A5087375405- Pharmacogenetics and Drug Metabolism
- Glutathione Transferases and Polymorphisms
- Drug Transport and Resistance Mechanisms
- Genomics, phytochemicals, and oxidative stress
- Estrogen and related hormone effects
- Eicosanoids and Hypertension Pharmacology
- Computational Drug Discovery Methods
- Carcinogens and Genotoxicity Assessment
- Epigenetics and DNA Methylation
- Analytical Chemistry and Chromatography
- Drug-Induced Hepatotoxicity and Protection
- Hormonal Regulation and Hypertension
- Cytokine Signaling Pathways and Interactions
- Metabolism and Genetic Disorders
- Chemical Reactions and Isotopes
- DNA Repair Mechanisms
- Cancer Treatment and Pharmacology
- PARP inhibition in cancer therapy
- RNA modifications and cancer
- Inflammatory mediators and NSAID effects
- Colorectal Cancer Treatments and Studies
- Genetic factors in colorectal cancer
- Cancer therapeutics and mechanisms
- Radiation Therapy and Dosimetry
- Receptor Mechanisms and Signaling
University of Dundee
2016-2025
Ninewells Hospital
2016-2025
Innovative Medicines Initiative
2019-2025
Allgemeine Unfallversicherungsanstalt
2023
Universität Hamburg
2023
FOM University of Applied Sciences for Economics and Management
2017-2021
Federal Ministry of Labour and Social Affairs
2021
Taconic (United States)
2012-2019
West Lothian Council
2019
University Hospital Ulm
2019
Colorectal cancer is one of the most significant causes death. A genetic model for colorectal has been proposed in which sequential accumulation mutations specific genes, including adenomatous polyposis coli (APC), Kirsten-ras (K-ras), and p53, drives transition from healthy colonic epithelia through increasingly dysplastic adenoma to cancer. We have characterized tumor mutation spectra a large cohort patients. In marked contrast predictions accumulation, only 6.6% tumors were found contain...
Mice that lack the Nrf2 basic-region leucine-zipper transcription factor are more sensitive than wild-type (WT) animals to cytotoxic and genotoxic effects of foreign chemicals oxidants. To determine basis for decrease in tolerance homozygous null mice xenobiotics, enzyme assay, Western blotting gene-specific real-time PCR (TaqMan®) have been used examine extent which hepatic expression GSH-dependent enzymes is influenced by factor. The amounts protein mRNA class Alpha, Mu Pi glutathione...
Mammalian cytosolic glutathione S-transferases (GSTs; EC 2.5.1.18) form a supergene family consisting of four distinct families, named alpha, mu, pi and theta. In humans one member the mu class gene (GSTM1) has been shown to be polymorphic is only expressed in 55–60% individuals. Previous studies have possible link with null phenotype susceptibility cancer, particular lung cancer. this study we genotyped individuals breast, bladder colorectal A total 490 cancer were studied, consisted 97...
Abstract The potential to differentiate human embryonic stem cells (hESCs) in vitro provide an unlimited source of hepatocytes for use biomedical research, drug discovery, and the treatment liver diseases holds great promise. Here we describe a three-stage process efficient reproducible differentiation hESCs by priming towards definitive endoderm with activin A sodium butyrate prior further dimethyl sulfoxide, followed maturation hepatocyte growth factor oncostatin M. We have demonstrated...
To standardize CYP2D6 allele nomenclature, and to conform with international human gene nomenclature guidelines, an alternative the current arbitrary system is described. Based on recommendations for genome we propose that alleles be designated by followed asterisk a combination of roman letters arabic numerals distinct each number specifying key mutation and, where appropriate, letter additional mutations. Criteria classification as separate protein are also presented.
Bile acids are synthesized from cholesterol in the liver and subjected to multiple metabolic biotransformations hepatocytes, including oxidation by cytochromes P450 (CYPs) conjugation with taurine, glycine, glucuronic acid, sulfate. Mice rats can hydroxylate chenodeoxycholic acid (CDCA) at 6β-position form α-muricholic (MCA) ursodeoxycholic (UDCA) β-MCA. However, MCA is not formed humans any appreciable degree mechanism for this species difference known. Comparison of several Cyp-null mouse...
The vast majority of cancers arise as a consequence exposure to environmental agents that are toxic or mutagenic. In response this, all higher organisms have evolved complex mechanisms by which they can protect themselves from challenge. many cases, this involves an adaptive in the levels expression enzymes active metabolism and detoxification foreign chemical induced. best characterized these enzyme systems cytochrome P450s, GSTs NATs. An unfortunate reactions, however, is creation...
The activity of chemical carcinogens is a complex balance between metabolic activation by cytochrome P450 monooxygenases and detoxification enzymes such as glutathione S-transferase (GST). Regulation these proteins may have profound effects on carcinogenic activity, although it has proved impossible to ascribe the observed single protein. GstP appears play very important role in carcinogenesis, precise nature its involvement unclear. We deleted murine gene cluster established skin...
An overview is provided of the cancer chemo-prevention actions phenolic antioxidants and 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline (ethoxyquin). These agents principally appear to exert their beneficial effects through induction phase II drug-metabolizing enzymes such as glutathione S-transferase (GST). The requirement for oxidative metabolism synthetic carbonyl-containing compounds, including quinones, in order that they can induce gene expression discussed. Previous work has shown...
Cytochrome P450 CYP2C9 metabolizes a wide variety of clinically important drugs, including phenytoin, tolbutamide, warfarin and large number non-steroidal anti-inflammatory drugs. Previous studies have shown that even relatively conservative changes in the amino acid composition this enzyme can affect both its activity substrate specificity. To date six different human cDNA sequences, as well highly homologous CYP2C10 sequence been reported suggesting gene is polymorphic. Only nine single...
Abstract The NF-E2 p45-related factor 2 (Nrf2) regulates cytoprotective genes that contain an antioxidant response element (ARE) in their promoters. To investigate whether anticancer drugs can induce ARE-driven gene expression, we have developed a stable human mammary MCF7-derived reporter cell line called AREc32, which contains luciferase construct controlled by eight copies of the cis-element. In these cells, activity was increased up to 50-fold following treatment with 50 μmol/L...
Isothiocyanates and phenolic antioxidants can prevent cancer through activation of Nrf2 (NF-E2 p45-related factor 2), a transcription that controls expression cytoprotective genes the antioxidant response element (ARE) enhancer. Using human mammary MCF7-derived AREc32 reporter cell line, we now report all-trans retinoic acid (ATRA), other receptor alpha (RARalpha) agonists, markedly reduces ability to mediate induction ARE-driven by chemopreventive agents including metabolite butylated...
Journal Article Glutathione S-transferase mu locus: use of genotyping and phenotyping assays to assess association with lung cancer susceptibility Get access Shan Zhong, Zhong Search for other works by this author on: Oxford Academic PubMed Google Scholar A. Forbes Howie, Howie 1Department Clinical Chemistry, University EdinburghEdinburgh Royal Infirmary. Edinburgh EH3 9YW Brian Ketterer, Ketterer 2CRC Molecular Toxicology Group, Department Biochemistry, College Middlesex School...
The peroxisome proliferator-activated receptors (PPARs) are a family of fatty acid-activated transcription factors which control lipid homeostasis and cellular differentiation. PPARalpha (NR1C1) controls oxidation clearance in hepatocytes PPARgamma (NR1C3) promotes preadipocyte differentiation lipogenesis. Drugs that activate effective lowering plasma levels lipids have been used the management hyperlipidemia. agonists increase insulin sensitivity type 2 diabetes. In contrast, there no...
Generation Scotland: the Scottish Family Health Study aims to identify genetic variants accounting for variation in levels of quantitative traits underlying major common complex diseases (such as cardiovascular disease, cognitive decline, mental illness) Scotland. Scotland will recruit a family-based cohort up 50,000 individuals (comprising siblings and parent-offspring groups) across It be six-year programme, beginning Glasgow Tayside first two years (Phase 1) before extending other parts...
Glutathione S-transferases play a central role in drug detoxification and have been implicated the sensitivity of tumour cells to anticancer drugs. In this study, glutathione S-transferase (GST) isozyme expression normal tissue from human lung, colon, stomach, breast, kidney liver has quantified using sensitive subunit specific radioimmunoassays (RIA), together with Western blot analysis measurement substrate metabolism. pi was predominant GST majority tumours examined. The concentration...