A TiO2/SiO2 composite prepared by the sol-gel route can produce highly emissive broadband room-temperature phosphorescence at an excitation wavelength of 403 nm. The white phosphorescence of TiO2/SiO2 could be quenched by H2O2. The phosphorescence quenching effect demonstrated excellent sensitivity and high selectivity to H2O2. Furthermore, the phosphorescence of TiO2/SiO2 can be recovered when it is dipped in a hydroxylamine hydrochloride solution. Therefore, the TiO2/SiO2 was used to develop a reproducible phosphorescence sensor for H2O2. It has been successfully applied to the determination of H2O2 in the enzymatic catalytic reaction and real samples.

Background Glioblastoma (GBM) is a fatal brain tumor, lacking effective treatment. Epidermal growth factor receptor (EGFR) is recognized as an attractive target for GBM treatment. However, GBMs have very poor responses to the first- and second-generation EGFR inhibitors. The third-generation EGFR-targeted drug, AZD9291, is a novel and irreversible inhibitor. It is noteworthy that AZD9291 shows excellent blood–brain barrier penetration and has potential for the treatment of brain tumors. Methods In this study, we evaluated the anti-tumor activity and effectiveness of AZD9291 in a preclinical GBM model. Results AZD9291 showed dose-responsive growth inhibitory activity against six GBM cell lines. Importantly, AZD9291 inhibited GBM cell proliferation > 10 times more efficiently than the first-generation EGFR inhibitors. AZD9291 induced GBM cell cycle arrest and significantly inhibited colony formation, migration, and invasion of GBM cells. In an orthotopic GBM model, AZD9291 treatment significantly inhibited tumor survival and prolonged animal survival. The underlying anti-GBM mechanism of AZD9291 was shown to be different from that of the first-generation EGFR inhibitors. In contrast to erlotinib, AZD9291 continuously and efficiently inhibited the EGFR/ERK signaling in GBM cells. Conclusion AZD9291 demonstrated an efficient preclinical activity in GBM in vitro and in vivo models . AZD9291 has been approved for the treatment of lung cancer with good safety and tolerability. Our results support the possibility of conducting clinical trials of anti-GBM therapy using AZD9291. Electronic supplementary material The online version of this article (10.1186/s13046-019-1235-7) contains supplementary material, which is available to authorized users.

BackgroundMalignant gliomas are associated with a high mortality rate, and effective treatment options are limited. Thus, the development of novel targeted treatments to battle this deadly disease is imperative.MethodsIn this study, we investigated the in vitro effects of the novel reversible chromosomal region maintenance 1 (CRM1) inhibitor S109 on cell proliferation in human gliomas. S109 was also evaluated in an intracranial glioblastoma xenograft model.ResultsWe found that high expression of CRM1 in glioma is a predictor of short overall survival and poor patient outcome. Our data demonstrate that S109 significantly inhibits the proliferation of human glioma cells by inducing cell cycle arrest at the G1 phase. Notably, we observed that high-grade glioma cells are more sensitive to S109 treatment compared with low-grade glioma cells. In an intracranial mouse model, S109 significantly prolonged the survival of tumor-bearing animals without causing any obvious toxicity. Mechanistically, S109 treatment simultaneously perturbed the three core pathways (the RTK/AKT/Foxos signaling pathway and the p53 and Rb1 tumor-suppressor pathways) implicated in human glioma cells by promoting the nuclear retention of multiple tumor-suppressor proteins.ConclusionsTaken together, our study highlights the potential role of CRM1 as an attractive molecular target for the treatment of human glioma and indicates that CRM1 inhibition by S109 might represent a novel treatment approach.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0338-2) contains supplementary material, which is available to authorized users.

Dysregulation of Hippo/YAP signaling leads to aberrant cell growth and neoplasia. Although the roles and regulation of Hippo/YAP signaling were extensively studied in cancer biology recently, study systematically checking the expression pattern of core components of this pathway at the tumor tissue level remains lacking. In this study, we thoroughly examined the profile of core components of Hippo/YAP signaling in patient specimens both at the mRNA and at protein levels. We found that the mRNA level of YAP1/TAZ and their target genes, CRY61, CTGF, and BIRC5, was remarkably amplified in glioma tissues. Consistently, the protein level of YAP1/TAZ increased and meanwhile those of p-YAP1/p-TAZ and LATS1/2 decreased in gliomas. Unexpectedly, both the mRNA and protein levels of MST1/2 increased in the glioma tissues, inconsistent with its presumed tumor suppressor identity. In addition, over-expression of LATS2 decreased, while over-expression of YPA1 increased the cell proliferation ability. Furthermore, based on the data from the free public database, YAP1/TAZ and BIRC5 were positively associated with the prognosis of glioma patients, while LATS1/2 exhibited negative correlation with the glioma patient prognosis. Collectively, we deduce that, in glioma tissue context, MST1/2 may not be the essential component of the hippo/YAP pathway. Moreover, our findings uncover a new evidence supporting that YAP1/TAZ-BIRC5 might be abnormally activated due to LATS1/2 down-regulation, which in turn promote the occurrence and development of gliomas, paving the way to identify the potential therapeutic molecular target for gliomas.

Decreased function of the anterior cingulate cortex (ACC) is crucially involved in the pathogenesis of depression. A key role of nitric oxide (NO) has also been proposed. We aimed to determine the NO content in the cerebrospinal fluid (CSF) and the expression of NO synthase (NOS) isoforms, that is, NOS1, NOS2, and NOS3 in the ACC in depression. In depressive patients, CSF-NOx levels (the levels of the NO metabolites nitrite and nitrate) were significantly decreased (P = 0.007), indicating a more general decrease of NO production in this disorder. This agreed with a trend toward lower NOS1-mRNA levels (P = 0.083) and a significant decrease of NOS1-immunoreactivity (ir) (P = 0.043) in ACC. In controls, there was a significant positive correlation between ACC-NOS1-ir cell densities and their CSF-NOx levels. Furthermore, both localization of NOS1 in pyramidal neurons that are known to be glutamatergic and co-localization between NOS1 and GABAergic neurons were observed in human ACC. The diminished ACC-NOS1 expression and decreased CSF-NOx levels may be involved in the alterations of ACC activity in depression, possibly by affecting glutamatergic and GABAergic neurotransmission.