Woo Suk Choi

Cytotoxic effects of escin on human castration-resistant prostate cancer cells through the induction of apoptosis and G2/M cell cycle arrest.

OBJECTIVE To evaluate the in vitro and in vivo effects of escin on human castration-resistant prostate cancer (CRPC) cells, PC-3 and DU-145. MATERIALS AND METHODS The inhibition of cell proliferation and its mechanism were assessed through a cytotoxicity assay, flow cytometry, and Western blot. The in vivo efficacy of escin in CRPC cells was assessed using a xenograft tumor model subcutaneously established in BALB/c nude mice. RESULTS The treatment with escin significantly reduced cell viability of CRPC cells in a dose- and time-dependent manner. Escin induced apoptosis in a time-dependent manner, which was accompanied by increases in pro-apoptotic (BCL-2 associated X protein, cleaved-caspase3, and cleaved-poly [adenosine diphosphate-ribose] polymerase) proteins and decreases in antiapoptotic (X-linked inhibitor of apoptosis protein, cellular inhibitor of apoptosis protein-1, cellular inhibitor of apoptosis protein-2B-cell leukemia/lymphoma-2, and B-cell lymphoma-extra large) proteins. Escin induced G2/M-phase cell cycle arrest and thus led to a significant decrease in the expression of cyclinB1 and its activating partner cyclin-dependent kinase 1, with the concomitant induction of p21. In addition, escin significantly inhibited the growth of CRPC cells in xenograft models. CONCLUSION The results show that escin induced cytotoxic effects on CRPC cells through the induction of apoptosis and G2/M cell cycle arrest, indicating it may be a novel therapeutic agent for CRPC.

S100A3 suppression inhibits in vitro and in vivo tumor growth and invasion of human castration-resistant prostate cancer cells.

OBJECTIVE To investigate the role of S100A3 and the effect of S100A3 inhibition on human castration-resistant prostate cancer (CRPC) cells by using in vitro and in vivo functional assays. MATERIALS AND METHODS Using human CRPC cells (PC3 and DU145), S100A3 expression levels were assessed by reverse transcription-polymerase chain reaction and Western blot analysis. After S100A3-specific small interfering ribonucleic acid (RNA) treatment, cell viability was determined by Cell Counting Kit-8 assay, and apoptotic cell fractions were evaluated by flow cytometry. The invasive properties of these cells and the expression pattern of matrix metalloproteinases (MMPs) were assessed using transwell migration assays, reverse transcription-polymerase chain reaction, and gelatin zymography. Finally, the in vivo efficacy of S100A3 inhibition on human CRPC cells was investigated using human tumor xenograft models in nude mice. RESULTS Human CRPC cells showed overexpression of S100A3, and its suppression reduced cell viability owing to apoptotic cell death. Additionally, S100A3 inhibition decreased the invasiveness of human CRPC cells. Moreover, MMP-2 and MMP-9 were downregulated in PC3, whereas only MMP-9 was downregulated in D145 after S100A3 inhibition. In human CRPC xenograft models, we noted a marked reduction in tumor growth in mice injected with S100A3 short hairpin RNA-transfected PC3 and DU145 cells. CONCLUSION Human CRPC cells showed upregulation of S100A3 expression, and S100A3 inhibition reduced tumor cell viability. S100A3 inhibition reduced invasion capability with downregulation of MMP expression. More importantly, S100A3 inhibition resulted in tumor growth suppression in human CRPC xenograft models, suggesting S100A3 could serve as a novel therapeutic target for the treatment of human CRPC.

Effect of chronic administration of PDE5 combined with glycemic control on erectile function in streptozotocin-induced diabetic rats.

INTRODUCTION Chronic treatment with phosphodiesterase type 5 inhibitors (PDE5) is effective in an animal model of diabetes-induced erectile dysfunction (DMED). In addition, recent research indicates that glycemic control can restore DMED. AIMS We evaluated the effect of chronic administration of PDE5 combined with glycemic control on DMED. METHODS Sprague-Dawley rats (8 weeks old) were divided into five groups (n = 10 each): normal control (C), diabetes (DM), DM treated with insulin (DM-I), DM treated with PDE5 (DM-P), and DM treated with insulin and PDE5 (DM-I + P). Rats in the diabetic groups received an injection of streptozotocin (45 mg/kg). After 10 weeks of induced diabetes, the DM-I group was treated with a daily injection of neutral protamine Hagedorn, and the DM-P group was treated with a daily dosage of 20 mg/kg PDE5 (DA-8159) for 4 weeks. The DM-I + P group was treated with both treatments simultaneously. After 14 weeks of induced diabetes, an evaluation of erectile function and histological and biochemical markers of corporal tissue was performed. MAIN OUTCOME MEASURES Erectile function and histological and biochemical markers in corporal tissue. RESULTS Rats in the DM group showed markedly lower erectile parameters than those in the C group, whereas rats in the DM-I and DM-P groups showed intermediate erectile function between the DM and C groups. Rats in the DM-I + P group showed restored erectile function, comparable with group C. A comparison of apoptotic index, expression of the endothelial marker, and phosphorylation of endothelial nitric oxide synthase and Akt displayed a similar pattern with the results from cavernosometry (DM < DM-I = DM-P < DM-I + P = C, P < 0.05). The distribution of phosphorylated myosin phosphatase target subunit 1 was in the reverse order. CONCLUSIONS Chronic administration of PDE5 or glycemic control with insulin resulted in restoration of overt DMED. The combination of both treatments was superior to monotherapy with insulin or PDE5.

Change of Nocturnal Polyuria After Holmium Laser Enucleation of the Prostate in Patients With Benign Prostatic Hyperplasia

OBJECTIVE To evaluate changes of nocturnal polyuria (NP) after holmium laser enucleation of the prostate (HoLEP) in patients with nocturia preoperatively. PATIENTS AND METHODS This retrospective study included patients who underwent HoLEP for benign prostatic hyperplasia and recorded 3-day frequency-volume chart strictly. Patients who had a history of prostate cancer, sleep apnea, renal failure, heart failure, or medication of desmopressin were excluded. Nocturia is defined as ≥ 1 void at night, and NP is defined by nocturnal polyuria index (NPI) >33%. Among 472 patients included in the final analysis, 352 men (74.6%) presented nocturia preoperatively. Among those, 205 men (58.2%) who had NP preoperatively were allocated to group NP, and 147 men who did not were allocated to group non-NP. RESULTS In total patients, nocturnal frequency was decreased significantly starting from 3 months after the HoLEP. In NP group, mean value of NPI decreased by 4.1% ± 10.7%, 6.0% ± 9.4%, 6.2% ± 9.5%, and 4.8% ± 11.4% at postoperative months 1, 3, 6, and 12, respectively. The proportion of patients who showed decreased NPI to the normal range (≤ 33%) were 32.5%, 36.1%, 37.7%, and 31.0% at postoperative months 1, 3, 6, and 12, respectively. On receiver operating characteristics curve analysis, an absolute reduction of NPI of ≥ 6.0% was shown as a significant predictor for improved nocturia (≥ 50% reduction of nocturnal frequency). CONCLUSION In our study, the improvement of NP after HoLEP was observed. This suggests that relieving lower urinary tract obstruction has a positive influence on NP, and it could be a new strategy for treatment of NP.

Comparison of Effectiveness between Tension-Free Vaginal Tape (TVT) and Trans-Obturator Tape (TOT) in Patients with Stress Urinary Incontinence and Intrinsic Sphincter Deficiency.

Background The aim of this study was to compare the two types of mid-urethral slings for stress urinary incontinence (SUI) with intrinsic sphincter deficiency (ISD). Methods This retrospective study included patients who underwent tension-free vaginal tape (TVT) procedure or transobturator tape (TOT) procedure by a single surgeon for SUI with ISD, defined as Valsalva leak point pressure (VLPP) < 60 cmH2O in a urodynamic study. Cases of neurogenic bladder, previous SUI surgery, and concomitant cystocele repair were excluded. The primary outcome was treatment success at 12 months, defined by self-reported absence of symptoms, no leakage episodes recorded, and no retreatment. Results Among the 157 women who were included in the final analysis, 105 patients received TVT and 52 patients received TOT. Age, underlying diseases, Stamey grade, cystocele grade, and presence of urge incontinence were not significantly different between the two groups. Urodynamic parameters including maximal urethral closing pressure, detrusor overactivity, VLPP, urethral hypermobility (Q-tip ≥ 30°), were also comparable between the two groups. Success rate was significantly higher in the TVT group than in the TOT group (95.2% vs. 82.7%, p = 0.009). On multivariate analysis, only TOT surgery (OR = 3.922, 95%CI = 1.223–12.582, p = 0.022) was a risk factor for failure following surgical treatment. Conclusion TVT is more effective than TOT in treatment of female SUI with ISD.

Varicocele and Testicular Pain: A Review

Varicocele is the dilatation of the scrotal portion of pampiniform plexus and the internal spermatic venous system. About 15% of men suffer from scrotal varicocele and 2% to 10% of them complain of pain. The probable mechanisms for pain include compression of the surrounding neural fibers by the dilated venous complex, elevated testicular temperature, increased venous pressure, hypoxia, oxidative stress, hormonal imbalances, and the reflux of toxic metabolites of adrenal or renal origin. Testicular pain associated with varicoceles is typically described as a dull, aching, or throbbing pain in the testicle, scrotum, or groin; rarely, it can be acute, sharp, or stabbing. The management of testicular pain associated with varicocele starts with a conservative, non-surgical approach and a period of observation. Varicocelectomy in carefully selected candidates with clinically palpable varicocele resolves nearly 80% of all cases of testicular pain. Microsurgical techniques for varicocelectomy have gained popularity with minimal complication rates and favorable outcomes. The grade of varicocele, the nature and duration of pain, body mass index, prior conservative management, and the type of surgical method used, are predictors for the success of varicocelectomy.

Prospective Randomized Controlled Study on the Efficacy of Multimedia Informed Consent for Patients Scheduled to Undergo Green-Light High-Performance System Photoselective Vaporization of the Prostate

Purpose The aim of this study was to evaluate the efficacy of a multimedia informed consent (IC) presentation on the understanding and satisfaction of patients who were scheduled to receive 120-W green-light high-performance system photoselective vaporization of the prostate (HPS-PVP). Materials and Methods A multimedia IC (M-IC) presentation for HPS-PVP was developed. Forty men with benign prostatic hyperplasia who were scheduled to undergo HPS-PVP were prospectively randomized to a conventional written IC group (W-IC group, n=20) or the M-IC group (n=20). The allocated IC was obtained by one certified urologist, followed by a 15-question test (maximum score, 15) to evaluate objective understanding, and questionnaires on subjective understanding (range, 0~10) and satisfaction (range, 0~10) using a visual analogue scale. Results Demographic characteristics, including age and the highest level of education, did not significantly differ between the two groups. No significant differences were found in scores reflecting the objective understanding of HPS-PVP (9.9±2.3 vs. 10.6±2.8, p=0.332) or in subjective understanding scores (7.5±2.1 vs. 8.6±1.7, p=0.122); however, the M-IC group showed higher satisfaction scores than the W-IC group (7.4±1.7 vs. 8.4±1.5, p=0.033). After adjusting for age and educational level, the M-IC group still had significantly higher satisfaction scores. Conclusions M-IC did not enhance the objective knowledge of patients regarding this surgical procedure. However, it improved the satisfaction of patients with the IC process itself.

Clinical outcome of single-incision slings, excluding TVT-Secur, vs standard slings in the surgical management of stress incontinence: an updated systematic review and meta-analysis

The aim of the present paper was to assess and compare the long‐term efficacy and safety of single‐incision mini‐slings (SIMSs), except tension‐free vaginal tape (TVT)‐Secur, with standard midurethral slings (SMUSs) for female stress urinary incontinence through an updated systematic review and meta‐analysis of randomized controlled trials (RCTs) comparing these two surgical methods. A literature review of all RCTs comparing SIMSs (Mini‐Arc, Contasure‐Needleless, Ophira, Tissue Fixation System and Ajust), except TVT‐Secur, with SMUSs was performed. The Medline, Embase, Scopus, Web of Science and Cochrane Controlled Trial Register databases were reviewed. We retrieved 29 RCTs (including a total of 2 986 patients) that compared SIMSs, except TVT‐Secur, with SMUSs. Meta‐analysis of long‐term results showed no significant difference in the patient‐reported cure rate (odds ratio [OR] 0.67, 95% confidence interval [CI] 0.44–1.60); however, we found that SMUSs had a significantly superior objective cure rate (OR 0.68, 95% CI 0.47–0.99; P = 0.04). SIMSs were associated with a significantly shorter operation time, lower immediate postoperative pain based on a visual analogue scale score, lower intra‐operative blood loss, and lower postoperative voiding dysfunction. The meta‐analysis showed clear evidence of the superiority of SMUSs over SIMSs, except TVT‐Secur, in terms of the objective cure rate, after long‐term follow‐up; however, SIMSs were superior with respect to immediate postoperative pain, intra‐operative blood loss, and postoperative voiding dysfunction.

Efficacy and safety of silodosin in the treatment of lower urinary tract symptoms in elderly men taking antihypertensive medications

Background Both hypertension and lower urinary tract symptoms (LUTS) are common conditions in the elderly population. This study investigated the efficacy and safety of silodosin in the treatment of LUTS in elderly men who were taking antihypertensive medications. Methods This is an observational study which collected the medical records of patients who started silodosin medication for their LUTS between April 2015 and December 2015. Inclusion criteria were age ≥ 65 years, currently taking antihypertensive medication, and International Prostate Symptom Score (IPSS) ≥ 8. Pretreatment evaluation included IPSS, Male Sexual Health Questionnaire, systemic symptoms, blood pressure, and uroflowmetry. Post-treatment evaluation was performed 3 months after the initial administration of silodosin medication. Results Mean age of the total 48 patients was 70.7 ± 5.2 years. Thirty-two (66.7%) patients who continued silodosin single treatment showed a significant decrease in IPSS Quality of life scores (4.2 ± 1.1 vs. 3.0 ± 1.6, P = 0.001) and an increase in the maximum flow rate (10.7 ± 6.0 mL/s vs. 14.0 ± 4.5 mL/s, P = 0.001). Blood pressures did not change, and none of the patients needed to adjust their antihypertensive medication. New development of orthostatic hypotension was observed in one (2.5%) patient. Among the six patients who had orthostatic hypotension before silodosin treatment, none of the patients showed symptom aggravation. Ejaculatory dysfunction that required discontinuation of silodosin medication developed in only one (2.5%) patient. Conclusion Silodosin is an effective and safe agent in elderly men who are taking antihypertensive medications. Silodosin has an advantage in the treatment of LUTS in this population, even if the patients have orthostatic hypotension before treatment.

Effect of combined solifenacin and aclatonium in preventing dry mouth in patients with overactive bladder

The aim of the present study was to prospectively evaluate the effect of aclatonium on dry mouth in patients with overactive bladder (OAB) after treatment with solifenacin.