Plakophilin-2の上昇とPlakophilin-3の低下は膀胱癌の浸潤に相関する

A draft fish survey report on comprehensive analysis for water rights claims in the Upper Klamath River Basin, Oregon

Mineralocorticoid receptor expression in human penile corpus cavernosum

Objectives : Mineralocorticoid receptor (MR) is known to play physiological and pathophysiological roles in the cardiovascular system, and MR activation directly damages these organs. The aim of this study was to evaluate the expression of MR and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in the human penile corpus cavernosum. Methods : MR and 11β-HSD2 expression was assayed in human penile tissues, and also in human renal tissues as a positive control. Expressions of MR mRNA and 11β-HSD2 mRNA were evaluated using reverse transcription polymerase chain reaction (RT-PCR). MR and 11β-HSD2 were visually identified using immunofluorescence analysis. Results : MR mRNA expression in human penis was confirmed by RT-PCR. On quantitative RT-PCR analysis, 11β-HSD2 mRNA expression was detected at minimal levels in penile tissue. Immunofluorescence analysis revealed positive staining for MR and negative staining for 11β-HSD2 in smooth muscle cells of the corpus cavernosum. Conclusions : This study demonstrated the presence of MR and the absence of 11β-HSD2 in human penile corpus cavernosum. Considering that MR activation causes various organ damages, MR blockade in human penile corpus cavernosum may have therapeutic benefits. Investigations for the penile effects of MR activation have the potential to provide new treatment approaches for erectile dysfunction

Mineralocorticoid receptor expression in human penile corpus cavernosum

Objectives : Mineralocorticoid receptor (MR) is known to play physiological and pathophysiological roles in the cardiovascular system, and MR activation directly damages these organs. The aim of this study was to evaluate the expression of MR and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in the human penile corpus cavernosum. Methods : MR and 11β-HSD2 expression was assayed in human penile tissues, and also in human renal tissues as a positive control. Expressions of MR mRNA and 11β-HSD2 mRNA were evaluated using reverse transcription polymerase chain reaction (RT-PCR). MR and 11β-HSD2 were visually identified using immunofluorescence analysis. Results : MR mRNA expression in human penis was confirmed by RT-PCR. On quantitative RT-PCR analysis, 11β-HSD2 mRNA expression was detected at minimal levels in penile tissue. Immunofluorescence analysis revealed positive staining for MR and negative staining for 11β-HSD2 in smooth muscle cells of the corpus cavernosum. Conclusions : This study demonstrated the presence of MR and the absence of 11β-HSD2 in human penile corpus cavernosum. Considering that MR activation causes various organ damages, MR blockade in human penile corpus cavernosum may have therapeutic benefits. Investigations for the penile effects of MR activation have the potential to provide new treatment approaches for erectile dysfunction

Changes in levels of prostate-specific antigen and testosterone following discontinuation of long-term hormone therapy for non-metastatic prostate cancer

Introduction : We evaluated changes in levels of prostate-specific antigen (PSA) and testosterone following discontinuation of long-term hormone therapy for non-metastatic prostate cancer. Patients and Methods : Treatment was discontinued in 31 patients with non-metastatic prostate cancer (clinical stage B-C) after≧5 years of hormone therapy, during which time PSA level had been maintained less than 0.5 ng/ml. PSA and testosterone levels were measured after discontinuation of therapy. PSA>4.0 ng/ml was defined as PSA relapse in this study. Results : Mean age at discontinuation of hormone therapy was 78.7 years (range, 66-90). Mean duration of follow-up after discontinuation of therapy was 25.5 months. PSA non-relapse rate was quite high (87.1%). 4 of the 31 patients showed PSA relapse, after 12-24 months. Testosterone level exceeded castration level (<1.0 ng/ml) in 3 patients, each of whom developed PSA relapse. Conclusions : During follow-up, the PSA relapse rate was relatively low. These results suggest that treatment may be safely discontinued in many prostate cancer patients. In addition, rate of testosterone recovery after treatment discontinuation may be associated with PSA relapse. When considered the adaptation of discontinued, or intermittent hormone therapy for aged people, these findings may be useful

膀胱癌進展、浸潤におけるHGF-MET-MMP1 signalingの関与とMET阻害薬、カボザンチニブの有効性

OBJECTIVES To clarify the invasive mechanisms of muscle-invasive bladder cancer (BCa) would be useful for the determination of appropriate treatment strategies.We previously showed that hepatocyte growth factor (HGF)-MET signaling is correlated with invasiveness of BCa cells. Here, we investigated the effects of the MET inhibitor, cabozantinib (XL184), on BCa cells. METHODS We first conducted Western blot analysis to investigate MET expression in BCa cell lines. Next, we examined the effect of cabozantinib on their proliferation and invasive abilities using MTT and Matrigel invasion assays, respectively. Invasion assays were performed using the xCELLigence system. Additionally, to investigate the biological function of HGF-MET signaling, we analyzed gene expression profiles and performed real-time polymerase chain reaction analyses of 5637 cells that were cultivated with or without HGF stimulation, with or without cabozantinib. RESULTS MET was highly expressed in 4 of 5 BCa cell lines, and 5637 and T24 cells showed especially high protein expression of MET. Cabozantinib suppressed cell proliferation and invasion (cell index; mock, 1.49 vs HGF, 2.26 vs HGF + XL184, 1.47, P < .05). Gene expression profile analysis indicated that matrix metalloproteinase 1 (MMP1) was significantly elevated at the mRNA level with addition of HGF. Moreover, cabozantinib suppressed HGF-induced MMP1 expression in 5637 T24 cells. CONCLUSIONS These data indicate that cabozantinib suppressed MMP1 expression by blocking HGF-MET signaling and that HGF-MET-MMP1 signaling is involved in the invasiveness and proliferation of BCa cells. These results suggest that cabozantinib might prove useful for future treatment of muscleinvasive BCa

Detection of the Onset of Ischemia and Carcinogenesis by Hypoxia-Inducible Transcription Factor-Based In Vivo Bioluminescence Imaging

An animal model for the early detection of common fatal diseases such as ischemic diseases and cancer is desirable for the development of new drugs and treatment strategies. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates oxygen homeostasis and plays key roles in a number of diseases, including cancer. Here, we established transgenic (Tg) mice that carry HRE/ODD-luciferase (HOL) gene, which generates bioluminescence in an HIF-1-dependent manner and was successfully used in this study to monitor HIF-1 activity in ischemic tissues. To monitor carcinogenesis in vivo, we mated HOL mice with rasH2 Tg mice, which are highly sensitive to carcinogens and are used for short-term carcinogenicity assessments. After rasH2-HOL Tg mice were treated with N-methyl-N-nitrosourea, bioluminescence was detected noninvasively as early as 9 weeks in tissues that contained papillomas and malignant lesions. These results suggest that the Tg mouse lines we established hold significant potential for monitoring the early onset of both ischemia and carcinogenesis and that these lines will be useful for screening chemicals for carcinogenic potential