1,721,052 research outputs found
Abstract 2939: Tumor associated myeloid cell transcriptome signatures in an inducible Kras-positive lung adenocarcinoma murine model
No full textAbstract
Tumorigenesis is modified by dynamic activities in the tumor microenvironment and mechanisms driving these alterations during tumor progression may be tumor- and patient-specific. Of well-established functions for tumor-associated stromal cells (e.g. angiogenesis, chemotaxis) immune system regulation by the tumor microenvironment is less well understood in their mechanism and effects. However, diminished activity of antigen-specific T cell lymphocytes tumor cytotoxicity is tumor promoting and recent cancer immunotherapy have targeted immune inhibitory checkpoints (e.g. anti-PD-L1) to restore T cell activity. Recent studies suggest that tumor-associated myeloid cells play a role in immunosuppression in several human cancers, including lung cancer. We hypothesize that early tumors of the lung promote changes in the phenotype of tumor-proximal myeloid cells, establishing an immunosuppressive microenvironment. As a component to observe this immunosuppressive role for myeloid cells, we performed specific transcriptome profiling of myeloid cells by immunomagnetic selection of CD11b-positive cells from lung tumors of a murine inducible Kras-positive, p53-negative cancer model. RNA sequencing of isolated myeloid cells as a function of tumorigenesis duration (3-18 weeks) establishes the kinetics of gene expression changes associated with tumor-supporting and immune-suppressing functions. Genome-wide expression analysis of myeloid cells between tumor-inducing adenovirus-Cre injected and normal control subjects resulted in identifying 1,883 genes with differential expression. Gene set enrichment analysis resulted in the stratification of samples by well-established gene signatures and tumor-promoting activity for angiogenesis (32 genes), lung tissue remodeling (47 genes) and cell survival (11 genes). Interestingly, a significant downregulated gene signature was observed in tumor-associated myeloid cells for immune cell chemotaxis (12 genes) and positive regulation of immune system activation (12 genes). These non-canonical gene signatures may identify a myeloid phenotype for immunosuppressive function with altered expression of genes such as L-selectin (Sell), C-C chemokine receptor type 7 (Ccr7), C-C motif chemokine (Ccl20) and CMRF35-like molecule 7 (CD300lb). The results shown are first steps in our tasks to define the phenotypes and mechanisms linking myeloid cells to tumor-associated immunosuppression in lung cancer.
Citation Format: Clifton L. Dalgard, Mouna Lagraoui, Gauthaman Sukumar, Celeste Huaman, Corey A. Carter, Brian C. Schaefer. Tumor associated myeloid cell transcriptome signatures in an inducible Kras-positive lung adenocarcinoma murine model [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 2939. doi:10.1158/1538-7445.AM2017-2939</jats:p
Abstract 4000: Establishing the natural history of the immunosuppressive myeloid microenvironment in an inducible model of lung adenocarcinoma
No full textAbstract
Tumorigenesis is accompanied by broad changes to the surrounding tissue microenvironment in a tumor- and patient-specific manner. Phenotype shifts in tissue-resident immune cells promote cancer progression by establishing a proliferative inflammatory environment, activating angiogenesis, stimulating tumor cell invasion and suppressing anti-tumor immunity. While the former mechanisms are well appreciated and often targeted by current cancer therapeutics, the nature of the mechanisms controlling establishment of the local immunosuppressive state that contribute to a failure of anti-tumor immunity are less clearly defined. Blockade of tumor antigen-specific T cell killing is clearly a major contributor to the failure to control tumorigenesis. However, evidence suggests that phenotypic shifts in innate immune cell populations also contribute to the failure of anti-tumor immunity. We hypothesize that the emergence of early lung adenocarcinomas is accompanied by a shift in myeloid phenotypes, rapidly establishing a microenvironment favorable to tumor growth, survival and vascularization, and hostile to cell-mediated anti-tumor immune responses. Through the utilization of a Cre-inducible mouse model of p53-null, Kras-G12D+ lung adenocarcinoma, we have begun to define the natural history of the myeloid component of the tumor microenvironment, from tumor initiation to a point equivalent to human stage I adenocarcinoma. Histological, flow cytometry and real-time PCR approaches collectively demonstrate that tumor-associated myeloid phenotypes emerge at a very early stage of disease. These data are consistent with our hypothesis that the myeloid component of the tumor microenvironment plays a crucial role in establishing an immunosuppressive state during early tumorigenesis. Implications of these findings for current and emerging immunotherapies will be discussed.
Citation Format: Mouna Lagraoui, Clifton L. Dalgard, Gauthaman Sukumar, Celeste Huaman, Thomas Summers, Corey A. Carter, Brian C. Schaefer. Establishing the natural history of the immunosuppressive myeloid microenvironment in an inducible model of lung adenocarcinoma [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 4000. doi:10.1158/1538-7445.AM2017-4000</jats:p
Abstract 3569: Comparative RNA-seq analysis reveals dys-regulation of major canonical pathways in ERG-inducible LNCaP cell progression model of prostate cancer
No full textAbstract
Prostate Cancer (CaP) is the most common non-cutaneous form of cancer in men and is the second leading cause of cancer mortality in men in the USA. In human CaP, gene fusion between androgen responsive regulatory elements at the 5' untranslated region of TMPRSS2 and ETS-related genes (ERG) is present in at least 50% of the prostate tumors. To identify and investigate the underlying mechanisms of ERG-associated CaP, we developed ERG-inducible LNCaP cell system. In this present study, we investigated the unique cellular transcriptome associated with over-expressed ERG in CaP cells. Our data from comprehensive transcriptome analyses, illustrate a distinct signature that distinguishes ERG-dependent and ERG-independent CaP. The data highlight the significant heterogeneity among the transcript. Out of the 527 differentially expressed genes, 232 genes were up-regulated and 295 genes were down-regulated in response to ERG. Subsequent, in silico analyses indicate that these differentially expressed genes were associated with many pathways and functions. The most significantly differentially expressed genes were associated with cell cycle regulation. The top-ranked biological functions affected by ERG over-expression include Cell Cycle (p &lt; 1.42E-04), Cellular Growth and Proliferation (p &lt; 1.23E-04), Cellular Development (p &lt;1.23E-04), Cell Death and Survival (p &lt; 1.37E-04), and Cellular Assembly and Organization (p &lt; 1.42E-04). Further analyses indicate a strong association with known cancer networks. The top-ranked canonical pathways enriched in ERG-positive compared to ERG-negative LNCaP cells include, Cell Cycle Control of Chromosomal Replication (p=2.69E-16), Role of CHK Proteins in Cell Cycle Checkpoint Control (p=3.16E-11), Cell Cycle: G2/M DNA Damage Checkpoint Regulation (p=1.34E-09), Role of BRCA1 in DNA Damage Response (p=4.05E-08) and Estrogen-mediated S-phase Entry (p =5.51E-08). These findings indicate new insights into the complexity of TMPRESS2-ERG gene fusion, and may help understand mechanistic pathways which promote growth and progression of CaP.
Citation Format: Parameet Kumar, Joyeeta Chakraborty, Raghunath Chatterjee, Gauthaman Sukumar, Clifton L. Dalgard, Kevin Babcock, Albert Dobi, Taduru L. Sreenath, Roopa Biswas. Comparative RNA-seq analysis reveals dys-regulation of major canonical pathways in ERG-inducible LNCaP cell progression model of prostate 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 3569. doi:10.1158/1538-7445.AM2017-3569</jats:p
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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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