This evidence challenges conventional knowledge of the mechanism of action of alpha(1)-adrenoceptor antagonists, and points to a new therapeutic value for these drugs by providing a differential molecular basis for their anti-tumor efficacy. The present review focuses on the characterization of the apoptotic/anti-angiogenic effect of quinazoline-based alpha(1)-adrenoceptor antagonists against prostate cancer cells and discusses the clinical significance of this action in the prevention and treatment of prostate cancer.
Prostate cancer is the second most common cause of cancer death in men in the United States. Patients with prostate cancer are initially treated with surgical resection, radiation or antiandrogen therapy. After an initial remission however, the majority of prostate tumors evolve into a highly aggressive, metastatic androgen-independent state for which successful therapy has not yet been established. During recent years, new perspectives have emerged towards the development of preventive and therapeutic approaches for prostate cancer. The quinazoline-based α 1 -blockers have been shown to have antitumor efficacy against prostate cancer cells via their potency to induce apoptosis and anoikis via an α 1 -adrenoceptor-independent mechanism. Specifically, doxazosin and terazosin can induce apoptosis, inhibit invasion and migration of prostate cancer cells and endothelial cells and reduce their adhesion potential to extracellular matrix components (ECM), thus enhancing their susceptibility to anoikis. In this review we discuss recent evidence suggesting the apoptotic efficacy of quinazoline-based α 1 adrenoceptor antagonists, doxazosin and terazosin and we speculate on the therapeutic promise of these drugs as novel antitumor agents against prostate cancer. From a drug discovery perspective, separation of the effect of doxazosin on apoptosis in prostate cancer cells from its original pharmacological activity in normal prostate cells, will provide a molecular basis to develop a novel class of apoptosis-inducing agents through lead optimization.
Urinothorax (UT) is a rare and often undiagnosed condition, defined as the presence of urine in the pleural cavity due to the retroperitoneal leakage of urine accumulation, known as urinoma, into the pleural space. UT usually is a transudative pleural effusion that presents in patients with obstructive uropathy and it may occur following surgical procedures in the ureter or kidney such as ESWL, PCNL, and URS. Its diagnosis requires a high degree of clinical suspicion since the respiratory symptoms tend to be absent or mild and the urological signs tend to dominate. However, UT may rarely present with severe and acute dyspnea as well. The objectives of this study are to describe two new cases of this rare entity, a bilateral case and an ipsilateral case focusing on the side that occurs according to the affected renal insult, and to alert the physicians to include UT in their differential diagnosis of pleural effusions especially in patients with recent urinary tract disorders.
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 alpha 1 -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.
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