ANNUAL REPORT 2016
CANCER RESEARCH CENTER OF TOULOUSE
Annual Report 2016
Content Message from the Director ...... 3 Research teams ...... 5 Team 1 – Antitumor immunity and immunotherapy ...... 6 Team 2 – Regulation of DNA Replication & Genetic Instability in Cancers ...... 8 Team 3 - Cellular signaling, oncogenesis and therapeutics ...... 10 Team 4 - Sphingolipid metabolism, cell death & tumor progression ...... 12 Team 5 – RNA-binding proteins and post-transcriptional regulation in cancer ...... 14 Team 6 – Protein Synthesis & Secretion in Oncogenesis ...... 16 Team 7 – RNA biology in hematological cancers ...... 18 Team 8 – Cell cycle and cancer ...... 20 Team 9 – Therapeutic Innovations in B lymphomas ...... 22 Team 10 – Molecular heterogeneity of pancreatic tumors ...... 24 Team 11 – Glioblastoma radioresistance: from signaling pathways to clinical trials ...... 26 Team 12 – Cholesterol metabolism and therapeutic innovations ...... 28 Team 13 – Pharmacogenomics of multiple myeloma ...... 30 Team 14 - Dose individualization of anticancer drugs ...... 32 Team 15 – Multiscale dosimetry for radiotherapy optimization ...... 34 Team 16 – Alteration of transcription factors in acute leukemias ...... 36 Team 17 - SIGDYN Group - PI3K isoforms, Signalling & Cancerogenesis ...... 38 Team 18 - RESISTAML – Drug resistance and oncometabolism in acute myeloid leukemia ...... 40 Core facilities ...... 43 Technology Cluster of the CRCT ...... 44 Biological Resource Centre (BRC) ...... 46 Cytometry & Cell sorting ...... 46 Cell Imaging ...... 46 Monoclonal Antibodies ...... 46 Genomics & Transcriptomics...... 47 Proteomics ...... 47 Gene transfer Vector ...... 47 Post-graduate education programmes ...... 49
[1]
Scientific and administrative staff ...... 50 Flow chart ...... 50 CRCT administration ...... 51 CRCT Resources ...... 52 Scientific Advisory Board ...... 54 Scientific production ...... 55 Publications in 2016 ...... 56 Awards in 2016 ...... 70 International symposium : Toulouse Onco Week 2016 (TOW 2016) ...... 70 Seminars held in the CRCT...... 71
[2]
Message from the Director
I am pleased to present the first activity report of the Cancer Research Center of Toulouse (CRCT) for 2016.
Five years after its creation and two years only after its establishment on the Oncopole site, the CRCT has seen its staff and team numbers rapidly growing. This report describes their activities and scientific production. The technological facilities have been gradually built and also enriched in order to give researchers an ever more efficient environment.
The CRCT is a new Center which is going to rise in importance in close relationship with the « Institut Universitaire du Cancer de Toulouse » and through the recruitment of new teams. The next years will allow the CRCT to gain international recognition.
I hope that this report will provide information about the CRCT to more people, induce numerous exchanges, and initiate successful collaborations with the scientific community.
I wish you a pleasant reading of this report.
Gilles Favre Director
[3]
[4]
Research teams
[5]
Team Leader Maha Ayyoub University Professor- Hospital practitioner, Faculty of Pharmacy - IUCT
Staff Françoise Lauzéral- Vizcaino, Research associate Clara-Maria Scarlata, Research associate Jamila Elhmioui, Research assistant Alejandra Martinez, Team 1 – Antitumor immunity and Hospital practitioner
PhD students immunotherapy Decades-long efforts in tumor immunology research have recently Camille-Charlotte Balança come to fruition with the clinical success of monoclonal antibodies Carlos Martinez targeting immune checkpoints. These therapies have allowed, on Gomez
one hand, to confirm the central role of adaptive immunity in the M2 Students control of tumor growth and, on the other, to underline the Marie Michelas importance of immune regulatory mechanisms in the ability of Victor Sarradin tumors to escape immune control. The aim of our research is to decipher the molecular and cellular mechanisms underlying
tumors sensitivity/resistance to immunotherapy in order to design
combination therapies able to prevail over resistance.
Objectives
Despite its efficacy across several malignancies, underlying the immunogenicity of these antigen only a proportion of treated patients experience categories and of the evolution of tumor-specific clinical benefit from immune checkpoint T cell responses along immune checkpoint modulation monotherapy. In addition, a number modulation therapy; of tumor types, while being immunogenic, do not ii) Investigating the contribution of the T cell respond to current immunotherapies. response type (type 1/Th1/Tc1; type 2/th2; type In order to understand the molecular and cellular 3/Th17; Treg) to anti-tumor immunity according mechanisms of tumors sensitivity/resistance to to tumor histological type and anatomic location. spontaneous or therapeutic immune responses, The results of our studies have potential impact our studies are focused on: on the identification of clinically meaningful i) Deciphering the impact of tumor antigen- biomarkers of response to immunotherapy and specific adaptive responses to tumor immune on the development of combination therapies, in sensitivity through the assessment of T cell particular cancer vaccines associated to immune responses to neoantigens, oncoviral antigens and checkpoint modulation, which can enhance the cancer testis antigens, of the mechanisms extent of clinical responses to immunotherapy.
Keywords: Antitumor T cell response, CD4 T cell populations, immune checkpoint modulators, anticancer vaccines
[6]
Highlights
We joined CRCT in 2017 to establish a new research team. Our research focus at CRCT is based on the team’s expertise in the analysis of tumor antigens specific T cells, the immune monitoring of patients receiving immunotherapy and the investigation of the development and plasticity of human CD4 T cell subsets (Figure).
Labels / Grants: Cancer Vaccine Collaborative Clinical Trials Network (Cancer Research Institute/Ludwig Cancer Research); ImCore network of cancer immunotherapy centers of excellence (Roche/Genentech).
Some publications in 2016 Jacquelot, N., M. P. Roberti, D. Halabi N.M., A. Martinez, H. Al- Zitvogel, L., M. Ayyoub, B. P. Enot, S. Rusakiewicz, M. Farsi, E. Mery, L. Puydenus, P. Routy, and G. Kroemer. Semeraro, S. Jégou, C. Flores, L. Pujol, H.G. Khalak, C. McLurcan, Microbiome and anticancer Chen, B. S. Kwon, C. Borg, B. G. Ferron, D. Querleu, I. Al- immunosurveillance. Cell. 2016 Weide, F. Aubin, S. Dalle, H. Azwani, E. Al-Dous, Y.A. Apr 7;165(2):276-87. Kohrt, M. Ayyoub, G. Kroemer, Mohamoud, J.A. Malek, and A. Zitvogel, L., S. Rusakiewicz, B. A. Marabelle, A. Cavalcanti, A. Rafii. Preferential Allele Routy, M. Ayyoub, and G. Eggermont, and L. Zitvogel. Expression Analysis Identifies Kroemer. Immunological off- Immunophenotyping of Stage Shared Germline and Somatic target effects of the first III Melanoma Reveals Driver Genes in Advanced precision drug, imatinib Parameters Associated with Ovarian Cancer. PLoS Genet. mesylate. Nat Rev Clin Oncol. Patient Prognosis. J Invest 2016 Jan 6;12(1):e1005755. 2016 Jul;13(7):431-46. Dermatol. 2016 May; 136(5):994-1001.
[7]
Team Leader Jean-Sébastien Hoffmann DR1 Inserm
Staff
Marie-Jeanne Pillaire, CR1 Inserm Valérie Bergoglio, CR1 CNRS Malik Lutzmann, CR1 CNRS Sophie Queille, Team 2 – Regulation of DNA Replication & Research assistant Genetic Instability in Cancers Guillaume Labrousse, Research associate The past decade has seen a dramatic advance in our understanding of how genomic integrity is compromised in Postdoc fellows Rémy Bétous cancer and has revealed that replicative stress (RS) in S phase, Alessandra Pellegrini which leads to chromosomal breakage and unresolved DNA, is a Dana Hodroj
highly relevant mechanism, placing RS studies at the forefront of PhD students
cancer research. Our team is exploring (i) how genetic, Elodie Bournique
environmental, and cell signaling sources can explain RS in Marina Dal’Osto Lilas Courtot several types of cancers and (ii) how the transmission of unresolved DNA regions to the next cell generation can be essential for cancer progression and therapeutic resistance.
Objectives
The team, by exploring these issues, have and exacerbate replicative stress and, hence, ultimately opened novel research lines. We have provoke therapeutic resistance. discovered that daughter cells can modify their Our main objectives are (i) to study the own replication program to better ensure mechanisms used by mother cells to limit the replication of DNA sequences that experienced transmission of the replication problems, (ii) to problems in the previous cell cycle. This process monitor the fate of the transmitted damages in may explain why a cancer cellular clone could G1 daughter cells, (iii) to analyze a totally sustain efficient DNA replication and cell unexplored field, the impact of transmitted DNA proliferation despite a high degree of damage on the DNA Replication initiation endogenous replicative stress and unstable program, (iv) to explore the physiological and genome, a major question that is still unsolved. pathological relevance of the process of DNA Our research lines have also revealed a novel damage transmission and its impact on DNA crosstalk pathway between replication and repair replication of daughter cells, and (v) to evaluate of damaged DNA, a process that could equip a how these processes contribute to the malignant cellular clone with an escape therapeutic response of tumors treated with the mechanism in presence of chemotherapeutic multiple anticancer agents that impede the treatments which target DNA replication forks progression of the replication forks.
Keywords: Replicative stress, genetic instability, therapeutic resistance
[8]
Highlights
Pol contributes to the replication of CHK1 as a therapeutic target to bypass telomeric sequences in human cells chemoresistance to Cytarabine in AML
Labels / Grants: Label Equipe LNCC ; LabEx TOUCAN
Some publications in 2016 Mansilla SF, Bertolin AP, David L*, Fernandez-Vidal A*, Garcia-Exposito L* Bournique Bergoglio V, Pillaire MJ, Bertoli S, Grgurevic S, Lepage B, E*, Bergoglio V*, Bose A, González Besteiro MA, Luzzani Deshaies D, Prade N, Cartel M, Barroso-Gonzalez J, Zhang S, C, Miriuka SG, Cazaux C, Larrue C, Sarry JE, Delabesse E, Roncaioli JL, Lee M, Wallace CT, Hoffmann JS, Gottifredi V. Cazaux C, Didier C, Récher C**, Watkins SC, Opresko PL, Cyclin Kinase-independent role Manenti S**, & Hoffmann JS**. Hoffmann JS**, O'Sullivan of p21CDKN1A in the CHK1 as a therapeutic target to RJ.**. Proteomic Profiling promotion of nascent DNA bypass chemoresistance in Reveals a Specific Role for elongation in unstressed cells. AML. Science Signal. Translesion DNA Polymerase η Elife. 2016 Oct 14;5. 2016;9(445). in the Alternative Lengthening Grgurevic S, Berquet L, Quillet- Bétous R, Renoud ML, Hoede C, of Telomeres. Cell Rep. 2016; Mary A, Laurent G, Récher C, Gonzalez I, Jones N, Longy M, 17(7):1858-71. Ysebaert L, Cazaux C, and Sensebé L, Cazaux C, & T. Goullet de Rugy, M. Hoffmann JS*, 3R gene Hoffmann JS*. Human Adipose- Bashkurov, A. Datti, R. Betous, expression in chronic Derived Stem Cells Expanded L. Guitton-Sert, C. Cazaux, D. lymphocytic leukemia reveals Under Ambient Oxygen Durocher and J. S. Hoffmann, the chromatin remodeling Concentration Accumulate Excess Polθ functions in factor ASF1A as an independent Oxidative DNA Lesions and response to replicative stress in prognostic marker of disease Experience Procarcinogenic homologous recombination- evolution, Blood Cancer Res. DNA Replication Stress. Stem proficient cancer cells, Biology 2016, 6, e429; Cells Transl Med. 2016 Aug 24. Open (2016) 5, 1485-92. doi:10.1038/bcj.2016.39
[9]
Team Leader Gilles Favre Professor
Staff
Researchers, clinicians Olivier Sordet Stéphanie Cabantous Aurélien Olichon Sylvie Monferran Isabelle Lajoie-Mazenc Anne Pradines Julien Mazières Nicolas Meyer Laura Keller Research associates Claire Medale- Giamarchi Patrick Chinestra Post-doctoral fellows Team 3 - Cellular signaling, oncogenesis and Olivier Calvayrac therapeutics Julia Cherrier Faten Koraichi Claudine Tardy Cancer cells have deregulated signaling pathways that are PhD students Laetita Mouly involved in cell proliferation, survival, and tumor progression. Sarah Figarol
Our team is working to better understand the molecular Magdalena Pohorecka mechanisms of these deregulations and to allow the Simona Salimbeni Technicians development of new cancer treatments by the transfer of our Catherine Bouchenot findings to the clinic, in particular in lung cancers and melanoma. Anne Casanova Rémy Gence
Objective Our general aim is to understand molecular in oncogenesis and resistance to targeted therapies. pathway abnormalities in cancer cells and to Team strengths in the leading-edge biotechnologies translate these laboratory results into the of GFP-based protein/protein interaction and development of new therapeutic strategies. We nanobody-based biosensors contribute to the focus first on the receptor tyrosine kinase discovery of new biological and clinical findings. (RTK)/RAS/MAPK and RHOGTPase pathways to Expertise in signal transduction and DNA damage understand their connections with the control of response pathway has contributed directly and cell proliferation, survival and tumor progression, indirectly to new concepts in the resistance to and to design new therapeutic strategies. Second, targeted therapies and new target discovery. we study the signaling and repair mechanisms of In close collaboration with clinical departments, we DNA double-strand breaks (DSB) produced in develop translational and clinical research in lung transcribed regions in order to understand their role cancers and melanoma.
Keywords: Oncogenic signaling, RTK/RAS/MAPK and RHOGTPase pathways, cell stress and double-strand break signaling, biotechnology, nanobodies, Split GFP, lung cancers, melanoma, translational research, biomarkers, clinical trials
[10]
Highlights
Emphasizing RHOB/PP2A/AKT/RAC1 Genomic instability by transcription-induced signaling axis in lung cancer progression DNA double-strand breaks Metastatic dissemination is the cause of death in DNA double-strand breaks (DSBs) can cause the vast majority of cancers including lung genomic instability and contributes to the genesis cancers. In order to metastasize tumor cells must of many human diseases including cancer. undergo a well-known series of changes. Although the majority of mammalian cells are non- However, the molecular details of how they or slow-replicating (stem cells, most cells in solid manage to overcome the barriers at each stage tumors…) the processes of the production and remain incomplete. One critical step is acquiring signaling of DSBs in the absence of replication are the ability to migrate through the extracellular largely unknown. We previously reported that matrix. We previously demonstrated that loss of DSBs are generated in non-replicating cells when expression of the RAS-related small GTPase RHOB an ongoing transcription complex encounters a is a common feature of lung cancer progression. trapped topoisomerase I-DNA cleavage complex We report here that RHOB loss induces epithelial- (Top1cc) onto chromatin. Top1cc trapping is a to-mesenchymal transition (EMT) characterized frequent event that results from a wide range of by a 3-D cell shape reorganization and the DNA alterations, as well as from genetic defects increased invasiveness of bronchial cells. These (e.g. ATM, TDP1) found in some tumors. Here we effects depend on SLUG overexpression and E- showed that transcription- and Top1-dependent Cadherin inhibition. RHOB loss maintains AKT1 DSBs are generated from single-strand DNA break activation which in turn activates RAC1 through its intermediates generated during Top1cc removal GEF TRIO. Further investigation revealed that by the TDP1 pathway. Analysis of DSB signaling RHOB interacts with and activates PP2A, one of further reveals a novel function of the kinase DNA- the major serine-threonine phosphatases, by PK in promoting protein ubiquitination leading to recruiting its regulatory subunit B55. enhancement of Top1cc removal in a feedback Altogether, these results highlight a novel loop as well as to full ATM activity at DSB sites. RHOB/PP2A/AKT1/RAC1 signaling axis and Altogether, these findings provide new molecular describe new molecular mechanisms that could insights on the genesis of genomic instability in explain the tumor suppressor role of RHOB in lung non-replicating cells. cancer.
Labels / Grants: ARC, Fondation de France, Ligue contre le cancer, IdEx, ANR
Some publications in 2016 RHOB expression controls the activity Dynamic effects of Topoisomerase I DNA-PK triggers histone ubiquitination of serine/threonine protein inhibition on R-Loops and short trans- and signaling in response to DNA phosphatase PP2A to modulate cripts at active promoters. Marinello J double-strand breaks produced during mesenchymal phenotype and invasion et al. PLoS One. 2016;11(1):e0147053. the repair of transcription-blocking in non-small cell lung cancers. Bevacizumab for newly diagnosed topoisomerase I lesions. Cristini A et al. Calvayrac O et al. Small GTPases. pleural mesothelioma in the Nucleic Acids Res. 2016;44(3):1161- 2016:1-6. Mesothelioma Avastin Cisplatin 78. Detection and Monitoring of the BRAF Pemetrexed Study (MAPS): a rando- RhoB loss induces Rac1-dependent Mutation in Circulating Tumor Cells mised, controlled, open-label, phase 3 mesenchymal cell invasion in lung cells and Circulating Tumor DNA in BRAF- trial. Zalcman G et al. 2016. Lancet. through PP2A inhibition. Bousquet E et Mutated Lung Adenocarcinoma. 387:1405-14. al. Oncogene. 2016;35(14):1760-9. Guibert N et al. J Thorac Oncol. Combined nivolumab and ipilimumab NaLi-H1: A universal synthetic library of 2016;11(9):e109-12. versus ipilimumab alone in patients humanized nanobodies providing Identification of a circulating with advanced melanoma: 2-year highly functional antibodies and MicroRNA Profile as a Biomarker of overall survival outcomes in a intrabodies. Moutel S et al. Elife. Metastatic Cutaneous Melanoma. multicentre, randomised, controlled, 2016;5. Armand-Labit V et al. Acta Derm phase 2 trial. Hodi FS et al. Lancet Venereol. 2016;96(1) :29-34. Oncol. 2016 ; 17(11):1558-68.
[11]
Team Leaders Thierry Levade Professor & Nathalie Andrieu Inserm DR
Staff Senior scientists Céline Colacios Joëlle Riond Frédérique Sabourdy Bruno Ségui
Technicians Stéphane Carpentier Patricia Clavé Team 4 - Sphingolipid metabolism, cell death & Marine Fraisse Virginie Garcia
tumor progression Post-doctoral fellows Abnormal lipid profiles are often associated with an altered Florie Bertrand metabolic phenotype in tumor cells, which has been recognized as Anne Montfort a hallmark of cancer. Our aim is to elucidate how sphingolipid (SL) Alexandre Ghenassia (recruited in 2017) metabolism affects key biological processes underlying cancer development including cell death, proliferation, migration, tumor PhD students
stroma remodeling as well as immune response. In particular, the Leonardo Astudillo* contribution of SLs to skin melanoma and breast cancer is Fatima Bilal David Garandeau* examined. Not only these forms of cancer are frequent and/or Caroline Imbert resistant to current therapies, but also they exhibit altered SL Marguerite Mrad* metabolism. Our ultimate goal is to target SL metabolism in order Michaël Peres Justine Noujarède to improve therapeutic approach, i.e., to prevent tumor progression and overcome resistance to anticancer drugs, Maxime Sahun *PhD defended in 2016 cytokines and immune cells.
Objectives
Two main questions are addressed: - How SL metabolism affects the anticancer - How SL metabolism controls melanoma cells immune response? and their microenvironment? We postulate that SL metabolism alterations in The purpose of our project is triple: (i) The cancer cells modulate immune response, identification and role of variants in genes facilitating tumor escape from the immune encoding enzymes of SL metabolism in familial system. We will investigate : (i) the levels of SL melanoma ; (ii) The delineation of the effects of metabolites in plasma and tumors according to the oncometabolite sphingosine 1-phosphate the tumor infiltration by leukocytes, (S1P) and its receptors on the communication (ii) the causal role of SL metabolism alterations in between melanoma cells and their cellular the immunogenicity of cancer cells and their microenvironment during initial progression; (iii) responses to immune and death effector The understanding of the molecular mechanisms molecules, and underlying the role of SL metabolism in the (iii) the role of tumor SLs on tumor-infiltrating resistance of melanoma cells to current leukocytes in mouse models. therapies.
[12]
Keywords: Ceramide, sphingosine 1-phosphate, melanoma, metabolism, oncometabolite, oncoimmunology, tumor microenvironment, tumor necrosis factor
Highlights
IMMUSPHINX Sphingolipids Funded by the European program Transcan-2 H2020-SC1 SPHINGOLIPIDS TICIMEL (PI: Dr. N. Andrieu) TNF inhibitors
A Phase Ib clinical study Patents MELANFα TNF WO2017129769A1 TNF WO2017134116A1 EP16306138.5 Patents EP16306139.3 WO2015173259A1 IMMUNE ESCAPE EP16305085
Team 4: Clinical trials - metastatic melanoma - PI: Prof N. Meyer (IUCT)
Labels / Grants: Ligue contre le Cancer, Inserm Transfert, Inserm, Université Paul Sabatier, INCa, Cancéropôle Grand Sud-Ouest
Some publications in 2016 Redox Homeostasis Independently P, Levade T, Naderer T, Savchenko Downregulation of sphingosine of p53. Riscal R, Schrepfer E, Arena A, Buchrieser C. Proc Natl Acad Sci kinase-1 induces protective tumor G, Cissé MY, Bellvert F, Heuillet M, U S A 2016, 113(7):1901-6. immunity by promoting M1 Rambow F, Bonneil E, Sabourdy F, A Natural Variant of the T Cell macrophage response in Vincent C, Ait-Arsa I, Levade T, Receptor-Signaling Molecule Vav1 melanoma. Mrad M, Imbert C, Thibaut P, Marine JC, Portais JC, Reduces Both Effector T Cell Garcia V, Rambow F, Therville N, Sarry JE, Le Cam L, Linares LK. Mol Functions and Susceptibility to Carpentier S, Ségui B, Levade T, Cell 2016, 62(6):890-902. Neuro-inflammation. Kassem S, Azar R, Marine JC, Diab-Assaf M, Targeting TNFalpha as a novel Gaud G, Bernard I, Benamar M, Colacios C, Andrieu-Abadie N. strategy to enhance CD8+ T cell- Dejean AS, Liblau R, Fournié GJ, Oncotarget 2016, 7(44):71873-86. dependent immune response in Colacios C, Malissen B, Saoudi A. PARKIN Inactivation Links melanoma? Bertrand F, Rochotte J, PLoS Genet 2016 Jul Parkinson's Disease to Melanoma. Colacios C, Montfort A, Andrieu- 20;12(7):e1006185. Hu HH, Kannengiesser C, Lesage S, Abadie N, Levade T, Benoist H, A sequential bioorthogonal dual André J, Mourah S, Michel L, Ségui B. Onco-immunology 2016, strategy: ManNAl and SiaNAl as Descamps V, Basset-Seguin N, 5(1) e1068495. distinct tools to unravel sialic acid Bagot M, Bensussan A, Lebbé C, Legionella pneumophila S1P-lyase metabolic pathways. Gilormini PA, Deschamps L, Saiag P, Leccia MT, targets host sphingolipid Lion C, Vicogne D, Levade T, Potelle Bressac-de-Paillerets B, Tsalamlal metabolism and restrains S, Mariller C, Guérardel Y, Biot C, A, Kumar R, Klebe S, Grandchamp autophagy. Rolando M, Escoll P, Foulquier F. Chem Commun B, Andrieu-Abadie N, Thomas L, Nora T, Botti J, Boitez V, Bedia C, (Camb) 2016, 52(11):2318-21. Brice A, Dumaz N, Soufir N. J Natl Daniels C, Abraham G, Stogios PJ, Glucosylceramidases and Cancer Inst 2016, 108(3) djv340. Skarina T, Christophe C, Dervins- malignancies in mammals. Chromatin-Bound MDM2 Ravault D, Cazalet C, Hilbi H, Astudillo L, Therville N, Colacios C, Regulates Serine Metabolism and Rupasinghe TW, Tull D, McConville Ségui B, Andrieu-Abadie N, Levade MJ, Ong SY, Hartland EL, Codogno T. Biochimie 2016, 125:267-80.
[13]
Team Leader Stefania Millevoi CR1 Inserm Staff
Anne Cammas* Hervé Prats* Florence Cabon Eric Lacazette Corinne Hieblot* Catherine Zanibellato*
Non permanent Team 5 – RNA-binding proteins and post- Juliette Bertorello* (AI)
transcriptional regulation in cancer Post-doc fellows Raouia Ben-Naya Marie Cargnello* Post-transcriptional gene expression is deregulated in cancer, PhD students resulting in altered programs of protein biosynthesis that can Morgane Le Bras* drive tumor progression and resistance to therapy. Our research Guillaume Labrousse program brings together clinicians, biologists and experts in Julie Tenet Florence Bonnet biostatistics to unveil how molecular mechanisms of
translational regulation by RNA-binding proteins are *Present members
orchestrated in cancer cells and are linked to patient outcome.
Nina CAILLET Objectives Alteration of post-transcriptional gene Our research focuses on understanding the expression regulation is a hallmark of cancer. role of RBPs in post-transcriptional gene RNA -binding proteins (RBPs) are master expression reprogramming in response to regulators required for all post- stress and to the deregulation associated to transcriptional processes, including transcript cancer pathobiology. maturation, mRNA stability and translation. Our objectives are: These factors allow dynamic regulation in 1- to provide a mechanistic and functional normal and various stress conditions, and understanding into how RBPs impact on contribute to deregulations in the RNA cancer development, progression and metabolism of cancer cells. They can also treatment, directly impact genome instability by 2- to improve our understanding of RNA G- establishing a direct link between DNA- and quadruplexes regulation and targeting in RNA -mediated processes. RBPs recognize cancer cells, specific elements of diverse sequences and 3- to investigate the emerging concept that structures. Among these, RNA G-quadruplex DNA-damage proteins, beside effects on DNA structures have been shown to affect the and signaling, target mRNAs to regulate post- expression of cancer relevant genes by transcriptional gene expression. modulating post-transcriptional steps.
Keywords: Post-transcriptional gene expression, mRNA, RNA-binding proteins, mRNA translation, DNA damage response, RNA G-quadruplex structure
[14]
Highlights
RNA G-quadruplex structures impact Ku acts as a post-transcriptional protein synthesis in cancer regulator of gene expression High expression of the RNA-binding protein The DNA repair protein Ku suppresses p53 hnRNP-A1 is associated to metastatic relapse in mRNA translation in cells grown under normal patients with invasive breast cancer. conditions, thereby contributing to the low steady‐ state level of p53. Cytoplasmic hnRNP-A1 increases the translation of the mRNA encoding the tyrosine In cells stressed with DNA‐damaging agents, kinase receptor RON/MST1R through RNA G- Ku acetylation abrogates the Ku‐dependent quadruplex structures in the RON 5’-untranslated suppression of translation and permits increased region (UTR). translation of p53 mRNA.
Cammas et al., (2016) Oncotarget 2016 Lamaa et al., (2016) EMBO Reports
Labels / Grants: Ligue contre le cancer, ARC, Cancéropôle Grand Sud-Ouest, Fondation de l’Avenir, Région Midi-Pyrénées, LabEx TOUCAN
Some publications in 2016 linked to tumor progression. angiogenic growth factors after A novel cytoprotective function (2016) Cammas et al., ischemic stress. (2016) Philippe for the DNA repair protein Ku in Oncotarget 7:16793-805. C et al., Sci. Signal; 9(426):ra44. regulating p53 mRNA Dual Roles for CXCL4 Hypoxia and ER stress promote translation and function. (2016) Chemokines and CXCR3 in Staufen1 expression through an Lamaa et al., EMBO Reports; Angiogenesis and Invasion of alternative translation 17(4):508-18. Pancreatic Cancer. (2016) mechanism. (2016) Bonnet- hnRNP A1-mediated Quemener et al., Cancer Magnaval et al., Biochem translational regulation of the G Research 76: 6507-19. Biophys Res Commun 2: 365- quadruplex-containing RON PERK mediates the IRES- 71. receptor tyrosine kinase mRNA dependent translational activation of mRNAs encoding
[15]
Team Leaders Stéphane Pyronnet DR Inserm & Corinne Bousquet DR Inserm
Staff Yvan Martineau Christine Jean Marjorie Fanjul Philippe Caron Delphine Vezzosi Catherine Marboeuf Stéphanie Cassant- Sourdy Team 6 – Protein Synthesis & Secretion in Amandine Alard Oncogenesis Manon Strehaïano Emilie Decaup Julia Rochotte Cancer cells must double their protein content before dividing Zeina Bash Imam (proliferation), and both cancer and surrounding cells (especially Rémi Samain cancer-activated fibroblasts) synthetize and secrete proteins Christophe Quémerais critical for tumor growth, metastasis spreading and resistance to Sauyeun Shin treatment. Our group searches how protein synthesis and related Sonia Zaghdoudi signaling pathways are regulated in healthy cells, how they become altered in malignant tumors and whether they can be targeted for therapeutic intervention.
Objectives
Through biochemical, cellular and in vivo uncovered mechanisms are validated in models our fundamental objective is to patient samples, and known or new understand how mRNA translation into pharmaceutical compounds are tested for protein is regulated. The function of both their therapeutic potential. global (through canonical translation We have a solid background in pancreatic initiation complexes) and mRNA-specific tumors (and accumulating evidence in acute translational factors and their respective myeloid leukemia) showing that selective regulations by selective signaling pathways translational regulators and/or signaling are explored. These new mechanistic insights pathways appears as attractive therapeutic are then very helpful in searching whether targets. Their targeting can affect tumor and how alterations in the control of protein growth, metastatic spreading or response to synthesis play a role in oncogenesis and in conventional treatments through either resistance to treatment. Thanks to direct effects on cancer cells or indirect collaborations with clinicians and local and effects on tumor microenvironment. international industrial partners, the
[16]
Keywords: Protein synthesis, mRNA translation, signaling pathways, tumor microenvironment, somatostatin, pancreatic cancer, acute myeloid leukemia
Highlights
During the last years, we have identified protein synthesis mechanisms and their regulation pathways which are altered in cancer cells, and showed that they could be potential therapeutic targets.
More recently, our work focused on the tumor microenvironment: We recently showed that targeting the mTOR/4E-BP1-protein synthesis pathway selectively in cancer-activated fibroblasts (CAFs) restrains metastases spreading and sensitizes pancreatic tumors to chemotherapy. Duluc EMBO Mol Med 2015 Moatassim-Billah Oncotarget 2016
Labels / Grants: Ligue contre le cancer, LabEx TOUCAN, PHUC CAPTOR
Some publications in 2016 S6K1 Is Required for Increasing ischemic stress. Philippe C et al. Anti-metastatic potential of Skeletal Muscle Force during Sci Signal. 2016; 9(426):ra44. somatostatin analog SOM230: Hypertrophy. Marabita M, et al. Essential role for SphK1/S1P Indirect pharmacological Cell Rep. 2016; 17:501-13. signaling to regulate hypoxia- targeting of pancreatic cancer- Nucleolin Promotes Heat inducible factor 2α expression associated fibroblasts. Shock-Associated Translation of and activity in cancer. Moatassim-Billah S, et al. VEGF-D to Promote Tumor Bouquerel P, et al. Oncotarget. 2016; 7:41584-98. Lymphangiogenesis. Morfoisse Oncogenesis. 2016; 5:e209. Cancer-associated fibroblast- F, et al. Cancer Res. 2016; Challenging the Roles of NSP3 derived annexin A6+ 76:4394-405. and Untranslated Regions in extracellular vesicles support PERK mediates the IRES- Rotavirus mRNA Translation. pancreatic cancer dependent translational Gratia M, et al. PLoS One. 2016; aggressiveness. Leca J, et al. J activation of mRNAs encoding 11:e0145998. Clin Invest. 2016; 126:4140-56. angiogenic growth factors after
[17]
Team Leader Pierre Brousset Professor
Staff
Fabienne Meggetto Laurence Lamant Christian Touriol Marina Bousquet Estelle Espinos Coralie Hoareau-Aveilla Margherita Ghisi Avédis Torossian Team 7 – RNA biology in hematological cancers Céline Philippe Morgane Gourvest Non coding RNA (ncRNA) are RNA without protein-coding Nina Caillet Cathy Quelen potential. Despite intensive research on ncRNA, our overall Ouafa Zaki knowledge of ncRNA function in carcinogenesis remains very Annabelle Congras limited. One of the main challenges of our team in understanding Nicolas Broin the function of a specific non-coding RNA such as long and micro ncRNA in cancer, is deciphering their interactome (other RNAs,
specific protein complexes, regions of DNA…), and regulations.
Objectives
In the last decade, it has become increasingly clear potential of resistance Nina are CAILLET investigated: T-cell that post-transcriptional control of gene lymphoma including anaplastic large cell expression plays an essential role in tumor cell lymphoma and acute myeloid leukemia. dysregulation. Studies at the RNA level have been Our objectives are: focused for a long time on mRNA, the best known - to decipher how ncRNAs dysregulation in RNA family that represents only a small part of leukemias/lymphomas could impact their transcripts (2 to 5% of total RNAs). However, the prognosis (relapse, response and resistance to human genome contains much more than just treatment), and ideally to identify prognostic protein-coding genes and the majority of biomarkers, transcribed RNAs are non-coding (ncRNA) such as - to investigate the role of ER stress on ncRNAs microRNAs (miRNA), long non-coding RNAs expression in leukemia and their impact on tumor (lncRNA), interfering RNAs, piwiRNAs, or small progression and response to treatment, nucleolar RNAs (snoRNA). Evidence is - to study the physiological and pathological role accumulating that these ncRNAs play key roles in of these ncRNA including the identification of their regulating numerous pathways involved in cancer downstream target genes, whose role in classical development and progression. (proliferation, survival, invasion) pathways of The lab explores the expression profiles and cancerogenesis will be functionally characterized, functions of microRNAs and lncRNAs in - to study the upstream mechanisms of ncRNA hematological malignancies, their interaction with regulation (epigenetic control of their expression, proteins and their protein coding potential (with a control of their expression by microRNA encoded focus on primary miRNA transcripts, pri-miR). Two peptites (miPEPs), control of their stability by types of tumors for which our team has an specific endoribonucleases). international expertise or represent cancers with
[18]
Keywords: miRNA, lncRNA, acute myeloid leukemia, anaplastic large cell lymphoma, ALK, target therapy, ER stress, resistance
Highlights
• Identification of a specific new lncRNA biomarker in AML LncRNA XLOC_109948 expression levels can predict clinical outcome especially in NPM1-mutated AML patients. De Clara et al, Haematologica, 2017, 2017 102: 1718-26.
• Decitabine treatment, via the STAT3/miR-150/MYB axis, inhibits growth of the crizotinib-resistant KARPAS-299-CR06 mutant. Hoareau-Aveilla et al, J Clin Invest. 2015 Sep;125(9):3505-18.
Label / Grants: Ligue Contre le Cancer, LabEx TOUCAN, ITN-Horizon 2020 ALKATRAS
Some publications in 2016 Ysebaert L. Br J Haematol. Cell Lymphoma development. RNA editing in acute myeloid 2016;172(5):819-23. Malcolm TI*, Villarese P*, leukaemia with normal PERK mediates the IRES- Fairbairn C, Lamant L, karyotype. Quelen C, Eloit Y, dependent translational Trinquand A, Hook CE, Burke Noirot C, Bousquet M, Brousset activation of mRNAs encoding GA, Brugières L, Hughes K, P. Br J Haematol. angiogenic growth factors after Payet D, Merkel O, Schiefer AI, 2016;173(5):788-90. ischemic stress. Philippe C, Mian S, Wasik M, Turner M, Small nucleolar RNA expression Dubrac A, Quelen C, Kenner L, Asnafi V, Macintyre E, profiles refine the prognostic Desquesnes A, Van Den Berghe Turner SD. Nat Commun impact of IGHV mutational L, Ségura C, Filleron T, Pyronnet 2016;7:10087 (* co-first status on treatment-free S, Prats H, Brousset P, Touriol C. authors). survival in chronic lymphocytic Sci Signal. 2016;9(426):ra44. Anaplastic Large Cell leukaemia. Berquet L, Valleron NPM-ALK mimics thymic pre-T Lymphoma. Turner SD, Lamant W, Grgurevic S, Quelen C, Zaki cell receptor (TCR) expansion L, Kenner L, Brugieres L. Br J O, Quillet-Mary A, Davi F, but requires transient TCR Haematol 2016; 173 :560-72 Brousset P, Bousquet M, expression for thymic egress (review). and peripheral Anaplastic Large
[19]
Team Leaders Arnaud Besson DR CNRS & Stéphane Manenti DR CNRS
Staff Sarah Bertoli, Hospital practionner Véronique De Mas, Associate professor Christine Didier, CR CNRS Christine Dozier, CR CNRS Carine Joffre, CR Inserm Laurent Mazzolini, CR CNRS Team 8 – Cell cycle and cancer Alexandre Gay,
Research assistant We try to identify proteins which are important for the response of leukemic cells to therapeutic drugs. We then investigate how PhD students these proteins work in these cells, and how they are regulated by Justine Creff the oncogenes responsible of the disease. We focus our studies Quentin Heydt on proteins which have important functions in cell cycle Ada Nowosad Renaud Perchey regulation, as well as in autophagy, a cellular process recently Gabrielle Sueur identified as an important pathway of resistance to several Maëlle Cartel therapeutic drugs.
Objectives
Our general aim is to decipher the transcriptional mechanisms of regulation. mechanisms that link oncogenic signaling, We also investigate how autophagy regulates cell cycle regulation, and autophagy. We try signaling pathways (signalophagy) in cancer to understand how cell signaling pathways cells, more specifically in acute myeloid activated by oncogenes, in particular leukemia subtypes. We estimate in parallel mutated tyrosine kinases, regulate key cell how these cell cycle actors or autophagy cycle actors, like the CDC25A phosphatase or impact the response and the resistance of the DNA damage checkpoint kinase CHK1, for these cancer cells to therapeutic agents. We instance. We identify by different approaches finally translate these basic research new regulatory modifications of these questions into the identification of potential proteins, such as new phosphorylation sites therapeutic targets in acute myeloid or new transcriptional and post- leukemia.
Keywords: Cell cycle, autophagy, signaling, acute myeloid leukemia, checkpoints, CDK inhibitor
[20]
Highlights
The CDC25A phosphatase is regulated by CDK phosphorylations at the G2/M transition. We identified Ser 283 as a new phosphorylation site on the CDC25A phosphatase by mass spectrometry analysis. The G2 and mitotic CDK complexes are involved into the phosphorylation of this residue, which is important for the G2/M transition functions of CDC25A. This phosphorylation loop participates to the tight regulation necessary for correct completion of mitosis in normal and cancer cells.
The CHK1 protein kinase is an independent prognostic marker and a therapeutic target in AML. Patients presenting the highest levels of CHK1 mRNA and protein have lower survival probability and higher risks of relapse. CHK1 is involved in the resistance of AML cells of these patients to the therapeutic drug cytarabin, and inhibiting CHK1 consequently sensitizes leukemic cells to this genotoxic drug. CHK1 is also involved in the deregulated proliferation of these leukemic cells, since cells from patients with high CHK1 level are characterized by higher clonogenic potential.
FLT3-ITD induces autophagy through an ATF4-dependent pathway in AML (Heydt et al, in revision). We demonstrate that the mutant receptor FLT3-ITD, expressed in 25% of AML and associated with a poor prognosis for the patients, induces basic constitutive autophagy in AML cells. This autophagy drives the proliferation of AML cells in vitro, as well as in vivo in a NSG mice xenograft model. The transcription factor ATF4 is tightly regulated by FLT3-ITD, and we identified it as a master inducer of the autophagic process in this model.
Labels / Grants: Labex TOUCAN, Label Ligue contre le Cancer 2016
Some publications in 2016 2016. J. Cell Biol. 214: 555-69. transformation. Oncotarget. Larrue C, Saland E, Boutzen H, (cover article). *Equal 2016 7(28):44142-60. David M, Joffre C, Hospital MA contribution. Faculty of 1000 Mazzolini L, Broban A, Froment Tamburini J, Delabesse E, recommended article. C, Burlet-Schiltz O, Besson A,
Manenti S, Sarry JE, Récher C. Barrow R*, Kishi N*, Joffre C*, Manenti S and Dozier C. Proteasome inhibitors induce Menard L, Hervieu A, Mai A, Phosphorylation of CDC25A on FLT3-ITD degradation through Robert-Masson L, Iturrioz X, ser283 in G2 by CDK/Cyclin autophagy in AML cells. Blood Hulit J, Brennan C, Hart IR, complexes accelerates mitotic 2016;127(7):882-92. Parker PJ, Ivaska J, Kermorgant entry. Cell Cycle, 2016; 15(20): Duquesnes N, Callot C, Jeannot S. Beta 1-integrin- c-Met 2742-52. P, Daburon V, Nakayama K.I., cooperation : an inside-in David L*, Fernandez-Vidal A*, Manenti S, Davy A and Besson survival signalling on Autophagy Bertoli S, Grgurevic S, Lepage B, A. p57Kip2 knock-in mouse Related Endomem-branes. Deshaies D, Prade N, Cartel M, reveals CDK-independent Nature Commun, 2016; Larrue C, Sarry JE, Delabesse E, contribution in the 7:11942 (*equal participation). Cazaux C, Didier C, Récher C**, development of Beckwith- Bettoun A, Joffre C, Zago G, Manenti S** and Hoffmann Wiedemann syndrome. J Surdez D, Vallerand D, JS**. Chk1 as a therapeutic Pathol, 2016, 239(3):250-61. Gundogdu R, Sharif AA, Gomez target to bypass chemo- Jungas T, Perchey RT, Fawal M, M, Cascone I, Meunier B, White resistance in AML. Science Callot C, Froment C, Burlet- MA, Codogno P, Parrini MC, Signaling, 2016;9 (445): ra90 Schiltz O, Besson A* and Davy Camonis JH, Hergovich A. (*equal participation; **co- A*. Eph-mediated tyrosine Mitochondrial clearance by the corresponding authors). phospho-rylation of Citron STK38 kinase supports Kinase controls abscission. oncogenic Ras-induced cell
[21]
Team leader Jean-Jacques Fournié DRCE1 CNRS
Staff Anne Quillet-Mary, DR2 CNRS, HDR Mary Poupot, CR1 Inserm, HDR Christine Bezombes, CR1 Inserm, HDR Camille Laurent, MCU-PH IUCT, HDR Loïc Ysebaert, PH IUCT, HDR Olivia Lanvin, Team 9 – Therapeutic Innovations in B IE2 Inserm, Pauline Gravelle, lymphomas IE IUCT Marie Tosolini, Non-Hodgkin B cell lymphoma (NHL) including chronic IE IUCT Sarah Cadot, lymphocytic leukemia (CLL) are increasingly frequent TR Inserm hematopoietic malignancies. The patients care relies on chemotherapies, immunotherapies and radiotherapy Post-Doc Fellows Don-Marc Franchini combinations, but relapse and/or unresponsiveness are far too Objectives : Guillaume Poiroux frequent. So our team aims at improving the efficacy of treatments for NHL, PhD students notably by assessing immune checkpoint blockade (ICB) in this Cedric Rossi, MD Julie Bordenave context.
Objectives
More specifically, we develop novel tools This includes : including analytic methods and biological 1- Predicting response of patients to models to find new molecular pathways for treatment (ibrutinib in CLL, ICB in NHL) targeting NHL by novel drugs, and assess 2- Harnessing innate immunity against them in preclinical models, prior to translate lymphoma models our most promising new approaches in Phase 3- Development of a humanized anti- l/ll clinical trials of IUC-Toulouse Oncopole. TAM mAb neutralizing the stromal support of NHL.
Key words: Lymphoma, MALC models, datamining, bioinformatics, deep learning, RNAseq, therapy, drugs, immune checkpoints, flow cytometry
[22]
Highlights Four stages of immune escape in DLBCL (Diffuse Large B-cell lymphoma) patients
Genome-wide gene expression profiles from 1200 DLBCL tumours evidence four stages of immune escape in these cancer patients. The patients at stage 2 (Green: high T cell activation, low immune escape) benefit longer OS than those with immune escape stage 3 (red: high T cell activation and immune escape) Stage 4 patients (low activation high immune escape) have the shortest survival. Stage 1 patients are currently under study (Tosolini et al. OncoImmunology, 2016).
Labels / Grants: LabEx TOUCAN, Institut Carnot III : CALYM, PHUC CAPTOR
Some publications in 2016 Guggino G, Ciccia F, Di Liberto through LFA-3/CD2 Tosolini M, Algans C, Pont F, D, Lo Pizzo M, Ruscitti P, Cipriani interactions. Oncotarget 2016. Ycart B, Fournié JJ. Large-scale P, Ferrante A, Sireci G, Dieli F, Boissard F, Laurent C, Ramsay microarray profiling reveals Fournié JJ, Giacomelli R, Triolo AG, Quillet-Mary A, Fournié JJ, four stages of immune escape G. Interleukin (IL)-9/IL-9R axis Poupot M, Ysebaert L. Nurse- in non-Hodgkin lymphoma. drives gamma delta T cells like cells impact on disease Oncoimmunology 2016. 5: activation in psoriatic arthritis progression in chronic e1188246. patients. Clin Exp Immunol lymphocytic leukemia. Blood Poupot M, Turrin CO, Caminade 2016. 186: 277-83. Cancer J 2016. 6:e381. AM, Fournié JJ, Attal M, Poupot Duault C, Franchini DM, Betrian S, Ysebaert L, Heider KH, R, Fruchon S. Poly(phosphor- Familliades J, Cayrol C, Roga S, Delord JP, Fournié JJ, Quillet- hydrazone) dendrimers: yin and Girard JP, Fournié JJ, Poupot M Mary A. Idelalisib improves yang of monocyte activation for TCRV gamma 9 gamma delta T CD37 antibody BI 836826 human NK cell amplification Cell Response to IL-33: A CD4 T cytotoxicity against chemo- applied to immunotherapy Cell-Dependent Mechanism. J resistant /relapse-initiating CLL against multiple myeloma. Immunol 2016. 196: 493-502. cells: a rationale for Nanomedicine – Nanotechno- Boissard F, Tosolini M, Ligat L, combination treatment. Blood logy, Biology and Medicine Quillet-Mary A, Lopez F, Fournié Cancer J 2016. 6 : e496. 2016. 12: 2321-30. JJ, Ysebaert L, Poupot M. Nurse- like cells promote CLL survival
[23]
Team Leader Pierre Cordelier DR Inserm
Staff Audrey Frances Pierre Garcin Louis Buscail Marlène Dufresne Naima Hanoun Delphine Pagan Hubert Lulka Lorraine Quillet Manon Brunet Team 10 – Molecular heterogeneity of pancreatic Guillaume Conzatti tumors Jean Cacheux Pancreatic tumors display a remarkable molecular variability that Dorian Larrieu Janick Selves results in a unique ability to escape and survive therapy. Our Rosine Guimbaud research effort is dedicated to improve the molecular Barbara Bournet understanding of pancreatic tumors and therefore to better Nicolas Carrère address the role of intra-tumor heterogeneity in diagnosis and Jean-Pierre Vinel Jérome Torrisani the development of therapeutic resistance.
Objectives
Our general objective is to better understand the we created with LAAS-CNRS novel nanodevices complex relationship between molecular for candidate biomarker identification / heterogeneity and therapeutic resistance of quantification. pancreatic adenocarcinoma (PDAC), to help Last, we are engaged in bench-to-bedside, alleviate the dismal prognosis of this disease with personalized, translational preclinical programs no cure. and first-in-man clinical trials using gene therapy To this end, we developed basic research to defeat pancreatic tumor resistance to programs to investigate the function of candidate conventional chemotherapy and next-generation proteins involved in the fine-tuning of mitosis, immunotherapies. DNA damage repair and replication, and tumor We expect that our scientific program will bring metabolism. We found that these proteins are new insights in the molecular heterogeneity of heterogeneously expressed in patients and tumors, to develop innovative strategies that will control experimental tumors growth. In cohorts overcome pancreatic adenocarcinoma resistance of patients, we identified specific molecular to treatment. signatures, including circulating, noninvasive nucleic acids for patients’ stratification. In parallel
Keywords: Pancreatic cancer, molecular heterogeneity, DNA damage repair, mitosis, DNA replication, tumor metabolism, gene therapy, oncolytic virus.
[24]
Highlights
In 2016, we devised novel gene therapy approaches to defeat PDAC. First, we engineered integrase-deficient lentiviral vectors (IDLVs) to prevent insertional mutagenesis while treating experimental tumors (1). Next, we participated to the development of a simple method relying on tumor metabolism to regulate gene expression in experimental pancreatic Figure 1. Transduction of PDAC cells with IDLV tumors (2). Both strategies may be applied HIV-1 vectors. Cancer cells were transduced in the future for the treatment of patients with IDLV D64V encoding for GFP. Cells were with PDAC. In the meantime, we obtained imaged 4 days later. the approval from ANSM to perform a
phase II clinical trial based on non-viral gene transfer to defeat resistance to treatment in hundred patients with advanced tumors (Thergap-2 trial, 3). Inclusion have started in Q1/2017. Also, we made substantial progress in the molecular characterization of pancreatic tumors to demonstrate that i) KRAS mutation testing identifies patients with high-risk precursor lesions who may benefit from surgical Figure 2. Molecular analysis of PDAC tumors. resection (4), and ii) KRAS G12D mutation is Tumor microbiopsies were sampled following an independent prognostic marker in endoscopic ultrasound (EUS). DNA was advanced pancreatic tumors (5). Last, we extracted from Fine-needle aspirates (FNA) and collaborated with chemists to generate subjected to Taqman allelic discrimination for biomaterials surface with unique identification of mutated forms of KRAS and bioadhesion properties for tunable GNAS. pancreatic cell adhesion (6).
Labels / Grants: Oncodevice consortium, Imcore project
Selected publications in 2016 3-Effect of Intratumoral Injection of Selves J, Guimbaud R, Cordelier P, 1-Hanoun N, Gayral M, Pointreau A, Gene Therapy for Locally Advanced Buscail L. KRAS G12D Mutation Buscail L, Cordelier P. Initial Pancreatic Cancer (THERGAP-02), Subtype Is A Prognostic Factor for Characterization of Integrase- https://clinicaltrials.gov/ct2/show/N Advanced Pancreatic Adenocar- Defective Lentiviral Vectors for CT02806687. cinoma. Clin Transl Gastroenterol. Pancreatic Cancer Gene Therapy. 4-Bournet B, Vignolle-Vidoni A, 2016 Mar 24;7:e157. Hum Gene Ther. 2016;27(2):184-92. Grand D, Roques C, Breibach F, Cros 6-Bournet B, Buscail C, Muscari F, 2-Chaveroux C, Bruhat A, Carraro V, J, Muscari F, Carrère N, Selves J, Cordelier P, Buscail L. Targeting KRAS Jousse C, Averous J, Maurin AC, Parry Cordelier P, Buscail L. Endoscopic for diagnosis, prognosis, and L, Mesclon F, Muranishi Y, Cordelier ultrasound-guided fine-needle treatment of pancreatic cancer: P, Meulle A, Baril P, Do Thi A, aspiration plus KRAS and GNAS Hopes and realities. Eur J Cancer. Ravassard P, Mallet J, Fafournoux P. mutation in malignant intraductal 2016 ;54:75-83. Regulating the expression of papillary mucinous neoplasm of the 7-Vassaux G, Angelova A, Baril P, therapeutic transgenes by controlled pancreas. Endosc Int Open. 2016 Midoux P, Rommelaere J, Cordelier intake of dietary essential amino ;4(12):E1228-E1235. P. The Promise of Gene Therapy for acids. Nat Biotechnol. 2016; 5-Bournet B, Muscari F, Buscail C, Pancreatic Cancer. Hum Gene Ther. 34(7):746-51. Assenat E, Barthet M, Hammel P, 2016 ;27(2):127-33.
[25]
Team Leaders Elizabeth Moyal Professor Christine Toulas Hospital practionner
Staff Catherine Seva Anthony Lemarie Laurent Barricault Emmanuelle Uro-Coste Monique Courtade Solene Evrard Valerie Gouaze Andersson Aline Chauvel Team 11 – Glioblastoma radioresistance: from M Julie Ghirardi Annie Behar signaling pathways to clinical trials Delmas Caroline Our team is a translational research team specialized in Florent Arnauduc optimizing the radiotherapy treatment of glioblastoma (GBM). Laure Malric We first decipher the biological mechanisms of GBM Sabrina Boyrie Anouchka Modesto radioresistance, then perform preclinical and clinical trials to Pauline Deshors evaluate the efficiency of combining radiotherapy with specific Laure Malric
inhibitors of the radioresistance mechanisms we previously identified. We focus our research more particularly on the role of GBM stem cells in the tumor radioresistance.
Objectives
Our team is a translational research team in imaging studies, as well as surrogate biomarkers. radiobiology , specialized in optimizing the This 3-axis strategy to improve the GBM radiotherapy treatment of glioblastoma (GBM). radiotherapy treatment efficiency is now
Our research is conducted in 3 complementary amplified by strengthening our research on approaches : i) first by deciphering the biological tumor heterogeneity and more particular on mechanisms of tumor radioresistance, ii) by GBM radiation-induced migration and plasticity performing preclinical trials to validate targets for as well as GBM stem cells (GSC) involvement in new radiosensitizer agents and to identify new GBM radioresistance. We also pursue our predictive markers, and iii) by conceiving and investigation concerning the mechanisms performing early phase clinical trials performed in sustaining glioblastoma differentiated cells our Institute (IUCT) associating targeted drugs radioresistance by investigating the role of directed against the target identified in the lab microenvironment factors as integrins and with radiotherapy and integrating metabolic growth factors.
Keywords: Glioblastoma, resistance to radiotherapy, stem cells, microenvironnement
[26]
Highlights
• We have investigated the role of micro-environment factors in tumor radioresistance. We first demonstrated the role of FGFR1 in the radioresistance of GBM cells. Silencing FGFR1 decreased radioresistance in vitro via PLC and HIF1in vitro and in vivo. These results offer a preclinical proof of concept that FGFR1 targeting can degrade radioresistance in glioblastoma, prompting clinical investigations of the use of FGFR1 inhibitors for radiosensitization (Gouazé-Andersson et al., 2016).
• We pursued our investigations concerning the impact of GBM cells plasticity in GBM radioresistance. We demonstrated the role of metabolism in GBM reprograming process.
• We identified a candidate biomarker from perfusion MRI to anticipate glioblastoma progression after chemoradiation (Khalifa et al., 2016). We developed clinical trials investigating the impact of GBM stem cells on tumor response to the treatment.
Labels / Grants: PHUC CAPTOR, ARC, Ligue contre le cancer, EDF
Some publications in 2016 Radioresistance through the 2016; 26(11):4194-203. 1- Goldbrunner et al, EANO PLCγ/Hif1α Pathway. Cancer 4- Kamoun et al, Integrated guidelines for the diagnosis and Res. 2016; 76(10):3036-44. multi-omics analysis of treatment of meningiomas. 3- Khalifa et al, Identification of oligodendroglial tumours Lancet Oncol. 2016;17(9): a candidate biomarker from identifies three subgroups of e383-91. perfusion MRI to anticipate 1p/19q co-deleted gliomas. Nat 2- Gouazé-Andersson V et al, glioblastoma progression after Commun. 2016 ;7:11263. FGFR1 Induces Glioblastoma chemoradiation. Eur Radiol.
[27]
Team Leaders Sandrine Silvente- Poirot, DR CNRS Marc Poirot, DR Inserm
Staff Michel Record Florence Dalenc Frédéric Courbon, Lavinia Vija Séverine Brillouet Régis Soules Elodie Bacquié Aurélie Mougel Post-doctoral fellows Team 12 – Cholesterol metabolism and R Bartölke, E Huc- therapeutic innovations Claustre, Julie Leignadier, E Noguer, N Serhan We are studying the role of cholesterol metabolism in the control PhD students or progression of cancers and in resistance to therapies, with a M Bauriaud-Mallet, N Rossetto, A Mallinger particular focus in breast cancer.
Objectives We want to identify and validate new therapeutic properties opens up new perspectives for the targets, to identify new mechanisms of resistance to development of novel therapies. It will help to treatments and to improve outcome through a understand fine mechanisms involved in acquired better stratification of cancers. Specifically, we are and intrinsic resistances to various therapies studying the contribution of cholesterol metabolism (Silvente-Poirot & Poirot, Science 2014). Our in the response to the endocrine therapy with objectives are : Tamoxifen (Tam) and aromatase inhibitors (AI). We 1) to characterize the molecular actors controlling identified a new metabolic pathway centered on this metabolic pathway, 2) to elucidate the cholesterol-5,6-epoxide hydrolase (ChEH). ChEH mechanism of action of these new metabolites, controls cholesterol-5,6-epoxide (5,6-EC) including their impact on exosome production and metabolism and is a direct target of Tam (de Medina phenotypes, 3) to characterize their impact on the et al, PNAS 2010). We showed its importance in the tumor microenvironment (in particular on the anticancer action of Tam. ChEH controls the immune system). Our objectives are also to propose production of metabolites with opposite properties innovative therapeutic approaches to counter or in cancers. We have first identified dendrogenin A circumvent resistances to therapy and to identify (DDA), an amino-oxysterol tumor suppressor new surrogate biomarkers of responses. produced by healthy tissues (de Medina et al, Nat Our approach links basic research to medical Commun 2013). Recently we discovered an onco- applications with a goal of valorization in metabolite tumor promoter produced by cancer partnership with our spin off, Affichem (9 patents cells. The identification of these two end-products filed over the last 5 years). of the cholesterol metabolism with opposite
Keywords: Tamoxifen, SERM, oxysterols, cholesterol biosynthesis, cholesterol metabolism, dendrogenin, cholesterol-5,6-epoxide hydrolase, cholesteryl esters, nuclear receptors, enzymology, medicinal chemistry, LC/MS, radiolabeling, cell differentiation, cell death, autophagy, immune system, tumor suppressor, tumor promoter, exosomes, imaging
[28]
Highlights
Vitamin E are phytoestrogens: Vitamin E include a family of structurally-related antioxidants which includes tocopherols (TP) and tocotrienols (TT). Using a pharmacophore approach, we found that they are ligands of estrogen receptors (ER), display estrogenic properties and stimulate ER(+) breast cancer (BC) proliferation (Khallouki et al, Front Oncol 2016). These data, in addition to previous studies showing that they inhibit Tam Chemical structure of vitamin E compounds. They anticancer action through the blockage of 5,6- are modulators of estrogen receptors. EC formation, highlight that Vitamin E could represent a risk factor in BC and may impair the therapeutic outcome. This is especially important when considering that patients are often taking vitamin-based auto-medications or vitamin-enriched diets.
Oxysterols as potential surrogate markers of response to hormonotherapy in hormone receptor-positive BC. We previously reported that Tam stimulated 5,6-EC formation and accumulation, 5,6-EC being second messengers involved in Tam anticancer action. Chemical structure of oxygenation products of The analyses of the oxysterol profile in sera cholesterol (oxysterols). from a cohort of 29 patients (Oxytam trial) treated with Tam or AI showed that treatments increased the levels of specific oxysterols, including 5,6-EC. This may reflect an activation of BC cells differentiation and death pathways, confirming our preclinical works. Interestingly, AI increased the levels of estrogenic oxysterols (25HC and 27HC) tumor promoters, and this may reflect a mechanism of acquired resistance and risk of cancer Clinical trial using Tamoxifen or aromatase relapse. We planned to confirm these results inhibitors in the treatment of ER(+) breast cancers in larger cohorts of patients. showed that they modulate blood circulating oxysterol levels selectively highlighting new surrogate markers of efficacy or relapse.
Labels / Grants: GenHomme, CAPTOR, IDEX
Some publications/patents in dendrogenin A: a tumour Methods and pharmaceutical 2016 suppressor metabolite. Poirot M & compositions for reprograming Silvente-Poirot S. Biochem Soc immune environment in a subject From tamoxifen to dendrogenin A: the discovery of a mammalian Trans, 2016:631-7. and need thereof. Silvente-Poirot S tumor suppressor and cholesterol Molecular and biochemical et al, Patent 2016, EP16306214.4 metabolite. Silvente-Poirot S et al. analysis of the estrogenic and Methods of diagnosing and
Biochimie, 2016:109-14. proliferative properties of vitamin treating cancer. Silvente-Poirot S et When cholesterol meets E compounds. Front Oncol. al. Patent 2016, WO2016034742. histamine, it gives rise to Khallouki F et al. 2016:1-10.
[29]
Team Leader Hervé Avet-Loiseau Professor
Staff
Ludovic Martinet
Michel Attal Jill Corre Murielle Roussel Laure Buisson Nadège Carrié Marie-Lorraine Chrétien Charlotte Fontan Fanny Grimal
Augustin Le Naour Team 13 – Pharmacogenomics of multiple Léa Lemaitre myeloma Marianne Weulersse Virgine Féliu Our team is entirely focused on multiple myeloma (MM), a cancer of Bettina Couderc the bone marrow. We develop three main axes: Marie-Véronique - Massive sequencing of tumors to understand how molecular Joubert abnormalities impact patient survival Sabrina Mahéo
- Analysis of the immune system of these patients in order to Sébastien Robiou du try to activate it to eliminate the tumor cells Pont - Analysis of the interactions between tumor cells and the
medullary microenvironment.
Objectives
Our objective is mainly translational, that is to try complete response, in order to adapt the to improve the therapeutic management of the treatment to the residual tumor mass. The patients in order to prolong their survival. To second axis aims to better characterize the achieve this, we have created a national network immune system of patients with MM, with a dual that has enabled to build the world’s largest objective: (i) to understand the causes of tumor bank, linked to a computer database that immunodepression of patients by characterizing brings together the clinical and evolutionary the different immune compartments, and (ii) to ch aracteristics of these thousands of patients. propose therapeutic approaches based on Our first axis aims at sequencing the genome of monoclonal antibodies targeting immune cells. these tumors with the aim of identifying Our third objective is to better understand the subgroups of patients who would be better able interactions between tumor cells and other to respond to specific treatments in order to help normal bone marrow cells, which contribute clinicians in their therapeutic choices. In the same largely to the clinical expression of the disease, vein, we have developed a technique for mainly bone fractures. We focus our research on quantifying minimal residual disease in patients in mesenchymal stem cells.
Keywords: Multiple Myeloma, pharmacogenomics, immunology, microenvironment, NGS
[30]
Highlights
We performed high-throughput RNA sequencing of 350 tumors to detect novel fusion transcripts in myeloma. This work is currently being published in Nature Communication.
We have shown that the quantification of minimal residual disease (MRD) made it possible to identify a subset of patients with an excellent prognosis.
Some publications in 2016 Avet-Loiseau H, et al. Dejoie T, Corre J, et al. Serum Avet-Loiseau H. Minimal Carfilzomib significantly free light chains should be the residual disease by next- improves the progression-free target of response evaluation generation sequencing: pros survival of high-risk patients in in light chain multiple and cons. Am Soc Clin Oncol multiple myeloma. Blood. myeloma rather than urines. Educ Book. 2016; 35:e425-30. 2016; 128:1174-80. Blood. 2016; 128:2941-8.
Sonneveld P, Avet-Loiseau H, Kumar S, et al. International M, Szalat R, Avet-Loiseau H, et al. Treatment of multiple yeloma Working Group Munshi NC. Gene Expression myeloma with high-risk consensus criteria for Profiles in Myeloma: Ready for cytogenetics: a consensus of response and minimal residual the Real World? Clin Cancer the International Myeloma disease assessment in multiple Res. 2016; 22:5434-42. Working Group. Blood. 2016; myeloma. Lancet Oncol. 2016; 127:2955-62. 17:e328-46.
[31]
Team Leader Etienne Chatelut Professor
Staff
Ben Allal Cécile Arellano Caroline Delmas Thierry Lafont Isabelle Lochon Sabrina Marsili Sotheara Moeung Marie-Noëlle Paludetto Florent Puisset Fabienne Thomas Christelle Vachoux Mélanie White-Koning Team 14 - Dose individualization of anticancer Alicja Puszkiel drugs
Our team focuses on pharmacokinetics of anticancer drugs in order to better individualize the dose.
Objectives
The main objective of our team is to promote and practice in oncology is mainly due to the carry out translational and clinical studies in the administration schedule of cytotoxics (i.e. field of pharmacology to drive dose intravenous administration every three weeks). individualization of anticancer drugs. Indeed, these schedules make PK exploration This is made possible by increasing our difficult to perform in the first place, as several understanding of the sources of interindividual blood samples are needed in order to determine variability in drug disposition and tumor accurately the area-under-the-curve of drug response. Our main projects focus on plasma concentrations versus time (AUC), and pharmacokinetics and pharmacogenetics as secondly the PK results obtained are useless once interindividual variability factors. the administration is over. More than 99% of anticancer treatments are Our team uses the nonlinear mixed effects prescribed according to standard doses (in mg/m² approach (commonly known as “population PK”) for cytotoxics or in mg for several targeted to improve dose individualization of anticancer therapies). However, a number of observations drugs. Our research may be divided into 3 areas: have shown that interindividual pharmacokinetic (i) covariate identification to explain PK (PK) variability contributes to differences variability, (ii) Bayesian approach to determine between patients both in terms of toxicity and individual PK parameters from limited blood antitumor response. The very limited number of sampling, and (iii) pharmacokinetic- examples of individual dosing in everyday pharmacodynamic (PK-PD) modeling.
Keywords: Population pharmacokinetics, Platinum compounds, Tyrosine kinase inhibitors, therapeutic drug monitoring, PK-PD relationships
[32]
Highlights
DPYD Genotype-phenotype relationship within a family with complete DPD deficiency
DPD Phenotype : UH2/U ratio = 0.1 I Complete DPD deficiency
Uracil U
UH2/U = 1 2 3 4 5 reflects DPD DihydroUracil UH2 activity
II
1 Patient with 5-FU toxic death Pedigree of the patient’s family = complete DPD deficiency III = partial DPD deficiency = normal DPD activity = individuals not tested 1) Discovery of novel rare mutations: = new mutation p.Phe59Ter and p.Thr343Pro = c.1679C>T Full DPYD sequencing reveals a DPYD genotyping focused on 3 SNPs novel mutation seems insufficient to predict the risk of DPYD exon3 toxicity to 5-FU GGAGAATAATT GAATAATT TTGAT 2) Significant correlation between genotype and UH /U (p=0.01) c.168_175dupGAATAATT 2 A good tool to detect DPD deficiency 5-FU toxic deaths could be avoided by translation stop codon: p.(Phe59Ter) DPD deficiency testing with phenotypic analysis (UH /U) of DPD activity before Truncated protein: 58 amino acids 2 treatment. instead of 1025 amino-acids
Thomas F, et al. Genotyping of a family with a novel deleterious DPYD mutation supports the pretherapeutic screening of DPD deficiency with dihydrouracil/uracil ratio. Clin Pharmacol Ther 2016.
Some publications in 2016 peripheral lymphocytes Imbs DC, Paludetto MN, Negrier Gandia P, Jaudet C, Everaert H, depletion in BRAF-mutated S, Powell H, Lafont T, White- Heemskerk J, Vanbinst AM, de melanoma patients. Pharmacol Koning M, Chatelut E, Thomas F: MJ, Duerinck J, Neyns B, de RM, Res 2016; 113:709-18. Determination of unbound Chatelut E, Concordet D: Sauzay C, White-Koning M, fraction of pazopanib in vitro Population pharmacokinetic Hennebelle I, Deluche T, Delmas and in cancer patients reveals approach applied to positron C, Imbs DC, Chatelut E, Thomas albumin as the main binding emission tomography : F: Inhibition of OCT2, MATE1 site. Invest New Drugs 2016; computed tomography for and MATE2-K as a possible 34:41- 8. tumor tissue identification in mechanism of drug interaction Thomas F, Hennebelle I, Delmas patients with glioma. Clin between pazopanib and C, Lochon I, Dhelens C, Garnier Pharmacokinet 2016. cisplatin. Pharmacol Res 2016; TC, Bonadona A, Penel N, Puszkiel A, White-Koning M, 110:89-95. Goncalves A, Delord JP, Toulas Dupin N, Kramkimel N, Thomas- Imbs DC, Dieras V, Bachelot T, C, Chatelut E: Genotyping of a Schoemann A, Noe G, Chapuis Campone M, Isambert N, Joly F, family with a novel deleterious N, Vidal M, Goldwasser F, Jimenez M, Lafont T, Chatelut E: DPYD mutation supports the Chatelut E, Blanchet B: Plasma Pharmacokinetic interaction pretherapeutic screening of vemurafenib exposure and pre- between pazopanib and DPD deficiency with dihydro- treatment hepatocyte growth cisplatin regimen. Cancer uracil/uracil ratio. Clin factor level are two factors Chemother Pharmacol 2016; Pharmacol Ther 2016; 99:235- contributing to the early 77:385-92. 42.
[33]
Team Leader Manuel Bardiès Inserm DR
Staff
Marie-Claude Bordage Emmanuelle Cassol Régis Ferrand Xavier Franceries Luc Simon Laure Vieillevigne Maxime Chauvin Julien Bordes Richard Brown Jonathan Tranel Team 15 – Multiscale dosimetry for radiotherapy Tony Younes Erick Mora Ramirez optimization Gustavo Costa
Frédéric Chatrie Radiotherapy efficacy relies on treatment personalisation: Irradiation must be elevated in tumour targets, whereas healthy/critical organs/tissues irradiation must be minimized. Our team works at optimizing several forms of radiotherapy, by measuring or modelling radiation transport at various scales, from cell to patient.
Objecti ves
Targeted RadioTherapy (TRT) is a cancer each patient benefits from a personalised therapy based on the administration of treatment. radiolabelled selective vectors. Currently, With this aim, our team develops innovative administration is based on fixed activities, dosimetric approaches at all scales (cell, eventually modulated by patient mass or tissue, patient) by quantifying activity body surface area. This approach disregards distributions (quantitative imaging) and phar macokinetics inter-patient variability, modelling radiation transport for various and does not benefit from the possibility to emitters (alpha, beta, Auger) used for TRT. perform a patient-specific assessment of These developments in radiation transport delivered irradiation. modelling are progressively extended to Our objective is to implement a paradigm preclinical and clinical external beam shift from "radioactive chemotherapy" radiotherapy, mainly in a context of complex towards "systemic radiotherapy", where irradiation or/and small irradiation beams.
Keywords: Dosimetry, Monte Carlo modelling
[34]
Highlights
On-going projects and Highlights OpenDose We initiated at the end of 2016 an international Medirad: NFRP-9 Euratom Fission2016-2017 collaboration that aims at generating reference dosimetric data for nuclear medicine, based on This 48-month European project aims at the new voxel models proposed by the studying the effects of low doses in medical International Commission on Radiological applications. Our team is in charge of Protection (ICRP). modelling irradiation at distance of tumour targets for TRT of thyroid cancers, and evaluations the dosimetric consequences of hybrid imaging in nuclear medicine.
MRTdosimetry: EMPIR 15HLT06
This 3-year European project started mid- 2016, and aims at optimising the metrology of clinical implementation of TRT dosimetry. We are responsible of scintigraphic imaging modelling with the Monte Carlo Gate. ICRP Female Reference Model
Sterepid: Multicellular dosimetry
This national sponsored project (ANR PhysiCancer 2016) project aims at defining the performances of portal detectors (EPID) and developing quality control and in vivo dosimetry for complex fields in stereotactic radiotherapy.
J Bordes: Modelling energy deposition for several isotopes (131I, 177Lu, 90Y) in realistic 3D models of follicular lymphoma (accepted for oral presentation at the forthcoming European Association of Nuclear Medicine congress – EANM - Vienna October 2017)
International collaborations: OpenGate, Geant4/Geant4-DNA, EFOMP, EANM, AIEA
Selected publications in 2016 Arnaud et al. 2016. Complex cell for stereotactic body radiation Garcia et al. 2016. Accelerated geometry and sources therapy: Impact of the size of the GPU based SPECT Monte Carlo distribution model for Monte PTV on dynamic conformal arc simulation. Physics in Medicine Carlo single cell dosimetry with and volumetric modulated arc and Biology 61(11): 4001-18. iodine 125 radio-immuno- therapy. Physica Medica 32(11): Marcatili et al. 2016. Realistic therapy. Nuclear Instruments & 1405-14. multicellular dosi-metry for Lu- Methods in Physics Research Bordage et al. 2016. 177-labelled antibodies: model Section B 366: 227-33. Implementation of new physics and application. Physics in Vieillevigne et al. 2016. models for low energy electrons Medicine and Biology 61(19): Dosimetric comparison of in liquid water in Geant4-DNA. 6935-52. flattened and unflattened beams Physica Medica 32(12): 1833-40.
[35]
Team Leader Eric Delabesse Professor
Staff
Cyril Broccardo CR Inserm, Bastien Gerby CR CNRS, Sylvie Hébrard Technician, Laura Jamrog Research assistant, PhD student Stéphanie Lagarde Team 16 – Alteration of transcription factors in Research assistant, Marlène Pasquet acute leukemias Oncopediatrician, Our team's work is part of a translational research through a Isabelle Luquet hospital component that allows diagnosis and also to investigate Hospital practitionner, Naïs Prade the molecular causes (mutations) in patients with leukemia, and a Research associate, fundamental research component that models these causes in Stéphanie Struski cells or in mouse models in order to identify new therapeutic Research associate
targets.
Objectives The deregulation of hematopoiesis at an early mice expressing one of these fusion. These mice stage can lead to the transformation of develop a disease similar to a human B-ALL and progenitors and finally to acute leukemia (AL) we are studying this model by new-generation defined as early blockage of differentiation sequencing, FACS, transcriptomic analyzes to
(blastic stage) and uncontrolled proliferation of explain how this fusion can lead to oncogenesis. blasts. The impact of transcription factors (TF) The germline mutations of GATA2 represent a alterations in the oncogenic process is poorly familial disease with diverse clinical features, for characterized. Since TF alterations are not which bone marrow transplantation is the only directly targeted, we seek to find therapeutic curative treatment (Pasquet, 2013). The absence tar gets by identifying the oncogenic relays of TF of genotype / phenotype correlation is in favor of alterations: To this purpose, we identify TF a distinct functional impact of the GATA2 alterations, study their impact on normal mutants. We have modeled these alterations at differentiation and evaluate their role in the the cellular and animal levels in order to establish leukemic process. Recently, we have identified the molecular links between GATA2 alterations recurrent mutations in AL patients that involve and leukemic phenotype. We have shown in vitro two PAX5 and GATA2 TFs. that the R396Q mutation identified in a Toulouse The somatic mutations of PAX5 are found in 1/3 family recapitulates the events of an AML of B-ALL (Familiades, 2009). To decipher the (blockade of myeloid differentiation and oncogenic mechanisms of PAX5 fusions excessive blast proliferation). (Bousquet, 2007; Coyaud, 2010), we generated
[36]
Keywords: Acute leukemia, transcription factors, Pax5, gata2
Highlights
Labels / Grants:
Some publications in 2016 MQ, Akasaka T, Parker A, Roa S, Luna JL, Garcia-Muñoz R, Pena Homeobox NKX2-3 promotes Panizo C, Martin-Guerrero I, E, Bellosillo B, Salar A, Baptista marginal-zone lymphomage- Siebert R, Segura V, Agirre X, MJ, Hernandez-Rivas JM, nesis by activating B-cell Macri-Pellizeri L, Aldaz B, Vilas- Gonzalez M, Terol MJ, Climent J, receptor signalling and shaping Zornoza A, Zhang S, Moody S, Ferrandez A, Sagaert X, Melnick lymphocyte dynamics. Robles Calasanz MJ, Tousseyn T, AM, Prosper F, Oscier DG, EF, Mena-Varas M, Barrio L, Broccardo C, Brousset P, Carrasco YR, Dyer MJ, Martinez- Merino-Cortes SV, Balogh P, Du Campos-Sanchez E, Cobaleda C, Climent JA. Nat Commun. 2016 Sanchez-Garcia I, Fernandez- Jun 14;7:11889.
[37]
Team Leader Julie Guillermet- Guibert CR Inserm
Staff
Jean-Pierre Delord Professor Céline Basset Professor associate Nicole Therville Research assistant
Postdoc fellow Benoit Thibaud
Team 17 - SIGDYN Group - PI3K isoforms, PhD students Signalling & Cancerogenesis Silvia Arcucci Fernanda Ramos- Cancer cells communicate in the organ where they develop: this Delgado Aurélie Vertut communication aim to prevent the host to kill them, but cancer cells also use these signals at their advantage to create a Adrien Thole favorable environment towards their development. This Internship communication "network" in a tumour called signal network is
thus the result of their interaction but also an Achille's heel that could be annihilated by targeted therapies. We accumulated data demonstrating that primary tumour development and its development at distance (metastasis) are directed by a family of molecules at the cross bridge of signaling networks, PI3Ks. They are present in 8 forms, so called "isoforms", both in cancer cells and in surrounding cells. We demonstrated that each of them have different actions.
Objectives
Using innovative technologies, we study the networks, and thus the tumour progression. roles of these PI3K isoforms in inter-cellular We apply our research to pancreatic cancer & interactions so as to propose innovative ovarian cancer, two cancers with a poor therapies inhibiting PI3K-driven signalling pronostic.
Key words: Inter- and intra-cellular signaling, membrane lipids, genetically modified mouse models, pancreatic cancer, ovarian cancer, cancerogenesis, PI3K
[38]
Highlights
Class I PI3K isoforms & Therapeutic opportunities in Cancer
Towards a signal targeted therapy in pancreatic cancer. Pancreatic cancer is a lethal and aggressive cancer and few therapeutic options are available for these patients. We discovered that the PI3Kα is transmitting the signal of the main oncogene found in pancreatic cancer, KrasG12D, towards pancreatic cancer initiation, also when other cancer-promoting factors are present such as p53 activating mutation or inflammatory conditions. These results could serve as a base for an innovative targeted therapy for pancreatic cancer annihilating this signal. (PMID: 25452273)
Infertility could be the only secondary toxic effect of anti-PI3Kβ targeted therapy. Cancer treatment can be harmful for the normal surrounding cells. We discovered that the only secondary action of PI3Kβ inhibitors is masculine infertility. This occurs in the support cells of spermatogenesis, Sertoli cells, and could be reversible (PMID: 26132308).
Our work was awarded by Prix d'excellence scientifique Forcheur- Jean-Marie Lehn, at the French embassy in Berlin, with Dr Maximilien Reichert, Technische University Munich, Germany, in June 2017.
Labels / Grants: ARC, Fondation pour la Recherche Médicale, Ligue contre le cancer, LabEx TOUCAN, PHUC CAPTOR
Publications in 2016 Brouchet A, Ligat L, Lopez F, Heat Shock-Associated Pyronnet S, Courty J, Translation of VEGF-D to Morfoisse F, Tatin F, Hantelys F, Guillermet-Guibert J, Marzi S, Promote Tumor Lymphangio- Adoue A, Helfer AC, Cassant- Schneider RJ, Prats AC, Garmy- genesis. Cancer Res. 2016 Aug Sourdy S, Pujol F, Gomez- Susini BH. Nucleolin Promotes 1;76(15):4394-405.
[39]
Team Leader Jean-Emmanuel Sarry CR Inserm
Staff Researchers / Professors Christian Récher François Vergez Florence Cabon Odile Beyne-Rauzy Lucille Stuani Mohsen Hosseini Clément Larrue
Team 18 - RESISTAML – Drug resistance and Research assistants Latifa Jarrou oncometabolism in acute myeloid leukemia Estelle Saland
Mathilde Gotanegre Despite a high rate of complete remission after treatment with genotoxic PhD students agents, the prognosis is poor in human acute myeloid leukemia (AML). Nesrine Aroua Indeed, 5-year overall survival is about 30 to 40% in patients younger than Gabriel Lemercier 60 years old and less than 20% in patients over 60. Front-line Pierre-Luc Mouchel chemotherapy is highly effective in ablating leukemic cells, but distant Thomas Farge Claudie Bosc relapses are observed in the majority of patients, characterized by a refractory phase during which no other treatment has shown any efficacy Alumni thus far. Relapses are caused by tumor regrowth initiated by resistant Héléna Boutzen Sarah Scotland leukemic clones (RLCs). The goal of our team is to understand the causes of the drug resistance for the development of new treatments eradicating
RLCs and overcoming patient relapses.
Objectives The biology of therapeutic resistance currently Using diverse metabolomic, transcriptomic, represents an active area of research. However, pharmacological and functional approaches as the molecular mechanisms underlying AML well as patient samples and a newly developed chemoresistance are still poorly understood, AML-engrafted immunodeficient model, we aim especially in the in vivo context. Our specific aim to : i) elucidate the stemness and functional is to understand and target the mechanisms heterogeneity of RLCs in response to genotoxics involved in the drug resistance in AML. We in vivo, ii) determine how mitochondrial energy primarily focus on the role of the mitochondrial and metabolic networks drive the drug resistance energetic and metabolic flexibility in the drug of RLCs in vivo, and iii) define the role of the resistance of AML cells. We also study the energetic symbiosis and metabolic dialogue int eractions with stromal cells, which modulate between the stromal compartment and leukemic their therapeutic resistance in the tumoral niche. blasts in the bone marrow niche.
Keywords: Leukemia, drug resistance, patient derived xenograft, mitochondria, énergetics, oncometabolism, catabolic flexibility, clonal heterogeneity, single cell signature, cancer stem cells, inflammation, signaling, innovative therapeutics
[40]
Highlights Cytarabine (AraC) resistant AML cells are not enriched in immature (CD34+CD38-) cells, quiescent cells, LSCs but have HIGH OXPHOS gene signature and functions, depend on fatty acid oxidation and overexpress fatty acid transporter CD36. Metabolic redirection and flexibility, redox homeostasis, ROS and iron metabolism, MPTP and VDAC- HK2 supra-complex, and autophagy-driven nutriment oxidation are key players in mitochondrial oxidative phosphorylation and AraC resistance in AML cells in vivo. We have established a robust PDX-based preclinical model to predict response to AraC in mice and in patients to characterize MRD and chemoresistance, and to identify new therapeutic targets (CD36, CD39, MPO and new GPCRs). Future studies will address in vivo resistance to other conventional (IDA alone, IDA+AraC) or targeted therapies (FLT3i, BCL2i, MCL1i, IDHmi) in AML cells. Using this robust PDX-chemo model, RESISTAML team will assess single cell-based clonal heterogeneity and predict relapse in patients to assist interventional decision for consolidation chemotherapies and/or treatment at relapse (Project & clinical trial COMPAML: mice COMpanion for Acute Myeloid Leukemia).
Selected grants/awards: Projet Hospitalo-Universitaire en Cancérologie CAPTOR, LabEx TOUCAN, Programme d'Excellence PSPC IMODI, LabEx OncoDevice Co-founder and coordinator of the Cancéropole GSO Network “MetaboCancer GSO”
Some publications in 2016 acute myeloid leukemia. J Exp. Med. Moschoi R, Imbert V, Nebout M, Boutzen H, Saland E, Larrue C, de 2016; 213(4):483-97. Chiche J, Mary D, Prebet T, Saland E, Toni F, Gales L, Castelli F, Stuani L, Larrue C, Saland E, Boutzen H, Vergez Castellano R, Pouyet L, Collette Y, Zaghdoudi S, David M, Mansat-de F, David M, Joffre C, Hospital MA, Vey N, Chabannon C, Récher C, Sarry Mas V, Delabesse E, Kaoma T, Vallar Tamburini J, Delabesse E, Manenti S, JE, Alcor D, Peyron JF, Griessinger E. L, Linares L, Junot C, Portais JC, Sarry JE, Récher C. Proteasome Protective mitochondrial transfer Vergez F, Récher C, Sarry JE. inhibitors induce FLT3-ITD from bone marrow stromal cells to Isocitrate dehydrogenase 1 muta- degradation through autophagy in acute myeloid leukemic cells during tions prime the all-trans-retinoic acid AML cells. Blood. 2016 ;127(7):882- chemotherapy. Blood. 2016;128(2): myeloid differentiation pathway in 92. 253-64.
[41]
[42]
Core facilities
[43]
Cluster manager Frédéric Lopez Research associate
Staff
Ouafa Boulahian-Zaki Véronique de Mas Manon Farcé Tiphaine Fraineau Laetitia Ligat Frédéric Pont Nathalie Saint-Laurent Emeline Sarot Christèle Ségura Laure Tonini Carine Valle Technology Cluster of the CRCT Loïc van den Berghe
The Technology Cluster of CRTC gathers several core facilities in order to enable their collegial operation and the sharing of facilities and resources.
Overview
The members of the Technology Cluster provide scientific and technical expertise in a broad range of areas :
Proteomics (biochemical & mass Gene transfer vector (biosafety L3 lab) spectrometry) and molecular Transcriptomics interactions (Biacore technology) Production of monoclonal antibodies
Imaging (confocal microscope and Bioinformatics video microscope) Inserm Biological Resource Centre for Flow cytometry and cell sorting Blood Malignancies (HIMIP).
Their mission is to provide support for any projects regarding design, experiments, training with specific equipments, and interpretation of results.
[44]
Highlights
In 2016, the resources received by the techologival cluster were provided by Inserm, remainder budget from 2015, contracts and services (Fig.1).
The services have doubled compared to 2015, and have Fig.1 : Fundings obtained by the cluster Fig.2 : Evolution of the resources generated 46 % of resulting from the services the resources (Fig.2). Fig.3: % Total resources
The distribution of the resources generated by the different cores are 8 DOTATION INSERM 6 9 shown in the Fig.3. CYTO Tri Cellulaire 1 12 20 CYTOTHEQUE HIMIP Fig.4 shows the 15 Vectorologie 24 comparison Protéomique between the 4 INTER MOL Biacore activity of the Imagerie Transcriptomique different cores in Bioinformatique 2015 and 2016.
60000
50000
40000
30000 RECETTES 2016 HT
20000 RECETTES 2015 HT
10000
0
Fig.4 : Distribution of income generated by the different services of the technological cluster
[45]
Biological Resource Centre (BRC)
The BRC houses the HIMIP tumour library (samples from Blood Malignancies in the Midi-Pyrénées Region) for storing human samples both for treatment purposes and for research. The tumour library was set up in order to participate in research programmes on blood malignancies concerning both the characterisation of oncogenetic mechanisms, therapeutic optimisation and the identification of new prognostic criteria.
HIMIP includes samples from patients with acute myeloid leukaemia, chronic lymphoid leukaemia, acute lymphoblastic leukaemia, myelodysplastic syndromes, chronic myelomonocytic leukaemia, chronic myeloid leukaemia, myeloproliferative syndromes, lymphomas and lymphoproliferative syndromes.
Cytometry & Cell sorting
The Cytometry and Cell Sorting Core is open to academic and private scientists. The Platform is equipped with 4 analysers, a high-speed cell sorter and a magnetic automated cell sorting system.
Services : Cell analysis and sorting Advice and assistance for users regarding the acquisition, analysis and interpretation of data Training of independant users Cell sorting only by the Platform’s staff Maintenance of all equipment, and technology watch Compilation and communication of analytical results.
Cell Imaging
The Cell Imaging Core is open to the academic and private scientists. The platform is equipped with
3 fluorescence microscopes, and is based in a Biosafety L2 section of the Technology Cluster. The platform also benefits from a fully-equipped cell culture laboratory and a service area dedicated to data analysis.
Services : Cell imaging for public or private sector research organisations Advice and assistance for users regarding image acquisitions and analysis Training of users so they can use the microscopes independently Maintenance of all equipment and technology watch Compilation and communication of analytical results.
Monoclonal Antibodies
The Monoclonal Antibody Core Facility is under the responsibility of Prof. Pierre Brousset, and results from the research activities of his team. The facility provides mouse monoclonal antibodies for the CRCT teams.
[46]
Genomics & Transcriptomics
Dedicated to the analysis of nucleic sequences and their expression, the Platform currently benefits from quantitative PCR systems and polysome fractionation equipment for analysis of the traductome. The Platform recently acquired a high-performance array scanner (Illumina iScan) that enables methylation, expression, genotyping, cytogenomics analyses …
Services :
qPCR: two StepOne Plus systems (Applied Biosystems, Life Technologies) qPCR: one Abi7500 (Applied, Life Technologies) polysome profiling: a fraction collector for density gradient (ISCO) iScan array scanner (Illumina)
Proteomics
The Proteomics Core Facility offers technological expertise on protein fractionation and profiling, and on the study of molecular interactions to academic and private teams. The Proteomics Core Facility is operating on technological developments dedicated to issues of both clinical and basic research, from the establishment of protein profiles (2D-DIGE, SELDI-TOF) and peptide (CE-MS, Chip-MS) to the identification by mass spectrometry of interaction partners (BIA-MS) and
biomarkers or potential pharmacological targets for the development of diagnostic tools.
Gene transfer Vector
The Vector Core Facility has developed know-how centered on the production of two types of recombinant viral vectors : lentiviruses and adeno-associated viruses (AAV).
Apart from the Technology Cluster, the researchers of the CRCT are working in close collabora tion with the the animal facility – CREFRE – UMS006 - which is located in the same building. This core facility provides its expertise in transgenesis, microsurgery, non invasive phenotyping, irradiation, exploration and imaging.
[47]
[48]
Post-graduate education programmes
Master students were registered in various education programmes : • Bioinformatics – Bioinformatics & Systemic biology • Biology - Health – Oncology – Genes, cells, development – Immunology & infectious diseases – Pharmacology Innovation and drug profession – Pathophysiology : from molecule to medicine – Digestive health & nutrition – Gene transfer vector, gene therapy & vaccines • Biotechnologies – Gene expression & recombinant proteins – Molecular microbiology – Structural and functional biochemistry • Chemistry – Chemistry - Health • Ethics – Health & Research ethics • Public health – Coordination of health care pathway for patients with chronic / degenerative diseases
In 2016, the CRCT hosted 61 PhD students, from France and 11 other countries.
Other students from graduate (64) and undergraduate (37) programmes as well as students from Medicine (3) & Pharmacy (1) faculties, and Engineer schools (4) have done training courses or internships in the CRCT.
[49]
Scientific and administrative staff
In 2016, the CRCT gathered - 121 researchers, professors, associate professors, and hospital practitioners - 67 researchers with HDR - 109 research asssociates, research assistants, and technicians - 28 post-doctoral fellows - 61 PhD students - 112 trainees.
From the creation of the CRCT to the end of 2016, Jean-Jacques Fournié was the director of the CRCT, with Stéphane Pyronnet as the deputy director and Sébastien Guibert as the administrative director. Gilles Favre succeeded Jean-Jacques Fournié as the new director on January 1st, 2017. Flow chart
Direction of CRCT Research teams 1 Ayyoub Technology Support services 2 Hoffmann Cluster 3 Favre 4 Levade/ Bioinformatics Administration Logistics HS Andrieu 5 Millevoi Biological Prevention General Scientific Building 6 Pyronnet/ ressources / H&S administration partnerships & supervision Bousquet communication 7 Brousset Cytometry & Radio- 8 Manenti/ cell sorting Technical Teams & Techno. services protection Besson Center ressources 9 Fournié Cellular imaging management 10 Cordelier General 11 Moyal/Toulas storehouse Trainees conventions 12 Poirot/ mAB Silvente-Poirot production 13 Avet-Loiseau Reception desk IT 14 Chatelut Proteomics & 15 Bardiès molecular Glass wash & 16 Delabesse interactions sterilization 17 Guillermet- Guibert/Delord Security 18 Sarry/Récher Genomics & transcriptomics
Vectorology
[50]
CRCT administration
The CRCT benefits from the support of the Administration Déléguée de l’Inserm Midi- Pyrénées-Limousin (now Occitanie Pyrénées) for the financial and human resources management of the projects. However, a management team also operates in-door for the global operating of the CRCT.
As the Administrative director, Sébastien Guibert supervises the management team.
General administration Health & Safety, Radioprotection Laurence Granier Catherine Ordener Magali Diette Welcome desk Ambre Santin Building supervision department Pauline Lironcourt Administrative & financial ressources Nathalie Delanne department Anne-Marie Bénot : Teams 7-9, 11, 18 Storehouse department Marie-Hélène Lalaux : Teams 1-2, 12-16 Joël Teyssier Marie-Josèphe Lignon : Teams 5-6, 10, 17 Nathalie Perez Géraldine Touriol : Teams 3-4, and Core facilities Glass wash & media preparation Emilie Martin : Management team Nathalie Perez Patricia Clavé Trainee conventions department Christiane Bejarano Technical services Cédric Capilla IT department Julien Bories Pierre Cosso
Scientific partnerships Dominique Lautier
[51]
CRCT Resources
The CRCT received public fundings from Inserm, Université Toulouse III Paul Sabatier 780,344 € and CNRS.
In addition to these fundings, Inserm, CNRS, ICR Other 635 949 59 486 Université Paul Sabatier, Toulouse hospital and CHU 475 828 Institut Claudius Regaud provide salaries for their respective permanent personal, including CNRS Inserm researchers, clinicians, professors and 1 236 734 3 944 206 professor associates, research associates and 9,490,054 € assistants, and technicians. Moreover, non-permanent staff (for an
UT3 additional budget of 4,972,080 €) are also 3 137 851 employed by the CRCT.
Following succesful applications to various Calls for proposals, the CRCT received competitive grants from : Agence Nationale de la Recherche, Cancéropole Grand Sud-Ouest, Fondation ARC, 5,325,746 € Association Laurette Fugain, EURAMET, Euratom, Fondation Bettencourt-Schueller, Fondation de France, Fondation pour la Recherche Médicale, Fondation Toulouse Cancer Santé, Horizon 2020, Institut Claudius Regaud, Institut National du Cancer, Ligue contre le Cancer, Région Occitanie, Toulouse Hospital, Toulouse Métropole, Transcan-2, Université Fédérale Toulouse Midi-Pyrénées.
Other fundings result from contracts with pharmaceuticals Companies (AstraZeneca, Celgene, Cisbio, Evotec, Genentech, GSK, Novartis, Pierre Fabre, Roche, Sanofi… )
[52]
5 3 2 5 7 4 6 €
[53]
Scientific Advisory Board
The scientific Advisory Board (SAB) includes scientists and clinicians from France and abroad. The SAB members have been chosen for their expertise and their independance from the CRCT researchers.
Member Institution Town, Country Centro Nacional de Investigaciones Maria Blasco Madrid, Spain Oncologicas Patrick Couvreur Université Paris-Sud Paris, France
Anne Dejean Institut Pasteur Paris, France Institut de Génétique et de Biologie Jean-Marc Egly Strasbourg, France Moléculaire et Cellulaire Bruno Goud Institut Curie Paris, France
John A. Hickman IMI Coordinator Paris, France Rigshospitalet, University of Copenhagen, Liselotte Hoejgaard Copenhagen Denmark Cyril M. Kay University of Alberta Edmonton, Canada Oxford Institute for Radiation Oxford, United Gillies McKenna Oncology Kingdom Institut de Recherche sur le Cancer et Jacques Pouysségur Nice, France le Vieillissement Josep Tabernero Vall d'Hebron Institute of Oncology Barcelona, Spain
William Vainchenker Institut Gustave Roussy Villejuif, France
Benoit Van den Eynde Ludwig Institute Bruxelles, Belgium
[54]
Scientific production
[55]
Publications in 2016
Abbo O, Gas J, Pinnagoda K, Tournier E, Bouali O, Astudillo L, Therville N, Colacios C, Ségui B, Andrieu- Castex MP, Lamant L, Galinier P. Pediatr Blood Cancer. Abadie N, Levade T. Biochimie. 2016 Jun;125:267-80. 2016 Nov 1. Sclerosing sweat duct carcinoma of the penis in Glucosylceramidases and malignancies in mammals. a 4-year-old child. Avet-Loiseau H, Fonseca R, Siegel D, Dimopoulos MA, Adsay V, Mino-Kenudson M, Furukawa T, Basturk O, Špička I, Masszi T, Hájek R, Rosiñol L, Goranova-Marinova Zamboni G, Marchegiani G, Bassi C, Salvia R, Malleo G, V, Mihaylov G, Maisnar V, Mateos MV, Wang M, Niesvizky Paiella S, Wolfgang CL, Matthaei H, Offerhaus GJ, Adham R, Oriol A, Jakubowiak A, Minarik J, Palumbo A, Bensinger M, Bruno MJ, Reid MD, Krasinskas A, Klöppel G, Ohike N, W, Kukreti V, Ben-Yehuda D, Stewart AK, Obreja M, Tajiri T, Jang KT, Roa JC, Allen P, Fernández-del Castillo C, Moreau P. Blood. 2016 Sep 1;128(9):1174-80. Carfilzomib Jang JY, Klimstra DS, Hruban RH; Members of Verona significantly improves the progression-free survival of high- Consensus Meeting, 2013.. Ann Surg. 2016 Jan;263(1):162- risk patients in multiple myeloma. 77. Pathologic Evaluation and Reporting of Intraductal Papillary Mucinous Neoplasms of the Pancreas and Other Avet-Loiseau H. Am Soc Clin Oncol Educ Book. Tumoral Intraepithelial Neoplasms of Pancreatobiliary Tract: 2016;35:e425-30. Minimal Residual Disease by Next- Recommendations of Verona Consensus Meeting. Generation Sequencing: Pros and Cons. Alberto C, Konstantinou MP, Martinage C, Casassa E, Baert-Desurmont S, Charbonnier F, Houivet E, Ippolito Tournier E, Bagheri H, Sibaud V, Mourey L, Mazereeuw- L, Mauillon J, Bougeard M, Abadie C, Malka D, Duffour J, Hautier J, Meyer N, Paul C, Bulai Livideanu C. J Dermatol Desseigne F, Colas C, Pujol P, Lejeune S, Dugast C, Buecher Case Rep. 2016 Nov 13;10(2):35-8. Enzalutamide induced B, Faivre L, Leroux D, Gesta P, Coupier I, Guimbaud R, acute generalized exanthematous pustulosis. Berthet P, Manouvrier S, Cauchin E, Prieur F, Laurent-Puig P, Lebrun M, Jonveaux P, Chiesa J, Caron O, Morin-Meschin Alric L, Besson C, Lapidus N, Jeannel J, Michot JM, ME, Polycarpe-Osaer F, Giraud S, Zaanan A, Bonnet D, Cacoub P, Canioni D, Pol S, Davi F, Rabiega P, Ysebaert L, Mansuy L, Bonadona V, El Chehadeh S, Duhoux F, Gauthier- Bonnet D, Hermine O. PLoS One. 2016 Oct Villars M, Saurin JC, Collonge-Rame MA, Brugières L, 17;11(10):e0162965. Antiviral Treatment of HCV-Infected Wang Q, Bressac-de Paillerets B, Rey JM, Toulas C, Buisine Patients with B-Cell Non-Hodgkin Lymphoma: ANRS HC- MP, Bronner M, Sokolowska J, Hardouin A, Cailleux AF, 13 Lympho-C Study. Sebaoui H, Blot J, Tinat J, Benichou J, Frebourg T. Eur J Hum Genet. 2016 Jan;24(1):99-105. Clinical relevance of 8q23, Alyami M, Lundberg P, Kepenekian V, Goéré D, Bereder 15q13 and 18q21 SNP genotyping to evaluate colorectal JM, Msika S, Lorimier G, Quenet F, Ferron G, Thibaudeau E, cancer risk. Abboud K, Lo Dico R, Delroeux D, Brigand C, Arvieux C, Marchal F, Tuech JJ, Guilloit JM, Guyon F, Peyrat P, Pezet Baranger L, Cuccuini W, Lefebvre C, Luquet I, Perot C, D, Ortega-Deballon P, Zinzindohoue F, de Chaisemartin C, Radford I, Lafage-Pochitaloff M. Ann Biol Clin (Paris). 2016 Kianmanesh R, Glehen O, Passot G; BIG-RENAPE and Oct 1;74(5):547-60. Review. Cytogenetics in the RENAPE Working Groups.. Ann Surg Oncol. 2016 management of children and adult acute lymphoblastic Dec;23(Suppl 5):737-45. Cytoreductive Surgery and leukemia (ALL): an update by the Groupe francophone de Hyperthermic Intraperitoneal Chemotherapy for Peritoneal cytogénétique hématologique (GFCH). Carcinomatosis in the Elderly: A Case-Controlled, Multicenter Study. Barlesi F, Mazieres J, Merlio JP, Debieuvre D, Mosser J, Lena H, Ouafik L, Besse B, Rouquette I, Westeel V, Escande Arcondéguy T, Touriol C, Lacazette E. Methods Mol F, Monnet I, Lemoine A, Veillon R, Blons H, Audigier- Biol. 2016;1459:127-34. Quantification of a Non- Valette C, Bringuier PP, Lamy R, Beau-Faller M, Pujol JL, conventional Protein Secretion: The Low-Molecular-Weight Sabourin JC, Penault-Llorca F, Denis MG, Lantuejoul S, FGF-2 Example. Morin F, Tran Q, Missy P, Langlais A, Milleron B, Cadranel J, Soria JC, Zalcman G; Biomarkers France contributors.. Armand-Labit V, Meyer N, Casanova A, Bonnabau H, Lancet. 2016 Apr 2;387(10026):1415-26. Routine molecular Platzer V, Tournier E, Sansas B, Verdun S, Thouvenot B, profiling of patients with advanced non-small-cell lung Hilselberger B, Doncescu A, Lamant L, Lacroix-Triki M, cancer: results of a 1-year nationwide programme of the Favre G, Pradines A. Acta Derm Venereol. 2016 French Cooperative Thoracic Intergroup (IFCT). Jan;96(1):29-34. Identification of a Circulating MicroRNA Profile as a Biomarker of Metastatic Cutaneous Melanoma. Barrow-McGee R, Kishi N, Joffre C, Ménard L, Hervieu A, Bakhouche BA, Noval AJ, Mai A, Guzmán C, Robert- Arnaud FX, Paillas S, Pouget JP, Incerti S, Bardies M, Masson L, Iturrioz X, Hulit J, Brennan CH, Hart IR, Parker Bordage MC.. Nucl Instrum Meth B. 2016;366:227-33. PJ, Ivaska J, Kermorgant S. Nat Commun. 2016 Jun Complex cell geometry and sources distribution model for 23;7:11942. Beta 1-integrin-c-Met cooperation reveals an Monte Carlo single cell dosimetry with iodine 125 inside-in survival signalling on autophagy-related radioimmunotherapy. endomembranes. Nat Commun. 2016 Jul 22;7:12392. Astudillo L, Sabourdy F, Touati G, Levade T. Presse Corrigendum: Beta 1-integrin-c-Met cooperation reveals an Med. 2016 Mar;45(3):302-12. doi: inside-in survival signalling on autophagy-related 10.1016/j.lpm.2015.05.009. Epub 2016 Feb 18. Review. endomembranes. French. [Hereditary peroxisomal diseases]. Becht E, de Reyniès A, Giraldo NA, Pilati C, Buttard B, Lacroix L, Selves J, Sautès-Fridman C, Laurent-Puig P,
[56]
Fridman WH. Clin Cancer Res. 2016 Aug 15;22(16):4057- Mouret-Reynier MA, Bachelot T, Lerebours F, Eymard JC, 66. Immune and Stromal Classification of Colorectal Cancer Deblock M, Lortholary A, Hardy-Bessard AC, Barthelemy P, Is Associated with Molecular Subtypes and Relevant for Bonnefoi H, Charafe-Jauffret E, Bidard FC, Viens P, Precision Immunotherapy. Lemonnier J, Pierga JY. Lancet Oncol. 2016 May;17(5):600- 11. dBevacizumab plus neoadjuvant chemotherapy in Becht E, Giraldo NA, Lacroix L, Buttard B, Elarouci N, patients with HER2-negative inflammatory breast cancer Petitprez F, Selves J, Laurent-Puig P, Sautès-Fridman C, (BEVERLY-1): a multicentre, single-arm, phase 2 study. Fridman WH, de Reyniès A. Genome Biol. 2016 Oct 20;17(1):218. Estimating the population abundance of tissue- Besson-Fournier C, Martinez M, Vinel JP, Aguilar- infiltrating immune and stromal cell populations using gene Martinez P, Coppin H, Roth MP. Hepatology. 2016 expression. Erratum in: Genome Biol. 2016 Dec 1;17 (1):249. Jun;63(6):2054-5. Further support for the association of Genome Biol. 2016 Dec 1;17(1):249. Erratum to: Estimating GNPAT variant rs11558492 with severe iron overload in the population abundance of tissue-infiltrating immune and hemochromatosis. stromal cell populations using gene expression. Bétous R, Renoud ML, Hoede C, Gonzalez I, Jones N, Belliere J, Meyer N, Mazieres J, Ollier S, Boulinguez S, Longy M, Sensebé L, Cazaux C, Hoffmann JS. Stem Cells Delas A, Ribes D, Faguer S. Br J Cancer. 2016 Dec Transl Med. 2016 Aug 24. pii: sctm.2015-0401. Human 6;115(12):1457-61. Acute interstitial nephritis related to Adipose-Derived Stem Cells Expanded Under Ambient immune checkpoint inhibitors. Oxygen Concentration Accumulate Oxidative DNA Lesions and Experience Procarcinogenic DNA Replication Stress. Bennani Smires Y, Victor G, Ribes D, Berry M, Cognet T, Méjean S, Huart A, Roussel M, Petermann A, Roncalli J, Betrian S, Ysebaert L, Heider KH, Delord JP, Fournié JJ, Carrié D, Rousseau H, Berry I, Chauveau D, Galinier M, Quillet-Mary A. Blood Cancer J. 2016 Nov 11;6(11):e496. Lairez O. Int J Cardiovasc Imaging. 2016 Sep;32(9):1403-13. Idelalisib improves CD37 antibody BI 836826 cytotoxicity Pilot study for left ventricular imaging phenotype of patients against chemo-resistant /relapse-initiating CLL cells: a over 65 years old with heart failure and preserved ejection rationale for combination treatment. fraction: the high prevalence of amyloid cardiomyopathy. Bettoun A, Joffre C, Zago G, Surdez D, Vallerand D, Béroud C, Letovsky SI, Braastad CD, Caputo SM, Gundogdu R, Sharif AA, Gomez M, Cascone I, Meunier B, Beaudoux O, Bignon YJ, Bressac-De Paillerets B, Bronner White MA, Codogno P, Parrini MC, Camonis JH, Hergovich M, Buell CM, Collod-Béroud G, Coulet F, Derive N, A. Oncotarget. 2016 Jul 12;7(28):44142-60. Mitochondrial Divincenzo C, Elzinga CD, Garrec C, Houdayer C, Karbassi clearance by the STK38 kinase supports oncogenic Ras- I, Lizard S, Love A, Muller D, Nagan N, Nery CR, Rai G, induced cell transformation. Revillion F, Salgado D, Sévenet N, Sinilnikova O, Sobol H, Stoppa-Lyonnet D, Toulas C, Trautman E, Vaur D, Vilquin Bielle F, Ducray F, Mokhtari K, Dehais C, Adle-Biassette P, Weymouth KS, Willis A; Laboratory Corporation of H, Carpentier C, Chanut A, Polivka M, Poggioli S, Rosenberg America Variant Classification Group.; Quest Diagnostics S, Giry M, Marie Y, Duyckaerts C, Sanson M, Figarella- Variant Classification Group.; UNICANCER Genetic Group Branger D, Idbaih A; Pola Network.. Brain Pathol. 2016 Aug BRCA Laboratory Network., Eisenberg M, Strom CM. Hum 20. Tumor cells with neuronal intermediate progenitor Mutat. 2016 Dec;37(12):1318-28. BRCA Share: A Collection features define a subgroup of 1p/19q co-deleted anaplastic of Clinical BRCA Gene Variants. gliomas. Berquet L, Valleron W, Grgurevic S, Quelen C, Zaki O, Blake SJ, Stannard K, Liu J, Allen S, Yong MC, Mittal Quillet-Mary A, Davi F, Brousset P, Bousquet M, Ysebaert D, Aguilera AR, Miles JJ, Lutzky VP, de Andrade LF, L. Br J Haematol. 2016 Mar;172(5):819-23. Small nucleolar Martinet L, Colonna M, Takeda K, Kühnel F, Gurlevik E, RNA expression profiles refine the prognostic impact of Bernhardt G, Teng MW, Smyth MJ. Cancer Discov. 2016 IGHV mutational status on treatment-free survival in chronic Apr;6(4):446-59. Suppression of Metastases Using a New lymphocytic leukaemia. Lymphocyte Checkpoint Target for Cancer Immunotherapy. Berthon C, Raffoux E, Thomas X, Vey N, Gomez-Roca Boissard F, Laurent C, Ramsay AG, Quillet-Mary A, C, Yee K, Taussig DC, Rezai K, Roumier C, Herait P, Kahatt Fournié JJ, Poupot M, Ysebaert L. Blood Cancer J. 2016 Jan C, Quesnel B, Michallet M, Recher C, Lokiec F, 15;6:e381. Nurse-like cells impact on disease progression in Preudhomme C, Dombret H. Lancet Haematol. 2016 chronic lymphocytic leukemia. Apr;3(4):e186-95. Bromodomain inhibitor OTX015 in Boissard F, Tosolini M, Ligat L, Quillet-Mary A, Lopez patients with acute leukaemia: a dose-escalation, phase 1 F, Fournié JJ, Ysebaert L, Poupot M. Oncotarget. 2016 Nov study. 26. Nurse-like cells promote CLL survival through LFA- Bertoli S, Sterin A, Tavitian S, Oberic L, Ysebaert L, 3/CD2 interactions. Bouabdallah R, Vergez F, Sarry A, Bérard E, Huguet F, Bolli N, Li Y, Sathiaseelan V, Raine K, Jones D, Ganly Laurent G, Prébet T, Vey N, Récher C. Oncotarget. 2016 Dec P, Cocito F, Bignell G, Chapman MA, Sperling AS, Anderson 27;7(52):85937-47. Therapy-related acute myeloid leukemia KC, Avet-Loiseau H, Minvielle S, Campbell PJ, Munshi NC. following treatment of lymphoid malignancies. Blood Cancer J. 2016 Sep 2;6(9):e467. A DNA target- Bertrand F, Rochotte J, Colacios C, Montfort A, Andrieu- enrichment approach to detect mutations, copy number Abadie N, Levade T, Benoist H, Ségui B. Oncoimmunology. changes and immunoglobulin translocations in multiple 2016; 5(1): e1068495. Targeting TNF alpha as a novel myeloma. strategy to enhance CD8+ T cell-dependent immune response Bonafé L, Kariminejad A, Li J, Royer-Bertrand B, Garcia in melanoma? V, Mahdavi S, Bozorgmehr B, Lachman RL, Mittaz-Crettol Bertucci F, Fekih M, Autret A, Petit T, Dalenc F, Levy C, L, Campos-Xavier B, Nampoothiri S, Unger S, Rivolta C, Romieu G, Bonneterre J, Ferrero JM, Kerbrat P, Soulie P, Levade T, Superti-Furga A. Arthritis Rheumatol. 2016
[57]
Sep;68(9):2323-7. Brief Report: Peripheral Osteolysis in Boutzen H, Saland E, Larrue C, de Toni F, Gales L, Adults Linked to ASAH1 (Acid Ceramidase) Mutations: A Castelli FA, Cathebas M, Zaghdoudi S, Stuani L, Kaoma T, New Presentation of Farber's Disease. Riscal R, Yang G, Hirsch P, David M, De Mas-Mansat V, Delabesse E, Vallar L, Delhommeau F, Jouanin I, Ouerfelli Bonnefoi H, Grellety T, Tredan O, Saghatchian M, O, Le Cam L, Linares LK, Junot C, Portais JC, Vergez F, Dalenc F, Mailliez A, L'Haridon T, Cottu P, Abadie- Récher C, Sarry JE. J Exp Med. 2016 Apr 4;213(4):483-97. Lacourtoisie S, You B, Mousseau M, Dauba J, Del Piano F, Isocitrate dehydrogenase 1 mutations prime the all-trans Desmoulins I, Coussy F, Madranges N, Grenier J, Bidard FC, retinoic acid myeloid differentiation pathway in acute Proudhon C, MacGrogan G, Orsini C, Pulido M, Gonçalves myeloid leukemia. A. Ann Oncol. 2016 May;27(5):812-8. A phase II trial of abiraterone acetate plus prednisone in patients with triple- Boyle E, Manier S, Lejeune J, Fouquet G, Guidez S, negative androgen receptor positive locally advanced or Bonnet S, Debarri H, Demarquette H, Dulery R, Gay J, metastatic breast cancer (UCBG 12-1). Hennache B, Onraed B, Faucompré JL, Schraen S, Facon T, Avet-Loiseau H, Chevret S, Leblond V, Harding S, Leleu X. Bonnet-Magnaval F, Philippe C, Van Den Berghe L, Clin Cancer Res. 2016 Oct 15;22(20):5152-8. IgMκ and Prats H, Touriol C, Lacazette E. Biochem Biophys Res IgMλ Measurements for the Assessment of Patients with Commun. 2016 Oct 14;479(2):365-71. Hypoxia and ER Waldenström's Macroglobulinaemia. stress promote Staufen1 expression through an alternative translation mechanism. Branco B, Metsu D, Dutertre M, Marchou B, Delobel P, Recher C, Martin-Blondel G. Ann Hematol. 2016 Bordage MC, Bordes J, Edel S, Terrissol M, Franceries Jun;95(7):1207-9. Use of rifampin for treatment of X, Bardiès M, Lampe N, Incerti S. Phys Med. 2016 disseminated tuberculosis in a patient with primary Dec;32(12):1833-40. Implementation of new physics models myelofibrosis on ruxolitinib. for low energy electrons in liquid water in Geant4-DNA. Buhard O, Lagrange A, Guilloux A, Colas C, Chouchène Bouchahda M, Boige V, Smith D, Karaboué A, Ducreux M, Wanherdrick K, Coulet F, Guillerm E, Dorard C, Marisa M, Hebbar M, Lepère C, Focan C, Guimbaud R, Innominato L, Bokhari A, Greene M, El-Murr N, Bodo S, Muleris M, P, Awad S, Carvalho C, Tumolo S, Truant S, De Baere T, Sourouille I, Svrcek M, Cervera P, Blanché H, Lefevre JH, Castaing D, Rougier P, Morère JF, Taieb J, Adam R, Lévi F; Parc Y, Lepage C, Chapusot C, Bouvier AM, Gaub MP, ARTBC International.. Eur J Cancer. 2016 Nov;68:163-72. Selves J, Garrett K, Iacopetta B, Soong R, Hamelin R, Early tumour response as a survival predictor in previously- Garrido C, Lascols O, André T, Fléjou JF, Collura A, Duval treated patients receiving triplet hepatic artery infusion and A. J Med Genet. 2016 Jun;53(6):377-84. HSP110 T17 intravenous cetuximab for unresectable liver metastases from simplifies and improves the microsatellite instability testing wild-type KRAS colorectal cancer. in patients with colorectal cancer. Bouquerel P, Gstalder C, Müller D, Laurent J, Brizuela L, Bulai Livideanu C, Apoil PA, Lepage B, Eischen M, Sabbadini RA, Malavaud B, Pyronnet S, Martineau Y, Ader Laurent C, Laharrague P, Lamant L, Tournier E, Tavitian S, I, Cuvillier O. Oncogenesis. 2016 Mar 14;5:e209. Essential Pouplard C, Recher C, Laroche M, Mailhol C, Dubreuil P, role for SphK1/S1P signaling to regulate hypoxia-inducible Hermine O, Blancher A, Paul C. Clin Exp Allergy. 2016 factor 2α expression and activity in cancer. Jan;46(1):133-41. Bone marrow tryptase as a possible Bournet B, Buscail C, Muscari F, Cordelier P, Buscail L. diagnostic criterion for adult systemic mastocytosis. Eur J Cancer. 2016 Feb;54:75-83. Targeting KRAS for Bureau C, Laurent J, Robic MA, Christol C, Guillaume diagnosis, prognosis, and treatment of pancreatic cancer: M, Ruidavets JB, Ferrieres J, Péron JM, Vinel JP. J Hepatol. Hopes and realities. 2016 Feb;64(2):427-32. Central obesity is associated with Bournet B, Muscari F, Buscail C, Assenat E, Barthet M, non-cirrhotic portal vein thrombosis. Hammel P, Selves J, Guimbaud R, Cordelier P, Buscail L. Cabarrou B, Belin L, Somda SM, Falcou MC, Pierga JY, Clin Transl Gastroenterol. 2016 Mar 24;7:e157. KRAS G12D Kirova Y, Delord JP, Asselain B, Filleron T. Breast Cancer Mutation Subtype Is A Prognostic Factor for Advanced Res Treat. 2016 Apr;156(3):577-85. Prediction of long-term Pancreatic Adenocarcinoma. cumulative incidences based on short-term parametric model Bournet B, Vignolle-Vidoni A, Grand D, Roques C, for competing risks: application in early breast cancer. Breibach F, Cros J, Muscari F, Carrère N, Selves J, Cordelier Cabarrou B, Boher JM, Bogart E, Tresch-Bruneel E, P, Buscail L. Endosc Int Open. 2016 Dec;4(12):E1228- Penel N, Ravaud A, Escudier B, Mahier Ait-Oukhatar C, E1235. Endoscopic ultrasound-guided fine-needle aspiration Delord JP, Roché H, Filleron T. Ann Oncol. 2016 plus KRAS and GNAS mutation in malignant intraductal Aug;27(8):1633-8. How to report toxicity associated with papillary mucinous neoplasm of the pancreas. targeted therapies? Bousquet E, Calvayrac O, Mazières J, Lajoie-Mazenc I, Calvayrac O, Pradines A, Favre G. Small GTPases. 2016 Boubekeur N, Favre G, Pradines A. Oncogene. 2016 Apr Sep 27:1-6. RHOB expression controls the activity of 7;35(14):1760-9. RhoB loss induces Rac1-dependent serine/threonine protein phosphatase PP2A to modulate mesenchymal cell invasion in lung cells through PP2A mesenchymal phenotype and invasion in non-small cell lung inhibition. cancers. Bousquet M, Noirot C, Accadbled F, Sales de Gauzy J, Camilleri J, Mazurier J, Franck D, Dudouet P, Latorzeff Castex MP, Brousset P, Gomez-Brouchet A. Ann Oncol. I, Franceries X. Phys Med. 2016 Jan;32(1):133-40. 2D EPID 2016 Apr;27(4):738-44. Whole-exome sequencing in dose calibration for pretreatment quality control of conformal osteosarcoma reveals important heterogeneity of genetic and IMRT fields: A simple and fast convolution approach. alterations.
[58]
Cammas A, Lacroix-Triki M, Pierredon S, Le Bras M, response to DNA double-strand breaks produced during the Iacovoni JS, Teulade-Fichou MP, Favre G, Roché H, Filleron repair of transcription-blocking topoisomerase I lesions. T, Millevoi S, Vagner S. Oncotarget. 2016 Mar 29;7(13):16793-805. hnRNP A1-mediated translational Dalenc F, Iuliano L, Filleron T, Zerbinati C, Voisin M, regulation of the G quadruplex-containing RON receptor Arellano C, Chatelut E, Marquet P, Samadi M, Roché H, tyrosine kinase mRNA linked to tumor progression. Poirot M, Silvente-Poirot S. J Steroid Biochem Mol Biol. 2016 Jun 22. pii: S0960-0760(16)30182-0. Circulating Caplin ME, Pavel M, Ćwikła JB, Phan AT, Raderer M, oxysterol metabolites as potential new surrogate markers in Sedláčková E, Cadiot G, Wolin EM, Capdevila J, Wall L, patients with hormone receptor-positive breast cancer: Rindi G, Langley A, Martinez S, Gomez-Panzani E, Results of the OXYTAM study. Ruszniewski P; CLARINET Investigators.. Endocr Relat Cancer. 2016 Mar;23(3):191-9. Anti-tumour effects of David L, Fernandez-Vidal A, Bertoli S, Grgurevic S, lanreotide for pancreatic and intestinal neuroendocrine Lepage B, Deshaies D, Prade N, Cartel M, Larrue C, Sarry tumours: the CLARINET open-label extension study. JE, Delabesse E, Cazaux C, Didier C, Récher C, Manenti S, Hoffmann JS. Sci Signal. 2016 Sep 13;9(445):ra90. CHK1 as Carré J, Grunenwald S, Vezzosi D, Mazerolles C, Bennet a therapeutic target to bypass chemoresistance in AML. A, Meduri G, Caron P. Gynecol Endocrinol. 2016 Aug;32(8):662-6. Virilizing oncocytic adrenocortical de Bonnecaze G, Chaput B, Woisard V, Uro-Coste E, carcinoma: clinical and immunohistochemical studies. Swider P, Vergez S, Serrano E, Casteilla L, Planat-Benard V. Laryngoscope. 2016 Aug;126(8):E278-85. Adipose stromal Cartier N, Cordelier P. Hum Gene Ther. 2016 cells improve healing of vocal fold scar: Morphological and Feb;27(2):96-7. Hopes, Promises, and Future Directions of functional evidences. Gene and Cell Therapies in France. de Pablos-Martinez C, Porte L, Fraissinet F, Berry A, Chandesris MO, Damaj G, Canioni D, Brouzes C, Séraissol P, Lavit M, Chatelut E, Concordet D, Gandia P. Lhermitte L, Hanssens K, Frenzel L, Cherquaoui Z, Durieu I, Therapie. 2016 Oct;71(5):487-9. Quinine unbound Durupt S, Gyan E, Beyne-Rauzy O, Launay D, Faure C, concentration is the best marker for therapeutic drug Hamidou M, Besnard S, Diouf M, Schiffmann A, Niault M, monitoring. Jeandel PY, Ranta D, Gressin R, Chantepie S, Barete S, Dubreuil P, Bourget P, Lortholary O, Hermine O; de Pablos-Martinez C, Porte L, Fraissinet F, Berry A, CEREMAST Study Group.. N Engl J Med. 2016 Jun Séraissol P, Lavit M, Chatelut E, Concordet D, Gandia P. 30;374(26):2605-7. Midostaurin in Advanced Systemic Ther Drug Monit. 2016 Aug;38(4):556-7. Quinine Unbound Mastocytosis. Concentration Has to Be Used for Therapeutic Drug Monitoring. Chantalat E, Boudou F, Laurell H, Palierne G, Houtman R, Melchers D, Rochaix P, Filleron T, Stella A, Burlet-Schiltz Decaup E, Rochotte J, Pyronnet S, Bousquet C, Jean C. O, Brouchet A, Flouriot G, Métivier R, Arnal JF, Fontaine C, Clin Res Hepatol Gastroenterol. 2016 Dec 6. pii: S2210- Lenfant F. Breast Cancer Res. 2016 Dec 7;18(1):123. The 7401(16)30191-7. Focal Adhesion Kinase: A promising AF-1-deficient estrogen receptor ERα46 isoform is therapeutic target in pancreatic adenocarcinoma. frequently expressed in human breast tumors. Dejoie T, Attal M, Moreau P, Harousseau JL, Avet- Chaveroux C, Bruhat A, Carraro V, Jousse C, Averous J, Loiseau H. Haematologica. 2016 Mar;101(3):356-62. Maurin AC, Parry L, Mesclon F, Muranishi Y, Cordelier P, Comparison of serum free light chain and urine Meulle A, Baril P, Do Thi A, Ravassard P, Mallet J, electrophoresis for the detection of the light chain component Fafournoux P. Nat Biotechnol. 2016 Jul;34(7):746-51. of monoclonal immunoglobulins in light chain and intact Regulating the expression of therapeutic transgenes by immunoglobulin multiple myeloma. controlled intake of dietary essential amino acids. Dejoie T, Corre J, Caillon H, Hulin C, Perrot A, Caillot Chesnais V, Renneville A, Toma A, Lambert J, Passet M, D, Boyle E, Chretien ML, Fontan J, Belhadj K, Brechignac S, Dumont F, Chevret S, Lejeune J, Raimbault A, Stamatoullas Decaux O, Voillat L, Rodon P, Fitoussi O, Araujo C, A, Rose C, Beyne-Rauzy O, Delaunay J, Solary E, Fenaux P, Benboubker L, Fontan C, Tiab M, Godmer P, Luycx O, Dreyfus F, Preudhomme C, Kosmider O, Fontenay M; Allangba O, Pignon JM, Fuzibet JG, Legros L, Stoppa AM, Groupe Francophone des Myélodysplasies.. Blood. 2016 Feb Dib M, Pegourie B, Orsini-Piocelle F, Karlin L, Arnulf B, 11;127(6):749-60. Effect of lenalidomide treatment on clonal Roussel M, Garderet L, Mohty M, Meuleman N, Doyen C, architecture of myelodysplastic syndromes without 5q Lenain P, Macro M, Leleu X, Facon T, Moreau P, Attal M, deletion. Avet-Loiseau H. Blood. 2016 Dec 22;128(25):2941-8. Serum free light chains, not urine specimens, should be used to Chng WJ, Chung TH, Kumar S, Usmani S, Munshi N, evaluate response in light-chain multiple myeloma. Avet-Loiseau H, Goldschmidt H, Durie B, Sonneveld P. Leukemia. 2016 May;30(5):1071-8. Gene signature Delaloge S, Pérol D, Courtinard C, Brain E, Asselain B, combinations improve prognostic stratification of multiple Bachelot T, Debled M, Dieras V, Campone M, Levy C, Jacot myeloma patients. W, Lorgis V, Veyret C, Dalenc F, Ferrero JM, Uwer L, Kerbrat P, Goncalves A, Mouret-Reynier MA, Petit T, Courtade-Saïdi M, Aziza J, d'Aure D, Bérard E, Evrard S, Jouannaud C, Vanlemmens L, Chenuc G, Guesmia T, Robain Basset C, Lacoste-Collin L. Cytopathology. 2016 M, Cailliot C. Ann Oncol. 2016 Sep;27(9):1725-32. Dec;27(6):456-64. Immunocytochemical staining for p53 and Paclitaxel plus bevacizumab or paclitaxel as first-line Ki-67 helps to characterise urothelial cells in urine cytology. treatment for HER2-negative metastatic breast cancer in a multicenter national observational study. Cristini A, Park JH, Capranico G, Legube G, Favre G, Sordet O. Nucleic Acids Res. 2016 Feb 18;44(3):1161-78. Deutsch E, Cohen-Jonathan Moyal E, Gregorc V, Zucali DNA-PK triggers histone ubiquitination and signaling in PA, Menard J, Soria JC, Kloos I, Hsu J, Luan Y, Liu E, Vezan
[59]
R, Graef T, Rivera S. Oncotarget. 2016 Dec 24. A phase 1 Blood. 2016 Jun 16;127(24):3040-53. Haploinsufficiency for dose-escalation study of the oral histone deacetylase inhibitor NR3C1, the gene encoding the glucocorticoid receptor, in abexinostat in combination with standard hypofractionated blastic plasmacytoid dendritic cell neoplasms. radiotherapy in advanced solid tumors. Engert A, Balduini C, Brand A, Coiffier B, Cordonnier C, Dhelens C, Bonadona A, Thomas F, Chapuis C, Potton L, Döhner H, de Wit TD, Eichinger S, Fibbe W, Green T, de Marsili S, Bedouch P, Schwebel C. Int J Colorectal Dis. 2016 Haas F, Iolascon A, Jaffredo T, Rodeghiero F, Salles G, Mar;31(3):699-701. Lethal 5-fluorouracil toxicity in a Schuringa JJ; EHA Roadmap for European Hematology colorectal patient with severe dihydropyrimidine Research.. Haematologica. 2016 Feb;101(2):115-208. The dehydrogenase (DPD) deficiency. European Hematology Association Roadmap for European Hematology Research: a consensus document. Diéras V, Bachelot T, Campone M, Isambert N, Joly F, Le Tourneau C, Cassier P, Bompas E, Fumoleau P, Noal S, Faguer S, Roussel M. Eur J Haematol. 2016 Orsini C, Jimenez M, Imbs DC, Chatelut E. Oncol Ther. Jun;96(6):547-8. 'Patients with multiple myeloma have 2016;4(2):211-23. A Phase I, Dose-Escalation Trial of excellent long-term outcomes after recovery from dialysis- Pazopanib in Combination with Cisplatin in Patients with dependent acute kidney injury'. Advanced Solid Tumors: A UNICANCER Study. Faguer S, Vergez F, Peres M, Ferrandiz I, Casemayou A, Dimopoulos MA, Cheung MC, Roussel M, Liu T, Belliere J, Cointault O, Lavayssiere L, Nogier MB, Prevot G, Gamberi B, Kolb B, Derigs HG, Eom H, Belhadj K, Lenain Huart A, Recher C, Rostaing L. Hematol Oncol. 2016 P, Van der Jagt R, Rigaudeau S, Dib M, Hall R, Jardel H, Mar;34(1):55-7. Tocilizumab added to conventional therapy Jaccard A, Tosikyan A, Karlin L, Bensinger W, Schots R, reverses both the cytokine profile and CD8+Granzyme+ T- Leupin N, Chen G, Marek J, Ervin-Haynes A, Facon T. cells/NK cells expansion in refractory hemophagocytic Haematologica. 2016 Mar;101(3):363-70. Impact of renal lymphohistiocytosis. impairment on outcomes with lenalidomide and dexamethasone treatment in the FIRST trial, a randomized, Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, open-label phase 3 trial in transplant-ineligible patients with Vansteenkiste J, Mazieres J, Park K, Smith D, Artal-Cortes multiple myeloma. A, Lewanski C, Braiteh F, Waterkamp D, He P, Zou W, Chen DS, Yi J, Sandler A, Rittmeyer A; POPLAR Study Group.. Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis Lancet. 2016 Apr 30;387(10030):1837-46. Atezolizumab NJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, versus docetaxel for patients with previously treated non- Suzuki K, Plesner T, Yoon SS, Ben Yehuda D, Richardson small-cell lung cancer (POPLAR): a multicentre, open-label, PG, Goldschmidt H, Reece D, Lisby S, Khokhar NZ, phase 2 randomised controlled trial. O'Rourke L, Chiu C, Qin X, Guckert M, Ahmadi T, Moreau P; POLLUX Investigators.. N Engl J Med. 2016 Oct Figarella-Branger D, Mokhtari K, Dehais C, Carpentier 6;375(14):1319-31. Daratumumab, Lenalidomide, and C, Colin C, Jouvet A, Uro-Coste E, Forest F, Maurage CA, Dexamethasone for Multiple Myeloma. Vignaud JM, Polivka M, Lechapt-Zalcman E, Eimer S, Viennet G, Quintin-Roué I, Aubriot-Lorton MH, Diebold Duault C, Franchini DM, Familliades J, Cayrol C, Roga MD, Loussouarn D, Lacroix C, Rigau V, Laquerrière A, S, Girard JP, Fournié JJ, Poupot M. J Immunol. 2016 Jan Vandenbos F, Michalak S, Sevestre H, Peoch M, Labrousse 1;196(1):493-502. TCRVγ9 γδ T Cell Response to IL-33: A F, Christov C, Kemeny JL, Chenard MP, Chiforeanu D, CD4 T Cell-Dependent Mechanism. Ducray F, Idbaih A, Delattre JY; POLA Network.. Neuro Oncol. 2016 Jun;18(6):888-90. Mitotic index, microvascular Dubois F, Keller M, Calvayrac O, Soncin F, Hoa L, proliferation, and necrosis define 3 pathological subgroups of Hergovich A, Parrini MC, Mazières J, Vaisse-Lesteven M, prognostic relevance among 1p/19q co-deleted anaplastic Camonis J, Levallet G, Zalcman G. Cancer Res. 2016 Mar oligodendrogliomas. 15;76(6):1627-40. RASSF1A Suppresses the Invasion and Metastatic Potential of Human Non-Small Cell Lung Cancer Fouquet G, Pegourie B, Macro M, Petillon MO, Karlin L, Cells by Inhibiting YAP Activation through the GEF- Caillot D, Roussel M, Arnulf B, Mathiot C, Marit G, Kolb B, H1/RhoB Pathway. Stoppa AM, Brechiniac S, Richez V, Rodon P, Banos A, Wetterwald M, Garderet L, Royer B, Hulin C, Benbouker L, Duquesnes N, Callot C, Jeannot P, Daburon V, Nakayama Decaux O, Escoffre-Barbe M, Fermand JP, Attal M, Avet- KI, Manenti S, Davy A, Besson A. J Pathol. 2016 Loiseau H, Moreau P, Facon T, Leleu X; IFM (Intergroupe Jul;239(3):250-61. p57(Kip2) knock-in mouse reveals CDK- Francophone du Myélome). Ann Oncol. 2016 independent contribution in the development of Beckwith- May;27(5):902-7. Safe and prolonged survival with long- Wiedemann syndrome. term exposure to pomalidomide in relapsed/refractory Durand Bechu M, Rouget A, Recher C, Azoulay E, myeloma. Bounes V. Case Rep Emerg Med. 2016;2016:5347039. A Gamonet C, Bole-Richard E, Delherme A, Aubin F, Systemic Capillary Leak Syndrome (Clarkson Syndrome) in Toussirot E, Garnache-Ottou F, Godet Y, Ysebaert L, a Patient with Chronic Lymphocytic Leukemia: A Case Tournilhac O, Caroline D, Larosa F, Deconinck E, Saas P, Report in an Out-of-Hospital Setting. Borg C, Deschamps M, Ferrand C. Exp Hematol Oncol. 2016 Emadali A, Hoghoughi N, Duley S, Hajmirza A, Mar 1;5:7. New CD20 alternative splice variants: molecular Verhoeyen E, Cosset FL, Bertrand P, Roumier C, Roggy A, identification and differential expression within Suchaud-Martin C, Chauvet M, Bertrand S, Hamaidia S, hematological B cell malignancies. Exp Hematol Oncol. 2016 Rousseaux S, Josserand V, Charles J, Templier I, Maeda T, Apr 14;5:10. Erratum to: New CD20 alternative splice Bruder-Costa J, Chaperot L, Plumas J, Jacob MC, Bonnefoix variants: molecular identification and differential expression T, Park S, Gressin R, Tensen CP, Mecucci C, Macintyre E, within hematological B cell malignancies. Leroux D, Brambilla E, Nguyen-Khac F, Luquet I, Penther D, Gandia P, Jaudet C, Everaert H, Heemskerk J, Vanbinst Bastard C, Jardin F, Lefebvre C, Garnache F, Callanan MB. AM, de Mey J, Duerinck J, Neyns B, de Ridder M, Chatelut
[60]
E, Concordet D. Clin Pharmacokinet. 2016 Dec 19. response to replicative stress in homologous recombination- Population Pharmacokinetic Approach Applied to Positron proficient cancer cells. Emission Tomography: Computed Tomography for Tumor Tissue Identification in Patients with Glioma. Gratia M, Vende P, Charpilienne A, Baron HC, Laroche C, Sarot E, Pyronnet S, Duarte M, Poncet D. PLoS One. 2016 Garcia MP, Bert J, Benoit D, Bardiès M, Visvikis D. Phys Jan 4;11(1):e0145998. Challenging the Roles of NSP3 and Med Biol. 2016 Jun 7;61(11):4001-18. Accelerated GPU Untranslated Regions in Rotavirus mRNA Translation. based SPECT Monte Carlo simulations. Gravelle P, Do C, Franchet C, Mueller S, Oberic L, Garcia MP, Charil A, Callaghan P, Wimberley C, Busso Ysebaert L, Larocca LM, Hohaus S, Calmels MN, Frenois F, Gregoire MC, Bardies M, Reilhac A. IEEE Trans Med FX, Kridel R, Gascoyne RD, Laurent G, Brousset P, Valitutti Imaging. 2016 Jul;35(7):1696-706. OSSI-PET: Open-Access S, Laurent C. Oncoimmunology. 2016 Aug Database of Simulated [(11)C]Raclopride Scans for the 24;5(10):e1224044. Impaired functional responses in Inveon Preclinical PET Scanner: Application to the follicular lymphoma CD8+TIM-3+ T lymphocytes following Optimization of Reconstruction Methods for Dynamic TCR engagement. Studies. Grgurevic S, Berquet L, Quillet-Mary A, Laurent G, Garcia-Exposito L, Bournique E, Bergoglio V, Bose A, Récher C, Ysebaert L, Cazaux C, Hoffmann JS. Blood Cancer Barroso-Gonzalez J, Zhang S, Roncaioli JL, Lee M, Wallace J. 2016 Jun 3;6(6):e429. 3R gene expression in chronic CT, Watkins SC, Opresko PL, Hoffmann JS, O'Sullivan RJ. lymphocytic leukemia reveals insight into disease evolution. Cell Rep. 2016 Nov 8;17(7):1858-71. Proteomic Profiling Reveals a Specific Role for Translesion DNA Polymerase η Guenounou S, Borel C, Bérard E, Yon E, Fort M, in the Alternative Lengthening of Telomeres. Mengelle C, Bertoli S, Sarry A, Tavitian S, Huguet F, Attal M, Récher C, Huynh A. Medicine (Baltimore). 2016 Georgin-Lavialle S, Moura DS, Salvador A, Chauvet- Nov;95(48):e5356. Prognostic impact of viral reactivations in Gelinier JC, Launay JM, Damaj G, Côté F, Soucié E, acute myeloid leukemia patients undergoing allogeneic stem Chandesris MO, Barète S, Grandpeix-Guyodo C, Bachmeyer cell transplantation in first complete response. C, Alyanakian MA, Aouba A, Lortholary O, Dubreuil P, Teyssier JR, Trojak B, Haffen E, Vandel P, Bonin B; French Guggino G, Ciccia F, Di Liberto D, Lo Pizzo M, Ruscitti Mast Cell Study Group., Hermine O, Gaillard R. Mol P, Cipriani P, Ferrante A, Sireci G, Dieli F, Fourniè JJ, Psychiatry. 2016 Nov;21(11):1511-6. Mast cells' Giacomelli R, Triolo G. Clin Exp Immunol. 2016 involvement in inflammation pathways linked to depression: Dec;186(3):277-83. Interleukin (IL)-9/IL-9R axis drives γδ T evidence in mastocytosis. cells activation in psoriatic arthritis patients. Ghazavi F, De Moerloose B, Van Loocke W, Wallaert A, Guibert N, Mazieres J, Didier A, Porte SJ, Projetti F, Helsmoortel HH, Ferster A, Bakkus M, Plat G, Delabesse E, Hermant C. Ann Thorac Surg. 2016 Apr;101(4):1591-4. Uyttebroeck A, Van Nieuwerburgh F, Deforce D, Van Roy Tracheal Glomangioleiomyoma Treated by Multimodal N, Speleman F, Benoit Y, Lammens T, Van Vlierberghe P. Interventional Bronchoscopy. Oncotarget. 2016 Nov 8;7(45):73769-80. Unique long non- Guibert N, Mhanna L, Droneau S, Plat G, Didier A, coding RNA expression signature in ETV6/RUNX1-driven Mazieres J, Hermant C. J Thorac Dis. 2016 Nov;8(11):3343- B-cell precursor acute lymphoblastic leukemia. 60. Review. Techniques of endoscopic airway tumor Gilormini PA, Lion C, Vicogne D, Levade T, Potelle S, treatment. Mariller C, Guérardel Y, Biot C, Foulquier F. Chem Commun Guibert N, Pradines A, Casanova A, Farella M, Keller L, (Camb). 2016 Feb 7;52(11):2318-21. A sequential Soria JC, Favre G, Mazières J. J Thorac Oncol. 2016 bioorthogonal dual strategy: ManNAl and SiaNAl as distinct Sep;11(9):e109-12. Detection and Monitoring of the BRAF tools to unravel sialic acid metabolic pathways. Mutation in Circulating Tumor Cells and Circulating Tumor Goichot B, Caron P, Landron F, Bouée S. Clin Endocrinol DNA in BRAF-Mutated Lung Adenocarcinoma. (Oxf). 2016 Mar;84(3):445-51. Clinical presentation of Guibert N, Pradines A, Farella M, Casanova A, Gouin S, hyperthyroidism in a large representative sample of Keller L, Favre G, Mazieres J. Lung Cancer. 2016 Oct;100:1- outpatients in France: relationships with age, aetiology and 4. Monitoring KRAS mutations in circulating DNA and hormonal parameters. tumor cells using digital droplet PCR during treatment of Goldbrunner R, Minniti G, Preusser M, Jenkinson MD, KRAS-mutated lung adenocarcinoma. Sallabanda K, Houdart E, von Deimling A, Stavrinou P, Guillaume M, Robic MA, Péron JM, Selves J, Otal P, Lefranc F, Lund-Johansen M, Moyal EC, Brandsma D, Sirach E, Vinel JP, Bureau C. Eur J Gastroenterol Hepatol. Henriksson R, Soffietti R, Weller M. EANO guidelines for 2016 Nov;28(11):1268-74. Clinical characteristics and the diagnosis and treatment of meningiomas. Lancet Oncol. outcome of cirrhotic patients with high protein concentrations 2016 Sep;17(9):e383-91. Review. in ascites: a prospective study. Gouazé-Andersson V, Delmas C, Taurand M, Martinez- Guinault D, Canet E, Huart A, Jaccard A, Ribes D, Gala J, Evrard S, Mazoyer S, Toulas C, Cohen-Jonathan- Lavayssiere L, Venot M, Cointault O, Roussel M, Nogier Moyal E. Cancer Res. 2016 May 15;76(10):3036-44. FGFR1 MB, Pichereau C, Lemiale V, Arnulf B, Attal M, Chauveau Induces Glioblastoma Radioresistance through the D, Azoulay E, Faguer S. Br J Haematol. 2016 PLCγ/Hif1α Pathway. Sep;174(6):868-75. Short- and long-term outcomes of AL Goullet de Rugy T, Bashkurov M, Datti A, Betous R, amyloidosis patients admitted into intensive care units. Guitton-Sert L, Cazaux C, Durocher D, Hoffmann JS. Biol Gyan E, Andrieu V, Sanna A, Caille A, Schemenau J, Open. 2016 Oct 15;5(10):1485-92. Excess Polθ functions in Sudaka I, Siguret V, Malet M, Park S, Bordessoule D, Mairesse J, Gelsi-Boyer V, Cheze S, Beyne-Rauzy O, Sébert
[61]
M, Sapena R, Zerazhi H, Legros L, Guerci-Bresler A, Amé Grandchamp B, Andrieu-Abadie N, Thomas L, Brice A, SN, Germing U, Santini V, Salvi F, Gioia D, Lunghi M, Dumaz N, Soufir N. J Natl Cancer Inst. 2016 Mars;108(3) Dreyfus F, Fenaux P; Groupe Francophone des djv340. PARKIN Inactivation Links Parkinson's Disease to Myélodysplasies, Fondazione Italiana per le Sindromi Melanoma. Mielodisplastiche (FISMonlus), and Düsseldorf MDS Registry.. Br J Haematol. 2016 Dec;175(5):975-9. Hurlot Q, Fillaux J, Laurent C, Berry A, Hofman P, Myelodysplastic syndromes with single neutropenia or Marchou B, Delobel P, Brousset P, Martin-Blondel G. thrombocytopenia are rarely refractory cytopenias with Medicine (Baltimore). 2016 Jul;95(29):e3932. A case report unilineage dysplasia by World Health Organization 2008 of isolated lymphadenopathy revealing localized leishmanial criteria and have favourable prognosis. lymphadenopathy in an asthenic 25-year-old man. Halabi NM, Martinez A, Al-Farsi H, Mery E, Puydenus Husseini F, Delord JP, Fournel-Federico C, Guitton J, L, Pujol P, Khalak HG, McLurcan C, Ferron G, Querleu D, Erbs P, Homerin M, Halluard C, Jemming C, Orange C, Al-Azwani I, Al-Dous E, Mohamoud YA, Malek JA, Rafii A. Limacher JM, Kurtz JE. Ann Oncol. 2016 Sep 29. pii: PLoS Genet. 2016 Jan 6;12(1):e1005755. Preferential Allele mdw440. Vectorized Gene Therapy of Liver Tumors: Proof Expression Analysis Identifies Shared Germline and Somatic of Concept of TG4023 (MVA-FCU1) in Combination with Driver Genes in Advanced Ovarian Cancer. Erratum in: PLoS Flucytosine. Genet. 2016 Feb;12(2):e1005892. Imbs DC, Diéras V, Bachelot T, Campone M, Isambert Hamouda MA, Jacquel A, Robert G, Puissant A, Richez N, Joly F, Jimenez M, Lafont T, Chatelut E. Cancer V, Cassel R, Fenouille N, Roulland S, Gilleron J, Griessinger Chemother Pharmacol. 2016 Feb;77(2):385-92. E, Dubois A, Bailly-Maitre B, Goncalves D, Mallavialle A, Pharmacokinetic interaction between pazopanib and cisplatin Colosetti P, Marchetti S, Amiot M, Gomez-Bougie P, Rochet regimen. N, Deckert M, Avet-Loiseau H, Hofman P, Karsenti JM, Imbs DC, Paludetto MN, Négrier S, Powell H, Lafont T, Jeandel PY, Blin-Wakkach C, Nadel B, Cluzeau T, Anderson White-Koning M, Chatelut E, Thomas F. Invest New Drugs. KC, Fuzibet JG, Auberger P, Luciano F. J Exp Med. 2016 2016 Feb;34(1):41-8. Determination of unbound fraction of Aug 22;213(9):1705-22. BCL-B (BCL2L10) is pazopanib in vitro and in cancer patients reveals albumin as overexpressed in patients suffering from multiple myeloma the main binding site. (MM) and drives an MM-like disease in transgenic mice. Jacot W, Pons E, Frenel JS, Guiu S, Levy C, Heudel PE, Hanoun N, Gayral M, Pointreau A, Buscail L, Cordelier Bachelot T, D'Hondt V, Darlix A, Firmin N, Romieu G, P. Hum Gene Ther. 2016 Feb;27(2):184-92. Initial Thezenas S, Dalenc F. Breast Cancer Res Treat. 2016 Characterization of Integrase-Defective Lentiviral Vectors Jun;157(2):307-18. Efficacy and safety of trastuzumab for Pancreatic Cancer Gene Therapy. emtansine (T-DM1) in patients with HER2-positive breast Hardonnière K, Saunier E, Lemarié A, Fernier M, Gallais cancer with brain metastases. I, Héliès-Toussaint C, Mograbi B, Antonio S, Bénit P, Rustin Jacquelot N, Roberti MP, Enot DP, Rusakiewicz S, P, Janin M, Habarou F, Ottolenghi C, Lavault MT, Benelli C, Semeraro M, Jégou S, Flores C, Chen L, Kwon BS, Borg C, Sergent O, Huc L, Bortoli S, Lagadic-Gossmann D. Sci Rep. Weide B, Aubin F, Dalle S, Kohrt H, Ayyoub M, Kroemer G, 2016 Aug 4;6:30776. The environmental carcinogen Marabelle A, Cavalcanti A, Eggermont A, Zitvogel L. J benzo[a]pyrene induces a Warburg-like metabolic Invest Dermatol. 2016 May;136(5):994-1001. reprogramming dependent on NHE1 and associated with cell Immunophenotyping of Stage III Melanoma Reveals survival. Parameters Associated with Patient Prognosis. Hardy JM, Marguery MC, Huynh A, Borel C, Apoil PA, Joffre C, Codogno P, Fanto M, Hergovich A, Camonis J. Lamant L, Tournier E, Alberto C, Pauwels C, Thomas M, Autophagy. 2016;12(3):594-5. STK38 at the crossroad Mazereeuw Hautier J, Paul C, Bulai Livideanu C. between autophagy and apoptosis. Photodermatol Photoimmunol Photomed. 2016 Sep;32(5- 6):291-5. Photo-induced graft-versus-host disease. Jungas T, Perchey RT, Fawal M, Callot C, Froment C, Burlet-Schiltz O, Besson A, Davy A. J Cell Biol. 2016 Aug Havelange V, Ameye G, Théate I, Callet-Bauchu E, 29;214(5):555-69. Eph-mediated tyrosine phosphorylation of Lippert E, Luquet I, Raphaël M, Vikkula M, Poirel HA. citron kinase controls abscission. Cancer Genet. 2016 Mar;209(3):117-8. The peculiar 11q- gain/loss aberration reported in a subset of MYC-negative Kamoun A, Idbaih A, Dehais C, Elarouci N, Carpentier high-grade B-cell lymphomas can also occur in a MYC- C, Letouzé E, Colin C, Mokhtari K, Jouvet A, Uro-Coste E, rearranged lymphoma. Martin-Duverneuil N, Sanson M, Delattre JY, Figarella- Branger D, de Reyniès A, Ducray F; POLA network.. Nat Hodi FS, Chesney J, Pavlick AC, Robert C, Grossmann Commun. 2016 Apr 19;7:11263. Integrated multi-omics KF, McDermott DF, Linette GP, Meyer N, Giguere JK, analysis of oligodendroglial tumours identifies three Agarwala SS, Shaheen M, Ernstoff MS, Minor DR, Salama subgroups of 1p/19q co-deleted gliomas. AK, Taylor MH, Ott PA, Horak C, Gagnier P, Jiang J, Wolchok JD, Postow MA. Lancet Oncol. 2016 Kassem S, Gaud G, Bernard I, Benamar M, Dejean AS, Nov;17(11):1558-68. Combined nivolumab and ipilimumab Liblau R, Fournié GJ, Colacios C, Malissen B, Saoudi A. versus ipilimumab alone in patients with advanced PLoS Genet. 2016 Jul 20;12(7):e1006185. A Natural Variant melanoma: 2-year overall survival outcomes in a multicentre, of the T Cell Receptor-Signaling Molecule Vav1 Reduces randomised, controlled, phase 2 trial. Both Effector T Cell Functions and Susceptibility to Neuroinflammation. Hu HH, Kannengiesser C, Lesage S, André J, Mourah S, Michel L, Descamps V, Basset-Seguin N, Bagot M, Kepenekian V, Elias D, Passot G, Mery E, Goere D, Bensussan A, Lebbé C, Deschamps L, Saiag P, Leccia MT, Delroeux D, Quenet F, Ferron G, Pezet D, Guilloit JM, Meeus Bressac-de-Paillerets B, Tsalamlal A, Kumar R, Klebe S, P, Pocard M, Bereder JM, Abboud K, Arvieux C, Brigand C,
[62]
Marchal F, Classe JM, Lorimier G, De Chaisemartin C, ventriculography for the assessment of left and right Guyon F, Mariani P, Ortega-Deballon P, Isaac S, Maurice C, ventricular volumes and function in patients with left Gilly FN, Glehen O; French Network for Rare Peritoneal ventricular assist devices. Malignancies (RENAPE).. Eur J Cancer. 2016 Sep;65:69-79. Diffuse malignant peritoneal mesothelioma: Evaluation of Lamaa A, Le Bras M, Skuli N, Britton S, Frit P, Calsou systemic chemotherapy with comprehensive treatment P, Prats H, Cammas A, Millevoi S. EMBO Rep. 2016 through the RENAPE Database: Multi-Institutional Apr;17(4):508-18. A novel cytoprotective function for the Retrospective Study. DNA repair protein Ku in regulating p53 mRNA translation and function. Khalifa J, Duprez-Paumier R, Filleron T, Lacroix Triki M, Jouve E, Dalenc F, Massabeau C. Breast J. 2016 Lamy S, Bettiol C, Grosclaude P, Compaci G, Albertus Sep;22(5):510-9. Paclitaxel plus bevacizumab or paclitaxast G, Récher C, Nogaro JC, Despas F, Laurent G, Delpierre C. Cancer with or without Lymph Node Irradiation: A Single BMC Health Serv Res. 2016 Aug 2;16(a):336. The care Institution Experience. center influences the management of lymphoma patients in a universal health care system: an observational cohort study. Khalifa J, Tensaouti F, Chaltiel L, Lotterie JA, Catalaa I, Sunyach MP, Ibarrola D, Noël G, Truc G, Walker P, Magné Larrue C, Saland E, Boutzen H, Vergez F, David M, N, Charissoux M, Ken S, Peran P, Berry I, Moyal EC, Laprie Joffre C, Hospital MA, Tamburini J, Delabesse E, Manenti S, A. Eur Radiol. 2016 Nov;26(11):4194-203. Identification of Sarry JE, Récher C. Blood. 2016 Feb 18;127(7):882-92. a candidate biomarker from perfusion MRI to anticipate Proteasome inhibitors induce FLT3-ITD degradation through glioblastoma progression after chemoradiation. autophagy in AML cells. Khalifa J, Tensaouti F, Lotterie JA, Catalaa I, Chaltiel L, Laruelo A, Chaari L, Tourneret JY, Batatia H, Ken S, Benouaich-Amiel A, Gomez-Roca C, Noël G, Truc G, Péran Rowland B, Ferrand R, Laprie A. NMR Biomed. 2016 P, Berry I, Sunyach MP, Charissoux M, Johnson C, Cohen- Jul;29(7):918-31. Spatio-spectral regularization to improve Jonathan Moyal E, Laprie A. J Neurooncol. 2016 magnetic resonance spectroscopic imaging quantification. Oct;130(1):181-92. Do perfusion and diffusion MRI predict Laubach J, Garderet L, Mahindra A, Gahrton G, Caers J, glioblastoma relapse sites following chemoradiation? Sezer O, Voorhees P, Leleu X, Johnsen HE, Streetly M, Khallouki F, de Medina P, Caze-Subra S, Bystricky K, Jurczyszyn A, Ludwig H, Mellqvist UH, Chng WJ, Pilarski Balaguer P, Poirot M, Silvente-Poirot S. Front Oncol. 2016 L, Einsele H, Hou J, Turesson I, Zamagni E, Chim CS, Jan 5;5:287. Molecular and Biochemical Analysis of the Mazumder A, Westin J, Lu J, Reiman T, Kristinsson S, Estrogenic and Proliferative Properties of Vitamin E Joshua D, Roussel M, O'Gorman P, Terpos E, McCarthy P, Compounds. Dimopoulos M, Moreau P, Orlowski RZ, Miguel JS, Anderson KC, Palumbo A, Kumar S, Rajkumar V, Durie B, Klionsky DJ, et al. Autophagy. 2016;12(1):1-222. Richardson PG. Leukemia. 2016 May;30(5):1005-17. Guidelines for the use and interpretation of assays for Management of relapsed multiple myeloma: monitoring autophagy (3rd edition). Erratum in: Autophagy. recommendations of the International Myeloma Working 2016;12(2):443. Selliez, Iban [corrected to Seiliez, Iban]. Group. Kosmider O, Passet M, Santini V, Platzbecker U, Andrieu Laurent C, Delas A, Gaulard P, Haioun C, Moreau A, V, Zini G, Beyne-Rauzy O, Guerci A, Masala E, Balleari E, Xerri L, Traverse-Glehen A, Rousset T, Quintin-Roue I, Bulycheva E, Dreyfus F, Fenaux P, Fontenay M, Park S; Petrella T, Emile JF, Amara N, Rochaix P, Chenard-Neu MP, GFM, FISM AND D-MDS.. Haematologica. 2016 Tasei AM, Menet E, Chomarat H, Costes V, Andrac-Meyer Jul;101(7):e280-3. Are somatic mutations predictive of L, Michiels JF, Chassagne-Clement C, de Leval L, Brousset response to erythropoiesis stimulating agents in lower risk P, Delsol G, Lamant L. Ann Oncol. 2016 Feb;27(2):306-14. myelodysplastic syndromes? Breast implant-associated anaplastic large cell lymphoma: two distinct clinicopathological variants with different Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, outcomes. Moreau P, Munshi N, Lonial S, Bladé J, Mateos MV, Dimopoulos M, Kastritis E, Boccadoro M, Orlowski R, Laurent C, Fabiani B, Do C, Tchernonog E, Cartron G, Goldschmidt H, Spencer A, Hou J, Chng WJ, Usmani SZ, Gravelle P, Amara N, Malot S, Palisoc MM, Copie-Bergman Zamagni E, Shimizu K, Jagannath S, Johnsen HE, Terpos E, C, Glehen AT, Copin MC, Brousset P, Pittaluga S, Jaffe ES, Reiman A, Kyle RA, Sonneveld P, Richardson PG, McCarthy Coppo P. Haematologica. 2016 Aug;101(8):976-84. Immune- P, Ludwig H, Chen W, Cavo M, Harousseau JL, Lentzsch S, checkpoint expression in Epstein-Barr virus positive and Hillengass J, Palumbo A, Orfao A, Rajkumar SV, San Miguel negative plasmablastic lymphoma: a clinical and pathological J, Avet-Loiseau H. Lancet Oncol. 2016 Aug;17(8):e328-46. study in 82 patients. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple Laurent V, Guérard A, Mazerolles C, Le Gonidec S, myeloma. Toulet A, Nieto L, Zaidi F, Majed B, Garandeau D, Socrier Y, Golzio M, Cadoudal T, Chaoui K, Dray C, Monsarrat B, Lacroix J, Pélofy S, Blatché C, Pillaire MJ, Huet S, Schiltz O, Wang YY, Couderc B, Valet P, Malavaud B, Chapuis C, Hoffmann JS, Bancaud A. Small. 2016 Muller C. Nat Commun. 2016 Jan 12;7:10230. Periprostatic Nov;12(43):5963-70. Analysis of DNA Replication by adipocytes act as a driving force for prostate cancer Optical Mapping in Nanochannels. progression in obesity. Lairez O, Delmas C, Fournier P, Cassol E, Méjean S, Le Bris Y, Struski S, Guièze R, Rouvellat C, Prade N, Pascal P, Petermann A, Dambrin C, Minville V, Carrié D, Troussard X, Tournilhac O, Béné MC, Delabesse E, Ysebaert Rousseau H, Galinier M, Roncalli J, Marcheix B, Berry I. J L. Hematol Oncol. 2016 Sep 28. Major prognostic value of Nucl Cardiol. 2016 Nov 30. Feasibility and accuracy of gated complex karyotype in addition to TP53 and IGHV mutational blood pool SPECT equilibrium radionuclide status in first-line chronic lymphocytic leukemia.
[63]
Leca J, Martinez S, Lac S, Nigri J, Secq V, Rubis M, Luquet I, Bidet A, Cuccuini W, Lafage-Pochitaloff M, Bressy C, Sergé A, Lavaut MN, Dusetti N, Loncle C, Roques Mozziconacci MJ, Terré C. Ann Biol Clin (Paris). 2016 Oct J, Pietrasz D, Bousquet C, Garcia S, Granjeaud S, Ouaissi M, 1;74(5):535-46. Review. Cytogenetics in the management of Bachet JB, Brun C, Iovanna JL, Zimmermann P, Vasseur S, acute myeloid leukemia: an update by the Groupe Tomasini R. J Clin Invest. 2016 Nov 1;126(11):4140-56. francophone de cytogénétique hématologique (GFCH). Cancer-associated fibroblast-derived annexin A6+ extracellular vesicles support pancreatic cancer Magrangeas F, Kuiper R, Avet-Loiseau H, Gouraud W, aggressiveness. Guérin-Charbonnel C, Ferrer L, Aussem A, Elghazel H, Suhard J, Der Sakissian H, Attal M, Munshi NC, Sonneveld Lefebvre C, Bachelot T, Filleron T, Pedrero M, Campone P, Dumontet C, Moreau P, van Duin M, Campion L, M, Soria JC, Massard C, Lévy C, Arnedos M, Lacroix-Triki Minvielle S. Clin Cancer Res. 2016 Sep 1;22(17):4350-5. A M, Garrabey J, Boursin Y, Deloger M, Fu Y, Commo F, Scott Genome-Wide Association Study Identifies a Novel Locus V, Lacroix L, Dieci MV, Kamal M, Diéras V, Gonçalves A, for Bortezomib-Induced Peripheral Neuropathy in European Ferrerro JM, Romieu G, Vanlemmens L, Mouret Reynier Patients with Multiple Myeloma. MA, Théry JC, Le Du F, Guiu S, Dalenc F, Clapisson G, Bonnefoi H, Jimenez M, Le Tourneau C, André F. PLoS Med. Malcolm TI, Villarese P, Fairbairn CJ, Lamant L, 2016 Dec 27;13(12):e1002201. Mutational Profile of Trinquand A, Hook CE, Burke GA, Brugières L, Hughes K, Metastatic Breast Cancers: A Retrospective Analysis. Payet D, Merkel O, Schiefer AI, Ashankyty I, Mian S, Wasik M, Turner M, Kenner L, Asnafi V, Macintyre E, Turner SD. Leguellec S, Tournier E, Karanian M, Brousset P, Nat Commun. 2016 Jan 12;7:10087. Anaplastic large cell Mazereeuw J, Coindre JM, Lamant L. Histopathology. 2016 lymphoma arises in thymocytes and requires transient TCR Jan;68(2):297-302. Cutaneous inflammatory myofibroblastic expression for thymic egress. tumours can be anaplastic lymphoma kinase-positive: report of the first four cases. Manfredi L, Meyer N, Tournier E, Grand D, Uro-Coste E, Rochaix P, Brousset P, Lamant L. Acta Derm Venereol. Lena H, Rizvi NA, Wolf J, Cappuzzo F, Zalcman G, Baas 2016 Jun 15;96(5):630-4. Highly Concordant Results P, Mazieres J, Farsaci B, Blackwood-Chirchir MA, Between Immunohistochemistry and Molecular Testing of Ramalingam S. J Thorac Oncol. 2016 Apr;11(4 Suppl):S115- Mutated V600E BRAF in Primary and Metastatic Melanoma. 6. 137O: Nivolumab in patients (pts) with advanced refractory squamous (SQ) non-small cell lung cancer Manfredi L, Uro-Coste E, Brousset P. Hum Pathol. 2016 (NSCLC): 2-year follow-up from CheckMate 063 and Jun;52:197-8. Anti-CD8 (SP57) rabbit monoclonal antibody exploratory cytokine profling analyses. is a useful tool for detecting Toxoplasma gondii on formalin- fixed, paraffin-embedded tissue sections. Levade M, Severin S, Gratacap MP, Ysebaert L, Payrastre B. Curr Pharm Des. 2016;22(16):2315-22. Mansilla SF, Bertolin AP, Bergoglio V, Pillaire MJ, Targeting Kinases in Cancer Therapies: Adverse Effects on González Besteiro MA, Luzzani C, Miriuka SG, Cazaux C, Blood Platelets. Hoffmann JS, Gottifredi V. Elife. 2016 Oct 14;5. pii: e18020. Cyclin Kinase-independent role of p21CDKN1A in the Lévi FA, Boige V, Hebbar M, Smith D, Lepère C, Focan promotion of nascent DNA elongation in unstressed cells. C, Karaboué A, Guimbaud R, Carvalho C, Tumolo S, Innominato P, Ajavon Y, Truant S, Castaing D, De Baere T, Marabita M, Baraldo M, Solagna F, Ceelen JJ, Sartori R, Kunstlinger F, Bouchahda M, Afshar M, Rougier P, Adam R, Nolte H, Nemazanyy I, Pyronnet S, Kruger M, Pende M, Ducreux M; Association Internationale pour Recherche sur Blaauw B. Cell Rep. 2016 Oct 4;17(2):501-13. S6K1 Is Temps Biologique et Chronothérapie (ARTBC Required for Increasing Skeletal Muscle Force during International).. Ann Oncol. 2016 Feb;27(2):267-74. Hypertrophy. Conversion to resection of liver metastases from colorectal Marcatili S, Pichard A, Courteau A, Ladjohounlou R, cancer with hepatic artery infusion of combined Navarro-Teulon I, Repetto-Llamazares A, Heyerdahl H, chemotherapy and systemic cetuximab in multicenter trial Dahle J, Pouget JP, Bardiès M. Phys Med Biol. 2016 Oct OPTILIV. 7;61(19):6935-52. Realistic multi-cellular dosimetry for 177 Lhermusier T, Severin S, Van Rothem J, Garcia C, Lu-labelled antibodies: model and application. Bertrand-Michel J, Le Faouder P, Hechler B, Broccardo C, Marinello J, Bertoncini S, Aloisi I, Cristini A, Malagoli Couvert P, Chimini G, Sié P, Payrastre B. J Thromb Haemost. Tagliazucchi G, Forcato M, Sordet O, Capranico G. PLoS 2016 Mar;14(3):585-95. ATP-binding cassette transporter 1 One. 2016 Jan 19;11(1):e0147053. Dynamic Effects of (ABCA1) deficiency decreases platelet reactivity and reduces Topoisomerase I Inhibition on R-Loops and Short Transcripts thromboxane A2 production independently of hematopoietic at Active Promoters. ABCA1. Mazières J, Barlesi F, Filleron T, Besse B, Monnet I, Loiseau C, Requena M, Mavigner M, Cazabat M, Carrere Beau-Faller M, Peters S, Dansin E, Früh M, Pless M, Rosell N, Suc B, Barange K, Alric L, Marchou B, Massip P, Izopet R, Wislez M, Fournel P, Westeel V, Cappuzzo F, Cortot A, J, Delobel P. Mucosal Immunol. 2016 Sep;9(5):1137-50. Moro-Sibilot D, Milia J, Gautschi O. Ann Oncol. 2016 CCR6(-) regulatory T cells blunt the restoration of gut Th17 Feb;27(2):281-6. Lung cancer patients with HER2 mutations cells along the CCR6-CCL20 axis in treated HIV-1-infected treated with chemotherapy and HER2-targeted drugs: results individuals. from the European EUHER2 cohort. Loncle C, Bonjoch L, Folch-Puy E, Lopez-Millan MB, Mazières J, Merlio JP, Missy P, Moro-Sibilot D, Barlesi Lac S, Molejon MI, Chuluyan E, Cordelier P, Dubus P, F. Lancet. 2016 Sep 10;388(10049):1054-5. Routine Lomberk G, Urrutia R, Closa D, Iovanna JL. Cancer Res. molecular profiling of patients with NSCLC - Authors' reply. 2016 Apr 1;76(7):2051. REG3β Plays a Key Role in IL17RA Protumoral Effect-Response. Mazzolini L, Broban A, Froment C, Burlet-Schiltz O, Besson A, Manenti S, Dozier C. Cell Cycle. 2016 Oct
[64]
17;15(20):2742-52. Phosphorylation of CDC25A on SER283 Moulis G, Germain J, Adoue D, Beyne-Rauzy O, in late S/G2 by CDK/cyclin complexes accelerates mitotic Derumeaux H, Sailler L, Lapeyre-Mestre M. Eur J Intern entry. Med. 2016 Jul;32:e21-2. Validation of immune thrombocytopenia diagnosis code in the French hospital Mbatchi LC, Robert J, Ychou M, Boyer JC, Del Rio M, electronic database. Gassiot M, Thomas F, Tubiana N, Evrard A. Clin Pharmacokinet. 2016 Sep;55(9):1145-57. Effect of Single Moutel S, Bery N, Bernard V, Keller L, Lemesre E, de Nucleotide Polymorphisms in the Xenobiotic-sensing Marco A, Ligat L, Rain JC, Favre G, Olichon A, Perez F. Receptors NR1I2 and NR1I3 on the Pharmacokinetics and Elife. 2016 Jul 19;5. pii: e16228. NaLi-H1: A universal Toxicity of Irinotecan in Colorectal Cancer Patients. synthetic library of humanized nanobodies providing highly functional antibodies and intrabodies. Menguy S, Gros A, Pham-Ledard A, Battistella M, Ortonne N, Comoz F, Balme B, Szablewski V, Lamant L, Mrad M, Imbert C, Garcia V, Rambow F, Therville N, Carlotti A, Lorton MH, de Muret A, Le Gall F, Franck F, Carpentier S, Ségui B, Levade T, Azar R, Marine JC, Diab- Croue A, Cappellen D, Beylot-Barry M, Merlio JP, Vergier Assaf M, Colacios C, Andrieu-Abadie N. Oncotarget. 2016 B. J Invest Dermatol. 2016 Aug;136(8):1741-4. MYD88 Nov 1;7(44):71873-86. Downregulation of sphingosine Somatic Mutation Is a Diagnostic Criterion in Primary kinase-1 induces protective tumor immunity by promoting Cutaneous Large B-Cell Lymphoma. M1 macrophage response in melanoma. Meunier G, Ysebaert L, Nguyen-Thi PL, Lepretre S, Nguyen-Khac F, Daudignon A, Eclache V, Lafage- Quinquenel A, Dupuis J, Lemal R, Aurran T, Tomowiak C, Pochitaloff M, Lefebvre C, Luquet I, Penther D. Ann Biol Cymbalista F, Dilhuydy MS, Brion A, Morel P, Cazin B, Clin (Paris). 2016 Oct 1;74(5):509-10. Review. Cytogenetics Leblond V, Cartron G, Ré D, Béné MC, Michallet AS, in the management of hematologic malignancies: an update Feugier P. Hematol Oncol. 2016 Nov 22. First-line therapy by the Groupe francophone de cytogénétique hématologique for chronic lymphocytic leukemia in patients older than (GFCH). 79 years is feasible and achieves good results: A FILO retrospective study. Ofaiche J, Lopez R, Bérard E, André A, Bulai-Livideanu C, Méresse T, Vairel BB, Grolleau JL, Paul C, Meyer N. Moatassim-Billah S, Duluc C, Samain R, Jean C, Perraud Dermatology. 2016;232(5):550-7. Surgical Treatment of A, Decaup E, Cassant-Sourdy S, Bakri Y, Selves J, Schmid Facial Basal Cell Carcinoma: Patient-Based Assessment of H, Martineau Y, Mathonnet M, Pyronnet S, Bousquet C. Clinical Outcome in a Prospective Cohort Study. Oncotarget. 2016 Jul 5;7(27):41584-98. Anti-metastatic potential of somatostatin analog SOM230: Indirect Paci A, Hescot S, Seck A, Jublanc C, Mercier L, Vezzosi pharmacological targeting of pancreatic cancer-associated D, Drui D, Quinkler M, Fassnacht M, Bruckert E, Lombès M, fibroblasts. Leboulleux S, Broutin S, Baudin E. Endocrinol Diabetes Metab Case Rep. 2016;2016:150135. Dyslipidemia causes Moreau P, Hulin C, Macro M, Caillot D, Chaleteix C, overestimation of plasma mitotane measurements. Roussel M, Garderet L, Royer B, Brechignac S, Tiab M, Puyade M, Escoffre M, Stoppa AM, Facon T, Pegourie B, Patat O, Pagin A, Siegfried A, Mitchell V, Chassaing N, Chaoui D, Jaccard A, Slama B, Marit G, Laribi K, Godmer P, Faguer S, Monteil L, Gaston V, Bujan L, Courtade-Saïdi M, Luycx O, Eisenmann JC, Allangba O, Dib M, Araujo C, Marcelli F, Lalau G, Rigot JM, Mieusset R, Bieth E. Am J Fontan J, Belhadj K, Wetterwald M, Dorvaux V, Fermand JP, Hum Genet. 2016 Aug 4;99(2):437-42. Truncating Mutations Rodon P, Kolb B, Glaisner S, Malfuson JV, Lenain P, Biron in the Adhesion G Protein-Coupled Receptor G2 Gene L, Planche L, Caillon H, Avet-Loiseau H, Dejoie T, Attal M. ADGRG2 Cause an X-Linked Congenital Bilateral Absence Blood. 2016 May 26;127(21):2569-74. VTD is superior to of Vas Deferens. VCD prior to intensive therapy in multiple myeloma: results Péron JM, Abravanel F, Guillaume M, Gérolami R, Nana of the prospective IFM2013-04 trial. J, Anty R, Pariente A, Renou C, Bureau C, Robic MA, Alric Moreau P, Masszi T, Grzasko N, Bahlis NJ, Hansson M, L, Vinel JP, Izopet J, Kamar N. Liver Int. 2016 Pour L, Sandhu I, Ganly P, Baker BW, Jackson SR, Stoppa Mar;36(3):328-33. Treatment of autochthonous acute AM, Simpson DR, Gimsing P, Palumbo A, Garderet L, Cavo hepatitis E with short-term ribavirin: a multicenter M, Kumar S, Touzeau C, Buadi FK, Laubach JP, Berg DT, retrospective study. Lin J, Di Bacco A, Hui AM, van de Velde H, Richardson PG; Phelip JM, Mineur L, De la Fouchardière C, Chatelut E, TOURMALINE-MM1 Study Group.. N Engl J Med. 2016 Quesada JL, Roblin X, Pezet D, Mendoza C, Buc E, Rivoire Apr 28;374(17):1621-34. Oral Ixazomib, Lenalidomide, and M. Ann Surg Oncol. 2016 Jul;23(7):2161-6. High Dexamethasone for Multiple Myeloma. Resectability Rate of Initially Unresectable Colorectal Liver Morfoisse F, Tatin F, Hantelys F, Adoue A, Helfer AC, Metastases After UGT1A1-Adapted High-Dose Irinotecan Cassant-Sourdy S, Pujol F, Gomez-Brouchet A, Ligat L, Combined with LV5FU2 and Cetuximab: A Multicenter Lopez F, Pyronnet S, Courty J, Guillermet-Guibert J, Marzi Phase II Study (ERBIFORT). S, Schneider RJ, Prats AC, Garmy-Susini BH. Cancer Res. Philippe C, Dubrac A, Quelen C, Desquesnes A, Van Den 2016 Aug 1;76(15):4394-405. Nucleolin Promotes Heat Berghe L, Ségura C, Filleron T, Pyronnet S, Prats H, Brousset Shock-Associated Translation of VEGF-D to Promote Tumor P, Touriol C. Sci Signal. 2016 May 3;9(426):ra44. PERK Lymphangiogenesis. mediates the IRES-dependent translational activation of Moschoi R, Imbert V, Nebout M, Chiche J, Mary D, mRNAs encoding angiogenic growth factors after ischemic Prebet T, Saland E, Castellano R, Pouyet L, Collette Y, Vey stress. N, Chabannon C, Recher C, Sarry JE, Alcor D, Peyron JF, Piaton E, Fabre M, Goubin-Versini I, Bretz-Grenier MF, Griessinger E. Blood. 2016 Jul 14;128(2):253-64. Protective Courtade-Saïdi M, Vincent S, Belleannée G, Thivolet F, mitochondrial transfer from bone marrow stromal cells to Boutonnat J, Debaque H, Fleury-Feith J, Vielh P, Egelé C, acute myeloid leukemic cells during chemotherapy.
[65]
Bellocq JP, Michiels JF, Cochand-Priollet B. Cytopathology. Rabeau A, Mazieres J, Hermant C, Projetti F, Didier A, 2016 Oct;27(5):359-68. Guidelines for May-Grünwald- Guibert N. J Bronchology Interv Pulmonol. 2016 Giemsa staining in haematology and non-gynaecological Oct;23(4):340-2. Bronchoscopic Multimodal Management of cytopathology: recommendations of the French Society of Tracheal Neurofibroma. Clinical Cytology (SFCC) and of the French Association for Quality Assurance in Anatomic and Cytologic Pathology Regenet N, Carrere N, Boulanger G, de Calan L, Humeau (AFAQAP). M, Arnault V, Kraimps JL, Mathonnet M, Pessaux P, Donatini G, Venara A, Christou N, Bachelier P, Hamy A, Pich C, Sarrabayrouse G, Teiti I, Mariamé B, Rochaix P, Mirallié E. Surgery. 2016 Mar;159(3):901-7. Is the 2-cm size Lamant L, Favre G, Maisongrosse V, Tilkin-Mariamé AF. Br cutoff relevant for small nonfunctioning pancreatic J Cancer. 2016 Jan 12;114(1):63-70. Melanoma-expressed neuroendocrine tumors: A French multicenter study. CD70 is involved in invasion and metastasis. Remon J, Girard N, Mazieres J, Dansin E, Pichon E, Pilorge S, Harel S, Ribrag V, Larousserie F, Willems L, Grellier L, Dubos C, Lindsay CR, Besse B. Lung Cancer. Franchi P, Legoff M, Biau D, Anract P, Roux C, Blanc- 2016 Jul;97:99-104. Sunitinib in patients with advanced Autran E, Delarue R, Gisselbrecht C, Ketterer N, Recher C, thymic malignancies: Cohort from the French RYTHMIC Bonnet C, Peyrade F, Haioun C, Tilly H, Salles G, Brice P, network. Lung Cancer. 2016 Nov;101:146. Erratum to Bouscary D, Deau B, Tamburini J. Leuk Lymphoma. 2016 "Sunitinib in patients with advanced thymic malignancies: Dec;57(12):2820-6. Primary bone diffuse large B-cell cohort from the French RYTHMIC network" [Lung Cancer, lymphoma: a retrospective evaluation on 76 cases from 97 (July 2016), 99-104]. French institutional and LYSA studies. Ribes D, Casemayou A, El Hachem H, Laurent C, Planchard D, Besse B, Groen HJ, Souquet PJ, Quoix E, Guilbeau-Frugier C, Vergez F, Tavitian S, Schanstra JP, Baik CS, Barlesi F, Kim TM, Mazieres J, Novello S, Rigas Chauveau D, Bascands JL, Ysebaert L, Faguer S. Clin Exp JR, Upalawanna A, D'Amelio AM Jr, Zhang P, Mookerjee B, Nephrol. 2016 Dec 26. Asymptomatic circulating T-cell clone Johnson BE. Lancet Oncol. 2016 Jul;17(7):984-93. cause renal polymorphic inflammatory fibrosis. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: Ribrag V, Koscielny S, Bosq J, Leguay T, Casasnovas O, an open-label, multicentre phase 2 trial. Fornecker LM, Recher C, Ghesquieres H, Morschhauser F, Girault S, Le Gouill S, Ojeda-Uribe M, Mariette C, Cornillon Planchard D, Kim TM, Mazieres J, Quoix E, Riely G, J, Cartron G, Verge V, Chassagne-Clément C, Dombret H, Barlesi F, Souquet PJ, Smit EF, Groen HJ, Kelly RJ, Cho BC, Coiffier B, Lamy T, Tilly H, Salles G. Lancet. 2016 Jun Socinski MA, Pandite L, Nase C, Ma B, D'Amelio A Jr, 11;387(10036):2402-11. Rituximab and dose-dense Mookerjee B, Curtis CM Jr, Johnson BE. Lancet Oncol. 2016 chemotherapy for adults with Burkitt's lymphoma: a May;17(5):642-50. Dabrafenib in patients with randomised, controlled, open-label, phase 3 trial. BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Riscal R, Schrepfer E, Arena G, Cissé MY, Bellvert F, Heuillet M, Rambow F, Bonneil E, Sabourdy F, Vincent C, Poirot M, Silvente-Poirot S. Biochem Soc Trans. 2016 Ait-Arsa I, Levade T, Thibaut P, Marine JC, Portais JC, Sarry Apr 15;44(2):631-7. Review. When cholesterol meets JE, Le Cam L, Linares LK. Mol Cell. 2016 Jun 16;62(6):890- histamine, it gives rise to dendrogenin A: a tumour suppressor 902. Chromatin-Bound MDM2 Regulates Serine Metabolism metabolite. and Redox Homeostasis Independently of p53. Poupot M, Turrin CO, Caminade AM, Fournié JJ, Attal Robles EF, Mena-Varas M, Barrio L, Merino-Cortes SV, M, Poupot R, Fruchon S. Nanomedicine. 2016 Balogh P, Du MQ, Akasaka T, Parker A, Roa S, Panizo C, Nov;12(8):2321-30. Poly(phosphorhydrazone) dendrimers: Martin-Guerrero I, Siebert R, Segura V, Agirre X, Macri- yin and yang of monocyte activation for human NK cell Pellizeri L, Aldaz B, Vilas-Zornoza A, Zhang S, Moody S, amplification applied to immunotherapy against multiple Calasanz MJ, Tousseyn T, Broccardo C, Brousset P, Campos- myeloma. Sanchez E, Cobaleda C, Sanchez-Garcia I, Fernandez-Luna JL, Garcia-Muñoz R, Pena E, Bellosillo B, Salar A, Baptista Puszkiel A, White-Koning M, Dupin N, Kramkimel N, MJ, Hernandez-Rivas JM, Gonzalez M, Terol MJ, Climent J, Thomas-Schoemann A, Noé G, Chapuis N, Vidal M, Ferrandez A, Sagaert X, Melnick AM, Prosper F, Oscier DG, Goldwasser F, Chatelut E, Blanchet B. Pharmacol Res. 2016 Carrasco YR, Dyer MJ, Martinez-Climent JA. Nat Commun. Nov;113(Pt A):709-718. Plasma vemurafenib exposure and 2016 Jun 14;7:11889. Homeobox NKX2-3 promotes pre-treatment hepatocyte growth factor level are two factors marginal-zone lymphomagenesis by activating B-cell contributing to the early peripheral lymphocytes depletion in receptor signalling and shaping lymphocyte dynamics. BRAF-mutated melanoma patients. Rolando M, Escoll P, Nora T, Botti J, Boitez V, Bedia C, Quelen C, Eloit Y, Noirot C, Bousquet M, Brousset P. Br Daniels C, Abraham G, Stogios PJ, Skarina T, Christophe C, J Haematol. 2016 Jun;173(5):788-90. RNA editing in acute Dervins-Ravault D, Cazalet C, Hilbi H, Rupasinghe TW, Tull myeloid leukaemia with normal karyotype. D, McConville MJ, Ong SY, Hartland EL, Codogno P, Quemener C, Baud J, Boyé K, Dubrac A, Billottet C, Levade T, Naderer T, Savchenko A, Buchrieser C. Proc Natl Soulet F, Darlot F, Dumartin L, Sire M, Grepin R, Daubon T, Acad Sci U S A. 2016 Feb 16;113(7):1901-6. Legionella Rayne F, Wodrich H, Couvelard A, Pineau R, Schilling M, pneumophila S1P-lyase targets host sphingolipid metabolism Castronovo V, Sue SC, Clarke K, Lomri A, Khatib AM, and restrains autophagy. Hagedorn M, Prats H, Bikfalvi A. Cancer Res. 2016 Nov Rougé Bugat ME, Dufossé V, Paul C, Oustric S, Meyer 15;76(22):6507-6519. Dual Roles for CXCL4 Chemokines N. J Eur Acad Dermatol Venereol. 2016 Dec;30(12):e192- and CXCR3 in Angiogenesis and Invasion of Pancreatic e194. Communicating information to the general practitioner: Cancer. the example of vemurafenib for metastatic melanoma.
[66]
Rougé Bugat ME, Omnes C, Delpierre C, Escourrou E, Sibaud V, Lebœuf NR, Roche H, Belum VR, Gladieff L, Boussier N, Oustric S, Delord JP, Bauvin E, Grosclaude P. Deslandres M, Montastruc M, Eche A, Vigarios E, Dalenc F, Support Care Cancer. 2016 Jun;24(6):2473-9. Primary care Lacouture ME. Eur J Dermatol. 2016 Oct 1;26(5):427-43. physicians and oncologists are partners in cancer Dermatological adverse events with taxane chemotherapy. announcement. Sibaud V, Meyer N, Lamant L, Vigarios E, Mazieres J, Rouyer M, Fourrier-Réglat A, Smith D, Becouarn Y, Delord JP. Curr Opin Oncol. 2016 Jul;28(4):254-63. Guimbaud R, Tubiana-Mathieu N, Robinson P, Jové J, Dermatologic complications of anti-PD-1/PD-L1 immune Grelaud A, Noize P, Moore N, Ravaud A. J Geriatr Oncol. checkpoint antibodies. 2016 May;7(3):187-94. Effectiveness and safety of first-line bevacizumab plus FOLFIRI in elderly patients with Sibaud V, Nougarolis S, Borjesson C, Gangloff D, Delord metastatic colorectal cancer: Results of the ETNA JP, Pompa V, Saintenac D, Roche H. J Eur Acad Dermatol observational cohort. Venereol. 2016 Jul;30(7):1235-6. T-DM1 extravasation: first description. Rouyer M, Smith D, Laurent C, Becouarn Y, Guimbaud R, Michel P, Tubiana-Mathieu N, Balestra A, Jové J, Sibaud V, Tournier E, Roché H, Del Giudice P, Delord Robinson P, Noize P, Moore N, Ravaud A, Fourrier-Réglat JP, Hubiche T. Clin Exp Dermatol. 2016 Jan;41(1):34-7. Late A; ETNA study group.. Target Oncol. 2016 Feb;11(1):83-92. epidermal growth factor receptor inhibitor-related Secondary Metastases Resection After Bevacizumab Plus papulopustular rash: a distinct clinical entity. Irinotecan-Based Chemotherapy in First-Line Therapy of Siegfried A, Bertozzi AI, Bourdeaut F, Sevely A, Loukh Metastatic Colorectal Cancer in a Real-Life Setting: Results N, Grison C, Miquel C, Lafon D, Sevenet N, Pietsch T, of the ETNA Cohort. Dufour C, Delisle MB. Clin Neuropathol. 2016 May- Royer B, Minvielle S, Diouf M, Roussel M, Karlin L, Jun;35(3):106-13. Clinical, pathological, and molecular data Hulin C, Arnulf B, Macro M, Cailleres S, Brion A, on desmoplastic/nodular medulloblastoma: case studies and a Brechignac S, Belhadj K, Chretien ML, Wetterwald M, review of the literature. Chaleteix C, Tiab M, Leleu X, Frenzel L, Garderet L, Silvente-Poirot S, de Medina P, Record M, Poirot M. Choquet S, Fuzibet JG, Dauriac C, Forneker LM, Benboubker Biochimie. 2016 Nov;130:109-14. Review. From tamoxifen L, Facon T, Moreau P, Avet-Loiseau H, Marolleau JP. J Clin to dendrogenin A: The discovery of a mammalian tumor Oncol. 2016 Jun 20;34(18):2125-32. Bortezomib, suppressor and cholesterol metabolite. Doxorubicin, Cyclophosphamide, Dexamethasone Induction Followed by Stem Cell Transplantation for Primary Plasma Sincennes MC, Humbert M, Grondin B, Lisi V, Veiga Cell Leukemia: A Prospective Phase II Study of the DF, Haman A, Cazaux C, Mashtalir N, Affar el B, Verreault Intergroupe Francophone du Myélome. A, Hoang T. Proc Natl Acad Sci U S A. 2016 Feb 2;113(5):1393-8. The LMO2 oncogene regulates DNA Sachchithanantham S, Roussel M, Palladini G, Klersy C, replication in hematopoietic cells. Mahmood S, Venner CP, Gibbs S, Gillmore J, Lachmann H, Hawkins PN, Jaccard A, Merlini G, Wechalekar AD. J Clin Sonneveld P, Avet-Loiseau H, Lonial S, Usmani S, Siegel Oncol. 2016 Jun 10;34(17):2037-45. European Collaborative D, Anderson KC, Chng WJ, Moreau P, Attal M, Kyle RA, Study Defining Clinical Profile Outcomes and Novel Caers J, Hillengass J, San Miguel J, van de Donk NW, Einsele Prognostic Criteria in Monoclonal Immunoglobulin M- H, Bladé J, Durie BG, Goldschmidt H, Mateos MV, Palumbo Related Light Chain Amyloidosis. A, Orlowski R. Blood. 2016 Jun 16;127(24):2955-62. Treatment of multiple myeloma with high-risk cytogenetics: Santin Y, Sicard P, Vigneron F, Guilbeau-Frugier C, a consensus of the International Myeloma Working Group. Dutaur M, Lairez O, Couderc B, Manni D, Korolchuk VI, Lezoualc'h F, Parini A, Mialet-Perez J. Antioxid Redox Stathis A, Zucca E, Bekradda M, Gomez-Roca C, Delord Signal. 2016 Jul 1;25(1):10-27. Oxidative Stress by JP, de La Motte Rouge T, Uro-Coste E, de Braud F, Pelosi G, Monoamine Oxidase-A Impairs Transcription Factor EB French CA. Cancer Discov. 2016 May;6(5):492-500. Clinical Activation and Autophagosome Clearance, Leading to Response of Carcinomas Harboring the BRD4-NUT Cardiomyocyte Necrosis and Heart Failure. Oncoprotein to the Targeted Bromodomain Inhibitor OTX015/MK-8628. Sauzay C, White-Koning M, Hennebelle I, Deluche T, Delmas C, Imbs DC, Chatelut E, Thomas F. Pharmacol Res. Szalat R, Avet-Loiseau H, Munshi NC. Clin Cancer Res. 2016 Aug;110:89-95. Inhibition of OCT2, MATE1 and 2016 Nov 15;22(22):5434-42. Gene Expression Profiles in MATE2-K as a possible mechanism of drug interaction Myeloma: Ready for the Real World? between pazopanib and cisplatin. Tabouret E, Nguyen AT, Dehais C, Carpentier C, Ducray Severino M, Chandesris MO, Barete S, Tournier E, Sans F, Idbaih A, Mokhtari K, Jouvet A, Uro-Coste E, Colin C, B, Laurent C, Apoil PA, Lamant L, Mailhol C, Laroche M, Chinot O, Loiseau H, Moyal E, Maurage CA, Polivka M, Fraitag S, Hanssens K, Dubreuil P, Hermine O, Paul C, Bulai Lechapt-Zalcman E, Desenclos C, Meyronet D, Delattre JY, Livideanu C. J Am Acad Dermatol. 2016 May;74(5):885- Figarella-Branger D; For POLA Network.. Acta Neuropathol. 91.e1. Telangiectasia macularis eruptiva perstans (TMEP): A 2016 Oct;132(4):625-34. Prognostic impact of the 2016 form of cutaneous mastocytosis with potential systemic WHO classification of diffuse gliomas in the French POLA involvement. cohort. Severino-Freire M, Sibaud V, Tournier E, Pauwels C, Taïeb D, Bournaud C, Eberle MC, Catargi B, Schvartz C, Christol C, Lamant L, Hautier-Mazeereuw J, Peron JM, Paul Cavarec MB, Faugeron I, Toubert ME, Benisvy D, Archange C, Bulai Livideanu C. J Eur Acad Dermatol Venereol. 2016 C, Mundler O, Caron P, Abdullah AE, Baumstarck K. Eur J Feb;30(2):328-30. Acquired perforating dermatosis Endocrinol. 2016 Apr;174(4):491-502. Quality of life, associated with sorafenib therapy. clinical outcomes and safety of early prophylactic levothyroxine administration in patients with Graves'
[67] hyperthyroidism undergoing radioiodine therapy: a microarray profiling reveals four stages of immune escape in randomized controlled study. non-Hodgkin lymphomas. Tavitian S, Denis A, Vergez F, Berard E, Sarry A, Huynh Tout M, Gagez AL, Leprêtre S, Gouilleux-Gruart V, A, Delabesse E, Luquet I, Huguet F, Récher C, Bertoli S. Am Azzopardi N, Delmer A, Mercier M, Ysebaert L, Laribi K, J Hematol. 2016 Feb;91(2):193-8. Impact of obesity in Gonzalez H, Paintaud G, Cartron G, Ternant D. Clin favorable-risk AML patients receiving intensive Pharmacokinet. 2016 Oct 25. Influence of FCGR3A-158V/F chemotherapy. Genotype and Baseline CD20 Antigen Count on Target- Mediated Elimination of Rituximab in Patients with Chronic Terrier LM, Bauchet L, Rigau V, Amelot A, Zouaoui S, Lymphocytic Leukemia: A Study of FILO Group. Filipiak I, Caille A, Almairac F, Aubriot-Lorton MH, Bergemer-Fouquet AM, Bord E, Cornu P, Czorny A, Dam Tramunt B, Buffet A, Grunenwald S, Vezzosi D, Bennet Hieu P, Debono B, Delisle MB, Emery E, Farah W, A, Huyghe E, Zerdoud S, Caron P. Clin Case Rep. 2016 Feb Gauchotte G, Godfraind C, Guyotat J, Irthum B, Janot K, Le 12;4(3):298-300. Local recurrence of pheochromocytoma in Reste PJ, Liguoro D, Loiseau H, Lot G, Lubrano V, multiple endocrine neoplasia type 2A: a diagnostic and Mandonnet E, Menei P, Metellus P, Milin S, Muckenstrum B, therapeutic challenge. Roche PH, Rousseau A, Uro-Coste E, Vital A, Voirin J, Wager M, Zanello M, François P, Velut S, Varlet P, Figarella- Tsao AS, Scagliotti GV, Bunn PA Jr, Carbone DP, Branger D, Pallud J, Zemmoura I; Club de Neuro-Oncologie Warren GW, Bai C, de Koning HJ, Yousaf-Khan AU, of the Société Française de Neurochirurgie.. Neuro Oncol. McWilliams A, Tsao MS, Adusumilli PS, Rami-Porta R, 2016 Aug 30. pii: now186. Natural course and prognosis of Asamura H, Van Schil PE, Darling GE, Ramalingam SS, anaplastic gangliogliomas: a multicenter retrospective study Gomez DR, Rosenzweig KE, Zimmermann S, Peters S, of 43 cases from the French Brain Tumor Database. Ignatius Ou SH, Reungwetwattana T, Jänne PA, Mok TS, Wakelee HA, Pirker R, Mazières J, Brahmer JR, Zhou Y, Thépot S, Ben Abdelali R, Chevret S, Renneville A, Herbst RS, Papadimitrakopoulou VA, Redman MW, Wynes Beyne-Rauzy O, Prébet T, Park S, Stamatoullas A, Guerci- MW, Gandara DR, Kelly RJ, Hirsch FR, Pass HI. J Thorac Bresler A, Cheze S, Tertian G, Choufi B, Legros L, Bastié JN, Oncol. 2016 May;11(5):613-38. Scientific Advances in Lung Delaunay J, Chaury MP, Sanhes L, Wattel E, Dreyfus F, Vey Cancer 2015. N, Chermat F, Preudhomme C, Fenaux P, Gardin C; Groupe Francophone des Myélodysplasies (GFM).. Haematologica. Turner SD, Lamant L, Kenner L, Brugières L. Br J 2016 Aug;101(8):918-25. A randomized phase II trial of Haematol. 2016 May;173(4):560-72. Anaplastic large cell azacitidine +/- epoetin-β in lower-risk myelodysplastic lymphoma in paediatric and young adult patients. syndromes resistant to erythropoietic stimulating agents. Ung M, Rouquette I, Filleron T, Taillandy K, Brouchet L, Thibault B, Clement E, Zorza G, Meignan S, Delord JP, Bennouna J, Delord JP, Milia J, Mazières J. Clin Lung Couderc B, Bailly C, Narducci F, Vandenberghe I, Cancer. 2016 Sep;17(5):391-7. Characteristics and Clinical Kruczynski A, Guilbaud N, Ferré P, Annereau JP. Cancer Outcomes of Sarcomatoid Carcinoma of the Lung. Lett. 2016 Jan 1;370(1):10-8. F14512, a polyamine- van de Donk NW, Moreau P, Plesner T, Palumbo A, Gay vectorized inhibitor of topoisomerase II, exhibits a marked F, Laubach JP, Malavasi F, Avet-Loiseau H, Mateos MV, anti-tumor activity in ovarian cancer. Sonneveld P, Lokhorst HM, Richardson PG. Blood. 2016 Feb Thomas F, Hennebelle I, Delmas C, Lochon I, Dhelens C, 11;127(6):681-95. Clinical efficacy and management of Garnier Tixidre C, Bonadona A, Penel N, Goncalves A, monoclonal antibodies targeting CD38 and SLAMF7 in Delord JP, Toulas C, Chatelut E. Clin Pharmacol Ther. 2016 multiple myeloma. Feb;99(2):235-42. Genotyping of a family with a novel Vassaux G, Angelova A, Baril P, Midoux P, Rommelaere deleterious DPYD mutation supports the pretherapeutic J, Cordelier P. Hum Gene Ther. 2016 Feb;27(2):127-33. screening of DPD deficiency with dihydrouracil/uracil ratio. Review. The Promise of Gene Therapy for Pancreatic Cancer. Thompson PA, Lévy V, Tam CS, Al Nawakil C, Goudot Verhoeyen E, Gomez S, Galy A, Ayuso E, Midoux P, FX, Quinquenel A, Ysebaert L, Michallet AS, Dilhuydy MS, Pucéat M, Vassaux G, Cordelier P. Hum Gene Ther. 2016 Van Den Neste E, Dupuis J, Keating MJ, Meune C, Jul;27(7):555-8. Twelfth Annual Meeting of the French Cymbalista F. Br J Haematol. 2016 Nov;175(3):462-6. Atrial Society of Cell and Gene Therapy. fibrillation in CLL patients treated with ibrutinib. An international retrospective study. Vey N, Delaunay J, Martinelli G, Fiedler W, Raffoux E, Prebet T, Gomez-Roca C, Papayannidis C, Kebenko M, Toma A, Kosmider O, Chevret S, Delaunay J, Paschka P, Christen R, Guarin E, Bröske AM, Baehner M, Stamatoullas A, Rose C, Beyne-Rauzy O, Banos A, Guerci- Brewster M, Walz AC, Michielin F, Runza V, Meresse V, Bresler A, Wickenhauser S, Caillot D, Laribi K, De Renzis B, Recher C. Oncotarget. 2016 May 31;7(22):32532-42. Phase I Bordessoule D, Gardin C, Slama B, Sanhes L, Gruson B, clinical study of RG7356, an anti-CD44 humanized antibody, Cony-Makhoul P, Chouffi B, Salanoubat C, Benramdane R, in patients with acute myeloid leukemia. Legros L, Wattel E, Tertian G, Bouabdallah K, Guilhot F, Taksin AL, Cheze S, Maloum K, Nimuboma S, Soussain C, Vieillevigne L, Bessieres S, Ouali M, Lanaspeze C. Phys Isnard F, Gyan E, Petit R, Lejeune J, Sardnal V, Renneville Med. 2016 Nov;32(11):1405-14. Dosimetric comparison of A, Preudhomme C, Fontenay M, Fenaux P, Dreyfus F. flattened and unflattened beams for stereotactic body Leukemia. 2016 Apr;30(4):897-905. Lenalidomide with or radiation therapy: Impact of the size of the PTV on dynamic without erythropoietin in transfusion-dependent conformal arc and volumetric modulated arc therapy. erythropoiesis-stimulating agent-refractory lower-risk MDS Villeneuve L, Thivolet A, Bakrin N, Mohamed F, Isaac without 5q deletion. S, Valette PJ, Glehen O, Rousset P; BIG-RENAPE and Tosolini M, Algans C, Pont F, Ycart B, Fournié JJ. RENAPE Working Groups.. Eur J Surg Oncol. 2016 Oncoimmunology. 2016 May 19;5(7):e1188246. Large-scale Jun;42(6):877-82. A new internet tool to report peritoneal
[68] malignancy extent. PeRitOneal MalIgnancy Stage Evaluation Intergroup (IFCT).. Lancet. 2016 Apr 2;387(10026):1405-14. (PROMISE) application. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study Volpin F, Casaos J, Sesen J, Mangraviti A, Choi J, (MAPS): a randomised, controlled, open-label, phase 3 trial. Gorelick N, Frikeche J, Lott T, Felder R, Scotland SJ, Erratum in: Lancet. 2016 Apr 2;387(10026):e24. Eisinger-Mathason TS, Brem H, Tyler B, Skuli N. Oncogene. 2016 Dec 12. Use of an anti-viral drug, Ribavirin, as an anti- Zitvogel L, Ayyoub M, Routy B, Kroemer G. Cell. 2016 glioblastoma therapeutic. Apr 7;165(2):276-87. Review. Microbiome and Anticancer Immunosurveillance. Zalcman G, Mazieres J, Margery J, Greillier L, Audigier- Valette C, Moro-Sibilot D, Molinier O, Corre R, Monnet I, Zitvogel L, Rusakiewicz S, Routy B, Ayyoub M, Gounant V, Rivière F, Janicot H, Gervais R, Locher C, Kroemer G. Nat Rev Clin Oncol. 2016 Jul;13(7):431-46. Milleron B, Tran Q, Lebitasy MP, Morin F, Creveuil C, Review. Immunological off-target effects of imatinib. Parienti JJ, Scherpereel A; French Cooperative Thoracic
[69]
Awards in 2016
Professor Michel Attal received the Griffuel Award from the Fondation ARC in 2016 for his work on the myeloma.
Scientific events
International symposium : Toulouse Onco Week 2016 (TOW 2016)
The scientific Symposium was part of a week programme – TOW 2016 - centered around the World Cancer Day, and was held in Toulouse on February 3-5, 2016. It included 6 sessions :
. Genetic instability & Cell cycle . Tumor biology & Stem cells Thomas Helleday (KI, Stockholm) Mariano Barbacid (CNIO, Madrid) Targeting DNA repair in cancer treatment Targeting k-ras driven lung and pancreatic tumors Marcos Malumbres (CNIO, Madrid) Craig Logsdon (MD Anderson, Houston) Targeting mitosis and mitotic exit in cancer Oncogenic ras and inflammation form a Oscar Fernandez-Capetillo (CNIO, Madrid) pathological partnership that transforms normal Targeting oncogene-induced replication stress for cells into cancer cancer therapy Dominik Rüttinger (Roche, Munich) Tumor-associated macrophages as therapeutic . Gene expression & Epigenetics target in oncology Mario Fraga Fernandez (CINN-CSIC, Oviedo) The role of 5-hydroxymethylcytosine in the . Immunity aberrant DNA methylation in cancer Jules Hoffmann (USIAS, Strasbourg) François Fuks (ULB, Bruxelles) Innate Immunity : from flies to humans Epigenetics and Epigenomics in Cancer Eric Vivier (CIML, Marseille) Eric Solary (IGR, Villejuif) Towards the manipulation of innate lymphoid Genetic and epigenetic insights in chronic cells in cancer myelomonocytic leukemia Benoit van den Eynde (Ludwig CR, Bruxelles) Restoring immune control of cancer progresses . Metabolism and challenges of cancer immunotherapy Jordan Virgil Craig (MD Anderson, Houston) Sex Steroid - Induced apoptosis in steroid . Health technologies deprived breast cancer : a general principal for Gerd Binning (LMU, Munich) breast, prostate and ovarian cancer treatment Tissue Phenomics – Characterizing the Immuno- strategies Tumor Ecosystem by a New Method Lewis Cantley (S&E Meyer Cancer Center) Peter Campbell (CRUK, Cambridge) Targeting PI 3-kinase for cancer therapy Interrogating the architecture of cancer genomes Stéphane De Botton (IGR, Villejuif) Mickael Tanter (Institut Langevin, Paris) Targeting isocitrate dehydrogenase (idh)1 and Breaking of Space and Time resolution Limits in idh2 mutations : clinical results in advanced Biomedical Ultrasound hematologic malignancies
The next international Symposium will be held on February 5-7, 2018 (Toulouse Onco Week 2018).
[70]
Seminars held in the CRCT
Thanks to its Scientific Committee, the CRCT organises many in-doors seminars. In 2016, 27 speakers were invited :
Françoise Pflumio (CEA, Paris) Erik Sahai (Francis Crick Institute, London) Investigating normal and leukemic hematopoiesis Cellular origin and mechanisms of pancreatic in humans with the SCL/TAL1 transcription factor cancer as a model of hematopoietic (dys)regulation Marie Cargnello (McGill University, Montreal) Serge Plaza (CBD– CBI, Toulouse) Dysregulation of mRNA translation and energy Deciphering the molecular Function of Pro small metabolism in neoplasia peptides encoded by a putative non coding RNA. Lessons from Drosophila studies Loïc Dupré (CPTP, Toulouse) Multi-scale exploration of migration in normal Juan Iovana (CRCM Marseille) and tumoral lymphoid cells "Vendredis de l'Oncopole" : Towards an individualized treatment for patients with a Raffaella Santoro (IVBMV, Zurich) pancreatic adenocarcinoma The epigenetics of prostate cancer : from molecular mechanisms to biomarker signature of Toshiro Okazaki (Kanazawa University, Japan) disease recurrence Role of ceramide in ataxia telangiectasia mutated (ATM)-related cell death in leukemia cells Laurent Nguyen (GIGA-Neurosciences, Liège) A dynamic unfolded protein response controls Vincent Cavaillès (IRCM Montpellier) cortical neurogenesis Transcriptional regulation of intestinal tumorigenesis by RIP140/NRIP1 Massimo Lopes (IMCR, Zurich) Replication fork remodelling upon replication François-Xavier Mahon (Institut Bergonié, stress in cancer and stem cells Bordeaux) « Les vendredis de l’oncopole » : Peut-on guérir la Patrick Jacquemin (Université de Duve) leucémie myéloïde chronique : données cliniques Molecular mechanisms involved in pancreatic cell et biologiques ? plasticity and cancer
Matthew Collin (Newcastle University) Lionel Larue (Institut Curie, Paris) Haematopoietic and immune defects associated β-catenin in the melanocyte lineage with GATA2 mutation
Mario Tschan (Institute of Pathology, Bern) Frédéric Chibon (Institut Bergonié, Bordeaux) Autophagy in retinoic acid therapy of acute Hétérogénéïté intra-tumorale et instabilité myeloid leukemia chromosomique des sarcomes pléomorphes : le couple moteur de l'oncogenèse ? Antonio Maraver (IRCM, Montpellier) Role of the Notch pathway in lung Patrick Mehlen (Léon Bérard, Lyon) adenocarcinoma : beyond the KrasG12V mouse The Dependance Receptor Notion : From a Cell model Death Paradigm to Alternative Anti-Cancer Therapies Cyrille Delpierre (UMR1027, Toulouse) Stress chronique depuis l'enfance et cancer à Thomas Pradeu (CIRID Bordeaux) l'âge adulte : quelles évidences ? "Les Vendredis de l'Oncopole" : Cancer & Therapeutics : A Philosophical Approach
[71]
Arnaud Vigneron (CRCL, Lyon) Esther Castellano (Barts Cancer Institute, London) A glucocorticoid-dependent metabolic program The many functions of RAS-PI3K signaling in lung supports cancer stem cell properties in breast cancer development cancer Els Verhoyen (CIRI, ENS Lyon) Fatima Mami-Chouaib (IGR, Villejuif) New lentiviral vector pseudotypes for gene of Rôle des cellules T mémoires résidentes dans le human hematopoietic healthy and cancer target tissu (Trm) dans la réponse immunitaire cells antitumorale : implication de l'intégrine CD103 Gareth Veal (University of Newcastle) Daniel Fisher (IG2M, Montpellier) Therapeutic Drug Monitoring and Clinical The cell proliferation antigen Ki-67 controls Pharmacology Studies in Paediatric Oncology - a heterochromatin organisation and tumorigenesis UK Experience but not cell proliferation
Ulf Nehrbass (Ksilink & FGTAC, Strasbourg) From Drugs to Genes : implementing target free approaches in Cancer drug discovery
CRCT Retreat, November 3-4, 2016
In 2016, the retreat was held at the Institut Universitaire du Cancer de Toulouse-Oncopole (IUCT-Oncopole). Following the introduction by the former Director, Jean-Jacques Fournié, and the current one, Gilles Favre, the published results and the work in progress were presented by the different teams. This event provided an opportunity to highlight the translational projects from the CRCT with the Comprehensive Cancer Center IUCT-Oncopole.
In 2017, the retreat will be held outside of Toulouse, as every other year.
[72]
Cancer Research Center of Toulouse (CRCT) UMR 1037 Inserm – Université Toulouse III Paul Sabatier ERL 5294 CNRS 2 avenue Hubert Curien 31037 Toulouse Cedex 1 France
Telephone : +33 (0)5 82 74 15 75 www.crct-inserm.fr