Nakajima, Miki, Fukami, T., Yamanaka, H., Higashi, E., Sakai, H., Yoshida, R., ...
Human cytochrome P450 (CYP) 2A6 metabolizes nicotine to cotinine and is a possible modulator of nicotine addiction. Quantitative and qualitative differences in nicotine addiction have been observed...
Irinotecan pathway genotype analysis to predict pharmacokinetics (2003)
Mathijssen, R.H., Marsh, S., Karlsson, M.O., Xie, R., Baker, S.D., Verweij, J., ...
PURPOSE: The purpose was to explore the relationships between irinotecan disposition and allelic variants of genes coding for adenosine triphosphate binding cassette transporters and enzymes of...
Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism (2002)
Peters, G.J., Backus, H.H.J., Freemantle, S., Triest, B. Van, Codacci-Pisanelli, G., ...
Pharmacogenetics in rheumatology: the prospects and limitations of an emerging field (2002)
Siva, C., Yokoyama, W. M., McLeod, H. L.
Objectives. To review the fundamental concepts of pharmacogenetics and analyse how the broad principles of this rapidly emerging field may influence the treatment of rheumatic disease in future....
Dihydropyrimidine dehydrogenase pharmacogenetics in Caucasian subjects (1998)
Ridge, S.A., Sludden, J., Brown, O., Robertson, L., Wei, X., Sapone, A., ...
Nomenclature for human DPYD alleles (1998)
McLeod, H.L., Johnson, M.R., Wei, X., Sapone, A., Diasio, R.B., ...
Mckay, J.A., Murray, G.I., Keith, W.N., Mcleod, H.L.
Fluorescent in situ hybridisation (FISH) is a powerful tool for the evaluation of chromosomal alterations in formalin fixed paraffin wax embedded sections of colorectal cancer. However, initial...
Multicentre phase II pharmacological evaluation of rhizoxin (1996)
Verweij, J., Aamdal, S., Wagener, D.J.T., Heinrich, B., Pavlidis, N., ...
Mckay, J.A., Murray, G.I., Keith, W.N., Mcleod, H.L.
Fluorescent in situ hybridisation (FISH) is a powerful tool for the evaluation of chromosomal alterations in formalin fixed paraffin wax embedded sections of colorectal cancer. However, initial...
Evans, W E, Relling, M V, Rahman, A, McLeod, H L, Scott, E P, Lin, J S
Debrisoquin hydroxylase (CYP2D6) is a cytochrome P450 enzyme that catalyzes the metabolism of > 30 commonly prescribed medications. Deficiency in CYP2D6 activity, inherited as an autosomal recessive...
McKay, J A, Murray, G I, Keith, W N, McLeod, H L
Fluorescent in situ hybridisation (FISH) is a powerful tool for the evaluation of chromosomal alterations in formalin fixed paraffin wax embedded sections of colorectal cancer. However, initial...
Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity.
Wei, X, McLeod, H L, McMurrough, J, Gonzalez, F J, Fernandez-Salguero, P
Dihydropyrimidine dehydrogenase (DPD) deficiency constitutes an inborn error in pyrimidine metabolism associated with thymine-uraciluria in pediatric patients and an increased risk of toxicity in...
Curran, S, McKay, J A, McLeod, H L, Murray, G I
Human tissues are composed of complex admixtures of different cell types and their biologically meaningful analysis necessitates the procurement of pure samples of the cells of interest. Many...
Application of laser capture microdissection and proteomics in colon cancer
Lawrie, L C, Curran, S, McLeod, H L, Fothergill, J E, Murray, G I
Aims—Laser capture microdissection is a recent development that enables the isolation of specific cell types for subsequent molecular analysis. This study describes a method for obtaining proteome...
Evans, W E, Relling, M V, Rahman, A, McLeod, H L, Scott, E P, Lin, J S
Debrisoquin hydroxylase (CYP2D6) is a cytochrome P450 enzyme that catalyzes the metabolism of > 30 commonly prescribed medications. Deficiency in CYP2D6 activity, inherited as an autosomal recessive...
McKay, J A, Murray, G I, Keith, W N, McLeod, H L
Fluorescent in situ hybridisation (FISH) is a powerful tool for the evaluation of chromosomal alterations in formalin fixed paraffin wax embedded sections of colorectal cancer. However, initial...
Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity.
Wei, X, McLeod, H L, McMurrough, J, Gonzalez, F J, Fernandez-Salguero, P
Dihydropyrimidine dehydrogenase (DPD) deficiency constitutes an inborn error in pyrimidine metabolism associated with thymine-uraciluria in pediatric patients and an increased risk of toxicity in...
Curran, S, McKay, J A, McLeod, H L, Murray, G I
Human tissues are composed of complex admixtures of different cell types and their biologically meaningful analysis necessitates the procurement of pure samples of the cells of interest. Many...
Application of laser capture microdissection and proteomics in colon cancer
Lawrie, L C, Curran, S, McLeod, H L, Fothergill, J E, Murray, G I
Aims—Laser capture microdissection is a recent development that enables the isolation of specific cell types for subsequent molecular analysis. This study describes a method for obtaining proteome...
Nakajima, Miki, Fukami, T., Yamanaka, H., Higashi, E., Sakai, H., Yoshida, R., ...
Human cytochrome P450 (CYP) 2A6 metabolizes nicotine to cotinine and is a possible modulator of nicotine addiction. Quantitative and qualitative differences in nicotine addiction have been observed...
Mckay, J.A., Murray, G.I., Keith, W.N., Mcleod, H.L.
Fluorescent in situ hybridisation (FISH) is a powerful tool for the evaluation of chromosomal alterations in formalin fixed paraffin wax embedded sections of colorectal cancer. However, initial...
Analysis of the dihydropyrimidine dehydrogenase polymorphism in a British population
Subjects with low or absent dihydropyrimidine dehydrogenase activity (DPD) are at risk of excessive toxicity or death when undergoing fluoropyrimidine chemotherapy. The DPD polymorphism has not been...
Mutations at codon 974 of the DPYD gene are a rare event.
Ridge, S. A., Brown, O., McMurrough, J., Fernandez-Salguero, P., Evans, W. E., Gonzalez, F. J., ...
A mutation at codon 974 of the dihydropyrimidine dehydrogenase (DPD) gene was previously described in a cancer patient with undetectable DPD enzyme activity who experienced severe toxicity when...
Variation in topoisomerase I gene copy number as a mechanism for intrinsic drug sensitivity.
DNA topoisomerase I (topo I) is the principle target for camptothecin and its derivatives such as SN38. Levels of topo I expression vary widely between and within tumour types and the basis for this...
McLeod, H. L., Murray, L. S., Wanders, J., Setanoians, A., Graham, M. A., Pavlidis, N., ...
Rhizoxin is a macrocyclic lactone compound that binds to tubulin and inhibits microtubule assembly. Rhizoxin demonstrated preclinical anti-tumour activity against a variety of human tumour cell lines...
In vivo pharmacology and anti-tumour evaluation of the tyrphostin tyrosine kinase inhibitor RG13022.
McLeod, H. L., Brunton, V. G., Eckardt, N., Lear, M. J., Robins, D. J., Workman, P., ...
Amplification and increased expression of many growth factor receptors, including the epidermal growth factor receptor (EGFR), has been observed in human tumours. One therapeutic strategy for...
Dihydropyrimidine dehydrogenase pharmacogenetics in patients with colorectal cancer.
Ridge, S. A., Sludden, J., Wei, X., Sapone, A., Brown, O., Hardy, S., ...
Individuals with a deficiency in the enzyme dihydropyrimidine dehydrogenase (DPD) may experience severe life-threatening toxicity when treated with 5-fluorouracil (5-FU). As routine measurement of...
Characterization of dihydropyrimidine dehydrogenase in human colorectal tumours.
McLeod, H. L., Sludden, J., Murray, G. I., Keenan, R. A., Davidson, A. I., Park, K., ...
Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme for degradation of 5-fluorouracil (5-FU). DPD activity is highly variable in liver and peripheral mononuclear cells (PMNCs) and it...
Phase I study of pegylated liposomal doxorubicin and the multidrug-resistance modulator, valspodar
Fracasso, P M, Blum, K A, Ma, M K, Tan, B R, Wright, L P, Goodner, S A, ...
Valspodar, a P-glycoprotein modulator, affects pharmacokinetics of doxorubicin when administered in combination, resulting in doxorubicin dose reduction. In animal models, valspodar has minimal...
Unfavourable expression of pharmacologic markers in mucinous colorectal cancer
Glasgow, S C, Yu, J, Carvalho, L P, Shannon, W D, Fleshman, J W, McLeod, H L
Patients with mucinous colorectal cancer generally have worse prognoses than those with the nonmucinous variety. The reason for this disparity is unclear, but may result from a differential response...
Comparative genomic hybridization and chromosomal instability in solid tumours
Rooney, P H, Murray, G I, Stevenson, D A J, Haites, N E, Cassidy, J, McLeod, H L
Phase I dose-escalation and pharmacokinetic study of a novel folate analogue AG2034
Bissett, D, McLeod, H L, Sheedy, B, Collier, M, Pithavala, Y, Paradiso, L, ...
The novel folate analogue AG2034, which was designed as an inhibitor of GARFT (glycinamide ribonucleotide formyltransferase), was evaluated in this phase I study under the auspices of The Cancer...
Colorectal cancer genomics: evidence for multiple genotypes which influence survival
Rooney, P H, Boonsong, A, McKay, J A, Marsh, S, Stevenson, D A J, Murray, G I, ...
Colorectal cancer (CRC) is a leading cause of cancer death and the mechanism for variable outcome in this disease is not yet fully understood. It is hypothesized that differences in the genetic...
Cytochrome P450 CYP1B1 over-expression in primary and metastatic ovarian cancer
McFadyen, M C E, Cruickshank, M E, Miller, I D, McLeod, H L, Melvin, W T, Haites, N E, ...
Ovarian cancer is the most frequent cause of death from gynaecological malignancies world wide. Little improvement has been made in the long-term outcome of this disease, with the 5-year survival of...
c-erbB-2 is not a major factor in the development of colorectal cancer
McKay, J A, Loane, J F, Ross, V G, Ameyaw, M-M, Murray, G I, Cassidy, J, ...
We have investigated c-erbB-2 protein expression in a large cohort of well-characterized colorectal tumours, and in a subset of lymph node metastases. We have also evaluated a Val655Ile single...
Disposition of antineoplastic agents in the very young child.
McLeod, H. L., Relling, M. V., Crom, W. R., Silverstein, K., Groom, S., Rodman, J. H., ...
Maturation of physiologic process which govern the disposition of pharmacologic agents can yield significant changes in absorption, distribution, metabolism, and elimination of drugs in neonates,...
RNA profiling of cyclooxygenases 1 and 2 in colorectal cancer
Church, R D, Yu, J, Fleshman, J W, Shannon, W D, Govindan, R, McLeod, H L
Cyclooxygenases (particularily Cox-2) are involved in carcinogenesis and metastatic cancer progression. The expression profiles of the cyclooxygenases and the roles they play in established tumours...