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Yu-Ting Chen,1,* Chen-Pang Hou,1– 3,* Horng-Heng Juang,1,4 Yu-Hsiang Lin,1,2 Pei-Shan Yang,1,4 Phei-Lang Chang,1 Chien-lun Chen,1 Shu-Chuan Weng,3 Ke-Hung Tsui1,5 1Department of Urology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan City, Taiwan; 3Health and Management, Yuanpei University of Medical Technology, Hsinchu, Taiwan; 4Department of Anatomy, School of Medicine, Chang Gung University, Tao-Yuan, Taipei, Taiwan; 5Department of Urology, Shuang Ho Hospital, TMU Research Center of Urology and Kidney, School of Medicine, College of Medical, Taipei Medical University, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Ke-Hung Tsui, Taiwan Innovative Medical Association, Department of Urology, Shuang Ho Hospital, College of Medical, Taipei Medical University, Taipei, Taiwan, Email t2130@s.tmu.edu.tw Shu-Chuan Weng, Department of Healthcare Management, Yuanpei University of Medical Technology, Hsinchu, Taipei, Taiwan, Email scweng303@mail.ypu.edu.twBackground and Purpose: In this study, we compared patient outcomes between the 120-W thulium laser (Vela™XL) prostate enucleation (ThuLEP) and bipolar transurethral enucleation of the prostate (B-TUEP) techniques.Methods: We excluded patients with concomitant prostate cancer and bladder cancer and prospectively analyzed patients with benign prostatic obstruction (BPO) who underwent ThuLEP and B-TUEP from October 2018 to January 2021 in our institution. Patients’ demographics, comorbidities, prostate volumes, prostate-specific antigen (PSA) levels, and International Prostate Symptoms Score (IPSS) were recorded. Perioperative outcomes including intraoperative blood loss, prostate resection percentage of the transition zone, postoperative pain score (numeric rating scale, NRS), complications, changes in postoperative uroflowmetry parameters, IPSS, and the rate of reuse of BPH medications were also evaluated.Results: The data of a total of 111 patients (ThuLEP: 49, B-TUEP: 62) met the inclusion criteria were collected and analyzed prospectively. Our results revealed no significant differences between ThuLEP and B-TUEP in terms of operation time, prostate tissue enucleated, and days of hospitalization. However, patients in the ThuLEP group reported less pain after surgery than those in the B-TUEP group, and a higher proportion of patients in the B-TUEP group returned to the emergency department due to complications within one month postoperatively, with hematuria being the main cause. No significant differences were observed between the groups in changes in uroflowmetry parameters and IPSS at 2 weeks, 3 months, and 6 months postoperatively.Conclusion: The efficacy of ThuLEP was comparable to that of B-TUEP in terms of maximal flow rate, voiding volume, IPSS, and quality of life. ThuLEP also had several advantages over B-TUEP, including less blood loss and less postoperative pain. Therefore, ThuLEP can be considered a treatment of choice for BPH/bladder outlet obstruction, specifically for patients with a bleeding tendency and fear of pain.Keywords: prostate, laser, prostatectomy, prostatic hyperplasia, quality

This study compared the surgical outcomes of the 120-W Thulium laser (Vela™ XL) enucleation of the prostate and bipolar transurethral resection of the prostate (TURP) in terms of efficacy, safety, and improvements of quality of life (QoL) in patients with benign prostate hyperplasia (BPH). Records were obtained from January 2014 to September 2018 for selected patients with symptomatic BPH who underwent 120-W Thulium laser (Vela™XL) prostate enucleation and bipolar TURP in our institution. All the patients selected met the surgical criteria for TURP and had received medical treatment for at least 3 months. Patients were excluded if their ECOG performance status was >1, if they had active malignant disease, of if they had a history of prostate surgery or reconstruction surgery of the urinary system. Patients decided which treatment option would be performed. Both the procedures were conducted by a single surgeon. Clinical outcomes such as changes in the International Prostate Symptom Score (IPSS) score, urodynamic parameters, drug consumption, pain scores, and QoL were evaluated. The rate of urinary tract infection, recatheterization, additional analgesic requirement, return to the emergency department for treatment, and other surgical complications was analyzed and compared between the two cohorts. A total of 276 patients met the inclusion criteria. Among them, 141 patients received bipolar TURP, where as 135 decided to receive laser vaporesection. No significant difference was observed in age, PSA level, prostate volume, and comorbidities between the two cohorts. Pre-operative (pre-op) urodynamic parameters were also identical, except that the laser surgery group had a higher rate of admission with a urinary catheter (24.4% vs. 14.2%, p=0.044). The operating time was longer in the laser surgery group (79.3 minutes vs. 62.4 minutes, p

In this study, we compared patient outcomes between the 120-W thulium laser (Vela™XL) prostate enucleation (ThuLEP) and bipolar transurethral enucleation of the prostate (B-TUEP) techniques.We excluded patients with concomitant prostate cancer and bladder cancer and prospectively analyzed patients with benign prostatic obstruction (BPO) who underwent ThuLEP and B-TUEP from October 2018 to January 2021 in our institution. Patients' demographics, comorbidities, prostate volumes, prostate-specific antigen (PSA) levels, and International Prostate Symptoms Score (IPSS) were recorded. Perioperative outcomes including intraoperative blood loss, prostate resection percentage of the transition zone, postoperative pain score (numeric rating scale, NRS), complications, changes in postoperative uroflowmetry parameters, IPSS, and the rate of reuse of BPH medications were also evaluated.The data of a total of 111 patients (ThuLEP: 49, B-TUEP: 62) met the inclusion criteria were collected and analyzed prospectively. Our results revealed no significant differences between ThuLEP and B-TUEP in terms of operation time, prostate tissue enucleated, and days of hospitalization. However, patients in the ThuLEP group reported less pain after surgery than those in the B-TUEP group, and a higher proportion of patients in the B-TUEP group returned to the emergency department due to complications within one month postoperatively, with hematuria being the main cause. No significant differences were observed between the groups in changes in uroflowmetry parameters and IPSS at 2 weeks, 3 months, and 6 months postoperatively.The efficacy of ThuLEP was comparable to that of B-TUEP in terms of maximal flow rate, voiding volume, IPSS, and quality of life. ThuLEP also had several advantages over B-TUEP, including less blood loss and less postoperative pain. Therefore, ThuLEP can be considered a treatment of choice for BPH/bladder outlet obstruction, specifically for patients with a bleeding tendency and fear of pain.

Few studies have addressed the impact of diagnostic urine metabolites and the clinical outcomes associated with genitourinary urothelial (GU) cancer to date. Furthermore, longitudinal analysis of the dynamics of urine metabolites contributing to the detection of GU cancer has not yet been fully investigated; therefore, the discovery of novel diagnostic urine biomarkers is of enormous interest. We explored the correlation of the urine metabolomic profiles to GU cancers. The aqueous metabolites of the GU cancer and the control were also identified and analyzed through high-resolution1H nuclear magnetic resonance (NMR) spectroscopy. Compared with the control, the urine metabolites of the tumor were studied in relation to changes over time in a linear mixed model for repeated measures. The urine metabolites of sixty-three (44 male and 19 female) patients with GU cancers were systemically analyzed. The urine metabolite profile in GU cancer was significantly higher than those in the control group (p

Introduction: The effects of Gassless single port retroperitoneoscopic surgery with urologic diseaseremain unclear. In this retrospective review, we aim to elucidate the effect of the Gassless retroperitoneoscopy for urologic disease. Methods: We retrospectively enrolled five consecutive patients who visited the urologic department for urologic disease from January 2016 to October 2016. All cases were followed up at least 12 months postoperatively. Of these, two renal mass, two adrenal tumors and one ureter stricture were reports. Result: There were no significant differences between the characteristics of these groups. (p

To evaluate the surgical outcomes of stroke patients with symptomatic benign prostatic hyperplasia (BPH) who underwent transurethral resection of the prostate (TURP) and compare the clinical outcomes between patients with stroke and those without stroke receiving this procedure.This retrospective cohort study analyzed claims data collected during the period of 1997-2012 from Taiwan National Health Insurance Research Database. We enrolled 6625 patients who had persistent lower urinary tract symptoms and underwent TURP for BPH. They were categorized into a stroke (n = 577) and nonstroke (n = 6048) group. Patient characteristics, postoperative clinical outcomes, medication records, and medical expenses were compared.Compared with the stroke group patients, those in the nonstroke group were younger, had fewer comorbidities, and more favorable postoperative clinical outcomes. Nevertheless, TURP achieved favorable outcomes in stroke patients with symptomatic BPH. In the stroke group, the rate of urinary tract infection (UTI) decreased from 34.7% during 1 year preoperatively to 29.8% during 1 year postoperatively (p = .05). The rate of urinary retention (UR) also decreased from 55.5% during 1 year preoperatively to 22.5% during 1 year postoperatively (p = .05). TURP reduced the overall medical expenses of patients with stroke. Annual patient medical expense during 1 year preoperatively, 1 year postoperatively, 2 years postoperatively, and 3 years postoperatively was NT$659,000, NT$646,000, NT$560,000, and NT$599,000, respectively.In patients with stroke, TURP reduces the risks of UTI and UR and annual total medical expense.

Hung-Cheng Kan,1 Chen-Pang Hou,1,2 Yu-Hsiang Lin,1,2 Ke-Hung Tsui,1,2 Phei-Lang Chang,1,2 Chien-Lun Chen1,2 1Department of Urology, Chang Gung Memorial Hospital, 2School of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China Purpose: Prostate cancer patients with surprisingly high prostate-specific antigen (PSA) are encountered clinically. However, descriptions of this group of patients are extremely rare in the published literature. This study reports treatment outcome and long-term prognosis for this group of patients.Patients and methods: Between January 2007 and December 2012, 2,064 patients with PCa diagnosed at a tertiary medical center were retrospectively reviewed. A total of 90 PCa cases were identified with initial PSA (iPSA) >1,000 ng/mL at diagnosis. A retrospective study was conducted in this cohort, with comparison among stratified patient age groups, PSA, treatment options, and overall survival.Results: The mean PSA at PCa diagnosis in this cohort was 3,323 ng/mL (1,003–23,126, median: 2,050ng/mL). Most patients were in the age group 65–79 years (55/90, 61%). Males older than 80 years had a poor prognosis (P90% of iPSA following primary androgen deprivation therapy (reaching true nadir) could be a predictor of longer survival (P1,000 ng/mL. Reaching a true nadir of PSA following primary androgen deprivation therapy could be a predictor of longer survival. Bilateral orchiectomy is recommended for this group of patients. Keywords: prostate cancer, PSA, nadir, androgen deprivation, orchiectomy

Purpose: To analyze the outcomes of thulium vapoenucleation of the prostate (ThuVEP) in the management of benign prostatic hyperplasia. The outcomes of this increasingly popular procedure are yet to be confirmed in patients with various prostate sizes and health status. Materials and methods: Three hundred and three patients who underwent ThuVEP were included and stratified in subgroups according to prostate size and age. We analyzed patient demographics, preoperative disease-related parameters, and perioperative and follow-up results. Correlation of prostate size and operation time were also assessed. Results: Baseline mean prostate volume was 61.0 mL (range 19.3–226 mL), mean urinary peak flow rate (Qmax) was 8.6 mL/second (range 1.4–23.25 mL/second), mean postvoid residual volume was 126.2 mL (range 0–649 mL) and mean International Prostate Symptom Score was 25.1 (range 8–35). The mean operation time was 84.0 minutes and 88.6 minutes for total and prostate volume >80 mL, respectively. After laser surgery, there were mean reductions of 5.3 ng/mL, 7.5 ng/mL, 3.7 ng/mL, and 3.5 ng/mL (38.0%, 49.7%, 30.3%, and 36.5% change from baseline) in prostate-specific antigen level among the four groups. As for postvoid residual volume, there was a significant reduction in volume in the total, prostate volume >80 mL and prostate volume

The surgical outcomes of patients with single ureteral stones who had undergone ureteroscopic Holmium laser lithotripsy as outpatients and compare them with those of patients who had received the same procedure as inpatients. Records were obtained from January 2012 to December 2016 for selected patients who had undergone the above mentioned procedure at our institution. Patients were excluded if their ECOG performance status was ≥2, presented with multiple stones or concomitant renal stones, had histories of cancer or congenital urinary system abnormalities, or had undergone urinary system reconstruction surgery. Patients could decide whether to receive the procedure as an outpatient or inpatient. All surgeries were performed by a single surgeon. Patients preoperative, operative, and postoperative data were recorded. The clinical results, such as urinary tract infection, analgesic requirement, rate of returning to the emergency room, stone clearance, surgical complications, and medical expenditure for the treatment courses were analyzed and compared between the 2 cohorts. In total, 303 patients met the inclusion criteria. Among them, 119 patients decided to receive ureteroscopic laser lithotripsy as outpatients, whereas 184 decided to be inpatients. The outpatient cohort was younger (P

Background To evaluate the long-term surgical outcomes of patients with urinary retention (UR) caused by a benign prostatic obstruction (BPO) who underwent transurethral resection of the prostate (TURP), and compare their outcomes with those of patients who received medication without surgical intervention. Methods This retrospective cohort study analyzed claims data collected during the period of 1997–2012 from Taiwan’s National Health Insurance Research Database. We examined geriatric adverse events among patients who had received a diagnosis of symptomatic benign prostatic hyperplasia and whom experienced UR, and compared those who received TURP and medication only. Primary outcomes included urinary tract infection (UTI), UR, inguinal hernia, hemorrhoids, stroke, acute myocardial infarction, and bony fracture. We excluded patients who had concomitant prostate cancer, bladder cancer, or a long-term urinary catheter indwelling, as well as those who did not receive α-blocker medication regularly. Those aged 90 years were also excluded. The enrolled patients were categorized into TURP (n = 1218) and medication only (n = 795) groups. After 1:1 propensity score matching, we recorded and compared patients’ characteristics, postoperative clinical outcomes, and geriatric adverse events. Results The TURP cohort had a lower incidence of UTI and UR during the postoperative follow-up period from 2 months to 3 years than did the medication only group (20.7% vs. 28.9% and 12.5% vs. 27.6%, respectively, p

BACKGROUND Liver X receptor (LXR) isoforms, LXRα and LXRβ, have similar protein structures and ligands, but diverse tissue distribution. We used two synthetic, non-steroidal LXR agonists, T0901317 and GW3965, to investigate the effects of LXR agonist modulation on prostate specific antigen (PSA) via the expressions of androgen receptors (AR), LXRα, or LXRβ, in prostate carcinoma cells. METHODS LXRα- or LXRβ-knockdown cells were transduced with specific shRNA lentiviral particles. LXRα and LXRβ expressions were assessed by immunoblotting and RT-qPCR assays. Cell proliferation was determined by 3H-thymidine incorporation assays. The effects of LXR agonists and epigallocatechin gallate (EGCG) on PSA expression were determined by ELISA, immunoblotting, or transient gene expression assays. RESULTS Treatment with either T0901317 or GW3965 significantly attenuated cell proliferation of LNCaP cells. T0901317 treatment suppressed PSA expression while GW3965 treatment enhanced PSA expression. The increase of PSA promoter activity by GW3965 was dependent on the expression of AR. Either LXRα- or LXRβ-knockdown did not affect the activation of androgen on PSA gene expression. However, as compared with mock knockdown-LNCaP cells, the LXRα-knockdown but not the LXRβ-knockdown attenuated the effects of T0901317 and GW3965 on PSA expressions. The effect of GW3965 on PSA expression was blocked by the addition of EGCG. CONCLUSIONS Our results indicate that T0901317 and GW3965 have divergent effects on PSA expressions. The effects of LXR agonists on PSA expression are LXRα-dependent and AR-dependent. EGCG blocks the inducing effect of GW3965 on PSA expression. Prostate 75: 603–615, 2015. © 2015 Wiley Periodicals, Inc.

Yu-Hsiang Lin,1–3,* Chen-Pang Hou,1,2,* Tien-Hsing Chen,2,4 Horng-Heng Juang,5 Phei-Lang Chang,1,2 Pei-Shan Yang,1,2 Yu-Sheng Lin,2,6 Chien-Lun Chen,1,2 Ke-Hung Tsui1,2 1Department of Urology, Chang Gung Memorial Hospital – Linkou, 2School of Medicine, 3Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, 4Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, 5Department of Anatomy, School of Medicine, Chang Gung University, Kwei-shan, Tao-Yuan, 6Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan, Republic of China *These authors contributed equally to this work Purpose: We assessed the lower urinary tract symptoms (LUTSs) and clinical outcomes between diabetes mellitus (DM) patients and non-diabetic (non-DM) patients receiving transurethral resection of prostate (TUR-P). Methods: This analysis was a retrospective cohort study using 13years (2000–2012) of claims data from Taiwan’s National Health Insurance Research Database (NHIRD). A total of 4,887 patients who had persistent LUTSs and underwent TUR-P for prostate enlargement (benign prostate enlargement [BPE]) were enrolled and divided into two groups: DM and non-DM groups. The patients’ characteristics, postoperative clinical outcomes, and the medication records after TUR-P were compared. Chi-square test was used for categorical variables and independent samples t-test for continuous variables. Multivariable logistic regression analysis was used to compare the risk of postoperative outcomes. Finally, we estimated the medication-free survival rate after TUR-P using Kaplan–Meier method and compared it between study groups using log-rank test. Results: DM group patients had a higher prevalence of comorbidities. Postoperatively, the DM group had lower rates of urinary tract infection (UTI; odds ratio [OR], 0.78; P=0.009) and higher rates of urinary retention requiring catheterization (OR, 1.35; P=0.01) within 1month after TUR-P. A higher proportion of patients with DM took anti-muscarinics (OR, 1.23; P=0.032) within the first 3months and α-blockers (OR, 1.18; P=0.049) during 3–12months after receiving TUR-P. Overall, the DM group patients had a worse postoperative medication-free survival compared to that of non-DM group patients (95% confidence interval [95% CI], 1.14; P=0.005). Conclusion: DM patients require higher rates of continuing medication after TUR-P, especially anti-muscarinics in 3months postoperatively and alpha-blocker after 3months postoperatively. DM patients also had higher incidence of urine retention after surgery. DM patients had relatively poor treatment outcomes compared to DM-free patients. Keywords: benign prostate hyperplasia, infection, overactive bladder, prostatectomy, urinary tract infection, lower urinary tract symptoms

The associations between the treatment outcomes of benign prostatic hyperplasia/benign prostatic obstruction and lifelong health status, including urologic cancer incidence as well as geriatric adverse events (AEs), are unknown. This retrospective cohort study analyzed claims data collected during the period of 1997&ndash, 2012 from Taiwan&rsquo, s Longitudinal Health Insurance Database 2000. Patients who received transurethral resection of the prostate (TURP) were prioritized, and the remaining patients who were prescribed alpha-blockers were, subsequently, identified. Patients in the TURP and medication-only groups were further divided into two groups, according to the presence or absence of AEs during the first six-month follow-up. Outcomes of primary interest were all-cause mortality, occurrence of prostate cancer, transurethral resection of the bladder tumor, and radical cystectomy for bladder cancer. Compared with patients in the AE-free TURP group, those in the TURP with AEs had a higher risk of lifelong bladder cancer (subdistribution hazard ratio: 2.3, 95% confidence interval (CI): 1.56&ndash, 3.39), whereas the risk of prostate cancer was comparable between the two groups (SHR: 1.2, 95% CI: 0.83&ndash, 1.74). In the medication cohorts, patients undergoing alpha-blocker treatment who had AEs had a higher risk of all-cause mortality (hazard ratio: 1.63, 95% CI: 1.49&ndash, 1.78) and a higher risk of lifelong bladder cancer (SHR: 2.72, 95% CI: 1.99&ndash, 3.71) when compared with those without AE. Our study reveals that unfavorable treatment outcomes of benign prostate hyperplasia, whether caused by medication or surgical treatment, are associated with a higher incidence of bladder cancer. Unfavorable outcomes of surgical treatment are associated with higher risk of geriatric AEs, and unfavorable outcomes of medication treatment are associated with a higher risk of all-cause mortality.

Wei-Chang Lee,1,* Yu-Hsiang Lin,1,* Chen-Pang Hou,1 Phei-Lang Chang,1 Chien-Lun Chen,1 Horng-Heng Juang,2 Ke-Hung Tsui1 1Department of Urology, Chang Gung Memorial Hospital-Linko and Chang Gung University, College of Medicine, Taiwan, 2Department of Anatomy, College of Medicine, Chang Gung University, Kweishan-Shan, Taoyuan, Taiwan, Republic of China *These authors contributed equally to this work Purpose: Endoscopic lasers have become a treatment option for benign prostate hyperplasia (BPH). The study reported here sought to elucidate the benefits and drawbacks of different laser systems in the treatment of patients with BPH. Methods: The study enrolled 741 patients diagnosed with lower urinary tract symptoms secondary to BPH during the period January 2005 to December 2011. The techniques used in the study were photoselective vaporization of the prostate, thulium laser prostatectomy, and diode laser prostatectomy. Patients were assigned to one of three groups according to the type of laser treatment they received. Outcomes were evaluated using the International Prostate Symptom Score (IPSS), quality of life, maximal urinary flow rate, post-voiding residual urine volume, and prostate-specific antigen (PSA) level. Results: The baseline characteristics of patients who received diode laser prostatectomy show a significant elevated risk and high American Society of Anesthesiology score (P=0.001). Operative time and catheter removal time differed significantly between the three groups (P=0.001). No cases were converted to transurethral resection of the prostate intraoperatively due to bleeding (P=0.142). Among the three groups, there were no significant differences in maximal flow rate, lower post-void residual urine, and postoperative PSA level during the entire follow-up period (P

Objective To evaluate whether using the direct observation of procedural skills (DOPS) tool improves the accuracy of students’ performance for clinical skill assessment. Materials and Methods Outcome- and clinical-based evidence results were analyzed for prostate size measurement for benign prostatic hyperplasia (BPH), including digital rectal examination (DRE) and transrectal ultrasonography (TRUS). Patients were stratified into three clinical groups based on the results of DRE and TRUS. Clinical outcomes were correlated between DRE and TRUS for prostate size. We designed a DOPS study in a clinical setting with actual patients in which DRE and TRUS results for prostate volume measurement were compared in order to determine their correlation. Results The DRE of patients with mild, moderate, and severe BPH showed prostate size variations. The correlation between DRE and TRUS showed that DRE underestimated prostate size in the severe hyperplasia group (>60 mL) and was more accurate in the moderate hyperplasia group (40–60 mL). The implementation of DOPS for prostate size measurement improved students' self-assessed communication and counseling skills. The study results show that the DOPS tool improved students' prostate measurement techniques and skills (Cronbach's α > 0.70). Conclusion We demonstrated that students’ clinical skills for the measurement of prostate size improved after the implementation of the DOPS tool in DRE to determine prostate size accurately in the clinical teaching program. Clinicians can enhance clinical skills education in certain circumstances with strategic incorporation of tools for direct observation into medical student training programs. By using the DOPS scoring system and reviewing faculty feedback, trainees can improve their accuracy of prostate size measurements.

BACKGROUND Metallothioneins (MT1, MT2, MT3, and MT4) are regarded as modulators regulating a number of biological processes including cell proliferation, differentiation, and invasion. We determined the effects of androgen, cadmium, and arsenic on MT1/2 and MT3 in prostate carcinoma cells, and evaluated the functional effects of MT3 on cell proliferation, invasion, and tumorigenesis. METHODS We determined the expression of MT1/2 and MT3 in prostate carcinoma cells by immunoblotting assays or real-time reverse transcription-polymerase chain reactions. The effects of ectopic MT3 overexpression or MT3-knockdown on cell proliferation, invasion, and tumorigenesis were determined by 3H-thymidine incorporation, matrigel invasion, and murine xenograft studies. The effects of androgen, cadmium, and arsenic on target genes were assessed using immunoblotting and reporter assays. RESULTS Androgen, cadmium, and arsenic treatments enhanced gene expression of MT1/2 and MT3 in prostate carcinoma LNCaP cells. Results of immunohistochemical staining indicated MT3 overexpression was found predominantly in the nuclear areas of PC-3 cells overexpressing MT3. Overexpression of MT3 significantly increased cell proliferation, invasion, and tumorigenic activities in PC-3 cells in vitro and in vivo. MT3 overexpression downregulated the gene expressions of N-myc downstream regulated gene 1 (Ndrg1) and maspin, and attenuated blocking effects of doxorubicin in PC-3 cells on cell proliferation. MT3-knockdown enhanced Ndrg1 and maspin expressions in LNCaP cells. CONCLUSIONS The experiments indicate that MT3 is an androgen-upregulated gene, and promotes tumorigenesis of prostate carcinoma cells. The downregulation of Ndrg1 and maspin gene expressions appears to account for the enhancement of proliferative and invasive functions of MT3 in PC-3 cells. Prostate 73: 1495–1506, 2013 © 2013 Wiley Periodicals, Inc.

Hypoxia induces metabolic alteration in cancer cells by stabilizing hypoxia-inducible factor 1α (HIF-1α (HIF1A)), which regulates the bioenergetic genes of glycolysis and lipid metabolic pathways. However, the target genes of hypoxia-induced metabolic alterations in the prostate remain uncertain. Mitochondrial aconitase (mACON) (ACONM) is an enzyme that is central to carbohydrate and energy metabolism and is responsible for the interconversion of citrate to isocitrate as part of the citric acid cycle in the human prostate. We evaluated the effects of the molecular mechanisms of hypoxia onmACONgene expression in PC-3 and LNCaP human prostate carcinoma cells. Immunoblotting assays revealed that hypoxia modulated mACON and lactate dehydrogenase A (LDHA) protein expression, while these effects were attenuated whenHIF-1αwas knocked down. Hypoxia induced fatty acid synthase (FASN) in PC-3 cells while hypoxia blockedFASNgene expression in LNCaP cells after 24-h incubation. Results of real-time RT-qPCR, immunoblotting, and transient gene expression assays revealed that hypoxia treatment or co-transfection withHIF-1αexpression vector enhanced gene expression ofmACON, implying that hypoxia modulatedmACONat the transcriptional level. Hypoxia-inducedmACONpromoter activity is dependent on the DNA fragment located at −1013 to −842 upstream of the translation initiation site.l-mimosine, an iron chelator, stabilized HIF-1α but downregulatedmACONgene expression, suggesting that iron chelation blocked the hypoxia-inducedmACONgene expression. These results suggest that hypoxia dysregulates the expressions ofLDHA,FASN, andmACONgenes, and the hypoxia-inducedmACONgene expression is via the HIF-1α-dependent and iron-dependent pathways in prostate carcinoma cells.

Interleukin-6, a multifunctional cytokine, contributes to tumor cell proliferation and differentiation. However, the biological mechanisms that are affected by the expression of interleukin-6 in bladder cancer cells remain unclear. We evaluated the effects of interleukin-6 expression in human bladder carcinoma cellsin vitroandin vivo. The results of interleukin-6-knockdown experiments in T24 cells and interleukin-6-overexpression experiments in HT1376 cells revealed that interleukin-6 reduced cell proliferation, migration, and invasionin vitro. Xenograft animal studies indicated that the overexpression of interleukin-6 downregulated tumorigenesis of bladder cells and that interleukin-6 knockdown reversed this effect. The results of RT-PCR, immunoblotting, and reporter assays indicated that the overexpression of interleukin-6 upregulated the expression of the mammary serine protease inhibitor (MASPIN), N-myc downstream gene 1 (NDRG1), and KAI1 proteins in HT1376 cells and that interleukin-6 knockdown reduced the expression of these proteins in T24 cells. In addition, results of immunoblotting assays revealed that interleukin-6 modulated epithelial-mesenchymal transitions by upregulating the expression of the E-cadherin, while downregulation N-cadherin and vimentin proteins. Our results suggest that the effects of interleukin-6 on the regulation of epithelial-mesenchymal transitions and the expressions of the MASPIN, NDRG1, and KAI1 genes attribute to the modulation of tumorigenesis in human bladder carcinoma cells.

Bladder cancer is a common urologic cancer whose incidence continues to rise annually. Urinary microparticles are an attractive material for noninvasive bladder cancer biomarker discovery. In this study, we applied isotopic dimethylation labeling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to discover bladder cancer biomarkers in urinary microparticles isolated from hernia (control) and bladder cancer patients. This approach identified 2964 proteins based on more than two distinct peptides, of which 2058 had not previously been reported as constituents of human urine exosomes/microparticles. A total of 107 differentially expressed proteins were identified as candidate biomarkers. Differences in the concentrations of 29 proteins (41 signature peptides) were precisely quantified by LC-MRM/MS in 48 urine samples of bladder cancer, hernia, and urinary tract infection/hematuria. Concentrations of 24 proteins changed significantly (p0.05) between bladder cancer (n=28) and hernia (n=12), with area-under-the-curve values ranging from 0.702 to 0.896. Finally, we quantified tumor-associated calcium-signal transducer 2 (TACSTD2) in raw urine specimens (n=221) using a commercial ELISA and confirmed its potential value for diagnosis of bladder cancer. Our study reveals a strong association of TACSTD2 with bladder cancer and highlights the potential of human urinary microparticles in the noninvasive diagnosis of bladder cancer.

BACKGROUND. Glycoprotein transmembrane nmb (GPNMB) gene was originally identified in osteoblasts and belongs to the pmel-17/nmb family. The function or regulation of GPNMB in the human prostate remains unknown. METHODS. The expression of GPNMB in prostate carcinoma cells were determined by real-time reverse transcription-polymerase chain reaction (RT-qPCR) and immunoblot assays. Effects of ectopic GPNMB overexpression on cell proliferation, invasion, and tumorigenesis were determined by 3 H-thymidine incorporation, matrigel invasion, soft agar cloning assays, and murine xenograft study. Effects of GPNMB, p53, and androgen on target gene were assessed using RT-PCR, immunoblotting, and transient gene expression assays. RESULTS. In vitro analysis using several prostate cell lines suggested that expression of GPNMB may be relevant to the extent of neoplasia. Ectopic overexpression of GPNMB significantly attenuated cell proliferation and invasion and exerted antitumorigenic activity on PC-3 cells in vitro and in vivo. GPNMB overexpression induced the gene expressions of N-myc downstream regulated gene 1 (Ndrg1) and maspin in PC-3 cells. Doxorubicin treatment or transient overexpression of p53 increased GPNMB expression. Androgen (R1881) treatment has a divergent effect on gene expression of prostate-specific antigen (PSA) and GPNMB in LNCaP cells. Androgen treatment enhanced cell proliferation but downregulated GPNMB protein expression in stably overexpressed androgen receptor (AR) CA-HPV-10 cells. CONCLUSIONS. Together these results suggest that GPNMB gene is a p53- and androgen-dysregulated gene and should be regarded as an anti-tumor gene for prostate cancer. The enhancement of Ndrg1 and maspin gene expressions may account for the anti-proliferative and anti-invasive function of GPNMB in PC-3 cells. Prostate 72:1431–1442

Prostate-derived Ets (E-twenty six) factor (PDEF), an epithelium-specific member of the Ets family of transcription factors, has been shown to play a role in suppressing the development of many epithelium-derived cancers such as prostate and breast cancer. It is not clear, however, whether PDEF is involved in the development or progression of bladder cancer. In a comparison between normal urothelium and bladder tumor tissue, we identified significant decreases of PDEF in the tumor tissue. Further, the immunohistochemistry assays indicated a significantly higher immunostaining of PDEF in low-grade bladder tumors. Additionally, the highly differentiated transitional-cell bladder carcinoma RT-4 cells expressed significantly more PDEF levels than the bladder carcinoma HT1376 and the T24 cells. Ectopic overexpression of PDEF attenuated proliferation, invasion, and tumorigenesis of bladder carcinoma cells in vitro and in vivo. PDEF enhanced the expression levels of mammary serine protease inhibitor (MASPIN), N-myc downstream regulated gene 1 (NDRG1), KAI1, and B-cell translocation gene 2 (BTG2). PDEF modulated epithelial-mesenchymal-transition (EMT) by upregulating E-cadherin expression and downregulating the expression of N-cadherin, SNAIL, SLUG, and vimentin, leading to lower migration and invasion abilities of bladder carcinoma cells. Filamentous actin (F-actin) polarization and remodeling were observed in PDEF-knockdown RT-4 cells. Our results suggest that PDEF gene expression is associated with the extent of bladder neoplasia and PDEF modulated the expressions of EMT-related genes. The induction of BTG2, NDRG1, MASPIN, and KAI1 gene expressions by PDEF may explain the inhibitory functions of PDEF on the proliferation, invasion, and tumorigenesis in bladder carcinoma cells.

Scope: Prostate-specific antigen (PSA) is a well-known marker for diagnosing and monitoring prostate cancer. Curcumin, a yellow curry pigment, has been reported to enhance androgen receptor (AR) degradation. We examined the effects of curcumin on increasing PSA expression by hypoxia and prolyl hydroxylase inhibitors, L-mimosine and dimethyloxalylglycine (DMOG), in human prostate carcinoma LNCaP cells. Methods and results: The 3 H-thymidine incorporation assay revealed that either L-mimosine or DMOG treatments attenuated cell proliferation. Immunoblot and enzyme-linked immunosor- bent assays (ELISA) indicated that both L-mimosine and DMOG have an effect similar to hypoxia, which stabilized hypoxia-inducible factor-1a (HIF-1a) and induced PSA gene expression. The results of the immunoblot and transient gene expression assays indicated that induction of the PSA expression by hypoxia is both HIF-1a- and AR-dependent. Immunoblot assays revealed that a curcumin treatment (10mM) decreased the protein abundance of AR but did not significantly affect the protein levels of HIF-1a and vascular endothelial growth factor, which were induced by hypoxia. ELISA and transient gene expression assays indicated that curcumin blocked the acti- vation of L-mimosine or DMOG treatment on PSA expression. Conclusions: These results indicate that curcumin blocked the enhanced effect of PSA expression by L-mimosine and DMOG that induce hypoxia condition.