Featured Publications
Poly (ADP-ribose) polymerase inhibitors
Ratner ES, Sartorelli AC, Lin ZP. Poly (ADP-ribose) polymerase inhibitors. Current Opinion In Oncology 2012, 24: 564-571. PMID: 22759740, PMCID: PMC3799945, DOI: 10.1097/cco.0b013e3283564230.Peer-Reviewed Original ResearchConceptsEpithelial ovarian cancerOvarian cancerOverall survivalEOC patientsPARP inhibitorsBRCA mutationsHereditary epithelial ovarian cancerLower chemotherapy response rateDNA repair defectsDeleterious BRCA1/2 mutationsPlatinum-based chemotherapyRecurrence-free survivalChemotherapy response rateRecent clinical trialsPoor overall survivalNew treatment optionsShorter survival timeSporadic epithelial ovarian cancerPoly (ADP-ribose) polymerasePoly (ADP-ribose) polymerase (PARP) inhibitorsEffect of cisplatinPARP inhibitor olaparibRecurrent diseaseClinical outcomesTherapeutic challengeIn silico screening identifies a novel small molecule inhibitor that counteracts PARP inhibitor resistance in ovarian cancer
Lin ZP, Al Zouabi NN, Xu ML, Bowen NE, Wu TL, Lavi ES, Huang PH, Zhu YL, Kim B, Ratner ES. In silico screening identifies a novel small molecule inhibitor that counteracts PARP inhibitor resistance in ovarian cancer. Scientific Reports 2021, 11: 8042. PMID: 33850183, PMCID: PMC8044145, DOI: 10.1038/s41598-021-87325-5.Peer-Reviewed Original ResearchConceptsEpithelial ovarian cancerSmall molecule inhibitorsPARP inhibitor resistancePARP inhibitorsBRCA mutationsOvarian cancerEOC cellsPoly ADP-ribose polymerase inhibitorsMolecule inhibitorsInhibitor resistanceADP-ribose polymerase inhibitorsTumor-bearing miceNovel small molecule inhibitorPARP inhibitor olaparibDefective homologous recombination (HR) repairEOC xenograftsClinical efficacySurvival timePutative small molecule inhibitorsInhibitor olaparibPolymerase inhibitorsHR repairInhibitorsCancerHomologous recombination repair
2016
Triapine potentiates platinum-based combination therapy by disruption of homologous recombination repair
Ratner ES, Zhu YL, Penketh PG, Berenblum J, Whicker ME, Huang PH, Lee Y, Ishiguro K, Zhu R, Sartorelli AC, Lin ZP. Triapine potentiates platinum-based combination therapy by disruption of homologous recombination repair. British Journal Of Cancer 2016, 114: 777-786. PMID: 26964031, PMCID: PMC4984868, DOI: 10.1038/bjc.2016.54.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCarboplatinCarcinoma, Ovarian EpithelialCisplatinDoxorubicinDrug Resistance, NeoplasmFemaleHumansMiceMice, NudeNeoplasms, Glandular and EpithelialOvarian NeoplasmsPhthalazinesPiperazinesPolyethylene GlycolsRecombinational DNA RepairTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsPlatinum-based combination therapyEpithelial ovarian cancerCombination therapyWild-type cancer cellsEOC cellsPlatinum-resistant epithelial ovarian cancerPlatinum resistanceHomologous recombination repairEOC tumor growthPlatinum-based combinationsXenograft tumor mouse modelCancer cellsWild-type BRCATumor growth delayTumor mouse modelClonogenic survival assaysClinical efficacyBRCA statusOvarian cancerMouse modelTumor growthGrowth delayHRR activityTherapySurvival assays
2014
p53 protein aggregation promotes platinum resistance in ovarian cancer
Yang-Hartwich Y, Soteras MG, Lin ZP, Holmberg J, Sumi N, Craveiro V, Liang M, Romanoff E, Bingham J, Garofalo F, Alvero A, Mor G. p53 protein aggregation promotes platinum resistance in ovarian cancer. Oncogene 2014, 34: 3605-3616. PMID: 25263447, DOI: 10.1038/onc.2014.296.Peer-Reviewed Original ResearchConceptsPro-apoptotic functionP53 aggregationProtein aggregationP53 aggregatesNormal transcriptional activationTwo-dimensional gel electrophoresisCancer cellsCancer cell survivalKey transcriptional factorGenetic mutationsHigh-grade serous ovarian carcinomaP53 inactivationP53 proteinStem cell propertiesCancer stem cell propertiesCellular homeostasisTranscriptional activationCancer stem cellsTranscriptional factorsTumor-initiating capacityP53 turnoverCell survivalHGSOC cellsStem cellsPotential therapeutic target
2007
Disruption of cAMP and Prostaglandin E2 Transport by Multidrug Resistance Protein 4 Deficiency Alters cAMP-Mediated Signaling and Nociceptive Response
Lin ZP, Zhu YL, Johnson DR, Rice KP, Nottoli T, Hains BC, McGrath J, Waxman SG, Sartorelli AC. Disruption of cAMP and Prostaglandin E2 Transport by Multidrug Resistance Protein 4 Deficiency Alters cAMP-Mediated Signaling and Nociceptive Response. Molecular Pharmacology 2007, 73: 243-251. PMID: 17959714, PMCID: PMC2780335, DOI: 10.1124/mol.107.039594.Peer-Reviewed Original ResearchConceptsNociceptive responsesPG synthesisInflammatory nociceptive responsesInflammatory pain thresholdWild-type miceCyclooxygenase-2 expressionMrp4 knockout miceMultidrug resistance protein 4Accumulation of intracellularMEF cellsMRP4 knockdownNucleotide agentsPain thresholdDisruptions of cAMPPGE metabolitePG levelsEnergy-dependent effluxProtein 4MiceMRP4PG transportIntracellular levelsProstaglandinsATP-binding cassette (ABC) familyPronounced reduction
2004
Age-Related Differences in Vincristine Toxicity and Biodistribution in Wild-Type and Transporter-Deficient Mice
Muramatsu T, Johnson DR, Finch RA, Johnson LK, Leffert JJ, Lin ZP, Pizzorno G, Sartorelli AC. Age-Related Differences in Vincristine Toxicity and Biodistribution in Wild-Type and Transporter-Deficient Mice. Oncology Research Featuring Preclinical And Clinical Cancer Therapeutics 2004, 14: 331-343. PMID: 15301424, DOI: 10.3727/0965040041292387.Peer-Reviewed Original Research
2002
Comparative study of the importance of multidrug resistance-associated protein 1 and P-glycoprotein to drug sensitivity in immortalized mouse embryonic fibroblasts.
Lin ZP, Johnson DR, Finch RA, Belinsky MG, Kruh GD, Sartorelli AC. Comparative study of the importance of multidrug resistance-associated protein 1 and P-glycoprotein to drug sensitivity in immortalized mouse embryonic fibroblasts. Molecular Cancer Therapeutics 2002, 1: 1105-14. PMID: 12481434.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnticarcinogenic AgentsAntineoplastic AgentsAntineoplastic Agents, PhytogenicATP Binding Cassette Transporter, Subfamily B, Member 1Biological TransportBlotting, WesternCell SurvivalCells, CulturedChemokines, CCDose-Response Relationship, DrugEtoposideFibroblastsFluoresceinsInhibitory Concentration 50MiceMice, KnockoutPrecipitin TestsReverse Transcriptase Polymerase Chain ReactionRNATime FactorsTransfectionTumor Cells, CulturedVincristineConceptsMultidrug resistance-associated protein 1P-glycoproteinWT fibroblastsDKO fibroblastsCalcein accumulationDrug sensitivityProtein 1Unrelated anticancer agentsAnticancer agentsImmortalized mouse embryonic fibroblastsWestern blot analysisKnockout miceCompensatory mechanismsAccumulation assaysMouse embryonic fibroblastsCompensatory changesEmbryonic fibroblastsMRP1Drug substratesBlot analysisCell viabilityMajor determinantFamily membersFibroblastsFibroblast lines