2023
Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs new combination cancer therapy strategies
Glasner A, Rose S, Sharma R, Gudjonson H, Chu T, Green J, Rampersaud S, Valdez I, Andretta E, Dhillon B, Schizas M, Dikiy S, Mendoza A, Hu W, Wang Z, Chaudhary O, Xu T, Mazutis L, Rizzuto G, Quintanal-Villalonga A, Manoj P, de Stanchina E, Rudin C, Pe’er D, Rudensky A. Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs new combination cancer therapy strategies. Nature Immunology 2023, 24: 1020-1035. PMID: 37127830, PMCID: PMC10232368, DOI: 10.1038/s41590-023-01504-2.Peer-Reviewed Original ResearchConceptsTreg cell depletionRegulatory T cellsT cellsCell depletionEffector T cellsInjury-induced inflammationTreg cell functionSolid organ cancersAntigen presenting cellsExperimental lung cancerLung adenocarcinoma progressionAccessory cell typesT cell activationRational combination treatmentsTreg cellsCorresponding monotherapiesOrgan cancersLung cancerInjury settingPresenting cellsVEGF blockadeAdenocarcinoma progressionCombination treatmentMyeloid cellsCell activationSociety for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors with targeted therapies
Atkins M, Ascierto P, Feltquate D, Gulley J, Johnson D, Khushalani N, Sosman J, Yap T, Kluger H, Sullivan R, Tawbi H. Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors with targeted therapies. Journal For ImmunoTherapy Of Cancer 2023, 11: e005923. PMID: 36918225, PMCID: PMC10016252, DOI: 10.1136/jitc-2022-005923.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsConsensus definitionCheckpoint inhibitorsAntiangiogenic therapySingle-agent immune checkpoint inhibitorsConsensus clinical definitionSolid tumor settingTumor immune microenvironmentImmunotherapy of cancerDurable disease controlClinical trial designSignal transduction inhibitorsICI combinationsEndometrial cancerImproved survivalRandomized trialsImmune microenvironmentMechanisms of resistanceHepatocellular carcinomaClinical definitionKidney cancerImmunotherapyTumor settingsCombination treatmentTrial designRegistered clinical trials investigating ketamine and esketamine for treatment-resistant depression: A systematic review
Brendle M, Ragnhildstveit A, Slayton M, Smart L, Cunningham S, Zimmerman M, Seli P, Gaffrey M, Averill L, Robison R. Registered clinical trials investigating ketamine and esketamine for treatment-resistant depression: A systematic review. Journal Of Psychedelic Studies 2023, 6: 176-187. DOI: 10.1556/2054.2022.00234.Peer-Reviewed Original ResearchTreatment-resistant depressionMontgomery-Asberg Depression Rating ScaleDepression Rating ScaleLate-phase trialsTrial eligibilityPatient characteristicsDrug regimensClinical outcomesResults databaseRegistered trialsClinical trialsTreatment responseEsketaminePharmacological approachesPRISMA guidelinesCombination treatmentMost trialsClinical practiceElectronic registryKetamineSystematic reviewFinal reviewTherapeutic useQualitative synthesisStudy design
2022
The oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with hormone receptor-positive HER2-negative (HR + /HER2 −) advanced/metastatic breast cancer
Bardia A, Mayer I, Winer E, Linden H, Ma C, Parker B, Bellet M, Arteaga C, Cheeti S, Gates M, Chang C, Fredrickson J, Spoerke J, Moore H, Giltnane J, Friedman L, Chow Maneval E, Chan I, Jhaveri K. The oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with hormone receptor-positive HER2-negative (HR + /HER2 −) advanced/metastatic breast cancer. Breast Cancer Research And Treatment 2022, 197: 319-331. PMID: 36401732, PMCID: PMC9823088, DOI: 10.1007/s10549-022-06797-9.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerSelective estrogen receptor degraderDose escalationESR1 mutationsPostmenopausal womenBreast cancerEstrogen receptorCombination treatmentNon-complete response/non-progressive diseaseAdvanced/Metastatic Breast CancerOral selective estrogen receptor degraderPreliminary anti-tumor activityESR1 mutation statusPhase 2 dosePlasma ctDNA samplesCommon adverse eventsNon-progressive diseaseDose-limiting toxicityHormone-releasing hormoneSelective estrogen receptorAnti-tumor activityStable diseaseAdverse eventsPartial responseProgressive diseasePoster: MDS-476 Sabatolimab (MBG453) Combination Treatment Regimens for Patients With Higher-Risk Myelodysplastic Syndromes (HR-MDS): The Myelodysplastic Syndromes Studies in the STIMULUS Immuno-Myeloid Clinical Trial Program
Zeidan A, Al-Kali A, Borate U, Cluzeau T, DeZern A, Esteve J, Giagounidis A, Kobata K, Lyons R, Platzbecker U, Sallman D, Santini V, Sanz G, Sekeres M, Wei A, Xiao Z, Van Hoef M, Nourry-Boulot C, Sadek I, Ma F, Iordan A, Sabo J, Garcia-Manero G. Poster: MDS-476 Sabatolimab (MBG453) Combination Treatment Regimens for Patients With Higher-Risk Myelodysplastic Syndromes (HR-MDS): The Myelodysplastic Syndromes Studies in the STIMULUS Immuno-Myeloid Clinical Trial Program. Clinical Lymphoma Myeloma & Leukemia 2022, 22: s155. DOI: 10.1016/s2152-2650(22)00947-8.Peer-Reviewed Original ResearchTargeting Krebs-cycle-deficient renal cell carcinoma with Poly ADP-ribose polymerase inhibitors and low-dose alkylating chemotherapy
Ueno D, Vasquez JC, Sule A, Liang J, van Doorn J, Sundaram R, Friedman S, Caliliw R, Ohtake S, Bao X, Li J, Ye H, Boyd K, Huang RR, Dodson J, Boutros P, Bindra RS, Shuch B. Targeting Krebs-cycle-deficient renal cell carcinoma with Poly ADP-ribose polymerase inhibitors and low-dose alkylating chemotherapy. Oncotarget 2022, 13: 1054-1067. PMID: 36128328, PMCID: PMC9477221, DOI: 10.18632/oncotarget.28273.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine Diphosphate RiboseAnimalsCarcinoma, Renal CellCitric Acid CycleDioxygenasesDNAFumarate HydrataseFumaratesHumansJumonji Domain-Containing Histone DemethylasesKidney NeoplasmsLysineMicePoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsSuccinate DehydrogenaseSuccinatesTemozolomideConceptsRenal cell carcinomaPoly ADP-ribose polymerase inhibitorsADP-ribose polymerase inhibitorsCell carcinomaSDH-deficient renal cell carcinomaPolymerase inhibitorsLow-dose temozolomideAggressive renal cell carcinomaHereditary cancer syndromesNovel therapeutic strategiesDeficient murine modelStandard dosingTMZ resultsMurine modelTherapeutic strategiesCombination treatmentCancer syndromesTumor growthHomologous recombination DNA repair pathwayAccumulation of fumarateHR deficiencyPARP inhibitionTemozolomideChemotherapyCarcinomaAzacitidine and Durvalumab in First-line Treatment of Elderly Patients With Acute Myeloid Leukemia
Zeidan AM, Boss I, Beach C, Copeland WB, Thompson E, Fox BA, Hasle VE, Hellmann A, Taussig D, Tormo M, Voso MT, Cavenagh J, O’Connor T, Previtali A, Rose S, Silverman LR. Azacitidine and Durvalumab in First-line Treatment of Elderly Patients With Acute Myeloid Leukemia. Blood Advances 2022, 6: 2219-2229. PMID: 34933333, PMCID: PMC9006260, DOI: 10.1182/bloodadvances.2021006138.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaFirst-line therapyOlder patientsDay 1First-line combination therapyTreatment-emergent adverse eventsRandomized phase 2 trialSafety of durvalumabNew safety signalsPD-L1 expressionPhase 2 studyPhase 2 trialDuration of responseOverall response rateDurvalumab 1500Adverse eventsOverall survivalClinical efficacyCombination therapyMyeloid leukemiaSafety signalsTreatment responseCombination treatmentAzacitidineResponse rate
2021
Cigarette Smoking and Heavy Alcohol Drinking: The Challenges and Opportunities for Combination Treatments
King A, Fucito L. Cigarette Smoking and Heavy Alcohol Drinking: The Challenges and Opportunities for Combination Treatments. American Journal Of Psychiatry 2021, 178: 783-785. PMID: 34516230, DOI: 10.1176/appi.ajp.2021.21070692.Peer-Reviewed Original ResearchEthical, Regulatory and Market related aspects of Deploying Triple Artemisinin-Based Combination Therapies for Malaria treatment in Africa: A study protocol.
Tindana P, de Haan F, Mokuolu O, Guissou R, Bolarinwa O, Ouedraogo J, Tou F, Boon W, Moors E, Dondorp A, Dhorda M, Amaratunga C, Cheah P. Ethical, Regulatory and Market related aspects of Deploying Triple Artemisinin-Based Combination Therapies for Malaria treatment in Africa: A study protocol. Wellcome Open Research 2021, 6: 75. PMID: 34458588, PMCID: PMC8378406, DOI: 10.12688/wellcomeopenres.16065.1.Peer-Reviewed Original ResearchArtemisinin combination therapyCombination therapyQualitative research methodsViews of stakeholdersDepth interviewsPosition issuesMarket-related issuesCommunity membersNational Malaria Control ProgrammeGlobal malaria deathsArtemisinin combination treatmentSoutheast AsiaGroup discussionsNational regulatory authoritiesMalaria control programmesResearch methodsAfricaACT resistanceMalaria deathsMalaria treatmentStudy protocolMalaria prevalenceAntimalarial medicinesCombination treatmentStakeholders
2020
The radiosensitizer Onalespib increases complete remission in 177Lu-DOTATATE-treated mice bearing neuroendocrine tumor xenografts
Lundsten S, Spiegelberg D, Raval NR, Nestor M. The radiosensitizer Onalespib increases complete remission in 177Lu-DOTATATE-treated mice bearing neuroendocrine tumor xenografts. European Journal Of Nuclear Medicine And Molecular Imaging 2020, 47: 980-990. PMID: 31912256, PMCID: PMC7075859, DOI: 10.1007/s00259-019-04673-1.Peer-Reviewed Original ResearchConceptsComplete remissionToxicity profileNeuroendocrine tumorsSomatostatin receptorsCombination treatmentHistological analysisFavorable toxicity profileBetter therapeutic resultsDose-limiting organHeat shock protein 90 inhibitorShock protein 90 inhibitorsNeuroendocrine tumor xenograftsMonotherapy groupGlomerular injuryUnwanted side effectsCombination groupTherapeutic resultsTherapeutic effectTumor xenograftsSide effectsTumor uptakeRemissionXenograftsTumorsHSP70 upregulation
2019
Intratumoral delivery of RIG-I agonist induces robust anti-tumor immune responses
Jiang X, Fedorova O, Linehan M, Dong H, Pyle A, Iwasaki A. Intratumoral delivery of RIG-I agonist induces robust anti-tumor immune responses. The Journal Of Immunology 2019, 202: 194.28-194.28. DOI: 10.4049/jimmunol.202.supp.194.28.Peer-Reviewed Original ResearchAnti-tumor efficacyRobust anti-tumor immune responseAnti-tumor immune responseTumor microenvironmentNucleic acid-sensing pathwaysT-cell depletionTumor-infiltrating lymphocytesCytosolic nucleic acid-sensing pathwaysB16 melanoma growthVivo anti-tumor efficacyPromising therapeutic agentLong-term survivalRemarkable antitumor effectImmunogenic tumorsInnate cellsCell depletionCancer immunotherapyMouse survivalImmune responseTumor volumeCombination treatmentIntratumoral deliveryAntitumor effectsMelanoma growthTumor subtypes
2018
Inhibition of PRMT1 Mediated FLT3 Arginine Methylation As a Potent Therapeutic Strategy for MLL-r ALL
Zhu Y, He X, Dong H, Sun J, Wang H, Zhang L, Miao Y, Jin J, Shen Y, Chen J, Muschen M, Chen C, Konopleva M, Sun W, Zhang B, Kuo Y, Carlesso N, Marcucci G, Li L. Inhibition of PRMT1 Mediated FLT3 Arginine Methylation As a Potent Therapeutic Strategy for MLL-r ALL. Blood 2018, 132: 892. DOI: 10.1182/blood-2018-99-115139.Peer-Reviewed Original Research
2017
Phase Ib Study of Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Combination with Pembrolizumab (MK-3475) in Patients with Advanced Solid Tumors
Tolcher AW, Sznol M, Hu-Lieskovan S, Papadopoulos KP, Patnaik A, Rasco DW, Di Gravio D, Huang B, Gambhire D, Chen Y, Thall AD, Pathan N, Schmidt EV, Chow LQM. Phase Ib Study of Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Combination with Pembrolizumab (MK-3475) in Patients with Advanced Solid Tumors. Clinical Cancer Research 2017, 23: 5349-5357. PMID: 28634283, DOI: 10.1158/1078-0432.ccr-17-1243.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCombined Modality TherapyDiagnostic ImagingDrug MonitoringFemaleHumansImmunoglobulin GMaleMaximum Tolerated DoseMiddle AgedMolecular Targeted TherapyNeoplasm StagingNeoplasmsRetreatmentT-Lymphocyte SubsetsTreatment OutcomeTumor Necrosis Factor Receptor Superfamily, Member 9ConceptsAdvanced solid tumorsSolid tumorsTreatment-emergent adverse eventsPeripheral blood CD8Phase Ib studyTreatment-related discontinuationsDose-limiting toxicityCostimulatory receptor 4Event continual reassessment methodT cell costimulatory receptor 4Clin Cancer ResSupport further investigationBlood CD8Partial responseAdverse eventsDose escalationReceptor 4Clinical activityT cellsIb studyCombination treatmentContinual reassessment methodPatientsGrade 1Cancer ResDifferential predictive value of PTSD symptom clusters for mental health care among Iraq and Afghanistan veterans following PTSD diagnosis
Smith NB, Tsai J, Pietrzak RH, Cook JM, Hoff R, Harpaz-Rotem I. Differential predictive value of PTSD symptom clusters for mental health care among Iraq and Afghanistan veterans following PTSD diagnosis. Psychiatry Research 2017, 256: 32-39. PMID: 28622572, DOI: 10.1016/j.psychres.2017.06.005.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderAfghanistan veteransPTSD symptom clustersNational VA administrative dataVeterans AffairsSymptom clustersMental health service utilizationTreatment-related variablesHealth service utilizationVA administrative dataSelection of treatmentMental health carePTSD symptom cluster severitySymptom cluster severityTrauma-exposed veteransInitial diagnosisClinical variablesPsychotherapy visitsAdequate doseService utilizationDifferential predictive valueLarge cohortCombination treatmentPsychotherapy initiationTreatment approachesSystematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer
Wali VB, Langdon CG, Held MA, Platt JT, Patwardhan GA, Safonov A, Aktas B, Pusztai L, Stern DF, Hatzis C. Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer. Cancer Research 2017, 77: 566-578. PMID: 27872098, PMCID: PMC5582957, DOI: 10.1158/0008-5472.can-16-1901.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerTNBC cell linesPairwise drug combinationsClinical translationAggressive diseaseCombination therapyBreast cancerPreclinical proofDrug combinationsCombination treatmentInvestigational drugsSingle agentSensitivity patternCell sensitivityCell linesTherapyApoptotic activityAnticancer activityDownregulated genesMitogenic signalingCrizotinibBlockadeClinicAgentsCancer
2016
Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma
Wallin JJ, Bendell JC, Funke R, Sznol M, Korski K, Jones S, Hernandez G, Mier J, He X, Hodi FS, Denker M, Leveque V, Cañamero M, Babitski G, Koeppen H, Ziai J, Sharma N, Gaire F, Chen DS, Waterkamp D, Hegde PS, McDermott DF. Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma. Nature Communications 2016, 7: 12624. PMID: 27571927, PMCID: PMC5013615, DOI: 10.1038/ncomms12624.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntigens, NeoplasmAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBevacizumabCarcinoma, Renal CellCD8-Positive T-LymphocytesCell MovementDrug SynergismFemaleHumansKidneyKidney NeoplasmsMaleMaximum Tolerated DoseMiddle AgedTreatment OutcomeVascular Endothelial Growth Factor AConceptsAntigen-specific T-cell migrationT cell migrationT cellsCombination treatmentAnti-tumor immune activationPD-L1 checkpoint inhibitionMetastatic renal cell carcinomaAddition of atezolizumabIntra-tumoral CD8Subset of patientsT cell infiltrationImmune cell activityRenal cell carcinomaEndothelial cell activationVariety of cancersLymphocytes increasesPeripheral CD8Checkpoint inhibitorsDurable responsesCheckpoint inhibitionImmune activationCell carcinomaVascular normalizationReceptor increasesCell activationPhase I study of pemetrexed with sorafenib in advanced solid tumors
Poklepovic A, Gordon S, Shafer DA, Roberts JD, Bose P, Geyer CE, McGuire WP, Tombes MB, Shrader E, Strickler K, Quigley M, Wan W, Kmieciak M, Massey HD, Booth L, Moran RG, Dent P. Phase I study of pemetrexed with sorafenib in advanced solid tumors. Oncotarget 2016, 7: 42625-42638. PMID: 27213589, PMCID: PMC5173162, DOI: 10.18632/oncotarget.9434.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCohort StudiesFemaleHumansInflammationMaleMaximum Tolerated DoseMiddle AgedNeoplasmsNiacinamidePemetrexedPhenylurea CompoundsPTEN PhosphohydrolaseSorafenibTreatment OutcomeTriple Negative Breast NeoplasmsConceptsAdvanced solid tumorsDay 1Solid tumorsOral sorafenibDose scheduleBreast cancerTriple-negative breast cancerDose-escalation schemaPhase II dosePhase I trialSorafenib dosingSorafenib therapyStable diseaseCohort BComplete responseI trialPartial responseTolerable combinationRadiographic assessmentCumulative toxicityCombination treatmentPatientsSorafenibPhase IAntitumor activity
2014
Transmission blocking activity of Azadirachta indica and Guiera senegalensis extracts on the sporogonic development of Plasmodium falciparum field isolates in Anopheles coluzzii mosquitoes
Yerbanga R, Lucantoni L, Ouédraogo R, Da D, Yao F, Yaméogo K, Churcher T, Lupidi G, Taglialatela-Scafati O, Gouagna L, Cohuet A, Christophides G, Ouédraogo J, Habluetzel A. Transmission blocking activity of Azadirachta indica and Guiera senegalensis extracts on the sporogonic development of Plasmodium falciparum field isolates in Anopheles coluzzii mosquitoes. Parasites & Vectors 2014, 7: 185. PMID: 24735564, PMCID: PMC3996177, DOI: 10.1186/1756-3305-7-185.Peer-Reviewed Original ResearchConceptsOocyst prevalencePlasmodium falciparum fieldMalaria control toolsLate-stage gametocytesAnopheles coluzzii femalesEvidence of transmissionPharmacological strategiesAntiplasmodial effectCombination treatmentAnopheles coluzzii mosquitoesAntimalarial drugsMalaria controlMalaria parasitesPlasmodium falciparumMembrane feedingMosquito midgutHerbal formulationsGuiera senegalensisEthyl acetate extractPlant extractsEthanol extractHuman hostColuzzii mosquitoesNeem tree Azadirachta indicaOocyst density
2012
Population Pharmacokinetics and Pharmacodynamics of Piperaquine in Children With Uncomplicated Falciparum Malaria
Tarning J, Zongo I, Somé FA, Rouamba N, Parikh S, Rosenthal PJ, Hanpithakpong W, Jongrak N, Day NP, White NJ, Nosten F, Ouedraogo J, Lindegardh N. Population Pharmacokinetics and Pharmacodynamics of Piperaquine in Children With Uncomplicated Falciparum Malaria. Clinical Pharmacology & Therapeutics 2012, 91: 497-505. PMID: 22258469, PMCID: PMC3736305, DOI: 10.1038/clpt.2011.254.Peer-Reviewed Original ResearchConceptsUncomplicated falciparum malariaFalciparum malariaPopulation pharmacokineticsThree-compartment distribution modelNonlinear mixed-effects modelingRecurrent malaria infectionsTotal piperaquine exposureArtemisinin combination treatmentWeight-normalized dosePlasma concentration-time profilesYoung childrenMixed-effects modelingConcentration-time profilesPiperaquine concentrationsPiperaquine exposureDose regimenMalaria infectionPlasma concentrationsPharmacodynamic propertiesCombination treatmentBody weightPiperaquineSignificant covariatesOlder childrenMalaria
2011
Survivin Inhibition Is Critical for Bcl-2 Inhibitor-Induced Apoptosis in Hepatocellular Carcinoma Cells
Zhao X, Ogunwobi O, Liu C. Survivin Inhibition Is Critical for Bcl-2 Inhibitor-Induced Apoptosis in Hepatocellular Carcinoma Cells. PLOS ONE 2011, 6: e21980. PMID: 21829603, PMCID: PMC3148218, DOI: 10.1371/journal.pone.0021980.Peer-Reviewed Original ResearchConceptsBcl-2 inhibitorsCombination treatmentHCC cellsABT-263Survivin inhibitionHepatocellular carcinomaHuman liver cancer tissuesSingle treatmentFuture clinical trialsApoptotic effectsLiver cancer tissuesLiver cancer therapyERK activationHCC cell linesHepatocellular carcinoma cellsPreclinical dataClinical trialsTherapeutic effectLow doseNormal human hepatocytesCancer tissuesYM-155High dosesNovel Bcl-2 inhibitorABT-263-induced apoptosis
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