2020
Estimation of the carrier frequency of fumarate hydratase alterations and implications for kidney cancer risk in hereditary leiomyomatosis and renal cancer
Shuch B, Li S, Risch H, Bindra RS, McGillivray PD, Gerstein M. Estimation of the carrier frequency of fumarate hydratase alterations and implications for kidney cancer risk in hereditary leiomyomatosis and renal cancer. Cancer 2020, 126: 3657-3666. PMID: 32413184, PMCID: PMC10316675, DOI: 10.1002/cncr.32914.Peer-Reviewed Original ResearchConceptsFumarate hydrataseExome Aggregation ConsortiumAllele frequenciesFH geneGenome ProjectDifferent world populationsFH alterationsHereditary leiomyomatosisKidney cancer riskCancer penetranceMissense alterationsGenesOverall allele frequencyRare variantsLow penetranceRenal cancerExACKidney cancerCancer riskPenetranceGermline mutationsLethal formWorld populationCancer syndromesAlterations
2019
Temozolomide Sensitizes MGMT-Deficient Tumor Cells to ATR Inhibitors
Jackson CB, Noorbakhsh SI, Sundaram RK, Kalathil AN, Ganesa S, Jia L, Breslin H, Burgenske DM, Gilad O, Sarkaria JN, Bindra RS. Temozolomide Sensitizes MGMT-Deficient Tumor Cells to ATR Inhibitors. Cancer Research 2019, 79: 4331-4338. PMID: 31273061, PMCID: PMC6810597, DOI: 10.1158/0008-5472.can-18-3394.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, AlkylatingAntineoplastic Combined Chemotherapy ProtocolsAtaxia Telangiectasia Mutated ProteinsCell Cycle CheckpointsCell Line, TumorCheckpoint Kinase 1DNA Breaks, Double-StrandedDNA DamageDNA Modification MethylasesDNA Repair EnzymesDrug SynergismFemaleHumansIsoxazolesMice, NudePyrazinesTemozolomideTumor Suppressor ProteinsXenograft Model Antitumor AssaysConceptsMGMT-deficient cellsPPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma
Fons NR, Sundaram RK, Breuer GA, Peng S, McLean RL, Kalathil AN, Schmidt MS, Carvalho DM, Mackay A, Jones C, Carcaboso ÁM, Nazarian J, Berens ME, Brenner C, Bindra RS. PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma. Nature Communications 2019, 10: 3790. PMID: 31439867, PMCID: PMC6706443, DOI: 10.1038/s41467-019-11732-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBrain Stem NeoplasmsCell Line, TumorChildCytokinesDiffuse Intrinsic Pontine GliomaDNA MethylationEpigenetic RepressionFemaleGene Expression Regulation, NeoplasticHumansMiceNicotinamide PhosphoribosyltransferasePonsPrimary Cell CultureProtein Phosphatase 2CSynthetic Lethal MutationsXenograft Model Antitumor AssaysConceptsNicotinic acid phosphoribosyltransferaseSynthetic lethal interactionsNAMPT inhibitorsTumor-specific cell killingProtein phosphataseEpigenetic silencingMutant cellsKey genesCpG islandsLethal interactionsNAD biosynthesisGene expressionInhibitor sensitivityNAD metabolismOncogenic rolePediatric gliomasMutationsModel systemCell killingDriver mutationsPediatric high-grade gliomasMutant tumorsOncogenic driver mutationsNicotinamide phosphoribosyltransferase (NAMPT) inhibitionGenomeDefining an Intermediate-risk Group for Low-grade Glioma: A National Cancer Database Analysis
JAIRAM V, KANN BH, PARK HS, MICCIO JA, BECKTA JM, YU JB, PRABHU RS, GAO SJ, MEHTA MP, CURRAN WJ, BINDRA RS, CONTESSA JN, PATEL KR. Defining an Intermediate-risk Group for Low-grade Glioma: A National Cancer Database Analysis. Anticancer Research 2019, 39: 2911-2918. PMID: 31177129, DOI: 10.21873/anticanres.13420.Peer-Reviewed Original ResearchConceptsIntermediate-risk groupInferior overall survivalOverall survivalAdjuvant therapyLow-grade gliomasTumor sizePrognostic featuresMultivariate analysisPre-operative tumor sizeNational Cancer Database AnalysisNational Cancer DatabaseLow-risk patientsCohort of patientsKaplan-Meier methodPoor prognostic featuresGross total resectionHigh-risk groupPatterns of careAdditional prognostic featuresRTOG 9802Clinical factorsTotal resectionCancer DatabaseRisk groupsClinical classification
2018
The Higher the Grade, the Bigger the Field
Beckta JM, Bindra RS. The Higher the Grade, the Bigger the Field. International Journal Of Radiation Oncology • Biology • Physics 2018, 102: 488-489. PMID: 30238899, DOI: 10.1016/j.ijrobp.2018.08.019.Peer-Reviewed Original ResearchResidual Convolutional Neural Network for Determination of IDH Status in Low- and High-grade Gliomas from MR Imaging
Chang K, Bai HX, Zhou H, Su C, Bi WL, Agbodza E, Kavouridis VK, Senders JT, Boaro A, Beers A, Zhang B, Capellini A, Liao W, Shen Q, Li X, Xiao B, Cryan J, Ramkissoon S, Ramkissoon L, Ligon K, Wen PY, Bindra RS, Woo J, Arnaout O, Gerstner ER, Zhang PJ, Rosen BR, Yang L, Huang RY, Kalpathy-Cramer J. Residual Convolutional Neural Network for Determination of IDH Status in Low- and High-grade Gliomas from MR Imaging. Clinical Cancer Research 2018, 24: clincanres.2236.2017. PMID: 29167275, PMCID: PMC6051535, DOI: 10.1158/1078-0432.ccr-17-2236.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBrainBrain NeoplasmsDatasets as TopicFemaleGliomaHumansImage Processing, Computer-AssistedIsocitrate DehydrogenaseMagnetic Resonance ImagingMaleMiddle AgedMutationNeoplasm GradingNeural Networks, ComputerPredictive Value of TestsPreoperative PeriodRetrospective StudiesYoung AdultConceptsResidual convolutional neural networkConvolutional neural networkNeural networkDeep learning techniquesTesting setNeural network modelMulti-institutional data setCancer Imaging ArchiveLearning techniquesTesting accuracyNetwork modelTraining setPrediction accuracyPreoperative radiographic dataClin Cancer ResData setsConventional MR imagingHospital of UniversityIsocitrate dehydrogenase (IDH) mutationPreoperative imagingLonger survivalWomen's HospitalGrade IINetworkTreatment decisionsResponse to the BRAF/MEK inhibitors dabrafenib/trametinib in an adolescent with a BRAF V600E mutated anaplastic ganglioglioma intolerant to vemurafenib
Marks AM, Bindra RS, DiLuna ML, Huttner A, Jairam V, Kahle KT, Kieran MW. Response to the BRAF/MEK inhibitors dabrafenib/trametinib in an adolescent with a BRAF V600E mutated anaplastic ganglioglioma intolerant to vemurafenib. Pediatric Blood & Cancer 2018, 65: e26969. PMID: 29380516, DOI: 10.1002/pbc.26969.Peer-Reviewed Original ResearchConceptsAnaplastic gangliogliomaBRAF/MEK inhibitor combinationsBRAF V600ESubsequent tumor responseDabrafenib/trametinibLarge clinical trialsSquamous cell carcinomaMEK inhibitor combinationsSignificant side effectsSignificant skin reactionsCell carcinomaCase reportSkin reactionsTumor responseClinical trialsBrain tumorsInhibitor combinationsSide effectsAdolescent femalesGangliogliomaTrametinibPrevious reactionsV600EMonotherapyRash
2017
Angiotensin receptor blockade: a novel approach for symptomatic radiation necrosis after stereotactic radiosurgery
Chowdhary M, Okwan-Duodu D, Switchenko JM, Press RH, Jhaveri J, Buchwald ZS, Zhong J, Chapman BV, Bindra RS, Contessa JN, Park HS, Yu JB, Decker RH, Olson JJ, Oyesiku NM, Abrams RA, Shu HG, Curran WJ, Crocker IR, Patel KR. Angiotensin receptor blockade: a novel approach for symptomatic radiation necrosis after stereotactic radiosurgery. Journal Of Neuro-Oncology 2017, 136: 289-298. PMID: 29124649, PMCID: PMC5784434, DOI: 10.1007/s11060-017-2652-0.Peer-Reviewed Original ResearchConceptsSymptomatic radiation necrosisOverall survivalStereotactic radiosurgeryIntracranial efficacyRadiation necrosisKaplan-Meier methodLate radiation toxicitySignificant predictive factorsArteriovenous malformation patientsCumulative incidence modelsIntracranial outcomesBaseline characteristicsBlockade therapyBrain metastasesProspective trialABT groupConsecutive patientsMedian ageMeier methodPreclinical evidencePredictive factorsAVM cohortsRadiation toxicityPrognostic analysisMultivariate analysisPatterns of care and outcomes for use of concurrent chemoradiotherapy over radiotherapy alone for anaplastic gliomas
Yeboa DN, Rutter CE, Park HS, Lester-Coll NH, Corso CD, Mancini BR, Bindra RS, Contessa J, Yu JB. Patterns of care and outcomes for use of concurrent chemoradiotherapy over radiotherapy alone for anaplastic gliomas. Radiotherapy And Oncology 2017, 125: 258-265. PMID: 29054377, DOI: 10.1016/j.radonc.2017.09.027.Peer-Reviewed Original ResearchConceptsUse of CCRTConcurrent chemoradiotherapyPatterns of careAnaplastic gliomasOverall survivalCox proportional hazards regression modelingProportional hazards regression modelingMultivariable logistic regression analysisConcurrent CRTNational Cancer DatabaseKaplan-Meier analysisLog-rank testLogistic regression analysisGrade III gliomasAdjusted hazardAdult patientsImproved survivalCancer DatabaseDesign cohortRadiotherapyPropensity scorePatientsGliomasChemoradiotherapyRegression modelingBi‐allelic alterations in DNA repair genes underpin homologous recombination DNA repair defects in breast cancer
Mutter RW, Riaz N, Ng CK, Delsite R, Piscuoglio S, Edelweiss M, Martelotto LG, Sakr RA, King TA, Giri DD, Drobnjak M, Brogi E, Bindra R, Bernheim G, Lim RS, Blecua P, Desrichard A, Higginson D, Towers R, Jiang R, Lee W, Weigelt B, Reis‐Filho J, Powell SN. Bi‐allelic alterations in DNA repair genes underpin homologous recombination DNA repair defects in breast cancer. The Journal Of Pathology 2017, 242: 165-177. PMID: 28299801, PMCID: PMC5516531, DOI: 10.1002/path.4890.Peer-Reviewed Original ResearchConceptsBreast cancerGermline BRCA1/BRCA2 mutationsBRCA1/BRCA2 mutationsPrecision medicine-based approachPrimary breast cancerTumour-specific DNA repair defectsSporadic breast cancerGermline genetic alterationsBi-allelic lossWhole-exome sequencingSpecific mutational signaturesComprehensive genetic assessmentBRCA2 mutationsLarge-scale state transitionsBi-allelic alterationsCancerGenetic alterationsDNA repair defectsMutational signaturesTherapyAlterationsRepair defectsGene expressionGenetic assessmentHR genes2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity
Sulkowski PL, Corso CD, Robinson ND, Scanlon SE, Purshouse KR, Bai H, Liu Y, Sundaram RK, Hegan DC, Fons NR, Breuer GA, Song Y, Mishra-Gorur K, De Feyter HM, de Graaf RA, Surovtseva YV, Kachman M, Halene S, Günel M, Glazer PM, Bindra RS. 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity. Science Translational Medicine 2017, 9 PMID: 28148839, PMCID: PMC5435119, DOI: 10.1126/scitranslmed.aal2463.Peer-Reviewed Original ResearchConceptsIsocitrate dehydrogenase 1PARP inhibitor sensitivityPossible therapeutic strategiesHomologous recombination defectsTherapeutic strategiesTumor xenograftsInhibitor sensitivityPathologic processesSmall molecule inhibitorsIDH1/2 mutationsTumor progressionIDH2 mutationsMutant IDHPolymerase inhibitorsGlioma cellsTumor cellsHR deficiencyPARP inhibitionIDH mutationsInhibitory effectDehydrogenase 1Neomorphic activityMutant IDH1 enzymeDependent dioxygenasesMutant cells
2016
Postoperative Radiotherapy Patterns of Care and Survival Implications for Medulloblastoma in Young Children
Kann BH, Park HS, Lester-Coll NH, Yeboa DN, Benitez V, Khan AJ, Bindra RS, Marks AM, Roberts KB. Postoperative Radiotherapy Patterns of Care and Survival Implications for Medulloblastoma in Young Children. JAMA Oncology 2016, 2: 1574-1581. PMID: 27491009, DOI: 10.1001/jamaoncol.2016.2547.Peer-Reviewed Original ResearchConceptsPostoperative radiotherapyOverall survivalMultivariable logistic regressionNational Cancer Data BaseLogistic regressionAdjuvant chemotherapy strategyLow facility volumeNational treatment patternsMultivariable Cox regressionLong-term morbidityYear of diagnosisDay of surgeryKaplan-Meier analysisNational database analysisPoor overall survivalLog-rank testYoung childrenAge 3Adjuvant chemotherapyRadiotherapy patternsRadiotherapy utilizationWorse survivalDistant metastasisMultivariable analysisTreatment patternsAdjuvant chemotherapy and overall survival in adult medulloblastoma
Kann BH, Lester-Coll NH, Park HS, Yeboa DN, Kelly JR, Baehring JM, Becker KP, Yu JB, Bindra RS, Roberts KB. Adjuvant chemotherapy and overall survival in adult medulloblastoma. Neuro-Oncology 2016, 19: 259-269. PMID: 27540083, PMCID: PMC5464064, DOI: 10.1093/neuonc/now150.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCerebellar NeoplasmsChemoradiotherapy, AdjuvantChemotherapy, AdjuvantCraniospinal IrradiationFemaleFollow-Up StudiesHumansMaleMedulloblastomaMiddle AgedNeoplasm StagingPrognosisRadiotherapy, AdjuvantSurvival RateYoung AdultConceptsGy craniospinal irradiationCraniospinal irradiationOverall survivalM0 patientsAdjuvant chemotherapyAdult MBMultivariable Cox proportional hazard modelingHigh-dose craniospinal irradiationNational Cancer Data BaseCox proportional hazard modelingSuperior overall survivalPlanned subgroup analysisMultivariable logistic regressionNational database analysisLog-rank testProportional hazard modelingPediatric medulloblastoma patientsCSI dosesPostoperative chemotherapySurgical resectionSurvival impactYear OSMultivariable analysisSubgroup analysisRisk factors
2004
Down-Regulation of Rad51 and Decreased Homologous Recombination in Hypoxic Cancer Cells
Bindra RS, Schaffer PJ, Meng A, Woo J, Måseide K, Roth ME, Lizardi P, Hedley DW, Bristow RG, Glazer PM. Down-Regulation of Rad51 and Decreased Homologous Recombination in Hypoxic Cancer Cells. Molecular And Cellular Biology 2004, 24: 8504-8518. PMID: 15367671, PMCID: PMC516750, DOI: 10.1128/mcb.24.19.8504-8518.2004.Peer-Reviewed Original ResearchMeSH KeywordsCell CycleDNA RepairDNA-Binding ProteinsDown-RegulationFemaleGene Expression RegulationHumansHypoxiaHypoxia-Inducible Factor 1Hypoxia-Inducible Factor 1, alpha SubunitIronMaleNuclear ProteinsProstatic NeoplasmsRecombination, GeneticRNA, MessengerTranscription FactorsTranscription, GeneticUterine Cervical NeoplasmsConceptsHomologous recombinationExpression of RAD51RAD51 expressionGenetic instabilityCancer cellsCritical DNA repair pathwaysDNA damage responseMultiple cancer cell typesDNA repair pathwaysLevels of RAD51Homologous recombination pathwayGene promoter activityTranscriptional repressionCell cycle profileCancer cell typesDamage responseMammalian cellsHypoxia-inducible factorDNA repairProtein stabilityRepair pathwaysAberrant regulationPromoter activityRAD51Hypoxic cancer cells