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Title: NMR-based metabolomic studies of breast cancer
Author: Yabsley, Warren
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2013
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Breast cancer is the most frequently diagnosed form of cancer and leading cause of cancer death in females. Current screening techniques, such as mammography, are inadequate. Screening reduces the number of deaths caused by breast cancer but also results in a large number of women with non-life threatening forms of the disease being treated unnecessarily. Initial screening can produce a false positive result, which causes much anxiety. Clearly there is a need for a more reliable approach; nuclear magnetic resonance (NMR)-based metabolomics has been used to this end. Plasma and urine from female patients with breast cancer or abnormal but non-cancerous breast state and extracts from tumour and adjacent normal tissue obtained from those afflicted with the disease have been analysed in an attempt to elucidate a biomarker of disease presence or tumour grade. Aqueous extracts of tumour tissue compared to healthy adjacent (normal) tissue revealed increased levels of lactate, alanine, creatine, glutamate, glutamine, glycerophosphocholine (GPC), glycerophospholipids, phosphocholine (PCho), taurine, uridine-5'-diphosphate-N-acetylgalactosamine, (UDP-GaINAc) and uridine-5'-diphosphate-N-acetylglucosamine (UDP-GlcNAc) and decreased levels of glucose. Increased lactate and decreased glucose is in agreement with the Warburg effect whereby cancer cells predominantly produce energy by a high rate of glycolysis. Analysis of lipophilic extracts did not reveal a difference between tumour and normal samples. Metabolite levels did not indicate the tumour grade using either type of extracts. Singly, plasma and urine data did not identify changing metabolite levels with breast cancer or tumour grade but correlations between the two biofluids were established using statistical heterospectroscopy (SHY). Through an unidentified species it was implied that a negative correlation existed between glycerol and certain lipids for patients with breast cancer. These studies have provided useful insights into tumour metabolism and correlations of metabolites in different biofluids.
Supervisor: Fisher, J. ; Speirs, V. ; Homer-Vanniasinkam, S. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available