2021
Effects of MTX-23, a Novel PROTAC of Androgen Receptor Splice Variant-7 and Androgen Receptor, on CRPC Resistant to Second-Line Antiandrogen Therapy
Lee G, Nagaya N, Desantis J, Madura K, Sabaawy H, Kim W, Vaz R, Cruciani G, Kim I. Effects of MTX-23, a Novel PROTAC of Androgen Receptor Splice Variant-7 and Androgen Receptor, on CRPC Resistant to Second-Line Antiandrogen Therapy. Molecular Cancer Therapeutics 2021, 20: 490-499. PMID: 33277442, DOI: 10.1158/1535-7163.mct-20-0417.Peer-Reviewed Original ResearchConceptsCastration-resistant prostate cancerSecond-line antiandrogen therapyAR full lengthAndrogen receptor splice variant 7AR-V7Antiandrogen therapyAndrogen-responsive prostate cancer cellsProstate cancer cellular proliferationHuman prostate cancer cell linesProstate cancer cell linesStandard of careCancer cellular proliferationCellular proliferationPotential therapeutic valueProstate cancer cellsAgents abirateroneCancer cell linesProteolysis Targeting ChimerasMechanisms of resistanceAndrogen receptorAR DNAProstate cancerTumor growthTherapeutic valueAntiproliferative effects
2020
Plasma, Prostate and Urine Levels of Tocopherols and Metabolites in Men after Supplementation with a γ-Tocopherol-Rich Vitamin E Mixture
Goodin S, Kim I, Lee M, Shih W, Orlick M, Zheng X, Yang C. Plasma, Prostate and Urine Levels of Tocopherols and Metabolites in Men after Supplementation with a γ-Tocopherol-Rich Vitamin E Mixture. Nutrition And Cancer 2020, 73: 2740-2750. PMID: 33319628, PMCID: PMC8670097, DOI: 10.1080/01635581.2020.1857412.Peer-Reviewed Original ResearchConceptsVitamin E mixtureProstate tissue levelsUrine samplesReported adverse eventsDay of surgeryProstate cancer patientsPhase 0 trialsDays of supplementationCancer preventive activityAdverse eventsBlood lossTreatment armsUrine levelsCancer patientsRadical prostatectomyAnimal modelsVitamin EProstate tissueTissue levelsPreventive activitiesProstate levelsSupplementationPatientsProstatectomySurgery
2019
TCF4 induces enzalutamide resistance via neuroendocrine differentiation in prostate cancer
Lee G, Rosenfeld J, Kim W, Kwon Y, Palapattu G, Mehra R, Kim W, Kim I. TCF4 induces enzalutamide resistance via neuroendocrine differentiation in prostate cancer. PLOS ONE 2019, 14: e0213488. PMID: 31536510, PMCID: PMC6752758, DOI: 10.1371/journal.pone.0213488.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzamidesBeta CateninCell Line, TumorDisease Models, AnimalDrug Resistance, NeoplasmHumansMaleMiceMice, KnockoutNeuroendocrine CellsNitrilesPhenylthiohydantoinProstatic NeoplasmsProtein BindingProtein TransportTranscription Factor 7-Like 2 ProteinXenograft Model Antitumor AssaysConceptsCastration-resistant prostate cancerEnzalutamide resistanceTranscription factor 4Neuroendocrine differentiationProstate cancerSecond-generation androgen receptor antagonistHuman prostate cancer cell linesLNCaP human prostate cancer cell lineResistant prostate cancerProstate cancer cell linesStandard of careAndrogen receptor antagonistMouse xenograft modelExpression levelsCell linesTCF4 overexpressionCancer cell linesMedian timeClinical benefitReceptor antagonistNeuroendocrine markersMetastatic CaPTreatment resistanceXenograft modelParental cell lineDihydrotestosterone Increases Cytotoxic Activity of Macrophages on Prostate Cancer Cells via TRAIL
Lee G, Kim J, Kwon S, Stein M, Hong J, Nagaya N, Billakanti S, Kim M, Kim W, Kim I. Dihydrotestosterone Increases Cytotoxic Activity of Macrophages on Prostate Cancer Cells via TRAIL. Endocrinology 2019, 160: 2049-2060. PMID: 31184711, PMCID: PMC6691685, DOI: 10.1210/en.2019-00367.Peer-Reviewed Original ResearchConceptsAndrogen deprivation therapyCell linesHuman peripheral blood monocytesMetastatic prostate cancerPotential treatment optionPeripheral blood monocytesCytotoxicity of macrophagesHuman monocyte cell lineProstate cancer cellsCaP cell linesMonocyte cell lineVivo mouse studiesCytotoxic activityMurine macrophage cell lineApoptosis-inducing ligandConcentration-dependent mannerDeprivation therapyClodronate liposomesTreatment optionsM1 polarizationCaP tumorsAndrogen receptorMacrophage cell lineProstate cancerImmune response
2018
The Anticancer Effects of Garlic Extracts on Bladder Cancer Compared to Cisplatin: A Common Mechanism of Action via Centromere Protein M
Kim W, Seo S, Byun Y, Kang H, Kim Y, Lee S, Jeong P, Song H, Choe S, Kim D, Kim S, Ha Y, Moon S, Lee G, Kim I, Yun S, Kim W. The Anticancer Effects of Garlic Extracts on Bladder Cancer Compared to Cisplatin: A Common Mechanism of Action via Centromere Protein M. The American Journal Of Chinese Medicine 2018, 46: 689-705. PMID: 29595070, DOI: 10.1142/s0192415x18500362.Peer-Reviewed Original ResearchConceptsCentromere protein MBladder cancerBC patientsGarlic extractBetter progression-free survivalNude mouse xenograft modelProgression-free survivalCisplatin-treated miceBALB/cTissue microarray analysisNegative control miceMouse xenograft modelBC cell linesEffect of garlicMicroarray analysisCisplatin groupControl miceTumor weightControl tumorsTumor volumeNormal controlsXenograft modelSide effectsBody weightTumor tissue
2017
Garlic extract in bladder cancer prevention: Evidence from T24 bladder cancer cell xenograft model, tissue microarray, and gene network analysis
Kim W, Seo S, Byun Y, Kang H, Kim Y, Lee S, Jeong P, Seo Y, Choe S, Kim D, Kim S, Moon S, Choi Y, Lee G, Kim I, Yun S, Kim W. Garlic extract in bladder cancer prevention: Evidence from T24 bladder cancer cell xenograft model, tissue microarray, and gene network analysis. International Journal Of Oncology 2017, 51: 204-212. PMID: 28498422, DOI: 10.3892/ijo.2017.3993.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBiomarkers, TumorCell ProliferationGarlicGene Expression Regulation, NeoplasticGene Regulatory NetworksHumansMaleMiceMice, Inbred BALB CMice, NudePlant ExtractsSignal TransductionTissue Array AnalysisTumor Cells, CulturedUrinary Bladder NeoplasmsXenograft Model Antitumor AssaysConceptsCancer preventionBladder cancerGarlic extractXenograft modelNude mouse xenograft modelAcceptable safety profileBladder cancer preventionCancer prevention activitiesCell xenograft modelBALB/cTissue microarray analysisMouse xenograft modelMicroarray analysisTumor weightBC patientsSafety profileTumor volumeTissue microarrayControl groupGene network analysisControl dietPrevention activitiesPreventionExtract intakePotential mechanismsIntracrine androgen biosynthesis in renal cell carcinoma
Lee G, Han C, Kwon Y, Patel R, Modi P, Kwon S, Faiena I, Patel N, Singer E, Ahn H, Kim W, Kim I. Intracrine androgen biosynthesis in renal cell carcinoma. British Journal Of Cancer 2017, 116: 937-943. PMID: 28253524, PMCID: PMC5379152, DOI: 10.1038/bjc.2017.42.Peer-Reviewed Original ResearchMeSH KeywordsAbiraterone AcetateAndrogensAnimalsAntineoplastic AgentsApoptosisBenzamidesBlotting, WesternCarcinoma, Renal CellCell ProliferationDihydrotestosteroneFemaleHumansImmunoenzyme TechniquesKidney NeoplasmsMaleMiceMice, NudeNitrilesOrchiectomyPhenylthiohydantoinPrognosisProstatic NeoplasmsProstatic Neoplasms, Castration-ResistantReal-Time Polymerase Chain ReactionReceptors, AndrogenReverse Transcriptase Polymerase Chain ReactionRNA, MessengerTestosteroneTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsRenal cell carcinomaCastration-resistant prostate cancerRCC cell linesAnti-androgen therapyHuman RCC cell linesAndrogen biosynthesisAbiraterone acetateCell carcinomaAndrogen receptorTumor volumeCell linesAndrogen deprivation therapyHigher tumor stageProstate cancer patientsMouse xenograft studiesGenitourinary cancersTumor suppressionSignificant tumor suppressionRCC patientsTumor stageCancer patientsMale miceProstate cancerIntratumoral steroidogenesisXenograft studies
2016
BMI-1 Targeting Interferes with Patient-Derived Tumor-Initiating Cell Survival and Tumor Growth in Prostate Cancer
Bansal N, Bartucci M, Yusuff S, Davis S, Flaherty K, Huselid E, Patrizii M, Jones D, Cao L, Sydorenko N, Moon Y, Zhong H, Medina D, Kerrigan J, Stein M, Kim I, Davis T, DiPaola R, Bertino J, Sabaawy H. BMI-1 Targeting Interferes with Patient-Derived Tumor-Initiating Cell Survival and Tumor Growth in Prostate Cancer. Clinical Cancer Research 2016, 22: 6176-6191. PMID: 27307599, PMCID: PMC5159329, DOI: 10.1158/1078-0432.ccr-15-3107.Peer-Reviewed Original ResearchConceptsTumor-initiating cellsProstate tumor-initiating cellsBmi-1Androgen receptor-directed therapyIntrinsic therapy resistanceReceptor-directed therapyProstate cancer managementProstate cancer treatmentMore effective therapiesBmi-1 expressionProstate cancer cellsStem cell-like traitsSelf-renewing tumor-initiating cellsCell-like traitsPatient-derived cellsEffective therapyTumor relapseCancer managementXenograft modelTherapy resistancePharmacologic inhibitionBmi-1 functionTherapyNormal tissuesCancer treatmentPharmacodynamics, pharmacokinetics and clinical efficacy of phosphodiesterase-5 inhibitors
Hong J, Kwon Y, Kim I. Pharmacodynamics, pharmacokinetics and clinical efficacy of phosphodiesterase-5 inhibitors. Expert Opinion On Drug Metabolism & Toxicology 2016, 13: 183-192. PMID: 27690667, DOI: 10.1080/17425255.2017.1244265.Peer-Reviewed Original ResearchConceptsErectile dysfunctionClinical efficacyEvidence-based clinical efficacyTreatment of EDNon-urological conditionsDrug-related toxicityFirst-line drugsType 5 inhibitorsPhosphodiesterase-5 inhibitorsNew clinical usesChronic administrationBasic science articlesNeuroprotective roleClinical trialsPDE5IsBeneficial effectsClinical usesFurther studiesPharmacodynamicsPharmacokineticsEfficacyInhibitorsImpactful studiesBroad spectrumPDE5i
2014
Enzalutamide: looking back at its preclinical discovery
Ha Y, Kim I. Enzalutamide: looking back at its preclinical discovery. Expert Opinion On Drug Discovery 2014, 9: 837-845. PMID: 24820058, DOI: 10.1517/17460441.2014.918947.Peer-Reviewed Original ResearchConceptsCastration-recurrent PCaFirst-line therapyProstate cancerClinical developmentCastration-recurrent prostate cancerStandard first-line therapyAndrogen-AR axisAR agonist activityMetastatic prostate cancerAR nuclear translocationSelective AR modulatorsFurther clinical studiesAndrogen receptor antagonistPre-clinical discoveryDrug clinical developmentSequential therapyOverall survivalTargeted agentsReceptor antagonistClinical studiesPreclinical discoveryNew agentsAR modulatorsAgonist activityFDA approval
2013
Enrichment of human prostate cancer cells with tumor initiating properties in mouse and zebrafish xenografts by differential adhesion
Bansal N, Davis S, Tereshchenko I, Budak‐Alpdogan T, Zhong H, Stein M, Kim I, DiPaola R, Bertino J, Sabaawy H. Enrichment of human prostate cancer cells with tumor initiating properties in mouse and zebrafish xenografts by differential adhesion. The Prostate 2013, 74: 187-200. PMID: 24154958, PMCID: PMC3939797, DOI: 10.1002/pros.22740.Peer-Reviewed Original ResearchMechanism of pro‐tumorigenic effect of BMP‐6: Neovascularization involving tumor‐associated macrophages and IL‐1α
Kwon S, Lee G, Lee J, Iwakura Y, Kim W, Kim I. Mechanism of pro‐tumorigenic effect of BMP‐6: Neovascularization involving tumor‐associated macrophages and IL‐1α. The Prostate 2013, 74: 121-133. PMID: 24185914, DOI: 10.1002/pros.22734.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Morphogenetic Protein 6CarcinogenesisCell DifferentiationCell Line, TumorCell ProliferationCoculture TechniquesEndothelium, VascularHumansInterleukin-1alphaMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutNeovascularization, PathologicNF-kappa BProstatic NeoplasmsSignal TransductionSmad1 ProteinConceptsBone morphogenetic protein 6Prostate cancer growthTumor-associated macrophagesIL-1APro-tumorigenic effectsCancer growthHuman prostate cancer cell linesHuman prostate cancer tissuesLNCaP human prostate cancer cell lineProstate cancer cell linesTube formationProstate cancer tissuesTHP-1 cellsEndothelial tube formationCancer cell linesIL-1αProstate cancerKnockout miceCD11b-DTRCancer tissuesTumor growthNF-kB1Endothelial cellsMacrophagesConditioned mediaBone morphogenetic protein‐6 induces castration resistance in prostate cancer cells through tumor infiltrating macrophages
Lee G, Jung Y, Ha Y, Kim J, Kim W, Kim I. Bone morphogenetic protein‐6 induces castration resistance in prostate cancer cells through tumor infiltrating macrophages. Cancer Science 2013, 104: 1027-1032. PMID: 23710822, PMCID: PMC7657257, DOI: 10.1111/cas.12206.Peer-Reviewed Original ResearchMeSH KeywordsAndrogen Receptor AntagonistsAndrogensAnilidesAnimalsBenzamidesBenzofuransBone Morphogenetic Protein 6Cell Line, TumorDihydrotestosteroneHumansInterleukin-6Lymphocytes, Tumor-InfiltratingMacrophagesMaleMiceNitrilesPhenylthiohydantoinPromoter Regions, GeneticProstatic Neoplasms, Castration-ResistantQuinolinesReceptors, AndrogenTosyl CompoundsUp-RegulationConceptsCaP cell linesCastration resistanceInterleukin-6Castration-resistant prostate cancerContext of macrophagesHuman CaP cell linesExpression of ARRemoval of macrophagesAndrogen receptor mRNAProstate cancer progressionBMP-6Presence of dihydrotestosteroneProstate cancer cellsCell linesPresence of macrophagesPleiotropic growth factorBone morphogenetic proteinClodronate liposomesTRAMP-C1AR upregulationProstate cancerAndrogen hypersensitivityMacrophage coculturesReceptor mRNACell countBMP-6 in Renal Cell Carcinoma Promotes Tumor Proliferation through IL-10–Dependent M2 Polarization of Tumor-Associated Macrophages
Lee J, Lee G, Woo S, Ha Y, Kwon S, Kim W, Kim I. BMP-6 in Renal Cell Carcinoma Promotes Tumor Proliferation through IL-10–Dependent M2 Polarization of Tumor-Associated Macrophages. Cancer Research 2013, 73: 3604-3614. PMID: 23633487, DOI: 10.1158/0008-5472.can-12-4563.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Morphogenetic Protein 6Carcinoma, Renal CellCell LineCell Line, TumorCell ProliferationClodronic AcidDoxycyclineHumansImmunoblottingInterleukin-10Kaplan-Meier EstimateKidney NeoplasmsMacrophagesMiceMice, Inbred BALB CMice, KnockoutMicroscopy, FluorescenceReverse Transcriptase Polymerase Chain ReactionRNA InterferenceSmad5 ProteinSTAT3 Transcription FactorTumor BurdenRadium Ra 223 dichloride in castration-resistant prostate cancer.
Joung J, Ha Y, Kim I. Radium Ra 223 dichloride in castration-resistant prostate cancer. Drugs Of Today 2013, 49: 483-90. PMID: 23977665, DOI: 10.1358/dot.2013.49.8.1968670.Peer-Reviewed Original ResearchConceptsRadium Ra 223 dichlorideCastration-resistant prostate cancerRa-223 dichlorideBone metastasesProstate cancerLarge randomized phase III trialsRandomized phase III trialMedian overall survivalPhase III trialsPlacebo groupIII trialsOverall survivalPreclinical studiesAntitumor effectsBone marrowCanine modelHigh biological effectPatientsMetastasisCancerBiological effectsKBq/Low toxicityRatsMarrowEnzalutamide for the treatment of castration-resistant prostate cancer.
Ha Y, Goodin S, DiPaola R, Kim I. Enzalutamide for the treatment of castration-resistant prostate cancer. Drugs Of Today 2013, 49: 7-13. PMID: 23362491, DOI: 10.1358/dot.2013.49.1.1910724.Peer-Reviewed Original ResearchConceptsCastration-resistant prostate cancerPhase III trialsAndrogen receptorIII trialsProstate cancerTreatment of CRPCMetastatic castration-resistant prostate cancerPhase I/II studyEffectiveness of enzalutamidePrior docetaxel chemotherapyBinding of AROptimal safety profileMajor clinical challengeSignificant antitumor activityPrior chemotherapyDocetaxel chemotherapyII studySafety profileClinical challengePreclinical studiesDrug AdministrationTumor growthChemotherapyU.S. FoodAntitumor activity
2011
Bone morphogenetic protein 6-induced interleukin-1β expression in macrophages requires PU.1/Smad1 interaction
Lee G, Jung Y, Lee J, Kim W, Kim I. Bone morphogenetic protein 6-induced interleukin-1β expression in macrophages requires PU.1/Smad1 interaction. Molecular Immunology 2011, 48: 1540-1547. PMID: 21571370, DOI: 10.1016/j.molimm.2011.04.019.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Morphogenetic Protein 6Bone Morphogenetic Protein Receptors, Type IBone Morphogenetic Protein Receptors, Type IICells, CulturedExtracellular Signal-Regulated MAP KinasesFluorescent Antibody TechniqueImmunoblottingImmunoprecipitationInterleukin-1betaJNK Mitogen-Activated Protein KinasesMacrophagesMiceNitric Oxide Synthase Type IIProto-Oncogene ProteinsReverse Transcriptase Polymerase Chain ReactionSignal TransductionSmad1 ProteinTrans-ActivatorsMacrophages induce neuroendocrine differentiation of prostate cancer cells via BMP6‐IL6 Loop
Lee G, Kwon S, Lee J, Jeon S, Jang K, Choi H, Lee H, Kim W, Lee D, Kim I. Macrophages induce neuroendocrine differentiation of prostate cancer cells via BMP6‐IL6 Loop. The Prostate 2011, 71: 1525-1537. PMID: 21374653, DOI: 10.1002/pros.21369.Peer-Reviewed Original ResearchConceptsProstate cancer cellsHormone-refractory prostate cancerRefractory prostate cancerNeuroendocrine differentiationBone morphogenetic protein 6IL-6Cancer cellsProstate cancerInterleukin-6 knockout miceTRAMP-C2 cell lineHuman prostate cancer tissuesNeuroendocrine cellsCell linesParathyroid hormone-related peptideTRAMP-C2 prostate cancer cellsTRAMP-C2 cellsMacrophage-depleted miceProstate Cancer Neuroendocrine DifferentiationIL-6 expressionTHP-1 human monocytic cell lineHormone-related peptideProstate cancer tissuesHuman monocytic cell lineRAW 264.7 murine macrophage cell lineEffect of macrophages
2010
Induction of Interleukin-6 Expression by Bone Morphogenetic Protein-6 in Macrophages Requires Both SMAD and p38 Signaling Pathways*
Lee G, Kwon S, Lee J, Jeon S, Jang K, Choi H, Lee H, Kim W, Kim S, Kim I. Induction of Interleukin-6 Expression by Bone Morphogenetic Protein-6 in Macrophages Requires Both SMAD and p38 Signaling Pathways*. Journal Of Biological Chemistry 2010, 285: 39401-39408. PMID: 20889504, PMCID: PMC2998138, DOI: 10.1074/jbc.m110.103705.Peer-Reviewed Original ResearchConceptsBone morphogenetic protein 6BMP receptor type IIProtein 6Activin-like kinase 2Non-Smad pathwaysTranscription factor GATA4P38 Signaling PathwayTarget genesKnockdown experimentsKinase 2Signaling pathwaysSignaling mechanismReceptor type IISmadIntracellular levelsIL-6 inductionPathwayGrowth factorInductionExpressionInterleukin-6 expressionTranscriptionMacrophagesGenesGATA4
2009
Bone morphogenetic protein‐6 induces the expression of inducible nitric oxide synthase in macrophages
Kwon S, Lee G, Lee J, Kim W, Kim I. Bone morphogenetic protein‐6 induces the expression of inducible nitric oxide synthase in macrophages. Immunology 2009, 128: e758-e765. PMID: 19740337, PMCID: PMC2753926, DOI: 10.1111/j.1365-2567.2009.03079.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeutralizingBone Morphogenetic Protein 6Cells, CulturedCycloheximideDactinomycinHumansInterleukin-1betaMacrophages, PeritonealMiceNF-kappa BNitric Oxide Synthase Type IIProtein Synthesis InhibitorsRecombinant ProteinsSignal TransductionSmad ProteinsTumor Necrosis Factor-alphaConceptsBone morphogenetic proteinBMP-6Effects of BMPBone morphogenetic protein 6New protein synthesisMorphogenetic proteinsMurine macrophage cell lineMacrophage cell lineImportant regulatorProtein synthesisProtein 6Cell typesMouse peritoneal macrophagesCell linesActinomycin DNF-kappaBSmadExpressionDose-dependent mannerSynthaseNitric oxide synthasePathwayInductionInducible nitric oxide synthasePeritoneal macrophages