Publications
197 results found
Gant T, Lutz U, Parry J, et al., 2009, Two electron reduction of 2,3-dimethoxy-1,4-naphthoquinone metabolism <i>in vivo</i> prevents redox stress but interaction with the electron transport chain may be a mechanism of toxicity, 46th Congress of the European-Societies-of-Toxicology, Publisher: ELSEVIER IRELAND LTD, Pages: S119-S119, ISSN: 0378-4274
Robinette SL, Veselkov KA, Bohus E, et al., 2009, Cluster Analysis Statistical Spectroscopy Using Nuclear Magnetic Resonance Generated Metabolic Data Sets from Perturbed Biological Systems, ANALYTICAL CHEMISTRY, Vol: 81, Pages: 6581-6589, ISSN: 0003-2700
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- Citations: 29
Stebbing J, Keun HC, Sidhu J, et al., 2009, Serum molecular signatures of weight change during early breast cancer chemotherapy., J Clin Oncol, Vol: 27
e11534 Background: Weight gain in women receiving chemotherapy following breast cancer diagnosis has negative implications on quality of life and those who gain weight during treatment appear to be at higher risk of disease recurrence. The mechanism(s) implicated in chemotherapy associated weight gain are poorly understood. METHODS: To investigate this further, we assessed the metabolic, cytokine and appetite related peptide alterations before and during adjuvant FEC chemotherapy for early breast cancer in post-menopausal women, and correlated these with body mass measurements. Specifically, we performed global metabolic profiling (metabonomics/ metabolomics) using (1)H nuclear magnetic resonance spectroscopy of sequential sera, examined ghrelin immunoreactivity, performed radioimmunoassays for glucagon like peptide-1 (GLP-1) and peptide YY (PYY) and electro-chemiluminescent cytokine analyses (tumor necrosis factor-α and interleukin-6; TNF-α, IL-6) on the sequential samples. RESULTS: In those who gained ≥ 1.5kg (on average ∼5% of initial body weight), several metabolite levels were positively associated with weight change, in particular lactate which was 55% greater in patients with increased body weight during chemotherapy compared to those with stable weight during chemotherapy (p<0.01; the pre-specified primary end-point). A significant inverse relationship was also observed between levels of TNF-α and weight change group (ρ 0.476, p<0.05). Baseline lactate, alanine and body fat were all prognostic for weight gain (ROC AUC >0.77, p<0.05). No significant associations were observed between any other parameter and weight gain, nor any parameter and tumor burden, including cytokine and appetite peptide alterations. CONCLUSIONS: Metabonomics identifies pathways perturbed during early chemotherapy for breast cancer, and establishes a positive association between serum lactate, body fat, TNF-α and substantive weight changes
Stebbing J, Keun HC, Sidhu J, et al., 2009, Serum molecular signatures of weight change during early breast cancer chemotherapy, 45th Annual Meeting of the American-Society-of-Clinical-Oncology, Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
Scott E, Steward W, Gescher A, et al., 2009, Three month treatment of HCA7 colon cancer cells with resveratrol at clinically relevant concentrations, Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Parry JD, Pointon AV, Lutz U, et al., 2009, Pivotal Role for Two Electron Reduction in 2,3-Dimethoxy-1,4-naphthoquinone and 2-Methyl-1,4-naphthoquinone Metabolism and Kinetics in Vivo That Prevents Liver Redox Stress, CHEMICAL RESEARCH IN TOXICOLOGY, Vol: 22, Pages: 717-725, ISSN: 0893-228X
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- Citations: 15
Backshall A, Allferez D, Telchert F, et al., 2009, Detection of Metabolic Alterations in Non-tumor Gastrointestinal Tissue of the <i>Apc</i><SUP>Min/+</SUP> Mouse by <SUP>1</SUP>H MAS NMR Spectroscopy, JOURNAL OF PROTEOME RESEARCH, Vol: 8, Pages: 1423-1430, ISSN: 1535-3893
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- Citations: 33
Cavill R, Keun HC, Holmes E, et al., 2009, Genetic algorithms for simultaneous variable and sample selection in metabonomics, BIOINFORMATICS, Vol: 25, Pages: 112-118, ISSN: 1367-4803
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- Citations: 42
Chan ECY, Koh PK, Mal M, et al., 2009, Metabolic Profiling of Human Colorectal Cancer Using High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HR-MAS NMR) Spectroscopy and Gas Chromatography Mass Spectrometry (GC/MS), JOURNAL OF PROTEOME RESEARCH, Vol: 8, Pages: 352-361, ISSN: 1535-3893
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- Citations: 370
Mycielska ME, Patel A, Rizaner N, et al., 2009, Citrate transport and metabolism in mammalian cells Prostate epithelial cells and prostate cancer, BIOESSAYS, Vol: 31, Pages: 10-20, ISSN: 0265-9247
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- Citations: 104
Keun H, 2009, Predicting drug response and toxicity from molecular profiles: the potential of metabonomics, Publisher: PHARMACEUTICAL PRESS-ROYAL PHARMACEUTICAL SOC GREAT BRITIAN, Pages: A155-A155, ISSN: 0022-3573
Bohus E, Coen M, Keun HC, et al., 2008, Temporal metabonomic modeling of L-arginine-induced exocrine pancreatitis, JOURNAL OF PROTEOME RESEARCH, Vol: 7, Pages: 4435-4445, ISSN: 1535-3893
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- Citations: 47
Pearce JTM, Athersuch TJ, Ebbels TMD, et al., 2008, Robust algorithms for automated chemical shift calibration of 1D <SUP>1</SUP>H NMR spectra of blood serum, ANALYTICAL CHEMISTRY, Vol: 80, Pages: 7158-7162, ISSN: 0003-2700
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- Citations: 44
Teichert F, Verschoyle RD, Greaves P, et al., 2008, Metabolic profiling of Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) tissue by <SUP>1</SUP>H-NMR analysis:: Evidence for unusual phospholipid metabolism, PROSTATE, Vol: 68, Pages: 1035-1047, ISSN: 0270-4137
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- Citations: 28
Lauridsen M, Maher AD, Keun H, et al., 2008, Application of the FLIPSY pulse sequence for increased sensitivity in <SUP>1</SUP>H NMR-based metabolic profiling studies, ANALYTICAL CHEMISTRY, Vol: 80, Pages: 3365-3371, ISSN: 0003-2700
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- Citations: 12
Vinken M, Doktorova T, Ellinger-Ziegelbauer H, et al., 2008, The carcinoGENOMICS project:: Critical selection of model compounds for the development of omics-based <i>in vitro</i> carcinogenicity screening assays, MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH, Vol: 659, Pages: 202-210, ISSN: 1383-5742
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- Citations: 49
Bictash M, Holmes E, Keun H, et al., 2008, Exploring the Contribution of Metabolic Profiling to Epidemiological Studies, Pages: 167-180
Keun HC, Athersuch TJ, Beckonert O, et al., 2008, Heteronuclear <SUP>19</SUP>F-<SUP>1</SUP>H statistical total correlation spectroscopy as a tool in drug metabolism:: Study of flucloxacillin biotransformation, ANALYTICAL CHEMISTRY, Vol: 80, Pages: 1073-1079, ISSN: 0003-2700
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- Citations: 47
Keun HC, 2008, Biomarker discovery for drug development and translational medicine using metabonomics, ONCOGENES MEET METABOLISM: FROM DEREGULATED GENES TO A BROADER UNDERSTANDING OF TUMOUR PHYSIOLOGY, Vol: 4, Pages: 79-98, ISSN: 0947-6075
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- Citations: 3
Keun HC, 2008, Biomarker discovery for drug development and translational medicine using metabonomics, Pages: 79-98
There exists at present an urgent desire for better biomarkers, especially in the context of pharmaceutical drug development and in the detection and management of disease. Many researchers in the area of biomarker discovery and development have turned to the "-omics" sciences as a way of addressing these needs. Metabolic profiling, or metabonomics, defines the metabolic phenotype and offers a Source of novel biomarkers that have better potential to translate effectively. This review will discuss the broad philosophy and motivations behind metabonomics, and illustrate the case with applications relevant to pharmaceutical development and patient management. Particular focus will be paid to the potential of metabonomics to contribute to biomarker discovery in toxicology and cancer research.
Nicholson J, Keun H, Ebbels T, 2007, COMET and the challenge of drug safety screening, JOURNAL OF PROTEOME RESEARCH, Vol: 6, Pages: 4098-4099, ISSN: 1535-3893
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- Citations: 10
Ebbels TMD, Keun HC, Beckonert OP, et al., 2007, Prediction and Classification of Drug Toxicity Using Probabilistic Modeling of Temporal Metabolic Data: The Consortium on Metabonomic Toxicology Screening Approach, Journal of Proteome Research, Vol: 6, Pages: 3944-3951
Griffin JL, Nicholls AW, Daykin CA, et al., 2007, Standard reporting requirements for biological samples in metabolomics experiments: mammalian/in vivo experiments, METABOLOMICS, Vol: 3, Pages: 179-188, ISSN: 1573-3882
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- Citations: 56
Keun HC, Athersuch TJ, 2007, Application of metabonomics in drug development, PHARMACOGENOMICS, Vol: 8, Pages: 731-741, ISSN: 1462-2416
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- Citations: 51
Bundy JG, Keun HC, Sidhu JK, et al., 2007, Metabolic profile biomarkers of metal contamination in a sentinel terrestrial species are applicable across multiple sites, Environmental Science & Technology, Vol: 41, Pages: 4458-4464, ISSN: 0013-936X
Beckonert O, Keun HC, Ebbels TMD, et al., 2007, Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts, NATURE PROTOCOLS, Vol: 2, Pages: 2692-2703, ISSN: 1754-2189
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- Citations: 1584
Dumas ME, Wilder SP, Bihoreau MT, et al., 2007, Direct quantitative trait locus mapping of mammalian metabolic phenotypes in diabetic and normoglycemic rat models, Nat Genet, Vol: 39, Pages: 666-672, ISSN: 1061-4036
Teahan O, Gamble S, Holmes E, et al., 2006, Impact of analytical bias in metabonomic studies of human blood serum and plasma, ANALYTICAL CHEMISTRY, Vol: 78, Pages: 4307-4318, ISSN: 0003-2700
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- Citations: 205
Ekman DR, Keun HC, Eads CD, et al., 2006, Metabolomic evaluation of rat liver and testis to characterize the toxicity of triazole fungicides, METABOLOMICS, Vol: 2, Pages: 63-73, ISSN: 1573-3882
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- Citations: 34
Athersuch TJ, Keun H, Tang H, et al., 2006, Quantitative urinalysis of the mercapturic acid conjugates of allyl formate using high-resolution NMR spectroscopy, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 40, Pages: 410-416, ISSN: 0731-7085
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- Citations: 6
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