Recent studies have shown that epigenetic alterations lead to oncogenic activation, thus indicating that these are therapeutic targets. Herein, we analyzed the efficacy and therapeutic potential of our developed histone lysine demethylase 1 (LSD1) inhibitor, NCL1, in castration-resistant prostate cancer (CRPC). The CRPC cell lines 22Rv1, PC3, and PCai1CS were treated with NCL1, and LSD1 expression and cell viability were assessed. The epigenetic effects and mechanisms of NCL1 were also evaluated. CRPC cells showed strong LSD1 expression, and cell viability was decreased by NCL1 in a dose-dependent manner. Chromatin immunoprecipitation analysis indicated that NCL1 induced histone H3 lysine 9 dimethylation accumulation at promoters of P21. As shown by Western blot and flow cytometry analyses, NCL1 also dose-dependently induced caspase-dependent apoptosis. The stimulation of autophagy was observed in NCL1-treated 22Rv1 cells by transmission electron microscopy and LysoTracker analysis. Furthermore, WST-8 assay revealed that the anti-tumor effect of NCL1 was reinforced when autophagy was inhibited by chloroquine in 22Rv1 cells. Combination index analysis revealed that a concurrent use of these drugs had a synergistic effect. In ex vivo analysis, castrated nude mice were injected subcutaneously with PCai1 cells and intraperitoneally with NCL1. Tumor volume was found to be reduced with no adverse effects in NCL1-treated mice compared with controls. Finally, immunohistochemical analysis using consecutive human specimens in pre- and post-androgen deprivation therapy demonstrated that LSD1 expression levels in CRPC, including neuroendocrine differentiation cases, were very high, and identical to levels observed in previously examined prostate biopsy specimens. NCL1 effectively suppressed prostate cancer growth in vitro and ex vivo without adverse events via the regulation of apoptosis and autophagy, suggesting that NCL1 is a potential therapeutic agent for CRPC.

The purpose of this study was to assess the efficacy of Bacillus Calmette-Guerin (BCG) therapy after a second transurethral resection (TUR) in new onset high-grade T1 bladder cancer. From January 2008 to September 2013, 207 patients with new onset high-grade T1 bladder cancer after an initial TUR were treated at our university and at affiliated hospitals. Residual cancer rate, intravesical recurrence-free survival (RFS), and risk factors for intravesical recurrence were analyzed. Among a total of 207 patients, 42 patients were treated with BCG therapy following a second TUR (group 1), 23 were treated with second TUR alone (group 2), 72 were treated with BCG alone (group 3), and 70 were treated without a second TUR or BCG. The median patients’ age was 72.0 years, and the median follow-up period was 33.5 months. The second TUR revealed that 34 patients (52 %) had residual cancer. Between groups 1 and 2 and groups 1 and 3, the differences in RFS were statistically significant (p = 0.002 and 0.045, respectively). In addition, BCG therapy was the most significant factor to predict RFS after the second TUR. Among the 31 patients whose pathology of the second TUR was pT0, only 1 of 12 patients (8 %) in group 1 and 11 of 19 patients (58 %) in group 2 had a recurrence. BCG instillation following a second TUR decreases intravesical recurrence, even if the pathology of the second TUR is pT0.

Management of late relapse of a testicular germ cell tumor is difficult because few cases have been reported and the tumors are intractable to chemotherapy. Here we present a case with a single brain metastasis from late relapse of a testicular germ cell tumor. This is the first report of a brain metastasis that was treated successfully only by surgery. A 19-year-old Japanese man presented with breathing difficulties and left testis enlargement and he was diagnosed with a yolk sac tumor following a left orchiectomy. At the time of diagnosis, multiple lung metastases were apparent on computed tomography, and serum alpha-fetoprotein level was elevated to 10,245 ng/ml. The patient received three postoperative courses of bleomycin, etoposide and cisplatin and etoposide and cisplatin respectively and a complete response was obtained. Four years after surgery, the patient was admitted to the hospital due to a sudden seizure. High alpha-fetoprotein levels (539 ng/ml) were evident and magnetic resonance imaging suggested a 45-mm single brain tumor in the right parietal lobe, for which surgery was performed. The pathological diagnosis was yolk sac tumor. The alpha-fetoprotein level remained normal at 2 months after operation. There was no recurrence 24 months post-operation. Chemoresistance and late neurotoxicity are concerns in treating brain metastasis with chemotherapy or cerebral radiotherapy. Surgery is believed to be the optimal treatment choice if the size of the brain metastasis is larger than 35-mm and the late relapse area is surgically accessible.

Objective: To analyze the effectiveness and complication rate of magnetic resonance imaging (MRI)–guided prostate needle biopsies using real-time virtual sonography (RVS) versus BioJet navigation. Methods: We retrospectively reviewed 171 patients who underwent an MRI–guided prostate needle biopsy at our institution. Patients whose prostate-specific antigen level was >4.0 ng/mL and who had suspicious prostate cancer (PCa) lesions by multiparametric MRI (mpMRI) underwent 2-core MRI-guided targeted needle biopsy (TB) and conventional 12-core systematic biopsy (SB). We used two types of navigation system for MRI–guided TB: RVS and BioJet. RVS navigation synchronized mpMRI images with transrectal ultrasound (TRUS) images. BioJet navigation used a software program that merged images from mpMRI and TRUS to produce a composite image. We retrospectively compared the detection rate of PCa and the frequency of severe adverse events (AE) between these two navigation systems, focusing on patients. In addition, we compared the detection rate of MRI-guided TB cores of two navigation systems regarding anatomical position (transitional zone [TZ] or peripheral zone [PZ]). Results: Data from RVS and BioJet biopsy groups were from 65 and 106 patients, respectively. Of these, RVS-TB included 141 cores (PZ: 49 cores, TZ: 92 cores), and BioJet-TB included 276 cores (PZ: 73 cores, TZ: 203 cores). In detecting PCa, by conducting both SB and TB, and AEs in patients, a significant difference was not noted between RVS and BioJet navigation systems. In addition, there was no significant difference in the total detection rate for PCa in TB cores between the two methods. However, in the TZ, BioJet navigation showed a significantly higher detection rate of PCa than RVS navigation (35.0% vs. 17.4%, p = 0.0023) by analyzing the cores of MRI–guided TB. Conclusion: When targeting TZ lesions, BioJet navigation had a greater detection rate for PCa compared to that of RVS navigation.