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Frontiers of Medicine 2024年第4期18卷 735-743页

作者： Rui Fu Yuanyuan Xiong Miao Cai Fang Li Rongrong Chen Yilong Wu Wenzhao Zhong School of Medicine South China University of TechnologyGuangzhou510006China 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 UniversityGuangzhou510080China Geneplus-Beijing Beijing102206China

Gene fusions and MET alterations are rare and difficult to detect in plasma *** clinical detection efficacy of molecular residual disease(MRD)based on circulating tumor DNA(ctDNA)in patients with non-small cell lung cancer(NSCLC)with these mutations remains *** prospective,non-intervention study recruited 49 patients with operable NSCLC with actionable gene fusions(ALK,ROS1,RET,and FGFR1),MET exon 14 skipping or de novo MET *** analyzed 43 tumor tissues and 111 serial perioperative plasma samples using 1021-and 338-gene panels,*** MRD correlated with a significantly higher recurrence rate(P<0.001),yielding positive predictive values of 100%and 90.9%,and negative predictive values of 82.4%and 86.4%at landmark and longitudinal time points,*** with detectable MRD showed reduced disease-free survival(DFS)compared to those with undetectable MRD(P<0.001).Patients who harbored tissue-derived fusion/MET alterations in their MRD had reduced DFS compared to those who did not(P=0.05).To our knowledge,this is the first comprehensive study on ctDNA-MRD clinical detection efficacy in operable NSCLC patients with gene fusions and MET *** with detectable tissue-derived fusion/MET alterations in postoperative MRD had worse clinical outcomes.

关键词： ctDNA molecular residual disease operable NSCLC gene fusion MET exon skipping MET amplification

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

Mex-3 RNA binding family member A(MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2091-2103页

作者： Ri-Xin Chen Shui-Dan Xu Min-Hua Deng Shi-Hui Hao Jie-Wei Chen Xiao-Dan Ma Wei-Tao Zhuang Jing-Hua Cao Yong-Rui Lv Jin-Long Lin Si-Yu Li Gui-Bin Qiao Dan Xie Feng-Wei Wang Department of Thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China Medical Research institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China Department of Pathology Sun Yat-sen University Cancer CenterGuangzhou 510060China

RNA-binding proteins(RBPs)-RNA networks have contributed to cancer *** RNAs(circRNAs)are considered as protein recruiters;nevertheless,the patterns of circRNA-protein interactions in colorectal cancer(CRC)are still *** bodies(PBs)formed through liquid-liquid phase separation(LLPS)are membrane-less organelles(MLOs)consisting of RBPs and *** evidence suggests a connection between PBs dynamics and cancer *** the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs,there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in ***,we identify that MEX-3 RNA binding family member A(MEX3A),frequently upregulated in CRC tissues,predicts poorer patient *** MEX3A accelerates malignance and inhibits autophagy of CRC ***,MEX3A undergoes intrinsically disordered regions(IDRs)-dependent LLPS in the ***,circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs *** MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A(PDE5A)mRNA degradation,consequently leading to the aggressive properties of CRC ***,CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall *** findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation,which provides prognostic markers and/or therapeutic targets for CRC.

关键词： colorectal inhibiting MPP

IMpower210:A phase Ⅲ study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer

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Chinese Journal of cancer Research 2024年第2期36卷 103-113页

作者： Yi-Long Wu Shun Lu Gongyan Chen Jianxing He Jifeng Feng Yiping Zhang Liyan Jiang Hongming Pan Jianhua Chang Jian Fang Amy Cai Lilian Bu Jane Shi Jinjing Xia guangdong lung cancer institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People's Hospital&Guangdong Academy of Medical SciencesSouthern Medical UniversityGuangzhou 510080China Shanghai lung cancer Center Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200025China Department of Respiration Harbin Cancer HospitalHarbin Medical UniversityHarbin 150081China Department of Thoracic Oncology and Surgery the First Affliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Department of Medical Oncology Jiangsu Cancer HospitalNanjing 210009China Department of Medical Oncology Zhejiang Cancer HospitalHangzhou 330022China Department of Pulmonary Medicine Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China Department of Medical Oncology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Department of Medical Oncology Shenzhen HospitalCancer Hospital of Chinese Academy of Medical SciencesShenzhen 518116China Department of Thoracic Oncology Beijing Cancer HospitalBeijing 100142China Product Development Shanghai Roche Pharmaceutical LtdShanghai 201203China

Objective: IMpower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab *** as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian ***: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International cancer Control/American Joint Committee on cancer staging system(7th edition);Eastern Cooperative Oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). The primary study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epidermal growth factor receptor expression(ITT EGFR-WT) and in the overall ITT ***: Median OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel ***: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.

关键词： Atezolizumab East Asia non-small cell lung cancer programmed death-ligand 1 inhibitors monoclonal antibody

Impact of baseline steroids on the efficacy of neoadjuvant immunochemotherapy in locally advanced esophageal squamous cell carcinoma

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World Journal of Gastrointestinal Oncology 2024年第9期16卷 3887-3897页

作者： Yuan-Heng Huang Guo-Zhen Yang Hui-Guo Chen Xiao-Jun Li Yong-Hui Wu Kai Zhang Jian-Nan Xu Jian Zhang Department of Cardiothoracic Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630Guangdong ProvinceChina State Key Laboratory of Oncology in South China Collaborative Innovation Center of Cancer MedicineGuangzhou 510060Guangdong ProvinceChina guangdong Esophageal cancer institute Guangzhou 510060Guangdong ProvinceChina

BACKGROUND Immunochemotherapy involving the combination of programmed cell death 1/programmed cell death ligand 1 inhibitors with chemotherapy has advanced the treatment of locally advanced esophageal squamous cell carcinoma(ESCC).The use of corticosteroids as pretreatment might reduce immunotherapy *** To investigate the impact of baseline corticosteroid use on neoadjuvant immunochemotherapy(nIC)outcomes in locally advanced ESCC *** Patients with locally advanced ESCC who received nIC at Sun Yat-sen University cancer Center and the Third Affiliated Hospital of Sun Yat-sen University were *** were divided into dexamethasone and antihistamine groups on the basis of the administered *** efficacy and safety were evaluated,as well as its impact on short-term efficacy[complete pathological response(pCR),major pathological response(MPR)]and long-term efficacy[overall survival(OS),progression-free survival(PFS)]of *** From September 2019 to September 2023,142 patients were *** severe treatment-related adverse events or deaths were *** occurrence was greater in the antihistamine group(P=0.014).Short-term efficacy was not significantly different:The pCR rates were 29.9%and 40.0%,and the MPR rates were 57.9%and 65.7%in the dexamethasone and antihistamine groups,*** long-term efficacy was not significantly different:The 2 years OS rates were 95.2%and 93.5%,and the 2 years PFS rates were 90.3%and 87.8%.Subgroup analysis revealed no difference in OS between the 20 mg dexamethasone group and the<20 mg dexamethasone group,but PFS was significantly greater in the 20 mg dexamethasone group(93.9%vs 56.4%,P=0.001).CONCLUSION Dexamethasone or antihistamines can be used before nIC in locally advanced ESCC without affecting short-or long-term *** 20 mg dexamethasone before nIC may improve PFS in ESCC.

关键词： Esophageal squamous cell carcinoma Neoadjuvant immunochemotherapy Dexamethasone Antihistamines Treatment efficacy

RIOK1 synergizes with TRIP13 by regulating the E2F-Rb signaling pathway to promote the proliferation of esophageal cancer cells

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Genes & Diseases 2024年第3期11卷 55-58页

作者： Chengyu Li Deyuan Pan Wan Lin Danxia Deng Yingxin Zhou Hui Zhao Feng Pan Liyan Xu Enmin Li Lin Long The Key Laboratory of Molecular Biology for High cancer Incidence Coastal Chaoshan Area Department of Biochemistry and Molecular BiologyShantou University Medical CollegeShantouGuangdong 515041China guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology Institute of Oncologic PathologyShantou University Medical CollegeShantouGuangdong 515041China institute of Basic Medical Science Cancer Research CenterShantou University Medical CollegeShantouGuangdong 515041China Clinical Research Center Shantou Central HospitalShantouGuangdong 515041China

Esophageal cancer is one of the leading causes of cancer death in the world,with approximately half of the new cases occurring in China every year.^(1)Esophageal squamous cell carcinoma(ESCC)is the main subtype,accounting for more than 90%,and the five-year survival rate is less than 10%.Using large-scale genome analysis,many driver mutations and key pathways associated with ESCC have been ***,these genomic signatures have not improved the clinical management of EscC patients,or established effective targeted therapy.^(2)Esophageal cancer still lacks representative molecular markers.

关键词： cancer esophageal Esophageal

Lipid metabolism analysis in esophageal cancer and associated drug discovery

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Journal of Pharmaceutical Analysis 2024年第1期14卷 1-15页

作者： Ruidi Jiao Wei Jiang Kunpeng Xu Qian Luo Luhua Wang Chao Zhao Bionic Sensing and Intelligence Center Institute of Biomedical and Health EngineeringShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong518000China Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdong518116China School of Medicine Southern University of Science and TechnologyShenzhenGuangdong518000China University of Chinese Academy of Sciences Beijing100049China Shenzhen Key Laboratory of Precision Diagnosis and Treatment of Depression Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong518000China

Esophageal cancer is an upper gastrointestinal malignancy with a bleak *** is still being explored in depth due to its complex molecular mechanisms of occurrence and *** play a crucial role in cells by participating in energy supply,biofilm formation,and signal transduction processes,and lipid metabolic reprogramming also constitutes a significant characteristic of malignant *** and more studies have found esophageal cancer has obvious lipid metabolism abnormalities throughout its beginning,progress,and treatment *** inhibition of tumor growth and the enhancement of antitumor therapy efficacy can be achieved through the regulation of lipid ***,we reviewed and analyzed the research results and latest findings for lipid metabolism and associated analysis techniques in esophageal cancer,and comprehensively proved the value of lipid metabolic reprogramming in the evolution and treatment resistance of esophageal cancer,as well as its significance in exploring potential therapeutic targets and biomarkers.

关键词： Lipid metabolism Esophageal cancer Progression Treatment resistance New therapeutic targets

BioTreasury:a community-based repository enabling indexing and rating of bioinformatics tools

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Science China(Life Sciences) 2024年第2期67卷 221-229页

作者： Qi Zhao Xin Zhou Jingxing Wu Jieyi Cai Xiaoqiong Bao Lin Tang Chaoye Wang Chunlei Liu Yukai Wang Yuyan Teng Mohan Zheng Weiping Mu Zhixiang Zuo Yubin Xie Xiaotong Luo Jian Ren School of Life Sciences State Key Laboratory of Oncology in South ChinaCancer CenterGuangdong Provincial Clinical Research Center for CancerSun Yat-sen UniversityGuangzhou 510060China institute of Precision Medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China guangdong institute of Gastroenterology Department of General SurgeryGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseasesThe Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510275China

The exponential growth of bioinformatics tools in recent years has posed challenges for scientists in selecting the most suitable one for their data analysis ***,to aid scientists in making informed choices,a community-based platform that indexes and rates bioinformatics tools is urgently *** this study,we introduce Bio Treasury(http://***),an integrated communitybased repository that provides an interactive platform for users and developers to share their experiences in various bioinformatics *** Treasury offers a comprehensive collection of well-indexed bioinformatics software,tools,and databases,totaling over 10,000 *** the past two years,we have continuously improved and maintained Bio Treasury,adding several exciting features,including creating structured homepages for every tool and user,a hierarchical category of bioinformatics tools and classifying tools using large language model(LLM).Bio Treasury streamlines the tool submission process with intelligent ***,Bio Treasury provides a wide range of social features,for example,enabling users to participate in interactive discussions,rate tools,build and share tool collections for the *** believe Bio Treasury can be a valuable resource and knowledge-sharing platform for the biomedical *** empowers researchers to effectively discover and evaluate bioinformatics tools,fostering collaboration and advancing bioinformatics research.

关键词： bioinformatics tools index tool database rating system large language model tool collections shari

Genetically modified non-human primate models for research on neurodegenerative diseases

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Zoological Research 2024年第2期45卷 263-274页

作者： Ming-Tian Pan Han Zhang Xiao-Jiang Li Xiang-Yu Guo guangdong Key Laboratory of Non-human Primate Research Guangdong-Hongkong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong 510632China

Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical *** the population ages,NDs are imposing a huge burden on public health systems and affected *** models are important tools for preclinical investigations to understand disease pathogenesis and test potential *** numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation *** World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to *** is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience ***,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel *** review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.

关键词： Neurodegeneration Non-human primate Macaque monkey Animal model Gene modification

A review of the neurotransmitter system associated with cognitive function of the cerebellum in Parkinson's disease

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Neural Regeneration Research 2024年第2期19卷 324-330页

作者： Xi Chen Yuhu Zhang Department of Neurology Guangdong Neuroscience InstituteGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina Shantou University Medical College ShantouGuangdong ProvinceChina

The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially *** dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and *** contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial *** from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s *** research has reported evidence that the cerebellum receives both dopaminergic and cholinergic ***,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully ***,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains ***,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional *** findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.

关键词： anterior brain system cerebellum cholinergic cognitive impairment dopaminergic dual syndrome hypothesis neuroimage neurotransmitter Parkinson’s disease posterior brain system therapeutic targets