1,720,962 research outputs found
2-MeOE2bisMATE induces caspase-dependent apoptosis in CAL51 breast cancer cells and overcomes resistance to TRAIL via cooperative activation of caspases
No full text2-Methoxyoestradiol (2-MeOE2) is an endogenous oestrogen metabolite which inhibits tubulin polymerisation and has anti-tumour and anti-angiogenic activity. 2-MeOE2 induces apoptosis in a wide range of cancer cell types and has recently been demonstrated to cooperate with TRAIL to induce apoptosis in breast cancer cells. 2-Methoxyoestradiol-3,17-bis-O,O-sulphamate (2-MeOE2bisMATE) is a sulfamoylated derivative of 2-MeOE2 with enhanced activity and improved pharmacokinetic properties, and 2-MeOE2bisMATE is a promising candidate for early clinical trials. It is important, therefore, to understand the mechanisms by which 2-MeOE2bisMATE acts, and whether it retains the ability to cooperate with TRAIL. We demonstrate that 2-MeOE2bisMATE-induced apoptosis of CAL51 breast cancer cells was associated with rapid activation of caspase 3 and 9, but not caspase 8 (as measured by BID cleavage) and was completely prevented by the caspase inhibitor zVADfmk. Interfering with Fas- or TRAIL-receptor function did not prevent 2-MeOE2bisMATE-induced apoptosis. Whereas CAL51 cells were resistant to TRAIL-induced apoptosis, 2-MeOE2bisMATE and TRAIL cooperated to induce cell death. This apoptosis was associated with enhanced activation of caspases, but not increased expression of the DR5 TRAIL receptor, previously demonstrated to be induced by 2-MeOE2. Therefore, 2-MeOE2bisMATE-induced apoptosis is dependent on caspases and like 2-MeOE2, 2-MeOE2bisMATE can overcome resistance to TRAIL by stimulating activation of downstream caspases. Our results suggest that 2-MeOE2bisMATE and TRAIL might be a particularly effective combination of anti-cancer agents
The effect of 2-methoxyoestrone-3-O-sulphamate on the growth of breast cancer cells and induced mammary tumours
No full text2-Methoxyoestrogens are emerging as a new class of drug that can inhibit tumour growth and angiogenesis. As sulphamoylation of oestrogens enhances their potency and bioavailability we have synthesized 2-methoxyoestrone-3-O-sulphamate (2-MeOEMATE) and compared its ability to inhibit the proliferation of breast cancer cells with that of 2-methoxyoestrone (2-MeOE1). 2-MeOEMATE (1 microM) inhibited the growth of oestrogen receptor positive MCF-7 breast cancer cells by 52% whereas 2-MeOE1 had little effect at this concentration. 2-MeOEMATE also inhibited the growth of oestrogen receptor negative MDA-MB-231 breast cancer cells. Exposure of cells to 2-MeOEMATE caused them to round up and become detached suggesting that this compound may induce cells to undergo apoptosis. Cell cycle analysis revealed that 2-MeOEMATE caused cells to arrest in the G(2)/M phase with the increase in G(2)/M arrested cells being detectable by 12 hr. Exposure of MCF-7 cells to 2 L-MeOEMATE for 24 hr followed by culture in drug-free medium for 24 hr did not reverse the arrest of cells in the G(2)/M phase. TUNEL analysis confirmed that 2-MeOEMATE induced apoptosis in a significant proportion of treated MCF-7 cells. In an in vivo study, employing nitrosomethylurea-induced mammary tumours in intact rats, 2-MeOE1 (20mg/kg/d, p.o. for 11 days) had little effect on tumour growth. In contrast, the same dose of 2-MeOEMATE resulted in the almost complete regression of 2/3 tumours over an 11-day period. We conclude that 2-MeOEMATE should have considerable therapeutic potential for the treatment of breast tumours
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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 PDFWe 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
Inhibition of superoxide dismutase by 2-methoxyoestradiol analogues and oestrogen derivatives - structure-activity relationships
No full textSuperoxide dismutases catalyse the dismutation of highly reactive superoxide ions to produce hydrogen peroxide and several lines of evidence suggest that these enzymes play important roles in the development and response to treatment of human cancers. For example, Mn-containing superoxide dismutase is frequently overexpressed in various cancer types and can contribute to resistance to apoptosis. 2-Methoxyoestradiol is a naturally occurring metabolic product of 17bgr-oestradiol that inhibits tubulin polymerization and possesses growth inhibitory and cytotoxic activity in vitro and in vivo. More recently 2-methoxyoestradiol has also been shown to inhibit superoxide dismutase (SOD) in a tetrazolium salt based enzyme assay, suggesting that oestrogen derivatives might be useful starting points for the development of effective, non-toxic enzyme inhibitors. Here we have tested the SOD inhibiting activity of a range of oestrogen derivatives to determine structural features important for enzyme inhibition
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
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