2024
Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2
Mutlu L, McNamara B, Bellone S, Manavella D, Demirkiran C, Greenman M, Verzosa M, Buza N, Hui P, Hartwich T, Harold J, Yang-Hartwich Y, Zipponi M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Santin A. Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2. Clinical & Experimental Metastasis 2024, 41: 765-775. PMID: 38909139, DOI: 10.1007/s10585-024-10297-z.Peer-Reviewed Original ResearchHigh-grade serous ovarian cancerClear cell carcinomaHER2-targeting antibody-drug conjugateAntibody-drug conjugatesT-DXdReceptor over-expressionTrastuzumab deruxtecanXenograft modelCell linesOvarian clear cell carcinomaOvarian cancer cell linesTumors overexpressing HER2Biologically aggressive tumorsFluorescence in situ hybridization assaySerous ovarian cancerEffective antibody-drug conjugatesIn vivo antitumor activityMouse xenograft modelMetastatic cell linesDS-8201aCancer cell linesAggressive tumorsHER2 expressionCell carcinomaOvarian cancer
2023
NRF2 controls iron homeostasis and ferroptosis through HERC2 and VAMP8
Anandhan A, Dodson M, Shakya A, Chen J, Liu P, Wei Y, Tan H, Wang Q, Jiang Z, Yang K, Garcia J, Chambers S, Chapman E, Ooi A, Yang-Hartwich Y, Stockwell B, Zhang D. NRF2 controls iron homeostasis and ferroptosis through HERC2 and VAMP8. Science Advances 2023, 9: eade9585. PMID: 36724221, PMCID: PMC9891695, DOI: 10.1126/sciadv.ade9585.Peer-Reviewed Original ResearchConceptsLabile iron poolNFE2L2/Human ovarian cancer tissuesCancer cellsOvarian cancer cell linesOvarian cancer tissuesIntracellular labile iron poolIron homeostasisCancer cell linesPreclinical modelsNrf2 inhibitionCancer tissuesNrf2 levelsCancer treatmentFerroptotic deathNrf2Ferroptosis resistanceKnockout cellsCell linesUntapped strategyFerroptosisIron poolCellsHomeostasisExpressionThe Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo
Han C, McNamara B, Bellone S, Harold J, Manara P, Hartwich T, Mutlu L, Yang-Hartwich Y, Zipponi M, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Dottino P, Schwartz P, Santin A. The Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo. Gynecologic Oncology 2023, 170: 172-178. PMID: 36706643, PMCID: PMC10023457, DOI: 10.1016/j.ygyno.2023.01.015.Peer-Reviewed Original ResearchConceptsCombination of olaparibOvarian cancerHER2 expressionSingle agentCell linesGynecologic cancer mortalityHER2-negative tumorsOvarian cancer cell linesOvarian cancer patientsEpithelial ovarian carcinomaNovel therapeutic optionsOC cell linesUnmet medical needPoly (ADP-ribose) polymerase (PARP) inhibitorsPan-ErbB inhibitorSingle-agent olaparibPolymerase inhibitor olaparibPoly (ADP-ribose) polymerase (PARP) inhibitor olaparibPrimary HER2Cancer cell linesNegative tumorsTherapeutic optionsCancer mortalityCancer patientsNeu expression
2020
Identification of miPEP133 as a novel tumor-suppressor microprotein encoded by miR-34a pri-miRNA
Kang M, Tang B, Li J, Zhou Z, Liu K, Wang R, Jiang Z, Bi F, Patrick D, Kim D, Mitra AK, Yang-Hartwich Y. Identification of miPEP133 as a novel tumor-suppressor microprotein encoded by miR-34a pri-miRNA. Molecular Cancer 2020, 19: 143. PMID: 32928232, PMCID: PMC7489042, DOI: 10.1186/s12943-020-01248-9.Peer-Reviewed Original ResearchConceptsNon-coding RNA transcriptsNasopharyngeal carcinomaCancer cell linesP53 transcriptional activationPrognostic markerTumor suppressor functionAmino acid residuesCell linesTumor growthNovel microproteinWild-type p53Cellular functionsMetastatic nasopharyngeal carcinomaTranscriptional activationPotential prognostic markerMitochondrial membraneUnfavorable prognostic markerCervical cancer cell linesRNA transcriptsMitochondrial massTumor suppressorMiR-34a expressionAcid residuesNormal human colonNPC clinical samples
2019
Inhibition of Heat Shock Protein 90 suppresses TWIST1 Transcription
Chong KY, Kang M, Garofalo F, Ueno D, Liang H, Cady S, Madarikan O, Pitruzzello N, Tsai CH, Hartwich T, Shuch B, Yang-Hartwich Y. Inhibition of Heat Shock Protein 90 suppresses TWIST1 Transcription. Molecular Pharmacology 2019, 96: 168-179. PMID: 31175180, DOI: 10.1124/mol.119.116137.Peer-Reviewed Original ResearchMeSH KeywordsBenzoquinonesCell Line, TumorDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHSP90 Heat-Shock ProteinsHumansKidney NeoplasmsLactams, MacrocyclicNasopharyngeal NeoplasmsNuclear ProteinsOvarian NeoplasmsPhosphorylationPromoter Regions, GeneticSTAT3 Transcription FactorTissue Array AnalysisTranscription, GeneticTwist-Related Protein 1ConceptsEpithelial-mesenchymal transitionHsp90 inhibitorsTwist1 transcriptionMolecular chaperone heat shock protein 90Chaperone heat shock protein 90Involvement of Hsp90Heat shock protein 90Cancer cell linesRole of Hsp90Binding of STAT3Inhibition of Hsp90Shock protein 90Cell linesProximity ligation assayHsp90 inhibitor 17TWIST1 mRNA expressionTranscription factorsSignal transducerProtein 90Promoter activityTranscription 3New therapeutic opportunitiesHsp90Molecular mechanismsSTAT3 activity
2014
Detection of p53 Protein Aggregation in Cancer Cell Lines and Tumor Samples
Yang-Hartwich Y, Bingham J, Garofalo F, Alvero AB, Mor G. Detection of p53 Protein Aggregation in Cancer Cell Lines and Tumor Samples. Methods In Molecular Biology 2014, 1219: 75-86. PMID: 25308263, DOI: 10.1007/978-1-4939-1661-0_7.Peer-Reviewed Original ResearchConceptsCancer cell linesPro-apoptotic functionAggregation of p53P53 proteinCancer cellsCell linesP53 aggregationAmyloid-like oligomersProtein aggregationApoptotic signalsInactive conformationTumor samplesFunctional p53ProteinGenetic mutationsTumor progressionCentral roleP53Dysfunctional p53 proteinCellsAggregationMutationsApoptosisDeregulationLines