Identification of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible genes in human amniotic epithelial cells

BACKGROUND: Exposure to dioxins results in a broad range of pathophysiological disorders in human fetuses. In order to evaluate the effects of dioxins on the feto-placental tissues, we analyzed the gene expression in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treated primary cultures of human amniotic epithelial cells. METHODS: Human amniotic epithelial cells were dispersed by trypsin from amniotic membranes and cultured in DME/Ham's F12 medium supplemented with 10% FBS. Two weeks after plating, cells were treated with 50 nM TCDD or DMSO (control), further incubated for 48 hrs, and the gene expression was analyzed by DNA microarray technology and quantitative real-time PCR. RESULTS: Thirty eight TCDD-inducible genes, including cytochromeP4501A1 and cytochromeP4501B1, were identified. One of the remarkable profiles of the gene expression was the prominent up-regulation of interferon-inducible genes. The genes involved in the interferon gene expression and interferon signaling pathways were also up-regulated. Furthermore, the expression of genes related to collagen synthesis or degradation was enhanced by TCDD. CONCLUSION: Using DNA microarray and quantitative real-time PCR analyses, we identified TCDD-inducible genes, including interferon-inducible genes and genes related to collagen synthesis or degradation, in human amniotic epithelial cells

Effectsof Nifedipine , 8-(N,N-Diethylamino)Octyl-3 ,4,5- Trimethoxybenzoate Hydrochloride andAtrialNatriuretic Peptide on Endothelin-Induced Antinatriuresis in Dogs

ABSTRACT octyl-3,4,5-trimethoxybenzoate hydroch@de (TMB-8) or atrial natiiuretlc peptlde (ANP) was infused Into the renal artery before and during intrarenal arte@a1 Infusionof endothelin-1(El) in anesthetizeddogs. Before El infusion, nifedipine (0.1 @t9 kg1 min'), TMB-8 (75 @ig kg1 min1) or ANP (10 ng kg1 min') increased the urine flow rate, urinary sodium excretion and fractional sodium excretion with little change in renal blood flow or glomerular filtratlon rate. ET (2 ng kg1 m1n1) reØucedthe basal renal t@oodflow, glomerular filtra tion rate, urine flow rate, urinary sodium excretion and fractional (Cao and Banks, 1990; Goetz et aL, 1988; ET raises the free calciumconcentrationin vascularsmooth Received for publication April 15, 1993. (Yanagisawa et aL, 1988) and in viv

Long‐term outcomes of proton therapy for prostate cancer in Japan: a multi‐institutional survey of the Japanese Radiation Oncology Study Group

This is the first multi‐institutional retrospective survey of the long‐term outcomes of proton therapy (PT) for prostate cancer in Japan. This retrospective analysis comprised prostate cancer patients treated with PT at seven centers between January 2008 and December 2011 and was approved by each Institutional Review Board. The NCCN classification was used. Biochemical relapse was based on the Phoenix definition (nadir + 2.0 ng/mL). Toxicities were evaluated with the Common Terminology Criteria for Adverse Events version 4.0. There were 215, 520, and 556 patients in the low‐risk, intermediate‐risk, and high‐risk groups, respectively. The median follow‐up period of surviving patients was 69 months (range: 7–107). Among all patients, 98.8% were treated using a conventional fractionation schedule and 1.2% with a hypofractionation schedule; 58.5% and 21.5% received neoadjuvant and adjuvant androgen deprivation therapy, respectively. The 5‐year biochemical relapse‐free survival (bRFS) and overall survival rates in the low‐risk, intermediate‐risk, and high‐risk groups were 97.0%, 91.1%, and 83.1%, and 98.4%, 96.8%, and 95.2%, respectively. In the multivariate analysis, the NCCN classification was a significant prognostic factor for bRFS, but not overall survival. The incidence rates of grade 2 or more severe late gastrointestinal and genitourinary toxicities were 4.1% and 4.0%, retrospectively. This retrospective analysis of a multi‐institutional survey suggested that PT is effective and well‐tolerated for prostate cancer. Based on this result, a multi‐institutional prospective clinical trial (UMIN000025453) on PT for prostate cancer has just been initiated in order to define its role in Japan