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The effect of eicosapentaenoic acid on biomarkers of growth and vascularity of human colorectal cancer liver metastases

Cockbain, Andrew James (2013) The effect of eicosapentaenoic acid on biomarkers of growth and vascularity of human colorectal cancer liver metastases. M.D. thesis, University of Leeds.

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Background: The omega-3 fatty acid eicosapentaenoic acid (EPA) has been demonstrated to be incorporated into tumours and inhibit tumour growth in pre-clinical models of colorectal cancer liver metastases (CRCLM). Aims: To test the safety, tolerability and effect on tumour biomarkers of growth and vascularity of orally administered EPA in patients awaiting liver resection surgery for CRCLM. Methods: In a Phase II randomised, double-blind, placebo-controlled trial, patients with CRCLM received EPA 2g daily (n=43) or placebo (n=45) prior to surgery. CRCLM tissue was analysed for fatty acid content, PGE2 content, proliferation index (Ki-67), apoptosis index and vascularity. Blood was collected for platelet function and monocyte NFkB binding studies, and urine for measurement of PGE-M. Supplementary in vitro endothelial cell studies investigated the effects of EPA on angiogenesis. Results: The two treatment groups were well matched for burden of disease and previous chemotherapy exposure. Mean duration of EPA treatment was 30 days (range 12-65 days). EPA was safe and well tolerated, with a small excess of diarrhoea (p=0.09), and no excess of post-operative complications. Tumours from the EPA group had a 40% higher EPA content (p<0.01), no difference in proliferation or apoptosis, and a trend to reduced vascularity. EPA treatment was associated with a 36% reduction in urinary PGE-M (p=0.03) compared to placebo, and reduced monocyte NFкB DNA binding compared to baseline (p=0.03). EPA inhibited angiogenesis in vitro. Conclusions: EPA 2g daily is safe and well-tolerated in patients with CRCLM before liver resection. EPA incorporates into CRCLMs, exhibits systemic anti-inflammatory effects, and may have anti-angiogenic activity. Phase III clinical evaluation of prolonged EPA treatment is warranted in patients with, or at risk of, CRCLM.

Item Type: Thesis (M.D.)
ISBN: 978-0-85731-643-1
Academic Units: The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds)
Identification Number/EthosID: uk.bl.ethos.605311
Depositing User: Repository Administrator
Date Deposited: 07 May 2014 09:57
Last Modified: 06 Oct 2016 14:41
URI: http://etheses.whiterose.ac.uk/id/eprint/5903

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