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dc.contributor.authorCook, Jenny Anne
dc.date.accessioned2015-07-22T10:32:15Z
dc.date.available2015-07-22T10:32:15Z
dc.date.issued2014-08-28
dc.identifier.citationCook, JA. 2014. Classical monocytes from patients with pancreatic ductal adenocarcinoma exhibit a significantly altered transcriptome profile compared with healthy volunteers. Queen Mary University of Londonen_US
dc.identifier.urihttp://qmro.qmul.ac.uk/jspui/handle/123456789/7977
dc.descriptionThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the authoren_US
dc.description.abstractPancreatic Ductal Adenocarcinoma (PDAC) affects approximately 8000 people every year in the UK and is the fifth leading cause of cancer related death. At a molecular level PDAC is characterized by a significant immune infiltrate. Tumour-associated macrophages (TAMs) infiltrate the tumour and contribute to a worse prognosis by promoting growth, metastasis and resistance to chemotherapy. TAMs are derived from circulating ‘classical’ CD14++ CD16- monocytes in the peripheral blood. Current work in murine models suggests targeting monocyte recruitment in PDAC can reduce TAM infiltration and disease burden therefore improving survival. This project aims to identify markers specific to monocytes from PDAC patients and to investigate their biological relevance and potential for therapeutic intervention. Gene expression and metabolomics analysis was carried out on classical CD14++ CD16- monocytes from locally advanced PDAC patients and age matched healthy donors. Transcriptomic profiling revealed a significantly altered gene expression profile in classical monocytes from patients and genes with the highest fold change difference were chosen for validation using qPCR. Validated gene targets were investigated further in vitro and large-scale gene expression analysis from pancreatic tumours assessed. The results from my work demonstrate that the gene expression profile of classical monocytes from PDAC patients is significantly different compared to healthy volunteers. Identification and validation of up-regulated genes and their biological relevance may represent a relevant novel novel biomarker or therapeutic strategyies to target monocytes and myeloid recruitment in cancer.en_US
dc.description.sponsorshipThis work is funded by MedImmune (Grant number CIF1RA3R)en_US
dc.language.isoenen_US
dc.publisherQueen Mary University of Londonen_US
dc.subjectPancreatic Ductal Adenocarcinomaen_US
dc.subjectcancer related deathen_US
dc.subjectTumour-associated macrophagesen_US
dc.subjectmonocytesen_US
dc.subjecttherapeutic intervention.en_US
dc.titleClassical monocytes from patients with pancreatic ductal adenocarcinoma exhibit a significantly altered transcriptome profile compared with healthy volunteersen_US
dc.typeThesisen_US


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