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Pancreatic Neoplasms: HELP
Articles by Lucy Oldfield
Based on 2 articles published since 2009
(Why 2 articles?)
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Between 2009 and 2019, Lucy Oldfield wrote the following 2 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article S100A8 and S100A9 proteins form part of a paracrine feedback loop between pancreatic cancer cells and monocytes. 2018

Nedjadi, Taoufik / Evans, Anthony / Sheikh, Adnan / Barerra, Lawrence / Al-Ghamdi, Suliman / Oldfield, Lucy / Greenhalf, W / Neoptolemos, John P / Costello, Eithne. ·King Abdullah International Medical Research Centre, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, P. O. Box 9515, Jeddah, 21423, Saudi Arabia. nedjadita@ngha.med.sa. · Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, The University of Liverpool, Liverpool, UK. · King Abdullah International Medical Research Centre, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, P. O. Box 9515, Jeddah, 21423, Saudi Arabia. ·BMC Cancer · Pubmed #30558665.

ABSTRACT: BACKGROUND: The secretion of soluble factors enables communication between tumour cells and the surrounding microenvironment and plays an important role in oncogenesis. Pancreatic ductal adenocarcinoma (PDAC) is characterised by a highly reactive microenvironment, harbouring a variety of cell types, including S100A8/S100A9-expressing monocytes. S100A8/S100A9 proteins regulate the behaviour of cancer cells by inducing pre-metastatic cascades associated with cancer spread. The aim of this study was to examine how S100A8/A9 proteins mediate tumour-stroma crosstalk in PDAC. METHODS: Cytokine profiling of pancreatic cancer cell-derived conditioned media was performed using Bio-Plex Pro 27 Plex Human Cytokine assays. Protein expression and activation of downstream signalling effectors and NF-κB were assessed by western blotting analysis and reporter assays respectively. RESULTS: Stimulation of cultured pancreatic cancer cells with S100A8 and S100A9 increased the secretion of the pro-inflammatory cytokines IL-8, TNF-α, and FGF. S100A8, but not S100A9 induced PDGF secretion. Conversely, pancreatic cancer cell-derived conditioned media and the individual cytokines, TNF-α and TGF-β induced the expression of S100A8 and S100A9 proteins in the HL-60 monocytic cell line and primary human monocytes, while FGF and IL-8 induced the expression of S100A9 only. S100A8 and S100A9 activated MAPK and NF-κB signalling in pancreatic cancer. This was partially mediated via activation of the receptor of advanced glycosylation end-product (RAGE). CONCLUSION: S100A8 and S100A9 proteins induce specific cytokine secretion from PDAC cells, which in turn enhances the expression of S100A8/A9. This paracrine crosstalk could have implications for PDAC invasiveness and metastatic potential.

2 Article Decreased Serum Thrombospondin-1 Levels in Pancreatic Cancer Patients Up to 24 Months Prior to Clinical Diagnosis: Association with Diabetes Mellitus. 2016

Jenkinson, Claire / Elliott, Victoria L / Evans, Anthony / Oldfield, Lucy / Jenkins, Rosalind E / O'Brien, Darragh P / Apostolidou, Sophia / Gentry-Maharaj, Aleksandra / Fourkala, Evangelia-O / Jacobs, Ian J / Menon, Usha / Cox, Trevor / Campbell, Fiona / Pereira, Stephen P / Tuveson, David A / Park, B Kevin / Greenhalf, William / Sutton, Robert / Timms, John F / Neoptolemos, John P / Costello, Eithne. ·Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK. · National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, UK. · MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, University of Liverpool, UK. · Department of Women's Cancer, Institute for Women's Health, University College London, UK. · Faculty of Medical & Human Sciences, 1.018 Core Technology Facility, University of Manchester, UK. · Department of Pathology, University of Liverpool, UK. · Institute for Liver and Digestive Health, University College London. · Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. ·Clin Cancer Res · Pubmed #26573598.

ABSTRACT: PURPOSE: Identification of serum biomarkers enabling earlier diagnosis of pancreatic ductal adenocarcinoma (PDAC) could improve outcome. Serum protein profiles in patients with preclinical disease and at diagnosis were investigated. EXPERIMENTAL DESIGN: Serum from cases up to 4 years prior to PDAC diagnosis and controls (UKCTOCS,n= 174) were studied, alongside samples from patients diagnosed with PDAC, chronic pancreatitis, benign biliary disease, type 2 diabetes mellitus, and healthy subjects (n= 298). Isobaric tags for relative and absolute quantification (iTRAQ) enabled comparisons of pooled serum from a test set (n= 150). Validation was undertaken using multiple reaction monitoring (MRM) and/or Western blotting in all 472 human samples and samples from a KPC mouse model. RESULTS: iTRAQ identified thrombospondin-1 (TSP-1) as reduced preclinically and in diagnosed samples. MRM confirmed significant reduction in levels of TSP-1 up to 24 months prior to diagnosis. A combination of TSP-1 and CA19-9 gave an AUC of 0.86, significantly outperforming both markers alone (0.69 and 0.77, respectively;P< 0.01). TSP-1 was also decreased in PDAC patients compared with healthy controls (P< 0.05) and patients with benign biliary obstruction (P< 0.01). Low levels of TSP-1 correlated with poorer survival, preclinically (P< 0.05) and at clinical diagnosis (P< 0.02). In PDAC patients, reduced TSP-1 levels were more frequently observed in those with confirmed diabetes mellitus (P< 0.01). Significantly lower levels were also observed in PDAC patients with diabetes compared with individuals with type 2 diabetes mellitus (P= 0.01). CONCLUSIONS: Circulating TSP-1 levels decrease up to 24 months prior to diagnosis of PDAC and significantly enhance the diagnostic performance of CA19-9. The influence of diabetes mellitus on biomarker behavior should be considered in future studies.