Effect of terazosin on tissue vascularity and apoptosis in transitional cell carcinoma of bladder.
OBJECTIVE
To present a pilot study to determine whether the alpha1-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.
Tahmatzopoulos
Anastasios
A
Department of Surgery, Markey Cancer Center, University of Kentucky Medical Center, Lexington, Kentucky, USA.
Lagrange
Chad A
CA
Zeng
Li
L
Mitchell
Bonnie L
BL
Conner
William T
WT
Kyprianou
Natasha
N
D000317:Adrenergic alpha-Antagonists; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002295:Carcinoma, Transitional Cell / Q000098:blood supply / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007633:Keratins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011224:Prazosin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001749:Urinary Bladder Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology*
D000317:Adrenergic alpha-Antagonists; D000970:Antineoplastic Agents; D007633:Keratins; C041226:Terazosin; D011224:Prazosin