2022
SaliVISION: a rapid saliva-based COVID-19 screening and diagnostic test with high sensitivity and specificity
DeFina SM, Wang J, Yang L, Zhou H, Adams J, Cushing W, Tuohy B, Hui P, Liu C, Pham K. SaliVISION: a rapid saliva-based COVID-19 screening and diagnostic test with high sensitivity and specificity. Scientific Reports 2022, 12: 5729. PMID: 35388102, PMCID: PMC8986854, DOI: 10.1038/s41598-022-09718-4.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Severe acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Diagnostic testingRespiratory syndrome coronavirus 2Reverse transcription loop-mediated isothermal amplificationTranscription loop-mediated isothermal amplificationTranscription-quantitative polymerase chain reactionSyndrome coronavirus 2COVID-19 diagnostic testingCoronavirus disease 2019Public health challengeRapid diagnostic testingCOVID-19 screeningQuantitative polymerase chain reactionLoop-mediated isothermal amplificationCoronavirus 2Polymerase chain reactionLaboratory testingRapid diagnostic assaysDisease 2019RT-LAMPInvasive sample collectionDiagnostic testsChain reactionRapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons
Chaguza C, Coppi A, Earnest R, Ferguson D, Kerantzas N, Warner F, Young HP, Breban MI, Billig K, Koch RT, Pham K, Kalinich CC, Ott IM, Fauver JR, Hahn AM, Tikhonova IR, Castaldi C, De Kumar B, Pettker CM, Warren JL, Weinberger DM, Landry ML, Peaper DR, Schulz W, Vogels CBF, Grubaugh ND. Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons. Med 2022, 3: 325-334.e4. PMID: 35399324, PMCID: PMC8983481, DOI: 10.1016/j.medj.2022.03.010.Peer-Reviewed Original ResearchConceptsSpike gene target failureSARS-CoV-2 Omicron variantPositivity rateOmicron variantOmicron infectionVaccine dosesVaccine-induced immunityNumber of dosesTest positivity rateOdds of infectionSARS-CoV-2Significant reductionDominant Delta variantUnvaccinated personsVaccination statusHigher oddsDelta variantInfectionVaccine manufacturersDisease controlVirus copiesDosesPCR testOddsTarget failureInterferon drives HCV scarring of the epigenome and creates targetable vulnerabilities following viral clearance
Hlady RA, Zhao X, Khoury L, Luna A, Pham K, Wu Q, Lee J, Pyrsopoulos NT, Liu C, Robertson KD. Interferon drives HCV scarring of the epigenome and creates targetable vulnerabilities following viral clearance. Hepatology 2022, 75: 983-996. PMID: 34387871, PMCID: PMC9416882, DOI: 10.1002/hep.32111.Peer-Reviewed Original ResearchConceptsDNA methylationHistone modificationsWide DNA methylationAberrant DNA methylationGene expression analysisDNA methyltransferase inhibitorOpen chromatinEpigenetic mechanismsEpigenetic targetsHuman patient samplesEpigenetic changesEpigenomeMethyltransferase inhibitorTargetable vulnerabilitiesMethylationHCC cell linesImmortalized hepatocytesCell linesFunctional effectsChronic HCV infectionChromatinHCV infectionImmune responsePatient samplesSynergizes
2021
Potential role of IFN-α in COVID-19 patients and its underlying treatment options
Yang L, Wang J, Hui P, Yarovinsky TO, Badeti S, Pham K, Liu C. Potential role of IFN-α in COVID-19 patients and its underlying treatment options. Applied Microbiology And Biotechnology 2021, 105: 4005-4015. PMID: 33950278, PMCID: PMC8096625, DOI: 10.1007/s00253-021-11319-6.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSARS-CoV-2 infectionIFN-α subtypesRespiratory virus diseasesCOVID-19 patientsImmunoregulatory effectsInflammatory responseSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2COVID-19 pathogenesisTreatment of patientsUncontrolled inflammatory responseSyndrome coronavirus 2Interferon-stimulated gene expressionPotential therapeutic strategySeverity of infectionSARS-CoV-2Virus diseaseInnate immune systemPossible side effectsCOVID-19 diseaseViral infection treatmentDrug candidatesCoronavirus 2Treatment options
2020
Electronic Cigarettes Induce Mitochondrial DNA Damage and Trigger TLR9 (Toll-Like Receptor 9)-Mediated Atherosclerosis
Li J, Huynh L, Cornwell WD, Tang MS, Simborio H, Huang J, Kosmider B, Rogers TJ, Zhao H, Steinberg MB, Thu Thi Le L, Zhang L, Pham K, Liu C, Wang H. Electronic Cigarettes Induce Mitochondrial DNA Damage and Trigger TLR9 (Toll-Like Receptor 9)-Mediated Atherosclerosis. Arteriosclerosis Thrombosis And Vascular Biology 2020, 41: 839-853. PMID: 33380174, PMCID: PMC8608030, DOI: 10.1161/atvbaha.120.315556.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAtherosclerosisDisease Models, AnimalDNA DamageDNA, MitochondrialE-Cigarette VaporFemaleHumansInflammationInflammation MediatorsMacrophagesMaleMiceMice, Inbred C57BLMice, Knockout, ApoEMiddle AgedMitochondriaRAW 264.7 CellsSignal TransductionSmokersToll-Like Receptor 9VapingConceptsECV exposureTLR9 expressionInflammatory cytokinesClassical monocytesTLR9 activationAtherosclerotic plaquesEight-week-old ApoEUpregulation of TLR9Expression of TLR9Atherosclerotic lesion developmentOil Red O stainingToll-like receptorsDays/weekE-cig exposureMonocytes/macrophagesNormal laboratory dietRed O stainingPotential pharmacological targetElectronic cigarette useHours/dayProinflammatory cytokinesCig vaporPlasma levelsTLR9 antagonistTLR9 inhibitorE-cigarette promotes breast carcinoma progression and lung metastasis: Macrophage-tumor cells crosstalk and the role of CCL5 and VCAM-1
Pham K, Huynh D, Le L, Delitto D, Yang L, Huang J, Kang Y, Steinberg MB, Li J, Zhang L, Liu D, Tang MS, Liu C, Wang H. E-cigarette promotes breast carcinoma progression and lung metastasis: Macrophage-tumor cells crosstalk and the role of CCL5 and VCAM-1. Cancer Letters 2020, 491: 132-145. PMID: 32829009, PMCID: PMC9703643, DOI: 10.1016/j.canlet.2020.08.010.Peer-Reviewed Original ResearchConceptsBC cell growthCig exposureLung metastasesBreast cancerVCAM-1V-CAM-1Role of CCL5Upregulated protein expressionBC cell survivalE-cig exposurePro-tumorigenic factorsBC cell apoptosisBreast carcinoma progressionMetastatic lung colonizationCCR5 axisMFP tumorsTAMs infiltrationInfiltrated macrophagesCell growthCo-culture systemImmunohistochemical stainsCell crosstalkBC cellsBC growthProliferation indexIdentification of small molecules by screening a mixture-based scaffold compound library for treatment of alpha-1 antitrypsin deficiency
Zhang X, Santos R, Debevec G, Li D, Schutte R, Pham K, Liu C, Ostrov DA, Giulianotti M. Identification of small molecules by screening a mixture-based scaffold compound library for treatment of alpha-1 antitrypsin deficiency. Biochemical And Biophysical Research Communications 2020, 527: 317-323. PMID: 32446387, DOI: 10.1016/j.bbrc.2020.04.037.Peer-Reviewed Original ResearchConceptsSmall moleculesCompound librariesStructural diversityActive compoundsPreliminary structure-activity relationshipScaffold libraryIndividual active compoundsStructure-activity relationshipsMixture librariesTitration experimentsCrystal structureMolecular dockingPolymerization sitePromising scaffoldCompoundsMixture formatMoleculesPosition R1Mixture samplesScaffoldsPotential binding sitesBinding sitesDockingThe role of survivin in the progression of pancreatic ductal adenocarcinoma (PDAC) and a novel survivin-targeted therapeutic for PDAC
Brown M, Zhang W, Yan D, Kenath R, Le L, Wang H, Delitto D, Ostrov D, Robertson K, Liu C, Pham K. The role of survivin in the progression of pancreatic ductal adenocarcinoma (PDAC) and a novel survivin-targeted therapeutic for PDAC. PLOS ONE 2020, 15: e0226917. PMID: 31929540, PMCID: PMC6957139, DOI: 10.1371/journal.pone.0226917.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaTypes of cancerDuctal adenocarcinomaSurvivin expressionSurvivin inhibitorClinical response rateNovel survivin inhibitorHalf of patientsElevated survivin expressionLower patient survivalPancreatic tumor microenvironmentPotential therapeutic targetExpression of survivinRole of survivinField of oncologyPancreatic cancer linesImmunotherapeutic approachesPatient survivalUntreated cohortTherapeutic responseInhibitor of survivinTreatment resistancePDAC progressionEffective treatmentTumor cell migration
2019
A Novel Small Molecule Inhibits Intrahepatocellular Accumulation of Z-Variant Alpha 1-Antitrypsin In Vitro and In Vivo
Zhang X, Pham K, Li D, Schutte RJ, Gonzalo DH, Zhang P, Oshins R, Tan W, Brantly M, Liu C, Ostrov DA. A Novel Small Molecule Inhibits Intrahepatocellular Accumulation of Z-Variant Alpha 1-Antitrypsin In Vitro and In Vivo. Cells 2019, 8: 1586. PMID: 31817705, PMCID: PMC6953066, DOI: 10.3390/cells8121586.Peer-Reviewed Original ResearchConceptsLiver diseaseAssociated liver injuryChronic liver diseaseMutant alpha 1Common genetic causePiZ miceCurative therapyLiver injuryLiver fibrosisNovel small moleculesAnimal modelsAlpha 1Genetic causeDiseaseIntracellular accumulationAlphaCandidate compoundsHuman alphaMutant alphaCell modelAATDFibrosisInjuryTherapySmall moleculesEnhancement of sorafenib-mediated death of Hepatocellular carcinoma cells by Carnosic acid and Vitamin D2 analog combination
Wu Q, Wang X, Pham K, Luna A, Studzinski GP, Liu C. Enhancement of sorafenib-mediated death of Hepatocellular carcinoma cells by Carnosic acid and Vitamin D2 analog combination. The Journal Of Steroid Biochemistry And Molecular Biology 2019, 197: 105524. PMID: 31704246, PMCID: PMC7015782, DOI: 10.1016/j.jsbmb.2019.105524.Peer-Reviewed Original ResearchConceptsHepatocellular carcinomaVitamin DOral multi-kinase inhibitorTreatment of HCCAutophagy markers Beclin1Vitamin D insufficiencyCarnosic acidAdvanced hepatocellular carcinomaPromising therapeutic optionVitamin D analogsMulti-kinase inhibitorCell linesElevated protein levelsAnti-oxidant propertiesHCC cell linesHuman neoplastic cellsD insufficiencyGlobal cancer mortalityHepatocellular carcinoma cellsSystemic treatmentTherapeutic optionsCancer mortalityHCC cell deathPreclinical studiesLiver cancerTumor-intrinsic PIK3CA represses tumor immunogenecity in a model of pancreatic cancer
Sivaram N, McLaughlin PA, Han HV, Petrenko O, Jiang YP, Ballou LM, Pham K, Liu C, van der Velden A, Lin RZ. Tumor-intrinsic PIK3CA represses tumor immunogenecity in a model of pancreatic cancer. Journal Of Clinical Investigation 2019, 129: 3264-3276. PMID: 31112530, PMCID: PMC6668699, DOI: 10.1172/jci123540.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsB7-1 AntigenCell Line, TumorClass I Phosphatidylinositol 3-KinasesHistocompatibility Antigens Class IHumansLymphocytes, Tumor-InfiltratingMiceMice, KnockoutMice, SCIDNeoplasms, ExperimentalPancreatic NeoplasmsProto-Oncogene Proteins c-aktSignal TransductionT-LymphocytesXenograft Model Antitumor AssaysConceptsPancreatic cancerT cellsT cell-deficient miceTumor-infiltrating T cellsAntigen-experienced T cellsCell-deficient miceFavorable patient outcomesOrthotopic implantation modelComplete tumor regressionMost pancreatic cancersT cell surveillanceT cell recognitionPancreatic cancer cellsMHC class IAvailable immunotherapiesAdoptive transferEffective immunotherapyTumor immunogenicityTumor regressionPancreatic tumorsPatient outcomesHost miceImmunodeficient miceCell surveillanceTumorsTargeting the site encoded by SERPINA1*E342K for treating alpha‐1 antitrypsin deficiency‐associated liver diseases
Zhang X, Pham K, Li D, Schutte RJ, Brantly M, Liu C, Ostrov DA. Targeting the site encoded by SERPINA1*E342K for treating alpha‐1 antitrypsin deficiency‐associated liver diseases. FEBS Letters 2019, 593: 1849-1862. PMID: 31116417, DOI: 10.1002/1873-3468.13452.Peer-Reviewed Original ResearchIntegrating the Epigenome to Identify Drivers of Hepatocellular Carcinoma
Hlady RA, Sathyanarayan A, Thompson JJ, Zhou D, Wu Q, Pham K, Lee J, Liu C, Robertson KD. Integrating the Epigenome to Identify Drivers of Hepatocellular Carcinoma. Hepatology 2019, 69: 639-652. PMID: 30136421, PMCID: PMC6351162, DOI: 10.1002/hep.30211.Peer-Reviewed Original ResearchConceptsHistone modification profilesPromoter/enhancer functionGenome-wide assessmentTranscription of genesEpigenetic marksHistone modificationsEpigenome deregulationEpigenetic regulatorsBioinformatics strategyEpigenetic mechanismsModification profilesEpigenetic underpinningsLiver epigenomeEpigenetic profilesEnhancer functionEpigenetic parametersEpigenomeDecrease cell viabilityDriver lociSignificant deregulationCancer initiationTranscriptionHuman cancersCancer cell linesCell lines
2018
RET rearrangements are actionable alterations in breast cancer
Paratala BS, Chung JH, Williams CB, Yilmazel B, Petrosky W, Williams K, Schrock AB, Gay LM, Lee E, Dolfi SC, Pham K, Lin S, Yao M, Kulkarni A, DiClemente F, Liu C, Rodriguez-Rodriguez L, Ganesan S, Ross JS, Ali SM, Leyland-Jones B, Hirshfield KM. RET rearrangements are actionable alterations in breast cancer. Nature Communications 2018, 9: 4821. PMID: 30446652, PMCID: PMC6240119, DOI: 10.1038/s41467-018-07341-4.Peer-Reviewed Original ResearchMeSH KeywordsAnilidesAnimalsAntineoplastic AgentsBreast NeoplasmsCell Line, TumorCell Transformation, NeoplasticFemaleGene Expression Regulation, NeoplasticHumansMCF-7 CellsMiceMice, NudeMitogen-Activated Protein KinasesNIH 3T3 CellsNuclear Receptor CoactivatorsOncogene Proteins, FusionPhosphatidylinositol 3-KinasesPiperidinesProto-Oncogene Proteins c-retPyridinesQuinazolinesRas Guanine Nucleotide Exchange FactorsReceptor, ErbB-2Signal TransductionXenograft Model Antitumor AssaysConceptsBreast cancerRET amplificationRET gene alterationsMetastatic breast cancerNCOA4-RET fusionXenograft tumor formationPI3K pathwayRadiographic responseActionable alterationsLung cancerRET fusionsRET alterationsRET inhibitionIndex caseTherapeutic targetRET rearrangementsCancerGenomic profilingGene alterationsK pathwayTumor formationGene RETNon-tumorigenic cellsSubsequent treatmentOncogenic potential
2017
Human Pancreatic Cancer Cells Induce a MyD88-Dependent Stromal Response to Promote a Tumor-Tolerant Immune Microenvironment
Delitto D, Delitto AE, DiVita BB, Pham K, Han S, Hartlage ER, Newby BN, Gerber MH, Behrns KE, Moldawer LL, Thomas RM, George TJ, Brusko TM, Mathews CE, Liu C, Trevino JG, Hughes SJ, Wallet SM. Human Pancreatic Cancer Cells Induce a MyD88-Dependent Stromal Response to Promote a Tumor-Tolerant Immune Microenvironment. Cancer Research 2017, 77: 672-683. PMID: 27864347, PMCID: PMC5290036, DOI: 10.1158/0008-5472.can-16-1765.Peer-Reviewed Original ResearchConceptsTumor-associated stromaPancreatic cancerTumor microenvironmentT cell-mediated cytotoxicityCancer cell-conditioned mediumImmunosuppressive tumor microenvironmentT cell proliferationCell-conditioned mediumHuman cell culture modelsTh1 ratioProtective immunityCancer differsHealthy controlsMemory Th17Pancreatic lysatesCell culture modelPrimary human cell culture modelsRobust secretionCancer cellsCD8TA responsesPatientsImmunomodulatory characterCancerCulture model
2016
Isolation of Pancreatic Cancer Cells from a Patient-Derived Xenograft Model Allows for Practical Expansion and Preserved Heterogeneity in Culture
Pham K, Delitto D, Knowlton AE, Hartlage ER, Madhavan R, Gonzalo DH, Thomas RM, Behrns KE, George TJ, Hughes SJ, Wallet SM, Liu C, Trevino JG. Isolation of Pancreatic Cancer Cells from a Patient-Derived Xenograft Model Allows for Practical Expansion and Preserved Heterogeneity in Culture. American Journal Of Pathology 2016, 186: 1537-1546. PMID: 27102771, PMCID: PMC4901138, DOI: 10.1016/j.ajpath.2016.02.009.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsSubcutaneous injectionHuman leukocyte antigen class IICancer stem cell marker CD44Class I human leukocyte antigenHuman PC specimensHuman PC cellsPancreatic cancer cell linesDeath ligand 1Human leukocyte antigenStem cell marker CD44PC cell linesPancreatic cancer cellsCell linesCell marker CD44Epithelial cell adhesion moleculeLimited translational valueCancer cell linesLeukocyte antigenCell adhesion moleculePC cellsTherapeutic approachesFrequency of cellsXenograft modelCytokeratin 19
2015
Downstream mediators of the intratumoral interferon response suppress antitumor immunity, induce gemcitabine resistance and associate with poor survival in human pancreatic cancer
Delitto D, Perez C, Han S, Gonzalo DH, Pham K, Knowlton AE, Graves CL, Behrns KE, Moldawer LL, Thomas RM, Liu C, George TJ, Trevino JG, Wallet SM, Hughes SJ. Downstream mediators of the intratumoral interferon response suppress antitumor immunity, induce gemcitabine resistance and associate with poor survival in human pancreatic cancer. Cancer Immunology, Immunotherapy 2015, 64: 1553-1563. PMID: 26423423, PMCID: PMC5129167, DOI: 10.1007/s00262-015-1760-y.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityCell Line, TumorChemokine CXCL10DeoxycytidineDrug Resistance, NeoplasmEnzyme-Linked Immunosorbent AssayFlow CytometryGemcitabineGene Expression Regulation, NeoplasticHLA AntigensHumansInterferon-gammaInterferonsPancreatic NeoplasmsReceptors, CXCR3Tumor Cells, CulturedTumor MicroenvironmentConceptsPC cell linesPancreatic cancerAntitumor immunityPoor survivalPC microenvironmentHuman leukocyte antigen (HLA) class IMinimal inflammatory cell infiltrationEffective antitumor immunityImmune checkpoint ligandsUpregulation of PDL1Inflammatory cell infiltrationAntigen class IHuman pancreatic cancerAbsence of CD80Tumor-associated stromaCell linesCancer epithelial cellsCheckpoint ligandsCXCL10 concentrationsCell typesIFNγ responsesIndependent predictorsCD86 expressionChronic pancreatitisCell infiltrationPatient-Derived Xenograft Models for Pancreatic Adenocarcinoma Demonstrate Retention of Tumor Morphology through Incorporation of Murine Stromal Elements
Delitto D, Pham K, Vlada AC, Sarosi GA, Thomas RM, Behrns KE, Liu C, Hughes SJ, Wallet SM, Trevino JG. Patient-Derived Xenograft Models for Pancreatic Adenocarcinoma Demonstrate Retention of Tumor Morphology through Incorporation of Murine Stromal Elements. American Journal Of Pathology 2015, 185: 1297-1303. PMID: 25770474, PMCID: PMC4419203, DOI: 10.1016/j.ajpath.2015.01.016.Peer-Reviewed Original ResearchConceptsPancreatic adenocarcinoma specimensStromal elementsTumor morphologyAdenocarcinoma specimensSuccessful engraftmentXenograft modelPatient-derived xenograft modelsCancer cellsPatient-derived xenograftsPancreatic adenocarcinoma xenograftsAdenocarcinoma xenograft modelTumor-stromal interactionsPatient demographicsClinicopathologic factorsPatient survivalNonobese diabeticPancreatic adenocarcinomaSurgical specimensImmunodeficiency miceInitial implantationPathological analysisPreclinical platformAdenocarcinoma xenograftsXenograft microenvironmentTumor growthVEGFR inhibitors upregulate CXCR4 in VEGF receptor-expressing glioblastoma in a TGFβR signaling-dependent manner
Pham K, Luo D, Siemann DW, Law BK, Reynolds BA, Hothi P, Foltz G, Harrison JK. VEGFR inhibitors upregulate CXCR4 in VEGF receptor-expressing glioblastoma in a TGFβR signaling-dependent manner. Cancer Letters 2015, 360: 60-67. PMID: 25676691, PMCID: PMC7294457, DOI: 10.1016/j.canlet.2015.02.005.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAngiogenesis InhibitorsAnimalsBenzylaminesBrain NeoplasmsCell Line, TumorCell MovementCyclamsFemaleGlioblastomaHeterocyclic CompoundsHumansInterleukin-2 Receptor alpha SubunitMaleMice, Inbred NODMice, KnockoutMice, SCIDMiddle AgedNeoplasm InvasivenessPiperidinesProtein Kinase InhibitorsQuinazolinesReceptor Cross-TalkReceptors, CXCR4Receptors, Transforming Growth Factor betaReceptors, Vascular Endothelial Growth FactorSignal TransductionTime FactorsUp-RegulationXenograft Model Antitumor AssaysConceptsTGFβ/TGFβRAnti-VEGF/VEGFR therapiesSignaling-dependent mannerMechanisms of crosstalkEnhanced invasive phenotypeVEGFR inhibitorsSurvival benefitHGF/METGBM cell linesInvasive phenotypeCXCL12/CXCR4 pathwayGreater survival benefitExpression of CXCR4VEGF/VEGFRMalignant phenotypeTumor-bearing animalsUpregulation of CXCR4Alternative therapeutic strategiesGBM progressionCell linesTGFβRRecurrent tumorsCXCR4 pathwayStandard treatmentCXCR4 antagonist
2013
Expression and Functional Heterogeneity of Chemokine Receptors CXCR4 and CXCR7 in Primary Patient-Derived Glioblastoma Cells
Liu C, Pham K, Luo D, Reynolds BA, Hothi P, Foltz G, Harrison JK. Expression and Functional Heterogeneity of Chemokine Receptors CXCR4 and CXCR7 in Primary Patient-Derived Glioblastoma Cells. PLOS ONE 2013, 8: e59750. PMID: 23555768, PMCID: PMC3605406, DOI: 10.1371/journal.pone.0059750.Peer-Reviewed Original ResearchConceptsFunction of CXCR4Chemokine receptor CXCR4CXCR4-CXCR7Receptor CXCR4Common primary brain tumorPrimary human GBM cellsPrimary brain tumorsPersonalized treatment approachesTube formationSurface expressionPatient-derived GBM cell linesNew therapeutic targetsCell linesHuman GBM cellsPatient-derived glioblastoma cellsGBM cell linesClinical benefitPoor prognosisSuccessful treatmentCell surface expressionCXCR7 axisCXCL12-CXCR4Intracranial tumorsGBM patientsBrain tumors