title: Cardiopulmonary Fitness and Its Clinical Determinants of a Population of Childhood Cancer Survivor: a Controlled Retrospective Study

acronym: ONCO-SPORT

summary:
Medical progress have made it possible to considerably improve the survival of children with an oncological disease. Currently, the survival rate increased to above 90 % in the most developed countries . This increase of childhood cancer survivors (CCS) asks us about their future and their quality of life. Assessing health related life quality , previous studies observe that in this particular population of patients, it is related to a poor physical capacity , physical activity level and many of these patients do not meet the activity level recommended by the world health organization due to fatigability and sedentary behaviours . In addition to these habits, the CCS are more susceptible to develop cardiovascular risk (CVR) leading to cardiovascular disease in adulthood and increases them mortality . Furthermore, CCS who have been experiencing hematopoietic stem cells transplantation (HSCT) are more susceptible to develop these CVR. In parallel with the common CVR, lower cardiopulmonary fitness assessed by cardiopulmonary exercise test (CPET) in the general population has been established as a major and independent CVR for cardiologic events.

Cardiopulmonary fitness assessed by maximal cardiopulmonary exercise test (CPET) allows physicians to measure metabolic response to maximal effort in a population that is known as VO2max. This domain of applied physiology permits a new way to approach the understanding of global health prognosis in chronic disease. For example, decrease of VO2max is involved in lower quality of life in patients with congenital heart disease. Cardiopulmonary exercise test for VO2max exploration has been demonstrated feasible in child patients with leukemia or other tumors after intensive chemotherapy, prior to HSCT.

Assessment of cardiopulmonary fitness in CCS is already described in previous studies, but this study aimed to compare a maximal CPET assessment on a large childhood cancer survivors cohort with healthy control, on a quite young cohort, during the oncologic follow up and find out its determinants.


title: Differential Vulnerability of Individual Thalamic Nuclei: Toward New Biomarkers in Multiple Sclerosis

acronym: THALNUC-MS

summary: The thalamus is composed of several nuclei interlocked in a complex anatomy. In multiple sclerosis (MS), the thalamus can be altered due to disconnection by white matter lesions and due to direct damages that could be partly mediated by CSF. Due to such pathophysiology and complex anatomy, some nuclei could be more vulnerable to multiple sclerosis than others. We will test this hypothesis by using a new algorithm to automatically segment several nuclei that we will be applied to the French national MS database

study_start_date_type: Actual

status: Recruiting

study_completion_date_type: Anticipated

study_type: Observational

time_perspective: Other

enrollment_type: Anticipated

lead_sponsor: University Hospital, Bordeaux

lead_sponsor_type: academique

status_simplified: Ongoing


title: Involvement of Polymorphonuclear Neutrophils and Platelets in Severe Form of COVID-19

acronym: NeutroVID

summary: The main objective is to quantify the population of reverse migrating neutrophils in patients with COVID-19.

time_perspective: Prospective

ipd_sharing: Undecided

lead_sponsor: Assistance Publique - Hôpitaux de Paris

location_facility: Intensive care department, Hôpital Saint Antoine


title: Set up a Community Online in a Virtual Community Game for Tobacco Prevention in Teenagers

acronym: SCOTT

summary:
The main objective of the SCOTT project is to reduce tobacco experimentation of teenagers through an online intervention based on social networking and empowerment of users.

Specific objectives of this emerging project are : 1. To develop or identify an online community dedicated to teenagers where the investigators will develop anti-smoking skills and norms. It will be based on social cognitive theory and will combine multiple functionalities based on the current practices and preferences of adolescents on internet and mobile; ensuring user safety, regulatory and ethical issues ; 2. To analyse the adoption, acceptance and the usability of SCOTT among users in a limited scale 3.To develop SCOTT process and impact assessment methodology.

Research hypothesis Providing access to prevention in an online community will: 1) Strengthen anti-smoking skills 2) Enhance the empowerment of users 3) Allow the implementation of health interventions 4) Improve indicators of tobacco consumption in young people Methods The overall methodology of the project relies on a multidisciplinary approach with a consortium of French experts in public health (health promotion and epidemiology), education science, information and communication technologies, medical informatics, adolescent medicine, adolescent addictology, social sciences, ethics and law. The project will be led in 3 parts: 1) Development of the intervention - using the Integrate, Design, Assess, and Share (IDEAS) framework. Using qualitative methods (individual interview, focus groups), multidisciplinary team brainstorming, works meeting and quantitative assessment of SCOTT quality; the investigators will (a) empathize with target users, (b) specify target behavior, (c) ground in behavioral theory, (d) ideate implementation strategies, (e) prototype potential products, (f) gather user feedback, (g) build a minimum viable product, 2) Pilot study : (h) SCOTT will be deploying on a small scale to assess its usability; 3) Development of the large-scale evaluation protocol - following the recommendations of the Medical Research Council concerning the evaluation of complex interventions. The investigators will (i) develop, based on the results of the pilot test, the SCOTT process evaluation methodology, (j) develop the SCOTT impact / effectiveness evaluation methodology.

status: Completed

study_completion_date_type: Actual

study_type: Interventional

design_allocation: Randomized

primary_purpose: Prevention

enrollment_type: Actual

ipd_sharing: No

intervention_type: Behavioral

status_simplified: Completed


title: Detection of Subclinical Cerebral Suffering Related to Hypertension Using Multimodal MRI (SOUCHY) Brain Changes Due to Hypertension: a Multimodal MRI

acronym: SOUCHY

summary: Investigators propose here to study the brain consequences of hypertension in patients without cognitive complaints and neurological signs. The evaluation of brain suffering requires considering various possible brain damage. The team developed a multimodal MRI approach capable of detecting and quantifying numerous indices (e.g. morphometric, microstructural) to evaluate possible brain suffering. This project aims to identify individually signs of cerebral suffering in hypertensive patients compared to a population of normotensive volunteers, using advanced multiparametric MRI methods.

design_allocation: Non-Randomized

primary_purpose: Diagnostic

lead_sponsor: University Hospital, Toulouse

intervention_type: Diagnostic Test


title: Postoperative Painful Chronicization After Knee Replacement Surgery : Exploratory Study of BDNF's Kinetics

acronym: KNEE BDNF

summary:
Chronic pain is an extremely disabling disease. It is a major public health problem due to the lack of effective therapy.

Chronic postoperative pain (CPOP) is defined by a painful symptomatology in the operated area unrelated to previous pain, present for more than 3 months, and without any link to surgical complication.

The prevalence of chronicization of postoperative pain is 30% after total knee arthroplasty.

Identification of clinical, biological and psychological profiles are crucial to prevent CPOP.

A biologic factor, Brain Derived Neurotrophic Factor (BDNF) produced by a variety of cells is a key regulator of neuroplasticity. BDNF is increasingly studied in the mechanisms of cerebral sensitization and pain chronicization. The role of BDNF in pain of patients remains to be explored in a prospective study. The aim of this observational study is to compare the kinetics of BDNF after total knee arthroplasty in patients with and without CPOP.

Patients will be included in the study at the preanesthetic consultation. Serum BDNF levels will be measured preoperatively, 48h postoperatively, 3 and 6 months after surgery.

lead_sponsor: University Hospital, Montpellier

location_facility: Department of Anesthesiology and critical care, Lapeyronie University Hospital


title: Qualitative Study of the Experience of Adolescents and Health Professionals Faced With the Necessity for Changing to Remote Care During the COVID-19 Outbreak Quarantine

summary: The Maison des Adolescents (MDA) at Cochin Hospital (Paris) is a multidisciplinary service which welcomes adolescents in three different units: consultation, day care and hospitalization. However, the epidemic of coronavirus (COVID-19) in March 2020 which imposed the extreme limitation of contacts and then the confinement of the entire population, required urgent adaptation of care practices. Teleconsultation quickly became essential for most consultations (psychiatrists, psychologists, nurses, but also pediatricians and somatic physicians). In day hospital, daily reception could not be carried out, therapeutic workshops, family interviews, or speaking groups were organized remotely. In hospital unit, the interruption of visits required the organization of remote interviews with families. Far from the comfort of an organized and structured telepsychiatry, the use of videoconferencing was done in an emergency and without preparation. The objective is to explore the experience of adolescents, doctors and psychologists regarding emergency changes in the methods of their follow-up by setting up teleconsultation in the context of the COVID-19 epidemic.

study_start_date_type: Anticipated

status: Not yet recruiting

lead_sponsor: Hôpital Cochin


title: Ultrasonographic and MRI Explorations of Infraspinatus Muscle in Postero-superior Rotator Cuff Tear

acronym: VISUMIR

summary: The project aims to evaluate the contribution of texture analysis on MRI sections, and the technical feasibility, reproducibility, and clinical relevance of quantitative ultrasound and elastography to characterize the composition and volume of infraspinatus muscle in postero-superior rotator cuff tears. The perspectives are to optimize the imaging to allow a quantitative, objective and reproducible analysis of the muscle tissue and its characteristics.

lead_sponsor: University Hospital, Tours

intervention_type: Other


title: Impact of a Mobile Geriatric Team With a Pharmacist on the Optimisation of Prescriptions in Elderly Inpatients

acronym: PHARMOG

summary: In patients aged 75 years and older, polypathology is frequent and often associated with polypharmacy. This polypharmacy coupled with a lack of proactive elderly care can sometimes lead to hospitalisation. Due to comorbidities and complex problems, management of geriatric patients usually requires a multidisciplinary approach. In Toulouse University Hospital, elderly inpatients can benefit from a geriatric assessment by a Geriatric Mobile Team. Whether this team improve the prescriptions through the advice of a clinical pharmacist has not been demonstrated yet.

primary_purpose: Supportive Care

ReferenceType: background

ReferenceCitation: Pagès A, Roland C, Qassemi S, Abdeljalil AB, Houles M, Romain M, Toulza O, Belloc A, McCambridge C, Voisin T, Cestac P, Juillard-Condat B; PharMoG study group. Impact of a Pharmacist-included Mobile Geriatrics team intervention on potentially inappropriate drug prescribing: protocol for a prospective feasibility study (PharMoG study). BMJ Open. 2020 Dec 2;10(12):e040917. doi: 10.1136/bmjopen-2020-040917.


type: Other Identifier

title: Phenotypic and Functional Characterisation of Human B-cell Response in Pemphigus and Application to Other Auto-immune Diseases

acronym: CaReLyBP

summary: Pemphigus is a rare autoimmune disease involving skin and mucous membranes characterized by the production of pathogenic autoantibodies directed against desmosomal transmembrane glycoproteins belonging to the cadherin family,responsible for the disruption of desmosomes leading to the acantholysis phenomenon.Two main classical subtypes of pemphigus have been individualized:pemphigus vulgaris and foliaceus,in which pathogenic autoantibodies are directed against desmoglein 3 and 1 respectively.The knowledge about B-cell populations responsible for pemphigus activity increased a lot.In pemphigus patients,B-cell population was shown to comprise auto-reactive B lymphocytes producing antibodies targeting desmogleins,directly responsible for disease activity,and regulatory B lymphocytes.After rituximab treatment,clinical activity was proved to be associated with circulating auto-antibodies high titers and an increase of auto-reactive B-cells,whereas clinical remission was associated with a change in B-cell populations,as B cell repertoire changed from oligoclonal to polyclonal when reconstituting after treatment,with an increase of immatures and transitional B-cells producing IL-10.The mechanisms leading to autoreactive B-cells appearance,the precise role of B-reg in immune tolerance and the factors triggering the imbalance between pro autoimmune and regulatory immune B-cells leading to pemphigus activity remain to be discovered.Polymorphonuclear neutrophil granulocytes(PMN) are the first responders of the immune system to threats by invading microorganisms.Since 2004, PMN were shown to produce neutrophil extracellular traps(NET),structures consisting of decondensed chromatin embedded with histones,granular and cytoplasmic proteins that trap and kill microbes.In lupus recent works demonstrated evidences that NETs components are found in immune complexes responsible for tissue inflammation and that polyclonal activation of B-cell as well as memory B-cell activation could be obtain in presence of immune complexes derived from NET.Besides lupus,other works showed evidence of NETs implication in inflammatory and auto-immune states in rheumatoid arthritis and small vessel vasculitis.The hypotheses is that B-cell activation by NET might not be restricted to autoimmune diseases of which antibodies target NETs components.The aim is to assess the effects on B-cell activation and the phenotypic changes in B-cell population from pemphigus patients after stimulation by NET.

primary_purpose: Basic Science

ReferenceCitation: Langan SM, Smeeth L, Hubbard R, Fleming KM, Smith CJ, West J. Bullous pemphigoid and pemphigus vulgaris--incidence and mortality in the UK: population based cohort study. BMJ. 2008 Jul 9;337:a180. doi: 10.1136/bmj.a180.

ReferenceCitation: Hashimoto T, Amagai M, Garrod DR, Nishikawa T. Immunofluorescence and immunoblot studies on the reactivity of pemphigus vulgaris and pemphigus foliaceus sera with desmoglein 3 and desmoglein 1. Epithelial Cell Biol. 1995;4(2):63-9.

ReferenceCitation: Martel P, Joly P. Pemphigus: autoimmune diseases of keratinocyte's adhesion molecules. Clin Dermatol. 2001 Nov-Dec;19(6):662-74. Review.

ReferenceCitation: Amagai M, Tsunoda K, Zillikens D, Nagai T, Nishikawa T. The clinical phenotype of pemphigus is defined by the anti-desmoglein autoantibody profile. J Am Acad Dermatol. 1999 Feb;40(2 Pt 1):167-70.

ReferenceCitation: Mahoney MG, Wang Z, Rothenberger K, Koch PJ, Amagai M, Stanley JR. Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris. J Clin Invest. 1999 Feb;103(4):461-8.


title: Interaction of HIV/Platelets and HIV-platelets/Lymphocytes in HIV Patients Under cART Treatment But Immunological Non Responders

acronym: PLAQUEVIH

summary:
The investigators propose that the lack of immune response in InR is driven by HIV-containing platelets that might interact with macrophages and CD4+ T-cells although by different mechanisms. In the one hand, HIV-sheltering platelets might fuel tissue HIV macrophage and in turn T cell reservoirs as observed in InRs and/or maintain a low-level viral replication in macrophages, sustaining a persistent inflammatory profile on in these cells. In the other hand,HIV-sheltering platelets might induce CD4+ T-cells dysfunctions via platelets/ectosomes, although without promoting platelet-to-T-cell HIV transfer/infection, thereby increasing the number of peripheral inflammatory TH17 cells and a TH17/Treg unbalance as observed in InRs.

Main Objectives:

i) To characterize and the molecular and functional level the platelet factors implicated in HIV transfer to tissue-like macrophages as well as in the immunomodulatory activity of HIV-containing platelets on macrophages and CD4+ T-cells.

ii) To interrogate the transfer of HIV-containing platelet-derived mRNA and microRNA to tissue-like macrophages and CD4+ T-cells as one major mechanism of target cell immunomodulation.

iii) To investigate the therapeutic potential of anti-platelet aggregation/activation agents (e.g. Abciximab), known to block platelet-immune cell interaction, in improving immune cell functions in vitro and promoting immunological recovery in vivo.

ReferenceCitation: Ganor Y, Real F, Sennepin A, Dutertre CA, Prevedel L, Xu L, Tudor D, Charmeteau B, Couedel-Courteille A, Marion S, Zenak AR, Jourdain JP, Zhou Z, Schmitt A, Capron C, Eugenin EA, Cheynier R, Revol M, Cristofari S, Hosmalin A, Bomsel M. HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy. Nat Microbiol. 2019 Apr;4(4):633-644. doi: 10.1038/s41564-018-0335-z. Epub 2019 Feb 4.

ReferenceCitation: Real F, Sennepin A, Ganor Y, Schmitt A, Bomsel M. Live Imaging of HIV-1 Transfer across T Cell Virological Synapse to Epithelial Cells that Promotes Stromal Macrophage Infection. Cell Rep. 2018 May 8;23(6):1794-1805. doi: 10.1016/j.celrep.2018.04.028.

ReferenceCitation: Kaufmann GR, Perrin L, Pantaleo G, Opravil M, Furrer H, Telenti A, Hirschel B, Ledergerber B, Vernazza P, Bernasconi E, Rickenbach M, Egger M, Battegay M; Swiss HIV Cohort Study Group. CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study. Arch Intern Med. 2003 Oct 13;163(18):2187-95.

ReferenceCitation: Baker JV, Peng G, Rapkin J, Krason D, Reilly C, Cavert WP, Abrams DI, MacArthur RD, Henry K, Neaton JD; Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). Poor initial CD4+ recovery with antiretroviral therapy prolongs immune depletion and increases risk for AIDS and non-AIDS diseases. J Acquir Immune Defic Syndr. 2008 Aug 15;48(5):541-6. doi: 10.1097/QAI.0b013e31817bebb3.

ReferenceCitation: Kelley CF, Kitchen CM, Hunt PW, Rodriguez B, Hecht FM, Kitahata M, Crane HM, Willig J, Mugavero M, Saag M, Martin JN, Deeks SG. Incomplete peripheral CD4+ cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment. Clin Infect Dis. 2009 Mar 15;48(6):787-94. doi: 10.1086/597093.

ReferenceCitation: Chêne G, Sterne JA, May M, Costagliola D, Ledergerber B, Phillips AN, Dabis F, Lundgren J, D'Arminio Monforte A, de Wolf F, Hogg R, Reiss P, Justice A, Leport C, Staszewski S, Gill J, Fatkenheuer G, Egger ME; Antiretroviral Therapy Cohort Collaboration. Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: analysis of prospective studies. Lancet. 2003 Aug 30;362(9385):679-86.

ReferenceCitation: Deeks SG, Kitchen CM, Liu L, Guo H, Gascon R, Narváez AB, Hunt P, Martin JN, Kahn JO, Levy J, McGrath MS, Hecht FM. Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load. Blood. 2004 Aug 15;104(4):942-7. Epub 2004 Apr 29.

ReferenceCitation: Hunt PW, Martin JN, Sinclair E, Bredt B, Hagos E, Lampiris H, Deeks SG. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J Infect Dis. 2003 May 15;187(10):1534-43. Epub 2003 Apr 23.

ReferenceCitation: Marziali M, De Santis W, Carello R, Leti W, Esposito A, Isgrò A, Fimiani C, Sirianni MC, Mezzaroma I, Aiuti F. T-cell homeostasis alteration in HIV-1 infected subjects with low CD4 T-cell count despite undetectable virus load during HAART. AIDS. 2006 Oct 24;20(16):2033-41.

ReferenceCitation: Nunes-Alves C, Nobrega C, Behar SM, Correia-Neves M. Tolerance has its limits: how the thymus copes with infection. Trends Immunol. 2013 Oct;34(10):502-10. doi: 10.1016/j.it.2013.06.004. Epub 2013 Jul 16. Review.

ReferenceCitation: Wilson EM, Singh A, Hullsiek KH, Gibson D, Henry WK, Lichtenstein K, Önen NF, Kojic E, Patel P, Brooks JT, Sereti I, Baker JV; Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) Investigators. Monocyte-activation phenotypes are associated with biomarkers of inflammation and coagulation in chronic HIV infection. J Infect Dis. 2014 Nov 1;210(9):1396-406. doi: 10.1093/infdis/jiu275. Epub 2014 May 9.

ReferenceCitation: Ballem PJ, Belzberg A, Devine DV, Lyster D, Spruston B, Chambers H, Doubroff P, Mikulash K. Kinetic studies of the mechanism of thrombocytopenia in patients with human immunodeficiency virus infection. N Engl J Med. 1992 Dec 17;327(25):1779-84.

ReferenceCitation: Grozovsky R, Hoffmeister KM, Falet H. Novel clearance mechanisms of platelets. Curr Opin Hematol. 2010 Nov;17(6):585-9. doi: 10.1097/MOH.0b013e32833e7561. Review.

ReferenceCitation: Hatano H, Hayes TL, Dahl V, Sinclair E, Lee TH, Hoh R, Lampiris H, Hunt PW, Palmer S, McCune JM, Martin JN, Busch MP, Shacklett BL, Deeks SG. A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4+ T cell response. J Infect Dis. 2011 Apr 1;203(7):960-8. doi: 10.1093/infdis/jiq138.

ReferenceCitation: Green SA, Smith M, Hasley RB, Stephany D, Harned A, Nagashima K, Abdullah S, Pittaluga S, Imamichi T, Qin J, Rupert A, Ober A, Lane HC, Catalfamo M. Activated platelet-T-cell conjugates in peripheral blood of patients with HIV infection: coupling coagulation/inflammation and T cells. AIDS. 2015 Jul 17;29(11):1297-308. doi: 10.1097/QAD.0000000000000701.

ReferenceCitation: Starossom SC, Veremeyko T, Yung AW, Dukhinova M, Au C, Lau AY, Weiner HL, Ponomarev ED. Platelets Play Differential Role During the Initiation and Progression of Autoimmune Neuroinflammation. Circ Res. 2015 Oct 9;117(9):779-92. doi: 10.1161/CIRCRESAHA.115.306847. Epub 2015 Aug 20.

ReferenceCitation: Miossec P, Kolls JK. Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov. 2012 Oct;11(10):763-76. doi: 10.1038/nrd3794. Review.

ReferenceCitation: Rodríguez-Muñoz A, Martínez-Hernández R, Ramos-Leví AM, Serrano-Somavilla A, González-Amaro R, Sánchez-Madrid F, de la Fuente H, Marazuela M. Circulating Microvesicles Regulate Treg and Th17 Differentiation in Human Autoimmune Thyroid Disorders. J Clin Endocrinol Metab. 2015 Dec;100(12):E1531-9. doi: 10.1210/jc.2015-3146. Epub 2015 Oct 19.

ReferenceCitation: De Benedetto I, Masetti M, Fabbiani M, Biasin M, Muscatello A, Squillace N, Clerici M, Trabattoni D, Gori A, Bandera A. Higher Levels of Peripheral Th17 T CD4+ Cells Are Associated With Immunological Non Response in HIV-Infected Patients Under Effective ART. J Acquir Immune Defic Syndr. 2018 Apr 15;77(5):e45-e47. doi: 10.1097/QAI.0000000000001627.

ReferenceCitation: Deeks SG. HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med. 2011;62:141-55. doi: 10.1146/annurev-med-042909-093756. Review.

ReferenceCitation: Joosse SA, Pantel K. Tumor-Educated Platelets as Liquid Biopsy in Cancer Patients. Cancer Cell. 2015 Nov 9;28(5):552-554. doi: 10.1016/j.ccell.2015.10.007.

ReferenceCitation: Laffont B, Corduan A, Plé H, Duchez AC, Cloutier N, Boilard E, Provost P. Activated platelets can deliver mRNA regulatory Ago2•microRNA complexes to endothelial cells via microparticles. Blood. 2013 Jul 11;122(2):253-61. doi: 10.1182/blood-2013-03-492801. Epub 2013 May 7.

ReferenceCitation: Risitano A, Beaulieu LM, Vitseva O, Freedman JE. Platelets and platelet-like particles mediate intercellular RNA transfer. Blood. 2012 Jun 28;119(26):6288-95. doi: 10.1182/blood-2011-12-396440. Epub 2012 May 17.

ReferenceCitation: Mann M, Mehta A, Zhao JL, Lee K, Marinov GK, Garcia-Flores Y, Lu LF, Rudensky AY, Baltimore D. An NF-κB-microRNA regulatory network tunes macrophage inflammatory responses. Nat Commun. 2017 Oct 11;8(1):851. doi: 10.1038/s41467-017-00972-z. Erratum in: Nat Commun. 2018 Aug 16;9(1):3338.

ReferenceCitation: Rowley JW, Chappaz S, Corduan A, Chong MM, Campbell R, Khoury A, Manne BK, Wurtzel JG, Michael JV, Goldfinger LE, Mumaw MM, Nieman MT, Kile BT, Provost P, Weyrich AS. Dicer1-mediated miRNA processing shapes the mRNA profile and function of murine platelets. Blood. 2016 Apr 7;127(14):1743-51. doi: 10.1182/blood-2015-07-661371. Epub 2016 Jan 14.

ReferenceCitation: Du C, Liu C, Kang J, Zhao G, Ye Z, Huang S, Li Z, Wu Z, Pei G. MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol. 2009 Dec;10(12):1252-9. doi: 10.1038/ni.1798. Epub 2009 Oct 18. Erratum in: Nat Immunol. 2010 Jun;11(6):543.

ReferenceCitation: Plé H, Landry P, Benham A, Coarfa C, Gunaratne PH, Provost P. The repertoire and features of human platelet microRNAs. PLoS One. 2012;7(12):e50746. doi: 10.1371/journal.pone.0050746. Epub 2012 Dec 4.

ReferenceCitation: Podshivalova K, Salomon DR. MicroRNA regulation of T-lymphocyte immunity: modulation of molecular networks responsible for T-cell activation, differentiation, and development. Crit Rev Immunol. 2013;33(5):435-76. Review.

ReferenceCitation: Fink L, Hölschermann H, Kwapiszewska G, Muyal JP, Lengemann B, Bohle RM, Santoso S. Characterization of platelet-specific mRNA by real-time PCR after laser-assisted microdissection. Thromb Haemost. 2003 Oct;90(4):749-56.

location_facility: Service Hématologie Immunologie, Hôpital Ambroise Paré


title: Characterization of the Subclass of Donor-specific Antibody Determined in Mass Spectrometry as a Risk Factor of Antibody Mediated Rejection in Renal Transplantation

acronym: COR-HUM

summary:
Antibody-mediated rejection is now recognized as the first cause of long-term kidney transplant loss. This type of rejection is mediated by the presence of graft-specific antibodies, usually directed against HLA (Human Leukocyte Antigens), called DSA (Donor Specific Antibody).

De novo DSA (ie, post-transplantation) is detected in approximately 20% of transplant recipients in the first five years, and is a major risk factor for antibody mediated rejection and graft loss.

All anti-HLA antibodies therefore do not have the same pathogenicity. Some teams have shown that the detection of IgG3 anti-HLA by cytometry is associated with a higher risk of humoral rejection but these results have not been confirmed by others. One of the limitations of the cytometry by Luminex technique is that it only informs the detection of each subclass but does not allow analysis of the distribution of the different subclasses of a DSA.

A method has been developed for the relative detection and quantification of different subclasses of the DSA using the mass spectrometry technique and will be tested during this study. This new quantification method therefore opens up the prospect of studying whether, not only the presence but especially the distribution of IgG subclasses, in particular IgG3, could constitute a reliable and robust marker of humoral rejection.

ReferenceType: derived

ReferenceCitation: Pernin V, Beyze A, Szwarc I, Bec N, Salsac C, Perez-Garcia E, Mourad G, Merville P, Visentin J, Perrochia H, Larroque C, Couzi L, Le Quintrec M. Distribution of de novo Donor-Specific Antibody Subclasses Quantified by Mass Spectrometry: High IgG3 Proportion Is Associated With Antibody-Mediated Rejection Occurrence and Severity. Front Immunol. 2020 Jun 2;11:919. doi: 10.3389/fimmu.2020.00919. eCollection 2020.

family: Pernin

full_name: Vincent Pernin

given: Vincent

sequence: first

family: Beyze

full_name: Anais Beyze

given: Anais

sequence: additional

family: Szwarc

full_name: Ilan Szwarc

given: Ilan

family: Bec

full_name: Nicole Bec

given: Nicole

family: Salsac

full_name: Céline Salsac

given: Céline

family: Perez-Garcia

full_name: Esther Perez-Garcia

given: Esther

family: Mourad

full_name: Georges Mourad

given: Georges

family: Merville

full_name: Pierre Merville

given: Pierre

family: Visentin

full_name: Jonathan Visentin

given: Jonathan

family: Perrochia

full_name: Helene Perrochia

given: Helene

family: Larroque

full_name: Christian Larroque

given: Christian

family: Couzi

full_name: Lionel Couzi

given: Lionel

family: Le Quintrec

full_name: Moglie Le Quintrec

given: Moglie

bso_classification: Medical research

currency_apc_doaj: USD

datasource: user

genre: journal-article

genre_raw: journal-article

journal_name: Frontiers in Immunology

oa_colors: green gold

oa_host_type: publisher;repository

evidence: oa journal (via doaj)

host_type: publisher

license: cc-by

license_normalized: cc-by

version: publishedVersion

evidence: oa repository (via OAI-PMH doi match)

host_type: repository

repository_institution: PubMed Central - Europe PMC

repository_normalized: PubMed Central

evidence: oa repository (via pmcid lookup)

license_normalized: no license

publisher: Frontiers Media SA

publisher_dissemination: Frontiers

publisher_group: Frontiers

publisher_normalized: Frontiers


title: Angiogenic Function at Normal Term on Placenta

acronym: ANNOTEP

summary: In vivo and ex vivo study of trophoblastic angiogenic trophoblastic function in placentas from normal pregnancies, at term

lead_sponsor: Centre Hospitalier Intercommunal Creteil

location_facility: Centre Hospitalier Intercommunal de Créteil


title: Modeling Clinical Failure in Prostate Cancer Patients Based on a Two-stage Statistical Model

acronym: PREDYC

summary:
Biomarker series can indicate disease progression and predict clinical endpoints. When a treatment is prescribed depending on the biomarker, confounding by indication might be introduced if the treatment modifies the marker profile and risk of failure.

The two-stage model fitted within a Bayesian Markov Chain Monte Carlo framework is particularly flexible to account for such data. Prostate-specific antigens in prostate cancer patients treated with external beam radiation therapy can be monitored. In the presence of rising prostate-specific antigens after external beam radiation therapy, salvage hormone therapy can be prescribed to reduce both the prostate-specific antigens concentration and the risk of clinical failure, an illustration of confounding by indication. The prognostic value of hormone therapy and prostate-specific antigens trajectory on the risk of failure based on a two-stage model within a Bayesian framework to assess the role of the prostate-specific antigens profile on clinical failure while accounting for a secondary treatment prescribed by indication. the aim of this research is to model prostate specific antigens using a hierarchical piecewise linear trajectory with a random changepoint. Residual prostate-specific antigens variability can be expressed as a function of prostate-specific antigens concentration. Covariates in the survival model can include : hormone therapy, baseline characteristics, and individual predictions of the prostate-specific antigens nadir and timing and prostate-specific antigens slopes before and after the nadir as provided by the longitudinal process.

time_perspective: Retrospective

ReferenceType: result

ReferenceCitation: Bellera C, Proust-Lima C, Joseph L, Richaud P, Taylor J, Sandler H, Hanley J, Mathoulin-Pélissier S. A two-stage model in a Bayesian framework to estimate a survival endpoint in the presence of confounding by indication. Stat Methods Med Res. 2018 Apr;27(4):1271-1281. doi: 10.1177/0962280216660127. Epub 2016 Sep 1.

name: Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, F-33000 Bordeaux, France

name: INSERM CIC-EC 14.01 (Clinical Epidemiology), Bordeaux, France

name: INSERM, ISPED, Centre INSERM U1219 Bordeaux Population Health Center, Epicene Team, F-33000 Bordeaux, France

name: Univ. Bordeaux, ISPED, Centre INSERM U1219 Bordeaux Population Health, Epicene Team, F-33000 Bordeaux, France

family: Bellera

full_name: Carine Bellera

given: Carine

name: INSERM, ISPED, Centre INSERM U1219 Bordeaux Population Health Center, Biostatistics Team, F-33000 Bordeaux, France

name: Univ. Bordeaux, ISPED, Centre INSERM U1219 Bordeaux Population Health, Biostatistics Team, F-33000 Bordeaux, France

family: Proust-Lima

full_name: Cécile Proust-Lima

given: Cécile

name: Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada

family: Joseph

full_name: Lawrence Joseph

given: Lawrence

name: Department of Radiotherapy, Comprehensive Cancer Center, Institut Bergonié, France

family: Richaud

full_name: Pierre Richaud

name: Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA

family: Taylor

full_name: Jeremy Taylor

given: Jeremy

name: Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, USA

family: Sandler

full_name: Howard Sandler

given: Howard

family: Hanley

full_name: James Hanley

given: James

family: Mathoulin-Pélissier

full_name: Simone Mathoulin-Pélissier

given: Simone

bso_classification: Mathematics

journal_name: Statistical Methods in Medical Research

publisher: SAGE Publications

publisher_dissemination: SAGE Publications

publisher_group: SAGE Publications

publisher_normalized: SAGE Publications

lead_sponsor: Institut Bergonié

intervention_type: Radiation

lead_sponsor_type: industriel


title: Sample Size Determination in Heterogeneous Populations for Multivariate Time-to-event Data

summary: Most of randomized clinical trials (RCT) using time-to-event criteria as the primary endpoint are designed, powered and analyzed based on an hypothetical hazard ratio (HR) corresponding to the targeted effect size between experimental and control arms. Usually, one assumes that populations are homogeneous within each treatment arm, that is, within each arm, (i) the baseline risk is identical for all patients, and (ii) the treatment effect is identical for all patients. This assumption however may not hold in all circumstances. This project aims at providing a statistical method for the estimation of sample size in RCT, in the presence of heterogenous populations, such as assuming populations with distinct underlying baseline risks or assuming different treatment effects.

status: Active, not recruiting

location_facility: Institut Bergonié, Comprehensive Cancer Center

intervention_type: Drug


title: Takayasu Arteritis Activity Evaluation by Ultrafast Ultrasound Imaging

acronym: TAK-UF

summary:
The general activity of Takayasu vasculitis is correlated with the perfusion rate of the carotid arterial wall. This can be quantified with ultrafast ultrasound imaging in sensitive Doppler sequence associated with the concomitant injection of microbubbles (SonoVue®).

The hypothesis is that the carotid artery wall flow parameters obtained with ultrafast ultrasound imaging make possible to discriminate an active disease from an inactive disease because of the fibrous sequential arterial thickening. Thus, to improve the evaluation of Takayasu vasculitis activity and to refine the criteria for response to the various immunomodulatory treatments used.

lead_sponsor: French Cardiology Society


type: Registry Identifier

title: Phenotypic Characterization Tumor-infiltrating Lymphocytes at Diagnosis and After Chemotherapy in Advanced High-grade Serous Ovarian Cancer in Blood, Ascites, Peritoneal Biopsy

summary: This is a monocenter, interventional, non-randomized study among women patients with an ovarian or tubal cancer who will receive a surgery or adjuvant chemotherapy treatment, or a neo-adjuvant chemotherapy then surgery +/- adjuvant chemotherapy. The planned interventions are collection of biological samples at different times. The study will aim to describe the immunological profile at diagnosis in terms of phenotypic : PBMCs (peripheral blood, mononuclear cells) in peripheral blood, TILs (tumor-infiltrating lymphocytes) in ascites and in carcinomatosis.

primary_purpose: Other

ReferenceCitation: Bobisse S, Genolet R, Roberti A, Tanyi JL, Racle J, Stevenson BJ, Iseli C, Michel A, Le Bitoux MA, Guillaume P, Schmidt J, Bianchi V, Dangaj D, Fenwick C, Derré L, Xenarios I, Michielin O, Romero P, Monos DS, Zoete V, Gfeller D, Kandalaft LE, Coukos G, Harari A. Sensitive and frequent identification of high avidity neo-epitope specific CD8 (+) T cells in immunotherapy-naive ovarian cancer. Nat Commun. 2018 Mar 15;9(1):1092. doi: 10.1038/s41467-018-03301-0.

ReferenceCitation: Zhang AW, McPherson A, Milne K, Kroeger DR, Hamilton PT, Miranda A, Funnell T, Little N, de Souza CPE, Laan S, LeDoux S, Cochrane DR, Lim JLP, Yang W, Roth A, Smith MA, Ho J, Tse K, Zeng T, Shlafman I, Mayo MR, Moore R, Failmezger H, Heindl A, Wang YK, Bashashati A, Grewal DS, Brown SD, Lai D, Wan ANC, Nielsen CB, Huebner C, Tessier-Cloutier B, Anglesio MS, Bouchard-Côté A, Yuan Y, Wasserman WW, Gilks CB, Karnezis AN, Aparicio S, McAlpine JN, Huntsman DG, Holt RA, Nelson BH, Shah SP. Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer. Cell. 2018 Jun 14;173(7):1755-1769.e22. doi: 10.1016/j.cell.2018.03.073. Epub 2018 May 10.

ReferenceCitation: Mayor P, Starbuck K, Zsiros E. Adoptive cell transfer using autologous tumor infiltrating lymphocytes in gynecologic malignancies. Gynecol Oncol. 2018 Aug;150(2):361-369. doi: 10.1016/j.ygyno.2018.05.024. Epub 2018 May 24. Review.

ReferenceCitation: van Driel WJ, Koole SN, Sikorska K, Schagen van Leeuwen JH, Schreuder HWR, Hermans RHM, de Hingh IHJT, van der Velden J, Arts HJ, Massuger LFAG, Aalbers AGJ, Verwaal VJ, Kieffer JM, Van de Vijver KK, van Tinteren H, Aaronson NK, Sonke GS. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med. 2018 Jan 18;378(3):230-240. doi: 10.1056/NEJMoa1708618.

ReferenceCitation: Odunsi K. Immunotherapy in ovarian cancer. Ann Oncol. 2017 Nov 1;28(suppl_8):viii1-viii7. doi: 10.1093/annonc/mdx444. Review.

ReferenceCitation: Tran E, Robbins PF, Rosenberg SA. 'Final common pathway' of human cancer immunotherapy: targeting random somatic mutations. Nat Immunol. 2017 Feb 15;18(3):255-262. doi: 10.1038/ni.3682. Review.

ReferenceCitation: Ovarian Tumor Tissue Analysis (OTTA) Consortium, Goode EL, Block MS, Kalli KR, Vierkant RA, Chen W, Fogarty ZC, Gentry-Maharaj A, Tołoczko A, Hein A, Bouligny AL, Jensen A, Osorio A, Hartkopf A, Ryan A, Chudecka-Głaz A, Magliocco AM, Hartmann A, Jung AY, Gao B, Hernandez BY, Fridley BL, McCauley BM, Kennedy CJ, Wang C, Karpinskyj C, de Sousa CB, Tiezzi DG, Wachter DL, Herpel E, Taran FA, Modugno F, Nelson G, Lubiński J, Menkiszak J, Alsop J, Lester J, García-Donas J, Nation J, Hung J, Palacios J, Rothstein JH, Kelley JL, de Andrade JM, Robles-Díaz L, Intermaggio MP, Widschwendter M, Beckmann MW, Ruebner M, Jimenez-Linan M, Singh N, Oszurek O, Harnett PR, Rambau PF, Sinn P, Wagner P, Ghatage P, Sharma R, Edwards RP, Ness RB, Orsulic S, Brucker SY, Johnatty SE, Longacre TA, Ursula E, McGuire V, Sieh W, Natanzon Y, Li Z, Whittemore AS, Anna A, Staebler A, Karlan BY, Gilks B, Bowtell DD, Høgdall E, Candido dos Reis FJ, Steed H, Campbell IG, Gronwald J, Benítez J, Koziak JM, Chang-Claude J, Moysich KB, Kelemen LE, Cook LS, Goodman MT, García MJ, Fasching PA, Kommoss S, Deen S, Kjaer SK, Menon U, Brenton JD, Pharoah PDP, Chenevix-Trench G, Huntsman DG, Winham SJ, Köbel M, Ramus SJ. Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer. JAMA Oncol. 2017 Dec 1;3(12):e173290. doi: 10.1001/jamaoncol.2017.3290.

ReferenceCitation: Delcourt V, Franck J, Leblanc E, Narducci F, Robin YM, Gimeno JP, Quanico J, Wisztorski M, Kobeissy F, Jacques JF, Roucou X, Salzet M, Fournier I. Combined Mass Spectrometry Imaging and Top-down Microproteomics Reveals Evidence of a Hidden Proteome in Ovarian Cancer. EBioMedicine. 2017 Jul;21:55-64. doi: 10.1016/j.ebiom.2017.06.001. Epub 2017 Jun 3.

ReferenceCitation: Murakami R, Matsumura N, Mandai M, Yoshihara K, Tanabe H, Nakai H, Yamanoi K, Abiko K, Yoshioka Y, Hamanishi J, Yamaguchi K, Baba T, Koshiyama M, Enomoto T, Okamoto A, Murphy SK, Mori S, Mikami Y, Minamiguchi S, Konishi I. Establishment of a Novel Histopathological Classification of High-Grade Serous Ovarian Carcinoma Correlated with Prognostically Distinct Gene Expression Subtypes. Am J Pathol. 2016 May;186(5):1103-13. doi: 10.1016/j.ajpath.2015.12.029. Epub 2016 Mar 15.

ReferenceCitation: Blank CU, Haanen JB, Ribas A, Schumacher TN. CANCER IMMUNOLOGY. The "cancer immunogram". Science. 2016 May 6;352(6286):658-60. doi: 10.1126/science.aaf2834.

ReferenceCitation: Santoiemma PP, Powell DJ Jr. Tumor infiltrating lymphocytes in ovarian cancer. Cancer Biol Ther. 2015;16(6):807-20. doi: 10.1080/15384047.2015.1040960. Epub 2015 Apr 20. Review.

ReferenceCitation: Hiraoka N, Ino Y, Yamazaki-Itoh R, Kanai Y, Kosuge T, Shimada K. Intratumoral tertiary lymphoid organ is a favourable prognosticator in patients with pancreatic cancer. Br J Cancer. 2015 May 26;112(11):1782-90. doi: 10.1038/bjc.2015.145. Epub 2015 May 5.

ReferenceCitation: Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, Wienert S, Van den Eynden G, Baehner FL, Penault-Llorca F, Perez EA, Thompson EA, Symmans WF, Richardson AL, Brock J, Criscitiello C, Bailey H, Ignatiadis M, Floris G, Sparano J, Kos Z, Nielsen T, Rimm DL, Allison KH, Reis-Filho JS, Loibl S, Sotiriou C, Viale G, Badve S, Adams S, Willard-Gallo K, Loi S; International TILs Working Group 2014. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015 Feb;26(2):259-71. doi: 10.1093/annonc/mdu450. Epub 2014 Sep 11.

ReferenceCitation: Galluzzi L, Vacchelli E, Bravo-San Pedro JM, Buqué A, Senovilla L, Baracco EE, Bloy N, Castoldi F, Abastado JP, Agostinis P, Apte RN, Aranda F, Ayyoub M, Beckhove P, Blay JY, Bracci L, Caignard A, Castelli C, Cavallo F, Celis E, Cerundolo V, Clayton A, Colombo MP, Coussens L, Dhodapkar MV, Eggermont AM, Fearon DT, Fridman WH, Fučíková J, Gabrilovich DI, Galon J, Garg A, Ghiringhelli F, Giaccone G, Gilboa E, Gnjatic S, Hoos A, Hosmalin A, Jäger D, Kalinski P, Kärre K, Kepp O, Kiessling R, Kirkwood JM, Klein E, Knuth A, Lewis CE, Liblau R, Lotze MT, Lugli E, Mach JP, Mattei F, Mavilio D, Melero I, Melief CJ, Mittendorf EA, Moretta L, Odunsi A, Okada H, Palucka AK, Peter ME, Pienta KJ, Porgador A, Prendergast GC, Rabinovich GA, Restifo NP, Rizvi N, Sautès-Fridman C, Schreiber H, Seliger B, Shiku H, Silva-Santos B, Smyth MJ, Speiser DE, Spisek R, Srivastava PK, Talmadge JE, Tartour E, Van Der Burg SH, Van Den Eynde BJ, Vile R, Wagner H, Weber JS, Whiteside TL, Wolchok JD, Zitvogel L, Zou W, Kroemer G. Classification of current anticancer immunotherapies. Oncotarget. 2014 Dec 30;5(24):12472-508. Review.

ReferenceCitation: Tangye SG, Ma CS, Brink R, Deenick EK. The good, the bad and the ugly - TFH cells in human health and disease. Nat Rev Immunol. 2013 Jun;13(6):412-26. doi: 10.1038/nri3447. Epub 2013 May 17. Review.

ReferenceCitation: Bachmayr-Heyda A, Aust S, Heinze G, Polterauer S, Grimm C, Braicu EI, Sehouli J, Lambrechts S, Vergote I, Mahner S, Pils D, Schuster E, Thalhammer T, Horvat R, Denkert C, Zeillinger R, Castillo-Tong DC. Prognostic impact of tumor infiltrating CD8+ T cells in association with cell proliferation in ovarian cancer patients--a study of the OVCAD consortium. BMC Cancer. 2013 Sep 17;13:422. doi: 10.1186/1471-2407-13-422.

ReferenceCitation: Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012 Jun 10;30(17):2039-45. doi: 10.1200/JCO.2012.42.0505. Epub 2012 Apr 23.

ReferenceCitation: Hwang WT, Adams SF, Tahirovic E, Hagemann IS, Coukos G. Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis. Gynecol Oncol. 2012 Feb;124(2):192-8. doi: 10.1016/j.ygyno.2011.09.039. Epub 2011 Oct 29.

ReferenceCitation: Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX; Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2473-83. doi: 10.1056/NEJMoa1104390.

ReferenceCitation: Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011 Jun 29;474(7353):609-15. doi: 10.1038/nature10166. Erratum in: Nature. 2012 Oct 11;490(7419):298.

ReferenceCitation: Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, Kepner J, Odunsi T, Ritter G, Lele S, Chen YT, Ohtani H, Old LJ, Odunsi K. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18538-43. Epub 2005 Dec 12.

ReferenceCitation: Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004 Sep;10(9):942-9. Epub 2004 Aug 22.

ReferenceCitation: Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003 Jan 16;348(3):203-13.

ReferenceCitation: Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002 Nov;3(11):991-8. Review.

lead_sponsor: Centre Oscar Lambret

intervention_type: Procedure


title: Identifying New Therapeutic Targets for Lupus Treatment

acronym: ELUDIAL

summary: Lupus is an autoimmune disease affecting mainly young women (9/1). Lupus nephritis (LN) occurs in 30% of the cases of lupus and is associated with end stage renal disease (ESRD) in 17 to 25% of cases after 10 years. Overall, nearly 7% of lupus patients will develop ESRD due to LN. Historically, 5-year survival after LN was lower than 20%. Nowadays, 45% of patients suffer from multiple relapses that are associated with an intermediate risk of ESRD. When ESRD occurs, lupus activity decreases progressively to reach a stable extinct state. At this stage it is possible to stop all medications to control lupus, without any flare of lupus activity. Lupus extinction following ESRD corresponds to a state of complete remission. Obtaining such a result before ESRD would avoid damages to several organs and side effects of immunosuppressive therapy. Understanding the mechanisms responsible for lupus extinction following ESRD is an innovative approach to decipher lupus pathophysiology. The objective of the study is to identify the mechanisms responsible for lupus extinction and to propose new therapeutic options based on these new mechanisms. Mechanisms responsible for lupus extinction are unknown. Lupus extinction depends on the duration of ESRD. Accumulation of several toxins that kidneys would normally eliminate in the urine is a hallmark of ESRD. Such toxins are called "uremic toxins" since they accumulate during "uremia" (ESRD). They affect biological systems such as fertility and immunity that are both closely related to lupus pathophysiology. The investigators hypothesize that studying LN extinction after ESRD will provide novel therapeutic targets to extinct lupus before ESRD. To this end, they will investigate several non-exclusive hypotheses based on previous findings of our consortium, or issued from clinical observations: the sexual dysfunction hypothesis and the ESRD-associated immune cells dysfunction hypothesis. In parallel, they will conduct an open screening of new mechanisms underlying the lupus extinction through the characterization of the differential gene expression profile associated with lupus extinction in patients undergoing dialysis.

time_perspective: Cross-Sectional


title: Biological Collection for Studying Vaccine-induced Immune Responses

acronym: BioCol-VIR

summary:
Introduction: Vaccination is a powerful weapon in the fight against infectious diseases, which has led to dramatic reduction in mortality and complications from some diseases. In this respect, vaccination is a real worldwide public health challenge (WHO). Thus, vaccine research benefits from an exponential development of knowledge in immunology and biotechnology. In particular, the advent of recent tools ("omics", new cytometric assays) and the description of new categories of immune cells (Tfh, BReg...) have revolutionized the characterization of immune responses, particularly post-vaccination. To study of the immune response following vaccination remains essential in order to define the immunological correlates to vaccine protection. This response also varies according to parameters related to the vaccine (type, adjuvant, dose, regimen…) and to the vaccinated host (genetics, age, morbidity, treatment …). Analyzing with new generation immune assays, new data on immunological responses post-vaccination from a clinical cohort is therefore essential to better define these correlates.

Objective: To develop new vaccines (HIV, emerging infectious diseases) the investigators use a "System vaccinology" method to decipher the mechanisms of immune responses set up against vaccines currently being developed or marketed, specifically in specific populations (patients with primary immune deficiency, sickle cell patients, solid organ transplanted patients, COPD).

Method: Description of the genetic, molecular and cellular mechanisms of the immune response to vaccines recommended for adults, in particular influenza and pneumococcal vaccines, but also other mandatory vaccines (MMR,...) or vaccine for travelers (yellow fever, ...) as part of routine care in different population categories (healthy subjects, HIV+ subjects, COPD patients, …), using qualitative and quantitative immunological assays: transcriptional analysis of the dynamic innate immune response, analysis of the lymphocytes B & T responses (phenotype, repertoire analysis, functional analysis including T reg and TFH populations, antibody response), genetic analysis in the context of primary immune deficiencies) Conclusion: The data generated will allow the best possible analysis of vaccine responses according to vaccines and vaccinated populations, providing important information for the research developed within the department.


title: Involvement of the Mediodorsal Nucleus of the Thalamus in Higher Order Cognitive Processes : a Study in Patients With a Thalamic Infarct

summary: The aim is to expand evidence about the importance of the mediodorsal nucleus of the thalamus as a key node in human higher-order cognitive functions such as learning, decision-making, and adaptive behavior. Thus, the project proposes to assess global cognition along with higher-order cognition integrity via sensitive behavior tasks in patients with well localized lesions (mediodorsal thalamic infarcts) compared with healthy participants.

ReferenceCitation: Kopelman MD. What does a comparison of the alcoholic Korsakoff syndrome and thalamic infarction tell us about thalamic amnesia? Neurosci Biobehav Rev. 2015 Jul;54:46-56. doi: 10.1016/j.neubiorev.2014.08.014. Epub 2014 Sep 16. Review.

ReferenceCitation: Pergola G, Güntürkün O, Koch B, Schwarz M, Daum I, Suchan B. Recall deficits in stroke patients with thalamic lesions covary with damage to the parvocellular mediodorsal nucleus of the thalamus. Neuropsychologia. 2012 Aug;50(10):2477-91. doi: 10.1016/j.neuropsychologia.2012.06.019. Epub 2012 Jun 30.

ReferenceCitation: Cipolotti L, Husain M, Crinion J, Bird CM, Khan SS, Losseff N, Howard RS, Leff AP. The role of the thalamus in amnesia: a tractography, high-resolution MRI and neuropsychological study. Neuropsychologia. 2008 Sep;46(11):2745-58. doi: 10.1016/j.neuropsychologia.2008.05.009. Epub 2008 May 21.

ReferenceCitation: Danet L, Barbeau EJ, Eustache P, Planton M, Raposo N, Sibon I, Albucher JF, Bonneville F, Peran P, Pariente J. Thalamic amnesia after infarct: The role of the mammillothalamic tract and mediodorsal nucleus. Neurology. 2015 Dec 15;85(24):2107-15. doi: 10.1212/WNL.0000000000002226. Epub 2015 Nov 13.


title: Study of the Role of Innate Lymphoid Cells and Natural Killer Cells in Immune Activation of Vitiligo

acronym: INNATEvitiligo

summary: The cohort included only major patients with non-segmental vitiligo and no other autoimmune or inflammatory associated diseases (except thyroiditis). Control subjects should have no autoimmune or inflammatory diseases. Patients and controls should not take treatment with corticosteroids or other potentially immunomodulatory therapies. Patients and controls are recruited in the Dermatology Department of the University Hospital of Nice and the Hospital of Fréjus. The investigators have already initiated the collection of tissues and blood from patients and control subjects and we have succeeded in isolating ILCs and NKs from a blood volume of 50ml. We were able to sort the ILC subpopulations. Early data suggest an increase in Natural Killer (NK) and Innate Lymphoïdes Cells 1 (ILC1) in the blood of vitiligo patients compared to control subjects. The investigators also managed to extract the melanocytes from the skin biopsies of the first patients and control subjects.

ReferenceCitation: Spritz RA. Six decades of vitiligo genetics: genome-wide studies provide insights into autoimmune pathogenesis. J Invest Dermatol. 2012 Feb;132(2):268-73. doi: 10.1038/jid.2011.321. Epub 2011 Oct 13. Review.

ReferenceCitation: Jin Y, Birlea SA, Fain PR, Ferrara TM, Ben S, Riccardi SL, Cole JB, Gowan K, Holland PJ, Bennett DC, Luiten RM, Wolkerstorfer A, van der Veen JP, Hartmann A, Eichner S, Schuler G, van Geel N, Lambert J, Kemp EH, Gawkrodger DJ, Weetman AP, Taïeb A, Jouary T, Ezzedine K, Wallace MR, McCormack WT, Picardo M, Leone G, Overbeck A, Silverberg NB, Spritz RA. Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo. Nat Genet. 2012 May 6;44(6):676-80. doi: 10.1038/ng.2272.

ReferenceCitation: Jin Y, Andersen G, Yorgov D, Ferrara TM, Ben S, Brownson KM, Holland PJ, Birlea SA, Siebert J, Hartmann A, Lienert A, van Geel N, Lambert J, Luiten RM, Wolkerstorfer A, Wietze van der Veen JP, Bennett DC, Taïeb A, Ezzedine K, Kemp EH, Gawkrodger DJ, Weetman AP, Kõks S, Prans E, Kingo K, Karelson M, Wallace MR, McCormack WT, Overbeck A, Moretti S, Colucci R, Picardo M, Silverberg NB, Olsson M, Valle Y, Korobko I, Böhm M, Lim HW, Hamzavi I, Zhou L, Mi QS, Fain PR, Santorico SA, Spritz RA. Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants. Nat Genet. 2016 Nov;48(11):1418-1424. doi: 10.1038/ng.3680. Epub 2016 Oct 10.

ReferenceCitation: Chatterjee S, Eby JM, Al-Khami AA, Soloshchenko M, Kang HK, Kaur N, Naga OS, Murali A, Nishimura MI, Caroline Le Poole I, Mehrotra S. A quantitative increase in regulatory T cells controls development of vitiligo. J Invest Dermatol. 2014 May;134(5):1285-1294. doi: 10.1038/jid.2013.540. Epub 2013 Dec 23.

ReferenceCitation: Mosenson JA, Zloza A, Nieland JD, Garrett-Mayer E, Eby JM, Huelsmann EJ, Kumar P, Denman CJ, Lacek AT, Kohlhapp FJ, Alamiri A, Hughes T, Bines SD, Kaufman HL, Overbeck A, Mehrotra S, Hernandez C, Nishimura MI, Guevara-Patino JA, Le Poole IC. Mutant HSP70 reverses autoimmune depigmentation in vitiligo. Sci Transl Med. 2013 Feb 27;5(174):174ra28. doi: 10.1126/scitranslmed.3005127.

ReferenceCitation: Harris JE, Harris TH, Weninger W, Wherry EJ, Hunter CA, Turka LA. A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8⁺ T-cell accumulation in the skin. J Invest Dermatol. 2012 Jul;132(7):1869-76. doi: 10.1038/jid.2011.463. Epub 2012 Feb 2.

ReferenceCitation: Rashighi M, Agarwal P, Richmond JM, Harris TH, Dresser K, Su MW, Zhou Y, Deng A, Hunter CA, Luster AD, Harris JE. CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo. Sci Transl Med. 2014 Feb 12;6(223):223ra23. doi: 10.1126/scitranslmed.3007811.

ReferenceCitation: Boniface K, Jacquemin C, Darrigade AS, Dessarthe B, Martins C, Boukhedouni N, Vernisse C, Grasseau A, Thiolat D, Rambert J, Lucchese F, Bertolotti A, Ezzedine K, Taieb A, Seneschal J. Vitiligo Skin Is Imprinted with Resident Memory CD8 T Cells Expressing CXCR3. J Invest Dermatol. 2018 Feb;138(2):355-364. doi: 10.1016/j.jid.2017.08.038. Epub 2017 Sep 18.

ReferenceCitation: Yu R, Broady R, Huang Y, Wang Y, Yu J, Gao M, Levings M, Wei S, Zhang S, Xu A, Su M, Dutz J, Zhang X, Zhou Y. Transcriptome analysis reveals markers of aberrantly activated innate immunity in vitiligo lesional and non-lesional skin. PLoS One. 2012;7(12):e51040. doi: 10.1371/journal.pone.0051040. Epub 2012 Dec 10.

ReferenceCitation: Regazzetti C, Joly F, Marty C, Rivier M, Mehul B, Reiniche P, Mounier C, Rival Y, Piwnica D, Cavalié M, Chignon-Sicard B, Ballotti R, Voegel J, Passeron T. Transcriptional Analysis of Vitiligo Skin Reveals the Alteration of WNT Pathway: A Promising Target for Repigmenting Vitiligo Patients. J Invest Dermatol. 2015 Dec;135(12):3105-3114. doi: 10.1038/jid.2015.335. Epub 2015 Aug 31.

ReferenceCitation: Bernardini G, Gismondi A, Santoni A. Chemokines and NK cells: regulators of development, trafficking and functions. Immunol Lett. 2012 Jul 30;145(1-2):39-46. doi: 10.1016/j.imlet.2012.04.014. Review.

ReferenceCitation: Brüggen MC, Bauer WM, Reininger B, Clim E, Captarencu C, Steiner GE, Brunner PM, Meier B, French LE, Stingl G. In Situ Mapping of Innate Lymphoid Cells in Human Skin: Evidence for Remarkable Differences between Normal and Inflamed Skin. J Invest Dermatol. 2016 Dec;136(12):2396-2405. doi: 10.1016/j.jid.2016.07.017. Epub 2016 Jul 22.

lead_sponsor: Centre Hospitalier Universitaire de Nice


title: iPS Cells of Patients for Models of Retinal Dystrophies

acronym: RETIPS

summary:
The investigators are focused on inherited retinal dystrophies with an aim to further understand disease pathophysiology and to elaborate novel treatments, as, to date, there is no effective treatment to prevent blindness.

The main goal of this study is to generate human cellular models of healthy and disease retinas and perform studies to evaluate the efficiency of gene therapy approaches for different diseases.

Skin biopsies of volunteers are cultured to isolate fibroblasts that are then reprogrammed into iPS cells. Healthy and disease-specific iPS cells are then differentiated into retinal models.

This study should help to elucidate disease pathways and to provide proof-of-concept for various therapeutic approaches.


title: Influence of the Surgical Technique Used for Colectomies on the Concentration of Circulating Tumor DNA and the Presence of Circulating Tumor Cells: Comparison of the "no Touch" Technic With Either First Clamping of the Mesenteric Vessels or First Mobilization of the Tumor Followed by Clamping.

acronym: ADNCHIR

summary: Colectomy is the most commonly used therapeutic approach for the treatment of non-metastatic colorectal cancer. This approach is generally very effective however the rate of recurrence and the appearance of metachronous metastasis remains a major problem in the postoperative period. One of the hypothesis that can explain this tumor progression is the dissemination of tumor cells at the time of tumor mobilization. In this work, we wish to verify this hypothesis by comparing two surgical technics used in our department for left or right colectomies: respectively either first section of the mesenteric vessels followed by the mobilization of the tumor or first mobilization of the tumor followed by the section of the mesenteric vessels. To evaluate the dissemination, we will study two disseminations markers that have shown their prognostic value: i) circulating tumor cells (which represent a direct marker of dissemination) and ii) tumor circulating DNA (which is an indirect marker) but has the advantage of being more representative of all tumor clones and therefore the tumor burden released into the blood at the time of surgery).

status: Unknown status

location_facility: Department of Digestive Surgery, Hôpital Saint-Antoine

status_simplified: Unknown


title: Characterization of Manual Dexterity by Finger Force Manipuladum (FFM) in Patients With Writer's Cramp and in Control Subjects

summary:
Writer's cramp is a focal dystonia characterized by abnormal movements and postures during writing. Limited finger independence during writing manifests as difficulty suppressing unwanted activations of neighbouring non task-relevant fingers. Patients with Writer's cramp also have difficulty in fine control of grip force.

The investigators have recently developed the Finger Force Manipulandum which quantifies the forces applied by each fingers in different tasks. This method is sensitive for detection and quantification of small unwanted contractions in non-active ('stationary') fingers. Different tasks have been developed to assess abilities such as finger individuation but also fine finger force control, finger movement regularity and speed.

The aim of this study is to assess if developed tasks allow to precisely characterize writer's cramp condition in terms of abilities aforementioned.

To do so, performance of 20 writer's cramp patients in the developed task will be compared with performance of 20 control participants (matched in age, sex and writing hand) in the same tasks.

lead_sponsor: Fondation Ophtalmologique Adolphe de Rothschild

intervention_type: Device


title: Evaluation of Individual Sensitivity to the Gonadotoxicity of Chemotherapy in Young Patients With Breast Cancer

acronym: ESIGON

summary:
Over the past decade, advances in diagnosis and treatments have dramatically increased the rates of cure for young patients with cancer. As a consequence, a new population of cancer survivors has emerged whose fertility is compromised after cancer therapy. Indeed, gonadotoxicity is a well-known long-term side effect of cancer treatment in young patients having survived malignant diseases. More than 80% of women of childbearing age, treated for breast cancer with standard protocol of neoadjuvant (4 cycles of 5-fluorouracile - epirubicin- cyclophosphamide (FEC) and 4 cycles of docetaxel) or adjuvant chemotherapy (3 FEC and 3 docetaxel), show an alteration of their ovarian reserve 2 years after completion of the treatment, as a result of chemotherapy-related follicular loss. Therefore, according to the extent of the follicular damages, the gonadal function may vary from moderate to severe diminished ovarian reserve (DOR) and possibly to the ultimate stage of premature ovarian insufficiency (POI).

Investigators propose a multicentric and prospective study of a cohort of young women with breast cancer to evaluate whether genetic polymorphisms, previously identified as being correlated with age at menopause in the healthy population, are associated with the intensity of the follicular decline following chemotherapy in young breast cancer survivors.

primary_purpose: Screening


title: Evaluation of the Location and the Treatment by High-intensity Focused Ultrasounds (HIFU) of Posterior Deep Infiltrating Endometriosis (DIE) Lesions With Intestinal Involvement

summary:
Deep invasive endometriosis (DIE) includes lesions of the rectosigmoid. Theses lesions are associated with painful symptoms that can alter quality of life. High Intensity Focused Ultrasound (HIFU) is a non-invasive ablative procedure using a high-intensity ultrasound probe to induce tissue devitalization using acoustic cavitation and thermal ablation. Focal One® is a transrectal HIFU device, which is validated to treat prostatic cancer.

The primary objective of this clinical trial is to evaluate the ability of the Focal One® HIFU device to detect and target posterior DIE lesions with intestinal involvement. The secondary objectives are to perform a HIFU lesion, to evaluate morphological modifications of the nodule in post-therapeutic imaging scans, to assess evolution of gynecological symptoms, intestinal symptoms, and patients' quality of life after treatment by HIFU and to collect safety data.

primary_purpose: Treatment

lead_sponsor: EDAP TMS S.A.


title: Study of Arterial Properties by Ultra-high Frequency Ultrasound in Fibromuscular Dysplasia and Vascular Ehlers-Danlos Syndrome

acronym: FUCHSIA-FR

summary:
Ultra-high frequency ultrasound may be useful in the field of vascular research, given its ability to accurately characterize arterial wall thickness and ultrastructure.

In patients with fibromuscular dysplasia (FMD), it may help identify the "triple signal" pattern in carotid arterial wall, while in Vascular Ehlers Danlos Syndrome (V-EDS) it may help to accurately measure carotid intima-media thickness, which may be extremely small and difficult to measure with standard equipment. Furthermore, novel features might be identified in small-to-medium sized arteries by ultra-high frequency ultrasound.

The main aim of this study is to demonstrate that ultra-high frequency ultrasound has the same accuracy of standard ultrasound for the identification of "triple signal" in the carotid artery of FMD.

Secondary aims of this study are to evaluate carotid, radial and digital intima-media thickness, wall ultrastructure and distensibility in 60 patients with FMD and in 30 patients with V-EDS.


title: Monitoring of Immune Checkpoint Inhibitors Adverse Drug Reactions Through the WHO Vigilyze and French Pharmaco-vigilance Database (Base Nationale de Pharmacovigilance BNPV)

acronym: CHIMeRA

summary: Immune checkpoint inhibitors (ICIs) might have high grade immune-related adverse events (irAEs) from rhumatologic, endocrinologic, cardiac or other system origin. This study investigates reports of drug induced irAEs with treatment including anti-PD1, Anti-PDL-1, and Anti-CTLA4 classes using the World Health Organization (WHO) database VigiBase and the french database Base Nationale de PharmacoVigilance (BNPV).

ReferenceCitation: Davis EJ, Salem JE, Young A, Green JR, Ferrell PB, Ancell KK, Lebrun-Vignes B, Moslehi JJ, Johnson DB. Hematologic Complications of Immune Checkpoint Inhibitors. Oncologist. 2019 May;24(5):584-588. doi: 10.1634/theoncologist.2018-0574. Epub 2019 Feb 28.

ReferenceCitation: Salem JE, Allenbach Y, Vozy A, Brechot N, Johnson DB, Moslehi JJ, Kerneis M. Abatacept for Severe Immune Checkpoint Inhibitor-Associated Myocarditis. N Engl J Med. 2019 Jun 13;380(24):2377-2379. doi: 10.1056/NEJMc1901677.

ReferenceCitation: Johnson DB, Manouchehri A, Haugh AM, Quach HT, Balko JM, Lebrun-Vignes B, Mammen A, Moslehi JJ, Salem JE. Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study. J Immunother Cancer. 2019 May 22;7(1):134. doi: 10.1186/s40425-019-0617-x.

ReferenceCitation: Johnson DB, McDonnell WJ, Gonzalez-Ericsson PI, Al-Rohil RN, Mobley BC, Salem JE, Wang DY, Sanchez V, Wang Y, Chastain CA, Barker K, Liang Y, Warren S, Beechem JM, Menzies AM, Tio M, Long GV, Cohen JV, Guidon AC, O'Hare M, Chandra S, Chowdhary A, Lebrun-Vignes B, Goldinger SM, Rushing EJ, Buchbinder EI, Mallal SA, Shi C, Xu Y, Moslehi JJ, Sanders ME, Sosman JA, Balko JM. A case report of clonal EBV-like memory CD4(+) T cell activation in fatal checkpoint inhibitor-induced encephalitis. Nat Med. 2019 Aug;25(8):1243-1250. doi: 10.1038/s41591-019-0523-2. Epub 2019 Jul 22.

ReferenceCitation: Bonaca MP, Olenchock BA, Salem JE, Wiviott SD, Ederhy S, Cohen A, Stewart GC, Choueiri TK, Di Carli M, Allenbach Y, Kumbhani DJ, Heinzerling L, Amiri-Kordestani L, Lyon AR, Thavendiranathan P, Padera R, Lichtman A, Liu PP, Johnson DB, Moslehi J. Myocarditis in the Setting of Cancer Therapeutics: Proposed Case Definitions for Emerging Clinical Syndromes in Cardio-Oncology. Circulation. 2019 Jul 2;140(2):80-91. Review.

ReferenceCitation: Arnaud L, Lebrun-Vignes B, Salem JE. Checkpoint inhibitor-associated immune arthritis. Ann Rheum Dis. 2019 Jul;78(7):e68. doi: 10.1136/annrheumdis-2018-213470. Epub 2018 May 3.

family: Arnaud

full_name: Laurent Arnaud

given: Laurent

family: Lebrun-Vignes

full_name: Bénédicte Lebrun-Vignes

given: Bénédicte

family: Salem

full_name: Joe-Elie Salem

given: Joe-Elie

journal_name: Annals of the Rheumatic Diseases

oa_host_type: publisher

evidence: open (via free pdf)

publisher: BMJ

publisher_dissemination: British Medical Journal

publisher_group: British Medical Journal

publisher_normalized: British Medical Journal

ReferenceCitation: Wang DY, Salem JE, Cohen JV, Chandra S, Menzer C, Ye F, Zhao S, Das S, Beckermann KE, Ha L, Rathmell WK, Ancell KK, Balko JM, Bowman C, Davis EJ, Chism DD, Horn L, Long GV, Carlino MS, Lebrun-Vignes B, Eroglu Z, Hassel JC, Menzies AM, Sosman JA, Sullivan RJ, Moslehi JJ, Johnson DB. Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis. JAMA Oncol. 2018 Dec 1;4(12):1721-1728. doi: 10.1001/jamaoncol.2018.3923. Erratum in: JAMA Oncol. 2018 Dec 1;4(12):1792.

name: Vanderbilt Ingram Cancer Center, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee

family: Wang

full_name: Daniel Y. Wang

given: Daniel Y.

name: Department of Pharmacology, Pharmacovigilance Unit, AP-HP, Pitié-Salpêtrière Hospital, Paris, France

name: INSERM, UMR ICAN 1166, Sorbonne Universités, UPMC Univ Paris 06, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France

name: Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts

family: Cohen

full_name: Justine V. Cohen

given: Justine V.

name: Robert H. Lurie Cancer Center, Department of Medicine, Northwestern University Medical Center, Chicago, Illinois

family: Chandra

full_name: Sunandana Chandra

given: Sunandana

name: National Center for Tumor Diseases, Department of Dermatology, University Hospital Heidelberg, Heidelberg, Germany

family: Menzer

full_name: Christian Menzer

name: Vanderbilt Ingram Cancer Center, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee

family: Ye

full_name: Fei Ye

given: Fei

family: Zhao

full_name: Shilin Zhao

given: Shilin

family: Das

full_name: Satya Das

given: Satya

family: Beckermann

full_name: Kathryn E. Beckermann

given: Kathryn E.

family: Ha

full_name: Lisa Ha

given: Lisa

family: Rathmell

full_name: W. Kimryn Rathmell

given: W. Kimryn

family: Ancell

full_name: Kristin K. Ancell

given: Kristin K.

family: Balko

full_name: Justin M. Balko

given: Justin M.

family: Bowman

full_name: Caitlin Bowman

given: Caitlin

family: Davis

full_name: Elizabeth J. Davis

given: Elizabeth J.

name: Melanoma Institute of Australia, Sydney, New South Wales, Australia

name: University of Sydney, Sydney, New South Wales, Australia

name: Royal North Shore Hospital, Sydney, New South Wales, Australia

name: Mater Hospital, Sydney, New South Wales, Australia

name: Department of Medical Oncology, Westmeade Hospital, Sydney, New South Wales, Australia

name: Department of Medical Oncology, Blacktown Hospital, Sydney, New South Wales, Australia

name: Department of Cutaneous Oncology, The Moffitt Cancer Center and Research Institute, Tampa, Florida

ReferenceCitation: Alexandre J, Moslehi JJ, Bersell KR, Funck-Brentano C, Roden DM, Salem JE. Anticancer drug-induced cardiac rhythm disorders: Current knowledge and basic underlying mechanisms. Pharmacol Ther. 2018 Sep;189:89-103. doi: 10.1016/j.pharmthera.2018.04.009. Epub 2018 Apr 24. Review.

ReferenceCitation: Wright JJ, Salem JE, Johnson DB, Lebrun-Vignes B, Stamatouli A, Thomas JW, Herold KC, Moslehi J, Powers AC. Increased Reporting of Immune Checkpoint Inhibitor-Associated Diabetes. Diabetes Care. 2018 Dec;41(12):e150-e151. doi: 10.2337/dc18-1465. Epub 2018 Oct 10.

title: Increased Reporting of Immune Checkpoint Inhibitor–Associated Diabetes

ReferenceCitation: Anquetil C, Salem JE, Lebrun-Vignes B, Johnson DB, Mammen AL, Stenzel W, Léonard-Louis S, Benveniste O, Moslehi JJ, Allenbach Y. Immune Checkpoint Inhibitor-Associated Myositis: Expanding the Spectrum of Cardiac Complications of the Immunotherapy Revolution. Circulation. 2018 Aug 14;138(7):743-745. doi: 10.1161/CIRCULATIONAHA.118.035898.

name: Department of Internal Medicine and Clinical Immunology (C.A., O.B., Y.A.)

name: Institut National de la Santé et de la Recherche Médicale, Association Institut de Myologie, Centre de Recherche en Myologie, UMRS974, Paris, France (C.A., O.B., Y.A.)

name: Department of Pharmacology, Regional Center of Pharmacovigilance (J.-E.S., B.L.-V.), Sorbonne Universités, Pitié-Salpêtrière University Hospital, Paris, France

name: Division of Cardiovascular Medicine and Cardio-Oncology Program, Department of Medicine (J.-E.S., W.S., J.J.M.)

name: Division of Oncology, Department of Medicine (D.B.J., J.J.M.), Vanderbilt University Medical Center, Nashville, TN

name: Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Expression, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD (A.L.M.)

name: Department of Neurology and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (A.L.M.)

name: Departments of Neuropathology, Charité-Universitätsmedizin, Berlin, Germany (W.S.).

publisher: Ovid Technologies (Wolters Kluwer Health)

title: Immune Checkpoint Inhibitor–Associated Myositis

ReferenceCitation: Nguyen LS, Raia L, Lebrun-Vignes B, Salem JE. Graft Versus Host Disease Associated with Immune Checkpoint Inhibitors: A Pharmacovigilance Study and Systematic Literature Review. Front Pharmacol. 2021 Feb 5;11:619649. doi: 10.3389/fphar.2020.619649. eCollection 2020.

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - Inserm

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - Diderot

ReferenceCitation: Vozy A, De Martin E, Johnson DB, Lebrun-Vignes B, Moslehi JJ, Salem JE. Increased reporting of fatal hepatitis associated with immune checkpoint inhibitors. Eur J Cancer. 2019 Dec;123:112-115. doi: 10.1016/j.ejca.2019.09.022. Epub 2019 Nov 1.

location_facility: AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM.


title: Aberrant Splicings Due to Microsatellite Instability in Colorectal Cancer : Physiopathological and Clinical Impact (MICROSPLICOTHER)

summary:
MSI (Microsatellite Instability) colorectal cancer (CRC) show improved survival, are less prone to metastasis and show poor response to chemotherapy (compared to MSS tumors). The underlying reasons for these characteristics are still not understood and no specific therapeutic approach for MSI colon tumours (15% of CRC overall) has yet been developed.

The MSI process is oncogenic when it affects DNA repeat sequences that have a functional role, e.g. Small Coding Repeats (SCR). MSI also frequently affects Long Non-Coding Repeats (LNCR) in tumour DNA. In contrast to SCR, only a few LNCR are endowed with biological activity. Consequently, this area has received very little attention. Our group recently identified HSP110 mutant chaperone protein in MSI CRC that was generated by somatic deletion of a LNCR. Of interest, HSP110 mutant (due to exon skipping) have anti-oncogenic properties and the survival of MSI CRC patients receiving chemotherapy is positively associated with HSP110 mutations in tumour DNA.

The aim of the current project is to identify additional clinically relevant MSI-associated splicing aberrations due to mutations in LNCR located in splice acceptor sites. The four main steps are as follows:

To identify exon/intron sites affected by aberrant splicing events due to MSI in CRC . All RNASeq data will be exploited to identify recurrent splicing aberrations (mostly exon skipping) that occur specifically in MSI colon tumours;
To investigate for possible functional links between MSI and any detected aberrant splicing events . All specific aberrant splicing events detected by RNAseq in MSI CRC samples will be first confirmed (quantitative RT-PCR) in order to eliminate false positive cases. For validated exon candidates, the allelic profiles of adjacent intronic LNCR will be analysed (PCR and fluorescence genotyping) in CRC cell lines and primary tumours (MSI and MSS), as well as in matching normal mucosa samples in order to assess their polymorphic status;
To identify splicing events and LNCR mutations with clinical relevance in MSI CRC patients . All LNCR with a confirmed role in gene splicing in MSI CRC will be analysed. The clinical relevance of candidate genes will be assessed using multivariate survival regression models for Relapse- Free Survival, with interaction terms (response to chemotherapy);
To initiate functional studies on a limited number of clinically relevant, cancer-related genes whose splicing is perturbed in MSI cancer cells, and to develop biological tools to simplify screening in future clinical assays Similar to HSP110, we will focus on 4 or 5 mutant proteins that are promising drug therapeutic targets. Functional assays will be developed to further elucidate their role in the pathophysiology of MSI tumours. We also aim to develop biological tools for these candidate genes, such as the detection of wild-type or mutant proteins by immunohistochemistry.

location_facility: Service d'Anatomie et de Cytologie Pathologique


title: Rhythm and the Multisensoriality's Effects on the Motor Development in Children With Cerebral Palsy

acronym: APP-PaC

summary:
Cerebral palsy (CP) affects the motor function but also the cognitive function of the child. Physical activity brings motor and cognitive benefits and appears as an important aspect of the therapy that is offered to them.

The child is seating in front of a computer, seating comfortably on a chair during 1 hour. The experimental task consists in learning a sequence of taps on "Serial reaction time task" type buzzers (SRTT) in which the child must press a buzzer corresponding to one of the 4 squares that on the screen. The sequence corresponds to 10 steps in a particular order.


title: Methyl-qPCR : a New Predictive Marker for Epstein-Barr Virus-associated Lymphoproliferations During Allogeneic Hematopoietic Stem Cell Transplantation

acronym: EBVALLO

summary:
Scientific context

Epstein-Barr virus has a causal role in the pathogenesis of multiple distinct lymphomas. Post-transplant lymphoproliferative diseases (PTLD) are the most frequent EBV-induced proliferations. PTLD after allogeneic stem cell transplantation has an incidence lower than 5% but may increase up to 10-20% in patients with established risk factors. EBV-DNAemia is predictive of EBV-PTLD and is routinely performed using qPCR on whole blood. Preemptive therapeutic strategies with anti-CD20 antibody are used when patients are above a defined EBV-DNAemia threshold. This approach remains limited since it does not discriminate between an EBV-induced lymphoproliferation (latent cycle) and/or a replicating virus (replicative cycle).

Epigenetic modifications plays a central role in regulating the switch from latent to lytic gene expression. Specific DNA modifications can be regarded as molecular signatures for EBV genomes associated with the status of the viral infection (latent vs lytic). Accordingly, these signatures may be envisioned as a potent tool to characterize the state of the viral infection in vivo.

Description of the project Our primary objective is to estimate the respective percentages of EBV-lytic and EBV-latent genomes (proliferating cells) in patients presenting with a high EBV-DNAemia after allogeneic stem cell transplantation HSCT by analysing the epigenetic modifications of EBV genome on specific sites. Our secondary objectives are i) to determine risk factors associated with each "latent versus lytic EBV" profiles and ii) to correlate the "latent versus lytic EBV" profiles with response to rituximab infusion and patient outcomes.

For this purpose, a retrospective study (n=80) and a prospective study (estimation n=58) will be established. The different steps of this project are:

To study epigenetic modifications. The laboratory is developing a new approach to distinguish between latent and lytic genomes.
To realize quantitative analysis by RT-PCR of different EBV transcripts specific of the latent or of the lytic phase of the virus This method will be applied on RNA extracted from patient blood samples with elevated EBV viral load, under condition preserving RNA integrity. The results will be validated on a prospective cohort of HSCT patients (n=58) (Saint-Antoine Hospital and La Pitié-Salpêtrière Hospital).
To perform quantitative analysis of EBV genomes in plasma, saliva and total blood samples by current routine procedures In addition to total blood samples, plasma and saliva will be collected since free viral particles are known to accumulate in these biological fluids upon EBV reactivation. These samples will be treated by normalized procedures that are routinely used in the medical virology laboratory to quantify EBV in human samples.

Expected results By establishing a simple method for studying epigenetic modifications of EBV genomes, we expect to understand the significance of high EBV viral load and the pathophysiology of post-HSCT PTLD. We aim to distinguish between the latent / lytic profiles of HSCT patients and to correlate their respective risks for developing PTLD. Establishing the epigenetic EBV profile in the post-HSCT setting when facing increase viral load and PTLD will improve our understanding of the biological mechanisms determining EBV-status in post-HSCT. This should improve major medical and economical issues. These results could have a major therapeutic

intervention_type: Biological


title: Memorial Anxiety Scale for Patients With Prostate Cancer: French Validation, Links With Quality Of Life and Future Temporal Perspective.

summary: A specific scale allowing the measure of anxiety of patients with protate cancer has been designed and validated but the French version needs to be validated. This study aims at validating the French translation of this scale.

lead_sponsor: Institut Paoli-Calmettes


title: Study of the Predictive Impact of MMP2 and MMP9 Levels for Patients With Metastatic Kidney Cancer Treated With Anti-angiogenic Agents Compared to Patients Not Treated With Antiangiogenic (Localized Kidney Cancer and Oligometastatic)

summary: Prospective research of Matrix Metalloproteinases (MMP) 2 and 9 as predictive biomarkers in metastatic kidney cancer patients treated with 2 anti angiogenic agents (Sunitinib or Pazopanib).

ReferenceCitation: Jubb AM, Harris AL. Biomarkers to predict the clinical efficacy of bevacizumab in cancer. Lancet Oncol. 2010 Dec;11(12):1172-83. doi: 10.1016/S1470-2045(10)70232-1. Review.

family: Jubb

full_name: Adrian M Jubb

given: Adrian M

family: Harris

full_name: Adrian L Harris

given: Adrian L

journal_name: The Lancet Oncology

publisher: Elsevier BV

publisher_dissemination: Elsevier

publisher_group: Elsevier

publisher_normalized: Elsevier

ReferenceCitation: Tabouret E, Boudouresque F, Barrie M, Matta M, Boucard C, Loundou A, Carpentier A, Sanson M, Metellus P, Figarella-Branger D, Ouafik L, Chinot O. Association of matrix metalloproteinase 2 plasma level with response and survival in patients treated with bevacizumab for recurrent high-grade glioma. Neuro Oncol. 2014 Mar;16(3):392-9. doi: 10.1093/neuonc/not226. Epub 2013 Dec 9.

family: Tabouret

full_name: Emeline Tabouret

given: Emeline

family: Boudouresque

full_name: Françoise Boudouresque

given: Françoise

family: Barrie

full_name: Maryline Barrie

given: Maryline

family: Matta

full_name: Mona Matta

given: Mona

family: Boucard

full_name: Celine Boucard

given: Celine

family: Loundou

full_name: Anderson Loundou

given: Anderson

family: Carpentier

full_name: Antoine Carpentier

given: Antoine

family: Sanson

full_name: Marc Sanson

given: Marc

family: Metellus

full_name: Philippe Metellus

given: Philippe

family: Figarella-Branger

full_name: Dominique Figarella-Branger

given: Dominique

family: Ouafik

full_name: L'Houcine Ouafik

given: L'Houcine

family: Chinot

full_name: Olivier Chinot

given: Olivier

journal_name: Neuro-Oncology

oa_colors: green hybrid

publisher: Oxford University Press (OUP)

publisher_dissemination: Oxford University Press

publisher_group: Oxford University Press

publisher_normalized: Oxford University Press

ReferenceCitation: Tabouret E, Boudouresque F, Farina P, Barrié M, Bequet C, Sanson M, Chinot O. MMP2 and MMP9 as candidate biomarkers to monitor bevacizumab therapy in high-grade glioma. Neuro Oncol. 2015 Aug;17(8):1174-6. doi: 10.1093/neuonc/nov094.

ReferenceCitation: Tabouret E, Bertucci F, Pierga JY, Petit T, Levy C, Ferrero JM, Campone M, Gligorov J, Lerebours F, Roché H, Bachelot T, van Laere S, Ueno NT, Toiron Y, Finetti P, Birnbaum D, Borg JP, Viens P, Chinot O, Gonçalves A. MMP2 and MMP9 serum levels are associated with favorable outcome in patients with inflammatory breast cancer treated with bevacizumab-based neoadjuvant chemotherapy in the BEVERLY-2 study. Oncotarget. 2016 Apr 5;7(14):18531-40. doi: 10.18632/oncotarget.7612.

name: Institut Paoli-Calmettes, Medical Oncology Department, Marseille, France

name: CRO2, Neuro-Oncology Department, UMRS_911, Marseille, France

name: Aix-Marseille University, Marseille, France

name: Centre de Recherche en Cancérologie de Marseille, Inserm, Marseille, France

name: Centre de Recherche en Cancérologie de Marseille, CNRS, Marseille, France

name: Institut Curie & Université Paris Descartes, Medical Oncology Department, Paris, France

name: Centre Paul Strauss, Medical Oncology Department, Strasbourg, France

name: Centre François Baclesse, Medical Oncology Department, Caen, France

name: Centre Antoine Lacassagne, Medical Oncology Department, Nice, France

name: Centre René Gauducheau, Medical Oncology Department, Saint-Herblin, France

name: IUC-UPMC, Sorbonne University, Paris, France

name: Hopital Rene Huguenin-Institut Curie, Medical Oncology Department, Saint-Cloud, France

name: Institut Claudius Regaud, Medical Oncology Department, Toulouse, France

name: Institut Leon Berard, Medical Oncology Department, Lyon, France

name: Translational Cancer Research Unit, GZA Hospitals Sint-Augustinus, Wilrijk, Belgium

name: Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium

name: Department of Oncology, KU Leuven, Leuven, Belgium

name: The University of Texas MD Anderson Cancer Center, Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, Houston, TX, USA

repository_institution: University of Antwerp - Institutional Repository University of Antwerp

repositories:
PubMed Central
irua
pdfs.semanticscholar.org


title: Relation Between Pregnenolone Endocannabinoids in Normal-weight and Obese Men

acronym: CannaPREG

summary: Measured plasmatic concentration of pregnenolone and endocannabinoid in fasting conditions and over a meal in obese and normal-weight men subjects, to research a dysfunction in the negative feed-back between pregnenolone and CB1 ligand in obese subjects. This dysfunction could participate to the hyperactivity of endocannabinoid system saw in obesity.


title: ELR+CXCL Cytokines in Metastatic Kidney Cancers: Predictive Markers of Resistance to Sunitinib and New Relevant Therapeutic Targets in Refractory Patients

acronym: SUNITRES

summary: Metastatic renal cell carcinomas (mRCC) are highly angiogenic tumors because of mutation of the pVHL gene leading to over-expression of VEGF. Therefore, mRCC represent a paradigm for the use of anti-angiogenic treatments targeting the VEGF/VEGFR pathway. Despite an increase of the time to progression these treatments, taken alone, are not curative with ineluctable progression especially for the reference treatment sunitinib a multi kinase inhibitors of VEGF, PDGF, CSF1 receptors and c-kit, FLT3 and RET. At progression on sunitinib, patients received mTOR inhibitors which is responsible, at least, of HIF1A mRNA translation, then on a third line sorafenib that inhibits VEGFR2, 3 PDGFR, c-KIT and B-RAF. The access to these different lines of treatment has finally prolonged survival but this situation is not satisfactory. Unexpected aspect associated with the use of anti-angiogenesis treatments was the diversity of the patients' response. Some patients are right away refractory and die rapidly, but the majority of patient has a transient response then progress and a few percentages of them are responder for a very long period of time. By only targeting normal endothelial cells and tumor neo-vascularization, the response should have been more homogenous, thus highlighting that the treatment induced a "Darwinian" adaptation of tumor cells and cells of the microenvironment. Two conclusions follow from these observations: 1- The need to identify predictive markers of efficacy; 2-The identification of druggable targets participating in progression on anti-angiogenic treatments. Our results have highlighted the ELR+CXCL cytokines, pro-inflammatory and pro-angiogenic cytokines as prognosis markers of survival of mRCC patients and relevant therapeutic targets on experimental tumors in mice. As VEGF/VEGFR, these cytokines are produced by tumor, endothelial and inflammatory cells. Their receptors (CXCR1, 2) are expressed physiologically by immune and endothelial cells and aberrantly by tumor cells generating at the same time autocrine proliferation loops, chronic angiogenesis and inflammation. Therefore, the CXCL/CXCR1,2 axis constitutes an independent axis of cancer development and propagation. However, the current standard of care is to administer anti-angiogenic therapies as the first line treatment. The objective of this project is linked to the identification of potent predictive markers of efficacy, easily measured in plasma samples. Deciphering the molecular mechanisms associated with the production of such cytokines by tumor cells and by cells of the microenvironment represents an interesting intellectual challenge and a relevant way to improve the current treatments by targeting, at progression on the current standard of care, other pathways than the VEGF/VEGFR axis.

lead_sponsor: Centre Antoine Lacassagne


type: EudraCT Number

title: A Pilot Study of the Feasibility of Intraoperative Photodynamic Therapy of Glioblastoma.

acronym: INDYGO

summary: The study pilot evaluate the feasibility of a "5-ALA- PpIX (protoporhyrin IX) mediated per-PDT protocol" in patients with glioblastoma accessible for complete surgical removal of contrast. This treatment will be carried out in addition to the current reference treatment of glioblastoma: maximum resection surgery followed by radiochemotherapy according to the protocol Stupp

ReferenceCitation: Vermandel M, Dupont C, Lecomte F, Leroy HA, Tuleasca C, Mordon S, Hadjipanayis CG, Reyns N. Standardized intraoperative 5-ALA photodynamic therapy for newly diagnosed glioblastoma patients: a preliminary analysis of the INDYGO clinical trial. J Neurooncol. 2021 May;152(3):501-514. doi: 10.1007/s11060-021-03718-6. Epub 2021 Mar 20.

family: Vermandel

full_name: Maximilien Vermandel

given: Maximilien

family: Dupont

full_name: Clément Dupont

given: Clément

family: Lecomte

full_name: Fabienne Lecomte

given: Fabienne

family: Leroy

full_name: Henri-Arthur Leroy

given: Henri-Arthur

family: Tuleasca

full_name: Constantin Tuleasca

given: Constantin

family: Mordon

full_name: Serge Mordon

given: Serge

family: Hadjipanayis

full_name: Constantinos G. Hadjipanayis

given: Constantinos G.

family: Reyns

full_name: Nicolas Reyns

given: Nicolas

journal_name: Journal of Neuro-Oncology

publisher: Springer Science and Business Media LLC

publisher_dissemination: Springer-Nature

publisher_group: Springer-Nature

publisher_normalized: Springer

lead_sponsor: University Hospital, Lille


title: Phase III Multicenter Randomized Trial Evaluating in Patients at the Time of the Primary HIV-1 Infection, the Impact on the Viral Reservoir of a Combination Including Tenofovir/Emtricitabine and Dolutegravir or Tenofovir/Emtricitabine and Darunavir/Cobicistat

summary: The purpose of this study is to compare the impact of two combination of two tablets once daily: dolutegravir associated with emtricitabine / tenofovir versus darunavir / cobicistat associated with emtricitabine / tenofovir on DNA HIV measured in PBMC at 48 weeks in patients with primary HIV-1 infection.

lead_sponsor: ANRS, Emerging Infectious Diseases


title: Physiological Characteristics of High Altitude Climbers

acronym: ALTIPERF

summary: Climbing at high altitude and tolerating hypoxic environment require specific physiological adaptations. Large intersubjects differences exist regarding the ability to adapt to high altitude and hypoxia. The present study aims to characterise the physiological responses to hypoxia in a group of elite climbers by comparison to sea level athletes. We hypothesised that elite climbers would show better physiological responses to hypoxia and more preserved performances compared to sea level.

primary_purpose: Health Services Research

ReferenceCitation: Verges S, Rupp T, Jubeau M, Wuyam B, Esteve F, Levy P, Perrey S, Millet GY. Cerebral perturbations during exercise in hypoxia. Am J Physiol Regul Integr Comp Physiol. 2012 Apr 15;302(8):R903-16. doi: 10.1152/ajpregu.00555.2011. Epub 2012 Feb 8. Review.

lead_sponsor: University Hospital, Grenoble


title: High-flow Nasal Oxygen Therapy (Optiflow) in Hospitalized Infant With Moderate-to-severe Bronchiolitis: Multicentric Randomized Controlled Trial

acronym: BRONCHOPTI

summary:
Over the last decade, high-flow nasal oxygen therapy (HFN) has emerged as a new method to provide respiratory support in children with moderate to severe bronchiolitis.

However, any randomized clinical trial (RCT) have demonstrated that earlier support with HFN is superior to standard care including low -flow nasal oxygen therapy to reduce the risk of acute respiratory failure requiring non invasive (or tracheal) ventilation and subsequently the need of PICU transfer.

lead_sponsor: Assistance Publique - Hôpitaux de Paris


title: Melanoma Cells Dissemination Study in Healthy Patients' Tissues

acronym: DISSEMELA

summary: The objective of this project is to evaluate the presence of melanoma quiescent or initiating clonal cells in peritumoral healthy tissue displaying the same molecular signature than those of the tumor/metastasis and to correlate this presence to the prognostic value.

ReferenceCitation: Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, Cho KH, Aiba S, Bröcker EB, LeBoit PE, Pinkel D, Bastian BC. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005 Nov 17;353(20):2135-47.

ReferenceCitation: Faries MB, Steen S, Ye X, Sim M, Morton DL. Late recurrence in melanoma: clinical implications of lost dormancy. J Am Coll Surg. 2013 Jul;217(1):27-34; discussion 34-6. doi: 10.1016/j.jamcollsurg.2013.03.007. Epub 2013 May 3.

ReferenceCitation: Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ. Efficient tumour formation by single human melanoma cells. Nature. 2008 Dec 4;456(7222):593-8. doi: 10.1038/nature07567.

ReferenceCitation: How-Kit A, Tost J. Pyrosequencing®-Based Identification of Low-Frequency Mutations Enriched Through Enhanced-ice-COLD-PCR. Methods Mol Biol. 2015;1315:83-101. doi: 10.1007/978-1-4939-2715-9_7.

location_facility: Name:: INSERM - UMRS 938, UPMC Saint-Antoinen Hospital, Team "Stem cells and transition from pre-invasive tumors"