1,720,980 research outputs found

    Lactate is a potential promoter of tamoxifen resistance in MCF7 cells

    Get PDF
    Background: Tamoxifen is a widely used estrogen receptor inhibitor, whose clinical success is limited by the development of acquired resistance. This compound was also found to inhibit mitochondrial function, causing increased glycolysis and lactate production. Lactate has been widely recognized as a signaling molecule, showing the potential of modifying gene expression. These metabolic effects of tamoxifen can by hypothesized to contribute in driving drug resistance. Methods: To test this hypothesis, we used MCF7 cells together with a tamoxifen resistant cell line (MCF7-TAM). Experiments were aimed at verifying whether enhanced lactate exposure can affect the phenotype of MCF7 cells, conferring them features mirroring those observed in the tamoxifen resistant culture. Results: The obtained results suggested that enhanced lactate in MCF7 cells medium can increase the expression of tafazzin (TAZ) and telomerase complex (TERC, TERT) genes, reducing the cells' attitude to undergo senescence. In long term lactate-exposed cells, signs of EGFR activation, a pathway related to acquired tamoxifen resistance, was also observed. Conclusions: The obtained results suggested lactate as a potential promoter of tamoxifen resistance. The off-target effects of this compound could play a role in hindering its therapeutic efficacy. General significance: The features of acquired tamoxifen resistance have been widely characterized at the molecular level; in spite of their heterogeneity, poorly responsive cells were often found to display upregulated glycolysis. Our results suggest that this metabolic asset is not simply a result of neoplastic progression, but can play an active part in driving this process

    Going Beyond Counting First Authors in Author Co-citation Analysis

    Get PDF
    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

    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 PDF
    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

    Phytochemicals from the genus Beta and their cytotoxic activity on Caco-2 colon cancer cells.

    No full text
    Introduction: Colon cancer is one of the most aggressive tumor. Caco-2 are colon cancer cells characterized by the mutated TP53 gene and over expression of Multi Drug Resistance (MDR) proteins. Beta vulgaris con-tains molecules able to inhibit the proliferation of Caco-2 [1], namely vitexin-2-O xyloside (VOX) purified from Swiss chard seeds and betalains (BLS) purified from red beetroot. The aim of this work was to study the individual and combined anticancer activity of VOX and BLS on Caco-2 cells as well as to identify their mechanisms of action.Materials and methods: Caco-2 colon cancer cells were grown in complete DMEM+NEAA and Sulforho-damine B assay was performed as described [1]; VOX was purified as described [2]; BLS were purified on DEAE FF anion exchange resin. Three fractions were obtained: R1 with 3 betaxanthins, R2 with 2 betacya-nins, R3 with 2 betaxanthins. In order to identify the involved apoptotic pathway, western blots for BAX, Bcl-2, PARP1/ARTD1 and Caspase 3 were performed as described [1].Results: Cells were incubated with phytochemicals at 24, 48 and 72 h and cytotoxicity was assessed. Indivi-dually VOX was the most cytotoxic compound (IC50: 25 μg/ml), whereas R1, R2, R3 showed a weaker, but significant cytotoxic effect. When combined in couples at concentrations: 25 μg/ml VOX plus 350 ng/ml R1, or 250 ng/ml R2 or 35 ng/ml R3, these phytochemicals showed a synergistic cytotoxic effect at 72h. Western blots showed an increase in the levels of BAX, cleaved PARP1/ARTD1, cleaved caspase 3 and a decrease of Bcl-2 levels in both individual and coupled treatments.Discussion: VOX and BLS exhibit on Caco-2 cells a significant cytotoxicity on Caco-2 cells, by means of the activation of intrinsic apoptotic pathway. When VOX and BLS were used in couples, a highest cytotoxicity was evident, probably due to remarkable cytotoxic effects of their metabolic products

    Season and Cooking May Alter Fatty Acids Profile of Polar Lipids from Blue-Back Fish

    Get PDF
    Polar lipids (PoL) represent a new promising dietary approach in the prevention and treatment of many human diseases, due to their potential nutritional value and unique biophysical properties. This study investigates the effects of catching season and oven baking on the fatty acid profiles (FAP) of PoL in four species of blue-back fish widely present in the North Adriatic Sea: anchovy (Engraulis encrasicholus), sardine (Sardina pilchardus), sprat (Sprattus sprattus), and horse mackerel (Trachurus trachurus). PoL levels (427-652 mg/100 g flesh) varied among the four species, with no significant seasonal variations within species. FAP of raw fillets were particularly high in polyunsaturated fatty acid (PUFA), especially docosahexaenoic acid (DHA) and EPA; total PUFA was constant in all species throughout the year, while long-chain n-3 polyunsaturated fatty acid (n-3 PUFA) rose in spring (except in sprat), especially due to the contribution of DHA. The FAP response for PoL to oven baking was species-specific and, among n-3 PUFA, DHA exhibited the greatest heat resistance; the influence of oven baking on FAP was found to be correlated with the catching season, especially for anchovy and sardine, while sprat PoL were not affected by cooking processes. The four species analyzed in this study presented very low n-6/n-3 fatty acid ratios and highly favorable nutritional indices, emphasizing their PoL qualities and promoting their role in increasing human n-3 PUFA intake. The four species can be considered as superior sources of n-3 PUFA and can be employed as supplements in functional food manufacturing and in pharmaceutical and cosmetic industries

    Dispelling the Myths Behind First-author Citation Counts

    Get PDF
    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

    No full text
    Nao informado
    corecore