2016
KDR Amplification Is Associated with VEGF-Induced Activation of the mTOR and Invasion Pathways but does not Predict Clinical Benefit to the VEGFR TKI Vandetanib
Nilsson MB, Giri U, Gudikote J, Tang X, Lu W, Tran H, Fan Y, Koo A, Diao L, Tong P, Wang J, Herbst R, Johnson BE, Ryan A, Webster A, Rowe P, Wistuba II, Heymach JV. KDR Amplification Is Associated with VEGF-Induced Activation of the mTOR and Invasion Pathways but does not Predict Clinical Benefit to the VEGFR TKI Vandetanib. Clinical Cancer Research 2016, 22: 1940-1950. PMID: 26578684, PMCID: PMC4834253, DOI: 10.1158/1078-0432.ccr-15-1994.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Non-Small-Cell LungCell Line, TumorCell MovementCell ProliferationHumansHypoxia-Inducible Factor 1, alpha SubunitLung NeoplasmsP38 Mitogen-Activated Protein KinasesPiperidinesProtein Kinase InhibitorsProto-Oncogene Proteins c-metQuinazolinesSignal TransductionTOR Serine-Threonine KinasesTreatment OutcomeVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsNon-small cell lung cancerTyrosine kinase inhibitorsVEGFR tyrosine kinase inhibitorsNSCLC cell linesZODIAC studyClinical benefitLung cancerPlatinum-refractory non-small cell lung cancerAdvanced non-small cell lung cancerImproved progression-free survivalDifferent lung cancersObjective response rateProgression-free survivalVEGF pathway inhibitorsCell lung cancerArchival tumor samplesCell linesActivation of mTORVandetanib armOverall survivalNSCLC modelsNSCLC cellsPreclinical studiesPatientsVEGFR inhibition
2010
Treatment 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 model
2004
Quantitative 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