The present study strongly suggests that an antibody to TGF-beta is a promising agent to prevent renal tubular fibrosis and apoptosis in UUO.

Summary This study was undertaken to investigate the intracellular induction of reactive oxygen species (ROS) by cis-dichlorodiammineplatinum (CDDP) and the augmentation of their cytotoxicity in bladder cancer cells (KU7) by enhancement of ROS generation by the glutathione (GSH) depletors buthionine sulphoximine (BSO) and diethylmaleate (DEM). CDDP-induced cytotoxicity in KU7 cells and its modulation by GSH depletors were determined using spectrophotometric measurement with crystal violet staining. The effects of GSH depletors on intracellular GSH levels were confirmed using the GSH reductase-DTNB recycling method. Intracellular ROS generation induced by CDDP with or without GSH depletors was estimated from the amount of intracellular dichlorofluorescein (DCF), an oxidized product of dichlorofluorescein (DCFH), which was measured with an anchored cell analysis and sorting system. The cytotoxic effects of CDDP (IC50 15.0 ± 2.5 gIM) were significantly enhanced by BSO (IC50 9.3 ± 2.6 gM, P < 0.01) and DEM (IC50 10.3 ± 0.3 gM, P < 0.01). BSO and DEM produced a significant depletion in intracellular GSH levels (9.6 ± 0.4 nmol 10-6 cells, 17.9 ± 1.0 nmol 10-6 cells) compared with the controls (30.5 ± 0.6 nmol 10-6 cells). Intracellular DCF production in KU7 cells treated with CDDP (1.35 ± 0.33 g1M) was significantly enhanced by the addition of BSO (4.43 ± 0.33 gM) or DEM (3.12 ± 0.22 gM) at 150 min. These results suggest that ROS may play a substantial role in CDDPinduced cytotoxicity and that GSH depletors augment its cytotoxicity through an enhancement of ROS generation in bladder cancer cells.

Candesartan exerted preventive effects on HRPC, rather than on androgen-sensitive PCa, through the inhibition of tumor angiogenesis.

This study demonstrated that stone size, location and number are significant predictors of extracorporeal shock wave lithotripsy outcome. We have developed nomograms for predicting the stone-free rate of extracorporeal shock wave lithotripsy, which is useful for counseling patients with urolithiasis before surgery.

On image analysis preoperative hydronephrosis grade was associated with features of aggressive disease and predicted an advanced pathological outcome in patients with upper tract urothelial carcinoma. This information could prove useful to select candidates for neoadjuvant chemotherapy and make decisions concerning surgical options.

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These results suggest that mechanical stretch is related to renal tubular apoptosis and that NO plays a protective role in this system in UUO.

Purpose: There have been several studies on the antitumor activity of angiotensin II type 1 receptor (AT1R) antagonists. In this study, we evaluated the efficacy of the AT1R antagonist candesartan in bladder cancer. Experimental Design: For the study in vitro, human bladder cancer cells (KU-19-19) were cultured with or without angiotensin II and candesartan. Various cytokines and cell viability were analyzed. For the study in vivo, a tumor xenograft model was prepared in nude mice using KU-19-19 cells. Mice were given candesartan daily by oral gavage. Microvessel density, expression of vascular endothelial growth factor (VEGF), and apoptosis were assessed. Results: Candesartan did not induce direct toxicity in KU-19-19 cells, but VEGF and interleukin-8 were significantly lower in candesartan-treated cells (2.55 ± 0.25 and 6.58 ± 0.48 pg/103 cells) than in the angiotensin II–treated control cells (3.16 ± 0.42 and 7.91 ± 0.69 pg/103 cells). In mice, candesartan both at doses of 2 and 10 mg/kg/d significantly suppressed tumor growth in mice (35.4% and 33.5% reduction in tumor volume). Microvessel density was significantly decreased by candesartan (9.8 ± 2.8 per field) compared with the control group (17.6 ± 6.0 per field), and VEGF expression was significantly suppressed by this AT1R antagonist. However, candesartan did not induce apoptosis of cancer cells in the tumor. Conclusions: Specific blockade of AT1R prevented bladder tumor growth by inhibiting angiogenesis. However, its antitumor effect was not due to direct toxicity. Because AT1R antagonists are widely used to treat hypertension, and a 2 mg/kg/d dose level of candesartan is clinically achievable, this AT1R antagonist could also be used to treat bladder cancer.