Circulating endothelial cells as a therapeutic marker for thalidomide in combined therapy with chemotherapy drugs in a human prostate cancer model
Article first published online: 7 DEC 2007
© 2007 BJU INTERNATIONAL; NO CLAIM TO ORIGINAL US GOVERNMENT WORKS
Volume 101, Issue 7, pages 884–888, April 2008
How to Cite
Li, H., Raia, V., Bertolini, F., Price, D. K. and Figg, W. D. (2008), Circulating endothelial cells as a therapeutic marker for thalidomide in combined therapy with chemotherapy drugs in a human prostate cancer model. BJU International, 101: 884–888. doi: 10.1111/j.1464-410X.2007.07342.x
- Issue published online: 8 JAN 2008
- Article first published online: 7 DEC 2007
- Accepted for publication 7 September 2007
- prostate cancer;
- endothelial cells;
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.
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.
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.