Up-regulation of KLF17 expression increases the sensitivity of gastric cancer to 5-fluorouracil.

It has been reported that the expression of Krüppel-like factor 17 (KLF17) was associated with the occurrence, development, invasion, metastasis and chemotherapy resistance of various tumors. However, the detailed mechanisms by which KLF17 promotes chemotherapy resistance in gastric cancer (GC) have not been fully investigated. In the present study, we collected the GC tissues and non-tumor tissues (matched adjacent normal tissues with corresponding GC tissues) of 60 GC patients, used qRT-PCR, Western blot and immunohistochemistry assay to analyze the relationship between the expression of KLF17 and the clinical pathological data of the patients. The effect of KLF17 on the sensitivity of GC cell lines to 5-fluorouracil (5-FU), and the potential mechanism were detected by MTS assay, Flow cytometry assay, and Western blot. Compared with non-tumor tissues, the expression level of KLF17 in GC tissue was significantly down-regulated, and the expression level of KLF17 in GES-1 cell line and GC cell lines also had a similar trend. Down-regulated expression of KLF17 is related to tumor size, invasion, regional lymph node metastasis, and TNM staging. Furthermore, through upregulating the expression of KLF17, the sensitivity of BGC-823 and SGC-7901 cell lines to 5-FU was obviously increased. Mechanistically, upregulation the expression of KLF17 can inhibit the expressions of P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and B-Cell lymphoma-2 (BCL-2), which have been reported to be associated with drug resistance and cell proliferation. Collectively, these data implied that KLF17 has the biological effect of inhibiting chemotherapy resistance of GC, and it could be a potential strategy for the GC chemotherapy resistance.

Comprehensive Transcriptomic Analysis and Experimental Validation Identify lncRNA HOXA-AS2/miR-184/COL6A2 as the Critical ceRNA Regulation Involved in Low-Grade Glioma Recurrence.

PURPOSE: The recurrence and metastasis of glioma are closely related to complex regulatory networks among protein-coding genes, lncRNAs and microRNAs. The aim of this study was to investigate core genes, lncRNAs, miRNAs and critical ceRNA regulatory mechanisms, which are involved in lower-grade glioma (LGG) recurrence. MATERIALS AND METHODS: We employed multiple datasets from Chinese Glioma Genome Atlas (CGGA) database and The Cancer Genome Atlas (TCGA) to perform comprehensive transcriptomic analysis. Further in vitro experiments including cell proliferation assay, luciferase reporter assay, and Western blot were performed to validate our results. RESULTS: Recurrent LGG and glioblastoma (GBM) showed different transcriptome characteristics with less overlap of differentially expressed protein-coding genes (DEPs), lncRNAs (DELs) and miRNAs (DEMs) compared with primary samples. There were no overlapping gene in ontology (GO) terms related to GBM recurrence in the TCGA and CGGA databases, but there were overlaps associated with LGG recurrence. GO analysis and protein-protein interaction (PPI) network analysis identified three core genes: TIMP1, COL1A1 and COL6A2. By hierarchical cluster analysis of them, LGGs could be clustered as Low_risk and High_risk group. The High_risk group with high expression of TIMP1, COL1A1, and COL6A2 showed worse prognosis. By coexpression networks analysis, competing endogenous RNA (ceRNA) network analysis, cell proliferation assay and luciferase reporter assay, we confirmed that lncRNA HOXA-AS2 functioned as a ceRNA for miR-184 to regulate expression of COL6A2, which induced cell proliferation of low-grade glioma. CONCLUSION: In this study, we revealed a 3-hub protein-coding gene signature to improve prognostic prediction in LGG, and identified a critical ceRNA regulation involved in LGG recurrence.

Outbreak of mumps in a student population with high vaccination coverage in China: time for two-dose vaccination.

In 2016, an outbreak of mumps occurred in a primary school in China with a student population having high vaccination coverage. An unmatched case-control study was performed to identify risk factors contributing to this outbreak, and a retrospective cohort study was conducted to evaluate the effectiveness of mumps-containing vaccine (MuCV). A total of 97 cases were identified during the outbreak, and the overall attack rate was 8.2%. Among students with confirmed vaccination status, 90% had received at least one dose of MuCV. Cases were more likely than non-cases to report taking the school bus during the epidemic period (adjusted OR = 2.3, 95% CI: 1.4-3.7). Vaccine effectiveness (VE) was higher for two-dose MuCV (76%, 95% CI:49â€"89%) than for one-dose MuCV (59%, 95% CI: 36â€"74%. The protection afforded by both one-dose and two-dose MuCV waned over time, from 82% among students vaccinated within 5 years to 41% among those vaccinated more than 10 years previously for one-dose VE, and from 90% to 25% over the same time period for two-dose VE. We found that outbreaks of mumps can occur in schools despite high coverage of one-dose MuCV vaccination. Although the VE of both two-dose and one-dose MuCV wanes over time, the overall VE for two-dose MuCV was superior than that of one-dose MuCV. Therefore, a two-dose MuCV schedule through routine services is likely needed in order to control mumps epidemics in China.

The relationship between serum lipoprotein (a) levels and ischemic stroke risk: a cohort study in the Chinese population.

The role of atherosclerosis in ischemic stroke has been intensively investigated in recent years, and lipoprotein (a) [Lp(a)] is found to have roles during the process. The aim of this study was to investigate the relationship between acute ischemic stroke (AIS) and serum Lp(a) levels in the Chinese population. All consecutive patients with first-ever acute ischemic stroke during 2011-2012 were recruited to participate in the study. Serum Lp(a) levels and routine tests were examined in both groups. The National Institutes of Health Stroke Scale (NIHSS) score was assessed on admission blinded to Lp(a) levels. In this study, 181 patients with acute ischemic stroke were included. There was a significant difference in median serum Lp(a) levels between acute ischemic stroke patients and control cases (328 [IQR, 173-554] vs. 145 [IQR, 66-254] mg/L, respectively; P = 0.000). Lp(a) levels increased with increasing severity of stroke as defined by the NIHSS score (P = 0.000). For the entire group, when adjusting for other possible risk factors, an elevated Lp(a) level was an independent risk factor for stroke, and a serum Lp(a) level ≥300 mg/L was associated with a 2.23-fold increase in AIS (P = 0.015). In addition, this association was stronger in male than in female patients. High Lp(a) levels are significantly related to stroke, independent from other traditional and emerging risk factors, suggesting that they may play a role in its pathogenesis. It should be considered as a routine risk factor for stroke in the Chinese population.

Bystander effect in suicide gene therapy using immortalized neural stem cells transduced with herpes simplex virus thymidine kinase gene on medulloblastoma regression.

Medulloblastomas (MBs) are the most common malignant brain tumor in children. The current therapeutic strategies are ineffective against the infiltrative and disseminative nature of MBs in about one-third of patients. Based on studies which have revealed the tumor-tropic characteristic of neural stem cells (NSCs), we used an immortalized neural stem cell line C17.2 as a cellular therapeutic delivery system to evaluate the antitumor effect of herpes simplex virus thymidine kinase gene (HSVtk) on MBs. We first stably transfected the HSVtk gene into C17.2 cells to produce C17.2tk cells, and then mixed C17.2tk with the human MB cell line Daoy at various ratios supplemented with ganciclovir (GCV). Both in vitro and in vivo experiments yielded promising results. Even at a C17.2tk: Daoy ratio as low as 1:16, more than 25% cells were killed in vitro. In vivo co-implantation study showed that when C17.2tk: Daoy ratio was 1:8, tumor growth inhibition was still evident and the mice had significantly prolonged survival. These results might partially be explained by the inherent tumor-tropic properties of NSCs and the bystander effect coupled with expression of connexin-43 (Cx43) between C17.2tk and Daoy cells. Our study clearly showed for the first time that immortalized neural stem cells used as vectors to deliver HSVtk gene therapy have a strong tumoricidal effect on MBs.