1,720,980 research outputs found

    Minor role of pregnane-x-receptor for acquired multidrug resistance in head and neck squamous cell carcinoma in vitro

    Get PDF
    Purpose: Acquired multidrug resistance (MDR) has been linked to overexpression of drug-metabolising and transporting proteins mediated by pregnane-x-receptor (PXR). The aim of this work was to establish the relevance of PXR for MDR in head and neck squamous cell carcinoma (HNSCC). Methods: Using eight HNSCC cell lines, we determined the efficacy of paclitaxel, cisplatin and 5-fluorouracil (5-FU) via proliferation assays and determined the expression and activity of PXR through quantitative real-time polymerase chain reaction, western blotting and luciferase-based reporter gene assay. PXR knockdown approaches using shRNA-encoding vectors were applied to estimate the role of PXR for native MDR. Results: Drug resistance ranged between 5.2 and 620 nM for paclitaxel, varied between 4.5 and 58 μM for cisplatin, and varied between 1.1 and 5,467 μM for 5-FU. Lack of PXR mRNA expression was mostly accompanied by the absence of mRNA expression of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp, ABCB1) expression. Neither mRNA nor protein expression of PXR correlated with drug resistance. However, PXR activity tended to correlate with IC50 values of paclitaxel (p = 0.08). Knockdown of PXR in one of the cell lines had a slight but not significant impact on paclitaxel efficacy compared to scrambled sequence control. Surprisingly, only in two cell lines, PXR activity was increased by the well-known inductor rifampicin. Conclusion: This study suggests a malfunctioning of PXR and thus a minor relevance for iatrogenic chemotherapy resistance in HNSCC.Fil: Rigalli, Juan Pablo. University of Heidelberg. Department of Clinical Pharmacology and Pharmacoepidemiology; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Reuter, Tasmin. University of Heidelberg. Department of Clinical Pharmacology and Pharmacoepidemiology; AlemaniaFil: Herold Mende, Christel. University of Heidelberg; AlemaniaFil: Dyckhoff, Gerhard. University of Heidelberg; AlemaniaFil: Haefeli, Walter Emil. University of Heidelberg. Department of Clinical Pharmacology and Pharmacoepidemiology; AlemaniaFil: Weiss, Johanna. University of Heidelberg. Department of Clinical Pharmacology and Pharmacoepidemiology; AlemaniaFil: Theile, Dirk. University of Heidelberg. Department of Clinical Pharmacology and Pharmacoepidemiology; Alemani

    Arzneimitteltherapie im Alter – sieben kritische Fehler sind zu vermeiden

    No full text
    Arzneimitteltherapien sind im Alter komplexer, weil mehr Krankheiten vorliegen, mehr Medikamente benötigt werden und alles aufeinander abgestimmt sein muss. Die häufige Nierenfunktionsstörung kann Dosisreduktionen erfordern oder den Einsatz bestimmter Medikamente verbieten. Außerdem können frei verkäufliche Medikamente (z.B. Schmerzmittel) die Niere schädigen, weshalb sie kurz und niedrig dosiert eingenommen werden sollten. Patienten können die Qualität ihrer Therapien günstig beeinflussen, indem sie Rezepte rasch einlösen, früh mit der Therapie beginnen und diese solange verlässlich weiterführen, wie es medizinisch sinnvoll ist (gute Adhärenz und Persistenz). Unklarheiten zur Verabreichung sollten sofort geklärt und die aktuelle Therapie umfassend auf einem Medikationsplan dokumentiert werden. Dieses Dokument informiert nicht nur Angehörige und Patienten selbst, sondern auch Ärzte und Apotheker. Vortragender: Prof. Dr. Walter E. Haefeli, Abteilung Klinische Pharmakologie und Pharmakoepidemiologie, Universitätsklinikum Heidelber

    Going Beyond Counting First Authors in Author Co-citation Analysis

    Get PDF
    The 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 PDF
    We 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 PDF
    We 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

    Author Index

    No full text
    Nao informado

    koamabayili/VECTRON-author-checklist: VECTRON author checklist

    No full text
    We 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
    corecore