ABSTRACT
Background: Lymph node tuberculosis (LNTB) is the leading type of extrapulmonary tuberculosis (EPTB) causing death in children. The Xpert MTB/RIF assay is a novel rapid test for the diagnosis of LNTB. Although previous evidence suggests that Xpert is reliably accurate in diagnosing EPTB in children, information is lacking for the specific type of LNTB in children. The aim of this study was to systematically assess the accuracy and reliability of Xpert for the diagnosis of LNTB in children. Methods: We systematically searched four databases, Embase, Cochrane Library, PubMed, and Web of Science, which extracted relevant data according to predefined inclusion and exclusion criteria. The data were analyzed by meta-Disc 1.4 and Stata 12.0 software to determine sensitivity, specificity, diagnostic odds ratio (DOR), etc. Results: A total of 646 samples from 8 studies were included in the analysis. The pooled sensitivity, specificity, negative likelihood ratio (NLR), positive likelihood ratio (PLR,) and combined diagnostic odds ratio (DOR) of Xpert for all samples were 0.79 (95% CI 0.70, 0.87), 0.90 (95% CI 0.86, 0.92), 0.29 (95% CI 0.19, 0.43), 7.20 (95% CI 3.32, 15.60), and 37.56 (95% CI 13.04, 108.15), respectively. The area under the curve (AUC) of the summary receiver operating characteristic (sROC) curve was 0.9050. Conclusion: Overall, Xpert showed moderate sensitivity and high specificity compared with culture in the diagnosis of LNTB in children. In addition, after analyzing the combined diagnostic odds ratio and positive LR, our study showed that Xpert has excellent diagnostic accuracy.
ABSTRACT
AIMS: Our laboratory previously reported that olanzapine treatment inhibited growth of glioma cell lines and hypothesized that autophagy may be involved in the proliferation inhibitory effects of olanzapine. However, the mechanisms of olanzapine-contributed autophagy activation are unclear. METHODS: The inhibitory effects of olanzapine on glioma cells were evaluated by CCK8 assay, Hoechst 33258 staining and annexin V-FITC/PI staining. Western blotting, nuclear separation techniques, and immunofluorescence assays were used to investigate the relationship between the inhibition of NF-κB and autophagy activation by olanzapine. RESULTS: In this work, we verified that olanzapine increased autophagic flux and autophagic vesicles. In addition, we confirmed that autophagy was related to NF-κB inhibition in cancer progression, especially with the nuclear translocation of p65. Furthermore, we demonstrated that autophagy induced by olanzapine could be impaired with TNFα cotreatment. We also found that olanzapine had an inhibitory effect on T98 cells with positive MGMT protein expression, which may involve the inhibition of MGMT through effects on NF-κB. CONCLUSIONS: Our findings identify a pathway by which olanzapine induces autophagy by depressing NF-κB in a glioma cell line, providing evidence which supports the use of olanzapine as a potential anticancer drug.
Subject(s)
Autophagy/drug effects , Glioma/metabolism , NF-kappa B/antagonists & inhibitors , NF-kappa B/metabolism , Olanzapine/toxicity , Selective Serotonin Reuptake Inhibitors/toxicity , Antineoplastic Agents/toxicity , Autophagy/physiology , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/physiology , Dose-Response Relationship, Drug , Glioma/pathology , HumansABSTRACT
The aim of this study was to investigate the effects of olanzapine on growth inhibition as well as autophagy in glioma cells in vitro and in vivo. The proliferation of both LN229 and T98 glioma cells, measured by MTT assay, was suppressed in a concentration-dependent and time-dependent manner. Moreover, apoptosis of both cells was significantly increased with the treatment of olanzapine as evidenced by increased Bcl-2 expression, Hoechst 33258 staining and annexinV-FITC/PI staining. Olanzapine treatment also enhanced activation of autophagy with increased expression of LC3-II, expression of protein p62, a substrate of autophagy, being decreased. The growth inhibition by olanzapine in both glioma cell lines could be blocked by co-treatment with 3-MA, an autophagy inhibitor. Furthermore, olanzapine effectively blocked the growth of subcutaneous xenografts of LN229 glioma cells in vivo. The increased level of protein LC3-II and decreased level of p62 followed by a decreased level of Bcl-2, suggesting that autophagy may contribute to apoptosis. In addition, reduced proliferation of glioma cells was shown by a decrease of Ki-67 staining and increased caspase-3 staining indicative of apoptosis in mouse xenografts. These results indicated that olanzapine inhibited the growth of glioma cells accompanied by induction of autophagy and apoptosis both in vitro and in vivo. Olanzapine-induced autophagy plays a tumor-suppressing role in glioma cells.
