Silodosin appears to improve detrusor overactivity and obstruction grade in patients with BPH. With silodosin treatment, LUTS could be managed effectively for more than a year in at least 44% of the patients.

To clarify the role of the Rho small GTP-binding protein (Rho) and its major downstream target, ROCK (Rho-associated serine-threonine protein kinase), in progression of renal cell carcinoma (RCC), we examined mRNA expression for Rho and ROCK genes in surgical specimen of RCC tissues from 78 Japanese patients and in the corresponding non-tumor tissues originating from the same patient using a real-time reverse transcription polymerase chain reaction (RT-PCR). Expression of mRNA for RhoA did not differ between tumor and non-tumor tissues. RhoB mRNA expression was higher in the tumor (P < 0.05), but expression was not associated with tumor grade, stage, or prognosis. However, degree of RhoC and ROCK mRNA expression was related to tumor grade (P < 0.05) and stage (P < 0.0001). A positive relationship was seen between expression of mRNA for RhoC and that for ROCK in tumor tissues (P < 0.0001). Kaplan-Meier plots showed high RhoC and ROCK mRNA expression to be negatively associated with overall survival (P < 0.0001). Multivariate analysis showed mRNA expression of RhoC and ROCK to be independent poor prognostic factors concerning overall survival. Our findings implicate the RhoC/ROCK pathway in carcinogenesis and progression of RCC, indicating that RhoC/ROCK may be a useful prognostic marker and a possible molecular target for treatment of the disease.Annual estimates of new diagnoses of renal cell carcinoma (RCC) are increasing steadily (17). RCC is resistant to chemotherapy and radiotherapy (17,28,29), while immunotherapy with interferon and/or interleukin (IL)-2 achieves responses in 10% to 20% of advanced RCC (17, 18). Although surgical resection of the primary tumor for patients remains the mainstay of therapy, RCC is characterized by a high proportion of cases with metastases present at diagnosis or appearing as a relapse following nephrectomy. Patients with distant metastases have a poor prognosis, with a 5-year survival rate of less than 10% in stage IV disease (17). Although inhibition of metastases logically would be a promising treatment strategy in advanced RCC, much of the molecular mechanism of progression and metastasis in RCC is yet to be eluidated.Cell migration is central to metastasis of malignant tumors (20). The Rho small GTP-binding protein (Rho) regulates formation of stress fibers, focal adhesions, and cell migration through reorganization of the actin cytoskeleton (7,25). Overexpression of Rho in human cancer tissues in comparison to nontumor tissues has been reported, with higher expression of Rho correlating with higher stage (6,13,24). Several lines of evidence directly link Rho to acquisition of a migratory, invasive, and metastatic phenotype (2, 3). Furthermore, Rho-kinase (ROCK), one of the major downstream effectors of Rho, induces stress-fiber formation and assembly for focal contact by regulating contractility of the actin-myo-

Silodosin appears to be effective for both storage and voiding symptoms by increasing bladder capacity in patients with LUTS/BPH.

Objectives:To assess the incidence of detrusor overactivity and reproducibility of data from ambulatory urodynamic monitoring (AUM) in male volunteers. Methods: Sixteen asymptomatic healthy male volunteers with a mean age of 26.3 years (range: 22-30) underwent AUM by natural filling cystometry followed by a pressure/flow study. The studies were repeated three times. Results: Detrusor overactivity (DO) was detected in six subjects (37.5%), but clinically significant detrusor overactivity was noted only in three (18.8%). Q max , detrusor opening pressure, and P det Q max were similar among the three measurements. The bladder outlet obstruction index (BOOI) varied, and there was a significant difference between the first and third measurements (P = 0.0371). Obstruction grade was ranked as unobstructed in all studies for 13 subjects, equivocal (BOOI 45 and 46) in one subject, and both unobstructed and equivocal (BOOI 30, 43 and 30) in one subject. There was a significant difference in bladder contractility index (BCI) between the first and third studies (P = 0.0186). The BCI was always strong in five subjects, always normal in eight subjects, and strong to normal in three subjects. Conclusion: DO was found in 37.5% of male volunteers. BOOI and BCI may not be highly reproducible, and the third study may provide the best result if the first and second studies differ. However, 87.5% of subjects were rated as unobstructed and all subjects were rated as normal or strong, with the categories of obstruction and bladder contractility showing no change in most subjects. AUM with three studies seem adequate for the evaluation of lower urinary tract dysfunction in males.

Objectives:To investigate the effects of fasudil, a Rho-associated serine-threonine protein kinase inhibitor, on contraction of the pig urinary bladder tissues with or without urothelium. Methods: Cumulative concentration-response curves (CRCs) to carbachol were obtained with and without 3-10 mM fasudil. Drug effects were evaluated in detrusor with and without urothelium. Inhibitory responses to fasudil were also examined in tissues precontracted with KCl and carbachol, and in response to electrical field stimulation, in pig bladder with and without urothelium. Results: In detrusor without urothelium, maximum contraction (Emax) decreased after administration of fasudil at 3 or 10 mmol/L (both P < 0.01), or 30 mmol/L (72.5 Ϯ 7.43%, 58.4 Ϯ 8.04% and 68.4 Ϯ 9.6%, respectively, of the first curve). In detrusor with urothelium, Emax decreased significantly (all P < 0.05) after the addition of 3, 10 or 30 mmol/L of fasudil (84.9 Ϯ 6.7%, 67.9 Ϯ 5.2% and 35.2 Ϯ 4.1%, respectively). In tissues precontracted with 80 mmol/L KCl or 100 mmol/L carbachol, tension after administration of fasudil (1 nmol/L to 100 mmol/L) decreased (by approximately 40%), only after administration of fasudil at high concentration (>1 mmol/L), in detrusor both with and without urothelium. In tissues with and without urothelium, responses to electrical field stimulation at 1-50 Hz decreased significantly in a concentrationdependent manner after addition of fasudil (3 to 30 mmol/L). Conclusions: Fasudil seems to provoke relaxation of the bladder detrusor via both urothelium-dependent and independent pathways.