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Abstract 5864: Targeting brain cancer stem cells by potentiating radiation-induced ER stress
No full textAbstract
Background. Glioblastoma (GBM) is one of the most malignant brain tumors occurring in both children and adults. Despite an aggressive treatment regimen consisting of surgical resection, radiation therapy and chemotherapy the five-year survival rate is less than 5%. This poor outcome has been attributed to the existence of therapy-resistant GBM stem-like cells (GSCs), which are believed to be responsible for tumor recurrence and patient relapse. Understanding the resistance mechanisms employed by brain tumor stem cells and developing novel methods to target these cells is necessary for prolonged patient survival. Recent evidence suggests that the endoplasmic reticulum stress response pathway may mediate therapeutic resistance in cancer. Here we sought to examine the ER stress response pathway of GSCs in response to ionizing radiation and to increase the extent of ER stress in an effort to promote cell death using the glycolytic inhibitor, 2-deoxy glucose (2-DG).
Methods. GSC lines were derived from resected tumor sections. GSCs were irradiated using the Rad Source 2000 Series Biological Irradiator. Transmission Electron Microscopy (TEM) was used to investigate the ultra-structural alterations of GSCs following exposure to 8 Gy radiation. Viability was determined using trypan blue exclusion, MTS and LDH assays. Cell signaling pathways were investigated by western blot analysis.
Results. Consistent with previous findings, minimal cell death was observed in GSCs exposed to 2-20 Gy radiation. TEM analysis revealed that exposure to 8 Gy significantly increased ER lumen dilation, suggestive of ER stress. Western blot analysis indicated an increase in ER stress markers GRP78, GRP94 and CHOP, confirming that radiation induces ER stress in GSCs. Treatment with 2-DG induced an increase in ER lumen diameter and ER stress markers. Combined 2-DG (0.5mM and 2mM) and radiotherapy (8 Gy) significantly increased ER luminal diameter and ER stress marker expression over radiation or 2-DG alone. In addition, combined radiation and 2-DG (0.1-2mM) significantly reduced GSC viability compared to radiation or 2-DG alone.
Conclusion. The ER stress response pathway is an adaptive mechanism and thought to mediate therapeutic resistance. Here we demonstrate that radiation induces ER stress response pathway including ER lumen dilation and an increase in molecular chaperone expression in GSCs. Potentiating ER stress can switch the pathway from one of adaptation to cell death. 2-DG increased radiation-induced ER stress and promoted cell death. Our data suggests that targeting this adaptive response could increase the efficacy of radiotherapy and prolong patient survival
Note: This abstract was not presented at the meeting.
Citation Format: Regina M. Graham, Sumedh S. Shah, Alexis J. Musick, Winston Walters, Ricardo J. Komotar, Jeffery S. Prince, Steven Vanni. Targeting brain cancer stem cells by potentiating radiation-induced ER stress [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 5864. doi:10.1158/1538-7445.AM2017-5864</jats:p
Motels: [Arbor Motel, 5864 N. 99 Highway]
No full textArbor Motel, 5864 N. 99 Highway - Stockton 5, Calif. Phone 466-5111. Twenty modern units, luxuriously furnished, air-conditioned, individual heat, full tile showers, wall to wall carpets, TV, Pool, room, coffee, near restaurants
Block Card 5864 Fryer Avenue
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: Ranch houses | 5864 Fryer Avenue (Toledo, Ohio) | Dwelling | Glynn Place (Subdivision) (Toledo, Ohio) | Reynolds Corners Area (Toledo, Ohio
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
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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