1,720,974 research outputs found
Abstract 5055: Multiplatform metabolomics analysis of growth arrest in pancreatic tumor xenografts
Abstract
R,S-4-Methoxy-1-naphthylfenoterol, MNF, inhibits the G protein-coupled receptor GPR55. In this study, we determine the effect of MNF on human PANC-1 pancreatic tumor growth in mice and apply multiplatform metabolomics analysis to identify pathways associated with growth arrest.
Methods: Female Balb/c nude mice, 6-8 weeks old, 18-20g, were inoculated subcutaneously with 5 x 106 PANC-1 cells. On Day 8, mice were placed in groups of 10 using random block design based upon tumor volume. Mice received daily ip injections of vehicle or 40mgxkg-1 MNF 5 days/week for 3 treatment cycles. Mice were monitored daily and tumor volumes measured at beginning and end of each dosing cycle. On Day 33, mice were euthanized, and plasma samples and tumors collected. Tumor tissue was homogenized, extracted and analyzed using liquid chromatography-QTOF-MS, capillary electrophoresis-TOF-MS and gas chromatography-EI-Q-MS. Differences between groups were evaluated by unpaired t-test or Mann−Whitney test with post hoc Benjamini-Hochberg correction. Statistical significance was set at P≤0.05. Compound identification was accomplished using online databases and in-house standards
Results Tumor volume increased in vehicle-treated mice by ~700%, 142 ± 8 mm3 to 957 ± 79 mm3 and only ~250% in MNF-treated mice, 143 ± 8 mm3 to 259 ± 27 mm3. On Day 33, MNF was not detected in plasma but accumulated in tumor tissues, 43.9 ± 32.7 ng/g. Plasma L-lactate levels were reduced from 3.29 ± 0.66 mmol/L το 2.81 ± 0.60 mmol/L, P≤0.001. Differences in tumor tissue metabolome were observed with MNF compared to vehicle, which was reflected by significant, P≤0.05, changes in relative metabolite signals. MNF treatment was accompanied by the disruption of pyrimidine nucleotide biosynthesis at uridine 5'-monophosphate, UMP, and increased UMP degradation. Moreover, the +237% increase in ophthalmic acid and +95% increase in its precursor 2-aminobutyrate indicate higher oxidative stress and the +51% increase in 2-hydroxyproline suggest greater HFI-1α proteolysis upon MNF treatment.
Conclusions These results are consistent with our previous observations in PANC-1 cells showing that GPR55 inhibition attenuates activation of the EGFR-MEK-ERK, Wnt-β-catenin and PI3K/AKT pathways resulting in lower cyclin D1 expression and halting the cell cycle in G1. The reduction in HIF-1α expression and glycolytic flux in MNF-treated PANC-1 cells is in line with the decline in L-lactate plasma levels in MNF-treated mice. The data from this study indicate that MNF may be useful in the treatment of pancreatic cancer.
Citation Format: Irving W. Wainer, Danuta Dudzik, Michel Bernier, Coral Barbas. Multiplatform metabolomics analysis of growth arrest in pancreatic tumor xenografts [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 5055. doi:10.1158/1538-7445.AM2017-5055</jats:p
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
We 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
We 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.
Author-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
In 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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