1,720,968 research outputs found
Decoding the role of HSPGs in tumor onset and progression through use of branched peptide probe
Heparan sulfate Proteoglycans (HSPGs) play a number of signaling and structural roles in tumor progression and metastasis spread. The biological function of HSPGs resides in their ability of interaction with many different types of ligands like growth factors, morphogens, chemokines and proteins of extracellular matrix (ECM). These bindings activate signaling pathways that modulate major transformations of cancer cells, leading to tumor growth, migration, invasion and metastasis. HSPGs are over-expressed on cancer cell membranes. The tetra-branched peptide NT4 binds with high selectivity to different human cancer cells and tissues. Its ability to discriminate between tumor and healthy tissues resides in the high-affinity binding to HSPGs and can be exploited by conjugating NT4 with different functional units, like chemotherapeutical drugs and tracers for cancer cell imaging and therapy. In this work, we test NT4 ability to interfere with processes mediated by HSPGs in tumor cell adhesion, migration and matrix invasiveness. Since HSPGs modulate also neo-angiogenesis, because of their expression by endothelial cells of microvessels that generate new vasculature, we focus also on NT4 role in endothelial cell proliferation, migration and tube formation, in the presence of Fibroblast Growth Factor-2 (FGF-2). Since the internalization and trafficking behaviour of HSPGs seems to reveal a clathrin and caveolin- independent, but dynamin-dependent endocytic pathway, we investigate
the pathway used by NT4 to enter cells. Last, but not least, we radiolabel NT4 with 18F in order to measure tumor uptake and whole-body biodistribution in a mouse model of breast cancer, using in vivo PET imaging. NT4-HSPG interactions and consequent modulation of signaling pathways can prove the importance of NT4 peptide as a specific tool to enlighten the role of HSPG in tumor onset and progression
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
Abstract 1153: Heparan sulfate proteoglycans as novel target in cancer precise therapy
Abstract
Heparan sulfate proteoglycans (HSPGs) have crucial regulatory roles in tumor onset and progression. HSPGs
are composed of a core protein and glycan chains characterized by repeated disaccharide units which can
be sulfated at different amount and position. HSPG have enormous structural diversity due to the different
possible modifications of the single saccharide units within the polysaccharide, such as position, sulphation
and acetylation. As a result HSPG can bind and modulate their binding to signaling molecules such as
growth factors, morphogens and chemokines1 .
HSPG proved to be important in mediating cancer development and progression by enhancing the binding
of growth factors, morphogens and cytokines to their cognate receptors, thus activating signaling pathways
that give rise to angiogensis, cell growth and proliferation, together with invasion and metastasis 2-3.
NT4 is a branched peptides that targets HSPGs. NT4 specifically binds to sulfated glycosaminoglycans on
cancer cells and tissues. NT4 can be conjugated to many different cytotoxic units and tracers. NT4
conjugated to paclitaxel produced tumor regression in a breast cancer orthotopic mouse model 4. NT4
conjugated to tracers can discriminate between tumor and healthy tissue in different human cancer
specimen5.
We will show the ability of NT4 to drive tracers onto tumor lesions by means of Qdots and in vivo imaging,
proving their promising features as theranostics. We will also show NT4 ability to interfere with HSPG-
modulated activities such as: tumor cell proliferation, migration and invasion of matrix; as well as
endothelial cells proliferation, migration and tube formation. NT4-HSPG interactions and consequent
modulation of signaling pathways will prove the importance of this versatile tool, NT4, in addressing tumor
cells and interfering in their cell-cell and cell-matrix communications.
Bibliography
1. Gharbaran R. et al. Tumour Biol. 2016; 37:11573-11588.
2. Purushothaman A et al. Blood. 2010; 115:2449-57.
3. Lee JH et al. J Biol Chem. 2009; 284:27167-75.
4. Brunetti, J. et al. Scientific Reports. DOI:10.1038/srep17736
5. Falciani C. et al. J Med Chem. 2013; 56:5009-18.
Citation Format: Chiara Falciani, Jlenia Brunetti, Lorenzo Depau, Alessandro Pini, Giulia Riolo, Elisabetta Mandarini, Luisa Bracci. Heparan sulfate proteoglycans as novel target in cancer precise therapy [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 1153. doi:10.1158/1538-7445.AM2017-1153</jats:p
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
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