PURPOSE: Overproduction of lipid peroxidation byproducts and disturbances in the antioxidant defense system have been implicated in the pathogenesis of several diseases, including prostate cancer. Although several studies have investigated the level of lipid peroxidation and antioxidants in prostate cancer, there are no reports on alpha-lipoic acid (ALA) in prostate cancer. Here we assessed the effects of ALA on the antioxidant system in prostate cancer cells. MATERIALS AND METHODS: PC-3, LNCaP, and RWPE-2 cell lines were used in this study. Redox factor (Ref)-1 protein was measured by Western blot analysis after treatment with ALA. Real-time polymerase chain reaction (RT-PCR) was performed to detect superoxide dismutase (SOD)-1 and -2, catalase, and glutathione peroxidase (GSH-Px) mRNA expression. RESULTS: Ref-1 was expressed in the PC-3, LNCaP, and RWPE-2 cell lines. The expression of Ref-1 protein was increased after treatment with 125, 250, and 500 microM ALA in the PC-3 (p<0.05) and LNCaP (p>0.05) cells compared with the RWPE-2 cells at 48 hours. In PC-3 cells, the mRNA expression of SOD-1, SOD-2, catalase, and GSH-Px decreased at 24 and 48 hours dose-dependently compared with that in RWPE-2 cells (p<0.05). The mRNA expression of SOD-2, catalase, and GSH-Px in LNCaP cell decreased at 48 hours dose-dependently (p<0.05). CONCLUSIONS: The expression of Ref-1 protein and antioxidant enzymes changed after ALA exposure in prostate cancer cells. Our findings suggest that ALA affects the antioxidant system in prostate cancer cells and may be related to compensatory changes in the antioxidant defense system of the cells.
Antioxidants ; Blotting, Western ; Catalase ; Cell Line ; Glutathione Peroxidase ; Lipid Peroxidation ; Oxidation-Reduction ; Prostate ; Prostatic Neoplasms ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Superoxide Dismutase ; Thioctic Acid

PURPOSE: We wanted to compare the efficacy and toxicity of chemotherapy with methotrexate, vinblastine, adriamycin, cisplatin(M-VAC) versus gemcitabine and cisplatin(GC) for patients with advanced or metastatic urothelial carcinoma. MATERIALS AND METHODS: Forty-nine patients diagnosed with advanced urothelial cell carcinoma and who were started on chemotherapy were divided into two groups. All of them had a 0-1 Eastern Cooperative Oncology Group performance status. 19 patients received M-VAC chemotherapy and 30 patients received the GC regimen. Among them, the subjects who completed more than 3 cycles of their recommended formula (13/19 for M-VAC, 28/30 for GC) were included in this study. They were evaluated for their overall response rate, the 5-year survival rate, toxicities and the drop-out rate. RESULTS: The overall response rate and median survival period of the M-VAC and G-C groups were 38%(5/13 cases) and 46%(13/28 cases), and 16.7 months and 43.9 months, respectively. The 5-year survival rates in the two groups were 10% in the M-VAC group and 46% in the G-C treated group(p=0.013). The main hematologic complication was leukopenia and this occurred in 10/19 patients and more than grade 3 leukopenia was noted in 4/10 patients in the M-VAC group and in 19/30 patients and more than grade 3 was noted in 10/19 patients in the GC group.The common non-hematologic side effects between the two groups were nausea/vomiting(84.2% vs 47.7%), alopecia(47.4% vs 26.7%), diarrhea(15.8% vs 16.7%), and nephrotoxicity(15.8% vs 6.7%), respectively. The drop-out rates were 31.6% in the M-VAC group and 6.7% with the GC group. CONCLUSIONS: For patients with a good performance status with advanced or metastatic urothelial carcinoma, GC chemotherapy is more effective and it has more tolerable toxicities than does the M-VAC regimen.
Doxorubicin ; Drug Therapy* ; Humans ; Leukopenia ; Methotrexate ; Survival Rate ; Vinblastine

Primary signet ring cell carcinoma of the urinary bladder is a relatively rare histological variant of mucus-producing adenocarcinoma usually of poor prognosis. We report two cases of primary bladder signet ring carcinoma. The first patient underwent a radical cystectomy with ileal conduit (pT3bN1M0), radiotherapy, and chemotherapy (M-VAC regimen) and subsequently expired 37 months after surgery. The other was initially diagnosed with peritoneal metastasis from the primary bladder signet ring cell carcinoma and was treated with partial cystectomy (pT3bNOM1). Postoperative adjuvant therapy was not done because of patient's refusal.
Adenocarcinoma ; Carcinoma, Signet Ring Cell ; Cystectomy ; Disulfiram ; Humans ; Neoplasm Metastasis ; Prognosis ; Urinary Bladder ; Urinary Diversion