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Improvement of histone deacetylase inhibitor efficacy by SN38 through TWIST1 suppression in synovial sarcoma

Cancer Innovation 2024年第2期3卷 80-95页

作者： Satoru Sasagawa Jun Kumai Toru Wakamatsu Yoshihiro Yui Molecular Biology laboratory Research InstituteNozaki Tokushukai HospitalDaitoOsakaJapan Sarcoma Treatment laboratory Research InstituteNozaki Tokushukai HospitalDaitoOsakaJapan Department of Musculoskeletal oncology Service Osaka International Cancer InstituteOsakaJapan

Background:Synovial sarcoma(SS)is an SS18-SSX fusion gene-driven soft tissue sarcoma with mesenchymal characteristics,associated with a poor prognosis due to frequent metastasis to a distant organ,such as the *** deacetylase(HDAC)inhibitors(HDACis)are arising as potent molecular targeted drugs,as HDACi treatment disrupts the SS oncoprotein complex,which includes HDACs,in addition to general HDACi *** provide further molecular evidence for the advantages of HDACi treatment and its limitations due to drug resistance induced by the microenvironment in SS cells,we examined cellular responses to HDACi treatment in combination with two-dimensional(2D)and 3D culture ***:Using several SS cell lines,biochemical and cell biological assays were performed with romidepsin,an HDAC1/2 selective ***38 was concomitantly used as an ameliorant drug with romidepsin ***,apoptosis induction,and MHC class I polypeptide-related sequence A/B(MICA/B)induction were monitored to evaluate the drug *** addition to the conventional 2D culture condition,spheroid culture was adopted to evaluate the influence of cell-mass microenvironment on ***:By monitoring the cellular behavior with romidepsin and/or SN38 in SS cells,we observed that responsiveness is diverse in each cell *** the apoptotic inducible cells,co-treatment with SN38 enhanced cell *** nonapoptotic inducible cells,cytostasis and MICA/B induction were observed,and SN38 improved MICA/B induction *** a novel efficacy of SN38,we revealed TWIST1 suppression in SS *** the spheroid(3D)condition,romidepsin efficacy was severely restricted in TWIST1-positive *** demonstrated that TWIST1 downregulation restored romidepsin efficacy even in spheroid form,and concomitant SN38 treatment along with romidepsin reproduced the ***:The current study demonstrated the benefits and concerns of using HDACi for SS treatment in 2D and

关键词： HDAC inhibitor MICA/B SN38 spheroid synovial sarcoma TWIST1

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Iris:a multi-constraint graphic layout generation system

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Frontiers of Information Technology & Electronic Engineering 2024年第7期25卷 968-987页

作者： Liuqing CHEN Qianzhi JING Yixin TSANG Tingting ZHOU College of Computer Science and Technology Zhejiang UniversityHangzhou 310030China Zhejiang–Singapore Innovation and AI Joint research lab Hangzhou 310058China Alibaba Group Hangzhou 310034China

In graphic design,layout is a result of the interaction between the design elements in the foreground and background ***,prevalent research focuses on enhancing the quality of layout generation algorithms,overlooking the interaction and controllability that are essential for designers when applying these methods in realworld *** paper proposes a user-centered layout design system,Iris,which provides designers with an interactive environment to expedite the workflow,and this environment encompasses the features of user-constraint specification,layout generation,custom editing,and final *** satisfy the multiple constraints specified by designers,we introduce a novel generation model,multi-constraint LayoutVQ-VAE,for advancing layout generation under intra-and inter-domain *** and quantitative experiments on our proposed model indicate that it outperforms or is comparable to prevalent state-of-the-art models in multiple *** studies on Iris further demonstrate that the system significantly enhances design efficiency while achieving human-like layout designs.

关键词： Graphic layout generation Deep generative model Layout design system

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Theoretical study of the nonlinear force-loading control in single-molecule stretching experiments

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Communications in Theoretical Physics 2024年第4期76卷 167-175页

作者： Xingyu Qi Zilong Guo Shimin Le Hu Chen research Institute for Biomimetics and Soft Matter Fujian Provincial Key Lab for Soft Functional Materials ResearchDepartment of PhysicsXiamen UniversityXiamen 361005China Center of Biomedical Physics Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325000China

Force spectrum measurements with constant loading rates are widely used in single-molecule manipulation experiments to study the mechanical stability and force response of ***-dependent transition rates can be obtained from the transition force distribution,but it is limited to the force range with non-zero force *** constant loading rate control can be realized with magnetic tweezers,the loading rate range is limited due to the slow movement of permanent ***-linear exponential and exponential squared force loading functions are more feasible in magnetic tweezers,while there is no theoretical result available for these two kinds of non-linear force loading *** this study,we solved the unfolding process of a protein following Bell's model under nonlinear exponential and exponential squared force loading functions,which offer a broader range of unfolding force distribution compared to the traditional constant loading rate ***,we derived two force loading functions,which can produce uniform unfolding force *** research contributes fundamental equations for the analysis of experimental data obtained through single-molecule manipulation under nonlinear force loading controls,paving the way for the use of nonlinear force control in magnetic tweezer experiments.

关键词： single-molecule manipulation magnetic tweezers force loading transition rates force distribution

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Cooperative User-Scheduling and Resource Allocation Optimization for Intelligent Reflecting Surface Enhanced LEO Satellite Communication

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China Communications 2024年第2期21卷 227-244页

作者： Meng Meng Bo Hu Shanzhi Chen Jianyin Zhang State Key lab of Networking and Switching Technology Beijing University of Posts and TelecommunicationsBeijing 100876China State Key lab of Wireless Mobile Communication China Academy of Telecommunication TechnologyBeijing 100191China research Institute of China Mobile Beijing 100053China

Lower Earth Orbit(LEO) satellite becomes an important part of complementing terrestrial communication due to its lower orbital altitude and smaller propagation delay than Geostationary satellite. However, the LEO satellite communication system cannot meet the requirements of users when the satellite-terrestrial link is blocked by obstacles. To solve this problem, we introduce Intelligent reflect surface(IRS) for improving the achievable rate of terrestrial users in LEO satellite communication. We investigated joint IRS scheduling, user scheduling, power and bandwidth allocation(JIRPB) optimization algorithm for improving LEO satellite system *** optimization problem of joint user scheduling and resource allocation is formulated as a non-convex optimization problem. To cope with this problem, the nonconvex optimization problem is divided into resource allocation optimization sub-problem and scheduling optimization sub-problem firstly. Second, we optimize the resource allocation sub-problem via alternating direction multiplier method(ADMM) and scheduling sub-problem via Lagrangian dual method ***, we prove that the proposed resource allocation algorithm based ADMM approaches sublinear convergence theoretically. Finally, we demonstrate that the proposed JIRPB optimization algorithm improves the LEO satellite communication system throughput.

关键词： convex optimization intelligent reflecting surface LEO satellite communication OFDM

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The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions:insights from a single-arm,phase II trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2202-2214页

作者： Bo Cheng Caichen Li Jianfu Li Longlong Gong Peng Liang Ying Chen Shuting Zhan Shan Xiong Ran Zhong Hengrui Liang Yi Feng Runchen Wang Haixuan Wang Hongbo Zheng Jun Liu Chengzhi Zhou Wenlong Shao Yuan Qiu Jiancong Sun Zhanhong Xie Zhu Liang Chenglin Yang Xiuyu Cai Chunxia Su Wei Wang Jianxing He Wenhua Liang Department of Thoracic Surgery and oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Medical Department Genecast Biotechnology Co.LtdWuxiChina Department of Radiation oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Department of Respiratory Medicine the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Department of Cardiothoracic Surgery Affiliated Hospital of Guangdong Medical UniversityZhanjiangChina Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenChina Department of VIP Inpatient Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaSun Yat-sen UniversityGuangzhouChina Department of Medical oncology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina

Immune checkpoint inhibitors targeting the programmed cell death-1(PD-1)protein significantly improve survival in patients with advanced non-small-cell lung cancer(NSCLC),but its impact on early-stage ground-glass opacity(GGO)lesions remains *** is a single-arm,phase II trial(NCT04026841)using Simon’s optimal two-stage design,of which 4 doses of sintilimab(200 mg per 3 weeks)were administrated in 36 enrolled multiple primary lung cancer(MPLC)patients with persistent high-risk(Lung-RADS category 4 or had progressed within 6 months)*** primary endpoint was objective response rate(ORR).T/B/NK-cell subpopulations,TCR-seq,cytokines,exosomal RNA,and multiplexed immunohistochemistry(mIHC)were monitored and compared between responders and ***,two intent-to-treat(ITT)lesions(pure-GGO or GGO-predominant)showed responses(ORR:5.6%,2/36),and no patients had progressive disease(PD).No grade 3-5 TRAEs *** total response rate considering two ITT lesions and three non-intent-to-treat(NITT)lesions(pure-solid or solid-predominant)was 13.9%(5/36).The proportion of CD8^(+)T cells,the ratio of CD8^(+)/CD4^(+),and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over ***,the mIHC analysis showed more CD8^(+)T cells infiltrated in ***,responders’cytokine concentrations of EGF and CTLA-4 increased during *** exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among ***,PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety *** effects were associated with specific T-cell re-distribution,EGF/CTLA-4 cytokine compensation,and regulation of metabolism pathways.

关键词： lesions metabolism doses

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Mapping the intellectual structure and emerging trends for the application of nanomaterials in gastric cancer:A bibliometric study

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World Journal of Gastrointestinal oncology 2024年第5期16卷 2181-2199页

作者： Bo-Na Liu Xiao-Li Gao Ying Piao Department of oncology General Hospital of Northern Theater CommandShenyang 110015Liaoning ProvinceChina

BACKGROUND Recent reviews have outlined the main nanomaterials used in relation to gastrointestinal tumors and described the basic properties of these ***,the research hotspots and trends in the application of nanomaterials in gastric cancer(GC)remain *** To demonstrate the knowledge structure and evolutionary trends of research into the application of nanomaterials in *** Publications related to the application of nanomaterials in GC were retrieved from the Web of Science Core Collection for this systematic review and bibliometric *** and CiteSpace were used for bibliometric and visualization *** From 2000 to 2022,the application of nanomaterials in GC developed *** keyword co-occurrence analysis showed that the related research topics were divided into three clusters:(1)The application of nanomaterials in GC treatment;(2)The application and toxicity of nanomaterials in GC diagnosis;and(3)The effects of nanomaterials on the biological behavior of GC ***,silver nanoparticles,and green synthesis are the latest high-frequency keywords that represent promising future research *** The application of nanomaterials in GC diagnosis and treatment and the mechanisms of their effects on GC cells have been major themes in this field over the past 23 years.

关键词： Nanomaterials Gastric cancer Bibliometrics Drug delivery VOSviewer CiteSpace Systematic review

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An overview of the physiopathology and various treatment strategies for polycystic ovary syndrome

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生殖与发育医学(英文) 2024年第1期08卷 50-60页

作者： Rajabi Ayda Babaie Soraya Oskouei Behnaz Sadeghzadeh Mehdizadeh Amir Farshbaf-Khalili Azizeh Department of Reproductive Biology Faculty of Advanced Medical Sciences Hematology and oncology research Center Student research Committee 2. Department of Anatomy 3. Faculty of Medicine 4. Yasouj University of Medical Sciences 5. Yasouj 63614 6. Iran Physical Medicine and Rehabilitation research Center Aging research Institute 9. Tabriz University of Medical Sciences 10. Tabriz 51368

Polycystic ovary syndrome (PCOS), a common endocrine disorder with metabolic and reproductive consequences, affects a significant percentage of women of reproductive age. Because of its complexity and impact on the quality of life, PCOS requires timely diagnosis and screening for complications. The most common clinical manifestations of PCOS are hirsutism, hyperandrogenism, acne, irregular cycles, amenorrhea, and anovulation. Although PCOS has different clinical manifestations in women, hyperandrogenism, and anovulation are the most common symptoms. A good medical history, examination, blood tests, and ultrasound findings facilitate the diagnosis of PCOS. Novel treatments have also undergone clinical trials to improve the symptoms of PCOS. However, comprehensive review articles investigating the different communities of this disease are limited, and this review aimed to collect data on the different etiologies of PCOS along with the latest diagnostic methods and the most common and up-to-date treatments for this disease.

关键词： Polycystic ovary syndrome Endocrine disorder Hyperandrogenism Hyperinsulinemia Anovulation Amenorrhea

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Prognosis prediction and immune microenvironment features of breast cancer indicated by a cuproptosis-associated long non-coding RNA signature

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Genes & Diseases 2024年第5期11卷 66-69页

作者： Siyi Liu Juanchan Huang Wei Zhao Department of Radiation oncology Guangxi Medical University Cancer HospitalNanningGuangxi 530000China Guangxi Medical University NanningGuangxi 530000China Department of oncology Affiliated Wuming Hospital of Guangxi Medical UniversityNanningGuangxi 530000China

Cuproptosis is a newly discovered type of programmed cell death that involves the depletion of intracellular copper and is not influenced by other inhibitors of programmed cell *** modality was first identified and named by Tsvetkov et al in the previous year.1 To further explore the relationship between cuproptosis,the tumor microenvironment,immunotherapy,and prognosis for breast cancer(BC),the expression patterns of 19 cuproptosis-related long non-coding RNAs(lncRNAs)were determined using data from the Cancer Genome Atlas(TCGA).

关键词： breast cancer microenvironment

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Reversal of tamoxifen resistance by artemisinin in ER+breast cancer:bioinformatics analysis and experimental validation

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oncology research 2024年第6期32卷 1093-1107页

作者： ZHILI ZHUO DONGNI ZHANG WENPING LU XIAOQING WU YONGJIA CUI WEIXUAN ZHANG MENGFAN ZHANG Department of oncology China Academy of Chinese Medical Sciences Guang’anmen HospitalBeijingChina

Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant ***(TAM)serves as the primary treatment for HR+breast ***,drug resistance often leads to recurrence,underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence ***(ART)has demonstrated efficacy in inhibiting the growth of drug-resistant cells,positioning art as a viable option for counteracting endocrine *** study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental *** characterized genes(ar,cdkn1a,erbb2,esr1,hsp90aa1)and seven drug-disease crossover genes(cyp2e1,rorc,mapk10,glp1r,egfr,pgr,mgll)were identified using WGCNA crossover *** functional enrichment analyses were *** findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and-sensitized ***-seq analysis revealed high expression of key cluster genes in epithelial cells,suggesting artemisinin’s specific impact on tumor cells in estrogen receptor(ER)-positive BC *** target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance *** results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.

关键词： Artemisinin Tamoxifen resistance Breast cancer

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Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo

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oncology research 2024年第6期32卷 1109-1118页

作者： ZHIGANG XIA MENGYAO TIAN YUCAI CHENG WENFANG YI ZEFAN DU TIANWEN LI YUCHEN WEN LINDI LI YONG LIU CHUN CHEN Pediatric Hematology laboratory Division of Hematology/OncologyDepartment of PediatricsThe Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Scientific research Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological ***,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion *** and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell ***,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment ***:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological ***,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.

关键词： CD19 CAR-T B-cell hematologic malignancies Metabolism In vivo

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