1,721,034 research outputs found
Abstract 3336: Comparison of epithelial mesenchymal transition mediated TKI resistanc NSCLC cells containing wild type EGFR and mutant EGFR
No full textAbstract
Epithelial to mesenchymal transition (EMT) is a vital process in development and of metastasis and occurs when epithelial cell lose their polarized structure, by reducing adherent junction proteins E-cadherin, Claudin and ZO-1 on the membrane. Cells with EMT are elongated spindle like structures due to upregulation of mesenchymal markers Vimentin and N-cadherin. EMT may be responsible for resistance to molecular targeted therapies such as tyrosine kinase inhibitors (TKIs) against EGFR which is used in patients with activated EGFR mutations. However, these patients acquire resistance to TKIs after prolonged use. This acquired resistance to TKIs may also be due to a secondary T790M mutation in the kinase domain which could be responsible for inducing EMT. EMT is regulated by p120-catenin which interacts with the Kaiso factor in the cell nucleus and inhibits the transcriptional repressor activity of Kaiso factor. Kaiso factor represses Wnt target genes such as ZEB-1. The binding of p120-catenin to Kaiso factor also increases Wnt signaling which results in loss of E-cadherin. Cells undergoing EMT can acquire cancer stem-cell like characteristics by expressing stem-cell marker ABCB1. Thus we investigated EMT characteristics in TKI-resistant NSCLC cells, H2170 ER (Erlotinib resistant), H358 ER and H1975. To determine modulation of EMT biomarkers in TKI-resistant cells, H1975 with L858R and T790M mutations was compared to TKI-sensitive cell line H3255 with L858R mutation, using immunoblotting, and qPCR. Expression of stem-cell markers ABCB1 and EMT biomarker E-cadherin are measured using flow cytometry. Key EMT-related proteins such as PRMT-1, Slug, Snail, Twist, p120-catenin, and Vimentin were upregulated by 3.2, 3.18, 6.2, 1.68, 4 and 6.5 fold, respectively, and E-cadherin, Claudin and ZO-1 were downregulated by 89%, 90% and 99% fold as compared to the H3255 TKI-sensitive cell line. We also observed upregulation of N-cadherin, ZEB-1 and Vimentin by 2.4, 2.6, and 12 fold and downregulation of E-cadherin by 50% in H1975 by qPCR. Immunofluorescence studies for Vimentin showed that H1975 cells were more elongated and stratified as compared to the H3255 that had polarized structures. 90% colocalization of p120-catenin and Kaiso factor was seen H1975 cells whereas 10% colocalization was seen in H3255 cells. Flow cytometry results indicated that there was significant increase in expression of stem cell marker ABCB1 in TKI resistant cells H2170 ER, H358 ER and H1975 in comparison to H2170 P(Parental), H358 P and H3255 TKI sensitive cells. In conclusion, our results indicate that EMT is mediated through PRMT-1, which methylates Twist, transcriptional repressor of E-cadherin along with Slug and Snail in H1975 cells with T790M mutation. Cancer stem-cell marker ABCB1 is specific for TKI resistant NSCLC cells which exhibit EMT.
Citation Format: Tsatsral Iderzorig, Sanjana Singh, Gagan Chhabra, Neelu Puri. Comparison of epithelial mesenchymal transition mediated TKI resistanc NSCLC cells containing wild type EGFR and mutant EGFR [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 3336. doi:10.1158/1538-7445.AM2017-3336</jats:p
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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