Salt-inducible kinase 2 functions as a tumor suppressor in hepatocellular carcinoma.

Salt-inducible kinase 2 (SIK2) has been reported to be involved in cancer progression in a dichotomous manner. However, the role and mechanism of action of SIK2 in hepatocellular carcinoma (HCC) progression remain elusive. SIK2 expression in HCC tissues in The Cancer Genome Atlas (TCGA) database was analyzed using the AIPuFu platform. SIK2 expression in HCC cells was examined by quantitative real-time PCR and western blot analysis. The expression of N-cadherin, E-cadherin, ß-catenin, and c-Myc was detected by western blot analysis. SIK2 was downregulated in HCC tissues compared with normal patients, and low SIK2 expression was correlated with poor prognosis in HCC patients in TCGA database. SIK2 was lowly expressed in HCC cells than that in normal human liver epithelial cells. SIK2 overexpression inhibited cell proliferation and invasion and promoted apoptosis in HCC cells, while SIK2 silencing exerted the opposite effects. Additionally, SIK2 overexpression inactivated the Wnt/ß-catenin pathway in HCC cells, as evidenced by the reduced expression of ß-catenin and c-Myc. ß-catenin overexpression rescued the inhibitory effects of SIK2 on the malignant properties of HCC cells. Xenograft tumor experiment confirmed that SIK2 suppressed the growth of HCC cells in vivo. In conclusion, SIK2 exerted anti-tumor activity in HCC via inactivating the Wnt/ß-catenin signaling pathway.

Consumer use of over-the-counter proton pump inhibitors in patients with gastroesophageal reflux disease.

OBJECTIVES: Optimal administration of proton pump inhibitor (PPI) for the treatment of gastroesophageal reflux disease (GERD) requires consideration of meal timing. Since becoming available over the counter (OTC), no studies have assessed treatment patterns and symptom control in OTC consumers. The objective of this study was to survey dosing patterns and symptom control in OTC and prescription PPI users. METHODS: Patients at five clinics were surveyed regarding diagnosis of GERD, use of OTC or prescription PPIs, information on time of day dosing, demographics, and Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS; 2001, Johnson & Johnson). RESULTS: Of the 1,959 patients surveyed, 610 (31%) used PPIs for GERD. Of these, 190 (31%) and 223 (37%) received prescriptions from gastroenterologists (GIs) and primary care physicians (PCPs), respectively; 197 (32%) purchased OTC PPIs. Of the patients prescribed PPIs by GIs, 71% were optimal users, whereas 47% of patients receiving prescriptions from PCPs and 39% of consumers used PPIs optimally (P<0.001 compared with GIs). GSAS symptom, frequency, and severity scores were significantly better in patients prescribed PPIs by GIs (all P<0.001, GI compared with PCP and consumer). GSAS symptom, frequency, and severity scores were also significantly better in patients using PPIs optimally (P<0.001 for all parameters) compared with those taking PPIs suboptimally or excessively. CONCLUSIONS: Patients receiving prescription PPI from a GI are more likely to be optimal users with better symptom control. Conversely, consumers are more likely to be suboptimal users with inadequate symptom control.