1,721,048 research outputs found
ZNF224 is a transcriptional repressor of AXL in chronic myeloid leukemia cells
No full textZNF224 is a KRAB-zinc finger transcription factor that exerts a key tumor suppressive role in chronic myelogenous leukemia.
In this study, we identify the receptor tyrosine kinase Axl as a novel target of ZNF224 transcriptional repression activity. Axl overexpression is found in many types of cancer and is frequently associated with drug resistance. Interestingly, we also found that sensitivity to imatinib can be partly restored in imatinib-resistant chronic myelogenous leukemia cells by ZNF224 overexpression and the resulting suppression of Axl expression.
These results, in accordance with our previous findings, support the role of ZNF224 in imatinib responsiveness and shed new insights into potential therapeutic use of ZNF224 in imatinib-resistant chronic myelogenous leukemia
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Multiple myeloma : from pathogenesis to chemoresistance
No full textLe myélome multiple (MM) est un cancer hématologique qui se caractérise par une prolifération et une accumulation de cellules plasmocytaires malignes au niveau de la moelle osseuse (MO). Il représente 10% des hémopathies malignes et 2% de la mortalité par cancer dans le monde occidental. La principale conséquence de l’expansion plasmocytaire clonale médullaire est la sécrétion excessive d’une immunoglobuline (Ig) unique qui va être à l’origine du caractère multi-symptomatique de cette pathologie. Ainsi, les manifestations du MM se caractérisent par des lésions osseuses, une atteinte rénale, une anémie, une hypercalcémie et une immunodéficience humorale conduisant à des infections récidivantes. Son pronostic est mauvais avec une médiane de survie qui se situe entre cinq et sept ans sous chimiothérapie qui vise à éliminer les cellules plasmocytaires malignes.A partir de la lignée U266 de myélome, nous avons dérivé des clones résistants au bortézomib (R6). Grâce à une analyse par biopuces à ADN, nous avons identifié 160 gènes significativement régulés dans les cellules R6 par rapport à la lignée parentale U266. Nous avons établi, par une approche fonctionnelle, que la surexpression de la protéine HspB8 conduit, via l’activation de la dégradation autophagique, à l’élimination des agrégats protéiques et à compenser l’effet de l’inhibition du protéasome conférant ainsi la résistance des cellules de myélome aux inhibiteurs du protéasome.Dans un second temps, nous nous sommes intéressés à l’implication de la protéine Bcl-B (BCL2L10) dans la pathogenèse du MM. Nous avons confirmé que Bcl-B est impliqué dans la pathogénèse du MM (patients et modèle murin).Velcade is one of the inescapable drug to treat patient suffering from multiple myeloma (MM) and resistance to this drug represents a major drawback for patients. However, the mechanisms underlying velcade resistance remain incompletely understood. We derived several U266 MM cell clones that resist to velcade. We derived several U266 MM cell clones that resist to velcade. U266- resistant cells were resistant to velcade-induced cell death but exhibited a similar sensitivity to various proapoptotic stimuli. Careful analysis of proteosomal subunits and proteasome enzymatic activities showed that neither the composition nor the activity of the proteasome was affected in velcade-resistant cells.In addition, pangenomic profiling of velcade-sensitive and resistant cells showed that the small heat shock protein HSPB8 was overexpressed in resistant cells. Finally, gain and loss of function experiment demonstrated that HSPB8 is a key factor for velcade resistance. In conclusion, HSPB8 plays an important role for the elimination of aggregates in velcade-resistant cells that contributes to their enhanced survival. Multiple myeloma (MM) evolves from a premalignant condition known as monoclonal gammopathy of undetermined significance (MGUS). However, the factors underlying the malignant transformation of plasmocytes in MM are not fully characterized. We report an MM phenotype in transgenic mice with Eμ-directed expression of the Bcl-B protein. With age, Eμ-bcl-b transgenic mice develop the characteristic features of human MM. In addition, this MM-like disease is serially transplantable, underlying the tumoral origin of plasmocytes
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
Mechanisms of resistance to targeted therapies in cutaneous metastatic melanoma and myelodysplastic syndromes : Characterization and preclinical validation of innovative compounds
No full textLe mélanome cutané métastatique et les syndromes myélodysplasiques (SMD) sont deux cancers incurables développant des résistances à leurs traitements antitumoraux de référence. Les cellules résistantes à ces thérapies sont caractérisées par une reprogrammation métabolique qui influence et facilite la progression tumorale. Par conséquent, l’inhibition des voies métaboliques semble être une stratégie thérapeutique prometteuse dans ces deux pathologies.Les deux équipes impliquées dans ce projet de thèse collaborent de longue date dans le domaine du cancer. Dans ce contexte et en partenariat avec l’Institut de Chimie de Nice, nos deux équipes ont mis au point des composés innovants ciblant les balances énergétiques intra cellulaires et la voie de l’AMPK. Parmi ces composés nous nous sommes intéressés plus précisément à l’AICAR (Acadésine). Un criblage d’efficacité et des études de structure-activité, nous ont permis d’optimiser la structure de nos composés. Sur la base de leur solubilité, de leur stabilité et sur leur capacité à induire la mort cellulaire de cellules tumorales, nous avons identifié le HA 344 comme composé « lead ». Cette étude propose de caractériser et de valider un nouvel inhibiteur covalent, le HA 344, dérivé de l’Acadésine, efficace sur des lignées de mélanomes et SMD sensibles et résistants à leur traitement de référence mais également sur cellules de patients. En combinant des techniques de click chimie, protéomique et métabolomique, nous avons identifié cette molécule comme un inhibiteur covalent de deux hubs métaboliques différents au sein des cellules tumorales. HA 344 inhibe l’étape finale et limitante de la glycolyse par sa liaison covalente à l’enzyme pyruvate kinase M2 (PKM2), et bloque simultanément l’activité de l’inosine monophosphate déshydrogénase (IMPDH), l’enzyme limitante de la synthèse de novo de guanylate. HA 344 bloque la croissance tumorale in vitro et in vivo de cellules de mélanome sensibles et résistantes aux inhibiteurs de BRAF. Ainsi, ce mécanisme d'action spécifique du HA 344 offre une nouvelle voie thérapeutique potentielle pour les patients atteints de mélanome cutané métastatique et d’autres cancers.Cutaneous metastatic melanoma (CMM) and myelodysplastic syndromes (MDS) are two incurable cancers developing resistance to their reference antitumor treatments. Cells resistant to these therapies are characterized by a metabolic reprogramming which profoundly influences and promotes tumor progression. Therefore, inhibition of metabolic pathways seems to be a promising therapeutic strategy to overcome resistance in these two pathologies.The two teams involved in this thesis project have a long-lasting collaboration in the field of cancer. In this context and in partnership with the Nice Institute of Chemistry, our two teams have developed innovative compounds targeting intra-cellular energy balances and the AMPK pathway. Among these compounds, we were more specifically interested in AICAR (Acadesine). Screening efficiency and structure-activity studies enabled us to optimize the structure of our compounds. Based on their solubility, their stability, and their ability to induce tumor cells death, we have identified HA 344 as a lead compound.This study describes the characterization and validation of a new covalent inhibitor, HA 344, derived from Acadesine, effective on CMM and MDS cell lines either sensitive or resistant to their reference treatment but also on CMM and MDS patient cells. By combining click chemistry, proteomics, and metabolomics approaches, we have identified this molecule as a covalent inhibitor of two different metabolic hubs within cancer cells. HA 344 inhibits the final and rate-limiting step of glycolysis through its covalent binding to the pyruvate kinase M2 (PKM2) enzyme, and concurrently blocks the activity of inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme of de novo guanylate synthesis. HA 344 efficiently eliminates tumor growth of BRAF inhibitor sensitive- and resistant-CMM cells both in vitro and in vivo. Thus, this specific mechanism of action of HA 344 provides potential therapeutic avenues not only for patients with CMM but also a broad range of cancers
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
- …
