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43 results on '"Oncogenesis, Stress, Signaling (OSS)"'

1. Cancer de l’ovaire : la rechute précoce

Author: Franck Bonnetain, Elsa Kalbacher, Patricia Pautier, Anne Lesoin, Thibault De La Motte Rouge, Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Oncogenesis Stress Signaling ( OSS ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CRLCC Eugène Marquis ( CRLCC ), Cancéropôle du Grand Est, Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), 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]), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), and 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)
Subjects: 0301 basic medicine, Cancer Research, Cancer de l’ovaire, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, General Medicine, [ CHIM ] Chemical Sciences, 3. Good health, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, ovarian cancer, Oncology, 030220 oncology & carcinogenesis, [CHIM]Chemical Sciences, Radiology, Nuclear Medicine and imaging, Early relapse, Rechute précoce
Abstract: National audience; La rechute précoce est définie par une récidive qui survient moins de 6 mois après la dernière injection de chimiothérapie à base de platine. Elle peut être primaire ou secondaire, et après une ou plusieurs lignes de traitements avec un sel de platine. Il n’y a pas d’indication à une chirurgie carcinologique. Il est recommandé une monochimiothérapie sans platine (doxorubicine liposomale pégylée [DLP], paclitaxel hebdomadaire, topotécan ou gemcitabine) en association avec du bévacizumab si la patiente n’en a pas reçu antérieurement (niveau de preuve 1, grade A). Early relapse (primary or secondary) is defined by relapse of disease less than 6 months before the last infusion of chemotherapy (with a platinum compound). There is no carcinological surgical indication. Disease should be treated with a non-platinum single agent (pegylated liposomal doxorubicin, weekly paclitaxel, gemcitabine or topotecan). Bevacizumab can be added if patients have not already received it (level of proof 1, grade A).
Published: 2017
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2. Clinical practice guidelines from the French College of Gynecologists and Obstetricians (CNGOF): benign breast tumors–Short Text

Author: Cédric Nadeau, Cyril Touboul, Guillaume Legendre, Carole Mathelin, Françoise Beltjens, Jean-Yves Seror, Enora Laas, Xavier Fritel, Foucauld Chamming's, Catherine Uzan, Geoffroy Canlorbe, Emile Daraï, Arash Rafii, Marie-Noëlle Roedlich, Jeremy Seror, Olivier Kerdraon, Sofiane Bendifallah, Nicolas Guilhen, Martine Boisserie-Lacroix, Vincent Lavoué, Julie Demetz, Isabelle Thomassin Naggara, Charles Coutant, L. Boulanger, Sophie Catteau-Jonard, Nathalie Chabbert-Buffet, Jocelyne Chopier, Martine Antoine, Raffaèle Fauvet, Charlotte Ngo, Elisabeth Chereau, Lobna Ouldamer, Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service d'anatomie pathologique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Régional de Lutte Contre le Cancer Bergognié, Hôpital Jeanne de Flandre [Lille], Service de radiologie cardio-vasculaire [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Biologie Pathologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Gynecology and Obstetrics, Chirurgie cancérologique gynécologique et mammaire, Université Paris Descartes - Paris 5 (UPD5)-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), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Faculté de Médecine, Université de Tours, Stem cell and microenvironment laboratory, Weill Cornell Medicine [Qatar], Department Genetic Medicine, Corneil University-Weill Medical College of Cornell University [New York], Développement embryonnaire précoce humain et pluripotence EmbryoPluripotency (UMR 1203), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-CHU Montpellier, Medical Practice, Imagerie Duroc, Service de Gynécologie-Obstétrique, Centre Hospitalier Intercommunal Créteil, CHI Créteil-CHI Créteil, Service de Gynécologie et Obstétrique, CHU Pitié-Salpêtrière [AP-HP], Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT), 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 (UR)-CRLCC Eugène Marquis (CRLCC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et cytologie pathologiques [CHU Tenon], Service de Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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)-Université Paris Descartes - Paris 5 (UPD5), Brenner, Nelly, Service de Gynécologie et Obstétrique [Rennes], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes]-Hôpital Sud, Oncogenesis Stress Signaling ( OSS ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CRLCC Eugène Marquis ( CRLCC ), Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ) -Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Service de Gynécologie-Obstétrique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Département de radiologie, CHU Tenon [APHP], Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre Hospitalier Universitaire d'Angers ( CHU Angers ), PRES Université Nantes Angers Le Mans ( UNAM ), Institut de génétique et biologie moléculaire et cellulaire ( IGBMC ), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ) -AP-HP Hôpital européen Georges-Pompidou (Paris), Nutrition, croissance et cancer (U 1069) ( N2C ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Tours, CHRU Tours, Weill Cornell Medical College in Qatar, Ultrasound Department, and CHU Pitié-Salpêtrière [APHP]
Subjects: Breast biopsy, medicine.medical_specialty, Radial scar, Biopsy, Lobular carcinoma, Breast Neoplasms, Mastitis, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Breast cysts, Nipple discharge, 03 medical and health sciences, Breast Diseases, Pathological examination, 0302 clinical medicine, Phyllodes Tumor, BI-RADS classification, Breast Cyst, Ultrasound, Atypia, Nipple Discharge, Medicine, Humans, skin and connective tissue diseases, [ SDV.MHEP.GEO ] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Breast ultrasound, 030219 obstetrics & reproductive medicine, Hyperplasia, medicine.diagnostic_test, business.industry, Mammogram, Obstetrics and Gynecology, Phyllodes tumor, Calcinosis, medicine.disease, 3. Good health, Surgery, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Reproductive Medicine, 030220 oncology & carcinogenesis, Female, France, Ultrasonography, Mammary, medicine.symptom, business, Mastodynia, Mammography, Benign breast tumor
Abstract: International audience; Screening with breast ultrasound in combination with mammography is needed to investigate a clinical breast mass (Grade B), colored single-pore breast nipple discharge (Grade C), or mastitis (Grade C). The BI-RADS system is recommended for describing and classifying abnormal breast imaging findings. For a breast abscess, a percutaneous biopsy is recommended in the case of a mass or persistent symptoms (Grade C). For mastalgia, when breast imaging is normal, no MRI or breast biopsy is recommended (Grade C). Percutaneous biopsy is recommended for a BI-RADS category 4-5 mass (Grade B). For persistent erythematous nipple or atypical eczema lesions, a nipple biopsy is recommended (Grade C). For distortion and asymmetry, a vacuum core-needle biopsy is recommended due to the risk of underestimation by simple core-needle biopsy (Grade C). For BI-RADS category 4-5 microcalcifications without any ultrasound signal, a minimum 11-G vacuum core-needle biopsy is recommended (Grade B). In the absence of microcalcifications on radiography cores additional samples are recommended (Grade B). For atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, flat epithelial atypia, radial scar and mucocele with atypia, surgical excision is commonly recommended (Grade C). Expectant management is feasible after multidisciplinary consensus. For these lesions, when excision margins are not clear, no new excision is recommended except for LCIS characterized as pleomorphic or with necrosis (Grade C). For grade 1 phyllodes tumor, surgical resection with clear margins is recommended. For grade 2 phyllodes tumor, 10 mm margins are recommended (Grade C). For papillary breast lesions without atypia, complete disappearance of the radiological signal is recommended (Grade C). For papillary breast lesions with atypia, complete surgical excision is recommended (Grade C)
Published: 2016
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3. Chemotherapy with ceramide in TNBC

Author: Patrick Legembre, Bruno Ségui, Olivier Micheau, Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Lipides - Nutrition - Cancer (U866) (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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Oncogenesis Stress Signaling ( OSS ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CRLCC Eugène Marquis ( CRLCC ), Lipides - Nutrition - Cancer (U866) ( 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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), INSERM UMR 1037, CNRS ERL 505294, CRCT ( UPS ), UNIVERSITE TOULOUSE, Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cancer Research, Ceramide, [SDV]Life Sciences [q-bio], TRAIL, Biology, medicine.disease_cause, Metastasis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, metastasis, Epithelial–mesenchymal transition, Ceramide synthase, PI3K/AKT/mTOR pathway, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, sphingolipids, [ SDV ] Life Sciences [q-bio], EMT, medicine.disease, 3. Good health, Editorial, Oncology, chemistry, 030220 oncology & carcinogenesis, Immunology, Cancer cell, Cancer research, CD95, Signal transduction, Carcinogenesis
Abstract: Metastasis remains the major cause of cancer-related mortality, and currently there is a lack of therapies to eliminate this risk. Therefore, it is of crucial interest to better understand this multi-step cellular process and find the best markers to identify patients who will develop early and distant relapse. This latter objective may allow clinicians to adapt their treatments and propose combination of therapeutic drugs to patients who are at the highest risk of metastasis. CD95L belongs to the Tumor Necrosis Factor (TNF) superfamily and binds CD95 (also known as Fas). In contrast to its ubiquitously expressed receptor, CD95L exhibits a restricted expression pattern, being mainly found at the surface of activated T lymphocytes and natural killer (NK) cells where it contributes to the elimination of transformed and infected cells. Metalloproteases can cleave CD95L leading to its release in the bloodstream. While transmembrane CD95L (m-CD95L) is a potent apoptotic inducer that participates in immune surveillance and tolerance, metalloprotease-cleaved CD95L (cl-CD95L) fails to trigger apoptosis, but implements non-apoptotic signaling pathways (PI3K, K-Ras, NFkB, MAPK) promoting cell survival, proliferation and migration [1]. By doing so, CD95 behaves as an oncogene. We recently established that high concentrations of serum CD95L are present in triple negative breast cancers (TNBC). Among breast cancers, TNBCs are characterized by lack of estrogen and progesterone receptor expressions and absence of HER2 overexpression. Unlike others breast cancer categories, TNBC women do not benefit from targeted therapies and thereby, these patients relapse earlier than other breast cancer patients. Importantly, high amounts of cl-CD95L in TNBC women are associated with poor prognoses and administration of cl-CD95L in mice promotes the metastatic dissemination of TNBC cells [2]. Epithelial to mesenchymal transition (EMT) is a cellular reprogramming that plays pivotal role in embryonic development and that can be partly phenocopied in carcinogenesis, giving rise to aggressive tumors with increased metastatic capacity. EMT reprograms the apoptotic machinery in cancer cells to allow them to resist CD95-mediated cell death [3]. But not only, we recently demonstrated that EMT also enhances plasma membrane fluidity and thereby, promotes cell migration of breast cancer cells [4]. Sphingolipids (SLs) are sphingoid base-containing lipids, which are membrane components enriched in membrane microdomains, being concentrated into the outer leaflet of the plasma membrane and modulating its biochemical and biophysical properties such as membrane fluidity. EMT is associated with changes in SL metabolism, and some SL metabolites, such as gangliosides (i.e., sialic acid-containing glycosphingolipids), can affect this cellular reprograming [5]. An integrative analysis of the gene expression in NCI-60 tumor cell lines revealed that the expression level of a ceramide synthase, namely ceramide synthase-6 (CerS6) decreases during EMT. CerS6 expression level mainly regulates the amount of C16:0-ceramide in cancer cells. Interestingly, whereas reducing the amounts of C16:0- ceramide in TNBC cells by down-regulating CerS6 expression level, increased plasma membrane fluidity and promoted cell motility, exogenous addition of non-cytotoxic doses of C16:0-ceramide or over-expression of CerS6 in TNBC cells led to a stiffening of plasma membrane, abrogating both basal and cl-CD95L-mediated cell migration [4]. These findings led us to postulate that administration of low doses (that may reduce side effects for the patients) of C16:0-ceramide in combination with chemotherapy in TNBC women may apply the brake on metastatic dissemination. Like CD95L, tumor-necrosis-factor related apoptosis-inducing ligand (TRAIL) belongs to the TNF family. In line with CD95's pro-metastatic potential, DR5 (TRAIL-R2), one of the two agonistic TRAIL receptors, can promote breast cancer skeletal metastasis in a mouse xenograft model [6]. Earlier evidence already pointed to TRAIL promoting migration in TRAIL-resistant colon carcinomas [7]. More recently, it has been reported that DR5 displays pro-metastatic activity in KRAS derived non-small-cell lung cancers and pancreatic ductal adenocarcinoma (PDAC), and high expression levels of DR5 are correlated with increased invasion and reduced metastasis-free survival in KRAS mutated patients suffering from PDAC or colorectal cancer, respectively [8]. Although, regulation of SL membrane composition induced by TRAIL, is mostly ascribed to its pro-apoptotic potential, changes in SL content are also likely to contribute to regulation of DR5 pro-metastatic potential. This growing body of evidence put forward that like TNF-R, CD95 and DR5 might correspond to pro-inflammatory receptors modulating the quantity and composition of SLs in cancer cells to affect the biophysical properties of their plasma membrane. These observations raise now the question of how the so-called “death receptors” can affect the SL metabolism to enhance cancer cell migration. Identification of the molecular mechanism linking these receptors to SL metabolism is likely to reveal new therapeutic options and targets to prevent tumor dissemination in cancers.
Published: 2015
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4. 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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5. 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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6. 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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7. 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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8. 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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9. Place of anti-EGFR therapy in older patients with metastatic colorectal cancer in 2020

Author: Marine Gilabert, Frédérique Rousseau, Astrid Lièvre, Brice Chanez, Simon Triby, Pauline Ries, Eric Francois, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Amgen Inc., Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Les Laboratories Pierre Fabre, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), 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), and CCSD, Accord Elsevier
Subjects: medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Older patients, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, 030212 general & internal medicine, Epidermal growth factor receptor, Contraindication, Aged, Anti-EGFR, Chemotherapy, biology, Rectal Neoplasms, business.industry, Metastatic colorectal cancer, Antibodies, Monoclonal, medicine.disease, 3. Good health, Clinical trial, Regimen, Oncology, Treatment dose, 030220 oncology & carcinogenesis, Colonic Neoplasms, biology.protein, Geriatrics and Gerontology, Colorectal Neoplasms, business
Abstract: International audience; Almost half of the new cases of colorectal cancer concern patients aged ≥70 years. However, very few clinical trials have specifically included older patients. As a consequence, the treatment of these patients is controversial because the balance between clinical benefits and toxicities remains uncertain. In patients without comorbidities and with an ECOG performance score of 0-1, treatment indications are similar to those of younger patients. For frail patients, chemotherapy is possible, but a comprehensive geriatric assessment is recommended. Anti-EGFR (epidermal growth factor receptor) therapy is indicated either in combination with chemotherapy in the first-line or second-line setting or as monotherapy in the third-line setting (i.e., after failure of chemotherapy). For fit older patients, clinical trials that compared chemotherapy alone with doublet chemotherapy plus anti-EGFR in either first-line or second-line setting suggested that age is not an absolute contraindication for the use of this regimen. In frail patients, anti-EGFR monotherapy in the first-line, second-line or third-line setting has shown feasibility and antitumor activity and had mainly cutaneous toxicities that were easily managed. In any case, administration of treatment must be very cautious in older patients and the treatment dose needs to be adapted according to comorbidities.
Published: 2020
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10. Outcomes of Patients With Advanced NSCLC From the Intergroupe Francophone de Cancérologie Thoracique Biomarkers France Study by KRAS Mutation Subtypes

Author: Fabrice Barlesi, H. Janicot, Pierre-Jean Souquet, Didier Debieuvre, Michel Poudenx, Virginie Westeel, Julien Mazieres, Michèle Beau-Faller, M. Wislez, Isabelle Monnet, Fabienne Escande, Pierre-Paul Bringuier, L'Houcine Ouafik, Pascal Foucher, Alexandra Langlais, Isabelle Rouquette, Jean-Philippe Merlio, Antoinette Lemoine, Anne-Marie Ruppert, Franck Morin, Charles Ricordel, Groupe de recherche clinique Biomarqueurs Théranostiques des Cancers Bronchiques Non à Petites Cellules (GRC 4 - Theranoscan), Sorbonne Université (SU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Biochimie et Biologie Moléculaire [Strasbourg] (HUS), Les Hôpitaux Universitaires de Strasbourg (HUS), Univ Strasbourg, INSERM, IRFAC, UMR S1113, F-67200 Strasbourg, France, Groupe hospitalier de la région de Mulhouse Sud-Alsace (GHRMSA), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Transfert d'Oncologie Biologique [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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 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), Service Pneumologie-Allergologie [CHU Toulouse], Pôle Clinique des Voies respiratoires [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL), Centre Hospitalier Intercommunal de Créteil (CHIC), Laboratoire de Biochimie et Biologie Moléculaire [CHRU Lille] (Pôle de Biologie Pathologie Génétique), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Rennes (CHU Rennes), INSERM U1053, Université Bordeaux, Bordeaux, France., Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, INSERM UMR S1193, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Service de pneumologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (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), AstraZeneca, Roche, 2011-038, Institut National Du Cancer, France, Novartis, France, Ouafik, L'Houcine, Theranoscan [CHU Tenon] (GRC 4), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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 Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité pneumologie et oncologie thoracique [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pneumologie [CHU Toulouse], Groupement hospitalier lyon Est (Hospices Civils de Lyon), INSERM U1242, Université Rennes 1, and 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)
Subjects: Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, endocrine system diseases, [SDV.CAN]Life Sciences [q-bio]/Cancer, medicine.disease_cause, NSCLC, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Non-small cell lung cancer, Internal medicine, medicine, Overall survival, Non–small cell lung cancer, Stage (cooking), neoplasms, 030304 developmental biology, 0303 health sciences, Mutation, Transition (genetics), business.industry, KRAS mutation, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, Confidence interval, digestive system diseases, 3. Good health, respiratory tract diseases, 030220 oncology & carcinogenesis, Adenocarcinoma, Original Article, KRAS, business, Kras mutation
Abstract: Introduction KRAS mutations are detected in 20% to 30% of NSCLC. However, KRAS mutation subtypes may differently influence the outcome of patients with advanced NSCLC. Methods In the Biomarkers France study, 4894 KRAS mutations (26.2%) were detected in 4634 patients from the 17,664 enrolled patients with NSCLC. Survival and treatment data on noncurative stage III to IV NSCLC were available for 901 patients. First- and second-line treatment effects on progression-free survival and overall survival were analyzed according to the KRAS mutations subtype. Results Over 95% of patients with KRAS mutation were smokers or former smokers who were white (99.5%), presenting with adenocarcinoma (82.5%). The most common KRAS mutation subtype was G12C (374 patients; 41.5%), followed by G12V (168; 18.6%), G12D (131; 14.5%), G12A (62; 6.9%), G13C (45; 5.0%), G13D (31; 3.4%), and others (10; 1%). Approximately 21% of patients had transition mutation and 68.2% had a transversion mutation. G12D and transition mutations were predominant in never-smokers. The median overall survival for patients with KRAS-mutated NSCLC was 8.1 months (95% confidence interval [CI]: 7.5–9.5), without any differences according to the different KRAS subtypes mutations. The median progression-free survival was 4.6 months (95% CI: 4.2–5.1) for first-line treatment and 4.8 months (95% CI: 4.3–6.8) for second-line treatment, without any differences according to the different KRAS subtypes mutations. Conclusions KRAS mutation subtypes influenced neither treatment responses nor outcomes. The KRAS G12C mutation was detected in 41.5% of patients, who are now eligible for potent and specific G12C inhibitors.
Published: 2020
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11. Surgery in reference centers improves survival of sarcoma patients: a nationwide study

Author: A. Giraud, P. Soibinet, Sébastien Carrère, E. Stoeckle, G. Vaz, J. Guiramand, J.-C. Ruzic, A. Dufresne, Jean-Yves Blay, F. Gouin, A. Rochwerger, F. Duffaud, A. Le Cesne, Francis Guillemin, J.-P. Spano, M. Rios, P. Meeus, Isabelle Ray-Coquard, A. Di Marco, G. Ferron, François Bertucci, François Sirveaux, N. Firmin, F. Fiorenza, O. Collard, S. Bonvalot, Emmanuelle Bompas, S. Causeret, P. Anract, M. Jafari, D. Pérol, J.-C. Machiavello, O. Marco, F. Ducimetière, C. Honore, A. Italiano, A. Michot, M. Karanian-Philippe, Nicolas Penel, P. Gimbergues, Mickaël Ropars, M. Toulmonde, F. Marchal, M. Brahmi, C. Le Pechoux, L.R. Le Nail, C. Perrin, F. Le Loarer, C. Chevreau, A. Dupré, J.-M. Guilloit, L. Chaigneau, F. Dujardin, Department of Medical Oncology [Lyon], Centre Léon Bérard [Lyon], Institut de Cancérologie Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Département de Chirurgie cancérologique, Institut Gustave Roussy (IGR), Département d'oncologie médicale, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), Service d’Oncologie Médicale [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pontchaillou [Rennes], Centre Eugène Marquis (CRLCC), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Paul Strauss, CRLCC Paul Strauss, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de chirurgie [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Department of Surgical Oncology, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Jean Godinot [Reims], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Claudius Regaud, Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de radiothérapie [Gustave Roussy], Centre de Recherches sur les Macromolécules Végétales (CERMAV ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire Interdisciplinaire de Recherche Impliquant la Géologie et la Mécanique, Université Joseph Fourier - Grenoble 1 (UJF), Institut Curie [Paris], NetSARC, INCa & DGOS, RREPS, RESOS (INCa & DGOS) and LYRICAN, Association DAM’s, Ensemble contre Le GIST, FP7-278742, Eurosarc, ANR-10-LABX-0061, la Fondation ARC, Infosarcome, Ligue de L’Ain contre le Cancer, La Ligue contre le Cancer, EC 739521, EURACAN, ANR-10-LABX-0061,DEVWECAN,Development Cancer and Targeted Therapies(2010), CHU Saint-Etienne, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-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)-CRLCC Eugène Marquis (CRLCC), Laboratoire des Mécanismes et Transfert en Géologie (LMTG), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Université Lille Nord de France (COMUE)-UNICANCER, Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Université de Lille, Université Claude Bernard Lyon 1 [UCBL], METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, Institut Gustave Roussy [IGR], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Hôpital Cochin [AP-HP], Hôpital de la Timone [CHU - APHM] [TIMONE], Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] [UNICANCER/ICL], CHU Strasbourg, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] [UNICANCER/CRLCC-CGFL], Centre Jean Perrin [Clermont-Ferrand] [UNICANCER/CJP], Centre Hospitalier Régional Universitaire de Besançon [CHRU Besançon], CRLCC Jean Godinot, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] [UNICANCER/CRLC], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen [CLCC Henri Becquerel], Centre Hospitalier Universitaire de La Réunion [CHU La Réunion], and Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Subjects: 0301 basic medicine, Male, Multivariate analysis, sarcoma, medicine.medical_treatment, [SDV]Life Sciences [q-bio], surgery, 0302 clinical medicine, Prospective Studies, Registries, resection, Referral and Consultation, Aged, 80 and over, relapse, Hazard ratio, Hematology, Middle Aged, Prognosis, Corrigenda, 3. Good health, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Surgical Procedures, Operative, Female, Sarcoma, France, Adult, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, reference center, Relapse free survival, survival, 03 medical and health sciences, Young Adult, medicine, Humans, Neurofibromatosis, Pathological, Aged, business.industry, Cancer, Original Articles, medicine.disease, Surgery, Radiation therapy, Editor's Choice, 030104 developmental biology, Neoplasm Recurrence, Local, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: International audience; BackgroundNETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry.Patients and methodsPatients’ characteristics and follow-up are prospectively collected and data monitored. Descriptive, uni- and multivariate analysis of prognostic factors were conducted in the entire series (N = 35 784) and in the subgroup of incident patient population (N = 29 497).ResultsAmong the 35 784 patients, 155 different histological subtypes were reported. 4310 (11.6%) patients were metastatic at diagnosis. Previous cancer, previous radiotherapy, neurofibromatosis type 1 (NF1), and Li–Fraumeni syndrome were reported in 12.5%, 3.6%, 0.7%, and 0.1% of patients respectively. Among the 29 497 incident patients, 25 851 (87.6%) patients had surgical removal of the sarcoma, including 9949 (33.7%) operated in a NETSARC center. Location, grade, age, size, depth, histotypes, gender, NF1, and surgery outside a NETSARC center all correlated to overall survival (OS), local relapse free survival (LRFS), and event-free survival (EFS) in the incident patient population. NF1 history was one of the strongest adverse prognostic factors for LRFS, EFS, and OS. Presentation to an MDTB was associated with an improved LRFS and EFS, but was an adverse prognostic factor for OS if surgery was not carried out in a reference center. In multivariate analysis, surgery in a NETSARC center was positively correlated with LRFS, EFS, and OS [P
Published: 2019
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12. Role of the unfolded protein response in tumor cell characteristics and cancer outcome

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

Author: Emile Daraï, Gilles Body, Vincent Lavoué, Sofiane Bendifallah, Marcos Ballester, Lobna Ouldamer, Pierre Collinet, Emilie Raimond, Jean Lévêque, Charles Coutant, Olivier Graesslin, Cyril Touboul, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Epidemiologie, Systèmes d'information, Modélisation, Institut National de la Santé et de la Recherche Médicale (INSERM), Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Expert en Endométriose [CHU Tenon] (GRC6 C3E), Institut Mère Enfant Alix de Champagne, Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CHU Pontchaillou [Rennes], Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe de recherche clinique Centre Expert en Endométriose (GRC 6 - C3E), Sorbonne Université (SU), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
Subjects: 0301 basic medicine, Oncology, Risk, Cancer Research, medicine.medical_specialty, recurrence, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, nomogram, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, medicine, metastasis, Humans, 10. No inequality, Retrospective Studies, Receiver operating characteristic, Proportional hazards model, business.industry, Endometrial cancer, peritoneal carcinomatosis, Retrospective cohort study, Nomogram, medicine.disease, Prognosis, Confidence interval, Endometrial Neoplasms, Nomograms, 030104 developmental biology, 030220 oncology & carcinogenesis, endometrial cancer, Clinical Study, Lymphadenectomy, Female, business
Abstract: International audience; Background - The purpose of this study was to develop a nomogram to predict 'poor prognosis recurrence' (PPR) in women treated for endometrial cancer (EC). Methods - The data of 861 women who received primary surgical treatment between January 2001 and December 2013 were abstracted from a prospective multicenter database. Data were randomly split into two sets: training and validation with a predefined 2/3 ratio. A Cox proportional hazards multivariate model of selected prognostic features was performed in the training cohort (n=574) to develop a nomogram predicting PPRs. The nomogram was validated in the validation cohort of 287 patients. Results - In the training cohort, 82 (14.3%) developed subsequent PPR. Age, histologic type and grade, lymphovascular space invasion status, FIGO stage, and nodal staging (SLN±pelvic and/or para-aortic lymphadenectomy) were independently associated with subsequent PPR. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.82 (95% confidence interval (CI), 0.73-0.89) in the training set. The validation set showed a good discrimination with an AUC of 0.75 (95% CI, 0.65-0.83). Conclusions - We have developed a robust tool that is able to predict subsequent PPRs in women with FIGO I-III EC.
Published: 2016
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14. Impact of age on surgical staging and approaches (laparotomy, laparoscopy and robotic surgery) in endometrial cancer management

Author: Jérémy Lévêque, G. Houvenaeghel, F. Foucher, C. Bourgin, Vincent Lavoué, Eric Lambaudie, CHU Pontchaillou [Rennes], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Laboratoire Pluridisciplinaire de Recherche en Ingénierie des Systèmes, Mécanique et Energétique (PRISME), Ecole Nationale Supérieure d'Ingénieurs de Bourges (ENSI Bourges)-Université d'Orléans (UO), Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Acknowlegments are due to Estelle Bauville as surgeons of patients and to Tracey Wescott for editing the draft. VL obtains funding from La Vannetaise., Université d'Orléans (UO)-Ecole Nationale Supérieure d'Ingénieurs de Bourges (ENSI Bourges), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
Subjects: medicine.medical_treatment, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 0302 clinical medicine, Postoperative Complications, Robotic Surgical Procedures, Laparotomy, Hysterectomy, Vaginal, Medicine, Laparoscopy, Aged, 80 and over, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, Age Factors, General Medicine, Middle Aged, 3. Good health, Oncology, 030220 oncology & carcinogenesis, endometrial cancer, Female, Adult, medicine.medical_specialty, Ovariectomy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Surgical staging, Hysterectomy, elderly, 03 medical and health sciences, Salpingectomy, Young Adult, Humans, Minimally Invasive Surgical Procedures, Robotic surgery, Aged, Neoplasm Staging, Retrospective Studies, surgical approach, business.industry, General surgery, Endometrial cancer, Cancer, Retrospective cohort study, Perioperative, Length of Stay, medicine.disease, surgical staging, Surgery, Endometrial Neoplasms, Lymph Node Excision, business
Abstract: International audience; Objective: This study aims to evaluate the different surgical approaches, perioperative morbidity and surgical staging according to age in patients with endometrial cancer. Methods: Multicentre retrospective study. Cancer characteristics and perioperative data were collected for patients surgically treated for endometrial cancer. The patients were divided into 2 groups according to their age: younger or older than 75 years. Results: Surgery was performed on 270 women = 75 years old. Minimally invasive surgery was performed less often in the elderly compared with their younger counterparts (58.2% vs. 74.8%; p = 0.006). Independently of the surgical approach, the rate of pelvic and para-aortic lymphadenectomy was lower in women older than 75 years old than their younger counterparts (52.7% vs. 74.8%; p < 0.001; 8.1% vs. 21.8%; p = 0.007 respectively). According to the guidelines, more frequent surgical understaging was seen in the elderly compared with the younger (37% vs. 15.2%; p = 0.002). In the comparison of complications for each surgical approach, there was no statistical difference in the >= 75-year-old age group in terms of intra- or postoperative complications between the laparotomy, laparoscopy or robotic surgery group. We found a shorter length of hospital stay for the women who underwent laparoscopy or robotic surgery compared with laparotomy (p < 0.0001). Conclusion: Elderly women with endometrial cancer are often surgically understaged whereas there is no evidence of greater perioperative complications than for their younger counterparts. They should benefit from minimally invasive surgery and optimal surgical staging to the same extent as younger women. (C) 2016 Elsevier Ltd, BASO - The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
Published: 2017
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15. T cell landscape in triple negative breast cancer patients

Author: Patrick Legembre, Amanda Poissonnier, M. Le Gallo, Florence Godey, Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
Subjects: Oncology, medicine.medical_specialty, business.industry, T cell, health care facilities, manpower, and services, education, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Internal medicine, Medicine, Surgery, 030212 general & internal medicine, business, skin and connective tissue diseases, Triple-negative breast cancer, health care economics and organizations
Abstract: International audience; 15th St.Gallen International Breast Cancer Conference - P228
Published: 2017
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16. Correction to: Surgery in reference centers improves survival of sarcoma patients: a nationwide study

Author: M. Karanian-Philippe, Isabelle Ray-Coquard, A. Di Marco, J.-M. Guilloit, C. Perrin, M. Toulmonde, J.-P. Spano, G. Ferron, C. Le Pechoux, O. Collard, M. Rios, François Sirveaux, J. Guiramand, A. Dufresne, L. Chaigneau, C. Chevreau, S. Causeret, P. Gimbergues, L.R. Le Nail, M. Jafari, J.-C. Ruzic, O. Marco, F. Gouin, G. Vaz, A. Dupré, P. Anract, E. Stoeckle, A. Michot, F. Dujardin, Jean-Yves Blay, Emmanuelle Bompas, F. Guillemin, C. Honore, F. Duffaud, P. Meeus, A. Rochwerger, Nicolas Penel, F. Fiorenza, F. Le Loarer, S. Bonvalot, Mickaël Ropars, A. Le Cesne, F. Ducimetière, D. Pérol, A. Italiano, F. Marchal, P. Soibinet, Sébastien Carrère, J.-C. Machiavello, A. Giraud, François Bertucci, N. Firmin, M. Brahmi, AIRPARIF - Surveillance de la qualité de l'air en Île-de-France, Institut Bergonié - CRLCC Bordeaux, Centre Léon Bérard [Lyon], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique (LHEEA), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Centre chirurgical Émile-Gallé, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Department of Surgical Oncology, Jean Perrin Comprehensive Cancer Centre, Service de Chirurgie orthopédique et traumatologique [CHU Limoges], CHU Limoges, Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes (LCP-A2MC), CHU Pitié-Salpêtrière [APHP], Institut Claudius Regaud, CRLCC Institut Claudius Regaud, Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR), Centre de Recherches sur les Macromolécules Végétales (CERMAV), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire Interdisciplinaire de Recherche Impliquant la Géologie et la Mécanique, Université Joseph Fourier - Grenoble 1 (UJF), Centre Oscar Lambret, Laboratoire des Mécanismes et Transfert en Géologie (LMTG), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, medicine.medical_specialty, Multivariate analysis, [SDV]Life Sciences [q-bio], medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Relapse free survival, 03 medical and health sciences, 0302 clinical medicine, medicine, Neurofibromatosis, Pathological, ComputingMilieux_MISCELLANEOUS, business.industry, Hazard ratio, Cancer, Hematology, medicine.disease, 3. Good health, Surgery, Radiation therapy, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Sarcoma, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background NETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry. Patients and methods Patients’ characteristics and follow-up are prospectively collected and data monitored. Descriptive, uni- and multivariate analysis of prognostic factors were conducted in the entire series (N = 35 784) and in the subgroup of incident patient population (N = 29 497). Results Among the 35 784 patients, 155 different histological subtypes were reported. 4310 (11.6%) patients were metastatic at diagnosis. Previous cancer, previous radiotherapy, neurofibromatosis type 1 (NF1), and Li–Fraumeni syndrome were reported in 12.5%, 3.6%, 0.7%, and 0.1% of patients respectively. Among the 29 497 incident patients, 25 851 (87.6%) patients had surgical removal of the sarcoma, including 9949 (33.7%) operated in a NETSARC center. Location, grade, age, size, depth, histotypes, gender, NF1, and surgery outside a NETSARC center all correlated to overall survival (OS), local relapse free survival (LRFS), and event-free survival (EFS) in the incident patient population. NF1 history was one of the strongest adverse prognostic factors for LRFS, EFS, and OS. Presentation to an MDTB was associated with an improved LRFS and EFS, but was an adverse prognostic factor for OS if surgery was not carried out in a reference center. In multivariate analysis, surgery in a NETSARC center was positively correlated with LRFS, EFS, and OS [P
Published: 2019
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17. Les nouveaux profils moléculaires dans le cancer de l’ovaire peuvent-ils modifier les stratégies thérapeutiques ? [Can new molecular profiles in epithelial ovarian cancer modify therapeutics?]

Author: Jean Levêque, F. Foucher, M. Pinsard, Sébastien Henno, Sophie Delplanque, Vincent Lavoué, A. Rousselin, T. de la Motte Rouge, Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), CHU Pontchaillou [Rennes], CRLCC Eugène Marquis (CRLCC), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
Subjects: 0301 basic medicine, endocrine system diseases, DNA repair, Cancer de l’ovaire, [SDV.CAN]Life Sciences [q-bio]/Cancer, Therapeutics, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, medicine.disease_cause, thérapies ciblées, 03 medical and health sciences, 0302 clinical medicine, Medicine, Gene, Mutation, molecular classification, classifications moléculaires, business.industry, BRCA mutation, Obstetrics and Gynecology, medicine.disease, female genital diseases and pregnancy complications, 3. Good health, Serous fluid, 030104 developmental biology, ovarian cancer, Reproductive Medicine, 030220 oncology & carcinogenesis, Cancer research, business, Homologous recombination, Ovarian cancer, Carcinogenesis
Abstract: National audience; Epithelial ovarian cancer (EOC) affects 4500 women a year in France, with a survival of 30% at 5 years. Treatment is based on extensive surgery and chemotherapy. Around 15% of EOCs are due to genetic mutation predisposition essentially with mutated BRCA1 and BRCA2 genes. Four histological subtypes are described (serous, endometrioid, and mucinous cells to clear), corresponding to different carcinogenesis and distinct molecular mutations. High-grade serous EOCs have a mutation of the BRCA genes in 20-30% of cases. This mutation causes a deficit of repair by homologous recombination of DNA in case of double strand break, allowing greater sensitivity to platinum salts and the use of PARP inhibitors, a protein involved in the repair of single-strand breaks of DNA. PARP inhibitors have shown efficacy in patients mutated BRCA but this effectiveness remains to be demonstrated in patients without congenital mutation, but with acquired BRCAness profile EOC. The BRCAness profile is defined by a tumor having a defect in DNA repair counterpart (not limited to BRCA mutation). Molecular definition of BRCAness is still not consensual but is necessary for the use of PARP inhibitors. Gene expression analyses have identified four subgroups of high-grade serous CEO: mesenchymal, proliferative, differentiated and immunoreactive. These four subtypes, not mutually exclusive, although correlated with prognosis, are not yet used in clinical routine.
Published: 2017
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18. Call for Surgical Nodal Staging in Women with ESMO/ESGO/ESTRO High-Intermediate Risk Endometrial Cancer: A Multicentre Cohort Analysis from the FRANCOGYN Study Group

Author: Vincent Lavoué, Emile Daraï, Lobna Ouldamer, Marcos Ballester, Geoffroy Canlorbe, Sofiane Bendifallah, Emilie Raimond, Jérémy Lévêque, Charles Coutant, Gilles Body, Cyril Touboul, Olivier Graesslin, Pierre Collinet, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Epidemiologie, Systèmes d'information, Modélisation, Institut National de la Santé et de la Recherche Médicale (INSERM), Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Expert en Endométriose [CHU Tenon] (GRC6 C3E), Pathologies biliaires, fibrose et cancer du foie, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Institut Mère Enfant Alix de Champagne, Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CHU Pontchaillou [Rennes], Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe de recherche clinique Centre Expert en Endométriose (GRC 6 - C3E), Sorbonne Université (SU), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
Subjects: Adult, Oncology, medicine.medical_specialty, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Medical Oncology, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Surgical oncology, Internal medicine, medicine, Humans, Neoplasm Invasiveness, Prospective Studies, Prospective cohort study, Lymph node, Survival rate, Societies, Medical, Aged, Neoplasm Staging, Aged, 80 and over, Gynecology, 030219 obstetrics & reproductive medicine, Sentinel Lymph Node Biopsy, business.industry, Endometrial cancer, Middle Aged, medicine.disease, Endometrial Neoplasms, 3. Good health, Survival Rate, Radiation therapy, medicine.anatomical_structure, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Lymph Node Excision, Female, Surgery, Lymphadenectomy, Neoplasm Recurrence, Local, business, Follow-Up Studies, Cohort study
Abstract: International audience; Background - The European Society of Medical Oncology (ESMO)/European Society of Gynaecological Oncology (ESGO)/European Society for Radiotherapy & Oncology (ESTRO) classification for endometrial cancer (EC) now includes a high-intermediate risk (HIR) group of recurrence due to the adverse prognostic role of lymphovascular space involvement (LVSI) and grade 3 for women at intermediate risk. However, optimal surgical staging, and especially the place of lymphadenectomy, remains to be elucidated. We aimed to establish whether systematic nodal staging should be part of surgical staging for women with HIR EC. Methods - We abstracted from a prospectively maintained multicentre database the data of 181 women with HIR EC based on uterine factors (endometrioid type 1, grade 1-2 tumors with deep (≥50%) myometrial invasion and unequivocally positive LVSI, and those with grade 3 tumors with
Published: 2017
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19. Application des recommandations dans la prise en charge du cancer de l’endomètre en pratique clinique. Étude rétrospective bretonne

Author: O. De Kerdaniel, N. Body, E. Davoine, F. Foucher, S. Henno, A. Tavenard, B. Laviolle, C. Rozel, M. Leblanc, V. Lavoué, J. Levêque, CHU Pontchaillou [Rennes], Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Sentinel lymph node, Risk classification, 03 medical and health sciences, 0302 clinical medicine, medicine, Gynecology, 030219 obstetrics & reproductive medicine, Hysterectomy, business.industry, Endometrial cancer, Obstetrics and Gynecology, Cancer, General Medicine, Pathological analysis, medicine.disease, ésCancer de l’endomètre, Stratification du risque, 3. Good health, Reproductive Medicine, Anatomopathologie, 030220 oncology & carcinogenesis, Risk stratification, endometrial cancer, business, IRM, MRI
Abstract: Objectif : Evaluer l’application des recommandations de l’Institut national du cancer concernant la prise en charge diagnostique et therapeutique du cancer de l’endometre. Methodes Etude retrospective observationnelle portant sur 137 patientes traitees pour un cancer de l’endometre entre 2011 et 2013. Resultats : Le bilan preoperatoire etait conforme aux recommandations dans 66,4 % des cas et sous-estimait le risque d’envahissement ganglionnaire dans 44,9 % des cas. La sous-estimation du risque sur le bilan preoperatoire entrainait une sous-stadification chirurgicale dans 26,3 % des cas. Conclusion Pour ameliorer la pertinence du bilan preoperatoire dans le cancer de l’endometre, une expertise radiologique et anatomopathologique est necessaire sur le meme modele que ce qui est reclame pour la prise en charge chirurgicale. Cependant, meme realisee de maniere optimale, l’evaluation preoperatoire peine a proposer une stratification du risque d’envahissement ganglionnaire satisfaisante dans le cancer de l’endometre poussant a modifier les prises en charge chirurgicales recommandees en associant par exemple le prelevement du ganglion sentinelle en association a l’hysterectomie dans les cancers de l’endometre estimes a bas risque. [Objective: To assess the use of French Cancer Institute recommendations for the diagnosis and treatment of endometrial cancer. Methods Retrospective observational study involving 137 patients with endometrial cancer between 2011 and 2013. Results: Both MRI and pathological assessment with correct report as recommended were used for 66.4% of patients with endometrial cancer. For patients with correct preoperative assessment, 44.9% of patients were uncorrectly classified and upgraded on final pathological analysis of hysterectomy concerning lymph node involvement risk. These patients did not have confident surgical assessment, according this risk. Conclusion To improve relevance of preoperative assessment in endometrial cancer, radiological and pathological expertise is required. However, even performed optimally, preoperative assessment does not allow correct risk stratification of lymph node involvement in endometrial cancer. This ineffective stratification leads to propose sentinel lymph node biopsy with hysterectomy in case of preoperative low risk endometrial cancer assessment]
Published: 2016
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20. Uterus transplantation in France: for which patients?

Author: Marie Essig, Aubert Agostini, Olivier Garbin, N. Pichon, Vincent Lavoué, Antoine Tardieu, J. F. Therme, P. Piver, Jean-Marc Ayoubi, T. Gauthier, S. Huet, Y. Aubard, Alessandro Piccardo, Matthieu Filloux, Pierre Collinet, Laboratoire d'ingénierie pour les systèmes complexes (UR LISC), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Protéines : biochimie structurale et fonctionnelle (PBSF), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Coordination des Prélèvements d’Organes et de Tissus (CHPOT), CHU Limoges, Service de Gynécologie-Obstétrique [CHU Limoges], Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Dipartimento di Matematica e Fisica, Università degli Studi Roma Tre = Roma Tre University (ROMA TRE), CHU Pontchaillou [Rennes], Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Limoges Universitary Hospital, French association MRKH, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Università degli Studi Roma Tre, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)
Subjects: Adult, Infertility, medicine.medical_specialty, medicine.medical_treatment, [SHS.PSY]Humanities and Social Sciences/Psychology, Uterine Agenesis, 03 medical and health sciences, 0302 clinical medicine, Complete androgen insensitivity syndrome, Uterus transplantation, medicine, Humans, Gynecology, 030219 obstetrics & reproductive medicine, Hysterectomy, Marital Status, business.industry, Patient Selection, Uterus, Obstetrics and Gynecology, medicine.disease, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, 3. Good health, Clinical trial, Transplantation, Treatment Outcome, Reproductive Medicine, quality, Urogenital Abnormalities, 030220 oncology & carcinogenesis, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Etiology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business, Infertility, Female
Abstract: International audience; Objective - Uterine infertility (UI), which can be caused by a variety of congenital or acquired factors, affects several thousand women in Europe. Uterus transplantation (UTx), at the current stage of research, offers hope for these women to be both the biological mother and the carrier of their child. However, the indications of UTx still need to be defined. The main aim of the study was to describe the different etiologies of UI and other data as marital and parental status from women requesting UTx who contacted us in the framework of a UTx clinical trial. Secondarily, we discussed the potential indications of UTx and their feasibility. Study design - This is an observational study. Results - Of a total of 139 patients with UI, 105 patients (75.5%) had uterine agenesis, making it the leading cause of UI in this sample. Among the patients with uterine agenesis, 25% had a solitary kidney and 44.7% had undergone vaginal reconstruction. Peripartum hysterectomy, hysterectomy for cancer, and hysterectomy for benign pathologies accounted for 9.4%, 7.2% and 5% of cases, respectively. Less common causes of UI included complete androgen insensitivity syndrome (2.2% of patients) and prenatal diethylstilbestrol exposure (0.7%). Approximately 14% of the women already had at least one child and 66% were in a couple living together for at least 2 years. Conclusion - UTx is still under evaluation and further research is under way. Nulliparous patients with no major medical or surgical history and with normal ovarian function, who meet the legal criteria for medically assisted reproduction, represent the best indications for UTx at this stage of its development.
Published: 2016
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21. Pre- and per-treatment 18F-FDG PET/CT parameters to predict recurrence and survival in cervical cancer

Author: Joël Castelli, Vincent Lavoue, Geoffrey Roman-Jimenez, D. Williaume, Renaud de Crevoisier, Pierre Terve, Anne Devillers, Julie Leseur, Juan D. Ospina-Arango, Etienne Garin, Florence Lejeune, Oscar Acosta, CRLCC Eugène Marquis (CRLCC), Département de médecine nucléaire [Rennes], 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), Keosys, Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], Oncogenesis Stress Signaling (OSS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de médecine nucléaire [Rennes], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR)
Subjects: Multivariate analysis, medicine.medical_treatment, Uterine Cervical Neoplasms, Kaplan-Meier Estimate, carcinoma, 030218 nuclear medicine & medical imaging, 0302 clinical medicine, Positron Emission Tomography Computed Tomography, Prospective Studies, Neoplasm Metastasis, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Cervical cancer, fdg-pet, medicine.diagnostic_test, radiation-therapy, Chemoradiotherapy, Hematology, Middle Aged, Prognosis, Tumor Burden, 3. Good health, metabolic-response, Oncology, Positron emission tomography, 030220 oncology & carcinogenesis, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Glycolysis, Adult, prognostic-significance, Standardized uptake value, positron-emission-tomography, 03 medical and health sciences, Fluorodeoxyglucose F18, medicine, Carcinoma, Humans, Radiology, Nuclear Medicine and imaging, mri, radiotherapy, Aged, Neoplasm Staging, Proportional hazards model, business.industry, medicine.disease, Radiation therapy, tumor volume, Concomitant, standardized uptake value, Neoplasm Recurrence, Local, Nuclear medicine, business, Follow-Up Studies
Abstract: Purpose To describe the evolution and to assess the predictive value of metabolic parameters with different SUV threshold segmentations calculated from two 18F-FDG-PET/CT, one prior to and the other one during concomitant chemoradiation therapy (CCRT), for locally-advanced cervical cancer (LACC). Material and methods 53 patients treated for LACC by CCRT underwent FDG-PET/CT before treatment (PET1) and another one at 40Gy (PET2). The PET analyzed parameters were: maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). MTVs were automatically segmented using various percentage SUVmax thresholds (30–70%) and fixed SUV thresholds (all voxels with SUV >1–20). The parameters' predictive capabilities for disease-free (DFS) and overall survival (OS) were assessed using the Harrell's C-index ( c ) and Cox regression model. Results Depending on the SUVmax threshold, the relative decreases in MTV and TLG from PET1 to PET2 were, on average, 65% (range: 63–70%) and 85% (range: 83–86%), respectively. The strongest predictive threshold segmentations were 55% SUVmax in PET1 and 32% in PET2. Significant predictors of DFS in multivariate analysis ( c =0.82) were MTV1 (55% SUVmax) in PET1 and TLG2 (32% SUVmax) in PET2. MTV1 (55%) was the most significant OS predictor. Conclusions MTV and TLG calculated with a threshold of 55% SUVmax and 32% SUVmax from pre- and per-treatment PET scans respectively, can be used to predict patient outcome after CCRT for LACC.
Published: 2016
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22. Atypical epithelial hyperplasia of the breast: state of the art

Author: Susie Brousse, Aurélie Cauchois, Charles Coutant, Jean Levêque, Adelaïde Racin, Ludivine Dion, Vincent Lavoué, Françoise Beltjens, CHU Pontchaillou [Rennes], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)
Subjects: Risk, Pathology, medicine.medical_specialty, surgical excision, Biopsy, Lobular carcinoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Atypical ductal hyperplasia, core needle biopsy, 030218 nuclear medicine & medical imaging, atypical lobular hyperplasia, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, breast cancer, Atypia, Medicine, Humans, Pharmacology (medical), Epithelial hyperplasia, Breast, skin and connective tissue diseases, lobular carcinoma in situ, Hyperplasia, medicine.diagnostic_test, business.industry, medicine.disease, Immunohistochemistry, 3. Good health, Oncology, columnar cell lesions with atypia, 030220 oncology & carcinogenesis, Female, business, lobular neoplasia, Precancerous Conditions, Lobular Neoplasia
Abstract: International audience; Introduction: Atypical epithelial hyperplasia (AEH) of the breast is considered benign histological lesions with breast cancer risk. This review focuses on clinical signification and management of AEH that remains controversial. Areas covered: A review of published studies was performed using medline database. In this review, we fully describe the current evidence available. In particular, we describe 1) data from immunohistochemistry and molecular studies that suggest AEH is a precursor of breast cancer; 2) epidemiological studies demonstrate low rate of breast cancer in women with AEH; 3) surgical excision is necessary after diagnosis of AEH, such as lobular carcinoma in situ or atypical ductal hyperplasia, on core needle biopsy; 4) although current recommendations are evolving to fewer (if not no) excisions for flat epithelial with atypia and classic lobular neoplasia found on percutaneous biopsy (without radiologic indications for excision). Expert commentary: HEA management steel need prospective evidences, but recent retrospective data give some clue for less invasive management for some of HEA. © 2016 Informa UK Limited, trading as Taylor & Francis Group.
Published: 2016
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23. The cleaved FAS ligand activates the Na+/H+ exchanger NHE1 through Akt/ROCK1 to stimulate cell motility

Author: Patrick Legembre, Sébastien Tauzin, Dominique Lagadic-Gossmann, Michael Monet, Laurent Counillon, Mallorie Poët, Auréa Cophignon, Pierre Vacher, Amélie Fouqué, Laboratoire de PhysioMédecine Moléculaire (LP2M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by CNRS and the University of Nice-Sophia Antipolis, the ICST Labex, grants from INCa PLBIOL, Ligue Contre le Cancer (Comités d’Ille-et-Vilaine/du Morbihan/des Côtes d’Armor/du Maine et Loire), ARC, Région Bretagne, Rennes Métropole., Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), and Jonchère, Laurent
Subjects: 0301 basic medicine, Fas Ligand Protein, RHOA, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Article, Fas ligand, Cell Line, Metastasis, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Movement, Humans, ROCK1, Cell migration, Phosphorylation, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Protein kinase B, PI3K/AKT/mTOR pathway, ComputingMilieux_MISCELLANEOUS, rho-Associated Kinases, Sodium-Hydrogen Exchanger 1, Multidisciplinary, biology, Fas receptor, Cell biology, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Protons, Signal transduction, rhoA GTP-Binding Protein, Proto-Oncogene Proteins c-akt, Signal Transduction
Abstract: Transmembrane CD95L (Fas ligand) can be cleaved to release a promigratory soluble ligand, cl-CD95L, which can contribute to chronic inflammation and cancer cell dissemination. The motility signaling pathway elicited by cl-CD95L remains poorly defined. Here, we show that in the presence of cl-CD95L, CD95 activates the Akt and RhoA signaling pathways, which together orchestrate an allosteric activation of the Na+/H+ exchanger NHE1. Pharmacologic inhibition of Akt or ROCK1 independently blocks the cl-CD95L-induced migration. Confirming these pharmacologic data, disruption of the Akt and ROCK1 phosphorylation sites on NHE1 decreases cell migration in cells exposed to cl-CD95L. Together, these findings demonstrate that NHE1 is a novel molecular actor in the CD95 signaling pathway that drives the cl-CD95L-induced cell migration through both the Akt and RhoA signaling pathways.
Published: 2016
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24. Cancer de l’endomètre au stade pécoce : ganglion sentinelle ou curage pelvien ? [Early-stage endometrial cancer: Sentinel node or lymphadenectomy?]

Author: N. Body, O. de Kerdaniel, V. Lavoué, M. Leblanc, S. Henno, J. Levêque, CHU Pontchaillou [Rennes], Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)
Subjects: medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Lymph node metastasis, 03 medical and health sciences, 0302 clinical medicine, cancer de l'endomètre, medicine, lymphadénectomie, Stage (cooking), Lymph node, ComputingMilieux_MISCELLANEOUS, 030219 obstetrics & reproductive medicine, business.industry, ganglion sentinelle, Endometrial cancer, Obstetrics and Gynecology, Cancer, Lymphadenectomy, General Medicine, Sentinel node, medicine.disease, 3. Good health, Surgery, Dissection, medicine.anatomical_structure, Reproductive Medicine, 030220 oncology & carcinogenesis, endometrial cancer, Radiology, business
Abstract: The endometrial cancers are mainly discovered at an early stage justifying a less aggressive treatment. The therapeutic choices are today based on preoperative classifications themselves based on histo-prognostic factors of the tumor and its extension measured in MRI: consequently, lymph node dissection in case of low and intermediate risk cancer is not systematically achieved. But a number of patients have lymph node involvement finally, probably justifying an adapted surgical and adjuvant treatment. The technique of sentinel node would compensate the weaknesses of preoperative prognostic evaluation. This new operative technique needs to be precised and evaluated: the topics subject to discussion are the technical implementation, the definition of its quality standards and the management of its histological results especially in cases of low volume lymph node metastasis.
Published: 2016
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25. L’exentération pelvienne curative en cas de récurrence d’un cancer du col de l’utérus à l’ère de la radio-chimiothérapie concomitante : revue de la littérature

Author: Jean Levêque, Vincent Lavoué, F. Foucher, Hugo Sardain, CHU Pontchaillou [Rennes], Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)
Subjects: Gynecology, medicine.medical_specialty, 030219 obstetrics & reproductive medicine, Pelvic exenteration, business.industry, Exentération pelvienne, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Obstetrics and Gynecology, General Medicine, medicine.disease, 3. Good health, Cancer du col de l’utérus, 03 medical and health sciences, 0302 clinical medicine, Reproductive Medicine, Recurrence, 030220 oncology & carcinogenesis, Cervical carcinoma, medicine, Carcinoma, business, ComputingMilieux_MISCELLANEOUS
Abstract: Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 45 - N° 4 - p. 315-329
Published: 2016
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26. Role of the tumor microenvironment in regulating apoptosis and cancer progression

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

Author: M. A. Traore, I. Jaffré, G. Ferron, Jean Levêque, Philippe Descamps, J-M Classe, Sandrine Baffert, D. Raudrant, Virginie Fourchotte, Gilles Body, C. Binelli, C. Simondi, C. Loustalot, G. Houvenaeghel, Séverine Alran, Emmanuel Barranger, Patrice Mathevet, Pierre-François Dupré, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Institut Curie [Paris], CHU de Lyon, Service de chirurgie [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Chirurgie gynécologique, Clinique Jules Verne, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Department of Surgical Oncology Institut Claudius Regaud, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), This study was supported by a grant from the French National Cancer Institute dedicated to economic studies of innovative techniques (STIC COELIO COL 2007)., Fondation Adolphe de Rothschild, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)
Subjects: medicine.medical_treatment, Cost-Benefit Analysis, [SDV]Life Sciences [q-bio], Uterine Cervical Neoplasms, Pilot Projects, Abdominal wall, 0302 clinical medicine, Postoperative Complications, Quality of life, Laparotomy, Prospective Studies, Prospective cohort study, Laparoscopy, Cervical cancer, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, General Medicine, Chemoradiotherapy, Middle Aged, Prognosis, 3. Good health, medicine.anatomical_structure, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, France, laparoscopic hysterectomy, Adult, medicine.medical_specialty, cost comparison, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hysterectomy, Risk Assessment, Statistics, Nonparametric, 03 medical and health sciences, medicine, Humans, Neoplasm Invasiveness, Neoplasm Staging, Analysis of Variance, business.industry, General surgery, Length of Stay, medicine.disease, Advanced cervical cancer, Surgery, Quality of Life, business
Abstract: International audience; Objective Laparoscopy allows hysterectomies after chemoradiation to be performed without opening the abdominal wall. We measured the costs and quality of life for locally advanced cervical cancer patients operated on via laparoscopy compared to laparotomy. Study design We conducted an observational prospective multicenter study on locally advanced cervical cancer patients undergoing an extrafascial hysterectomy after concurrent chemoradiotherapy (CRT). We assessed the costs from the medical visit before surgery up to the first month after surgery from the providers’ perspective and measured the quality of life using the EORTC QLQ-C30 and QLQ-CX24 up to six months. Results 62 patients (39 laparoscopy and 23 laparotomy) from December 2008 to November 2011 were included. There was no difference in operative time, or intraoperative and postoperative complication rates between the two groups. Intraoperative transfusion and abdominal drain were significantly lower in the laparoscopy group (respectively, p=0.04 and p
Published: 2016
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28. Wild-type VHL Clear Cell Renal Cell Carcinomas Are a Distinct Clinical and Histologic Entity: A 10-Year Follow-up

Author: Jean Mosser, Marc-Antoine Belaud-Rotureau, Angélique Brunot, Jean-Jacques Patard, Karim Bensalah, Alexandra Lespagnol, Julien Dagher, Solène-Florence Kammerer-Jacquet, F Dugay, Cécile Vigneau, Gregory Verhoest, Nathalie Rioux-Leclercq, Christophe Perrin, Adélaïde Pladys, 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 ), Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CRLCC Eugène Marquis (CRLCC), École des Hautes Études en Santé Publique [EHESP] (EHESP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), and Jonchère, Laurent
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Pathology, Survival, Urology, Lymphocyte, [SDV]Life Sciences [q-bio], Locus (genetics), Gene mutation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, VHL, medicine, Clear cell renal carcinoma, business.industry, Wild type, Kidney cancer, medicine.disease, Prognosis, 3. Good health, [SDV] Life Sciences [q-bio], Vascular endothelial growth factor, Clear cell renal cell carcinoma, 030104 developmental biology, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, business, Clear cell
Abstract: Background Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor with 50% risk of metastases at initial diagnosis or at follow-up. An inactivation of the tumor-suppressor gene von Hippel-Lindau ( VHL ) is present in >70% of sporadic cases by two of three different mechanisms: locus deletion, gene mutation, or promoter hypermethylation. Objective To correlate the complete status of the VHL gene with clinical and pathologic criteria. Design, setting, and participants We retrospectively included 98 patients with ccRCC who underwent surgery between 2002 and 2005. VHL gene deletions (71 of 98; 72.4%), mutations (68 of 98; 69.4%), and promoter hypermethylations (13 of 98; 13.3%) were screened by gene copy analysis, gene sequencing, and methylation-specific multiplex ligation-dependent probe amplification, respectively. Outcome measurements and statistical analysis Relationships between VHL subgroups and the studied criteria were analyzed using chi-square and Student t tests. Survival was analyzed with the log-rank test and Kaplan-Meier curves. Results and limitations Compared with ccRCCs with two events (66.3%), tumors with no or one genetic event (33.6%) were associated with a higher nuclear grade IV ( p =0.02), metastases ( p =0.04), sarcomatoid component ( p =0.01), dense lymphocyte infiltrate ( p =0.013), and vascular endothelial growth factor overexpression (>30%) ( p =0.003), which was also an independent factor after multivariate analysis. Furthermore, wild-type VHL tumors (no inactivating event, 11.2%) were associated with nodal involvement ( p =0.019), and patients with this type of tumor had a specific survival of 33 mo compared with patients with ccRCCs having one or two VHL inactivating events (107 mo; p =0.016). The retrospective design with small number of wild-type tumors was a limitation of this work. Conclusions This long-term study (10-yr clinical follow-up) confirms that ccRCCs with wild-type VHL are highly aggressive tumors that need to be formally identified. Patient summary Among activated VHL tumors, the wild-type subgroup defines an aggressive phenotype with worse survival rates, suggesting that these tumors must be more thoroughly screened.
Published: 2016
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29. Benefits of Minimal Access Surgery in Elderly Patients with Pelvic Cancer

Author: Walter H. Gotlieb, Vincent Lavoué, Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), McGill University = Université McGill [Montréal, Canada], and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
Subjects: Cancer Research, medicine.medical_specialty, medicine.medical_treatment, minimal invasive surgery, [SDV]Life Sciences [q-bio], Review, Malignancy, lcsh:RC254-282, elderly, 03 medical and health sciences, 0302 clinical medicine, Laparotomy, robotic surgery, medicine, Robotic surgery, 030212 general & internal medicine, Cancer, Minimal access surgery, business.industry, General surgery, Pelvic cancer, Surgical procedures, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Surgery, Oncology, 030220 oncology & carcinogenesis, business, Hospital stay
Abstract: International audience; An increasing proportion of patients requiring treatment for malignancy are elderly, which has created new challenges for oncologic surgeons. Aging is associated with an increasing prevalence of frailty and comorbidities that may affect the outcome of surgical procedures. By decreasing complications and shortening length of hospital stay without affecting oncologic safety, surgery performed using the robot, rather than traditional laparotomy, improves the chances of a better outcome in our growing elderly populations. In addition to age, surgeons should take into account factors, such as frailty and comorbidities that correlate with outcome
Published: 2016
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30. Endometrial cancer in elderly women: Which disease, which surgical management? A systematic review of the literature

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

Author: Scott A. Oakes, Eric Chevet, Claudio Hetz, Biomedical Neuroscience Institute, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
Subjects: 0303 health sciences, Stress sensor, Published Erratum, Schematic, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Biology, Computational biology, Biology, Cell biology, 03 medical and health sciences, 0302 clinical medicine, Proteostasis, 030220 oncology & carcinogenesis, Unfolded protein response, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: Nat. Cell Biol. 17, 829–838 (2015); published online 30 June 2015; corrected after print 13 July 2015 In the version of this Review originally published, Fig. 1 contained a superfluous IRE1α stress sensor at the top of the schematic. This error has been corrected in all online versions.
Published: 2015
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32. Use of human papillomavirus genotyping and biomarkers for targeted screening of anal dysplasia in human immunodeficiency virus-infected patients

Author: Cédric Arvieux, Clarisse Dupin, Laurent Siproudhis, Sébastien Henno, Sophie Minjolle, Pierre Tattevin, Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], Service des maladies de l'appareil digestif, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Oncogenesis Stress Signaling (OSS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Fonction, structure et inactivation d'ARN bactériens, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hologic Inc. (Bedford, MA) offered the test kits for E6/E7 viral mRNA detection of 14 high risk HPV types (APTIMA assay). There was no other funding., Jonchère, Laurent, Service des Maladies de l'Appareil Digestif [CHU Rennes], Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Male, Pathology, Papillomavirus E7 Proteins, [SDV]Life Sciences [q-bio], Anal Canal, HIV Infections, Proctoscopy, Gastroenterology, 0302 clinical medicine, Genotype, 030212 general & internal medicine, Papillomaviridae, Cervical cancer, medicine.diagnostic_test, Anal dysplasia, Middle Aged, Anus Neoplasms, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Female, Adult, medicine.medical_specialty, HPV, Physical examination, [SDV.CAN]Life Sciences [q-bio]/Cancer, p16INK4A/Ki-67, Sensitivity and Specificity, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, RNA, Messenger, Genotyping, Cyclin-Dependent Kinase Inhibitor p16, Mass screening, Anus Diseases, High-risk HPV genotypes, Hepatology, business.industry, Anoscopy, HIV, High-risk HPV E6/E7 mRNA, Oncogene Proteins, Viral, medicine.disease, Ki-67 Antigen, Dysplasia, business, Biomarkers
Abstract: International audience; BACKGROUND: Screening for anal dysplasia in human immunodeficiency virus (HIV)-infected patients is not standardized. High-resolution imaging is not adequate for mass screening, and anal cytology requires expertise. New biomarkers, selected because of their use in cervical cancer mass screening, have been originally tested for targeted and easy-to-perform screening. METHODS: 120 HIV-infected individuals (males 96.4%, mean age 47±11 years) were referred for clinical examination, anoscopy, and cytological studies on anal swab. Dysplasia grading, Human Papilloma Virus genotyping, E6/E7mRNA detection and p16(INK4A)/Ki-67 immunostaining were performed. High-grade lesions were histologically confirmed by anal biopsies after high-resolution anoscopy. RESULTS: Among the 120 anal swabs analyzed, 36 (30%) had low grade and 6 (5%) had high-grade lesions. Virus genotype was identified in 88 patients (73.3%), and 77 (64.2%) were positive for high-risk genotype(s). High-risk genotype was associated to low-grade or high-grade lesions with a sensitivity of 0.93 and a specificity of 0.51. For E6/E7mRNA, sensitivity and specificity for low-grade and high-grade lesions were, respectively, 0.88 and 0.78. Combination of genotyping, E6/E7mRNA and p16(INK4A)/Ki-67 appropriately ruled out dysplasia in 55% of patients. CONCLUSIONS: Three routine biomarkers may avoid unnecessary invasive procedures with the perspective of an improvement of patient compliance. A decision making algorithm, based on the combination of these three biomarkers, is proposed.
Published: 2015
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33. Plasma cell mastitis in women with rheumatoid arthritis treated with TNFα antagonists: Report of 2 cases

Author: Aleth Perdriger, Ophélie Caillot, Marine Faccin, Jean Levêque, Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)
Subjects: 0301 basic medicine, Plasma cell mastitis, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Arthritis, Rheumatoid Arthritis, TNFα antagonists, Plasma cell, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, Duct ectasia of breast, medicine, ComputingMilieux_MISCELLANEOUS, business.industry, Joint bone, medicine.disease, 3. Good health, Surgery, Mastitis, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Rheumatoid arthritis, Tumor necrosis factor alpha, business
Abstract: Joint Bone Spine - In Press.Proof corrected by the author Available online since jeudi 14 janvier 2016
Published: 2016
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34. Genome-wide screen identifies a novel p97/CDC-48-dependent pathway regulating ER-stress-induced gene transcription

Author: Esther Marza, Nestor Pallares-Lupon, Saïd Taouji, Marc Bonneu, Denis Dupuy, Jean Rosenbaum, Jean-William Dupuy, Léo Guignard, Anne-Aurélie Raymond, Kim Barroso, Martin E. Fernandez-Zapico, Francesca Palladino, Eric Chevet, Régulations Naturelles et Artificielles (ARNA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), 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), Modeling plant morphogenesis at different scales, from genes to phenotype (VIRTUAL PLANTS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de la Recherche Agronomique (INRA)-Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), Centre Génomique Fonctionnelle Bordeaux [Bordeaux] (CGFB), Institut Polytechnique de Bordeaux-Université de Bordeaux Ségalen [Bordeaux 2], Schulze Center for Novel Therapeutics, Division of Oncology Research [Rochester], Mayo Clinic [Rochester], Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), 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 la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, nstitut National du Cancer, Association Francaise contre les Myopathie, Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en Biologie cellulaire de Montpellier (CRBM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)
Subjects: Proteomics, Transcription, Genetic, Repressor, Cell Cycle Proteins, [SDV.CAN]Life Sciences [q-bio]/Cancer, UPR, Biology, Protein degradation, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Valosin Containing Protein, RNA interference, Transcription (biology), Genetics, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Molecular Biology, 030304 developmental biology, Adenosine Triphosphatases, 0303 health sciences, proteostasis, Endoplasmic reticulum, Scientific Reports, Endoplasmic Reticulum Stress, AAA proteins, Cell biology, Repressor Proteins, Proteostasis, 030220 oncology & carcinogenesis, Unfolded Protein Response, Unfolded protein response, RNA Interference, AAA+ ATPase, Signal Transduction
Abstract: International audience; The accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the Unfolded Protein Response (UPR(ER)) to restore ER homeostasis. The AAA(+) ATPase p97/CDC-48 plays key roles in ER stress by promoting both ER protein degradation and transcription of UPR(ER) genes. Although the mechanisms associated with protein degradation are now well established, the molecular events involved in the regulation of gene transcription by p97/CDC-48 remain unclear. Using a reporter-based genome-wide RNAi screen in combination with quantitative proteomic analysis in Caenorhabditis elegans, we have identified RUVB-2, a AAA(+) ATPase, as a novel repressor of a subset of UPR(ER) genes. We show that degradation of RUVB-2 by CDC-48 enhances expression of ER stress response genes through an XBP1-dependent mechanism. The functional interplay between CDC-48 and RUVB-2 in controlling transcription of select UPR(ER) genes appears conserved in human cells. Together, these results describe a novel role for p97/CDC-48, whereby its role in protein degradation is integrated with its role in regulating expression of ER stress response genes
Published: 2015
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35. Curative pelvic exenteration for recurrent cervical carcinoma in the era of concurrent chemotherapy and radiation therapy. A systematic review

Author: Vincent Lavoué, M. Redpath, Jean Levêque, Hugo Sardain, N. Bertheuil, F. Foucher, CHU Pontchaillou [Rennes], Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), McGill University = Université McGill [Montréal, Canada], Service de chirurgie plastique, reconstructive et esthétique [Rennes] = Cosmetic Reconstructive and Plastic surgery [Rennes], VL received grants from la Vannetaise 2014., and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
Subjects: medicine.medical_specialty, medicine.medical_treatment, Uterine Cervical Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cochrane Library, Complete resection, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Concurrent chemotherapy, Recurrence, medicine, Humans, Cervical carcinoma, MESH: Chemoradiotherapy, Cervical cancer, MESH: Humans, Pelvic exenteration, business.industry, Vulvectomy, General surgery, General Medicine, Chemoradiotherapy, medicine.disease, Recurrent Cervical Carcinoma, 3. Good health, Surgery, Pelvic Exenteration, Radiation therapy, Oncology, 030220 oncology & carcinogenesis, Female, Neoplasm Recurrence, Local, business, MESH: Female
Abstract: International audience; OBJECTIVE: Pelvic exenteration requires complete resection of the tumor with negative margins to be considered a curative surgery. The purpose of this review is to assess the optimal preoperative evaluation and surgical approach in patients with recurrent cervical cancer to increase the chances of achieving a curative surgery with decreased morbidity and mortality in the era of concurrent chemoradiotherapy. METHODS: Review of English publications pertaining to cervical cancer within the last 25 years were included using PubMed and Cochrane Library searches. RESULTS: Modern imaging (MRI and PET-CT) does not accurately identify local extension of microscopic disease and is inadequate for preoperative planning of extent of resection. Today, only half of pelvic exenteration procedures obtain uninvolved surgical margins. CONCLUSION: Clear margins are required for curative pelvic exenterations, but are poorly predictable by pre-operative assessment. More extensive surgery, i.e. the infra-elevator exenteration with vulvectomy, is a logical surgical choice to increase the rate of clear margins and to improve patient survival following surgery for recurrent cervical carcinoma.
Published: 2015
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36. Drugging the unfolded protein response in acute leukemias

Author: Edgar Jost, Behzad Kharabi Masouleh, Tim H. Bruemmendorf, Michael O'Dwyer, Jens Panse, Afshin Samali, Eric Chevet, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Medizinische Klinik IV, Universitaetsklinikum Aachen, ID0EOWAI519, Deutsche Krebshilfe, ID0EIJBI522, Breast Cancer Campaign, ID0ESKBI523, Irish Cancer Society, ID0EGQAI518, Ernst Jung Foundation, ID0EY3AI520, RWTH START, ID0EADBI521, RWTH START UP, ID0E3LBI524, Belgian grant, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)
Subjects: Cancer Research, endoplasmic-reticulum stress, [SDV]Life Sciences [q-bio], Review, er stress, 0302 clinical medicine, 0303 health sciences, Acute leukemia, Leukemia, Hematology, leukemia stem cells, unfolded protein response, 3. Good health, small-molecule inhibitors, Oncology, 030220 oncology & carcinogenesis, acute myeloid-leukemia, Signal transduction, xbp1, Signal Transduction, medicine.medical_specialty, endocrine system, XBP1, Cell Survival, acute myelogenous leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, 03 medical and health sciences, Internal medicine, medicine, Humans, ddc:610, Molecular Biology, 030304 developmental biology, xbp1 messenger-rna, business.industry, induced cell-death, cancer stem-cells, Endoplasmic reticulum, fungi, acute lymphoblastic-leukemia, acute promyelocytic leukemia, medicine.disease, pml-rar-alpha, Immunology, Cancer cell, Unfolded protein response, business, Neuroscience
Abstract: International audience; The unfolded protein response (UPR), an endoplasmic reticulum (ER) stress-induced signaling cascade, is mediated by three major stress sensors IRE-1α, PERK, and ATF6α. Studies described the UPR as a critical network in selection, adaptation, and survival of cancer cells. While previous reviews focused mainly on solid cancer cells, in this review, we summarize the recent findings focusing on acute leukemias. We take into account the impact of the underlying genetic alterations of acute leukemia cells, the leukemia stem cell pool, and provide an outline on the current genetic, clinical, and therapeutic findings. Furthermore, we shed light on the important oncogene-specific regulation of individual UPR signaling branches and the therapeutic relevance of this information to answer the question if the UPR could be an attractive novel target in acute leukemias
Published: 2015
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37. Identification of two glioblastoma-associated stromal cell subtypes with different carcinogenic properties in histologically normal surgical margins

Author: Audrey Rousseau, Clément Tétaud, Amandine Etcheverry, Tony Avril, Jean Mosser, Philippe Menei, Cécile Henry, Anne Clavreul, Lecoupe-Grainville, Marie, Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Service de neurochirurgie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Université d'Angers (UA), 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 ), Hôpital Pontchaillou, Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), This work was supported by the Pays de la Loire and Bretagne regions and Ligue contre le cancer-49-Comite´ de Maine-et-Loire., Service de neurochirurgie [CHU Angers], 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), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)
Subjects: Cancer Research, Pathology, medicine.medical_treatment, Apoptosis, Transcriptome, Mice, 0302 clinical medicine, Cell Movement, Tumor Cells, Cultured, Oligonucleotide Array Sequence Analysis, 0303 health sciences, Brain Neoplasms, Brain, Flow Cytometry, 3. Good health, Cell Transformation, Neoplastic, Neurology, Oncology, 030220 oncology & carcinogenesis, DNA methylation, Female, cancer-associated fibroblasts, medicine.medical_specialty, Stromal cell, Blotting, Western, Mice, Nude, Translational study, peritumoral brain zone, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, 03 medical and health sciences, Stroma, In vivo, Glioma, Biomarkers, Tumor, Human Umbilical Vein Endothelial Cells, medicine, Animals, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Cell Proliferation, 030304 developmental biology, Gene Expression Profiling, glioblastoma, DNA Methylation, medicine.disease, Xenograft Model Antitumor Assays, Radiation therapy, Cancer-Associated Fibroblasts, Neurology (clinical), Stromal Cells
Abstract: International audience; Glioblastoma (GB) is a highly infiltrative tumor recurring within a few centimeters of the resection cavity in 90% of cases, even in cases of complete tumor resection and adjuvant chemo/radiotherapy. We recently isolated GB-associated stromal cells (GASCs) from the GB peritumoral zone, with phenotypic and functional properties similar to those of the cancer-associated fibroblasts (CAFs) present in the stroma of carcinomas. In particular, GASCs promote blood vessel development and have tumor-promoting effects on glioma cells in vitro and in vivo. In this study, we characterized these cells further, by analyzing the transcriptome and methylome of 14 GASC and five control stromal cell preparations derived from non-GB peripheral brain tissues. We identified two subtypes of GASCs in surgical margins in GB patients: GASC-A and GASC-B. GASC-B promoted the development of tumors and endothelium, whereas GASC-A did not. A difference in DNA methylation may underlie these two subtypes. We identified various proteins as being produced in the procarcinogenic GASC-B. Some of these proteins may serve as prognostic factors for GB and/or targets for anti-glioma treatment. In conclusion, in this era of personalized therapy, the status of GASCs in GB-free surgical margins should be taken into account, to improve treatment and the prevention of recurrence.
Published: 2015
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38. Le carcinome rénal à cellules claires (CRCC) sans altération du gène de Von Hippel-Lindau (VHL) : une entité anatomo-clinique à part ?

Author: Julien Dagher, A. Brunot, Christophe Perrin, Solène-Florence Kammerer-Jacquet, Marc-Antoine Belaud-Rotureau, J.J. Patard, Gregory Verhoest, Florence Jouan, Nathalie Rioux-Leclercq, Karim Bensalah, Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Institut de Génétique et Développement de Rennes (IGDR), 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 ), Cancer du rein : bases moléculaires de la tumorogenèse, 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 )-Université de Rennes 1 (UR1), Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UR)-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)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Gynecology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, 030220 oncology & carcinogenesis, Urology, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, medicine, business, 3. Good health
Abstract: National audience; Objectifs Le CRCC est caractérisé par une inactivation du gène suppresseur de tumeur VHL dans plus de 70 % des cas. La voie VHL/HIF est une voie principale d’oncogenèse aboutissant lorsque VHL est inactivé à une surexpression de gènes cibles pro-angiogéniques. L’objectif est de corréler le statut complet de VHL 1/aux critères anatomopathologiques, 2/à l’expression intra-tumorale de VEGF et 3/au suivi clinique des patients. Méthodes 98 CRCC opérés entre 2002 et 2005 ont été inclus rétrospectivement avec un suivi moyen de 10,5 ans. Dix critères histopronostiques et l’expression en immunohistochimie de VEGFA ont été étudiés. À partir des prélèvements congelés, la recherche de délétion de VHL par analyse de copies du gène (MLPA), de mutation de VHL par séquençage, d’une méthylation de son promoteur par MS-MLPA a été menée. Résultats Les CRCC présentaient une délétion, une mutation et/ou une méthylation du promoteur dans respectivement 72,4 %, 69,4 % et 14,2 % des cas, méthylation et mutation étant mutuellement exclusives. 33,6 % des CRCC avaient 0 ou 1 altération de VHL contre 66,3 % avec 2 anomalies. Ces CRCC étaient associés à un grade de Furhman 4 (p = 0,039), aux métastases synchrones (p = 0,043) et à une surexpression de VEGFA \textgreater 50 % (p = 0,003). De plus, les CRCC sans aucune anomalie de VHL (11,2 % de cas) étaient associés à une composante sarcomatoïde \textgreater 20 % (p \textless 0,001) et aux métastases ganglionnaires (p = 0,019), avec une survie spécifique de 33 mois comparés aux CRCC avec 1 ou 2 altérations de VHL (107 mois, p = 0,016). Conclusion Il s’agit de la première étude menée avec un suivi de 10 ans corrélant dans le CRCC le statut complet de VHL avec des critères anatomopathologiques et de suivi clinique. Nous montrons que les CRCC sans aucune altération de VHL sont des tumeurs hautement agressives, qu’il convient d’isoler
Published: 2014
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39. Posttranscriptional Regulation of PER1 Underlies the Oncogenic Function of IRE

Author: Arisa Higa, Raphael Pineau, Michael Hallett, Stéphanie Lhomond, Olivier Pluquet, Marion Bouchecareilh, Anne Vital, Sandrine Loriot, Gaelle Cubel, Jann N. Sarkaria, Maylis Delugin, Hugues Loiseau, Wenting Wu, Nicolas Dejeans, Keith Anderson, Sara J. C. Gosline, Frédéric Saltel, Martin E. Fernandez-Zapico, Fausto J. Rodriguez, C. Combe, Jean Rosenbaum, Eric Chevet, Nathalie Dugot-Senant, Saïd Taouji, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), DIPI (DIPI), ENISE, Ecosystèmes aquatiques et changements globaux (UR EABX), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Centre de Recherche sur la Matière Divisée (CRMD), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Department of Health and Human Services, National Institutes of Health [Bethesda] (NIH), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), This work was supported by an Avenir program (INSERM), grants from the Institut National du Cancer (INCa), Ligue contre le cancer, a Marie Curie International Reintegration Grant (E. Chevet), a grant from the Mayo Clinic Cancer Centre (M.E. Fernandez-Zapico), a grant from Institut Fédératif de Recherche 66 (O. Pluquet). O. Pluquet was supported by fellowships from INSERM and Association pour la Recherche contre le Cancer. M. Bouchecareilh was supported from a fellowship from le Conseil Régional d'Aquitaine and la Fondation pour la Recherche Française (FRM). Human glioblastoma samples were collected through the Bordeaux Tumor Bank (JP Merlio, CHU Bordeaux, France) funded by the Cancéropôle Grand Sud-Ouest and by a CEREPEG project grant (PHRC 2003, H. Loiseau) or through the Mayo Clinic Department of Clinical Pathology and funded by the Mayo Clinic SPORE in Brain Cancer P50 CA108961 (Rochester)., The authors thank M. Moenner (Université Bordeaux 1, Bordeaux, France) for precious help and fruitful discussions, S. Manié (UMR CNRS 5286, INSERM 1052, Cancer Research Center of Lyon, Lyon, France), and the Chevet lab for critical reading of the manuscript. The authors also thank Dr S. Gery (University of California, Los Angeles, CA) for the gift of pcDNA3.1-hPER1 expression vector and Dr U. Albrecht (Freiburg, Switzerland) for providing us with the pPER1-Luc vector., Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), Diagnostics et imageries des procédés industriels (ENISE-DIPI), Ecole Nationale d'Ingénieurs de Saint Etienne (ENISE), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
Subjects: Cancer Research, Endoribonuclease activity, [SDV]Life Sciences [q-bio], Circadian clock, MESH: Base Sequence, MESH: Period Circadian Proteins/metabolism, Mice, 0302 clinical medicine, RNA interference, MESH: Glioblastoma/metabolism, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Animals, RNA Processing, Post-Transcriptional, MESH: Gene Expression Regulation, Neoplastic/physiology, Oligonucleotide Array Sequence Analysis, Regulation of gene expression, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, Period Circadian Proteins, MESH: Protein-Serine-Threonine Kinases/genetics, Cell biology, Gene Expression Regulation, Neoplastic, Oncology, MESH: Endoribonucleases/metabolism, 030220 oncology & carcinogenesis, MESH: Glioblastoma/genetics, RNA Interference, PER1, MESH: RNA Processing, Post-Transcriptional, endocrine system, MESH: Xenograft Model Antitumor Assays, XBP1, Molecular Sequence Data, MESH: RNA Interference, MESH: Endoribonucleases/genetics, [SDV.CAN]Life Sciences [q-bio]/Cancer, Protein Serine-Threonine Kinases, Biology, Transfection, Article, 03 medical and health sciences, Endoribonucleases, MESH: Unfolded Protein Response/physiology, Animals, Humans, Gene silencing, MESH: Protein-Serine-Threonine Kinases/metabolism, RNA, Messenger, MESH: Mice, 030304 developmental biology, MESH: RNA, Messenger, MESH: Period Circadian Proteins/genetics, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, MESH: Transfection, Xenograft Model Antitumor Assays, Molecular biology, MESH: Oligonucleotide Array Sequence Analysis, Unfolded Protein Response, Unfolded protein response, Glioblastoma
Abstract: Growing evidence supports a role for the unfolded protein response (UPR) in carcinogenesis; however, the precise molecular mechanisms underlying this phenomenon remain elusive. Herein, we identified the circadian clock PER1 mRNA as a novel substrate of the endoribonuclease activity of the UPR sensor IRE1α. Analysis of the mechanism shows that IRE1α endoribonuclease activity decreased PER1 mRNA in tumor cells without affecting PER1 gene transcription. Inhibition of IRE1α signaling using either siRNA-mediated silencing or a dominant-negative strategy prevented PER1 mRNA decay, reduced tumorigenesis, and increased survival, features that were reversed upon PER1 silencing. Clinically, patients showing reduced survival have lower levels of PER1 mRNA expression and increased splicing of XBP1, a known IRE-α substrate, thereby pointing toward an increased IRE1α activity in these patients. Hence, we describe a novel mechanism connecting the UPR and circadian clock components in tumor cells, thereby highlighting the importance of this interplay in tumor development. Cancer Res; 73(15); 4732–43. ©2013 AACR.
Published: 2013
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40. 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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41. Purification of a heparin binding FGF receptor (HB-FGFR) from adult bovine brain membranes

Author: E Chevet, Denis Barritault, Agnes Mereau, José Courty, Mylène Perderiset, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Oncogenesis Stress Signaling (OSS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), OTR3 Sarl, OTR3, MEREAU, Agnès, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
Subjects: Receptor complex, [SDV]Life Sciences [q-bio], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Fibroblast growth factor, Biochemistry, Chromatography, Affinity, 03 medical and health sciences, 0302 clinical medicine, Affinity chromatography, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Receptor, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Chromatography, High Pressure Liquid, 030304 developmental biology, Brain Chemistry, 0303 health sciences, Affinity labeling, Heparin, Biological membrane, General Medicine, Ligand (biochemistry), Receptors, Fibroblast Growth Factor, [SDV] Life Sciences [q-bio], Cross-Linking Reagents, Fibroblast growth factor receptor, 030220 oncology & carcinogenesis, Cattle, Electrophoresis, Polyacrylamide Gel
Abstract: International audience; A new form of high affinity fibroblast growth factor receptor has been purified from adult bovine brain membranes. Purification was performed by chromatography on DEAE-Trisacryl and wheat germ agglutinin-agarose followed by FGF-2 affinity chromatography. Affinity labeling of purified fractions with 125I-FGF-2 showed after cross-linking a 170-kDa complex, suggesting the existence of a 150-kDa FGF receptor. No cross-reactivity with anti-FGF receptor 1 (FGFR-1 or flg) or with anti-receptor 2 (FGFR-2 or bek) antibodies could be detected with this partially purified receptor. Heparitinase treatment of the partially purified FGF receptor abolished the formation of the ligand receptor complex. The complex was restored in the presence of heparin in a dose dependent fashion, supporting the idea that heparin-like molecules are needed for proper binding. Further purification of the receptor was achieved by heparin-Sepharose affinity chromatography and yielded a purification of over 320,000-fold. The purified receptor fraction was radiolabeled and loaded on RPLC C4 column. Eluted fractions were analysed by SDS-PAGE. A major 150-kDa band was detected. These data show for the first time a new form of FGF receptor isolated from bovine brain membranes. This purified receptor displays affinity for heparin and was therefore named heparin binding FGF receptor (HB-FGFR). It remains unclear whether the receptor is a proteo-heparin sulfate or whether heparans are strongly associated and therefore are copurified. Large scale preparations are in progress for core protein structure studies.
Published: 1992
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42. Review of PI3K/mTOR inhibitors entering clinical trials to treat triple negative breast cancers

Author: Patrick Legembre, Amélie Fouqué, Mickael Jean, Pierre van de Weghe, Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), 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), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and 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)
Subjects: 0301 basic medicine, Oncology, Drug, Cancer Research, medicine.medical_specialty, media_common.quotation_subject, Antineoplastic Agents, Triple Negative Breast Neoplasms, Pharmacology, Structure-Activity Relationship, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, Drug Discovery, Animals, Humans, [CHIM]Chemical Sciences, Medicine, Pharmacology (medical), Molecular Targeted Therapy, Protein Kinase Inhibitors, Protein kinase B, PI3K/AKT/mTOR pathway, Phosphoinositide-3 Kinase Inhibitors, media_common, Clinical Trials as Topic, Molecular Structure, business.industry, TOR Serine-Threonine Kinases, Cancer, General Medicine, Discovery and development of mTOR inhibitors, medicine.disease, 3. Good health, Clinical trial, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer cell, Female, Phosphatidylinositol 3-Kinase, business, Signal Transduction
Abstract: International audience; Background: Constitutive activation of the PI3K/mTOR signaling pathway is observed in most, if not all, breast cancers. Accordingly, many PI3K and/or mTOR inhibitors have entered clinical trials, and completed studies should soon reveal the efficacy of these new drug families in the treatment of cancer patients. Objective: We present the PI3K/Akt/mTOR signaling pathway and the structure and the anti-tumor efficiency of some mTOR inhibitors such as rapalogues and competitive inhibitors, which have entered clinical trials. We also discuss some of the clinical trial results associated with these molecules mainly focusing on studies performed on relapsing breast cancer patients-but not only. Results: Most of the clinical trials with PI3K/mTOR inhibitors alone or in combination with chemotherapies were performed in heavily pre-treated patients and revealed non-negligible amounts of partial responses and long-term stable disease for these patients. Therefore, these compounds seem to prevent tumor growth and survival of cancer cells in Human, representing a new range of anti-tumor drugs that can be utilized not only as first-line treatments but as second-and third-line agents for patients who relapse. Conclusion: Drugs inhibiting the PI3K/mTOR signaling pathway may represent tailored anti-tumor agents, paving the way for their clinical application in different tumor types. © 2016 Bentham Science Publishers.
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43. Are preoperative histology and MRI useful for classification of endometrial cancer risk?

Author: F. Foucher, Olivier De Kerdaniel, Sébastien Henno, Bruno Laviolle, Marc Leblanc, Aurélie Cauchois, Noemie Body, Vincent Lavoué, Jean Levêque, CHU Pontchaillou [Rennes], Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pharmacologie [Rennes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Teaching Hospital of Rennes, Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Cancer Research, medicine.medical_treatment, multicenter, carcinoma, myometrial invasion, Likelihood ratios in diagnostic testing, Endometrium, 0302 clinical medicine, Endometrial cancer, Endometrial sample, Risk Factors, senti-endo, Stage (cooking), Aged, 80 and over, 030219 obstetrics & reproductive medicine, Risk group, Middle Aged, trial, Magnetic Resonance Imaging, 3. Good health, Oncology, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Female, Radiology, Risk assessment, management, Research Article, MRI, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Risk Assessment, Preoperative care, 03 medical and health sciences, Preoperative Care, medicine, Genetics, Humans, biopsy, Aged, Neoplasm Staging, Retrospective Studies, Gynecology, business.industry, Reproducibility of Results, Cancer, Lymphadenectomy, Retrospective cohort study, lymphovascular space invasion, medicine.disease, Endometrial Neoplasms, of-the-literature, lymph-node metastasis, Lymph Node Excision, Lymph Nodes, Neoplasm Recurrence, Local, business
Abstract: International audience; Background: The 2010 guidelines of the French National Cancer Institute (INCa) classify patients with endometrial cancer into three risk groups for lymph node invasion and recurrence on the basis of MRI and histological analysis of an endometrial specimen obtained preoperatively. The classification guides therapeutic choices, which may include pelvic and/or para-aortic lymphadenectomy. The purpose of this study was to evaluate the diagnostic performance of preoperative assessment to help identify intermediate- or high-risk patients requiring lymphadenectomy. Methods: The study included all patients who underwent surgery for endometrial cancer between January 2010 and December 2013 at either Rennes University Hospital or Vannes Regional Hospital. The criteria for eligibility included a preoperative assessment with MRI and histological examination of an endometrial sample. A histological comparison was made between the preoperative and surgical specimens. Results: Among the 91 patients who underwent a full preoperative assessment, the diagnosis of intermediate-or high-risk endometrial cancer was established by MRI and histology with a sensitivity of 70 %, specificity of 82 %, positive predictive value (PPV) of 87 %, negative predictive value (NPV) of 61 %, positive likelihood ratio (LR+) of 3.8 and negative likelihood ratio (LR-) of 0.3. The risk group was underestimated in 32 % of patients and overestimated in 7 % of patients. MRI underestimated endometrial cancer stage in 20 % of cases, while endometrial sampling underestimated the histological type in 4 % of cases and the grade in 9 % of cases. Conclusion: The preoperative assessment overestimated or underestimated the risk of recurrence in nearly 40 % of cases, with errors in lesion type, grade or stage. Erroneous preoperative risk assessment leads to suboptimal initial surgical management of patients with endometrial cancer.
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