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Antiangiogenic activity of the selective cyclooxygenase 2 inhibitor rofecoxib in human colorectal cancer liver metastases
  1. C R Chalmers1,
  2. D J Wilson2,
  3. J Ward3,
  4. P J Robinson3,
  5. G J Toogood4,
  6. M A Hull5
  1. 1Leeds Institute of Molecular Medicine, University of Leeds, St James’s University Hospital, Leeds, UK
  2. 2Department of Medical Physics, St James’s University Hospital, Leeds, UK
  3. 3Department of Radiology, St James’s University Hospital, Leeds, UK
  4. 4Department of Hepatobiliary Surgery, St James’s University Hospital, Leeds, UK
  5. 5Leeds Institute of Molecular Medicine, University of Leeds, St James’s University Hospital, Leeds, UK
  1. Correspondence to:
    Professor M A Hull
    Molecular Gastroenterology, Leeds Institute of Molecular Medicine, University of Leeds, St James’s University Hospital, Leeds LS9 7TF, UK; M.A.Hull{at}leeds.ac.uk

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We have previously reported that colorectal cancer (CRC) liver metastases from patients, who had received the selective cyclooxygenase 2 (COX-2) inhibitor rofecoxib (Vioxx) 25 mg daily for a mean period of 26 days, had a 31% lower mean microvessel density compared with tumours from individuals who had received placebo only.1 These data suggest that one mechanism of action of rofecoxib in human CRC liver metastases might be inhibition of angiogenesis. Therefore, we investigated the potential antiangiogenic activity of rofecoxib in human CRC liver metastases by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), before and after treatment with oral rofecoxib 25 mg daily for 28 days. As short term treatment of rats with the selective COX-2 inhibitor celecoxib is associated with an increase in serum levels of the endogenous antiangiogenic factor endostatin,2 we also measured serum levels of endostatin and the proangiogenic factor vascular endothelial growth factor (VEGF), at the same time as DCE-MRI.

Patients undergoing liver resection of CRC liver metastases were enrolled if diagnostic MRI identified a single metastasis greater than 1.5 cm …

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