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32 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. 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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4. 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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5. Pulmonary manifestations induced by osimertinib

Author: Le Guen, Y, Lederlin, M, Triquet, L, Lesouhaitier, M, Le Tulzo, Y, Ricordel, C, CHU Pontchaillou [Rennes], Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and CRLCC Eugène Marquis (CRLCC)
Subjects: Pulmonary and Respiratory Medicine, 0303 health sciences, Pneumopathie interstitielle, Adverse drug reactions, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, respiratory tract diseases, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Effets secondaires indésirables des médicaments, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cancer bronchique, Lung cancer, Osimertinib, Interstitial pneumonia, 030304 developmental biology
Abstract: National audience; INTRODUCTION: The third-generation tyrosine kinase inhibitor (TKI) osimertinib is recommended as a first-line treatment in advanced non-small cell lung cancer harboring an activating mutation of Epidermal Growth Factor Receptor (EGFR). Adverse pulmonary events related to osimertinib exposure have been reported, primarily in Japanese patients. They rarely occur in the Caucasian population. OBSERVATION: Herein we report two clinical cases of osimertinib-induced lung toxicities in patients diagnosed with advanced lung adenocarcinoma harboring an EGFR mutation. In the first case, interstitial pneumonia was asymptomatic and evolved favorably after osimertinib discontinuation. The second patient presented a more extensive form of lung injuries and despite systemic corticosteroid therapy, the evolution was fatal. CONCLUSION: Osimertinib-related lung toxicities remain exceptional. While most forms are mild, consideration of TKI treatment discontinuation may be necessitated. Introduction of another TKI or rechallenge with osimertinib might be considered along with corticosteroid therapy if necessary. Diffuse alveolar damage is a pejorative prognostic factor.
Published: 2022
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6. 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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7. 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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8. Treatment, outcome, and prognostic factors in non-metastatic anal cancer: The French nationwide cohort study FFCD-ANABASE

Author: Vendrely, Véronique, Lemanski, Claire, Pommier, Pascal, Le Malicot, Karine, Saint, Angélique, Rivin del Campo, Eleonor, Regnault, Pauline, Baba-Hamed, Nabil, Ronchin, Philippe, Crehange, Gilles, Tougeron, David, Menager-Tabourel, Elodie, Diaz, Olivia, Hummelsberger, Michael, Minsat, Mathieu, Drouet, Franck, Larrouy, Anne, Peiffert, Didier, Lievre, Astrid, Zasadny, Xavier, Hautefeuille, Vincent, Mornex, Françoise, Lepage, Côme, Quero, Laurent, BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Institut du Cancer de Montpellier (ICM), Centre Léon Bérard [Lyon], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Clinique Tivoli Ducos [Bordeaux], Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Azuréen de Cancérologie [Mougins, France], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Institut Daniel Hollard [Grenoble], Centre de radiothérapie et d'oncologie médicale privée (Béziers), Institut Curie - Saint Cloud (ICSC), Clinique Mutualiste de l'Estuaire (Saint Nazaire), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Polyclinique de Limoges - site François Chénieux [Limoges], CHU Amiens-Picardie, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), and Fédération Francophone de Cancérologie Digestive.
Subjects: Oncology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Radiology, Nuclear Medicine and imaging, Chemoradiotherapy, Hematology, Anal cancer, IMRT, Observational cohort
Abstract: International audience; Introduction: International guidelines regarding the treatment of squamous cell carcinoma of the anus (SCCA) recommend intensity-modulated radiotherapy (IMRT) combined with mitomycin-based chemotherapy (CT). The French FFCD-ANABASE cohort aimed at evaluating clinical practices, treatment, and outcomes of SCCA patients.Methods: This prospective multicentric observational cohort included all non-metastatic SCCA patients treated in 60 French centers from January 2015 to April 2020. Patients and treatment characteristics, colostomy-free survival (CFS), disease-free survival (DFS), overall survival (OS), and prognostic factors were analyzed.Results: Among 1015 patients (male: 24.4 %; female: 75.6 %; median age: 65 years), 43.3 %presented with early-stage(T1-2, N0) and 56.7 % with locally advanced stage (T3-4 or N + ) tumors. IMRT was used for 815 patients (80.3 %) and a concurrent CT was administered in 781 patients, consisting of mitomycin-based CT for 80 %. The median follow-up was 35.5 months. DFS, CFS, and OS at 3 years were 84.3 %, 85.6 %, and 91.7 % respectively in the early-stage group compared to 64.4 %, 66.9 %, and 78.2 % in the locally-advanced group (p < 0.001). In multivariate analyses, male gender, locally-advanced stage, and ECOG PS ≥ 1 were associated with poorer DFS, CFS, and OS. IMRT was significantly associated with a better CFS in the whole cohort and almost reached significance in the locally-advanced group.Conclusion: Treatment of SCCA patients showed good respect for current guidelines. Significant differences in outcomes advocate for personalized strategies by either de-escalation for early-stage tumors or treatment intensification for locally-advanced tumors.
Published: 2023
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9. 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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10. 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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11. 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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12. Nal-IRI/LV5-FU versus paclitaxel as second-line therapy in patients with metastatic esophageal squamous cell carcinoma (OESIRI)-PRODIGE 62: A multicentre, randomised, non-comparative phase II study

Author: Laetitia Dahan, Emilie Barbier, David Tougeron, Jean Philippe Metges, Samy Louafi, Christophe Borg, Roger Faroux, Lila Gaba, Christophe Louvet, Jérôme Desramé, Astrid Lièvre, Violaine Randrian, Frédéric Di Fiore, Sylvain Manfredi, Antoine Adenis, Gilles Breysacher, Pierre Laurent-Puig, Laurent Mineur, Guillaume Roquin, Anthony Lopez, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Hôpital privé Jean Mermoz, Fédération Francophone de la Cancérologie Digestive, FFCD, Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), 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), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Sainte Catherine [Avignon], Hôpital Louis Pasteur [Colmar] (CH Colmar), Servier, Faculté de Médecine - Clermont-Auvergne (FM - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Université de Rennes 1 (UR1), and 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)
Subjects: Oncology, medicine.medical_specialty, Esophageal Neoplasms, Paclitaxel, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Esophageal cancer, Phases of clinical research, Irinotecan, 03 medical and health sciences, chemistry.chemical_compound, Clinical Trials, Phase II as Topic, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Multicenter Studies as Topic, ComputingMilieux_MISCELLANEOUS, Randomized Controlled Trials as Topic, 030304 developmental biology, Cisplatin, 0303 health sciences, Chemotherapy, Hepatology, Performance status, business.industry, Gastroenterology, medicine.disease, 3. Good health, Survival Rate, chemistry, Docetaxel, 030220 oncology & carcinogenesis, Disease Progression, Quality of Life, Squamous cell cancer, Esophageal Squamous Cell Carcinoma, Fluorouracil, France, Neoplasm Recurrence, Local, business, medicine.drug
Abstract: Half of patients newly diagnosed with esophageal squamous cell cancer (ESCC) have metastatic disease (mESCC) and therefore a poor prognosis. Furthermore, half of patients with initial loco-regional disease present disease recurrence after surgery and/or chemoradiation. In mESCC, the recommended first-line treatment combines 5-fluorouracil and cisplatin, although this has not been validated by a phase III trial. Patients with disease progression or recurrence after platinum-based chemotherapy and good performance status probably benefit from second-line chemotherapy. Several molecules have been evaluated in phase I/II trials or retrospective studies (docetaxel, paclitaxel and irinotecan) but no randomised studies are available. OESIRI is a multicentre, randomised, open-label phase II trial designed to evaluate efficacy and safety of liposomal irinotecan (nal-IRI) plus 5-FU versus paclitaxel as second-line therapy in patients with mESCC. The main inclusion criteria are histologically proven mESCC in progression after first-line platinum-based chemotherapy. Patients with initial resectable disease can be included if recurrence occurred within 6 months. The primary objective is to evaluate the percentage of patients alive 9 months after randomisation. Secondary endpoints are progression-free survival, overall survival, response rate, safety and quality of life. In addition, circulating tumour DNA will be monitored to assess its prognostic value.
Published: 2020
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13. pBFK, a new thermosensitive shuttle vector for Streptococcus pyogenes gene deletion by homologous recombination

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

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

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

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

Author: Astrid Lièvre, Mathilde Cosson, Jean-François Bretagne, Christine Piette, G. Durand, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Université de Rennes (UR), ADECI35, Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and CCSD, Accord Elsevier
Subjects: Male, Adenoma, medicine.medical_specialty, Colorectal cancer, Population, Colonoscopy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Occult blood test, Colorectal cancer screening, Feces, Hemoglobins, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, Mass Screening, Advanced adenoma, education, Early Detection of Cancer, ComputingMilieux_MISCELLANEOUS, Aged, education.field_of_study, Guaiac faecal occult blood test, Hepatology, medicine.diagnostic_test, Crc screening, business.industry, Gastroenterology, Outcome measures, Immunochemical faecal occult blood test, Middle Aged, medicine.disease, 3. Good health, Occult Blood, 030220 oncology & carcinogenesis, Female, Indicators and Reagents, 030211 gastroenterology & hepatology, Faecal occult blood test, Colorectal Neoplasms, Guaiac, business
Abstract: International audience; Background: Compared with the guaiac-faecal occult blood test (gFOBT), faecal immunological tests (FIT) are considered to be more effective for colorectal cancer (CRC) screening. However, only scarce research has examined the outcomes of switching to FIT within a mature gFOBT-based CRC screening programme.Methods: We reported a 15-year experience of biennial FOBT screening in a well-defined population of approximately one million inhabitants, including six gFOBT-based screening rounds and one round with FIT at the 30 μg Hb/g cut-off. The main outcome measures were screening participation, FOBT positivity and advanced neoplasia detection in each round.Results: In this study, 647 676 screenings were performed in 228 716 different individuals, leading to 17 819 positives and 16 580 follow-up colonoscopies. Compared with the last gFOBT round, switching to FIT led to an increased participation of nearly 20% points, and a fivefold increased detection of CRC and advanced adenoma among invitees (3-fold among attendees). The numbers needed to screen and scope to detect one advanced neoplasia declined from 221 to 66 and from 4.7 to 2.6, respectively.Conclusions: The present population-based study demonstrated a dramatical increase in the diagnostic yield of advanced neoplasia by switching to FIT within a mature gFOBT-based CRC screening programme.
Published: 2019
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18. Rethinking Alkylating(-Like) Agents for Solid Tumor Management

Author: Bénédicte Lelièvre, Emmanuel Garcion, Philippe Lecomte, Elodie Vauleon, Hélène Lajous, Université de Liège, Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA-ÉQUIPE 17), 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)-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), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), 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), CRLCC Eugène Marquis (CRLCC), PL-BIO 2014-2020, Molecular Programmation, La Région Pays-de-la-Loire, Institut National de la Santé et de la Recherche Médicale (INSERM, University of Angers (Angers, France), Fonds de la Recherche Scientifique’ (F.R.S.-FNRS)., 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 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), and Jonchère, Laurent
Subjects: 0301 basic medicine, synergies, Bioactive molecules, cisplatin, [SDV.CAN]Life Sciences [q-bio]/Cancer, Toxicology, 03 medical and health sciences, Drug Delivery Systems, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, local treatment, Neoplasms, alkylating agents, medicine, Humans, Solid tumor, Cytotoxicity, Antineoplastic Agents, Alkylating, Pharmacology, Cisplatin, business.industry, Drug Synergism, solid tumors, nanomedicine, 3. Good health, 030104 developmental biology, Systemic toxicity, Treatment Schedule, Drug delivery, Cancer research, Nanomedicine, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: International audience; Although old molecules, alkylating agents and platinum derivatives are still widely used in the treatment of various solid tumors. However, systemic toxicity and cellular resistance mechanisms impede their efficacy. Innovative strategies, including local administration, optimization of treatment schedule/dosage, synergistic combinations, and the encapsulation of bioactive molecules in smart, multifunctional drug delivery systems, have shown promising results in potentiating anticancer activity while circumventing such hurdles. Furthermore, questioning of the old paradigm according to which nuclear DNA is the critical target of their anticancer activity has shed light on subcellular alternative and neglected targets that obviously participate in the mediation of cytotoxicity or resistance. Thus, rethinking of the use of these pivotal antineoplastic agents appears critical to improve clinical outcomes in the management of solid tumors.
Published: 2019
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19. Impact of severe obesity in the management of patients with high-risk endometrial cancer: A FRANCOGYN study

Author: Ombline Simon, Ludivine Dion, Krystel Nyangoh Timoh, Pierre François Dupré, Henri Azaïs, Sofiane Bendifallah, Cyril Touboul, Yohan Dabi, Olivier Graesslin, Emilie Raimond, Hélène Costaz, Yohan Kerbage, Cyrille Huchon, Camille Mimoun, Martin Koskas, Cherif Akladios, Lise Lecointre, Geoffroy Canlorbe, Pauline Chauvet, Lobna Ouldamer, Jean Levêque, Vincent Lavoué, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CHU Lille, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Strasbourg, CHU Pitié-Salpêtrière [AP-HP], CHU Clermont-Ferrand, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: MESH: Humans, Clinical management, MESH: Lymph Node Excision, [SDV]Life Sciences [q-bio], Obstetrics and Gynecology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, MESH: Obesity, Morbid, Endometrial Neoplasms, Obesity, Morbid, [SDV] Life Sciences [q-bio], [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, [SDV.CAN] Life Sciences [q-bio]/Cancer, Endometrial cancer, Reproductive Medicine, Humans, Lymph Node Excision, MESH: Obesity, Female, Surgery, Obesity, MESH: Endometrial Neoplasms, Neoplasm Recurrence, Local, MESH: Female, MESH: Neoplasm Recurrence, Local
Abstract: International audience; Objective: To assess the surgical management and survival of severely obese patients with high-risk endometrial cancer.Materials and methods: Data from 269 patients with high-risk endometrial cancer who were treated between 2001 and 2018 were collected from a multicenter database (11 centers). We classified the patients according to their BMI and compared outcomes in two groups: a normal weight group of women with a BMI < 25 kg/m2, and a severe obesity group of women with a BMI ≥ 35 kg/m2. The groups were compared for epidemiologic, pathologic, management, relapse-free survival (RFS) and overall survival (OS) elements.Results: Patients in the severe obesity group were younger (64 years vs. 68 years, p < 0.05) and had more comorbidities (hypertension, diabetes). They also had more locally advanced tumors and pelvic lymph node involvement (47% vs 24%, p < 0.05). The severely obese patients were less likely to undergo recommended surgical staging, with fewer lumbar aortic dissections than women of normal weight (23% vs 36%, p < 0.05) and fewer pelvic sentinel lymph node biopsies (26.5% vs 12.1%, p < 0.05). No difference in RFS or OS were observed between the two groups.Conclusion: Patients with severe obesity and high-risk endometrial cancer have more locally advanced tumors, and are less likely to be managed according to surgical recommendations. However, RFS and OS do not seem to be affected.
Published: 2022
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20. Structure simplification of the Securinine skeleton reveals the importance of BCD ring system for the cytotoxic activity on HCT116 and HL60 cell lines

Author: Myriam Le Roch, Damien Afonso, Egor Chirkin, Xavier Guillory, François-Hugues Porée, 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), Institut Pasteur [Paris] (IP), Collection des Cyanobactéries, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), 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), Université de Rennes 1 and CNRS are acknowledged for their financial support. XG is grateful to the ‘Fondation ARC pour la recherche sur le cancer’ for his post-doctoral fellowship (PDF20191209830)., Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Institut Pasteur [Paris]-Université Paris Cité (UPC), Université de Rennes 1 (UR1), and 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)
Subjects: Cell Survival, Clinical Biochemistry, Molecular Conformation, simplified analogs, Pharmaceutical Science, Antineoplastic Agents, HL-60 Cells, [SDV.CAN]Life Sciences [q-bio]/Cancer, HCT116, Biochemistry, Lactones, Structure-Activity Relationship, Piperidines, Drug Discovery, Tumor Cells, Cultured, [CHIM]Chemical Sciences, Humans, Molecular Biology, Density Functional Theory, Cell Proliferation, Dose-Response Relationship, Drug, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Securinega, Azepines, molecular editing, HCT116 Cells, Heterocyclic Compounds, Bridged-Ring, HL60, cytotoxicity, Molecular Medicine, Drug Screening Assays, Antitumor
Abstract: International audience; Function-oriented molecular editing of the polycyclic scaffold of securinine led to the preparation of a library of simplified analogs that have been evaluated for their cytotoxicity potential against HCT116 and HL60 human cell lines. Chemical diversity at the C14 position (securinine numbering) was generated through the site-selective γ-iodination followed by Pd-catalyzed Sonogashira and Suzuki-Miyaura reactions. To explain the selectivity in the iodination step, a reaction mechanism has been proposed. Surprisingly, the piperidine ring (ring A) of the securinine skeleton has been found to be irrelevant for the cytotoxic activity. Based on this finding, the pharmacophoric core of securinine could be simplified to the key BCD motif. The nature of the substituent at the nitrogen can vary from a methyl or an isobutyl group to a benzyl or a carbamate moiety. Interestingly, the N-benzyl substituted simplified analog exhibited the same cytotoxic activity as the parent compound securinine. This functional group tolerance paves the way for the installation of reactive handles for the synthesis of molecular probes for target identification.
Published: 2022
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21. Natural and human-driven selection of a single non-coding body size variant in ancient and modern canids

Author: Jocelyn Plassais, Bridgett M. vonHoldt, Heidi G. Parker, Alberto Carmagnini, Nicolas Dubos, Ilenia Papa, Kevin Bevant, Thomas Derrien, Lauren M. Hennelly, D. Thad Whitaker, Alex C. Harris, Andrew N. Hogan, Heather J. Huson, Victor F. Zaibert, Anna Linderholm, James Haile, Thierry Fest, Bilal Habib, Benjamin N. Sacks, Norbert Benecke, Alan K. Outram, Mikhail V. Sablin, Mietje Germonpré, Greger Larson, Laurent Frantz, Elaine A. Ostrander, National Human Genome Research Institute (NHGRI), Princeton University, Queen Mary University of London (QMUL), Territoires, Environnement, Télédétection et Information Spatiale (UMR TETIS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), 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 ), Hôpital Sud [CHU Rennes], 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), CRLCC Eugène Marquis (CRLCC), 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 ), University of California [Davis] (UC Davis), University of California (UC), Cornell University [New York], Al-Farabi Kazakh National University [Almaty] (KazNU), Stockholm University, University of Oxford, German Archaeological Institute (DAI), University of Exeter, Zoological Institute of Russian Academy of Sciences, Russian Academy of Sciences [Moscow] (RAS), Royal Belgian Institute of Natural Sciences (RBINS), Ludwig Maximilian University [Munich] (LMU), Intramural Program of the National Human Genome Research Institute (J.P., H.G.P., A.N.H., and E.A.O.). J.P. is also funded by Region Bretagne and Ligue Contre le Cancer. B.M.v.H. is funded by Princeton University. L.F., J.H., and G.L. were supported by the ERC (grant ERC-2013-StG-337574-UNDEAD and ERC-2019-StG-853272-PALAEOFARM) and Natural Environment Research Council grants (NE/K005243/1 and NE/K003259/1). L.F. and A.C. were supported by the Wellcome Trust (210119/Z/18/Z). B.H.’s research was funded by DST, the Government of India, and Maharashtra Forest Department., and Jonchère, Laurent
Subjects: canine, [SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics, Breeding, canid evolution, Medical and Health Sciences, Article, General Biochemistry, Genetics and Molecular Biology, domestication, wolf, [SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Genetics, Animals, Humans, Body Size, ancient DNA, Alleles, Canidae, Wolves, long non-coding RNA, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], IGF1, Psychology and Cognitive Sciences, Biological Sciences, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, dog, antisense lncRNA, body size, General Agricultural and Biological Sciences, Developmental Biology
Abstract: Domestic dogs (Canis lupus familiaris) are the most variable-sized mammalian species on Earth displaying a 40-fold size difference between breeds(1). Although dogs of variable size are found in the archeological record(2–4), the most dramatic shifts in body size are the result of selection over the last two centuries, as dog breeders selected and propagated phenotypic extremes within closed breeding populations(5). Analyses of over 200 domestic breeds have identified approximately 20 body size genes regulating insulin processing, fatty acid metabolism, TGFβ signaling and skeletal formation(6–10). Of these, Insulin-like Growth Factor 1 (IGF1) predominates, controlling approximately 15% of body size variation between breeds(8). The identification of a functional mutation associated with IGF1 has thus far proven elusive(6,10,11). Here, to identify and elucidate the role of an ancestral IGF1 allele in the propagation of modern canids, we analyzed 1,431 genome sequences from 13 species, including both ancient and modern canids, thus allowing us to define the evolutionary history of both ancestral and derived alleles at this locus. We identified a single variant in an antisense long non-coding RNA (IGF1-AS) that interacts with the insulin-like growth factor-1 (IGF1) gene creating a duplex. While the derived mutation predominates in both modern grey wolves and large domestic breeds, the ancestral allele, which predisposes to small size, was common in small-sized breeds and smaller wild canids. Our analyses demonstrate that this major regulator of canid body size nearly vanished in Pleistocene wolves, before its recent resurgence resulting from human-imposed selection for small-sized breed dogs.
Published: 2022
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22. Fecal immunological blood test is more appealing than the guaiac-based test for colorectal cancer screening

Author: Fanny Le Pimpec, Grégoire Moutel, Jean-François Bretagne, Christine Piette, Astrid Lièvre, Université de Rennes - Faculté de Médecine (UR Médecine), Université de Rennes (UR), Cancers et préventions, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), ADECI35, 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], Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), 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)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), and 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)
Subjects: Male, medicine.medical_specialty, media_common.quotation_subject, General Practice, Population, Directive Counseling, Fecal immunological testing, [SDV.CAN]Life Sciences [q-bio]/Cancer, Immunologic Tests, Colorectal cancer screening, Fecal occult blood test, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Blood test, education, Early Detection of Cancer, Feces, Aged, media_common, Response rate (survey), Gynecology, education.field_of_study, Hepatology, medicine.diagnostic_test, Barriers and facilitators, business.industry, Fecal occult blood, Age Factors, Gastroenterology, Middle Aged, 3. Good health, Test (assessment), Feeling, Occult Blood, 030220 oncology & carcinogenesis, Family medicine, Patient Compliance, Female, Indicators and Reagents, Perception, 030211 gastroenterology & hepatology, Colorectal Neoplasms, Guaiac, business
Abstract: International audience; BACKGROUND: The reasons for participation in fecal immunological testing (FIT) of subjects who were previously non-respondents to guaiac fecal occult blood testing (g-FOBT) have not been assessed. POPULATION AND METHODS: We aimed to determine the reasons for current compliance with FIT among non-responders to g-FOBT, termed "converts‿, in a French district. A questionnaire was returned by 170 converts aged from 55 to 75 years (response rate 75.2% after exclusions). RESULTS: The major barriers to participation in screening with g-FOBT were test-related: the test was perceived as complicated (24%) and it required three consecutive stools (28%). Among the test-related major determinants of FIT compliance was the perception that the test was less complicated than previous test (30%) and that a unique stool sample was required (29%). Among the non-test related major determinants of FIT compliance were the perception that the general practitioner was more convincing (31%) and the feeling to be more concerned because of age (21%). The reasons for compliance among converts did not differ according to age, sex, and rural or urban residence. CONCLUSIONS: Our study demonstrated that the simplicity of FIT and the endorsement of practitioners were both major motivations for FIT compliance among non-respondents in at least two previous consecutive campaigns.
Published: 2017
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23. Mechanisms of action and structure-activity relationships of cytotoxic flavokawain derivatives

Author: Yann Barguil, Yoshinori Asakawa, Cyril Antheaume, Mohammed Nour, Charlotte Thieury, Rémy Le Guével, Thierry Guillaudeux, Edouard Hnawia, Gaëtan Herbette, Nicolas Lebouvier, Laboratoire Insulaire du Vivant et de l'Environnement (LIVE), Université de la Nouvelle-Calédonie (UNC), Plate-forme ImPACcell (ImPACcell), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Territorial de Noumea, Spectropôle - Aix Marseille Université (AMU SPEC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Tokushima Bunri University, Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), ImPACcell platform of UMS Biosit, Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: p53, 0301 basic medicine, Spectrometry, Mass, Electrospray Ionization, Cytotoxic, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Proton Magnetic Resonance Spectroscopy, Clinical Biochemistry, Pharmaceutical Science, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Pharmacology, Biochemistry, Cell Line, Structure-Activity Relationship, 03 medical and health sciences, Chalcone, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Drug Discovery, Humans, Cytotoxic T cell, Carbon-13 Magnetic Resonance Spectroscopy, Cytotoxicity, Cyclin B1, Molecular Biology, Protein kinase B, PI3K/AKT/mTOR pathway, Cancer, Flavonoids, Chemistry, Organic Chemistry, Akt/mTor, Cell cycle, 3. Good health, 030104 developmental biology, Cell culture, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Molecular Medicine, Drug Screening Assays, Antitumor, Flavokawain, Structure activity relationships
Abstract: International audience; 22 Flavokawain derivatives (FKd) were obtained by one step syntheses in order to conduct a SAR study to understand the structural requirements for optimum and selective cytotoxicity. FKd and natural flavokawains A and B found into kava, a South Pacific traditional beverage, were evaluated against nine cancer and one healthy cell lines. The targeted cell cycle phases as well as the effects on the induction of apoptosis and cell cycle protein levels were investigated. Therapeutic improvements (more activity and selectivity) were achieved with FKd compared to natural flavokawains and notably with the 2',3,4',6'-tetramethoxychalcone (FKd 19). FKd induced a G1/S arrest on p53 wild-type cells and an M arrest on p53 mutant-type, via the up-regulation of p21 and cyclin B1 proteins, followed by apoptosis. Moreover, FKd exhibited a 24h-effect on Akt/mTor normal cells versus a 48h-effect on Akt/mTor up-regulated cells. The SAR study resulted in the conclusion that trimethoxy A-ring allowed the best compromise between cytotoxicity and selectivity, as well as the substitution of the meta position on the B-ring and the use of halogens substituents.
Published: 2017
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24. Moving towards green anaesthesia: Are patient safety and environmentally friendly practices compatible? A focus on single-use devices

Author: Pierre Albaladejo, Hélène Beloeil, Thibault Reynier, Mathilde Berahou, CHU Grenoble, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Jonchère, Laurent, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: disposable equipment, [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine, Anaesthesia, Greenhouse Gases, Anesthesiology, Hospital-acquired infection, life cycle, medicine, Humans, Anesthesia, Environmental impact assessment, Carbon Footprint, business.industry, durable medical equipment, General Medicine, Energy consumption, medicine.disease, Environmentally friendly, Durable medical equipment, 3. Good health, [SDV] Life Sciences [q-bio], Anesthesiology and Pain Medicine, Work (electrical), nosocomial infection, Carbon footprint, Patient Safety, Disposable Equipment, business, environment
Abstract: International audience; OBJECTIVE: Discuss if the use of disposable or reusable medical devices leads to a difference in terms of hospital acquired infection or bacterial contamination. Determine which solution is less expensive and has less environmental impact in terms of carbon footprint, energy and water consumption and amount of waste. METHODS: A narrative review, including a literature review of articles published in English and French from January 2000 to April 2020 were identified from PubMed. RESULTS: We retrieved 81 articles, including 12 randomised controlled trial, 21 literature reviews, 13 descriptive studies, 6 experimental studies, 9 life-cycle studies, 6 cohort studies, 2 meta-analysis, 4 case reports and 8 other studies. It appears that pathogen transmission in the anaesthesia work area is mainly due to the lack of hand hygiene among the anaesthesia team. The benefit of single-use devices on infectious risk is based on weak scientific arguments, while reusable devices have benefits in terms of costs, water consumption, energy consumption, waste, and reducing greenhouse gas emissions. CONCLUSION: Disposable medical devices and attire in the operating theatre do not mitigate the infectious risk to the patients but have a greater environmental, financial and social impact than the reusable ones. This study is the first step towards recommendations for more environmental-friendly practices in the operating theatre.
Published: 2021
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25. Extracellular AGR2 triggers lung tumour cell proliferation through repression of p21CIP1

Author: Thomas Grenier, Claire de Barbeyrac, Ines Boutin, Frédéric Delom, Eric Chevet, Delphine Fessart, Jacques Robert, David Bernard, Elodie Richard, Hughes Begueret, Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, 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), CRLCC Eugène Marquis (CRLCC), 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), Centre Léon Bérard [Lyon], Fondation ARC pour la Recherche sur le Cancer, Agence Nationale de la Recherche, Institut National Du Cancer, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-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), and Jonchère, Laurent
Subjects: 0301 basic medicine, medicine.medical_treatment, AGR2, [SDV.CAN]Life Sciences [q-bio]/Cancer, law.invention, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, law, Extracellular, medicine, Molecular Biology, Psychological repression, Tumour microenvironment, Cell growth, Chemistry, Growth factor, Endoplasmic reticulum, Cell Biology, Cell biology, 030104 developmental biology, Proteostasis, 030220 oncology & carcinogenesis, Suppressor, Lung cancer, p21CIP1
Abstract: International audience; The human Anterior GRadient 2 (AGR2) protein is an Endoplasmic Reticulum (ER)-resident protein which belongs to the Protein-Disulfide Isomerase (PDI) superfamily and is involved to productive protein folding in the ER. As such AGR2, often found overexpressed in adenocarcinomas, contributes to tumour development by enhancing ER proteostasis. We previously demonstrated that AGR2 is secreted (extracellular AGR2 (eAGR2)) in the tumour microenvironment and plays extracellular roles independent of its ER functions. Herein, we show that eAGR2 triggers cell proliferation and characterize the underlying molecular mechanisms. We demonstrate that eAGR2 enhances tumour cell growth by repressing the tumour suppressor p21(CIP1). Our findings shed light on a novel mechanism through which eAGR2 behaves as a growth factor in the tumour microenvironment, independently of its ER function, thus promoting tumour cell growth through repression of p21(CIP1). Our results provide a rationale for targeting eAGR2/p21(CIP1)-based signalling as a potential therapeutic target to impede tumour growth.
Published: 2021
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26. Patients Lung Derived Tumoroids (PLDTs) to model therapeutic response

Author: Delphine Fessart, Geraldine Siegfried, Jacques Robert, Hugues Begueret, Abdel-Majid Khatib, Fabienne Soulet, Thomas Grenier, Inaki Begiristain, Frédéric Delom, Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), Université Sciences et Technologies - Bordeaux 1-Institut National de la Santé et de la Recherche Médicale (INSERM), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), UNICANCER, This work was supported by grants from the 'Région Nouvelle-Aquitaine'. FD was supported by grants from the 'Fondation ARC pour la Recherche sur le Cancer'. DF has been supported by the 'Agence Nationale de la Recherche (ANR)'. TG was supported by the 'SIRIC Brio'., Université Sciences et Technologies - Bordeaux 1 (UB)-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), and Jonchère, Laurent
Subjects: 0301 basic medicine, Oncology, Drug, medicine.medical_specialty, Lung Neoplasms, media_common.quotation_subject, Primary Cell Culture, [SDV.CAN]Life Sciences [q-bio]/Cancer, Mice, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Internal medicine, Tumor Microenvironment, medicine, Animals, Humans, Lung cancer, Lung, Molecular Biology, media_common, Tumor microenvironment, Radiation, business.industry, Cell Biology, medicine.disease, Precision medicine, Xenograft Model Antitumor Assays, Anticancer drug, Three-dimensional culture, 3. Good health, Tumoroids, 030104 developmental biology, medicine.anatomical_structure, Lung cancer cell, 030220 oncology & carcinogenesis, Chemotherapeutic drugs, Drug Screening Assays, Antitumor, business, Ex vivo
Abstract: International audience; Preclinical lung cancer models are essential for a basic understanding of lung cancer biology and its translation into efficient treatment options for affected patients. Lung cancer cell lines and xenografts derived directly from human lung tumors have proven highly valuable in fundamental oncology research and anticancer drug discovery. Both models inherently comprise advantages and caveats that have to be accounted for. Recently, we have enabled reliable in vitro culture techniques from lung cancer biopsies as Patients Lung Derived Tumoroids (PLDTs). This breakthrough provides the possibility of high-throughput drug screening covering the spectrum of lung cancer phenotypes seen clinically. We have adapted and optimized our in vitro three-dimensional model as a preclinical lung cancer model to recapitulate the tumor microenvironment (TME) using matrix reconstitution. Hence, we developed directly PLDTs to screen for chemotherapeutics and radiation treatment. This original model will enable precision medicine to become a reality, allowing a given patient sample to be screened for effective ex vivo therapeutics, aiming at tailoring of treatments specific to that individual. Hence, this tool can enhance clinical outcomes and avoid morbidity due to ineffective therapies.
Published: 2020
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27. Controlling the unfolded protein response-mediated life and death decisions in cancer

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

Author: Nathalie Duchange, Sylviane Darquy, Astrid Lièvre, Grégoire Moutel, Cancers et préventions, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Laboratoire d'éthique médicale et de médecine légale (EA 4569), Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), 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), CHU Pontchaillou [Rennes], Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-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 - Faculté de Médecine (UR Médecine), Université de Rennes (UR), Service des Maladies de l'Appareil Digestif, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire d'éthique médicale et de médecine légale ( EA 4569 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université Sorbonne Paris Cité ( USPC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Chemistry, Oncogenesis, Stress and Signaling ( COSS ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CRLCC Eugène Marquis ( CRLCC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Bordeaux population health ( BPH ), and Université de Bordeaux ( UB ) -Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Male, medicine.medical_specialty, MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, Personal autonomy, 0603 philosophy, ethics and religion, [ CHIM ] Chemical Sciences, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Individualism, 0302 clinical medicine, medicine, Humans, [CHIM]Chemical Sciences, 030212 general & internal medicine, Early Detection of Cancer, ComputingMilieux_MISCELLANEOUS, Aged, Hepatology, business.industry, Public health, Gastroenterology, 06 humanities and the arts, Middle Aged, Patient Acceptance of Health Care, Colorectal cancer screening, Family medicine, Personal Autonomy, Female, France, Public Health, 060301 applied ethics, Colorectal Neoplasms, business
Abstract: International audience; no abstract
Published: 2017
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29. Mutational Landscape of DDR2 Gene in Lung Squamous Cell Carcinoma Using Next-generation Sequencing

Author: Francisco Llamas-Gutierrez, Houda Hamdi-Rozé, Alice Fiévet, Charles Ricordel, Benoit Desrues, Amyrat Aliouat, Marie de Tayrac, Jean Mosser, Mallorie Kerjouan, Hervé Lena, Alexandra Lespagnol, 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), CHU Pontchaillou [Rennes], 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 (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and 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 )
Subjects: Male, 0301 basic medicine, Cancer Research, Molecular biology, Biopsy, DNA Mutational Analysis, Mutant, medicine.disease_cause, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Cohort Studies, Exon, 0302 clinical medicine, Aged, 80 and over, Mutation, High-Throughput Nucleotide Sequencing, Discoidin domain receptor 2, Exons, Middle Aged, 3. Good health, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Female, KRAS, Adult, Pulmonary and Respiratory Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, lung neoplasms, White People, Epidermoid lung carcinoma, 03 medical and health sciences, Germline mutation, medicine, Humans, Lung cancer, Gene, Aged, Retrospective Studies, Lung, business.industry, Somatic mutation, medicine.disease, Survival Analysis, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Cancer research, Squamous cell lung carcinoma, business, Follow-Up Studies
Abstract: International audience; Background - Lung cancer represents the leading cause of cancer-related death worldwide. Despite great advances in lung cancer management with the recent emergence of molecular targeted therapies for non-squamous non-small-cell lung cancer, no dramatic improvements have been achieved in lung squamous cell carcinoma (SCC). Mutations in discoidin domain receptor 2 (DDR2) gene were recently identified as promising molecular targets in this histology. The aim of this study is to describe the DDR2 mutational landscape of lung SCC and investigate the associated clinical factors. Methods - Next-generation sequencing of the DDR2 gene was performed on 271 samples of lung SCC. Patients followed in our institution from January 2011 to August 2014 were retrospectively selected for data collection. Other driver gene alterations (EGFR, KRAS, BRAF, HER2, and PI3KCA) were analyzed using pyrosequencing. Results - A total of 11 patients harboring a DDR2 mutation was detected among the 271 sequenced lung SCC samples (4%). We describe 10 unreported mutations, comprising a novel DDR2 exon 7 splice mutant. DDR2 mutations were not mutually exclusive with other driver gene alterations. One hundred thirty-six patients were included for clinical comparison and logistic regression analysis. No difference was detected between DDR2-mutant and DDR2 wild-type lung SCC regarding clinical characteristics or survival. Conclusion - DDR2 mutations were observed in 4% of cases of lung SCC of European descent. DDR2-mutated tumors can exhibit other driver gene alterations. No clinical characteristics were significantly associated with DDR2 mutation.
Published: 2018
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30. Novel roles of the unfolded protein response in the control of tumor development and aggressiveness

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

Author: Aleth Perdriger, Ophélie Caillot, Marine Faccin, Jean Levêque, Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)
Subjects: 0301 basic medicine, Plasma cell mastitis, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Arthritis, Rheumatoid Arthritis, TNFα antagonists, Plasma cell, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, Duct ectasia of breast, medicine, ComputingMilieux_MISCELLANEOUS, business.industry, Joint bone, medicine.disease, 3. Good health, Surgery, Mastitis, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Rheumatoid arthritis, Tumor necrosis factor alpha, business
Abstract: Joint Bone Spine - In Press.Proof corrected by the author Available online since jeudi 14 janvier 2016
Published: 2016
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32. Purification of a heparin binding FGF receptor (HB-FGFR) from adult bovine brain membranes

Author: E Chevet, Denis Barritault, Agnes Mereau, José Courty, Mylène Perderiset, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Oncogenesis Stress Signaling (OSS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), OTR3 Sarl, OTR3, MEREAU, Agnès, 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 ), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
Subjects: Receptor complex, [SDV]Life Sciences [q-bio], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Fibroblast growth factor, Biochemistry, Chromatography, Affinity, 03 medical and health sciences, 0302 clinical medicine, Affinity chromatography, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Receptor, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Chromatography, High Pressure Liquid, 030304 developmental biology, Brain Chemistry, 0303 health sciences, Affinity labeling, Heparin, Biological membrane, General Medicine, Ligand (biochemistry), Receptors, Fibroblast Growth Factor, [SDV] Life Sciences [q-bio], Cross-Linking Reagents, Fibroblast growth factor receptor, 030220 oncology & carcinogenesis, Cattle, Electrophoresis, Polyacrylamide Gel
Abstract: International audience; A new form of high affinity fibroblast growth factor receptor has been purified from adult bovine brain membranes. Purification was performed by chromatography on DEAE-Trisacryl and wheat germ agglutinin-agarose followed by FGF-2 affinity chromatography. Affinity labeling of purified fractions with 125I-FGF-2 showed after cross-linking a 170-kDa complex, suggesting the existence of a 150-kDa FGF receptor. No cross-reactivity with anti-FGF receptor 1 (FGFR-1 or flg) or with anti-receptor 2 (FGFR-2 or bek) antibodies could be detected with this partially purified receptor. Heparitinase treatment of the partially purified FGF receptor abolished the formation of the ligand receptor complex. The complex was restored in the presence of heparin in a dose dependent fashion, supporting the idea that heparin-like molecules are needed for proper binding. Further purification of the receptor was achieved by heparin-Sepharose affinity chromatography and yielded a purification of over 320,000-fold. The purified receptor fraction was radiolabeled and loaded on RPLC C4 column. Eluted fractions were analysed by SDS-PAGE. A major 150-kDa band was detected. These data show for the first time a new form of FGF receptor isolated from bovine brain membranes. This purified receptor displays affinity for heparin and was therefore named heparin binding FGF receptor (HB-FGFR). It remains unclear whether the receptor is a proteo-heparin sulfate or whether heparans are strongly associated and therefore are copurified. Large scale preparations are in progress for core protein structure studies.
Published: 1992
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32 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

2. The Appendix Orchestrates T-Cell Mediated Immunosurveillance in Colitis-Associated Cancer

3. 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

4. Safety of Extended-Interval Dosing Strategy of Immune Checkpoint Inhibitors for Advanced NSCLC

5. Pulmonary manifestations induced by osimertinib

6. Human iPSC-derived neurons reveal early developmental alteration of neurite outgrowth in the late-occurring neurodegenerative Wolfram syndrome

7. 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)

8. Treatment, outcome, and prognostic factors in non-metastatic anal cancer: The French nationwide cohort study FFCD-ANABASE

9. Pharmacological Targeting of IRE1 in Cancer

10. Immune-related Encephalitis in Two Patients Treated With Immune Checkpoint Inhibitor

11. 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)

12. Nal-IRI/LV5-FU versus paclitaxel as second-line therapy in patients with metastatic esophageal squamous cell carcinoma (OESIRI)-PRODIGE 62: A multicentre, randomised, non-comparative phase II study

13. pBFK, a new thermosensitive shuttle vector for Streptococcus pyogenes gene deletion by homologous recombination

14. Development of sensitive and robust multiplex digital PCR assays for the detection of ESR1 mutations in the plasma of metastatic breast cancer patients

15. TACE and conformal radiotherapy vs. TACE alone for hepatocellular carcinoma: A randomised controlled trial

16. Newly identified tumor suppressor functions of ING proteins

17. Switching from guaiac to immunochemical faecal occult blood test increases participation and diagnostic yield of colorectal cancer screening

18. Rethinking Alkylating(-Like) Agents for Solid Tumor Management

19. Impact of severe obesity in the management of patients with high-risk endometrial cancer: A FRANCOGYN study

20. Structure simplification of the Securinine skeleton reveals the importance of BCD ring system for the cytotoxic activity on HCT116 and HL60 cell lines

21. Natural and human-driven selection of a single non-coding body size variant in ancient and modern canids

22. Fecal immunological blood test is more appealing than the guaiac-based test for colorectal cancer screening

23. Mechanisms of action and structure-activity relationships of cytotoxic flavokawain derivatives

24. Moving towards green anaesthesia: Are patient safety and environmentally friendly practices compatible? A focus on single-use devices

25. Extracellular AGR2 triggers lung tumour cell proliferation through repression of p21CIP1

26. Patients Lung Derived Tumoroids (PLDTs) to model therapeutic response

27. Controlling the unfolded protein response-mediated life and death decisions in cancer

28. Addressing low participant in colorectal cancer screening: Respect for individual freedom versus the community good

29. Mutational Landscape of DDR2 Gene in Lung Squamous Cell Carcinoma Using Next-generation Sequencing

30. Novel roles of the unfolded protein response in the control of tumor development and aggressiveness

31. Plasma cell mastitis in women with rheumatoid arthritis treated with TNFα antagonists: Report of 2 cases

32. Purification of a heparin binding FGF receptor (HB-FGFR) from adult bovine brain membranes

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

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