OBJECTIVE: To investigate the antiproliferative activity of Salvia miltiorrhiza Bunge. (SM) on the castration-resistant prostate cancer (CRPC) cell line DU-145, in vitro and in vivo. METHODS: Prostate cancer cell line (DU-145) and normal prostate cell line (RWPE-1) were treated with SM at different concentrations (3.125, 12.5, 25 and 50 μg/mL) to investigate the antiproliferative effects. DNA laddering analysis was performed to investigate the apoptosis of DU-145 cells. Molecular mechanism was investigated by Western blot analysis of p53, Bcl-2, prostate specific antigen (PSA), and androgen receptor (AR). Six-week-old male BALB/c nude mice were randomly divided into normal control group (n=101) and treated group (n=101) which administered 500 mg/kg SM for 2 weeks. Tumor volumes were measured. RESULTS: Treatment with SM resulted in a dose-dependent decrease in cell number of DU-145 cells in comparison with RWPE-1. DNA laddering analysis indicated the apoptosis of DU-145 cells. Treatment with SM increased the expression of p53 and reduced the expression of Bcl-2 proteins. The levels of PSA were considerably reduced in SM-treated group compared to the controls, and a decrease in AR expression was observed when cells were treated with SM in the same pattern as a reduction in PSA. In the tumour xenograft study, SM given once a day for 2 weeks significantly inhibited tumour growth. CONCLUSION SM might contribute to the anticancer actions such as induction of apoptosis and inhibition of proliferation of prostate cancer cells.

Pathogenic gram-negatives that produce 16S ribosomal RNA methyltransferases (16S RMTases) have already been distributed all over the world. To investigate the predominance of aminoglycoside resistance associated with 16S RMTases in Korea, we collected a total of 222 amikacin resistant Gram-negative clinical isolates from patient specimens between 1999 and 2015 from three hospital banks across Korea. ArmA and rmtB were the predominant 16S RMTase genes responsible for aminoglycoside-resistant isolates circulating in Korean community settings although only one rmtA-producing isolate was detected in 2006.
Amikacin ; Humans ; Korea* ; Methyltransferases ; RNA, Ribosomal, 16S

BACKGROUND/AIMS: Although endoscopic bilateral stent-in-stent placement is challenging, many recent studies have reported promising outcomes regarding technical success and endoscopic re-intervention. This study aimed to evaluate the technical accessibility of stent-in-stent placement using large cell-type stents in patients with inoperable malignant hilar biliary obstruction. METHODS: Forty-three patients with inoperable malignant hilar biliary obstruction from four academic centers were prospectively enrolled from March 2013 to June 2015. RESULTS: Bilateral stent-in-stent placement using two large cell-type stents was successfully performed in 88.4% of the patients (38/43). In four of the five cases with technical failure, the delivery sheath of the second stent became caught in the hook-cross-type vertex of the large cell of the first stent, and subsequent attempts to pass a guidewire and stent assembly through the mesh failed. Functional success was achieved in all cases of technical success. Stent occlusion occurred in 63.2% of the patients (24/38), with a median patient survival of 300 days. The median stent patency was 198 days. The stent patency rate was 82.9%, 63.1%, and 32.1% at 3, 6, and 12 months postoperatively, respectively. Endoscopic re-intervention was performed in 14 patients, whereas 10 underwent percutaneous drainage. CONCLUSIONS: Large cell-type stents for endoscopic bilateral stent-in-stent placement had acceptable functional success and stent patency when technically successful. However, the technical difficulty associated with the entanglement of the second stent delivery sheath in the hook-cross-type vertex of the first stent may preclude large cell-type stents from being considered as a dedicated standard tool for stent-in-stent placement.
Cholangiopancreatography, Endoscopic Retrograde ; Cholestasis, Intrahepatic ; Drainage ; Humans ; Klatskin Tumor ; Prospective Studies* ; Self Expandable Metallic Stents ; Stents*

PURPOSE: The effects of gonadotropin-releasing hormone agonist (GnRHa) treatment on body mass index (BMI) are controversial in girls with central precocious puberty (CPP). We therefore evaluated auxological parameters during GnRHa therapy in patients with CPP, specifically focusing on changes in BMI. METHODS: Seventy-seven girls with idiopathic CPP who underwent GnRHa therapy were retrospectively recruited. We investigated BMI changes during the treatment period after stratifying them according to baseline BMI status as follows: normal (BMI percentile of <85th) and overweight groups (BMI percentile of ≥85th). RESULTS: The incidence of overweight/obesity (40.3%/23.4%) was very high in the girls with CPP. In the overall study population, no significant BMI change was observed during the GnRHa treatment period. However, when stratified according to baseline BMI status, the normal-weight group showed a significant increase in BMI-standard deviation score (SDS), whereas the overweight group showed no change in BMI-SDS. Baseline BMI-SDS was an independent predictor of changes in BMI during the GnRHa treatment period. Changes in weight-SDS were similar, but changes in height-SDS were significantly greater in the overweight group than in the normal-weight group, which explains the observed difference in BMI-SDS. CONCLUSION: Our results demonstrate that the difference in the pattern of BMI changes among our CPP patients suggests that delayed puberty induced by GnRHa treatment may have different effects on linear growth according to baseline body composition. This study underscores the importance of individualized lifestyle intervention in CPP children.
Body Composition ; Body Mass Index* ; Child ; Female* ; Gonadotropin-Releasing Hormone* ; Humans ; Incidence ; Life Style ; Obesity ; Overweight* ; Puberty, Delayed ; Puberty, Precocious* ; Retrospective Studies

PURPOSE: We aimed to assess whether nerve-sparing radical prostatectomy (nsRP) is associated with improved recovery of urinary continence compared to non-nerve-sparing radical prostatectomy (nnsRP) in patients with localized prostate cancer and preoperative erectile dysfunction. METHODS: A total of 360 patients with organ-confined prostate cancer and an International Index of Erectile Function score of less than 17 were treated with nsRP or nnsRP in Seoul St. Mary's Hospital. Patients who received neoadjuvant or adjuvant androgen deprivation therapy or had a history of prostate-related surgery were excluded. Recovery of urinary continence was assessed at 0, 1, 3, 6, and 12 months. Postoperative recovery of continence was defined as zero pad usage. The association between nerve-sparing status and urinary continence was assessed by using univariate and multivariate Cox regression analyses after controlling for known predictive factors. RESULTS: Urinary continence recovered in 279 patients (77.5%) within the mean follow-up period of 22.5 months (range, 6-123 months). Recovery of urinary continence was reported in 74.6% and 86.4% of patients after nnsRP and nsRP, respectively, at 12 months (P=0.022). All groups had comparable perioperative criteria and had no significant preoperative morbidities. Age, American Society of Anesthesiologists score, and nerve-sparing status were significantly associated with recovery of urinary continence on univariate analysis. On multivariate analysis, age (hazard ratio [HR], 1.254; 95% confidence interval [CI], 1.002-1.478; P=0.026) and nerve-sparing status (HR, 0.713; 95% CI, 0.548-0.929; P=0.012) were independently associated with recovery of urinary continence. CONCLUSIONS: nsRP, as compared to nnsRP, improves recovery rates of urinary incontinence and decreases surgical morbidity without compromising pathologic outcomes.
Erectile Dysfunction* ; Follow-Up Studies ; Humans ; Male ; Multivariate Analysis ; Prostatectomy* ; Prostatic Neoplasms ; Seoul ; Urinary Incontinence

Diabetes is related with a number of cystopathic complications. However, there have been no studies about the influence of alcohol consumption in the bladder of type 2 diabetes. Thus, we investigated the effect of moderate alcohol intake in the bladder of the Otsuka Long Evans Tokushima Fatty (OLETF) diabetic rat. The non-diabetic Long-Evans Tokushima Otsuka (LETO, n=14) and the OLETF control group (n=14) were fed an isocaloric diet; the LETO (n=14) and the OLETF ethanol group (n=14) were fed 36% ethanol 7 g/kg/day. After ten weeks, muscarinic receptors, RhoGEFs, myogenic change, and the level of oxidative stress were evaluated. Moderate alcohol intake significantly decreased excessive muscarinic receptor and Rho kinase expressions in the OLETF rats compared with the LETO rats. In addition, iNOS and collagen expression were not changed in the OLETF rats in spite of alcohol consumption. Superoxide dismutase levels, which is involved in antioxidant defense, in the LETO rats were significantly decreased after alcohol consumption, however those in the OLETF rats were similar. Moderate alcohol consumption reduces the oxidative stress, and may prevent molecular and pathologic changes of the bladder of rats with type 2 diabetes.
Alcohol Drinking/adverse effects ; Animals ; Diabetes Mellitus, Type 2/*complications/*metabolism/pathology ; Ethanol/*toxicity ; Humans ; Rats ; Rats, Inbred OLETF ; Reactive Oxygen Species/*metabolism ; Urinary Bladder/*drug effects/*metabolism/pathology

PURPOSE: The goal of this study was to evaluate changes in nocturia and other lower urinary tract symptoms (LUTS) after laparoscopic radical prostatectomy (LRP) and robot-assisted laparoscopic radical prostatectomy (RALP). MATERIALS AND METHODS: We reviewed the medical records of 96 patients who underwent LRP or RALP for clinically localized prostate cancer and completed the International Prostate Symptom Score (IPSS) questionnaire, which provided a basis for assessing their symptoms. We also evaluated maximal flow rate and post-void residual urine volume over a follow-up period of at least 24 months. We divided the patients into three groups according to postoperative changes in the frequency of nocturia. RESULTS: Voiding symptoms significantly improved over the course of 24 months in patients who underwent LRP or RALP. However, most patients showed persistent or increased nocturia after LRP or RALP. Moreover, more than one third of the patients (33/96) presented with exacerbated nocturia (1.0+/-0.9 episodes of preoperative nocturia vs. 3.0+/-1.3 episodes of postoperative nocturia). Multiple regression analysis showed that preoperative IPSS storage sub-score had negative association with the nocturia after radical prostatectomy (p=0.005). However, patients' age, body mass index, preoperative prostate specific antigen, Gleason score, T-stage, and prostate volume had no association. CONCLUSIONS: The present study showed that nocturia was influenced by a range of factors, including other storage LUTS and the relief of bladder outlet obstruction after radical prostatectomy. Moreover, the preoperative storage symptoms are regarded as an important factor which influences the changes of nocturia after radical prostatectomy.
Body Mass Index ; Follow-Up Studies ; Humans ; Laparoscopy ; Lower Urinary Tract Symptoms* ; Medical Records ; Neoplasm Grading ; Nocturia* ; Prostate ; Prostate-Specific Antigen ; Prostatectomy* ; Prostatic Neoplasms ; Urinary Bladder Neck Obstruction

PURPOSE: To investigate the role of alpha3 and alpha7 nicotinic acetylcholine receptor subunits (nAChRs) in the bladder, using a rat model with detrusor overactivity induced by partial bladder outlet obstruction (BOO). METHODS: Forty Sprague-Dawley rats were used: 10 were sham-operated (control group) and 30 were observed for 3 weeks after partial BOO. BOO-induced rats were further divided into 3 groups: Two groups of 10 rats each received intravesicular infusions with hexamethonium (HM group; n=10) or methyllycaconitine (MLC group; n=10), which are antagonists for alpha3 and alpha7 nAChRs, respectively. The remaining BOO-induced rats received only saline infusion (BOO group; n=10). Based on the contraction interval measurements using cystometrogram, the contraction pressure and nonvoiding bladder contractions were compared between the control and the three BOO-induced groups. Immunofluorescent staining and Western blotting were used to analyze alpha3 and alpha7 nAChRs levels. RESULTS: The contraction interval of the MLC group was higher than that of the BOO group (P<0.05). Nonvoiding bladder contraction almost disappeared in the HM and MLC groups. Contraction pressure increased in the BOO group (P<0.05) compared with the control group and decreased in the HM and MLC groups compared with the BOO group (P<0.05). Immunofluorescence staining showed that the alpha3 nAChR signals increased in the urothelium, and the alpha7 nAChR signals increased in the urothelium and detrusor muscle of the BOO group compared with the control group. Western blot analysis showed that both alpha3 and alpha7 nAChR levels increased in the BOO group (P<0.05). CONCLUSIONS: Alpha3 and alpha7 nAChRs are associated with detrusor overactivity induced by BOO. Furthermore, nAChR antagonists could help in clinically improving detrusor overactivity.
alpha7 Nicotinic Acetylcholine Receptor ; Animals ; Blotting, Western ; Fluorescent Antibody Technique ; Hexamethonium ; Models, Animal ; Rats* ; Rats, Sprague-Dawley ; Receptors, Nicotinic* ; Urinary Bladder ; Urinary Bladder Neck Obstruction* ; Urinary Bladder, Overactive ; Urothelium

PURPOSE: To investigate the effects of anthocyanins extracted from black soybean, which have antioxidant activity, on apoptosis in vitro (in hormone refractory prostate cancer cells) and on tumor growth in vivo (in athymic nude mouse xenograft model). MATERIALS AND METHODS: The growth and viability of DU-145 cells treated with anthocyanins were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis was assessed by DNA laddering. Immunoblotting was conducted to evaluate differences in the expressions of p53, Bax, Bcl, androgen receptor (AR), and prostate specific antigen (PSA). To study the inhibitory effects of anthocyanins on tumor growth in vivo, DU-145 tumor xenografts were established in athymic nude mice. The anthocyanin group was treated with daily oral anthocyanin (8 mg/kg) for 14 weeks. After 2 weeks of treatment, DU-145 cells (2x106) were inoculated subcutaneously into the right flank to establish tumor xenografts. Tumor dimensions were measured twice a week using calipers and volumes were calculated. RESULTS: Anthocyanin treatment of DU-145 cells resulted in 1) significant increase in apoptosis in a dose-dependent manner, 2) significant decrease in p53 and Bcl-2 expressions (with increased Bax expression), and 3) significant decrease in PSA and AR expressions. In the xenograft model, anthocyanin treatment significantly inhibit tumor growth. CONCLUSION: This study suggests that anthocyanins from black soybean inhibit the progression of prostate cancer in vitro and in a xenograft model.
Animals ; Anthocyanins/*pharmacology ; Apoptosis/*drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Male ; Mice, Inbred C57BL ; Mice, Nude ; NAD/metabolism ; Prostate-Specific Antigen/metabolism ; Prostatic Neoplasms/genetics/*pathology ; Receptors, Androgen/metabolism ; Tumor Suppressor Protein p53/metabolism ; *Xenograft Model Antitumor Assays ; bcl-2-Associated X Protein/genetics/metabolism

PURPOSE: This single institutional study is aimed to observe the outcome of patients who received postoperative radiotherapy after radical prostatectomy. MATERIALS AND METHODS: A total of 59 men with histologically identified prostate adenocarcinoma who had received postoperative radiation after radical prostatectomy from August 2005 to July 2011 in Seoul St. Mary's Hospital of the Catholic University of Korea, was included. They received 45-50 Gy to the pelvis and boost on the prostate bed was given up to total dose of 63-72 Gy (median, 64.8 Gy) in conventional fractionation. The proportion of patients given hormonal therapy and the pattern in which it was given were analyzed. Primary endpoint was biochemical relapse-free survival (bRFS) after radiotherapy completion. Secondary endpoint was overall survival (OS). Biochemical relapse was defined as a prostate-specific antigen level above 0.2 ng/mL. RESULTS: After median follow-up of 53 months (range, 0 to 104 months), the 5-year bRFS of all patients was estimated 80.4%. The 5-year OS was estimated 96.6%. Patients who were given androgen deprivation therapy had a 5-year bRFS of 95.1% while the ones who were not given any had that of 40.0% (p < 0.01). However, the statistical significance in survival difference did not persist in multivariate analysis. The 3-year actuarial grade 3 chronic toxicity was 1.7% and no grade 3 acute toxicity was observed. CONCLUSION: The biochemical and toxicity outcome of post-radical prostatectomy radiotherapy in our institution is favorable and comparable to those of other studies.
Adenocarcinoma ; Follow-Up Studies ; Humans ; Korea ; Male ; Multivariate Analysis ; Pelvis ; Prostate ; Prostate-Specific Antigen ; Prostatectomy* ; Radiotherapy* ; Recurrence ; Seoul