加藤 卓

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.

We prospectively studied the usefulness of chlormadinone acetate (CMA) as an alternative therapy for prostate cancer relapse after combined androgen blockade (CAB) therapy. Sixteen patients with relapsed prostate cancer after treatment with CAB, including surgical or medical castration and nonsteroidal antiandrogens, 80 mg bicalutamide daily or 375 mg flutamide daily, were enrolled. After discontinuing the antiandrogen for evaluating the patient for the antiandrogen withdrawal syndrome, we administered 100 mg CMA daily as alternative antiandrogen andestimatedits effect. Four patients showeda ＞− 50% decline in prostate-specific antigen (PSA) levels andanother 4 patients showeda ＜50% decline in PSA levels but residual 8 patients showed no decline in PSA levels. In 8 patients with a decline in PSA levels, the median duration of alternative CMA therapy was 11.4 months. Patients with a PSA level of ＜1 ng/ml at the start of CMA therapy showed the tendency of decline in PSA levels. In contrast, patients with a nadir PSA level of ＞− 0.2 ng/ml during pretreatment showed no effectiveness of the alternative CMA therapy. The alternative CMA therapy may be useful in a part of patients with prostate cancer relapse after CAB therapy.

75歳男.患者は膀胱前壁を中心とした多発性乳頭状広基性腫瘍で,その内の1つは内尿道口に存在していた.膀胱癌T2aN0M0と診断し,M-VAC療法1コースが施行されたが,術後14ヵ月目に外尿道口からの血性分泌物を自覚した.放置していたものの,軟性膀胱鏡検査で尿道舟状窩に充満するように存在する多発性乳頭状腫瘍を認め,膀胱癌の尿道舟状窩への再発と診断された.陰茎部分切除術を施行後,合併症なく退院なったが,腹部CTにて膵腫瘍を指摘され,化学療法が施行された.膵尾部切除により病理組織学的所見ではtubular adenocarcinomaであり,膀胱癌の膵転移は否定された.以後,患者は膵癌の腹膜播種にて最終的に死亡となったWe report a case of bladder cancer recurrence in fossa navicularis of urethra 17 months after cystourethrectomy for bladder cancer. A 75-year-old man had undergone cystourethrectomy preserving between fossa navicularis and external meatus, and ileal conduit urinary diversion for advanced bladder cancer on June 24, 2002. Histopathological findings showed urothelial carcinoma, G2>G3, pT1N0. The patient had been followed regularly for 17 months without evidence of recurrence until he suffered the onset of hemorrhagic urethral discharge. Endoscopic examination of the residual urethra showed multiple, papillary sessile tumors which almost filled the fossa navicularis. He was admitted to our hospital on December 15, 2003. The urethral wash cytology revealed urothelial carcinoma. Since computed tomography, magnetic resonance imaging, and bone scintigraphy showed no evidence of lymph node and distant metastasis, partial penectomy was performed. Histopathological findings showed urothelial carcinoma pTa, G2>G3, which was identical to primary tumor. Tumor had not invaded the corpus cavernosum. Careful follow-up of the patients with preservation of fossa navicularis is important.