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Current Medical Science 2024年第2期44卷 261-272页

作者： Meng-jie WANG Yu XIA Qing-lei GAO Department of Obstetrics and Gynecology National Clinical Research Center for Obstetrics and GynecologyTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China key laboratory of cancer invasion and metastasis(Ministry of Education) Hubei Key Laboratory of Tumor Invasion and MetastasisTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

DNA damage occurs across tumorigenesis and tumor *** intrinsic DNA damage can not only increase the risk of mutations responsible for tumor generation but also initiate a cellular stress response to orchestrate the tumor immune microenvironment(TIME)and dominate tumor *** evidence documents that multiple signaling pathways,including cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)and ataxia telangiectasia-mutated protein/ataxia telangiectasia and Rad3-related protein(ATM/ATR),are activated downstream of DNA damage and they are associated with the secretion of diverse *** cytokines possess multifaced functions in the anti-tumor immune ***,it is necessary to deeply interpret the complex TIME reshaped by damaged DNA and tumor-derived cytokines,critical for the development of effective tumor *** manuscript comprehensively reviews the relationship between the DNA damage response and related cytokines in tumors and depicts the dual immunoregulatory roles of these *** also summarize clinical trials targeting signaling pathways and cytokines associated with DNA damage and provide future perspectives on emerging technologies.

关键词： DNA damage tumor immune microenvironment inflammatory cytokines cancer therapy

Multiomics analysis reveals metabolic subtypes and identifies diacylglycerol kinase α (DGKA) as a potential therapeutic target for intrahepatic cholangiocarcinoma

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cancer Communications 2024年第2期44卷 226-250页

作者： Weiren Liu Huqiang Wang Qianfu Zhao Chenyang Tao Weifeng Qu Yushan Hou Run Huang Zimei Sun Guiqi Zhu Xifei Jiang Yuan Fang Jun Gao Xiaoling Wu Zhixiang Yang Rongyu Ping Jiafeng Chen Rui Yang Tianhao Chu Jian Zhou Jia Fan Zheng Tang Dong Yang Yinghong Shi Department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityKey Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationShanghaiP.R.China Research Unit of Liver cancer Recurrence and metastasis Chinese Academy of Medical SciencesBeijingP.R.China State key laboratory of Medical Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijingP.R.China

Background:Intrahepatic cholangiocarcinoma(iCCA)is a highly heteroge-neous and lethal hepatobiliary tumor with few therapeutic *** metabolic reprogramming of tumor cells plays an essential role in the develop-ment of tumors,while the metabolic molecular classification of iCCA is largely ***,we performed an integrated multiomics analysis and metabolic classification to depict differences in metabolic characteristics of iCCA patients,hoping to provide a novel perspective to understand and treat ***:We performed integrated multiomics analysis in 116 iCCA samples,including whole-exome sequencing,bulk RNA-sequencing and proteome *** on the non-negative matrix factorization method and the protein abundance of metabolic genes in human genome-scale metabolic models,the metabolic subtype of iCCA was *** and prognostic gene analy-ses were used to compare overall survival(OS)differences between metabolic *** proliferation analysis,5-ethynyl-2’-deoxyuridine(EdU)assay,colony formation assay,RNA-sequencing and Western blotting were performed to investigate the molecular mechanisms of diacylglycerol kinaseα(DGKA)in iCCA ***:Three metabolic subtypes(S1-S3)with subtype-specific biomarkers of iCCA were *** metabolic subtypes presented with distinct prog-noses,metabolic features,immune microenvironments,and genetic *** S2 subtype with the worst survival showed the activation of some special metabolic processes,immune-suppressed microenvironment and Kirsten ratsar-coma viral oncogene homolog(KRAS)/AT-rich interactive domain 1A(ARID1A)*** the S2 subtype-specific upregulated proteins,DGKA was further identified as a potential drug target for iCCA,which promoted cell proliferation by enhancing phosphatidic acid(PA)metabolism and activating mitogen-activated protein kinase(MAPK)***:Viamultiomics analyses,we identified three metabolic subtypes of iCCA,revealing

关键词： diacylglycerol kinaseα intrahepatic cholangiocarcinoma MAPK signaling metabolic classifi-cation multiomics analysis phosphatidic acid metabolism

Role of adhesion molecules in cancer and targeted therapy

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Science China(Life Sciences) 2024年第5期67卷 940-957页

作者： Chunmei Fan Fang Xiong Shanshan Zhang Zhaojian Gong Qianjin Liao Guiyuan Li Can Guo Wei Xiong He Huang Zhaoyang Zeng NHC key laboratory of Carcinogenesis and Hunan key laboratory of cancer Metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410000China Department of Histology and Embryology Xiangya School of MedicineCentral South UniversityChangsha410013China Department of Stomatology Xiangya HospitalCentral South UniversityChangsha 410078China Department of Oral and Maxillofacial Surgery The Second Xiangya HospitalCentral South UniversityChangsha 410011China key laboratory of Carcinogenesis and cancer invasion of the Chinese Ministry of Education Cancer Research InstituteCentral South UniversityChangsha 410078China

Adhesion molecules mediate cell-to-cell and cell-to-extracellular matrix interactions and transmit mechanical and chemical signals among *** mechanisms deregulate adhesion molecules in cancer,enabling tumor cells to proliferate without restraint,invade through tissue boundaries,escape from immune surveillance,and survive in the tumor *** studies have revealed that adhesion molecules also drive angiogenesis,reshape metabolism,and are involved in stem cell *** this review,we summarize the functions and mechanisms of adhesion molecules in cancer and the tumor microenvironment,as well as the therapeutic strategies targeting adhesion *** studies have implications for furthering our understanding of adhesion molecules in cancer and providing a paradigm for exploring novel therapeutic approaches.

关键词： adhesion molecules tumor microenvironment invasion and metastasis reshaping metabolism angiogenesis immune evasion tumor stemness therapeutic strategy

Roles of THEM4 in the Akt pathway:a double-edged sword

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 541-556页

作者： Wen XIE Weidong LIU Lei WANG Bin ZHU Cong ZHAO Ziling LIAO Yihan LI Xingjun JIANG Jie LIU Caiping REN NHC key laboratory of Carcinogenesis Department of NeurosurgeryXiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China The key laboratory of Carcinogenesis and cancer invasion of the Ministry of Education Cancer Research InstituteSchool of Basic Medical ScienceCentral South UniversityChangsha 410078China Department of Critical Care Medicine Hainan Hospital of Chinese PLA General HospitalHainan Province Clinical Medical CenterSanya 572013China

The protein kinase B(Akt)pathway can regulate the growth,proliferation,and metabolism of tumor cells and stem cells through the activation of multiple downstream target genes,thus affecting the development and treatment of a range of *** superfamily member 4(THEM4),a member of the thioesterase superfamily,is one of the Akt kinase-binding *** studies on the mechanism of cancers and other diseases have shown that THEM4 binds to Akt to regulate its ***,THEM4 was considered an endogenous inhibitor of Akt,which can inhibit the phosphorylation of Akt in diseases such as lung cancer,pancreatic cancer,and liver cancer,but subsequently,THEM4 was shown to promote the proliferation of tumor cells by positively regulating Akt activity in breast cancer and nasopharyngeal carcinoma,which contradicts previous *** these two distinct views,this review summarizes the important roles of THEM4 in the Akt pathway,focusing on THEM4 as an Akt-binding protein and its regulatory relationship with Akt phosphorylation in various diseases,especially *** work provides a better understanding of the roles of THEM4 combined with Akt in the treatment of diseases.

关键词： Protein kinase B(Akt) Thioesterase superfamily member 4(THEM4) Tumor proliferation Tumor metastasis

PDCD2 as a prognostic biomarker in glioma correlates with malignant phenotype

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Genes & Diseases 2024年第5期11卷 390-406页

作者： Fengsheng Dai Yixiao Yuan Jiaqi Hao Xing Cheng Xiangyi Zhou Li Zhou Rui Tian Yi Zhao Tingxiu Xiang Department of Oncology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China Chongqing key laboratory of Translational Research for cancer metastasis and Individualized Treatment Chongqing University Cancer HospitalChongqing 400030China Department of Neurosurgery Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Neuro-Oncology Chongqing University Cancer HospitalChongqing 400030China

Programmed cell death 2(PDCD2)is related to cancer progression and chemotherapy *** role of PDCD2 in solid cancers(excluding hematopoietic malignancies)and their diagnosis and prognosis remains *** TCGA,CGGA,GEPIA,cBioPortal,and GTEx databases were analyzed for expression,prognostic value,and genetic modifications of PDCD2 in cancer *** enrichment analysis,CCK8,colony formation assay,transwell assay,and xenograft tumor model were undertaken to study the PDCD2’s biological function in glioma(GBMLGG).The PDCD2 gene was associated with solid cancer *** the functional enrichment analysis results,PDCD2 was shown to participate in several important GBMLGG biological *** cells may be inhibited in their proliferation,migration,invasion,and xenograft tumor growth by knocking down *** research can provide new insights into solid cancer prognostic biomarkers of PDCD2.

关键词： Biomarker Glioma Programmed cell death 2 Progression Solid cancer

IL-17 induces NSCLC cell migration and invasion by elevating MMP19 gene transcription and expression through the interaction of p300-dependent STAT3-K631 acetylation and its Y705-phosphorylation

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Oncology Research 2024年第4期32卷 625-641页

作者： WEN GE YA LI YUTING RUAN NINGXIA WU PEI MA TONGPENG XU YONGQIAN SHU YINGWEI WANG WEN QIU CHENHUI ZHAO Department of Immunology Nanjing Medical UniversityNanjing210000China key laboratory of Immunological Environment and Disease Nanjing Medical UniversityNanjing210000China Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing210000China Jiangsu key laboratory of cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing210000China

The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains *** the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and *** investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to ***,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and ***,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all ***,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.

关键词： NSCLC cell migration and invasion IL-17 p300 STAT3 MMP19 Acetylation and phosphorylation

Nano-formulated delivery of active ingredients from traditional Chinese herbal medicines for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1525-1541页

作者： Qi Shang Wandong Liu Faith Leslie Jiapei Yang Mingmei Guo Mingjiao Sun Guangji Zhang Qiang Zhang Feihu Wang School of Biomedical Engineering Shanghai Jiao Tong UniversityShanghai 200240China School of Basic Medical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China key laboratory of Blood-stasis-toxin Syndrome of Zhejiang Province Hangzhou 310053China Department of Chemical and Biomolecular Engineering Whiting School of Engineeringthe Johns Hopkins UniversityBaltimoreMD 21218USA Traditional Chinese Medicine“Preventing Disease”Wisdom Health Project Research Center of Zhejiang Hangzhou 310053China beijing key laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China

cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high costs compromise the additional benefits for patients treated with current chemical and biological agents. Chinese herbal medicines (CHMs) are a potential treasure trove of natural medicines and are gaining momentum in cancer immunomodulation with multi-component, multi-target, and multi-pathway characteristics. The active ingredient extracted from CHMs benefit generalized patients through modulating immune response mechanisms. Additionally, the introduction of nanotechnology has greatly improved the pharmacological qualities of active ingredients through increasing the hydrophilicity, stability, permeability, and targeting characteristics, further enhancing anti-cancer immunity. In this review, we summarize the mechanism of active ingredients for cancer immunomodulation, highlight nano-formulated deliveries of active ingredients for cancer immunotherapy, and provide insights into the future applications in the emerging field of nano-formulated active ingredients of CHMs.

关键词： Chinese herbal medicines Nano-formulation Activeingredients Drug delivery cancer immunotherapy Innate immune system Adaptive immune system

Non-coding RNA as future target for diagnose and treatment of perineural invasion in cancers

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BIOCELL 2024年第6期48卷 923-934页

作者： BINGJIE LI WENBO CAO JINJING XIAO YIXIAO CHEN QIYING WEI MINGJIN YUE SAIJUN MO Department of Pathophysiology School of Basic Medical SciencesZhengzhou UniversityZhengzhouChina Collaborative Innovation Center of Henan Province for cancer Chemoprevention ZhengzhouChina State key laboratory of Esophageal cancer Prevention and Treatment ZhengzhouChina Department of Research and Development Henan Tianxing Education and Media Company LimitedZhengzhouChina

Perineural invasion(PNI),a particularly insidious form of tumor metastasis distinct from hematogenous or lymphatic spread,has the capacity to extend well beyond the primary tumor site,inﬁltrating distant regions devoid of lymphatic or vascular *** often heralds a decrease in patient survival rates and is recognized as an indicator of an unfavorable prognosis across a variety of *** its clinical signiﬁcance,the underlying molecular mechanisms of PNI remain elusive,complicating the development of speciﬁc and efﬁcacious diagnostic and therapeutic *** the realm of cancer research,non-coding RNAs(ncRNAs)have attracted considerable attention due to their multifaceted roles and cancer-speciﬁc expression proﬁles,positioning them as promising candidates for applications in cancer diagnostics,prognostics,and *** the various types of ncRNAs,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)have emerged as inﬂuential players in *** involvement is increasingly recognized as a contributing factor to tumor progression and therapeutic *** study synthesizes and explores the diverse functions and mechanisms of ncRNAs in relation to PNI in *** comprehensive review aims to shed light on cutting-edge perspectives that could pave the way for innovative diagnostic and therapeutic approaches to address the challenges posed by PNI in oncology.

关键词： Perineural invasion Non-coding RNA Diagnose and treatment cancer Biomarker

Chinese expert consensus on refined diagnosis,treatment,and management of advanced primary liver cancer(2023 edition)

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Loss of GATA6-mediated up-regulation of UTX promotes pancreatic tumorigenesis and progression

肝脏研究（英文） 2024年第2期8卷 61-71页

作者： Xiufeng Liu Feng Xia Yue Chen Huichuan Sun Zhengqiang Yang Bo Chen Ming Zhao Xinyu Bi Tao Peng Aizier Ainiwaer Zhiwen Luo Fusheng Wang Yinying Lu National Clinical Research Center for Infectious Diseases Society of Hepatology,beijing Medical Association Translational Medicine Branch,China Association of Gerontology and Geriatrics Department of Medical Oncology Bayi Hospital Affiliated to Nanjing Chinese Medical University NanjingJiangsuChina Department of Hepatobiliary Surgery Southwest HospitalArmy Medical University ChongqingChina Senior Department of Hepatology The Fifth Medical Center of PLA General HospitalBeijingChina Department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghaiChina Department of Interventional Therapy National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Minimally Invasive Interventional Therapy Liver Cancer Study and Service GroupSun Yat-sen University Cancer CenterGuangzhouGuangdongChina Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Hepatobiliary Surgery The First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxiChina Senior Department of Infectious Diseases The Fifth Medical Center of PLA General HospitalBeijingChina Comprehensive Liver cancer Center The Fifth Medical Center of PLA General HospitalBeijingChina

Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in China,accounting for approximately 85％of all cancer cases in the *** guidelines have been used to diagnose and treat liver ***,these guidelines provide a broad definition for classifying advanced liver cancer,with an emphasis on a singular approach,without considering treatment options for individual ***,it is necessary to establish a comprehensive and practical expert consensus,specifically for China,to enhance the diagnosis and treatment of HCC using the Delphi *** classification criteria were refined for Chinese patients with HCC,and the corresponding optimal treatment regimen recommendations were *** recommendations took into account various factors,including tumor characteristics,vascular tumor thrombus grade,distant metastasis,liver function status,portal hypertension,and the hepatitis B virus replication status of patients with primary HCC,along with treatment *** findings and rec-ommendations provide detailed,scientific,and reasonable individualized diagnosis and treatment strategies for clinicians.

关键词： Hepatocellular carcinoma (HCC) Targeted therapy Immunotherapy Refined diagnosis and treatment Expert consensus

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Genes & Diseases 2024年第2期11卷 921-934页

作者： Hui-Qing Zhang Fanyang Kong Xiangyu Kong Tingting Jiang Muyuan Ma Shaojiang Zheng Junli Guo Keping Xie The Third Department of Medical Oncology Jiangxi Cancer HospitalNanchangJiangxi 330006China Departments of Gastroenterology Changhai HospitalSecond Military Medical UniversityShanghai 200433China Center for Pancreatic cancer Research The South China University of Technology School of MedicineGuangzhouGuangdong 510006China Hainan Clinical Medical Research Center of the First Affiliated Hospital Hainan Women and Children's Medical CenterHainan Medical UniversityHaikouHainan 570102China key laboratory of Tropical Cardiovascular Diseases Research of Hainan Province Key Laboratory of Emergency and Trauma of Ministry of EducationHainan Medical UniversityHaikouHainan 571199China

Ubiquitously transcribed tetratricopeptide repeat on chromosome X(UTX),also known as lysine(K)-specific demethylase 6A(KDM6A),functions as a tumor suppressor gene or oncogene depending on the tumor type and ***,its tumor-suppressive mechanisms remain largely ***,we investigated the clinical significance and biological effects of UTX expression in pancreatic ductal adenocarcinoma(PDA)and determined the potential mechanisms of its *** expression and its association with clinicopathologic characteristics of PDA patients were analyzed using *** mRNA and protein expression and their regulation in PDA cell lines were measured using quantitative polymerase chain reaction and Western blot *** biological functions of UTX in PDA cell growth,migration,and invasion were determined using gain-and loss-of-function assays with both in vitro and in vivo animal *** expression was reduced in human PDA cell lines and *** UTX expression was associated with poor differentiation and prognosis in *** UTX expression inhibited PDA proliferation,migration,and invasion in vitro and PDA growth and metastasis in vivo,whereas knockdown of UTX expression did the ***,UTX expression was trans-activated by GATA6 ***6-mediated PDA progression could be blocked,at least partially,by silencing UTX *** conclusion,loss of GATA6-mediated UTX expression was evident in human PDA and restored UTX expression suppressed PDA growth and ***,UTX is a tumor suppressor in PDA and may serve as a prognostic biomarker and therapeutic target.

关键词： Growth invasion metastasis Pancreatic cancer UTX