Effect of terazosin on tissue vascularity and apoptosis in transitional cell carcinoma of bladder

Anastasios Tahmatzopoulos, Chad A. LaGrange, Li Zeng, Bonnie L. Mitchell, William T. Conner, Natasha Kyprianou

Research output: Contribution to journalArticle

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Abstract

Objectives. To present a pilot study to determine whether the alpha 1-adrenoceptor antagonist terazosin can induce apoptosis in transitional cell carcinoma (TCC) of the bladder, similar to the effect seen with prostate cancer. The alpha1-adrenoceptor antagonist terazosin has recently been shown to induce apoptosis in prostate cancer cells both in vitro and in vivo and to reduce prostatic tissue vascularity by potentially affecting endothelial cell adhesion. Methods. The records of 24 men who underwent radical cystectomy for TCC of the bladder at the Lexington Veterans Affairs Medical Center were reviewed. The control group consisted of 15 men who were never exposed to terazosin. The study group consisted of 9 men who were treated with terazosin before cystectomy. Sections of the bladder tumor and normal trigone were subjected to immunohistochemical analysis for microvessel density, endothelial cell CD31 expression, and apoptosis detection (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling), as well as high-molecular-weight cytokeratin staining. Results. A significant reduction in tissue vascularity (14.0 versus 19.2, P <0.05) and a significant increase in the apoptotic index (3.0% versus 1.7%, P <0.05) was detected in terazosin-treated bladder tumors compared with untreated bladder tumors. Most TCC specimens (80%) exhibited strong and consistently uniform immunostaining for high-molecular-weight cytokeratin staining. Conclusions. These results suggest that terazosin reduces tumor vascularity and induces apoptosis in TCC of the bladder. Additional studies with more patients are necessary to reach definitive conclusions. However, considering the proven apoptotic action of terazosin in prostatic tissue, this study may have implications for the use of terazosin in the treatment of bladder TCC.

Original languageEnglish (US)
Pages (from-to)1019-1023
Number of pages5
JournalUrology
Volume65
Issue number5
DOIs
StatePublished - May 2005

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Terazosin
Transitional Cell Carcinoma
Urinary Bladder
Apoptosis
Urinary Bladder Neoplasms
Cystectomy
Keratins
Adrenergic Receptors
Prostatic Neoplasms
Endothelial Cells
Molecular Weight
Staining and Labeling
DNA Nucleotidylexotransferase
Veterans
Microvessels

ASJC Scopus subject areas

  • Urology

Cite this

Effect of terazosin on tissue vascularity and apoptosis in transitional cell carcinoma of bladder. / Tahmatzopoulos, Anastasios; LaGrange, Chad A.; Zeng, Li; Mitchell, Bonnie L.; Conner, William T.; Kyprianou, Natasha.

In: Urology, Vol. 65, No. 5, 05.2005, p. 1019-1023.

Research output: Contribution to journalArticle

Tahmatzopoulos, A, LaGrange, CA, Zeng, L, Mitchell, BL, Conner, WT & Kyprianou, N 2005, 'Effect of terazosin on tissue vascularity and apoptosis in transitional cell carcinoma of bladder', Urology, vol. 65, no. 5, pp. 1019-1023. https://doi.org/10.1016/j.urology.2004.12.015
Tahmatzopoulos, Anastasios ; LaGrange, Chad A. ; Zeng, Li ; Mitchell, Bonnie L. ; Conner, William T. ; Kyprianou, Natasha. / Effect of terazosin on tissue vascularity and apoptosis in transitional cell carcinoma of bladder. In: Urology. 2005 ; Vol. 65, No. 5. pp. 1019-1023.
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abstract = "Objectives. To present a pilot study to determine whether the alpha 1-adrenoceptor antagonist terazosin can induce apoptosis in transitional cell carcinoma (TCC) of the bladder, similar to the effect seen with prostate cancer. The alpha1-adrenoceptor antagonist terazosin has recently been shown to induce apoptosis in prostate cancer cells both in vitro and in vivo and to reduce prostatic tissue vascularity by potentially affecting endothelial cell adhesion. Methods. The records of 24 men who underwent radical cystectomy for TCC of the bladder at the Lexington Veterans Affairs Medical Center were reviewed. The control group consisted of 15 men who were never exposed to terazosin. The study group consisted of 9 men who were treated with terazosin before cystectomy. Sections of the bladder tumor and normal trigone were subjected to immunohistochemical analysis for microvessel density, endothelial cell CD31 expression, and apoptosis detection (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling), as well as high-molecular-weight cytokeratin staining. Results. A significant reduction in tissue vascularity (14.0 versus 19.2, P <0.05) and a significant increase in the apoptotic index (3.0{\%} versus 1.7{\%}, P <0.05) was detected in terazosin-treated bladder tumors compared with untreated bladder tumors. Most TCC specimens (80{\%}) exhibited strong and consistently uniform immunostaining for high-molecular-weight cytokeratin staining. Conclusions. These results suggest that terazosin reduces tumor vascularity and induces apoptosis in TCC of the bladder. Additional studies with more patients are necessary to reach definitive conclusions. However, considering the proven apoptotic action of terazosin in prostatic tissue, this study may have implications for the use of terazosin in the treatment of bladder TCC.",
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AB - Objectives. To present a pilot study to determine whether the alpha 1-adrenoceptor antagonist terazosin can induce apoptosis in transitional cell carcinoma (TCC) of the bladder, similar to the effect seen with prostate cancer. The alpha1-adrenoceptor antagonist terazosin has recently been shown to induce apoptosis in prostate cancer cells both in vitro and in vivo and to reduce prostatic tissue vascularity by potentially affecting endothelial cell adhesion. Methods. The records of 24 men who underwent radical cystectomy for TCC of the bladder at the Lexington Veterans Affairs Medical Center were reviewed. The control group consisted of 15 men who were never exposed to terazosin. The study group consisted of 9 men who were treated with terazosin before cystectomy. Sections of the bladder tumor and normal trigone were subjected to immunohistochemical analysis for microvessel density, endothelial cell CD31 expression, and apoptosis detection (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling), as well as high-molecular-weight cytokeratin staining. Results. A significant reduction in tissue vascularity (14.0 versus 19.2, P <0.05) and a significant increase in the apoptotic index (3.0% versus 1.7%, P <0.05) was detected in terazosin-treated bladder tumors compared with untreated bladder tumors. Most TCC specimens (80%) exhibited strong and consistently uniform immunostaining for high-molecular-weight cytokeratin staining. Conclusions. These results suggest that terazosin reduces tumor vascularity and induces apoptosis in TCC of the bladder. Additional studies with more patients are necessary to reach definitive conclusions. However, considering the proven apoptotic action of terazosin in prostatic tissue, this study may have implications for the use of terazosin in the treatment of bladder TCC.

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