2010
Measurement 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 setting
2007
Targeted 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
2006
Phase I Dose Escalation and Pharmacokinetic Study of Enzastaurin, an Oral Protein Kinase C Beta Inhibitor, in Patients With Advanced Cancer
Carducci MA, Musib L, Kies MS, Pili R, Truong M, Brahmer JR, Cole P, Sullivan R, Riddle J, Schmidt J, Enas N, Sinha V, Thornton DE, Herbst RS. Phase I Dose Escalation and Pharmacokinetic Study of Enzastaurin, an Oral Protein Kinase C Beta Inhibitor, in Patients With Advanced Cancer. Journal Of Clinical Oncology 2006, 24: 4092-4099. PMID: 16943527, DOI: 10.1200/jco.2005.05.3447.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAntineoplastic AgentsDose-Response Relationship, DrugDrug Administration ScheduleFemaleFlow CytometryGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHumansIndolesMaleMiddle AgedNeoplasmsProtein Kinase CProtein Kinase C betaProtein Kinase InhibitorsConceptsMaximum-tolerated doseProtein kinase C beta inhibitorStable diseaseAdvanced cancerEastern Cooperative Oncology Group performance statusSignificant grade 3/4 toxicityBeta inhibitorGrade 3/4 toxicitiesPhase II dosePhase II trialDose-limiting toxicityYears of ageExpansion cohortGI toxicityII trialStarting dosePerformance statusDose escalationAdditional patientsNeck cancerPrevalent malignancySafety dataPatientsSecondary objectiveEnzastaurinDevelopment and Validation of a Drug Activity Biomarker that Shows Target Inhibition in Cancer Patients Receiving Enzastaurin, a Novel Protein Kinase C-β Inhibitor
Green LJ, Marder P, Ray C, Cook CA, Jaken S, Musib LC, Herbst RS, Carducci M, Britten CD, Basche M, Eckhardt SG, Thornton D. Development and Validation of a Drug Activity Biomarker that Shows Target Inhibition in Cancer Patients Receiving Enzastaurin, a Novel Protein Kinase C-β Inhibitor. Clinical Cancer Research 2006, 12: 3408-3415. PMID: 16740765, DOI: 10.1158/1078-0432.ccr-05-2231.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBiomarkersCapecitabineCell Line, TumorClinical Trials, Phase I as TopicDeoxycytidineEnzyme ActivatorsEnzyme InhibitorsFlow CytometryFluorouracilFollow-Up StudiesHumansIndolesLeukocytes, MononuclearMonocytesNeoplasmsProtein Kinase CProtein Kinase C betaReproducibility of ResultsSensitivity and SpecificitySignal TransductionStructure-Activity RelationshipTreatment OutcomeConceptsPeripheral blood mononuclear cellsDaily oral dosesBlood mononuclear cellsCancer patientsOral dosesMononuclear cellsFlow cytometryDrug activity biomarkerPKC activityTarget cellsActivity biomarkersPhorbol esterNormal donorsPatientsActivity of PKCU937 cell lineTarget inhibitionEnzastaurinKinase inhibitorsΒ inhibitorSignificant decreaseCell linesU937 cellsIntracellular phosphoproteinsProtein kinase C
2002
Targeted therapy against human lung cancer in nude mice by high-affinity recombinant antimesothelin single-chain Fv immunotoxin.
Fan D, Yano S, Shinohara H, Solorzano C, Van Arsdall M, Bucana CD, Pathak S, Kruzel E, Herbst RS, Onn A, Roach JS, Onda M, Wang QC, Pastan I, Fidler IJ. Targeted therapy against human lung cancer in nude mice by high-affinity recombinant antimesothelin single-chain Fv immunotoxin. Molecular Cancer Therapeutics 2002, 1: 595-600. PMID: 12479219.Peer-Reviewed Original ResearchMeSH KeywordsADP Ribose TransferasesAnimalsBacterial ToxinsDose-Response Relationship, DrugExotoxinsFlow CytometryHumansImmunoglobulin FragmentsImmunotherapyKineticsLung NeoplasmsMesothelinMiceMice, NudeMicroscopy, FluorescenceMutationNeoplasm TransplantationPseudomonasRecombinant ProteinsTumor Cells, CulturedVirulence FactorsConceptsTargeted therapyNude miceHuman non-small cell lung cancer cellsNon-small cell lung cancer cellsNCI-H226 cellsHuman lung cancer cell linesCell lung cancer cellsSquamous cell carcinomaLung cancer cell linesHuman lung cancerExperimental lung metastasisLung cancer cellsPC14PE6 cellsCancer cell linesLung metastasesCell carcinomaCancer patientsLung cancerOvarian cancerNontoxic doseMesothelinDay 7Recombinant immunotoxinCertain cancersCancer