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cancer Communications 2024年第4期44卷 499-503页

作者： Xuechun Wang Anna Juncker-Jensen Gang Huang Mate Levente Nagy Xuemin Lu Liang Cheng Xin Lu Department of Biological Sciences Boler-Parseghian Center for Rare and Neglected DiseasesHarper Cancer Research InstituteUniversity of Notre DameNotre DameINUSA NeoGenomics Laboratories Inc.Aliso ViejoCAUSA Department of Pathology and Laboratory Medicine Brown University Warren Alpert Medical SchoolLifespan Academic Medical CenterLegorreta Cancer Center at Brown UniversityProvidenceRIUSA Tumor Microenvironment and Metastasis Program Indiana University Melvin and Bren Simon Comprehensive Cancer CenterIndianapolisINUSA

Dear Editor,Tertiary lymphoid structures(TLSs)are organized clus-ters of immune cells found in non-lymphoid tissues of chronic inflammation,including solid tumors[1].High endothelial venules(HEVs)positive for peripheral node addressin(PNAd)are present in TLSs and may pro-vide highway entry for ***-residing TLSs may be formed by the concerted actions of cytokines and chemokines,a finding supported by the relation between a 12-chemokine signature and TLSs[2].

关键词： bladder lymphoid inflammation

Self-assembled amphiphilic NIR-Ⅱ emissive nano-micelles for imaging-guided photothermal therapy of colorectal cancer

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Science China Chemistry 2024年第8期67卷 2767-2774页

作者： Axin He Fangfang Xia Da Han Qinglai Yang Weihong Tan institute of Molecular Medicine(IMM) Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200240China center for Molecular Imaging Probe Hunan Province Key Laboratory of Cancer Cellular and Molecular PathologyCancer Research InstituteHengyang Medical SchoolUniversity of South ChinaHengyang 421001China The Key Laboratory of Zhejiang Province for Aptamers and Theranostics Zhejiang Cancer Hospital Hangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhou 310022China Molecular Science and Biomedicine Laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringCollege of BiologyAptamer Engineering Center of Hunan ProvinceHunan UniversityChangsha 410082China

Colorectal cancer(CRC) is one of the major causes of cancer-related mortality worldwide. Most near-infrared(NIR) agents used in clinical CRC treatment are at NIR-I(700–900 nm) window, which has limitations on deep tissue, and fluorescent probes in the second NIR(1,000–1,700 nm) allow high-resolution bioimaging with deep tissue penetration. However, existing NIR-II fluorophores used in clinical are still rare. Herein, based on shielding-donor-acceptor-donor-shielding(S-D-A-D-S) scaffold, we developed an organic small-molecule fluorophore IR-BTGP with NIR-II emission for imaging-guided photothermal therapy(PTT) in CRC mice model. Amphiphilic IR-BTGP can be self-assembled into spherical nano-micelles, which presents reliable water solubility and photothermal conversion efficiency(30.2%). In vitro experiments indicate that cancer cells treated with IRBTGP were significantly killed upon 808 nm light irradiation. Furthermore, in vivo NIR-II fluorescence imaging confirms that IR-BTGP accumulates in the tumor region. Remarkably, a significant tumor inhibition rate(78.5%) was observed in tumorbearing mice when treated with IR-BTGP plus 808 nm irradiation. Therefore, this work shows that IR-BTGP holds great promise as an NIR-II fluorescence imaging-guided PTT platform for CRC in the future.

关键词： photothermal therapy(PTT) second near-infrared(NIR-Ⅱ)imaging organic molecule

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

Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1547-1563页

作者： Qiang Zou Hao-Wen Wang Xi-Liang Di Yuan Li Hui Gao Department of Interventional Therapy Tianjin Medical University Cancer Institute and HospitalTianjin 300060China National Clinical Research center for cancer Key Laboratory of Cancer Prevention and TherapyTianjin’s Clinical Research Center for CancerTianjin 300060China College of Animal Science and Technology Northeast Agricultural UniversityHarbin 150030Heilongjiang ProvinceChina Department of Hematology and Oncology Linyi People’s HospitalLinyi 251500Shandong ProvinceChina Department of Comprehensive Oncology Baotou Cancer HospitalBaotou 014030Inner Mongolia Autonomous RegionChina

BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is *** targeted microbubble destruction mediated gene transfection is a new method to overexpress *** To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of *** In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,*** addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell ***,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and *** vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation *** We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of ***,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of *** miR-873-5p mimic counteracted the impact of ***,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to *** discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/*** vivo results showed that HAND2-AS1 silencing sig

关键词： Hepatocellular carcinoma Ultrasound microbubbles Long noncoding RNA HAND2-AS1 miR-873-5p Tissue inhibitor of matrix metalloproteinase-2

Development and validation of the NCC‐BC‐A scale to assess patient‐reported outcomes for breast cancer patients in China

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cancer Innovation 2024年第6期3卷 45-57页

作者： Fei Ma Xiaoyan Yan Xiuwen Guan Tianmou Liu 无 National cancer center/National Clinical Research center for cancer/cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Clinical Research institute Institute of Advanced Clinical MedicinePeking UniversityBeijingChina Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijingChina PRO‐BC China Standards Committee

Background:The commonly used international patient‐reported outcome scales for breast cancer were developed before the advent of multiple targeted therapies and immunotherapies,rendering them potentially insufficient for current clinical ***,it is necessary to develop a specific patient‐reported outcome scale tailored for breast cancer patients in China to optimize the management model for these ***:A comprehensive literature search was performed in the PubMed,Embase,Wanfang,and CNKI databases to extract dimensions and items for a potential patient‐reported outcome *** Delphi method was used to modify,add,subtract,and adjust the language of items until the experts reached a consensus on the first *** draft was further refined using a cognitive test and a *** optimized scale was used for a formal survey,and the items were further analyzed and screened using metrics such as the coefficient of variation,correlation coefficient,internal item consistency,factor analysis,reliability,and ***:A total of 10,954 articles were analyzed,and 237 were used to create a pool of 277 patient‐reported outcome *** two rounds of Delphi expert consultation,the experts'authority coefficients were 0.739 and *** a cognitive test,several items were adjusted to enhance *** adjustments were made following a presurvey of 200 advanced breast cancer patients,resulting in a 38‐item patient‐reported outcomes scale,termed NCC‐BC‐*** the national formal survey,588 advanced breast cancer patients *** component analysis showed good consistency among the items and sufficient difference between the *** results were normally distributed with good *** Cronbach'sαcoefficient of the scale was 0.925 and the test–retest reliability was ***:The NCC‐BC‐A scale has high validity and *** comprehensively considered the characteristics of systemic trea

关键词： breast cancer patient‐reported outcome quality of life

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

Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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Science China Life Sciences 2024年

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research Laboratory Peking University Cancer Hospital &Institute Department of Gastrointestinal cancer center Peking University Cancer Hospital & Institute Department of Liver Surgery & Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education State Key Laboratory of Holistic Integrative Management of Gastrointestinal cancers Beijing Key Laboratory of Carcinogenesis and Translational Research Division of Gastrointestinal Cancer Translational Research Laboratory Peking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

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Modular Synthesis of Multi-substituted Cyclobutanones Enabled by Oxyallyl Cations

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Chinese Journal of Chemistry 2024年第5期42卷 459-463页

作者： Meng Wang Zhonggui Wang Ping Lu Research center for Molecular Recognition and Synthesis Department of ChemistryFudan University220 Handan LuShanghai200433 China Present address: Department of cancer Biology Dana-Farber Cancer Institute Department of Biological Chemistry and Molecular Pharmacology Harvard Medical SchoolBostonMA 02115USA

Stereoselective synthesis of multi-substituted cyclobutanes with different substituents is still a daunting challenge in organic *** report here a practical and facile approach to synthesizing all-trans 2,3,4-trisubstituted cyclobutanones from readily available *** substitution reaction proceeds smoothly via oxyallyl cation intermediates under mild basic *** transformation to the synthesis of 1,2,3,4-tetrasubstituted cyclobutanes was also explored.

关键词： Diastereoselectivity Modular synthesis Nucleophilic substitution Organohalides Oxyallyl cation Precision functionalization Strained molecules 1,2,3,4-Tetrasubstituted cyclobutanes

Unleashing the potential:super-resolution microscopy as the key to advanced mitochondrial research

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Medical Review 2024年第3期4卷 239-243页

作者： Xiaoyu Li Miao He Xiaoshuai Huang institute of Medical Technology Peking University Health Science CenterBeijingChina Biomedical Engineering Department Institute of Advanced Clinical MedicineInternational Cancer InstituteHealth Science CenterPeking UniversityBeijing 100191China Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Peking University Cancer Hospital and InstituteBeijing 100142China

Investigating the fine structure of mitochondria and their dynamic interactions with other organelles is crucial for unraveling the mechanisms underlying mitochondrial-related *** development of super-resolution techniques has provided powerful visualization tools for mitochondrial research,which is significant for investigating mitochondrial cristae structure,the localization of mitochondrial-related protein complex,and the interactions between mitochondria and other *** this perspective,we introduce several advanced super-resolution techniques and their applications in mitochondrial research,and discuss the potential roles these techniques may play in future studies of mitochondria.

关键词： super resolution microscopy mitochondria fluorescence microscopy

To explore the pathogenesis of anterior resection syndrome by magnetic resonance imaging rectal defecography

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 529-538页

作者： Ling-Hou Meng Xian-Wei Mo Bing-Yu Yang Hai-Quan Qin Qing-Zhou Song Xin-Xin He Qiang Li Zheng Wang Chang-Lin Mo Guo-Hai Yang Department of Gastrointestinal Surgery Guangxi Clinical Research Center for Colorectal CancerGuangxi Medical University Cancer HospitalNanning 530021Guangxi Zhuang Autonomous RegionChina Department of Colorectal and Anal Surgery Guangxi Medical University Cancer HospitalNanning 530021Guangxi Zhuang Autonomous RegionChina Department of radiology Guangxi Medical University Cancer HospitalNanning 530021Guangxi Zhuang Autonomous RegionChina First Department of Chemotherapy Guangxi Medical University Cancer HospitalNanning 530021Guangxi Zhuang Autonomous RegionChina

BACKGROUND Over 90%of rectal cancer patients develop low anterior resection syndrome(LARS)after sphincter-preserving *** current globally recognized evaluation method has many drawbacks and its subjectivity is too strong,which hinders the research and treatment of *** To evaluate the anorectal function after colorectal cancer surgery by quantifying the index of magnetic resonance imaging(MRI)defecography,and pathogenesis of *** We evaluated 34 patients using the standard LARS score,and a new LARS evaluation index was established using the dynamic images of MRI defecography to verify the LARS *** In the LARS score model,there were 10(29.41%)mild and 24(70.58%)severe cases of *** comparison of defecation rate between the two groups was 29.36±14.17%versus 46.83±18.62%(P=0.004);and MRI-rectal compliance(MRI-RC)score was 3.63±1.96 versus 7.0±3.21(P=0.001).Severe and mild LARS had significant differences using the two evaluation *** was a significant negative correlation between LARS and MRI-RC score(P<0.001),and they had a negative correlation with defecation rate(P=0.028).CONCLUSION MRI defecography and standard LARS score can both be used as an evaluation index to study the pathogenesis of LARS.

关键词： Anterior resection syndrome Colorectal cancer Diagnostic evaluation system Magnetic resonance imaging defecography Pathogenesis