2006
Human Chorionic Gonadotropin Modulates Prostate Cancer Cell Survival after Irradiation or HMG CoA Reductase Inhibitor Treatment
Yacoub A, Hawkins W, Hanna D, Young H, Park MA, Grant M, Roberts JD, Curiel DT, Fisher PB, Valerie K, Grant S, Hagan MP, Dent P. Human Chorionic Gonadotropin Modulates Prostate Cancer Cell Survival after Irradiation or HMG CoA Reductase Inhibitor Treatment. Molecular Pharmacology 2006, 71: 259-275. PMID: 17050804, DOI: 10.1124/mol.106.031153.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinase kinaseProtein kinase kinaseKinase 1/2 signalingOverexpression of BclDominant-negative AktInhibition of phosphatidylinositolCoA reductase inhibitor lovastatinPan-caspase inhibitorExpression of BclCancer cell survivalHMG-CoA reductase inhibitor lovastatinApoptosis-inducing factor expressionProstate cancer cell survivalTreatment of cellsEpidermal growth factor receptorDominant-negative IkappaBInhibition of erbB1Kinase kinaseReductase inhibitor lovastatinGeranylgeranyl transferase inhibitorPARP1 functionGrowth factor receptorCytotoxic effectsCaspase-9Prostate cancer cells
2005
Transient exposure of mammary tumors to PD184352 and UCN-01 causes tumor cell death in vivo and prolonged suppression of tumor re-growth
Hawkins W, Mitchell C, McKinstry R, Gilfor D, Starkey J, Dai Y, Dawson K, Ramakrishnan V, Roberts JD, Yacoub A, Grant S, Dent P. Transient exposure of mammary tumors to PD184352 and UCN-01 causes tumor cell death in vivo and prolonged suppression of tumor re-growth. Cancer Biology & Therapy 2005, 4: 1275-1284. PMID: 16319524, DOI: 10.4161/cbt.4.11.2286.Peer-Reviewed Original ResearchConceptsTumor cell deathTumor growthMDA-MB-231Drug exposureTumor volumeUCN-01Cell deathTumor cellsMCF7 tumor growthMDA-MB-231 tumorsMEK1/2 inhibitorMean tumor volumeMammary tumor growthTransient exposureTumor growth rateHuman mammary carcinoma cellsK-RAS expressionCombination index valuesMammary carcinoma cellsColony formation assaysPhosphorylation of ERK1/2Colony formation studiesEstrogen dependencyMammary tumorsProlonged suppression
2003
The use of cyclin-dependent kinase inhibitors alone or in combination with established cytotoxic drugs in cancer chemotherapy
Grant S, Roberts JD. The use of cyclin-dependent kinase inhibitors alone or in combination with established cytotoxic drugs in cancer chemotherapy. Drug Resistance Updates 2003, 6: 15-26. PMID: 12654284, DOI: 10.1016/s1368-7646(02)00141-3.Peer-Reviewed Original ResearchConceptsCyclin-dependent kinase inhibitorCytotoxic agentsKinase inhibitorsSingle-agent activityCDK inhibitorsConventional cytotoxic agentsAnti-tumor effectsApoptotic regulatory moleculesCell cycle dysregulationNeoplastic cell proliferationAbundant preclinical evidencePreclinical evidenceTumor cell typesCritical molecular targetsClinical studiesSpecific tumor cell typesPreclinical studiesClinical developmentSmall molecule inhibitorsCell cycle traverseCytotoxic drugsAntitumor efficacyClinical arenaCancer chemotherapyMolecular targets
2000
Pharmacokinetic and pharmacodynamic evaluation of the glycinamide ribonucleotide formyltransferase inhibitor AG2034.
McLeod HL, Cassidy J, Powrie RH, Priest DG, Zorbas MA, Synold TW, Shibata S, Spicer D, Bissett D, Pithavala YK, Collier MA, Paradiso LJ, Roberts JD. Pharmacokinetic and pharmacodynamic evaluation of the glycinamide ribonucleotide formyltransferase inhibitor AG2034. Clinical Cancer Research 2000, 6: 2677-84. PMID: 10914709.Peer-Reviewed Original ResearchConceptsGlycinamide ribonucleotide formyltransferaseCourse 1Systemic clearanceGrade III/IV toxicityGrade II toxicityMin/m2Rapid systemic clearanceVolume of distributionEvaluable patientsSystemic exposurePharmacodynamic evaluationClinical centersBolus injectionPharmacokinetic approachBlood samplesPatient toxicityPatientsElimination patternReproducible ELISAAG2034Course 3Phase IAnticancer agentsPurine synthesis pathwayDe novo purine synthesis pathwayPhase I study of AG2034, a targeted GARFT inhibitor, administered once every 3 weeks
Roberts J, Shibata S, Spicer D, McLeod H, Tombes M, Kyle B, Carroll M, Sheedy B, Collier M, Pithavala Y, Paradiso L, Clendeninn N. Phase I study of AG2034, a targeted GARFT inhibitor, administered once every 3 weeks. Cancer Chemotherapy And Pharmacology 2000, 45: 423-427. PMID: 10803927, DOI: 10.1007/s002800051012.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityPhase II doseCumulative toxicityAdvanced malignanciesIntravenous bolusAUC0-24Pharmacodynamic factorsFolate supplementationPlasma concentrationsIntermediate dosePharmacokinetic analysisDose levelsELISA assaysDosePhase IAG2034Progressive increaseGARFT inhibitorToxicityWeeksInhibitorsMucositisThrombocytopeniaDiarrheaHyperbilirubinemia
1999
Comparison of cytotoxicity and cellular accumulation of polynuclear platinum complexes in L1210 murine leukemia cell lines
Roberts J, Peroutka J, Beggiolin G, Manzotti C, Piazzoni L, Farrell N. Comparison of cytotoxicity and cellular accumulation of polynuclear platinum complexes in L1210 murine leukemia cell lines. Journal Of Inorganic Biochemistry 1999, 77: 47-50. PMID: 10626353, DOI: 10.1016/s0162-0134(99)00137-3.Peer-Reviewed Original ResearchConceptsPolynuclear platinum complexesPlatinum complexesDiamine linkerL1210 cell lineDinuclear platinum complexesTrinuclear platinum complexL1210 murine leukemia cell lineL1210/DDPDinuclear complexesAnticancer profileChemical featuresCytotoxicity profileCellular uptakeBBR3464LinkerMurine leukemia cell lineComplexesTransCharge contributesClinical agentsCytotoxicityUptake pathwayCellular accumulationAntitumor activityPlatinum