1,721,300 research outputs found
Eupatilin Inhibits Gastric Cancer Cell Growth by Blocking STAT3-Mediated VEGF Expression
Get PDFPurpose: Eupatilin is an antioxidative flavone and a phytopharmaceutical derived from Artemisia asiatica. It has been reported to possess anti-tumor activity in some types of cancer including gastric cancer. Eupatilin may modulate the angiogenesis pathway which is part of anti-inflammatory effect demonstrated in gastric mucosal injury models. Here we investigated the anti-tumor effects of eupatilin on gastric cancer cells and elucidated the potential underlying mechanism whereby eupatilin suppresses angiogenesis and tumor growth. Materials and Methods: The impact of eupatilin on the expression of angiogenesis pathway proteins was assessed using western blots in MKN45 cells. Using a chromatin immunoprecipitation assay, we tested whether eupatilin affects the recruitment of signal transducer and activator of transcription 3 (STAT3), aryl hydrocarbon receptor nuclear translocator (ARNT) and hypoxia-inducible factor- (HIF-) to the human VEGF promoter. To investigate the effect of eupatilin on vasculogenesis, tube formation assays were conducted using human umbilical vein endothelial cells (HUVECs). The effect of eupatilin on tumor suppression in mouse xenografts was assessed. Results: Eupatilin significantly reduced VEGF, ARNT and STAT3 expression prominently under hypoxic conditions. The recruitment of STAT3, ARNT and HIF- to the VEGF promoter was inhibited by eupatilin treatment. HUVECs produced much foreshortened and severely broken tubes with eupatilin treatment. In addition, eupatilin effectively reduced tumor growth in a mouse xenograft model. Conclusions: Our results indicate that eupatilin inhibits angiogenesis in gastric cancer cells by blocking STAT3 and VEGF expression, suggesting its therapeutic potential in the treatment of gastric cancer.ope
Abstract 542: Genomic and clonal characterization of immunogenic epitope landscape across The Cancer Genome Atlas
No full textAbstract
Recent advances in cancer immunotherapy and genomic sequencing technologies have created promising opportunities for precision cancer medicine. Somatic mutation in coding regions of cancer genomes may lead to amino acid alterations that generate immunogenic peptides, called neoantigens. These novel peptides are tumor-specific. An individual’s own MHC genotypes restricts the presentation of these tumor-specific peptides and thus there are a limited number of candidate epitopes for immune cellular recognition. Current studies have not comprehensively studied how MHC-restricted neoantigens are present across tens of thousands of cancer. Nor have these studies determined how somatic mutations and their associated neoantigens are represented among different subclonal populations existing within individual tumors. To address these limitations, we have mapped the complex immunogenomic topology of neoantigen epitopes across 8,000 tumors representing 18 different cancer types. This neoantigen landscape accounts for how neoepitope candidates are distributed among the various clonal subpopulations existing within any given tumor.Our study utilized genomic data from the Cancer Genome Atlas (TCGA). Our automated pipeline provides results from 8,000 samples from 18 cancer types that have somatic variant calls, copy number variation, whole exome sequence, and RNA-Seq data. Identification of somatic mutations that lead to highly immunogenic antigens involved five different steps; i) in-silico translation of identified mutations, ii) expression as measured per RNA-Seq, iii) patient’s own major histocompatibility complex genotype, iv) binding affinity specific to the MHC alleles for any given patient and v) occurrence of clonal subpopulations as demonstrated by intratumoral genetic heterogeneity. We mapped the neoantigen landscape with quantitative representation of the genetic clonal diversity existing within individual tumors. In average, 2% of missense mutations from a patient are detected in RNA-Seq, with binding affinity to own HLA genotypes, and from the dominant clonal subpopulation.In summary, our study demonstrates the various relationships among the number of optimal antigens, the number of clonal subpopulations, the number of mutations, and clinical phenotypes such as tumor stage. Our automated bioinformatics process facilitates the use of exome and RNA-Seq as potential diagnostic analytic process for precision immunotherapy.
Citation Format: HoJoon Lee, Stephanie Greer, Susan M. Grimes, Jae-Ho Cheong, Hanlee P. Ji. Genomic and clonal characterization of immunogenic epitope landscape across The Cancer Genome Atlas [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 542. doi:10.1158/1538-7445.AM2017-542</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
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