1,720,997 research outputs found
MUC1/EGFR/IL17 and autophagy are associated in the resistance of chemiotherapy or targeted therapy in triple negative breast cancer.
No full textLe cancer du sein triple négatif (TN) est un cancer présentant des résistances aux agents de chimiothérapie. Malgré la forte expression de l’EGFR, il est aussi résistant aux anti-EGFR. Ces mécanismes de résistance ne sont pas connus.MUC1 est une protéine transmembranaire largement glycosylée. Sa fonction extracellulaire est impliquée dans la régulation des récepteurs membranaires dont l’EGFR. Comme les autres glycoprotéines membranaires, son unité extracellulaire (MUC1-N) peut moduler la réponse cellulaire immune par hypersialylation. Son unité intracellulaire (MUC1-C) possède des sites de phosphorylation impliqués dans plusieurs voies de signalisation telles que PI3K/AKT/mTOR ou RAS/RAF/MEK/ERK. Ces dernières régulent l’autophagie qui est un mécanisme de survie cellulaire associé à la résistance aux agents de chimiothérapie.Nous avons démontré que les TN présentaient des modifications quantitatives et qualitatives de l’expression de MUC1, altérant probablement les régulations des voies associées à MUC1/EGFR dont l’autophagie. L’activation de l’autophagie explique la résistance aux traitements des agents de chimiothérapie. L’IL17 est un facteur pro-inflammatoire secrété par du microenvironnement tumoral et associé également à la résistance des agents de chimiothérapie des TN, par activation de la voie MEK/ERK, suggérant son implication à activer l’autophagie.En conclusion, nos travaux permettent d’émettre l’hypothèse que l’inhibition de l’autophagie et/ou MUC1 et/ou IL17 pourrait augmenter la sensibilité aux traitements de chimiothérapie ou des thérapies ciblées dirigées contre les TN.Triple negative breast cancer (TN) is often associated to chemioresistance. Moreover, despite an EGRF over-expression, TN is also resistant to anti-EGFR drugs. These resistance mechanisms are not known yet.MUC1 is a transmembrane broadly glycosylated protein. Its extracellular unit (MUC-N) is involved to membrane receptor regulations, as EGFR. As other membrane glycoproteins, MUC1 could modulate, by over-sialylation, the immune cellular response. Its intracellular unit (MUC-C) presents phosphorylation sites involved in numerous signal pathways such as PI3K/AKT/mTOR or RAS/RAF/MEK/ERK. Both pathways regulate autophagy which is a survival cellular mechanism associated to resistance of chemiotherapy drugs.We showed that TN presents quantitative and qualitative MUC1 alterations, likely associated with dys-regulation of autophagy/MUC1/EGFR pathways. The activation of autophagy explains the chemiotherapy resistance. IL17 is a proinflammatory interleukin secreted by the tumor microenvironment. In TN, IL17 is also associated to chemiorestistance throughout the MEK/ERK pathways, suggesting its involving activating autophagy.In conclusion, our work allows us to hypothesize that inhibition of autophagy and/or MUC1 and/or IL17 could be increase the sensibility to chemiotherapy or targeted therapies against TN
Role of the proinflammatory cytokines belonging to the interleukin 17 family in triple negative breast cancer
No full textLe cancer du sein est diagnostiqué chez 58 500 femmes chaque année et constitue leur première cause de mortalité par cancer, c’est donc un problème majeur de santé publique. Néanmoins les progrès thérapeutiques fulgurants des 20 dernières années permettent de guérir 8 cas sur 10 tous stades confondus. Pourtant, une entité particulière de CS touche les sujets jeunes et demeure un challenge pour les cliniciens en raison d’un pronostic effroyable : le cancer du sein triple négatif (CSTN), caractérisé par une négativité de l’expression des récepteurs hormonaux (RH-) et l’absence de surexpression de HER 2. Malgré une surexpression de HER 1 (aussi appelé EGFR) dans 50% des cas, ces tumeurs résistent aux thérapies anti-EGFR par la phosphorylation de kinases qui activent l’EGFR et sa translocation vers le noyau. Cette résistance reste à préciser à l’heure actuelle. Notre équipe a montré que le récepteur à l’interleukine 17 (IL-17R) était surexprimé dans les CSTN et de mauvais pronostic. En outre, l’IL-17A et E provoquent une résistance des cellules tumorales à la chimiothérapie. L’objectif de cette thèse est d’étudier les rôles des cytokines pro-inflammatoires de la famille de l’IL-17 dans la résistance aux anti-EGFR par les CSTN. Dans un premier temps, nous faisons la synthèse des connaissances fondamentales. Dans la partie expérimentale, nous évaluons les effets de l’IL-17E sur différentes lignées de CSTN résistantes aux anti-EGFR : Nous observons que l’IL-17E active l’EGFR de façon similaire à l’EGF, et qu’elle active aussi les kinases PYK-2, Src et STAT3 indispensables à l’activation de l’EGFR et sa translocation nucléaire. L’IL17E se fixe sur son récepteur spécifique IL-17RA/RB à la surface des cellules de CSTN et agit en synergie avec la voie de l’EGF pour induire une transactivation de l’EGFR dépendante de Src ainsi qu’une translocation de pSTAT3 et pEGFR vers le noyau. Nos résultats sont en faveur d’interactions entre les voies de l’IL17 et de l’EGF contribuant à une résistance des CSTN aux anti-EGFR. Nous suggérons que la combinaison d’inhibiteurs de l’IL-17R avec les anti-EGFR pourraient améliorer le traitement des CSTN et invitons à la réalisation d’expériences complémentaires.Each year 58500 women will be diagnosed with breast cancer (BC) which constitute the first cause of mortality by cancer, and is thus a major healthcare problème. Nevertheless, therapeutic advances of these last 20 years, allow curability in 8 case out of 10 all stades included. Yet, a particular entity of BC threatens younger subjects and remains a challenge for physicians because of its grim prognosis : the triple negative breast cancer (TNBC), characterized by hormone recpetors negativity (HR-) and a lack of HER2 overexpression. These tumors overexpress HER1 (also called EGFR) in 50% of cases, but usually resists to anti-EGFR therapies. This resistance remains to be explored. Our team has already showed that the interleukin 17 receptor (IL17R) was overexpressed in TNBC and associated with poor prognosis.Besides IL17A and IL17E creates drug resistance in tumor cell lines. The main goal of this thesis is to study the role of the pro-inflammatory cytokines of the IL17 family in the resistance to anti-EGFR drugs. First we review the fundamental knwoledge. Then in the experimental chapter, we evaluate the impact of IL17E on different TNBC cell lines anti-EGFR-resistant : we observe that similarly to EGF, IL17E activates EGFR and also activates PYK2, Src and STAT3 kinases criticals to EGFR activation and nuclear translocation. IL17E docks its specific receptor IL17RA/RB at the surface of TNBC cells and synergizes with the EGF pathway to induce Src-dependant EGFR-transactivation then pSTAT3 and pEGFR translocation to the nucleus. Our results are in favor of crosstalks between IL17 and EGF pathwalys contributing to anti-EGFR resistance in TNBC. We propose combination of IL17R inhibitors to anti-EGFR to improve TNBC treatment and we support the pursuit of complementary investigations
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
SARCOME PRIMITIF DU MYOCARDE (PARTICULARITES DIAGNOSTIQUES, ICONOGRAPHIQUES, EVOLUTIVES ET THERAPEUTIQUES : A PROPOS D'UNE OBSERVATION ET D'UNE REVUE DE LA LITTERATURE)
No full textBESANCON-BU Médecine pharmacie (250562102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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