1,720,961 research outputs found
Metabolic and molecular profiling of ovarian cancer stem cells and cancer non-stem counterpart
Full text linkEpithelial Ovarian Cancer (EOC) is a very malignant neoplasm, accounting for 5% of cancer mortality in women. Although progress has been made in EOC treatments by improved debulking surgery and platinum-taxane regimens, the 5-year survival rate of advanced-stage EOC remains below 30%. This poor prognosis relies on the one hand on the late diagnosis and on the other on the chemo-resistance occurring after only a few months from the completion of treatment.
The reasons for recurrence and cancer drug resistance remain uncertain. Recent evidence suggests that EOC, akin most tumors, contains a tiny population of cells, named cancer stem cells (CSC), probably responsible for chemotherapy resistance and tumor recurrence. Ovarian CSC are characterized by the co-expression of two surface markers: CD44 (hyaluronic acid receptor) and CD117 (stem cell factor receptor or c-kit). Recently, our research group demonstrated that ovarian CD44/CD117 co-expressing cells, which represent 1-2% of cancer cells from ascitic effusions of EOC-bearing patients, are endowed with canonical stemness properties and are able to resist in vitro and in vivo glucose starvation. We reported that this glucose deprivation resistance is mostly due to the ability of ovarian CSC to privilege oxidative phosphorylation, rather than the aerobic glycolysis (Warburg effect) exploited by the non-stem tumor bulk. However, independently of CSC fraction, our experiments also highlighted that not all the analyzed EOC samples presented a similar glucose addiction.
Thus, investigating this issue and its related metabolic aspects is the first aim of the current project. Concerning this aim, we showed that tumor cells from EOC patients can be categorized, according to their in vitro viability under glucose starvation, into glucose deprivation-sensitive (glucose-addicted, GA) and glucose deprivation-resistant (glucose non-addicted, GNA). Although deregulated glucose metabolism is usually observed in cancer, whether this metabolic trait influences response to or is modulated by cytotoxic drugs is unknown; therefore, we addressed the possible correlation of these glucose addiction profiles with the patient response to platinum (PLT) regimens. In this regard, when EOC cells were cultured in the absence of glucose, all samples from PLT-sensitive patients felt into the GA group; compared to GNA samples, they disclosed higher expression of glucose metabolic enzymes, higher proliferation rates and in vitro sensitivity to PLT, as well as reduced multi-drug resistance pump expression. On the other hand, the samples derived from PLT-resistant patients felt into the GNA category. The close association between PLT sensitivity and glucose metabolic profile was confirmed in a xenograft model, where a stringent parallelism between PLT sensitivity/resistance and glucose metabolism was identified. Finally, in a cohort of naïve EOC patients categorized as GA or GNA at diagnosis, Kaplan Meier curves showed that the GA phenotype was associated with significantly better progression-free survival, compared to GNA patients. Overall, these results suggest that in vitro glucose addiction of EOC cells could be regarded as a reliable marker to predict the patient response to platinum regimens.
Investigating the molecular traits leading to the distinctive glucose metabolism of EOC samples is the second aim of this project. In this regard, microRNA (miRNA), that are small non-coding RNA molecules, represent a promising field, in view of their ability to modulate many genes and pathways. Moreover, their involvement in cancer development and progression has already been reported in ovarian cancer, and recently miRNA also emerged to regulate cell metabolism in several normal and cancer tissues. Thus, we performed a miRNA profile on EOC patient-derived samples, comparing both GA versus GNA samples and CSC versus non-CSC, in order to establish whether the miRNA signature behind the metabolic differences of EOC samples is associated with the total tumor bulk or rather with a specific cell fraction. The data did not reveal any miRNA differentially expressed in GA compared to GNA cells, but several miRNA resulted significantly deregulated in CSC versus non-CSC. We focused our attention on mir-602, which was found up-regulated in CSC; indeed, despite little information about this miRNA, its target Casein Kinase 1 Delta (CSNK1D), which displays a key role in cell proliferation and asymmetric division, seemed very interesting in view of its involvement in breast cancer progression. We demonstrated that CSNK1D is down-regulated in CSC, according to mir-602 over-expression. Moreover, the in vitro inhibition of mir-602 reduced the expression of the major stemness-associated genes in CSC, suggesting that mir-602 could regulate some cell stemness pathways. Since none of the analyzed stemness genes is directly targeted by mir-602, it is reasonable to advance that mir-602 could indirectly activate the expression of such genes through its inhibitory function on CSNK1D; thus, we propose that cell stemness signaling is inhibited by casein kinase, whose translation is in turn repressed by mir-602. Although a few further experiments are needed to validate our idea, this project highlights a possible miRNA-mediated regulatory mechanism of cell stemness features in EOC
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
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
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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