D.G. Moon

NVP-BEZ235, a dual PI3K/mTOR inhibitor synergistically potentiates the antitumor effects of cisplatin in bladder cancer cells

The PI3K/Akt/mTOR pathway is a prototypic survival pathway and constitutively activated in many malignant conditions. Moreover, activation of the PI3K/Akt/mTOR pathway confers resistance to various cancer therapies and is often associated with a poor prognosis. In this study, we explored the antitumor effect of NVP-BEZ235, a dual PI3K/mTOR inhibitor in cisplatin-resistant human bladder cancer cells and its synergistic interaction with cisplatin. A human bladder cancer cell line with cisplatin resistance was exposed to escalating doses of NVP-BEZ235 alone or in combination with cisplatin and antitumor effects was determined by the CCK-8 assay. Based on a dose-response study, synergistic interaction between NVP-BEZ235 and cisplatin was evaluated by combination index (CI), three-dimensional model and clonogenic assay. The combination of NVP-BEZ235 and cisplatin caused significant synergistic antitumor effect in cisplatin-resistant bladder cancer cells over a wide dose range and reduced the IC50 of NVP-BEZ235 and cisplatin by 5.6- and 3.6-fold, respectively. Three-dimensional synergy analysis resulted in a synergy volume of 388.25 μM/ml2% indicating a strong synergistic effect of combination therapy. The combination therapy caused cell cycle arrest and caspase-dependent apoptosis. Although NVP-BEZ235 suppressed PI3K/mTOR signaling without any paradoxical induction of Akt activity, it caused MEK/ERK pathway activation. The present study demonstrated that the PI3K/mTOR dual inhibitor NVP-BEZ235 can synergistically potentiate the antitumor effects of cisplatin in cisplatin-resistant bladder cancer cells though the suppression of cell cycle progression and the survival pathway as well as induction of caspase-dependent apoptosis.

Adenovirus‐mediated suicide‐gene therapy using the herpes simplex virus thymidine kinase gene in cell and animal models of human prostate cancer: changes in tumour cell proliferative activity

Objectives To determine the feasibility and efficacy of suicide‐gene therapy using adenovirus (Ad)‐mediated herpes simplex virus thymidine kinase (HSV‐TK) and the prodrug acyclovir, and to evaluate changes in the biological phenotype for tumour cell proliferative activity after suicide‐gene therapy in animal models of human prostate cancer.

The effects of a selective noradrenaline reuptake inhibitor on the urethra: an in vitro and in vivo study

Objective To identify the effects of a selective noradrenaline reuptake inhibitor (venlafaxine) on urethral perfusion pressure (UPP) in rabbits and rats, and thus assess its therapeutic potential for treating stress urinary incontinence.

The influence of prostate volume on the prostate-specific antigen (PSA) level adjusted for the transition zone volume and free-to-total PSA ratio: a prospective study.

Objectives To evaluate the influence of prostate volume on the prostate‐specific antigen (PSA) level adjusted for the transition zone volume (PSAT) and free‐to‐total PSA ratio (f/tPSA) in detecting prostate cancer in men with intermediate PSA levels of 4.1–10.0u2003ng/mL.

Effect of Preoperative Low Maximal Flow Rate on Postoperative Voiding Trials after the Midurethral Sling Procedure in Women with Stress Urinary Incontinence

To evaluate the effects of preoperative low maximal flow rate (Qmax) on voiding trials after the midurethral sling (MUS) procedure in women with stress urinary incontinence (SUI).