Articles: signal-transducing-adaptor-proteins.
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Malignant mesothelioma is an aggressive cancer that is resistant to current therapy. The poor prognosis of mesothelioma has been associated with elevated Yes-associated protein (YAP) activity. In this study, we evaluated the effect of targeting YAP in mesothelioma. ⋯ Finally, we found concurrent immunohistochemistry staining of ROCK2 and YAP (P < 0.05). Inhibition of ROCK2 decreased GTIIC reporter activity in H2052 and 211H suggesting that Rho/ROCK signaling also contributed to YAP activation in mesothelioma cells. Our results indicate that YAP may be a potential therapeutic target in mesothelioma.
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Lung squamous cell cancer (SCC) is typically found in smokers and has a very low incidence in non-smokers, indicating differences in the tumor biology of lung SCC in smokers and non-smokers. However, the specific mutations that drive tumor growth in non-smokers have not been identified. To identify mutations in lung SCC of non-smokers, we performed a genetic analysis using arrays comparative genomic hybridization (ArrayCGH). ⋯ Immunohistochemical analyses showed that GAB2 protein was relatively upregulated in non-smoker than smoker tissues (37.5% vs. 9.0%, P = 0.007). GAB2 amplification may have an important role in the development of lung SCC in non-smokers. GAB2 may represent a potential biomarker for lung SCC in non-smokers.
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What is the physiological function of Yes-associated protein-1 (Yap1), a susceptibility gene for polycystic ovary syndrome (PCOS), in ovarian granulosa cells (GCs)? ⋯ This study is funded by the National Key Research and Development Program of China (2016YFC1000600 and 2017YFSF1001500) and National Natural Science Foundation of China (31528016, 31371449 and 31671558). The authors have no competing interests.
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Verteporfin (VP), a light-activated drug used in photodynamic therapy for the treatment of choroidal neovascular membranes, has also been shown to be an effective inhibitor of malignant cells. Recently, studies have demonstrated that, even without photo-activation, VP may still inhibit certain tumor cell lines, including ovarian cancer, hepatocarcinoma and retinoblastoma, through the inhibition of the YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human glioma cell lines (LN229 and SNB19). ⋯ In addition, we observed that expression of VEGFA and the pluripotent marker Oct-4 were also decreased. Verteporfin did not alter the Akt survival pathway or the mTor pathway but there was a modest increase in LC3-IIB, a marker of autophagosome biogenesis. This study suggests that verteporfin should be further explored as an adjuvant therapy for the treatment of glioblastoma.
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Int. Immunopharmacol. · Aug 2017
Chronic dexamethasone treatment results in hippocampal neurons injury due to activate NLRP1 inflammasome in vitro.
Neuroinflammation mediated by NLRP-1 inflammasome plays an important role in the pathogenesis of neurodegeneration diseases such as Alzheimer's disease (AD). Chronic glucocorticoids (GCs) exposure has deleterious effect on the structure and function of neurons and was found to be correlated with development and progression of AD. We hypothesize that chronic glucocorticoids may down-regulate the expression of glucocorticoids receptor (GR) and activate NLRP-1 inflammasome in hippocampal neurons, which may promote neuroinflammation and induce neuronal injury. ⋯ Moreover, DEX (1, 5μΜ) treatment for 3d significantly increased the expression of NF-κB in hippocampal neurons. The GR antagonist, mifepristone (RU486), had protective effects on chronic DEX induced hippocampal neurons injury and NLRP1 inflammasome activation. The results suggest that chronic GCs exposure can decrease GR expression and increase neuroinflammation via NLRP1 inflammasome and promote hippocampal neurons degeneration, which may play an important role in the progression and development of AD.