2024
RAD51 Expression as a Biomarker to Predict Efficacy of Platinum-Based Chemotherapy and PD-L1 Blockade for Muscle-Invasive Bladder Cancer.
Li B, Jin K, Liu Z, Su X, Xu Z, Liu G, Xu J, Chang Y, Wang Y, Zhu Y, Xu L, Wang Z, Liu H, Zhang W. RAD51 Expression as a Biomarker to Predict Efficacy of Platinum-Based Chemotherapy and PD-L1 Blockade for Muscle-Invasive Bladder Cancer. Journal Of Immunotherapy 2024 PMID: 38800996, DOI: 10.1097/cji.0000000000000525.Peer-Reviewed Original ResearchMuscle-invasive bladder cancerPD-L1 blockadePlatinum-based chemotherapyPD-L1Zhongshan HospitalBladder cancerProgrammed cell death ligand 1Muscle-invasive bladder cancer patientsResponse to platinum-based chemotherapyEfficacy of platinum-based chemotherapyCell death ligand 1DNA damage repairPD-L1 inhibitorsDeath-ligand 1Tumor immune contexturePredictive efficacyGenomic instabilityIMvigor210 cohortImmune contextureChemotherapeutic responseTherapeutic responseClinical benefitRetrospective studyClinical valueTherapeutic guidanceIntegration of CD4+ T cells and molecular subtype predicts benefit from PD‐L1 blockade in muscle‐invasive bladder cancer
Liu G, Jin K, Liu Z, Su X, Xu Z, Li B, Xu J, Liu H, Chang Y, Zhu Y, Xu L, Wang Z, Wang Y, Zhang W. Integration of CD4+ T cells and molecular subtype predicts benefit from PD‐L1 blockade in muscle‐invasive bladder cancer. Cancer Science 2024, 115: 1306-1316. PMID: 38402640, PMCID: PMC11007017, DOI: 10.1111/cas.16119.Peer-Reviewed Original ResearchMuscle-invasive bladder cancerImmune checkpoint blockadeCombination of immune checkpoint blockadeCD4<sup>+</sup> T cellsFibroblast growth factor receptor 3T cellsZhongshan HospitalMolecular subtypesBladder cancerMuscle-invasive bladder cancer patientsResponses to FGFR inhibitorsCD4+ T cellsPD-L1 blockadeImmune suppressive microenvironmentTransforming growth factor-bGrowth factor BIMvigor210 cohortCheckpoint blockadePD-L1Clinical responseSuppressive microenvironmentImmune microenvironmentImmunotherapeutic responseChemotherapeutic responseClinical outcomesTP53 disruptive mutation predicts platinum‐based chemotherapy and PD‐1/PD‐L1 blockade response in urothelial carcinoma
Jin K, Xu J, Su X, Xu Z, Li B, Liu G, Liu H, Wang Y, Zhu Y, Xu L, Zhang W, Liu Z, Wang Z, Chang Y, Xu J. TP53 disruptive mutation predicts platinum‐based chemotherapy and PD‐1/PD‐L1 blockade response in urothelial carcinoma. The Journal Of Pathology 2024, 263: 139-149. PMID: 38380548, DOI: 10.1002/path.6266.Peer-Reviewed Original ResearchPD-1/PD-L1TP53 mutationsOverall survivalUrothelial carcinomaGenetic alterationsClinical significance of TP53 mutationsPD-1/PD-L1 blockade therapyCD8<sup>+</sup> T cell infiltrationIncreased CD8<sup>+</sup> T cell infiltrationElevated tumor mutation burdenSignificance of TP53 mutationsPD-1/PD-L1 blockadeTP53 disruptive mutationsInflamed tumor microenvironmentPlatinum-based chemotherapyT cell infiltrationTumor immune microenvironmentTumor mutational burdenWild-type TP53P53 protein functionTP53 mutation statusSensitive to immunotherapyHeterogeneous clinical outcomesPoorer overall survivalImprove risk stratificationPOLQ identifies a better response subset to immunotherapy in muscle‐invasive bladder cancer with high PD‐L1
Liu G, Jin K, Liu Z, Su X, Xu Z, Li B, Xu J, Chang Y, Wang Y, Zhu Y, Xu L, Xu J, Wang Z, Liu H, Zhang W. POLQ identifies a better response subset to immunotherapy in muscle‐invasive bladder cancer with high PD‐L1. Cancer Medicine 2024, 13: e6962. PMID: 38457207, PMCID: PMC10922026, DOI: 10.1002/cam4.6962.Peer-Reviewed Original ResearchConceptsMuscle-invasive bladder cancerProgrammed cell death ligand 1Immune checkpoint blockadeTumor mutational burdenImmune microenvironmentZhongshan HospitalBladder cancerInfiltration of immune effector cellsEfficacy of immune checkpoint blockadePOLQ expressionCell death ligand 1High tumor mutational burdenChromosomal instabilityActive tumor immune microenvironmentAntitumor immune microenvironmentDeath-ligand 1Efficacy of immunotherapyPlatinum-based chemotherapyTumor immune microenvironmentSensitivity to chemotherapyImmune effector cellsProduction of neoantigensIMvigor210 cohortCheckpoint blockadePD-L1Integrative score based on CDK6, PD-L1 and TMB predicts response to platinum-based chemotherapy and PD-1/PD-L1 blockade in muscle-invasive bladder cancer
Su X, Jin K, Guo Q, Xu Z, Liu Z, Zeng H, Wang Y, Zhu Y, Xu L, Wang Z, Chang Y, Xu J. Integrative score based on CDK6, PD-L1 and TMB predicts response to platinum-based chemotherapy and PD-1/PD-L1 blockade in muscle-invasive bladder cancer. British Journal Of Cancer 2024, 130: 852-860. PMID: 38212482, PMCID: PMC10912081, DOI: 10.1038/s41416-023-02572-9.Peer-Reviewed Original ResearchMuscle-invasive bladder cancerImmune checkpoint blockadeResponse to ICBResponse to platinum-based chemotherapyPlatinum-based chemotherapyPD-L1Bladder cancerZhongshan HospitalPD-1/PD-L1 blockadePD-1/PD-L1Cox regression analysisKaplan-Meier survivalCheckpoint blockadeCDK6 expressionResponse scoresImmune microenvironmentTherapy responseClinical outcomesPoor prognosisCancer Genome AtlasClinical significanceChemotherapyClinical relevanceProgression of cell cycleCancer treatmentIntegrating molecular subtype and CD8+ T cells infiltration to predict treatment response and survival in muscle-invasive bladder cancer
Li B, Jin K, Liu Z, Su X, Xu Z, Liu G, Xu J, Liu H, Chang Y, Wang Y, Zhu Y, Wang Z, Xu L, Zhang W. Integrating molecular subtype and CD8+ T cells infiltration to predict treatment response and survival in muscle-invasive bladder cancer. Cancer Immunology, Immunotherapy 2024, 73: 66. PMID: 38430246, PMCID: PMC10908619, DOI: 10.1007/s00262-024-03651-3.Peer-Reviewed Original ResearchConceptsMuscle-invasive bladder cancerCD8+ T cell infiltrationT cell infiltrationMolecular subtypesBladder cancerEfficacy of antitumor responseElevated tumor mutation burdenPositive response to immunotherapyCD8+ T cellsPD-L1 expressionResponse to immunotherapyTumor mutational burdenResponse to chemotherapyOverall survival outcomesSubtype-specific treatmentAntitumor responsePD-L1Intrinsic subtypesMutational burdenZhongshan HospitalSurvival outcomesT cellsTreatment responseResultsAmong patientsCancer Genome Atlas
2023
Analysis of the human kidney transcriptome and plasma proteome identifies markers of proximal tubule maladaptation to injury
Wen Y, Su E, Xu L, Menez S, Moledina D, Obeid W, Palevsky P, Mansour S, Devarajan P, Cantley L, Cahan P, Parikh C, Project K, Injury T. Analysis of the human kidney transcriptome and plasma proteome identifies markers of proximal tubule maladaptation to injury. Science Translational Medicine 2023, 15: eade7287. PMID: 38091407, DOI: 10.1126/scitranslmed.ade7287.Peer-Reviewed Original Research
2022
Integration of Human Kidney Transcriptome and Plasma Proteome Identifies Novel Biomarkers of Proximal Tubule Maladaptation to Injury
Wen Y, Su E, Xu L, Menez S, Moledina D, Palevsky P, Cantley L, Cahan P, Parikh C. Integration of Human Kidney Transcriptome and Plasma Proteome Identifies Novel Biomarkers of Proximal Tubule Maladaptation to Injury. Journal Of The American Society Of Nephrology 2022, 33: 358-358. DOI: 10.1681/asn.20223311s1358b.Peer-Reviewed Original ResearchImmune-Mediated Tubule Atrophy Promotes AKI to CKD Transition
Xu L, Guo J, Moledina D, Cantley L. Immune-Mediated Tubule Atrophy Promotes AKI to CKD Transition. Journal Of The American Society Of Nephrology 2022, 33: 872-872. DOI: 10.1681/asn.20223311s1872b.Peer-Reviewed Original ResearchUrine Uromodulin as a Biomarker of Kidney Tubulointerstitial Fibrosis
Melchinger H, Calderon-Gutierrez F, Obeid W, Xu L, Shaw MM, Luciano RL, Kuperman M, Moeckel GW, Kashgarian M, Wilson FP, Parikh CR, Moledina DG. Urine Uromodulin as a Biomarker of Kidney Tubulointerstitial Fibrosis. Clinical Journal Of The American Society Of Nephrology 2022, 17: 1284-1292. PMID: 35948365, PMCID: PMC9625093, DOI: 10.2215/cjn.04360422.Peer-Reviewed Original ResearchConceptsInterstitial fibrosis/tubular atrophyUrine uromodulinTubular atrophyThick ascending limbUrine albuminSerum creatinineKidney biopsyTubulointerstitial fibrosisMultivariable linear regression modelsTime of biopsyKidney's thick ascending limbAcademic medical centerHuman kidney biopsiesKidney tubulointerstitial fibrosisTubular healthMultivariable analysisHistologic featuresHistologic findingsHistologic changesKidney fibrosisIndependent associationFibrotic modelMultivariable modelMedical CenterMurine modelImmune-mediated tubule atrophy promotes acute kidney injury to chronic kidney disease transition
Xu L, Guo J, Moledina DG, Cantley LG. Immune-mediated tubule atrophy promotes acute kidney injury to chronic kidney disease transition. Nature Communications 2022, 13: 4892. PMID: 35986026, PMCID: PMC9391331, DOI: 10.1038/s41467-022-32634-0.Peer-Reviewed Original ResearchConceptsAcute kidney injuryKidney injuryT cellsChronic kidney disease transitionIschemia-reperfusion kidney injuryKidney disease transitionChronic kidney diseaseDepletion of neutrophilsGlomerular filtration rateT cell recruitmentTubular cell lossMacrophage persistenceProinflammatory neutrophilsTubule damageKidney atrophyContralateral kidneyNeutrophil numbersContralateral nephrectomyKidney diseaseTubule atrophyFiltration rateCell recruitmentMore macrophagesDay 14Day 5Arginase-1 Is Required for Macrophage-Mediated Renal Tubule Regeneration
Shin NS, Marlier A, Xu L, Doilicho N, Linberg D, Guo J, Cantley LG. Arginase-1 Is Required for Macrophage-Mediated Renal Tubule Regeneration. Journal Of The American Society Of Nephrology 2022, 33: 1077-1086. PMID: 35577558, PMCID: PMC9161787, DOI: 10.1681/asn.2021121548.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryTubular cell proliferationArginase-1Contralateral nephrectomyRenal repairFl/Littermate controlsTubular cellsReceptor 1GM-CSFRenal tubular cell proliferationRenal tubule regenerationMacrophage scavenger receptor 1Mannose receptor 1Cell proliferative responsesCell proliferationScavenger receptor 1Coculture of macrophagesDead cell debrisKidney injuryKidney repairRenal responseProinflammatory activationTubule regenerationMouse survivalKidney-Targeted Renalase Agonist Prevents Cisplatin-Induced Chronic Kidney Disease by Inhibiting Regulated Necrosis and Inflammation
Guo X, Xu L, Velazquez H, Chen TM, Williams RM, Heller DA, Burtness B, Safirstein R, Desir GV. Kidney-Targeted Renalase Agonist Prevents Cisplatin-Induced Chronic Kidney Disease by Inhibiting Regulated Necrosis and Inflammation. Journal Of The American Society Of Nephrology 2022, 33: 342-356. PMID: 34921111, PMCID: PMC8819981, DOI: 10.1681/asn.2021040439.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntineoplastic AgentsCell LineCisplatinCreatinineDisease Models, AnimalGene ExpressionGlomerular Filtration RateHepatitis A Virus Cellular Receptor 1HumansKidneyMiceMice, Inbred C57BLMice, KnockoutMonoamine OxidaseNanocapsulesPeptidesRenal Insufficiency, ChronicConceptsRenal proximal tubulesSingle-cell RNA sequencing analysisMesoscale nanoparticlesFirst doseCisplatin chemotherapyProximal tubulesAgonist peptideInduced Chronic Kidney DiseaseGenetic deletionNeck squamous cell carcinomaRNA sequencing analysisCisplatin-induced AKIKidney-targeted deliveryChronic kidney diseaseDevelopment of CKDSquamous cell carcinomaAdministration of cisplatinPlasma renalaseAdvanced headCell carcinomaInflammatory cytokinesKidney diseasePlasma creatinineSystemic administrationRegulated necrosisCharacterization of temporospatial distribution of renal tubular casts by nephron tracking after ischemia-reperfusion injury
Shin NS, Marlier A, Xu L, Lam T, Cantley LG, Guo JK. Characterization of temporospatial distribution of renal tubular casts by nephron tracking after ischemia-reperfusion injury. American Journal Of Physiology. Renal Physiology 2022, 322: f322-f334. PMID: 35100823, PMCID: PMC8897010, DOI: 10.1152/ajprenal.00284.2021.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryCast formationGlomerular filtration rateTubular cast formationUrine 24 hDetached epithelial cellsDead cell debrisRenal recoveryRenal functionFiltration rateS3 tubulesTubular castsTubular cellsTubular nucleiKidney sectionsOuter medullaTrypsin levelsEntire nephronRenal tubular castsFuture interventionsInjurySelective lossTubule segmentsEpithelial cellsKidney
2021
The Role of Myeloid Cells in Acute Kidney Injury and Kidney Repair
Xu L. The Role of Myeloid Cells in Acute Kidney Injury and Kidney Repair. Kidney360 2021, 2: 1852-1864. PMID: 35372990, PMCID: PMC8785849, DOI: 10.34067/kid.0000672021.Peer-Reviewed Original ResearchBiomarkers of inflammation and repair in kidney disease progression
Puthumana J, Thiessen-Philbrook H, Xu L, Coca SG, Garg AX, Himmelfarb J, Bhatraju PK, Ikizler T, Siew E, Ware LB, Liu KD, Go AS, Kaufman JS, Kimmel PL, Chinchilli VM, Cantley L, Parikh CR. Biomarkers of inflammation and repair in kidney disease progression. Journal Of Clinical Investigation 2021, 131 PMID: 33290282, PMCID: PMC7843225, DOI: 10.1172/jci139927.Peer-Reviewed Original ResearchConceptsKidney disease progressionComposite kidney outcomeChronic kidney diseaseDisease progressionEGFR declineKidney outcomesRenal atrophyMouse modelMonocyte chemoattractant protein-1CHI3L1 mRNA expressionComposite renal outcomeGreater eGFR declineIntroductionAcute kidney injuryProspective cohort studyGlomerular filtration rateBiomarkers of inflammationProgressive renal fibrosisYKL-40 levelsChemoattractant protein-1Traditional clinical variablesLong-term progressionLoop of HenleMultimarker scoreRenal outcomesKidney injury
2019
Tubular GM-CSF Promotes Late MCP-1/CCR2-Mediated Fibrosis and Inflammation after Ischemia/Reperfusion Injury
Xu L, Sharkey D, Cantley LG. Tubular GM-CSF Promotes Late MCP-1/CCR2-Mediated Fibrosis and Inflammation after Ischemia/Reperfusion Injury. Journal Of The American Society Of Nephrology 2019, 30: 1825-1840. PMID: 31315923, PMCID: PMC6779361, DOI: 10.1681/asn.2019010068.Peer-Reviewed Original ResearchConceptsIschemia/reperfusion injuryWild-type miceTubular cellsTubular injuryReperfusion injuryImmune cellsKidney ischemia/reperfusion injuryUnilateral ischemia/reperfusion injuryMCP-1/CCR2Monocyte chemoattractant protein-1Initial kidney damageInjured tubular cellsKidney 14 daysKidney injury markersProgressive interstitial fibrosisProfibrotic growth factorsChemoattractant protein-1MCP-1 receptorGranulocyte-macrophage colony-stimulating factorRenal tubular cellsNumber of macrophagesTime of repairColony-stimulating factorCoculture of macrophagesMacrophages persistFolate-Decorated Polyamidoamine Dendrimer Nanoparticles for Head and Neck Cancer Gene Therapy
Xu L, Yang H. Folate-Decorated Polyamidoamine Dendrimer Nanoparticles for Head and Neck Cancer Gene Therapy. Methods In Molecular Biology 2019, 1974: 393-408. PMID: 31099016, DOI: 10.1007/978-1-4939-9220-1_26.BooksConceptsGene therapyGene delivery systemsNeck cancer gene therapyCancer gene therapyDelivery systemNanoparticle carriersGene deliveryDendrimer nanoparticlesHigh biocompatibilityGene transfectionKnockdown efficiencyTumor targetingSuitable platformFolic acidIRDye 800CWSustained retentionGeneration 4DendrimersNanoparticlesBioimagingCarriersBiocompatibilityHereinPlatformPlasmid
2017
Synthesis and Application of Injectable Bioorthogonal Dendrimer Hydrogels for Local Drug Delivery
Xu L, Cooper RC, Wang J, Yeudall WA, Yang H. Synthesis and Application of Injectable Bioorthogonal Dendrimer Hydrogels for Local Drug Delivery. ACS Biomaterials Science & Engineering 2017, 3: 1641-1653. PMID: 29147682, PMCID: PMC5683721, DOI: 10.1021/acsbiomaterials.7b00166.Peer-Reviewed Original ResearchStrain-promoted azide-alkyne cycloadditionAzide-alkyne cycloadditionDegree of PEGylationCross-linked networkDBCO groupsBioorthogonal chemistryDendrimer generationPEG spacerDrug deliveryChain lengthGeneration 4.0Sustained releaseHigh cytocompatibilityLocal drug deliveryPEG-BALoading densityDibenzocyclooctyneAnticancer drugsHydrogelsPhysical propertiesStructural parametersDendrimersBisazideChemistryCycloadditionBreast Regression Protein–39/Chitinase 3–Like 1 Promotes Renal Fibrosis after Kidney Injury via Activation of Myofibroblasts
Montgomery TA, Xu L, Mason S, Chinnadurai A, Lee CG, Elias JA, Cantley LG. Breast Regression Protein–39/Chitinase 3–Like 1 Promotes Renal Fibrosis after Kidney Injury via Activation of Myofibroblasts. Journal Of The American Society Of Nephrology 2017, 28: 3218-3226. PMID: 28679671, PMCID: PMC5661290, DOI: 10.1681/asn.2017010110.Peer-Reviewed Original ResearchConceptsBRP-39Kidney injuryKidney repairChitinase 3Unilateral ischemia-reperfusion injuryBreast regression protein 39Kidney 14 daysPromotes Renal FibrosisRobust inflammatory infiltrateSevere interstitial fibrosisIschemia-reperfusion injuryActivation of myofibroblastsTubular cell survivalProfibrotic growth factorsWild-type miceIL-13 receptorAnalysis of macrophagesMacrophage persistenceTubular injuryInflammatory infiltrateProfibrotic markersInterstitial fibrosisRenal fibrosisMyofibroblast accumulationProfibrotic signaling