Simvastatin induces heme oxygenase-1 via NF-E2-related factor 2 (Nrf2) activation through ERK and PI3K/Akt pathway in colon cancer

Objective.Several recent reviews of published studies have shown that the eradication ofH. pyloriinfection in patients with ITP improved thrombocytopenia in about half of the cases. However, most included studies were observational case series. We performed the first meta-analysis of randomized trials to gain a better insight into the effect ofH. pylorieradication in ITP patients.Methods.A systematic computerized search of the electronic databases including PubMed, EMBASE, Google Scholar, and Cochrane Library (up to December 2017) was conducted.Results.From six studies, a total of 241 patients (125 in eradication group and 116 in control group) were included in the meta-analysis. Patients in the eradication group showed significantly higher overall platelet response rate than those in the control group (odds ratio = 1.93, 95% confidence interval: 1.01–3.71,P=0.05). In the subgroup analysis, however, children in the eradication group failed to show statistically better response rate than those in the noneradication group (odds ratio = 1.80, 95% confidence interval: 0.88–3.65,P=0.11).Conclusions.This meta-analysis indicates thatH. pylorieradication has a significant therapeutic effect in patients with ITP. Considering the intrinsic limits in the design and sample size of the included studies, however, large randomized controlled trials are warranted to validate the therapeutic impact ofH. pylorieradication in adults as well as children with ITP.

Fibroblast growth factor receptor-2 (FGFR2) protein expression by immunohistochemistry has been reported in up to 60% of patients with gastric cancer (GC). However, the clicopathological impacts of high FGFR2 expression have not been consistent among studies. We conducted this meta-analysis to evaluate the pathological and prognostic significance of FGFR2 overexpression in patients with GC. A systematic search of the electronic databases including PubMed, PMC, EMBASE, and Google Scholar was performed. From ten studies, 4,294 patients were included in the pooled analyses of odds ratios (ORs) with 95% confidence intervals (CIs) for pathological features and hazard ratios (HRs) with 95% CIs for overall survival according to the FGFR2 expression status. Compared with tumors showing low FGFR2 expression, GCs with FGFR2 overexpression revealed deeper depth of invasion (pT3-4) (OR = 2.63, 95% CI: 1.70-4.06, p < 0.0001), higher rate of lymph node metastasis (OR = 1.87, 95% CI: 1.31-2.67, p < 0.0001), and more advanced stage (III-IV) (OR = 1.78, 95% CI: 1.07-2.96, p = 0.03). In addition, patients with FGFR2-overexpressed GC showed significantly worse survival than those with FGFR2-low tumor (HR = 1.40, 95% CI: 1.25-1.58, p < 0.00001). In conclusion, this meta-analysis indicates that FGFR2 overexpression is associated with poor pathological features and prognosis in patients with GC.

Eun Suk Jung, Sang Pyo Lee, Sea Hyub Kae, Jung Han Kim, Hyeong Su Kim, and Hyun Joo Jang. Gut and Liver 2021;15:732-41. https://doi.org/10.5009/gnl20249

Insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R) signaling plays an important role in tumor progression in patients with certain gastrointestinal tract cancers. In addition to lowering cholesterol in serum, statins have pleiotropic effects, including anti-oxidative, anti-inflammatory or anti-neoplastic effects. Therefore, the present study investigated whether statins could induce the apoptosis of colon cancer cells and regulate the expression of IGF-1R and its associated signaling pathways in the present study. It was demonstrated that simvastatin and pravastatin suppressed cell proliferation and induced cell death in human HT-29 cells, but simvastatin was more potent than pravastatin. Simvastatin induced apoptosis in a concentration-dependent manner. In addition, simvastatin suppressed the expression of IGF-1R and inhibited the activity of phosphorylated-extracellular signal-regulated kinase (ERK)1/2 and phosphorylated-Akt activated by IGF-1. Simvastatin and IGF-1 each stimulated the activity of phosphorylated ERK1/2. However, simvastatin inhibited cell proliferation and IGF-1 stimulated cell proliferation. Mevalonic acid and PD98059 reversed the ERK activation and apoptosis induced by treatment with simvastatin. It was concluded that simvastatin induces the apoptosis of human colon cancer cells and inhibits IGF-1-induced ERK and Akt expression via the downregulation of IGF-1R expression and proapoptotic ERK activation. Simvastatin may be beneficial for the treatment of colon cancer. The present study suggested that statin may possess therapeutic potential for the treatment of colon cancer.

Prognostic value of c-Met overexpression in hepatocellular carcinoma: a meta-analysis and review Prognostic value of c-Met overexpression in hepatocellular carcinoma: a meta-analysis and review