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
2001
Novel Approaches to Polynuclear Platinum Pro-Drugs. Selective Release of Cytotoxic Platinum−Spermidine Species through Hydrolytic Cleavage of Carbamates
Hegmans A, Qu Y, Kelland L, Roberts J, Farrell N. Novel Approaches to Polynuclear Platinum Pro-Drugs. Selective Release of Cytotoxic Platinum−Spermidine Species through Hydrolytic Cleavage of Carbamates. Inorganic Chemistry 2001, 40: 6108-6114. PMID: 11703107, DOI: 10.1021/ic010509a.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCarbamatesCatalysisChromatography, High Pressure LiquidFemaleHumansHydrogen-Ion ConcentrationHydrolysisInhibitory Concentration 50Leukemia L1210MiceMolecular StructureNuclear Magnetic Resonance, BiomolecularOrganoplatinum CompoundsOvarian NeoplasmsPolyaminesProdrugsSpermidineSpermineStereoisomerismStructure-Activity RelationshipTemperatureTumor Cells, CulturedConceptsDinuclear platinum compoundsPt–Cl bondsPreliminary biological assaysN-butyl side chainsMagnitude less cytotoxicPolynuclear platinumSecond generation analogsNMR spectroscopyPolyamine linkersQuaternary nitrogenFMOC derivativesConformational isomersDerivatives 4Electrostatic contributionSide chainsHydrolytic cleavageSpermidine moietyGreater selectivityOral deliveryTherapeutic indexPlatinum drugsRate constantsCellular uptakeN-propylBiological assays
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 activityPlatinumCellular pharmacology of polynuclear platinum anti-cancer agents
Roberts J, Peroutka J, Farrell N. Cellular pharmacology of polynuclear platinum anti-cancer agents. Journal Of Inorganic Biochemistry 1999, 77: 51-57. PMID: 10626354, DOI: 10.1016/s0162-0134(99)00147-6.Peer-Reviewed Original ResearchConceptsCisplatin-resistant cell linesCell linesCross-linking adductsWild-type cell linesDNA repair mechanismsL1210 murine leukemia cell lineCellular pharmacologyType cell linesGenomic accessMurine leukemia cell lineWild typeCytotoxic effectsLeukemia cell linesRepair mechanismsDNA interstrandAnti-cancer agentsDiminished accumulationDinuclear platinum complexesTrinuclear platinum complexBBR3464Enhanced activityPotential anticancer agentsPotent cytotoxic agentComplexesVivo activity
1996
Bryostatin 1 activates splenic lymphocytes and induces sustained depletion of splenocyte protein kinase C activity in vivo after a single intravenous administration
Bear H, McFadden A, Kostuchenko P, Lipshy K, Hamad G, Turner A, Roberts J, Carr M, Carr S, Grant S. Bryostatin 1 activates splenic lymphocytes and induces sustained depletion of splenocyte protein kinase C activity in vivo after a single intravenous administration. Anti-Cancer Drugs 1996, 7: 299-306. PMID: 8792004, DOI: 10.1097/00001813-199605000-00010.Peer-Reviewed Original ResearchConceptsBryostatin 1Normal murine spleen cellsT-cell activation marker CD69PKC activityActivation marker CD69Single bolus injectionEarly lymphocyte activationSingle intravenous administrationAnti-tumor effectsNormal host tissuesCell surface phenotypeProtein kinase CMurine spleen cellsPlasma levels resultsRegulate protein kinase CAnti-cancer agentsControl miceMarked splenomegalyBolus injectionIntravenous administrationC57BI/6 miceSpleen cellsSplenocyte proliferationSplenic lymphocytesSurface phenotype
1993
Nitric Oxide Modulates Lymphocyte Proliferation But Not Secretion of IL-2
Huot AE, Moore AL, Roberts JD, Hacker MP. Nitric Oxide Modulates Lymphocyte Proliferation But Not Secretion of IL-2. Immunological Investigations 1993, 22: 319-327. PMID: 7689536, DOI: 10.3109/08820139309063411.Peer-Reviewed Original ResearchConceptsLymphocyte proliferationBAL cellsIL-2Nitric oxideNO synthase inhibitor NG-monomethylSynthase inhibitor NG-monomethylExcess IL-2Bronchoalveolar lavage cellsInhibitor NG-monomethylCytokines IL-2Time of sacrificeIL-2 productionInterleukin-2 productionModulate lymphocyte proliferationSource of NOIL-2-dependent CTLL-2 cellsLavage cellsNG-monomethylCytokine releaseIntratracheal doseCTLL-2 cellsL-arginineLymphocyte growthMarked inhibitionNO inhibits
1992
Activation of the trans geometry in platinum antitumor complexes: a survey of the cytotoxicity of trans complexes containing planar ligands in murine L1210 and human tumor panels and studies on their mechanism of action.
Farrell N, Kelland LR, Roberts JD, Van Beusichem M. Activation of the trans geometry in platinum antitumor complexes: a survey of the cytotoxicity of trans complexes containing planar ligands in murine L1210 and human tumor panels and studies on their mechanism of action. Cancer Research 1992, 52: 5065-72. PMID: 1516063.Peer-Reviewed Original ResearchConceptsPlatinum antitumor complexesPlanar ligandsPyridine complexesAmmine complexesAntitumor complexesNew trans platinum complexesCell linesHuman tumor cell linesTrans-platinum complexesTumor cell linesPreliminary mechanistic studiesMurine L1210Rate of reactionFormula transMechanism of actionTrans complexesTrans geometryImportant biomoleculesSteric hindranceThymus DNAHuman tumor panelOvarian carcinoma cell linesCarcinoma cell linesPotential new classDNA synthesis
1991
Shikimic acid complexes of platinum. Preparation, reactivity, and antitumor activity of (R,R-1,2-diaminocyclohexane) bis(shikimato)platinum(II). Evidence for a novel rearrangement involving platinum—carbon bond formation
Farrell N, Roberts J, Hacker M, Farrell N, Roberts J, Hacker M. Shikimic acid complexes of platinum. Preparation, reactivity, and antitumor activity of (R,R-1,2-diaminocyclohexane) bis(shikimato)platinum(II). Evidence for a novel rearrangement involving platinum—carbon bond formation. Journal Of Inorganic Biochemistry 1991, 42: 237-246. PMID: 1880505, DOI: 10.1016/0162-0134(91)84038-b.Peer-Reviewed Original ResearchConceptsHigh-performance liquid chromatographyCarboxylate oxygenVinylic carbonBond formationAqueous solutionPerformance liquid chromatographyAcid complexesL1210 cell lineLiquid chromatographyHydrolysis productsComplexesComplex IIMajor hydrolysis productsL1210 leukemiaNovel rearrangementMoietyAntitumor activityPlatinumChromatographyReactivityOxygenPreparationCarbonComplex typeFormation
1986
Regional fibrosis after intraperitoneal administration of mafosfamide
Roberts J, Newman R, Kimberly P, Hacker M. Regional fibrosis after intraperitoneal administration of mafosfamide. Investigational New Drugs 1986, 4: 61-65. PMID: 2939038, DOI: 10.1007/bf00172019.Peer-Reviewed Original Research
1984
Efficacy and toxicity of 4-(2-sulfonatoethylthio)-cyclophosphamide cyclohexylamine salt (ASTA Z 7557, INN mafosfamide) after intraperitoneal administration to mice
Roberts J, Hacker M, Newman R, McCormack J, Krakoff I. Efficacy and toxicity of 4-(2-sulfonatoethylthio)-cyclophosphamide cyclohexylamine salt (ASTA Z 7557, INN mafosfamide) after intraperitoneal administration to mice. Investigational New Drugs 1984, 2: 215-220. PMID: 6469517, DOI: 10.1007/bf00232354.Peer-Reviewed Original ResearchConceptsBladder toxicityIntraperitoneal administrationAcute bladder toxicityPhosphoramide mustardAZ therapyHepatic fibrosisIntravenous administrationLocal toxicityTherapeutic indexMurine systemAdministrationCyclophosphamide analoguesFurther studiesSpontaneous activationAssociated riskToxicityCyclohexylamine saltFibrosisTherapyMice