Annals of Oncology Advance Access originally published online on September 28, 2006
Annals of Oncology 2006 17(11):1625-1630; doi:10.1093/annonc/mdl283
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© 2006 European Society for Medical Oncology
head and neck cancer |
Celecoxib reduces microvessel density in patients treated with nasopharyngeal carcinoma and induces changes in gene expression
1 Department of Haematology–Oncology, National University Hospital, Singapore
2 Department of Medicine, National University Hospital, Singapore
3 Department of Otolaryngology–Head and Neck Surgery, National University Hospital, Singapore
4 Cellular and Molecular Research, National Cancer Centre, Singapore
5 Cancer Epigenetics/Tumor Virology Laboratory, Prince of Wales Hospital, Hong Kong
6 Tumor Virology Laboratory, Johns Hopkins in Singapore, Singapore
7 Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
* Correspondence to: Dr R. A. Soo, Department of Haematology–Oncology, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074. Tel: +65 6772 4621; Fax: +65 6777 5545; E-mail: Ross_SOO{at}nuh.com.sg
Background: Celecoxib is a selective cyclooxygenase-2 inhibitor with antitumor and antiangiogenic activity. We sought to determine pharmacodynamic change in tumors of patients with nasopharyngeal carcinoma (NPC) treated with celecoxib.
Methods: Tumor biopsies were obtained before and after treatment with celecoxib 400 mg b.i.d. for 14 days in patients with newly diagnosed, untreated NPC. Tumor angiogenesis and cell proliferation were assessed by immunohistochemistry and gene expression by microarray analysis. Plasma celecoxib concentrations were obtained on days 8 and 14.
Results: Paired samples were analyzed in 15 patients. Microvessel density was reduced in post-treatment samples and mean celecoxib levels reached therapeutic levels. Thirty-five genes (27 down-regulated, eight up-regulated) were differentially expressed on microarray analysis (p < 0.001). Down-regulated genes included cell cycle regulation-related (cyclin-dependent kinase 2, YES1), transcription factor (TRIP-Br2), whereas the antigen processing and presentation-related gene HLA-DM B was up-regulated.
Conclusion: Celecoxib reduced angiogenesis and induced tumor transcriptional changes. Further characterization of these transcriptional changes in vivo is needed to provide further insights into the effects of celecoxib in neoplastic tissue. Our findings provide a rationale for clinical studies aimed at assessing the efficacy of celecoxib in the treatment of NPC.
Key words: antiangiogenesis, celecoxib, gene expression, nasopharyngeal carcinoma
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