1,720,964 research outputs found
Abstract 4163: Blockade of the interleukin-1 signaling pathway overcomes erlotinib resistance in head and neck cancer cells
No full textAbstract
The EGFR tyrosine kinase inhibitor erlotinib has demonstrated poor clinical response rates for head and neck squamous cell carcinoma (HNSCC) to date and the majority of respondents acquire resistance to erlotinib relatively quickly. Our previous data has shown that erlotinib activated interleukin-1 (IL-1) expression and signaling in HNSCC cells in vitro. We therefore investigated if upregulation of IL-1 signaling is involved in erlotinib resistance in HNSCC cells. We compared gene expression profiles of erlotinib-resistant (ER) and the parental erlotinib-sensitive (ES) HNSCC cell lines and observed a deregulation of the IL-1 signaling pathway in ER versus ES-HNSCC cells using microarray enrichment analysis. Secretion of IL-1 alpha (IL-1α) and IL-1 beta (IL-1β) were not significantly different in ER-SQ20B and ER-CAL 27 cells compared to their respective ES-cells, however secretion of the IL-1 receptor antagonist (IL-1RA) was significantly reduced in ER-cells compared to ES-cells. Blockade of IL-1 signaling using a recombinant IL-1R antagonist (anakinra) was able to significantly suppress the growth of ER-SQ20B but not ES-SQ20B xenografts as a single agent and in combination with erlotinib. ER-SQ20B xenografts treated with anakinra with or without erlotinib were found to be less vascularized (as determined by CD31 staining) than ER-SQ20B xenografts treated with water or erlotinib. Altogether, blockade of the IL-1 pathway using anakinra overcame erlotinib resistance in HNSCC xenografts and may represent a novel strategy to overcome EGFR inhibitor resistance for the treatment of HNSCC patients.
Citation Format: Andrean L. Simons, Aditya Stanam, Katherine N. Gibson-Corley. Blockade of the interleukin-1 signaling pathway overcomes erlotinib resistance in head and neck cancer cells [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 4163. doi:10.1158/1538-7445.AM2017-4163</jats:p
Abstract 48: Targeting IL-1 signaling to improve tumor response to erlotinib in HNSCC
No full textAbstract
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) including erlotinib have demonstrated poor clinical response rates for head and neck squamous cell carcinoma (HNSCC) to date compared to the EGFR monoclonal antibody cetuximab. Therefore we seek to identify molecular mechanisms involved in tumor response to erlotinib and ultimately improve the anti-tumor efficacy of erlotinib for HNSCC patients. We have shown that erlotinib-treated HNSCC cell lines induced the expression and secretion of a wide variety of genes involved in inflammation and immune response including interleukin-1 (IL-1) and interleukin-6 (IL-6) compared to control-treated cells. The secretion of IL-6 from HNSCC cells in response to erlotinib was found to be triggered by MyD88-dependent IL-1 signaling and suppression of IL-1 signaling (using a neutralizing IL-1α antibody) significantly enhanced the anti-tumor efficacy of erlotinib in vivo. In erlotinib-resistant HNSCC cell lines, IL-1 signaling was significantly upregulated compared to their respective parental cell lines. Blockade of IL-1 signaling using a neutralizing IL-1α antibody or an IL-1 receptor (IL-1R) antagonist was able to significantly suppress the growth of erlotinib-resistant HNSCC xenografts as a single agent and in combination with erlotinib which was associated with reduced immune cell recruitment and angiogenesis. Altogether, blockade of the IL-1 pathway may represent a novel strategy to improve tumor response to erlotinib and other EGFR TKIs in HNSCC patients.
Citation Format: Andrean Simons, Aditya Stanam, Adam Koch, Madelyn Espinosa-Cotton, Katherine Gibson-Corley. Targeting IL-1 signaling to improve tumor response to erlotinib in HNSCC [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 48.</jats:p
Abstract 4247: Predicting the prognosis for cancer patients with interleukins gene expression level
No full textGoing 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
Developing a DEVS-JAVA Model to Simulate and Pre-test Changes to Emergency Care Delivery in a Safe and Efficient Manner
No full textAbstract 4247: Predicting the prognosis for cancer patients with interleukins gene expression level
No full textVariations 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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