Sharon L. Eddie

Abstract B007: Unravel the role of extracellular NNMT (eNNMT) in the modulation of prostate cancer (PC) tumour immune microenvironment (TIME)

Agata Carreira, Marianna Ciuffreda, Nathakan Thongon, Elena Cerri et autres

Abstract Cellular plasticity enables cancer cells to acquire new biological properties and become resistant to therapy. Late-stage castration resistant prostate cancer (CRPC) present heterogenous phenotypes in response to antiandrogen therapy, which likely arise from widely plastic adenocarcinomas, but invariably renders hormonal therapy …

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Nicotinamide N-Methyl Transferase (NNMT) Sustains Innate Sensitivity to NAMPT Inhibition in YAP-dependent Stem-like/Mesenchymal Prostate Cancer

Ágata Sofia Assunção Carreira, Marianna Ciuffreda, Nathakan Thongon, Charles M. Haughey et autres

Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the NAD + salvage pathway and a promising therapeutic target in cancer.Resistance to NAMPT inhibitors, such as FK866, remains a key limitation to their clinical translation.While acquired resistance in cancer cell lines has been …

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NNMT drives innate sensitivity to NAMPT inhibition in YAP-dependent stem-like/ mesenchymal prostate cancer

Ágata Sofia Assunção Carreira, Marianna Ciuffreda, Natthakan Thongon, Charles M. Haughey et autres

ABSTRACT Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the NAD+ salvage pathway and a promising therapeutic target in cancer. Resistance to NAMPT inhibitors, such as FK866, remains a key limitation to their clinical translation. While acquired resistance in cancer cell lines …

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TBX2 acts as a potent transcriptional silencer of tumour suppressor genes through interaction with the CoREST complex to sustain the proliferation of breast cancers

Alexander J. McIntyre, Charlotte Zoe Angel, James S. Smith, Amy Templeman et autres

Chromosome 17q23 amplification occurs in 20% of primary breast tumours and is associated with poor outcome. The TBX2 gene is located on 17q23 and is often over-expressed in this breast tumour subset. TBX2 is an anti-senescence gene, promoting cell growth and survival …

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Investigating Radiotherapy Response in a Novel Syngeneic Model of Prostate Cancer

Charles M. Haughey, Debayan Mukherjee, Rebecca E. Steele, Amy L. Popple et autres

mouse, termed DVL3 which when subcutaneously implanted in immunocompetent C57BL/6 mice, forms tumours with distinct glandular morphology, strong cytokeratin 8 and androgen receptor expression, recapitulating high-risk localised human PCa. Compared to the commonly used TRAMP C1 model, generated with SV40 large T-antigen, …

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Development of a novel allograft model of prostate cancer: a new tool to inform clinical translation

Charles M. Haughey, Debayan Mukherjee, Rebecca E. Steele, Amy L. Popple et autres

Abstract Background Allograft models enable characterisation of genomic drivers and treatment responses by modelling immune and micro-environmental changes more accurately than xenografts. Despite this, few models are available to the prostate cancer (PCa) community. This study presents a novel allograft model of …

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Defining the molecular evolution of extrauterine high grade serous carcinoma

James Beirne, Darragh G. McArt, Aideen C. Roddy, Clara McDermott et autres

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Identification and SAR exploration of a novel series of Legumain inhibitors

Sharon L. Eddie, Aaron M. Gregson, Emma Graham, Stephanie Gail Burton et autres

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Abstract 3988: Legumain regulates advanced prostate cancer via HSD17B4

Sharon L. Eddie, Alice Ormrod, Richard D. Williams, Paul B. Mullan

Abstract Prostate cancer is the most common male cancer diagnosis. However, current treatment is limited and patients often develop resistant, metastatic disease. Novel targeted therapies which prevent recurrence and metastasis are essential to improve patient prognosis. A possible novel therapeutic target, the …

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Pan-cancer mesenchymal assay to predict response to MEK inhibitors.

Nuala McCabe, Laura A. Knight, Lara Dura Perez, Bethanie Price et autres

12111 Background: Unsupervised hierarchical clustering of gene expression data from 265 high grade serous ovarian cancer (HGSOC) patients identified 3 major molecular subgroups. One subgroup is driven by activation of the MAPK-pathway and is associated with a mesenchymal phenotype, poor prognosis and …

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Increasing mechanistic understanding of the role of p53 mutations in triple negative breast cancer and identifying potential roles in chemoresistance

Ruth Steele, Sharon L. Eddie, Simon S. McDade, P. B. Mullan

Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences

Afshan Dean, Sander van den Driesche, Yili Wang, Chris McKinnell et autres

Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC …

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