Circulating endothelial cells as a therapeutic marker for thalidomide in combined therapy with chemotherapy drugs in a human prostate cancer model

Haiqing Li, Valentina Raia, Francesco Bertolini, Douglas K. Price, William D. Figg

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: To investigate how thalidomide confers its survival benefit in prostate cancer, by assessing its effect on circulating endothelial cells (CECs) and progenitors (CEPs) in a combined therapy of thalidomide and chemotherapy drugs in a human prostate cancer xenograft model, as in clinical trials patients treated with both thalidomide and docetaxel had a >50% decrease in prostate-specific antigen (PSA) levels and longer median overall survival than those treated with docetaxel monotherapy. MATERIALS AND METHODS: A human prostate cancer xenograft model was used to evaluate the effect of either thalidomide, docetaxel or a combination of the two drugs on circulating ECs. Drug treatment was continued for 17 days, and tumours were measured two or three times a week. Blood samples were taken at three different time points: before the treatments, 4 days and 17 days into the treatments, and CECs and CEPs were measured by flow cytometry analysis. RESULTS: There was an increased level of apoptotic/dead CECs shortly after the intravenous injection of docetaxel, and the addition of thalidomide further increased the apoptotic/dead CEC level, showing that thalidomide enhances the cytotoxicity of docetaxel against tumour vascular ECs. CONCLUSION: Thalidomide increased the apoptotic/dead CEC level and enhanced the cytotoxicity of docetaxel against tumour vascular ECs, confirming its antiangiogenic property in vivo in combined anticancer treatments. In addition, there was a correlation between the increased apoptotic/dead CEC levels early in the treatment and antitumour efficacy later, suggesting that the apoptotic/dead CEC level could be used as a marker, at an early stage, to predict tumour response to antiangiogenic therapies.

Original languageEnglish
Pages (from-to)884-888
Number of pages5
JournalBJU International
Volume101
Issue number7
DOIs
Publication statusPublished - Apr 2008

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Keywords

  • Angiogenesis
  • Docetaxel
  • Endothelial cells
  • Prostate cancer
  • Thalidomide

ASJC Scopus subject areas

  • Urology

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