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您的检索式：作者名="Jingyao Tu"
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| 1 | Combining radiation and the ATR inhibitor berzosertib activates STING signaling and enhances immunotherapy via inhibiting SHP1 function in colorectal cancer显示文摘Background:Immune checkpoint inhibitors(ICIs)targeting programmed cell death protein 1(PD-1)and programmed death-ligand 1(PD-L1)have shown a moderate response in colorectal cancer(CRC)with deficient mismatch repair(dMMR)functions and poor response in patients with proficientMMR(pMMR).pMMRtumors are generally immunogenically“cold”,emphasizing combination strategies to turn the“cold”tumor“hot”to enhance the efficacy of ICIs.ATR inhibitors(ATRi)have been proven to cooperate with radiation to promote antitumor immunity,but it is unclear whether ATRi could facilitate the efficacy of IR and ICI combinations in CRCs.This study aimed to investigate the efficacy of combining ATRi,irradiation(IR),and anti-PD-L1 antibodies in CRC mouse models with different microsatellite statuses.Methods:The efficacy of combining ATRi,IR,and anti-PD-L1 antibodies was evaluated in CRC tumors.The tumor microenvironment and transcriptome signatures were investigated under different treatment regimens.The mechanisms were explored via cell viability assay,flow cytometry,immunofluorescence,immunoblotting,co-immunoprecipitation,and real-time quantitative PCR in multiple murine and human CRC cell lines.Results:Combining ATRi berzosertib and IR enhanced CD8+T cell infiltration and enhanced the efficacy of anti-PD-L1 therapy in mouse CRC models with different microsatellite statuses.The mechanistic study demonstrated that IR+ATRi could activate both the canonical cGAS-STING-pTBK1/pIRF3 axis by increasing cytosolic double-stranded DNA levels and the non-canonical STING signaling by attenuating SHP1-mediated inhibition of the TRAF6-STINGp65 axis,via promoting SUMOylation of SHP1 at lysine 127.By boosting the STING signaling,IR+ATRi induced type I interferon-related gene expression and strong innate immune activation and reinvigorated the cold tumor microenvironment,thus facilitating immunotherapy.Conclusions:The combination of ATRi and IR could facilitate anti-PD-L1 therapy by promoting STING signaling in CRC models with different microsatellite statuses.The new combination strategy raised by our study isworth investigating in the management of CRC. | Chaofan Liu Xi Wang Wan Qin Jingyao Tu Chunya Li Weiheng Zhao Li Ma Bo Liu Hong Qiu Xianglin Yuan | 2023 | Cancer Communications2023，43，4： | 1 |
| 2 | Non-directed highly para-selective C-H functionalization of TIPS-protected phenols promoted by a carboxylic acid ligand显示文摘Palladium-catalyzed non-directed C-H functionalization provides an efficient approach for direct functionalization of arenes, but it usually suffers from poor site selectivity, limiting its wide application.Herein, it is reported for the first time that the carboxylic acid ligand of 3,5-dimethyladamantane-1-carboxylic acid(1-DMAd CO_(2)H) can affect the site selectivity during the C-H activation step in palladiumcatalyzed non-directed C-H functionalization, leading to highly para-selective C-H olefination of TIPSprotected phenols. This transformation displayed good generality in realizing various other para-selective C-H functionalization reactions such as halogenation, and allylation reactions. A wide variety of phenol derivatives including bioactive molecules of triclosan, thymol, and propofol, were compatible substrates,leading to the corresponding para-selective products in moderate to good yields. A preliminary mechanism study revealed that the spatial repulsion factor between carboxylic acid ligand and bulky protecting group resulted in the selective C-H activation at the less sterically hindered para-position. This new model non-directed para-selective C-H functionalization can provide a straightforward route for remote site-selective C-H activations. | Jingyao Geng Zhang Fang Guangliang Tu Yingsheng Zhao | 2023 | Chinese Chemical Letters2023，34，3： | 0 |
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