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Screening for metastasis-related genes in mouse melanoma cells through sequential tail vein injection

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Biophysics Reports 2024年第1期10卷 15-21页

作者： Qinggang Hao Rui Dong Weiyu Bai Dong Chang Xinyi Yao Yingru Zhang Huangying Xu Huiyan Li Xiang Kui Feng Wang Yan Wang Chengqin Wang Yujie Lei Yan Chen Junling Shen Lei Sang Yan Bai Jianwei Sun Center for Life Sciences Yunnan Key Laboratory of Cell Metabolism and Diseases State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan School of Life Sciences Yunnan University key laboratory of tumor Immunological Prevention and Treatment of Yunnan Province Yan'an Hospital Affiliated to Kunming Medical University Shandong Provincial key laboratory of Animal Resistance biology Collaborative Innovation Center of Cell Biology in Universities of Shandong Center for Cell Structure and Function Institute of Biomedical Science College of Life Sciences Shandong Normal University Department of Pathology The Second Affiliated Hospital of Kunming Medical University State key laboratory of Bioactive Molecules and Druggability Assessment Institute of Genomic Medicine College of Pharmacy Jinan University Department of Pathology School of Basic Medicine Qingdao University Department of Thoracic Surgery Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center

tumor metastasis, responsible for approximately 90% of cancer-associated mortality, remains poorly understood. Here in this study, we employed a melanoma lung metastasis model to screen for metastasis-related genes. By sequential tail vein injection of mouse melanoma B16F10 cells and the subsequently derived cells from lung metastasis into BALB/c mice, we successfully obtained highly metastatic B16F15 cells after five rounds of in vivo screening. RNA-sequencing analysis of B16F15 and B16F10 cells revealed a number of differentially expressed genes, some of these genes have previously been associated with tumor metastasis while others are novel discoveries. The identification of these metastasis-related genes not only improves our understanding of the metastasis mechanisms, but also provides potential diagnostic biomarkers and therapeutic targets for metastatic melanoma.

关键词： Melanoma Lung metastasis model Gene screening Tail vein injection

Inhalable metal–organic framework-mediated cuproptosis combined with PD-L1 checkpoint blockade for lung metastasis synergistic immunotherapy

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2281-2297页

作者： Chongzheng Yan Ying Liu Guozhi Zhao Huatian Yang Huaiyou Lv Genju Li Yuhan Li Yaqing Fu Fengqin Sun Yafei Feng Yizhe Li Zhongxi Zhao Department of Pharmaceutics Key Laboratory of Chemical Biology of Ministry of EducationSchool of Pharmaceutical SciencesCheelloo College of MedicineShandong UniversityJinan 250012China key University laboratory of Pharmaceutics&Drug Delivery Systems of Shandong Province School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China

Cuproptosis shows enormous application prospects in lung metastasis ***,the glycolysis,Cu^(+)efflux mechanisms,and insufficient lung drug accumulation severely restrict cuproptosis ***,an inhalable poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate)(OPDEA)-coated copper-based metal–organic framework encapsulating pyruvate dehydrogenase kinase 1 siRNA(siPDK)is constructed for mediating cuproptosis and subsequently promoting lung metastasis immunotherapy,namely *** inhalation,OMP shows highly efficient lung accumulation and long-term retention,ascribing to the OPDEA-mediated pulmonary mucosa *** tumor cells,OMP is degraded to release Cu2+under acidic condition,which will be reduced to toxic Cu^(+)to induce cuproptosis under glutathione(GSH)***,siPDK released from OMP inhibits intracellular glycolysis and adenosine-5ʹ-triphosphate(ATP)production,then blocking the Cu^(+)efflux protein ATP7B,thereby rendering tumor cells more sensitive to OMP-mediated ***,OMP-mediated cuproptosis triggers immunogenic cell death(ICD)to promote dendritic cells(DCs)maturation and CD8^(+)T cells ***,OMP-induced cuproptosis up-regulates membrane-associated programmed cell death-ligand 1(PD-L1)expression and induces soluble PD-L1 secretion,and thus synergizes with anti-PD-L1 antibodies(aPD-L1)to reprogram immunosuppressive tumor microenvironment,finally yielding improved immunotherapy ***,OMP may serve as an efficient inhalable nanoplatform and afford preferable efficacy against lung metastasis through inducing cuproptosis and combining with aPD-L1.

关键词： Cuproptosis Immunogenic cell death PD-L1 checkpoint blockade Copper-based metal-organic framework Immunotherapy tumor microenvironment Transmucosal deliveryLung metastasis

PCK1 attenuates tumor stemness via activating the Hippo signaling pathway in hepatocellular carcinoma

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Genes & Diseases 2024年第4期11卷 340-352页

作者： Rui Liu Yi Liu Wenlu Zhang Guiji Zhang Zhirong Zhang Luyi Huang Ni Tang Kai Wang key laboratory of molecular biology for Infectious Diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400016China Department of Clinical laboratory Sichuan Clinical Research Center for CancerSichuan Cancer Hospital&InstituteSichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduSichuan 610041China

Liver cancer stem cells were found to rely on glycolysis as the preferred metabolic *** carboxylase 1(PCK1),a gluconeogenic metabolic enzyme,is down-regulated in hepatocellular carcinoma and is closely related to poor *** onco-genesis and progression of tumors are closely related to cancer stem *** is not completely clear whether the PCK1 deficiency increases the stemness of hepatoma cells and promotes the oncogenesis of hepatocellular ***,the results showed that PCK1 inhibited the self-renewal property of hepatoma cells,reduced the mRNA level of cancer stem cell markers,and inhibited ***,PCK1 increased the sensitivity of hepatocellular carci-noma cells to ***,we found that PCK1 activated the Hippo pathway by enhancing the phosphorylation of YAP and inhibiting its nuclear *** reduced the stemness of hepatoma cells and promoted the pro-apoptotic effect of ***,combined treatment with verteporfin and sorafenib may be a potential anti-tumor strat-egy in hepatocellular carcinoma.

关键词： Cancer stem cells Chemoresistance Gluconeogenesis Hepatocellular carcinoma YAP

Current status and trends in small nucleic acid drug development:Leading the future

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3802-3817页

作者： Yuxi Miao Chen Fu Zhaojin Yu Lifeng Yu Yu Tang Minjie Wei Department of Pharmacology School of PharmacyChina Medical UniversityShenyang 110122China Liaoning key laboratory of molecular Targeted Anti-tumor Drug Development and Evaluation China Medical UniversityShenyang 110122China Liaoning Medical Diagnosis and Treatment Center Shenyang 110000China Department of Oncology Cancer Hospital of China Medical UniversityLiaoning Cancer Hospital and InstituteShenyang 110042China

Small nucleic acid drugs,composed of nucleotides,represent a novel class of pharmaceuticals that differ significantly from conventional small molecule and antibody-based *** agents function by selectively targeting specific genes or their corresponding messenger RNAs(mRNAs),further modulating gene expression and regulating translation-related *** examples within this category include antisense oligonucleotides(ASO),small interfering RNAs(siRNAs),micro-RNAs(miRNAs),and *** emergence of small nucleic acid drugs as a focal point in contemporary biopharmaceutical research is attributed to their remarkable specificity,facile design,abbreviated development cycles,expansive target spectrum,and prolonged *** challenges such as poor stability,immunogenicity,and permeability issues have been addressed through the integration of chemical modifications and the development of drug delivery *** review provides an overview of the current status and prospective trends in small nucleic acid drug *** with a historical context,we introduce the primary classifications and mechanisms of small nucleic acid ***,we delve into the advantages of the *** and Drug Administration(FDA)approved drugs and mainly discuss the challenges encountered during their *** from researching chemical modification and delivery system that efficiently deliver and enrich small nucleic acid drugs to target tissues,promoting endosomal escape is a critical scientific question and important research direction in siRNA drug *** directions in this field will prioritize addressing these challenges to facilitate the clinical transformation of small nucleic acid drugs.

关键词： Small nucleic acid drugs Oligonucleotide drugs siRNA ASO miRNA Aptamer RNAi Drug development

Serum tumor markers (carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 72-4, carbohydrate antigen 24-2, ferritin) and gastric cancer prognosis correlation

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World Journal of Gastrointestinal Surgery 2024年第9期16卷 2808-2814页

作者： Jie-Wen Zhu Ling-Zhen Gong Qian-Wen Wang Department of Clinical laboratory Huangshi Central Hospital(Affiliated Hospital of Hubei Polytechnic University)Hubei Key Laboratory of Kidney Disease Pathogenesis and InterventionHuangshi Tumor Molecular Diagnosis and Treatment Key LaboratoryHuangshi 435000Hubei ProvinceChina

BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the *** some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of great significance to find reliable prog-nostic indicators to guide the treatment and management of patients with gastric *** To explore the relationship between serum levels of five biomarkers[carcinoem-bryonic antigen(CEA),carbohydrate antigen(CA)19-9,CA72-4,CA24-2,and ferritin]and prognosis in patients with gastric *** This study included 200 patients with gastric adenocarcinoma,and conducted an in-depth analysis of their baseline characteristics,relationship between tumor markers and staging,and *** study found that CA19-9 has a signi-ficant correlation with tumor stage,the average levels of CA24-2,CEA,CA72-4 and ferritin were slightly increased disregarding the stage of *** analysis showed that increases in CEA,CA19-9,CA24-2,and ferritin were all associated with shortened overall survival of *** multivariate ana-lysis revealed that elevated serum CA72-4 levels were an inde-pendent adverse prognostic *** This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA,CA19-9,CA72-4,CA24-2 and ferritin in patients with gastric cancer and prognosis,and can be used as important indicators for prognostic evaluation of gastric *** particular,markers that appear abnormally elevated initially may help identify gastric cancer patients with poor *** Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer,and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.

关键词： Gastric cancer Prognosis Carcinoembryonic antigen Carbohydrate antigen 19-9 Carbohydrate antigen 72-4 Carbohydrate antigen 24-2 Ferritin Serum markers Retrospective study

The structure of TRAF7 coiled-coil trimer provides insight into its function in zebrafish embryonic development

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Journal of molecular Cell biology 2024年第1期16卷 43-53页

作者： Xiaozhen Song Ruixing Hu Yi Chen Man Xiao Hong Zhang Shengnan Wu Qing Lu molecular Diagnostic laboratory Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200040China Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education)Shanghai Jiao Tong UniversityShanghai 200030China laboratory of Development and Diseases and State key laboratory for Medical Genomics Shanghai Institute of HematologyRuĳin HospitalShanghai JiaoTong University School of MedicineShanghai 200025China

TRAF7 serves as a crucial intracellular adaptor and E3 ubiquitin ligase involved in signal transduction pathways,contributing to immune responses,tumor progression,and embryonic *** mutations within the coiled-coil(CC)domain and WD40 repeat domain of TRAF7 could cause brain tumors,while germline pathogenic mutations contribute to severe developmental ***,the precise molecular mechanism underlying TRAF7 involvement in embryonic development remains *** this study,we employed zebrafish as an in vivo model ***7 knock down caused defects in zebrafish embryonic *** determined the crystal structure of TRAF7 CC domain at 3.3Åresolution and found that the CC region trimerization was essential for TRAF7 functionality during zebrafish embryonic ***,disease-causing mutations in TRAF7 CC region could impair the trimer formation,consequently impacting early embryonic development of ***,our study sheds light on the molecular mechanism of TRAF7 CC trimer formation and its pivotal role in embryonic development.

关键词： TRAF7 coiled-coil domain crystal structure trimerization embryonic development

Role of cancer stem cell ecosystem on breast cancer metastasis and related mouse models

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Zoological Research 2024年第3期45卷 506-517页

作者： Xilei Peng Haonan Dong Lixing Zhang Suling Liu Fudan University Shanghai Cancer Center&Institutes of Biomedical Sciences/State key laboratory of Genetic Engineering/Cancer Institutes/Department of Oncology/key laboratory of Breast Cancer in Shanghai/Shanghai key laboratory of Medical Epigenetics/Shanghai key laboratory of Radiation Oncology/International Co-laboratory of Medical Epigenetics and Metabolism Ministry of Science and Technology/Shanghai Medical College/Fudan UniversityShanghai 200032China

Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and *** cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and *** have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast *** tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ***,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer *** this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory ***,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during ***,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.

关键词： Breast cancer Metastasis Cancer stem cell Ecosystem tumor microenvironment Mouse model

Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2194-2209页

作者： Zhilin Li Qianfeng Zhang Zhiqian Li Long Ren Dayi Pan Qiyong Gong Zhongwei Gu Hao Cai Kui Luo Department of Radiology Huaxi MR Research Center(HMRRC)Clinical Research Center for BreastDepartment of Breast SurgeryDepartment of Thoracic Surgery and Institute of Thoracic OncologyFrontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China Hospital Sichuan UniversityChengdu 610041China Functional and molecular Imaging key laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610041China Department of Radiology West China Xiamen Hospital of Sichuan UniversityXiamen 361021China key laboratory of Medicinal Chemistry for Natural Resource Ministry of EducationYunnan Key Laboratory of Research and Development for Natural ProductsSchool of PharmacyYunnan UniversityKunming 650500China

Despite the great potential of anti-PD-L1 antibodies for immunotherapy,their low response rate due to an immunosuppressive tumor microenvironment has hampered their *** address this issue,we constructed a cell membrane-coated nanosystem(mB4S)to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor *** this system,Epirubicin(EPI)as an immunogenic cell death(ICD)inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes(STING)agonist was encapsulated into *** internalization of mB4S,EPI was acidic-responsively released to induce ICD,which was characterized by an increased level of calreticulin(CRT)exposure and enhanced ATP ***,diABZI effectively activated the STING *** with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells(DCs)and CD8+T cells,promoting cytokines secretion,up-regulating M1-like tumor-associated macrophages(TAMs)and down-regulating immunosuppressive myeloid-derived suppressor cells(MDSCs).Therefore,this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+T cells infiltration,creating an immuno-supportive microenvironment,thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.

关键词： Glycopolymer Polymer prodrug Immunogenic cell death Nanoassembly Epirubicin STING pathway Immuno-supportive microenvironment Immunotherapy

一种快速响应的光致变色SCC-MOF用于光开关和信息加密

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Science China Materials 2024年第2期67卷 698-704页

作者：宋玙潘张佳妮王俊如李恺袁迎雪李波臧双全 Henan key laboratory of Crystalline molecular Functional Materials Henan International Joint Laboratory of Tumor Theranostical Cluster MaterialsGreen Catalysis Centerand College of ChemistryZhengzhou UniversityZhengzhou 450001China College of Chemistry and Pharmaceutical Engineering Nanyang Normal UniversityNanyang 473061China

由于银硫簇的不稳定性和有限的刺激响应特性,构建新型的具有光开关性质的银-硫簇基金属有机框架(SCC-MOF)面临着重大挑战.基于此,本文设计并合成了一种新型光致变色的SCC-MOF(Ag_(12)-BMPTC),该材料利用二芳基乙烯配体和银硫簇前驱体通... 详细信息

由于银硫簇的不稳定性和有限的刺激响应特性,构建新型的具有光开关性质的银-硫簇基金属有机框架(SCC-MOF)面临着重大挑战.基于此,本文设计并合成了一种新型光致变色的SCC-MOF(Ag_(12)-BMPTC),该材料利用二芳基乙烯配体和银硫簇前驱体通过溶剂缓慢挥发而得到.Ag_(12)-BMPTC在365和500 nm光照射下表现出优异的可逆光响应特性.此外,这种光开关性质为其在信息加密和手性开关方面提供了潜在应用.本研究不仅扩大了SCC-MOF的种类,而且为设计和合成新型光致变色材料提供了新的思路和潜在应用.

关键词： silver nanoclusters metal-organic frameworks photochromism diarylethene information encryption