1,723,274 research outputs found
Abstract 5482: Constitutive overexpression of nrf2 in esophageal adenocarcinoma protects cancer cells from bile salts-induced DNA damage and favors cancer cell survival
No full textAbstract
Background: Esophageal adenocarcinoma (EAC) is the major type of malignant cancer of esophagus in the USA. The incidence rate has increased 4-10% per year among men since 1976 in the USA, more rapidly than for any other type of cancer. EAC is known to originate from premalignant Barrett’s esophagus (BE) through BE-dysplasia-EAC process. Normal cells have intact anti-oxidative mechanisms, among which NFE2-related factor 2 (Nrf2) plays a pivotal role in regulating cellular response to various stimuli. Cancer cells have high levels of reactive oxygen species and oxidative stress due to activation of oncogenes, inflammatory microenvironment, and dysfunction of anti-oxidative mechanisms. However, the role of NRF2 in Barrett’s related esophageal carcinogenesis is barely known.
Methods and Results: We have found that Nrf2 protein expression is significantly upregulated in EAC cell lines as compared to BE cell lines (CPA, BAR10T) and normal esophageal squamous cell lines. We detected a similar overexpression of NRF2 in primary EAC tissue samples. Using luciferase reporter assay, we demonstrated significant induction of NRF2 transcription activity in EAC cells in response to exposure to acidic bile acids, as compared to controls (P<.01). We detected significant increase in the expression of Heme Oxygenase 1 (HO-1) and Glutathione Reductase (GR) in these cells (P<.01). Knockdown of NRF2 by siRNA or crisp/cas9, significantly increased cellular ROS level, oxidative DNA damage (8-oxoguanine), and double strand DNA breaks (p-H2AX). Knockdown of NRF2 sensitized cells to apoptosis following exposure to bile acids and CDDP. Concordant with these results, the use of NRF2 inhibitor, Brusatol, sensitized EAC cells to CDDP treatment with a significant increase in cell death, as compared to single agent treatment (P<.01). Conclusion: These results indicate that constitutive overexpression of NRF2 in EAC cells protects cancer cells from high level of ROS and promotes cancer cell survival. Inhibition of NRF2 through its specific inhibitor may have therapeutic value in EAC.
Citation Format: Dunfa Peng, Tianling Hu, Shoumin Zhu, Wael El-Rifai. Constitutive overexpression of nrf2 in esophageal adenocarcinoma protects cancer cells from bile salts-induced DNA damage and favors cancer cell survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5482. doi:10.1158/1538-7445.AM2017-5482</jats:p
VPI‐5482 glycoside hydrolase family 66 homolog catalyzes dextranolytic and cyclization reactions
No full textBacteroides thetaiotaomicron VPI-5482 harbors a gene encoding a putative cycloisomaltooligosaccharide glucanotransferase (BT3087) belonging to glycoside hydrolase family 66. The goal of the present study was to characterize the catalytic properties of this enzyme. Therefore, we expressed BT3087 (recombinant endo-dextranase from Bacteroides thetaiotaomicron VPI-5482) in Escherichia coli and determined that recombinant endo-dextranase from Bacteroides thetaiotaomicron VPI-5482 preferentially synthesized isomaltotetraose and isomaltooligosaccharides (degree of polymerization > 4) from dextran. The enzyme also generated large cyclic isomaltooligosaccharides early in the reaction. We conclude that members of the glycoside hydrolase 66 family may be classified into three types: (a) endo-dextranases, (b) dextranases possessing weak cycloisomaltooligosaccharide glucanotransferase activity, and (c) cycloisomaltooligosaccharide glucanotransferases.open
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
EDUARDO BAURA – THIERRY SOL, Chiesa, persona e diritti. Corso introduttivo al diritto canonico, EDUSC, Roma 2022, 171 pp., ISBN 979-12-5482-028-5.
Get PDFBook review: Eduardo Baura – Thierry Sol, Chiesa, persona e diritti. Corso introduttivo al diritto canonico, EDUSC, Roma 2022, 171 pp., ISBN 979-12-5482-028-5.Recensión del libro: Eduardo Baura – Thierry Sol, Chiesa, persona e diritti. Corso introduttivo al diritto canonico, EDUSC, Roma 2022, 171 pp., ISBN 979-12-5482-028-5
MASSIMO DEL POZZO, Gli abusi liturgici: natura, storia e rimedi.: Roma: EDUSC, 2024, 221 pp., ISBN 979-12-5482-240-1
Get PDFBook review of: Massimo del Pozzo, Gli abusi liturgici: natura, storia e rimedi, Roma: EDUSC, 2024, 221 pp., ISBN 979-12-5482-240-1Recensión del libro: Massimo del Pozzo, Gli abusi liturgici: natura, storia e rimedi, Roma: EDUSC, 2024, 221 pp., ISBN 979-12-5482-240-
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
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