2017
JAK1/STAT3 Activation through a Proinflammatory Cytokine Pathway Leads to Resistance to Molecularly Targeted Therapy in Non–Small Cell Lung Cancer
Shien K, Papadimitrakopoulou VA, Ruder D, Behrens C, Shen L, Kalhor N, Song J, Lee JJ, Wang J, Tang X, Herbst RS, Toyooka S, Girard L, Minna JD, Kurie JM, Wistuba II, Izzo JG. JAK1/STAT3 Activation through a Proinflammatory Cytokine Pathway Leads to Resistance to Molecularly Targeted Therapy in Non–Small Cell Lung Cancer. Molecular Cancer Therapeutics 2017, 16: 2234-2245. PMID: 28729401, PMCID: PMC5628136, DOI: 10.1158/1535-7163.mct-17-0148.Peer-Reviewed Original ResearchMeSH KeywordsAgedApoptosisCancer-Associated FibroblastsCarcinoma, Non-Small-Cell LungCell Line, TumorCytokinesDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHumansInterleukin-6Janus Kinase 1MaleMiddle AgedMolecular Targeted TherapyNeoplasm StagingOncostatin MReceptors, Oncostatin MSignal TransductionSTAT3 Transcription FactorConceptsNon-small cell lung cancerCancer-associated fibroblastsNSCLC cellsOSM receptorMajority of patientsCell lung cancerProinflammatory cytokine IL6Proinflammatory cytokine pathwaysSignificant therapeutic advancesClinical NSCLC samplesMol Cancer TherSTAT3-dependent mannerOSMR expressionDrug-induced apoptosisWorse prognosisPrognostic significanceLung cancerTherapeutic advancesCytokines IL6Molecule expressionNSCLC samplesCytokine pathwaysLung adenocarcinomaTargeted drugsParacrine mechanisms
2012
Targeting the Apoptotic Pathway in Chondrosarcoma Using Recombinant Human Apo2L/TRAIL (Dulanermin), a Dual Proapoptotic Receptor (DR4/DR5) Agonist
Subbiah V, Brown RE, Buryanek J, Trent J, Ashkenazi A, Herbst R, Kurzrock R. Targeting the Apoptotic Pathway in Chondrosarcoma Using Recombinant Human Apo2L/TRAIL (Dulanermin), a Dual Proapoptotic Receptor (DR4/DR5) Agonist. Molecular Cancer Therapeutics 2012, 11: 2541-2546. PMID: 22914439, PMCID: PMC3496030, DOI: 10.1158/1535-7163.mct-12-0358.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisBone NeoplasmsCell SurvivalChondrosarcomaDNA Mutational AnalysisHumansImmunohistochemistryIsocitrate DehydrogenaseLung NeoplasmsMaleMiddle AgedProteomicsProto-Oncogene Proteins c-bcl-2Radiography, ThoracicReceptors, Death DomainRecombinant ProteinsSignal TransductionTNF-Related Apoptosis-Inducing LigandTomography, X-Ray ComputedTreatment OutcomeConceptsRecombinant human Apo2L/TRAILApo2L/TRAILRecent computed tomography scanSustained partial responseEvidence of diseaseComputed tomography scanP-ERK 1/2Partial responseProgressive diseaseNF-κBp65Receptor agonistTomography scanSubcentimeter nodulesPatient tumorsMetastatic chondrosarcomaP-mTORPatientsProlonged responseP-STAT3Proapoptotic receptor agonistsChondrosarcomaBcl-2DulanerminLungTumorsThe Microculture-Kinetic (MiCK) Assay: The Role of a Drug-Induced Apoptosis Assay in Drug Development and Clinical Care
Bosserman L, Prendergast F, Herbst R, Fleisher M, Salom E, Strickland S, Raptis A, Hallquist A, Perree M, Rajurkar S, Karimi M, Rogers K, Davidson D, Willis C, Penalver M, Homesley H, Burrell M, Garrett A, Rutledge J, Chernick M, Presant CA. The Microculture-Kinetic (MiCK) Assay: The Role of a Drug-Induced Apoptosis Assay in Drug Development and Clinical Care. Cancer Research 2012, 72: 3901-3905. PMID: 22865459, DOI: 10.1158/0008-5472.can-12-0681.Peer-Reviewed Original ResearchConceptsHigh response rateLonger survivalClinical trialsResponse rateGroup of patientsBlinded clinical trialEpithelial ovarian cancerApoptosis assaysAcute myelocytic leukemiaUnblinded clinical trialDrug developmentGeneric drug useMultiple tumor typesEfficient drug developmentCombination therapyOvarian cancerMyelocytic leukemiaClinical careTumor typesDrug useClinical therapyClinical useMolecular biomarkersDrug approvalHigher apoptosis
2011
Evaluation of pharmacodynamic biomarkers in a Phase 1a trial of dulanermin (rhApo2L/TRAIL) in patients with advanced tumours
Pan Y, Xu R, Peach M, Huang CP, Branstetter D, Novotny W, Herbst RS, Eckhardt SG, Holland PM. Evaluation of pharmacodynamic biomarkers in a Phase 1a trial of dulanermin (rhApo2L/TRAIL) in patients with advanced tumours. British Journal Of Cancer 2011, 105: 1830-1838. PMID: 22033270, PMCID: PMC3251880, DOI: 10.1038/bjc.2011.456.Peer-Reviewed Original ResearchConceptsCell death markersAdvanced tumorsPharmacodynamic biomarkersApoptotic markersPhase 1a studyPhase 1a trialDeath receptors DR4Colo205 tumorsSerum 8Patients 24Active caspase-3Patient seraColo205 xenograftsEvidence of activitySubsequent cell deathCytokeratin 18PatientsTransient increaseDulanerminReceptors DR4TumorsCaspase-3SerumCaspase-3/7Significant increaseUpregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor–resistant human lung adenocarcinoma
Cascone T, Herynk MH, Xu L, Du Z, Kadara H, Nilsson MB, Oborn CJ, Park YY, Erez B, Jacoby JJ, Lee JS, Lin HY, Ciardiello F, Herbst RS, Langley RR, Heymach JV. Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor–resistant human lung adenocarcinoma. Journal Of Clinical Investigation 2011, 121: 1313-1328. PMID: 21436589, PMCID: PMC3070607, DOI: 10.1172/jci42405.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAngiogenesis InhibitorsAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedApoptosisBevacizumabCell Line, TumorDrug Resistance, NeoplasmErbB ReceptorsGene Expression ProfilingHumansLung NeoplasmsMaleMiceMice, NudeNeovascularization, PathologicRNA, MessengerRNA, NeoplasmStromal CellsUp-RegulationVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Xenograft Model Antitumor AssaysConceptsMouse xenograft modelHuman lung adenocarcinomaTumor cellsPrimary resistanceLung adenocarcinomaXenograft modelFGFR pathwayProgression-free survivalVEGF inhibitor bevacizumabEndothelium of tumorsInhibitors of angiogenesisCombination regimensTreatment of cancerVEGF inhibitorsPericyte coverageAntiangiogenic therapyVascular remodelingAngiogenesis inhibitorsTherapeutic efficacyTumor growthStromal pathwaysClinical useEGFRAcquired ResistanceEGFR pathway
2010
Combination Treatment with MEK and AKT Inhibitors Is More Effective than Each Drug Alone in Human Non-Small Cell Lung Cancer In Vitro and In Vivo
Meng J, Dai B, Fang B, Bekele BN, Bornmann WG, Sun D, Peng Z, Herbst RS, Papadimitrakopoulou V, Minna JD, Peyton M, Roth JA. Combination Treatment with MEK and AKT Inhibitors Is More Effective than Each Drug Alone in Human Non-Small Cell Lung Cancer In Vitro and In Vivo. PLOS ONE 2010, 5: e14124. PMID: 21124782, PMCID: PMC2993951, DOI: 10.1371/journal.pone.0014124.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBenzimidazolesCarcinoma, Non-Small-Cell LungCell CycleCell Line, TumorCell SurvivalDose-Response Relationship, DrugDrug SynergismFemaleHeterocyclic Compounds, 3-RingHumansLung NeoplasmsMiceMice, Inbred BALB CMice, NudeMitogen-Activated Protein Kinase KinasesProto-Oncogene Proteins c-aktSignal TransductionSurvival AnalysisTumor BurdenXenograft Model Antitumor AssaysConceptsNon-small cell lung cancerCell lung cancerCombination of AZD6244Lung cancer cell linesCombination therapyLung cancerCancer cell linesTumor growthTumor tissueHuman non-small cell lung cancerLung cancer cell growthCell linesHuman lung cancer cell linesSingle drug treatmentSynergistic antitumor activityHuman lung tumorsAnimal survival timeMean animal survival timeCancer cell growthXenograft tumor growthP-AKT expressionLung tumorsDrug treatmentDrug combinationsSurvival timeMeasurement of conatumumab‐induced apoptotic activity in tumors by fine needle aspirate sampling
Zoog SJ, Y. C, Kaplan‐Lefko P, Hawkins JM, Moriguchi J, Zhou L, Pan Y, Hsu C, Friberg G, Herbst R, Hill J, Juan G. Measurement of conatumumab‐induced apoptotic activity in tumors by fine needle aspirate sampling. Cytometry Part A 2010, 77A: 849-860. PMID: 20623688, DOI: 10.1002/cyto.a.20940.Peer-Reviewed Original ResearchConceptsFine needle aspiratesDeath receptor 5Needle aspiratesNonsmall cell lung cancer patientsCell lung cancer patientsCaspase-3 activationLung cancer patientsTumor necrosis factorCaspase-3Tumor-bearing miceTumor cell deathReceptor therapyPharmacodynamic markersCancer patientsDrug exposureClinical trialsCaspase 3/7 activityNecrosis factorColo205 xenograftsClinical investigationReceptor 5FNA biopsyTumor typesPharmacological impactClinical settingTreatment with HIF-1α Antagonist PX-478 Inhibits Progression and Spread of Orthotopic Human Small Cell Lung Cancer and Lung Adenocarcinoma in Mice
Jacoby JJ, Erez B, Korshunova MV, Williams RR, Furutani K, Takahashi O, Kirkpatrick L, Lippman SM, Powis G, O'Reilly MS, Herbst RS. Treatment with HIF-1α Antagonist PX-478 Inhibits Progression and Spread of Orthotopic Human Small Cell Lung Cancer and Lung Adenocarcinoma in Mice. Journal Of Thoracic Oncology 2010, 5: 940-949. PMID: 20512076, PMCID: PMC3782111, DOI: 10.1097/jto.0b013e3181dc211f.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAnimalsApoptosisBlotting, WesternCarcinoma, Non-Small-Cell LungDisease ProgressionHumansHypoxia-Inducible Factor 1, alpha SubunitImmunoenzyme TechniquesLung NeoplasmsLymphatic MetastasisMaleMiceMice, NudeMustard CompoundsPhenylpropionatesSmall Cell Lung CarcinomaSurvival RateTreatment OutcomeTumor Cells, CulturedConceptsLung tumor volumePX-478Tumor volumeLung cancerNSCLC modelsLung adenocarcinomaNon-small cell lung cancer xenograftsSmall cell lung cancer modelCell lung cancer xenograftsHuman small cell lung cancerSmall cell lung cancerCell lung cancer modelsPhase I clinical trialPX-478 treatmentAntitumor activityDaily oral treatmentMedian survival durationVehicle-treated groupCell lung cancerLung cancer xenograftsLung cancer patientsLung adenocarcinoma cell modelsLung cancer cell linesLung cancer modelOrthotopic mouse modelPhase I Dose-Escalation Study of Recombinant Human Apo2L/TRAIL, a Dual Proapoptotic Receptor Agonist, in Patients With Advanced Cancer
Herbst RS, Eckhardt SG, Kurzrock R, Ebbinghaus S, O'Dwyer PJ, Gordon MS, Novotny W, Goldwasser MA, Tohnya TM, Lum BL, Ashkenazi A, Jubb AM, Mendelson DS. Phase I Dose-Escalation Study of Recombinant Human Apo2L/TRAIL, a Dual Proapoptotic Receptor Agonist, in Patients With Advanced Cancer. Journal Of Clinical Oncology 2010, 28: 2839-2846. PMID: 20458040, DOI: 10.1200/jco.2009.25.1991.Peer-Reviewed Original ResearchConceptsRecombinant human Apo2L/TRAILRhApo2L/TRAILDose-escalation studyAdverse eventsAdvanced cancerLiver metastasesDose escalationLiver functionApo2L/TRAILI dose-escalation studyDurable partial responseRapid tumor necrosisAntitumor activityCommon adverse eventsLiver enzyme elevationMetastatic liver diseaseSerious adverse eventsAbnormal liver functionNormal liver functionMultiple intravenous dosesNecrosis factor-related apoptosis-inducing ligandPreclinical antitumor efficacyTumor necrosis factor-related apoptosis-inducing ligandFactor-related apoptosis-inducing ligandHuman clinical trials
2008
To kill a tumor cell: the potential of proapoptotic receptor agonists
Ashkenazi A, Herbst RS. To kill a tumor cell: the potential of proapoptotic receptor agonists. Journal Of Clinical Investigation 2008, 118: 1979-1990. PMID: 18523647, PMCID: PMC2396896, DOI: 10.1172/jci34359.Peer-Reviewed Original ResearchConceptsProapoptotic receptor agonistsApo2L/TRAILReceptor agonistRecombinant human Apo2L/TRAILExtrinsic apoptosis pathwayPotential therapeutic interventionsNovel molecular biomarkersApoptosis pathwayAgonistic mAbConventional therapyPreclinical dataTherapeutic interventionsTumor cellsMolecular biomarkersAbnormal cellsLogical targetTherapyAgonistsCellsExciting opportunitiesTumorigenesisPatientsApoptosisPathwaySummary Report 7th Annual Targeted Therapies of the Treatment of Lung Cancer
Einhorn LH, Bonomi P, Bunn PA, Camidge DR, Carbone DP, Choy H, Dubinett SM, Gandara DR, Gaspar LE, Govindan R, Johnson DH, Minna JD, Scagliotti G, West HJ, Herbst RS. Summary Report 7th Annual Targeted Therapies of the Treatment of Lung Cancer. Journal Of Thoracic Oncology 2008, 3: 545-555. PMID: 18449013, PMCID: PMC3374724, DOI: 10.1097/jto.0b013e318170627f.Peer-Reviewed Original Research
2007
Endostatin improves radioresponse and blocks tumor revascularization after radiation therapy for A431 xenografts in mice
Itasaka S, Komaki R, Herbst RS, Shibuya K, Shintani T, Hunter NR, Onn A, Bucana CD, Milas L, Ang KK, O’Reilly M. Endostatin improves radioresponse and blocks tumor revascularization after radiation therapy for A431 xenografts in mice. International Journal Of Radiation Oncology • Biology • Physics 2007, 67: 870-878. PMID: 17293237, PMCID: PMC1976280, DOI: 10.1016/j.ijrobp.2006.10.030.Peer-Reviewed Original ResearchConceptsRadiation therapyConcurrent administrationTumor revascularizationDisease-free survivalVascular endothelial growth factorCombination of endostatinEffect of endostatinMatrix metalloproteinase-2Legs of miceEndothelial growth factorEndothelial cell apoptosisEndothelial cell proliferationAdvanced malignanciesA431 xenograftsClinical trialsInterleukin-8Antiangiogenic therapyAntiangiogenic agentsEpidermoid carcinomaPreclinical studiesHuman epidermoid carcinomaLeg tumorsTreatment groupsAntitumor effectsMetalloproteinase-2Targeted therapy of orthotopic human lung cancer by combined vascular endothelial growth factor and epidermal growth factor receptor signaling blockade
Wu W, Onn A, Isobe T, Itasaka S, Langley RR, Shitani T, Shibuya K, Komaki R, Ryan AJ, Fidler IJ, Herbst RS, O'Reilly MS. Targeted therapy of orthotopic human lung cancer by combined vascular endothelial growth factor and epidermal growth factor receptor signaling blockade. Molecular Cancer Therapeutics 2007, 6: 471-483. PMID: 17308046, DOI: 10.1158/1535-7163.mct-06-0416.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAngiogenesis InhibitorsAnimalsApoptosisBlotting, WesternCarcinoma, Squamous CellCell Line, TumorCell ProliferationEndothelium, VascularErbB ReceptorsFlow CytometryHumansLung NeoplasmsMaleMiceMice, Inbred BALB CMice, Inbred CBANeovascularization, PathologicPhosphorylationPiperidinesProto-Oncogene Proteins c-aktQuinazolinesSignal TransductionVascular Endothelial Growth Factor Receptor-2Xenograft Model Antitumor AssaysConceptsVascular endothelial growth factorVEGF receptor 2EGF receptorEpidermal growth factorLung cancerHuman lung cancerEndothelial growth factorGrowth factorMitogen-activated protein kinaseNon-small cell lung cancerOrthotopic human lung cancerProtein tyrosine kinase inhibitorEndothelial cellsTumor-associated endothelial cellsHuman lung cancer specimensAdvanced lung cancerSelective protein tyrosine kinase inhibitorCell lung cancerLung cancer patientsOrthotopic mouse modelEndothelial cell tube formationLung cancer specimensHuman lung adenocarcinoma cellsTyrosine kinase inhibitorsSmall molecule inhibitors
2005
Pharmacodynamic Analysis of Target Inhibition and Endothelial Cell Death in Tumors Treated with the Vascular Endothelial Growth Factor Receptor Antagonists SU5416 or SU6668
Davis DW, Takamori R, Raut CP, Xiong HQ, Herbst RS, Stadler WM, Heymach JV, Demetri GD, Rashid A, Shen Y, Wen S, Abbruzzese JL, McConkey DJ. Pharmacodynamic Analysis of Target Inhibition and Endothelial Cell Death in Tumors Treated with the Vascular Endothelial Growth Factor Receptor Antagonists SU5416 or SU6668. Clinical Cancer Research 2005, 11: 678-689. PMID: 15701856, DOI: 10.1158/1078-0432.678.11.2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsApoptosisDose-Response Relationship, DrugEndothelium, VascularFemaleHumansIndolesMaleMiceMice, NudeMiddle AgedNeovascularization, PathologicOxindolesPancreatic NeoplasmsPhosphorylationPropionatesPyrrolesReceptor, Platelet-Derived Growth Factor betaTransplantation, HeterologousVascular Endothelial Growth Factor Receptor-2ConceptsPlatelet-derived growth factor receptorTumor microvessel densityGrowth factor receptorMicrovessel densityCell apoptosisVascular endothelial growth factor receptorAdvanced solid malignanciesFactor receptorEndothelial growth factor receptorPrimary patient tumorsG core biopsyDose-dependent effectPhosphorylated VEGFR-2Primary human tumorsEndothelial cell deathCell deathEndothelial cell apoptosisTumor cell apoptosisTumor cell deathPost therapyCore biopsyPharmacodynamic analysisSolid malignanciesVessel sizeClinical trials
2004
Oblimersen Sodium (Genasense bcl-2 Antisense Oligonucleotide)A Rational Therapeutic to Enhance Apoptosis in Therapy of Lung Cancer
Herbst RS, Frankel SR. Oblimersen Sodium (Genasense bcl-2 Antisense Oligonucleotide)A Rational Therapeutic to Enhance Apoptosis in Therapy of Lung Cancer. Clinical Cancer Research 2004, 10: 4245s-4248s. PMID: 15217967, DOI: 10.1158/1078-0432.ccr-040018.Peer-Reviewed Original ResearchConceptsOblimersen sodiumLung cancerBcl-2 mRNASmall cell lung cancer patientsNon-small cell lung cancerBcl-2 protein translationFirst-line salvage therapyCell lung cancer patientsPhase IPrior chemotherapy regimenCombination of docetaxelBcl-2 antisense therapyCell lung cancerTraditional cytotoxic chemotherapyLung cancer patientsChemotherapy regimenSalvage therapyCytotoxic chemotherapyAntitumor responseCancer patientsHuman bcl-2 mRNAPreclinical studiesResponse durationResponse rateAnticancer treatmentQuantitative Analysis of Biomarkers Defines an Optimal Biological Dose for Recombinant Human Endostatin in Primary Human Tumors
Davis DW, Shen Y, Mullani NA, Wen S, Herbst RS, O’Reilly M, Abbruzzese JL, McConkey DJ. Quantitative Analysis of Biomarkers Defines an Optimal Biological Dose for Recombinant Human Endostatin in Primary Human Tumors. Clinical Cancer Research 2004, 10: 33-42. PMID: 14734449, DOI: 10.1158/1078-0432.ccr-0736-3.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsApoptosisBiomarkersCohort StudiesDiagnostic ImagingDose-Response Relationship, DrugEndostatinsEndothelial CellsHumansHypoxia-Inducible Factor 1, alpha SubunitIn Situ Nick-End LabelingNeoplasmsNeovascularization, PathologicPlatelet Endothelial Cell Adhesion Molecule-1Proto-Oncogene Proteins c-bcl-2Recombinant ProteinsTomography, Emission-ComputedTranscription FactorsConceptsHypoxia-inducible factor-1alphaRecombinant human endostatinMicrovessel densityLaser scanning cytometryTC deathHuman endostatinPhase I dose-finding studyTerminal deoxynucleotidyl transferase-mediated nick end labeling stainingTumor cellsEndothelial cellsTumor-associated endothelial cellsSignificant clinical activityFactor-1alphaRefractory solid tumorsCohort of patientsNick end labeling stainingPhase I trialDose-finding studyTumor microvessel densityTumor blood flowOptimal biological doseEnd labeling stainingWhole tissue sectionsPositron emission tomographyPrimary human tumors
2003
Mode of action of docetaxel – a basis for combination with novel anticancer agents
Herbst RS, Khuri FR. Mode of action of docetaxel – a basis for combination with novel anticancer agents. Cancer Treatment Reviews 2003, 29: 407-415. PMID: 12972359, DOI: 10.1016/s0305-7372(03)00097-5.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, PhytogenicAntineoplastic Combined Chemotherapy ProtocolsApoptosisDocetaxelDrug Resistance, NeoplasmDrug SynergismErbB ReceptorsFemaleFollow-Up StudiesHumansMaleNeoplasmsNeovascularization, PathologicPaclitaxelPharmacogeneticsSurvival AnalysisTaxoidsTreatment OutcomeConceptsPatient populationOptimal treatment strategySpecific patient populationsCertain chemotherapeutic drugsAnticancer agentsOptimal therapySpecific therapyTreatment strategiesNovel agentsClinical investigationNew anticancer agentsNovel anticancer agentsCancer growthDifferent tumorsStimulation pathwayChemotherapeutic drugsInhibitor of mitosisAntitumor activityTumorigenic mechanismsMode of actionAgent combinationsDocetaxelTherapyAgentsDifferent aberrationsInduction of p53-regulated genes and tumor regression in lung cancer patients after intratumoral delivery of adenoviral p53 (INGN 201) and radiation therapy.
Swisher SG, Roth JA, Komaki R, Gu J, Lee JJ, Hicks M, Ro JY, Hong WK, Merritt JA, Ahrar K, Atkinson NE, Correa AM, Dolormente M, Dreiling L, El-Naggar AK, Fossella F, Francisco R, Glisson B, Grammer S, Herbst R, Huaringa A, Kemp B, Khuri FR, Kurie JM, Liao Z, McDonnell TJ, Morice R, Morello F, Munden R, Papadimitrakopoulou V, Pisters KM, Putnam JB, Sarabia AJ, Shelton T, Stevens C, Shin DM, Smythe WR, Vaporciyan AA, Walsh GL, Yin M. Induction of p53-regulated genes and tumor regression in lung cancer patients after intratumoral delivery of adenoviral p53 (INGN 201) and radiation therapy. Clinical Cancer Research 2003, 9: 93-101. PMID: 12538456.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAgedAged, 80 and overApoptosisCarcinoma, Non-Small-Cell LungCombined Modality TherapyFemaleGene Transfer TechniquesGenes, p53Genetic TherapyGenetic VectorsHumansLung NeoplasmsMaleMiddle AgedRadiotherapyReverse Transcriptase Polymerase Chain ReactionRNA, MessengerTime FactorsTumor Suppressor Protein p53ConceptsNon-small cell lung cancerAd-p53 gene transferCell lung cancerRadiation therapyViable tumorLung cancerTumor regressionNonmetastatic non-small cell lung cancerProspective single-arm phase II studyIntratumoral injectionSingle-arm phase II studyAd-p53 gene therapyArm phase II studyCommon adverse eventsPhase II studyCompletion of therapyLung cancer patientsCourse of treatmentStable diseaseAdverse eventsBronchoscopic findingsII studyPartial responseProgressive diseaseComplete response
2002
Development of biologic markers of response and assessment of antiangiogenic activity in a clinical trial of human recombinant endostatin.
Herbst RS, Mullani NA, Davis DW, Hess KR, McConkey DJ, Charnsangavej C, O’Reilly M, Kim HW, Baker C, Roach J, Ellis LM, Rashid A, Pluda J, Bucana C, Madden TL, Tran HT, Abbruzzese JL. Development of biologic markers of response and assessment of antiangiogenic activity in a clinical trial of human recombinant endostatin. Journal Of Clinical Oncology 2002, 20: 3804-14. PMID: 12228200, DOI: 10.1200/jco.2002.05.102.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAngiogenesis InhibitorsApoptosisBiomarkersCD3 ComplexCollagenDose-Response Relationship, DrugEndostatinsEndotheliumFemaleFluorodeoxyglucose F18HumansIn Situ Nick-End LabelingLasersMaleMiddle AgedNeoplasmsNeovascularization, PathologicPeptide FragmentsProspective StudiesRecombinant ProteinsTomography, Emission-ComputedConceptsTumor blood flowRh-EndoTumor cell apoptosisPositron emission tomographyBlood flowEndothelial cell apoptosisCell apoptosisClinical trialsAntiangiogenic therapyEndothelial cellsWeeks of therapyStart of therapyDose-finding clinical trialsRecombinant human endostatinHuman recombinant endostatinTreatment of cancerBiologic markersAntiangiogenic treatmentBiopsy specimensAppropriate dosePET scansBiopsy analysisHuman endostatinTherapyTumor tissueAssessment of Antiangiogenic Effect Using 99mTc-EC-Endostatin
Yang DJ, Kim KD, Schechter NR, Yu DF, Wu P, Azhdarinia A, Roach JS, Kalimi SK, Ozaki K, Fogler WE, Bryant JL, Herbst R, Abbruzzes J, Kim EE, Podoloff DA. Assessment of Antiangiogenic Effect Using 99mTc-EC-Endostatin. Cancer Biotherapy & Radiopharmaceuticals 2002, 17: 233-246. PMID: 12030117, DOI: 10.1089/108497802753773856.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisCollagenCysteineEndostatinsEndothelial Growth FactorsFemaleFibroblast Growth Factor 2In Situ Nick-End LabelingIntercellular Signaling Peptides and ProteinsInterleukin-8LymphokinesMammary Neoplasms, ExperimentalNeovascularization, PathologicPaclitaxelPeptide FragmentsRadionuclide ImagingRatsRats, Inbred F344TechnetiumTumor Cells, CulturedVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsTumor-bearing ratsAnti-angiogenesis therapyTreatment responseTumor uptakeTUNEL assayAnti-angiogenic treatment responseTumor vascular densityIL-8 expressionTumor-bearing animal modelsCount density ratiosCell viabilityPrognostic indicatorMicrovessel densityVascular densityAnimal modelsEndostatin therapyAntiangiogenic effectsMetastatic potentialTherapyUptake doseCellular uptake assaysEndostatinTissue distributionRatsEthylenedicysteine