H L McLeod

Summary

Affiliation: University of Aberdeen
Country: UK

Publications

  1. ncbi request reprint Nomenclature for human DPYD alleles
    H L McLeod
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, UK
    Pharmacogenetics 8:455-9. 1998
  2. ncbi request reprint Pharmacokinetic and pharmacodynamic evaluation of the glycinamide ribonucleotide formyltransferase inhibitor AG2034
    H L McLeod
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, United Kingdom
    Clin Cancer Res 6:2677-84. 2000
  3. ncbi request reprint Ethnic differences in thiopurine methyltransferase pharmacogenetics: evidence for allele specificity in Caucasian and Kenyan individuals
    H L McLeod
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, UK
    Pharmacogenetics 9:773-6. 1999
  4. ncbi request reprint Analysis of thiopurine methyltransferase variant alleles in childhood acute lymphoblastic leukaemia
    H L McLeod
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen
    Br J Haematol 105:696-700. 1999
  5. ncbi request reprint Ethnic differences in catechol O-methyltransferase pharmacogenetics: frequency of the codon 108/158 low activity allele is lower in Kenyan than Caucasian or South-west Asian individuals
    H L McLeod
    Department of Medicine and Therapeutics, University of Aberdeen, UK
    Pharmacogenetics 8:195-9. 1998
  6. ncbi request reprint Evaluation of the linearity of docetaxel pharmacokinetics
    H L McLeod
    Department of Medicine and Therapeutics, University of Aberdeen, Institute of Medical Sciences, Foresterhill, UK
    Cancer Chemother Pharmacol 42:155-9. 1998
  7. ncbi request reprint Known variant DPYD alleles do not explain DPD deficiency in cancer patients
    E S Collie-Duguid
    University of Aberdeen, Department of Medicine and Therapeutics, Institute of Medical Sciences, Foresterhill, UK
    Pharmacogenetics 10:217-23. 2000
  8. ncbi request reprint Novel thymidylate synthase enhancer region alleles in African populations
    S Marsh
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom
    Hum Mutat 16:528. 2000
  9. pmc Dihydropyrimidine dehydrogenase pharmacogenetics in patients with colorectal cancer
    S A Ridge
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, UK
    Br J Cancer 77:497-500. 1998
  10. pmc c-erbB-2 is not a major factor in the development of colorectal cancer
    J A McKay
    Department of Medicine and Therapeutics, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2Z, UK
    Br J Cancer 86:568-73. 2002

Collaborators

Detail Information

Publications49

  1. ncbi request reprint Nomenclature for human DPYD alleles
    H L McLeod
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, UK
    Pharmacogenetics 8:455-9. 1998
    ..The number specifies the key mutation and, where appropriate, a letter following the number indicates an additional mutation on the mutant allele. Criteria for classification as a distinct allele are also presented...
  2. ncbi request reprint Pharmacokinetic and pharmacodynamic evaluation of the glycinamide ribonucleotide formyltransferase inhibitor AG2034
    H L McLeod
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, United Kingdom
    Clin Cancer Res 6:2677-84. 2000
    ..This study demonstrates rapid systemic clearance of AG2034 and suggests pharmacokinetic approaches that may minimize patient toxicity and aid the development of this interesting class of anticancer agents...
  3. ncbi request reprint Ethnic differences in thiopurine methyltransferase pharmacogenetics: evidence for allele specificity in Caucasian and Kenyan individuals
    H L McLeod
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, UK
    Pharmacogenetics 9:773-6. 1999
    ..This study confirms ethnic differences in the predominant mutant TPMT allele and the findings will be useful for the development of polymerase chain reaction-based strategies to prevent toxicity with thiopurine medications...
  4. ncbi request reprint Analysis of thiopurine methyltransferase variant alleles in childhood acute lymphoblastic leukaemia
    H L McLeod
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen
    Br J Haematol 105:696-700. 1999
    ..This study demonstrates that 11.6% of the children had variant TPMT alleles. Prospective identification of TPMT genotype may be a promising tool for decreasing excessive haematological toxicity in individuals with low activity...
  5. ncbi request reprint Ethnic differences in catechol O-methyltransferase pharmacogenetics: frequency of the codon 108/158 low activity allele is lower in Kenyan than Caucasian or South-west Asian individuals
    H L McLeod
    Department of Medicine and Therapeutics, University of Aberdeen, UK
    Pharmacogenetics 8:195-9. 1998
    ..Erythrocyte COMT activity was lower and less thermostable in individuals with homozygous low activity alleles. The data provide molecular evidence that low COMT is less common in African individuals than the Caucasian population...
  6. ncbi request reprint Evaluation of the linearity of docetaxel pharmacokinetics
    H L McLeod
    Department of Medicine and Therapeutics, University of Aberdeen, Institute of Medical Sciences, Foresterhill, UK
    Cancer Chemother Pharmacol 42:155-9. 1998
    ..The presence of nonlinear docetaxel pharmacokinetics at doses above 115 mg/m2 will have to be determined in case of further dose escalation...
  7. ncbi request reprint Known variant DPYD alleles do not explain DPD deficiency in cancer patients
    E S Collie-Duguid
    University of Aberdeen, Department of Medicine and Therapeutics, Institute of Medical Sciences, Foresterhill, UK
    Pharmacogenetics 10:217-23. 2000
    ..These data emphasize the complex nature of the molecular mechanisms controlling polymorphic DPD activity in vivo...
  8. ncbi request reprint Novel thymidylate synthase enhancer region alleles in African populations
    S Marsh
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom
    Hum Mutat 16:528. 2000
    ..This is a unique example suggesting the influence of multiple selection pressures within individual populations. Hum Mutat 16:528, 2000...
  9. pmc Dihydropyrimidine dehydrogenase pharmacogenetics in patients with colorectal cancer
    S A Ridge
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, UK
    Br J Cancer 77:497-500. 1998
    ..These studies highlight the need to combine DPD genotype and phenotype analysis to identify mutations that result in reduced enzyme activity...
  10. pmc c-erbB-2 is not a major factor in the development of colorectal cancer
    J A McKay
    Department of Medicine and Therapeutics, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2Z, UK
    Br J Cancer 86:568-73. 2002
    ..05 in each case), suggesting that c-erbB-2 is not a prognostic marker in colorectal cancer...
  11. ncbi request reprint Cloning and initial characterization of the human DPYD gene promoter
    E S Collie-Duguid
    Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, Scotland, AB25 2ZD, United Kingdom
    Biochem Biophys Res Commun 271:28-35. 2000
    ..Further insight into regulation of DPD expression may identify new avenues for the treatment of clinical problems associated with DPD deficiency...
  12. ncbi request reprint Expression of matrix metalloproteinases 1, 2, 9 and their tissue inhibitors in stage II non-small cell lung cancer: implications for MMP inhibition therapy
    S C Pritchard
    Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen AB25 2ZD, UK
    Oncol Rep 8:421-4. 2001
    ..These results suggest that a broad spectrum MMP inhibitor is worthy of evaluation as a therapeutic method of reducing tumor invasion and metastasis in stage II NSCLC...
  13. ncbi request reprint MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity
    M M Ameyaw
    University of Aberdeen, Department of Medicine and Therapeutics, Institute of Medical Sciences, Foresterhill, Aberdeen, UK
    Pharmacogenetics 11:217-21. 2001
    ..The high frequency of the C allele in the African group implies overexpression of PGP and may have important therapeutic and prognostic implications for use of PGP dependent drugs in individuals of African origin...
  14. pmc Colorectal cancer genomics: evidence for multiple genotypes which influence survival
    P H Rooney
    Department of Medicine and Therapeutics, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen
    Br J Cancer 85:1492-8. 2001
    ..Although genomic change in CRC is relevant to the survival of patients with Dukes' C CRC, careful analysis is required to identify cell lines which are representative models of CRC genomics...
  15. ncbi request reprint Polymorphism in the thymidylate synthase promoter enhancer region in colorectal cancer
    S Marsh
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK
    Int J Oncol 19:383-6. 2001
    ..This is consistent with previous studies where higher TS expression was associated with poor response to TS inhibitors. Prospective analysis of the influence of the TS polymorphism on patient outcome is warranted...
  16. ncbi request reprint Pharmacogenetics of catechol-O-methyltransferase: frequency of low activity allele in a Ghanaian population
    M M Ameyaw
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK
    Hum Mutat 16:445-6. 2000
    ....
  17. ncbi request reprint Cytochrome P450 CYP1B1 protein expression: a novel mechanism of anticancer drug resistance
    M C McFadyen
    Department of Pathology, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
    Biochem Pharmacol 62:207-12. 2001
    ..This study is the first to indicate that the presence of CYP1B1 in cells decreases their sensitivity to the cytotoxic effects of a specific anticancer drug...
  18. ncbi request reprint Thiopurine methyltransferase alleles in British and Ghanaian populations
    M M Ameyaw
    University of Aberdeen, Department of Medicine and Therapeutics, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK
    Hum Mol Genet 8:367-70. 1999
    ..This study provides the first analysis of TPMT mutant allele frequency in an African population and indicates that, unlike Caucasians, TPMT*3C is the most common allele in African subjects...
  19. ncbi request reprint Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph node metastases
    J A McKay
    Department of Medicine and Therapeutics, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen, UK
    Eur J Cancer 38:2258-64. 2002
    ..05). These results indicate that while EGFR overexpression is a common event in colorectal carcinogenesis, it does not influence patient prognosis...
  20. ncbi request reprint Expression of cell cycle control proteins in primary colorectal tumors does not always predict expression in lymph node metastases
    J A McKay
    Department of Medicine and Therapeutics, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, Scotland, United Kingdom
    Clin Cancer Res 6:1113-8. 2000
    ..In addition, PCNA-labeling indices between paired samples were neither consistently higher nor lower, suggesting that the proliferative capacity of tumor cells is not directly related to their ability to metastasize...
  21. ncbi request reprint The frequency and distribution of thiopurine methyltransferase alleles in Caucasian and Asian populations
    E S Collie-Duguid
    The University of Aberdeen, Department of Medicine and Therapeutics, Institute of Medical Sciences, Foresterhill, UK
    Pharmacogenetics 9:37-42. 1999
    ..TPMT*2 appears to be a more recent allele, which has only been detected in Caucasians to date. These ethnic differences may be important in the clinical use of thiopurine drugs...
  22. ncbi request reprint Primary pulmonary osteosarcoma: case report and molecular analysis
    A D Chapman
    Department of Pathology, University of Aberdeen, Aberdeen, Scotland, United Kingdom
    Cancer 91:779-84. 2001
    ..The novel regions of instability identified within the tumor genome may contribute toward the unique tumor phenotype and relative chemoresistance...
  23. ncbi request reprint Analysis of uracil DNA glycosylase in human colorectal cancer
    C Dusseau
    Department of Medicine and Therapeutics, Aberdeen Royal Infirmary, University of Aberdeen, UK
    Int J Oncol 18:393-9. 2001
    ..The high tumor:normal tissue ratio supports further interest in base excision repair, through UDG, as a potential source of fluoropyrimidine resistance in colorectal cancer...
  24. pmc Phase I dose-escalation and pharmacokinetic study of a novel folate analogue AG2034
    D Bissett
    Department of Medicine and Therapeutics, University of Aberdeen, UK
    Br J Cancer 84:308-12. 2001
    ..The AG2034 AUC(0-24)increased by a median of 184% (range 20-389%) from cycle 1 to 3 in all 10 patients examined. No objective antitumour responses were observed in the study...
  25. ncbi request reprint Human CYP1B1 and anticancer agent metabolism: mechanism for tumor-specific drug inactivation?
    B Rochat
    Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, Scotland, UK
    J Pharmacol Exp Ther 296:537-41. 2001
    ..The results obtained indicate that several anticancer agents inhibit CYP1B1 activity. Drug inactivation by CYP1B1 may represent a novel mechanism of resistance, influencing the clinical outcome of chemotherapy...
  26. pmc Characterization of dihydropyrimidine dehydrogenase in human colorectal tumours
    H L McLeod
    Department of Medicine, University of Aberdeen, Foresterhill, UK
    Br J Cancer 77:461-5. 1998
    ..As a large degree of the variation in tumour DPD activity is not explained by PMNC activity, more accurate alternatives are needed before DPD activity can be used for targeting 5-FU therapy...
  27. ncbi request reprint Therapeutic opportunities from tumour biology in metastatic colon cancer
    H L McLeod
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen, UK
    Eur J Cancer 36:1706-12. 2000
    ....
  28. pmc CYP3A4 and VDR gene polymorphisms and the risk of prostate cancer in men with benign prostate hyperplasia
    M T Tayeb
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresthill, UK
    Br J Cancer 88:928-32. 2003
    ..43; 95% CI=0.99-11.77). While independent confirmation is required in further studies, these results provide a potential tool to assist prediction strategies for this important disease...
  29. ncbi request reprint Thymidine phosphorylase and dihydropyrimidine dehydrogenase protein expression in colorectal cancer
    E S Collie-Duguid
    Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, Scotland
    Int J Cancer 94:297-301. 2001
    ..This suggests the presence of co-ordinated regulation of these pyrimidine metabolic enzymes and offers a strategy for optimising the use of pyrimidine-based chemotherapy...
  30. ncbi request reprint Pharmacogenomic dissection of resistance to thymidylate synthase inhibitors
    W Wang
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom
    Cancer Res 61:5505-10. 2001
    ..These data provide encouragement that comprehensive transcript analysis will aid the quest for more enlightened therapeutics...
  31. pmc Amplification of fluorescent in situ hybridisation signals in formalin fixed paraffin wax embedded sections of colon tumour using biotinylated tyramide
    J A McKay
    Department of Medicine and Therapeutics, University of Aberdeen, Institute of Medical Sciences, Foresterhill, UK
    Mol Pathol 50:322-5. 1997
    ....
  32. pmc Mutations at codon 974 of the DPYD gene are a rare event
    S A Ridge
    Department of Medicine and Therapeutics, University of Aberdeen, Foresterhill, UK
    Br J Cancer 75:178-9. 1997
    ..We detected no mutations in the 606 alleles studied and conclude that mutations at codon 974 are a rare event...
  33. ncbi request reprint Genomic instability at the BUB1 locus in colorectal cancer, but not in non-small cell lung cancer
    R G Jaffrey
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Scotland
    Cancer Res 60:4349-52. 2000
    ..Additional investigations may shed light on the mechanistic impact of the mitotic spindle checkpoint pathway in colorectal tumor initiation and progression...
  34. pmc Cytochrome P450 CYP1B1 over-expression in primary and metastatic ovarian cancer
    M C McFadyen
    Departments of Pathology, Obstetrics and Gynaecology, Medicine and Therapeutics, Molecular and Cell Biology, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK
    Br J Cancer 85:242-6. 2001
    ..005 Spearman's rank correlation test). In contrast no detectable CYP1B1 was found in normal ovary...
  35. pmc Application of laser capture microdissection and proteomics in colon cancer
    L C Lawrie
    Department of Pathology, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK
    Mol Pathol 54:253-8. 2001
    ..CONCLUSION: A method for performing two dimensional gel electrophoresis and mass spectrometry using laser capture microdissected tissue has been developed...
  36. ncbi request reprint CYP2A7 polymorphic alleles confound the genotyping of CYP2A6*4A allele
    T Fukami
    Department of Drug Metabolism and Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medical Science, Kanazawa University, Kakuma machi, Kanazawa, Japan
    Pharmacogenomics J 6:401-12. 2006
    ..7% in European-Americans was corrected to 0%. The comprehensible and reliable genotyping method developed in this study would be useful to evaluate associations between the genotype and phenotype...
  37. ncbi request reprint Allelotype frequency of the thiopurine methyltransferase (TPMT) gene in Japanese
    K Kumagai
    Second Department of Internal Medicine, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
    Pharmacogenetics 11:275-8. 2001
    ..The allele frequency was different from that in Caucasians, and investigation of TPMT polymorphisms with consideration of ethnic differences before administration of azathioprine or 6MP may provide clinically useful information...
  38. ncbi request reprint Irinotecan-induced diarrhea: functional significance of the polymorphic ABCC2 transporter protein
    F A De Jong
    Department of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
    Clin Pharmacol Ther 81:42-9. 2007
    ..As the association was seen in patients not genetically predisposed at risk for diarrhea due to UGT1A1*28, confirmatory studies of the relationships of ABCC2 genotypes and irinotecan disposition and toxicity are warranted...
  39. ncbi request reprint Ethnic differences in pharmacogenetically relevant genes
    R M Engen
    Department of Medicine, Washington University School of Medicine and the Siteman Cancer Center, St Louis, Missouri 63110, USA
    Curr Drug Targets 7:1641-8. 2006
    ..Understanding the influence of ethnicity on pharmacogenomics will allow for comprehensive strategies for using the genome to optimize therapy for patients throughout the world...
  40. ncbi request reprint Pharmacogenetic analysis of paclitaxel transport and metabolism genes in breast cancer
    S Marsh
    Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Pharmacogenomics J 7:362-5. 2007
    ..Alternatively, the role of CYP1B1 in estrogen metabolism may influence the risk of invasive or paclitaxel resistant breast cancer in patients carrying the CYP1B1*3 allele...
  41. pmc Unfavourable expression of pharmacologic markers in mucinous colorectal cancer
    S C Glasgow
    Department of Surgery, Washington University School of Medicine, St Louis, MI, USA
    Br J Cancer 92:259-64. 2005
    ..Likewise, DFS may be decreased in patients with mucinous tumours who receive 5-FU. The presence of mucin should be carefully evaluated in developmental trials of new agents for treating colorectal cancer...
  42. ncbi request reprint Comparison of mRNA expression levels determined with TaqMan and competitive template RT-PCR
    R Mauritz
    Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
    Nucleosides Nucleotides Nucleic Acids 23:1471-4. 2004
    ..Although the relative mRNA levels compared to beta-actin measured with competitive template RT-PCR were different from the data obtained with a TaqMan based PCR, a significant correlation between the two assays was found...
  43. ncbi request reprint Interethnic variability of ERCC2 polymorphisms
    C R King
    Department of Medicine, Division of Oncology, Washington University School of Medicine, Saint Louis, MO 63110, USA
    Pharmacogenomics J 5:54-9. 2005
    ..This information on ERCC2 genomic structure will allow the construction of definitive studies to clarify the clinical role of this important gene...
  44. pmc RNA profiling of cyclooxygenases 1 and 2 in colorectal cancer
    R D Church
    1Department of Surgery, Washington University School of Medicine, St Louis, MO 63110 1093, USA
    Br J Cancer 91:1015-8. 2004
    ..We report that Cox-1 and Cox-2 expression is highly variable in Dukes' C tumours, and changes in Cox-1 expression may be of importance...
  45. ncbi request reprint Identification and analysis of single-nucleotide polymorphisms in the gemcitabine pharmacologic pathway
    A K Fukunaga
    Department of Clinical Pharmacy and Pharmacy Practice, Purdue University, W Lafayette, IN, USA
    Pharmacogenomics J 4:307-14. 2004
    ..05). This study provides the first step to identify markers for predicting variability in gemcitabine response and toxicity...
  46. pmc Cancer pharmacogenetics
    S Marsh
    Department of Medicine, Washington University School of Medicine, 660 South Euclid Ave, Campus Box 8069, The Siteman Cancer Center, and the CREATE Pharmacogenetic Research Network, St Louis, MO 63110 1093, USA
    Br J Cancer 90:8-11. 2004
    ..In addition, the need for polygenic pharmacogenomic strategies to identify patients at risk for adverse drug reactions will be highlighted...
  47. ncbi request reprint Re: population-based, case-control study of HER2 genetic polymorphism and breast cancer risk
    M M Ameyaw
    J Natl Cancer Inst 92:1947. 2000
  48. ncbi request reprint The geographic distribution of monoamine oxidase haplotypes supports a bottleneck during the dispersion of modern humans from Africa
    J Balciuniene
    Section of Medical Genetics, Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden
    J Mol Evol 52:157-63. 2001
    ..This profound change in haplotype frequencies from Africans to non-Africans supports a possible bottleneck during the dispersion of modern humans from Africa...
  49. doi request reprint Pharmacogenetically relevant polymorphisms in Portugal
    E Oliveira
    University of Porto, Institute of Pathology and Molecular Immunology, 4200 465 Porto, Portugal
    Pharmacogenomics 8:703-12. 2007
    ....