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Purpose This study aimed to evaluate the trend of adjuvant chemotherapy (AC) and neoadjuvant chemotherapy (NAC) in patients who underwent radical nephroureterectomy with bladder cuff excision (NUx) for upper tract urothelial carcinoma (UTUC) to compare the perioperative outcomes and overall survival (OS) between AC and NAC using nationwide population-based data. Materials and methods We collected data on patients diagnosed with UTUC and treated with NUx between 2004 and 2016 using the National Health Insurance Service database, and evaluated the overall treatment trends. The AC and NAC groups were propensity score-matched. Cox proportional hazard and Kaplan-Meier analyses were used to assess survival. Results Of the 8,705 enrolled patients, 6,627 underwent NUx only, 94 underwent NAC, and 1,984 underwent AC. The rate of NUx without perioperative chemotherapy increased from 70.8 to 78.2% (R2 = 0.632; p Conclusion The use of NUx without perioperative chemotherapy has tended to increase in South Korea. Dialysis, TUR-BT, and radiotherapy rates after NUx were similar between the NAC and AC groups. There was no significant difference in OS between the NAC and AC groups. Proper perioperative chemotherapy according to patient and tumor conditions should be determined by obtaining more evidence of UTUC.

Purpose In this study, we tested whether the resveratrol-enriched peanut sprout extracts cultivated with fermented sawdust medium (PSEFS) could suppress benign prostatic hyperplasia (BPH) in vitro and in vivo. Materials and methods The mode of action of PSEFS was estimated by employing high-performance liquid chromatography analysis, MTT assay, cell counting, cell cycle analysis, immunoblots, and immunoprecipitation and electrophoretic mobility shift assay. In vivo efficacy of PSEFS was analyzed in BPH animal model via immunostaining and enzyme-linked immunosorbent assay. Results We selected the Yesan peanut sprout variety, which contains the highest level of resveratrol. The resveratrol levels in PSEFS were higher than those obtained with hydroponic technology. PSEFS treatment induced cell cycle arrest at the G1-phase by downregulating CDK4 and cyclin D1 via p21WAF1 induction in the RWPE-1 and WPMY prostate cells, thereby decreasing their proliferation. Treatment with PSEFS decreased ERK1/2 phosphorylation and increased JNK phosphorylation. The levels of DNA-bound transcription factors associated with proliferation (nuclear factor-κB, Sp-1, and AP-1) decreased upon PSEFS treatment in both prostate cells. Additionally, the levels of the molecular markers of BPH development (5α-reductase, androgen receptor, fibroblast growth factor, Bcl-2, and Bax) also changed by the addition of PSEFS. Finally, in a testosterone propionate-induced BPH model in rats, PSEFS administration attenuated the size, weight, and thickness of prostate tissues with no signs of death. Conclusions These results showed that PSEFS inhibited BPH both in vitro and in vivo and might be useful in the development of a potential BPH therapy.

INTRODUCTION AND OBJECTIVE:Although bacillus Calmette–Guerin cell wall skeleton (BCG-CWS) might function as a potential substitute for live BCG, its use in the treatment of bladder cancer remains l...

INTRODUCTION AND OBJECTIVE:To compare the survival outcomes between patients with metastatic renal cell carcinoma (RCC) treated with cytoreductive nephrectomy (CN) and without CN.METHODS:We evaluat...

Intravesical BCG (bacille Calmette-Guérin) instillation in patients with non-muscle-invasive bladder cancer decreases the risk for tumor recurrence and progression. After one BCG product was discontinued, a chronic global BCG shortage occurred. We focused on identifying a reduced dose of BCG that could maintain efficacy and reduce adverse effects.We conducted a comprehensive literature search of PubMed, Embase, the Cochrane Library, CINAHL, Web of Science, and Scopus to identify randomized controlled trials through April 2021. The odds ratios (ORs) and 95% confidence intervals (CIs) for the low and standard doses in nine studies were compared. A low dose was defined as a low volume of BCG compared with the standard BCG dose (Armand Frappier, 120 mg; Connaught, 81 mg; Danish 1331, 120 mg; modified Danish 1331, 120 mg; Tokyo 172, 80 mg).The low-dose group experienced aggravated recurrence (OR, 1.45; 95% CI, 1.09-1.94; p=0.01) but similar progression (OR, 1.11; 95% CI, 0.76-1.62; p=0.59), similar cancer-specific survival (OR, 1.02; 95% CI, 0.60-1.75; p=0.93), similar overall survival (OR, 1.09; 95% CI, 0.76-1.56; p=0.65), favorable adverse effects (OR, 0.41; 95% CI, 0.28-0.62; p0.0001), and favorable withdrawal (OR, 0.42; 95% CI, 0.25-0.71; p=0.001).Low-dose BCG had more unfavorable outcomes than did standard-dose BCG in terms of recurrence. Tumor progression, cancer-specific survival, and overall survival were similar between the doses. Low-dose BCG improved adverse effects and withdrawal. In the setting of BCG shortage, low-dose BCG may have strong potential as an alternative.

INTRODUCTION AND OBJECTIVE:We investigated the relationship between positive surgical margin (PSM)-related factors and biochemical recurrence (BCR) and the ability of intraoperative frozen sections...

INTRODUCTION AND OBJECTIVE:Two-dimensional (2D) cell culture is a valuable method for cell-based research but can provide unpredictable, misleading data about in vivo responses. In this study, we c...

Objective To determine whether sequence variants within the FGF23 gene are associated with the risk of developing prostate cancer in a Korean population. Patients and Methods Five common single nucleotide polymorphisms (SNPs) in the FGF23 gene were assessed in 272 patients with prostate cancer and 173 control subjects with benign prostatic hyperplasia. Single-locus analyses were conducted using conditional logistic regression. In addition, we performed a haplotype analysis for the five FGF23 SNPs tested. Results Three SNPs in the FGF23 gene (rs11063118, rs13312789 and rs7955866) were associated with an increased risk of prostate cancer in our study population. Odds ratios for homozygous variants vs wild-type variants ranged from 1.68 (95% confidence interval [CI]: 1.15–2.46) to 1.79 (95% CI: 1.16–2.75). Conclusion This is the first study showing that genetic variations in FGF23 increase prostate cancer susceptibility.

Epigenetic aberrations play crucial roles in prostate cancer (PCa) development and progression. The DEFB1 gene, which encodes human beta-defensin-1 (HBD-1), contributes to innate immune responses and functions as a potential tumor suppressor in urological cancers. We investigated whether differential DNA methylation at the low CpG-content promoter (LCP) of DEFB1 was associated with transcriptional regulation of DEFB1 in PCa cells. To identify distinct CpG loci within the DEFB1 LCP related to the epigenetic regulation of DEFB1, we performed an in vitro methylated reporter assay followed by bisulfite sequencing of the DEFB1 promoter fragment. The methylation status of two adjacent CpG loci in the DEFB1 LCP was found to be important for DEFB1 expression in PCa cells. Paired epithelial specimens of PCa patients (n = 60), which were distinguished as non-tumor and tumor tissues by microdissection, were analyzed by bisulfite pyrosequencing of site-specific CpG dinucleotide units in the DEFB1 LCP. CpG methylation frequencies in the DEFB1 LCP were significantly higher in malignant tissues than in adjacent benign tissues across almost all PCa patients. These results suggested that methylation status of each CpG site in the DEFB1 promoter could mediate downregulation of DEFB1 in PCa cells.

Objective To determine the correlation between metabolic syndrome and the distribution of stone components in patients with urolithiasis. Methods Between January 2007 and December 2010, renal or ureteral stones were collected from 712 patients (432 males, 280 females) who underwent surgical intervention at three hospitals in South Korea. Metabolic syndrome was defined according to the latest definition of the International Diabetes Federation, using ethnicity- and sex-specific cut-off values for central obesity. Patients were assessed by factors used in metabolic syndrome. All urinary stones were analyzed using infrared spectrophotometry and categorized according to their main component. Results The patients' mean age was 55.9 years (range 19–93 years). Of the 712 patients, 347 (48.7%; 205 males, 142 females) had a diagnosis of metabolic syndrome. Calcium oxalate (71.5%), uric acid (15.3%), carbonate apatite (8.0%) and struvite (4.1%) calculi were found as the main stone components. Overall, the proportion of uric acid calculi was markedly higher in patients with rather than without metabolic syndrome (19.6 vs 11.2%; P = 0.002). However, the proportion of calcium oxalate, carbonate apatite and struvite calculi did not differ between the two groups. The multivariable-adjusted odds ratio for uric acid calculi according to the metabolic syndrome components indicated that the presence of metabolic syndrome was associated with a 93% increased odds ratio of uric acid calculi compared with the absence of metabolic syndrome. Impaired fasting glucose and hypertriglyceridemia were independent risk factors for uric acid calculi. Conclusions Metabolic syndrome is associated with a significantly increased risk of uric acid calculi development, especially those with impaired fasting glucose and hypertriglyceridemia.

ARTIcLE InfO We had investigated whether sequence variants within DKK3 gene are associated with the development of prostate cancer in a Korean study cohort. We evaluated the association between 53 single nucleotide polymorphisms (SNPs) in the DKK3 gene and prostate cancer risk as well as clinical characteristics (PSA, clinical stage, pathological stage and Gleason score) in Korean men (272 prostate cancer subjects and 173 benign prostate hyperplasia subjects) using unconditional logistic regression analysis. Of the 53 SNPs and 25 common haplotypes, 5 SNPs and 4 haplotypes were associated with prostate cancer risk (P=0.02-0.04); 3 SNPs and 2 haplotypes were significantly associated with susceptibility to prostate cancer, however 2 SNPs and 2 haplotypes exhibited a significant protective effect on prostate cancer. Logistic analyses of the DKK3 gene polymorphisms with several prostate cancer related factors showed that several SNPs were significant; three SNPs and two haplotypes to PSA level, three SNPs and two haplotypes to clinical stage, nine SNPs and two haplotype to pathological stage, one SNP and one haplotypes to Gleason score. To the author’s knowledge, this is the first report documenting that DKK3 polymorphisms are not only associated with prostate cancer but also related to prostate cancer-related factors.

Objective To investigate whether altered prostate specific antigen (PSA) levels due to individual prostate growth may affect the PSA velocity (PSAV). Materials and Methods Between January 2000 and December 2009, a total of 159 men with at least 2 transrectal ultrasonography (TRUS) procedures and concurrent PSA measurements underwent prostate biopsy because of suspicion of prostate cancer. We measured PSAV, prostate volume velocity (PVV), PSA density (PSAD), PSAD velocity (PSADV), and PSAV per initial volume. We then classified the total group into a prostate cancer (PC) group and non-PC group, and compared the 2 groups. We investigated which variables were exact to predict prostate biopsy using univariate and multivariate analyses, and assessed the diagnostic performance using the receiver operating characteristic (ROC) curve. Results PVV showed a positive correlation with initial prostate volume in the total and non-PC group; PVV showed a positive correlation with PSAV, and initial prostate volume correlated with PSAV in the non-PC group. The PC group showed smaller prostate volumes, higher PSAD, higher PSADV, higher PSAV per initial volume, and longer follow-up periods. After adjusting for confounding factors, the odds ratios of prostate cancer across the quartile of PSAVD were 1, 1.889, 3.226, and 7.125 ( P for trend=.007 ), and PSAV per initial volume were 1, 2.924, 2.937, and 7.536 ( P for trend=.031 ). On the ROC curve, the areas under the curves (AUC) of PSAV per initial volume were higher than for PSAV and PSADV. Conclusion Altered PSA levels due to individual prostate growth may affect the use of PSAV to predict prostate biopsy outcomes in follow-up.

Chronic inflammation has been considered a potential risk factor for prostate cancer. Toll-like receptors (TLRs) are important in the innate immune response to pathogens and in cross talk between innate immunity and adaptive immunity. In this study, sequence variants in the TLR4 gene were investigated to determine whether they were associated with prostate cancer risk in a Korean cohort. An association study between 11 single-nucleotide polymorphisms (SNPs) of the TLR4 gene and prostate cancer was performed in 463 Korean male subjects including 240 prostate cancer patients and 223 healthy controls. SNPs were genotyped using the TaqMan assay, and their association with the risk of prostate cancer was evaluated using logistic regression analysis. The statistical analysis revealed that one SNP at the 3′UTR (rs11536889) showed significant association with the risk of prostate cancer (P corr = 0.005, OR = 1.81). One common haplotype (ht2) was also significantly associated with the risk of prostate cancer (P corr = 0.009, OR = 1.77). However, further analysis showed no association between any of the SNPs and prostate cancer prognostic factors such as the Gleason score or tumor stage. The findings of this study suggest that polymorphisms of the TLR4 gene might be associated with the risk of prostate cancer in Korean men.

OBJECTIVE To investigate the expression and regulation of human β-defensin-2 (HBD-2) in the prostate. PATIENTS AND METHODS Normal human prostate epithelial cell line (RWPE-1), human prostate cancer cell lines (DU-145, PC-3), and paraffin-embedded prostate tissue from patients with benign prostatic hyperplasia (BPH) were analysed by RT-PCR and immunohistochemical staining. HBD-2 expression was also analysed by RT-PCR and ELISA in RWPE-1 cells treated with lipopolysaccharide (LPS). Nuclear factor-κB (NF-κB) activation was assessed by IκBα immunoblotting and electrophoretic mobility shift assay (EMSA). RESULTS BPH tissue and all of the tested prostate cell lines other than PC-3 constitutively express HBD-2 mRNA. HBD-2 protein was strongly detected in prostate gland tissue surrounded by inflammatory cells including macrophages. Exposure to LPS induced HBD-2 upregulation and NF-κB activation, as assessed by IκBα phosphorylation and degradation in RWPE-1 cells. Bay11-7082, an NF-κB inhibitor prevented LPS-induced HBD-2 production in RWPE-1 cells. CONCLUSIONS Prostate epithelial cells may constitutively express HBD-2, and its expression was upregulated by LPS. Our data indicate that HBD-2 may be an important immunomodulatory factor in prostate function. Expression of HBD-2 in normal prostates and the potential role of HBD-2 in prostatitis and BPH should be addressed in the future.

What’s known on the subject? and What does the study add? We found that resistin, a member of adipokine family, is expressed in human prostate cancers and induces prostate cancer cell proliferation through PI3K/Akt signaling pathways. We are studying the effect of resistin on other urogenital tract diseases besides prostate cancer, and the relationship between other adipokines and the urogenital tract diseases. OBJECTIVES • To determine whether resistin, a novel adipokine, induces prostate cancer cell proliferation. • To identify the mechanisms underlying the activation of prostate cancer cells by resistin. MATERIALS AND METHODS • Semi-quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical staining were performed to investigate the intensity of prostate epithelial resistin expression. • Human full-length resistin gene (RETN) was transfected into the PC-3 cells using the pEGFP-N1 vector to assess the effect of overexpression of resistin in prostate cancer cell line PC-3. • Various concentrations of human recombinant protein resistin were added to the hormone-insensitive prostate cancer cell lines PC-3 and DU-145 for 48 h, and cell proliferation was assessed by a water-soluble tetrazolium salt assay. RESULTS • Human prostate cancer cell lines PC-3 and DU-145 were found to express the human resistin mRNA. • Resistin protein was strongly detected in high-grade prostate cancer tissue, whereas BPH or low-grade prostate cancer tissue revealed fainter expression of resistin. • Cell proliferation was stimulated by both the full-length resistin gene overexpression and resistin treatment. • Akt phosphorylation occurred after addition of resistin to PC-3 and DU-145 cells. LY294002, a pharmacological inhibitor of phosphatidylinositol 3-kinase (PI3K), significantly inhibited PC-3 and DU-145 cell proliferation after resistin treatment. CONCLUSIONS • Resistin is expressed in human prostate cancers. • Resistin induces prostate cancer cell proliferation through PI3K/Akt signalling pathways. • The proliferative effect of resistin on prostate cancer cells may account in part for prostate cancer progression.

The purpose of this study was to determine the relationship between insulin resistance, obesity and serum prostate-specific antigen (PSA) levels in healthy men with serum PSA level below 4 ng mL−1. The men included in the study cohort were 11 827 healthy male employees of the Korea Hydro and Nuclear Power Co., LTD who had undergone medical checkups including fasting glucose, fasting insulin and serum PSA between January 2003 and December 2008. Insulin resistance was calculated by homeostasis model assessment (HOMA [fasting glucose × fasting insulin]/22.5) and quantitative insulin sensitivity check index (QUICKI; 1/[log (fasting insulin) + log (fasting glucose)]). Age-adjusted body mass index (BMI) was significantly increased according to increasing quartile of insulin resistance as determined by HOMA and QUICKI, respectively, in analysis of variance (ANOVA) test and Duncan's multiple comparison test (P < 0.001), but age-adjusted serum PSA concentration was significantly decreased according to increasing quartile of insulin resistance as determined by HOMA and QUICKI (P < 0.001). Age, BMI, insulin resistance by HOMA or QUICKI were significantly independent variables to serum PSA level in a multivariate linear regression analysis (P < 0.001). Insulin resistance was a significant independent variable to serum PSA level along with BMI. Insulin resistance and BMI were negatively correlated with serum PSA level in healthy men. Insulin resistance was positively correlated with BMI.

Introduction Dehydroepiandrosterone (DHEA) is a multifunctional steroid that is increasingly available as a supplement aimed at improving libido and well-being in postmenopausal women in the recent times. Together with its sulfate version, DHEA-sulfate (DHEAS), it is the most abundant steroid in humans. The clitoris is an important component of the female sexual response, with its increased vascular response during sexual arousal that results in erection. Aims To elucidate the direct effects of DHEA/DHEAS on the vasomotor reactivity of the rabbit clitoral cavernosum. Methods Twenty New Zealand white female rabbits weighing approximately 2.5–3 kg were used in the study. Main Outcome Measures The contractile response of clitoral cavernous smooth muscle strips in response to phenylephrine (PE; 10 −9 –10 −4 M) were observed in rabbits. Additionally, DHEA/DHEAS effects on phenylephrine-induced contraction and/or acetylcholine-induced relaxation of phenylephrine-induced contraction were measured. Results DHEA/DHEAS did not elicit any remarkable response in the resting state. However, both DHEA and DHEAS evoked dose-dependent relaxations of PE-induced contraction. The contractile responses to high potassium were significantly decreased in the DHEA/DHEAS-pretreated strips, compared with the DHEA/DHEAS-nontreated strips. Additionally, contractions by Bay K 8644 (10 −7 –10 −6 M) treatment were also significantly inhibited by DHEA/DHEAS. DHEA-induced relaxation responses were stronger than DHEAS-induced relaxation responses. Various K channel blockers, tetraethylammonium (TEA; 1 mM, 10 mM), 4-aminopyridine (10 µM) and glibenclamide (10 µM) did not affect the DHEA/DHEAS-induced relaxation on muscle strips contracted by PE. Relaxation responses by acetylcholine or sodium nitroprusside (SNP) were not changed after DHEA/DHEAS pretreatment. Conclusions DHEA/DHEAS was found to induce a relaxation response in rabbit clitoral cavernosal smooth muscle, and this is thought to be mediated by direct inhibition of a voltage-dependent calcium channel. Lee SY, Myung SC, Lee MY, Kim TH, Kim SC, Kim KD, Park SH, and Kim WY. The effects of dehydroepiandrosterone (DHEA)/DHEA-sulfate (DHEAS) on the contraction responses of the clitoral cavernous smooth muscle from female rabbits. J Sex Med 2009;6:2653–2660.

Purpose: Smooth muscle cells of the vas deferens have an important role in carrying sperms to the exterior but little is known of their electrophysiological properties. We characterized the voltage-gated ion channel currents in single smooth muscle cells of the human vas deferens (HVSMCs). Materials and Methods: We observed contractile responses of 8 circular smooth muscle strips of the human vas deferens to a high concentration (10 mM) of tetraethylammonium. HVSMCs were isolated using proteolytic enzymes (collagenase and papain), and were used for an electro-physiological study using whole cell and inside-out patch clamp configurations. Results: The application of 10 mM tetraethylammonium induced rhythmic contractions of the strips. When HVSMCs were dialyzed with a KCl solution, step depolarizations of membrane potential evoked oscillatory outward K currents that were not inactivated. The large conductance Ca activated K (BK Ca ) and delayed rectifier components of the outward current were identified. The BK Ca channel showed a large single channel conductance (162.7 ± 13.2 pS with 5 mM K in the patch pipette). Two types of Ca currents were identified in the whole cell configuration. With a cell held at −50 mV an L-type Ca current was present during a depolarizing step pulse. From a holding potential of −90mV L-type and T-type Ca currents were elicited by depolarizing step pulses. Conclusions: HVSMCs have 2 (L and T) types of Ca channels and 2 types of K (BK Ca and delayed rectifier) channels. Voltage dependent changes of these ion channels and their interactions may be important in regulating vas contractility.

HEPSIN (HPN) gene is one of the most consistently overexpressed genes in patients with prostate cancer; furthermore, there is some evidence supporting an association between HPN gene variants and the risk of developing prostate cancer. In this study, sequence variants in the HPN gene were investigated to determine whether they were associated with prostate cancer risk in a Korean study cohort. We evaluated the association of 17 single-nucleotide polymorphisms (SNPs) in the HPN gene with prostate cancer risk and clinical characteristics (Gleason score and tumor stage) in Korean men (240 case subjects and 223 control subjects) using unconditional logistic regression. The statistical analysis suggested that three SNPs (rs45512696, rs2305745, rs2305747) were significantly associated with the risk of prostate cancer (odds ratio (OR)=2.22, P=0.04; OR=0.73, P=0.03; OR=0.76, P=0.05, respectively). The results of this study suggest that, in Korean men, some polymorphisms in the HPN gene might be associated with the risk of developing prostate cancer.

To examine the independent effect of metabolic syndrome (MS) on nephrolithiasis (NL) even with changes in MS status over time.From 2002-2003, 3872 men who were reexamined annually or biannually until 2009 were enrolled in the analysis and observed for development of NL. The examination included anthropometric measurements, biochemical measurement, and kidney ultrasonography (US). A standard Cox proportional hazards model and a time-dependent Cox model were used to calculate the adjusted hazard ratio in the NL model.After adjusting for age, baseline glomerular filtration rate, and uric acid level, MS at baseline was associated with a significantly increased risk of NL (HR, 1.771; 95% confidence interval, 1.157-2.711). MS over time as a time-dependent variable also predicted the development of NL (HR, 1.678; 95% CI, 1.151-2.447) after adjusted baseline covariate. After adjustment for potential confounding factors, there was a significant stepwise increase in risk of NL, with each additional MS trait compared with those with no traits of MS at baseline and follow-up. As the numbers of MS traits at baseline and follow-up increased, the urine pH of participants at baseline and follow-up decreased significantly (P.01). The prevalence of NL in participants with continual MS (6.6%) was higher than those with resolved MS, and continual MS was an independent factor to predict NL.Our findings suggest that MS is significantly associated with increased risk of developing urine acidification, even with changes in status of MS observed during follow-up.

Recently, it has been demonstrated that ureteral obstruction is associated with increased cyclooxygenase (COX)-2 expression and that selective COX-2 inhibitors provide potent analgesia with fewer side effects in patients with ureteral stones. Moreover, selective COX-2 inhibitors have been shown to decrease in vitro contractility of the human ureter. We aimed at evaluating the effects of the selective COX-2 inhibitor NS-398 on human ureteral smooth muscle contractility and compare its potency with that of nonselective COX inhibitors, COX-1 inhibitors, and other COX-2 inhibitors.Ureteral samples were obtained from human adult subjects undergoing radical nephrectomy. After isolating the upper ureteral strips, we analyzed the contractile responses of the ureteral strips to high potassium (KCl 35 mM) and Bay K 8644 and the relaxation responses of a nonspecific COX inhibitor (indomethacin), a COX-1 inhibitor (SC-560), and a COX-2 inhibitor (NS-398 and celecoxib) to KCl and Bay K 8644-induced contraction by measuring isometric tension.NS-398 produced dose-dependent (10⁻⁹-10⁻⁵ M) relaxation of KCl (35 mM)-precontracted strips of the ureter, whereas indomethacin (10⁻⁸-10⁻⁵ M) and SC-560 (10⁻⁹-10⁻⁵ M) did not. Both tonic and phasic contraction of Bay K 8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-2(trifluoromethylphenyl)pyridine-5-carboxylate) (1 μM) were significantly inhibited by NS-398 (10⁻⁵ M). Another selective COX-2 inhibitor, celecoxib, did not show potent inhibitory effects as strong as those of NS-398.We concluded that NS-398 reduces tonic or phasic contraction by inhibiting the action of voltage-dependent calcium channels. NS-398 has dual inhibitory effects with COX-2 inhibition on ureteral spasms due to renal or ureteral colic.

OBJECTIVE To determine the effect of endothelin-1 (ET-1) on the production of interleukin-6 (IL-6) in cultured human detrusor smooth muscle cells (HDSMCs) and the effect of IL-6 on the contractile response of bladder smooth muscle strips from rats. MATERIALS AND METHODS The expression of IL-6 mRNA and production of IL-6 protein in cultured HDSMCs treated with the different concentrations of ET-1 were assayed by reverse transcriptase-polymerase chain reaction and specific enzyme-linked immunosorbent assay, respectively. The strips from Sprague-Dawley rats were either untreated or treated with 1 ng/mL of IL-6 for 60 min. Using increasing cumulative concentrations of acetylcholine (ACh), bethanechol (BCh), or sodium nitroprusside, we assessed the concentration-contraction or the relaxation responses. In cystitis-induced strips, change of contractions induced by noradrenaline (NA) with or without treatment of IL-6 were assessed. The IL-6-treated strips were incubated for 30 min in the presence or absence indomethacin or SQ29548, and then the effects on ACh- or BCh-induced contractions were measured. RESULTS The expression of IL-6 mRNA and the production of IL-6 protein on the cultured HDSMCs pretreated by ET-1 were significantly higher than in the control (P

Aim: To evaluate the expression of leptin and leptin receptor in benign prostatic hyperplasia (BPH) and prostate cancer (PCa), and to investigate whether they are associated with the development and progression of PCa. Methods: Immunohistochemical staining was performed to examine the expression of leptin and leptin receptor in BPH and PCa. PCa was divided into three groups: localized PCa, locally advanced PCa and metastatic PCa. The positive staining was identified and the percentage of the positive staining was graded. We also assessed the relationship between both the Gleason score and body mass index (BMI) and PCa. Results: The percentage of the leptin expression in PCa was significantly higher than that in BPH (P < 0.01). For the PCa group, the expressed levels of leptin showed a considerable correlation with localized PCa and metastatic PCa (P < 0.05). Leptin receptor, however, did not reveal a definite difference between BPH and PCa. The expression of leptin indicated a significant difference between well-differentiated PCa (Gleason score ≤ 6) and poorly differentiated PCa (Gleason score 8–10) (P < 0.05). The relation between the leptin expression level in PCa and the BMI was not remarkable (P= 0.447). Conclusion: Our results suggest that leptin might have a promoting effect on the carcinogenesis and progression of PCa.

We investigated the association between body mass index and the concentration of tumor markers including carcinoembryonic antigen, alpha-fetoprotein, the carbohydrate antigen 19-9 and prostate specific antigen, as well as the association between body mass index changes and tumor marker concentration changes in a population of healthy men.We evaluated data on 8,776 men screened for tumor markers (carcinoembryonic antigen, alpha-fetoprotein, carbohydrate antigen 19-9 and prostate specific antigen) at least 3 times annually during an annual examination from 2001 to 2007. We assessed the tumor marker test findings for a trend in the age, alanine aminotransferase and creatinine adjusted tumor marker concentration by body mass index. We used multivariate regression analysis to determine whether a change in body mass index was associated with a tumor marker concentration change over time using calculated tumor markers, body mass index, creatinine and alanine aminotransferase concentration change per year.After adjusting for age, creatinine and alanine aminotransferase a higher body mass index was associated with lower prostate specific antigen (p for trend0.001), carcinoembryonic antigen (p for trend0.001) and carbohydrate antigen 19-9 (p for trend0.001). On multivariate regression analysis each 1 kg/m(2) of body mass index gain per year was associated with a -0.011 ng/ml change in prostate specific antigen concentration, a -0.030 ng/ml change in carcinoembryonic antigen concentration and a -0.192 IU/ml change in carbohydrate antigen 19-9 concentration per year.In this cohort of healthy men hemodilution from increased plasma volume may be responsible for the observed decreased tumor marker concentration in men with a higher body mass index. In addition, an increase in body mass index may predict a lower tumor marker concentration in an individual.

OBJECTIVE To assess the association between serum prostate-specific antigen (PSA) level and age, liver function tests (LFTs) including alkaline phosphatase (ALP), total bilirubin (TB), lipid profile (total cholesterol, TC, triglycerides, TG, high-density lipoprotein, HDL) and fasting blood sugar (FBS), and to determine the significant factors for predicting the serum PSA level in men with a low risk of having prostate cancer. SUBJECTS AND METHODS In all, 38 157 healthy male employees of the Korea Electric Power Corporation (KEPCO) who were aged

Recently, growing clinical evidence has suggested that sexual dysfunction is more prevalent in women with overactive bladder (OAB). Aims. However, there has been no basic research to clarify the relationship between OAB and female sexual dysfunction. Therefore, we investigated this issue using a rabbit model of OAB.Twenty-seven New Zealand white female rabbits were randomly divided into the OAB and control groups.The contractile responses of clitoral cavernous strips to K(+), phenylephrine (PE), Bay K 8644, and endothelin (ET)-1, and the relaxation responses of acetylcholine (ACh), sodium nitroprusside (SNP), and Y-27632 to PE-induced contraction by measuring isometric tension. Results. The contractile responses to K(+), PE, Bay K 8644, and ET-1 were significantly more increased in the OAB group in a dose-dependant manner than in the control group (P0.05), and the responses to ET-1 were more prominent than those to the remaining substances (P0.01). The increased contractile responses to ET-1 were blocked by BQ123 (ET(A) receptor antagonist) but not by BQ788 (ET(B) receptor antagonist). Clitoral cavernosal strips from the OAB group were more difficult to relax than those from the control group in terms of ACh- and SNP-induced relaxation (P0.05). The Y-27632-induced relaxant responses to PE- and ET-1-induced contraction were less prominent in the OAB group than in the control group. CONCLUSIONS; The results of this study provide evidence that female OAB may deteriorate clitoral engorgement, which is associated with a greater force generation by increased calcium sensitization and subsequently decreased of relaxation. The activation of ET and Rho-kinase system may be crucial to negatively effect the clitoral smooth muscle relaxation in experimentally induced OAB animal model. But whether these vasomotor effects are revived in human clitoris is still debatable.

To assess the correlation between age, body mass index, systolic and diastolic blood pressure (BP), triglycerides, high-density lipoprotein (HDL), and fasting blood glucose (FBG) and the serum prostate-specific antigen (PSA) level and to determine the significant factors for predicting the serum PSA level in men with a low risk of prostate cancer.A total of 38 356 healthy male employees of the Korea Electric Power Corporation who were60 years old and had a serum PSA level of4 ng/mL were enrolled in this study from January 2002 to December 2006. Their BP, body weight, and body height were measured, and biochemical analyses of FBG, triglycerides, HDL, and serum PSA were performed.The mean age +/- standard deviation was 44.38 +/- 7.90 years; the mean serum PSA level was 0.89 +/- 0.51 ng/mL; and the incidence of metabolic syndrome was 25.8%. On univariate analysis, significant correlations were noted between the serum PSA level and body mass index, diastolic BP, HDL, and FBG (P.05). Multiple logistic regression analyses using 4 percentiles (10th, 25th, 75th, and 90th percentile) of the serum PSA level revealed trends for a positive association between older age and diastolic BP and the serum PSA level. The body mass index, HDL, and FBG correlated negatively with the serum PSA level.These results suggest that the serum PSA level is significantly influenced by age and some components of the metabolic syndrome (obesity, diastolic BP, HDL, and FBG).

In this study, we evaluated genetic variants of the androgen metabolism genes CYP17A1, CYP3A4, and CYP3A43 to determine whether they play a role in the development of prostate cancer (PCa) in Korean men. The study population included 240 pathologically diagnosed cases of PCa and 223 age-matched controls. Among the 789 single-nucleotide polymorphism (SNP) database variants detected, 129 were reported in two Asian groups (Han Chinese and Japanese) in the HapMap database. Only 21 polymorphisms of CYP17A1, CYP3A4, and CYP3A43 were selected based on linkage disequilibrium in Asians (r2 = 1), locations (SNPs in exons were preferred), and amino acid changes and were assessed. In addition, we performed haplotype analysis for the 21 SNPs in CYP17A1, CYP3A4, and CYP3A43 genes. To determine the association between genotype and haplotype distributions of patients and controls, logistic analyses were carried out, controlling for age. Twelve sequence variants and five major haplotypes were identified in CYP17A1. Five sequence variants and two major haplotypes were identified in CYP3A4. Four sequence variants and four major haplotypes were observed in CYP3A43. CYP17A1 haplotype-2 (Ht-2) (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.18) was associated with PCa susceptibility. CYP3A4 Ht-2 (OR: 1.87; 95% CI: 1.02-3.43) was associated with PCa metastatic potential according to tumor stage. rs17115149 (OR: 1.96; 95% CI: 1.04-3.68) and CYP17A1 Ht-4 (OR: 2.01; 95% CI: 1.07-4.11) showed a significant association with histologic aggressiveness according to Gleason score. Genetic variants of CYP17A1 and CYP3A4 may play a role in the development of PCa in Korean men.

Objective To identify whether the genetic variations in HNF1B are associated with the development of prostate cancer in Korean patients. Genome-wide association studies have found the HNF1B gene at 17q12 to be a major causal gene for the risk of prostate cancer. Methods We evaluated the association of 47 single nucleotide polymorphisms (SNPs) in the HNF1B gene with prostate cancer risk and clinical characteristics (Gleason score and tumor stage) in Korean men (240 case subjects and 223 control subjects) using unconditional logistic regression analysis. Results Of the 47 SNPs, 14 were associated with prostate cancer risk ( P = .002-.02); 9 SNPs were associated with a lower risk of prostate cancer (odds ratio 0.67-0.71, P = .005-.05), and 5 SNPs were associated with a greater risk of disease (odds ratio 1.49-1.51, P = .002-.02). In an analysis involving only patients with prostate cancer, 1 SNP (rs11868513) in the HNF1B gene was more frequent in patients with tumors with a greater stage than in those with a lower tumor stage. Two SNPs (rs4430796 and rs2074429) and 1 haplotype ( Block3_ht1 ) were more frequent in patients with Gleason score of ≥7 than in those with Gleason score Conclusion As in studies from other populations, our findings indicate that HNF1B is also associated with prostate cancer risk in the Korean population.