Author: "Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)" / Topic: 0302 clinical medicine - Searchworks@Jio Institute Digital Library Search Results

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

1. 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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2. LncRNAs in domesticated animals: from dog to livestock species

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

Author: Etienne Garin, Yan Rolland, Luc Beuzit, Camille Goislard de Monsabert, Eveline Boucher, Astrid Lièvre, Yann Touchefeu, Samuel Le Sourd, David Tougeron, Karim Boudjema, Boris Campillo-Gimenez, Isabelle Baumgaertner, Olivier Farges, Ahmet Ayav, Marc Pracht, Julien Edeline, Boris Guiu, CRLCC Eugène Marquis (CRLCC), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CRHU Nancy, CHU Pontchaillou [Rennes], Chemistry, Oncogenesis, Stress and Signaling (COSS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), BTG, Ligue Contre le Cancer, Université de Montpellier (UM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Jonchère, Laurent, and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: vomiting, Yttrium-90, medicine.medical_treatment, insomnia, Brachytherapy, diarrhea, cisplatin, thrombocytopenia, chemotherapy, Gastroenterology, 030218 nuclear medicine & medical imaging, chemoradiotherapy, Cholangiocarcinoma, 0302 clinical medicine, Quality of life, dose response, pain, Embolization, RC254-282, clinical article, adult, gemcitabine, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, yttrium 90, nausea, humanities, 3. Good health, sirtuin, aged, female, anorexia, patient-reported outcomes, 030220 oncology & carcinogenesis, liver resection, [SDV.IB]Life Sciences [q-bio]/Bioengineering, medicine.symptom, medicine.drug, radioembolization, medicine.medical_specialty, Nausea, patient-reported outcome, Article, multiple cycle treatment, 03 medical and health sciences, male, Internal medicine, biliary tract cancer, medicine, follow up, neutropenia, Humans, human, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Cisplatin, loss of appetite, Chemotherapy, business.industry, questionnaire, constipation, dyspnea, Gemcitabine, Radiation therapy, phase 2 clinical trial, multicenter study, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, Concomitant, microsphere, Quality of Life, fatigue, asthenia, bile duct carcinoma, business
Abstract: Background: In the Yttrium-90 Microspheres in Cholangiocarcinoma (MISPHEC) single-arm phase 2 trial, concomitant chemotherapy and selective internal radiotherapy (SIRT) showed antitumor activity as a first-line treatment of unresectable intrahepatic cholangiocarcinomas (ICCs). In this sub-analysis, we aimed to evaluate one of the secondary endpoints, the health-related quality of life (QoL), evaluated with an EORTC QLQ-C30 instrument at the baseline and during treatment. Methods: The MISPHEC trial included treatment-naïve patients with an unresectable ICC between November 2013 and June 2016. Patients received concomitant first-line chemotherapy with cisplatin and gemcitabine for 8 cycles, SIRT was administered during cycle 1 (for patients with unilobar disease) or cycles 1 and 3 (for patients with bilobar disease) using glass Yttrium-90 microspheres. We evaluated the QoL—measured by the QLQ-C30 questionnaire—at the baseline, every 8 weeks during chemotherapy and follow-up, between 12 and 15 weeks after embolization and every 12 weeks after a liver resection if applicable. Results: A total of 41 patients were included, of which 34 completed questionnaires at the baseline. No clinically significant changes in the global health score or the sub-scales of the QLQ-C30 were observed during follow-up. The physical, social and role function mean score worsened during treatment and fatigue, nausea and pain scores increased although the differences were not clinically significant. In patients undergoing subsequent surgery, the QoL was not impaired. Conclusions: A combination of SIRT and chemotherapy with gemcitabine and cisplatin as the first-line treatment of unresectable ICCs was found to maintain the QoL.
Published: 2021
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4. 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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5. ETV6-RUNX1 and RUNX1 directly regulate RAG1 expression: one more step in the understanding of childhood B-cell acute lymphoblastic leukemia leukemogenesis

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

Author: Marion Bouchecareilh, Duc Thang Nguyên, Eric Chevet, Audrey Mulot, Daniel Boismenu, Frédéric Delom, Michael J. Wise, Arisa Higa, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], UNICANCER, Mécanismes moléculaires de l'angiogénèse, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Astrophysical Sciences [Princeton], Princeton University, Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)
Subjects: [SDV]Life Sciences [q-bio], AGR2, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, Endoplasmic Reticulum, Biochemistry, Ribosome, 03 medical and health sciences, Mice, 0302 clinical medicine, Dogs, Mucoproteins, Proto-Oncogene Proteins, Chlorocebus aethiops, Animals, Homeostasis, Humans, Protein disulfide-isomerase, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Oncogene Proteins, 0303 health sciences, Endoplasmic reticulum, Proteins, STIM1, Cell Biology, Translocon, Endoplasmic Reticulum Stress, Cell biology, Secretory protein, HEK293 Cells, Gene Expression Regulation, 030220 oncology & carcinogenesis, COS Cells, Unfolded protein response, Unfolded Protein Response
Abstract: The protein-disulfide isomerase (PDI) family member anterior gradient 2 (AGR2) is reportedly overexpressed in numerous cancers and plays a role in cancer development. However, to date the molecular functions of AGR2 remain to be characterized. Herein we have identified AGR2 as bound to newly synthesized cargo proteins using a proteomics analysis of endoplasmic reticulum (ER) membrane-bound ribosomes. Nascent protein chains that translocate into the ER associate with specific ER luminal proteins, which in turn ensures proper folding and posttranslational modifications. Using both imaging and biochemical approaches, we confirmed that AGR2 localizes to the lumen of the ER and indirectly associates with ER membrane-bound ribosomes through nascent protein chains. We showed that AGR2 expression is controlled by the unfolded protein response and is in turn is involved in the maintenance of ER homeostasis. Remarkably, we have demonstrated that siRNA-mediated knockdown of AGR2 significantly alters the expression of components of the ER-associated degradation machinery and reduces the ability of cells to cope with acute ER stress, properties that might be relevant to the role of AGR2 in cancer development.
Published: 2011
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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. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer

Author: Kelly, Ronan J, Ajani, Jaffer A, Kuzdzal, Jaroslaw, Zander, Thomas, Van Cutsem, Eric, Piessen, Guillaume, Mendez, Guillermo, Feliciano, Josephine, Motoyama, Satoru, Lièvre, Astrid, Uronis, Hope, Elimova, Elena, Grootscholten, Cecile, Geboes, Karen, Zafar, Syed, Snow, Stephanie, Ko, Andrew H, Feeney, Kynan, Schenker, Michael, Kocon, Piotr, Zhang, Jenny, Zhu, Lili, Lei, Ming, Singh, Prianka, Kondo, Kaoru, Cleary, James M, Moehler, Markus, CheckMate 577 Investigators, Van den Eynde, Marc, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Service d'hépato-gastro-entérologie, UCL - (SLuc) Service d'hématologie, Baylor University, MD Anderson Cancer Center [Houston], The University of Texas Health Science Center at Houston (UTHealth), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Universitätsklinikum Köln (Uniklinik Köln), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), CHU Lille, Favaloro Foundation, Johns Hopkins University (JHU), Akita University, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Duke Cancer Institute Durham, Duke University Medical Center, Princess Margaret Hospital, University of Toronto, Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Ghent University Hospital, Florida Hospital Cancer Institute, University of California [San Francisco] (UC San Francisco), University of California (UC), Bristol-Myers Squibb Company, Dana-Farber Cancer Institute [Boston], Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Bristol Myers Squibb Bristol-Myers Squibb, Ono Pharmaceutical, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of California [San Francisco] (UCSF), University of California, and Johannes Gutenberg - Universität Mainz (JGU)
Subjects: Adult, Male, medicine.medical_specialty, Esophageal Neoplasms, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, Adenocarcinoma, 030204 cardiovascular system & hematology, Gastroenterology, B7-H1 Antigen, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Stomach Neoplasms, Internal medicine, Medicine and Health Sciences, medicine, Carcinoma, Humans, 030212 general & internal medicine, Esophagus, Immune Checkpoint Inhibitors, Neoadjuvant therapy, Aged, Aged, 80 and over, Chemotherapy, business.industry, Cancer, Chemoradiotherapy, Adjuvant, General Medicine, Middle Aged, medicine.disease, Neoadjuvant Therapy, Intention to Treat Analysis, 3. Good health, Nivolumab, medicine.anatomical_structure, Chemotherapy, Adjuvant, Carcinoma, Squamous Cell, Female, Esophagogastric Junction, business, Adjuvant, Chemoradiotherapy
Abstract: BackgroundNo adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer. MethodsWe conducted CheckMate 577, a global, randomized, double-blind, placebo-controlled phase 3 trial to evaluate a checkpoint inhibitor as adjuvant therapy in patients with esophageal or gastroesophageal junction cancer. Adults with resected (R0) stage II or III esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy and had residual pathological disease were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by nivolumab at a dose of 480 mg every 4 weeks) or matching placebo. The maximum duration of the trial intervention period was 1 year. The primary end point was disease-free survival. ResultsThe median follow-up was 24.4 months. Among the 532 patients who received nivolumab, the median disease-free survival was 22.4 months (95% confidence interval [CI], 16.6 to 34.0), as compared with 11.0 months (95% CI, 8.3 to 14.3) among the 262 patients who received placebo (hazard ratio for disease recurrence or death, 0.69; 96.4% CI, 0.56 to 0.86; P
Published: 2021
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9. Multimodal management of surgery- and radiation-refractory meningiomas: an analysis of the French national tumor board meeting on meningiomas cohort

Author: Olivier Chinot, Marc Sanson, J. Jacob, Thomas Graillon, François Caire, Michel Kalamarides, Charlotte Bronnimann, Apolline Monfilliette, Ilyess Zemmoura, François Ducray, Charles-Henry Mallereau, Christelle Dufour, Sébastien Froelich, Mathieu Boone, Mélanie Dore, Aymeri Huchet, Anthony Joncour, Anne-Laure Boch, Denys Fontaine, Elodie Vauleon, Loïc Feuvret, Anna Luisa Di Stefano, Matthieu Helleringer, Emmanuel Jouanneau, Matthieu Peyre, Mariette Delaitre, Emmanuelle Le Fur, Amaury De Barros, Julien Boetto, Hugues Loiseau, Tuan Le Van, Julien Engelhardt, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Amiens-Picardie, CHU Bordeaux [Bordeaux], CHU Limoges, Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital pasteur [Colmar], Hôpital Foch [Suresnes], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Hospices Civils de Lyon (HCL), Institut Gustave Roussy (IGR), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Imagerie moléculaire et thérapies innovantes en oncologie (IMOTION), Université de Bordeaux (UB), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Strasbourg, CHU Lille, Clinique Armoricaine de Radiologie [St. Brieuc], CHU Trousseau [Tours], No funding, Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre hospitalier Saint-Brieuc, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Cancer Research, medicine.medical_specialty, Palliative care, Bevacizumab, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Octreotide, Radiosurgery, Disease-Free Survival, Meningioma, 03 medical and health sciences, 0302 clinical medicine, Meningeal Neoplasms, medicine, Humans, Everolimus, Progression-free survival, Retrospective Studies, Atypical meningioma, business.industry, medicine.disease, Combined Modality Therapy, 3. Good health, Surgery, Radiation therapy, Treatment Outcome, Neurology, Oncology, 030220 oncology & carcinogenesis, Cohort, High-grade meningioma, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Malignant meningioma, Neurology (clinical), business, 030217 neurology & neurosurgery, Progressive disease, Follow-Up Studies, medicine.drug
Abstract: International audience; PURPOSE: Meningiomas represent the most frequent tumor of the central nervous system in adults. While most meningiomas are efficiently treated by surgery and radiotherapy/radiosurgery, there is a small portion of radiation- and surgery-refractory tumors for which there is no clear recommendation for optimal management. The French National Tumor Board Meeting on Meningiomas (NTBM) offers a glimpse on the current management of such patients. METHODS: We retrospectively reviewed the charts of patients presented to the multidisciplinary Meeting between 2016 and 2019. We selected patients with a progressive disease after at least two treatments, including surgery and radiotherapy. RESULTS: In this multicentric cohort of 86 cases, patients harbored 17 (19.8%) WHO Grade I, 48 (55.8%) WHO Grade II and 21 (24.4%) WHO Grade III tumors. The median number of treatments received before inclusion was 3 (range: 2 - 11). Following the Board Meeting, 32 patients (37.2%) received chemotherapy, 11 (12.8%) surgery, 17 (19.8%) radiotherapy, 14 (16.3%) watchful observation and 12 (13.9%) palliative care. After a mean follow-up of 13 months post-inclusion, 32 patients (37.2%) had died from their disease. The mean progression free survival was 27 months after radiotherapy, 10 months after surgery, 8.5 months after chemotherapy (Bevacizumab: 9 months - Octreotide/Everolimus: 8 months). CONCLUSIONS: Surgery- and radiation-refractory meningiomas represent a heterogeneous group of tumors with a majority of WHO Grade II cases. If re-irradiation and redo-surgery are not possible, bevacizumab and octreotide-everolimus appear as a valuable option in heavily pre-treated patients considering the current EANO guidelines.
Published: 2021
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10. Does neoadjuvant FOLFOX chemotherapy improve the prognosis of high‐risk Stage II and III colon cancers? Three years' follow‐up results of the PRODIGE 22 phase II randomized multicentre trial

Author: Olivier Bouché, Guillaume Piessen, Benoit Romain, Claire Gallois, Emilie Barbier, Olivier Glehen, Jean-Marc Regimbeau, Mehdi Karoui, Gael Goujon, Johannes Hartwig, Julien Taieb, Guillaume Portier, Jean-Louis Legoux, Cécile de Chaisemartin, Astrid Lièvre, Francesco Brunetti, Hanifa Ammarguellat, Cedric Lecaille, Michel Prudhomme, Côme Lepage, for Prodige investigators, 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 Lille, Centre Hospitalier Régional d'Orléans (CHRO), Laboratoire de Neurosciences Cognitives & Computationnelles (LNC2), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Polyclinique Bordeaux Nord Aquitaine (PBNA), Centre Hospitalier Universitaire de Reims (CHU Reims), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Chirurgie digestive [CHU Amiens], CHU Amiens-Picardie, Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Cancer Research and Personalized Medicine - CARPEM [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), AOM10242, Ministère de la Santé, Polyclinique Bordeaux Nord Aquitaine, 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 Toulouse [Toulouse], and École pratique des hautes études (EPHE)
Subjects: Oncology, medicine.medical_specialty, Organoplatinum Compounds, Colorectal cancer, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, Leucovorin, survival, 03 medical and health sciences, 0302 clinical medicine, FOLFOX, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, education, Neoplasm Staging, Colectomy, education.field_of_study, business.industry, Hazard ratio, Gastroenterology, Perioperative, colectomy, Prognosis, Interim analysis, medicine.disease, Neoadjuvant Therapy, digestive system diseases, colon cancer, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Colonic Neoplasms, 030211 gastroenterology & hepatology, Fluorouracil, Neoplasm Recurrence, Local, business, neoadjuvant chemotherapy, Follow-Up Studies, medicine.drug
Abstract: International audience; Aim Neoadjuvant chemotherapy has proven valuable in locally advanced resectable colon cancer (CC) but its effect on oncological outcomes is uncertain. The aim of the present paper was to report 3-year oncological outcomes, representing the secondary endpoints of the PRODIGE 22 trial. Method PRODIGE 22 was a randomized multicentre phase II trial in high-risk T3, T4 and/or N2 CC patients on CT scan. Patients were randomized between 6 months of adjuvant FOLFOX (upfront surgery) or perioperative FOLFOX (four cycles before surgery and eight cycles after; FOLFOX perioperative). In wild-type RAS patients, a third arm testing perioperative FOLFOX-cetuximab was added. The primary endpoint was the tumour regression grade. Secondary endpoints were 3-year overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS) and time to recurrence (TTR). Results Overall, 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped for futility. The remaining 104 patients represented our intention-to-treat population. In the perioperative group, 96% received the scheduled four neoadjuvant cycles and all but one had adjuvant FOLFOX for eight cycles. In the control arm, 38 (73%) patients received adjuvant FOLFOX. The median follow-up was 54.3 months. Three-year OS was 90.4% in both arms [hazard ratio (HR) = 0.85], 3-year DFS, RFS and TTR were, respectively, 76.8% and 69.2% (HR=0.94), 73% and 69.2% (HR = 0.86) and 82% and 72% (HR = 0.67) in the perioperative and control arms, respectively. Forest plots did not show any subgroup with significant difference for survival outcomes. No benefit from adding cetuximab was observed. Conclusion Perioperative FOLFOX has no detrimental effect on long-term oncological outcomes and may be an option for some patients with locally advanced CC.
Published: 2021
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11. Long Noncoding RNAs in Cholangiocarcinoma

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

Author: Didier Quilliot, Bruno Raynard, Francisca Joly, Damien Vansteene, Société Nationale Française de Gastroentérologie, Didier Barnoud, Frédérique Peschaud, Valérie Garabige, Fédération Francophone de Cancérologie Digestive, Société française de radiothérapie oncologique, Société française de chirurgie digestive, Groupe Coopérateur multidisciplinaire en Oncologie, Astrid Lièvre, Vanessa Cottet, Eric Fontaine, Société Française des Professionnels en Activité Physique Adaptée, Xavier Hébuterne, Thomas Mouillot, Frédéric Chorin, Aude-Marie Foucaut, Florence Huguet, Cindy Neuzillet, Amélie Anota, Olivier Bouché, Anne-Laure Védie, Florian Scotté, Timothée Marchal, Société Française d’Endoscopie Digestive, Pascale Mariani, Stéphane M. Schneider, Fédération nationale des centres de lutte contre le cancer, Carole Bouleuc, Sami Antoun, Institut Curie [Paris], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Unité de Biostatistique et d'Evaluation des Thérapeutiques (UBET), Centre Léon Bérard [Lyon], Laboratoire éducations et promotion de la santé (LEPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Gustave Roussy (IGR), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Pasteur [Nice] (CHU), Laboratoire Motricité Humaine Expertise Sport Santé (LAMHESS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université de Toulon (UTLN)-Université Côte d'Azur (UCA), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de chirurgie générale, digestive et oncologique [CHU Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Endocrinologie - Diabète - Nutrition [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département interdisciplinaire d’organisation des parcours patients (DIOPP), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Hospitalier Universitaire de Reims (CHU Reims), Jonchère, Laurent, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Laboratoire Educations et Pratiques de Santé (LEPS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: medicine.medical_specialty, Medicine (miscellaneous), [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), symptoms and symptom management, Disease, gastrointestinal (lower), 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), [SDV.CAN] Life Sciences [q-bio]/Cancer, Endopeptidases, medicine, Humans, 030212 general & internal medicine, Stage (cooking), Intensive care medicine, Exercise, Societies, Medical, Oncology (nursing), business.industry, Cancer, General Medicine, Perioperative, Evidence-based medicine, medicine.disease, gastrointestinal (upper), 3. Good health, supportive care, Medical–Surgical Nursing, Malnutrition, pancreatic, 030220 oncology & carcinogenesis, Quality of Life, business, education and training, Follow-Up Studies
Abstract: International audience; This document is a summary of the French intergroup guidelines regarding the nutrition and physical activity (PA) management in digestive oncology. This collaborative work was produced under the auspices of all French medical and surgical societies involved in digestive oncology, nutrition and supportive care. It is based on published guidelines, recent literature review and expert opinions. Recommendations are graded according to the level of evidence. Malnutrition affects more than half of patients with digestive cancers and is often underdiagnosed. It has multiple negative consequences on survival, quality of life and risk of treatment complications. Consequently, in addition to anticancer treatments, supportive care including nutritional support and PA plays a central role in the management of digestive cancers. It is crucial to detect malnutrition (diagnostic criteria updated in 2019) early, to prevent it and to act against it at all stages of the cancer and at all times of the care pathway. In this context, we proposed recommendations for the evaluation and management in nutrition and PA in digestive oncology for each stage of the disease (perioperative setting, during radiation therapy, during systemic treatments, at the palliative phase, after cancer). Guidelines for nutrition and PA management aim at increasing awareness about malnutrition in oncology. They are continuously evolving and need to be regularly updated.
Published: 2020
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14. 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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15. 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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16. Starvation and antimetabolic therapy promote cytokine release and recruitment of immune cells

Author: Raffaella Iurlaro, Jaime Redondo-Pedraza, Sandrine Marchetti, Eric Eldering, Ernest Nadal, Jean-Ehrland Ricci, Cristina Muñoz-Pinedo, Franziska Püschel, Blanca Majem, Francesca Favaro, Eric Chevet, Estefanía Lucendo, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), University of Amsterdam [Amsterdam] (UvA), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universitat de Barcelona (UB), Graduate School, AII - Cancer immunology, CCA - Cancer biology and immunology, Experimental Immunology, Université Nice Sophia Antipolis (1965 - 2019) (UNS), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Chemokine, Angiogenesis, Antimetabolites, medicine.medical_treatment, Glutamine, Cell, cancer metabolism, 0302 clinical medicine, Immunology and Inflammation, Neoplasms, Citoquines, glucose, Càncer, Promoter Regions, Genetic, Cancer, 0303 health sciences, Multidisciplinary, biology, Cell Death, Chemistry, NF-kappa B, Biological Sciences, Metabolisme, Metformin, 3. Good health, Cell biology, Cytokine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cytokines, medicine.symptom, [SDV.CAN]Life Sciences [q-bio]/Cancer, Inflammation, Deoxyglucose, 03 medical and health sciences, Immune system, cancer immunity, Stress, Physiological, medicine, Integrated stress response, Humans, 030304 developmental biology, Interleukin-6, Macrophages, Interleukin-8, Chemotaxis, Epithelial Cells, biochemical phenomena, metabolism, and nutrition, Activating Transcription Factor 4, cytokines, Metabolism, Glucose, Gene Expression Regulation, Starvation, Glucosa, biology.protein, bacteria, HeLa Cells
Abstract: Significance Poorly irrigated tumors exhaust nutrients from their environment. On the other hand, innate immune cells, such as neutrophils and macrophages, have been frequently shown to infiltrate tumors and promote an immunosuppressive environment. Our results show that, when nutrients are low, tumor cells secrete factors related to wound healing that stimulate endothelial cells and attract innate immune cells. This suggests that targeting signals elicited by metabolic stress may help the immune system target malignant cells and that metabolites regulate the communication between immune and tumor cells also through modulation of peptidic signals., Cellular starvation is typically a consequence of tissue injury that disrupts the local blood supply but can also occur where cell populations outgrow the local vasculature, as observed in solid tumors. Cells react to nutrient deprivation by adapting their metabolism, or, if starvation is prolonged, it can result in cell death. Cell starvation also triggers adaptive responses, like angiogenesis, that promote tissue reorganization and repair, but other adaptive responses and their mediators are still poorly characterized. To explore this issue, we analyzed secretomes from glucose-deprived cells, which revealed up-regulation of multiple cytokines and chemokines, including IL-6 and IL-8, in response to starvation stress. Starvation-induced cytokines were cell type-dependent, and they were also released from primary epithelial cells. Most cytokines were up-regulated in a manner dependent on NF-κB and the transcription factor of the integrated stress response ATF4, which bound directly to the IL-8 promoter. Furthermore, glutamine deprivation, as well as the antimetabolic drugs 2-deoxyglucose and metformin, also promoted the release of IL-6 and IL-8. Finally, some of the factors released from starved cells induced chemotaxis of B cells, macrophages, and neutrophils, suggesting that nutrient deprivation in the tumor environment can serve as an initiator of tumor inflammation.
Published: 2020
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17. 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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18. TGFβ-induced FOXS1 controls epithelial-mesenchymal transition and predicts a poor prognosis in liver cancer

Author: Raphael Pineau, Stefano Caruso, David Gilot, Kevin Bévant, Cédric Coulouarn, Gaëlle Angenard, Panagiotis Papoutsoglou, Matthis Desoteux, Jessica Zucman-Rossi, L Sulpice, Corentin Louis, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), CHU Pontchaillou [Rennes], Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], 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), Supported by Fondation ARC pour la Recherche sur le Cancer, IREB, Institut National Du Cancer, Prix René and Andrée Duquesne–Comité de Paris Ligue Contre le Cancer, Coup d’Elan de la Fondation Bettencourt-Schueller, Raymond Rosen Award from the Fondation pour le Recherche Médicale, Université de Rennes 1, ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé) dans le cadre du Plan Cancer (C18007NS), Labex OncoImmunology (Investissement d’Avenir), Institut National de la Santé et de la Recherche Médicale, Ligue Contre le Cancer (CD22, CD35, and CD85), Ligue Nationale Contre le Cancer, Région Bretagne, Fondation Mérieux, and SIRIC CARPEM., École pratique des hautes études (EPHE), Gestionnaire, HAL Sorbonne Université 5, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), 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), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), and Dublin Institute for Advanced Studies (DIAS)
Subjects: Carcinoma, Hepatocellular, Epithelial-Mesenchymal Transition, SMAD, 03 medical and health sciences, 0302 clinical medicine, Transforming Growth Factor beta, Medicine, Humans, Epithelial–mesenchymal transition, Transcription factor, 030304 developmental biology, 0303 health sciences, Hepatology, biology, business.industry, Liver Neoplasms, Forkhead Transcription Factors, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Transforming growth factor beta, Prognosis, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Tumor progression, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Biomarker (medicine), Mothers against decapentaplegic, business, Transforming growth factor
Abstract: International audience; Transforming growth factor beta (TGFβ) plays a key role in tumor progression, notably as a potent inducer of epithelial-mesenchymal transition (EMT). However, all of the molecular effectors driving TGFβ-induced EMT are not fully characterized. Here, we report that forkhead box S1 (FOXS1) is a SMAD (mothers against decapentaplegic)dependent TGFβ-induced transcription factor, which regulates the expression of genes required for the initial steps of EMT (e.g., snail family transcription repressor 1) and to maintain a mesenchymal phenotype in hepatocellular carcinoma (HCC) cells. In human HCC, we report that FOXS1 is a biomarker of poorly differentiated and aggressive tumor subtypes. Importantly, FOXS1 expression level and activity are associated with a poor prognosis (e.g., reduced patient survival), not only in HCC but also in colon, stomach, and kidney cancers. Conclusion: FOXS1 constitutes a clinically relevant biomarker for tumors in which the pro-metastatic arm of TGFβ is active (i.e., patients who may benefit from targeted therapies using inhibitors of the TGFβ pathway). (Hepatology Communications 2021;0:1-15).
Published: 2022
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19. Characterization of the AGR2 interactome uncovers new players of Protein Disulfide Isomerase network in cancer cells

Author: Pavla Bouchalova, Lucia Sommerova, David Potesil, Andrea Martisova, Petr Lapcik, Veronika Koci, Alex Scherl, Petr Vonka, Joan Planas-Iglesias, Eric Chevet, Pavel Bouchal, Roman Hrstka, Masaryk University [Brno] (MUNI), Masaryk Memorial Cancer Institute (RECAMO), University of Geneva [Switzerland], 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), Masaryk Memorial Cancer Institute (MMCI), Université de Genève = University of Geneva (UNIGE), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and HAL UR1, Admin
Subjects: Protein Disulfide-Isomerases, protein-protein interactions, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biochemistry, Analytical Chemistry, 03 medical and health sciences, anterior gradient protein 2, Mucoproteins, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Tandem Mass Spectrometry, Neoplasms, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Protein Interaction Maps, Molecular Biology, 030304 developmental biology, mass spectrometry, Oncogene Proteins, 0303 health sciences, protein disulfide isomerase, secretory pathway, Molecular Docking Simulation, 030220 oncology & carcinogenesis, Chromatography, Liquid
Abstract: International audience; Anterior gradient 2 (AGR2) is an endoplasmic reticulum (ER)-resident protein disulfide isomerase (PDI) known to be overexpressed in many human epithelial cancers and is involved in cell migration, cellular transformation, angiogenesis, and metastasis. This protein inhibits the activity of the tumor suppressor p53, and its expression levels can be used to predict cancer patient outcome. However, the precise network of AGR2-interacting partners and clients remains to be fully characterized. Herein, we used label-free quantification and also stable isotope labeling with amino acids in cell culture-based LC-MS/MS analyses to identify proteins interacting with AGR2. Functional annotation confirmed that AGR2 and its interaction partners are associated with processes in the ER that maintain intracellular metabolic homeostasis and participate in the unfolded protein response, including those associated with changes in cellular metabolism, energy, and redox states in response to ER stress. As a proof of concept, the interaction between AGR2 and PDIA3, another ER-resident PDI, was studied in more detail. Pathway analysis revealed that AGR2 and PDIA3 play roles in protein folding in ER, including post-translational modification and in cellular response to stress. We confirmed the AGR2-PDIA3 complex formation in cancer cells, which was enhanced in response to ER stress. Accordingly, molecular docking characterized potential quaternary structure of this complex; however, it remains to be elucidated whether AGR2 rather contributes to PDIA3 maturation in ER, the complex directly acts in cellular signaling, or mediates AGR2 secretion. Our study provides a comprehensive insight into the protein-protein interaction network of AGR2 by identifying functionally relevant proteins and related cellular and biochemical pathways associated with the role of AGR2 in cancer cells.
Published: 2022
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20. One stone, two birds: circACTN4, a nexus for a coordinated activation of Hippo and Wnt/β-catenin pathways in cholangiocarcinoma

Author: Corentin Louis, Cédric Coulouarn, 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), Financial support: CC is supported by Inserm, Université de Rennes 1, Ligue Contre le Cancer (CD22, CD35, CD85), INCa, and ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé) dans le cadre du Plan cancer (Non-coding RNA in cancerology: fundamental to translational) and Fondation ARC pour la recherche sur le cancer. CL is supported by a PhD fellowship from Université de Rennes 1 and Fondation ARC pour la recherche sur le cancer., 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 Jonchère, Laurent
Subjects: Signaling pathways, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Cholangiocarcinoma, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Circular RNA, Transcription (biology), circACTN4, Humans, Wnt Signaling Pathway, beta Catenin, Intrahepatic Cholangiocarcinoma, 030304 developmental biology, 0303 health sciences, Hepatology, Wnt signaling pathway, 3. Good health, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, Catenin, Cancer research, 030211 gastroenterology & hepatology, Signal transduction
Abstract: International audience; Refers to:Qinjunjie Chen, Haibo Wang, Zheng Li, Fengwei Li, Leilei Liang, Yiran Zou, Hao Shen, Jun Li, Yong Xia, Zhangjun Cheng, Tian Yang, Kui Wang, Feng Shen - Circular RNA ACTN4 promotes intrahepatic cholangiocarcinoma progression by recruiting YBX1 to initiate FZD7 transcription -Journal of Hepatology, Available online 9 September 2021, Pages
Published: 2022
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21. Lymphovascular invasion as a criterion for adjuvant chemotherapy for FIGO stage I-IIa clear cell carcinoma, mucinous,low grade serous and low grade endometrioid ovarian cancer

Author: Geoffroy Canlorbe, Julie Delvallée, Lobna Ouldamer, Charles Coutant, Alexandre Bricou, Pierre Collinet, Emile Daraï, Cyril Touboul, Sofiane Bendifallah, Gilles Body, Cherif Akladios, Mathilde Cancel, Camille Mimoun, Pierre-Adrien Bolze, Xavier Carcopino, Cyrille Huchon, Marcos Ballester, Yohann Dabi, Vincent Lavoué, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHI Créteil, CHU Lille, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CHU Strasbourg, 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), Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], Hospices Civils de Lyon (HCL), Risques cliniques et sécurité en santé des femmes et en santé périnatale (RISCQ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Groupe Hospitalier Diaconesses Croix Saint-Simon, Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), Hôpital Lariboisière-Fernand-Widal [APHP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UMR237-Aix Marseille Université (AMU)-Avignon Université (AU), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), and Jonchère, Laurent
Subjects: Oncology, endocrine system diseases, Lymphovascular invasion, Adjuvant chemotherapy, 0302 clinical medicine, Overall survival, Stage (cooking), Neoplasm Metastasis, Aged, 80 and over, Ovarian Neoplasms, education.field_of_study, 030219 obstetrics & reproductive medicine, Obstetrics and Gynecology, Middle Aged, Prognosis, Adenocarcinoma, Mucinous, Lymphovascular, female genital diseases and pregnancy complications, 3. Good health, Serous fluid, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Clear cell carcinoma, Female, France, Adult, medicine.medical_specialty, Adolescent, Lymphovascular space invasion, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Decision Support Techniques, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Ovarian cancer, Internal medicine, medicine, Humans, education, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, Aged, Neoplasm Staging, Retrospective Studies, business.industry, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, medicine.disease, Recurrence-free survival, Endometrial Neoplasms, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Reproductive Medicine, business, Adenocarcinoma, Clear Cell
Abstract: International audience; BACKGROUND: The aim of this study was to evaluate the impact of lymphovascular space invasion (LVSI) on overall survival (OS) and recurrence-free survival (RFS) in patients managed for stage I-IIa clear cell carcinoma, mucinous, low-grade serous and low-grade endometrioid ovarian cancer MATERIAL AND METHODS: Retrospective multicentre study of the research group FRANCOGYN between January 2001 and December 2018. All patients managed for stage I-IIa clear cell carcinoma, mucinous /low grade serous and endometrioid ovarian cancer and for whom the presence of histological slides for the review of LVSI was available, were included. Patient’s characteristics with LVSI (LVSI group) were compared to those without LVSI (No LVSI group). A cox analysis for OS and RFS analysis were performed in all population. RESULTS: Over the study period, 133 patients were included in the thirteen institutions. Among them, 12 patients had LVSI (9%). LVSI was an independent predictive factor for poorer Overall and recurrence free survivals. LVSI affected OS (p
Published: 2021
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22. Idiopathic pulmonary fibrosis diagnosed concomitantly with diffuse squamous cell lung cancer on surgical lung biopsy: a case report

Author: Niel, C., Ricordel, C., Guy, T., Kerjouan, M., De Latour, B., Chiforeanu, D., Lederlin, Mathieu, Jouneau, S., 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), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), None, 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), 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 d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Jonchère, Laurent, 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), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, Lung Neoplasms, Biopsy, Nintedanib, Epithelial Cells, Case Report, Idiopathic pulmonary fibrosis, General Medicine, 3. Good health, 03 medical and health sciences, Surgical lung biopsy, 0302 clinical medicine, 030228 respiratory system, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Humans, Medicine, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Squamous cell lung cancer, Lung, Aged
Abstract: Background Idiopathic pulmonary fibrosis is a disease with a poor prognosis and has been associated with increased lung cancer incidence. Case presentation We report the case of a Caucasian 75-year-old woman, a former smoker, hospitalized for breathlessness with a chest computed tomography scan showing an interstitial lung disease. A surgical lung biopsy was performed, confirming a pattern of usual interstitial pneumonia but also numerous disseminated foci of well-differentiated focally invasive squamous cell carcinoma without hypermetabolic lung nodule, mass, or enlarged lymph node visualized on chest computed tomography or positron emission tomography scan. Nintedanib was started for its antifibrotic and antitumor properties, without any other antineoplastic treatment. Three years after initiation of nintedanib, clinical, functional, and computed tomography scan evaluations were stable, and there was no evidence for evolution of the squamous cell carcinoma. Conclusions Data are scarce regarding the benefit of nintedanib in patients with idiopathic pulmonary fibrosis-associated lung cancer, and it is unclear whether nintedanib could have a preventive role in lung carcinogenesis in idiopathic pulmonary fibrosis patients. This experience could help the scientific community in case of similar incidental findings.
Published: 2021
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23. Radiosensitizing Fe-Au Nanocapsules (Hybridosomes®) increase survival of GL261 brain tumor-bearing mice treated by radiotherapy

Author: Thierry Guillaudeux, Fabienne Gauffre, Rémy Pedeux, Mégane Bostoën, Ulrich Jarry, Myrtil L. Kahn, Clément Goubault, Pierre-Antoine Eliat, Soizic Chevance, Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Biosit : biologie, santé, innovation technologique (SFR UMS CNRS 3480 - INSERM 018), 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)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Biotrial, Plate-forme Rennaise d'Imagerie et Spectroscopie Structurale et Métabolique (PRISM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), 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), CRLCC Eugène Marquis (CRLCC), 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), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogenesis, Stress, Signaling (OSS), This work was supported by Biosit (Univ Rennes, CNRS, INSERM, BIOSIT-UMS 3480, US_S 018, Rennes F-35000 , France), the University of Rennes 1, the CNRS (Centre National de la Recherche Scientifique), the LCC (Laboratoire de Chimie de Coordination, UPR 8241), and the Région Bretagne (ARED- 107/ NAPOLI)., Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Biosit, University of Rennes 1, CNRS (Centre National de la Recherche Scientifique), LCC (Laboratoire de Chimie de Coordination, UPR 8241), Région Bretagne (ARED-107/ NAPOLI), Chevance, Soizic, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), 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: Iron Oxide and Gold Hybridosome® IR Irradiation MRI, Glioblastoma H®, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, medicine.medical_treatment, Metal Nanoparticles, Pharmaceutical Science, Medicine (miscellaneous), [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Hybridosomes®, Mice, chemistry.chemical_compound, 0302 clinical medicine, Magnetic Resonance Imaging NP, General Materials Science, Reactive Oxygen Species SPION, Iron oxide Hybridosome®, Blood Brain Barrier, 0303 health sciences, Brain Neoplasms, Iron oxide Hybridosome® H(Fe Au), SPION, ROS, H®, Magnetic Resonance Imaging, 3. Good health, MRI and bioluminescence, 030220 oncology & carcinogenesis, Blood Brain Barrier GBM, NTA, Molecular Medicine, H(Fe, Combined therapies, Iron oxide nanoparticles, Nanoparticle Tracking Analysis ROS, Iron Oxide and Gold Hybridosome®, MRI, Nanoparticle Tracking Analysis, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Biomedical Engineering, Brain tumor, Au), Bioengineering, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, GBM, Nanocapsules, NP, Hybridosome® H(Fe), 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, In vivo, Cell Line, Tumor, medicine, Animals, Chemotherapy, [CHIM]Chemical Sciences, H(Fe), mouse models, nanoparticle(s) NTA, 030304 developmental biology, Chemotherapy Mouse Models, iron oxide superparamagnetic nanoparticles, Radiotherapy, business.industry, Hybridosome®, Cancer, medicine.disease, nanoparticle(s), iron oxide superparamagnetic nanoparticles TEM, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Transmission Electron Microscopy Glioblastoma, Radiation therapy, chemistry, Cancer research, IR, TEM, Nanoparticles, Irradiation, Gold, business, Reactive Oxygen Species, Glioblastoma, BBB
Abstract: International audience; Glioblastoma remains a cancer for which the effectiveness of treatments has shown little improvement over the last decades. For this pathology, multiple therapies combining resection, chemotherapy and radiotherapy remain the norm. In this context, the use of high-Z nanoparticles such as gold or hafnium to potentiate radiotherapy is attracting more and more attention. Here, we evaluate the potentiating effect of hollow shells made of gold and iron oxide nanoparticles (hybridosomes®) on the radiotherapy of glioblastoma, using murine GL261-Luc+ brain tumor model. While iron oxide seems to have no beneficial effect for radiotherapy, we observe a real effect of gold nanoparticles —despite their low amount— with a median survival increase of almost 20% compared to radiotherapy only and even 33% compared to the control group. Cellular and in vivo studies show that a molecule of interest nano-precipitated in the core of the hybridosomes® is released and internalized by the surrounding brain cells. Finally, in vivo studies show that hybridosomes® injected intra-tumorally are still present in the vicinity of the brain tumor more than 5 days after injection (duration of the Stupp protocol’s radiation treatment). Interestingly, one mouse treated with radiotherapy in the presence of gold-containing hybridosomes® survived 78 days. Monitoring of the tumoral growth of this long-term survivor using both MRI and bioluminescence revealed a decrease of the tumor size after treatment. These very encouraging results are a proof-of-concept that hybridosomes®, are really effective tools for combined therapies development (chemo-radiotherapy).
Published: 2021
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24. Adherence to European ovarian cancer guidelines and impact on survival: a French multicenter study (FRANCOGYN)

Author: Tamara De Rozario, Denis Querleu, Geoffroy Canlorbe, Yohann Dabi, Cyril Touboul, Pierre Collinet, Charles Coutant, Alexandre Bricou, Lise Lecointre, Cherif Akladios, Mathieu Mezzadri, Lobna Ouldamer, Pierre-Adrien Bolze, Sofiane Bendifallah, Floriane Jochum, Thomas Boisramé, Cyrille Huchon, Vincent Lavoué, Emilie Faller, Les Hôpitaux Universitaires de Strasbourg (HUS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Intercommunal de Créteil (CHIC), Université de Rennes - Faculté de Médecine (UR Médecine), Université de Rennes (UR), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Hospices Civils de Lyon (HCL), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Jeanne de Flandre [Lille], Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], CHU Tenon [AP-HP], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Lariboisière-Fernand-Widal [APHP], Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors., Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1)
Subjects: medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gynecologic oncology, Carcinoma, Ovarian Epithelial, 03 medical and health sciences, surgical oncology, 0302 clinical medicine, Surgical oncology, Internal medicine, Animals, Humans, Medicine, 030212 general & internal medicine, Survival analysis, Aged, Retrospective Studies, Ovarian Neoplasms, Performance status, business.industry, Proportional hazards model, Hazard ratio, Obstetrics and Gynecology, Guideline, Middle Aged, Survival Analysis, medical oncology, 3. Good health, ovarian cancer, Oncology, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, Female, France, Guideline Adherence, business, Cohort study
Abstract: ObjectiveThe primary objective of the study was to validate the European Society for Medical Oncology (ESMO)–European Society of Gynecologic Oncology (ESGO) ovarian cancer guideline as a method of assessing quality of care, and to identify patient characteristics predictive of non-adherence to European guideline care. The secondary objectives were to analyze the evolution of practices over the years and to evaluate heterogeneity between centers.MethodsThis retrospective multicenter cohort study of invasive epithelial ovarian cancer reported to the FRANCOGYN database included data from 12 French centers between January 2000 and February 2017. The main outcome was adherence to ESMO–ESGO guidelines, defined by recommended surgical procedures according to the International Federation of Gynecology and Obstetrics (FIGO) stage and appropriate chemotherapy. Mixed multivariable logistic regression analysis with a random center effect was performed to estimate the probability of adherence to the guidelines. Survival analysis was carried out using the Kaplan–Meier method and a mixed Cox proportional hazards model.Results1463 patients were included in the study. Overall, 317 (30%) patients received complete guideline adherent care. Patients received appropriate surgical treatment in 69% of cases, while adequate chemotherapy was administered to 44% of patients. Both patient demographics and disease characteristics were significantly associated with the likelihood of receiving guideline adherent care, such as age, performance status, FIGO stage, and initial burden of disease. In univariate and multivariate survival analysis, adherence to the guidelines was a statistically significant and independent predictor of decreased overall survival. Patients receiving suboptimal care experienced an increased risk of death of more than 100% compared with those treated according to the guidelines (hazard ratio 2.14, 95% confidence interval 1.32 to 3.47, pConclusionsAdherence to ESMO–ESGO guidelines in ovarian cancer was associated with a higher overall survival and may be a useful method of assessing quality of care.
Published: 2021
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25. A Minimal Subset of Seven Genes Associated with Tumor Hepatocyte Differentiation Predicts a Poor Prognosis in Human Hepatocellular Carcinoma

Author: Corentin Louis, Kevin Bévant, Cédric Coulouarn, Matthis Desoteux, Denise Glaise, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This research was funded by Inserm, University of Rennes 1, Institut National du Cancer and Cancéropôle Ile-de-France. KB and MD are supported by a PhD fellowship from Ligue Contre le Cancer and Région Bretagne. CL is supported by a PhD fellowship from Université de Rennes 1., 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Jonchère, Laurent
Subjects: Cancer Research, [SDV]Life Sciences [q-bio], overall survival, Article, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Cancer stem cell, Gene expression, medicine, RC254-282, 030304 developmental biology, Hepatocyte differentiation, 0303 health sciences, business.industry, Cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, hepatocellular carcinoma, differentiation, medicine.disease, integrative transcriptomics, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Oncology, Tumor progression, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cancer research, prognosis, business, Pancreas, signature
Abstract: Simple Summary Liver cancer is one of the most commonly diagnosed cancers worldwide and the fourth leading cause of cancer-related deaths. Hepatocellular carcinoma (HCC) accounts for at least 80% of all malignant liver primary tumors. A better characterization of molecular mechanisms underlying HCC onset and progression may lead to discover new therapeutic targets and biomarkers. In this study, we performed an integrative transcriptomics analysis to evaluate the clinical relevance of genes associated with hepatocyte differentiation in human HCC. The HepaRG cell line model was used to define a gene expression signature reflecting the status of tumor hepatocyte differentiation. This signature was able to stratify HCC patients into clinically relevant molecular subtypes. Then, a minimal subset of seven differentiation-associated genes was identified to predict a poor prognosis in several cancer datasets. Abstract Hepatocellular carcinoma (HCC) is a deadly cancer worldwide as a result of a frequent late diagnosis which limits the therapeutic options. Tumor progression in HCC is closely correlated with the dedifferentiation of hepatocytes, the main parenchymal cells in the liver. Here, we hypothesized that the expression level of genes reflecting the differentiation status of tumor hepatocytes could be clinically relevant in defining subsets of patients with different clinical outcomes. To test this hypothesis, an integrative transcriptomics approach was used to stratify a cohort of 139 HCC patients based on a gene expression signature established in vitro in the HepaRG cell line using well-controlled culture conditions recapitulating tumor hepatocyte differentiation. The HepaRG model was first validated by identifying a robust gene expression signature associated with hepatocyte differentiation and liver metabolism. In addition, the signature was able to distinguish specific developmental stages in mice. More importantly, the signature identified a subset of human HCC associated with a poor prognosis and cancer stem cell features. By using an independent HCC dataset (TCGA consortium), a minimal subset of seven differentiation-related genes was shown to predict a reduced overall survival, not only in patients with HCC but also in other types of cancers (e.g., kidney, pancreas, skin). In conclusion, the study identified a minimal subset of seven genes reflecting the differentiation status of tumor hepatocytes and clinically relevant for predicting the prognosis of HCC patients.
Published: 2021
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26. An EMT–primary cilium–GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis

Author: Vincent J Guen, Jane E. Visvader, Qiong Ding, Philippe Juin, Matthieu Le Gallo, Anton M. Jetten, Tony E. Chavarria, Claude Prigent, Sophie G. Martin, Hong Soon Kang, Massimo Attanasio, Amandine Salamagnon, Patrick Tas, Arjun Bhutkar, Florence Godey, Roselyne Viel, Molly M. Wilson, Jacqueline A. Lees, Céline Callens, Svetlana Mironov, Robert A. Weinberg, Abena D. Peasah, Jonchère, Laurent, Massachusetts Institute of Technology (MIT), 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 ), 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), Carver College of Medicine, University of Iowa, H2P2 - Histo Pathologie Hight Precision (H2P2), Université de Rennes (UR)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CRLCC Eugène Marquis (CRLCC), National Institute of Environmental Health Sciences [Durham] (NIEHS-NIH), National Institutes of Health [Bethesda] (NIH), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), 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), University of Melbourne, Centre de recherche en Biologie cellulaire de Montpellier (CRBM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the MIT Stem Cell Initiative through Fondation MIT, Koch Institute Support (core) grant P30-CA14051 from the National Cancer Institute, Fondation ARC, Cancéropôle Grand Ouest, Université de Rennes 1, SIRIC ILIAD, and Fondation de France. M.M.W. was supported by the David H. Koch Graduate Fellowship. A.M.J. research was supported by the Intramural Research Program of the NIEHS, NIH Z01-ES-101585. V.J.G. was supported by Postdoctoral Fellowships from the Koch Institute and Fondation ARC., Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), 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), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-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 de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), and Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Ciliogenesis, medicine, Transcription factor, ComputingMilieux_MISCELLANEOUS, Cancer, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, Multidisciplinary, Fibroblast growth factor receptor 1, Cilium, SciAdv r-articles, Cell Biology, Claudin-Low, Cell biology, 030220 oncology & carcinogenesis, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Biomedicine and Life Sciences, Stem cell, Carcinogenesis, Ciliary base, Research Article
Abstract: Description, EMT induces cilium assembly and signaling to promote mammogenesis and tumorigenesis., The epithelial-mesenchymal transition (EMT) and primary ciliogenesis induce stem cell properties in basal mammary stem cells (MaSCs) to promote mammogenesis, but the underlying mechanisms remain incompletely understood. Here, we show that EMT transcription factors promote ciliogenesis upon entry into intermediate EMT states by activating ciliogenesis inducers, including FGFR1. The resulting primary cilia promote ubiquitination and inactivation of a transcriptional repressor, GLIS2, which localizes to the ciliary base. We show that GLIS2 inactivation promotes MaSC stemness, and GLIS2 is required for normal mammary gland development. Moreover, GLIS2 inactivation is required to induce the proliferative and tumorigenic capacities of the mammary tumor–initiating cells (MaTICs) of claudin-low breast cancers. Claudin-low breast tumors can be segregated from other breast tumor subtypes based on a GLIS2-dependent gene expression signature. Collectively, our findings establish molecular mechanisms by which EMT programs induce ciliogenesis to control MaSC and MaTIC stemness, mammary gland development, and claudin-low breast cancer formation.
Published: 2021
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27. Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma

Author: Franck Letourneur, Jérémy Augustin, Mark J. Kurth, Julie Le Naour, Sylvie Lachkar, Pamela Caudana, Eliane Piaggio, Youra Kim, Sarah Levesque, Jie S. Zhu, Guido Kroemer, Jonathan Pol, Bouchra Lekbaby, Andrea Checcoli, Patrick S.C. Leung, Allan Sauvat, Shashi Gujar, Agathe Delaune, Chantal Housset, Pierre de la Grange, Paule Opolon, Laura Fouassier, Noémie Robil, Laurence Zitvogel, Patrick Soussan, Juliette Paillet, Céleste Plantureux, Jimena Tosello Boari, M. Eric Gershwin, Isabelle Martins, Maria Chiara Maiuri, Cédric Coulouarn, Gautier Stoll, Norma Bloy, Gwennhael Autret, Juliette Hamroune, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institut Gustave Roussy (IGR), Institut Curie [Paris], Immunité et cancer (U932), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), GenoSplice [Paris], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of California [Los Angeles] (UCLA), University of California, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Dalhousie University [Halifax], 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), Université Paris-Saclay, Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Karolinska University Hospital [Stockholm], Association pour la lutte contre les maladies inflammatoires du foie et des voies biliaires, Dalhousie Medical Research Foundation, Agence National de la Recherche, ERA-Net for Research on Rare Diseases, Association pour la recherche sur le cancer, Cancéropôle Ile-de-France, Chancellerie des universités de Paris, Fondation pour la Recherche Médicale, Elior, European Research Area Network on Cardiovascular Diseases, Gustave Roussy Odyssea, European Union Horizon 2020, Canadian Cancer Society, Project Oncobiome, Fondation Carrefour, GDW20171100085, High-end Foreign Expert Program in China, Institut National du Cancer, Inserm, Institut Universitaire de France, LeDucq Foundation, LabEx, Recherche Hospitalo-Universitaire Torino Lumière, Seerave Foundation, Canadian Institutes of Health Research, Site de Recherche intégrée sur le Cancer Stratified Oncology Cell DNA Repair and Tumor Immune Elimination, Cancer Research and Personalized Medicine, Multi-Organism Institute (ITMO) Aviesan Cancer, Association Française d'Hépatologie, Site de Recherche intégrée sur le Cancer Cancer Research and Personalized Medicine, Ligue contre le Cancer, École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of California (UC), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: CD4-Positive T-Lymphocytes, Cholangitis, Autoimmunity, CD8-Positive T-Lymphocytes, Inbred C57BL, medicine.disease_cause, Medical and Health Sciences, Malignant transformation, Cholangiocarcinoma, Mice, 0302 clinical medicine, Immunologic, Neoplasms, 2.1 Biological and endogenous factors, Immunology and Allergy, Medicine, Aetiology, Cancer, 0303 health sciences, Tumor, Liver Disease, Forkhead Transcription Factors, 3. Good health, Immunosurveillance, medicine.anatomical_structure, Liver, Biliary tract, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, cardiovascular system, Cytokines, Female, Biotechnology, Liver Cancer, Monitoring, T cell, Chronic Liver Disease and Cirrhosis, Immunology, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Autoimmune Disease, digestive system, Cell Line, Primary sclerosing cholangitis, Experimental, 03 medical and health sciences, Rare Diseases, Monitoring, Immunologic, Cell Line, Tumor, parasitic diseases, Animals, cardiovascular diseases, Digestive Diseases - (Gallbladder), 030304 developmental biology, business.industry, Neoplasms, Experimental, medicine.disease, digestive system diseases, Mice, Inbred C57BL, Bile Duct Neoplasms, Cancer research, Digestive Diseases, business
Abstract: International audience; Cholangiocarcinoma (CCA) results from the malignant transformation of cholangiocytes. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are chronic diseases in which cholangiocytes are primarily damaged. Although PSC is an inflammatory condition predisposing to CCA, CCA is almost never found in the autoimmune context of PBC. Here, we hypothesized that PBC might favor CCA immunosurveillance. In preclinical murine models of cholangitis challenged with syngeneic CCA, PBC (but not PSC) reduced the frequency of CCA development and delayed tumor growth kinetics. This PBC-related effect appeared specific to CCA as it was not observed against other cancers, including hepatocellular carcinoma. The protective effect of PBC was relying on type 1 and type 2 T cell responses and, to a lesser extent, on B cells. Single-cell TCR/RNA sequencing revealed the existence of TCR clonotypes shared between the liver and CCA tumor of a PBC host. Altogether, these results evidence a mechanistic overlapping between autoimmunity and cancer immunosurveillance in the biliary tract.
Published: 2021
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28. Recent Progress in Genome Editing for Gene Therapy Applications: The French Perspective

Author: David Gilot, Célia Sourd, Mathieu Carrara, Marine Laurent, Alejandra Gutierrez-Guerrero, Annarita Miccio, Ana Buj-Bello, Els Verhoeyen, Aurélie Bedel, Giacomo Frati, Jean-Paul Concordet, François Moreau-Gaudry, Carine Giovannangeli, Julien Valton, Mario Amendola, Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Structure et Instabilité des Génomes (STRING), Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Biodiversité et Biotechnologie Fongiques (BBF), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CELLECTIS, ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-16-CE18-0012,STaHR,Stimulation de la Recombinaison Homologue pour la Thérapie Génique(2016), 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 International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Genetic enhancement, [SDV.CAN]Life Sciences [q-bio]/Cancer, Computational biology, Biology, 03 medical and health sciences, 0302 clinical medicine, Genome editing, Genetics, HSCs, gene editing toxicity, CRISPR, genome editing, Molecular Biology, CRISPR/Cas9, 030304 developmental biology, Gene Editing, 0303 health sciences, Cas9, Perspective (graphical), Gene Transfer Techniques, Palindrome, T cell, Genetic Therapy, Endonucleases, gene therapy, 3. Good health, 030220 oncology & carcinogenesis, Molecular Medicine, CRISPR-Cas Systems
Abstract: International audience; Recent advances in genome editing tools, especially novel developments in the clustered regularly interspaced short palindromic repeats associated to Cas9 nucleases (CRISPR/Cas9)-derived editing machinery, have revolutionized not only basic science but, importantly, also the gene therapy field. Their flexibility and ability to introduce precise modifications in the genome to disrupt or correct genes or insert expression cassettes in safe harbors in the genome underline their potential applications as a medicine of the future to cure many genetic diseases. In this review, we give an overview of the recent progress made by French researchers in the field of therapeutic genome editing, while putting their work in the general context of advances made in the field. We focus on recent hematopoietic stem cell gene editing strategies for blood diseases affecting the red blood cells or blood coagulation as well as lysosomal storage diseases. We report on a genome editing-based therapy for muscular dystrophy and the potency of T cell gene editing to increase anticancer activity of chimeric antigen receptor T cells to combat cancer. We will also discuss technical obstacles and side effects such as unwanted editing activity that need to be surmounted on the way toward a clinical implementation of genome editing. We propose here improvements developed today, including by French researchers to overcome the editing-related genotoxicity and improve editing precision by the use of novel recombinant nuclease-based systems such as nickases, base editors, and prime editors. Finally, a solution is proposed to resolve the cellular toxicity induced by the systems employed for gene editing machinery delivery.
Published: 2021
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29. Allosteric inhibition of HER2 by Moesin-mimicking compounds targets HER2-positive cancers and brain metastases

Author: Anaïs Domingot, Yanis Saidi, Jean-Luc Lenormand, Saïd Taouji, Haniaa Bouzinba-Segard, Camille Faure, Rym Djerbi-Bouillie, Sandra Bernard, Floriane Carallis, Sandrine Bourdoulous, Romy Rothe-Walther, Eric Chevet, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), 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), Inovarion, University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Translational microbial Evolution and Engineering (TIMC-TrEE), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), 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), Institut du Fer à Moulin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe de Recherche sur L’Étude du Foie [Bordeaux], Université de Bordeaux Ségalen [Bordeaux 2], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), SFI20101201780, Association pour la Recherche contre le Cancer, GEFLUC2016, GEFLUC Association, Société de Transfert de Technologies, ANR-10-SATT-05-01, Ile de France Innov, and Faure, Camille
Subjects: ERM family, Cancer Research, Receptor, ErbB-2, [SDV]Life Sciences [q-bio], Apoptosis, Receptor tyrosine kinase, Mice, 0302 clinical medicine, Ezrin, Biomimetics, Radixin, Moesin, Tumor Cells, Cultured, skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, biology, Brain Neoplasms, Chemistry, Microfilament Proteins, 3. Good health, [SDV] Life Sciences [q-bio], Gene Expression Regulation, Neoplastic, Oncology, 030220 oncology & carcinogenesis, Female, Allosteric regulation, Mice, Nude, Breast Neoplasms, 03 medical and health sciences, Allosteric inhibition, Allosteric Regulation, In vivo, medicine, Animals, Humans, HER2-positive breast cancer, neoplasms, Cell Proliferation, 030304 developmental biology, Cancer, Brain metastases, Clopenthixol, medicine.disease, Xenograft Model Antitumor Assays, biology.protein, Cancer research, Dopamine Antagonists, Brain metastasis
Abstract: Therapies targeting the tyrosine kinase receptor HER2 have significantly improved survival of patients with HER2+ cancer. However, both de novo and acquired resistance remain a challenge, particularly in the brain metastatic setting. Here we report that, unlike other HER tyrosine kinase receptors, HER2 possesses a binding motif in its cytosolic juxtamembrane region that allows interaction with members of the Ezrin/Radixin/Moesin (ERM) family. Under physiologic conditions, this interaction controls the localization of HER2 in ERM-enriched domains and stabilizes HER2 in a catalytically repressed state. In HER2+ breast cancers, low expression of Moesin correlated with increased HER2 expression. Restoring expression of ERM proteins in HER2+ breast cancer cells was sufficient to revert HER2 activation and inhibit HER2-dependent proliferation. A high-throughput assay recapitulating the HER2–ERM interaction allowed for screening of about 1,500 approved drugs. From this screen, we found Zuclopenthixol, an antipsychotic drug that behaved as a Moesin-mimicking compound, because it directly binds the juxtamembrane region of HER2 and specifically inhibits HER2 activation in HER2+ cancers, as well as activation of oncogenic mutated and truncated forms of HER2. Zuclopenthixol efficiently inhibited HER2+ breast tumor progression in vitro and in vivo and, more importantly, showed significant activity on HER2+ brain tumor progression. Collectively, these data reveal a novel class of allosteric HER2 inhibitors, increasing the number of approaches to consider for intervention on HER2+ breast cancers and brain metastases. Significance: This study demonstrates the functional role of Moesin in maintaining HER2 in a catalytically repressed state and provides novel therapeutic approaches targeting HER2+ breast cancers and brain metastasis using Moesin-mimicking compounds.
Published: 2021
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30. Outpatient laparoscopic sacrocolpopexy: Feasibility and patient satisfaction

Author: Chloé Rousseau, Emmanuel Della Negra, L. Corbel, Vincent Lavoué, Raissa Braguet, F. Trifard, Anne Cécile Pizzoferrato, Y. Codet, Krystel Nyangoh Timoh, Sonia Guérin, Zine-Eddine Khene, Lucie Bruneau, CHU Pontchaillou [Rennes], Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Outpatient procedure, [SDV]Life Sciences [q-bio], Context (language use), Feasibility study, Pelvic Organ Prolapse, 03 medical and health sciences, Gynecologic Surgical Procedures, 0302 clinical medicine, Patient satisfaction, Ambulatory Care, medicine, Humans, Laparoscopic sacrocolpopexy, Complication rate, Aged, Retrospective Studies, Same day discharge, Pelvic organ, 030219 obstetrics & reproductive medicine, business.industry, General surgery, Obstetrics and Gynecology, Retrospective cohort study, Middle Aged, Same-day discharge, 3. Good health, Reproductive Medicine, Outpatient hospitalisation, Patient Satisfaction, 030220 oncology & carcinogenesis, Feasibility Studies, Female, Laparoscopy, business
Abstract: International audience; Objective: Laparoscopic sacrocolpopexy is the standard surgery to correct apical pelvic organ prolapse. It is currently mainly practiced in the context of a conventional hospitalization, but more and more practitioners are developing it as an outpatient procedure. The objective of this study was to evaluate the feasibility of outpatient laparoscopic sacrocolpopexy and patient satisfaction. Methods: This was a retrospective study comparing outpatients with inpatients who had undergone laparoscopic sacrocolpopexy. The main outcome was the rate of unscheduled visits and the number of early readmissions (i.e.
Published: 2021
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31. Human TYRP1: two functions for a single gene?

Author: Arthur Gautron, David Gilot, Marie-Dominique Galibert, Mélodie Migault, Sébastien Corre, Laura Bachelot, Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), University of South Australia [Adelaide], CHU Pontchaillou [Rennes], Chemistry, Oncogenesis, Stress and Signaling (COSS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), CRLCC Eugène Marquis (CRLCC), The authors thank the Gene Expression and Oncogenesis team for helpful discussions. GEOteam is certified by the Fondation ARC (Association pour la Recherche sur le Cancer). Thisstudy received financial support from the following: Institut National du Cancer PAIRMelanoma program, Ouest Valorisation, Ligue National Contre le Cancer (LNCC)Départements du Grand-Ouest, Région Bretagne, University of Rennes 1, CNRS, and theSociété Française de Dermatologie. Further support was provided by fellowships from theRégion Bretagne and the LNCC Grand Ouest (A.G., M.M.) and from the Faculté des SciencesPharmaceutiques de l’Université de Rennes 1 (M.M.)., Chard-Hutchinson, Xavier, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Gautron, Arthur, Migault, Mélodie, Bachelot, Laura, Corre, Sébastien, Galibert, Marie Dominique, and Gilot, David
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Population, SNP, miRNA sponge, Single-nucleotide polymorphism, Skin Pigmentation, Dermatology, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, TYRP1, microRNA, medicine, melanoma, Humans, Genes, Tumor Suppressor, pigmentation, Neoplasm Metastasis, education, Gene, Transcription factor, Genetics, education.field_of_study, Membrane Glycoproteins, Melanoma, medicine.disease, Phenotype, Neoplasm Proteins, [SDV] Life Sciences [q-bio], MicroRNAs, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Melanocytes, Oxidoreductases
Abstract: International audience; In the animal kingdom, skin pigmentation is highly variable between species, and it contributes to phenotypes. In humans, skin pigmentation plays a part in sun protection. Skin pigmentation depends on the ratio of the two pigments pheomelanin and eumelanin, both synthesized by a specialized cell population, the melanocytes. In this review, we explore one important factor in pigmentation: the tyrosinase-related protein 1 (TYRP1) gene which is involved in eumelanin synthesis via the TYRP1 protein. Counterintuitively, high TYRP1 mRNA expression is associated with a poor clinical outcome for patients with metastatic melanomas. Recently, we were able to explain this unexpected TYRP1 function by demonstrating that TYRP1 mRNA sequesters microRNA-16, a tumor suppressor miRNA. Here, we focus on actors influencing TYRP1 mRNA abundance, particularly transcription factors, single nucleotide polymorphisms (SNPs), and miRNAs, as they all dictate the indirect oncogenic activity of TYRP1.
Published: 2021
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32. Open-label Phase II trial to evaluate safety and efficacy of second-line metronomic oral vinorelbine–atezolizumab combination for stage-IV non-small-cell lung cancer – VinMetAtezo trial, (GFPC‡ 04-2017)

Author: A. Bizieux, Marie Bernardi, Anne Marie Chiapa, Alain Vergnenegre, Hervé Lena, Gilles Robinet, Isabelle Monnet, Christos Chouaid, Service de Pathologie respiratoire et allergologie [CHU Limoges], CHU Limoges, Centre Hospitalier Intercommunal de Créteil (CHIC), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), 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), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Vinorelbine, Stage IV non-small cell lung cancer, 03 medical and health sciences, 0302 clinical medicine, Second line, Quality of life, Atezolizumab, Internal medicine, metronomic chemotherapy, medicine, Chemotherapy, business.industry, General Medicine, Immunotherapy, Metronomic Chemotherapy, 030104 developmental biology, non-small-cell lung cancer, 030220 oncology & carcinogenesis, immunotherapy, second line, business, medicine.drug
Abstract: Metronomic chemotherapy is defined as frequent low-dose administration without prolonged drug-free breaks. Combining immune-checkpoint inhibitors and metronomic chemotherapy is a new approach to improve responses and delay onset of resistance to immune-checkpoint inhibitors. This multicenter, Phase II, open-label, single-arm study was designed to assess the safety and efficacy of metronomic oral vinorelbine in combination with immune-checkpoint inhibitors in advanced non-small-cell lung cancers progressing after first-line platinum-based chemotherapy. The recommended metronomic oral vinorelbine dose will be determined during a safety run-in period including 12 patients; the main study will include 59 additional patients. The primary outcome is progression-free survival at 4 months. Secondary outcomes are safety of the combination, median overall survival, objective response rate, disease-control rate at 4 months and quality of life (NCT03801304).
Published: 2020
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33. 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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34. 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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35. The Anterior GRadient (AGR) family proteins in epithelial ovarian cancer

Author: Delphine Fessart, Eric Chevet, Jacques Robert, Frédéric Delom, Guillaume Babin, Cecile Hartog, Jonchère, Laurent, 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), 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), This work has been supported by the Fondation ARC pour la recherche sur le cancer and by the Site de recherche intégrée sur le cancer de Bordeaux (SIRIC Brio) (FD). This work has been supported by the Agence Nationale de la Recherche (ANR) (DF). This work was also funded by grants from the Institut National du Cancer (INCa), Fondation pour la Recherche Médicale (FRM, équipe labellisée) and Agence Nationale de la Recherche (ANR) to EC. This work been supported by the Institut Bergonié (GB)., 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: Cancer Research, endocrine system diseases, AGR2, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, Carcinoma, Ovarian Epithelial, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biomarkers, Tumor, Humans, Medicine, Clinical significance, Epithelial ovarian cancer, Amino Acid Sequence, Protein disulfide-isomerase, RC254-282, 030304 developmental biology, Ovarian Neoplasms, AGR3, 0303 health sciences, Epithelial ovarian Cancer, business.industry, Gene Expression Profiling, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, medicine.disease, female genital diseases and pregnancy complications, Neoplasm Proteins, 3. Good health, Endoplasmic reticulum proteins, Gynecologic malignancy, Oncology, 030220 oncology & carcinogenesis, Cancer research, Adenocarcinoma, Female, business
Abstract: Epithelial ovarian cancer (EOC) is the most common gynecologic disorder. Even with the recent progresses made towards the use of new therapeutics, it still represents the most lethal gynecologic malignancy in women from developed countries.The discovery of the anterior gradient proteins AGR2 and AGR3, which are highly related members belonging to the protein disulfide isomerase (PDI) family, attracted researchers’ attention due to their putative involvement in adenocarcinoma development. This review compiles the current knowledge on the role of the AGR family and the expression of its members in EOC and discusses the potential clinical relevance of AGR2 and AGR3 for EOC diagnosis, prognosis, and therapeutics.A better understanding of the role of the AGR family may thus provide new handling avenues for EOC patients.
Published: 2021
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36. Development of multiplex digital PCR assays for the detection of PIK3CA mutations in the plasma of metastatic breast cancer patients

Author: Fanny Le Du, Florence Godey, Thibault De La Motte Rouge, Christophe Perrin, Héloïse Bourien, Angélique Brunot, Julien Corné, Véronique Diéras, Véronique Quillien, Laurence Crouzet, C. Lefeuvre-Plesse, Lucie Robert, Centre 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), This work was supported by the association ‘La Vannetaise’, a French association for the prevention and awareness of cancer in women., Jonchère, Laurent, 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: Molecular biology, medicine.disease_cause, Polymerase Chain Reaction, chemistry.chemical_compound, 0302 clinical medicine, Medicine, Multiplex, Digital polymerase chain reaction, Child, Cancer, 0303 health sciences, Mutation, Multidisciplinary, Screening assay, Metastatic breast cancer, 3. Good health, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Clinical validity, Female, Cell-Free Nucleic Acids, Adolescent, Class I Phosphatidylinositol 3-Kinases, Science, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, Young Adult, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biomarkers, Tumor, Genetics, Humans, neoplasms, 030304 developmental biology, Base Sequence, business.industry, Infant, Newborn, Infant, Reproducibility of Results, medicine.disease, Circulating free DNA, chemistry, Cancer research, business, Biomarkers, DNA
Abstract: With the approval of new therapies targeting the PI3K pathway, the detection of PIK3CA mutations has become a key factor in treatment management for HR+/HER2− metastatic breast cancer (MBC). We developed multiplex digital PCR (dPCR) assays to detect and quantify PIK3CA mutations. A first screening assay allows the detection of 21 mutations, with a drop-off system targeting the 542–546 hotspot mutations combined with the simultaneous detection of N345K, C420R, H1047L and H1047R mutations. In the case of a positive result, a sequential strategy based on other assays that we have developped allows for precise mutation identification. Clinical validity was determined by analyzing plasma circulating free DNA (cfDNA) from 213 HR+/HER2− MBC samples, as well as DNA extracted from 97 available matched tumors from 89 patients. Our assays have shown reliable specificity, accuracy and reproducibility, with limits of blank of three and four droplets for the screening assay. Sixty-eight patients (32%) had at least one PIK3CA mutation detectable in their plasma, and we obtained 83.1% agreement between the cfDNA analysis and the corresponding tumors. The high sensitivity and robustness of these new dPCR assays make them well-suited for rapid and cost-effective detection of PIK3CA mutations in the plasma of MBC patients.
Published: 2021
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37. DNA Methylation of TGFβ Target Genes: Epigenetic Control of TGFβ Functional Duality in Liver Cancer

Author: Matthis Desoteux, Ayman M. Metwally, Kevin Bévant, Cédric Coulouarn, Abdel Hady A. Abdel Wahab, Sabrin A Abdel Wahab, 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), Cairo University, Misr University for Science & Technology (MUST), This research was funded by Inserm, Université de Rennes 1, Ligue Contre le Cancer (CD22, CD35, CD85), INCa, and ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé) dans le cadre du Plan cancer (Non-coding RNA in cancerology: fundamental to translational). K.B. and M.D. were supported by a PhD fellowship from Ligue Contre le Cancer (CD22) and Région Bretagne. This project was developed and supported by Campus France in the framework of the Franco-Egyptian partnership IMHOTEP Hubert Curien program between Univ Rennes 1, Inserm, UMR_S 1242, COSS (Chemistry, Oncogenesis Stress Signaling), Centre de Lutte contre le Cancer Eugène Marquis, Rennes, France and the Faculty of Applied Medical Sciences Misr University for science and technology, 6th October, Egypt (project N° 39530VD)., Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Carcinoma, Hepatocellular, Epithelial-Mesenchymal Transition, QH301-705.5, Decitabine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Article, Epigenesis, Genetic, 03 medical and health sciences, chemistry.chemical_compound, TGFβ, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Movement, Transforming Growth Factor beta, Cell Line, Tumor, medicine, Humans, Epigenetics, Epithelial–mesenchymal transition, Biology (General), Cell Proliferation, 030304 developmental biology, 0303 health sciences, DNA methylation, epigenetics, Liver Neoplasms, EMT, General Medicine, Transforming growth factor beta, hepatocellular carcinoma, 3. Good health, Demethylating agent, Gene Expression Regulation, Neoplastic, Cell Transformation, Neoplastic, Liver, chemistry, Tumor progression, 030220 oncology & carcinogenesis, SNAI1, Cancer research, biology.protein, Snail Family Transcription Factors, Neoplasm Recurrence, Local, Signal Transduction, Transcription Factors, medicine.drug
Abstract: International audience; Transforming growth factor beta (TGFβ) plays a key role in liver carcinogenesis. However, its action is complex, since TGFβ exhibits tumor-suppressive or oncogenic properties, depending on the tumor stage. At an early stage TGFβ exhibits cytostatic features, but at a later stage it promotes cell growth and metastasis, as a potent inducer of epithelial to mesenchymal transition (EMT). Here, we evaluated DNA methylation as a possible molecular mechanism switching TGFβ activity toward tumor progression in hepatocellular carcinoma (HCC). We report that decitabine, a demethylating agent already used in the clinic for the treatment of several cancers, greatly impairs the transcriptional response of SNU449 HCC cells to TGFβ. Importantly, decitabine was shown to induce the expression of EMT-related transcription factors (e.g., SNAI1/2, ZEB1/2). We also report that the promoter of SNAI1 was hypomethylated in poor-prognosis human HCC, i.e., associated with high grade, high AFP level, metastasis and recurrence. Altogether, the data highlight an epigenetic control of several effectors of the TGFβ pathway in human HCC possibly involved in switching its action toward EMT and tumor progression. Thus, we conclude that epidrugs should be carefully evaluated for the treatment of HCC, as they may activate tumor promoting pathways.
Published: 2021
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38. The unfolded protein response as regulator of cancer stemness and differentiation: Mechanisms and implications for cancer therapy

Author: Mohammad Khoonkari, Frank A.E. Kruyt, Eric Chevet, Tony Avril, Dong Liang, University of Groningen [Groningen], 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), DL was supported by the China Scholarship Council and the University of Groningen. MK was financially supported by the Zernike Institute for Advanced Materials at the University of Groningen, including funding from the Bonus Incentive Scheme (of the Dutch Ministry for Education, Culture and Science (OCW)). T. Avril was supported by La Ligue contre le cancer (comités 35, 56 and 85) and by l'Institut des Neurosciences Cliniques de Rennes (AAP 2020). EC was funded by Grants from Fondation pour la Recherche Médicale (FRM équipe labellisée 2018), Institut National du Cancer (INCa, PLBIO), Agence Nationale de la Recherche (ANR, ERAAT)., ANR-17-RAR3-0003,ERAAT,Enhancing Endoplasmic Reticulum Proteostasis to Rescue Alpha1 Antitrypsin Deficiency(2017), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Jonchère, Laurent, and Enhancing Endoplasmic Reticulum Proteostasis to Rescue Alpha1 Antitrypsin Deficiency - - ERAAT2017 - ANR-17-RAR3-0003 - E-RARE - VALID
Subjects: PERK, endocrine system, Cell Survival, medicine.medical_treatment, Cellular homeostasis, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, IRE1, Biology, Biochemistry, Targeted therapy, Unfolded protein response, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cancer stem cell, Neoplasms, medicine, Animals, Humans, Neoplasm Invasiveness, 030304 developmental biology, Pharmacology, 0303 health sciences, ATF6, Cancer stem cells, Cancer, Cell Differentiation, Tumor formation, medicine.disease, 3. Good health, Proteostasis, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, Cancer research, Therapy, Stem cell
Abstract: International audience; The unfolded protein response (UPR) is an adaptive mechanism that regulates protein and cellular homeostasis. Three endoplasmic reticulum (ER) membrane localized stress sensors, IRE1, PERK and ATF6, coordinate the UPR in order to maintain ER proteostasis and cell survival, or induce cell death when homeostasis cannot be restored. However, recent studies have identified alternative functions for the UPR in developmental biology processes and cell fate decisions under both normal and cancerous conditions. In cancer, increasing evidence points towards the involvement of the three UPR sensors in oncogenic reprogramming and the regulation of tumor cells endowed with stem cell properties, named cancer stem cells (CSCs), that are considered to be the most malignant cells in tumors. Here we review the reported roles and underlying molecular mechanisms of the three UPR sensors in regulating stemness and differentiation, particularly in solid tumor cells, processes that have a major impact on tumor aggressiveness. Mainly PERK and IRE1 branches of the UPR were found to regulate CSCs and tumor development and examples are provided for breast cancer, colon cancer and aggressive brain tumors, glioblastoma. Although the underlying mechanisms and interactions between the different UPR branches in regulating stemness in cancer need to be further elucidated, we propose that PERK and IRE1 targeted therapy could inhibit self-renewal of CSCs or induce differentiation that is predicted to have therapeutic benefit. For this, more specific UPR modulators need to be developed with favorable pharmacological properties that together with patient stratification will allow optimal evaluation in clinical studies.
Published: 2021
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39. Structural and molecular bases to IRE1 activity modulation

Author: Nicolas Gouault, Timothy Langlais, Xavier Guillory, Eric Chevet, François Carreaux, Diana Pelizzari-Raymundo, Leif A. Eriksson, Sayyed Jalil Mahdizadeh, Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), 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), University of Gothenburg (GU), Institut National du Cancer (INCa PLBIO) Institut National du Cancer (INCA) France, Fondation pour la Recherche Medicale (FRM) Fondation pour la Recherche Medicale [DEQ20180339169], ERANET, Agence Nationale de la Recherche (ERAAT) French National Research Agency (ANR), EU European Commission [H2020 MSCA ITN-675448, MSCA RISE-734749], Swedish Research Council (VR) Swedish Research Council [2019-3684], Vinnova Seal-of-Excellence programVinnova [2019-02205], Ecole Doctorale 3M, university of Rennes 1, Region BretagneRegion Bretagne, Fondation ARC pour la recherche sur le cancerFondation ARC pour la Recherche sur le Cancer [PDF20191209830], Vinnova Seal-of-Excellence program Vinnova [2019-02205], Region Bretagne Region Bretagne, Fondation ARC pour la recherche sur le cancer Fondation ARC pour la Recherche sur le Cancer [PDF20191209830], European Project: 675448,H2020,H2020-MSCA-ITN-2015,TRAIN-ERS(2015), European Project: 777657,H2020-EU.1.3.3. - Stimulating innovation by means of cross-fertilisation of knowledge,777657,MSCA-RISE(2018), 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), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and CRLCC Eugène Marquis (CRLCC)
Subjects: Protein Folding, RNase P, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, IRE1, Protein Serine-Threonine Kinases, Endoplasmic Reticulum, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Endoribonucleases, Animals, Homeostasis, Humans, [CHIM]Chemical Sciences, Enzyme Inhibitors, Mode of action, Molecular Biology, 030304 developmental biology, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Kinase, Chemistry, Endoplasmic reticulum, structure activity relationship (SAR), Cell Biology, unfolded protein response, Endoplasmic Reticulum Stress, Transmembrane protein, Cell biology, Cytosol, structure-based drug design (SBDD), 030220 oncology & carcinogenesis, Unfolded protein response, Protein folding, ER stress, Signal Transduction
Abstract: International audience; The Unfolded Protein response is an adaptive pathway triggered upon alteration of endoplasmic reticulum (ER) homeostasis. It is transduced by three major ER stress sensors, among which the Inositol Requiring Enzyme 1 (IRE1) is the most evolutionarily conserved. IRE1 is an ER-resident type I transmembrane protein exhibiting an ER luminal domain that senses the protein folding status and a catalytic kinase and RNase cytosolic domain. In recent years, IRE1 has emerged as a relevant therapeutic target in various diseases including degenerative, inflammatory and metabolic pathologies and cancer. As such several drugs altering IRE1 activity were developed that target either catalytic activity and showed some efficacy in preclinical pathological mouse models. In this review, we describe the different drugs identified to target IRE1 activity as well as their mode of action from a structural perspective, thereby identifying common and different modes of action. Based on this information we discuss on how new IRE1-targeting drugs could be developed that outperform the currently available molecules.
Published: 2021
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40. RNA, a new member in the glycan-club that gets exposed at the cell surface

Author: Maria Antonietta De Matteis, Eeva-Liisa Eskelinen, Eric Chevet, Hesso Farhan, 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), University of Naples Federico II = Università degli studi di Napoli Federico II, Telethon Institute of Genetics and Medicine = Istituto Telethon di Genetica e Medicina (TIGEM), University of Turku, Universität Innsbruck [Innsbruck], Jonchère, Laurent, 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), Università degli studi di Napoli Federico II, Chevet, E., De Matteis, M. A., Eskelinen, E. -L., and Farhan, H.
Subjects: 0303 health sciences, Glycan, Cell, RNA, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Biology, Biology, Biochemistry, Cell biology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, [SDV.CAN] Life Sciences [q-bio]/Cancer, Structural Biology, Genetics, medicine, biology.protein, Molecular Biology, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: In this article we discuss implications of the recent discovery of glycoRNAs found to be present at the cell surface of mammalian cells which was reported by Flynn et al. Cell 2021.
Published: 2021
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41. Lymphovascular space invasion and estrogen receptor status in high-grade serous ovarian cancer - A multicenter study by the FRANCOGYN group

Author: Camille Mimoun, Jerome Lorenzini, Geoffroy Canlorbe, Vincent Lavoué, Marion Deberti, Pierre Collinet, Cherif Akladios, Alexandre Bricou, Cyril Touboul, Charles Coutant, Xavier Carcopino, Cyrille Huchon, Yohann Dabi, Gilles Body, Pierre-Adrien Bolze, Sofiane Bendifallah, Lobna Ouldamer, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UMR237-Aix Marseille Université (AMU)-Avignon Université (AU), CHI Créteil, Hôpital Jeanne de Flandre [Lille], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CHU Strasbourg, CHU Pontchaillou [Rennes], 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), Hospices Civils de Lyon, Departement de Neurologie (HCL), Risques cliniques et sécurité en santé des femmes et en santé périnatale (RISCQ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHI Poissy-Saint-Germain, Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), and Jonchère, Laurent
Subjects: Oncology, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Serous ovarian cancer, Overall survival, Medicine, Humans, Estrogen Receptor Status, Pathology Examination, Aged, Retrospective Studies, Aged, 80 and over, Ovarian Neoplasms, 030219 obstetrics & reproductive medicine, business.industry, Overall Survival, Lymphovascular Space Invasion, Obstetrics and Gynecology, Middle Aged, Prognosis, Lymphovascular, 3. Good health, Predictive factor, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Serous fluid, Recurrence-Free Survival, Reproductive Medicine, Multicenter study, Receptors, Estrogen, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Female, France, business, High-Grade Serous
Abstract: International audience; BACKGROUND: The aim of this study was to evaluate the impact of Lymphovascular Space Invasion (LVSI) on Overall Survival (OS) and Recurrence-Free Survival (RFS) in patients managed for high-grade serous epithelial ovarian cancer (HGSOC). MATERIALS AND METHODS: Retrospective multicenter study by the FRANCOGYN research group between January 2001 and December 2018. All patients managed for HGSOC and for whom histological slides for the review of LVSI were available, were included. The characteristics of patients with LVSI (LVSI group) were compared to those without LVSI (No LVSI group). A Cox analysis for OS and RFS analysis was performed in all populations. RESULTS: Over the study period, 410 patients were included in the thirteen institutions. Among them, 289 patients had LVSI (33.9%). LVSI was an independent predictive factor for poorer Overall and Recurrence-Free Survival. LVSI affected OS (p
Published: 2021
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42. Pembrolizumab with Capox Bevacizumab in patients with microsatellite stable metastatic colorectal cancer and a high immune infiltrate: The FFCD 1703-POCHI trial

Author: Romain Coriat, Nicolas Loménie, Côme Lepage, Thierry Lecomte, Violaine Randrian, Camille Kurtz, Jean-Louis Legoux, Jean-Marc Phelip, Astrid Lièvre, Pierre Laurent-Puig, Julien Taieb, Jean-François Emile, Carole Monterymard, David Tougeron, Harry Sokol, Jérémie Bez, Laurent Mineur, Claire Gallois, Laetitia Dahan, Stefano Kim, Vincent Hautefeuille, Claude Capron, Marine Gilabert, 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), Hôpital Ambroise Paré [AP-HP], Hôpital JeanMinjoz, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), 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], Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institut Sainte Catherine [Avignon], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional d'Orléans (CHRO), CHU Amiens-Picardie, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire d'Informatique Paris Descartes (LIPADE (URP_2517)), Université de Paris (UP), HalioDX and the 'Ligue nationale contre le cancer', 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, Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Jonchère, Laurent, École Pratique des Hautes Études (EPHE), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Oncology, medicine.medical_specialty, Bevacizumab, Colorectal cancer, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pembrolizumab, Antibodies, Monoclonal, Humanized, DNA Mismatch Repair, 03 medical and health sciences, Antineoplastic Agents, Immunological, Clinical Trials, Phase II as Topic, 0302 clinical medicine, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Checkpoint blockade, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Humans, Medicine, Immune Checkpoint Inhibitors, Chemotherapy, Hepatology, business.industry, Tumour-infiltrating lymphocytes, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, 3. Good health, Oxaliplatin, Clinical trial, 030220 oncology & carcinogenesis, Microsatellite Instability, 030211 gastroenterology & hepatology, Colorectal Neoplasms, business, medicine.drug
Abstract: International audience; Pembrolizumab, a PD1 immune checkpoint inhibitor (ICI), was recently reported to be very effective in patients with microsatellite instable/deficient mismatch repair metastatic colorectal cancer (MSI/dMMR mCRC), unlike patients with microsatellite stable/proficient MMR (MSS/pMMR) mCRC, in whom ICIs are generally ineffective. However, about 15% of MSS/pMMR CRCs are highly infiltrated by tumour infiltrating lymphocytes. In addition, both oxaliplatin and bevacizumab have been shown to have immunomodulatory properties that may increase the efficacy of an ICI. We formulated the hypothesis that patients with MSS/pMMR mCRC with a high immune infiltrate can be sensitive to ICI plus oxalipatin and bevacizumab-based chemotherapy. POCHI is a multicenter, open-label, single-arm phase II trial to evaluate efficacy of Pembrolizumab with Capox Bevacizumab as first-line treatment of MSS/pMMR mCRC with a high immune infiltrate for which we plan to enrol 55 patients. Primary endpoint is progression-free survival (PFS) at 10 months, which is expected greater than 50%, but a 70% rate is hoped for. Main secondary objectives are overall survival, secondary resection rate and depth of response. Patients must have been resected of their primary tumour so as to evaluate two different immune scores (Immunoscore® and TuLIS) and are eligible if one score is "high";. The first patient was included on April 20, 2021.
Published: 2021
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43. Significant decrease in interval colorectal cancer incidence after implementing immunochemical testing in a multiple-round guaiac-based screening programme

Author: Aurore Carlo, Astrid Lièvre, Christine Piette, Jean-François Bretagne, Chloé Rousseau, Mathilde Cosson, Université de Rennes (UR), CHU Pontchaillou [Rennes], 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), The authors received no specific funding for this work., Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), 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 Jonchère, Laurent
Subjects: Male, Cancer Research, medicine.medical_specialty, Colorectal cancer, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Rate ratio, Logistic regression, Article, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Medicine, Humans, Mass Screening, Cumulative incidence, Poisson regression, education, Aged, education.field_of_study, business.industry, Incidence (epidemiology), Immunochemistry, Incidence, Middle Aged, medicine.disease, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Occult Blood, symbols, Interval (graph theory), 030211 gastroenterology & hepatology, Female, business, Colorectal Neoplasms, Guaiac
Abstract: International audience; Background and aims: We aimed to evaluate the effects of switching to faecal immunochemical testing (FIT) on the cumulative 2-year incidence rate of interval cancers, interval cancer rate and test sensitivity within a mature population-based colorectal cancer screening programme consisting of six rounds of biennial guaiac faecal occult blood testing (gFOBT).Methods: The FIT results were compared with those of gFOBT used in each of the previous two rounds. For the three rounds analysed, 279,041 tests were performed by 156,186 individuals. Logistic regression analysis was used to determine interval cancer risk factors (Poisson regression) and to compare the sensitivity of FIT to gFOBT.Results: There were 612 cases of screen-detected cancers and 209 cases of interval cancers. The sex- and age-adjusted cumulative 2-year incidence rates of interval cancers were 55.7 (95% CI, 45.3-68.5), 42.4 (95% CI, 32.6-55.2) and 15.8 (95% CI, 10.9-22.8) per 100,000 person-years after the last two rounds of gFOBT and FIT, respectively. The FIT/gFOBT incidence rate ratio was 0.38 [95% CI, 0.27-0.54] (P < 0.001). Sex- and age-adjusted sensitivity was significantly higher with FIT than with gFOBT (OR = 6.70 [95% CI, 4.48-10.01], P < 0.0001).Conclusions: This population-based study revealed a dramatic decrease in the cumulative incidence rates of interval cancers after switching from gFOBT to FIT. These data provide an additional incentive for countries still using gFOBT to switch to FIT.
Published: 2021
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44. Surgical rather than endoscopic resection of early-stage colorectal cancers promotes excessive imaging surveillance

Author: Jean-François Bretagne, Astrid Lièvre, Thomas Grainville, Mathilde Cosson, Christine Piette, Chloé Rousseau, Martin Bordet, CHU Pontchaillou [Rennes], ADECI35, 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), None, Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: medicine.medical_specialty, Colorectal cancer, Tumor resection, [SDV.CAN]Life Sciences [q-bio]/Cancer, Lymph node metastasis, Resection, Colorectal cancer screening, Screening programme, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Medicine, Humans, Endoscopic resection, Stage (cooking), Watchful Waiting, Neoplasm Staging, Retrospective Studies, Early-stage colorectal cancer, Surgical treatment, Hepatology, business.industry, Endoscopic therapy, Gastroenterology, Endoscopy, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Imaging surveillance, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Cohort, 030211 gastroenterology & hepatology, Radiology, business, Colorectal Neoplasms
Abstract: International audience; BACKGROUND AND AIMS: Imaging surveillance after curative resection of colorectal cancer (CRC) is debated, particularly in cases of early-stage CRC. The aim of this study was to retrospectively analyze whether and how patients with screened stage 0 and stage 1 CRC were monitored by imaging. METHODS: A cohort of patients with stage 0 (intramucosal) or stage 1 (T1N0) CRC detected from 2003 to 2015 through the French national screening programme was included. All imaging findings were recorded. Statistical analyses were performed for the entire cohort (n = 450) and separately for the two groups (stage 0 n = 268, stage 1 n = 182). Factors associated with imaging surveillance, including the patient’s referring gastroenterologist, were determined by logistic regression. RESULTS: A total of 450 patients were followed up for 6.6 ± 3.9 years. Imaging surveillance was performed for 159 (35.3%), more often for those with stage 1 (66.5%) than stage 0 (14.2%) tumours (p
Published: 2021
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45. ING2 tumor suppressive protein translocates into mitochondria and is involved in cellular metabolism homeostasis

Author: Audrey Mouche, Rémy Pedeux, Thierry Guillaudeux, Alice Blondel, Marie Tiercin, Charles Ricordel, Benoit Desrues, Hervé Lena, Agnès Burel, Florence Jouan, Laura Chaillot, Jérôme Archambeau, 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], CH de Saint-Malo [Broussais], Biosit : biologie, santé, innovation technologique (SFR UMS CNRS 3480 - INSERM 018), 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)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Microscopie de Rennes (MRic), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), La Ligue Contre le Cancer Ligue nationale contre le cancer, Nuovo-Soldati Fundation research grant, INSERM (Institut National de la Sante et de la Recherche Medicale) Institut National de la Sante et de la Recherche Medicale (Inserm), La Ligue Contre le Cancer (Grand Ouest), Association pour la Recherche sur le Cancer (ARC) Fondation ARC pour la Recherche sur le Cancer, Fondation pour la Recherche Medicale (FMR) Fondation pour la Recherche Medicale [DEQ20180339169], AIS Rennes Metropole Region Bretagne, Biosit, Action Incitative Universite de Rennes 1, Region Bretagne Region Bretagne, FHU Camin (CHU Rennes) doctoral followship, Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: 0301 basic medicine, Mitochondrial ROS, DNA Replication, Cancer Research, Mitochondrial DNA, Tumor suppressor gene, DNA Repair, Transcription, Genetic, DNA repair, [SDV]Life Sciences [q-bio], Receptors, Cytoplasmic and Nuclear, Mitochondrion, Biology, medicine.disease_cause, DNA, Mitochondrial, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Genetics, medicine, Homeostasis, Humans, Molecular Biology, Homeodomain Proteins, Tumor Suppressor Proteins, TFAM, Cell biology, Mitochondria, DNA-Binding Proteins, 030104 developmental biology, Mitochondrial respiratory chain, A549 Cells, 030220 oncology & carcinogenesis, Carcinogenesis
Abstract: International audience; ING2 (Inhibitor of Growth 2) is a tumor suppressor gene that has been implicated in critical biological functions (cell-cycle regulation, replicative senescence, DNA repair and DNA replication), most of which are recognized hallmarks of tumorigenesis occurring in the cell nucleus. As its close homolog ING1 has been recently observed in the mitochondrial compartment, we hypothesized that ING2 could also translocate into the mitochondria and be involved in new biological functions. In the present study, we demonstrate that ING2 is imported in the inner mitochondrial fraction in a redox-sensitive manner in human cells and that this mechanism is modulated by 14-3-3 eta protein expression. Remarkably, ING2 is necessary to maintain mitochondrial ultrastructure integrity without interfering with mitochondrial networks or polarization. We observed an interaction between ING2 and mtDNA under basal conditions. This interaction appears to be mediated by TFAM, a critical regulator of mtDNA integrity. The loss of mitochondrial ING2 does not impair mtDNA repair, replication or transcription but leads to a decrease in mitochondrial ROS production, suggesting a detrimental impact on OXPHOS activity. We finally show using multiple models that ING2 is involved in mitochondrial respiration and that its loss confers a protection against mitochondrial respiratory chain inhibition in vitro. Consequently, we propose a new tumor suppressor role for ING2 protein in the mitochondria as a metabolic shift gatekeeper during tumorigenesis.
Published: 2021
Full Text: View/download PDF

46. Vaccination contre la COVID-19 des patients atteints de cancer solide : revue et préconisations d’un inter-groupe oncologique français (CGO, TNCD, UNICANCER)

Author: Khê Hoang Xuan, Juliette Thariat, Jean Bourhis, Florence Huguet, David Tougeron, Jean-Yves Blay, Thomas Aparicio, Philippe Gorphe, Pierre Michel, Sébastien Gaujoux, Pascale Mariani, Amélie Servettaz, Michel Ducreux, Christophe Louvet, Olivier Bouché, Barbara Seitz-Polski, Thierry Lecomte, Boris Guiu, Astrid Lièvre, Anne-Claire Hardy-Bessard, Maxime Hentzien, Léon Maggiori, Firouzé Bani-Sadr, Virginie Westeel, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), UNICANCER, 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), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (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), CHU Pontchaillou [Rennes], Cooperator Multidisciplinary Oncology Group (GERCOR), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), 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), Centre Léon Bérard [Lyon], Aucun, Hôpital Lapeyronie [Montpellier] (CHU), Institut Universitaire de Cancérologie [Paris] (IUC), 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)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), 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), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, 2019-20 coronavirus outbreak, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV.CAN]Life Sciences [q-bio]/Cancer, Immunotherapy, Adoptive, 03 medical and health sciences, Cancers solides, 0302 clinical medicine, Neoplasms, medicine, Humans, Chemotherapy, Radiology, Nuclear Medicine and imaging, Molecular Targeted Therapy, Pandemics, Radiothérapie, Gynecology, Radiotherapy, business.industry, Contraindications, Vaccination, Synthèse, Neoplasms therapy, COVID-19, Hematology, General Medicine, 3. Good health, Coronavirus, 030104 developmental biology, Solid cancers, Oncology, 030220 oncology & carcinogenesis, France, business, Chimiothérapie
Abstract: La pandémie COVID-19 a un impact majeur à toutes les étapes de prise en charge des cancers. Le risque de décès de la COVID-19 chez les patients traités pour un cancer est élevé. La vaccination contre la COVID-19 représente une opportunité majeure pour réduire les risques de formes graves de la maladie et maintenir une filière de soins oncologiques normale. La définition de la population à vacciner est complexe, avec des données scientifiques très limitées et un contexte de pénurie en vaccin. Il apparaît théoriquement important de vacciner les patients atteints de cancers en cours de traitement ou avec un traitement datant de moins de trois ans, ainsi que leur entourage. Les patients actuellement prioritaires dits « à haut risque » sont ceux atteints de cancers en cours de chimiothérapie. Un groupe d’experts a préconisé une population « ultra-prioritaire » différente, incluant les patients sous chimiothérapie à visée curative ou palliative de première ou deuxième ligne, mais aussi ceux traités par chirurgie ou radiothérapie avec un grand volume pulmonaire, ganglionnaires et/ou de tissus hématopoïétiques. La vaccination doit idéalement être réalisée avant le début des soins. Malgré l’absence de données publiées, elle peut aussi s’effectuer pendant une chimiothérapie en évitant les périodes d’aplasie, avec possibilité de vacciner dans les établissements de soins. La mise en place de cohortes avec suivi immunologique et clinique des patients vaccinés atteints de cancer est nécessaire. Dans l’état actuel des connaissances, le rapport bénéfice/risque est très en faveur de la vaccination de tous les patients atteints de cancers.
Published: 2021
Full Text: View/download PDF

47. History of tonsillectomy and risk of oropharyngeal cancer

Author: Sophie Périé, Christian Righini, Sébastien Vergez, Nicolas Fakhry, Justine Lerat, Pierre Philouze, Nicolas Saroul, Jean-Damien Combes, Haitham Mirghani, Philippe Ceruse, Olivier Malard, Guillaume Buiret, Nicolas Voisin, Jean Lacau St Guily, Ritoungarte Nadjingar, Franck Jegoux, Emmanuel Bartaire, Gary M. Clifford, Renaud Garrel, Benjamin Verillaud, Silvia Franceschi, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Hospices Civils de Lyon (HCL), Clinique Hartmann [Neuilly-sur-Seine], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pontchaillou [Rennes], Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU), Institut Gustave Roussy (IGR), Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), CHU Lille, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Hôpital Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ligue nationale contre le cancerLigue nationale contre le cancer [LNCC CD69 2014], Institut National Du Cancer (INCa) Institut National du Cancer (INCA) France [2014/122], Italian Ministry of Health (Ricerca Corrente) Ministry of Health, Italy, Association pour la Recherche sur le Cancer (ARC)Fondation ARC pour la Recherche sur le Cancer [20111204169], Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier de Valence, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM), CHU Limoges, CHU Clermont-Ferrand, Hôpital Lariboisière-Fernand-Widal [APHP], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Rothschild [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Cancer Research, medicine.medical_specialty, Tonsillar cancer, Adolescent, medicine.medical_treatment, Palatine Tonsil, Oropharyngeal Tumor, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Tongue, Internal medicine, Base of the tongue cancer, medicine, Humans, 030223 otorhinolaryngology, Head and neck cancer, Tonsillectomy, Oropharyngeal cancer, business.industry, Cancer, Odds ratio, medicine.disease, 3. Good health, Oropharyngeal Neoplasms, medicine.anatomical_structure, Tonsil, Oncology, 030220 oncology & carcinogenesis, Oral Surgery, business
Abstract: International audience; Objective: To investigate whether palatine tonsillectomy in youth influences the risk of oropharyngeal cancers (OPC) by assessing the association between history of tonsillectomy and risk of tonsillar, base of tongue (BOT) cancer, and other head and neck cancers (HNC). Materials and Methods: RACKAM was a case-case study comparing frequency of tonsillectomy history in individuals diagnosed with HNC from 2013 to 2018 in 15 centers across France. History of tonsillectomy was defined using combined assessment of patients and rsquo; recollections and surgeons and rsquo; visualizations of tonsil area. OPC subsite-specific odds ratios (OR) of tonsillectomy were calculated using multinomial logistic regression with nonoropharyngeal HNC as reference. Results: 1045 patients were included in the study. Frequency of tonsillectomy was 19.5% in patients with tonsillar cancer (N = 85), 49.3% in BOT (N = 76), 33.8% in other oropharyngeal cancers (N = 202) and 38.0% in non-oropharyngeal HNC (N = 682). History of tonsillectomy was inversely associated with tonsillar cancer (adjusted OR 0.4; 95% CI 0.2 and ndash;0.8), and positively associated with BOT cancer (adjusted OR 1.8; 95% CI 1.1 and ndash;3.1), but was not associated with all OPC combined (adjusted OR 1.1; 95% CI 0.8 and ndash;1.4). Sensitivity analyses considering only patients and rsquo; or surgeons and rsquo; assessments of tonsillectomy provided comparable results. Conclusion: We confirm the long-term protective effect of tonsillectomy performed in youth on future risk of tonsillar cancer, and our study is the second to report a concurrent increased risk of BOT cancer. Our data suggest that tonsillectomy in youth shifts the site of the first diagnosed oropharyngeal tumor and has a limited impact on overall risk of OPC.
Published: 2021
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48. Identification of a novel CTNNA1 germline mutation predisposing to melanoma: Genotype and functional effects

Author: Thomas Roret, A. Forestier, Anne-Gaëlle Rio, Sébastien Corre, Agnès Burel, Laure Masson, Sarah Guégan, Ludivine Percevault, Lise Boussemart, Catherine Prost, Arnaud de la Fouchardière, Patrick R. Benusiglio, Sophie Fromentoux, Anthony Perrot, Siraj M. Ali, Alain Dupuy, Alexandra Lespagnol, Brigitte M Bressac-de Paillerets, David Gilot, Marie-Dominique Galibert, CHU Pontchaillou [Rennes], 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 ), 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), 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], Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Société Française de Dermatologie, Other Foundation, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1)
Subjects: Genetics, Cancer Research, business.industry, Melanoma, [SDV]Life Sciences [q-bio], Context (language use), medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Oncology, 030220 oncology & carcinogenesis, Genotype, Medicine, Identification (biology), business, ComputingMilieux_MISCELLANEOUS, 030215 immunology
Abstract: e21592 Background: While 10% of melanomas occur in a context suggesting hereditary predisposition, a clear molecular explanation has only been established for approximately 20% of families. In the course of clinical care, we identified a new CTNNA1 truncating germline mutation in a family affected by multiple early-onset melanomas. Methods: NGS and CGH-array were performed on the index case’s melanoma, followed by Sanger sequencing of the germline DNA of relatives. Immunochemistry (IHC) was employed to evaluate the level of αE-catenin (encoded by CTNNA1) in the family's samples. Stable CTNNA1 knockout human melanoma cell lines were generated to investigate the functional effects of CTNNA1 loss. Functional assays, including colony formation, 3-D tumor spheroid formation, wound healing, and transwell invasion were performed, as well as electron microscopy and RNAsequencing (RNAseq). CTNNA1 mutational status was determined in several databases and further sequencing of CTNNA1 in a DNA bank of families with multiple melanomas was done. Results: While the allele frequency in the index patient’s tumoral DNA was compatible with a germline mutation, the CTNNA1 F611fs*10 mutation was subsequently found cosegregating with individuals affected by melanoma in the family. CGH array on tumor DNA identified a segmental loss on chromosome 5, leading to a loss of heterozygosity of CTNNA1, resulting in a loss of αE-catenin observed by IHC. Clinically, the mean age of first melanoma diagnosis was 29,7 years (range: 18-56), 2 were metastatic, and the others were SSM (superficial spreading melanoma) in situ (n = 3) or Breslow index 0,56 mm (n = 1). Functional assays performed on CTNNA1 KO melanoma cell lines showed a loss of cell-to-cell adhesion phenotype, in accordance with the altered adherens junctions observed by electron microscopy, and the specific pathway enrichments observed by RNAseq. This specific phenotype could be rescued by transfection with a plasmid containing wild-type CTNNA1, as opposed to the CTNNA1 F611fs* plasmid. Germline CTNNA1 mutations are rare as none could be further identified in a DNA bank of 27 multiple melanoma families. In a database of 4743 melanomas somatically sequenced for CTNNA1, 131 of them had a CTNNA1 alteration (2,76%), with a median tumor mutational burden of 44 mut/MB of DNA (range from 0 to 451). Among them, 15 alterations were predicted to be inactivating, including 7 associated with a BRAF or NRAS activating mutation. Conclusions: Altogether, our results strongly support that CTNNA1 loss of function predisposes to melanoma formation characterized by a decreased cell adhesion. Since germline CTNNA1 alterations have already been implicated in lobular breast cancers and hereditary diffuse gastric cancers, CTNNA1 likely constitutes a tumor suppressor gene involved in familial melanoma, thus broadening the spectrum of syndromes associated with this gene.
Published: 2021
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49. Correction to: Orthotopic model of lung cancer: isolation of bone micro-metastases after tumor escape from Osimertinib treatment

Author: Ulrich Jarry, Marjorie Gournay, Laura Chaillot, Pierre Montagne, Thierry Guillaudeux, Raphael Pineau, Mégane Bostoën, Arnaud Le Goff, Rémy Pedeux, Valentine Mennessier, Emilie Motte, Biosit : biologie, santé, innovation technologique (SFR UMS CNRS 3480 - INSERM 018), 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)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Biotrial, 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), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Isolation (health care), [SDV]Life Sciences [q-bio], Bone Neoplasms, Mice, 03 medical and health sciences, 0302 clinical medicine, Surgical oncology, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Internal medicine, Genetics, medicine, Animals, Humans, Osimertinib, Lung cancer, RC254-282, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Acrylamides, Mice, Inbred BALB C, 0303 health sciences, Aniline Compounds, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Correction, medicine.disease, Xenograft Model Antitumor Assays, 3. Good health, ErbB Receptors, [SDV] Life Sciences [q-bio], Tumor Escape, Neoplasm Micrometastasis, 030220 oncology & carcinogenesis, Mutation, business
Abstract: Osimertinib is a third generation tyrosine kinase inhibitor (TKI) that targets the epidermal growth factor receptor (EGFR) in lung cancer. However, although this molecule is not subject to some of the resistance mechanisms observed in response to first generation TKIs, ultimately, patients relapse because of unknown resistance mechanisms. New relevant non-small cell lung cancer (NSCLC) mice models are therefore required to allow the analysis of these resistance mechanisms and to evaluate the efficacy of new therapeutic strategies.Briefly, PC-9 cells, previously modified for luciferase expression, were injected into the tail vein of mice. Tumor implantation and longitudinal growth, almost exclusively localized in the lung, were evaluated by bioluminescence. Once established, the tumor was treated with osimertinib until tumor escape and development of bone metastases.Micro-metastases were detected by bioluminescence and collected for further analysis.We describe an orthotopic model of NSCLC protocol that led to lung primary tumor nesting and, after osimertinib treatment, by metastases dissemination, and that allow the isolation of these small osimertinib-resistant micro-metastases. This model provides new biological tools to study tumor progression from the establishment of a lung tumor to the generation of drug-resistant micro-metastases, mimicking the natural course of the disease in human NSCLC patients.
Published: 2021
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50. Reflux of Endoplasmic Reticulum proteins to the cytosol inactivates tumor suppressors

Author: M. Aiman Mohtar, Reynald Gillet, Daniel Thomas, Pierre-Jean Le Reste, Federica G. Centonze, Sophie Chat, Ted R. Hupp, Luc Negroni, Aeid Igbaria, Raphael Pineau, Daria Sicari, Eric Chevet, 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), CHU Pontchaillou [Rennes], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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 Edinburgh, Ben-Gurion University of the Negev (BGU), This work was funded by grants from Institut National de la Santé et de la Recherche Médicale (INSERM‐U1242), Institut National du Cancer (INCa, PLBIO18, PLBIO19, PLBIO20), Fondation pour la Recherche Médicale (FRM, équipe labellisée 2018, DEQ20180339169), Agence National de la Recherche (ANR, ERANET ERAAT), MSCA RISE‐734749 (INSPIRED), Cancéropôle Grand Ouest (Gliotreat) grants to EC, the BBSRC UK (EM, BB/C511599/1, and BB/J00751X/1) and UKM Fellowship and Ministry of Higher Education (MOHE) of Malaysia KPT(BS)870809015063 (MAM). DS was supported by an AIRC #22319 fellowship for abroad., ANR-17-RAR3-0003,ERAAT,Enhancing Endoplasmic Reticulum Proteostasis to Rescue Alpha1 Antitrypsin Deficiency(2017), 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), 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), HAL UR1, Admin, and Enhancing Endoplasmic Reticulum Proteostasis to Rescue Alpha1 Antitrypsin Deficiency - - ERAAT2017 - ANR-17-RAR3-0003 - E-RARE - VALID
Subjects: AGR2, [SDV.CAN]Life Sciences [q-bio]/Cancer, Endoplasmic-reticulum-associated protein degradation, Biochemistry, Article, law.invention, 03 medical and health sciences, Mice, 0302 clinical medicine, Cytosol, [SDV.CAN] Life Sciences [q-bio]/Cancer, law, Genetics, Selective advantage, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, cancer, Translation & Protein Quality, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, 030304 developmental biology, Organelles, 0303 health sciences, Chemistry, Endoplasmic reticulum, Proteins, Endoplasmic Reticulum-Associated Degradation, Articles, ERAD, Endoplasmic Reticulum Stress, 3. Good health, Cell biology, endoplasmic reticulum, Proteostasis, Unfolded protein response, Suppressor, reflux, ER stress, 030217 neurology & neurosurgery
Abstract: In the past decades, many studies reported the presence of endoplasmic reticulum (ER)‐resident proteins in the cytosol. However, the mechanisms by which these proteins relocate and whether they exert cytosolic functions remain unknown. We find that a subset of ER luminal proteins accumulates in the cytosol of glioblastoma cells isolated from mouse and human tumors. In cultured cells, ER protein reflux to the cytosol occurs upon ER proteostasis perturbation. Using the ER luminal protein anterior gradient 2 (AGR2) as a proof of concept, we tested whether the refluxed proteins gain new functions in the cytosol. We find that refluxed, cytosolic AGR2 binds and inhibits the tumor suppressor p53. These data suggest that ER reflux constitutes an ER surveillance mechanism to relieve the ER from its contents upon stress, providing a selective advantage to tumor cells through gain‐of‐cytosolic functions—a phenomenon we name ER to Cytosol Signaling (ERCYS)., Endoplasmic Reticulum (ER) stress in cancer cells causes a subset of ER proteins to escape to the cytosol where they bind and inhibit key signaling pathways to increase cancer cell fitness.
Published: 2021
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