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The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions:insights from a single-arm,phase II trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2202-2214页

作者： Bo Cheng caichen Li Jianfu Li Longlong Gong Peng Liang Ying Chen Shuting Zhan Shan Xiong Ran Zhong Hengrui Liang Yi Feng Runchen Wang Haixuan Wang Hongbo Zheng Jun Liu Chengzhi Zhou Wenlong Shao Yuan Qiu Jiancong Sun Zhanhong Xie Zhu Liang Chenglin Yang xiuyu cai Chunxia Su Wei Wang Jianxing He Wenhua Liang Department of Thoracic Surgery and Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Medical Department Genecast Biotechnology Co.LtdWuxiChina Department of Radiation Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Department of Respiratory Medicine the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Department of Cardiothoracic Surgery Affiliated Hospital of Guangdong Medical UniversityZhanjiangChina Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenChina Department of VIP Inpatient Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaSun Yat-sen UniversityGuangzhouChina Department of Medical Oncology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina

Immune checkpoint inhibitors targeting the programmed cell death-1(PD-1)protein significantly improve survival in patients with advanced non-small-cell lung cancer(NSCLC),but its impact on early-stage ground-glass opacity(GGO)lesions remains *** is a single-arm,phase II trial(NCT04026841)using Simon’s optimal two-stage design,of which 4 doses of sintilimab(200 mg per 3 weeks)were administrated in 36 enrolled multiple primary lung cancer(MPLC)patients with persistent high-risk(Lung-RADS category 4 or had progressed within 6 months)*** primary endpoint was objective response rate(ORR).T/B/NK-cell subpopulations,TCR-seq,cytokines,exosomal RNA,and multiplexed immunohistochemistry(mIHC)were monitored and compared between responders and ***,two intent-to-treat(ITT)lesions(pure-GGO or GGO-predominant)showed responses(ORR:5.6%,2/36),and no patients had progressive disease(PD).No grade 3-5 TRAEs *** total response rate considering two ITT lesions and three non-intent-to-treat(NITT)lesions(pure-solid or solid-predominant)was 13.9%(5/36).The proportion of CD8^(+)T cells,the ratio of CD8^(+)/CD4^(+),and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over ***,the mIHC analysis showed more CD8^(+)T cells infiltrated in ***,responders’cytokine concentrations of EGF and CTLA-4 increased during *** exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among ***,PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety *** effects were associated with specific T-cell re-distribution,EGF/CTLA-4 cytokine compensation,and regulation of metabolism pathways.

关键词： lesions metabolism doses

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Cannabis suppresses antitumor immunity by inhibiting JAK/STAT signaling in T cells through CNR2

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Signal Transduction and Targeted Therapy 2022年第5期7卷 1657-1669页

作者： Xinxin Xiong Siyu Chen Jianfei Shen Hua You Han Yang Chao Yan Ziqian Fang Jianeng Zhang xiuyu cai Xingjun Dong Tiebang Kang Wende Li Penghui Zhou State Key Laboratory of Oncology in Southern China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhou 510060China Guangdong Provincial People’s Hospital Guangdong Academy of Medical SciencesGuangzhou 510515China Guangdong Laboratory Animals Monitoring Institute Guangdong Key Laboratory of Laboratory AnimalsGuangzhou 510663China Department of Thoracic Surgery Taizhou Hospital of Zhejiang ProvinceWenzhou Medical UniversityLinhai 317000China Affiliated Cancer Hospital&Institute of Guangzhou Medical University Guangzhou 510095China Department of Thoracic Surgery Sun Yat-sen University Cancer CenterGuangzhou 510060China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

The combination of immune checkpoint blockade(ICB)with chemotherapy significantly improves clinical benefit of cancer *** chemotherapy is often associated with adverse events,concomitant treatment with drugs managing side effects of chemotherapy is frequently used in the combination ***,whether these ancillary drugs could impede immunotherapy remains ***,we showed that∆9-tetrahydrocannabinol(THC),the key ingredient of drugs approved for the treatment of chemotherapy-caused nausea,reduced the therapeutic effect of PD-1 *** endogenous cannabinoid anandamide(AEA)also impeded antitumor immunity,indicating an immunosuppressive role of the endogenous cannabinoid system(ECS).

关键词： JAK/STAT drugs chemotherapy treatment

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Effects of traditional Chinese medicine on treatment outcomes in severe COVID-19 patients:a single-centre study

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Chinese Journal of Natural Medicines 2024年第1期22卷 89-96页

作者： XIAO Yongjiu LI Binbin LIU Chang HUANG xiuyu MA Ling QIAN Zhirong ZHANG Xiaopeng ZHANG Qian LI Dunqing cai Xiaoqing YAN Xiangyong LUO Shuping XIANG Dawei XIAO Kun Emergency Department the 940th Hospital of Jiont Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China Scientific Research Center the Seventh Affiliated HospitalSun Yat-sen UniversityShenzhen 518000China School of Medicine Nankai universityTianjin 300000China Department of Cardiology the 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China Department of Radiation Oncology Fujian Medical University Union HospitalFuzhou 350000China Department of Traditional Chinese Medicine the 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China Department of Geriatric Diseases the Seventh Medical Center of Chinese PLA General HospitalBeijing 100700China Health and Sport Administration Muskingum UniversityOhioanUSA Laboratory of Vaccine and Antibody Engineering Beijing Institute of BiotechnologyBeijing 100071China Department of Pulmonary and Critical Care Medicine the 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China Center of Pulmonary&Critical Care Medicine Chinese People’s Liberation Army(PLA)General HospitalBeijing 100853China

As the search for effective treatments for COVID-19 continues,the high mortality rate among critically ill patients in Intensive Care Units(ICU)presents a profound *** study explores the potential benefits of traditional Chinese medicine(TCM)as a supplementary treatment for severe COVID-19.A total of 110 critically ill COVID-19 patients at the Intensive Care Unit(ICU)of Vulcan Hill Hospital between Feb.,2020,and April,2020(Wuhan,China)participated in this observational *** patients received standard supportive care protocols,with a subset of 81 also receiving TCM as an adjunct *** characteristics during the treatment period and the clinical outcome of each patient were closely monitored and *** findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group(16 of 81 vs 24 of 29;0.3 vs 2.3 person/month).In the adjusted Cox proportional hazards models,TCM treatment was associated with improved survival odds(P<0.001).Furthermore,the analysis also revealed that TCM treatment could partially mitigate inflammatory responses,as evidenced by the reduced levels of proinflammatory cytokines,and contribute to the recovery of multiple organic functions,thereby potentially increasing the survival rate of critically ill COVID-19 patients.

关键词： COVID-19 Pneumonia Novel coronavirus Critically ill Traditional Chinese medicine Clinical outcome

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杆状病毒在昆虫宿主内的感染途径及其复制

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应用与环境生物学报 1999年第1期5卷 96-102页

作者：孙国勋丁翠蔡秀玉中国科学院动物研究所

昆虫病毒的发现始于１６世纪，但直到本世纪５０年代，伴随着电子显微镜的发明，昆虫病毒学的研究才得到飞速发展．近年来，昆虫病毒学的研究已引起人们的高度重视，主要是因为：１．杆状病毒可做为载体，以表达外源基因；２．做为杀虫... 详细信息

昆虫病毒的发现始于１６世纪，但直到本世纪５０年代，伴随着电子显微镜的发明，昆虫病毒学的研究才得到飞速发展．近年来，昆虫病毒学的研究已引起人们的高度重视，主要是因为：１．杆状病毒可做为载体，以表达外源基因；２．做为杀虫剂，可有效地控制农业病虫害的发生，...

关键词：杆状病毒复制感染途径

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初始不可切除IIIB期非小细胞肺癌免疫联合化疗后的根治性微创手术

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中国肺癌杂志 2022年第11期25卷 835-840页

作者： Hongsheng DENG Jun LIU xiuyu cai Jiawei CHEN Gaetano ROCCO Rene' Horsleben PETERSEN Alessandro BRUNELLI Calvin S.H.NG Thomas A.D'AMICO Wenhua LIANG Jianxing HE 雷杰 Department of Thoracic Surgery and Oncology the First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health Department of General Internal Medicine Sun Yat-sen University Cancer Centre State Key Laboratory of Oncology in South China Collaborative Innovation Centre for Cancer Medicine Department of Surgery Memorial Sloan Kettering Cancer Center Department of Cardiothoracic Surgery University Hospital of CopenhagenRigshospitalet Department of Thoracic Surgery St. James's University Hospital Division of Cardiothoracic Surgery Department of Surgery Prince of Wales Hospital the Chinese University of Hong Kong Division of Thoracic Surgery Department of Surgery Duke University Medical Center 空军军医大学第二附属医院胸腔外科

背景新辅助免疫治疗在局部晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）的应用仍存在争议。因此，本研究旨在报道通过免疫联合化疗将初始不可切除c IIIB期NSCLC患者转化为根治性微创手术的系列病例，评估手术效果和术后的生... 详细信息

背景新辅助免疫治疗在局部晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）的应用仍存在争议。因此，本研究旨在报道通过免疫联合化疗将初始不可切除c IIIB期NSCLC患者转化为根治性微创手术的系列病例，评估手术效果和术后的生存获益。方法回顾性分析2018年5月-2020年8月期间接受程序性细胞死亡受体1(programmed cell death-1,PD-1)抑制剂联合含铂双药化疗的51例c IIIB期NSCLC患者。收集入组患者手术相关数据和肿瘤相关数据。结果31例患者最终接受手术治疗，其中23例（74.2%）患者行肺叶切除术，1例（3.2%）患者行全肺切除术，5例（16.1%）患者行袖状肺叶切除术，2例（6.5%）患者行双肺叶切除术。中位手术时间为205 min（范围100-520），平均失血量为185 m L（范围10-1100）。15例患者出现致密粘连或纤维化。术后平均住院时间为6 d（范围3-13）。无手术相关死亡，仅5例（16.1%）患者发生术后并发症（无3级以上并发症）。10例（32.3%）患者达到主要病理缓解，22/31例（71.0%）患者出现纵隔病变降期。中位随访15.4个月，31例手术患者的中位无进展生存期/无病生存期（progression-free survival/disease-free survival, PFS/DFS）相对于未进行手术的无缓解或缓解的患者（分别为27.5个月vs 4.7个月vs 16.7个月）更长。结论初始不可切除的IIIB期NSCLC接受免疫联合化疗治疗后行根治性手术相对安全，手术相关死亡率和并发症发病率较低，与未手术患者相比DFS/PFS更长。

关键词：免疫联合化疗新辅助治疗初始不可切除非小细胞肺癌手术切除

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Efficacy,safety and pharmacokinetics of Unecritinib(TQ-B3101)for patients with ROS1 positive advanced non-small cell lung cancer:a Phase I/II Trial

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Signal Transduction and Targeted Therapy 2023年第7期8卷 3536-3546页

作者： Shun Lu Hongming Pan Lin Wu Yu Yao Jianxing He Yan Wang Xiuwen Wang Yong Fang Zhen Zhou Xicheng Wang xiuyu cai Yan Yu Zhiyong Ma Xuhong Min Zhixiong Yang Lejie Cao Huaping Yang Yongqian Shu Wu Zhuang Shundong Cang Jian Fang Kai Li Zhuang Yu Jiuwei Cui Yang Zhang Man Li Xinxuan Wen Jie Zhang Weidong Li Jianhua Shi Xingxiang Xu Diansheng Zhong Tao Wang Jiajia Zhu Department of Medical Oncology Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University200030 ShanghaiChina Department of Medical Oncology Sir Run Run Shaw HospitalZhejiang University310016 HangzhouChina Department of Thoracic Medical Oncology The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University(Hunan Cancer Hospital)410031 ChangshaChina Department of Medical Oncology The First Affiliated Hospital of Xi’an Jiaotong University710061 XianChina Department of Thoracic Surgery The First Affiliated Hospital of Guangzhou Medical University510120 GuangzhouChina Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College100021 BeijingChina Department of Oncology Qilu Hospital of Shandong University250012 JinanChina Department of Oncology The First Affiliated Hospital/School of Clinical Medicine of Guangdong Pharmaceutical University510699 GuangzhouChina Department of Medical Oncology Sun Yat-sen University Cancer Center510060 GuangzhouChina Department of Respiratory Medicine Harbin Medical University Cancer Hospital150081 HarbinChina Department of Medical Oncology Henan Tumor Hospital450003 ZhengzhouChina Department of Oncology Radiotherapy Anhui Chest Hospital230022 HefeiChina Department of Cancer Center Affiliated Hospital of Guangdong Medical University524000 ZhanjiangChina Department of Respiratory Medicine The First Affiliated Hospital of the University of Science and Technology of ChinaAnhui Provincial Hospital230031 HefeiChina Department of Respiratory and Critical Care Medicine Xiangya Hospital Central South University410008 ChangshaChina Department of Cancer Center Jiangsu Province Hospital210029 NanjingChina Department of Thoracic Oncology Fujian Cancer Hospital and Fujian Medical University Cancer Hospital350014 FuzhouChina Department of Medical Oncology Henan Province People’s Hospital450003 ZhengzhouCh

This phase I/II trial characterized the tolerability,safety,and antitumor activities of unecritinib,a novel derivative of crizotinib and a multi-tyrosine kinase inhibitor targeting ROS1,ALK,and c-MET,in advanced tumors and ROS1 inhibitor-naive advanced or metastatic non-small cell lung cancer(NSCLC)harboring ROS1 *** patients received unecritinib 100,200.

关键词： patients lung cancer

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Predilection site and risk factor of second primary cancer:A pancancer analysis based on the SEER database

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Chinese Medical Journal 2023年第12期136卷 1500-1502页

作者： Shan Xiong Hengrui Liang Peng Liang xiuyu cai caichen Li Ran Zhong Jianfu Li Bo Cheng Feng Zhu Limin Ou Zisheng Chen Yi Zhao Hongsheng Deng Zhuxing Chen Zhichao Liu Zhanhong Xie Feng Li Jianxing He Wenhua Liang Department of Thoracic Surgery and Oncology The First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouGuangdong 510120China Department of General Internal Medicine Sun Yat-sen University Cancer CentreState Key Laboratory of Oncology in South ChinaCollaborative Innovation Centre for Cancer MedicineGuangzhouGuangdong 510160China Department of General Internal Medicine Detroit Médica Center Sinai-Grace HospitalDetroit MI 48235USA Department of Oncology The First Affiliated HospitalJinan UniversityGuangzhouGuangdong 510660China Department of Respiratory Medicine The Sixth Affiliated Hospital of Guangzhou Medical UniversityQingyuan People’s HospitalQingyuanGuangdong 511518China Department of Thoracic Surgery Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China

To the Editor:Over the past few years,the number of cancer survivors has continued to increase,primarily driven by the growing and aging population and the improvements in cancer detection and *** than 16.9 million Americans with prior cancers were alive on January 1,2019,and the number of cancer survivors was estimated to reach>22.1 million by January 1,2030.[1]The lifetime risk of individual second primary cancer(SPC)has been confirmed when confronted with such a large amount of cancer survivors.[2]Definition of specific site is shown in supplementary material,http://***/CM9/B616.

关键词： lifetime continued primarily

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黄地老虎质型多角体病毒病的研究

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微生物学报 1983年第1期 20-25页

作者：丁翠蔡秀玉中国科学院动物研究所

黄地老虎质型多角体病毒的多角体有两种类型:多角形和四边形,大小分别为0.6—2.7μ和0.7—2.8μ。病毒粒子近球形,外壳上有管状物,病毒粒子大小为50—70nm。黄地老虎质型多角体的毒力较高,用1×10~8多角体/ml的浓度感染3龄幼虫,死亡率达... 详细信息

黄地老虎质型多角体病毒的多角体有两种类型:多角形和四边形,大小分别为0.6—2.7μ和0.7—2.8μ。病毒粒子近球形,外壳上有管状物,病毒粒子大小为50—70nm。黄地老虎质型多角体的毒力较高,用1×10~8多角体/ml的浓度感染3龄幼虫,死亡率达93.9%。石腊切片观察感染6和10天的黄地老虎幼虫,中肠柱状细胞和围食膜内都含有大量多角体。超薄切片观察感染2、4、7天的柱状细胞内形成病毒粒子和多角体。杯状细胞感染较柱状细胞晚。感染4天的围食膜内发现有带毛的游离病毒粒子。

关键词：黄地老虎质型多角体病毒病幼虫柱状细胞地下害虫多角体围食膜病毒粒子病毒体

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Asian,regional,and national burdens of respiratory tract cancers and associated risk factors from 1990 to 2019:A systematic analysis for the global burden of disease study 2019

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2023年第4期1卷 249-258页

作者： Ran Zhong xiuyu cai Jianfu Li Peiling Chen Runchen Wang Xinting Li Feng Li Shan Xiong caichen Li Huiting Wang Yang Xiang Shuting Zhan Ziwen Yu Haixuan Wang Chunyan Li Lixuan Lin Wenhai Fu Xin Zheng Shen Zhao Kang Zhang Jianxing He Department of Thoracic Surgery and Oncology The First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthGuangzhouGuangdong 510000China Guangzhou Medical University GuangzhouGuangdong 510000China Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong 510050China The First People Hospital of Zhaoqing ZhaoqingGuangdong 526000China Center for Biomedicine and Innovations Faculty of MedicineMacao University of Science and TechnologyMacao 999078China

Background:Respiratory cancer is the leading cause of cancer-related deaths worldwide,but its statistics vary between the East and *** study aimed to estimate the burdens of tracheal,bronchus,and lung(TBL)cancer and larynx cancer and their attributable risks from 1990 to 2019 in Asia,and at regional and national ***:This research evaluated the incidence,mortality,years lived with disability,years of life lost,and disability-adjusted life years(DALYs)for respiratory tract cancers using the Global Burden of Diseases,Injuries,and Risk Factors Study(GBD)2019 ***-standardized rates were calculated for TBL cancer from 1990 to 2019,adjusted for smoking and socio-demographic index(SDI).Deaths from TBL cancer and larynx cancer attributable to each risk factor were estimated for 33 Asian ***:The age-standardized incidence and death rates for TBL cancer in Asia declined from 2010 to 2019,while the incidence rate of larynx cancer *** was the leading specific risk factor for deaths from both TBL and larynx *** burden of TBL cancer in Asian countries was influenced by SDI and smoking,particularly among males in Central ***,DALYs,and incidences of larynx cancer in East Asia had not changed significantly over the past 30 years,but showed slight downward trends in males and both sexes combined,and an upward trend in females in recent ***:The past decade saw increases in numbers of incident cases and deaths from TBL cancer and larynx cancer in *** and smoking were the main factors influencing the disease burden of TBL cancer in Asian *** study highlights the need for tailored cancer control programs to address the burden of respiratory tract cancers in different Asian countries.

关键词： Tracheal,bronchus,and lung(TBL)cancer Larynx cancer Smoking Socio-demographic index Global burden of diseases,injuries,and risk factors study(GBD) Asia

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含氧多环芳烃促肝癌细胞侵袭转移过程中Hippo通路作用探究

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环境化学 2024年第4期43卷 1118-1126页

作者：高瑞武秀瑜蔡知洪桑楠山西医科大学法医学院晋中030600 山西大学环境与资源学院太原030006

由于氧化官能团的存在,含氧多环芳烃(oxy-PAHs)比母体多环芳烃具有更高的极性、溶解度、迁移率和生物反应活性,在环境中的分布更为广泛.许多oxy-PAHs具有更高的遗传毒性、促肿瘤活性和发育毒性,而目前关于其促肿瘤活性作用机制的研究较... 详细信息

由于氧化官能团的存在,含氧多环芳烃(oxy-PAHs)比母体多环芳烃具有更高的极性、溶解度、迁移率和生物反应活性,在环境中的分布更为广泛.许多oxy-PAHs具有更高的遗传毒性、促肿瘤活性和发育毒性,而目前关于其促肿瘤活性作用机制的研究较少.Hippo-YAP通路被发现是调节癌细胞免疫、增殖、转移等的关键因子.本研究基于肝癌细胞暴露模型,对环境含量丰富的含氧多环芳烃(9-芴酮)的促肿瘤作用及Hippo-YAP调控机制进行了探究.结果发现,较高浓度9-芴酮(9-Fluorenone)暴露可促进肝癌细胞侵袭、迁移及上皮间质转化(EMT)的发生,且Hippo-YAP通路在9-Fluorenone促肿瘤过程中有重要作用.具体而言,9-Fluorenone暴露可通过诱导Hippo上游激酶MST、LATS以及YAP蛋白的去磷酸化,未磷酸化的YAP可以直接进入细胞核内与TEAD结合,调控下游EMT的发生,进而促进侵袭转移.本研究结果为含氧多环芳烃的促肿瘤活性研究提供了实验基础,对于全面评估多环芳烃及衍生物的生态和健康风险具有重要参考作用.

关键词：含氧多环芳烃侵袭转移 Hippo EMT

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