2012
Phase I Trial of Bortezomib (PS-341; NSC 681239) and Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms - Update of the “Bolus” Infusion Schedule of Alvocidib.
Holkova B, Perkins E, Bose P, Sullivan D, Baz R, Tombes M, Shrader E, Ramakrishnan V, Wan W, Sankala H, Kmieciak M, Roberts J, Grant S. Phase I Trial of Bortezomib (PS-341; NSC 681239) and Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms - Update of the “Bolus” Infusion Schedule of Alvocidib. Blood 2012, 120: 2959. DOI: 10.1182/blood.v120.21.2959.2959.Peer-Reviewed Original ResearchAdverse eventsInfusion scheduleMultiple myelomaI trialDose levelsAbsolute neutrophil count decreaseGrade 2 adverse eventsCTCAE version 4Grade 5 eventsIndolent B-cell neoplasmsNeutrophil count decreasePrior systemic therapyPhase II studyECOG performance scoreRefractory multiple myelomaTreatment of recurrentTumor lysis syndromePhase I trialSchedule of administrationCombination of bortezomibIndolent B-cellExpression of pJNKB-cell neoplasmsNF-κB DNA bindingMcl-1
2008
Phase I Trial of Bortezomib (NSC 681239) and Flavopiridol (NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms.
Grant S, Sullivan D, Roodman D, Stuart R, Perkins E, Kolla S, Ramakrishnan V, Wright J, Colevas A, Tombes M, Roberts J. Phase I Trial of Bortezomib (NSC 681239) and Flavopiridol (NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms. Blood 2008, 112: 1573. DOI: 10.1182/blood.v112.11.1573.1573.Peer-Reviewed Original ResearchB-cell neoplasmsDose levelsBolus scheduleI trialMinor responseNF-kappaB nuclear localizationIndolent B-cell neoplasmsPhase II evaluationPhase I trialPhospho-JNKCorrelative laboratory studiesNF-kappaB DNA bindingChronic lymphocytic leukemiaB-cell malignanciesBone marrow CD138Mcl-1Evaluable patientsStable diseaseEligible patientsPostural hypotensionHerpes zosterPartial responseRefractory diseaseStandard therapySystemic therapyVorinostat and Sorafenib Synergistically Kill Tumor Cells via FLIP Suppression and CD95 Activation
Zhang G, Park MA, Mitchell C, Hamed H, Rahmani M, Martin AP, Curiel DT, Yacoub A, Graf M, Lee R, Roberts JD, Fisher PB, Grant S, Dent P. Vorinostat and Sorafenib Synergistically Kill Tumor Cells via FLIP Suppression and CD95 Activation. Clinical Cancer Research 2008, 14: 5385-5399. PMID: 18765530, PMCID: PMC2561272, DOI: 10.1158/1078-0432.ccr-08-0469.Peer-Reviewed Original ResearchConceptsPancreatic adenocarcinoma cellsLong-term colony formation assaysCaspase-8C-FLIPExtracellular signal-regulated kinase 1/2Full-length BidSignal-regulated kinase 1/2Activation of BaxKnockdown of CD95Multiple antiapoptotic proteinsExpression of BimColony formation assaysAdenocarcinoma cellsVorinostat treatmentCD95 activationKill Tumor CellsProapoptotic signalsProtease pathwayKinase 1/2Caspase-9Cathepsin proteasesAntiapoptotic proteinsBcl-xLFADD expressionMcl-1
2007
Low-Dose BBR3610 Toxicity in Colon Cancer Cells Is p53-Independent and Enhanced by Inhibition of Epidermal Growth Factor Receptor (ERBB1)-Phosphatidyl Inositol 3 Kinase Signaling
Mitchell C, Kabolizadeh P, Ryan J, Roberts JD, Yacoub A, Curiel DT, Fisher PB, Hagan MP, Farrell NP, Grant S, Dent P. Low-Dose BBR3610 Toxicity in Colon Cancer Cells Is p53-Independent and Enhanced by Inhibition of Epidermal Growth Factor Receptor (ERBB1)-Phosphatidyl Inositol 3 Kinase Signaling. Molecular Pharmacology 2007, 72: 704-714. PMID: 17578896, DOI: 10.1124/mol.107.038406.Peer-Reviewed Original ResearchConceptsColon cancer cellsEpidermal growth factor receptorGrowth factor receptorActive AktC-FLIPMolecular inhibitionCaspase-8 functionsPhosphatidyl inositol 3 kinaseActivation of BaxDominant-negative AktErbB1 inhibitorsFactor receptorHuman colon cancer cellsOverexpression of XIAPCancer cellsSmall moleculesKinase signalingPI3K inhibitorsAkt activityCaspase-9Bcl-xLNull cellsMcl-1SW480 cellsK-RAS
2005
Phase I Trial of Bortezomib (NSC 681239) and Flavopiridol (NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms.
Grant S, Sullivan D, Roodman D, Stuart R, Perkins E, Ramakrishnan V, Wright J, Colevas A, Roberts J. Phase I Trial of Bortezomib (NSC 681239) and Flavopiridol (NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms. Blood 2005, 106: 3338. DOI: 10.1182/blood.v106.11.3338.3338.Peer-Reviewed Original ResearchI trialDose levelsPre-existing peripheral neuropathyIndolent B-cell lymphomaNF-kappaB nuclear localizationIndolent B-cell neoplasmsCase of exacerbationPhase I trialPhase II evaluationPhospho-JNKCorrelative laboratory studiesNF-kappaB DNA bindingB-cell lymphomaB-cell malignanciesBone marrow CD138B-cell neoplasmsMcl-1Eligible patientsStable diseaseHerpes zosterPartial responseRefractory diseaseStandard therapySystemic therapyComplete response