Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Christopher Ross Carter
Based on 18 articles published since 2010
(Why 18 articles?)
||||

Between 2010 and 2020, C. R. Carter wrote the following 18 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Targeting inflammation in pancreatic cancer: Clinical translation. 2016

Steele, Colin William / Kaur Gill, Nina Angharad / Jamieson, Nigel Balfour / Carter, Christopher Ross. ·Colin William Steele, Nigel Balfour Jamieson, Christopher Ross Carter, Department of Pancreaticobiliary Surgery, Glasgow Royal Infirmary, Glasgow G4 0SF, United Kingdom. ·World J Gastrointest Oncol · Pubmed #27096033.

ABSTRACT: Preclinical modelling studies are beginning to aid development of therapies targeted against key regulators of pancreatic cancer progression. Pancreatic cancer is an aggressive, stromally-rich tumor, from which few people survive. Within the tumor microenvironment cellular and extracellular components exist, shielding tumor cells from immune cell clearance, and chemotherapy, enhancing progression of the disease. The cellular component of this microenvironment consists mainly of stellate cells and inflammatory cells. New findings suggest that manipulation of the cellular component of the tumor microenvironment is possible to promote immune cell killing of tumor cells. Here we explore possible immunogenic therapeutic strategies. Additionally extracellular stromal elements play a key role in protecting tumor cells from chemotherapies targeted at the pancreas. We describe the experimental findings and the pitfalls associated with translation of stromally targeted therapies to clinical trial. Finally, we discuss the key inflammatory signal transducers activated subsequent to driver mutations in oncogenic Kras in pancreatic cancer. We present the preclinical findings that have led to successful early trials of STAT3 inhibitors in pancreatic adenocarcinoma.

2 Review Exploiting inflammation for therapeutic gain in pancreatic cancer. 2013

Steele, C W / Jamieson, N B / Evans, T R J / McKay, C J / Sansom, O J / Morton, J P / Carter, C R. ·The Beatson Institute for Cancer Research, Glasgow G61 1BD, UK. ·Br J Cancer · Pubmed #23385734.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with <5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC.

3 Review Tissue biomarkers for prognosis in pancreatic ductal adenocarcinoma: a systematic review and meta-analysis. 2011

Jamieson, Nigel B / Carter, C Ross / McKay, Colin J / Oien, Karin A. ·West of Scotland Pancreatic Unit and Department of Pathology, Glasgow Royal Infirmary, Alexandra Parade, Glasgow, United Kingdom. ·Clin Cancer Res · Pubmed #21444679.

ABSTRACT: PURPOSE: The management of pancreatic ductal adenocarcinoma (PDAC) continues to present a great challenge particularly with regard to prediction of outcome following pancreaticoduodenectomy. Molecular markers have been extensively investigated by numerous groups with the aim of enhancing prognostication; however, despite hundreds of studies that have sought to assess the potential prognostic value of molecular markers in predicting the clinical course following resection of PDAC, at this time, no molecular marker assay forms part of recommended clinical practice. EXPERIMENTAL DESIGN: We conducted a systematic review and meta-analysis of the published literature for immunohistochemistry-based biomarkers of PDAC outcome. A dual search strategy was applied to the PubMed database on January 6, 2010, to identify cohort studies that reported associations between immunohistochemical biomarker expression and survival outcomes in PDAC, and conformed to the REMARK (REporting recommendations for tumor MARKer prognostic studies) criteria. RESULTS: A total of 103 distinct proteins met all inclusion criteria. Promising markers that emerged for the prediction of overall survival included BAX (HR = 0.31, 95% CI: 0.71-0.56), Bcl-2 (HR = 0.41, 95% CI: 0.27-0.63), survivin (HR = 0.46, 95% CI: 0.29-0.73), Ki-67: (HR = 2.42, 95% CI: 1.87-3.14), COX-2 (HR = 1.39, 95% CI: 1.13-1.71), E-cadherin (HR = 1.80, 95% CI: 1.33-2.42), and S100 calcium-binding proteins, in particular S100A2 (HR = 3.23, 95% CI: 1.58-6.62). CONCLUSIONS: We noted that that there was incomplete adherence to the REMARK guidelines with inadequate methodology reporting as well as failure to perform multivariate analysis. Addressing the persistent incomplete adoption of these criteria may eventually result in the incorporation of molecular marker assessment within PDAC management algorithms.

4 Article Recommended Workflow Methodology in the Creation of an Interactive Application for Patient's Diagnosed with Pancreatic Cancer. 2019

Knight, Olivia / Carter, C Ross / Loranger, Brian / Rea, Paul M. ·Anatomy Facility, Thomson Building, School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. · School of Simulation and Visualisation, Glasgow School of Art, The Hub, Pacific Quay, Glasgow, UK. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK. · Anatomy Facility, Thomson Building, School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. Paul.Rea@glasgow.ac.uk. ·Adv Exp Med Biol · Pubmed #31823242.

ABSTRACT: Pancreatic cancer is a leading cause of cancer related deaths in the UK. However, public knowledge and understanding of the pancreas is generally poor, therefore pancreatic cancer patients often have to contend with understanding large quantities of new information at a pivotal time in their lives.Despite utilisation of digital visualisation techniques in medical education, very rarely are they being used to help clinicians communicate information to their patients. Specifically, there is no literature describing use of an interactive digital application for use by healthcare professionals to aid discussions specific to pancreatic cancer.Therefore, we developed a workflow methodology, and created an interactive application, thus creating a tool that could help clinicians explain pancreatic cancer anatomy, and staging, to their patients. Three-dimensional (3D) digital models were created using ZBrush and Autodesk 3DS Max, and exported into the Unity game engine. Within Unity, the interactivity of models was maximally utilised, and a simple user interface created.The application centres on anatomically accurate, visually simple, 3D digital models, demonstrating a variety of common scenarios that arise in pancreatic cancer. The design of the application is such that the clinician can select which model is relevant to the patient, and can give an explanation of the anatomy and disease process at a speed and level appropriate to that person. This simple, robust and effective workflow methodology for the development of an application could be useful in any clinical setting that needs visual and interactive tools to enhance patient understanding of a clinical condition.

5 Article Feasibility and clinical utility of endoscopic ultrasound guided biopsy of pancreatic cancer for next-generation molecular profiling. 2019

Dreyer, Stephan B / Jamieson, Nigel B / Evers, Lisa / Duthie, Fraser / Cooke, Susie / Marshall, John / Beraldi, Dario / Knight, Stephen / Upstill-Goddard, Rosanna / Dickson, Euan J / Carter, C Ross / McKay, Colin J / Biankin, Andrew V / Chang, David K. ·Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. · Department of Clinical Surgery, University of Edinburgh, Edinburgh, UK. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK. david.chang@glasgow.ac.uk. ·Chin Clin Oncol · Pubmed #31070037.

ABSTRACT: Next-generation sequencing is enabling molecularly guided therapy for many cancer types, yet failure rates remain relatively high in pancreatic cancer (PC). The aim of this study is to investigate the feasibility of genomic profiling using endoscopic ultrasound (EUS) biopsy samples to facilitate personalised therapy for PC. Ninty-five patients underwent additional research biopsies at the time of diagnostic EUS. Diagnostic formalin-fixed (FFPE) and fresh frozen EUS samples underwent DNA extraction, quantification and targeted gene sequencing. Whole genome (WGS) and RNA sequencing was performed as proof of concept. Only 2 patients (2%) with a diagnosis of PC had insufficient material for targeted sequencing in both FFPE and frozen specimens. Targeted panel sequencing (n=54) revealed mutations in PC genes (KRAS, GNAS, TP53, CDKN2A, SMAD4) in patients with histological evidence of PC, including potentially actionable mutations (BRCA1, BRCA2, ATM, BRAF). WGS (n=5) of EUS samples revealed mutational signatures that are potential biomarkers of therapeutic responsiveness. RNA sequencing (n=35) segregated patients into clinically relevant molecular subtypes based on transcriptome. Integrated multi-omic analysis of PC using standard EUS guided biopsies offers clinical utility to guide personalized therapy and study the molecular pathology in all patients with PC.

6 Article Hypermutation In Pancreatic Cancer. 2017

Humphris, Jeremy L / Patch, Ann-Marie / Nones, Katia / Bailey, Peter J / Johns, Amber L / McKay, Skye / Chang, David K / Miller, David K / Pajic, Marina / Kassahn, Karin S / Quinn, Michael C J / Bruxner, Timothy J C / Christ, Angelika N / Harliwong, Ivon / Idrisoglu, Senel / Manning, Suzanne / Nourse, Craig / Nourbakhsh, Ehsan / Stone, Andrew / Wilson, Peter J / Anderson, Matthew / Fink, J Lynn / Holmes, Oliver / Kazakoff, Stephen / Leonard, Conrad / Newell, Felicity / Waddell, Nick / Wood, Scott / Mead, Ronald S / Xu, Qinying / Wu, Jianmin / Pinese, Mark / Cowley, Mark J / Jones, Marc D / Nagrial, Adnan M / Chin, Venessa T / Chantrill, Lorraine A / Mawson, Amanda / Chou, Angela / Scarlett, Christopher J / Pinho, Andreia V / Rooman, Ilse / Giry-Laterriere, Marc / Samra, Jaswinder S / Kench, James G / Merrett, Neil D / Toon, Christopher W / Epari, Krishna / Nguyen, Nam Q / Barbour, Andrew / Zeps, Nikolajs / Jamieson, Nigel B / McKay, Colin J / Carter, C Ross / Dickson, Euan J / Graham, Janet S / Duthie, Fraser / Oien, Karin / Hair, Jane / Morton, Jennifer P / Sansom, Owen J / Grützmann, Robert / Hruban, Ralph H / Maitra, Anirban / Iacobuzio-Donahue, Christine A / Schulick, Richard D / Wolfgang, Christopher L / Morgan, Richard A / Lawlor, Rita T / Rusev, Borislav / Corbo, Vincenzo / Salvia, Roberto / Cataldo, Ivana / Tortora, Giampaolo / Tempero, Margaret A / Anonymous5070887 / Hofmann, Oliver / Eshleman, James R / Pilarsky, Christian / Scarpa, Aldo / Musgrove, Elizabeth A / Gill, Anthony J / Pearson, John V / Grimmond, Sean M / Waddell, Nicola / Biankin, Andrew V. ·The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia. · QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; Department of Surgery, Bankstown Hospital, Bankstown, Sydney, New South Wales, Australia; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales Australia, Liverpool, New South Wales, Australia; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Australia, Darlinghurst, New South Wales, Australia. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia; Genetic and Molecular Pathology, Adelaide, South Australia, Australia; School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Australia, Darlinghurst, New South Wales, Australia. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; South Eastern Area Laboratory Services Pathology, Prince of Wales Hospital, Randwick, New South Wales, Australia; Sonic Genetics, Douglass Hanly Moir Pathology, New South Wales, Australia. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Macarthur Cancer Therapy Centre, Campbelltown Hospital, New South Wales, Australia. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Department of Anatomical Pathology, SydPath, St Vincent's Hospital, New South Wales, Australia. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; School of Environmental and Life Sciences, University of Newcastle, Ourimbah, New South Wales, Australia. · Department of Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia; University of Sydney, Sydney, New South Wales, Australia. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; University of Sydney, Sydney, New South Wales, Australia; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. · Department of Surgery, Bankstown Hospital, Bankstown, Sydney, New South Wales, Australia; School of Medicine, Western Sydney University, Penrith, New South Wales, Australia. · Department of Surgery, Fiona Stanley Hospital, Murdoch, Washington. · Department of Gastroenterology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, Australia. · Department of Surgery, Princess Alexandra Hospital, Woollongabba, Queensland, Australia. · School of Surgery, University of Western Australia, Australia and St John of God Pathology, Subiaco, Washington. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom; Academic Unit of Surgery, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow, United Kingdom. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; Department of Medical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom. · Department of Pathology, Southern General Hospital, Greater Glasgow & Clyde National Health Service, Glasgow, United Kingdom. · Greater Glasgow and Clyde Bio-repository, Pathology Department, Queen Elizabeth University Hospital, Glasgow, United Kingdom. · Cancer Research UK Beatson Institute, Glasgow, United Kingdom; Institute for Cancer Science, University of Glasgow, Glasgow, United Kingdom. · Universitätsklinikum Erlangen, Erlangen, Germany. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, Maryland. · ARC-NET Center for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy; Department of Pathology and Diagnostics, University of Verona, Verona, Italy. · Department of Medicine, University and Hospital Trust of Verona, Verona, Italy. · Division of Hematology and Oncology, University of California, San Francisco, California. · Australian Pancreatic Cancer Genome Initiative. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom. · Universitätsklinikum Erlangen, Department of Surgery, University of Erlangen-Nueremberg, Germany. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Australia, Darlinghurst, New South Wales, Australia. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; University of Sydney, Sydney, New South Wales, Australia; Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia; University of Melbourne Centre for Cancer Research, The University of Melbourne, Melbourne, Victoria, Australia. · QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. Electronic address: nic.waddell@qimrberghofer.edu.au. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; Department of Surgery, Bankstown Hospital, Bankstown, Sydney, New South Wales, Australia; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales Australia, Liverpool, New South Wales, Australia; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom. Electronic address: andrew.biankin@glasgow.ac.uk. ·Gastroenterology · Pubmed #27856273.

ABSTRACT: Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.

7 Article CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma. 2016

Steele, Colin W / Karim, Saadia A / Leach, Joshua D G / Bailey, Peter / Upstill-Goddard, Rosanna / Rishi, Loveena / Foth, Mona / Bryson, Sheila / McDaid, Karen / Wilson, Zena / Eberlein, Catherine / Candido, Juliana B / Clarke, Mairi / Nixon, Colin / Connelly, John / Jamieson, Nigel / Carter, C Ross / Balkwill, Frances / Chang, David K / Evans, T R Jeffry / Strathdee, Douglas / Biankin, Andrew V / Nibbs, Robert J B / Barry, Simon T / Sansom, Owen J / Morton, Jennifer P. ·Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK. · Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UK. · Oncology iMED, AstraZeneca, Alderley Park, Macclesfield SK10 4TG, UK. · Centre for Cancer and Inflammation, Barts Cancer Institute, London EC1M 6BQ, UK. · Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8QQ UK. · Department of Surgery, Glasgow Royal Infirmary, Glasgow G4 0SF, UK. · Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UK. · Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UK. Electronic address: o.sansom@beatson.gla.ac.uk. ·Cancer Cell · Pubmed #27265504.

ABSTRACT: CXCR2 has been suggested to have both tumor-promoting and tumor-suppressive properties. Here we show that CXCR2 signaling is upregulated in human pancreatic cancer, predominantly in neutrophil/myeloid-derived suppressor cells, but rarely in tumor cells. Genetic ablation or inhibition of CXCR2 abrogated metastasis, but only inhibition slowed tumorigenesis. Depletion of neutrophils/myeloid-derived suppressor cells also suppressed metastasis suggesting a key role for CXCR2 in establishing and maintaining the metastatic niche. Importantly, loss or inhibition of CXCR2 improved T cell entry, and combined inhibition of CXCR2 and PD1 in mice with established disease significantly extended survival. We show that CXCR2 signaling in the myeloid compartment can promote pancreatic tumorigenesis and is required for pancreatic cancer metastasis, making it an excellent therapeutic target.

8 Article SIRT3 & SIRT7: Potential Novel Biomarkers for Determining Outcome in Pancreatic Cancer Patients. 2015

McGlynn, Liane M / McCluney, Simon / Jamieson, Nigel B / Thomson, Jackie / MacDonald, Alasdair I / Oien, Karin / Dickson, Euan J / Carter, C Ross / McKay, Colin J / Shiels, Paul G. ·Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom; Academic Department of Surgery, University of Glasgow, Glasgow, United Kingdom. · Institute of Cancer Sciences, Pathology, Wolfson Building, Beatson Labs, Glasgow, United Kingdom. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom. ·PLoS One · Pubmed #26121130.

ABSTRACT: PURPOSE: The sirtuin gene family has been linked with tumourigenesis, in both a tumour promoter and suppressor capacity. Information regarding the function of sirtuins in pancreatic cancer is sparse and equivocal. We undertook a novel study investigating SIRT1-7 protein expression in a cohort of pancreatic tumours. The aim of this study was to establish a protein expression profile for SIRT1-7 in pancreatic ductal adenocarcinomas (PDAC) and to determine if there were associations between SIRT1-7 expression, clinico-pathological parameters and patient outcome. MATERIAL AND METHODS: Immunohistochemical analysis of SIRT1-7 protein levels was undertaken in a tissue micro-array comprising 77 resected PDACs. Statistical analyses determined if SIRT1-7 protein expression was associated with clinical parameters or outcome. RESULTS: Two sirtuin family members demonstrated significant associations with clinico-pathological parameters and patient outcome. Low level SIRT3 expression in the tumour cytoplasm correlated with more aggressive tumours, and a shorter time to relapse and death, in the absence of chemotherapeutic intervention. Low levels of nuclear SIRT7 expression were also associated with an aggressive tumour phenotype and poorer outcome, as measured by disease-free and disease-specific survival time, 12 months post-diagnosis. CONCLUSIONS: Our data suggests that SIRT3 and SIRT7 possess tumour suppressor properties in the context of pancreatic cancer. SIRT3 may also represent a novel predictive biomarker to determine which patients may or may not respond to chemotherapy. This study opens up an interesting avenue of investigation to potentially identify predictive biomarkers and novel therapeutic targets for pancreatic cancer, a disease that has seen no significant improvement in survival over the past 40 years.

9 Article Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy. 2015

Miller, Bryan W / Morton, Jennifer P / Pinese, Mark / Saturno, Grazia / Jamieson, Nigel B / McGhee, Ewan / Timpson, Paul / Leach, Joshua / McGarry, Lynn / Shanks, Emma / Bailey, Peter / Chang, David / Oien, Karin / Karim, Saadia / Au, Amy / Steele, Colin / Carter, Christopher Ross / McKay, Colin / Anderson, Kurt / Evans, Thomas R Jeffry / Marais, Richard / Springer, Caroline / Biankin, Andrew / Erler, Janine T / Sansom, Owen J. ·Cancer Research UK Beatson Institute Garscube Estate, Glasgow, UK. · The Garvan Institute of Medical Research, Sydney, NSW, Australia. · Cancer Research UK Manchester Institute, Withington Manchester, UK. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK. · Institute of Cancer Sciences University of Glasgow Garscube Estate, Glasgow, UK. · Cancer Research UK Beatson Institute Garscube Estate, Glasgow, UK Institute of Cancer Sciences University of Glasgow Garscube Estate, Glasgow, UK. · Institute of Cancer Research, London, UK. · Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Copenhagen (UCPH), Denmark janine.erler@bric.ku.dk o.sansom@beatson.gla.ac.uk. · Cancer Research UK Beatson Institute Garscube Estate, Glasgow, UK janine.erler@bric.ku.dk o.sansom@beatson.gla.ac.uk. ·EMBO Mol Med · Pubmed #26077591.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related mortality. Despite significant advances made in the treatment of other cancers, current chemotherapies offer little survival benefit in this disease. Pancreaticoduodenectomy offers patients the possibility of a cure, but most will die of recurrent or metastatic disease. Hence, preventing metastatic disease in these patients would be of significant benefit. Using principal component analysis (PCA), we identified a LOX/hypoxia signature associated with poor patient survival in resectable patients. We found that LOX expression is upregulated in metastatic tumors from Pdx1-Cre Kras(G12D/+) Trp53(R172H/+) (KPC) mice and that inhibition of LOX in these mice suppressed metastasis. Mechanistically, LOX inhibition suppressed both migration and invasion of KPC cells. LOX inhibition also synergized with gemcitabine to kill tumors and significantly prolonged tumor-free survival in KPC mice with early-stage tumors. This was associated with stromal alterations, including increased vasculature and decreased fibrillar collagen, and increased infiltration of macrophages and neutrophils into tumors. Therefore, LOX inhibition is able to reverse many of the features that make PDAC inherently refractory to conventional therapies and targeting LOX could improve outcome in surgically resectable disease.

10 Article Expression of KOC, S100P, mesothelin and MUC1 in pancreatico-biliary adenocarcinomas: development and utility of a potential diagnostic immunohistochemistry panel. 2014

Ali, Asif / Brown, Victoria / Denley, Simon / Jamieson, Nigel B / Morton, Jennifer P / Nixon, Colin / Graham, Janet S / Sansom, Owen J / Carter, C Ross / McKay, Colin J / Duthie, Fraser R / Oien, Karin A. ·Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden G61 1QH, UK. · Pathology Laboratory, Forth Valley Royal Hospital, Stirling Road, Larbert FK5 4WR, UK. · West of Scotland Pancreatic Unit and Glasgow Royal Infirmary, Alexandra Parade, Glasgow G31 2ER, UK. · Beatson Institute for Cancer Research, Glasgow G61 1BD, UK. · Medical Oncology, Beatson West of Scotland Cancer Centre, Glasgow G12 0YN, UK. · Department of Pathology, Southern General Hospital, Greater Glasgow & Clyde NHS, Glasgow G51 4TF, UK. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden G61 1QH, UK ; Department of Pathology, Southern General Hospital, Greater Glasgow & Clyde NHS, Glasgow G51 4TF, UK. ·BMC Clin Pathol · Pubmed #25071419.

ABSTRACT: BACKGROUND: Pancreatico-biliary adenocarcinomas (PBA) have a poor prognosis. Diagnosis is usually achieved by imaging and/or endoscopy with confirmatory cytology. Cytological interpretation can be difficult especially in the setting of chronic pancreatitis/cholangitis. Immunohistochemistry (IHC) biomarkers could act as an adjunct to cytology to improve the diagnosis. Thus, we performed a meta-analysis and selected KOC, S100P, mesothelin and MUC1 for further validation in PBA resection specimens. METHODS: Tissue microarrays containing tumour and normal cores in a ratio of 3:2, from 99 surgically resected PBA patients, were used for IHC. IHC was performed on an automated platform using antibodies against KOC, S100P, mesothelin and MUC1. Tissue cores were scored for staining intensity and proportion of tissue stained using a Histoscore method (range, 0-300). Sensitivity and specificity for individual biomarkers, as well as biomarker panels, were determined with different cut-offs for positivity and compared by summary receiver operating characteristic (ROC) curve. RESULTS: The expression of all four biomarkers was high in PBA versus normal ducts, with a mean Histoscore of 150 vs. 0.4 for KOC, 165 vs. 0.3 for S100P, 115 vs. 0.5 for mesothelin and 200 vs. 14 for MUC1 (p < .0001 for all comparisons). Five cut-offs were carefully chosen for sensitivity/specificity analysis. Four of these cut-offs, namely 5%, 10% or 20% positive cells and Histoscore 20 were identified using ROC curve analysis and the fifth cut-off was moderate-strong staining intensity. Using 20% positive cells as a cut-off achieved higher sensitivity/specificity values: KOC 84%/100%; S100P 83%/100%; mesothelin 88%/92%; and MUC1 89%/63%. Analysis of a panel of KOC, S100P and mesothelin achieved 100% sensitivity and 99% specificity if at least 2 biomarkers were positive for 10% cut-off; and 100% sensitivity and specificity for 20% cut-off. CONCLUSION: A biomarker panel of KOC, S100P and mesothelin with at least 2 biomarkers positive was found to be an optimum panel with both 10% and 20% cut-offs in resection specimens from patients with PBA.

11 Article Targeting mTOR dependency in pancreatic cancer. 2014

Morran, Douglas C / Wu, Jianmin / Jamieson, Nigel B / Mrowinska, Agata / Kalna, Gabriela / Karim, Saadia A / Au, Amy Y M / Scarlett, Christopher J / Chang, David K / Pajak, Malgorzata Z / Anonymous6310790 / Oien, Karin A / McKay, Colin J / Carter, C Ross / Gillen, Gerry / Champion, Sue / Pimlott, Sally L / Anderson, Kurt I / Evans, T R Jeffry / Grimmond, Sean M / Biankin, Andrew V / Sansom, Owen J / Morton, Jennifer P. ·CRUK Beatson Institute, Glasgow, UK. · The Kinghorn Cancer Centre and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK. · School of Environmental & Life Sciences, University of Newcastle, Ourimbah, New South Wales, Australia. · The Kinghorn Cancer Centre and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK Department of Surgery, Bankstown Hospital, Bankstown, Sydney, New South Wales, Australia Faculty of Medicine, South Western Sydney Clinical School, University of NSW, Liverpool, New South Wales, Australia The Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. · CRUK Beatson Institute, Glasgow, UK Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. · West of Scotland PET Centre, Gartnavel General Hospital, Glasgow, UK. · West of Scotland Radionuclide Dispensary, NHS Greater Glasgow and Clyde, Glasgow, UK. · The Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, St Lucia, Brisbane, Queensland, Australia. ·Gut · Pubmed #24717934.

ABSTRACT: OBJECTIVE: Pancreatic cancer is a leading cause of cancer-related death in the Western world. Current chemotherapy regimens have modest survival benefit. Thus, novel, effective therapies are required for treatment of this disease. DESIGN: Activating KRAS mutation almost always drives pancreatic tumour initiation, however, deregulation of other potentially druggable pathways promotes tumour progression. PTEN loss leads to acceleration of Kras(G12D)-driven pancreatic ductal adenocarcinoma (PDAC) in mice and these tumours have high levels of mammalian target of rapamycin (mTOR) signalling. To test whether these KRAS PTEN pancreatic tumours show mTOR dependence, we compared response to mTOR inhibition in this model, to the response in another established model of pancreatic cancer, KRAS P53. We also assessed whether there was a subset of pancreatic cancer patients who may respond to mTOR inhibition. RESULTS: We found that tumours in KRAS PTEN mice exhibit a remarkable dependence on mTOR signalling. In these tumours, mTOR inhibition leads to proliferative arrest and even tumour regression. Further, we could measure response using clinically applicable positron emission tomography imaging. Importantly, pancreatic tumours driven by activated KRAS and mutant p53 did not respond to treatment. In human tumours, approximately 20% of cases demonstrated low PTEN expression and a gene expression signature that overlaps with murine KRAS PTEN tumours. CONCLUSIONS: KRAS PTEN tumours are uniquely responsive to mTOR inhibition. Targeted anti-mTOR therapies may offer clinical benefit in subsets of human PDAC selected based on genotype, that are dependent on mTOR signalling. Thus, the genetic signatures of human tumours could be used to direct pancreatic cancer treatment in the future.

12 Article Fascin is regulated by slug, promotes progression of pancreatic cancer in mice, and is associated with patient outcomes. 2014

Li, Ang / Morton, Jennifer P / Ma, YaFeng / Karim, Saadia A / Zhou, Yan / Faller, William J / Woodham, Emma F / Morris, Hayley T / Stevenson, Richard P / Juin, Amelie / Jamieson, Nigel B / MacKay, Colin J / Carter, C Ross / Leung, Hing Y / Yamashiro, Shigeko / Blyth, Karen / Sansom, Owen J / Machesky, Laura M. ·CRUK Beatson Institute for Cancer Research, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. · Department of Surgery, West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK. · Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey. · CRUK Beatson Institute for Cancer Research, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. Electronic address: l.machesky@beatson.gla.ac.uk. ·Gastroenterology · Pubmed #24462734.

ABSTRACT: BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is often lethal because it is highly invasive and metastasizes rapidly. The actin-bundling protein fascin has been identified as a biomarker of invasive and advanced PDAC and regulates cell migration and invasion in vitro. We investigated fascin expression and its role in PDAC progression in mice. METHODS: We used KRas(G12D) p53(R172H) Pdx1-Cre (KPC) mice to investigate the effects of fascin deficiency on development of pancreatic intraepithelial neoplasia (PanIn), PDAC, and metastasis. We measured levels of fascin in PDAC cell lines and 122 human resected PDAC samples, along with normal ductal and acinar tissues; we associated levels with patient outcomes. RESULTS: Pancreatic ducts and acini from control mice and early-stage PanINs from KPC mice were negative for fascin, but approximately 6% of PanIN3 and 100% of PDAC expressed fascin. Fascin-deficient KRas(G12D) p53(R172H) Pdx1-Cre mice had longer survival times, delayed onset of PDAC, and a lower PDAC tumor burdens than KPC mice; loss of fascin did not affect invasion of PDAC into bowel or peritoneum in mice. Levels of slug and fascin correlated in PDAC cells; slug was found to regulate transcription of Fascin along with the epithelial-mesenchymal transition. In PDAC cell lines and cells from mice, fascin concentrated in filopodia and was required for their assembly and turnover. Fascin promoted intercalation of filopodia into mesothelial cell layers and cell invasion. Nearly all human PDAC samples expressed fascin, and higher fascin histoscores correlated with poor outcomes, vascular invasion, and time to recurrence. CONCLUSIONS: The actin-bundling protein fascin is regulated by slug and involved in late-stage PanIN and PDAC formation in mice. Fascin appears to promote formation of filopodia and invasive activities of PDAC cells. Its levels in human PDAC correlate with outcomes and time to recurrence, indicating it might be a marker or therapeutic target for pancreatic cancer.

13 Article Pre-operative cardiopulmonary exercise testing predicts adverse post-operative events and non-progression to adjuvant therapy after major pancreatic surgery. 2013

Chandrabalan, Vishnu V / McMillan, Donald C / Carter, Roger / Kinsella, John / McKay, Colin J / Carter, C Ross / Dickson, Euan J. ·Academic Department of Surgery, University of Glasgow, Glasgow, UK. · Department of Respiratory Medicine, Glasgow Royal Infirmary, Glasgow, UK. · Section of Anaesthesia, Glasgow Royal Infirmary, Glasgow, UK. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK. ·HPB (Oxford) · Pubmed #23458160.

ABSTRACT: BACKGROUND: Surgery followed by chemotherapy is the primary modality of cure for patients with resectable pancreatic cancer but is associated with significant morbidity. The aim of the present study was to evaluate the role of cardiopulmonary exercise testing (CPET) in predicting post-operative adverse events and fitness for chemotherapy after major pancreatic surgery. METHODS: Patients who underwent a pancreaticoduodenectomy or total pancreatectomy for pancreatic head lesions and had undergone pre-operative CPET were included in this retrospective study. Data on patient demographics, comorbidity and results of pre-operative evaluation were collected. Post-operative adverse events, hospital stay and receipt of adjuvant therapy were outcome measures. RESULTS: One hundred patients were included. Patients with an anaerobic threshold less than 10 ml/kg/min had a significantly greater incidence of a post-operative pancreatic fistula [International Study Group for Pancreatic Surgery (ISGPS) Grades A-C, 35.4% versus 16%, P = 0.028] and major intra-abdominal abscesses [Clavien-Dindo (CD) Grades III-V, 22.4% versus 7.8%, P = 0.042] and were less likely to receive adjuvant therapy [hazard ratio (HR) 6.30, 95% confidence interval (CI) 1.25-31.75, P = 0.026]. A low anaerobic threshold was also associated with a prolonged hospital stay (median 20 versus 14 days, P = 0.005) but not with other adverse events. DISCUSSION: CPET predicts a post-operative pancreatic fistula, major intra-abdominal abscesses as well as length of hospital stay after major pancreatic surgery. Patients with a low anaerobic threshold are less likely to receive adjuvant therapy.

14 Article Activation of the IL-6R/Jak/stat pathway is associated with a poor outcome in resected pancreatic ductal adenocarcinoma. 2013

Denley, Simon M / Jamieson, Nigel B / McCall, Pamela / Oien, Karin A / Morton, Jennifer P / Carter, C Ross / Edwards, Joanne / McKay, Colin J. ·West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, G31 2ER, UK. ·J Gastrointest Surg · Pubmed #23435739.

ABSTRACT: BACKGROUND AND OBJECTIVE: Chronic localized pancreatic inflammation in the form of chronic pancreatitis is an established risk factor for human pancreatic ductal adenocarcinoma (PDAC) development. Constitutive activation of inflammation-related signal transducer and activator of transcription (Stat)3 signaling has been implicated in the development and progression a number of malignancies, including PDAC. Although, the Janus Kinase (Jak)/Stat pathway is a potential drug target, clinicopathological, molecular, and prognostic features of Stat3-activated PDAC remain uncertain. Our aim was to determine the clinicopathological impact of this inflammatory pathway in resectable PDAC. METHODS: Using a tissue microarray-based cohort of PDAC from 86 patients undergoing pancreaticoduodenectomy with curative intent and complete clinicopathological data available, we evaluated expression of the interleukin-6 receptor (IL-6R)/Jak/Stat pathway by immunohistochemistry. IL-6R, Jak, phospho (p)-Jak, Stat3, pStat3(Tyr705), and pStat3(Ser727) were assessed in PDAC and pancreatic intraepithelial neoplasia. A Cox regression multivariate analysis model was used to determine factors influencing survival. Activation of the IL-6R/Jak/Stat3 pathway was compared with the systemic inflammatory response as measured by serum C-reactive protein levels. RESULTS: High pJak was associated with reduced overall survival in multivariate analysis when compared with those with moderate or low expression (p = 0.036; hazard ratio (HR) = 1.68) as was pStat3(Tyr705) (p < 0.001; HR = 2.66) independent of lymph node status and tumor grade. Patients with a combination of pJakhigh/pStat3(Tyr705) high expression had an especially poor prognosis (median survival of 8.8 months; 95 % CI, 4.4-13.2). While the IL-6R/Jak/Stat pathway did not correlate with serum C-reactive protein levels, high pStat3 expression was associated with a reduction in the density of the local tumoral immune response. CONCLUSION: Activation of the Jak/Stat3 pathway via phosphorylation was associated with adverse outcome following resection of PDAC with curative intent supporting potential roles for pJak and pStat3 as prognostic biomarkers markers and therapeutic targets.

15 Article The prognostic influence of resection margin clearance following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. 2013

Jamieson, Nigel B / Chan, Nigel I J / Foulis, Alan K / Dickson, Euan J / McKay, Colin J / Carter, C Ross. ·West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Alexandra Parade, Glasgow, G31 2ER, UK. nigel.jamieson@glasgow.ac.uk ·J Gastrointest Surg · Pubmed #23297028.

ABSTRACT: INTRODUCTION: The poor overall survival associated with pancreatic ductal adenocarcinoma (PDAC) despite complete resection suggests that occult metastatic disease is present in most at the time of surgery. Resection margin involvement (R1) following resection is an established poor prognostic factor. However, the definition of an R1 resection varies and the impact of margin clearance on outcome has not been examined in detail. METHODS: In a cohort of 217 consecutive patients who underwent pancreaticoduodenectomy for PDAC with curative intent at a single institution between 1996 and 2011, the prognostic significance of the proximity of margin clearance was investigated. Microscopic margin clearance was stratified by 0.5 mm increments from tumor present at the margin to >2.0 mm. Groups were dichotomized into clear and involved groups according to the different R1 definitions. Multivariate survival analysis was used to establish independent prognostic factors. RESULTS: For the 38 patients (17.5 %) where the tumor was >1.5 mm from the closest involved margin, there was a significantly prolonged overall median survival (63.1 months; 95 % confidence interval, 32.5-93.8) compared to R1 resections (16.9 months; 95 % confidence interval, 14.5-19.4; P < 0.0001, log-rank test). This cutoff represented the optimum distance for predicting long-term survival. As margin clearance increased, R1 status became a more powerful independent predictor of outcome; however, margin clearance did not relate to site of tumor recurrence. CONCLUSION: These data demonstrate that margin clearance by at least 1.5 mm identifies a subgroup of patients which may potentially achieve long-term survival. This study further confirms the need to achieve standardization across pancreatic specimen reporting. Stratification of patients into future clinical trials based upon the degree of margin clearance may identify those patients likely to benefit from adjuvant therapy.

16 Article The relationship between tumor inflammatory cell infiltrate and outcome in patients with pancreatic ductal adenocarcinoma. 2012

Jamieson, Nigel B / Mohamed, Mohamed / Oien, Karin A / Foulis, Alan K / Dickson, Euan J / Imrie, Clem W / Carter, C Ross / McKay, Colin J / McMillan, Donald C. ·West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom. nigeljamieson@yahoo.com ·Ann Surg Oncol · Pubmed #22555345.

ABSTRACT: BACKGROUND: The tumor-associated inflammatory cell infiltrate is recognized to have prognostic value in various common solid tumors. However, the prognostic value of the tumor inflammatory cell infiltrate has not been established in pancreatic ductal adenocarcinoma (PDAC) nor has its relationship with the systemic inflammatory response. METHODS: Retrospective study was made of 173 patients who underwent surgery between 1997 and 2009. Routine pathology specimens were scored according to density of the tumor inflammatory cell infiltrate, and biochemical data were collected preoperatively. RESULTS: Low-grade tumor inflammatory cell infiltrate was associated with earlier tumor recurrence (P < 0.001) and particularly in the liver (P = 0.027). It was also associated with T3 tumors (P < 0.05), lymph node involvement (P < 0.05), and resection margin involvement (P < 0.05). On univariate survival analysis, age <65 years (P < 0.05), mGPS (P < 0.001), increased tumor stage (P < 0.01), nodal involvement (P < 0.01), size (P < 0.05), grade (P < 0.05), perineural invasion (P < 0.05), venous invasion (P < 0.01), resection margin involvement (P ≤ 0.001), vascular reconstruction (P < 0.05), and no adjuvant chemotherapy (P < 0.05) were associated with poor survival. In contrast, high-grade tumor inflammatory cell infiltrate was associated with better survival (P < 0.001). On multivariate survival analysis, mGPS [hazard ratio (HR): 1.77, 95% confidence interval (95% CI): 1.19-2.62, P = 0.005], tumor stage (HR: 2.21, 95% CI: 1.16-4.23, P = 0.016), resection margin involvement (HR: 2.19, 95% CI: 1.41-3.44, P = 0.001), venous invasion (HR: 1.79, 95% CI: 1.22-2.63, P = 0.003), tumor inflammatory cell infiltrate (HR: 0.37, 95% CI: 0.25-0.55, P = 0.0001), and adjuvant chemotherapy (P = 0.04) were independently prognostic. CONCLUSIONS: The results of the study show, for the first time, that the presence of a high-grade tumor inflammatory cell infiltrate is an independent predictor of prolonged overall survival following resection for PDAC. Furthermore, measures of the local and the systemic inflammatory response were inversely associated.

17 Article MicroRNA molecular profiles associated with diagnosis, clinicopathologic criteria, and overall survival in patients with resectable pancreatic ductal adenocarcinoma. 2012

Jamieson, Nigel B / Morran, Douglas C / Morton, Jennifer P / Ali, Asif / Dickson, Euan J / Carter, C Ross / Sansom, Owen J / Evans, T R Jeffry / McKay, Colin J / Oien, Karin A. ·West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Alexandra Parade, Glasgow, G31 2ER, United Kingdom. nigeljamieson@yahoo.com ·Clin Cancer Res · Pubmed #22114136.

ABSTRACT: PURPOSE: MicroRNAs (miRNA) have potential as diagnostic and prognostic biomarkers and as therapeutic targets in cancer. We sought to establish the relationship between miRNA expression and clinicopathologic parameters, including prognosis, in pancreatic ductal adenocarcinoma (PDAC). EXPERIMENTAL DESIGN: Global miRNA microarray expression profiling of prospectively collected fresh-frozen PDAC tissue was done on an initial test cohort of 48 patients, who had undergone pancreaticoduodenectomy between 2003 and 2008 at a single institution. We evaluated association with tumor stage, lymph node status, and site of recurrence, in addition to overall survival, using Cox regression multivariate analysis. Validation of selected potentially prognostic miRNAs was done in a separate cohort of 24 patients. RESULTS: miRNA profiling identified expression signatures associated with PDAC, lymph node involvement, high tumor grade, and 20 miRNAs were associated with overall survival. In the initial cohort of 48 PDAC patients, high expression of miR-21 (HR = 3.22, 95% CI: 1.21-8.58) and reduced expression of miR-34a (HR = 0.15, 95% CI: 0.06-0.37) and miR-30d (HR = 0.30, 95% CI: 0.12-0.79) were associated with poor overall survival following resection independent of clinical covariates. In a further validation set of 24 patients, miR-21 and miR-34a expression again significantly correlated with overall survival (P = 0.031 and P = 0.001). CONCLUSION: Expression patterns of miRNAs are significantly altered in PDAC. Aberrant expression of a number of miRNAs was independently associated with reduced survival, including overexpression of miR-21 and underexpression of miR-34a. SUMMARY: miRNA expression profiles for resected PDAC were examined to identify potentially prognostic miRNAs. miRNA microarray analysis identified statistically unique profiles, which could discriminate PDAC from paired nonmalignant pancreatic tissues as well as molecular signatures that differ according to pathologic features. miRNA expression profiles correlated with overall survival of PDAC following resection, indicating that miRNAs provide prognostic utility.

18 Minor RE: nab-Paclitaxel Plus Gemcitabine for Metastatic Pancreatic Cancer: Long-Term Survival From a Phase III Trial. 2015

Palani Velu, Lavanniya K / Steele, Colin W / Dickson, Euan J / Carter, C Ross / McKay, Colin J / Horgan, Paul G / McMillan, Donald C / Jamieson, Nigel B. ·Academic Unit of Surgery, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow, Scotland (LKPV, PGH, DCM, NBJ) · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, Scotland (LKPV, CWS, EJD, CRC, CJM, PGH, DCM, NBJ). ·J Natl Cancer Inst · Pubmed #26251329.

ABSTRACT: -- No abstract --