Société Française de Radiologie, Société française de radiothérapie oncologique, Thomas Aparicio, David Sefrioui, Fédération nationale des centres de lutte contre le cancer, Société française de chirurgie digestive, 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), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, 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 Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, Digestive cancer, MEDLINE, Antineoplastic Agents, French Clinical Practice Guidelines, [SDV.CAN]Life Sciences [q-bio]/Cancer, Comorbidity, Malignancy, Betacoronavirus, 03 medical and health sciences, 0302 clinical medicine, Health care, Pandemic, Disease Transmission, Infectious, Humans, Chemotherapy, Medicine, Infection control, Intensive care medicine, Pandemics, Digestive System Surgical Procedures, Societies, Medical, Gastrointestinal Neoplasms, Infection Control, Hepatology, SARS-CoV-2, business.industry, Gastroenterology, COVID-19, Evidence-based medicine, medicine.disease, Patient Care Management, COVID-19 infection, 3. Good health, 030220 oncology & carcinogenesis, Surgery, 030211 gastroenterology & hepatology, France, Coronavirus Infections, business
Abstract: International audience; Introduction - Patients treated for malignancy are considered at risk of severe COVID-19. This exceptional pandemic has affected countries on every level, particularly health systems which are experiencing saturation. Like many countries, France is currently greatly exposed, and a complete reorganization of hospitals is ongoing. We propose here adaptations of diagnostic procedures, therapies and care strategies for patients treated for digestive cancer during the COVID-19 epidemic. Methods - French societies of gastroenterology and gastrointestinal (GI) oncology carried out this study to answer two main questions that have arisen (i) how can we limit high-risk situations for GI-cancer patients and (ii) how can we limit contact between patients and care centers to decrease patients' risk of contamination while continuing to treat their cancer. All recommendations are graded as experts' agreement according to the level of evidence found in the literature until March 2020. Results - A proposal to adapt treatment strategies was made for the main GI oncology situations. Considering the level of evidence and the heterogeneous progression of the COVID-19 epidemic, all proposals need to be considered by a multidisciplinary team and implemented with patient consent. Conclusion - COVID-19 epidemic may significantly affect patients treated for digestive malignancies. Healthcare teams need to consider adapting treatment sequences when feasible and according to the epidemic situation.
Published: 2020
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49. Starvation and antimetabolic therapy promote cytokine release and recruitment of immune cells

Author: Raffaella Iurlaro, Jaime Redondo-Pedraza, Sandrine Marchetti, Eric Eldering, Ernest Nadal, Jean-Ehrland Ricci, Cristina Muñoz-Pinedo, Franziska Püschel, Blanca Majem, Francesca Favaro, Eric Chevet, Estefanía Lucendo, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), University of Amsterdam [Amsterdam] (UvA), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 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), 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), Universitat de Barcelona (UB), Graduate School, AII - Cancer immunology, CCA - Cancer biology and immunology, Experimental Immunology, Université Nice Sophia Antipolis (1965 - 2019) (UNS), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Chemokine, Angiogenesis, Antimetabolites, medicine.medical_treatment, Glutamine, Cell, cancer metabolism, 0302 clinical medicine, Immunology and Inflammation, Neoplasms, Citoquines, glucose, Càncer, Promoter Regions, Genetic, Cancer, 0303 health sciences, Multidisciplinary, biology, Cell Death, Chemistry, NF-kappa B, Biological Sciences, Metabolisme, Metformin, 3. Good health, Cell biology, Cytokine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cytokines, medicine.symptom, [SDV.CAN]Life Sciences [q-bio]/Cancer, Inflammation, Deoxyglucose, 03 medical and health sciences, Immune system, cancer immunity, Stress, Physiological, medicine, Integrated stress response, Humans, 030304 developmental biology, Interleukin-6, Macrophages, Interleukin-8, Chemotaxis, Epithelial Cells, biochemical phenomena, metabolism, and nutrition, Activating Transcription Factor 4, cytokines, Metabolism, Glucose, Gene Expression Regulation, Starvation, Glucosa, biology.protein, bacteria, HeLa Cells
Abstract: Significance Poorly irrigated tumors exhaust nutrients from their environment. On the other hand, innate immune cells, such as neutrophils and macrophages, have been frequently shown to infiltrate tumors and promote an immunosuppressive environment. Our results show that, when nutrients are low, tumor cells secrete factors related to wound healing that stimulate endothelial cells and attract innate immune cells. This suggests that targeting signals elicited by metabolic stress may help the immune system target malignant cells and that metabolites regulate the communication between immune and tumor cells also through modulation of peptidic signals., Cellular starvation is typically a consequence of tissue injury that disrupts the local blood supply but can also occur where cell populations outgrow the local vasculature, as observed in solid tumors. Cells react to nutrient deprivation by adapting their metabolism, or, if starvation is prolonged, it can result in cell death. Cell starvation also triggers adaptive responses, like angiogenesis, that promote tissue reorganization and repair, but other adaptive responses and their mediators are still poorly characterized. To explore this issue, we analyzed secretomes from glucose-deprived cells, which revealed up-regulation of multiple cytokines and chemokines, including IL-6 and IL-8, in response to starvation stress. Starvation-induced cytokines were cell type-dependent, and they were also released from primary epithelial cells. Most cytokines were up-regulated in a manner dependent on NF-κB and the transcription factor of the integrated stress response ATF4, which bound directly to the IL-8 promoter. Furthermore, glutamine deprivation, as well as the antimetabolic drugs 2-deoxyglucose and metformin, also promoted the release of IL-6 and IL-8. Finally, some of the factors released from starved cells induced chemotaxis of B cells, macrophages, and neutrophils, suggesting that nutrient deprivation in the tumor environment can serve as an initiator of tumor inflammation.
Published: 2020
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50. Guidelines for clothing in the operating theatre, 2021

Author: Hafiani, El-Mahdi, Cassier, Pierre, Aho, Serge, Albaladejo, Pierre, Beloeil, Hélène, Boudot, Evelyne, Carenco, Philippe, Lallemant, Florence, Leroy, Marie Gabrielle, Muret, Jane, Tamames, Corinne, Garnier, Marc, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nice (CHU Nice), Association Française de Normalisation (AFNOR), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), 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], Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Lille, Institut Curie [Paris], CHU Pitié-Salpêtrière [AP-HP], Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Jonchère, Laurent, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Environmental impact, [SDV] Life Sciences [q-bio], Anesthesiology and Pain Medicine, Risk of infection, [SDV]Life Sciences [q-bio], Dress code, Operating theatre, General Medicine, Guidelines, Critical Care and Intensive Care Medicine
Abstract: International audience; OBJECTIVE: To provide guidelines for the choice of items of clothing (except sterile surgical gown) for staff working in the operating theatre. DESIGN: A committee of nine experts from SFAR and the SF2H learned societies was convened. A formal conflict-of-interest policy was developed at the beginning of the process and enforced throughout. Likewise, it did not benefit from any funding from a company marketing a health product (drug or medical device). The authors were required to follow the rules of the GRADE® method (Grading of Recommendations Assessment, Development and Evaluation) to assess the quality of the evidence on which the recommendations were based. METHODS: We aimed to formulate recommendations according to the GRADE® methodology for four different fields: operating theatre suits, operating theatre hats, masks, and shoes/over-shoes. Each question was formulated according to the PICO format (Patient, Intervention, Comparison, Outcome). The literature review and recommendations were formulated according to the GRADE® methodology. RESULTS: The experts’ synthesis work and their application of the GRADE® method resulted in 13 recommendations. As the GRADE® method could not be integrally applied to all questions, some recommendations were formulated as expert opinions. CONCLUSION: Based on strong agreement between experts, we produced 13 recommendations to guide the choice of operating theatre attire.
Published: 2022
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