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 ResearchMeSH KeywordsAndrogen AntagonistsAnimalsApoptosisHumansMaleMiceProtein IsoformsReceptors, AndrogenTransfectionConceptsCastration-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
2019
Dihydrotestosterone 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
2017
Intracrine 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 treatment
2015
Increased Expression of Androgen Receptor mRNA in Human Renal Cell Carcinoma Cells is Associated with Poor Prognosis in Patients with Localized Renal Cell Carcinoma
Ha Y, Lee G, Modi P, Kwon Y, Ahn H, Kim W, Kim I. Increased Expression of Androgen Receptor mRNA in Human Renal Cell Carcinoma Cells is Associated with Poor Prognosis in Patients with Localized Renal Cell Carcinoma. Journal Of Urology 2015, 194: 1441-1448. PMID: 25796113, DOI: 10.1016/j.juro.2015.03.078.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorBlotting, WesternCarcinoma, Renal CellCell Line, TumorDisease ProgressionFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticHumansKidney NeoplasmsMaleMiddle AgedNeoplasm StagingPrognosisReal-Time Polymerase Chain ReactionReceptors, AndrogenRetrospective StudiesRNA, NeoplasmTime FactorsYoung AdultConceptsRenal cell carcinomaAndrogen receptor mRNA expressionReceptor mRNA expression levelsCancer-specific survivalCell carcinomaCell carcinoma cell linesReceptor mRNA expressionHuman renal cell carcinoma cell linesRenal cell carcinoma cell linesAndrogen receptorMRNA expression levelsSpecific survivalCarcinoma cell linesMultivariate Cox regression analysisLocalized Renal Cell CarcinomaMRNA expressionT2 renal cell carcinomaCell linesPathological stage T1Androgen receptor expressionCox regression analysisKaplan-Meier estimatesReceptor-positive cell linesChain reactionPositive renal cell carcinomas
2014
Prostate cancer bone metastases acquire resistance to androgen deprivation via WNT5A-mediated BMP-6 induction
Lee G, Kang D, Ha Y, Jung Y, Chung J, Min K, Kim T, Moon K, Chung J, Lee D, Kim W, Kim I. Prostate cancer bone metastases acquire resistance to androgen deprivation via WNT5A-mediated BMP-6 induction. British Journal Of Cancer 2014, 110: 1634-1644. PMID: 24518599, PMCID: PMC3960605, DOI: 10.1038/bjc.2014.23.Peer-Reviewed Original ResearchMeSH KeywordsAdultAndrogen AntagonistsAnilidesBone Morphogenetic Protein 6Bone NeoplasmsCell CommunicationCell Growth ProcessesCell Line, TumorHumansMaleMiddle AgedNeoplasm MetastasisNitrilesOrchiectomyProstatic Neoplasms, Castration-ResistantProto-Oncogene ProteinsReceptors, AndrogenRetrospective StudiesStromal CellsTosyl CompoundsWnt ProteinsWnt-5a ProteinConceptsCastration-resistant prostate cancerBone stromal cellsBone metastasesBone morphogenetic protein 6Castration resistanceCaP cell linesStromal cellsProstate cancerPrimary androgen deprivation therapyProstate-specific antigen progressionProstate cancer bone metastasisAndrogen-deprived mediumBone-tumor interactionAndrogen deprivation therapyFirst-line therapyCancer bone metastasisMetastatic prostate cancerAbsence of androgenAndrogen-depleted conditionsNF-κB pathwayCell linesPolymerase chain reaction arrayBMP-6 expressionAdvanced CaPDeprivation therapy
2013
Bone 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 countEnzalutamide 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
Macrophages 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
2002
Raloxifene, a selective estrogen receptor modulator, induces apoptosis in androgen-responsive human prostate cancer cell line LNCaP through an androgen-independent pathway.
Kim I, Seong D, Kim B, Lee D, Remaley A, Leach F, Morton R, Kim S. Raloxifene, a selective estrogen receptor modulator, induces apoptosis in androgen-responsive human prostate cancer cell line LNCaP through an androgen-independent pathway. Cancer Research 2002, 62: 3649-53. PMID: 12097269.Peer-Reviewed Original ResearchConceptsSelective estrogen receptor modulatorsHuman prostate cancer cell line LNCaPAndrogen-independent pathwayProstate cancer cell line LNCaPCancer cell line LNCaPEstrogen receptor modulatorsCell line LNCaPLNCaP cellsER betaReceptor modulatorsAndrogen-sensitive human prostate cancer cell line LNCaPAndrogen-sensitive human prostate cancer cell line LNCaP.Mixed estrogen agonist/antagonistHuman prostate cancer cell line LNCaP.Estrogen agonist/antagonistProstate-specific antigen assaysEffects of raloxifeneProstate cancer cell line LNCaP.Androgen receptor activityPresence of antiandrogensDose-dependent mannerAgonists/antagonistsSelective ER modulatorsAndrogen response elementAntigen assays
2000
Absence of proximal duct apoptosis in the ventral prostate of transgenic mice carrying the C3(1)‐TGF‐β type II dominant negative receptor
Kundu S, Kim I, Yang T, Doglio L, Lang S, Zhang X, Buttyan R, Kim S, Chang J, Cai X, Wang Z, Lee C. Absence of proximal duct apoptosis in the ventral prostate of transgenic mice carrying the C3(1)‐TGF‐β type II dominant negative receptor. The Prostate 2000, 43: 118-124. PMID: 10754527, DOI: 10.1002/(sici)1097-0045(20000501)43:2<118::aid-pros6>3.0.co;2-v.Peer-Reviewed Original ResearchMeSH KeywordsActivin Receptors, Type IAnimalsApoptosisGenes, DominantGenomeImmunohistochemistryMaleMiceMice, TransgenicOrgan SizePromoter Regions, GeneticProstateProtein Serine-Threonine KinasesReceptor, Transforming Growth Factor-beta Type IReceptors, AndrogenReceptors, Transforming Growth Factor betaTestosteroneConceptsVentral prostateEpithelial cellsAnimal prostatesDominant negative receptorTransgenic miceNegative receptorProstate-specific promotersProstatic epithelial cellsTransgenic mouse systemTGF-beta resultsSerum levelsTGF-beta signalingProstate growthProstatic growthNormal prostateAndrogenic statusProstateProximal ductExperimental modelLoss of apoptosisInhibitory effectMouse systemSignificant differencesAbnormal morphologyLoss of sensitivity
1995
Regulation of proliferation and production of prostate-specific antigen in androgen-sensitive prostatic cancer cells, LNCaP, by dihydrotestosterone
Lee C, Sutkowski D, Sensibar J, Zelner D, Kim I, Amsel I, Shaw N, Prins G, Kozlowski J. Regulation of proliferation and production of prostate-specific antigen in androgen-sensitive prostatic cancer cells, LNCaP, by dihydrotestosterone. Endocrinology 1995, 136: 796-803. PMID: 7530653, DOI: 10.1210/endo.136.2.7530653.Peer-Reviewed Original ResearchConceptsHigher DHT concentrationsEffects of androgensConcentrations of dihydrotestosteroneDHT concentrationsPSA secretionAndrogen receptorCharcoal-stripped fetal bovine serumProstate-specific antigen (PSA) productionHuman prostatic cancer cell linesLow DHT concentrationsProstatic cancer cell linesDose-related mannerNuclear androgen receptorProstate-specific antigenCellular proliferationProstatic cancer cellsProduction of PSADose-dependent inductionWestern blot analysisCancer cell linesProportion of cellsDHT levelsLNCaP cellsM dihydrotestosteronePositive staining