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Neoadjuvant nivolumab with or without platinum-doublet chemotherapy based on PD-L1 expression in resectable NSCLC(CTONG1804):a multicenter open-label phase II study

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signal Transduction and Targeted Therapy 2024年第1期9卷 249-258页

作者： si-yang liu Song Dong Xue-Ning yang Ri-Qiang Liao Ben-Yuan Jiang Qun Wang Xiao-Song Ben Gui-Bin Qiao Jun-Tao Lin Hong-Hong Yan Li-Xu Yan Qiang Nie Hai-Yan Tu Bin-Chao Wang Jin-Ji yang Qing Zhou Hong-Rui Li Ke liu Wendy Wu si-yang maggie liu Wen-Zhao Zhong Yi-Long Wu Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Thoracic Surgery Zhongshan HospitalFudan UniversityShanghaiChina Department of Thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Pathology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis FuzhouChina Berry Oncology Corporation FuzhouChina Chinese Thoracic Oncology Group(CTONG) GuangzhouChina Department of Hematology The First Affiliated HospitalJinan UniversityGuangzhouChina

This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive(N)and nivolumab–chemotherapy(N/C)combinations based on PD-L1 *** patients exhibited resectable clinical stage IIA–IIIB(AJCC 8th edition)NSCLC without EGFR/ALK *** received either mono-nivolumab(N)or nivolumab+nabpaclitaxel+carboplatin(N/C)for three cycles based on PD-L1 *** primary endpoint was the major pathological response(MPR).Key secondary endpoints included the pathologic complete response(pCR),objective response rate(ORR),and event-free survival(EFS).Baseline PD-L1 expression and perioperative circulating tumor DNA(ctDNA)status were correlated with pCR and ***-two patients were enrolled,with 46 undergoing *** MPR was 50.0%(26/52),with 25.0%(13/52)achieving pCR,and 16.7%and 66.7%for patients with PD-L1≥50%in N and N/C groups,***(25.0%)patients experienced grade 3 or higher immune-related adverse events during neoadjuvant *** with post-neoadjuvant ctDNA negativity was more likely to have pCR(39.1%)compared with those remained positive(6.7%,odds ratio=6.14,95%CI 0.84-Inf,p=0.077).With a median follow-up of 25.1 months,the 18-month EFS rate was 64.8%(95%CI 51.9–81.0%).For patients with ctDNA–***+,the 18m-EFS rate was 93.8%vs 47.3%(HR,0.15;95%CI 0.04,0.94;p=0.005).Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression≥50%.ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits,which requires further confirmation in a prospective clinical trial(NCT04015778).

关键词： chemotherapy NSCLC treatment

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PD-L1表达指导的信迪利单抗与帕博利珠单抗联合或不联合含铂双药化疗治疗未经治晚期非小细胞肺癌患者:一项2期随机对照试验(CTONG1901)

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Science Bulletin 2024年第4期69卷 535-543页

作者：刘思阳黄婕邓嘉怡徐崇锐严红虹杨明意黎扬斯柯娥娥郑明英王震林嘉欣甘彬张绪超陈华军汪斌超涂海燕杨衿记钟文昭李扬秋周清吴一龙 Department of Hematology The First Affiliated HospitalJinan UniversityGuangzhou 510632China Guangdong Lung Cancer Institute Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China Chinese Thoracic Oncology Group(CTONG) Guangzhou 510055China Institute of Hematology School of MedicineKey Laboratory for Regenerative Medicine of Ministry of EducationJinan UniversityGuangzhou 510632China

No direct comparison has been performed between different programmed cell death-1(PD-1)inhibitors for first-line treatment in patients with advanced non-small cell lung cancer(NSCLC).The feasibility of using PD-L1-expression-guided immunotherapy remains *** this open-label,phase 2 study(NCT04252365),patients with advanced NSCLC without EGFR or ALK alterations were randomized(1:1)to receive sintilimab or pembrolizumab monotherapy(PD-L1 expression≥50%),or sintilimab or pembrolizumab plus platinum-based chemotherapy(PD-L1 expressionsize was calculated by optimal two-stage *** primary endpoint was the objective response rate(ORR).The study included 71 patients(sintilimab arms,n=35;pembrolizumab arms,n=36)and met its primary endpoint,with a confirmed ORR of 51.4%(18/35)in the sintilimab *** confirmed ORR(95%confidence interval)was 46.2%(19.2%,74.9%)and 42.9%(17.7%,71.1%)for patients treated with sintilimab and pembrolizumab monotherapy;and 54.5%(32.2%,75.6%)and 45.4%(24.4%,67.8%)for those treated with sintilimab-and pembrolizumab-based combination *** median progression-free survival was6.9 versus 8.1 months for all sintilimab-treated versus all pembrolizumab-treated patients,respectively,in which it was 7.6 versus 11.0 months in monotherapy and 7.4 versus 7.1 months in combination *** median overall survival was 14.9 versus 21.3 months for all sintilimab-treated versus all pembrolizumab-treated patients,respectively,in which it was 14.9 versus 22.6 months in monotherapy and 14.7 versus 17.3 months in combination ***-related adverse events were consistent with safety outcomes of monotherapy and combination therapy in previous phase III ***,the incidence of rash was higher with sintilimab than pembrolizumab *** is the first prospective phase 2 study to directly compare two anti-PD-1 antibodies as first-line treatment in advanced *** was efficacious and well-tolera

关键词： PD-1 inhibitor Non-small cell lung cancer Pembrolizumab sintilimab PD-L1 expression

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Toward a cure for lung cancer:important advances in operable non-small cell lung cancer

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Science Bulletin 2022年第14期67卷 1402-1405页

作者： si-yang maggie liu Guang-Ling Jie Yi-Long Wu Department of Hematology First Affiliated HospitalJinan UniversityGuangzhou 510632China Guangdong Lung Cancer Institute Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China School of Medicine South China University of TechnologyGuangzhou 510006China

Over the past 20 years,the discovery of genes driving non-small cell lung cancer(NSCLC)has intensified;today,NSCLC is divided into driven and non-driven *** therapy and programmed cell death-1(PD-1)inhibitors have bec... 详细信息

关键词：非小细胞肺癌 NSCLC lung

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Interacting with α7 nAChR is a new mechanism for AChE to enhance the inflammatory response in macrophages

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Acta Pharmaceutica sinica B 2020年第10期10卷 1926-1942,2020页

作者： Etta Y.L.liu Yingjie Xia Xiangpeng Kong maggie S.S.Guo Anna X.D.Yu Brody Z.Y.Zheng Shinghung Mak Miranda L.Xu Karl W.K.Tsim Key Laboratory of Food Quality and Safety of Guangdong Province College of Food ScienceSouth China Agricultural UniversityGuangzhou 510642China Shenzhen Key Laboratory of Edible and Medicinal Bioresources the Hong Kong University of Science and TechnologyShenzhen 518057China Division of Life Science Center for Chinese Medicinethe Hong Kong University of Science and TechnologyHong kongChina

Acetylcholine(ACh)regulates inflammation viaα7 nicotinic acetylcholine receptor(α7 nAChR).Acetylcholinesterase(AChE),an enzyme hydrolyzing ACh,is expressed in immune cells suggesting non-classical function in inflammatory ***,the expression of PRiMA-linked G4 AChE was identified on the surface of *** lipopolysaccharide-induced inflammatory processes,AChE was upregulated by the binding of NF-κB onto the ACHE ***,the overexpression of G4 AChE inhibited ACh-suppressed cytokine release and cell migration,which was in contrast to that of applied AChE ***,a DNA construct without enzymatic activity,was adopted to identify the protein role of AChE in immune *** of G4 AChEmt induced cell migration and inhibited ACh-suppressed cell *** co-localization ofα7 nAChR and AChE was found in macrophases,suggesting the potential interaction ofα7 nAChR and ***,immunoprecipitation showed a close association ofα7 nAChR and AChE protein in cell ***,the novel function of AChE in macrophage by interacting withα7 nAChR was *** with hydrolysis of ACh,AChE plays a direct role in the regulation of inflammatory *** such,AChE could serve as a novel target to treat age-related diseases by antiinflammatory responses.

关键词： Macrophage AChE Cholinergic anti-inflammatory pathway α7 nAChR

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Laminin-coated multifilament entubulation, combined with Schwann cells and glial cell line-derived neurotrophic factor, promotes unidirectional axonal regeneration in a rat model of thoracic spinal cord hemisection

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Neural Regeneration Research 2021年第1期16卷 186-191页

作者： Ling-Xiao Deng Nai-Kui liu Ryan Ning Wen Shuang-Ni yang Xuejun Wen Xiao-Ming Xu Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteIndiana University School of MedicineIndianapolisINUSA Department of Neurological Surgery Indiana University School of MedicineIndianapolisINUSA maggie L.Walker Governor’s School RichmondVAUSA Institute for Engineering and Medicine Department of Chemical and Life Science EngineeringVirginia Commonwealth UniversityRichmondVAUSA

Biomaterial bridging provides physical substrates to guide axonal growth across the *** achieve efficient directional guidance,combinatory strategies using permissive matrix,cells and trophic factors are *** the present study,we evaluated permissive effect of poly(acrylonitrile-co-vinyl chloride)guidance channels filled by different densities of laminin-precoated unidirectional polypropylene filaments combined with Schwann cells,and glial cell line-derived neurotrophic factor for axonal regeneration through a T10 hemisected spinal cord gap in adult *** found that channels with filaments significantly reduced the lesion cavity,astrocytic gliosis,and inflammatory responses at the graft-host *** laminin coated low density filament provided the most favorable directional guidance for axonal regeneration which was enhanced by co-grafting of Schwann cells and glial cell line-derived neurotrophic *** results demonstrate that the combinatorial strategy of filament-filled guiding scaffold,adhesive molecular laminin,Schwann cells,and glial cell line-derived neurotrophic factor,provides optimal topographical cues in stimulating directional axonal regeneration following spinal cord *** study was approved by Indiana University Institutional Animal Care and Use Committees(IACUC#:11011)on October 29,2015.

关键词： axonal regeneration extracellular molecule filament density hemisection laminin neurotrophic factor Schwann cell spinal cord injury thoracic transplantation

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Cancer-associated histone mutation H2BG53D disrupts DNA–histone octamer interaction and promotes oncogenic phenotypes

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signal Transduction and Targeted Therapy 2020年第1期5卷 2230-2233页

作者： Yi Ching Esther Wan Tsz Chui Sophia Leung Dongbo Ding Xulun Sun Jiaxian liu Lina Zhu Tze Zhen Evangeline Kang Du yang Yuchen Zhang Jitian Zhang Chengmin Qian Michael Shing Yan Huen Qing Li maggie Zi Ying Chow Zongli Zheng Junhong Han Ajay Goel Xin Wang Toyotaka Ishibashi Kui Ming Chan Department of Biomedical Sciences City University of Hong KongHong KongChina Key Laboratory of Biochip Technology Biotech and Health CentreShenzhen Research Institute of City University of Hong KongShenzhenChina Division of Life Science Hong Kong University of Science and TechnologyHong KongChina State Key Laboratory of Protein and Plant Gene Research School of Life Sciences and Peking-Tsinghua Center for Life SciencesPeking UniversityPekingChina School of Biomedical Sciences The University of Hong KongHong KongChina Ming Wai Lau Centre for Reparative Medicine Karolinska InstitutetHong KongChina State Key Laboratory of Biotherapy and Cancer Center West China HospitalWest China Medical SchoolSichuan UniversitySichuanChina Department of Molecular Diagnostics and Experimental Therapeutics Beckman Research Institute at City of Hope Comprehensive Cancer CenterDuarteCAUSA

Dear Editor,Recent studies from us and others have deciphered the clinical relevance of a variety of oncohistones1 in different *** H3K27M and H3K36M mutant histones exert dominant-negative effects on methylation levels of histone H3K27 and H3K36 on wildtype histone protein in pediatric brain cancers2–4 and chondroblastoma,5,6 *** contrast to H3K27M and H3K36M that act in trans to cause global reduction of methylation at the respective residues,the H3G34 mutations,including H3G34V/R and H3G34W/L found in pediatric high-grade glioma and giant cell tumor of the bone,affect the H3K36 methylation in cis and alter the H3K36 methylation on the nucleosome containing the H3G34 mutation(s).

关键词： Cancer clinical pediatric

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走向治愈:肺癌的长生存之道2023

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循证医学 2023年第4期23卷 193-196页

作者：刘思阳吴一龙广东省肺癌研究所南方医科大学附属广东省人民医院(广东省医学科学院)广州510080 暨南大学附属第一医院血液科广州510630

歌词曰:我们的未来不是梦,这句话恰如肺癌患者的现状。肺癌作为全球致死率排名第一的恶性肿瘤^([1]),严重危害着人类的健康,是全球肿瘤医生希望攻克的难题。在中国,肺癌代表着更为沉重的疾病负担。2022年预估中国肺癌新发病例约为870 98... 详细信息

歌词曰:我们的未来不是梦,这句话恰如肺癌患者的现状。肺癌作为全球致死率排名第一的恶性肿瘤^([1]),严重危害着人类的健康,是全球肿瘤医生希望攻克的难题。在中国,肺癌代表着更为沉重的疾病负担。2022年预估中国肺癌新发病例约为870 982例,死亡病例约为766 898例^([2])。幸运的是,近10年间肺癌的治疗格局发生了翻天覆地的变化,近两年先后公布的多项Ⅲ期临床研究的长期随访结果,让越来越多的非小细胞肺癌(non-small-cell lung cancer,NSCLC)患者看到了长生存乃至治愈的曙光。

关键词：肺癌靶向治疗免疫治疗

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郑志刚谈疫情当下的可持续发展

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中国服饰 2021年第2期 10022-10023页

作者： Rosemary Feitelberg maggie liu(编译) 无不详 Courtesy

任何人都能感受到,世界正处于动荡之中。但在郑志刚看来,动荡之下满是机遇,尤其在可持续方向上。作为香港三大开发商之一新世界发展(NWD)的CEO和执行副主席、致力于丰富日常消费生活的创新企业集合体K11集团的创建者.

关键词：日常消费可持续发展郑志 CEO 开发商集合体新世界创建者

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2022年非小细胞肺癌重要临床研究纵览与解读

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循证医学 2023年第5期23卷 311-320页

作者：刘思阳甘彬吴一龙广东省肺癌研究所南方医科大学附属广东省人民医院(广东省医学科学院)广州510080 暨南大学附属第一医院血液科广州510630

非小细胞肺癌(non-small cell lung cancer,NSCLC)研究在肿瘤学个体化治疗中一直处于领先地位,无论是围术期、局部晚期或晚期NSCLC都陆续有重磅的研究成果报导。值得强调的是,保持创新性对进一步改善肺癌个性化治疗具有非常重要的意义,... 详细信息

非小细胞肺癌(non-small cell lung cancer,NSCLC)研究在肿瘤学个体化治疗中一直处于领先地位,无论是围术期、局部晚期或晚期NSCLC都陆续有重磅的研究成果报导。值得强调的是,保持创新性对进一步改善肺癌个性化治疗具有非常重要的意义,如何做好临床试验和转化研究、甚至将二者更好的结合是目前亟待思考的问题。本文简要综述了2022年发表的重磅转化研究成果、改变临床实践的临床试验结果以及具有重要影响的肺癌研究进展。

关键词：非小细胞肺癌转化研究个体化治疗免疫治疗靶向治疗新辅助治疗

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Nrf2 protects against oxidative stress induced by siO2 nanoparticles

Nrf2 protects against oxidative stress induced by SiO2 nanop...

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2017环境与公共健康学术会议暨中国环境科学学会环境医学与健康分会、中国毒理学会生化与分子毒理专业委员会2017年年会

作者： Wei liu Tao Hu Li Zhou maggie Pui Man Hoi Desheng Wu Xinfeng Huang Xiaohu Ren Jianjun liu Key Laboratory of Modern Toxicology of Shenzhen Shenzhen Center for Disease Control and Prevention State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of Macau

Objective:The aim of this study was to investigate the role of nuclear factor erythroid2-related factor 2(Nrf2) in response to oxidative stress exposure to silica nanoparticles(siO NPs).Methods:The toxicity of siO NPs-induced oxidative stress,and the activation of Nrf2/ARE signaling pathway were investigated in A549 cells in vitro and mouse model in ***:Exposure to siO NPs induced significant cytotoxicity in A549 and A549-shNrf2 cells(A549 cells expressing Nrf2 shRNA),and induced activation of the Nrf2/ARE signaling *** Nrf2(-/-)mice,exposure to siONPs increased the levels of ROS and 8-hydroxy-2’-deoxyguanosine(8-OHdG),and decreased total antioxidant capacity(T-AOC).The disruption of Nrf2/ARE signaling pathway in Nrf2(-/-) mice led to reduced expression of heme oxygenase-1(HO-1) and up-regulation of ***:The Nrf2/ARE pathway might be involved in defending mild to moderate siO NPs-induced oxidative stress,and Nrf2 could protect against oxidative stress induced by siONPs.

关键词： Nrf2/ARE signaling pathway silica nanoparticles Nrf2(-/-) mice oxidative stress HO-1

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