1,720,992 research outputs found
In Vitro and in Vivo Models for Analysis of Resistance to Anticancer Molecular Therapies.
No full textThe efficacy of classical and molecular therapies in cancer is hampered by the occurrence of primary (intrinsic) and secondary (acquired) refractoriness of tumours to selected therapeutic regimens. Nevertheless, the increased knowledge of the genetic, molecular and metabolic mechanisms underlying cancer results in the generation of a correspondingly increasing number of druggable targets and molecular drugs. Thus, a current challenge in molecular oncology and medicinal chemistry is to cope with the increased need for modelling, both in cellular and animal systems, the genetic assets associated to cancer resistance to drugs. In this review, we summarize the current strategies for generation and analysis of in vitro and in vivo models, which may reveal useful to extract information on the molecular basis of intrinsic and acquired resistance to anticancer molecular agents
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
An interdisciplinary research perspective for tackling Vertiport design and developmental challenges
Full text linkProteomic Signatures in Thapsigargin-Treated Hepatoma Cells.
No full textThapsigargin, an inhibitor of the endoplasmic reticulum (ER) calcium transporters, generates Ca(2+)-store depletion within the ER and simultaneously increases Ca(2+) level in the cytosol. Perturbation of Ca(2+) homeostasis leads cells to cope with stressful conditions, including ER stress, which affect the folding of newly synthesized proteins and induce the accumulation of unfolded polypeptides and eventually apoptosis, via activation of the unfolded protein response pathway. In the present work, we analyzed the proteome changes in human hepatoma cells following acute treatment with thapsigargin. We highlighted a peculiar pattern of protein expression, marked by altered expression of calcium-dependent proteins, and of proteins involved in secretory pathways or in cell survival. For specific deregulated proteins, the thapsigargin-induced proteomic signature was compared by Western blotting to that resulting from the treatment of hepatoma cells with reducing agents or with proteasome inhibitors, to elicit endoplasmic reticulum stress by additional means and to reveal novel, potential targets of the unfolded protein response pathway
EXOSOMES DERIVED FROM METASTATIC COLON CANCER CELLS TRANSFER MALIGNANT PHENOTYPIC TRAITS TO SURROUNDING CELLS: THEIR EMERGING ROLE IN TUMOR HETEROGENEITY
No full textSeveral studies have clearly demonstrated that within a heterogeneous tumor mass the inter-clonal cooperation between metastatic and non-metastatic cells can facilitate the tumor progression. Recent accumulating evidence has highlighted that tumor-derived exosomes (TDEs) play a relevant role as mediator of the inter-clonal collaborative cooperation affecting the properties of both tumor and non-tumor component.
In this context, our goal was to understand if exosomes derived from highly metastatic cells may influence the behaviour of less aggressive tumor cells and the properties of endothelium.
We found that metastatic SW620 cells transfer through exosomes (SW620Exos) their round/amoeboid phenotype to elongated non-metastatic SW480 cells also inducing the increase of the motile and invasive activities. Moreover, SW620Exos caused endothelial hyperpermeability by altering the junctional complexes in HUVECs. The SWATH-based quantitative proteomic analysis highlighted that SW620Exos were significant enriched in several proteins related to the RhoA/ROCK sig¬naling, known to induce the amoeboid motility as well as the destabilization of endothelial junctional complexes. According to this data, we found that the treatment with ExoSW620 elicited in both SW480 cells and HUVECs the increase of RhoA activity, while the induced morphological and functional effects were reverted by co-treatment with a specific ROCK inhibitor. RacGap1 and thrombin were identified as putative key mediators of the effects induced by SW620Exos in target cells. Taken together our data indicates that within a heterogeneous tumor mass exosomes released by metastatic cells affect the features of both tumor and non-tumor cell components, thus contributing to accelerate the metastatic cascade
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