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INTRODUCTION AND OBJECTIVE:Recently, the role of the gut microbiome in inflammatory disease and carcinogenesis has become apparent. Specifically, higher gut microbiome diversity is associated with ...

INTRODUCTION AND OBJECTIVE:Reactive oxygen species (ROS) have been identified as important chemical mediators in cell growth and differentiation. The glutathione redox system is the main mechanism ...

INTRODUCTION AND OBJECTIVE:There is a need for seeking effective treatments for CRPC, because its emergence following ADT is a major clinical problem. In the present study, we investigated chemopre...

INTRODUCTION AND OBJECTIVE:Luteolin is a natural flavonoid with potent antioxidant properties. Although its antineoplastic effects have been demonstrated in several cancer types, little is known re...

INTRODUCTION AND OBJECTIVE:Lysine-specific demethylase 1 (LSD1), the first histone demethylase to be discovered, is a novel target in prostate cancer therapy. NCL1 and NCD38, novel selective cell-a...

INTRODUCTION AND OBJECTIVES: There is no standard second line treatment for patients with metastatic urothelial carcinoma (mUC) after the failure of platinum based first line chemotherapy. In previous study, we reported the efficacy of gemcitabine docetaxel (GD) combination as a second line treatment strategy for patients with mUC after failure of the first line treatment with platinum based chemotherapy. However, the efficacy of GD was not sufficient to be established as a standard second line treatment. The treatment options are limited for patients who demonstrate good performance status following GC or GD therapy. This study was conducted to evaluate the effectiveness of a combination of gemcitabine and paclitaxel (GP) therapy for patients with mUC that was previously treated with two lines of chemotherapy. METHODS: Between January 2006 and May 2015, 91 patients were treated with GD as second line chemotherapy. All had received first line chemotherapy consisting of cisplatin. After the failure of the second line GD therapy, 13 patients received GP therapy as a third line treatment. This consisted of gemcitabine (1000 mg/m2) on days 1, 8, and 15 and paclitaxel (200 mg/m2) on day 1 of each 21 day cycle. All patients were evaluated for toxicity and tumor responses. In addition, quality of life (QOL) was estimated by using the Short Form Health Survey (SF36) questionnaire. We analyzed the efficacy of GP as third line chemotherapy in followup study. RESULTS: The median number of GP treatment cycles was 4 (range 2 to 8). The objective response rate was 23.1%. The overall survival in third GP group after the end of second line GD therapy was longer than in untreated group. Univariate and multivariate analyses showed that good performance status was the only prognostic factor for tumor response. Grade 3 treatment related toxicity included neutropenia (77%) and thrombocytopenia (62%), and none of the patients showed grade 4 toxicity. The QOL score after 2 cycles of GP therapy was not significantly decreased compared to the pretreatment scores. CONCLUSIONS: GP combination chemotherapy as a third line regimen is a favorable option for patients with metastatic UC. Given the safety and benefit profile including QOL observed in this study, further prospective trials are warranted to evaluate this strategic chemotherapy approach for patients with mUC.

INTRODUCTION AND OBJECTIVES: Reactive oxygen species (ROS) have been identified as important chemical mediators of cell growth and differentiation, and the glutathione redox system is the main mechanism protecting against the damage caused by ROS in human body. In previous study, we established a new castration resistant prostate cancer (CRPC) animal model. Results of cDNA microarray analysis using this model revealed that glutathione peroxidase 2 (GPX2) had higher expression in CRPC. In this study, we investigated the role of the glutathione redox system in CRPC and the therapeutic potential of the antioxidant properties of luteolin. METHODS: (i) GPX2 siRNA and negative control siRNA (NC) were used to transfect castration resistant PCai1 and PC3 cells, respectively. After transfection, we investigated the proliferation rate and ROS levels through cell counts, DCFH assay, western blotting, and flow cytometry. (ii) siRNA or NC transfected cells were subcutaneously implanted into normal and castrated nude mice. Three weeks after implantation, the mice were sacrificed, and the subcutaneous tumors were isolated. (iii) The effects of luteolin on cell proliferation and apoptosis in PCai cells and on tumor growth of the subcutaneously implanted PCai1 cells in nude mice were analyzed. RESULTS: (i) Silencing of Gpx2 caused significant growth inhibition of PCai1 and PC3 cells, and the DCFH assay revealed that intracellular ROS were significantly elevated in the siRNA treated groups. The decrease in proliferation rate in the siRNA group was attributed to cyclin B1 dependent cell cycle arrest as assessed with flowcytometry. (ii) On PCai1 implantation in nude mice, the tumor growth of PCai1 was significantly inhibited by silencing Gpx2 in the castrated nude mice. (iii) Luteolin suppressed the cell proliferation in a dose dependent manner in vitro, and inhibited tumor growth in a xenograft model via induction of apoptosis and downregulation of Gpx2. CONCLUSIONS: These results suggest that GPX2 plays an important role in cell growth in the presence of ROS in prostate cancer, and the glutathione redox system can regulate cancer cell growth in castration environment. GPX2 expression may be a therapeutic target in CRPC. Luteolin may be a potentially effective chemotherapeutic agent for CRPC via regulation of expression of GPX2 and induction of apoptosis.