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Penpulimab,an anti-PD-1 antibody,for heavily pretreated metastatic nasopharyngeal carcinoma:a single-arm phase II study

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3056-3062页

作者： Xiaozhong Chen Wei Wang Qingfeng Zou Xiaodong Zhu Qin Lin Yi Jiang Yan Sun Liangfang Shen Lin Wang Guorong Zou Xiaoyan Lin Shaojun Lin Minying Li Ying Wang Ruilian Xu Rui Ao Rensheng Wang Haifeng Lin Shuang Huang Tingting Xu Wenting Li Mengying Xia Yu Xia Zhongmin Wang Baiyong Li Jingao Li Chaosu Hu Department of Radiation oncology Cancer Hospital of the University of ChineseAcademy of Sciences(Zhejiang Cancer Hospital)HangzhouChina Gastroenterology and Urology Department II Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaChina Clinical research Center for Gastrointestinal Cancer in Hunan Province ChangshaChina Department of Medical oncology Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhouChina Department of Radiation oncology Guangxi Medical University Affiliated Tumor Hospital&Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University)Ministry of Education&Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency TumorGuangxi Medical UniversityNanningChina Department of Radiation oncology Cancer CenterThe First Affiliated Hospital of Xiamen UniversityXiamenChina Department of Medical oncology Cancer Hospital of Shantou University Medical CollegeShantouChina Department of Radiation oncology Peking University Cancer Hospital&InstituteBeijingChina Department of oncology Xiangya Hospital Central South UniversityChangshaChina Department of Medical oncology Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikouChina Department of oncology The Affiliated Panyu Central Hospital of Guangzhou Medical UniversityGuangzhouChina Department of Medical oncology Fujian Medical University Union HospitalFuzhouChina Department of Radiation oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhouChina Department of Radiation Therapy for Thoracic Tumors Zhongshan City People’s HospitalZhongshanChina Tumor Radiotherapy Center Chongqing University Cancer HospitalChongqing Cancer HospitalChongqing Cancer InstituteChongqingChina Department of oncology Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSo

Penpulimab is an anti-programmed cell death-1(PD-1)IgG1 antibody with no Fc gamma receptor(FcγR)binding activity,and thus theoretically reduced immune-related adverse events(irAEs)while maintaining *** single-arm,phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma(NPC)who had failed two or more lines of previous systemic *** received 200-mg penpulimab intravenously every 2 weeks(4 weeks per cycle)until disease progression or intolerable *** primary endpoint was objective response rate(ORR)per RECIST(version 1.1),as assessed by an independent radiological review *** secondary endpoints included progression-free survival(PFS)and overall survival(OS).One hundred thirty patients were enrolled and 125 were efficacy *** the data cutoff date(September 28,2022),1 patient achieved complete response and 34 patients attained partial *** ORR was 28.0%(95%CI 20.3–36.7%).The response was durable,with 66.8%still in response at 9 ***-three patients(26.4%)were still on *** median PFS and OS were 3.6 months(95%CI=1.9–7.3 months)and 22.8 months(95%CI=17.1 months to not reached),***(7.6%)patients experienced grade 3 or higher *** has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients,supporting further clinical development as third-line treatment of metastatic NPC.

关键词： metastatic nasopharyngeal supporting

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XGCN:a library for large-scale graph neural network recommendations

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Frontiers of Computer Science 2024年第3期18卷 247-249页

作者： Xiran SONG Hong HUANG Jianxun LIAN Hai JIN National Engineering research Center for Big Data Technology and System Services Computing Technology and System LabCluster and Grid Computing LabSchool of Computer Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074China Microsoft research Asia Beijing 100080China

1 Introduction Graph Neural Networks(GNNs)have gained widespread adoption in recommendation systems,and nowadays there is a pressing need to effectively manage large-scale graph data[1].When it comes to large graphs,GNNs may encounter the scalability issue stemming from their multi-layer messagepassing ***,scaling GNNs has emerged as a crucial research area in recent years,with numerous scaling strategies being proposed.

关键词： scaling gained operations

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Targeting lncRNA16 by GalNAc-siRNA conjugates facilitates chemotherapeutic sensibilization via the HBB/NDUFAF5/ROS pathway

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Science China(Life Sciences) 2024年第4期67卷 663-679页

作者： Yanfang Liu Yan Wang Bing Liu Wenzhong Liu Yuanyuan Ma Yiren Cao Shi Yan Panpan Zhang Lixin Zhou Qimin Zhan Nan Wu Key laboratory of Carcinogenesis and Translational research(Ministry of Education/Beijing) Department of Thoracic Surgery IIPeking University Cancer Hospital and InstituteBeijing 100142China Key laboratory of Carcinogenesis and Translational research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital and InstituteBeijing 100142China Key laboratory of Carcinogenesis and Translational research(Ministry of Education/Beijing) Department of Thoracic Oncology IIPeking University Cancer Hospital and InstituteBeijing 100142China Key laboratory of Carcinogenesis and Translational research(Ministry of Education) Department of PathologyPeking University Cancer Hospital and InstituteBeijing 100142China Peking University International Cancer Institute Beijing 100191China Institute of Cancer research Shenzhen Bay LaboratoryShenzhen 518132China

Chemoresistance is a significant barrier to effective cancer *** mechanisms for chemoresistance include reactive oxygen species(ROS)accumulation and expression of chemoresistance-promoting ***,we report a novel function of lncRNA16 in the inhibition of ROS generation and the progression of *** analyzing the serum levels of lncRNA16 in a cohort of 35 patients with non-small cell lung cancer(NSCLC)and paired serum samples pre-and post-treatment from 10 NSCLC patients receiving neoadjuvant platinum-based chemotherapy,performing immunohistochemistry(IHC)assays on 188 NSCLC tumor samples,using comprehensive identification of RNA-binding proteins by mass spectrometry(ChIRP-MS)assays,as well as RNA immunoprecipitation(RIP)and RNA pull-down analyses,we discovered that patients with increased serum levels of lncRNA16 exhibited a poor response to platinum-based *** expression of hemoglobin subunit beta(HBB)and NDUFAF5 significantly increases with the development of ***16 binds to HBB and promotes HBB accumulation by inhibiting ***16 can also inhibit ROS generation via the HBB/NDUFAF5 axis and function as a scaffold to facilitate the colocalization of HBB and NDUFAF5 in the ***,preclinical studies in mouse models of chemo-resistant NSCLC have suggested that lncRNA16 targeting by trivalent N-acetylgalactosamine(GalNAc)-conjugated siRNA restores chemosensitivity and results in tumor growth inhibition with no detectable toxicity in ***,lncRNA16 is a promising therapeutic target for overcoming chemoresistance,and the combination of first-line platinum-based chemotherapy with lncRNA16 intervention can substantially enhance anti-tumor efficacy.

关键词： chemoresistance lncRNARNA interference ROs chemosensitizer

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Answering reachability queries with ordered label constraints over labeled graphs

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Frontiers of Computer Science 2024年第1期18卷 105-117页

作者： Daoliang HE Pingpeng YUAN Hai JIN National Engineering research Center for Big Data Technology and System Services Computing Technology and System LabCluster and Grid Computing LabSchool of Computer Science&TechnologyHuazhong University of Science and TechnologyWuhan 430074China

Reachability query plays a vital role in many graph analysis *** researches proposed many methods to efficiently answer reachability queries between vertex *** many real graphs are labeled graph,it highly demands label-Constrained Reachability(LCR)query inwhich constraint includes a set of labels besides vertex *** researches proposed several methods for answering some LCR queries which require appearance of some labels specified in constraints in the *** that constraint may be a label set,query constraint may be ordered labels,namely OLCR(Ordered-label-Constrained Reachability)queries which retrieve paths matching a sequence of ***,no solutions are available for ***,we propose DHL,a novel bloom filter based indexing technique for answering OLCR *** can be used to check reachability between vertex *** the answers are not no,then constrained DFS is ***,we employ DHL followed by performing constrained DFS to answer OLCR *** show that DHL has a bounded false positive rate,and it's powerful in saving indexing time and *** experiments on 10 real-life graphs and 12 synthetic graphs demonstrate that DHL achieves about 4.8-22.5 times smaller index space and 4.6-114 times less index construction time than two state-of-art techniques for LCR queries,while achieving comparable query response *** results also show that our algorithm can answer OLCR queries effectively.

关键词： graph ordered-label-constrained reachability partial index bloom filter query processing

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New clinical trial design in precision medicine:discovery,development and direction

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1293-1321页

作者： Xiao-Peng Duan Bao-Dong Qin Xiao-Dong Jiao Ke Liu Zhan Wang Yuan-Sheng Zang Department of Medical oncology Changzheng HospitalNaval Medical UniversityShanghaiChina

In the era of precision medicine,it has been increasingly recognized that individuals with a certain disease are complex and different from each *** to the underestimation of the significant heterogeneity across participants in traditional"one-sizefits-all"trials,patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket,umbrella,and platform trial designs under the master protocol *** recent years,the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous *** the rapid increase in the number of basket,umbrella,and platform trials,the current clinical and research understanding of these new trial designs,as compared with traditional trial designs,remains *** majority of the research focuses on methodologies,and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial ***,we provide this comprehensive review of the discovery and development of basket,umbrella,and platform trials and their underlying logic from the perspective of precision ***,we discuss future directions on the potential development of these new clinical design in view of the"Precision Pro","Dynamic Precision",and"Intelligent Precision".This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic,which be essential to accelerate the progression of precision medicine.

关键词： clinical approval successive

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Estrogen receptor beta suppresses the androgen receptor oncogenic effects in triple-negative breast cancer

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Chinese Medical Journal 2024年第3期137卷 338-349页

作者： Feng Xu Kun Xu Lingling Fan Xintong Li Yiqiu Liu Fang Yang Chengjun Zhu Xiaoxiang Guan Department of oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of oncology Jiangsu Cancer HospitalThe Affiliated Cancer Hospital of Nanjing Medical UniversityJiangsu Institute of Cancer ResearchNanjingJiangsu 210009China The Comprehensive Cancer Center of Nanjing Drum Tower Hospital Affiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu 210008China Jiangsu Key lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Personalized Cancer MedicineNanjing Medical UniversityNanjingJiangsu 211166China

Background:Triple-negative breast cancer(TNBC)is an aggressive type of breast cancer associated with poor prognosis and limited treatment *** androgen receptor(AR)has emerged as a potential therapeutic target for luminal androgen receptor(LAR)***,multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical *** study aimed to investigate the role of AR in TNBC and its detailed ***:Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4(NECTIN4)expression in TNBC ***,in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta(ERβ)in *** immunoprecipitation sequencing(ChIP-seq),co-immunoprecipitation(co-IP),molecular docking method,and luciferase reporter assay were performed to identify key molecules that affect the function of ***:Based on the TNBC tissue array analysis,we revealed that ERβand AR were positive in 21.92%(32/146)and 24.66%(36/146)of 146 TNBC samples,respectively,and about 13.70%(20/146)of TNBC patients were ERβpositive and AR *** further demonstrated the pro-tumoral effects of AR on TNBC cells,however,the oncogenic biology was significantly suppressed when ERβtransfection in LAR TNBC cell lines but not in AR-negative ***,we identified that NECTIN4 promoter–42 bp to–28 bp was an AR response element,and that ERβinteracted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial–mesenchymal transition in tumor ***:This study suggests that ERβfunctions as a suppressor mediating the effect of AR in TNBC prognosis and cell ***,our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.

关键词： Androgen receptor Estrogen receptor beta Triple-negative breast cancer NECTIN4 Oncogenic effects Tumor progression

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Comprehensive genomic analysis of early and late-onset hepatocellular carcinoma

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Genes & Diseases 2024年第4期11卷 77-81页

作者： Jialin Yang Chao Chen Song Wang Yaru Zhang Jiaohui Pang Yajun Wang Qiuxiang Ou Hao Jiang Juying Liu Department of Radiation oncology Sichuan Cancer Hospital&InstituteSichuan Cancer CenterSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan 610041China Jinling Hospital Department of OncologyNanjing Medical UniversityNanjingJiangsu 210002China Geneseeq research Institute Nanjing Geneseeq Technology Inc.NanjingJiangsu 210000China Department of oncology Haian Hospital of Traditional Chinese MedicineHaianJiangsu 226600China Interventional Therapy Department Jiangsu Cancer Hospital&Jiangsu Institute of Cancer Research&The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjingJiangsu 210009China

Hepatocellular carcinoma(HCC)is the major histologic type of primary liver cancer,accounting for approximately 75%of liver cancer cases.'Despite many advancements in its treatment,the prognosis and drug response of HCC patients are ***,there is an unmet clinical need to explore genomic aberrations underlying early-and lateonset HcC,which might facilitate drug discovery and provide personalized biomarker-driven treatment options for these patients.

关键词： patients prognosis cancer

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Pan-cancer immunogenic death analysis identifies key roles of CXCR3 and CCL18 in hepatocellular carcinoma

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Genes & Diseases 2024年第2期11卷 568-570页

作者： Jia Guo Xin Sun Guowei Pan Ce Li Xin He Xiaofang Che Zan Teng Xiujuan Qu Yunpeng Liu Bowen Yang Department of Medical oncology Provincial Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning ProvinceLiaoning Provincial Clinical Research Center for CancerClinical Cancer Research Center of ShenyangThe First Hospital of China Medical UniversityShenyangLiaoning 110001China research Center for Universal Health School of Public HealthChina Medical UniversityShenyangLiaoning 110122China

Immunogenic death is a form of programmed cell death that is common in the development and progression of ***,its impact on tumor progression differs depending on the location of the ***,it also plays an important role in antitumor immunity because the process of immunogenic death can release substances that activate immunity.1 Therefore,in this study,the key mechanism of mediating immunogenic death in hepatocellular carcinoma(HCC)was found from the excavation of the immunogenic death characteristics of pan-cancer and the in-depth investigation of its effects on different tumor types(Fig.1A).

关键词： death CXCR3 immunity

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Association of previously irradiated stable brain metastases with outcomes of atezolizumab-treated non-small cell lung cancer: A pooled analysis of individual patient data from three randomized trials

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Cancer Communications 2024年第2期44卷 278-281页

作者： Tiantian Guo Yue Zhou Fei Liang Zezhou Wang Vincent Bourbonne Lukas Käsmann Nora Sundahl Abraham Jing-Ching Wu Jianjiao Ni Zhengfei Zhu Department of Radiation oncology Fudan University Shanghai Cancer CenterShanghaiP.R.China Department of oncology Shanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Clinical research Center for Radiation oncology ShanghaiP.R.China Shanghai Key laboratory of Radiation oncology ShanghaiP.R.China Department of Biostatistics Zhongshan HospitalFudan UniversityShanghaiP.R.China Department of Cancer Prevention Fudan University Shanghai Cancer CenterShanghaiP.R.China Radiation oncology Department University HospitalBrestFrance Department of Radiation oncology University HospitalLMU MunichMunichGermany Department of Radiation oncology AZ GroeningeKortrijkBelgium Department of Radiation oncology Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUSA Institute of Thoracic oncology Fudan UniversityShanghaiP.R.China

Dear Editor:Brain metastasis(BM)has long been recognized as a prognostic factor associated with poor prognosis for non-small cell lung cancer(NSCLC)in the era of con-ventional chemotherapy and targeted therapy[1].In the era of immunotherapy,controversial findings have been reported regarding the prognostic significance of BM in patients with NSCLC treated with programmed death-1/programmed death-ligand 1(PD-1/PD-L1)inhibitors.

关键词： chemotherapy NSCLC metastasis death

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Emerging clinical relevance of microbiome in cancer:promising biomarkers and therapeutic targets

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Protein & Cell 2024年第4期15卷 239-260页

作者： Jia-Hao Dai Xi-Rong Tan Han Qiao Na Liu State Key laboratory of oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510050China

The profound influence of microbiota in cancer initiation and progression has been under the spotlight for years,leading to numerous researches on cancer microbiome entering clinical *** promising biomarkers and therapeutic targets,the critical involvement of microbiota in cancer clinical practice has been increasingly ***,recent progress in this field is *** describe the potential of tumor-associated microbiota as effective diagnostic and prognostic biomarkers,*** addition,we highlight the relationship between microbiota and the therapeutic efficacy,toxicity,or side effects of commonly utilized treatments for cancer,including chemotherapy,radiotherapy,and *** that microbial factors influence the cancer treatment outcome,we further summarize some dominating microbial interventions and discuss the hidden risks of these *** review aims to provide an overview of the applications and advancements of microbes in cancer clinical relevance.

关键词： microbiome cancer diagnosis prognosis therapy

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