1,731,224 research outputs found
Endothelin receptor type B counteracts tenascin-C-induced endothelin receptor type A-dependent focal adhesion and actin stress fiber disorganization
No full text10.1158/0008-5472.CAN-06-3348Cancer Research67136163-6173CNRE
UP 5472 coach at Salt Lake depot
No full textColor photograph of Union Pacific passenger coach number 5472 at the Salt Lake Union Pacific depot on May 24, 1980. It was part of the train led by UP 8444 during that day\u27s excursion to Provo. This car was sold to Mexico in 1987
Abstract 5472: Systems pharmacogenomics approach identifies synergistic molecular action of combined MTOR/HDAC inhibition on MYC
No full textAbstract
Multiple myeloma (MM) and murine plasmacytoma (PCT) are rare mature B-lymphoid malignancies. Allelic variants of Mtor and Cdkn2a affect susceptibility to PCT, and functional alterations in the PI3K/MTOR and CYCLIN/CDK/CDKI/RB (RB) pathways are common to both malignancies. We found that combining sirolimus (rapamycin), an inhibitor of mechanistic target of rapamycin (MTOR), with entinostat (MS-275), a selective class I histone deacytlase (HDAC) inhibitor, was synergistic in controlling 90% of tested cell lines derived from B cell malignancies in vitro, effective in limiting xenograft growth in vivo, and diminished cellular viability in ex vivo patient samples. Similarly, the combination reduced tumor burden and volume and increased survival in a long-term, in-vivo study in C.B6-Bcl2l1 mice. To examine the core synergistic consequence of combining entinostat with sirolimus, an integrated, systems-level approach was used. Weighted gene co-expression analysis (WGCNA) of GEP data from MM cells treated individually and in combination was used to identify a distinct module of 126 genes cooperatively affected by both drugs. Of the cooperatively affected genes, 37 were found to be differentially expressed in MM and predictive of survival (p<0.01). Ingenuity upstream analysis identified MYC as a potential core regulator of the synergistic transcriptional response. MYC protein, but not mRNA, decreased in response to the drug combination when examined by Western blot and NanoString analyses, respectively. Using tet-off, MYC-inducible transformed P493 cells, the necessity of MYC for the drop in cellular viability and response of the gene signature to the combination was evident. Using the translational and proteasomal inhibitors, cycloheximide and MG132, respectively, it was determined that MYC protein half-life decreased with the combination, largely due to proteasomal degradation. Utilizing a systems-level approach and biological filters, an alternative route to MYC inhibition was determined. Biologically relevant, this methodology can be used to define the molecular underpinnings of drug combinations, applicable to many diseases.
Citation Format: Benjamin J. Gamache, John K. Simmons, Aleksandra Michalowski, Jyoti Patel, Ke Zhang, Shuling Zhang, Wendy DuBois, Adriana Zingone, Michael Kuehl, Jing Huang, Ola Landgren, Beverly Mock. Systems pharmacogenomics approach identifies synergistic molecular action of combined MTOR/HDAC inhibition on MYC. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5472. doi:10.1158/1538-7445.AM2014-547
RUNX3 is frequently inactivated by dual mechanisms of protein mislocalization and promoter hypermethylation in breast cancer
No full text10.1158/0008-5472.CAN-06-0369Cancer Research66136512-652
Urinary levels of tobacco-specific nitrosamine metabolites in relation to lung cancer development in two prospective cohorts of cigarette smokers
No full text10.1158/0008-5472.CAN-08-4330Cancer Research6972990-2995CNRE
Role of RUNX3 in bone morphogenetic protein signaling in colorectal cancer
Get PDF10.1158/0008-5472.CAN-09-3805Cancer Research70104243-4252CNRE
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
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