1,724,617 research outputs found
Union Pacific (UP) 2876
No full textA photograph print showing Union Pacific (UP) 2876, 4-6-2, on westbound passenger train No. 333, Topeka, KS
Astronomische Nachrichten, nos 2876-2880
No full textAstronomische Nachrichten, nos 2876-2880. In: Bulletin astronomique, tome 6, 1889. pp. 235-240
2876. Walterus Gisburnensis
No full text2876. Walterus Gisburnensis. In: Molinier Auguste. Les Sources de l'histoire de France - Des origines aux guerres d'Italie (1494). III. Les Capétiens, 1180-1328. Paris : A. Picard et fils, 1903. p. 198
2876. Walterus Gisburnensis
No full text2876. Walterus Gisburnensis. In: Molinier Auguste. Les Sources de l'histoire de France - Des origines aux guerres d'Italie (1494). III. Les Capétiens, 1180-1328. Paris : A. Picard et fils, 1903. p. 198
Abstract 2876: Loss of the stem cell and basal lineage regulator LBH delays onset of basal-like triple negative breast cancer
No full textAbstract
There is increasing evidence that basal-like triple negative breast cancer (TNBC) originates from luminal mammary epithelial cells. Specific gene signatures have already been experimentally proven to serve as genetic lineage switches that, when overexpressed, transform pre-malignant luminal cells to oncogenic cells with basal, stem-like characteristics. Conversely, depletion of these genes in oncogenic cells with basal, stem-like characteristics leads to luminal differentiation. These studies suggest that during the earliest steps of neoplastic transformation, specific gene sets can alter cell fate decisions and differentiation status in mammary epithelial cells, which ultimately contributes to the heterogeneity of breast tumors.
Our lab has identified a novel Wnt/β-Catenin target gene, Limb bud and heart (LBH) that is majorly overexpressed in TNBC. LBH is a regulator of the basal mammary stem cell lineage and repressor of luminal differentiation via induction of ΔNp63 and repression of estrogen receptor alpha. LBH is required for the self-renewal and maintenance of adult basal mammary stem cells, which tend to be enriched in TNBC. Knockout studies in mice have shown that genetic ablation of LBH does not impair embryogenesis or normal adult organ function, making it a possible therapeutic target.
Using crosses between MMTV-Wnt-1 transgenic mice and K14Cre LBHloxP knockout mice, we are studying the effect of LBH ablation in the basal cells of the mammary epithelium downstream of ectopic Wnt expression in the mammary gland. We postulated that LBH may be an effector of Wnt-driven TNBC, therefore its inhibition would lead to decreased Wnt-induced mammary gland hyperplasia and tumor formation. In our model, LBH ablation in the basal mammary epithelium of female Wnt transgenic mice reduces mammary gland hyperplasia and delays tumor onset. MMTV-Wnt-1 driven, LBH-null tumors also exhibit histopathological differences indicative of a luminal to basal conversion.
There is an urgent need to elucidate mechanisms underlying TNBC development and progression and find reliable avenues for treatment. Our data indicates a role for Lbh as a novel effector for Wnt-driven TNBC and further studies may prove antagonism of Lbh to be a novel method to control TNBC progression.
Citation Format: Kilan C. Ashad-Bishop, Karoline Briegel. Loss of the stem cell and basal lineage regulator LBH delays onset of basal-like 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 2876. doi:10.1158/1538-7445.AM2017-2876</jats:p
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Abstract 2876: Adhesion GPCR CD97/ADGRE5 facilitates invasion in patient-derived glioma stem cells and induces changes in EGFR and Sox2 expression
No full textAbstract The main obstacles for effective treatment of Glioblastoma (GBM) are high invasiveness and heterogeneity. Each GBM tumor is composed of multiple genetically distinct subpopulations of Glioma Stem Cells (GSCs), exhibiting high cell plasticity affecting their invasive and proliferative properties. Treatment interventions and changes in microenvironment force GSCs to adapt through gene expression that supports therapeutic resistance. Expression level of the surface receptor CD97/ADRGE5 positively correlates with poor GBM patient prognosis, but its role in this tumor has not been elucidated. Here, we examined the function of CD97 in primary GSCs derived from five GBM tumors, which belong to three major genetic subtypes. We manipulated CD97 levels in these GSCs by knockdown and overexpression and analyzed the following: (i) expression of stem and subtype markers, (ii) in vitro invasive properties, (iii) cell proliferation, (iv) expression of the key proteins that regulate GSCs cellular state and influence their adaptive behavior. Our data showed that CD97 knockdown in GSCs of mesenchymal and classical subtype reduced their invasion rate in vitro. CD97 signaling positively affected expression of Epidermal Growth Factor Receptor, the main driver of astrocyte-like fate in GSCs and changed the expression of the astrocytic marker GFAP. Finally, we discovered a possible link between CD97 and expression of transcription factor Sox2, the key regulator of the endothelial-to-mesenchymal transition process that plays a crucial role in initiation of cancer cell invasion. Citation Format: Tatiana I. Slepak, Daniel G. Eichberg, Ana L. Pascoini, Ricardo J. Komotar, Michael E. Ivan. Adhesion GPCR CD97/ADGRE5 facilitates invasion in patient-derived glioma stem cells and induces changes in EGFR and Sox2 expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2876
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
No full text“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
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