Protective Effect of Administered Rolipram against Radiation-Induced Testicular Injury in Mice

PURPOSE: Pelvic irradiation for the treatment of cancer can affect normal cells, such as the rapidly proliferating spermatogenic cells of the testis, leading to infertility, a common post-irradiation problem. The present study investigated the radioprotective effect of rolipram, a specific phosphodiesterase type-IV inhibitor known to increase the expression and phosphorylation of the cyclic adenosine monophosphate response element-binding protein (CREB), a key factor for spermatogenesis, with the testicular system against pelvic irradiation. MATERIALS AND METHODS: Male C57BL/6 mice were treated with pelvic irradiation (2 Gy) and rolipram, alone or in combination, and were sacrificed at 12 hours and 35 days after irradiation. RESULTS: Rolipram protected germ cells from radiation-induced apoptosis at 12 hours after irradiation and significantly increased testis weight compared with irradiation controls at 35 days. Rolipram also ameliorated radiation-induced testicular morphological changes, such as changes in seminiferous tubular diameter and epithelial height. Additionally, seminiferous tubule repopulation and stem cell survival indices were higher in the rolipram-treated group than in the radiation group. Moreover, rolipram treatment counteracted the radiation-mediated decrease in the sperm count and mobility in the epididymis. CONCLUSIONS: These protective effects of rolipram treatment prior to irradiation may be mediated by the increase in pCREB levels at 12 hours post-irradiation and the attenuated decrease in pCREB levels in the testis at 35 days post-irradiation in the rolipram-treated group. These findings suggest that activation of CREB signaling by rolipram treatment ameliorates the detrimental effects of acute irradiation on testicular dysfunction and the related male reproductive functions in mice.

Prognostic Significance of Perirenal Infiltration in Renal Cell Carcinoma (<7 cm)

PURPOSE: Pathologic stage is the most accurate prognostic factor of renal cell carcinoma. We evaluated whether perirenal fat infiltration is a significant factor in tumors 7 cm or less in size. MATERIALS AND METHODS: We retrospectively reviewed the record of 164 cases of tumors 7 cm or less in size. We divided the patients into two groups according to the presence of perirenal fat infiltration (group A, pT1; group B, pT3a). We evaluated relationships, recurrence-free survival and disease-specific survival according to clinicopathologic parameters. Statistical differences were calculated by log-rank test. RESULTS: A total 131 patients were included in group A, with a mean age of 55.8 years, average tumor size was 4.2 cm, and a mean follow-up period of 43 months. Group B included 33 patients, with a mean age of 55.9 years, an average tumor size of 4.1 cm, and a mean follow-up period of 38 months. There was no significant difference in disease-specific survival; however, recurrence-free survival showed significantly different between two groups (group A: 95.5%, group B: 84.4%). CONCLUSION: In this study, perirenal fat infiltration proved to be an independent prognostic factor for predicting disease-free survival in patients with tumors of 7 cm or less in size. Therefore, as this study showed, the presence of perirenal fat infiltration requires stricter follow-up planning, even in small renal cell carcinoma.

Effects of alpha-Lipoic Acid on the Antioxidant System in Prostate Cancer Cells / 대한비뇨기과학회지

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 (p0.05) 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.

Effect of Decursin on the Expression of beta-Catenin and Matrix Metalloproteinase-7 in Prostate Cancer Cell Lines / 대한비뇨기과학회지

PURPOSE: Alterations in the Wnt/beta-catenin pathway are associated with the development and progression of human prostate cancer. Decursin can attenuate the Wnt/beta-catenin pathway. We investigated the relationship between the Wnt/beta-catenin pathway and decursin in prostate cancer cells. MATERIALS AND METHODS: PC-3 and LNCaP cell lines were used. Cell viability was measured with methyl-thiazole tetrazolium bromide (MTT) assays, and cell apoptosis analysis was performed by FACScan. The amount of beta-catenin protein after treatment with decursin was measured by Western blot analysis. Expression of MMP-7 mRNA was detected by real-time polymerase chain reaction (RT-PCR). RESULTS: Death and apoptosis were increased after treatment with decursin 0.5-100 micrometer in PC-3 and LNCaP cells. This was revealed dose and time-dependent increase of cancer cell death on 24, 48 and 72 hours. FACScan showed an increment of apoptosis on 24, 48 hours. Expression of intracellular beta-catenin protein was decreased dose-dependently in both of prostate cancer cell lines. Decursin reduced MMP-7 mRNA expression on 6, 12, 24, 48 hours dose-dependently. CONCLUSIONS: Decursin affects the viability of prostate cancer cells. Increased cancer cell death was associated with increased apoptosis. This study suggests that decursin may play a role in the treatment of prostate cancer.

Primary Signet Ring Cell Carcinoma of the Urinary Bladder

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.