1,720,973 research outputs found

    Secreted molecules inducing epithelial-to-mesenchymal transition in cancer development

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    The epithelial-mesenchymal transition (EMT) is a biologic process that allows a polarized epithelial cell to undergo multiple biochemical changes that enable it to assume a mesenchymal cell phenotype. EMT is involved in embryo development, wound healing, tissue regeneration, organ fibrosis and has also been proposed as the critical mechanism for the acquisition of malignant phenotypes by epithelial cancer cells. These cells have been shown to acquire a mesenchymal phenotype when localized at the invasive front of primary tumours increasing aggressiveness, invasiveness, metastatic potential and resistance to chemotherapy. There is now increasing evidence demonstrating that a crucial role in the development of this process is played by factors secreted by cells of the tumour microenvironment or by the tumour cells themselves. This review summarises the current knowledge of EMT induction in cancer by paracrine or autocrine mechanisms, by exosomes or free proteins and miRNAs

    A pH-sensor scaffold for mapping spatiotemporal gradients in three-dimensional in vitro tumour models

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    The detection of extracellular pH at single cell resolution is challenging and requires advanced sensibility. Sensing pH at high spatial and temporal resolution might provide crucial information in understanding the role of pH and its fluctuations in a wide range of physio-pathological cellular processes, including cancer. Here, a method to embed silica-based fluorescent pH sensors into alginate-based three-dimensional (3D) microgels tumour models, coupled with a computational method for fine data analysis, is presented. By means of confocal laser scanning microscopy, live-cell time-lapse imaging of 3D alginate microgels was performed and the extracellular pH metabolic variations were monitored in both in vitro 3D mono- and 3D co-cultures of tumour and stromal pancreatic cells. The results show that the extracellular pH is cell line-specific and time-dependent. Moreover, differences in pH were also detected between 3D monocultures versus 3D co-cultures, thus suggesting the existence of a metabolic crosstalk between tumour and stromal cells. In conclusion, the system has the potential to image multiple live cell types in a 3D environment and to decipher in real-time their pH metabolic interplay under controlled experimental conditions, thus being also a suitable platform for drug screening and personalized medicine

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    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

    In vitro studies on CSC-targeted therapy in pancreatic adenocarcinoma with nanoparticle formulations

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    Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease and one of the major causes of death among cancer patients. Diagnosis of PDAC during the early stages of cancer is difficult because no effective screening for detection of early stage tumors is yet available. PDAC is sustained by a distinct subset of quiescent cells, called cancer stem cells (CSCs) that are responsible for resistance to standard therapy, metastatic potential and disease relapse following treatments. The current therapy for PDAC preferentially targets the more differentiated cancer cell population, leaving CSCs as a source that supports the tumour, causing recurrence. For this reason, targeting pancreatic CSCs could contribute to the clinical development of more efficacious drugs treatment, aimed to permanently remove the tumor and prevent recurrence. In this study, we investigated two therapeutic approaches for the treatment of PDAC. First of all, we studied a pro-drug approach using gemcitabine conjugated with fatty acid chains, C12 GEM and C18 GEM, by testing their cytotoxic activity on Panc1 cell line and the derived CSCs. Both cell lines were more sensitive to the treatment with the lipophilic pro-drugs than GEM, but only Panc1 CSCs showed a high sensitivity to C18 GEM treatment. Furthermore, the two cell lines exhibited different intracellular uptake mechanisms of the drugs that involved mainly membrane nucleoside transporters in Panc1 parental cells or fatty acid translocase CD36 for C18 GEM uptake in both cell lines. Furthermore, we have highlighted a peculiar feature of CSCs regarding the apoptotic response to treatment. In Panc1 parental cells, the treatments induced a PARP-dependent apoptosis, while in Panc1 CSCs they involved a mechanism of caspase-independent apoptosis mediated by AIF. The second therapeutic approach concerned a targeted drug delivery system using PEGylated liposomes containing disulfiram (DSF) or diethyldithiocarbamate-copper (Cu(DDC)2) and liposomes selective for pancreatic CSCs expressing CD44 coated with HA. We evaluated the effect on cell proliferation of the various DSF formulations using pancreatic CSCs derived from cell lines or patients. The encapsulation of Cu(DDC)2 complex in liposomes increased its anti-proliferative activity on our cell models. This method represents a good strategy to make the Cu(DDC)2 complexes suitable for PDAC patients. In this study, we propose two valid and alternative therapeutic approaches with a promising potential to achieve efficient and encouraging results in PDAC treatment

    Variations on the Author

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    “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

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    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

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    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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    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
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