1,720,962 research outputs found
Targeted therapies for Malignant Mesothelioma
Full text linkMalignant mesothelioma (MM) is an aggressive neoplasia arising from mesothelial cells that line serous cavities, such as pleura, peritoneum, pericardium, and vaginal tunic. It is defined as an occupational disease because it is related to asbestos exposure. It mainly affects people between 50 and 70 years of age, with a male to female mortality ratio of 4:1. Despite traditional multidisciplinary treatment, involving the combination of chemotherapy, radiotherapy and surgery, prognosis remains poor. This is partly due to the delay of the diagnosis and partly due to the inadequacy of therapeutic approaches. The aim of this project is to find new therapeutic strategies for the treatment of MM based on a molecular targeted approach.
In this study the in vitro and in vivo anticancer effects of Bortezomib (Bor), the first selective and reversible proteasome inhibitor, on MM have been investigated. Bor was able to inhibit cell growth in a dose- and time-dependent manner; to induce apoptosis in treated cell lines, both human (H-Meso-1, MM-F1 and MM-B1) and murine (#40a); to modulate the expression of several molecules deregulated in MM, such as EGFR, ErbB2 and AKT; to induce Unfolded Protein Response, altering the expression of Grp78, CHOP and BiP. In vivo studies on C57BL/6 murine MM model have shown that Bor inhibited tumor growth and increased mice overall survival. Moreover, Bor treatment was able to modulate tumor immune microenvironment [1].
The ErbB receptor family is often overexpressed in MM patients and the use of EGFR-targeted drugs can inhibit MM cell proliferation. It is described that the use of a specific unitarget drugs can induce drug-resistance leading to the activation of different deregulated signaling pathways, such as those mediated by ErbB family receptor, Hedgehog, Axl, Wnt [2]. Recent studies in our laboratory, investigated the in vitro and in vivo effects of a specific inhibitor of ErbB family receptor, Afatinib (AFA), in combination with a multitarget molecule, Curcumin (CUR). CUR was able to enhance AFA effects increasing the AFA-induced reduction of the proliferation rate and pro-apoptotic effects in vitro. Indeed, in vivo AFA-antitumor activity was enhanced by its combination with CUR significantly increasing mice overall survival [3].
In another study from our laboratory the effects of inhibitors of Hh- (GANT-61) and ErbB receptors (AFA)-mediated signaling pathways, involved in neoplastic transformation and progression, were evaluated. The combined treatment with two inhibitors was more effective than the single treatments in reducing MM growth in vitro and in vivo, overcame the occurrence of drug resistance.
Based on these results, we are currently studying whether combined treatment using three different molecular targeted drugs, used at low doses, is more effective than single and dual treatments in inhibiting tumor growth in MM. Specifically, we are testing the combination of AFA, with Y15, a FAK inhibitor, and TP-0903, an Axl inhibitor.
Our preliminary data showed an increase of cell proliferation inhibition, with a proportional increase in cell death, in all cell lines treated with the triple combination compared to single and dual treatments in a time-dependent manner. Moreover, the use of 3D cultures has made possible to study the antitumor effects of these three inhibitors on systems that are more complex and more representative of in vivo tumor models. Spheroids treated with AFA, Y15 or TP-0903, used alone or in double combination, showed a significant inhibition of growth compared to control spheroids, and the triple combination significantly decreases spheroid growth compared to control, single or double treated spheroids. Finally, the triple combination reduced cell viability in treated spheroids compared to control ones.
In conclusion, targeted therapy offers significant promise in achieving better treatment outcomes with fewer side effects than conventional therapies. This study could be helpful in developing new personalized therapies that are more effective for MM patient
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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