1,725,549 research outputs found
Abstract 4861: The role of PRAME in promoting uveal melanoma metastasis
No full textAbstract
Uveal melanoma (UM) is the most common primary eye cancer and has a predisposition for fatal metastasis. Our group has shown that UMs can be categorized by gene expression profiling (GEP) into two molecular classes associated with metastatic risk: Class 1 (low metastatic risk) and Class 2 (high metastatic risk). While the majority of Class 2 UMs (71%) metastasize, only 38% of Class 1 UMs metastasize. Our group was the first to identify the cancer-testis antigen PRAME as a biomarker for increased metastatic risk in Class 1 UMs, and sub-categorized these tumors into Class1 PRAME+ (intermediate metastatic risk) and Class1 PRAME- (low metastatic risk) subgroups. Further we identified PRAME+ was associated with shorter time to metastasis and worse prognosis in class 2 patients. We have now shown that this PRAME expression is correlated with hypomethylation in the promoter region of the gene, suggesting a mechanism for its expression. Since we have previously shown that PRAME is associated with early metastasis in Class 1 and Class 2 UMs, we hypothesized that PRAME plays a direct role in UM metastasis. To better understand the role of PRAME in UM, we used Class1PRAME+ (F41) and Class1PRAME– (Mel290) UM cell lines to develop in vitro models to study the role of PRAME. Since F41 cells are PRAME+ and highly metastatic, we constitutively silenced PRAME with a V5 tag (F41 shPRAME-V5). For Mel290 cells, we overexpressed PRAME to see whether this cell line, which does not induce metastatic death, became more malignant. We confirmed the silencing and overexpression of PRAME in our transformed cells with western blot. For cell proliferation, we found a slight increase in the Mel290 PRAME+ cells compared to non-transformed Mel290. Strikingly, in F41 cells, knockdown of PRAME led to complete cell death. In a xenograft animal model, NSG male mice were injected with either Mel290 PRAME-V5, Mel290, F41 shPRAME-V5 or F41 TET-empty vector cells. We found that PRAME overexpressing cell lines (Mel290 PRAME-V5 and F41 TET-empty vector) induced rapid, multiple and aggressive liver metastases that led to death, whereas the non-expressing PRAME cells (Mel290 and F41 shPRAME-V5) did not present macro or micrometastasis in any cases. This data highly suggests that PRAME overexpression is involved in UM metastasis. Thus, PRAME mRNA expression is not only a prognostic biomarker but also could be an important target for treatment.
Citation Format: Margaret I. Sanchez, Matthew G. Field, Jeffim N. Kuznetsov, Stefan Kurtenbach, Dien Pham, James W. Harbour. The role of PRAME in promoting uveal melanoma metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4861. doi:10.1158/1538-7445.AM2017-4861</jats:p
Block Card 4861 Summit Street
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Dwelling | 4861 Summit Street (Toledo, Ohio) | Barge Inn (Toledo, Ohio) | 20th Century Commercial Style | Foxman Addition (Toledo, Ohio) | Point Place (Toledo, Ohio) | North Toledo Area (Toledo, Ohio) | Curved bay | Folk House Styl
Ccd imaging of ngc 4861 : morphology and brightness distribution
No full textWe discuss narrow band CCD imaging of NGC 4861 in continua at 4500 Å, 5300 Å and 6300 Å as well as in Hα, Hβ and [OIII] λ 5007Å lines. We find that the system exhibits a double nucleus structure anda counter-tail to the well-known NE chain of HII regions. The mean value of lines and continua frames for the main body brightness distribution ofNGC 4861 is R-2.04±0.35, comparable to the Hubble-Reynolds law R-². The three mentioned characteristics indicate that NGC 4861 might have undergone a merger process. The time elapsed from the beginning of the phenomenon is set to be smaller than three crossing times. New observations are proposed to confirm or reject the merger scenario for this peculiar galaxy
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
Optical counterparts of ULXs in two dwarf galaxies: NGC 4861 and NGC 4449
No full textWe present the results of a search for optical candidates of ultraluminous X-ray sources (ULXs) in two dwarf galaxies, NGC 4861 and NGC 4449, using Hubble Space Telescope (HST) archival data. With precise astrometry, we confirm that NGC 4861 X1 is associated with an H II complex and we conclude that NGC 4861 X2 resides in a young star group of mass 400 ± 80 M☉. We also find that NGC 4449 X7 is associated with three optical candidates within an error radius of 0.2 arcsec at the 90 per cent confidence level. Absolute magnitudes (Mv) of these candidates are determined as −5.0 and −4.1. The age and mass values for the three candidates are estimated as 40–50 Myr and ∼8 M☉, respectively, using stellar evolutionary tracks. The locations of optical candidates suggest a possible association with a nearby group of stars. In addition, we analysed previously unused archival data of XMM–Newton, Chandra, and Swift where the sources were detected. Although the X-ray spectral data do not allow us to discriminate between physical models, long-term data at hand are consistent with the sources being in luminous hard states
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
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