1,720,975 research outputs found
P53 AND MICROTUBULES TARGETING AS A NOVEL STRATEGY WITH POTENTIAL FOR TREATMENT OF AGGRESSIVE POORLY DIFFERENTIATED THYROID CANCER.
Full text linkThyroid cancer is the most common endocrine malignancy and his global incidence has rapidly increased in last decades. Despite the major part of thyroid cancer is represented by well differentiated hystotypes, the acquisition of additional mutations, such as p53 and β-catenin ones, causes loss of differentiation and confer high malignancy. Current treatment for undifferentiated thyroid cancers is regarded as almost ineffective, with a median survival of 3- 4 months, somewhat better in localized and worse in metastatic disease.
SP600125 is a multi-kinase inhibitor that has recently been shown to be a promising anticancer drug. In the last five years it has been proved able to induce endoreduplication and subsequent polyploidization, but there are contrasting results about its intracellular actions and there is no evidence on the specific mechanism of action. Moreover, in 2012, SP600125 has been found to be the most effective against p53 deficient cells among more than 300 screened compounds. However, opposite results have also been obtained depending on cell type, concentration and time of incubation.
In the current study the effects of micromolar doses of SP600125 have been characterized in six thyroid cancer cell lines with different p53 status. The results show that at low concentrations SP600125 dramatically reduces the proliferation of p53 mutated cells, with lesser effects on p53 null and no effects on the wild-type ones. In p53 mutated cells it has been proved able to induce p53 nuclear translocation and phosphorylation at serine 15; this modification resulted to be responsible of increased levels of p21.
Importantly other considerable novel effects have been revealed. Firstly, SP600125 caused alterations of microtubule dynamics in p53 mutated cells, with increase of acetylation levels and loss of Microtubule Organizing Center (MTOC)-periphery organization. These effects were accompanied by alterations in cellular morphology and in late endosome/lysosome trafficking. Endoreduplication and alteration of microtubule dynamics finally resulted in aberrant mitosis and cell death. The second mechanism involves alteration of cellular motility: different kinases involved in this process are affected by SP600125 treatment and β-catenin remains at the intercellular junctions in affected cells,consistent with a failure of cell detachment (a figure consistent with inhibition of cell migration/motility). Microtubule alterations concomitantly also account for motility alterations. Both tubulin and β-catenin variations are due to HDAC6 activity alterations. This enzyme regulates the levels of acetylation of these proteins and is profoundly inhibited following SP600125 in p53 deficient cells. Alteration of HDAC6 activity is hypothesized to be the result of SP600125 direct inhibition of ROCK2, an upstream kinase regulator of HDAC6 activity.
In conclusion SP600125 is a promising drug particularly active on p53-mutated cancers at concentrations unable to affect normal cell viability. The effects of SP600125 action include arrest of tumor growth, and importantly induction of tumor cell death and metastatic diffusion inhibition
8-Cl-cAMP and PKA I-selective cAMP analogs effectively inhibit undifferentiated thyroid cancer cell growth
No full textThe main purpose of our work was to evaluate the effects of different cyclic adenosine monophosphate analogs on thyroid cancer-derived cell lines. In particular we studied 8-chloroadenosine-3′,5′-cyclic monophosphate, the most powerful cyclic adenosine monophosphate analog, and the protein kinase A I-selective combination of 8-hexylaminoadenosine-3′,5′cyclic monophosphate and 8-piperidinoadenosine-3′,5′-cyclic monophosphate. The cyclic adenosine monophosphate/protein kinase A pathway plays a fundamental role in the regulation of thyroid cells growth. Site-selective cyclic adenosine monophosphate analogs are a class of cyclic adenosine monophosphate-derivate molecules that has been synthesized to modulate protein kinase A activity. Although the cyclic adenosine monophosphate/protein kinase A pathway plays a fundamental role in the regulation of thyroid cells proliferation, there are currently no studies exploring the role of cyclic adenosine monophosphate analogs in thyroid cancer. We evaluated the effects on cell proliferation, apoptosis activation and alterations of different intracellular pathways using 3-(4,5-dimetylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytofluorimetry, western blotting, and kinase inhibitors. Our results show that both compounds have antiproliferative potential. Both treatments were able to modify protein kinase A RI/RII ratio, thus negatively influencing cancer cells growth. Moreover, the two treatments differentially modulated various signaling pathways that regulate cell proliferation and apoptosis. Both treatments demonstrated interesting characteristics that prompt further studies aiming to understand the intimate interaction between different intracellular pathways and possibly develop novel anticancer therapies for undifferentiated thyroid cancer
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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