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1. The cecal appendix is correlated with greater maximal longevity in mammals

Author

Eric Ogier-Denis, Jérémie Bardin, M. Collard, Michel Laurin, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de Recherche en Paléontologie - Paris (CR2P), Muséum national d'Histoire naturelle (MNHN)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), HAL-SU, Gestionnaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
0106 biological sciences, Senescence, Aging, senescence, Histology, phylogenetic generalized least squares, media_common.quotation_subject, Longevity, diarrhea, Zoology, Appendix, Biology, Evolution of ageing, digestive system, 010603 evolutionary biology, 01 natural sciences, Social life, 03 medical and health sciences, Cecum, [SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, [SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], medicine, Selective advantage, Animals, gastrointestinal anatomy, convergent evolution, Life history, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, media_common, Mammals, Original Paper, 0303 health sciences, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], vermiform appendix, Cell Biology, bacterial infections and mycoses, Biological Evolution, Original Papers, medicine.anatomical_structure, [SDV.BA.ZV] Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, Anatomy, lifespan, extrinsic mortality, Developmental Biology
Abstract

The cecal appendix had been considered as a useless vestige since Darwin's work, but recent research questioned this idea demonstrating that the cecal appendix appeared among the mammals at least 80 million years ago and has made multiple and independent appearances without any obvious correlation with diet, social life, ecology, or size of the cecum. However, functions and probable selective advantage conferred by this anatomical structure still remain enigmatic. We found, through analyses of data on 258 mammalian species, that cecal appendix presence is correlated with increased maximal observed longevity. This is the first demonstration of a correlation between cecal appendix presence and life history. Interestingly, the classical evolutionary theory of aging that predicts an increased longevity when the extrinsic mortality is reduced has been questioned several times, but recent comparative studies asserted its validity in the taxa, which experience age‐dependent and density‐dependent mortality, as in mammals. Thus, the cecal appendix may contribute to the increase in longevity through a reduction of extrinsic mortality. A lower risk of fatal infectious diarrhea is one of the most plausible hypotheses that could explain it. However, several hypotheses coexist about the possible functions of the cecal appendix, and our results provide new insights about this much‐disputed question. In addition, we show that the cecal appendix arose at least 16 times and was lost only once during the evolutionary history of the considered mammals, an asymmetry that supports the existence of a positive selective of this structure., Most people think about the appendix as a useless and even harmful structure that is removed on emergency in case of appendicitis. This belief harks as far back as Darwin, but it has been questioned by recent works that suggests that the cecal appendix does have a function. In this study, we found that the presence of an appendix is correlated with greater longevity in mammals, even when controlling for the strong positive size effects and for the phylogeny.

Published
2021

2. Does neoadjuvant FOLFOX chemotherapy improve the prognosis of high‐risk Stage II and III colon cancers? Three years' follow‐up results of the PRODIGE 22 phase II randomized multicentre trial

Author

Olivier Bouché, Guillaume Piessen, Benoit Romain, Claire Gallois, Emilie Barbier, Olivier Glehen, Jean-Marc Regimbeau, Mehdi Karoui, Gael Goujon, Johannes Hartwig, Julien Taieb, Guillaume Portier, Jean-Louis Legoux, Cécile de Chaisemartin, Astrid Lièvre, Francesco Brunetti, Hanifa Ammarguellat, Cedric Lecaille, Michel Prudhomme, Côme Lepage, for Prodige investigators, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Lille, Centre Hospitalier Régional d'Orléans (CHRO), Laboratoire de Neurosciences Cognitives & Computationnelles (LNC2), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Polyclinique Bordeaux Nord Aquitaine (PBNA), Centre Hospitalier Universitaire de Reims (CHU Reims), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Chirurgie digestive [CHU Amiens], CHU Amiens-Picardie, Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Cancer Research and Personalized Medicine - CARPEM [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), AOM10242, Ministère de la Santé, Polyclinique Bordeaux Nord Aquitaine, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], and École pratique des hautes études (EPHE)

Subjects
Oncology, medicine.medical_specialty, Organoplatinum Compounds, Colorectal cancer, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, Leucovorin, survival, 03 medical and health sciences, 0302 clinical medicine, FOLFOX, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, education, Neoplasm Staging, Colectomy, education.field_of_study, business.industry, Hazard ratio, Gastroenterology, Perioperative, colectomy, Prognosis, Interim analysis, medicine.disease, Neoadjuvant Therapy, digestive system diseases, colon cancer, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Colonic Neoplasms, 030211 gastroenterology & hepatology, Fluorouracil, Neoplasm Recurrence, Local, business, neoadjuvant chemotherapy, Follow-Up Studies, medicine.drug
Abstract

International audience; Aim Neoadjuvant chemotherapy has proven valuable in locally advanced resectable colon cancer (CC) but its effect on oncological outcomes is uncertain. The aim of the present paper was to report 3-year oncological outcomes, representing the secondary endpoints of the PRODIGE 22 trial. Method PRODIGE 22 was a randomized multicentre phase II trial in high-risk T3, T4 and/or N2 CC patients on CT scan. Patients were randomized between 6 months of adjuvant FOLFOX (upfront surgery) or perioperative FOLFOX (four cycles before surgery and eight cycles after; FOLFOX perioperative). In wild-type RAS patients, a third arm testing perioperative FOLFOX-cetuximab was added. The primary endpoint was the tumour regression grade. Secondary endpoints were 3-year overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS) and time to recurrence (TTR). Results Overall, 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped for futility. The remaining 104 patients represented our intention-to-treat population. In the perioperative group, 96% received the scheduled four neoadjuvant cycles and all but one had adjuvant FOLFOX for eight cycles. In the control arm, 38 (73%) patients received adjuvant FOLFOX. The median follow-up was 54.3 months. Three-year OS was 90.4% in both arms [hazard ratio (HR) = 0.85], 3-year DFS, RFS and TTR were, respectively, 76.8% and 69.2% (HR=0.94), 73% and 69.2% (HR = 0.86) and 82% and 72% (HR = 0.67) in the perioperative and control arms, respectively. Forest plots did not show any subgroup with significant difference for survival outcomes. No benefit from adding cetuximab was observed. Conclusion Perioperative FOLFOX has no detrimental effect on long-term oncological outcomes and may be an option for some patients with locally advanced CC.

Published
2021

3. Endoplasmic reticulum stress signalling - from basic mechanisms to clinical applications

Author

Aitor, Almanza, Antonio, Carlesso, Chetan, Chintha, Stuart, Creedican, Dimitrios, Doultsinos, Brian, Leuzzi, Andreia, Luís, Nicole, McCarthy, Luigi, Montibeller, Sanket, More, Alexandra, Papaioannou, Franziska, Püschel, Maria Livia, Sassano, Josip, Skoko, Patrizia, Agostinis, Jackie, de Belleroche, Leif A, Eriksson, Simone, Fulda, Adrienne M, Gorman, Sandra, Healy, Andrey, Kozlov, Cristina, Muñoz-Pinedo, Markus, Rehm, Eric, Chevet, Afshin, Samali, Commission of the European Communities, National University of Ireland [Galway] (NUI Galway), University of Gothenburg (GU), National University of Ireland Maynooth (Maynooth University), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Austrian Workers' Compensation Board (AUVA), Goethe-University Frankfurt am Main, Neurogenetics Group, Laboratory of Cell Death and Cancer Therapy [Madrid, Spain], Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Institute of Cell Biology and Immunology, University of Stuttgart, Goethe-University, Goethe-Universität Frankfurt am Main, RISE-734749, Erzincan Üniversitesi, Federación Española de Enfermedades Raras, BFU2016-78154-R, Ministerio de Economía y Competitividad, CERCA, and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Proteomics, Biochemistry & Molecular Biology, TO-MESENCHYMAL TRANSITION, [SDV.CAN]Life Sciences [q-bio]/Cancer, PLASMA-CELL DIFFERENTIATION, Review Article, Proteòmica, Endoplasmic Reticulum, 0601 Biochemistry and Cell Biology, ER-STRESS, stress, BOX-BINDING PROTEIN-1, QUALITY-CONTROL, Reticle endoplasmàtic, Animals, Homeostasis, Humans, TRANSCRIPTION FACTOR, Review Articles, Science & Technology, proteostasis, MESSENGER-RNA DECAY, 0304 Medicinal and Biomolecular Chemistry, UNFOLDED PROTEIN RESPONSE, Endoplasmic Reticulum Stress, endoplasmic reticulum, 1101 Medical Biochemistry and Metabolomics, signalling pathway, PANCREATIC BETA-CELLS, GLUCOSE-HOMEOSTASIS, Life Sciences & Biomedicine, Signal Transduction
Abstract

The endoplasmic reticulum (ER) is a membranous intracellular organelle and the first compartment of the secretory pathway. As such, the ER contributes to the production and folding of approximately one‐third of cellular proteins, and is thus inextricably linked to the maintenance of cellular homeostasis and the fine balance between health and disease. Specific ER stress signalling pathways, collectively known as the unfolded protein response (UPR), are required for maintaining ER homeostasis. The UPR is triggered when ER protein folding capacity is overwhelmed by cellular demand and the UPR initially aims to restore ER homeostasis and normal cellular functions. However, if this fails, then the UPR triggers cell death. In this review, we provide a UPR signalling‐centric view of ER functions, from the ER's discovery to the latest advancements in the understanding of ER and UPR biology. Our review provides a synthesis of intracellular ER signalling revolving around proteostasis and the UPR, its impact on other organelles and cellular behaviour, its multifaceted and dynamic response to stress and its role in physiology, before finally exploring the potential exploitation of this knowledge to tackle unresolved biological questions and address unmet biomedical needs. Thus, we provide an integrated and global view of existing literature on ER signalling pathways and their use for therapeutic purposes., The current article reviews the most up‐to‐date literature on Endoplasmic Reticulum (ER) biology and articulates this information from a signalling perspective. Not only do we cover the basic cell biology aspects of adaptive ER signalling but also provide information about the latest discoveries on ER stress targeting drugs and their potential use in the clinic.

Published
2019

4. Physical Activity and Amyloid-β Brain Levels in Elderly Adults with Intact Cognition and Mild Cognitive Impairment

Author

Claire Vinel, Philipe De Souto Barreto, Marc Bonnefoy, Francois Cotton, PERRET Bertrand, Olivier Rouaud, Pierre Payoux, Christophe Cognard, Daviet, Jean-Christophe, Géosciences Paris Sud ( GEOPS ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CRLCC Eugène Marquis ( CRLCC ), Epidémiologie et anlyses en santé publique: risques, maladies chroniques et handicaps, Université Paul Sabatier - Toulouse 3 ( UPS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Géosciences Paris Sud (GEOPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées

Subjects
Male, Oncology, Gerontology, Apolipoprotein E, medicine.medical_specialty, Multivariate analysis, Amyloid, Physical activity, Standardized uptake value, Motor Activity, Cognition, Alzheimer Disease, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Internal medicine, Humans, Medicine, Dementia, Cognitive Dysfunction, Aged, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Amyloid beta-Peptides, medicine.diagnostic_test, business.industry, Brain, medicine.disease, Cross-Sectional Studies, Positron emission tomography, Positron-Emission Tomography, Female, Geriatrics and Gerontology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Objectives To examine the associations between amyloid-β brain deposition and physical activity (PA) in elderly adults without dementia and to investigate whether the association has a dose-response relationship. Design Cross-sectional study. Setting French community-dwelling people. Participants Elderly adults with normal or mildly impaired cognition (mean age 74.7 ± 4.2; 60.4% female) with available information on current self-reported PA and amyloid-β brain deposition measured using positron emission tomography (PET) using the PET-ligand florbetapir F 18 (n = 268). Measurements A standardized uptake value ratio (SUVR) was obtained for each subject. Participants were divided according to amyloid plaque cortical retention defined according to a SUVR cutoff of 1.10 (SUVR+ vs SUVR−). Results Bivariate and multivariate analyses showed that PA was not significantly associated with SUVR. SUVR+ and SUVR− participants did not differ in terms of volume (continuous PA variables) and levels (categorical PA variables) of PA. PA was not correlated with SUVR in apolipoprotein E e4 carriers or noncarriers. PA was not associated with cognitive function. Conclusion Although PA protects against dementia, there is no solid evidence that this protection involves a reduction in amyloid-β brain deposition. Further studies are needed to determine whether PA (ideally measured at several time-points using objective measures) is involved in the pathophysiology of Alzheimer's disease.

Published
2015

5. Chemotherapy in advanced pancreatic adenosquamous carcinoma: A retrospective multicenter AGEO study

Author

Marie Auvray Kuentz, Vincent Hautefeuille, Louis de Mestier, Clélia Coutzac, Thierry Lecomte, Victor Nardon, Pascal Artru, Anthony Turpin, Antoine Drouillard, David Malka, My‐Linh Tran‐Minh, Isabelle Trouilloud, Astrid Lièvre, Nicolas Williet, Simon Pernot, Yann Touchefeu, Julien Taieb, Pascal Hammel, Aziz Zaanan, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Amiens-Picardie, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Léon Bérard [Lyon], Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Strasbourg Europe (ICANS), Hôpital privé Jean Mermoz [Lyon], CHU Lille, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Gustave Roussy (IGR), Département de médecine oncologique, CRLCC Paul Strauss, Hopital Saint-Louis [AP-HP] (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pontchaillou [Rennes], Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut Bergonié [Bordeaux], UNICANCER, Centre hospitalier universitaire de Nantes (CHU Nantes), Cancer Research and Personalized Medicine - CARPEM [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], and None

Subjects
Cancer Research, Oncology, adenosquamous carcinoma, advanced disease, pancreatic cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, chemotherapy
Abstract

International audience; Pancreatic adenosquamous carcinoma (PASC) account for < 5% of pancreatic malignancies. The efficacy of modern chemotherapy regimens in patients with advanced PASC is unknown. Patients with advanced PASC from 2008 to 2021 were consecutively included in this retrospective multicenter study. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method. Ninety-four PASC from 16 French centers were included (median age, 67.3 years; males, 56.4%; metastatic disease, 85.1%). The first-line treatment was chemotherapy for 79 patients (84.0%) (37 FOLFIRINOX (FX), 7 Gemcitabine-nab paclitaxel (GN) and 35 for all other regimen) or best supportive care (BSC) alone for 15 patients (16.0%). No significant difference was observed between FX and GN in terms of PFS (P = .67) or OS (P = .5). Modern regimens pooled together (FX and GN) as compared to all others chemotherapy regimens showed an improvement of overall response rate (39.5% and 9.7%, P = .002), PFS (median, 7.8 vs 4.7 months, P = .02) and OS (median, 12.7 vs 9.2 months, P = .35). This large study evaluating first-line treatment regimens in advanced PASC suggests that modern regimens as FX or GN may be preferable to all other chemotherapy regimens. These results deserve confirmation in prospective studies.

Published
2023

6. Contour‐guided deep learning based deformable image registration for dose monitoring during CBCT‐guided radiotherapy of prostate cancer

Author

Cédric Hemon, Bastien Rigaud, Anais Barateau, Florian Tilquin, Vincent Noblet, David Sarrut, Philippe Meyer, Julien Bert, Renaud De Crevoisier, Antoine Simon, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Paul Strauss, CRLCC Paul Strauss, Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), This work was partly funded by the French National Research Association (ANR) as part of the Investissement d'Avenir program (Labex CAMI) under reference ANR- 11-LABX-0004, by France Life Imaging (grant ANR-11-INBS-0006), and by the DELPEL project with financial support from ITMO Cancer AVIESAN (National Alliance for Life Sciences & Health) within the framework of the Cancer Plan., ANR-11-LABX-0004,CAMI,Gestes Médico-Chirurgicaux Assistés par Ordinateur(2011), and ANR-11-INBS-0006,FLI,France Life Imaging(2011)

Subjects
prostate, Radiation, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], CBCT, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Radiology, Nuclear Medicine and imaging, deformable registration, Instrumentation, dose monitoring
Abstract

Purpose: To evaluate deep learning (DL)-based deformable image registration (DIR) for dose accumulation during radiotherapy of prostate cancer patients.Methods and materials: Data including 341 CBCTs (209 daily, 132 weekly) and 23 planning CTs from 23 patients was retrospectively analyzed. Anatomical deformation during treatment was estimated using free-form deformation (FFD) method from Elastix and DL-based VoxelMorph approaches. The VoxelMorph method was investigated using anatomical scans (VMorph_Sc) or label images (VMorph_Msk), or the combination of both (VMorph_Sc_Msk). Accumulated doses were compared with the planning dose.Results: The DSC ranges, averaged for prostate, rectum and bladder, were 0.60-0.71, 0.67-0.79, 0.93-0.98, and 0.89-0.96 for the FFD, VMorph_Sc, VMorph_Msk, and VMorph_Sc_Msk methods, respectively. When including both anatomical and label images, VoxelMorph estimated more complex deformations resulting in heterogeneous determinant of Jacobian and higher percentage of deformation vector field (DVF) folding (up to a mean value of 1.90% in the prostate). Large differences were observed between DL-based methods regarding estimation of the accumulated dose, showing systematic overdosage and underdosage of the bladder and rectum, respectively. The difference between planned mean dose and accumulated mean dose with VMorph_Sc_Msk reached a median value of +6.3 Gy for the bladder and -5.1 Gy for the rectum.Conclusion: The estimation of the deformations using DL-based approach is feasible for male pelvic anatomy but requires the inclusion of anatomical contours to improve organ correspondence. High variability in the estimation of the accumulated dose depending on the deformable strategy suggests further investigation of DL-based techniques before clinical deployment.

Published
2023

7. Prognostic impact of cytoreductive surgery conducted with primary intent, versus cytoreductive surgery after neoadjuvant chemotherapy, in the management of patients with advanced epithelial ovarian cancers: a multicentre, propensity score‐matched study from the <scp>FRANCOGYN</scp> group

Author

Henri Wohrer, Meriem Koual, Enrica Bentivegna, Louise Benoit, Marie Metairie, Pierre‐Adrien Bolze, Yohan Kerbage, Emilie Raimond, Cherif Akladios, Xavier Carcopino, Geoffroy Canlorbe, Jennifer Uzan, Vincent Lavoue, Camille Mimoun, Cyrille Huchon, Martin Koskas, Hélène Costaz, François Margueritte, Yohann Dabi, Cyril Touboul, Sofiane Bendifallah, Lobna Ouldamer, Nicolas Delanoy, Huyen‐Thu Nguyen‐Xuan, Anne‐Sophie Bats, Henri Azaïs, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Cancer Research and Personalized Medicine - CARPEM [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and None

Subjects
epithelial ovarian cancer, interval cytoreductive surgery, Obstetrics and Gynecology, [SDV.CAN]Life Sciences [q-bio]/Cancer, primary cytoreductive surgery, propensity score, neoadjuvant chemotherapy
Abstract

International audience; Objective: To compare survival and morbidity rates between primary cytoreductive surgery (pCRS) and interval cytoreductive surgery (iCRS) for epithelial ovarian cancer (EOC), using a propensity score.Design: We conducted a propensity score-matched cohort study, using data from the FRANCOGYN cohort.Setting: Retrospective, multicentre study of data from patients followed in 15 French department specialized in the treatment of ovarian cancer.Sample: Patients included were those with International Federation of Gynaecology and Obstetrics (FIGO) stage III or IV EOC, with peritoneal carcinomatosis, having undergone CRS.Methods: The propensity score was designed using pre-therapeutic variables associated with both treatment allocation and overall survival (OS).Main outcome measures: The primary outcome was OS. Secondary outcomes included recurrence-free survival (RFS), quality of CRS and other variables related to surgical morbidity.Results: A total of 513 patients were included. Among these, 334 could be matched, forming 167 pairs. No difference in OS was found (hazard ratio, HR = 0.8, p = 0.32). There was also no difference in RFS (median = 26 months in both groups) nor in the rate of CRS leaving no macroscopic residual disease (pCRS 85%, iCRS 81.4%, p = 0.76). The rates of gastrointestinal tract resections, stoma, postoperative complications and hospital stay were significantly higher in the pCRS group.Conclusions: Analysis of groups of patients made comparable by propensity score matching showed no difference in survival, but lower postoperative morbidity in patients treated with iCRS.

Published
2023

8. Systematic functional analysis of the Ras GTPase family unveils a conserved network required for anterograde protein trafficking

Author

Roger Bossé, David L. Baillie, Sarah Jenna, Eric Chevet, Jeremy C. Simpson, Saïd Taouji, Marie-Elaine Caruso, Jonchère, Laurent, Department of Surgery [Montréal], McGill University = Université McGill [Montréal, Canada], Department of Molecular Biology and Biochemistry, Simon Fraser University (SFU.ca), PerkinElmer, School of Biology & Environmental Science, University College Dublin [Dublin] (UCD), Conway Institute of Biomolecular & Biomedical Research, 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), Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), 09/IN.1/B2604, Science Foundation Ireland, Institut National Du Cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Bergonié [Bordeaux], and UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2

Subjects
Proteomics, 0301 basic medicine, Cell biology, GTP', Membrane trafficking, GTPase, Biochemistry, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Animals, Humans, Gene silencing, Caenorhabditis elegans, Molecular Biology, Gene, Monomeric GTP-Binding Proteins, GTPases, biology, Functional analysis, Cell Membrane, biology.organism_classification, Transport protein, Protein Transport, 030104 developmental biology, ras Proteins, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Global analysis
Abstract

International audience; Phylogeny is often used to compare entire families of genes/proteins. We previously showed that classification of Caenorhabditis elegans Rho GTPases on the basis of their enzymatic properties was significantly different from sequence alignments. To further develop this concept, we have developed an integrated approach to classify C. elegans small GTPases based on functional data comprising affinity for GTP, sub-cellular localization, tissue distribution and silencing impact. This analysis led to establish a novel functional classification for small GTPases. To test the relevance of this classification in mammals, we focused our attention on the human orthologs of small GTPases from a specific group comprising arf-1.2, evl-20, arl-1, Y54E10BR.2, unc-108 and rab-7. We then tested their involvement in protein secretion and membrane traffic in mammalian systems. Using this approach we identify a novel network containing 18 GTPases, and 23 functionally interacting proteins, conserved between C. elegans and mammals, which is involved in membrane traffic and protein secretion.

Published
2017

9. AVAPS‐AE versus ST mode: A randomized controlled trial in patients with obesity hypoventilation syndrome

Author

Vanessa Bironneau, Marjolaine Georges, Frédéric Gagnadoux, Pierre Cervantes, C. Llontop, Frederic Goutorbe, Maxime Patout, Jacqueline Delrieu, Antoine Cuvelier, Christophe Perrin, Renaud Tamisier, Claudio Rabec, Jean-François Muir, Adriana Portmann, Jean-Louis Pépin, Wojciech Trzepizur, Valérie Attali, Sandrine Pontier-Marchandise, Service de pneumologie, oncologie thoracique et soins intensifs respiratoires [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Neurophysiologie Respiratoire Expérimentale et Clinique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Service des Explorations Fonctionnelles de la Respiration, de l'Exercice et de la Dyspnée - R3S', Pôle PRAGUES, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service des Pathologies du sommeil [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, Pulmonary and Respiratory Medicine, Polysomnography, [SDV]Life Sciences [q-bio], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, law.invention, Positive-Pressure Respiration, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Quality of life, law, Obesity Hypoventilation Syndrome, Clinical endpoint, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Tidal volume, Obesity hypoventilation syndrome, Noninvasive Ventilation, medicine.diagnostic_test, business.industry, [SDV.BA]Life Sciences [q-bio]/Animal biology, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, 3. Good health, 030228 respiratory system, Anesthesia, Quality of Life, Breathing, Arterial blood, Female, Blood Gas Analysis, Sleep, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Follow-Up Studies
Abstract

Background and objective Average volume-assured pressure support-automated expiratory positive airway pressure (AVAPS-AE) combines an automated positive expiratory pressure to maintain upper airway patency to an automated pressure support with a targeted tidal volume. The aim of this study was to compare the effects of 2-month AVAPS-AE ventilation versus pressure support (ST) ventilation on objective sleep quality in stable patients with OHS. Secondary outcomes included arterial blood gases, health-related quality of life, daytime sleepiness, subjective sleep quality and compliance to NIV. Methods This is a prospective multicentric randomized controlled trial. Consecutive OHS patients included had daytime Pa CO2 > 6 kPa, BMI ≥ 30 kg/m2 , clinical stability for more than 2 weeks and were naive from home NIV. PSG were analysed centrally by two independent experts. Primary endpoint was sleep quality improvement at 2 months. Results Among 69 trial patients, 60 patients had successful NIV setup. Baseline and follow-up PSG were available for 26 patients randomized in the ST group and 30 in the AVAPS-AE group. At baseline, Pa CO2 was 6.94 ± 0.71 kPa in the ST group and 6.61 ± 0.71 in the AVAPS-AE group (P = 0.032). No significant between-group difference was observed for objective sleep quality indices. Improvement in Pa CO2 was similar between groups with a mean reduction of -0.87 kPa (95% CI: -1.12 to -0.46) in the ST group versus -0.87 kPa (95% CI: -1.14 to -0.50) in the AVAPS-AE group (P = 0.984). Mean NIV use was 6.2 h per night in both groups (P = 0.93). NIV setup duration was shorter in the AVAPS-AE group (P = 0.012). Conclusion AVAPS-AE and ST ventilation for 2 months had similar impact on sleep quality and gas exchange.

Published
2020

10. Quality‐of‐life assessment in French patients with metastatic melanoma in real life

Author

Florence Granel-Brocard, Alain Dupuy, D. Legoupil, Jean-Jacques Grob, Marie Beylot-Barry, Marie-Thérèse Leccia, Jean-Philippe Arnault, Florence Brunet-Possenti, A. Bardet, Pierre-Emmanuel Stoebner, Céleste Lebbe, Stéphane Dalle, Eve Maubec, Clara Allayous, Isabelle Borget, Bernard Guillot, Brigitte Dréno, Julie DeQuatrebarbes, Philippe Saiag, Laurent Mortier, Marguerite Kandel, Sophie Dalac, Caroline Dutriaux, Thierry Lesimple, Stefan Michiels, Henri Montaudié, François Aubin, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Gustave Roussy (IGR), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe hospitalier Saint-André, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Ambroise Paré [AP-HP], Centre Hospitalier Universitaire de Nice (CHU Nice), Service de dermatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CRLCC Eugène Marquis (CRLCC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Avicennes University Hospital, Service de Dermatologie et Allergologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Dermatologie [Rennes] = Dermatology [Rennes], CHU Pontchaillou [Rennes], Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Léon Bérard [Lyon], AP-HP. Université Paris Saclay, Amgen Pfizer Merck Novartis Roche Janssen Biotech Meso Scale Diagnostics, MSD Array BioPharma Takeda Pharmaceutical Company Sanofi Pasteur British Microcirculation Society, BMS Institut National Du Cancer, INCa: DOC 16‐009, This work was supported by the French National Cancer Institute (DOC 16‐009)., Stéphane Dalle reports institutional research funding Roche, institutional research funding and nonfinancial support from Bristol‐Myers Squibb (BMS), and an immediate family member who is employed by Sanofi and owns stock or other ownership interest in the company. Aurélie Bardet was employed by Roche and held stock and other ownership interest in the company until March of 2018. Clara Allayous reports nonfinancial support from BMS, Amgen, and Roche outside the submitted work. Laurent Mortier reports personal fees and nonfinancial support from Roche, Novartis, BMS, and Merck Sharp & Dohme (MSD) outside the submitted work. Caroline Dutriaux reports personal fees from Roche, BMS, Novartis, MSD, and Pierre Fabre Laboratories outside the submitted work. Philippe Saiag reports research funding and personal fees from Roche, grants, personal fees, and nonfinancial support from BMS, MSD, Novartis, and Pierre Fabre Laboratories, and personal fees from Array, Sanofi, and Merck, all outside the submitted work. Henri Montaudié reports institutional research funding from LeoPharma, institutional research funding, personal fees, and nonfinancial support from BMS, personal fees from Pierre Fabre Laboratories and MSD, and nonfinancial support from Novartis, all outside the submitted work. Jean‐Phillipe Arnault reports institutional research funding and personal fees from BMS and institutional research funding from Novartis outside the submitted work. Jean‐Jacques Grob reports personal fees and nonfinancial support from BMS, Roche, MSD, Novartis, Merck, Amgen, Pierre Fabre Laboratories, Sanofi, and Pfizer and nonfinancial support from Amgen, all outside the submitted work. Julie De Quatrebarbes reports nonfinancial support from BMS, MSD, and Janssen outside the submitted work. Thierry Lesimple reports research funding and personal fees from Roche and personal fees from BMS, MSD, Novartis, Pierre Fabre Laboratories, and Incyte, all outside the submitted work. François Aubin reports personal fees and nonfinancial support from Novartis, MSD, and Roche outside the submitted work. Eve Maubec reports grants, personal fees, and nonfinancial support from MSD, personal fees from Sanofi and Novartis, personal fees and nonfinancial support from BMS, and nonfinancial support from Pierre Fabre Laboratories, all outside the submitted work. Stefan Michiels reports personal fees from IDDI Belgium, Janssen Cilag France, Hexal, Johnson & Johnson, Ipsen, Genticel, Mabxience, Steba, IQVIA, Roche, Sensorion, Biophytis, and Servier, all outside the submitted work. Céleste Lebbe reports institutional research funding, personal fees, and nonfinancial support from BMS, institutional funding and personal fees from Roche, personal fees and nonfinancial support from MSD, and personal fees from Aventis, Novartis, Amgen, Pierre Fabre Laboratories, Pfizer, and Incyte, all outside the submitted work. Isabelle Borget reports research funding from the BMS Foundation during the course of the study and personal fees from Roche, Janssen, CSC Behring, Novartis, and Takeda outside the submitted work. The remaining authors made no disclosures., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), and Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)

Subjects
Male, Cancer Research, MESH: Adolescent, Adult, Aged, 80 and over, Cohort Studies, Disease Progression, Female, France / epidemiology, Humans, Disease, Clinical practice, Targeted therapy, 0302 clinical medicine, Second line, Quality of life, Advanced disease, Medicine, Molecular Targeted Therapy, Prospective Studies, 030212 general & internal medicine, Neoplasm Metastasis, Melanoma, MESH: Immunotherapy, Melanoma / epidemiology, Melanoma / immunology, Melanoma / pathology, Melanoma / therapy, MESH: Middle Aged, Neoplasms, Second Primary / epidemiology, Young Adult, Real-life, Neoplasms, Second Primary, Middle Aged, 3. Good health, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Cohort, France, Immunotherapy, medicine.medical_specialty, Adolescent, Metastatic melanoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Internal medicine, In real life, Survival rate, Aged, business.industry, MESH: Neoplasms, Second Primary / immunology, Neoplasms, Second Primary / pathology, Quality of Life, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract

International audience; Background: Significant progress was recently observed in the treatment of metastatic melanoma (MM). With >50% of patients now reaching a second line of treatment and a significant improvement in the survival rate, an assessment of quality of life (QoL) during the whole course of the disease becomes necessary. The objective of this study was to describe the QoL of patients with MM in France, from their diagnosis of advanced disease to their death, in real life. Methods: QoL data were collected through MelBase, a prospective, French, multicentric cohort dedicated to the follow-up of adults with MM. QoL was assessed using the EuroQoL-5D questionnaire and the Functional Assessment of Cancer Treatment (FACT)-Melanoma questionnaire at the time of study inclusion, every 3 months, and at the time of each treatment change until death. To assess longitudinal changes from baseline to death, mixed-effect models for repeated-measures analyses were used to control for baseline covariates. Results: QoL was assessed in 1435 patients who were included in the study between 2013 and 2018. The median follow-up was 9.4 months, and 47% of patients died during follow-up. During first-line treatment, the model-based, mean utility score was 0.830 (95% CI, 0.818-0.843), the mean FACT-General score was 77.22 (95% CI, 76.23-78.22), and the mean FACT-Melanoma score was 129.46 (95% CI, 128.02-130.90). At the time of a change in treatment line, there was a decrease of −0.027 (95% CI, −0.03, −0.02) in the utility score, −1.82 (95% CI, −1.88, −1.76) in the FACT-General score, and −2.98 (95% CI, −3.05, −2.91) in the FACT-Melanoma score compared with first-line treatment. Conclusions: In the MelBase cohort, the QoL among patients with MM seems to be fairly stable over the whole disease course, although a small but significant decrease at time therapy is changed is observed.

Published
2019

11. Real‐life activity of eribulin mesylate among metastatic breast cancer patients in the multicenter national observational ESME program

Author

Audrey Mailliez, Jean-Marc Ferrero, Marie Chaix, Julien Fraisse, Mathieu Robain, Sophie Gourgou, Paul Cottu, Anthony Gonçalves, Claudia Lefeuvre, Marc Debled, Séverine Guiu, Jean-Christophe Eymard, Christelle Levy, C. Courtinard, Mario Campone, Marianne Leheurteur, Pierre-Etienne Heudel, William Jacot, Lionel Uwer, Barbara Pistilli, Florence Dalenc, Thierry Petit, Marie-Ange Mouret-Reynier, 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 du Cancer de Montpellier (ICM), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, Centre Léon Bérard [Lyon], Université de Montpellier (UM), Institut Claudius Regaud, 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), Institut Gustave Roussy (IGR), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Bergonié [Bordeaux], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), CRLCC Eugène Marquis (CRLCC), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Jean Godinot [Reims], Centre Paul Strauss, CRLCC Paul Strauss, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Institut Curie [Paris], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), and Université Lille Nord de France (COMUE)-UNICANCER

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Receptor, ErbB-2, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, Antineoplastic Agents, Breast Neoplasms, Disease-Free Survival, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, real-life cohort, Randomized controlled trial, law, Internal medicine, Humans, Medicine, Furans, education, eribulin, Aged, Retrospective Studies, Chemotherapy, education.field_of_study, business.industry, Ketones, Middle Aged, medicine.disease, Metastatic breast cancer, Progression-Free Survival, 3. Good health, chemistry, 030220 oncology & carcinogenesis, Concomitant, Cohort, Female, metastatic breast cancer, business, Eribulin
Abstract

International audience; Eribulin mesylate (EM) was recently approved for metastatic breast cancer (MBC) chemotherapy (CT) in late lines by the FDA, with debated results in second line. We evaluated outcomes in breast cancer patients receiving EM as second, third and fourth line in a national real-life cohort of 16,703 consecutive MBC patients initiating their first metastatic therapeutic line between 2008 and 2014. Primary and secondary objectives were overall survival (OS) and progression-free survival (PFS). An imbalance was seen for HER2+ tumors and concomitant anti-HER2 targeted therapies use, we thus performed a subanalysis in HER2- patients. PFS and OS were significantly better in EM patients in third and fourth lines, compared to "Other chemotherapies" patients (PFS: 4.14 vs. 3.02 months, p = 0.0010; 3.61 vs. 2.53 months, p = 0.0102, third and fourth-line; OS: 11.27 vs. 7.65 months, p = 0.0001; 10.91 vs. 5.95 months, p

Published
2019

12. Tissue oxygenation mapping by combined chemical shift and T 1 magnetic resonance imaging

Author

Patrick Saulnier, Hervé Saint-Jalmes, Laurent Lemaire, Florence Franconi, Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Plate-forme de Recherche en Imagerie et Spectroscopie Multi-modales [SFR ICAT - UA] (PRISM), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA)-Université d'Angers (UA), 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), CRLCC Eugène Marquis (CRLCC), ′Comité Inter-Régional Grand Ouest de la Ligue Contre le Cancer (CIRGO), Plate-forme de Recherche en Imagerie et Spectroscopie Multi-modales (PRISM [SFR ICAT - UA]), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adipose tissue, 030218 nuclear medicine & medical imaging, longitudinal relaxation time, 03 medical and health sciences, 0302 clinical medicine, Nuclear magnetic resonance, Carbogen, chemical shift imaging, Brown adipose tissue, medicine, Radiology, Nuclear Medicine and imaging, Fat fraction, medicine.diagnostic_test, Chemistry, brown adipose tissue, Magnetic resonance imaging, Oxygenation, Magnetic Resonance Imaging, 3. Good health, Tissue oxygenation, medicine.anatomical_structure, fat fraction, [SDV.IB]Life Sciences [q-bio]/Bioengineering, oxygenation, Phase modulation, 030217 neurology & neurosurgery
Abstract

International audience; PURPOSE: To propose a method for determining tissue oxygenation via the measurement of fat T1 . The method is based on a 2D fat/water chemical shift-encoded and T1 -weighted acquisition. THEORY AND METHODS: A 2D data set was acquired with a fast spin echo sequence with several echo asymmetries and repetition times, wherein one dimension is related to the fat/water phase modulation and the other to the T1 saturation recovery. A joint magnitude-based process of phase modulation and T1 evolution allowed for the collection of the fat fraction and T1 maps with resolved fat or water dominance ambiguity while avoiding the phased error problem. RESULTS: In vitro imaging allowed for the attribution of fat content for different water/oil emulsions that demonstrated longitudinal relaxation rate (R1 ) sensitivity to the oxygenated emulsion environment. The fat R1 values were subsequently compared to reference values, which were measured using low receiver bandwidth acquisition to enhance water and fat signal separations. In vivo feasibility of tissue oxygenation assessment was demonstrated by investigating interscapular brown adipose tissue modifications during an air/carbogen challenge in rats. CONCLUSION: The proposed method offers a precise and robust estimate of tissue oxygenation illustrated by the method's ability to detect-brown adipose tissue oxygenation modifications. Magn Reson Med 79:1981-1991, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Published
2017

13. High impact of macroaggregated albumin-based tumour dose on response and overall survival in hepatocellular carcinoma patients treated with90Y-loaded glass microsphere radioembolization

Author

Laure-Anne Haumont, Habiba Mesbah, Laurence Lenoir, Tanguy Rohou, Samuel Le Sourd, Marc Pracht, Julien Edeline, Yan Rolland, Sophie Laffont, Vanessa Brun, Etienne Garin, Foie, métabolismes et cancer, 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 ), CRLCC Eugène Marquis (CRLCC), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine nucléaire [Rennes], Université de Rennes (UNIV-RENNES), Département de Radiologie [CHU de Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Département d'oncologie médicale [Rennes], Labex IRON, 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)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR), and Jonchère, Laurent

Subjects
radioembolization, overall survival, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030218 nuclear medicine & medical imaging, Lesion, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Overall survival, medicine, Dosimetry, response, Hepatology, business.industry, predictive dosimetry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Predictive value, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Clinical trial, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Macroaggregated albumin, medicine.symptom, Nuclear medicine, business
Abstract

International audience; BACKGROUND & AIMS: Efficacy of radioembolization is derived from radioinduced damage, whereas tumour dosimetry is not considered as yet in prospective clinical trials. OBJECTIVES: This study evaluates the impact of tumour dose (TD), based on (99m) Tc macroaggregated albumin (MAA) quantification, on response and overall survival (OS). MATERIALS AND METHODS: We consecutively included 85 patients with hepatocellular carcinoma treated with (90) Y-loaded glass microspheres. TD was calculated using a quantitative analysis of the MAA SPECT/CT. Responses were assessed after 3 months using the European Association for the Study of the Liver criteria. OS was assessed using Kaplan-Meier tests. RESULTS: Response rate was 80.3% on lesion-based analysis (n=132), and 77.5% on patient-based analysis. The response rate was only 9.1% for patients with TD

Published
2016

14. Role of routine computed tomography scan in the oncological follow up of patients treated by radical cystectomy for bladder cancer

Author

Romain Mathieu, Solène-Florence Kammerer-Jacquet, Karim Bensalah, Benoit Peyronnet, Brigitte Laguerre, Quentin Alimi, Andrea Manunta, Francois Guille, Nathalie Rioux-Leclercq, Gregory Verhoest, Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de Pathologie [Rennes] = Pathology [Rennes], CHU Pontchaillou [Rennes], Département d'oncologie médicale [Rennes], CRLCC Eugène Marquis (CRLCC), Service d'urologie [Rennes], CHU Pontchaillou [Rennes]-Hôpital Pontchaillou-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Service de Pathologie [CHU Rennes]

Subjects
medicine.medical_specialty, recurrence, Multivariate analysis, Urology, medicine.medical_treatment, 030232 urology & nephrology, Computed tomography, tomography, Cystectomy, survival, Asymptomatic, 03 medical and health sciences, 0302 clinical medicine, Median follow-up, Statistical significance, medicine, Humans, follow up, Neoplasm Staging, Retrospective Studies, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Bladder cancer, medicine.diagnostic_test, business.industry, Retrospective cohort study, medicine.disease, 3. Good health, Surgery, Treatment Outcome, Urinary Bladder Neoplasms, 030220 oncology & carcinogenesis, bladder cancer, Neoplasm Recurrence, Local, medicine.symptom, Tomography, X-Ray Computed, business, Follow-Up Studies
Abstract

International audience; Objectives: To assess the impact of a prolonged follow-up schedule using computed tomography scan on oncological outcomes after radical cystectomy for bladder cancer. Methods: A single-center retrospective study was carried out. All patients who underwent a radical cystectomy for bladder cancer between 1992 and 2012 were included. The protocol for postoperative oncological follow up included a thoracoabdominal computed tomography scan twice per year for 2 years and then annually for life. The patients with tumor recurrence were divided into two groups: asymptomatic recurrences and recurrences diagnosed because of symptoms. Cancer-specific survivals were estimated using the Kaplan–Meier method and compared with the log–rank test. Cox proportional hazards regression models were used to determine the predictive factors of cancer-specific survival. Results: Overall, 331 patients were included in this analysis, and, of them, 48.5% had a cancer recurrence after a median follow up of 52.6 months. A total of 30 of these recurrences were diagnosed at routine follow up among asymptomatic patients (18.8%). A total of 50% of recurrences occurred during the first 6 months and 75% during the first year. Just 10 of the recurrences (6.3%) appeared more than 3 years after radical cystectomy. The 5-year cancer-specific survival was higher in patients with asymptomatic recurrences (15.7% vs 32.1%), but this difference was not statistically significant (P = 0.10). On multivariate analysis, detection of asymptomatic recurrence reached statistical significance (HR 0.55; P = 0.04). Conclusion: Routine computed tomography scan surveillance after radical cystectomy for bladder cancer might provide a survival benefit. The risk of recurrence beyond 3 years seems to be low, and further studies are required to determine the role of routine computed tomography scan in the follow up beyond this timeframe. © 2016 The Japanese Urological Association

Published
2016

15. Intermediate analysis of a phase II trial assessing gemcitabine and cisplatin in locoregional or metastatic penile squamous cell carcinoma

Author

Laura Dupuy, Stéphane Culine, Brigitte Laguerre, Thomas Filleron, Christine Theodore, Philippe Beuzeboc, Christine Chevreau, Gwenaelle Gravis, Nadine Houede, Aude Flechon, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), 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 Daniel Hollard [Grenoble], Department of Medical Oncology [Lyon], Centre Léon Bérard [Lyon], Institut Curie [Paris], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Département d'oncologie médicale [Rennes], CRLCC Eugène Marquis (CRLCC), Hôpital Foch [Suresnes], Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Claudius Regaud, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Institut Curie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), and CRLCC Institut Claudius Regaud

Subjects
Adult, Male, squamous cell carcinoma, Oncology, medicine.medical_specialty, Urology, medicine.medical_treatment, Population, 030232 urology & nephrology, Phases of clinical research, Kaplan-Meier Estimate, Deoxycytidine, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Unresected, Internal medicine, medicine, Clinical endpoint, Humans, Penile cancer, Neoplasm Metastasis, education, Penile Neoplasms, Aged, gemcitabine and cisplatin combination, education.field_of_study, Chemotherapy, business.industry, Middle Aged, penile cancer, medicine.disease, Gemcitabine, 3. Good health, Treatment Outcome, Response Evaluation Criteria in Solid Tumors, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Cisplatin, Neoplasm Recurrence, Local, business, medicine.drug
Abstract

International audience; OBJECTIVE:To perform a phase II study evaluating a combination of gemcitabine and cisplatin in a population of patients with squamous cell carcinoma (SCC) of the penis and unresected locoregional lymph nodes and/or distant metastases, who had a poor prognosis with no standard of chemotherapy.PATIENTS AND METHODS:Eligible patients had histologically confirmed SCC of the penis with unresected locoregional lymph nodes and/or distant metastases, at initial diagnosis or at relapse, and measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Patients were treated with a combination of gemcitabine 1250 mg/m(2) on day 1 over 30 min and cisplatin 50 mg/m(2) on day 1 over 1 h, every 2 weeks. The primary endpoint was the objective response rate; secondary endpoints were time to progression (TTP) and overall survival (OS).RESULTS:In all, 25 patients were included in the first phase of the study between February 2004 and January 2010 and received a median of five cycles. For the intent-to-treat population, two patients (95% confidence interval [CI] 0.98-26.0) presented an objective response and 13 patients (52%) had stable disease (95% CI 35.5-76.8). The median TTP was at 5.48 months (95% CI 2.40-11.73). After a median follow-up of 26.97 months (95% CI 17.77, not reached), nine patients were still alive. The median OS and 2-year OS rate were respectively estimated at 14.98 months (95% CI 9.76-32.9) and 39.32% (95% CI 19.15-59.03). Eleven patients had a serious adverse event (44%), 24% being relied to chemotherapy.CONCLUSION:Every 2 weeks' administration of the combination of gemcitabine and cisplatin showed non-significant responses in patients with unresected locoregional or metastatic penile SCC. Despite manageable side-effects, this combination cannot be recommended as a standard of care, due to disappointing response rates seen in this negative study. Further regimens should be explored to improve the OS of these patients with poor prognosis.

Published
2015

16. Integrative genome-wide analysis reveals a robust genomic glioblastoma signature associated with copy number driving changes in gene expression

Author

André Le Treut, Stephan Saikali, Véronique Quillien, Marc Aubry, Marie-Dominique Galibert, Amandine Etcheverry, Abderrahmane Hamlat, Marie de Tayrac, Jean Mosser, 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), Service de néphrologie [Rennes], CHU Pontchaillou [Rennes]-Hôpital Pontchaillou-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Plate-forme transcriptome, Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], Centre de ressources biologiques de Rennes, Service de neurochirurgie [Rennes] = Neurosurgery [Rennes], Service de Biologie, CRLCC Eugène Marquis (CRLCC), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes (UR), and De Villemeur, Hervé

Subjects
Cancer Research, Gene Dosage, MESH: Genes, erbB-1, Genome, MESH: Cadherins, MESH: Gene Dosage, 0302 clinical medicine, Gene expression, Oligonucleotide Array Sequence Analysis, Regulation of gene expression, Genetics, 0303 health sciences, MESH: Glioblastoma, GTPase-Activating Proteins, Chromosome Mapping, DNA, Neoplasm, MESH: Gene Expression Regulation, Neoplastic, Cadherins, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Metabolic Networks and Pathways, MESH: DNA, Neoplasm, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Gene dosage, MESH: Gene Expression Profiling, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Humans, MESH: Chromosome Aberrations, MESH: Tumor Suppressor Proteins, Gene, MESH: Genome, Human, 030304 developmental biology, Chromosome Aberrations, MESH: Humans, Genome, Human, Microarray analysis techniques, Gene Expression Profiling, Tumor Suppressor Proteins, Genes, erbB-1, Protocadherins, Gene expression profiling, MESH: Metabolic Networks and Pathways, MESH: Oligonucleotide Array Sequence Analysis, Human genome, Glioblastoma, MESH: Chromosome Mapping
Abstract

International audience; Glioblastoma multiforme shows multiple chromosomal aberrations, the impact of which on gene expression remains unclear. To investigate this relationship and to identify putative initiating genomic events, we integrated a paired copy number and gene expression survey in glioblastoma using whole human genome arrays. Loci of recurrent copy number alterations were combined with gene expression profiles obtained on the same tumor samples. We identified a set of 406 "cis-acting DNA targeted genes" corresponding to genomic aberrations with direct copy-number-driving changes in gene expression, defined as genes with either significantly concordant or correlated changes in DNA copy number and expression. Functional annotation revealed that these genes participate in key processes of cancer cell biology, providing insights into the genetic mechanisms driving glioblastoma. The robustness of the gene selection was validated on an external microarray data set including 81 glioblastomas and 23 non-neoplastic brain samples. The integration of array CGH and gene expression data highlights a robust cis-acting DNA targeted genes signature that may be critical for glioblastoma progression, with two tumor suppressor genes PCDH9 and STARD13 that could be involved in tumor invasiveness and resistance to etoposide.

Published
2009

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