KDM4B promotes gastric cancer metastasis by regulating miR-125b-mediated activation of Wnt signaling.

Emerging evidence has demonstrated that the aberrant expression of histone-modifying enzymes such as histone demethylases contributes to gastric carcinogenesis and progression. The role of KDM4B in cancer progression has been gradually revealed. However, the underlying mechanisms regulating gastric cancer metastasis of KDM4B remain unclear. In the present study we determined KDM4B expression in gastric cancer and its biologic function in vitro and in vivo. We found that KDM4B expression was significantly increased in most gastric cancer tissues compared with the adjacent normal tissues. Upregulated expression of KDM4B in human gastric cancer was correlated with poor prognosis. In vitro, KDM4B overexpression in AGS cells promoted cell invasion, whereas knockdown of KDM4B inhibited cell invasion. Furthermore, KDM4B overexpression also promoted tumor metastasis in vivo. Mechanistically, KDM4B upregulated miR-125b expression and activated Wnt signaling pathway. More important, miR-125b partially mediated KDM4B-induced activation of Wnt signaling. Finally, we demonstrated that KDM4B promoted gastric cancer cell invasion in vitro and cancer metastasis in vivo, at least in part, by upregulating miR-125b expression. These data provided novel insights on the role of KDM4B-driven gastric cancer metastasis and indicated that KDM4B may be served as a potential target for gastric cancer.

Evaluating human liver reserve function by measuring serum concentrations of phenacetin and its metabolites.

OBJECTIVES: To evaluate human liver reserve function (LRF) by a simple and efficient method for measuring serum concentrations of phenacetin and its metabolites. METHODS: Overall 20 patients with liver cirrhosis (Child-Pugh score ≥ 7, aged 48-79 years), 30 healthy young volunteers (aged 18-40 years), and 20 healthy elderly volunteers (aged 61-80 years) were enrolled. All participants received a single oral dose of 0.5 g phenacetin. Liquid chromatography tandem mass spectrometry was used to determine the serum concentrations of phenacetin and its metabolites, including acetaminophen, acetaminophen glucuronide and acetaminophen sulfate. RESULTS: The serum concentration of phenacetin was significantly higher in cirrhotic patients than those in either of the healthy volunteer groups (P < 0.001). It was higher in healthy elderly volunteers than that in healthy young ones but there was no statistically significant difference (P > 0.05) between them. The serum concentrations of acetaminophen, acetaminophen glucuronide and acetaminophen sulfate were significantly lower in cirrhotic patients than in the healthy controls (P < 0.001). The serum concentrations of these three metabolites in healthy elderly volunteers were lower than those in healthy younger volunteers but again, there was no statistical significant difference (P > 0.05). The serum concentration of acetaminophen in healthy male volunteers was significantly higher than that in the women (P < 0.05). CONCLUSION: Monitoring cytochrome P450 1A2 (CYP450 1A2)-mediated phenacetin metabolism is a simple and efficient method for evaluating human LRF. This method would warrant further validation in a large cohort clinical study.