1,720,980 research outputs found
Abstract 650: B lymphocytes promote upregulation of an IL-1-NfkB dependent signaling and increase invasiveness of triple negative breast cancer
No full textAbstract
Triple negative breast cancer (TNBC) is an aggressive form of breast cancer that progresses quickly from a non-invasive carcinoma in situ to an invasive state. Chronic inflammation associated to humoral immune responses has been found to promote aggressiveness in a number of solid tumor types. In breast cancer, B lymphocytes are associated with microinvasive disease and correlate with expression of inflammatory genes. The purpose of our work is to study the impact of B lymphocytes on the tumor microenvironment and increased invasiveness of TNBC cells. Through real-time PCR, we demonstrate that co-culture of B lymphocytes and TNBC cells leads to increased mRNA levels of IL1β and its downstream target interleukin 8 (IL8) in both B lymphocytes and in TNBC cells. Western Blot analysis shows that co-culture also leads to increased phosphorylation of p65, indicating IL-1 β activation of NFκB signaling. Additionally, co-culture of B lymphocytes with TNBC cells leads to increased expression of matrix metalloproteinases (MMPs) and cellular invasion through a matrigel invasion chamber. Gelatin zymography reveals increased functional MMP2 and MMP9 in tumor cell supernatant following co-culture with B lymphocytes. To complement our in vitro studies, we examined the presence of CD20+ B cells and expression of inflammatory cytokines IL-1β and IL-8 by immunohistochemistry in serial sections of tissue microarrays from patients with estrogen receptor (ER) positive and negative ductal carcinoma in situ (DCIS) and invasive carcinoma. Large areas of densely populated B cells were observed in ER-DCIS and in invasive TNBC compared to ER+ DCIS. Furthermore, in ER- DCIS and TNBC, both B lymphocytes and tumor cells are found to express IL1β whereas IL8 is found more specifically to be expressed by tumor cells. Our findings support the hypothesis that B lymphocytes promote a chronic inflammatory environment leading to increased invasion of TNBC cells.
Citation Format: Nicole Flynn, Rajasekharan Somasundaram, Jennifer Sims-Mourtada. B lymphocytes promote upregulation of an IL-1-NfkB dependent signaling and increase invasiveness of triple negative breast cancer [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 650. doi:10.1158/1538-7445.AM2017-650</jats:p
Abstract 3369: Epigenetic DNA methylation profiling of triple negative breast cancer: a quantitative NGS approach
No full textAbstract
Triple negative breast cancer (TNBC) is an aggressive disease with a high degree of genomic instability. TNBC patients have poor prognosis and the risk of metastasis and death is increased for women who relapse within four years of treatment compared to other breast cancer subtypes. Currently, there are no reliable prognostic markers to identify which population is at risk for early relapse and the molecular mechanism for disease recurrence is not well understood. Epigenetic changes, especially DNA methylation, are common in breast cancer and have been found to be associated with increased metastatic capability. Therefore, the methylation states of genes in TNBC tumors compared to non-tumor breast tissue was examined in order to identify potential biomarkers and therapeutic targets in TNBC. Matched tumor and adjacent non-tumor tissue from patients with TNBC were obtained following surgical resection and genomic DNA was extracted. Epigenetic profiling of TNBC tumors and non-tumor tissue was performed using a highly sensitive and quantitative analytics platform, which utilizes methylation sensitive restriction endonucleases to detect changes in methylation of CpG sites. Millions of CpG sites exist within the human genome and many of these are altered with tumor formation and progression, therefore, changes in methylation profiles of CpG sites may be useful as a diagnostic and/or prognostic biomarker in TNBC patients. Non-metric multidimensional scaling ordination analysis of the CpG sites revealed highly distinct methylation patterns between tumor and non-tumor tissue. Approximately 326 sites had a significant methylation score difference (p&lt0.0025) between TNBC tumor and non-tumor tissue, with most of the CpG sites having greater than 2-fold change in methylation status. Analysis of functional gene classes using KEGG classifiers revealed a significant change in methylation patterns of genes involved in response to infections and other immune related functions. Additionally, the top ten genes with hyper- or hypomethylated sites within TNBC tumors when compared to non-tumor tissue were identified. Interestingly, Gli-1 was one of the top hypomethylated genes. Gli-1 has been shown in our lab and others to have significance in chemoresistance and recurrence in TNBC patients. Immunohistochemical analysis of TNBC tumors revealed Gli-1 overexpression in TNBC tumors compared to non-tumor tissue. Expression levels of Gli-1 in TNBC tumors correlated with stage (p&lt0.001) and recurrence free (p&lt0.0213) and overall survival (p&lt0.017). Thus, analysis of CpG methylated sites in TNBC tumors and non-tumor tissue revealed differences in epigenetic profiles allowing for distinction between tumor and non-tumor tissue. Genes in TNBC tumors with significant changes in methylation status may be potential candidate genes that serve as a diagnostic or prognostic biomarker for TNBC.
Citation Format: Kimberly M. Arnold, Adam G. Marsh, Jennifer Sims-Mourtada. Epigenetic DNA methylation profiling of triple negative breast cancer: a quantitative NGS approach [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 3369. doi:10.1158/1538-7445.AM2017-3369</jats:p
Boosting Response: The Impact of Immune Checkpoint Inhibitors on Radiation Treatment Schedules
No full textAbstract 3718: Taxane-induced hedgehog activation promotes stemness of breast cancer cells.
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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
Co‑activation of Hedgehog and Wnt signaling pathways is associated with poor outcomes in triple negative breast cancer
No full textAppropriate 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
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