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| 1 | FSIP1 enhances the therapeutic sensitivity to CDK4/6 inhibitors in triple-negative breast cancer patients by activating the Nanog pathway显示文摘CDK4/6 inhibitors are routinely recommended agents for the treatment of advanced HR+HER2-breast cancer.However,their therapeutic effectiveness in triple-negative breast cancer(TNBC)remains controversial.Here,we observed that the expression level of fibrous sheath interacting protein 1(FSIP1)could predict the treatment response of TNBC to CDK4/6 inhibitors.High FSIP1 expression level was related to a poor prognosis in TNBC,which was associated with the ability of FSIP1 to promote tumor cell proliferation.FSIP1 downregulation led to slowed tumor growth and reduced lung metastasis in TNBC.FSIP1knockout caused cell cycle arrest at the G0/G1 phase and reduced treatment sensitivity to CDK4/6 inhibitors by inactivating the Nanog/CCND1/CDK4/6 pathway.FSIP1 could form a complex with Nanog,protecting it from ubiquitination and degradation,which may facilitate the rapid cell cycle transition from G0/G1 to S phase and exhibit enhanced sensitivity to CDK4/6 inhibitors.Our findings suggest that TNBC patients with high FSIP1 expression levels may be suitable candidates for CDK4/6 inhibitor treatment. | Guanglei Chen Lisha Sun Xi Gu Liping Ai Jie Yang Zhan Zhang Pengjie Hou Yining Wang Xunyan Ou Xiaofan Jiang Xinbo Qiao Qingtian Ma Nan Niu Jinqi Xue Hao Zhang Yongliang Yang Caigang Liu | 2023 | Science China(Life Sciences)2023，66，12： | 1 |
| 2 | Consensus on potential biomarkers developed for use in clinical tests for schizophrenia显示文摘Background Schizophrenia is a serious mental illness affecting approximately 20 million individuals globally.Both genetic and environmental factors contribute to the illness.If left undiagnosed and untreated,schizophrenia results in impaired social function,repeated hospital admissions,reduced quality of life and decreased life expectancy.Clinical diagnosis largely relies on subjective evidence,including self-reported experiences,and reported behavioural abnormalities followed by psychiatric evaluation.In addition,psychoses may occur along with other conditions,and the symptoms are often episodic and transient,posing a significant challenge to the precision of diagnosis.Therefore,objective,specific tests using biomarkers are urgently needed for differential diagnosis of schizophrenia in clinical practice.Aims We aimed to provide evidence-based and consensus-based recommendations,with a summary of laboratory measurements that could potentially be used as biomarkers for schizophrenia,and to discuss directions for future research.Methods We searched publications within the last 10 years with the following keywords:‘schizophrenia’,‘gene’,‘inflammation’,‘neurotransmitter’,‘protein marker’,‘gut microbiota’,‘pharmacogenomics’and‘biomarker’.A draft of the consensus was discussed and agreed on by all authors at a round table session.Results We summarised the characteristics of candidate diagnostic markers for schizophrenia,including genetic,inflammatory,neurotransmitter,peripheral protein,pharmacogenomic and gut microbiota markers.We also proposed a novel laboratory process for diagnosing schizophrenia in clinical practice based on the evidence summarised in this paper.Conclusions Further efforts are needed to identify schizophrenia-specific genetic and epigenetic markers for precise diagnosis,differential diagnosis and ethnicity-specific markers for the Chinese population.The development of novel laboratory techniques is making it possible to use these biomarkers clinically to diagnose disease. | Ping Lin Junyu Sun Xiaoyan Lou Dan Li Yun Shi Zhenhua Li Peijun Ma Ping Li Shuzi Chen Weifeng Jin Shuai Liu Qing Chen Qiong Gao Lili Zhu Jie Xu Mengyuan Zhu Mengxia Wang Kangyi Liang Ling Zhao Huabin Xu Ke Dong Qingtian Li Xunjia Cheng Jinghong Chen Xiaokui Guo | 2022 | General Psychiatry2022，35，1： | 1 |
| 3 | KCNJ15 deficiency promotes drug resistance via affecting the function of lysosomes显示文摘The altered lysosomal function can induce drug redistribution which leads to drug resistance and poor prognosis for cancer patients.V-ATPase,an ATP-driven proton pump positioned at lysosomal surfaces,is responsible for maintaining the stability of lysosome.Herein,we reported that the potassium voltage-gated channel subfamily J member 15(KCNJ15)protein,which may bind to V-ATPase,can regulate the function of lysosome.The deficiency of KCNJ15 protein in breast cancer cells led to drug aggregation as well as reduction of drug efficacy.The application of the V-ATPase inhibitor could inhibit the binding between KCNJ15 and V-ATPase,contributing to the amelioration of drug resistance.Clinical data analysis revealed that KCNJ15 deficiency was associated with higher histological grading,advanced stages,more metastases of lymph nodes,and shorter disease free survival of patients with breast cancer.KCNJ15 expression level is positively correlated with a high response rate after receiving neoadjuvant chemotherapy.Moreover,we revealed that the small molecule drug CMA/BAF can reverse drug resistance by disrupting the interaction between KCNJ15 and lysosomes.In conclusion,KCNJ15 could be identified as an underlying indicator for drug resistance and survival of breast cancer,which might guide the choice of therapeutic strategies. | Xinbo Qiao Yixiao Zhang Zhan Zhang Nan Niu Haonan Li Lisha Sun Qingtian Ma Jiawen Bu Jinchi Liu Guanglei Chen Jinqi Xue Yongliang Yang Caigang Liu | 2023 | Asian Journal of Pharmaceutical Sciences2023，18，3： | 0 |
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