Taku Kato

BACKGROUND: The acquisition of drug resistance is one of the most malignant phenotypes of cancer and identification of its therapeutic target is a prerequisite for the development of novel therapy. MicroRNAs (miRNAs) have been implicated in various types of cancer and proposed as potential therapeutic targets for patients. In the present study, we aimed to identify miRNA that could serve as a therapeutic target for taxane-resistant prostate cancer. METHODS: In order to identify miRNAs related to taxane-resistance, miRNA profiling was performed using prostate cancer PC-3 cells and paclitaxel-resistant PC-3 cell lines established from PC-3 cells. Microarray analysis of mRNA expression was also conducted to search for potential target genes of miRNA. Luciferase reporter assay was performed to examine miRNA binding to the 3'-UTR of target genes. The effects of ectopic expression of miRNA on cell growth, tubulin polymerization, drug sensitivity, and apoptotic signaling pathway were investigated in a paclitaxel-resistant PC-3 cell line. RESULTS: The expression of miR-130a was down-regulated in all paclitaxel-resistant cell lines compared with parental PC-3 cells. Based on mRNA microarray analysis and luciferase reporter assay, we identified SLAIN1 as a direct target gene for miR-130a. Transfection of a miR-130a precursor into a paclitaxel-resistant cell line suppressed cell growth and increased the sensitivity to paclitaxel. Lastly, ectopic expression of miR-130a did not affect the polymerized tubulin level, but activated apoptotic signaling through activation of caspase-8. CONCLUSIONS: Our results suggested that reduced expression of miR-130a may be involved in the paclitaxel-resistance and that miR-130a could be a therapeutic target for taxane-resistant prostate cancer patients.

A 26-year-old woman with gross hematuria was seen in a previous hospital. Magnetic resonance imaging (MRI) showed a tumor at the dome of the urinary bladder with invasion outside of the bladder wall. The patient underwent transurethral resection of the bladder tumor (TUR-BT). From the result of the pathological examination, the tumor was suggested to be carcinosarcoma of the bladder. The patient was then referred to our hospital for treatment. We performed radical cystectomy and ileal conduit diversion. Pathological examination of the excised specimen revealed an inflammatory myofibroblastic tumor as the basis for immunostaining of anaplastic lymphoma kinase (ALK).

The management of urinoma after blunt renal trauma is still controversial, ranging from percutaneous drainage or ureteral stent placement for the symptomatic urinoma and waiting for spontaneous vanishment of the asymptomatic urinoma. We present two cases of symptomatic urinoma and a case of asymptomatic urinoma after renal laceration. All patients underwent selective renal arterial embolization for vascular complications, including active bleeding, pseudoaneurysm and arteriovenous fistula. Urinomas, which had been observed in all cases gradually reduced and vanished 1-24 months later. All cases were successfully managed without catheterization or percutaneous drainage for urinoma.

BACKGROUND/AIM: Exosomes have been demonstrated to be useful non-invasive biomarkers for several cancers including prostate cancer. Since normal cells also secrete exosomes, isolation of cancer-derived exosomes from blood is a prerequisite for their better understanding. The aim of this study is to establish the method for isolation of prostate cancer-related exosomes from blood. MATERIALS AND METHODS: Exosomes were collected from prostate cancer LNCaP and PC-3 cell lines by ultracentrifugation and by using magnetic beads conjugated with anti-CD9 antibody and anti-prostate-specific membrane antigen (PSMA) antibody. Prostate cancer-related exosomes were also isolated from the plasma of prostate cancer patients by anti-PSMA beads. Isolated exosomes were analyzed by western blotting. RESULTS: Exosomes were isolated from LNCaP cells by ultracentrifugation, contained PSMA and androgen receptor (AR). AR was also detected in exosomes isolated from LNCaP cells by anti-PSMA and anti-CD9 beads, showing that AR is present in prostate cancer-related exosomes. The amount of CD9 in isolated exosomes was much higher in advanced and chemo-resistant prostate cancer patients than in prostate cancer patients without metastasis and healthy volunteers, indicating that patients with aggressive prostate cancer exhibit higher levels of prostate cancer-related exosomes in blood. CONCLUSION: The immunoaffinity-based method we developed is capable of isolating prostate cancer-related exosomes from blood, the use of which will enhance investigation processes on exosomes in prostate cancer.