BackgroundThe cytoskeletal organizer ezrin is a member of the ezrin-radixin-moesin (ERM) family and plays important roles in not only cell motility, cell adhesion, and apoptosis, but also in various cell signaling pathways. Phosphorylation at Thr-567 and Tyr-353 are key regulatory events in the transition of the dormant to active form of ezrin. This study investigated the prognostic implications of ezrin and phosphorylated ezrin (p-ezrin) expression in non-small cell lung carcinoma (NSCLC).MethodsEzrin and p-ezrin protein expressions were examined by immunohistochemistry in 150 NSCLC and adjacent non-tumor tissues and 14 normal lung tissues. qRT-PCR was used to determine ezrin mRNA expression levels in fresh tissues. The correlations between overexpression of ezrin and p-ezrin and the clinicopathological features of NSCLC were analyzed. The survival rates were calculated by the Kaplan-Meier method for 108 NSCLC cases.ResultsEzrin and ezrinThr-567 proteins showed cytosolic and membranous staining patterns; however, ezrinTyr-353 protein only showed cytosolic staining. Ezrin and p-ezrin were significantly upregulated in NSCLC compared with the normal counterparts. Increased ezrin, ezrinThr-567, and ezrinTyr-353 levels were correlated with the late stage and poor differentiation of NSCLC. However, only ezrinThr-567 was correlated with the presence of lymph node metastasis. In regard to survival, only ezrinThr-567 was related with the overall survival time of patients with NSCLC, and both ezrin and ezrinThr-567 were associated with shortened survival time for patients with early stage NSCLC.ConclusionsEzrin and p-ezrin, especially ezrinThr-567, may prove to be useful as a novel prognostic biomarker of NSCLC.
Although gene therapy was regarded as a promising approach for glioma treatment, its therapeutic efficacy was often disappointing because of the lack of efficient drug delivery systems. Mesenchymal stem cells (MSCs) have been reported to have a tropism for brain tumors and thus could be used as delivery vehicles for glioma therapy. Therefore, in this study, we attempted to treat glioma by using MSCs as a vehicle for delivering replication-competent adenovirus. We firstly compared the infectivity of type 3, type 5, and type 35 fiber-modified adenoviruses in MSCs. We also determined suitable adenovirus titer in vitro and then used this titer to analyze the ability of MSCs to deliver replication-competent adenovirus into glioma in vivo. Our results indicated that type 35 fiber-modified adenovirus showed higher infectivity than did naked type 3 or type 5 fiber-modified adenovirus. MSCs carrying replication-competent adenovirus significantly inhibited tumor growth in vivo compared with other control groups. In conclusion, MSCs are an effective vehicle that can successfully transport replication-competent adenovirus into glioma, making it a potential therapeutic strategy for treating malignant glioma.
Objectives
Hepatocarcinoma is one of the most lethal cancers, leading to a 5‐year survival rate as low as 30% due to recurrence and metastasis. The treatment of liver cancer includes surgery and medication, of which, the former is more effective. However, surgical resection is applicable in less than 40% of patients. Therefore, it is imperative to find effective medication options for liver cancer therapy.
Methods
In this study, we found that two natural products, geraniol and lupeol, had antiproliferative and proapoptotic effects on the hepatocarcinoma cell lines SMMC7721 and HepG2. We also detected a lower expression level of Bcl‐2 and upregulation of BAX and caspase in the presence of geraniol and lupeol.
Results
Furthermore, geraniol or lupeol also altered the phosphorylation level of extracellular signal‐regulated protein kinase, P38, and c‐Jun NH2‐terminal kinases, suggesting involvement in mitogen‐activated protein kinase signaling.
Conclusions
This study provided direct evidence to support the effect of geraniol and lupeol in hepatocarcinoma cell growth and apoptosis, which indicated the potential application of these two natural products in anti–liver cancer therapy.
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