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1. A Phase I/IIa study of autologous tolerogenic dendritic cells immunotherapy in kidney transplant recipients

Author: Aurélie Moreau, Delphine Kervella, Laurence Bouchet-Delbos, Cécile Braudeau, Soraya Saïagh, Pierrick Guérif, Sophie Limou, Anne Moreau, Sylvain Bercegeay, Mathias Streitz, Birgit Sawitzki, Ben James, Paul N. Harden, David Game, Qizhi Tang, James F. Markmann, Ian S.D. Roberts, Edward K. Geissler, Brigitte Dréno, Régis Josien, Maria-Cristina Cuturi, Gilles Blancho, Julien Branchereau, Diego Cantarovich, Agnès Chapelet, Jacques Dantal, Clément Deltombe, Lucile Figueres, Raphael Gaisne, Claire Garandeau, Magali Giral, Caroline Gourraud-Vercel, Maryvonne Hourmant, Georges Karam, Clarisse Kerleau, Christophe Masset, Aurélie Meurette, Simon Ville, Christine Kandell, Karine Renaudin, Florent Delbos, Alexandre Walencik, Anne Devis, Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Team 1 : Mononuclear phagocytes, Immunopathology, Immunovirology (U1064 Inserm - CR2TI), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Team 3 : Integrative transplantation, HLA, Immunology and genomics of kidney injury (U1064 Inserm - CR2TI), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Néphrologie et Immunologie Clinique [CHU de Nantes], Unité de Thérapie Cellulaire et Génique [CHU Nantes] (UTCG), Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), UMR 1064 Centre de Recherche en Transplantation et Immunologie, Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1064, ITUN - Institut de Transplantation Urologie Nephrologie, Nantes Université - École Centrale de Nantes (Nantes Univ - ECN), Clinical and Translational Research in Skin Cancer (CRCINA-ÉQUIPE 2), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Friedrich-Loeffler-Institut (FLI), University of Regensburg, Oxford University Hospitals NHS Trust, University of Oxford, Guy's and St Thomas' Hospital [London], University of California [San Francisco] (UC San Francisco), University of California (UC), Massachusetts General Hospital [Boston], University Hospital Regensburg, Fraunhofer Institute for Toxicology and Experimental Medicine (Fraunhofer ITEM), Fraunhofer (Fraunhofer-Gesellschaft), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Service de dermatologie [Nantes], LabEX IGO Immunothérapie Grand Ouest, DIVAT consortium: Gilles Blancho, Julien Branchereau, Diego Cantarovich, Agnès Chapelet, Jacques Dantal, Clément Deltombe, Lucile Figueres, Raphael Gaisne, Claire Garandeau, Magali Giral, Caroline Gourraud-Vercel, Maryvonne Hourmant, Georges Karam, Clarisse Kerleau, Delphine Kervella, Christophe Masset, Aurélie Meurette, Simon Ville, Christine Kandell, Anne Moreau, Karine Renaudin, Florent Delbos, Alexandre Walencik, Anne Devis., and KERANDEL-DION, Céline
Subjects: [SDV] Life Sciences [q-bio], tolerance, Nephrology, [SDV]Life Sciences [q-bio], transplantation, clinical trial, dendritic cells, cell therapy
Abstract: International audience; Kidney transplant survival is shortened by chronic rejection and side effects of standard immunosuppressive drugs. Cell-based immunotherapy with tolerogenic dendritic cells has long been recognized as a promising approach to reduce general immunosuppression. Published trials report the safety and the absence of therapy-related adverse reactions in patients treated with tolerogenic dendritic cells suffering from several inflammatory diseases. Here, we present the first phase I clinical trial results using human autologous tolerogenic dendritic cells (ATDC) in kidney transplantation. Eight patients received ATDC the day before transplantation in conjunction with standard steroids, mycophenolate mofetil and tacrolimus immunosuppression with an option to taper mycophenolate mofetil. ATDC preparations were manufactured in a Good Manufacturing Practice-compliant facility and fulfilled cell count, viability, purity and identity criteria for release. A control group of nine patients received the same standard immunosuppression, except basiliximab induction replaced ATDC therapy and mycophenolate tapering was not allowed. During the three-year follow-up, no deaths occurred and there was 100% graft survival. No significant increase of adverse events was associated with ATDC infusion. Episodes of rejection were observed in two patients from the ATDC group and one patient from the control group. However, all rejections were successfully treated by glucocorticoids. Mycophenolate was successfully reduced/stopped in five patients from the ATDC group, allowing tacrolimus monotherapy for two of them. Regarding immune monitoring, reduced CD8 T cell activation markers and increased Foxp3 expression were observed in the ATDC group. Thus, our results demonstrate ATDC administration safety in kidney-transplant recipients.
Published: 2023

2. Interactions of radiation therapy with common and innovative systemic treatments: Antidiabetic treatments, antihypertensives, lipid-lowering medications, immunosuppressive medications and other radiosensitizing methods

Author: Y, Zhou, A, Larnaudie, Y, Ghannam, L, Ollivier, Y, Gounane, A, Laville, A, Coutte, A, Huertas, P, Maroun, C, Chargari, S, Bockel, Institut de Chimie et des Matériaux Paris-Est (ICMPE), Institut de Chimie du CNRS (INC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Département de Radio-Oncologie [Baclesse, Caen], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Université d'Angers (UA), Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Groupe Avril, Institut Gustave Roussy (IGR), Curiethérapie, Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), and Department of Radiotherapy
Subjects: Antidiabétiques, Lung Neoplasms, Antihypertenseurs, Statin, Antidiabetic treatments, Lipids, Médicaments hypolipémiants, Metformin, Oncology, Lipid-lowering medications, Immunosuppresseurs, Immunosuppressive medications, Humans, Hypoglycemic Agents, Nanoparticles, Radiology, Nuclear Medicine and imaging, Immunotherapy, Antihypertensive Agents, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Antihypertensives
Abstract: International audience; The invention and approval of innovative anticancer therapies in the last decade have revolutionized oncology treatment. Radiotherapy is one of the three traditional pillars in oncology treatment with surgery and systemic therapies. Some standard-of-care combinations of chemoradiotherapy widened the therapeutic window of radiation, while some other chemotherapies such as gemcitabine caused unacceptable toxicities when combined with radiation in lung cancers. Fast-paced progress are specially focused on immunotherapies, targeted-therapies, anti-angiogenic treatment, DNA repair inhibitors, hormonotherapy and cell cycle inhibitors. New anticancer therapeutic arsenals provided new possibilities of combined oncological treatments. The interactions of the radiotherapy with other systemic treatments, such as non-anticancer immunomodulatory/immunosuppressive medications are sometimes overlooked even though they could offer a real therapeutic benefit. In this review, we summarize the new opportunities and the risks of historical and novel combined therapies with radiation: non-anticancer immunomodulatory/immunosuppressive drugs, systemic reoxygenation, new therapies such as nanoparticles and SMAC mimetics. Key biological mechanisms, pre-clinical and available clinical data will be provided to demonstrate the promising opportunities in the years to come.
Published: 2022

3. Evaluation of Bosch processing at cryogenic temperatures

Author: Nos, Jack, Tillocher, T., Lefaucheux, Philippe, Dussart, Rémi, Girard, Aurélie, Cardinaud, Christophe, Boufnichel, Mohamed, Groupe de recherches sur l'énergétique des milieux ionisés (GREMI), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Môle Armoricain de Recherche sur la SOciété de l'information et des usages d'INternet (MARSOUIN), Université de Rennes (UR)-Université de Bretagne Sud (UBS)-Ecole Nationale de la Statistique et de l'Analyse de l'Information [Bruz] (ENSAI)-Université de Brest (UBO)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 2 (UR2)-Université Bretagne Loire (UBL)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT), Laboratoire d'économie et de management de Nantes Atlantique (LEMNA), Institut d'Économie et de Management de Nantes - Institut d'Administration des Entreprises - Nantes (IEMN-IAE Nantes), Université de Nantes (UN)-Université de Nantes (UN)-FR 3473 Institut universitaire Mer et Littoral (IUML), Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), and ANR-20-CE24-0014,PSICRYO,Etude fondamentale des interactions plasma-surface dans les procédés de gravure cryogénique avancés(2020)
Subjects: [PHYS]Physics [physics]
Abstract: Bosch processing is an etching technique extensively used in the semiconductor industry towards the obtention of deep aspect ratio features which are necessary for MEMS and TSV applications [1,2]. The process consists in the repetition of an isotropic etching step using SF6 plasma followed by a C4F8 plasma step to passivate the trench sidewalls in order to achieve anisotropic profiles [2,3]. Although other techniques can be used towards deep silicon etching, such as standard cryoetching and the STiGer process, Bosch process offers less constraints as it is performed at ambient temperature and is very robust [1]. However, the main difficulty of this process is the gradual accumulation of fluorocarbonated species on the reactor sidewalls which leads to process deviations. Subsequently, different solutions have been developed to increase process stability and reduce the occurrence of reactor cleanings such as the development of heater liners on the reactor edges to heat the sidewalls above the condensation temperature of the fluorocarbonated polymers formed during passivation steps [4]. In comparison, cryogenic processes present the advantage of enhanced process stability as the reactive species mainly interact with the cooled substrate due to its cryogenic temperature. However, there is no significant study which attests of the impact of performing Bosch process at cryogenic temperatures and the impact of temperature in general on the etching profiles.In this research study, a given set of Bosch process parameters were performed at different temperatures to evaluate the evolution of the etching profile. It will be shown that Bosch process is effectively temperature dependent and that the necessary C4F8 passivating gas flow can be significantly reduced at cryogenic temperatures towards the obtention of anisotropic profiles (Fig. 1).Figure 1: Comparison of two etching profiles obtained with the same Bosch process parameters at different temperatures (Fig 1.a: T = -100°C and Fig 1.b: T = +20°C).Furthermore, a slight increase of the etch rate is observed at lower temperatures although it strengthens aspect ratio dependent etching (ARDE). A comprehensive study on the influence of temperature on the formation and properties of the flurorocarbonated passivation layer will be shown. Consequently, additional tests will be presented to evaluate whether the reduction of the necessary C4F8 gas flow at lower temperatures effectively results in the extension of process stability.The study was carried out using a cryogenic ICP reactor equipped with an in-situ ellipsometer. The tests were performed on Si coupons with a 1 μm surface SiO2 hard-mask layer. The hard-mask pattern consisted of trenches from 2 to 10 μm wide. These coupons were sticked on SiO2 4” carrier wafers using a specific thermal glue used for cryogenic process tests.This research project is supported by the CERTeM 2020 platform, which provides most of the equipment and funded by the European Union (FEDER fund) as well as the French National Research Agency (ANR PSICRYO fund).References 1. T. Tillocher, J. Nos, G. Antoun, P. Lefaucheux, M. Boufnichel, and R. Dussart, Comparison between Bosch and STiGer Processes for Deep Silicon Etching, Micromachines 12, 1143 (2021).2. M. A. Blauw, T. Zijlstra, and E. van der Drift, Balancing the Etching and Passivation in Time-Multiplexed Deep Dry Etching of Silicon, J. Vac. Sci. Technol. B Microelectron. Nanometer Struct. 19, 2930 (2001).3. F. Laemer, and A. Schilp, Method for Anisotropic Plasma Etching of Substrates, U.S. Patent 5498312A (1996).4. M. Puech, Heating Jacket for Plasma Etching Reactor, and Etching Method Using Same, U.S. Patent 0224178A1 (2005).
Published: 2023

4. SARS-CoV-2 E and 3a Proteins Are Inducers of Pannexin Currents

Author: Barbara B. R. Oliveira-Mendes, Malak Alameh, Béatrice Ollivier, Jérôme Montnach, Nicolas Bidère, Frédérique Souazé, Nicolas Escriou, Flavien Charpentier, Isabelle Baró, Michel De Waard, Gildas Loussouarn, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), LabEx Ion Channels Science and Therapeutics [France], Signaling in Oncogenesis, Angiogenesis and Permeability - SOAP (CRCI2NA / Eq 6), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Département de Santé Globale - Department Global Health, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), We thank the Agence Nationale de la Recherche for its financial support to the Région Pays de la Loire (ANR FLASH Covid-19 - CoV2-E-TARGET) and the laboratory of excellence ‘Ion Channels, Science and Therapeutics’ (grant No. ANR-11-LABX-0015)., ANR-20-COVI-0058,CoV2-E-TARGET,Criblage d'inhibiteurs de la protéine E du SARS-CoV-2(2020), ANR-11-LABX-0015,ICST,Canaux ioniques d'intérêt thérapeutique(2011), Loussouarn, Gildas, Criblage d'inhibiteurs de la protéine E du SARS-CoV-2 - - CoV2-E-TARGET2020 - ANR-20-COVI-0058 - COVID-19 - VALID, Laboratoires d'excellence - Canaux ioniques d'intérêt thérapeutique - - ICST2011 - ANR-11-LABX-0015 - LABX - VALID, Signaling in Oncogenesis, Angiogenesis and Permeability (CRCINA-ÉQUIPE 15), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, COVID-19, SARS-CoV-2, viroporins, E protein, 3a protein, pannexin currents, cell death, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, General Medicine
Abstract: Controversial reports have suggested that SARS-CoV E and 3a proteins may be viroporins that conduct currents through the plasma membrane of the infected cells. If true, these proteins would represent accessible targets for the development of new antiviral drugs by using high-throughput patch-clamp techniques. Here we aimed at better characterizing the cell responses induced by E or 3a protein with a particular focus on the ion conductances measured at the cell surface. First, we show that expression of SARS-CoV-2 E or 3a protein in CHO cells gives rise to cells with newly-acquired round shape, tending to detach from the Petri dish. This suggests that cell death is induced upon expression of E or 3a protein. We confirmed this hypothesis by using flow cytometry, in agreement with earlier reports on other cell types. In adhering cells expressing E or 3a protein, whole-cell currents were in fact not different from the control condition indicating that E and 3a proteins are not plasma membrane viroporins. In contrast, recording currents on detached cells uncovered outwardly-rectifying currents, much larger than those observed in control. The current characteristics are reminiscent of what was previously observed in cells expressing SARS-CoV-1 E or 3a proteins. Herein, we illustrate for the first time that carbenoxolone blocks these outward currents suggesting that they are conducted by pannexin channels, mostly likely activated by cell morphology change and/or cell death. Alongside we also demonstrate that truncation of the C-terminal PDZ binding motifs reduces the proportion of dying cells but does not prevent pannexin currents suggesting distinct pathways for cell death and pannexin currents induced by E and 3a proteins. We conclude that SARS-CoV-2 E and 3a proteins are not acting as viroporins expressed at the plasma membrane.Author SummaryA viroporin (or viral porin) is a class of proteins that is encoded by a virus genome. It is named porin because its biological role is to conduct ions through a pore that it created in a lipid membrane such as the one surrounding a human cell. if such viroporin is present at the external membrane of a human cell infected by a virus, it can be an easy target of an antiviral agent which thus does not have to enter the cell to be active. One example of viroporin is the flu M2 protein that is the target of amantadine, an antiviral agent used against flu. In previous studies, two proteins of SARS-CoV viruses, named E protein and 3a protein, have been suggested to be viroporins at the surface of infected human cells, potentially opening a new research avenue against SARS. Here we demonstrate that both proteins are not viroporins at the external membrane but they rather trigger changes in the cell shape and promote cell death. They only indirectly induce the activity of a porin that is encoded by the cell genome, named pannexin.
Published: 2023
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5. Phosphoantigen-Stimulated γδ T Cells Suppress Natural Killer–Cell Responses to Missing-Self

Author: Katherine Walwyn-Brown, Jason Pugh, Alexander T.H. Cocker, Niassan Beyzaie, Bernhard B. Singer, Daniel Olive, Lisbeth A. Guethlein, Peter Parham, Zakia Djaoud, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), 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), Department of Structural Biology [Stanford], Stanford Medicine, Stanford University-Stanford University, Stanford University, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and EFS Centre-Pays de la Loire [Nantes]
Subjects: Cancer Research, Butyrophilins, [SDV]Life Sciences [q-bio], Immunology, Receptors, Antigen, T-Cell, gamma-delta, Article, Killer Cells, Natural, Antigens, CD, Neoplasms, Cytokines, Humans, Immunotherapy, Intraepithelial Lymphocytes, T-Lymphocytes, Cytotoxic
Abstract: γδ T cells stimulated by phosphoantigens (pAg) are potent effectors that secrete Th1 cytokines and kill tumor cells. Consequently, they are considered candidates for use in cancer immunotherapy. However, they have proven only moderately effective in several clinical trials. We studied the consequences of pAg-stimulated γδ T-cell interactions with natural killer (NK) cells and CD8+ T cells, major innate and adaptive effectors, respectively. We found that pAg-stimulated γδ T cells suppressed NK-cell responses to “missing-self” but had no effect on antigen-specific CD8+ T-cell responses. Extensive analysis of the secreted cytokines showed that pAg-stimulated γδ T cells had a proinflammatory profile. CMV-pp65–specific CD8+ T cells primed with pAg-stimulated γδ T cells showed little effect on responses to pp65-loaded target cells. By contrast, NK cells primed similarly with γδ T cells had impaired capacity to degranulate and produce IFNγ in response to HLA class I–deficient targets. This effect depended on BTN3A1 and required direct contact between NK cells and γδ T cells. γδ T-cell priming of NK cells also led to a downregulation of NKG2D and NKp44 on NK cells. Every NK-cell subset was affected by γδ T cell–mediated immunosuppression, but the strongest effect was on KIR+NKG2A– NK cells. We therefore report a previously unknown function for γδ T cells, as brakes of NK-cell responses to “missing-self.” This provides a new perspective for optimizing the use of γδ T cells in cancer immunotherapy and for assessing their role in immune responses to pAg-producing pathogens.See related Spotlight by Kabelitz, p. 543.
Published: 2022

6. Human MuStem cells repress T-cell proliferation and cytotoxicity through both paracrine and contact-dependent pathways

Author: Marine Charrier, Judith Lorant, Rafael Contreras-Lopez, Gautier Téjédor, Christophe Blanquart, Blandine Lieubeau, Cindy Schleder, Isabelle Leroux, Sophie Deshayes, Jean-François Fonteneau, Candice Babarit, Antoine Hamel, Armelle Magot, Yann Péréon, Sabrina Viau, Bruno Delorme, Patricia Luz-Crawford, Guillaume Lamirault, Farida Djouad, Karl Rouger, École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Saint-Éloi [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Universidad de los Andes [Santiago] (UANDES), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier universitaire de Nantes (CHU Nantes), Macopharma [Mouvaux], and Bernardo, Elizabeth
Subjects: Medicine (General), Research, Medicine (miscellaneous), Mesenchymal Stem Cells, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Biology, QD415-436, Lymphocyte Activation, Muscular dystrophy, Biochemistry, Genetics and Molecular Biology (miscellaneous), Biochemistry, Coculture Techniques, Cell therapy, Immunomodulation, Adult Stem Cells, R5-920, [SDV.CAN] Life Sciences [q-bio]/Cancer, T-cell, Human adult stem cell, Molecular Medicine, Humans, MuStem cell, Cell Proliferation
Abstract: Background Muscular dystrophies (MDs) are inherited diseases in which a dysregulation of the immune response exacerbates disease severity and are characterized by infiltration of various immune cell types leading to muscle inflammation, fiber necrosis and fibrosis. Immunosuppressive properties have been attributed to mesenchymal stem cells (MSCs) that regulate the phenotype and function of different immune cells. However, such properties were poorly considered until now for adult stem cells with myogenic potential and advanced as possible therapeutic candidates for MDs. In the present study, we investigated the immunoregulatory potential of human MuStem (hMuStem) cells, for which we previously demonstrated that they can survive in injured muscle and robustly counteract adverse tissue remodeling. Methods The impact of hMuStem cells or their secretome on the proliferative and phenotypic properties of T-cells was explored by co-culture experiments with either peripheral blood mononucleated cells or CD3-sorted T-cells. A comparative study was produced with the bone marrow (BM)-MSCs. The expression profile of immune cell-related markers on hMuStem cells was determined by flow cytometry while their secretory profile was examined by ELISA assays. Finally, the paracrine and cell contact-dependent effects of hMuStem cells on the T-cell-mediated cytotoxic response were analyzed through IFN-γ expression and lysis activity. Results Here, we show that hMuStem cells have an immunosuppressive phenotype and can inhibit the proliferation and the cytotoxic response of T-cells as well as promote the generation of regulatory T-cells through direct contact and via soluble factors. These effects are associated, in part, with the production of mediators including heme-oxygenase-1, leukemia inhibitory factor and intracellular cell adhesion molecule-1, all of which are produced at significantly higher levels by hMuStem cells than BM-MSCs. While the production of prostaglandin E2 is involved in the suppression of T-cell proliferation by both hMuStem cells and BM-MSCs, the participation of inducible nitric oxide synthase activity appears to be specific to hMuStem cell-mediated one. Conclusions Together, our findings demonstrate that hMuStem cells are potent immunoregulatory cells. Combined with their myogenic potential, the attribution of these properties reinforces the positioning of hMuStem cells as candidate therapeutic agents for the treatment of MDs.
Published: 2022

7. Cytokine release syndrome and tumor lysis syndrome in a multiple myeloma patient treated with palliative radiotherapy: A case report and review of the literature

Author: Bastien Jamet, Axel Cailleteau, Cyrille Touzeau, Stéphane Supiot, Valentine Guimas, Emmanuel Jouglar, Bernardo, Elizabeth, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Site de Recherche Intégrée sur le Cancer - SIRIC « ILIAD » [Nantes], and Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9)
Subjects: medicine.medical_specialty, medicine.medical_treatment, R895-920, [SDV.CAN]Life Sciences [q-bio]/Cancer, Case Report, Radiation oncology, Gastroenterology, Medical physics. Medical radiology. Nuclear medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cytokine release syndrome, Multiple myeloma, Total body irradiation, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, Respiratory system, Tumor lysis syndrome, RC254-282, Leukemia, Hematology, Radiotherapy, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Radiation therapy, Oncology, business
Abstract: Highlights • Radiotherapy can trigger cytokine release syndrome and tumor lysis syndrome in association with chemotherapy drugs. • Extreme caution must be given when irradiating large tumor volumes at high risk of tumor lysis. • Evidence of cytokine release following radiotherapy unveils the systemic interactions of radiotherapy with the immune system., We present the case of a 53-year-old woman treated with analgesic radiotherapy for a multiple myeloma bone lesion of the forearm. After a first fraction of 5 Gray (Gy), she presented with an acute respiratory syndrome with fever a few hours after the treatment. The same symptoms occurred after the second fraction 3 days later. The patient recovered quickly thanks to intravenous hydration and suspension of the radiotherapy. Biological tests revealed a tumor lysis syndrome. We concluded that the clinical symptoms could be defined as cytokine release syndrome. This is the second time in the literature that cytokine release syndrome has been described following radiotherapy. First, we synthesize TLS and radiotherapy to determine how radiotherapy could be a trigger associated with other well-known factors. Furthermore, we discuss radiotherapy and cytokine release syndrome. Summary We present the case of a woman treated with analgesic radiotherapy for a multiple myeloma bone lesion. Following the first and the second treatment fraction, the patient presented with an acute respiratory syndrome with fever and biological tests revealed a tumor lysis syndrome. We concluded that the clinical symptoms could be defined as cytokine release syndrome. Furthermore, we discuss how radiotherapy could be a trigger of cytokine release syndrome and tumor lysis syndrome in association with chemotherapy drugs.
Published: 2022

8. Eco-friendly processes for the synthesis of amorphous calcium carbonate nanoparticles in ethanol and their stabilisation in aqueous media

Author: Lauriane Chuzeville, Frank Boury, David Duday, Resmi Anand, Enzo Moretto, Jean-Sébastien Thomann, Luxembourg Institute of Science and Technology (LIST), University of Luxembourg [Luxembourg], Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA-ÉQUIPE 17), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, Environmental Chemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pollution
Abstract: International audience; Amorphous calcium carbonate nanoparticles (ACC NPs) are promising multifunctional materials for healthcare applications. Due to their instability in aqueous media, pure ACC NPs for the biomedical field are increasingly synthesised in absolute ethanol, using the ammonia diffusion method (ADM). Although this method presents the advantage of providing stable ACC NPs without additives, it requires the use of pure ethanol as solvent. New insights into the formation mechanisms of ACC NPs in ethanol using gas diffusion are presented in this article. The optimisation of the process according to these findings can increase the mass concentration of ACC NPs by a factor of 3.5. As a result, the amount of ethanol required to produce a target mass of particles is significantly decreased, reducing the ecological impact of the process. The stabilisation of the resulting ACC NPs in aqueous media is achieved by a short-time process using phospholipids based on the ethanol injection method. By using the natural electrostatic affinity of negatively charged materials for the positive surface of ACC NPs in ethanol, we reduced the process time from 24 h to 2 minutes, compared with the closest state of the art, decreasing the operating time and corresponding energy consumption. The process does not require the use of synthetic PEGylated lipids for steric stabilisation. In addition, a natural egg-sourced phospholipid was identified as an efficient stabiliser for the first time. The upscaling of our process was successfully demonstrated using a 50 L reactor for bulk synthesis, as well as a continuous flow reactor for industrial continuous flow production.
Published: 2022

9. Faeces‐derived extracellular vesicles participate in the onset of barrier dysfunction leading to liver diseases

Author: Lionel Fizanne, Alexandre Villard, Nadia Benabbou, Sylvain Recoquillon, Raffaella Soleti, Erwan Delage, Mireille Wertheimer, Xavier Vidal‐Gómez, Thibauld Oullier, Samuel Chaffron, M. Carmen Martínez, Michel Neunlist, Jérôme Boursier, Ramaroson Andriantsitohaina, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université Bretagne Loire (UBL), Institut des Maladies de l'Appareil Digestif, and Université de Nantes (UN)
Subjects: Histology, gut microbiota, intestinal permeability, [SDV]Life Sciences [q-bio], non-alcoholic fatty liver disease, Cell Biology, extracellular vesicles
Abstract: International audience; The role of extracellular vesicles (EVs) from faeces (fEVs) and small circulating EVs (cEVs) in liver diseases such as non-alcoholic fatty diseases (NAFLD) and nonalcoholic steatohepatitis (NASH) has not been demonstrated. fEVs and cEVs of healthy donors, NAFLD and NASH patients were isolated and characterized. The effects of EVs were evaluated in intestinal, endothelial, Kupffer and stellate cells. Nonmuscular myosin light chain kinase (nmMLCK) deficient mice were used in vivo. Bacterial origins of fEVs were analysed by 16s rDNA gene sequencing. fEVs and small cEVs were composed of prokaryotic and eukaryotic origins. Only NASH-fEVs exerted deleterious effects. NASH-fEVs increased intestinal permeability and reduced expression of tight junction proteins that were prevented by nmMLCK inhibition, increased endothelial cell permeability and inflammatory cytokines and chemokines requiring TLR4/lipopolysaccharide pathway. NASH-fEVs and NASH-cEVs activated profibrotic and proinflammatory proteins of hepatic stellate cells. Treatment with NASH-fEVs evoked an increase in intestinal permeability in wild type but not in nmMLCK deficient mice. Bacterial origins of fEVs were different between NAFLD and NASH patients and 16 amplicon sequence variants were differentially abundant. We demonstrate that fEVs actively participate in barrier dysfunctions leading to liver injuries underscoring the role of nmMLCK and lipopolysaccharide carried by fEVs.
Published: 2023

10. Flow cytometric analysis of myelodysplasia: Pre-analytical and technical issues—Recommendations from the European LeukemiaNet

Author: Vincent H. J. van der Velden, Frank Preijers, Ulrika Johansson, Theresia M. Westers, Alan Dunlop, Anna Porwit, Marie C. Béné, Peter Valent, Jeroen te Marvelde, Orianne Wagner‐Ballon, Uta Oelschlaegel, Leonie Saft, Sharham Kordasti, Robin Ireland, Eline Cremers, Canan Alhan, Carolien Duetz, Willemijn Hobo, Nicolas Chapuis, Michaela Fontenay, Peter Bettelheim, Lisa Eidenshink‐Brodersen, Patricia Font, Michael R. Loken, Sergio Matarraz, Kiyoyuki Ogata, Alberto Orfao, Katherina Psarra, Dolores Subirá, Denise A. Wells, Matteo G. Della Porta, Kate Burbury, Frauke Bellos, Elisabeth Weiß, Wolfgang Kern, Arjan van de Loosdrecht, Hematology laboratory, Internal medicine, Hematology, VU University medical center, AII - Cancer immunology, CCA - Cancer biology and immunology, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Radboudumc Nijmegen [The Netherlands], University Hospitals Bristol, Amsterdam UMC - Amsterdam University Medical Center, Royal Marsden Hospital [Surrey, UK], Lund University [Lund], Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Medizinische Universität Wien = Medical University of Vienna, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor, University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Karolinska Institutet [Stockholm], King‘s College London, Maastricht University [Maastricht], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Ordensklinikum Linz Elisabethinen, HematoLogics, Inc. [Seattle, WA, USA], Hospital General Universitario 'Gregorio Marañón' [Madrid], Universidad de Salamanca, Instituto de Salud Carlos III [Madrid] (ISC), Metropolitan Research and Treatment Centre for Blood Disorders [Tokyo, Japan] (MRTC Japan), Evangelismos Athens General Hospital, Universidad de Guadalajara, Humanitas University [Milan] (Hunimed), University of Melbourne, Munich Leukemia Laboratory [Munich, Germany], MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), RS: FHML non-thematic output, Immunology, and Bernardo, Elizabeth
Subjects: Histology, MASTOCYTOSIS, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], BONE-MARROW, DIAGNOSTIC-CRITERIA, [SDV.CAN]Life Sciences [q-bio]/Cancer, REFRACTORY CYTOPENIA, CLASSIFICATION, Pathology and Forensic Medicine, pre-analytic issues, 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, hemic and lymphatic diseases, MDS, 030304 developmental biology, 0303 health sciences, flow cytometry, Cell Biology, QUANTIFICATION, LOW-GRADE, 3. Good health, CONSENSUS STATEMENTS, ELN, 030215 immunology, STANDARDS
Abstract: Contains fulltext : 290818.pdf (Publisher’s version ) (Open Access) BACKGROUND: Flow cytometry (FCM) aids the diagnosis and prognostic stratification of patients with suspected or confirmed myelodysplastic syndrome (MDS). Over the past few years, significant progress has been made in the FCM field concerning technical issues (including software and hardware) and pre-analytical procedures. METHODS: Recommendations are made based on the data and expert discussions generated from 13 yearly meetings of the European LeukemiaNet international MDS Flow working group. RESULTS: We report here on the experiences and recommendations concerning (1) the optimal methods of sample processing and handling, (2) antibody panels and fluorochromes, and (3) current hardware technologies. CONCLUSIONS: These recommendations will support and facilitate the appropriate application of FCM assays in the diagnostic workup of MDS patients. Further standardization and harmonization will be required to integrate FCM in MDS diagnostic evaluations in daily practice. 01 januari 2023
Published: 2023

11. Clinical application of flow cytometry in patients with unexplained cytopenia and suspected myelodysplastic syndrome: A report of the European LeukemiaNet International MDS-Flow Cytometry Working Group

Author: Loosdrecht, Arjan, Kern, Wolfgang, Porwit, Anna, Valent, Peter, Kordasti, Sharham, Cremers, Eline, Alhan, Canan, Duetz, Carolien, Dunlop, Alan, Hobo, Willemijn, Preijers, Frank, Wagner‐ballon, Orianne, Chapuis, Nicolas, Fontenay, Michaela, Bettelheim, Peter, Eidenschink‐brodersen, Lisa, Font, Patricia, Johansson, Ulrika, Loken, Michael, Marvelde, Jeroen, Matarraz, Sergio, Ogata, Kiyoyuki, Oelschlaegel, Uta, Orfao, Alberto, Psarra, Katherina, Subirá, Dolores, Wells, Denise, Béné, Marie, Della Porta, Matteo, Burbury, Kate, Bellos, Frauke, Velden, Vincent, Westers, Theresia, Saft, Leonie, Ireland, Robin, MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), RS: FHML non-thematic output, Amsterdam UMC - Amsterdam University Medical Center, Munich Leukemia Laboratory [Munich, Germany] (M2L), Lund University [Lund], Medizinische Universität Wien = Medical University of Vienna, King‘s College London, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], The Royal Marsden, Radboud University Medical Center [Nijmegen], Hôpital Henri Mondor, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Ordensklinikum Linz Elisabethinen, HematoLogics, Inc. [Seattle, WA, USA], Hospital General Universitario 'Gregorio Marañón' [Madrid], University Hospitals Bristol, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Universidad de Salamanca, Metropolitan Research and Treatment Centre for Blood Disorders [Tokyo, Japan] (MRTC Japan), University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Evangelismos Athens General Hospital, Universidad de Guadalajara, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Humanitas University [Milan] (Hunimed), Istituto Clinico Humanitas [Milan] (IRCCS Milan), University of Melbourne, Karolinska Institutet [Stockholm], King's College Hospital (KCH), Hematology, CCA - Cancer biology and immunology, Internal medicine, Hematology laboratory, Immunology, and Bernardo, Elizabeth
Subjects: standardization, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], flow cytometry, CONSORTIUM, [SDV.CAN]Life Sciences [q-bio]/Cancer, PROGNOSTIC SCORING SYSTEM, DIAGNOSIS, CYTOGENETICS, myelodysplastic syndromes, CLASSIFICATION, VALIDATION, All institutes and research themes of the Radboud University Medical Center, [SDV.CAN] Life Sciences [q-bio]/Cancer, consensus, hemic and lymphatic diseases, CELLS, SUBGROUPS, ELN, CYTOMORPHOLOGY
Abstract: Contains fulltext : 290800.pdf (Publisher’s version ) (Open Access) This article discusses the rationale for inclusion of flow cytometry (FCM) in the diagnostic investigation and evaluation of cytopenias of uncertain origin and suspected myelodysplastic syndromes (MDS) by the European LeukemiaNet international MDS Flow Working Group (ELN iMDS Flow WG). The WHO 2016 classification recognizes that FCM contributes to the diagnosis of MDS and may be useful for prognostication, prediction, and evaluation of response to therapy and follow-up of MDS patients. 01 januari 2023
Published: 2023

12. Biological differences between two commercial anti-CD19 CAR T cells products and impact on outcomes in lymphoma patients

Author: Tessoulin, Benoit, Grain, Audrey, Ollier, Jocelyn, Gastinne, Thomas, Dubruille, Viviane, Mahé, Béatrice, Blin, Nicolas, Lok, Anne, Vantyghem, Sophie, Sortais, Clara, Touzeau, Cyrille, Moreau, Philippe, Le Gouill, Steven, Chevallier, Patrice, Clémenceau, Béatrice, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Manipulation of Lymphocytes for Immunotherapy (CRCI2NA / Eq 12), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie Clinique [CHU Nantes] (Unité d'Investigation Clinique), Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Département d'Hématologie Clinique [CHU Nantes], Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), 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), university hospital, University Hospital, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), and Ollier, Jocelyn
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Abstract: International audience
Published: 2022

13. A polygenic risk score for multiple myeloma risk prediction

Author: Angelica Macauda, Matteo Pelosini, Krzysztof Jamroziak, Mario Petrini, Annette Juul Vangsted, Chiara Piredda, Stephane Minvielle, Marek Dudziński, Hervé Avet-Loiseau, Aleksandra Butrym, Ulla Vogel, Niels Abildgaard, Fabienne Lesueur, Waldemar Tomczak, Vibeke Andersen, Herlander Marques, Daniele Campa, Judit Várkonyi, Rui Manuel Reis, Katalin Kadar, Gabriele Buda, Małgorzata Raźny, Charles Dumontet, Juan Sainz, Anna Suska, Enrico Orciuolo, Agnieszka Druzd-Sitek, Marcin Kruszewski, Daria Zawirska, Niels Frost Andersen, Artur Jurczyszyn, Grzegorz Mazur, Marcin Rymko, Federica Gemignani, Edyta Subocz, Federico Canzian, Katia Beider, Jan Maciej Zaucha, Marzena Wątek, Arnon Nagler, Genomic Epidemiology Group [Heidelberg, Germany] (GEP / DKFZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Pisa - Università di Pisa, University Hospital of Cracow/Szpital Uniwersytecki w Krakowie [Poland] (SUK), Aarhus University Hospital, Chaim Sheba Medical Center, Sea Hospital [Gdynia, Poland] (SH), Wroclaw Medical University [Wrocław, Pologne] (WMU), Hospices Civils de Lyon (HCL), Holycross Cancer Center of Kelce, Hematology Clinic, Kielce, Institute of Hematology and Transfusion Medicine [Warsaw, Poland] (IHTM), Centre for Genomics and Oncological Research Pfizer [Granada, Spain] (GENYO), University of Granada [Granada]-Andalusian Regional Government [Granada, Spain], Hospital Universitario Virgen de las Nieves [Granada, Spain] (HUVN), Semmelweis University [Budapest], Odense University Hospital (OUH), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Teaching Hospital No 1 [Rzeszów, Poland] (TH1), University of Copenhagen = Københavns Universitet (KU), Military Institute of Medicine [Warsaw, Poland] (MIM), Rydygier Specialistic Hospital [Cracow, Poland] (RSH), University of Minho [Braga], Jagiellonian University Medical College [Cracow, Poland] (JUMC), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), The National Research Center for Work Environment [Copenhagen, Denmark] (NRCWE), University of Southern Denmark (SDU), ICVS/3B's - PT Government Associate Laboratory [Braga/Guimarães, Portugal] (AL), Barretos Cancer Hospital [São Paulo, Brazil] (BCH), 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), University Hospital Bydgoszcz [Bydgoszcz, Poland] (UHB), Medical University of Lublin, N. Copernicus Town Hospital [Torun, Poland] (NCTH), Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Bernardo, Elizabeth, Wrocław Medical University, 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), Universidad de Granada = University of Granada (UGR)-Andalusian Regional Government [Granada, Spain], Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Copenhagen = Københavns Universitet (UCPH), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), 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), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Oncology, medicine.medical_specialty, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Single-nucleotide polymorphism, Genome-wide association study, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, Internal medicine, Genetics, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, education, Genetics (clinical), Multiple myeloma, 030304 developmental biology, Genetic association, 0303 health sciences, education.field_of_study, business.industry, medicine.disease, Penetrance, 3. Good health, 030220 oncology & carcinogenesis, Polygenic risk score, Multiple Myeloma, business, Genome-Wide Association Study
Abstract: This work was partially supported by intramural funds of the University of Pisa, DKFZ, and University Hospital of Southern Jutland, Denmark, and by a grant of the French National Cancer Institute (INCA). The authors wish to thank Dr. Dominic Edelmann (Division of Biostatistics, DKFZ) for helpful advice about data analysis., There is overwhelming epidemiologic evidence that the risk of multiple myeloma (MM) has a solid genetic background. Genome-wide association studies (GWAS) have identified 23 risk loci that contribute to the genetic susceptibility of MM, but have low individual penetrance. Combining the SNPs in a polygenic risk score (PRS) is a possible approach to improve their usefulness. Using 2361 MM cases and 1415 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium, we computed a weighted and an unweighted PRS. We observed associations with MM risk with OR = 3.44, 95% CI 2.53-4.69, p = 3.55 x 10(-15) for the highest vs. lowest quintile of the weighted score, and OR = 3.18, 95% CI 2.1 = 34-4.33, p = 1.62 x 10(-13) for the highest vs. lowest quintile of the unweighted score. We found a convincing association of a PRS generated with 23 SNPs and risk of MM. Our work provides additional validation of previously discovered MM risk variants and of their combination into a PRS, which is a first step towards the use of genetics for risk stratification in the general population., University of Pisa, DKFZ, University Hospital of Southern Jutland, Denmark, Institut National du Cancer (INCA) France
Published: 2021

14. IAEA Activities on 67Cu, 186Re, 47Sc Theranostic Radionuclides and Radiopharmaceuticals

Author: G. Pupillo, Mohamed A. Gizawy, Amir Reza Jalilian, Aruna Korde, Cyrille Alliot, Sandor Takacs, Katherine Gagnon, Joao A. Osso, Jeong H. Park, Kotaro Nagatsu, Mayeen Uddin Khandaker, Aleksander Bilewicz, Suzanne E. Lapi, Sudipta Chakarborty, Subhani Okarvi, Mohammad R.A. Rovais, Valeriia N. Starovoitova, Renata Mikolajczak, Abdul Hamid Al Rayyes, International Atomic Energy Agency [Vienna] (IAEA), Egyptian Atomic Energy Authority (EAEA), Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), GIPARRONAX [Saint-Herblain, France], Institute For Nuclear Research and Nuclear Energy (INRNE), Bulgarian Academy of Sciences (BAS), Bhabha Atomic Research Centre (BARC), Government of India, Department of Atomic Energy, Nuclear Science and Technology Research Institute [Tehran, Iran] (NSTRI), Istituto Nazionale di Fisica Nucleare (INFN), National Institutes for Quantum and Radiological Science and Technology (QST), Korea Atomic Energy Research Institute [Daejeon, south Korea] (KAERI), Sunway University [Malaysia], Radioisotope Centre POLATOM [Otwock, Pologne] (POLATOM), Institute of Nuclear Chemistry and Technology [Warsaw, Poland] (INCT), King Faisal Specialist Hospital and Resarch Centre [Riyadh, Saudi Arabia] (KFSHRC), Biacore/GE Healthcare [Uppsala], Atomic Energy Commission of Syria (AECS), Gouvernement de la Syrie, University of Alabama at Birmingham [ Birmingham] (UAB), and Bernardo, Elizabeth
Subjects: Pharmacology, Engineering, medicine.medical_specialty, 186Re, business.industry, theranostic, Member states, IAEA, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, research reactor, [SDV.CAN] Life Sciences [q-bio]/Cancer, 030220 oncology & carcinogenesis, 47Sc, 67Cu, medicine, cyclotron, Radiology, Nuclear Medicine and imaging, Medical physics, CRP, business
Abstract: Despite interesting properties, the use of 67Cu, 186Re and 47Sc theranostic radionuclides in preclinical studies and clinical trials is curtailed by their limited availability due to a lack of widely established production methods. An IAEA Coordinated Research Project (CRP) was initiated to identify important technical issues related to the production and quality control of these emerging radionuclides and related radiopharmaceuticals, based on the request from IAEA Member States. The international team worked on targetry, separation, quality control and radiopharmaceutical aspects of the radionuclides obtained from research reactors and cyclotrons leading to preparation of a standard recommendations for all Member States. The CRP was initiated in 2016 with fourteen participants from thirteen Member States from four continents. Extraordinary results on the production, quality control and preclinical evaluation of selected radionuclides were reported in this project that was finalized in 2020. The outcomes, outputs and results of this project achieved by participating Member States are described in this minireview.
Published: 2021

15. Interest of the bc-GenExMiner web tool in oncology

Author: Hamza Lasla, Mario Campone, Philippe Juin, Pascal Jézéquel, Agnes Basseville, Fadoua Ben Azzouz, Wilfried Gouraud, Stress Adaptation and Tumor Escape in Breast Cancer (CRCINA-ÉQUIPE 8), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, SIRIC ILIAD [Angers, Nantes], and Bernardo, Elizabeth
Subjects: Prioritization, Oncology, Transcriptomique, Cancer Research, medicine.medical_specialty, Computer science, [SDV.CAN]Life Sciences [q-bio]/Cancer, Web tool, Breast tumor, 03 medical and health sciences, Breast cancer, 0302 clinical medicine, Data visualization, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, Statistical analysis, Web-based tool, Biomarker discovery, Transcriptomics, Cancer du sein, 030304 developmental biology, Outil web, 0303 health sciences, business.industry, Hematology, General Medicine, medicine.disease, Expression génique, 3. Good health, 030220 oncology & carcinogenesis, Gene expression, Web resource, business
Abstract: We are taking advantage of the launch of the latest version (v4.6) of our web-based data mining tool "breast cancer gene-expression miner" (bc-GenExMiner) to take stock of its position within the oncology research landscape and to present an activity report ten years after its establishment (http://bcgenex.ico.unicancer.fr). bc-GenExMiner is an open-access, user-friendly tool for statistical mining on breast tumor transcriptomes, annotated with more than 20 clinicopathologic and molecular characteristics. The database comprises more than 16,000 patients from 64 cohorts - including TCGA, METABRIC and SCAN-B - for whom several thousands of genes have been quantified by microarrays or RNA-seq. Correlation, expression and prognostic analyses are available for targeted, exhaustive or customized explorations of queried genes. bc-GenExMiner facilitates the validation, investigation, and prioritization of discoveries and hypotheses on genes of interest. It allows users to analyse large databases, create data visualizations, and obtain robust statistical analysis, thereby accelerating biomarker discovery. Ten years after its launch, judging by the number of visits, analyses, and scientific citations of bc-GenExMiner, we conclude that this web resource serves its purpose in the international scientific community working in breast cancer research, with a never-ending rise in its use., Nous profitons de l’occasion de la mise en ligne de la dernière version (v.4.6) de l’outil web breast cancer gene-expression miner (bc-GenExMiner) pour rappeler sa place dans le paysage de la recherche en oncologie et réaliser un bilan d’activité, dix ans après sa création (http://bcgenex.ico.unicancer.fr). bc-GenExMiner est un outil web de fouille statistique de données d’expressions géniques issues du criblage du transcriptome de tumeurs du sein annotées par une vingtaine de critères clinicopathologiques et moléculaires. Sa base de données inclut plus de 16 000 patientes issues de 64 cohortes, dont les cohortes METABRIC, SCAN-B et TCGA, pour lesquelles l’expression de plusieurs milliers de gènes a été mesurée par des puces à ADN ou par RNAseq. Il est composé de trois modules : « Corrélation », « Expression » et « Pronostic », qui permettent différentes sortes d’analyses. bc-GenExMiner offre aux chercheurs des possibilités de validation, d’exploration, de hiérarchisation d’hypothèses et de découverte concernant leurs gènes d’intérêt. Il permet de s’autonomiser par rapport à l’analyse de grandes bases de données, la production de figures, d’obtenir des résultats robustes et ainsi de gagner du temps pour la découverte de biomarqueurs. Dix ans après sa mise en ligne, à en juger par le nombre de visites, d’analyses et de citations de bc-GenExMiner dans des articles scientifiques, nous pouvons conclure que cet outil web sert la communauté scientifique internationale engagée dans la recherche sur le cancer du sein, et qu’il est de plus en plus utilisé.
Published: 2021

16. Splenectomy for primary immune thrombocytopenia revisited in the era of thrombopoietin receptor agonists: New insights for an old treatment

Author: Thibault Comont, Amandine Dernoncourt, Antoinette Perlat, Stéphane Cheze, Bernard Bonnotte, O. Souchaud-Debouverie, Pierre-Yves Jeandel, Bertrand Godeau, Jean-François Viallard, Jean-Christophe Lega, Delphine Gobert, Marc Michel, Mikael Ebbo, Corentin Orvain, Julie Graveleau, Antoine Dossier, Nathalie Costedoat-Chalumeau, Marc Ruivard, Louis Terriou, Arthur Mageau, CHU Henri Mondor, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de référence des cytopénies auto-immunes [CHU Mondor] (CeReCAI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Lille, CHU Lille, Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier de Saint-Nazaire, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université de Bourgogne (UB), Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Hôpital l'Archet, Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Amiens-Picardie, 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-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Bernardo, Elizabeth, CHU Henri Mondor [Créteil], 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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and CHU Toulouse [Toulouse]
Subjects: Adult, Male, Thrombopoietin Receptor Agonists, medicine.medical_specialty, medicine.medical_treatment, Splenectomy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Humans, Medicine, Retrospective Studies, Purpura, Thrombocytopenic, Idiopathic, business.industry, Retrospective cohort study, Hematology, Middle Aged, Immune thrombocytopenia, Treatment Outcome, Curative treatment, Sustained response, Female, Rituximab, business, Receptors, Thrombopoietin, medicine.drug
Abstract: Although splenectomy is still considered the most effective curative treatment for immune thrombocytopenia (ITP), its use has significantly declined in the last decade, especially since the approval of thrombopoietin receptor agonists (TPO-RAs). The main objective of the study was to determine whether splenectomy was still as effective nowadays, particularly for patients with failure to respond to TPO-RAs. Our secondary objective was to assess, among patients who relapsed after splenectomy, the pattern of response to treatments used before splenectomy. This multicentre retrospective study involved adults who underwent splenectomy for ITP in France from 2011 to 2020. Response status was defined according to international criteria. We included 185 patients, 100 (54.1%) and 135 (73.0%) patients had received TPO-RAs and/or rituximab before the splenectomy. The median follow-up after splenectomy was 39.2 months [16.5-63.0]. Overall, 144 (77.8%) patients had an initial response and 23 (12.4%) experienced relapse during follow-up, for an overall sustained response of 65.4%, similar to that observed in the pre-TPO-RA era. Among patients who received at least one TPO-RA or rituximab before splenectomy, 92/151 (60.9%) had a sustained response. Six of 13 (46%) patients with previous lack of response to both TPO-RAs and rituximab had a sustained response to splenectomy. Among patients with relapse after splenectomy, 13/21 (61.2%) patients responded to one TPO-Ras that failed before splenectomy. In conclusion, splenectomy is still a relevant option for treating adult primary ITP not responding to TPO-RAs and rituximab. Patients with lack of response or with relapse after splenectomy should be re-challenged with TPO-RAs. This article is protected by copyright. All rights reserved.
Published: 2021

17. Different number of circulating CD34 + cells in essential thrombocythemia, prefibrotic/early primary myelofibrosis, and overt primary myelofibrosis

Author: Valérie Ugo, Marie-Christine Rousselet, Damien Luque Paz, Laurane Cottin, Eric Lippert, Barbara Burroni, Françoise Boyer, Corentin Orvain, Franck Geneviève, Jean-Christophe Ianotto, Jean-Baptiste Robin, Charles Bescond, Mathilde Hunault-Berger, Isabelle Quintin-Roué, Laboratoire d'Hématologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), PRES Université Nantes Angers Le Mans (UNAM), Service des maladies du sang [Angers], Département d'anatomopathologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de cancérologie et d'hématologie [Brest], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), and LUQUE PAZ, DAMIEN
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Oncology, medicine.medical_specialty, Hematology, Primary (chemistry), business.industry, Essential thrombocythemia, Cd34 cells, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, medicine.disease, Polycythemia vera, Bone Marrow, Primary Myelofibrosis, Internal medicine, medicine, Humans, Myeloproliferative Neoplasms, Essential Thrombocythemia, business, Myelofibrosis, ComputingMilieux_MISCELLANEOUS, Thrombocythemia, Essential
Abstract: International audience; No abstract available
Published: 2021

18. Place de l’imagerie moléculaire dans la prise en charge du cancer de la prostate

Author: Bruno Maucherat, Mathieu Frindel, Caroline Rousseau, Vincent Fleury, M. Le Thiec, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, CRLCC René Gauducheau, and Bernardo, Elizabeth
Subjects: Initial staging, Mri imaging, Disease detection, PET/CT, [SDV.CAN]Life Sciences [q-bio]/Cancer, Next generation imaging, Imagerie de nouvelle génération, Management of prostate cancer, Prostate cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Recurrence, Stadification, Prostate, Medicine, Radiology, Nuclear Medicine and imaging, Stage (cooking), business.industry, medicine.disease, Innovative Therapies, medicine.anatomical_structure, Oncology, Psma pet, Récidive, Cancer de prostate, business, Nuclear medicine, TEP/TDM
Abstract: International audience; In the management of prostate cancer in recent years, innovative therapies have appeared requiring precise and reliable disease detection. In 2021, new generation imaging (PET/CT, multiparametric MRI, PET/MRI) have their place at all stages of the prostate cancer natural history to help target the lesion(s) and guide therapy and improve the results obtained. PSMA PET/CT is currently the leader in this type of imaging with a complete offer during the disease: both from diagnosis, to recurrence or in the oligo-metastatic and metastatic stage resistant to castration with a pivotal role in the PSMA theranostic approach. However, multiparametric MRI also has many detection advantages when the prostate is left in place, which suggests the potential major benefit of hybrid PSMA PET/MRI imaging.
Published: 2021

19. LentiRILES, a miRNA-ON sensor system for monitoring the functionality of miRNA in cancer biology and therapy

Author: David Gosset, Loris Roncali, Yoan Laurent, Chantal Pichon, Flora Reverchon, Emmanuel Garcion, Patrick Baril, Audrey Rousseau, Francisco Martin, Patrick Midoux, Claire Loussouarn, Viorel Simion, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA-ÉQUIPE 17), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre for Genomics and Oncological Research Pfizer [Granada, Spain] (GENYO), University of Granada [Granada]-Andalusian Regional Government [Granada, Spain], Inca : PL-BIO 2014–2020 (consortium Marengo)Ligue Contre le Cancer [Région du Loiret : 2017-2019]ARD 2020 Biopharmaceuticals [RNA cell factory 2017-2020], ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), ANR-19-ENM3-0003,GLIOSILK,Silk-fibroin interventional nano-trap for the treatment of glioblastoma.(2019), Université d'Orléans (UO)-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 d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Universidad de Granada = University of Granada (UGR)-Andalusian Regional Government [Granada, Spain], Bernardo, Elizabeth, Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID, and Silk-fibroin interventional nano-trap for the treatment of glioblastoma. - - GLIOSILK2019 - ANR-19-ENM3-0003 - Euronanomed III - VALID
Subjects: Male, Cell, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biosensing Techniques, Mice, SCID, Computational biology, Biology, Cell therapy, Mice, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Movement, Genes, Reporter, microRNA, Biomarkers, Tumor, Tumor Cells, Cultured, medicine, Animals, Humans, Luciferase, Molecular Biology, Gene, Cell Proliferation, miRNA, 030304 developmental biology, 0303 health sciences, Technical Paper, Cell Cycle, Lentivirus, glioblastoma, RNA therapeutics, Cell Biology, Middle Aged, molecular imaging, RILES, 3. Good health, Gene Expression Regulation, Neoplastic, MicroRNAs, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Luminescent Measurements, Female, Molecular imaging, Function (biology), Intracellular
Abstract: International audience; A major unresolved challenge in miRNA biology is the capacity to monitor the spatiotemporal activity of miRNAs expressed in animal disease models. We recently reported that the miRNA-ON monitoring system called RILES (RNAi-inducible expression Luciferase system) implanted in lentivirus expression system (LentiRILES) offers opportunity to decipher the kinetics of miRNA activity in vitro, in relation with their intracellular trafficking in glioblastoma cells. In this study we describe in detail the method for production of LentiRILES stable cell lines and employed it in several applications in the field of miRNA biology and therapy. We show that LentiRILES is a robust, highly specific and sensitive miRNA sensor system that can be used in vitro as a single-cell miRNA monitoring method, cell-based screening platform for miRNA therapeutics and as a tool to analyze the structurefunction relationship of the miRNA duplex. Furthermore, we report the kinetic of miRNA activity upon the intracranial delivery of miRNA mimics in an orthotopic animal model of glioblastoma. This information is exploited to evaluate the tumor suppressive function of miRNA-200c as locoregional therapeutic modality to treat glioblastoma. Our data provide evidence that LentiRILES is a robust system, well-suited to resolve the activity of endogenous and exogenously expressed miRNAs for basic research to gene and cell therapy.
Published: 2021

20. Correlation between magnetic resonance, X-ray imaging alterations and histological changes in an ovine model of age-related disc degeneration

Author: Bouhsina, N, Decante, C, Hardel, J, Madec, S, Abadie, J, Hamel, A, Le Visage, C, Lesoeur, J, Guicheux, J, Clouet, J, Fusellier, M, Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de Nantes - UFR Odontologie, Université de Nantes (UN), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Femme, Enfant, Adolescent [CHU Nantes] (Pôle hospitalo-universitaire PHU5 - FEA), Centre hospitalier universitaire de Nantes (CHU Nantes), Animaux modèles pour la recherche en oncologie comparée (AMaROC), Stress Adaptation and Tumor Escape in Breast Cancer (CRCINA-ÉQUIPE 8), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Ostéo-articulaire - Tête et cou - Odontologie - Neurochirurgie - Neurotraumatologie [CHU Nantes] (Pôle hospitalo-universitaire PHU4 - OTONN), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Santé Publique, Pharmacie et Prévention [CHU Nantes] (Pôle hospitalo-universitaire PHU11 - S3P), Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Jehan, Frederic
Subjects: [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], sheep, Lumbar Vertebrae, Magnetic Resonance Spectroscopy, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, RD1-811, X-Rays, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, x-ray imaging, degeneration, Intervertebral Disc Degeneration, Diseases of the musculoskeletal system, histology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, RC925-935, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, magnetic resonance imaging, Female, intervertebral disc, Surgery
Abstract: International audience; Sheep are one of the many animal models used to investigate the pathophysiology of disc degeneration and the regenerative strategies for intervertebral disc (IVD) disease. To date, few studies have thoroughly explored ageing of ovine lumbar IVDs. Hence, the objective of the present study was to concomitantly assess the development of spontaneous age-related lumbar IVD degeneration in sheep using X-ray, magnetic resonance imaging (MRI) as well as histological analyses. 8 young ewes (< 48 months old) and 4 skeletally mature ewes (> 48 months old) were included. Disc height, Pfirrmann and modified Pfirrmann grades as well as T2-wsi and T2 times were assessed by X-ray and MRI. The modified Boos score was also determined using histology sections. Pfirrmann (2 to 3) and modified Pfirrmann (2 to 4) grades as well as Boos scores (7 to 13) gradually increased with ageing, while T2-weighted signal intensity (1.18 to 0.75), T2 relaxation time (114.36 to 70.65 ms) and disc height (4.1 to 3.2 mm) decreased significantly. All the imaging modalities strongly correlated with the histology (p < 0.0001). The present study described the suitability of sheep as a model of age-related IVD degeneration by correlation of histological tissue alterations with the changes observed using X-ray and MRI. Given the structural similarities with humans, the study demonstrated that sheep warrant being considered as a pertinent animal model to investigate IVD regenerative strategies without induction of degeneration.
Published: 2021

21. Imaginer les territoires de montagne de demain face aux aléas naturels et sanitaires : Quelle(s) trajectoire(s) pour le Pays des Ecrins ?

Author: Arnaud, Aurélie, Beck, Elise, Bonnemains, Anouk, Claeys, Cécilia, Chambru, Mikaël, Crévolin, Amandine, Krohmer, Cathy, Marçot, Nathalie, Vlès, Vincent, Zaza, Ornella, Laboratoire Interdisciplinaire En Urbanisme (LIEU), Aix Marseille Université (AMU), Image et ville (IV), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Institut de physique du globe de Strasbourg (IPGS), Institut national des sciences de l'Univers (INSU - CNRS)-Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Laboratoire Population-Environnement-Développement (LPED), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Groupe de Recherche sur les Enjeux de la Communication (GRESEC), Université Grenoble Alpes (UGA), Laboratoire d'économie et de management de Nantes Atlantique (LEMNA), IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Nantes Université - Institut d'Administration des Entreprises - Nantes (Nantes Univ - IAE Nantes), Nantes Université - pôle Sociétés, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sociétés, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-FR 3473 Institut universitaire Mer et Littoral (IUML), Le Mans Université (UM)-Université d'Angers (UA)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Le Mans Université (UM)-Université d'Angers (UA)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ), Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), Centre d'Etude et de Recherche Travail Organisation Pouvoir (CERTOP), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Architecture, Ville, Urbanisme, Environnement (LAVUE), Université Paris 8 Vincennes-Saint-Denis (UP8)-École nationale supérieure d'architecture de Paris-La Villette (ENSAPLV), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Nanterre (UPN)-École nationale supérieure d'architecture de Paris Val-de-Seine (ENSA PVDS)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Institut d'Économie et de Management de Nantes - Institut d'Administration des Entreprises - Nantes (IEMN-IAE Nantes), Université de Nantes (UN)-Université de Nantes (UN)-FR 3473 Institut universitaire Mer et Littoral (IUML), Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SHS]Humanities and Social Sciences
Published: 2022

22. Advances in the Chemistry of Astatine and Implications for the Development of Radiopharmaceuticals

Author: Gilles Montavon, François Guérard, Jean-François Gestin, Nicolas Galland, Romain Eychenne, Lu Liu, Clémence Maingueneau, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), GIPARRONAX [Saint-Herblain, France], Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), INCa-DGOSInserm_12558, ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Guérard, François, Nucléaire pour la Santé - - ARRONAXPLUS2011 - ANR-11-EQPX-0004 - EQPX - VALID, Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID, and NExT (I-SITE) - - NExT (I-SITE)2016 - ANR-16-IDEX-0007 - IDEX - VALID
Subjects: Halogen bond, 010405 organic chemistry, [SDV]Life Sciences [q-bio], chemistry.chemical_element, General Medicine, General Chemistry, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, 3. Good health, [SDV] Life Sciences [q-bio], chemistry, 13. Climate action, Computational chemistry, Electrophile, Halogen, Nucleophilic substitution, Fluorine, Molecule, Earth (chemistry), Astatine, ComputingMilieux_MISCELLANEOUS
Abstract: ConspectusAstatine (At) is the rarest on Earth of all naturally occurring elements, situated below iodine in the periodic table. While only short-lived isotopes (t1/2 ≤ 8.1 h) are known, 211At is the object of growing attention due to its emission of high-energy alpha particles. Such radiation is highly efficient to eradicate disseminated tumors, provided that the radionuclide is attached to a cancer-targeting molecule. The interest in applications of 211At in nuclear medicine translates into the increasing number of cyclotrons able to produce it. Yet, many challenges related to the minute amounts of available astatine are to be overcome in order to characterize its physical and chemical properties. This point is of paramount importance to develop synthetic strategies and solve the labeling instability in current approaches that limits the use of 211At-labeled radiopharmaceuticals. Despite its discovery in the 1940s, only the past decade has seen a significant rise in the understanding of astatine's basic chemical and radiochemical properties, thanks to the development of new analytical and computational tools.In this Account, we give a concise summary of recent advances in the determination of the physicochemical properties of astatine, putting in perspective the duality of this element which exhibits the characteristics both of a halogen and of a metal. Striking features were evidenced in the recent determination of its Pourbaix diagram such as the identification of stable cationic species, At+ and AtO+, contrasting with other halogens. Like metals, these species were shown to form complexes with anionic ligands and to exhibit a particular affinity for organic species bearing soft donor atoms. On the other hand, astatine shares many characteristics with other halogen elements. For instance, the At- species exists in water, but with the least range of EH-pH stability in the halogen series. Astatine can form molecular interactions through halogen bonding, and it was only recently identified as the strongest halogen-bond donor. This ability is nonetheless affected by relativistic effects, which translate to other peculiarities for this heavy element. For instance, the spin-orbit coupling boosts astatine's propensity to form charge-shift bonds, catching up with the behavior of the lightest halogens (fluorine, chlorine).All these new data have an impact on the development of radiolabeling strategies to turn 211At into radiopharmaceuticals. Inspired by the chemistry of iodine, the chemical approaches have sparsely evolved over the past decades and have long been limited to electrophilic halodemetalation reactions to form astatoaryl compounds. Conversely, recent developments have favored the use of the more stable At- species including the aromatic nucleophilic substitution with diaryliodonium salts or the copper-catalyzed halodeboronation of arylboron precursors. However, it is clear that new bonding modalities are necessary to improve the in vivo stability of 211At-labeled aryl compounds. The tools and data gathered over the past decade will contribute to instigate original strategies for overcoming the challenges offered by this enigmatic element. Alternatives to the C-At bond such as the B-At and the metal-At bonds are typical examples of exciting new axes of research.
Published: 2021

23. Deciphering the biology of KIR2DL3+ T lymphocytes that are associated to relapse in haploidentical HSCT

Author: Catherine Willem, Zakia Djaoud, Thierry Guillaume, Gaëlle David, Nolwenn Legrand, Patrice Chevallier, Katia Gagne, Alexandre Walencik, Christelle Retière, Pierre Mérieau, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), EFS Centre-Pays de la Loire [Nantes], Bernardo, Elizabeth, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: Cyclophosphamide, medicine.medical_treatment, T cell, T-Lymphocytes, Science, Cell, Immunology, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, chemical and pharmacologic phenomena, Hematopoietic stem cell transplantation, Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Immune system, Immune Reconstitution, [SDV.CAN] Life Sciences [q-bio]/Cancer, Receptors, KIR, Recurrence, immune system diseases, medicine, Humans, Receptor, 030304 developmental biology, Cancer, Interleukin-15, 0303 health sciences, Multidisciplinary, Hematopoietic Stem Cell Transplantation, In vitro, Killer Cells, Natural, medicine.anatomical_structure, Receptors, KIR2DL3, Transplantation, Haploidentical, Medicine, 030215 immunology, medicine.drug
Abstract: KIR are mainly expressed on NK cells and to a lesser extent on T lymphocytes. Although the KIR NK cell repertoire was well explored in haploidentical Hematopoietic Stem Cell Transplantation (HSCT), KIR T cell compartment remains to be investigated in this context. In this study, the investigation of NK receptors on T lymphocytes during immune reconstitution after T-cell-replete haploidentical HSCT with Post-Transplant Cyclophosphamide (PTCy) has shown a significant increase of KIR2DL2/3+T cell frequency at day 25. This was especially observed at day 30 in recipients who relapsed. IL-15 but not IL-12 increased in vitro KIR+T cell expansion suggesting that the raised IL-15 serum concentration observed after PTCy in haploidentical HSCT might increase KIR+T cell frequency. Moreover, investigations from healthy blood donors showed a higher inhibiting effect of KIR2DL3 on CMV specific T cell response against allogeneic than autologous C1+target cells. The association of KIR+T cell subset with relapse may suggest that inhibitory KIR2DL2/3 limit anti-leukemic effect of specific T lymphocytes at this early step of immune reconstitution. Further phenotypic and mechanistic investigations on this cell subset from a broader cohort of HSCT recipients should clarify its potential implication in relapse occurrence. Our results demonstrate that KIR-HLA interactions known to modulate NK cell functions also modulate T cell immune responses in the context of allogeneic HSCT.
Published: 2021

24. Recommendations for planning and delivery of radical radiotherapy for localized urothelial carcinoma of the bladder

Author: Renaud de Crevoisier, David Azria, Christophe Hennequin, Jonathan Khalifa, Pierre Graff-Cailleaud, Igor Latorzeff, Gilles Créhange, Pierre Blanchard, Arnaud Mejean, Nicolas Magné, Morgane Cabaillé, Olivier Riou, Morgan Rouprêt, Géraldine Pignot, S. Belhomme, Olivier Chapet, Paul Sargos, Stéphane Culine, David Pasquier, Stéphane Supiot, 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), Endothelium Radiobiology and Targeting (CRCINA-ÉQUIPE 14), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Gustave Roussy (IGR), Department of Radiotherapy, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut de Cancérologie Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut du Cancer de Montpellier (ICM), Institut Bergonié [Bordeaux], UNICANCER, Clinique Pasteur [Toulouse], Equipe IFTIM [ImViA - EA7535], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Imagerie et Vision Artificielle [Dijon] (ImViA), Université de Bourgogne (UB)-Université de Bourgogne (UB), Centre pour l'innovation en cancérologie de Lyon (CICLY), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Guidelines, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Medical physics, Adaptive radiotherapy, Adaptative radiotherapy, Urothelial carcinoma, Image-guided radiation therapy, Carcinoma, Transitional Cell, Bladder cancer, Image guided radiation therapy, Radiotherapy, business.industry, Radiotherapy Planning, Computer-Assisted, Standard treatment, Radiotherapy Dosage, Radical radiotherapy, Hematology, medicine.disease, Clinical trial, Radiation therapy, Urinary Bladder Neoplasms, Oncology, 030220 oncology & carcinogenesis, Radiotherapy, Intensity-Modulated, Trimodal therapy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Radiotherapy, Image-Guided
Abstract: International audience; Purpose: Curative radio-chemotherapy is recognized as a standard treatment option for muscle-invasive bladder cancer (MIBC). Nevertheless, the technical aspects for MIBC radiotherapy are heterogeneous with a lack of practical recommendations.Methods and materials: In 2018, a workshop identified the need for two cooperative groups to develop consistent, evidence-based guidelines for irradiation technique in the delivery of curative radiotherapy. Two radiation oncologists performed a review of the literature addressing several topics relative to radical bladder radiotherapy: planning computed tomography acquisition, target volume delineation, radiation schedules (total dose and fractionation) and dose delivery (including radiotherapy techniques, image-guided radiotherapy (IGRT) and adaptive treatment modalities). Searches for original and review articles in the PubMed and Google Scholar databases were conducted from January 1990 until March 2020. During a meeting conducted in October 2020, results on 32 topics were presented and discussed with a working group involving 15 radiation oncologists, 3 urologists and one medical oncologist. We applied the American Urological Association guideline development's method to define a consensus strategy.Results: A consensus was obtained for all 34 except 4 items. The group did not obtain an agreement on CT enhancement added value for planning, PTV margins definition for empty bladder and full bladder protocols, and for pelvic lymph-nodes irradiation. High quality evidence was shown in 6 items; 8 items were considered as low quality of evidence.Conclusion: The current recommendations propose a homogenized modality of treatment both for routine clinical practice and for future clinical trials, following the best evidence to date, analyzed with a robust methodology. The XXX group formulates practical guidelines for the implementation of innovative techniques such as adaptive radiotherapy.
Published: 2021

25. Immune checkpoint inhibitors for the treatment of myeloma: novel investigational options

Author: Cyrille Touzeau, Baptiste Le Calvez, Philippe Moreau, Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Site de Recherche Intégrée sur le Cancer [Nantes] (SIRIC), Imaging and Longitudinal Investigations to Ameliorate Decision-making [Nantes] (ILIAD), Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre hospitalier universitaire de Nantes (CHU Nantes), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Bernardo, Elizabeth, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: PD-L1, Oncology, medicine.medical_specialty, Standard of care, Immune checkpoint inhibitors, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pembrolizumab, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Refractory, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, PD-1, medicine, Animals, Humans, Pharmacology (medical), Molecular Targeted Therapy, Immune Checkpoint Inhibitors, Multiple myeloma, 030304 developmental biology, nivolumab, Pharmacology, 0303 health sciences, biology, business.industry, Drugs, Investigational, General Medicine, Immunotherapy, medicine.disease, 3. Good health, multiple myeloma, Treatment Outcome, pembrolizumab, 030220 oncology & carcinogenesis, Immune checkpoints, biology.protein, Nivolumab, business
Abstract: International audience; Introduction: Multiple myeloma (MM) is still considered incurable and the outcome of patients with triple-class refractory remains very poor. Immunotherapy is considered as a standard of care for the treatment of MM. Among immunotherapeutic approaches, the PD-1/PD-L1 axis is an attractive target because PD-L1 is highly expressed in most myeloma plasma cells. While many types of cancer benefit from checkpoint inhibitor treatment, their relevance in multiple myeloma needs to be defined.Areas covered: The authors evaluate the published data regarding the mechanism of action, safety profile, and clinical efficacy of the immune checkpoint inhibitors (ICI) for the treatment of multiple myeloma.Expert opinion: The use of ICI monotherapy does not offer any clinical benefit in myeloma patients. In combination with immunomodulatory drugs (IMID), ICI failed to demonstrate clinical benefit and were associated with increased toxicity. Given the toxicities of these treatments, predictive markers would be useful to select patients who would benefit most. Clinical studies are necessary to evaluate the safety and efficacy of checkpoint inhibitors in combination with other standards of care such as proteasome inhibitors and monoclonal antibodies. The combination of anti-PD-1 with T-cell engager (TCE) or CAR-T cells seems theoretically attractive and should be explored in clinical trials.
Published: 2021

26. Unsupervised flow cytometry analysis in hematological malignancies: A new paradigm

Author: Anna Porwit, Marie C. Béné, Francis Lacombe, Bernardo, Elizabeth, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Bordeaux [Bordeaux], Lund University [Lund], Skane University Hospital [Lund], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: Hematological disorders, Computer science, Clinical Biochemistry, Large array, [SDV.CAN]Life Sciences [q-bio]/Cancer, Field (computer science), Bioconductor, 03 medical and health sciences, 0302 clinical medicine, Data acquisition, Software, [SDV.CAN] Life Sciences [q-bio]/Cancer, Bone Marrow, Cluster Analysis, Humans, Cluster analysis, 030304 developmental biology, 0303 health sciences, business.industry, flow cytometry, unsupervised analysis, Biochemistry (medical), Computational Biology, Hematology, General Medicine, Models, Theoretical, artificial intelligence, Data science, machine learning, Hematologic Neoplasms, 030220 oncology & carcinogenesis, T cell subset, Disease Progression, business, Algorithms, Unsupervised Machine Learning
Abstract: International audience; Ever since hematopoietic cells became "events" enumerated and characterized in suspension by cell counters or flow cytometers, researchers and engineers have strived to refine the acquisition and display of the electronic signals generated. A large array of solutions was then developed to identify at best the numerous cell subsets that can be delineated, notably among hematopoietic cells. As instruments became more and more stable and robust, the focus moved to analytic software. Almost concomitantly, the capacity increased to use large panels (both with mass and classical cytometry) and to apply artificial intelligence/machine learning for their analysis. The combination of these concepts raised new analytical possibilities, opening an unprecedented field of subtle exploration for many conditions, including hematopoiesis and hematological disorders. In this review, the general concepts and progress achieved in the development of new analytical approaches for exploring high-dimensional data sets at the single-cell level will be described as they appeared over the past few years. A larger and more practical part will detail the various steps that need to be mastered, both in data acquisition and in the preanalytical check of data files. Finally, a step-by-step explanation of the solution in development to combine the Bioconductor clustering algorithm FlowSOM and the popular and widely used software Kaluza® (Beckman Coulter) will be presented. The aim of this review was to point out that the day when these progresses will reach routine hematology laboratories does not seem so far away
Published: 2021

27. Small RNA mediated gradual control of lipopolysaccharide biosynthesis affects antibiotic resistance in Helicobacter pylori

Author: Pernitzsch, Sandy, Alzheimer, Mona, Bremer, Belinda, Robbe-Saule, Marie, De Reuse, Hilde, Sharma, Cynthia, University of Würzburg, ATOMycA (CRCINA-ÉQUIPE 6), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Pathogenèse de Helicobacter / Helicobacter Pathogenesis, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Open Access funding enabled and organized by Projekt DEAL. This publication was supported by the Open Access Publication Fund of the University of Würzburg. The Sharma lab received financial support from the Deutsche Forschungsgemeinschaft (DFG) project Sh580/1-1, the Young Academy program of the Bavarian Academy of Sciences and Humanities (BAdW), and the Bavarian Research Network bayresq.net. The De Reuse’s lab was funded by the Agence National de la Recherche [ANR-12-BSV5-0025-Bactox1] and the Pasteur-Weizmann consortium 'The roles of noncoding RNAs in regulation of microbial life styles and virulence.', ANR-12-BSV5-0025,BacTox1,Rôle des systèmes toxine antitoxine de type I dans la persistence bactérienne(2012), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bernardo, Elizabeth, and BLANC - Rôle des systèmes toxine antitoxine de type I dans la persistence bactérienne - - BacTox12012 - ANR-12-BSV5-0025 - BLANC - VALID
Subjects: Lipopolysaccharides, Bacterial immune evasion, Science, [SDV.CAN]Life Sciences [q-bio]/Cancer, Salt Stress, Article, Helicobacter Infections, Mice, Bacterial Proteins, [SDV.CAN] Life Sciences [q-bio]/Cancer, Bacterial genetics, Drug Resistance, Bacterial, Animals, ddc:610, Polymyxin B, Repetitive Sequences, Nucleic Acid, Helicobacter pylori, Stomach, Small RNAs, O Antigens, Gene Expression Regulation, Bacterial, RNA, Bacterial, RNA, Small Untranslated, Pathogens, 5' Untranslated Regions
Abstract: The small, regulatory RNA RepG (Regulator of polymeric G-repeats) regulates the expression of the chemotaxis receptor TlpB in Helicobacter pylori by targeting a variable G-repeat in the tlpB mRNA leader. Here, we show that RepG additionally controls lipopolysaccharide (LPS) phase variation by also modulating the expression of a gene (hp0102) that is co-transcribed with tlpB. The hp0102 gene encodes a glycosyltransferase required for LPS O-chain biosynthesis and in vivo colonization of the mouse stomach. The G-repeat length defines a gradual (rather than ON/OFF) control of LPS biosynthesis by RepG, and leads to gradual resistance to a membrane-targeting antibiotic. Thus, RepG-mediated modulation of LPS structure might impact host immune recognition and antibiotic sensitivity, thereby helping H. pylori to adapt and persist in the host., The small RNA RepG modulates expression of chemotaxis receptor TlpB in Helicobacter pylori by targeting a length-variable G-repeat in the tlpB mRNA. Here, Pernitzsch et al. show that RepG also gradually controls lipopolysaccharide biosynthesis, antibiotic susceptibility, and in-vivo colonization of the stomach, by regulating a gene that is co-transcribed with tlpB.
Published: 2021

28. Éligibilité des patients aux cellules CAR-T : avis d’experts proposé par la SFGM-TC

Author: Franck Morschhauser, Florence Rabian, Catherine Thieblemont, Marie-Thérèse Rubio, Guillaume Cartron, David Beauvais, Steven Le Gouill, Jacques-Olivier Bay, André Baruchel, Sabine Furst, Gandhi Damaj, Denis Caillot, Emmanuel Bachy, Ibrahim Yakoub-Agha, Université de Lille, Hôpital Claude Huriez [Lille], CHU Lille, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Recherche clinique appliquée à l'hématologie (URP_3518), Université de Paris (UP), Hôpital Robert Debré, CHU Clermont-Ferrand, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Caen Normandie (UNICAEN), Normandie Université (NU), Institut d'Hématologie de Basse-Normandie (IHBN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Paris Diderot - Paris 7 (UPD7), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Paris Cité (UPCité), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, CAR T-cells, Leucémie aiguë lymphoblastique B, Lymphoblastic Leukemia, [SDV.CAN]Life Sciences [q-bio]/Cancer, Marketing authorization, B-cell acute lymphoblastic leukemia, CD19, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, Lymphome diffus à grandes cellules B, biology, business.industry, Diffuse large B-cell lymphoma, Hematology, General Medicine, medicine.disease, Tumor antigen, Chimeric antigen receptor, 3. Good health, Lymphoma, Cellules CAR-T, 030104 developmental biology, Anticancer treatment, 030220 oncology & carcinogenesis, Expert opinion, biology.protein, business
Abstract: International audience; The chimeric antigen receptor T-cells are a new class of anticancer treatment consisting in genetically modifying autologous or allogenic T-cells to make express a CAR directed against a membrane tumor antigen. In Europe, tisagenlecleucel (KymriahTM) has a marketing authorization for the treatment of relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia in children and young adults and of R/R diffuse large B-cell lymphoma (DLBCL). The marketing authorization for axicabtagene ciloleucel (YescartaTM) is the treatment of DLBCL and primary R/R mediastinal B-cell lymphoma. The two products are autologous T-cells directed against CD19. This collaborative work, part of a series of expert opinion-based work, aims to give practical advice to help centers in selection of patients for commercially available CAR T-cell treatment.
Published: 2021

29. COVID-19 vaccines: Frequently asked questions and updated answers

Author: B Wyplosz, R Cohen, B Pitard, E Botelho-Nevers, O Epaulard, M Lefebvre, Nicolas Vignier, Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Host-Pathogen Interactions in the Regulation of Immune Responses (CRCINA-ÉQUIPE 5), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'Investigation Clinique - Epidémiologie Clinique Saint-Etienne (CIC-EC), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Infovac-France, Centre Hospitalier Intercommunal de Créteil (CHIC), Centre d'Investigation Clinique [Grenoble] (CIC Grenoble), CHU Grenoble-Hôpital Michallon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), SPILF Vaccination Prevention group, Bernardo, Elizabeth, CIC Saint Etienne, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Nord (Saint Etienne), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), and Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Nord (Saint Etienne)
Subjects: medicine.medical_specialty, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, Article, World health, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Pandemic, medicine, Humans, 030212 general & internal medicine, Antiviral treatment, 030304 developmental biology, 0303 health sciences, SARS-CoV-2, business.industry, Frequently asked questions, 3. Good health, Clinical trial, Infectious Diseases, Action (philosophy), Family medicine, Covid-19, business, Vaccine
Abstract: International audience; At the end of December 2019, China notified the World Health Organization about a viral pneumonia epidemic soon to be named Covid-19, of which the infectious agent, SARS-CoV-2, was rapidly identified. Less than one year later, published phase 3 clinical trials underlined the effectiveness of vaccines utilizing hitherto unusual technology consisting in injection of the messenger RNA (m-RNA) of a viral protein. In the meantime, numerous clinical trials had failed to identify a maximally effective antiviral treatment, and mass vaccination came to be considered as the strategy most likely to put an end to the pandemic. The objective of this text is to address and hopefully answer the questions being put forward by healthcare professionals on the different anti-SARS-CoV-2 vaccines as regards their development, their modes of action, their effectiveness, their limits, and their utilization in different situations; we are proposing a report on both today's state of knowledge, and the 14 February 2021 recommendations of the French health authorities.
Published: 2021

30. SF6 Physisorption based cryo-ALE of silicon

Author: Nos, Jack, Antoun, Gaelle, Tillocher, Thomas, Lefaucheux, Philippe, Girard, Aurélie, Cardinaud, Christophe, Dussart, Rémi, Môle Armoricain de Recherche sur la SOciété de l'information et des usages d'INternet (MARSOUIN), Université de Rennes (UR)-Université de Bretagne Sud (UBS)-Ecole Nationale de la Statistique et de l'Analyse de l'Information [Bruz] (ENSAI)-Université de Brest (UBO)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 2 (UR2)-Université Bretagne Loire (UBL)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT), Laboratoire d'économie et de management de Nantes Atlantique (LEMNA), Institut d'Économie et de Management de Nantes - Institut d'Administration des Entreprises - Nantes (IEMN-IAE Nantes), Université de Nantes (UN)-Université de Nantes (UN)-FR 3473 Institut universitaire Mer et Littoral (IUML), Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Groupe de recherches sur l'énergétique des milieux ionisés (GREMI), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), and ANR-20-CE24-0014,PSICRYO,Etude fondamentale des interactions plasma-surface dans les procédés de gravure cryogénique avancés(2020)
Subjects: [PHYS]Physics [physics]
Abstract: International audience; Cryogenic Atomic Layer Etching (Cryo-ALE) using C4F8 as a precursor gas has been previously presented as an alternative method to achieve ALE of SiO2. In this process, C4F8 is injected in gas phase during the “chemical modification” step, in order to physisorb on a cooled SiO2 surface. The etching step is then achieved using an Ar plasma with a low energy ion bombardment. The temperature window of this process was between -120°C and -90°C 1,2. A self-limiting etching regime was obtained with a regular etch per cycle (EPC) through several tens of nanometers which demonstrates the process stability without any contamination of the reactor walls. In this paper, we show the results using SF6 molecules as precursors for cryo-ALE of silicon.In 1996, Royer et al. studied the chemisorption of sulfur and fluorine on Si during a simultaneous exposure to SF6 gas and Ne+ ion beam. In this work, they showed by XPS measurements that the fluorine quantity on the Si surface tends to increase as the temperature decreases, for a process window between 20°C and 130°C 3. Therefore, a cryo-ALE study based on SF6 physisorption was carried out to extend the use of this alternative approach to other materials.The work presented in this paper was carried out using a cryogenic ICP reactor equipped with in-situ diagnostics. Mass spectrometry measurements enabled to characterize the SF6 physisorption and its surface residence time at different temperatures. Spectroscopic ellipsometry was used to monitor the etching rate and to characterize the sample surface at the nanoscale during the three process steps: SF6 physisorption, pumping and Ar plasma etching. Tests were performed on SiO2, Si3N4 and p-Si coupons glued on SiO2 6” carrier wafers.SF6 physisorption experiments will first be presented notably to determine the optimal temperature and purging time for the process. Subsequently, cryo-ALE test results on Si, SiO2 and Si3N4 will be shown. These results will finally be compared to the ones obtained previously using C4F8 physisorption.This research project is supported by the CERTeM 2020 platform, which provides most of the equipment and funded by the European Union (FEDER fund) as well as the French National Research Agency (ANR PSICRYO fund).1. Antoun et al., Appl. Phys. Lett. 115, 153109, 20192. Antoun et al., Sci. Rep. 10, 20213. Royer et al., J. Vac. Sci. Technol. A 14, 234–239, 1996
Published: 2022

31. Co-création de valeur et image de la destination touristique : quels intérêts pour les acteurs et les espaces touristiques dans un contexte africain ?

Author: Koffi Selom AGBOKANZO, Joseph Kaswengi, Mariem Ghares, Éthique et Gouvernance de l’Entreprise et des Institutions (EGEI), Université Catholique de l'Ouest (UCO), Laboratoire d'économie et de management de Nantes Atlantique (LEMNA), Nantes Université - Institut d'Administration des Entreprises - Nantes (Nantes Univ - IAE Nantes), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-FR 3473 Institut universitaire Mer et Littoral (IUML), Nantes Université - École Centrale de Nantes (NU - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Le Mans Université (UM)-Université de Bretagne Sud (UBS)-Nantes Université - École Centrale de Nantes (NU - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Le Mans Université (UM)-Université de Bretagne Sud (UBS), Val de Loire Recherche en Management (VALLOREM), Université d'Orléans (UO)-Université de Tours (UT), Institut d'Économie et de Management de Nantes - Institut d'Administration des Entreprises - Nantes (IEMN-IAE Nantes), Université de Nantes (UN)-Université de Nantes (UN)-FR 3473 Institut universitaire Mer et Littoral (IUML), Université de Bretagne Sud (UBS)-Le Mans Université (UM)-Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Le Mans Université (UM)-Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Nantes (UN)-École Centrale de Nantes (ECN), Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS), and Université de Tours-Université d'Orléans (UO)
Subjects: marketing territorial, contexte africain, image de la destination touristique, patrimoine culturel, [SHS.GESTION]Humanities and Social Sciences/Business administration, Co-création de valeur, tourisme, ComputingMilieux_MISCELLANEOUS, [SHS]Humanities and Social Sciences
Abstract: International audience; Le marketing du tourisme s’intéresse de plus en plus au concept de co-création de valeur. Cependant, nous observons une absence d’études sur l’un de ses antécédents, l’image, laquelle pourrait contribuer particulièrement au succès des destinations touristiques territoriales. Nous observons également qu’un contexte, qui est pourtant pertinent en termes culturel et d’interaction des acteurs, est absent des investigations: l’Afrique. Ainsi, le but de cette recherche est de mettre en évidence le lien entre l’image et la co-création de valeur dans le contexte africain. L’étude conceptuelle et théorique réalisée souligne que les dimensions affective et sociétale (ex. partage) de l’image en Afrique constituent non seulement les leviers des attitudes et comportements favorables des visiteurs à la co-création, mais aussi de l’expérience de ces derniers avec les résidents des territoires. Toutefois, l’étude souligne en même temps l’insuffisance d’initiatives concrètes mobilisant la contribution de l’image des acteurs dans la co-création de valeur.
Published: 2022

32. No survival improvement in patients with high‐risk multiple myeloma harbouring del(17p) and/or t(4;14) over the two past decades

Author: Carole Barin, Lotfi Benboubker, Cyrille Touzeau, Nicolas Vallet, Olivier Theisen, Pascal Godmer, Thomas Chalopin, Hervé Avet-Loiseau, Olivier Herault, Steven Le Gouill, Marlene Ochmann, Philippe Moreau, Mourad Tiab, Emmanuel Gyan, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Université de Bretagne Sud - Vannes (UBS Vannes), Université de Bretagne Sud (UBS), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service d'Hématologie [Nantes], Site de Recherche Intégrée sur le Cancer [Nantes] (SIRIC), Imaging and Longitudinal Investigations to Ameliorate Decision-making [Nantes] (ILIAD), Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Toulouse [Toulouse]-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)-Université Toulouse III - Paul Sabatier (UT3), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université 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), and Bernardo, Elizabeth
Subjects: Adult, Male, Oncology, medicine.medical_specialty, MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Text mining, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, In patient, ComputingMilieux_MISCELLANEOUS, Multiple myeloma, Aged, Retrospective Studies, Aged, 80 and over, Chromosome Aberrations, business.industry, Hematology, Middle Aged, Prognosis, medicine.disease, Survival Analysis, 3. Good health, 030220 oncology & carcinogenesis, Female, Multiple Myeloma, business, 030215 immunology
Abstract: International audience; No abstract available
Published: 2021

33. Delivery of cancer therapies by synthetic and bio-inspired nanovectors

Author: Briolay, Tina, Petithomme, Tacien, Fouet, Morgane, Nguyen-Pham, Nelly, Blanquart, Christophe, Boisgerault, Nicolas, Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Bernardo, Elizabeth, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Drug Carriers, Targeting, Cancer therapy, Genetic Vectors, Vesicle, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Combined Modality Therapy, lcsh:RC254-282, Theranostic Nanomedicine, Virus, Nanoparticle, Drug Delivery Systems, Treatment Outcome, Nanomedicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neoplasms, Vectorization, Drug delivery, Animals, Humans, Nanoparticles, Nanotechnology
Abstract: International audience; Background: As a complement to the clinical development of new anticancer molecules, innovations in therapeutic vectorization aim at solving issues related to tumor specificity and associated toxicities. Nanomedicine is a rapidly evolving field that offers various solutions to increase clinical efficacy and safety. Main: Here are presented the recent advances for different types of nanovectors of chemical and biological nature, to identify the best suited for translational research projects. These nanovectors include different types of chemically engineered nanoparticles that now come in many different flavors of 'smart' drug delivery systems. Alternatives with enhanced biocompatibility and a better adaptability to new types of therapeutic molecules are the cell-derived extracellular vesicles and microorganism derived oncolytic viruses, virus-like particles and bacterial minicells. In the first part of the review, we describe their main physical, chemical and biological properties and their potential for personalized modifications. The second part focuses on presenting the recent literature on the use of the different families of nanovectors to deliver anticancer molecules for chemotherapy, radiotherapy, nucleic acid-based therapy, modulation of the tumor microenvironment and immunotherapy. Conclusion: This review will help the readers to better appreciate the complexity of available nanovectors and to identify the most fitting "type" for efficient and specific delivery of diverse anticancer therapies.
Published: 2021

34. L’apport des tensions de rôle dans l’ingénierie des espaces de discussion

Author: Nathalie Jeannerod-Dumouchel, Lambert Lanoë, Melia Arras-Djabi, Jeannerod-Dumouchel, Nathalie, Dauphine Recherches en Management (DRM), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay, Institut de Recherche en Gestion (IRG), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Gustave Eiffel, Université Gustave Eiffel, Laboratoire d'économie et de management de Nantes Atlantique (LEMNA), FR 3473 Institut universitaire Mer et Littoral (IUML), Université de Bretagne Sud (UBS)-Le Mans Université (UM)-Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Le Mans Université (UM)-Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Institut d'Économie et de Management de Nantes - Institut d'Administration des Entreprises - Nantes (IEMN-IAE Nantes), Université de Nantes (UN)-Université de Nantes (UN), Institut d'Économie et de Management de Nantes - Institut d'Administration des Entreprises - Nantes (IEMN-IAE Nantes), Université de Nantes (UN)-Université de Nantes (UN)-FR 3473 Institut universitaire Mer et Littoral (IUML), Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS), Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), and École Centrale de Nantes (ECN)-Université de Nantes (UN)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Le Mans Université (UM)-Université de Bretagne Sud (UBS)-École Centrale de Nantes (ECN)-Université de Nantes (UN)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Le Mans Université (UM)-Université de Bretagne Sud (UBS)
Subjects: Economics and Econometrics, Strategy and Management, tensions de rôle, ingénierie, IRG_AXE1, 06 humanities and the arts, 0603 philosophy, ethics and religion, 030210 environmental & occupational health, recherche-intervention, 03 medical and health sciences, 0302 clinical medicine, [SHS.GESTION]Humanities and Social Sciences/Business administration, espaces de discussion, 060301 applied ethics, Business and International Management, [SHS.GESTION] Humanities and Social Sciences/Business administration
Abstract: International audience; Pour contribuer à résoudre les tensions au travail, la mise en place d’espaces de discussion (EDD) a été plébiscitée par des auteurs majeurs dans l’ensemble des disciplines en sciences sociales. Nous poursuivons ces recherches en posant l’hypothèse que le concept de tensions de rôle peut contribuer au développement des EDD dans les organisations, aussi bien d’un point de vue théorique que d’un point de vue opératoire en favorisant les échanges grâce à l’introduction d’un langage commun centré sur le travail réel. À travers une expérimentation conduite en recherche-intervention chez Enedis, qui souhaite aider ses managers à parler autrement du travail, nos résultats montrent que traduites en mots simples, les tensions de rôle agissent en tant qu’opérateur de langage facilitant la construction d’un « terrain d’entente » entre les participants à un EDD et que cette méthode concourt à la (re)construction des collectifs de travail.
Published: 2021

35. Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma

Author: Hani Hassoun, Jacob P. Laubach, Jan S. Moreb, Sara Thuresson, Paula Rodriguez-Otero, Marcus Thuresson, Michele Cavo, Albert Oriol, Maria-Victoria Mateos, Joan Bladé, John W. Hiemenz, Adrian Alegre, Amitabha Mazumder, Horizon (Op ) Investigators, Kenneth C. Anderson, Omar Nadeem, Johan Harmenberg, Nicolaas A Bakker, Xavier Leleu, Alessandra Larocca, Christopher Maisel, Paul G. Richardson, Agne Paner, Anastasios Raptis, Cyrille Touzeau, Catriona Byrne, Harvard Medical School [Boston] (HMS), Hospital Universitari Germans Trias I Pujol [Badalona], Università degli studi di Torino = University of Turin (UNITO), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), University of Bologna/Università di Bologna, Clínica Universidad de Navarra [Pamplona], Centre hospitalier universitaire de Poitiers (CHU Poitiers), University of Florida [Gainesville] (UF), Memorial Sloane Kettering Cancer Center [New York], Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université d'Angers (UA), Université de Nantes (UN), Site de Recherche Intégrée sur le Cancer [Nantes] (SIRIC), Centre hospitalier universitaire de Nantes (CHU Nantes), SIRIC ILIAD [Angers, Nantes], Hospital Universitario Quironsalud, Rush University Medical Center [Chicago], Baylor Scott & White Charles A. Sammons Cancer Center [Dallas, TX, USA], Oncology Institute of Hope and Innovation [Glendale, CA, USA] (OIHI), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Novant Health Forsyth Medical Center [Winston-Salem, NC, USA] (NHFMC), Oncopeptides AB [Stockholm, Sweden], Instituto de Investigación Biomédica de Salamanca [Salamanca, Spain] (IBSAL/CIC), HORIZON (OP-106) Investigators, Bernardo, Elizabeth, Università degli studi di Torino (UNITO), University of Bologna, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Richardson P.G., Oriol A., Larocca A., Blade J., Cavo M., Rodriguez-Otero P., Leleu X., Nadeem O., Hiemenz J.W., Hassoun H., Touzeau C., Alegre A., Paner A., Maisel C., Mazumder A., Raptis A., Moreb J.S., Anderson K.C., Laubach J.P., Thuresson S., Thuresson M., Byrne C., Harmenberg J., Bakker N.A., and Mateos M.-V.
Subjects: Adult, Male, Cancer Research, Time Factors, Time Factor, Phenylalanine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Tumor cells, Drug resistance, Dexamethasone, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Recurrence, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Neoplasm, Progression-free survival, Melphalan, Aged, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, Antineoplastic Combined Chemotherapy Protocol, business.industry, Refractory Multiple Myeloma, Middle Aged, medicine.disease, Progression-Free Survival, United States, 3. Good health, Europe, Clinical trial, Oncology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Disease Progression, Cancer research, Female, Multiple Myeloma, business, Human, Conjugate, medicine.drug
Abstract: PURPOSE Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need. PATIENTS AND METHODS Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing. RESULTS Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class–refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class–refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade ≥ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4. CONCLUSION Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class–refractory and extramedullary disease.
Published: 2021

36. ABCC6 deficiency promotes dyslipidemia and atherosclerosis

Author: Daniel Henrion, Janna Zoll, Viola Pomozi, Li-Hsieh Chen, Ludovic Martin, Christopher Brampton, William A. Boisvert, Sheree Kuo, Sara McCurdy, Georges Leftheriotis, Ailea Apana, Simon Blanchard, Olivier Le Saux, Gilles Lambert, University of Hawai'i [Honolulu] (UH), Bio-Rad Laboratories, Partenaires INRAE, University of California [San Diego] (UC San Diego), University of California (UC), Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Laboratoire de PhysioMédecine Moléculaire (LP2M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), and Bernardo, Elizabeth
Subjects: Male, 0301 basic medicine, 030204 cardiovascular system & hematology, Ectopic calcification, chemistry.chemical_compound, 0302 clinical medicine, Pseudoxanthoma Elasticum, Multidisciplinary, biology, Pseudoxanthoma elasticum, Skin diseases, Experimental models of disease, Medicine, Female, lipids (amino acids, peptides, and proteins), Multidrug Resistance-Associated Proteins, medicine.symptom, medicine.medical_specialty, Science, ABCC6, [SDV.CAN]Life Sciences [q-bio]/Cancer, Inflammation, Article, Calcification, Bile Acids and Salts, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Animals, Humans, Dyslipidemias, Retrospective Studies, business.industry, Cholesterol, Macrophages, Atherosclerosis, medicine.disease, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, chemistry, Peripheral vascular disease, LDL receptor, biology.protein, business, Lipoprotein
Abstract: ABCC6 deficiency promotes ectopic calcification; however, circumstantial evidence suggested that ABCC6 may also influence atherosclerosis. The present study addressed the role of ABCC6 in atherosclerosis using Ldlr−/− mice and pseudoxanthoma elasticum (PXE) patients. Mice lacking the Abcc6 and Ldlr genes were fed an atherogenic diet for 16 weeks before intimal calcification, aortic plaque formation and lipoprotein profile were evaluated. Cholesterol efflux and the expression of several inflammation, atherosclerosis and cholesterol homeostasis-related genes were also determined in murine liver and bone marrow-derived macrophages. Furthermore, we examined plasma lipoproteins, vascular calcification, carotid intima-media thickness and atherosclerosis in a cohort of PXE patients with ABCC6 mutations and compared results to dysmetabolic subjects with increased cardiovascular risk. We found that ABCC6 deficiency causes changes in lipoproteins, with decreased HDL cholesterol in both mice and humans, and induces atherosclerosis. However, we found that the absence of ABCC6 does not influence overall vascular mineralization induced with atherosclerosis. Decreased cholesterol efflux from macrophage cells and other molecular changes such as increased pro-inflammation seen in both humans and mice are likely contributors for the phenotype. However, it is likely that other cellular and/or molecular mechanisms are involved. Our study showed a novel physiological role for ABCC6, influencing plasma lipoproteins and atherosclerosis in a haploinsufficient manner, with significant penetrance.
Published: 2021

37. Standardization of 18F-FDG–PET/CT According to Deauville Criteria for Metabolic Complete Response Definition in Newly Diagnosed Multiple Myeloma

Author: Elena Zamagni, Cristina Nanni, Luca Dozza, Thomas Carlier, Clément Bailly, Paola Tacchetti, Annibale Versari, Stephane Chauvie, Andrea Gallamini, Barbara Gamberi, Denis Caillot, Francesca Patriarca, Margaret Macro, Mario Boccadoro, Laurent Garderet, Simona Barbato, Stefano Fanti, Aurore Perrot, Francesca Gay, Peter Sonneveld, Lionel Karlin, Michele Cavo, Caroline Bodet-Milin, Philippe Moreau, Françoise Kraeber-Bodéré, Zamagni E., Nanni C., Dozza L., Carlier T., Bailly C., Tacchetti P., Versari A., Chauvie S., Gallamini A., Gamberi B., Caillot D., Patriarca F., Macro M., Boccadoro M., Garderet L., Barbato S., Fanti S., Perrot A., Gay F., Sonneveld P., Karlin L., Cavo M., Bodet-Milin C., Moreau P., Kraeber-Bodere F., Bernardo, Elizabeth, The Institute of Hematology and Oncology L. and A. Seràgnoli [Bologna, Italy], Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Policlinico S. Orsola-malpighi, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO)-Servizio sanitario regionale Emilia-Romagna, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Santa Croce e Carle Hospital [Cuneo, Italy], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Università degli Studi di Udine - University of Udine [Italie], Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Università degli studi di Torino = University of Turin (UNITO), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [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), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Università degli Studi di Modena e Reggio Emilia, Università degli studi di Torino (UNITO), and Hematology
Subjects: Cancer Research, [SDV.CAN]Life Sciences [q-bio]/Cancer, Computed tomography, Newly diagnosed, 18F-Fluorodeoxyglucose, FDG, positron emission tomography, PET, computed tomography, CT, minimal residual disease, multiple myeloma, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Deauville Criteria, 18 F-FDG-PET/CT, Medicine, Multiple myeloma, Complete response, 18F-FDG-PET/C, Multiple Myeloma, medicine.diagnostic_test, business.industry, medicine.disease, Standard technique, Minimal residual disease, Oncology, Positron emission tomography, 030220 oncology & carcinogenesis, Fdg pet ct, 18F-FDG, myeloma, Deauville, Nuclear medicine, business, 030215 immunology
Abstract: PURPOSE 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is currently the standard technique to define minimal residual disease (MRD) status outside the bone marrow (BM) in patients with multiple myeloma (MM). This study aimed to define criteria for PET complete metabolic response after therapy, jointly analyzing a subgroup of newly diagnosed transplantation-eligible patients with MM enrolled in two independent European randomized phase III trials (IFM/DFCI2009 and EMN02/HO95). PATIENTS AND METHODS Two hundred twenty-eight patients were observed for a median of 62.9 months. By study design, PET/CT scans were performed at baseline and before starting maintenance (premaintenance [PM]). The five-point Deauville scale (DS) was applied to describe BM (BM score [BMS]) and focal lesion (FL; FL score [FS]) uptake and tested a posteriori in uni- and multivariable analyses for their impact on clinical outcomes. RESULTS At baseline, 78% of patients had FLs (11% extramedullary), 80% with an FS ≥ 4. All patients had BM diffuse uptake (35.5% with BMS ≥ 4). At PM, 31% of patients had visually detectable FLs (2% extramedullary), 24% and 67.7% of them with an FS of 3 and ≥ 4, respectively. At PM, 98% of patients retained residual BM diffuse uptake, which was significantly lower than at baseline (mainly between BMS 2 and 3, BMS was ≥ 4 in only 8.7% of patients). By both uni- and multivariable analysis, FS and BMS < 4 were associated with prolonged progression-free survival (PFS) and overall survival (OS) at PM (OS: hazard ratio [HR], 0.6 and 0.47, respectively; PFS: HR, 0.36 and 0.24, respectively) CONCLUSION FL and BM FDG uptake lower than the liver background after therapy was an independent predictor for improved PFS and OS and can be proposed as the standardized criterion of PET complete metabolic response, confirming the value of the DS for patients with MM.
Published: 2021

38. A new cytokine‐based dynamic stratification during induction is highly predictive of survivals in acute myeloid leukemia

Author: Amandine Le Bourgeois, Marion Eveillard, Camille Debord, Joëlle Gaschet, Marie-C. Béné, Cyrille Touzeau, Soraya Wuilleme, Michel Chérel, Thierry Guillaume, Thomas Gastinne, Patrice Chevallier, Philippe Moreau, Catherine Godon, Benoit Tessoulin, Beatrice Mahe, Olivier Theisen, Nicolas Blin, Alice Garnier, Viviane Dubruille, Anne Lok, Pierre Peterlin, Yannick Le Bris, Steven Le Gouill, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre hospitalier universitaire de Nantes (CHU Nantes), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), CRLCC René Gauducheau, Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, Response to therapy, medicine.medical_treatment, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, prognostic biomarker, Original Research, Potential impact, biology, Myeloid leukemia, Induction Chemotherapy, Middle Aged, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Pathophysiology, 3. Good health, Survival Rate, Leukemia, Myeloid, Acute, Cytokine, 030220 oncology & carcinogenesis, Female, Adult, medicine.medical_specialty, Induction Phase, [SDV.CAN]Life Sciences [q-bio]/Cancer, acute myeloid leukemia, lcsh:RC254-282, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Biomarkers, Tumor, Humans, FLT3 ligand, Radiology, Nuclear Medicine and imaging, Interleukin 6, Aged, IL-6, business.industry, Interleukin-6, Clinical Cancer Research, Membrane Proteins, IL‐6, 030104 developmental biology, biology.protein, business, Intermediate risk, Follow-Up Studies
Abstract: The aim of this study was to assess the potential impact of the kinetics of serum levels of seven cytokines during induction in acute myeloid leukemia (AML) patients. Indeed, the role of cytokines, in the pathophysiology and response to therapy of AML patients, remains under investigation. Here, we report on the impact of peripheral levels of two cytokines, the Fms‐like tyrosine kinase 3 ligand (FL) and interleukin‐6 (IL‐6), evaluated during first‐line intensive induction. A new risk stratification can be proposed, which supersedes the ELN 2017 classification to predict survivals in AML patients by examining the kinetic profile of these cytokines during the induction phase. It segregates three groups of, respectively, high‐risk, characterized by a stagnation of low FL levels, intermediate risk, with dynamic increasing FL levels and high IL‐6 at day 22, and favorable risk with increasing FL levels but low IL‐6 at day 22., Here we report on the impact of the peripheral levels of two cytokines, the Fms‐like tyrosine kinase 3 ligand (FL), and interleukin‐6 (IL‐6), evaluated during first‐line intensive induction. Indeed, a new risk stratification can be proposed, which supersedes the ELN 2017 classification to predict survivals in AML patients by examining their profile during the induction phase.
Published: 2021

39. Laparoscopic closure of the pouch of Douglas by a peritoneal running suture. A minimally invasive and prosthetic-free technique to prevent excessive dose delivery to the small bowel during pelvic irradiation for prostate cancer

Author: Martina-Aida Angeles, Ciprian Chira, Pierre Graff-Cailleaud, Bernard Malavaud, Maxime Loo, Elodie Martin, Lucie Piram, Carlos Martínez-Gómez, Gwenael Ferron, Jonathan Khalifa, Laboratoire Joliot Curie, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), Anti-Tumor Immunosurveillance and Immunotherapy (CRCINA-ÉQUIPE 3), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre 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), École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and CCSD, Accord Elsevier
Subjects: medicine.medical_specialty, Intraoperative Complication, medicine.medical_treatment, [SDV]Life Sciences [q-bio], R895-920, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Prostate cancer, Medical physics. Medical radiology. Nuclear medicine, 0302 clinical medicine, Suture (anatomy), medicine, Radiology, Nuclear Medicine and imaging, Hernia, Laparoscopy, Pelvis, RC254-282, medicine.diagnostic_test, Radiotherapy, business.industry, digestive, oral, and skin physiology, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Small bowel, digestive system diseases, 3. Good health, Surgery, [SDV] Life Sciences [q-bio], Radiation therapy, medicine.anatomical_structure, Douglas’ pouch, Oncology, Radiation-induced enteritis, 030220 oncology & carcinogenesis, Pouch, business, Prostatic neoplasm
Abstract: Highlights • The radiation tolerance of the small bowel is limited. • Chronic radiation-induced enteritis affects patients quality of life. • Ectopic small bowel loops trapped in the pelvis may challenge prostate radiotherapy. • A laparoscopic prosthetic-free technique to cordon off bowel loops from the pelvis., Background and purpose Prostate radiotherapy relies on the delivery of high doses that can be obstructed when a small bowel loop descends in the pelvis. We present a laparoscopic minimally invasive prosthetic-free technique closing the Douglas’ pouch with a peritoneal running suture to cordon off the bowel from the pelvis and hence allow optimal irradiation. Materials and methods Prostate cancer patients referred for radiotherapy and whose planning-CT revealed a bowel loop trapped in the pelvis were proposed the procedure, followed by a new planning-CT. This proof-of-concept study reports postoperative follow-up and dosimetric benefits. Results The procedure was performed in ten patients (2016–2020) as a same-day surgery for nine. Median operative time was 34 min (range 22–50) and no relevant intraoperative complication occurred. The third patient of the series presented a small bowel hernia through the peritoneal suture at the 15th postoperative day requiring a laparotomic desincarceration without major consequences. Regarding the small bowel, median D1cc (dose to 1 cc) was 65.5 Gy and 55.5 Gy (p = 0.005) before and after procedure. Median V60 (volume receiving ≥60 Gy) was 10.2 cc and 0.0 cc (p = 0.005). In the immediate vicinity of the small bowel (5 mm), median D1cc was 68.3 Gy and 57.7 Gy (p = 0.005). Radiotherapy was safely delivered to all patients. Conclusion Laparoscopic closure of the Douglas’ pouch by a peritoneal suture is an efficient technique to cordon off inconvenient ectopic small bowel loops. It prevents excessive bowel irradiation and hence facilitates curative prostate radiotherapy. The technique could be applied to other pelvic malignancies.
Published: 2021

40. Covid-19 and blood groups: ABO antibody levels may also matter

Author: Adrien Breiman, Valéry Daubie, Hanane El Kenz, Francis Corazza, Jean-François Fils, Nathalie Ruvoën-Clouet, Marie Deleers, Bhavna Mahadeb, Jacques Jani, Mieke Cannie, Isabelle Barreau, Béatrice Clémenceau, Tatiana Besse, Virginie Doyen, Jacques Le Pendu, Evelyne Maillart, Philippe Van der Linden, Nabil Hayef, Carine Maggetto, Centre Hospitalier Universitaire Brugmann [Bruxelles] (CHU), Université libre de Bruxelles (ULB), Host-Pathogen Interactions in the Regulation of Immune Responses (CRCINA-ÉQUIPE 5), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Ars Statistica [Nivelles, Belgium], Clinical sciences, Supporting clinical sciences, Radiology, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
Subjects: 0301 basic medicine, Male, Epitope, Epitopes, 0302 clinical medicine, hemic and lymphatic diseases, 030212 general & internal medicine, Aged, 80 and over, biology, ABO antibody levels, General Medicine, Covid-19 infection risk, Middle Aged, Galactosyltransferases, 3. Good health, medicine.anatomical_structure, Infectious Diseases, Radiology Nuclear Medicine and imaging, Spike Glycoprotein, Coronavirus, Female, Disease Susceptibility, medicine.symptom, Antibody, Microbiology (medical), Adult, Risk, congenital, hereditary, and neonatal diseases and abnormalities, 030106 microbiology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Lower risk, Asymptomatic, Article, Antibodies, lcsh:Infectious and parasitic diseases, ABO Blood-Group System, 03 medical and health sciences, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Polysaccharides, ABO blood group system, Glycosyltransferase, parasitic diseases, medicine, Humans, lcsh:RC109-216, Aged, business.industry, SARS-CoV-2, ABO blood group, COVID-19, Epithelial Cells, Agglutination (biology), Immunoglobulin M, Immunology, biology.protein, ABO antibodies, business, Respiratory tract
Abstract: Highlights • The SARS-CoV-2 spike protein can be tagged with A and/or B blood group antigens. • Upper respiratory tract epithelial cells express A and B antigens. • ABO antibody levels are significantly lower in Covid-19 patients compared to controls. • ABO-related anti-xenoantigen levels do not differ between patients and controls. • People with low levels of ABO antibodies may be at a higher risk of being infected., Background Susceptibility to Covid-19 has been found to be associated with the ABO blood group, with O type individuals being at a lower risk. However, the underlying mechanism has not been elucidated. Here, we aimed to test the hypothesis that Covid-19 patients might have lower levels of ABO antibodies than non-infected individuals as they could offer some degree of protection. Methods After showing that the viral spike protein harbors the ABO glycan epitopes when produced by cells expressing the relevant glycosyltransferases, like upper respiratory tract epithelial cells, we enrolled 290 patients with Covid-19 and 276 asymptomatic controls to compare their levels of natural ABO blood group antibodies. Results We found significantly lower IgM anti-A + anti-B agglutination scores in blood group O patients (76.93 vs 88.29, P-value = 0.034) and lower levels of anti-B (24.93 vs 30.40, P-value = 0.028) and anti-A antibodies (28.56 vs 36.50, P-value = 0.048) in blood group A and blood group B patients, respectively, compared to controls. Conclusion In this study, we showed that ABO antibody levels are significantly lower in Covid-19 patients compared to controls. These findings could indicate that patients with low levels of ABO antibodies are at higher risk of being infected.
Published: 2020

41. Cryo-ALE of Si and SiO2 using SF6 Physisorption

Author: Nos, Jack, Antoun, Gaelle, Tillocher, T., Lefaucheux, Philippe, Dussart, Rémi, Girard, Aurélie, Cardinaud, Christophe, Groupe de recherches sur l'énergétique des milieux ionisés (GREMI), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Môle Armoricain de Recherche sur la SOciété de l'information et des usages d'INternet (MARSOUIN), Université de Rennes (UR)-Université de Bretagne Sud (UBS)-Ecole Nationale de la Statistique et de l'Analyse de l'Information [Bruz] (ENSAI)-Université de Brest (UBO)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 2 (UR2)-Université Bretagne Loire (UBL)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT), Laboratoire d'économie et de management de Nantes Atlantique (LEMNA), Institut d'Économie et de Management de Nantes - Institut d'Administration des Entreprises - Nantes (IEMN-IAE Nantes), Université de Nantes (UN)-Université de Nantes (UN)-FR 3473 Institut universitaire Mer et Littoral (IUML), Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), and ANR-20-CE24-0014,PSICRYO,Etude fondamentale des interactions plasma-surface dans les procédés de gravure cryogénique avancés(2020)
Subjects: [PHYS]Physics [physics]
Abstract: Cryogenic Atomic Layer Etching (Cryo-ALE) using C4F8 as a precursor gas has beenpreviously presented as an alternative method to achieve ALE of SiO2. In this process, C4F8 isinjected in gas phase during the “chemical modification” step, in order to physisorb on a cooledSiO2 surface. The etching step is then achieved using an Ar plasma with a low energy ionbombardment. The temperature window of this process was between -120°C and -90°C 1,2.However, C4F8 injection at cryogenic temperatures does not allow high etching selectivity ofSiO2 over Si and Si3N4 as the deposited CFx passivation layer is not thick enough to efficientlypassivate Si and Si3N4 surfaces. As a result, another gas chemistry has to be tested in order toachieve higher etching selectivity.In 1996, Royer et al. studied the chemisorption of sulfur and fluorine on Si during asimultaneous exposure to SF6 gas and Ne+ ion beam. In this work, they showed by XPSmeasurements that the fluorine quantity on the Si surface tends to increase as the temperaturedecreases, for a process window between 20°C and -130°C 3. Therefore cryo-ALE study basedon SF6 physisorption was carried out to extend the use of this alternative approach to other materials.This work was carried out using a cryogenic ICP reactor equipped with in-situ diagnostics.Mass spectrometry measurements enabled to characterize the SF6 physisorption and its surfaceresidence time at different temperatures. Spectroscopic ellipsometry was used to monitor theetching rate and to characterize the sample surface at the nanoscale during the three processsteps: SF6 physisorption, pumping and Ar plasma etching. Tests were performed on SiO2, Si3N4and p-Si coupons glued on SiO2 6” carrier wafers.SF6 physisorption experiments will first be studied and presented notably to find the optimaltemperature and purging time for the process. Subsequently, cryo-ALE test results on Si, SiO2and Si3N4 will be shown. These results will finally be compared to the ones obtained previouslyusing C4F8 physisorption.This research project is supported by the CERTeM 2020 platform, which provides most of theequipment and funded by the European Union (FEDER fund) as well as the French NationalResearch Agency (ANR PSICRYO fund).1. Antoun et al., Appl. Phys. Lett. 115, 153109, 20192. Antoun et al., Sci. Rep. 10, 20213. Royer et al., J. Vac. Sci. Technol. A 14, 234–239, 1996
Published: 2022

42. Fluorescent Peptide Biosensor for Probing CDK6 Kinase Activity in Lung Cancer Cell Extracts

Author: Mathieu Galibert, Christophe Blanquart, Morgan Pellerano, Karine Puget, Magali Jullian, Sebastien Diot, Jessica Soamalala, May C. Morris, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), GENEPEP [France], Bernardo, Elizabeth, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Genepep SA
Subjects: Cell Extracts, Lung Neoplasms, CDK6, Angiogenesis, Cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, Peptide, Biosensing Techniques, kinase activity, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, medicine, Humans, Amino Acid Sequence, Kinase activity, Molecular Biology, Fluorescent Dyes, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, biology, Rhodamines, Kinase, Organic Chemistry, technology, industry, and agriculture, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Recombinant Proteins, lung cancer, Spectrometry, Fluorescence, medicine.anatomical_structure, chemistry, Cell culture, mesothelioma, 030220 oncology & carcinogenesis, biology.protein, fluorescent peptide biosensor, Molecular Medicine, Cyclin-dependent kinase 6, Peptides, Biosensor
Abstract: International audience; CDK6 kinase regulates cell cycle progression in G1, together with CDK4, but has cell-, tissue- and developmentally-distinct functions associated with transcription, angiogenesis and metabolism. Although CDK6 constitutes an attractive cancer biomarker and target there are no means of assessing its activity in a complex environment. In this study we describe design, engineering and characterization of a fluorescent peptide biosensor derived from 6-phosphofructokinase that reports on CDK6 kinase activity through sensitive changes in fluorescence intensity. This biosensor can report on CDK6 activity in a dose-dependent fashion, thereby enabling quantification of differences in kinase activity in complex and physiologically-relevant environments. Further implementation of this biosensor in different lung and melanoma cell lines, as well as in mesothelioma cell lines derived from patients together with a CDK4 biosensor highlighted differences in kinase activity between CDK6 and CDK4 kinase. This work demonstrates the utility of these selective tools for monitoring two closely related kinases comparatively and simultaneously in the same samples, thereby offering attractive perspectives for diagnostic and therapeutic purposes.
Published: 2020

43. Mitochondria transfer from tumor-activated stromal cells (TASC) to primary Glioblastoma cells

Author: Fanny Geraldo, Víctor M. Pérez-García, Gabriel F. Calvo, Claire Pecqueur, Juan Belmonte-Beitia, Arturo Álvarez-Arenas, Lisa Oliver, François M. Vallette, Céline Salaud, Catherine Gratas, Delphine Garnier, Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), University of Castilla-La Mancha (UCLM), Endothelium Radiobiology and Targeting (CRCINA-ÉQUIPE 14), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM), and Bernardo, Elizabeth
Subjects: 0301 basic medicine, Stromal cell, medicine.medical_treatment, Population, Mesenchymal stromal cells, Biophysics, Brain tumor, [SDV.CAN]Life Sciences [q-bio]/Cancer, Mitochondrion, Biochemistry, Cell Line, Extracellular Vesicles, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Tumor Cells, Cultured, Tumor Microenvironment, Organoid, medicine, Humans, education, Molecular Biology, Cell Proliferation, education.field_of_study, Tumor microenvironment, Chemotherapy, Primary GBM cultures, Brain Neoplasms, Chemistry, Mesenchymal stem cell, Mesenchymal Stem Cells, Cell Biology, medicine.disease, Coculture Techniques, Mitochondria, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, Glioblastoma, Tunneling nanotubes
Abstract: International audience; The tumor microenvironment (TME) controls many aspects of cancer development but little is known about its effect in Glioblastoma (GBM), the main brain tumor in adults. Tumor-activated stromal cell (TASC) population, a component of TME in GBM, was induced in vitro by incubation of MSCs with culture media conditioned by primary cultures of GBM under 3D/organoid conditions. We observed mito-chondrial transfer by Tunneling Nanotubes (TNT), extracellular vesicles (EV) and cannibalism from the TASC to GBM and analyzed its effect on both proliferation and survival. We created primary cultures of GBM or TASC in which we have eliminated mitochondrial DNA [Rho 0 (r 0) cells]. We found that TASC, as described in other cancers, increased GBM proliferation and resistance to standard treatments (radio-therapy and chemotherapy). We analyzed the incorporation of purified mitochondria by r 0 and r þ cells and a derived mathematical model taught us that r þ cells incorporate more rapidly pure mitochondria than r 0 cells.
Published: 2020

44. La résilience entrepreneuriale, un nouvel enjeu de formation ?

Author: Sattin, Jean-François, Catherine, Léger-Jarniou, Chabaud, Didier, Sammut, Sylvie, Maus, Amandine, Schieb-Bienfait, Nathalie, Hamelin, Anais, Pfiffelmann, Marie, Université de Montpellier (UM), Labex Entreprendre, Aix-Marseille Université - Faculté d'économie et de gestion (AMU ECO), Aix Marseille Université (AMU), Centre d'Études et de Recherche en Gestion d'Aix-Marseille (CERGAM), Aix Marseille Université (AMU)-Université de Toulon (UTLN), Laboratoire d'économie et de management de Nantes Atlantique (LEMNA), Institut d'Économie et de Management de Nantes - Institut d'Administration des Entreprises - Nantes (IEMN-IAE Nantes), Université de Nantes (UN)-Université de Nantes (UN)-FR 3473 Institut universitaire Mer et Littoral (IUML), Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Laboratoire de Recherche en Gestion et Economie (LARGE), Université de Strasbourg (UNISTRA), and Académie de l’Entrepreneuriat et de l’Innovation
Subjects: [QFIN.GN]Quantitative Finance [q-fin]/General Finance [q-fin.GN], Economics and Econometrics, Strategy and Management, 0502 economics and business, 05 social sciences, [SHS.GESTION]Humanities and Social Sciences/Business administration, 060301 applied ethics, 06 humanities and the arts, Business and International Management, 0603 philosophy, ethics and religion, 050203 business & management
Abstract: International audience; Dans quelle mesure la résilience entrepreneuriale peut-elle constituer un nouvel enjeu de formation des étudiants-entrepreneurs ? Forte d’une expérience de plus de 20 années au contact des acteurs de l’entrepreneuriat, l’Académie de l’Entrepreneuriat et de l’Innovation (AEI) a mobilisé son expertise, ses ressources et ses réseaux afin de répondre à cette question3. La démarche proposée conduit à interroger la portée formative des outils et pratiques pédagogiques utilisés pour développer la résilience entrepreneuriale des étudiants-entrepreneurs, notamment dans le contexte d’accompagnement en distanciel apparu avec la crise de la Covid-19.
Published: 2020

45. Decision-based territorial life cycle assessment for the management of cement concrete demolition waste

Author: Nicolas Antheaume, Marjan Mousavi, Anne Ventura, Institut de Recherche en Génie Civil et Mécanique (GeM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Granulats et Procédés d'Elaboration des Matériaux (MAST-GPEM ), Université Gustave Eiffel, Laboratoire d'économie et de management de Nantes Atlantique (LEMNA), Institut d'Économie et de Management de Nantes - Institut d'Administration des Entreprises - Nantes (IEMN-IAE Nantes), Université de Nantes (UN)-Université de Nantes (UN)-FR 3473 Institut universitaire Mer et Littoral (IUML), and Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Environmental Engineering, RECYCLING, geographical downscale, 020209 energy, media_common.quotation_subject, ANALYSE DU CYCLE DE VIE, 02 engineering and technology, recycling, 010501 environmental sciences, CYCLE DE VIE, 01 natural sciences, 12. Responsible consumption, Waste Management, URBAN METABOLISM, RECYCLAGE DES MATERIAUX, Teknik och teknologier, 11. Sustainability, 0202 electrical engineering, electronic engineering, information engineering, Animals, Quality (business), Life-cycle assessment, 0105 earth and related environmental sciences, media_common, Urban metabolism, Life Cycle Stages, Construction Materials, MATERIAL FLOW ANALYSIS, business.industry, Material flow analysis, Scale (chemistry), Environmental resource management, Land-use planning, Pollution, Product (business), [SPI.GCIV]Engineering Sciences [physics]/Civil Engineering, material flow analysis, Demolition waste, [SDE]Environmental Sciences, Engineering and Technology, Environmental science, GEOGRAPHICAL DOWNSCALE, France, business
Abstract: Existing territorial life cycle assessments (LCAs) consider all activities in a given geographical area, defined as the foreground system, but cannot lead to operational decisions. In product scale LCA, the foreground system is defined as the part of the system directly controlled by an actor and is thus more adapted to compare possible scenarios within a decision perimeter. The present paper uses that concept applied to a geographical area. The developed method consists of five steps: (a) definition of the foreground material flow analysis (MFA) or LCA system corresponding to the decision perimeter; (b) territorial MFA; (c) geo-location of activities and downscaling of territorial flows to individual activities; (d) calculation of local transport distances; and (e) calculation of LCA impact indicators. The case study concerns the management of primary and secondary resources of basic quality aggregates (BQAs) in the Loire-Atlantique department (France) in 2012. Our results show that the amount of recycled cement concrete is only 7% of total consumed BQAs, although 90% of cement concrete demolition waste (CCDW) is recycled. The environmental impacts are importantly related to off-site activities. Local impacts are mainly driven by the transport of aggregates. For land planning, a concentration of fewer recycling facilities with high authorised production capacities in main cities, close to where CCDW is mainly produced, would divide transport needs in half and thus considerably reduce environmental impacts.
Published: 2020

46. Selective SIRPα blockade reverses tumor T cell exclusion and overcomes cancer immunotherapy resistance

Author: Riad Abes, Kevin Biteau, Alexandre Glémain, Christophe Blanquart, Dominique Costantini, Catherine Ruiz, David Laplaud, Hélène Aublé, Stéphanie Le Bas-Bernardet, E. Sergio Trombetta, Véronique Catros, Gilles Blancho, Isabelle Archambeaud, Sylvie Métairie, Isabelle Girault, Emmanuelle Wilhelm, Masayuki Miyasaka, Jean-François Mosnier, Vanessa Gauttier, Sabrina Pengam, Charlène Trilleaud, Alexandra Garcia, Pierre-Antoine Gouraud, Pierre Duplouye, Bernard Martinet, Géraldine Teppaz, Georgia Porto, Fabienne Haspot, Sarah Bruneau, Aurore Morello, Justine Durand, Caroline Mary, Richard Danger, Sophie Conchon, Nathalie Labarrière, Kerry L. M. Ralph, Virginie Thepenier, Nicolas Vince, Nicolas Poirier, Bernard Vanhove, Virginie Vignard, Mélanie Néel, Safa Dehmani, OSE Immunotherapeutics [Nantes, France], Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Boehringer Ingelheim Pharma GmbH & Co. KG, Osaka University, Anti-Tumor Immunosurveillance and Immunotherapy (CRCINA-ÉQUIPE 3), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Nantes (UN), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Nutrition, Métabolismes et Cancer (NuMeCan), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Centre de Ressources Biologiques Santé (CRB Santé), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC), Institut des maladies de l'appareil digestif [Nantes] (IMAD), BPI EFFI-CLIN PSPC grant,INCA MDSCAN PRT-K15-136, the French Public Bank of Investment and French Institut National du Cancer, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC), and Jonchère, Laurent
Subjects: 0301 basic medicine, T-Lymphocytes, [SDV]Life Sciences [q-bio], T cell, medicine.medical_treatment, Immunology, T cells, Cancer immunotherapy, Therapeutics, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Receptors, Immunologic, Mice, Inbred BALB C, Tumor microenvironment, Chemistry, Macrophages, CD47, Mammary Neoplasms, Experimental, General Medicine, Immune checkpoint, Neoplasm Proteins, 3. Good health, Blockade, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Chemokine secretion, Cancer research, Female, Immunotherapy, Immunologic Memory, Memory T cell, Research Article
Abstract: International audience; T cell exclusion causes resistance to cancer immunotherapies via immune checkpoint blockade (ICB). Myeloid cells contribute to resistance by expressing signal regulatory protein-α (SIRPα), an inhibitory membrane receptor that interacts with ubiquitous receptor CD47 to control macrophage phagocytosis in the tumor microenvironment. Although CD47/SIRPα-targeting drugs have been assessed in preclinical models, the therapeutic benefit of selectively blocking SIRPα, and not SIRPγ/CD47, in humans remains unknown. We report a potent synergy between selective SIRPα blockade and ICB in increasing memory T cell responses and reverting exclusion in syngeneic and orthotopic tumor models. Selective SIRPα blockade stimulated tumor nest T cell recruitment by restoring murine and human macrophage chemokine secretion and increased anti-tumor T cell responses by promoting tumor-antigen crosspresentation by dendritic cells. However, nonselective SIRPα/SIRPγ blockade targeting CD47 impaired human T cell activation, proliferation, and endothelial transmigration. Selective SIRPα inhibition opens an attractive avenue to overcoming ICB resistance in patients with elevated myeloid cell infiltration in solid tumors.
Published: 2020

47. Rethinking Observation: Challenges and Practices

Author: Lionel Garreau, Chahrazad Abdallah, Maja Korica, Thibaut Bardon, Benoît Journé, Bardon, Thibaut, Audencia Business School, University of Warwick (University of Warwick) (University of Warwick), Audencia Recherche, Dauphine Recherches en Management (DRM), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Département de management et de technologie (ESG UQAM), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Laboratoire d'économie et de management de Nantes Atlantique (LEMNA), Institut d'Économie et de Management de Nantes - Institut d'Administration des Entreprises - Nantes (IEMN-IAE Nantes), Université de Nantes (UN)-Université de Nantes (UN)-FR 3473 Institut universitaire Mer et Littoral (IUML), École Centrale de Nantes (ECN)-Université de Nantes (UN)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Le Mans Université (UM)-Université de Bretagne Sud (UBS)-École Centrale de Nantes (ECN)-Université de Nantes (UN)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Le Mans Université (UM)-Université de Bretagne Sud (UBS), Warwick Business School (WBS), University of Warwick [Coventry], and Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)
Subjects: HD, observation, 060101 anthropology, Strategy and Management, 05 social sciences, Media studies, challenges, 06 humanities and the arts, ethnography, General Business, Management and Accounting, methods, [SHS]Humanities and Social Sciences, 0502 economics and business, Ethnography, JEL: C - Mathematical and Quantitative Methods/C.C8 - Data Collection and Data Estimation Methodology • Computer Programs/C.C8.C80 - General, H1, [SHS.GESTION]Humanities and Social Sciences/Business administration, 0601 history and archaeology, LB, [SHS] Humanities and Social Sciences, Sociology, [SHS.GESTION] Humanities and Social Sciences/Business administration, ComputingMilieux_MISCELLANEOUS, 050203 business & management
Abstract: International audience
Published: 2020

48. Slower degradation rate of cytarabine in blood samples from acute myeloid leukemia by comparison with control samples

Author: Philippe Guardiola, Sarah Ghamrawi, Séverine Férec, Mathilde Hunault-Berger, Simon Souchet, Chadi Abbara, Guillaume Drevin, Marie Briet, Jean-Baptiste Robin, Aline Schmidt, Département de Pharmacologie-Toxicologie [CHU Angers], 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), Service de Génomique Onco-Hématologique [CHU Angers], Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service des maladies du sang [CHU Angers], Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), and Bernardo, Elizabeth
Subjects: Male, 0301 basic medicine, Cancer Research, Time Factors, medicine.medical_treatment, Toxicology, Gastroenterology, 0302 clinical medicine, Drug Stability, AML, Tandem Mass Spectrometry, hemic and lymphatic diseases, Pharmacology (medical), Chromatography, High Pressure Liquid, Randomized Controlled Trials as Topic, Cytarabine, In vitro degradation, Area under the curve, Myeloid leukemia, Middle Aged, 3. Good health, Leukemia, Myeloid, Acute, Oncology, Deamination, 030220 oncology & carcinogenesis, Female, Multiple linear regression analysis, Stability, Half-Life, medicine.drug, Adult, Antimetabolites, Antineoplastic, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, Clinical pharmacokinetic, Specimen Handling, Young Adult, 03 medical and health sciences, Clinical Trials, Phase II as Topic, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cytidine Deaminase, Internal medicine, medicine, Humans, Clinical significance, Pharmacology, Chemotherapy, business.industry, 030104 developmental biology, Clinical Trials, Phase III as Topic, Case-Control Studies, business
Abstract: International audience; Purpose: Cytarabine, a key chemotherapy agent for acute myeloid leukemia (AML) treatment, is deaminated into inactive uracil-arabinoside by cytidine deaminase. This deamination leads to samples stability issues with respect to clinical pharmacokinetic trials. The aim of our study was to study in vitro cytarabine stability in blood samples obtained from AML patients.Methods: Cytarabine quantification was performed using a fully validated LC/MS/MS method. In vitro cytarabine stability was assessed at room temperature over 24 h in samples coming from 14 AML patients and 7 control patients (CTRL) with no hematological malignancy. In vitro concentrations versus time data were analyzed using a noncompartmental approach.Results: Cytarabine in vitro area under the curve (AUCIVlast) was 22-fold higher in AML samples as compared to CTRL samples (AML mean (standard deviation (SD)), 51,829 (27,004) h ng/mL; CTRL mean (SD), 2356 (1250) h ng/mL, p = 0.00019). This increase was associated with a prolonged in vitro degradation half-life (t1/2IVdeg AML mean (SD), 15 (11.8) h; CTRL mean (SD), 0.36 (0.37) h, p = 0.0033). Multiple linear regression analysis showed that AML diagnosis significantly influenced t1/2IVdeg and AUCIVlas relationship.Conclusion: Cytarabine stability is higher in AML than in CTRL samples. The absence of correlation between t1/2IVdeg and AUCIVlast in AML samples suggests that in vitro cytarabine degradation in AML is complex. These results open perspectives including the evaluation of the clinical relevance and the involved molecular mechanisms.
Published: 2020

49. Innovative SMEs in search of ambidexterity: a challenge for HRM!

Author: Lise Gastaldi, Cathy Krohmer, Romain Lonceint, Marie-Laure Buisson, Bénédicte Geffroy, Laboratoire d'Economie et de Sociologie du Travail (LEST), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'économie et de management de Nantes Atlantique (LEMNA), Institut d'Économie et de Management de Nantes - Institut d'Administration des Entreprises - Nantes (IEMN-IAE Nantes), Université de Nantes (UN)-Université de Nantes (UN)-FR 3473 Institut universitaire Mer et Littoral (IUML), Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Département Sciences sociales et de gestion (IMT Atlantique - SSG), IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Nantes Université - Institut d'Administration des Entreprises - Nantes (Nantes Univ - IAE Nantes), Nantes Université - pôle Sociétés, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sociétés, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-FR 3473 Institut universitaire Mer et Littoral (IUML), Le Mans Université (UM)-Université d'Angers (UA)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Le Mans Université (UM)-Université d'Angers (UA)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ), Laboratoire d'économie et de sociologie du travail (LEST), Université de Bretagne Sud (UBS)-Le Mans Université (UM)-Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Le Mans Université (UM)-Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Nantes (UN)-École Centrale de Nantes (ECN), École Centrale de Nantes (ECN)-Université de Nantes (UN)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Le Mans Université (UM)-Université de Bretagne Sud (UBS)-École Centrale de Nantes (ECN)-Université de Nantes (UN)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Le Mans Université (UM)-Université de Bretagne Sud (UBS), and Krohmer, Cathy
Subjects: Organizational Behavior and Human Resource Management, Knowledge management, business.industry, media_common.quotation_subject, 05 social sciences, 050209 industrial relations, Work (electrical), Originality, Human resource management, 0502 economics and business, Industrial relations, Research studies, [SHS.GESTION]Humanities and Social Sciences/Business administration, Longitudinal method, [SHS.GESTION] Humanities and Social Sciences/Business administration, business, Function (engineering), Human resources, ComputingMilieux_MISCELLANEOUS, 050203 business & management, Ambidexterity, media_common
Abstract: PurposeInnovative small and medium-sized enterprises (SMEs) are key economic actors, but they are fragile. Their innovation trajectory requires an evolution in their competencies as their strategy evolves, and this is a particularly critical concern when they are engaged in both exploration and exploitation activities and want to develop organisational ambidexterity. In turn, this brings challenges for human resource management (HRM): some research studies have identified “mobilising” practices for innovation, but few authors have taken a dynamic approach. This study aims to fill this double-theoretical gap by answering the following two questions: how does HRM respond to the challenges associated with the search for ambidexterity in an innovative SME's trajectory? What HRM practices are mobilised in the innovation trajectory of SMEs?Design/methodology/approachThe authors carried out two longitudinal case studies concerning innovative SMEs in the medical equipment sector, which are now over 10 years old and seeking to stabilise an ambidextrous way of operating. The authors conducted 37 semi-structured interviews in 2018–2019 and collected public and internal documents. For each case, the authors identified sequences (Bidart et al., 2013) displaying a certain homogeneity in terms of innovation strategy. The authors then performed a cross-case analysis.FindingsThese case studies produced two main results. First, the trajectory of innovative SMEs consisted of sequences during which competency needs and HRM practices evolved. Despite their similar modes of ambidexterity, the two SMEs have mobilised different human resource (HR) practices. Second, the HRM practices implemented struggle to support the firm at key turning points in the innovation trajectories and can even hinder such changes in direction.Originality/valueThe originality of this work lies in two major dimensions. First, the authors choose to explore innovation and the search for ambidexterity, two themes that are traditionally studied in large firms, in the setting of SMEs. Second, the authors choose a longitudinal method to explore the evolution over time in modes of ambidexterity and HRM, along these SMEs' innovation trajectory. This is a departure from more traditional approaches seeking to identify which HR practices, or configurations of practices, are best able to foster ambidexterity and innovation. It leads the authors to show, in a contingent, dynamic perspective, the importance of the Human Resources Foundation’s (HRF's) positioning and attitude in supporting diversified SMEs’ innovation trajectories. This requires allocation of the necessary resources to the function, which needs time and resources to reflect on how to build the ambidextrous HRM that is essential for the firm's survival.
Published: 2020

50. Universal scaling laws rule explosive growth in human cancers

Author: Ángel Acosta Rojas, Esther Hernández-San Miguel, María Pérez-Cano, Gabriel F. Calvo, Lucía Zhu, Ana María García Vicente, Juan Belmonte-Beitia, Juan J. Jiménez, David Albillo, Philippe Schucht, Víctor M. Pérez-García, Pedro García-Gómez, Antonio Francisco Honguero Martínez, François M. Vallette, Manuel Valiente, Jesús J. Bosque, Álvaro Martínez, Julián Pérez-Beteta, David Molina-García, Youness Azimzade, Odelaisy León-Triana, Michael Murek, Pilar Sánchez-Gómez, Ana Ortiz de Mendivil, Rafael Hortigüela, Germán Andrés Jiménez Londoño, Estanislao Arana, Universidad de Castilla-La Mancha (UCLM), Spanish National Cancer Research Center (CNIO), Institute of Health Carlos III, University of Tehran, Sanchinarro University Hospita [HM Hospitales, Madrid], Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Bern University Hospital [Berne] (Inselspital), MD Anderson Cancer Center [Madrid, Spain], Hospital General Universitario de Albacete, Hospital General Universitario de Ciudad Real [Ciudad Real, Spain], Fundación Instituto Valenciano de Oncología [Valencia, Spain], James S. McDonnell Foundation 21st Century Science Initiative in Mathematical and Complex Systems Approaches for Brain Cancer, European Regional Development Fund (ERDF/FEDER), Junta de Comunidades de Castilla-La Mancha, Ministerio de Economia y Competividad (MINECO), Bristol-Myers Squibb, Beug Foundation's Prize for Metastasis Research 2017, Fundacion Ramon Areces, Worldwide Cancer Research, H2020-FETOPEN, Fundacio La Marato de TV3, Clinic and Laboratory Integration Program CRI Award 2018, AECC Coordinated Translational Groups 2017, LAB AECC 2019, La Caixa INPhINIT Fellowship, La Caixa-Severo Ochoa International PhD Program Fellowship, European Molecular Biology Organization Young Investigators programme, Bernardo, Elizabeth, Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Scaling law, Explosive material, Computer science, General Physics and Astronomy, [SDV.CAN]Life Sciences [q-bio]/Cancer, 01 natural sciences, Measure (mathematics), Article, 010305 fluids & plasmas, [SDV.CAN] Life Sciences [q-bio]/Cancer, GENERAL-MODEL, 0103 physical sciences, RATES, Statistical physics, Tissues and Organs (q-bio.TO), 010306 general physics, Set (psychology), Evolutionary dynamics, Mathematical model, TUMOR-GROWTH, Quantitative Biology - Tissues and Organs, Observable, EVOLUTION, PREDICTS, 3. Good health, PET, Oncología matemática, FOS: Biological sciences, SURVIVAL, Biomedicina, Value (mathematics)
Abstract: Most physical and other natural systems are complex entities composed of a large number of interacting individual elements. It is a surprising fact that they often obey the so-called scaling laws relating an observable quantity with a measure of the size of the system. Here we describe the discovery of universal superlinear metabolic scaling laws in human cancers. This dependence underpins increasing tumour aggressiveness, due to evolutionary dynamics, which leads to an explosive growth as the disease progresses. We validated this dynamic using longitudinal volumetric data of different histologies from large cohorts of cancer patients. To explain our observations we put forward increasingly-complex biologically-inspired mathematical models that captured the key processes governing tumor growth. Our models predicted that the emergence of superlinear allometric scaling laws is an inherently three-dimensional phenomenon. Moreover, the scaling laws thereby identified allowed us to define a set of metabolic metrics with prognostic value, thus providing added clinical utility to the base findings. This research has been supported by the James S. McDonnell Foundation 21st Century Science Initiative in Mathematical and Complex Systems Approaches for Brain Cancer (collaborative awards 220020560 and 220020450), Ministerio de Economia y Competitividad/FEDER, Spain (grant no. MTM2015-71200-R), Junta de Comunidades de Castilla-La Mancha (grant no. SBPLY/17/180501/000154). Research in the Brain Metastasis Group is supported by MINECO grant MINECO-Retos SAF2017-89643-R (M.V.), Bristol-Myers Squibb Melanoma Research Alliance Young Investigator Award 2017 (498103) (M.V.), Beug Foundation's Prize for Metastasis Research 2017 (M.V.), Fundacion Ramon Areces (CIVP19S8163) (M.V.), Worldwide Cancer Research (19-0177) (M.V.), H2020-FETOPEN (828972) (M.V.), Fundacio La Marato de tv3 (141), Clinic and Laboratory Integration Program CRI Award 2018 (54545) (M.V.), AECC Coordinated Translational Groups 2017 (GCTRA16015SEOA) (M.V.), LAB AECC 2019 (LABAE19002VALI) (M.V.), La Caixa INPhINIT Fellowship (LCF/BQ/IN17/11620028) (P.G.-G.), La Caixa-Severo Ochoa International PhD Program Fellowship (LCF/BQ/SO16/52270014) (L.Z.). M.V. is a member of the European Molecular Biology Organization Young Investigators programme (4053). We would like to acknowledge J. Cervera and J. C. Penalver from the IVO Foundation (Valencia, Spain). No
Published: 2020

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