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A novel strategy for NQO1 (NAD(P)H:quinone oxidoreductase, EC 1.6.99.2) mediated therapy of bladder cancer based on the pharmacological properties of EO9
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  • Open access
  • Published: 16 October 2001

A novel strategy for NQO1 (NAD(P)H:quinone oxidoreductase, EC 1.6.99.2) mediated therapy of bladder cancer based on the pharmacological properties of EO9

  • G A Choudry1,2,3,
  • P A Hamilton Stewart3,
  • J A Double1,
  • M R L Krul5,
  • B Naylor4,
  • G M Flannigan3,
  • T K Shah3,
  • J E Brown2 &
  • …
  • R M Phillips1 

British Journal of Cancer volume 85, pages 1137–1146 (2001)Cite this article

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Abstract

The indolequinone EO9 demonstrated good preclinical activity but failed to show clinical efficacy against a range of tumours following intravenous drug administration. A significant factor in EO9's failure in the clinic has been attributed to its rapid pharmacokinetic elimination resulting in poor drug delivery to tumours. Intravesical administration of EO9 would circumvent the problem of drug delivery to tumours and the principal objective of this study is to determine whether or not bladder tumours have elevated levels of the enzyme NQO1 (NAD(P)H:quinone oxidoreductase) which plays a key role in activating EO9 under aerobic conditions. Elevated NQO1 levels in human bladder tumour tissue exist in a subset of patients as measured by both immunohistochemical and enzymatic assays. In a panel of human tumour cell lines, EO9 is selectively toxic towards NQO1 rich cell lines under aerobic conditions and potency can be enhanced by reducing extracellular pH. These studies suggest that a subset of bladder cancer patients exist whose tumours possess the appropriate biochemical machinery required to activate EO9. Administration of EO9 in an acidic vehicle could be employed to reduce possible systemic toxicity as any drug absorbed into the blood stream would become relatively inactive due to an increase in pH. © 2001 Cancer Research Campaign http://www.bjcancer.com

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  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

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Author information

Authors and Affiliations

  1. Cancer Research Unit, Bradford, BD7 1DP

    G A Choudry, J A Double & R M Phillips

  2. Department of Pharmaceutical Chemistry, University of Bradford, Bradford, BD7 1DP

    G A Choudry & J E Brown

  3. Department of Urology, Bradford, BD9 6RJ

    G A Choudry, P A Hamilton Stewart, G M Flannigan & T K Shah

  4. Department of Histopathology, Bradford NHS Trust, Bradford, BD9 6RJ

    B Naylor

  5. Department of Medical & Scientific Affairs, NDDO Oncology, Amsterdam

    M R L Krul

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From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

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Choudry, G., Stewart, P., Double, J. et al. A novel strategy for NQO1 (NAD(P)H:quinone oxidoreductase, EC 1.6.99.2) mediated therapy of bladder cancer based on the pharmacological properties of EO9. Br J Cancer 85, 1137–1146 (2001). https://doi.org/10.1054/bjoc.2001.2056

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  • Received: 19 January 2001

  • Revised: 03 June 2001

  • Accepted: 04 July 2001

  • Published: 16 October 2001

  • Issue Date: 19 October 2001

  • DOI: https://doi.org/10.1054/bjoc.2001.2056

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Keywords

  • bioreductive drugs: EO9
  • mitomycin C: bladder cancer
  • NQO1

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