2025
Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain Metastases.
Weiss S, Djureinovic D, Wei W, Tran T, Austin M, Markowitz J, Eroglu Z, Khushalani N, Hegde U, Cohen J, Sznol M, Anderson G, Johnson B, Piteo C, Mahajan A, Adeniran A, Jilaveanu L, Goldberg S, Chiang V, Forsyth P, Kluger H. Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain Metastases. Journal Of Clinical Oncology 2025, jco2402219. PMID: 40048689, DOI: 10.1200/jco-24-02219.Peer-Reviewed Original ResearchMelanoma brain metastasesOverall survivalBrain metastasesAnti-vascular endothelial growth factor therapyMedian intracranial progression-free survivalFour-year OS ratesIntracranial progression-free survivalResponse rateCirculating angiopoietin-2Median overall survivalTrial of pembrolizumabYears of pembrolizumabDose of bevacizumabProgression-free survivalPhase II trialGrowth factor therapyAdverse event ratesAssociated with responseOS ratesPD-1Radiation necrosisLocal therapyOn-therapyMetastatic tumorsFactor therapy
2024
Gold-siRNA supraclusters enhance the anti-tumor immune response of stereotactic ablative radiotherapy at primary and metastatic tumors
Jiang Y, Cao H, Deng H, Guan L, Langthasa J, Colburg D, Melemenidis S, Cotton R, Aleman J, Wang X, Graves E, Kalbasi A, Pu K, Rao J, Le Q. Gold-siRNA supraclusters enhance the anti-tumor immune response of stereotactic ablative radiotherapy at primary and metastatic tumors. Nature Biotechnology 2024, 1-14. PMID: 39448881, DOI: 10.1038/s41587-024-02448-0.Peer-Reviewed Original ResearchStereotactic ablative radiotherapyAnti-tumor immune responseSmall interfering RNAAblative radiotherapyMetastatic tumorsEffect of stereotactic ablative radiotherapyModel of head and neck cancerHead and neck cancerImmunosuppressive cell populationsPD-1 inhibitorsSmall interfering RNA complexesPD-1Primary tumorImmunotherapeutic effectsNeck cancerGranzyme BGal-1Mouse modelPassive deliveryTumorReduced toxicityCell populationsRadiotherapyRadiosensitivityRenal filtration thresholdUtility of next generation sequencing to unequivocally establish clonality in synchronous vs metastatic endometrial and ovarian carcinomas
Greenman M, Bellone S, Hartwich T, Buza N, Santin A. Utility of next generation sequencing to unequivocally establish clonality in synchronous vs metastatic endometrial and ovarian carcinomas. Gynecologic Oncology Reports 2024, 56: 101524. PMID: 39435258, PMCID: PMC11492078, DOI: 10.1016/j.gore.2024.101524.Peer-Reviewed Original ResearchOvarian carcinomaNext generation sequencingPrimary uterine tumorsDiagnostically challenging casesOvarian tumorsPrimary tumorUterine tumorsEndometrial malignancyMetastatic tumorsAdjuvant treatmentClonal relationshipTargeted therapyUtilization of next generation sequencingTumor clonalityGeneration sequencingProtein expression profilesTumorChallenging casesImprove outcomesCarcinomaGold standardGenetic landscapeMalignancyClonalityExpression profilesMelanocortin-1 Receptor Expression as a Marker of Progression in Melanoma
Su D, Djureinovic D, Schoenfeld D, Marquez-Nostra B, Olino K, Jilaveanu L, Kluger H. Melanocortin-1 Receptor Expression as a Marker of Progression in Melanoma. JCO Precision Oncology 2024, 8: e2300702. PMID: 38662983, PMCID: PMC11513442, DOI: 10.1200/po.23.00702.Peer-Reviewed Original ResearchConceptsMC1R expressionMelanoma progressionAssociated with shorter survivalStages of melanoma progressionCases of benign neviChronic sun exposureMarkers of progressionHuman melanoma tissuesBreslow thicknessMelanocortin-1Metastatic melanomaOverall survivalPrimary melanomaMetastatic tumorsMelanoma cohortReceptor expressionPredictive biomarkersAggressive melanomaPrimary lesionTissue microarrayShorter survivalMale sexQuantitative immunofluorescenceBenign neviClinical trials154 Elucidating the Immune Landscape of Radiation Necrosis Through Single Cell Analysis of Recurrent Brain Lesions in Patients After Stereotactic Radio Surgery
Robert S, Kiziltug E, Lu B, Arnal-Estape A, Nguyen D, Chiang V. 154 Elucidating the Immune Landscape of Radiation Necrosis Through Single Cell Analysis of Recurrent Brain Lesions in Patients After Stereotactic Radio Surgery. Neurosurgery 2024, 70: 35-36. DOI: 10.1227/neu.0000000000002809_154.Peer-Reviewed Original ResearchRadiation necrosisFluorescence-activated cell sortingInterferon-stimulated genesStereotactic radiosurgeryNatural killerMyeloid cellsImmune cellsRadiosurgical treatment of brain metastasesTreatment of brain metastasesCD4+ T cellsExpression of immune cellsMorbid side effectsTreatment of RNSubpopulations of myeloid cellsStereotactic radio surgeryMetastatic brain tumorsInvasive brain biopsyCellular immune profilesInflammatory immune responseCSF of patientsRN patientsBrain metastasesCD8+Immunotherapy optionsMetastatic tumors
2023
CD70 is Consistently Expressed in Primary and Metastatic Clear Cell Renal Cell Carcinoma
Huang R, Chen Z, Kroeger N, Pantuck A, Said J, Kluger H, Shuch B, Ye H. CD70 is Consistently Expressed in Primary and Metastatic Clear Cell Renal Cell Carcinoma. Clinical Genitourinary Cancer 2023, 22: 347-353. PMID: 38195301, DOI: 10.1016/j.clgc.2023.12.003.Peer-Reviewed Original ResearchRenal cell carcinomaClear cell renal cell carcinomaCell renal cell carcinomaMetastatic clear cell renal cell carcinomaMetastatic renal cell carcinomaCell carcinomaClear cell carcinomaCD70 expressionMetastatic tumorsRenal tumorsTherapeutic targetAdvanced renal cell carcinomaMetastatic clear cell carcinomaCancer-specific survivalPapillary renal cell carcinomaExpression of CD70Normal renal parenchymaPrimary renal tumorsPrimary tumor tissuesPromising therapeutic targetPotential therapeutic targetHypoxia pathway proteinsHypoxia-inducible factorSarcomatoid differentiationNormal human tissuesMetal‐DNA Nanocomplexes Enhance Chemo‐dynamic Therapy by Inhibiting Autophagy‐Mediated Resistance
Gu C, Liu X, Luo L, Chen J, Zhou X, Chen G, Huang X, Yu L, Chen Q, Yang Y, Yang Y. Metal‐DNA Nanocomplexes Enhance Chemo‐dynamic Therapy by Inhibiting Autophagy‐Mediated Resistance. Angewandte Chemie 2023, 135 DOI: 10.1002/ange.202307020.Peer-Reviewed Original ResearchInduce immunogenic cell deathChemo-dynamic therapyMn-based catalystsExpression of autophagy-associated proteinsFenton-like reactionAutophagy-associated proteinsInhibition of autophagyImmune checkpoint blockade therapyCancer cellsSelf-protective pathwaysBilateral tumor modelCheckpoint blockade therapyImmunogenic cell deathSelf-protective mechanism of cancer cellsEffective treatment modalityHydroxyl radicalsHighest hydroxyl radicalInhibit tumor metastasisMechanism of cancer cellsKill cancer cellsIn vivo modelsBlockade therapyAutophagy inhibitionMetastatic tumorsTreatment modalitiesMetal‐DNA Nanocomplexes Enhance Chemo‐dynamic Therapy by Inhibiting Autophagy‐Mediated Resistance
Gu C, Liu X, Luo L, Chen J, Zhou X, Chen G, Huang X, Yu L, Chen Q, Yang Y, Yang Y. Metal‐DNA Nanocomplexes Enhance Chemo‐dynamic Therapy by Inhibiting Autophagy‐Mediated Resistance. Angewandte Chemie International Edition 2023, 62: e202307020. PMID: 37920913, DOI: 10.1002/anie.202307020.Peer-Reviewed Original ResearchConceptsInduce immunogenic cell deathChemo-dynamic therapyMn-based catalystsExpression of autophagy-associated proteinsFenton-like reactionAutophagy-associated proteinsImmune checkpoint blockade therapyInhibition of autophagyCancer cellsSelf-protective pathwaysBilateral tumor modelCheckpoint blockade therapyImmunogenic cell deathSelf-protective mechanism of cancer cellsEffective treatment modalityHydroxyl radicalsHighest hydroxyl radicalInhibit tumor metastasisMechanism of cancer cellsKill cancer cellsIn vivo modelsBlockade therapyMetastatic tumorsAutophagy inhibitionTreatment modalitiesExtrauterine epithelioid trophoblastic tumour and its somatic carcinoma mimics: short tandem repeat genotyping meets the diagnostic challenges
Niu N, Ordulu Z, Burak Z, Buza N, Hui P. Extrauterine epithelioid trophoblastic tumour and its somatic carcinoma mimics: short tandem repeat genotyping meets the diagnostic challenges. Histopathology 2023, 84: 325-335. PMID: 37743102, DOI: 10.1111/his.15054.Peer-Reviewed Original ResearchConceptsEpithelioid trophoblastic tumorGestational trophoblastic tumorsTrophoblastic tumorExtrauterine sitesSomatic carcinomasDifferential diagnosisDiagnosis of ETTExtrauterine epithelioid trophoblastic tumorsTriple-negative breast carcinomaTrophoblastic differentiationMetastatic triple-negative breast carcinomaPrimary lung carcinomaMain differential diagnosisMajor differential diagnosisEctopic gestationImmunohistochemical featuresDiagnostic challengeMetastatic tumorsLung carcinomaBreast carcinomaPatient managementEpithelioid malignanciesImmunohistochemical levelCarcinomaTumor tissueMetastatic Bladder Cancer Expression and Subcellular Localization of Nectin-4 and Trop-2 in Variant Histology: A Rapid Autopsy Study
Ghali F, Vakar-Lopez F, Roudier M, Garcia J, Arora S, Cheng H, Schweizer M, Haffner M, Lee J, Yu E, Grivas P, Montgomery B, Hsieh A, Wright J, Lam H. Metastatic Bladder Cancer Expression and Subcellular Localization of Nectin-4 and Trop-2 in Variant Histology: A Rapid Autopsy Study. Clinical Genitourinary Cancer 2023, 21: 669-678. PMID: 37344281, PMCID: PMC10674028, DOI: 10.1016/j.clgc.2023.05.014.Peer-Reviewed Original ResearchConceptsMetastatic urothelial carcinomaVariant histologySacituzumab govitecanTrop-2Nectin-4Antibody-drug conjugatesMetastatic lesionsADC targetCytoplasmic stainingProminent cytoplasmic stainingMembrane stainingTrop-2 expressionCytoplasmic protein expressionMetastatic sitesAutopsy studyUrothelial carcinomaMetastatic tumorsSquamous differentiationClinical relevanceCancer expressionHistologyNeuroendocrineProtein expressionMRNA levelsProtein levelsThe correlation of ESR1 genetic aberrations with estrogen receptor and progesterone receptor status in metastatic and primary estrogen receptor-positive breast carcinomas
Moreira-Dinzey J, Zhan H, Rozenblit M, Krishnamurti U, Harigopal M, Zhong M, Liang Y. The correlation of ESR1 genetic aberrations with estrogen receptor and progesterone receptor status in metastatic and primary estrogen receptor-positive breast carcinomas. Human Pathology 2023, 137: 56-62. PMID: 37127079, DOI: 10.1016/j.humpath.2023.04.017.Peer-Reviewed Original ResearchConceptsMetastatic tumorsBreast carcinomaGenetic aberrationsPR statusPrimary tumorBreast cancerControl groupER/PR statusEstrogen receptor-positive breast carcinomasER-positive breast cancerER positivity rateMetastatic breast cancerProgesterone receptor statusMetastatic breast carcinomaMore liver metastasesPrimary breast carcinomaWild-type groupEstrogen receptor 1 geneReceptor 1 geneWild-type controlsLiver metastasesReceptor statusClinicopathological featuresER expressionControl tumors465 Defining the Immune Profile of Radiation Necrosis Through Single-cell Analysis of Intracranial Lesions
Robert S, Lu B, Arnal-Estape A, Nguyen D, Chiang V. 465 Defining the Immune Profile of Radiation Necrosis Through Single-cell Analysis of Intracranial Lesions. Neurosurgery 2023, 69: 97-98. DOI: 10.1227/neu.0000000000002375_465.Peer-Reviewed Original ResearchRadiation necrosisFluorescence-activated cell sortingImmune profileNatural killer (NK) cellsIncidence of radiation necrosisManagement of brain metastasesMetastatic brain tumor patientsMorbid side effectsTreatment of RNRecurrent metastatic diseaseExpression of Foxp3Cytotoxic T cellsInvasive brain biopsyCellular immune profilesInterleukin-7 receptorBrain tumor patientsBrain metastasesMetastatic diseaseMetastatic tumorsImmune landscapeIntraoperative samplesPatient survivalT cellsBrain biopsyIntracranial lesions
2022
IMMU-01. DEFINING THE IMMUNE PROFILE OF RADIATION NECROSIS THROUGH SINGLE-CELL ANALYSIS OF INTRACRANIAL LESIONS
Robert S, Lu B, Kiziltug E, Estape A, Nguyen D, Chiang V. IMMU-01. DEFINING THE IMMUNE PROFILE OF RADIATION NECROSIS THROUGH SINGLE-CELL ANALYSIS OF INTRACRANIAL LESIONS. Neuro-Oncology 2022, 24: vii131-vii131. DOI: 10.1093/neuonc/noac209.499.Peer-Reviewed Original ResearchRadiation necrosisFluorescence-activated cell sortingNatural killer (NK) cellsIncidence of radiation necrosisManagement of brain metastasesMetastatic brain tumor patientsMorbid side effectsTreatment of RNRecurrent metastatic diseaseExpression of Foxp3Invasive brain biopsyCellular immune profilesInterleukin-7 receptorBrain tumor patientsNeuroimmune profileBrain metastasesMetastatic diseaseCytotoxic TMetastatic tumorsImmune landscapeIntraoperative samplesImprove patient diagnosisImmune profilePatient survivalBrain biopsyPD53-09 ANTIBODY DRUG CONJUGATES AND VARIANT HISTOLOGY MUSCLE-INVASIVE BLADDER CANCER: ARE THE TARGETS PRESENT IN PRIMARY AND/OR METASTATIC TUMORS?
Ghali F, Roudier M, Vakar-Lopez F, Garcia J, Wang Y, Ha G, Grivas P, Lee J, Yu E, Montgomery B, Hsieh A, Wright J, Lam H. PD53-09 ANTIBODY DRUG CONJUGATES AND VARIANT HISTOLOGY MUSCLE-INVASIVE BLADDER CANCER: ARE THE TARGETS PRESENT IN PRIMARY AND/OR METASTATIC TUMORS? Journal Of Urology 2022, 207: e913. DOI: 10.1097/ju.0000000000002630.09.Peer-Reviewed Original Research
2021
Radiotherapy is associated with a deletion signature that contributes to poor outcomes in patients with cancer
Kocakavuk E, Anderson K, Varn F, Johnson K, Amin S, Sulman E, Lolkema M, Barthel F, Verhaak R. Radiotherapy is associated with a deletion signature that contributes to poor outcomes in patients with cancer. Nature Genetics 2021, 53: 1088-1096. PMID: 34045764, PMCID: PMC8483261, DOI: 10.1038/s41588-021-00874-3.Peer-Reviewed Original ResearchConceptsWorse clinical outcomesNon-irradiated tumorsClinical outcomesRecurrent cancerPatient survivalPoor outcomeMetastatic tumorsRecurrent gliomaRadiation therapyRadiation-induced DNA damageDNA damageGlioma Longitudinal Analysis ConsortiumMutational signature analysisCancer treatmentDeletion burdenRadiotherapyMedical FoundationAPOBEC mutagenesisSignificant increaseTumorsCancerDNA damage repairDeletion signatureMutational spectrumSmall deletionsCan primary hepatocellular carcinoma histomorphology predict extrahepatic metastasis?
Kumar D, Hafez O, Jain D, Zhang X. Can primary hepatocellular carcinoma histomorphology predict extrahepatic metastasis? Human Pathology 2021, 113: 39-46. PMID: 33905775, DOI: 10.1016/j.humpath.2021.04.008.Peer-Reviewed Original ResearchConceptsMetastatic hepatocellular carcinomaHepatocellular carcinomaHistologic patternHistomorphologic featuresPrimary tumorMetastatic tumorsMacrotrabecular-massive hepatocellular carcinomaCommon histologic patternPathogenesis of metastasisSignificant intratumoral heterogeneityExtrahepatic metastasesLymph nodesMicrovascular invasionAdrenal glandCommon subtypeNoncirrhotic liverCirrhotic liverCommon siteMetastatic tissuesLarge cohortAbdominal cavityHCC subtypesPathology archivesMetastasisHCC metastasisMiscellaneous Neoplasia of the Ovary
Hui P, Banet N. Miscellaneous Neoplasia of the Ovary. Practical Anatomic Pathology 2021, 283-295. DOI: 10.1007/978-3-030-68608-6_11.Peer-Reviewed Original ResearchMetastatic carcinomaOvarian malignant epithelial tumorsPrimary ovarian lymphomaUnknown cell originSmall cell carcinomaBilateral ovarian involvementPrimary ovarian carcinomasMalignant epithelial tumorsLow-grade appearanceBreast primaryOvarian lymphomaStromal luteinizationOvarian involvementTumor thrombusCell carcinomaOvarian tumorsPrimary carcinomaAggressive tumorsCystic appearanceHypercalcemic typeMetastatic tumorsOvarian carcinomaTumor nodulesEpithelial tumorsCarcinomaNon-HPV-Associated Cervical Neoplasia
Quddus M, Ou J, Hui P. Non-HPV-Associated Cervical Neoplasia. Practical Anatomic Pathology 2021, 95-111. DOI: 10.1007/978-3-030-68608-6_4.Peer-Reviewed Original ResearchCervical adenocarcinomaHigh-risk human papilloma virusDaily practiceGestational trophoblastic tumorsHuman papilloma virusSquamous cell carcinomaUterine cervical carcinomaBiopsy/resectionTrophoblastic tumorCervical neoplasiaCell carcinomaCervical carcinomaDiagnostic challengeMetastatic tumorsPapilloma virusMalignant melanomaBenign lesionsTumorsHrHPVAdenocarcinomaCarcinomaSignificant percentagePathologistsHPVResectionHDAC Inhibition Induces Cell Cycle Arrest and Mesenchymal-Epithelial Transition in a Novel Pleural-Effusion Derived Uterine Carcinosarcoma Cell Line
Stockhammer P, Okumus Ö, Hegedus L, Rittler D, Ploenes T, Herold T, Kalbourtzis S, Bankfalvi A, Sucker A, Kimmig R, Aigner C, Hegedus B. HDAC Inhibition Induces Cell Cycle Arrest and Mesenchymal-Epithelial Transition in a Novel Pleural-Effusion Derived Uterine Carcinosarcoma Cell Line. Pathology & Oncology Research 2021, 27: 636088. PMID: 34257602, PMCID: PMC8262245, DOI: 10.3389/pore.2021.636088.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarcinosarcomaCell Cycle CheckpointsCisplatinEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHistone DeacetylasesHumansMiddle AgedMutationPaclitaxelPhthalazinesPiperazinesPleural Effusion, MalignantPrognosisPyrazolesQuinolinesTumor Cells, CulturedUterine NeoplasmsVorinostatConceptsEpithelial-mesenchymal transitionUterine carcinosarcomaPleural effusionMesenchymal-epithelial transitionCell linesPatient-derived preclinical modelsMalignant pleural effusionMetastatic tumor lesionsVimentin-positive tumorsE-cadherinCarcinosarcoma cell lineInduces cell cycle arrestHistone deacetylase inhibitionFirst-line chemotherapeuticsΒ-catenin expressionE-cadherin expressionPSmad2 expressionCell cycle analysisPositive tumorsAggressive malignancyMetastatic tumorsDisease progressionCell cycle arrestNovel therapiesPreclinical modelsGenomic Characterization of de novo Metastatic Breast Cancer
Garrido-Castro AC, Spurr LF, Hughes ME, Li YY, Cherniack AD, Kumari P, Lloyd MR, Bychkovsky B, Barroso-Sousa R, Di Lascio S, Jain E, Files J, Mohammed-Abreu A, Krevalin M, MacKichan C, Barry WT, Guo H, Xia D, Cerami E, Rollins BJ, MacConaill LE, Lindeman NI, Krop IE, Johnson BE, Wagle N, Winer EP, Dillon DA, Lin NU. Genomic Characterization of de novo Metastatic Breast Cancer. Clinical Cancer Research 2021, 27: 1105-1118. PMID: 33293374, PMCID: PMC7887078, DOI: 10.1158/1078-0432.ccr-20-1720.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerPrimary tumorOverall survivalBreast cancerDe novo metastatic breast cancerNovo metastatic breast cancerDifferential therapeutic sensitivityBetter OSPoor OSShorter OSInitial diagnosisHigh TMBMetastatic tumorsDnMBCCurrent treatmentMutational burdenTreatment selectionMetastatic driversStage IMultiple comparison adjustmentTherapeutic sensitivityTumorsPatientsCancerIntrinsic resistance
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