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| 1 | Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing,locally advanced or metastatic gastric or gastroesophageal junction cancer:a single-arm phase II study显示文摘Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 immunohistochemistry(IHC)2+and fluorescence in-situ hybridization-negative patients.Here,we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer.Methods:Patients with HER2-overexpressing(IHC 2+or 3+),locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC482.5 mg/kg alone every 2 weeks.The primary endpoint was the objective response rate(ORR)assessed by an independent review committee.Secondary endpoints included progressionfree survival(PFS),overall survival(OS),duration of response,time to progression,disease control rate,and safety.Results:Of 179 patients screened,125 were eligible and received RC48 treatment.The ORR was 24.8%(95%confidence interval[CI]:17.5%-33.3%).The median PFS and OS were 4.1 months(95%CI:3.7-4.9 months)and 7.9 months(95%CI:6.7-9.9 months),respectively.The most frequently reported adverse events were decreased white blood cell count(53.6%),asthenia(53.6%),hair loss(53.6%),decreased neutrophil count(52.0%),anemia(49.6%),and increased aspartate aminotransferase level(43.2%).Serious adverse events(SAEs)occurred in 45(36.0%)patients,and RC48-related SAEs were mainly decreased neutrophil count(3.2%).Seven patients had adverse events that led to death were not RC48-related.Conclusions:RC48 showed promising activity with manageable safety,suggesting potential application in patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy. | Zhi Peng Tianshu Liu Jia Wei Airong Wang Yifu He Liuzhong Yang Xizhi Zhang Nanfeng Fan Suxia Luo Zhen Li Kangsheng Gu Jianwei Lu Jianming Xu Qingxia Fan Ruihua Xu Liangming Zhang Enxiao Li Yuping Sun Guohua Yu Chunmei Bai Yong Liu Jiangzheng Zeng Jieer Ying Xinjun Liang Nong Xu Chao Gao Yongqian Shu Dong Ma Guanghai Dai Shengmian Li Ting Deng Yuehong Cui Jianmin Fang Yi Ba Lin Shen | 2021 | Cancer Communications2021，41，11： | 29 |
| 2 | The jasmonate-induced bHLH gene SlJIG functions in terpene biosynthesis and resistance to insects and fungus显示文摘Jasmonic acid(JA)is a key regulator of plant defense responses.Although the transcription factor MYC2,the master regulator of the JA signaling pathway,orchestrates a hierarchical transcriptional cascade that regulates the JA responses,only a few transcriptional regulators involved in this cascade have been described.Here,we identified the basic helix-loop-helix(bHLH)transcription factor gene in tomato(Solanum lycopersicum),METHYL JASMONATE(MeJA)-INDUCED GENE(SlJIG),the expression of which was strongly induced by MeJA treatment.Genetic and molecular biology experiments revealed that SlJIG is a direct target of MYC2.SlJIG knockout plants generated by gene editing had lower terpene contents than the wild type from the lower expression of TERPENE SYNTHASE(TPS)genes,rendering them more appealing to cotton bollworm(Helicoverpa armigera).Moreover,SlJIG knockouts exhibited weaker JA-mediated induction of TPSs,suggesting that SlJIG may participate in JA-induced terpene biosynthesis.Knocking out SlJIG also resulted in attenuated expression of JA-responsive defense genes,which may contribute to the observed lower resistance to cotton bollworm and to the fungus Botrytis cinerea.We conclude that SlJIG is a direct target of MYC2,forms a MYC2-SlJIG module,and functions in terpene biosynthesis and resistance against cotton bollworm and B.cinerea. | Yunyun Cao Lun Liu Kangsheng Ma Wenjing Wang Hongmei Lv Ming Gao Xinman Wang Xichun Zhang Shuxin Ren Na Zhang Yang-Dong Guo | 2022 | Journal of Integrative Plant Biology2022，64，5： | 4 |
| 3 | miRNAs targeting CYP6ER1 and CarE1 are involved in nitenpyram resistance in Nilaparvata lugens显示文摘The evolution of nitenpyram resistance has been confirmed to be related to overexpression of two key metabolic enzyme genes, CYP6ER1 and CarE1, in Nilaparvata lugens, a highly destructive rice pest that causes substantial economic losses and has developed insecticide resistance. As microRNAs (miRNAs) are important post-transcriptional regulators of gene expression, whether they are involved in nitenpyram resistance is poorly understood in N. lugens. In this study, knockdown of key genes in the miRNA biogenesis pathway (Dicer1, Drosha, and Argonaute1) changed CYP6ER1 and CarE1 abundance, which confirmed the importance of miRNAs in nitenpyram resistance. Furthermore, global screening of miRNAs associated with nitenpyram resistance in N. lugens was performed, and a total of 42 known and 178 novel miRNAs were identified;of these, 57 were differentially expressed between the susceptible and resistant strains, and two (novel_85 and novel_191) were predicted to target CYP6ER1 and CarE1, respectively. Luciferase reporter assays demonstrated that novel_85 and novel_191 bind to the CYP6ER1 and CarE1 coding regions, respectively, and downregulate their expression. Moreover, modulating novel_85 and novel_191 expression by injection of miRNA inhibitors and mimics significantly altered N. lugens nitenpyram susceptibility. This is the first study to systematically screen and identify miRNAs associated with N. lugens nitenpyram resistance, and provides important information that can be used to develop new miRNA-based targets in insecticide resistance management. | Kaikai Mao Ruoheng Jin Zhijie Ren Junjie Zhang Zhao Li Shun He Kangsheng Ma Hu Wan Jianhong Li | 2022 | Insect Science2022，29，1： | 2 |
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