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Purpose: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent because of its tumor selectivity and its ability to induce apoptosis in cancer cells while sparing most normal cells. We evaluated whether docetaxel enhances TRAIL-mediated apoptosis in prostate cancer (PCa) cells and its mechanism. Materials and Methods: LNCap-LN3, PC3, and DU 145 PCa cell lines were used to investigate the effects of TRAIL with docetaxel treatment (dosages, 1, 3, 5, and 10 nmol). To evaluate the mechanism, death receptor 4 (DR4), DR5, enhancer of zeste homolog 2 (EZH2) and E2F1 levels were assessed in PCa cells. Results: Hormone-sensitive LNCap-LN3 showed apoptosis in proportion to the concentration of docetaxel. Castration-resistant PC3 and DU 145 showed no change irrespective of the docetaxel concentration. However, combinations of docetaxel (2 nM) and TRAIL (100 ng/mL) had a significant effect on apoptosis of DU 145 cells. In DU 145 cells, docetaxel reduced EZH2 and elevated expression of DR4. The decrease of EZH2 by docetaxel was correlated with the E2F1 level, which was considered as the promoter of EZH2. DZNep reduced EZH2 and elevated DR4 in all PCa cells. Additionally, DZNep-enhanced TRAIL mediated reduction of PCa cell viability. Conclusions: Docetaxel and the EZH2 inhibitor reduced EZH2 and elevated expression of DR4 in all PCa cell lines. Docetaxel-enhanced TRAIL mediated apoptosis in PCa via elevation of DR4 through epigenetic regulation by EZH2. To improve the efficacy of TRAIL for PCa treatment, adding docetaxel or EZH2 inhibitors to TRAIL may be promising.

Purpose: Owing to the safety and cost effectiveness of conditioned medium (CM), its therapeutic effects have attracted significant attention from many researchers. To date, numerous studies have been conducted on CM; however, little has been done with regard to erectile dysfunction (ED). In this research, the potential of human mesenchymal stem cell-derived CM (MSC-CM) for the treatment of ED was investigated. Materials and Methods: A high concentration of MSC-CM was prepared through 3D spheroid culturing with bone marrowderived MSCs and cut-off filtering. The composition of CM was analyzed using biochemical assays, and the effect of the preparation process on the quality of CM was investigated. The therapeutic effects of MSC-CM were evaluated through animal studies using a cavernous nerve (CN) injury rat model. Results: 3D spheroid culturing afforded a 278-fold increase in the total protein content of CM, as compared to that from 2D cultures; the protein concentration increased by 19 times on increasing the centrifugation time for cut-off filtering. Biochemical assays indicated that the CM contains various types of angiogenic, neurotrophic, and anti-inflammatory factors. Histological assay results showed that MSC-CM has angio- and neuro-trophic effect in a CN injury rat model in vivo, and these therapeutic effects appear in a dose-dependent manner. Conclusions: The experimental results confirmed the therapeutic effect of MSC-CM in healing damaged cavernosal tissue and restoring erectile function. These results successfully demonstrated that MSC-CM has significant potential for the treatment of ED.

Purpose: We investigated the effects of holmium laser enucleation of the prostate (HoLEP) in patients with a small prostate (≤30 mL) in whom medical treatment was ineffective. Materials and Methods: Data from 132 patients who underwent HoLEP by a single surgeon between 2012 and 2015 were retrospectively analyzed. All patients received benign prostatic hyperplasia medication for at least 6 months before surgery. The patients were divided into 2 groups according to prostate size: group 1, ≤30 mL (n=30); and group 2, ＞30 mL (n=102). Clinical characteristics and the International Prostate Symptom Score (IPSS), including quality of life (QoL), peak urinary flow rate (Qmax), and postvoid residual urine (PVR), before surgery and 3 months postoperatively, were compared between the 2 groups. Results: In group 1, the IPSS, QoL, and PVR significantly decreased and the Qmax significantly increased 3 months after surgery. The voiding subscore also significantly decreased 3 months after surgery (p＜0.001), but the storage subscore was not significantly different (p=0.055). In group 2, hemoglobin, the IPSS, QoL, and PVR significantly decreased and the Qmax significantly increased 3 months after surgery. In these patients, both the storage subscore and voiding subscore significantly decreased after surgery (both p＜0.001). There were no significant differences between the groups in hemoglobin, IPSS, QoL, Qmax, and PVR either before or 3 months after surgery. Conclusions: When other medical treatments are ineffective, HoLEP is an effective intervention for patients with a small prostate.

Purpose: Microsurgical vasovasostomy is associated with high patency and pregnancy rates, but is difficult and requires significant effort and time to learn. Therefore, we assessed a simplified loupe-assisted vasovasostomy method using a Prolene stent. Materials and Methods: The medical records of 82 patients who underwent loupe-assisted vasovasostomy with a Prolene stent by a single surgeon between January 2004 and December 2015 were reviewed. The association between the vasal obstructive interval (VOI) and the success rate was evaluated. Results: The average age at the time of vasovasostomy was 39.8 years (range, 29∼57 years). The mean VOI was 6.6 years (range, 1∼19 years). The mean operation time was 87.0 minutes (range, 55.0∼140.0 minutes). The overall patency and natural pregnancy rates were 90.2% and 45.1%, respectively. The success rate decreased as time after vasectomy increased (odds ratio, 0.869; 95% confidence interval, 0.760∼0.993; p=0.039). The cases were divided into 2 groups according to the mean VOI: group A (＞7 years) and group B (≤7 years), with 31 cases (37.8%) and 51 cases (62.2%), respectively. The patency and pregnancy rates of group A were 80.6% and 51.6%, respectively, while those of group B were 96.1% and 41.2%, respectively. Conclusions: Loupe-assisted vasovasostomy using a Prolene stent is a safe and effective method.

Purpose: The goal of this study was to investigate the association between hypercholesterolemia and the time required for progression to castration-resistant prostate cancer (CRPC) in patients who have undergone androgen deprivation therapy (ADT). Materials and Methods: Data from 154 patients with prostate cancer between 2005 and 2012 were reviewed retrospectively. ADT was employed as a treatment modality for these patients either due to multiple bone metastases at the time of diagnosis or due to old age in combination with other morbidities. Serum cholesterol levels and statin use were reviewed. We analyzed the factors associated with the development of CRPC after ADT treatment. The mean follow-up period was 34.8 months. Results: The mean age of the patients was 71.3 years old and their mean prostate-specific antigen level was 141.8±212.6 ng/mL. Their mean cholesterol level was 175.9±37.7 mg/dL, and 14 patients (9.1%) were statin users. CRPC developed in 44 patients (28.6%), and the mean duration from ADT treatment to CRPC was 24.1 months. In a multivariate analysis, hypercholesterolemia was associated with the development of CRPC (hazard ratio [HR]=1.017, p＜0.001), depending on clinical T stage (p=0.005) and the presence of bone metastasis (p＜0.001). A subanalysis showed that hypercholesterolemia was associated with the development of CRPC in patients with bone metastasis (HR=1.032, p＜0.001), but not in patients without bone metastasis. Conclusions: Hypercholesterolemia may be associated with the development of CRPC after ADT in patients with bone metastasis. Further studies with longer follow-up periods and larger samples are needed to validate this finding.