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A histological, histochemical and biochemical study of the macroscopically normal white matter in multiple sclerosis
The present study showed a significant elevation of the lysosomal enzyme beta-glucosaminidase in the microscopically normal white matter in MS as compared with controls, suggesting that the white matter may be rendered more susceptible to the pathogenetic process in this disease. Expand
Defining normoxia, physoxia and hypoxia in tumours-implications for treatment response.
- S. McKeown
- Medicine, Biology
- The British journal of radiology
- 29 January 2014
This review seeks to clarify the oxygen levels that are pertinent to tumour hypoxia, and it is argued that normoxia (20% oxygen) is an extremely poor comparator for "physoxia", i.e. the much lower levels of oxygen universally found in normal tissues. Expand
Mutant SOD1 mediated pathogenesis of Amyotrophic Lateral Sclerosis.
There is a need to identify new approaches for treatment of this ultimately fatal disease, as no definitive treatment option can provide a cure and currently ALS is managed by drugs and other supportive therapies. Expand
AQ4N: a new approach to hypoxia-activated cancer chemotherapy
AQ4N is a bioreductive prodrug of a potent, stable, reduction product which binds non-covalently to DNA, facilitating antitumour activity in both hypoxic and proximate oxic tumour cells. Expand
Bioreductive drugs: from concept to clinic.
- S. McKeown, R. Cowen, K. Williams
- Clinical oncology (Royal College of Radiologists…
- 1 August 2007
This paper reviews the pre-clinical data and discusses the clinical studies that have been reported on the development of bioreductive drugs that are specifically designed to target hypoxic tumour cells. Expand
Potential use of the comet assay in the clinical management of cancer.
The potential of the comet assay as a tool for predicting an individual's tumour sensitivity to radiation and to various chemotherapeutic drugs is examined, as well as outlining the usefulness of the assay in assessing oxidative stress within tumours. Expand
Modification of the alkaline Comet assay to allow simultaneous evaluation of mitomycin C-induced DNA cross-link damage and repair of specific DNA sequences in RT4 cells.
- D. McKenna, Massimo Gallus, S. McKeown, C. Downes, V. McKelvey-Martin
- Biology, Medicine
- DNA repair
- 12 August 2003
The results suggest that repair of the TP53 gene region is most rapid within the first 4 h following MMC treatment, and the novel experimental protocol presented here has considerable potential in evaluating DNA damage and sequence-related repair responses to cross-linking agents. Expand
Antitumour prodrug development using cytochrome P450 (CYP) mediated activation.
- L. H. Patterson, S. McKeown, T. Robson, R. Gallagher, S. Raleigh, S. Orr
- Chemistry, Medicine
- Anti-cancer drug design
- 1 December 1999
This study shows that freshly isolated murine T50/80 mammary carcinoma and RIF-1 fibrosarcoma 4-electron reduces AQ4N to its cytotoxic metabolite, AQ4, and suggests that cyp3A protein is stabilized in the absence of air, despite a decrease in cyP3A mRNA, which is a particularly interesting application of CYPs for tumour-specific prodrug activation. Expand
AQ4N: an alkylaminoanthraquinone N-oxide showing bioreductive potential and positive interaction with radiation in vivo.
- S. McKeown, M. Hejmadi, I. A. McIntyre, J. McAleer, L. H. Patterson
- Biology, Medicine
- British Journal of Cancer
- 1 July 1995
AQ4N shows significant potential as a bioreductive drug for combination with fractionated radiotherapy in mice bearing the T50/80 mammary carcinoma and was potentiated in vivo by combination with hypobaric hypoxia with a dose enhancement ratio of 5.1. Expand
Enhancement of chemotherapy and radiotherapy of murine tumours by AQ4N, a bioreductively activated anti-tumour agent
In combination with chemotherapy it is shown that AQ4N potentiates the activity of cyclophosphamide, cisplatin and thiotepa, and provides indirect evidence that in the combination chemotherapy experiments there is some tumour selectivity in the enhanced action of the drugs. Expand