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Combinaison de la chimiothérapie conventionnelle à l'Ellipticine avec la thérapie ciblée sur l'intégrine Alpha5beta1 dans les glioblastomes humaines
No full textLes glioblastomes sont des tumeurs cérébrales agressives pour lesquelles les thérapies classiques se révèlent souvent inefficaces. Les intégrines peuvent aussi réguler l'angiogénèse, l'embryogenèse, la prolifération, la différentiation, la migration et la survie. Nous avons proposé l`intégrine a5b1 comme un cible thérapeutique pour les glioblastomes, comme elle est surexprimée dans les gliomes en fonction du grade tumoral et comme les travaux récents l`indiquent ayant un rôle central dans un réseau fonctionnel de la cellule tumoral. Les deux lignées cellulaires de glioblastome testés (U87MG et U373) ont été sensibles à l`ellipticine. Dans le contexte de la protéine p53 fonctionnelle (U87MG), l`ellipticine induit la sénescence, alors que dans U373 (p53mt), il induit l'apoptose. Les deux lignées cellulaires expriment des enzymes générant les métabolites de l'ellipticine connus pour se lier de façon covalente à l'ADN. Ensuite, nous montrons que en inhibant l'intégrine a5b1 avec ses deux ligands sélectifs (SJ749 et K34c) diminue la sénescence induite par la chimiothérapie et facilite l'apoptose dans un contexte p53 fonctionnelle. Lorsque la p53 est muté et inactif, la chimiothérapie provoque de l'apoptose p53-indépendante au lieu de la sénescence, ce qui n'a pas été améliorée par les antagonistes des intégrines. Les antagonistes de l'intégrine a5b1 modulent la p53 signalisation chimio-induite. Ce travail fournit des nouvelles preuves des avantages de la combinaison de la chimiothérapie conventionnelle avec la thérapie ciblée sur l'intégrine a5b1 sous-tendent l'importance de connaître les caractéristiques de base de la tumeur pour estimer le bénéfit de la thérapie finale.Gliomas are highly aggressive and resistant brain tumors difficult to cure with conventional therapies. Therefore, targeted therapies are needed. Integrins are implicated in angiogenesis, cell proliferation, differentiation, migration and survival. We have identified the a5b1 integrin as a promising therapeutic target as its expression correlates with tumor grade and recent studies predispose it to play a key role in tumor cell functional network. Ellipticine was shown to be brain tumor specific. Its pharmacological efficiency and/or genotoxic side effects are dependent on its enzymatic activation. U87MG and U373 glioblastoma cell lines are sensitive to ellipticine. p53 plays an important role in their response to it. In the context of functional p53 (U87MG), ellipticine induced senescence, whereas in U373 (p53mt) it induced apoptosis. Both cell lines express enzymes generating ellipticine metabolites known to covalently bind to DNA. We next investigated whether blocking a5b1 integrin concomitantly with chemotherapy may impact the response to chemotherapy of human glioblastoma. Inhibiting a5b1 integrin with two selective ligands (SJ749 and K34c) decreases drug-induced senescence and facilitates cell apoptosis in a functional p53 background. When p53 is mutated and/or inactive, chemotherapy provoked cell apoptosis instead of senescence, which was not improved by integrin antagonists. Results were confirmed using multiple models. In summary, this work provides novel evidences of profitability of combining conventional chemotherapy with a5b1 integrin-targeted therapy underlying the importance of knowing basic tumor characteristics to may estimate the final therapy outcome
Combination of ellipticine chemotherapy and alpha5beta1 integrin-targeted therapy in human glioblastoma
No full textLes glioblastomes sont des tumeurs cérébrales agressives pour lesquelles les thérapies classiques se révèlent souvent inefficaces. Les intégrines peuvent aussi réguler l’angiogénèse, l’embryogenèse, la prolifération, la différentiation, la migration et la survie. Nous avons proposé l`intégrine α5β1 comme un cible thérapeutique pour les glioblastomes, comme elle est surexprimée dans les gliomes en fonction du grade tumoral et comme les travaux récents l`indiquent ayant un rôle central dans un réseau fonctionnel de la cellule tumoral. Les deux lignées cellulaires de glioblastome testés (U87MG et U373) ont été sensibles à l`ellipticine. Dans le contexte de la protéine p53 fonctionnelle (U87MG), l`ellipticine induit la sénescence, alors que dans U373 (p53mt), il induit l'apoptose. Les deux lignées cellulaires expriment des enzymes générant les métabolites de l'ellipticine connus pour se lier de façon covalente à l’ADN. Ensuite, nous montrons que en inhibant l'intégrine α5β1 avec ses deux ligands sélectifs (SJ749 et K34c) diminue la sénescence induite par la chimiothérapie et facilite l'apoptose dans un contexte p53 fonctionnelle. Lorsque la p53 est muté et inactif, la chimiothérapie provoque de l'apoptose p53-indépendante au lieu de la sénescence, ce qui n'a pas été améliorée par les antagonistes des intégrines. Les antagonistes de l'intégrine α5β1 modulent la p53 signalisation chimio-induite. Ce travail fournit des nouvelles preuves des avantages de la combinaison de la chimiothérapie conventionnelle avec la thérapie ciblée sur l'intégrine α5β1 sous-tendent l'importance de connaître les caractéristiques de base de la tumeur pour estimer le bénéfit de la thérapie finale.Gliomas are highly aggressive and resistant brain tumors difficult to cure with conventional therapies. Therefore, targeted therapies are needed. Integrins are implicated in angiogenesis, cell proliferation, differentiation, migration and survival. We have identified the α5β1 integrin as a promising therapeutic target as its expression correlates with tumor grade and recent studies predispose it to play a key role in tumor cell functional network. Ellipticine was shown to be brain tumor specific. Its pharmacological efficiency and/or genotoxic side effects are dependent on its enzymatic activation. U87MG and U373 glioblastoma cell lines are sensitive to ellipticine. p53 plays an important role in their response to it. In the context of functional p53 (U87MG), ellipticine induced senescence, whereas in U373 (p53mt) it induced apoptosis. Both cell lines express enzymes generating ellipticine metabolites known to covalently bind to DNA. We next investigated whether blocking α5β1 integrin concomitantly with chemotherapy may impact the response to chemotherapy of human glioblastoma. Inhibiting α5β1 integrin with two selective ligands (SJ749 and K34c) decreases drug-induced senescence and facilitates cell apoptosis in a functional p53 background. When p53 is mutated and/or inactive, chemotherapy provoked cell apoptosis instead of senescence, which was not improved by integrin antagonists. Results were confirmed using multiple models. In summary, this work provides novel evidences of profitability of combining conventional chemotherapy with α5β1 integrin-targeted therapy underlying the importance of knowing basic tumor characteristics to may estimate the final therapy outcome
Combinaison de la chimiothérapie conventionnelle à l'Ellipticine avec la thérapie ciblée sur l'intégrine Alpha5beta1 dans les glioblastomes humaines
No full textLes glioblastomes sont des tumeurs cérébrales agressives pour lesquelles les thérapies classiques se révèlent souvent inefficaces. Les intégrines peuvent aussi réguler l angiogénèse, l embryogenèse, la prolifération, la différentiation, la migration et la survie. Nous avons proposé lintégrine a5b1 comme un cible thérapeutique pour les glioblastomes, comme elle est surexprimée dans les gliomes en fonction du grade tumoral et comme les travaux récents lindiquent ayant un rôle central dans un réseau fonctionnel de la cellule tumoral. Les deux lignées cellulaires de glioblastome testés (U87MG et U373) ont été sensibles à lellipticine. Dans le contexte de la protéine p53 fonctionnelle (U87MG), lellipticine induit la sénescence, alors que dans U373 (p53mt), il induit l'apoptose. Les deux lignées cellulaires expriment des enzymes générant les métabolites de l'ellipticine connus pour se lier de façon covalente à l ADN. Ensuite, nous montrons que en inhibant l'intégrine a5b1 avec ses deux ligands sélectifs (SJ749 et K34c) diminue la sénescence induite par la chimiothérapie et facilite l'apoptose dans un contexte p53 fonctionnelle. Lorsque la p53 est muté et inactif, la chimiothérapie provoque de l'apoptose p53-indépendante au lieu de la sénescence, ce qui n'a pas été améliorée par les antagonistes des intégrines. Les antagonistes de l'intégrine a5b1 modulent la p53 signalisation chimio-induite. Ce travail fournit des nouvelles preuves des avantages de la combinaison de la chimiothérapie conventionnelle avec la thérapie ciblée sur l'intégrine a5b1 sous-tendent l'importance de connaître les caractéristiques de base de la tumeur pour estimer le bénéfit de la thérapie finale.Gliomas are highly aggressive and resistant brain tumors difficult to cure with conventional therapies. Therefore, targeted therapies are needed. Integrins are implicated in angiogenesis, cell proliferation, differentiation, migration and survival. We have identified the a5b1 integrin as a promising therapeutic target as its expression correlates with tumor grade and recent studies predispose it to play a key role in tumor cell functional network. Ellipticine was shown to be brain tumor specific. Its pharmacological efficiency and/or genotoxic side effects are dependent on its enzymatic activation. U87MG and U373 glioblastoma cell lines are sensitive to ellipticine. p53 plays an important role in their response to it. In the context of functional p53 (U87MG), ellipticine induced senescence, whereas in U373 (p53mt) it induced apoptosis. Both cell lines express enzymes generating ellipticine metabolites known to covalently bind to DNA. We next investigated whether blocking a5b1 integrin concomitantly with chemotherapy may impact the response to chemotherapy of human glioblastoma. Inhibiting a5b1 integrin with two selective ligands (SJ749 and K34c) decreases drug-induced senescence and facilitates cell apoptosis in a functional p53 background. When p53 is mutated and/or inactive, chemotherapy provoked cell apoptosis instead of senescence, which was not improved by integrin antagonists. Results were confirmed using multiple models. In summary, this work provides novel evidences of profitability of combining conventional chemotherapy with a5b1 integrin-targeted therapy underlying the importance of knowing basic tumor characteristics to may estimate the final therapy outcome.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF
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
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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