Aldehyde dehydrogenase 1 (ALDH1) expression is associated with a poor prognosis of bladder cancer.

Aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, has been reported to be altered in human carcinogenesis. This study assessed the expression of ALDH1 protein in invasive vs. noninvasive bladder cancer tissues for association with clinicopathological factors and bladder cancer prognosis. Tissue samples were collected from 227 bladder cancer patients, including 118 with noninvasive and 109 with invasive bladder cancer for immunostaining of ALDH1 expression. ALDH1 expression in tumor tissues was significantly greater than that in adjacent normal tissues. ALDH1 protein was highly expressed in 29.07% (66/227) of bladder tumor tissues (i.e., 24.58% of noninvasive bladder cancer tissues vs. 33.94% of invasive bladder cancer tissues). In patients with noninvasive bladder cancer, ALDH1 protein expression was significantly associated with an advanced tumor grade and frequent tumor recurrence (P≤0.05). In patients with invasive bladder cancer, ALDH1 protein expression was significantly associated with an advanced tumor grade, stage, as well as lymph node and distant metastases (P≤0.05). After adjusting for the confounding factors, ALDH1 protein expression was significantly associated with relapse-free survival in noninvasive bladder cancer patients [HR (95% CI)=4.45 (1.32-15.04); P=0.027] and overall survival in invasive bladder cancer patients [HR (5% CI)=2.86 (1.72-8.83); P=0.020]. These data indicate that ALDH1 expression plays an important role in bladder cancer development and prognosis. Further validation of our results is warranted in a larger sample cohort, and further investigation of ALDH1 signaling and function will increase our understanding of ALDH1 in bladder cancer progression.

Tissue accumulation and toxicity of isothiazolinone in Ctenopharyngodon idellus (grass carp): association with P-glycoprotein expression and location within tissues.

Isothiazolinone is widely used as a broad-spectrum fungicide in various industries, such as oil, paper, pesticide, dyes, tanning and cosmetics. There is an increasing concern over protection of the aquatic environment due to its large-scale use. The acute toxicity (LC50) of isothiazolinone in Ctenopharyngodon idellus was investigated. The residual time and accumulation in tissues, P-glycoprotein mRNA level and localization of P-glycoprotein in the liver and kidney were also analyzed. The LC50 (48 h) values of isothiazolinone to C. idellus were 0.53±0.17 mg/L and 0.41±0.08 mg/L at 15 °C and 25 °C, respectively. The LC50 values decreased as the temperature increased. The accumulation of isothiazolinone in livers and kidneys in the high temperature group (25 °C) was significantly greater than that of the low temperature group (15 °C). Prolonged tissue residual time of isothiazolinone was seen in all the groups. There were significant differences in P-glycoprotein mRNA expression between isothiazolinone-treated groups and control samples (P<0.05-0.01). Temperature affected accumulation and toxicity of isothiazolinone.

Regulation of type V adenylate cyclase by Ric8a, a guanine nucleotide exchange factor.

In the present study, we demonstrate that AC5 (type V adenylate cyclase) interacts with Ric8a through directly interacting at its N-terminus. Ric8a was shown to be a GEF (guanine nucleotide exchange factor) for several alpha subunits of heterotrimeric GTP binding proteins (Galpha proteins) in vitro. Selective Galpha targets of Ric8a have not yet been revealed in vivo. An interaction between AC5 and Ric8a was verified by pull-down assays, co-immunoprecipitation analyses, and co-localization in the brain. Expression of Ric8a selectively suppressed AC5 activity. Treating cells with pertussis toxin or expressing a dominant negative Galphai mutant abolished the suppressive effect of Ric8a, suggesting that interaction between the N-terminus of AC5 and a GEF (Ric8a) provides a novel pathway to fine-tune AC5 activity via a Galphai-mediated pathway.