1,721,034 research outputs found
Abstract SY22-02: Tumor suppression by p62 through the metabolic reprogramming of the stroma
No full textAbstract
Large-scale genomic and transcriptomic interrogation of cancer has underscored the complexity of its genetic landscape, revealing a massive number of genetic alterations that results in the impossibility of distinguishing ‘‘driver’’ from ‘‘passenger’’ mutations. This makes oncogene-targeting therapies extremely challenging. This variability is well exemplified in hepatocellular carcinoma (HCC), in which more than 28,000 different somatic mutations have been identified. HCC development is a relatively long and complex process including chronic hepatitis, fibrosis, cirrhosis, and stromal activation, which are key mediators of a microenvironment conducive to tumorigenesis. Infection with hepatitis B and C viruses (HBV and HCV) has been considered the major HCC risk factor. Not surprisingly, obesity-induced nonalcoholic fatty liver disease (NAFLD), and its more severe consequence nonalcoholic steatohepatitis (NASH), have progressively become critical promoters of HCC. Chronic liver injury sets in motion a vicious circle of hepatocyte cell death, inflammation, and fibrosis that results in cirrhosis and cancer. A critical player in that process is hepatic stellate cells (HSCs). Recent reports highlight the potential central role of HSCs in the generation of proinflammatory signals important for HCC development. More recently, the study of pancreatic cancer suggests that pancreatic stellate cell reprogramming by targeting the vitamin D receptor (VDR) might improve therapeutic responses. Nononcogenic addiction can reveal new tumor vulnerabilities that can be exploited therapeutically for cancer treatment. In this regard, metabolic reprogramming and autophagy are progressively being considered as a new, rich source of possible therapeutic targets in cancer irrespective of the genetic landscape of the tumor. p62 is a signaling and autophagy adaptor that accumulates in premalignant liver diseases and most hepatocellular carcinomas (HCCs). p62 was the first identified autophagy adaptor; however, at least other four other proteins have similar functions, including NBR1, TAX1BP1, NDP52, and OPTN. Importantly, p62 is a signaling regulator residing in the late endosome lysosome, and unlike other autophagy adaptors except for NBR1, p62 is also a central regulator of signaling pathways controlling cell survival and growth. This is because it interacts with key signaling proteins through well-defined structural elements. Although p62 was proposed to participate in the formation of benign adenomas in autophagy-deficient livers, its role in HCC initiation was not explored. Importantly, we show that the upregulation of p62 in hepatocytes during HCC initiation is necessary and sufficient for tumor induction in mice and is highly expressed in human HCC patients. The mechanism for this relies on the ability of p62 to activate hepatocyte NRF2 and mTORC1 pathways and differs from its protumorigenic role in lung adenocarcinomas that mostly relies on the activation of NF-κB. However, although p62 is a protumorigenic molecule in epithelial cancer cells, more recent results reveal that it plays a tumor-suppressor role in the stroma. Interestingly, most studies addressing the role of p62 in cancer have focused on its function in transformed epithelial cells, but only very recently has the concept of p62 as a tumor suppressor in the cancer stroma emerged from our studies of prostate cancer. We discuss recent observations demonstrating a novel role of p62 as a promoter of stromal reprogramming in both prostate cancer and HCC due to its ability to repress the stromal activation of prostate fibroblasts and HSCs in the liver, through different mechanisms. This suggests that in parallel to epithelial cancer heterogeneity, there is a completely unexplored diversity of stromal cells that utilize distinct mechanisms to impact tumor initiation and progression. We propose that therapies aimed at repressing the downregulation of stromal p62, and likely that of other autophagy adaptors, will positively impact therapies targeting the tumor epithelium.
Citation Format: Jorge Moscat. Tumor suppression by p62 through the metabolic reprogramming of the stroma [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 SY22-02. doi:10.1158/1538-7445.AM2017-SY22-02</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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