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| 1 | SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade显示文摘Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both in vitro and in vivo. However, whether SHP099-mediated SHP2 inhibition retards tumor growth in vivo via anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099.Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system.SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8tIFN-γtT cells and the upregulation of cytotoxic T-cell related genes including Granzyme B andPerforin, which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and antiPD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growthin two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy. | Mingxia Zhao Wenjie Guo Yuanyuan Wu Chenxi Yang Liang Zhong Guoliang Deng Yuyu Zhu Wen Liu Yanhong Gu Yin Lu Lingdong Kong Xiangbao Meng Qiang Xu Yang Sun | 2019 | Acta Pharmaceutica Sinica B2019，9，2： | 18 |
| 2 | Loss of hnRNP A1 in murine skeletal muscle exacerbates high-fat diet-induced onset of insulin resistance and hepatic steatosis显示文摘Impairment of glucose(Glu)uptake and storage by skeletal muscle is a prime risk factor for the development of metabolic diseases.Heterogeneous nuclear ribonucleoprotein A1(hnRNP Al)is a highly abundant RNA-binding protein that has been implicated in diverse cellular functions.The aim of this study was to investigate the function of hnRNP A1 on muscle tissue insulin sensitivity and systemic Glu homeostasis.Our results showed that conditional deletion of hnRNP Al in the muscle gave rise to a severe insulin resistance phenotype in mice fed a high-fat diet(HFD).Conditional knockout mice fed a HFD showed exacerbated obesity,insulin resistance,and hepatic steatosis.In vitro interference of hnRNP Al in C2C12 myotubes impaired insulin signal transduction and inhibited Glu uptake,whereas hnRNP Al overexpression in C2C12 myotubes protected against insulin resistance induced by supraphysiological concentrations of insulin.The expression and stability of glycogen synthase(gysl)mRNA were also decreased in the absence of hnRNP A l.Mechanistically,hnRNP Al interacted with gys l and stabilized its mRNA,thereby promoting glycogen synthesis and maintaining the insulin sensitivity in muscle tissue.Taken together,our findings are the first to show that reduced expression of hnRNP Al in skeletal muscle affects the metabolic properties and systemic insulin sensitivity by inhibiting glycogen synthesis. | Mingxia Zhao Lihong Shen Zijun Ouyang Manru Li Guoliang Deng Chenxi Yang Wei Zheng Lingdong Kong Xuefeng Wu Xudong Wu Wenjie Guo Ye Yin Qiang Xu Yang Sun | 2020 | Journal of Molecular Cell Biology2020，12，4： | 2 |
| 3 | Recent developments in sample preparation techniques for chromatography analysis of traditional Chinese medicines显示文摘 | Chunhui Deng Ning Liu Mingxia Gao Xiangmin Zhang | 2007 | Journal of Chromatography A2007，，1： | 1 |
| 4 | Recent developments in sample preparation techniques for chromatography analysis of traditional Chinese medicines 显示文摘 | DENG Chunhui LIU Ning GAO Mingxia | 2007 | J Chromatogr A2007，，12： | 1 |
| 5 | Recent developments in sample preparation techniques for chromatography analysis of traditional Chinese medicines显示文摘 | DENG Chunhui LIU Ning GAO Mingxia | 2007 | J Chromatogr A2007，1153，12： | 1 |
| 6 | Recent developments in sample preparation techniques for chromatography analysis of traditional Chinese medicines显示文摘 | DENG Chunhui LIU Ning GAO Mingxia | 2007 | J Chromatogr A2007，，12： | 1 |
| 7 | Recent developments in sample preparation techniques for chromatography analysis of traditional Chinese medicines显示文摘 | DENG Chunhui LIU Ning GAO Mingxia | 2007 | J Chromatogr A2007，1153，12： | 1 |
| 8 | Recent development of multi-dimensional chromatography strategies in proteome research显示文摘 | Jia Tang Mingxia Gao Chunhui Deng Xiangming Zhang | 2008 | Journal of Chromatography B2008，，1： | 1 |
| 9 | Recent developments in sample preparation techniques for chromatography analysis of traditional Chinese medicines显示文摘 | DENG Chunhui LIU Ning GAO Mingxia | 2007 | J Chromatogr A2007，，12： | 1 |
| 10 | Recent developments in sample preparation techniques for chromatography analysis of traditional Chinese medicines显示文摘 | DENG Chunhui LIU Ning GAO Mingxia | 2007 | J Chromatogr: A2007，，1153： | 1 |
| 11 | Recent developments in sample preparation techniques for chromatography analysis of traditional Chinese medicines显示文摘 | DENG Chunhui LIU Ning GAO Mingxia | 2007 | J Chromatogr A2007，，12： | 1 |
| 12 | CFTR is a negative regulator ofγδT cell IFN-γproduction and antitumor immunity显示文摘CFTR,a chloride channel and ion channel regulator studied mostly in epithelial cells,has been reported to participate in immune regulation and likely affect the risk of cancer development.However,little is known about the effects of CFTR on the differentiation and function ofγδT cells.In this study,we observed that CFTR was functionally expressed on the cell surface ofγδT cells.Genetic deletion and pharmacological inhibition of CFTR both increased IFN-γrelease by peripheralγδT cells and potentiated the cytolytic activity of these cells against tumor cells both in vitro and in vivo.Interestingly,the molecular mechanisms underlying the regulation ofγδT cell IFN-γproduction by CFTR were either TCR dependent or related to Ca^(2+)influx.CFTR was recruited to TCR immunological synapses and attenuated Lck-P38 MAPK-c-Jun signaling.In addition,CFTR was found to modulate TCR-induced Ca^(2+)influx and membrane potential(Vm)-induced Ca^(2+)influx and subsequently regulate the calcineurin-NFATc1 signaling pathway inγδT cells.Thus,CFTR serves as a negative regulator of IFN-γproduction inγδT cells and the function of these cells in antitumor immunity.Our investigation suggests that modification of the CFTR activity ofγδT cells may be a potential immunotherapeutic strategy for cancer. | Yuanyuan Duan Guangqiang Li Miaomiao Xu Xiaofei Qi Mingxia Deng Xuejia Lin Zhiwei Lei Yi Hu Zhenghu Jia Quanli Yang Guangchao Cao Zonghua Liu Qiong Wen Zhenhua Li Jie Tang Wei Kevin Zhang Pingbo Huang Limin Zheng Richard A.Flavell Jianlei Hao Zhinan Yin | 2021 | Cellular & Molecular Immunology2021，18，8： | 0 |
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