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Risk factors and a predictive nomogram for lymph node metastasis in superficial esophageal squamous cell carcinoma

World Journal of Gastroenterology 2023年第47期29卷 6138-6147页

作者： Jin Wang Xian Zhang Tao Gan Ni-Ni Rao Kai Deng Jin-Lin Yang Department of Gastroenterology and Hepatology Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal CancerFrontiers Science Center for Disease-Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Pathology West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina School of Life Science and Technology University of Electronic Science and Technology of ChinaChengdu 610064Sichuan ProvinceChina

BACKGROUND Superficial esophageal squamous cell carcinoma(ESCC)is defined as cancer infiltrating the mucosa and submucosa,regardless of regional lymph node metastasis(LNM).Endoscopic resection of superficial ESCC is suitable for lesions that have no or low risk of *** with a high risk of LNM always need further treatment after endoscopic ***,accurately assessing the risk of LNM is critical for additional treatment *** To analyze risk factors for LNM and develop a nomogram to predict LNM risk in superficial ESCC *** Clinical and pathological data of superficial ESCC patients undergoing esophagectomy from January 1,2009 to January 31,2016 were *** regression analysis was used to predict LNM risk factors,and a nomogram was developed based on risk factors derived from multivariate logistic regression *** receiver operating characteristic(ROC)curve was used to obtain the accuracy of the nomogram *** total of 4660 patients with esophageal cancer underwent *** these,474 superficial ESCC patientswere enrolled in the final analysis,with 322 patients in the training set and 142 patients in the validation *** of LNM was 3.29%(5/152)for intramucosal cancer and increased to 26.40%(85/322)for *** logistic analysis showed that tumor size,invasive depth,tumor differentiation,infiltrativegrowth pattern,tumor budding,and lymphovascular invasion were significantly correlated with *** using these six variables showed good discrimination with an area under the ROC curve of 0.789(95%CI:0.737-0.841)in the training set and 0.827(95%CI:0.755-0.899)in the validation *** developed a useful nomogram model to predict LNM risk for superficial ESCC patients which will facilitateadditional decision-making in treating patients who undergo endoscopic resection.

关键词： Superficial esophageal squamous cell carcinoma Lymph node metastasis Risk factors Nomogram Predictive model

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Polyurethane scaffold-based 3D lung cancer model recapitulates in vivo tumor biological behavior for nanoparticulate drug screening

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Regenerative Biomaterials 2023年第1期10卷 1618-1631页

作者： Lu Sun Xiaofei Wang Yushui He Boran Chen Baoyin Shan Jinlong Yang Ruoran Wang Xihang Zeng Jiehua Li Hong Tan Ruichao Liang Department of Targeting Therapy&Immunology Department of Radiation OncologyCancer CenterWest China HospitalSichuan UniversityChengdu 610041People's Republic of China Department of Medical Polymer Materials Department of Artificial OrganismCollege of Polymer Science and EngineeringState Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu 610065People’s Republic of China Department of Neurosurgery West China HospitalSichuan UniversityChengdu 610041People’s Republic of China

Lung cancer is the leading cause of cancer mortality *** studies in lung cancer hold the promise of screening for effective antitumor agents,but mechanistic studies and drug discovery based on 2D cell models have a high failure rate in getting to the ***,there is an urgent need to explore more reliable and effective in vitro lung cancer ***,we prepared a series of three-dimensional(3D)waterborne biodegradable polyurethane(WBPU)scaffolds as substrates to establish biomimetic tumor models in *** 3D WBPU scaffolds were porous and could absorb large amounts of free water,facilitating the exchange of substances(nutrients and metabolic waste)and cell *** scaffolds at wet state could simulate the mechanics(elastic modulus∼1.9 kPa)and morphology(porous structures)of lung tissue and exhibit good biocompatibility.A549 lung cancer cells showed adherent growth pattern and rapidly formed 3D spheroids on WBPU *** results showed that the scaffold-based 3D lung cancer model promoted the expression of anti-apoptotic and epithelial-mesenchymal transition-related genes,giving it a more moderate growth and adhesion pattern compared to 2D *** addition,WBPU scaffold-established 3D lung cancer model revealed a closer expression of proteins to in vivo tumor,including tumor stem cell markers,cell proliferation,apoptosis,invasion and tumor resistance *** on these features,we further demonstrated that the 3D lung cancer model established by the WBPU scaffold was very similar to the in vivo tumor in terms of both resistance and tolerance to nanoparticulate *** together,WBPU scaffold-based lung cancer model could better mimic the growth,microenvironment and drug response of tumor in *** emerging 3D culture system holds promise to shorten the formulation cycle of individualized treatments and reduce the use of animals while providing valid research data for clinical trials.

关键词： WBPU scaffolds 3D culture lung cancer biomimetic nanoparticulate drug screening

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Predictors of efficacy of corticosteroid switching from abiraterone plus prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer

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Asian Journal of Andrology 2022年第2期24卷 154-160页

作者： Yu-Chao Ni Jin-Ge Zhao Meng-Ni Zhang Yi-Jun Zhang Zhen-Yu Yang Ni Chen Jun-Ru Chen Peng-Fei Shen Guang-Xi Sun Xing-Ming Zhang Yong-Hong Li Hao Zeng Department of Urology Institute of UrologyWest China HospitalSichuan UniversityChengdu 610041China Department of Pathology West China HospitalSichuan UniversityChengdu 610041China Department of Pathology Sun Yat-Sen University Cancer CenterGuangzhou 510060China Department of Urology Sun Yat-Sen University Cancer CenterGuangzhou 510060China

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer(mCRPC).Here,we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate(AA).We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from west china hospital and Sun Yat-Sen University Cancer Center between January 2016 and December *** cases received AA plus prednisone as first-line therapy during *** end points were biochemical progression-free survival(bPFS)and overall survival(OS).The risk groups were defined based on multivariate analysis.A total of 42(41.6%)and 25(24.8%)patients achieved 30%and 50%decline in prostate-specific antigen(PSA),respectively,after corticosteroid *** median bPFS and median OS on AA plus dexamethasone were 4.9(95%confidence interval[CI]:3.7–6.0)months and 18.8(95%CI:16.2–30.2)months,***-keto reductase family 1 member C3(AKR1C3)expression(hazard ratio[HR]:2.15,95%Cl:1.22–3.80,P=0.008)and baseline serum alkaline phosphatase(ALP;HR:4.95,95%Cl:2.40–10.19,P160 IU l−1(HR:3.41,95%Cl:1.57–7.38,P=0.002)together with PSA level at switch≥50 ng ml−1(HR:2.59,95%Cl:1.22–5.47,P=0.013)independently predicted poorer *** on the predictive factors in multivariate analysis,we developed two risk stratification tools to select candidates for corticosteroid *** of serum ALP level,PSA level,and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.

关键词： abiraterone acetate alkaline phosphatase corticosteroid switching dexamethasone metastatic castration-resistant prostate cancer

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Exosomes rewire the cartilage microenvironment in osteoarthritis:from intercellular communication to therapeutic strategies

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International Journal of Oral Science 2022年第3期14卷 259-274页

作者： Yuangang Wu Jiao Li Yi Zeng Wenchen Pu Xiaoyu Mu Kaibo Sun Yong Peng Bin Shen Orthopedic research Institute Department of OrthopedicsWest China HospitalSichuan UniversityChengduChina Laboratory of Molecular Oncology Frontiers Science Center for Disease-related Molecular NetworkState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduChina

Osteoarthritis(OA)is a prevalent degenerative joint disease characterized by cartilage loss and accounts for a major source of pain and disability ***,effective strategies for cartilage repair are lacking,and patients with advanced OA usually need joint *** comprehending OA pathogenesis may lead to transformative *** studies have reported that exosomes act as a new means of cell-to-cell communication by delivering multiple bioactive molecules to create a particular microenvironment that tunes cartilage ***,exosome cargos,such as noncoding RNAs(ncRNAs)and proteins,play a crucial role in OA progression by regulating the proliferation,apoptosis,autophagy,and inflammatory response of joint cells,rendering them promising candidates for OA monitoring and *** review systematically summarizes the current insight regarding the biogenesis and function of exosomes and their potential as therapeutic tools targeting cell-to-cell communication in OA,suggesting new realms to improve OA management.

关键词： Exosomes rewire the cartilage microenvironment in osteoarthritis from intercellular communication to therapeutic strategies

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Nanoparticles (NPs)-mediated Siglec15 silencing and macrophage repolarization for enhanced cancer immunotherapy

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Acta Pharmaceutica Sinica B 2023年第12期13卷 5048-5059页

作者： Xiaodi Liu Qi Zhang Yixia Liang Shiyu Xiong Yan Cai Jincheng Cao Yanni Xu Xiaolin Xu Ye Wu Qiang Lu Xiaoding Xu Baoming Luo Department of Ultrasound Laboratory of Ultrasound Imaging and DrugWest China HospitalSichuan UniversityChengdu 610041China Department of Ultrasound Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Ultrasound Central People's Hospital of ZhanjiangZhanjiang 524045China

cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer *** evidence has shown that interferon-gamma(IFN)could enhance CXCL9 secretion from macrophages to recruit T cells,but Siglec15 expressed on TAMs can attenuate T cell ***,targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor *** herein developed reductionresponsive nanoparticles(NPs)made with poly(disulfide amide)(PDSA)and lipid-poly(ethylene glycol)(lipid-PEG)for systemic delivery of Siglec15 siRNA(siSiglec15)and IFN for enhanced cancer *** intravenous administration,these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages(TAMs).With the highly concentrated glutathione(GSH)in the cytoplasm to destroy the nanostructure,the loaded IFN and si-Siglec15 could be rapidly released,which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation,leading to significant inhibition of hepatocellular carcinoma(HCC)growth when combining with the immune checkpoint *** strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.

关键词： Nanoparticles Tumor-associated macrophages Macrophage repolarization T cell infiltration T cell proliferation Cancer immunotherapy Siglec15 Hepatocellular carcinoma

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Dendritic nanomedicine enhances chemoimmunotherapy by disturbing metabolism of cancer-associated fibroblasts for deep penetration and activating function of immune cells

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3680-3696页

作者： Yunkun Li Xiaoding Shen Haitao Ding Yuxin Zhang Dayi Pan Liping Su Yahui Wu Zaixiang Fang Jie Zhoua Qiyong Gong Kui Luo Department of Radiology Huaxi MR Research Center(HMRRC)Frontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China HospitalSichuan 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

Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune ***,we constructed a PEGylated dendritic epirubicin(Epi)prodrug(Epi-P4D)to regulate the metabolism of cancer-associated fibroblasts(CAFs),thus enhancing Epi penetration into both multicellular tumor spheroids(MTSs)and tumor tissues in mouse colon cancer(CT26),mouse breast cancer(4T1)and human breast cancer(MDA-MB-231)*** cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin,α-SMA,and collagen ***,thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell(DC)maturation and subsequent immune activation,including elevating the CD4^(+)T cell population,reducing CD4^(+)and CD8^(+)T cell hyperactivation and exhaustion,and amplifying the natural killer(NK)cell proportion and effectively activating *** a result,this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy.

关键词： Dendritic prodrug Enhanced penetration Metabolic intervention Cancer-associated fibroblasts Immunogenic cell death Chemotherapy Immunotherapy Immune microenvironment reconstitution

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Identification of lncRNAs associated with T cells as potentialbiomarkers and therapeutic targets in lung adenocarcinoma

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Oncology research 2023年第6期31卷 967-988页

作者： LU SUN HUAICHENG TAN TING YU RUICHAO LIANG Department of Targeting Therapy&Immunology Cancer CenterWest China HospitalSichuan UniversityChengdu610041China Department of Radiation Oncology Cancer CenterWest China HospitalSichuan UniversityChengdu610041China Department of Pathology West China HospitalSichuan UniversityChengdu610041China Department of Neurosurgery West China HospitalSichuan UniversityChengdu610041China

Lung adenocarcinoma (LUAD) is the most common and deadliest subtype of lung cancer. To select moretargeted and effective treatments for individuals, further advances in classifying LUAD are urgently needed. Thenumber, type, and function of T cells in the tumor microenvironment (TME) determine the progression andtreatment response of LUAD. Long noncoding RNAs (lncRNAs), may regulate T cell differentiation, development,and activation. Thus, our aim was to identify T cell-related lncRNAs (T cell-Lncs) in LUAD and to investigatewhether T cell-Lncs could serve as potential stratifiers and therapeutic targets. Seven T cell-Lncs were identified tofurther establish the T cell-related lncRNA risk score (TRS) in LUAD. Low TRS individuals were characterized byrobust immune status, fewer genomic alterations, and remarkably longer survival than high TRS individuals. Theexcellent accuracy of TRS in predicting overall survival (OS) was validated in the TCGA-LUAD training cohort andthe GEO-LUAD validation cohort. Our data demonstrated the favorable predictive power of the TRS-basednomogram, which had important clinical significance in estimating the survival probability for individuals. Inaddition, individuals with low TRS could respond better to chemotherapy and immunotherapy than those with highTRS. LINC00525 was identified as a valuable study target, and the ability of LUAD to proliferate or invade wassignificantly attenuated by downregulation of LINC00525. In conclusion, the TRS established by T cell-Lncs couldunambiguously classify LUAD patients, predict their prognosis and guide their management. Moreover, our identifiedT cell-Lncs could provide potential therapeutic targets for LUAD.

关键词： Biomarkers T cell-related lncRNAs Tumor classification Tumor treatment Lung adenocarcinoma

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Implantable Polyurethane Scaffolds Loading with PEG-Paclitaxel Conjugates for the Treatment of Glioblastoma Multiforme

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Chinese Journal of Polymer Science 2022年第5期40卷 491-503页

作者： He-Cheng Wu Yuan Feng Xing-Ying Song Chun-Yang Song Jin-Lin Chen Yan-Chao Wang Xue-Ling He Rui-Chao Liang Jie-Hua Li Hong Tan College of Polymer Science and Engineering State Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu 610065China Department of Neurosurgery West China HospitalSichuan UniversityChengdu 610041China Laboratory Animal Center of Sichuan University Chengdu 610041China

Improvement of the treatment for Glioblastoma multiforme(GBM)especially the development of in situ controllable drug release is still a major *** this study,we developed waterborne biodegradable polyurethane(WBPU)scaffolds incorporated with redox-sensitive and RGD-decorated paclitaxel(PTX)polymer-drug conjugates(PDCs)for targeted GBM therapy in *** drug scaffolds could be implanted at residual GBM site ***-targeting PTX-PDCs were obtained through step-by-step conjugation of disulfide linked PTX,poly(ethylene glycol)(PEG),and arginine-glycine-aspartic acid(RGD).The RGD-modified PTX-PDCs were spherical nanoparticles(NPs)that would be released from scaffolds and identified GBM cells *** redox-sensitive PTX-PDCs would be decomposed and release PTX inside GBM cells under the circumstances of glutathione(GSH).The release profiles of PTX from the scaffolds with/without GSH were *** vitro cytotoxicity assay revealed that the dual-targeting PTX-PDCs from scaffolds could specifically kill GBM cells and protect normal cells,suggesting that dual-targeting PTX-PDC-loaded scaffolds may have the potential to repair tumor-induced brain *** vivo anti-recurrence assay indicated that the PTX-PDC-scaffolds could deliver PTX-PDCs to the GBM cells followed by inhibiting tumor growth and inducing *** general,the PTX prodrug-loaded devices exhibited significant anti-GBM effects and normal tissue protection simultaneously,indicating that the WBPU scaffolds incorporated with dual-targeting PTX-PDCs may be a promising strategy for local therapy of GBM.

关键词： GBM PDCs WBPU Scaffolds Controlled release

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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

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Morphine Re-arranges Chromatin Spatial Architecture of Primate Cortical Neurons

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Genomics, Proteomics & Bioinformatics 2023年第3期21卷 551-572页

作者： Liang Wang Xiaojie Wang Chunqi Liu Wei Xu Weihong Kuang Qian Bu Hongchun Li Ying Zhao Linhong Jiang Yaxing Chen Feng Qin Shu Li Qinfan Wei Xiaocong Liu Bin Liu Yuanyuan Chen Yanping Dai Hongbo Wang Jingwei Tian Gang Cao Yinglan Zhao Xiaobo Cen National Chengdu Center for Safety Evaluation of Drugs State Key Laboratory of Biotherapy/Collaborative Innovation Center for BiotherapyWest China Hospital of Sichuan UniversityChengdu 610041China Shenzhen Key Laboratory of Drug Addiction Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Department of Psychiatry West China Hospital of Sichuan UniversityChengdu 610041China School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University)Ministry of EducationCollaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of ShandongYantai UniversityYantai 264005China State Key Laboratory of Agricultural Microbiology Hubei Hongshan LaboratoryHuazhong Agricultural UniversityWuhan 430070China

The expression of linear DNA sequence is precisely regulated by the three-dimensional(3D)architecture of ***-induced aberrant gene networks of neurons have been extensively investigated;however,how morphine impacts the 3D genomic architecture of neurons is still ***,we applied digestion-ligation-only high-throughput chromosome conformation capture(DLO Hi-C)technology to investigate the effects of morphine on the 3D chromatin architecture of primate cortical *** receiving continuous morphine administration for 90 days on rhesus monkeys,we discovered that morphine re-arranged chromosome territories,with a total of 391 segmented compartments being *** altered over half of the detected topologically associated domains(TADs),most of which exhibited a variety of shifts,followed by separating and fusing *** of the looping events at kilobase-scale resolution revealed that morphine increased not only the number but also the length of differential ***,all identified differentially expressed genes from the RNA sequencing data were mapped to the specific TAD boundaries or differential loops,and were further validated for changed ***,an altered 3D genomic architecture of cortical neurons may regulate the gene networks associated with morphine *** finding provides critical hubs connecting chromosome spatial organization and gene networks associated with the morphine effects in humans.

关键词： Morphine Rhesus monkey Chromatin spatial architecture Topologically associated domain Loop

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