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Chemical Research in Chinese Universities 2024年第1期40卷 136-144页

作者： DU Xiaohui LI Encheng WANG Qi YOU Xin lung cancer Transitional Medicine Center The Second Affiliated Hospital of Dalian Medical UniversityDalian116023P.R.China Department of Scientific Research Center The Second Affiliated Hospital of Dalian Medical UniversityDalian116023P.R.China Department of Respiratory Medicine The Second Affiliated Hospital of Dalian Medical UniversityDalian116023P.R.China

lung cancer produces a high incidence of malignant *** have been many studies on lung cancer using mass spectrometry(MS)***,most studies have focused on humoral *** this work,26 pairs of tissue samples(tumor ***-tumor)from patients with lung cancer were analyzed using liquid chromatography-tandem MS(LC-MS/MS)with data-independent acquisition *** total,3152 proteins were quantified from tissue samples with high confidence,including 189 up-regulated and 522 down-regulated proteins(tumor ***-tumor).In addition,79 and 690 proteins were identified only in para-cancerous samples and cancerous samples,*** results from bio-informatics tools indicated that altered proteins like PEBP1,HRG and LYZ could be ideal reservoirs for screening the potential biomarkers for lung *** is believed these tissue-specific proteomics results will assist in the studies of lung cancer.

关键词： lung cancer Proteome Data-independent aquisition

Discovery of first-in-class DOT1L inhibitors against the R231Q gain-of-function mutation in the catalytic domain with therapeutic potential of lung cancer

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3605-3623页

作者： Zehui Tan Ning Guo Zhi Cao Shuyu Liu Jiayu Zhang Deyi Ma Jiahao Zhang Wencai Lv Nan Jiang Linghe Zang Lihui Wang Xin Zhai Key Laboratory of Structure-Based Drug Design and Discovery Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmacology Shenyang Pharmaceutical UniversityShenyang 110016China

Recent research certified that DOT1L and its mutations represented by R231Q were potential targets for the treatment of lung ***,a series of adenosine-containing derivatives were identified with DOT1LR231Q inhibition through antiproliferation assay and Western blot analysis in the H460R231Q *** most promising compound 37 significantly reduced DOT1LR231Q mediated H3K79 methylation and effectively inhibited the proliferation,self-renewal,migration,and invasion of lung cancer cell lines at low micromolar *** cell permeability and cellular target engagement of 37 were verified by both CETSA and DARTS *** the H460R231Q OE cell-derived xenograft(CDX)model,37 displayed pronounced tumor growth inhibition after intraperitoneal administration at 20 mg/kg dose for 3 weeks(TGI=54.38%),without obvious toxicities.A pharmacokinetic study revealed that 37 possessed tolerable properties(t_(1/2)=1.93±0.91 h,F=97.2%)after intraperitoneal administration in *** study confirmed that 37 suppressed malignant phenotypes of lung cancer carrying R231Q gain-of-function mutation via the MAPK/ERK signaling ***,analysis of the binding modes between molecules and DOT1LWT/R231Q proteins put forward the“Induced-fit”allosteric model in favor to the discovery of potent DOT1L candidates.

关键词： DOT1L R231Q mutation lung cancer Adenosine-containing inhibitors Epigenetics

Bronchoalveolar lavage fluid assessment facilitates precision medicine for lung cancer

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cancer Biology & Medicine 2024年第3期21卷 230-251页

作者： Hantao Zhang Dan Deng Shujun Li Jing Ren Wei Huang Dan Liu Weiya Wang Department of Pathology West China HospitalSichuan UniversityChengdu 610000China West China Biobank West China HospitalSichuan UniversityChengdu 610000China Department of Respiratory and Critical Care Medicine Clinical Research Center for Respiratory DiseaseWest China HospitalSichuan UniversityChengdu 610000China

lung cancer is the most common and fatal malignant disease worldwide and has the highest mortality rate among tumor-related causes of *** diagnosis and precision medicine can significantly improve the survival rate and prognosis of lung cancer *** present,the clinical diagnosis of lung cancer is challenging due to a lack of effective non-invasive detection methods and biomarkers,and treatment is primarily hindered by drug resistance and high tumor *** biopsy is a method for detecting circulating biomarkers in the blood and other body fluids containing genetic information from primary tumor *** lavage fluid(BALF)is a potential liquid biopsy medium that is rich in a variety of bioactive substances and cell *** contains information on the key characteristics of tumors,including the tumor subtype,gene mutation type,and tumor environment,thus BALF may be used as a diagnostic supplement to lung *** this review,the current research on BALF in the diagnosis,treatment,and prognosis of lung cancer is *** advantages and disadvantages of different components of BALF,including cells,cell-free DNA,extracellular vesicles,and micro RNA are *** particular,the great potential of extracellular vesicles in precision diagnosis and detection of drug-resistant for lung cancer is *** addition,the performance of liquid biopsies with different body fluid sources in lung cancer detection are compared to facilitate more selective studies involving BALF,thereby promoting the application of BALF for precision medicine in lung cancer patients in the future.

关键词： lung cancer bronchoalveolar lavage fluid extracellular vesicles liquid biopsy precision medicine

Secondary metabolites of mulberry leaves exert anti-lung cancer activity through regulating the PD-L1/PD-1 signaling pathway

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Journal of Pharmaceutical Analysis 2024年第6期14卷 914-925页

作者： Guiqin Ye Xin Sun Jiuzhou Li Yuanyuan Mai Ruilan Gao Jianbin Zhang cancer Center Department of Medical OncologyKey Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang ProvinceZhejiang Provincial People's HospitalAffiliated People's HospitalHangzhou Medical CollegeHangzhou310014China Clinical Laboratory Yuhuan City HospitalTaizhouZhejiang317600China Hangzhou Medical College Hangzhou311300China Department of Neurosurgery Binzhou People's HospitalBinzhouShandong256600China Institute of Hematology Research The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou310060China

lung cancer ranks the top of malignancies that cause cancer-related deaths *** leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory *** previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf,but their mechanism of action has still not fully *** synthesized Moracin N(MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic *** and its probe exerted similar growth-inhibitory effect on human lung cancer *** proteomic results showed that MAN targeted the programmed death ligand 1(PD-L1)checkpoint pathway and T cell receptor(TCR)signaling pathway,indicating its immune-regulatory ***-free surface plasmon resonance(SPR)results showed the direct interaction of MAN with PD-L1 *** docking analysis demonstrated that MAN bound to E158 residue of PD-L1 *** downregulated the expression levels of PD-L1 in a time-and dose-dependent manner and disrupted the PD-L1/programmed death 1(PD-1)binding,including other secondary metabolites of mulberry leaves Guangsangon E(GSE)and Chalcomoracin(CMR).Human peripheral blood mononuclear cells(PBMCs)co-cultured with MAN-treated A549 cells,resulting in the increase of CD8^(+)GZMB^(+)T cells and the decrease of CD8^(+)PD-1^(+)T *** suggested that MAN exerts anti-cancer effect through blocking the PD-L1/PD-1 *** vivo,MAN combined with anti-PD-1 antibody significantly inhibited lung cancer development and metastasis,indicating their synergistic *** together,secondary metabolites of mulberry leaves target the PD-L1/PD-1 signaling,enhance T cell-mediated immunity and inhibit the tumorigenesis of lung *** modulatory effect on tumor microenvironment makes them able to enhance the therapeutic efficacy of immune checkpoint inhibitors in lung cancer.

关键词： Moracin N Click chemistry PD-L1 T cell lung cancer

Emerging mechanisms of ferroptosis and its implications in lung cancer

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Chinese Medical Journal 2024年第7期137卷 818-829页

作者： Qian Li Qibin Song Huadong Pei Yali Chen cancer Center Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Department of Oncology Georgetown Lombardi Comprehensive Cancer CenterGeorgetown University Medical CenterWashington D.C.20057USA State Key Laboratory of Medical Proteomics National Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijing 102206China

lung cancer is one of the most common malignancies and has the highest number of deaths among all *** continuous advances in medical strategies,the overall survival of lung cancer patients is still low,probably due to disease progression or drug *** is an iron-dependent form of regulated cell death triggered by the lethal accumulation of lipid peroxides,and its dysregulation is implicated in cancer *** evidence has shown that targeting the ferroptosis pathway could be a potential strategy for improving lung cancer treatment *** this review,we summarize the underlying mechanisms and regulatory networks of ferroptosis in lung cancer and highlight ferroptosis-targeting preclinical attempts to provide new insights for lung cancer treatment.

关键词： lung cancer Ferroptosis Ferroptosis regulators Ferroptosis inducers cancer treatment

Inhalable iron redox cycling powered nanoreactor for amplified ferroptosis-apoptosis synergetic therapy of lung cancer

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Nano Research 2024年第6期17卷 5435-5451页

作者： Linjing Wu Wenhao Wang Mengqin Guo Fangqin Fu Wenhua Wang Tszching Sung Meihong Zhang Ziqiao Zhong Chuanbin Wu Xin Pan Zhengwei Huang College of Pharmacy Jinan UniversityGuangzhou 511436China School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China

Fenton reaction centered ferroptosis-apoptosis synergetic therapy has emerged as a promising tumor elimination ***,the low intracellular Fenton level and accumulation of therapeutics at the lesion site greatly limit the efficacy of ferroptosis *** overcome these two bottlenecks,an inhalable metal polyphenol network(MPN)-hybrid liposome,encoded as LDG,was proposed for enhancing the intracellular Fenton reaction level by co-delivering the ferroptosis inducer dihydroartemisinin(DHA)and the ferrous ion(Fe2+)donor *** synthesized LDG had excellent nebulization performance which significantly improved the accumulation in the lungs,about 8.2 times of intravenous *** terms of anticancer mechanisms,MPN raised the intracellular level of Fe2+by constructing iron cycling in the weakly acidic environment of *** by Fe2+,DHA with peroxide-bridge structure underwent a high level of Fenton-like reaction,promoted the production of intracellular reactive oxygen species(ROS)and induced strong ferroptosis while cooperating with *** exhibited extraordinary antitumor ability in an orthotopic lung tumor model,whose tumor inhibition efficiency was 1.53(P=0.0014)and 1.32(P=0.0183)times of the LG group(liposomes coated with gallic acid(GA)-Fe MPN)and LD group(liposomes loaded with DHA),respectively,showing the strongest anticancer *** conclusion,the constructed MPN-hybrid liposomes could be a potent custom nanoplatform for pulmonary delivery and underscored the great potential of ferroptosis-apoptosis synergetic therapy.

关键词： lung cancer pulmonary delivery ferroptosis metallic polyphenol network

Empowering Diagnosis: Cutting-Edge Segmentation and Classification in lung cancer Analysis

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Computers, Materials & Continua 2024年第6期79卷 4963-4977页

作者： Iftikhar Naseer Tehreem Masood Sheeraz Akram Zulfiqar Ali Awais Ahmad Shafiq Ur Rehman Arfan Jaffar Faculty of Computer Sciences&Information Technology The Superior UniversityLahore54000Pakistan Intelligent Data Visual Computing Research(IDVCR) Lahore54000Pakistan Information System Department College of Computer and Information SciencesImam Mohammad Ibn Saud Islamic University(IMSIU)Riyadh11432Saudi Arabia School of Computer Science and Electronic Engineering(CSEE) University of EssexWivenhoe ParkColchesterCO43SQUK

lung cancer is a leading cause of global mortality *** detection of pulmonary tumors can significantly enhance the survival rate of ***,various Computer-Aided Diagnostic(CAD)methods have been developed to enhance the detection of pulmonary nodules with high ***,the existing method-ologies cannot obtain a high level of specificity and *** present study introduces a novel model for lung cancer Segmentation and Classification(LCSC),which incorporates two improved architectures,namely the improved U-Net architecture and the improved AlexNet *** LCSC model comprises two distinct *** first stage involves the utilization of an improved U-Net architecture to segment candidate nodules extracted from the lung ***,an improved AlexNet architecture is employed to classify lung *** the first stage,the proposed model demonstrates a dice accuracy of 0.855,a precision of 0.933,and a recall of 0.789 for the segmentation of candidate *** suggested improved AlexNet architecture attains 97.06%accuracy,a true positive rate of 96.36%,a true negative rate of 97.77%,a positive predictive value of 97.74%,and a negative predictive value of 96.41%for classifying pulmonary cancer as either benign or *** proposed LCSC model is tested and evaluated employing the publically available dataset furnished by the lung Image Database Consortium and Image Database Resource Initiative(LIDC-IDRI).This proposed technique exhibits remarkable performance compared to the existing methods by using various evaluation parameters.

关键词： lung cancer segmentation AlexNet U-Net classification

cancer-educated neutrophils promote lung cancer progression via PARP-1-ALOX5-mediated MMP-9 expression

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cancer Biology & Medicine 2024年第2期21卷 175-192页

作者： Lulu Han Yuxin Chen Nan Huang Xiaowan Zhou Yanfang Lv Huizhong Li Dafei Chai Junnian Zheng Gang Wang cancer Institute Xuzhou Medical University209 Tongshan RoadXuzhou 221004China Center of Clinical Oncology The Affiliated Hospital of Xuzhou Medical University99 West Huaihai RoadXuzhou 221002China Jiangsu Center for the Collaboration and Innovation of cancer Biotherapy Xuzhou Medical University209 Tongshan RoadXuzhou 221004China Department of Oncology Suzhou Xiangcheng People’s HospitalSuzhou 215131China

Objective:Neutrophils are one of the most predominant infiltrating leukocytes in lung cancer tissues and are associated with lung cancer *** neutrophils promote lung cancer progression,however,has not been ***:Kaplan–Meier plotter online analysis and tissue immunohistochemistry were used to determine the relationship between neutrophils and overall survival in lung cancer *** effect of neutrophils on lung cancer was determined using the Transwell migration assay,a proliferation assay,and a murine tumor *** knockdown was used to determine poly ADPribose polymerase(PARP)-1 function in lung cancer-educated *** blot analysis and gelatin zymography were used to demonstrate the correlation between PARP-1 and matrix metallopeptidase 9(MMP-9).Immunoprecipitation coupled to mass spectrometry(IP/MS)was used to identify the proteins interacting with ***-immunoprecipitation(Co-IP)was used to confirm that PARP-1 interacts with arachidonate 5-lipooxygenase(ALOX5).Neutrophil PARP-1 blockage by AG14361 rescued neutrophil-promoted lung cancer ***:An increased number of infiltrating neutrophils was negatively associated with overall survival in lung cancer patients(Plung cancer cell invasion,migration,and proliferation in vitro,and murine lung cancer growth in ***,PARP-1 was shown to be involved in lung cancer cell-induced neutrophil activation to increase MMP-9 expression through interacting and stabilizing ALOX5 by post-translational protein modification(PARylation).Blocking PARP-1 by gene knockdown or AG14361 significantly decreased ALOX5 expression and MMP-9 production,and eliminated neutrophil-mediated lung cancer cell invasion and in vivo tumor ***:We identified a novel mechanism by which PARP-1 mediates lung cancer cell-induced neutrophil activation and PARylates ALOX5 to regulate MMP-9 expression,which exacerbates lung cancer

关键词： lung cancer neutrophils PARP-1 ALOX5 MMP-9

Recent advances and remaining challenges in lung cancer therapy

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Chinese Medical Journal 2024年第5期137卷 533-546页

作者： Tasha Barr Shoubao Ma Zhixin Li Jianhua Yu Department of Hematology and Hematopoietic Cell Transplantation City of Hope National Medical CenterLos AngelesCalifornia 91010USA Comprehensive cancer Center City of HopeLos AngelesCalifornia 91010USA Department of Immuno-Oncology Beckman Research InstituteLos AngelesCalifornia 91010USA

lung cancer remains the most common cause of cancer *** the continued research into new drugs and combination therapies,outcomes in lung cancer have been improved,and clinical benefits have been expanded to a broader patient ***,the overall cure and survival rates for lung cancer patients remain low,especially in metastatic *** the available lung cancer treatment options,such as surgery,radiation therapy,chemotherapy,targeted therapies,and alternative therapies,immunotherapy has shown to be the most *** exponential progress in immuno-oncology research and recent advancements made in the field of immunotherapy will further increase the survival and quality of life for lung cancer *** progress has been made in targeted therapies using tyrosine kinase inhibitors and monoclonal antibody immune checkpoint inhibitors with many US Food And Drug Administration(FDA)-approved drugs targeting the programmed cell death ligand-1 protein(e.g.,durvalumab,atezolizumab),the programmed cell death-1 receptor(e.g.,nivolumab,pembrolizumab),and cytotoxic T-lymphocyte-associated antigen 4(e.g.,tremelimumab,ipilimumab).Cytokines,cancer vaccines,adoptive T cell therapies,and Natural killer cell mono-and combinational therapies are rapidly being studied,yet to date,there are currently none that are FDA-approved for the treatment of lung *** this review,we discuss the current lung cancer therapies with an emphasis on immunotherapy,including the challenges for future research and clinical applications.

关键词： lung cancer Therapy Immunotherapy Combination therapy Adoptive T cell therapies

Multilevel Attention Unet Segmentation Algorithmfor lung cancer Based on CT Images

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Computers, Materials & Continua 2024年第2期78卷 1569-1589页

作者： Huan Wang Shi Qiu Benyue Zhang Lixuan Xiao Xi’an Institute of Optics and Precision Mechanics Chinese Academy of SciencesXi’anChina School of Biomedical Engineering Fourth Military Medical UniversityXi’anChina University of Illinois at Urbana Champion ChampaignUSA

lung cancer is a malady of the lungs that gravely jeopardizes human ***,early detection and treatment are paramount for the preservation of human *** computed tomography(CT)image sequences can explicitly delineate the pathological condition of the *** meet the imperative for accurate diagnosis by physicians,expeditious segmentation of the region harboring lung cancer is of utmost *** utilize computer-aided methods to emulate the diagnostic process in which physicians concentrate on lung cancer in a sequential manner,erect an interpretable model,and attain segmentation of lung *** specific advancements can be encapsulated as follows:1)Concentration on the lung parenchyma region:Based on 16-bit CT image capturing and the luminance characteristics of lung cancer,we proffer an intercept histogram algorithm.2)Focus on the specific locus of lung malignancy:Utilizing the spatial interrelation of lung cancer,we propose a memory-based Unet architecture and incorporate skip connections.3)Data Imbalance:In accordance with the prevalent situation of an overabundance of negative samples and a paucity of positive samples,we scrutinize the existing loss function and suggest a mixed loss *** results with pre-existing publicly available datasets and assembled datasets demonstrate that the segmentation efficacy,measured as Area Overlap Measure(AOM)is superior to 0.81,which markedly ameliorates in comparison with conventional algorithms,thereby facilitating physicians in diagnosis.

关键词： lung cancer computed tomography computer-aided diagnosis Unet segmentation