1,720,961 research outputs found
Human Surfactant Protein D Suppresses Epithelial-to-Mesenchymal Transition in Pancreatic Cancer Cells by Downregulating TGF-β
Full text linkHuman surfactant protein-D (SP-D), an innate immune pattern recognition soluble factor, is known to modulate a range of cytokines and chemokines, such as TNF-α and TGF-β at mucosal surfaces during infection, allergy, and inflammation. A recent study has shown that treatment with a recombinant fragment of human SP-D (rfhSP-D) for 48 h induces apoptosis in pancreatic cancer cells. Our hypothesis is that at earlier time points, SP-D can also influence key cytokines as a part of its putative role in the immune surveillance against pancreatic cancer, where the inflammatory tumor microenvironment contributes to the epithelial-to-mesenchymal transition (EMT), invasion, and metastasis. Here, we provide the first evidence that rfhSP-D can suppress the invasive-mesenchymal properties of highly aggressive pancreatic cancer cells. Mechanistically, rfhSP-D inhibited TGF-β expression in a range of pancreatic cancer cell lines, Panc-1, MiaPaCa-2, and Capan-2, thereby reducing their invasive potential. Smad2/3 expression diminished in the cytoplasm of rfhSP-D-treated cells as compared to the untreated control, suggesting that an interrupted signal transduction negatively affected the transcription of key mesenchymal genes. Thus, expressions of Vimentin, Zeb1, and Snail were found to be downregulated upon rfhSP-D treatment in the pancreatic cancer cell lines. Furthermore, blocking TGF-β with neutralizing antibody showed similar downregulation of mesenchymal markers as seen with rfhSP-D treatment. This study highlights yet another novel innate immune surveillance role of SP-D where it interferes with EMT induction by attenuating TGF-β pathway in pancreatic cancer
A Recombinant Fragment of Human Surfactant Protein D induces Apoptosis in Pancreatic Cancer Cell Lines via Fas-Mediated Pathway
Full text linkHuman surfactant protein D (SP-D) is a potent innate immune molecule, which is emerging as a key molecule in the recognition and clearance of altered and non-self targets. Previous studies have shown that a recombinant fragment of human SP-D (rfhSP-D) induced apoptosis via p53-mediated apoptosis pathway in an eosinophilic leukemic cell line, AML14.3D10. Here, we report the ability of rfhSP-D to induce apoptosis via TNF-α/Fas-mediated pathway regardless of the p53 status in human pancreatic adenocarcinoma using Panc-1 (p53mt), MiaPaCa-2 (p53mt), and Capan-2 (p53wt) cell lines. Treatment of these cell lines with rfhSP-D for 24 h caused growth arrest in G1 cell cycle phase and triggered transcriptional upregulation of pro-apoptotic factors such as TNF-α and NF-κB. Translocation of NF-κB from the cytoplasm into the nucleus of pancreatic cancer cell lines was observed via immunofluorescence microscopy following treatment with rfhSP-D as compared to the untreated cells. The rfhSP-D treatment caused upregulation of pro-apoptotic marker Fas, as analyzed via qPCR and western blot, which then triggered caspase cascade, as evident from cleavage of caspase 8 and 3 analyzed via western blot at 48 h. The cell number following the rfhSP-D treatment was reduced in the order of Panc-1 (~67%) > MiaPaCa-2 (~60%) > Capan-2 (~35%). This study appears to suggest that rfhSP-D can potentially be used to therapeutically target pancreatic cancer cells irrespective of their p53 phenotype
Innate immune surveillance in ovarian and pancreatic cancer
Full text linkThis thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonActivation of innate immune surveillance mechanisms during the development of cancer is well-documented. However, knowledge of how these innate immune proteins, when added exogenously, independent of tumour microenvironment, affect tumour cells is limited. In Chapter 3, the effects of human C1q and its individual
globular domains (ghA, ghB and ghC) on an ovarian cancer cell line, SKOV3, have been examined. C1q and globular head modules induced apoptosis in approximately 55% of cells, which involved upregulation of TNF-α and Fas and activation of the caspase cascade. This occurred in parallel to the downregulation of mTOR, RICTOR and RAPTOR survival pathways, which are often over-expressed in the majority of the cancers. Thus, this study provided evidence for another complement-independent role of C1q. The second part of this thesis was to investigate the effect of Human Surfactant Protein-D (SP-D), which is known to modulate secretion of a range of cytokines and chemokines by effector immune cells, such as TNF-a and TGF-β, at mucosal surfaces during infection and inflammation. Our hypothesis was that SP-D can influence these soluble factors as a part of its putative role in the immune surveillance against pancreatic cancer, where the inflammatory tumour microenvironment contributes to the epithelial-to-mesenchymal transition (EMT) invasion and metastases. In this study, a recombinant fragment of human SP-D (rfhSP-D) inhibited TGF-β expression in a range of pancreatic cancer cell lines, thereby reducing their invasive potential by downregulating Smad2/3 expression that may have interrupted signal transduction negatively, which affected the transcription of key mesenchymal genes such as Vimentin, Zeb1 and Snail. Furthermore, prolonged treatment with rfhSP-D induced apoptosis in the pancreatic cancer cell lines via activation of the caspase cascade. Thus, this study added another layer to the well-known protective role of SP-D
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
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