2023
Intrahepatic Cholangiocarcinoma Developing in Patients with Metabolic Syndrome Is Characterized by Osteopontin Overexpression in the Tumor Stroma
Cadamuro M, Sarcognato S, Camerotto R, Girardi N, Lasagni A, Zanus G, Cillo U, Gringeri E, Morana G, Strazzabosco M, Campello E, Simioni P, Guido M, Fabris L. Intrahepatic Cholangiocarcinoma Developing in Patients with Metabolic Syndrome Is Characterized by Osteopontin Overexpression in the Tumor Stroma. International Journal Of Molecular Sciences 2023, 24: 4748. PMID: 36902188, PMCID: PMC10003180, DOI: 10.3390/ijms24054748.Peer-Reviewed Original ResearchMeSH KeywordsBile Duct NeoplasmsBile Ducts, IntrahepaticCholangiocarcinomaHumansMetabolic SyndromeNon-alcoholic Fatty Liver DiseaseOsteopontinConceptsMetS patientsMetabolic syndromeNon-alcoholic fatty liver disease/non-alcoholic steatohepatitisNon-alcoholic steatohepatitisIntrahepatic cholangiocarcinoma developmentPutative therapeutic targetDeposition of osteopontinCell-like phenotypeBiliary tumorigenesisExtracellular matrix depositionVascular complicationsSurgical resectionIntrahepatic cholangiocarcinomaICCA cellsOverexpression of osteopontinPredictive biomarkersLiver tumorsCommon conditionHuCCT-1Tumor stromaCholangiocarcinoma developmentPeritumoral areaTherapeutic targetBiliary differentiationOsteopontin overexpression
2022
Locoregional Therapy in the Management of Intrahepatic Cholangiocarcinoma: Is There Sufficient Evidence to Guide Current Clinical Practice?
Wang Y, Strazzabosco M, Madoff DC. Locoregional Therapy in the Management of Intrahepatic Cholangiocarcinoma: Is There Sufficient Evidence to Guide Current Clinical Practice? Current Oncology Reports 2022, 24: 1741-1750. PMID: 36255606, PMCID: PMC10878124, DOI: 10.1007/s11912-022-01338-5.Peer-Reviewed Original ResearchMeSH KeywordsBile Duct NeoplasmsBile Ducts, IntrahepaticCholangiocarcinomaHepatectomyHumansRetrospective StudiesConceptsLocoregional therapyIntrahepatic cholangiocarcinomaManagement of ICCFuture prospective randomized studiesComparable survival outcomesSafety of hepatectomyProspective Randomized StudyLocal tumor controlNon-surgical approachCurrent clinical practicePurpose of reviewUnresectable diseaseSurgical candidatesSystemic therapyVenous embolizationRandomized studyTransarterial embolizationDismal prognosisMultimodal treatmentSafety profileSurvival outcomesAblative therapyTumor controlPreoperative hypertrophyLiver lobeInflammatory pathways and cholangiocarcioma risk mechanisms and prevention
Cadamuro M, Strazzabosco M. Inflammatory pathways and cholangiocarcioma risk mechanisms and prevention. Advances In Cancer Research 2022, 156: 39-73. PMID: 35961707, PMCID: PMC10916841, DOI: 10.1016/bs.acr.2022.02.001.Peer-Reviewed Original ResearchMeSH KeywordsBile Duct NeoplasmsBile Ducts, IntrahepaticCholangiocarcinomaCholangitis, SclerosingHumansRisk FactorsConceptsDevelopment of cholangiocarcinomaNonalcoholic fatty liver diseaseAdequate therapeutic treatmentPrimary sclerosing cholangitisFatty liver diseasePro-inflammatory mechanismsMain risk factorsProdromal diseaseSclerosing cholangitisCaroli's diseaseMetabolic syndromeChronic cholangiopathiesLiver diseasePoor prognosisInflammatory pathwaysBiliary treeCCA developmentRisk factorsImmune responseImmunological responseTherapeutic targetCholangiocarcinomaFluke infestationRole of cellExtrahepatic areas
2021
Targeted therapies for extrahepatic cholangiocarcinoma: preclinical and clinical development and prospects for the clinic
Cadamuro M, Lasagni A, Lamarca A, Fouassier L, Guido M, Sarcognato S, Gringeri E, Cillo U, Strazzabosco M, Marin JJ, Banales JM, Fabris L. Targeted therapies for extrahepatic cholangiocarcinoma: preclinical and clinical development and prospects for the clinic. Expert Opinion On Investigational Drugs 2021, 30: 377-388. PMID: 33622120, PMCID: PMC8194059, DOI: 10.1080/13543784.2021.1880564.Peer-Reviewed Original ResearchMeSH KeywordsBile Duct NeoplasmsCholangiocarcinomaHumansImmunotherapyMolecular Targeted TherapyPrecision MedicinePrognosisTumor MicroenvironmentConceptsExtrahepatic CCAMinority of patientsComplex molecular landscapePro-oncogenic pathwaysSystematic literature searchDeep phenotyping studyOutcome predictorsExtrahepatic cholangiocarcinomaOverlooked diseaseActionable driversClinical developmentActionable targetsMolecular alterationsOncogenic driversTumor microenvironmentHeterogeneous tumorsLiterature searchDistinct entityMolecular profilingSpecific alterationsMolecular landscapePrecision medicinePerturbed pathwaysImmunotherapyPhenotyping studiesThe Tumor Microenvironment in Cholangiocarcinoma Progression
Fabris L, Sato K, Alpini G, Strazzabosco M. The Tumor Microenvironment in Cholangiocarcinoma Progression. Hepatology 2021, 73: 75-85. PMID: 32500550, PMCID: PMC7714713, DOI: 10.1002/hep.31410.Peer-Reviewed Original Research
2020
Intrahepatic cholangiocarcinoma: Morpho-molecular pathology, tumor reactive microenvironment, and malignant progression
Sirica AE, Strazzabosco M, Cadamuro M. Intrahepatic cholangiocarcinoma: Morpho-molecular pathology, tumor reactive microenvironment, and malignant progression. Advances In Cancer Research 2020, 149: 321-387. PMID: 33579427, PMCID: PMC8800451, DOI: 10.1016/bs.acr.2020.10.005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Duct NeoplasmsCholangiocarcinomaDisease ProgressionHumansTumor MicroenvironmentConceptsIntrahepatic cholangiocarcinomaMalignant progressionCommon primary liver cancerPrimary hepatic malignancyPrimary liver cancerStandard of careHigh mortality rateICCA developmentMalignant aggressivenessHepatic malignanciesHepatobiliary cancersTumor immunobiologyDesmoplastic stromaHepatocellular carcinomaLiver cancerMortality rateTherapy resistanceEpithelial cancersDeleterious roleCell originCancerReactive microenvironmentMicroenvironmental factorsProgressionManagement optionsCholangiocarcinoma 2020: the next horizon in mechanisms and management
Banales JM, Marin JJG, Lamarca A, Rodrigues PM, Khan SA, Roberts LR, Cardinale V, Carpino G, Andersen JB, Braconi C, Calvisi DF, Perugorria MJ, Fabris L, Boulter L, Macias RIR, Gaudio E, Alvaro D, Gradilone SA, Strazzabosco M, Marzioni M, Coulouarn C, Fouassier L, Raggi C, Invernizzi P, Mertens JC, Moncsek A, Ilyas S, Heimbach J, Koerkamp BG, Bruix J, Forner A, Bridgewater J, Valle JW, Gores GJ. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nature Reviews Gastroenterology & Hepatology 2020, 17: 557-588. PMID: 32606456, PMCID: PMC7447603, DOI: 10.1038/s41575-020-0310-z.Peer-Reviewed Original ResearchConceptsPrimary liver cancerExpert consensus statementCancer-related deathCell of originBiliary malignant tumorsStudy of CholangiocarcinomaGastrointestinal malignanciesHistological confirmationAvailable therapiesBiliary treeNew diagnostic toolsSilent presentationPatient outcomesConsensus statementMalignant tumorsLiver cancerCholangiocarcinomaAggressive natureAlarming mortalityCurrent diagnosisMolecular alterationsNon-invasive approachTumorsDiagnostic toolTherapyLiver Matrix in Benign and Malignant Biliary Tract Disease
Fabris L, Cadamuro M, Cagnin S, Strazzabosco M, Gores G. Liver Matrix in Benign and Malignant Biliary Tract Disease. Seminars In Liver Disease 2020, 40: 282-297. PMID: 32162285, DOI: 10.1055/s-0040-1705109.Peer-Reviewed Original ResearchConceptsMalignant biliary tract diseasesBiliary tract diseaseExtracellular matrixReactive ductular cellsPro-oncogenic effectsHepatic progenitor cellsExtracellular matrix undergoesBiliary repairDuctular reactionTract diseaseBiliary damageMalignant transformationResident cellsDuctular cellsMain molecular factorsProgenitor cellsMolecular factorsMechanical signalsLiver matrixNoncollagenous glycoproteinsStructural alterationsDirect interactionBiochemical compositionCellsMultifunctional molecules
2019
The tumour microenvironment and immune milieu of cholangiocarcinoma
Fabris L, Perugorria M, Mertens J, Björkström NK, Cramer T, Lleo A, Solinas A, Sänger H, Lukacs‐Kornek V, Moncsek A, Siebenhüner A, Strazzabosco M. The tumour microenvironment and immune milieu of cholangiocarcinoma. Liver International 2019, 39: 63-78. PMID: 30907492, PMCID: PMC10878127, DOI: 10.1111/liv.14098.Peer-Reviewed Original ResearchConceptsTumor microenvironmentAbundant desmoplastic reactionCancer-associated fibroblastsHigh mortality rateTumor-promoting functionsEpithelial cancer cellsImmune milieuImmune cellsPancreatic cancerEffective therapyDesmoplastic reactionMortality rateCholangiocarcinomaInvasive abilityTherapeutic gainStromal cellsTumor cellsEndothelial cellsEpithelial counterpartsCancer cellsIntrahepatic variantCellular populationsMicroenvironmentCellsRecent studiesIntrahepatic Cholangiocarcinoma: Continuing Challenges and Translational Advances
Sirica AE, Gores GJ, Groopman JD, Selaru FM, Strazzabosco M, Wang X, Zhu AX. Intrahepatic Cholangiocarcinoma: Continuing Challenges and Translational Advances. Hepatology 2019, 69: 1803-1815. PMID: 30251463, PMCID: PMC6433548, DOI: 10.1002/hep.30289.Peer-Reviewed Original ResearchConceptsIntrahepatic cholangiocarcinomaMortality rateFuture translational research opportunitiesNonalcoholic fatty liver diseasePlatelet-derived growth factor DPrimary hepatobiliary cancerFatty liver diseaseRecent clinical trialsTranslational research findingsHigh mortality rateCancer-associated myofibroblastsTranslational research opportunitiesGrowth factor DNonspecific cirrhosisLiver diseaseHepatobiliary cancersSerum biomarkersRisk factorsClinical trialsExtracellular vesicle biomarkersLiver cancerMedical conditionsAggressive cancerIntrahepatic cholangiocarcinogenesisTherapeutic implications
2018
Platelet-derived growth factor-D enables liver myofibroblasts to promote tumor lymphangiogenesis in cholangiocarcinoma
Cadamuro M, Brivio S, Mertens J, Vismara M, Moncsek A, Milani C, Fingas C, Cristina Malerba M, Nardo G, Dall'Olmo L, Milani E, Mariotti V, Stecca T, Massani M, Spirli C, Fiorotto R, Indraccolo S, Strazzabosco M, Fabris L. Platelet-derived growth factor-D enables liver myofibroblasts to promote tumor lymphangiogenesis in cholangiocarcinoma. Journal Of Hepatology 2018, 70: 700-709. PMID: 30553841, PMCID: PMC10878126, DOI: 10.1016/j.jhep.2018.12.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Duct NeoplasmsCancer-Associated FibroblastsCell Line, TumorCholangiocarcinomaDisease Models, AnimalEndothelial CellsHeterograftsHumansImatinib MesylateLiverLymphangiogenesisLymphokinesMaleMiceMice, SCIDMyofibroblastsPlatelet-Derived Growth FactorProtein Kinase InhibitorsRatsRats, Inbred F344Receptor, Platelet-Derived Growth Factor betaVascular Endothelial Growth Factor AVascular Endothelial Growth Factor CConceptsCancer-associated fibroblastsLymphatic endothelial cellsCholangiocarcinoma specimensMetastatic spreadStromal reactionLiver myofibroblastsGrowth factorExtensive stromal reactionLymph node metastasisEarly metastatic spreadLevels of VEGFBH3 mimetic navitoclaxPlatelet-derived growth factorRole of PDGFVascular growth factorsTumor-associated lymphangiogenesisVEGF-C secretionTransendothelial electric resistanceCholangiocarcinoma invasivenessHuman lymphatic endothelial cellsCurative therapyNode metastasisBiliary treeEarly metastasisPDGFRβ inhibitorAnimal models of cholangiocarcinoma: What they teach us about the human disease
Cadamuro M, Brivio S, Stecca T, Kaffe E, Mariotti V, Milani C, Fiorotto R, Spirli C, Strazzabosco M, Fabris L. Animal models of cholangiocarcinoma: What they teach us about the human disease. Clinics And Research In Hepatology And Gastroenterology 2018, 42: 403-415. PMID: 29753731, DOI: 10.1016/j.clinre.2018.04.008.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAnimal modelsNovel therapeutic approachesRelevant animal modelsPathogenesis of cholangiocarcinomaBiliary carcinogenesisTreatment optionsTherapeutic approachesRodent modelsLethal cancersClinical phenotypeExperimental modelCholangiocarcinomaAggressive behaviorCell interactionsHuman diseasesComplex cell biologyMultiple cell interactionsMolecular perturbationsPathogenesisTumorsCancerDiseaseCarcinogenesis
2017
Molecular Mechanisms Driving Cholangiocarcinoma Invasiveness: An Overview
Brivio S, Cadamuro M, Fabris L, Strazzabosco M. Molecular Mechanisms Driving Cholangiocarcinoma Invasiveness: An Overview. Gene Expression 2017, 18: 31-50. PMID: 29070148, PMCID: PMC5860940, DOI: 10.3727/105221617x15088670121925.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Duct NeoplasmsCholangiocarcinomaHumansNeoplasm InvasivenessSignal TransductionTumor MicroenvironmentConceptsMajority of patientsPrimary liver cancerCancer-related deathPotential prognostic relevanceDevelopment of metastasesPro-oncogenic pathwaysNovel druggable targetsMechanism of actionCholangiocarcinoma invasivenessMesenchymal-like phenotypeDevastating malignancyCurative treatmentMolecular mechanismsPoor prognosisPrognostic relevancePrimary tumorBiliary epitheliumLiver cancerUseful biomarkerAbnormal activationCCA cell invasionMost carcinomasCCA cellsTumor microenvironmentCholangiocarcinomaThe deleterious interplay between tumor epithelia and stroma in cholangiocarcinoma
Cadamuro M, Stecca T, Brivio S, Mariotti V, Fiorotto R, Spirli C, Strazzabosco M, Fabris L. The deleterious interplay between tumor epithelia and stroma in cholangiocarcinoma. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2017, 1864: 1435-1443. PMID: 28757170, PMCID: PMC6386155, DOI: 10.1016/j.bbadis.2017.07.028.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTumor reactive stromaReactive stromaMain cellular componentsDeleterious interplayCyto/chemokinesCellular componentsParacrine signalsPrognosis of cholangiocarcinomaTumor epithelial cellsCell interactionsEarly invasivenessJesus BanalesMarco MarzioniNicholas LaRussoPeter JansenDifferent cell elementsEpithelial cellsEpithelial malignanciesTumor behaviorTumor epitheliumGrowth factorNeoplastic cellsTumor progressionCentral roleStromal componentsAutocrine and Paracrine Mechanisms Promoting Chemoresistance in Cholangiocarcinoma
Cadamuro M, Brivio S, Spirli C, Joplin RE, Strazzabosco M, Fabris L. Autocrine and Paracrine Mechanisms Promoting Chemoresistance in Cholangiocarcinoma. International Journal Of Molecular Sciences 2017, 18: 149. PMID: 28098760, PMCID: PMC5297782, DOI: 10.3390/ijms18010149.Peer-Reviewed Original ResearchMeSH KeywordsAutocrine CommunicationCell Line, TumorCholangiocarcinomaDrug Resistance, NeoplasmHumansParacrine CommunicationStromal Cells
2016
Low-Dose Paclitaxel Reduces S100A4 Nuclear Import to Inhibit Invasion and Hematogenous Metastasis of Cholangiocarcinoma
Cadamuro M, Spagnuolo G, Sambado L, Indraccolo S, Nardo G, Rosato A, Brivio S, Caslini C, Stecca T, Massani M, Bassi N, Novelli E, Spirli C, Fabris L, Strazzabosco M. Low-Dose Paclitaxel Reduces S100A4 Nuclear Import to Inhibit Invasion and Hematogenous Metastasis of Cholangiocarcinoma. Cancer Research 2016, 76: 4775-4784. PMID: 27328733, PMCID: PMC4987167, DOI: 10.1158/0008-5472.can-16-0188.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAnimalsAntineoplastic Agents, PhytogenicBile Duct NeoplasmsBlotting, WesternCell Line, TumorCell ProliferationCholangiocarcinomaHumansMiceMice, SCIDNeoplasm InvasivenessNeoplasm MetastasisPaclitaxelS100 Calcium-Binding Protein A4SumoylationXenograft Model Antitumor AssaysConceptsLow-dose paclitaxelNuclear S100A4Nuclear expressionSCID mouse xenograft modelPrimary liver cancerLocal tumor growthEGI-1 cellsCandidate therapeutic targetMouse xenograft modelMMP-9 secretionCholangiocarcinoma cell linesCholangiocarcinoma invasivenessLung disseminationMT1-MMP expressionCalcium binding proteinDismal prognosisRate of proliferationMetastatic spreadLiver cancerTumor massPaclitaxel treatmentXenograft modelTherapeutic targetTreatment opportunitiesMetastatic progression
2015
Malignancies in Primary Sclerosing Cholangitis - A Continuing Threat
Bonato G, Cristoferi L, Strazzabosco M, Fabris L. Malignancies in Primary Sclerosing Cholangitis - A Continuing Threat. Digestive Diseases 2015, 33: 140-148. PMID: 26641079, PMCID: PMC4939833, DOI: 10.1159/000440826.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseaseUlcerative colitisEffective medical treatmentGallbladder carcinomaColorectal carcinomaUnknown etiologyEarly diagnosisMedical treatmentChronic inflammatory liver diseaseManagement of PSCInflammatory liver diseasePrimary sclerosing cholangitisGroup of patientsChronic inflammatory conditionsChronic inflammatory diseaseBile duct systemRisk of cancerDevelopment of malignancyEffective surveillance strategiesExtensive histologicLiver transplantationNeoadjuvant chemoradiotherapySclerosing cholangitisFeared complicationFrequent complicationLeukemia inhibitory factor protects cholangiocarcinoma cells from drug-induced apoptosis via a PI3K/AKT-dependent Mcl-1 activation
Morton SD, Cadamuro M, Brivio S, Vismara M, Stecca T, Massani M, Bassi N, Furlanetto A, Joplin RE, Floreani A, Fabris L, Strazzabosco M. Leukemia inhibitory factor protects cholangiocarcinoma cells from drug-induced apoptosis via a PI3K/AKT-dependent Mcl-1 activation. Oncotarget 2015, 6: 26052-26064. PMID: 26296968, PMCID: PMC4694885, DOI: 10.18632/oncotarget.4482.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsApoptosisBile Duct NeoplasmsBlotting, WesternCell Line, TumorCholangiocarcinomaCisplatinDeoxycytidineGemcitabineGene Expression Regulation, NeoplasticHumansLeukemia Inhibitory FactorLeukemia Inhibitory Factor Receptor alpha SubunitMicroscopy, FluorescenceMyeloid Cell Leukemia Sequence 1 ProteinPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReverse Transcriptase Polymerase Chain ReactionRNA InterferenceSignal TransductionConceptsLeukemia inhibitory factorDrug-induced apoptosisChemotherapy-induced apoptosisPI3K inhibitionLIF effectsLIFR expressionExpression of LIFInhibitory factorRole of LIFCholangiocarcinoma cellsK inhibitionPI3K/Akt-dependent pathwayTumor stromal cellsHuman cholangiocarcinoma cell linesCell-like phenotypeCholangiocarcinoma cell linesMcl-1Akt-dependent pathwayUp-regulating Mcl-1IL-6 family cytokinesLIF secretionLiver malignanciesCholangiocarcinoma cell proliferationAnti-apoptotic proteinsFamily cytokines
2013
Platelet‐derived growth factor‐D and Rho GTPases regulate recruitment of cancer‐associated fibroblasts in cholangiocarcinoma
Cadamuro M, Nardo G, Indraccolo S, Dall'Olmo L, Sambado L, Moserle L, Franceschet I, Colledan M, Massani M, Stecca T, Bassi N, Morton S, Spirli C, Fiorotto R, Fabris L, Strazzabosco M. Platelet‐derived growth factor‐D and Rho GTPases regulate recruitment of cancer‐associated fibroblasts in cholangiocarcinoma. Hepatology 2013, 58: 1042-1053. PMID: 23505219, PMCID: PMC3732815, DOI: 10.1002/hep.26384.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBenzamidesBile Duct NeoplasmsBile Ducts, IntrahepaticCell Line, TumorCell MovementCell ProliferationCells, CulturedCholangiocarcinomaEpithelial-Mesenchymal TransitionFibroblastsHeterograftsHumansImatinib MesylateIn Vitro TechniquesLymphokinesMaleMiceMice, SCIDPiperazinesPlatelet-Derived Growth FactorPyrimidinesRho GTP-Binding ProteinsSignal TransductionConceptsCancer-associated fibroblastsPlatelet-derived growth factorEpithelial-mesenchymal transitionCCA cellsSecretion of PDGFRole of PDGFGrowth factorAbundant stromal reactionAlpha-smooth muscle actinPDGF-D expressionNovel therapeutic approachesPotential therapeutic targetSmooth muscle actinCCA cell linesPDGF-D signalingFibroblast migrationC-Jun N-terminal kinaseEMT biomarkersImmunodeficient miceStromal reactionTherapeutic approachesStroma interactionsTherapeutic targetCholangiocarcinomaMesenchymal markersIsolation and characterization of biliary epithelial and stromal cells from resected human cholangiocarcinoma: A novel in vitro model to study tumor-stroma interactions
MASSANI M, STECCA T, FABRIS L, CARATOZZOLO E, RUFFOLO C, FURLANETTO A, MORTON S, CADAMURO M, STRAZZABOSCO M, BASSI N. Isolation and characterization of biliary epithelial and stromal cells from resected human cholangiocarcinoma: A novel in vitro model to study tumor-stroma interactions. Oncology Reports 2013, 30: 1143-1148. PMID: 23807641, DOI: 10.3892/or.2013.2568.Peer-Reviewed Original ResearchMeSH KeywordsBile Duct NeoplasmsBile Ducts, IntrahepaticBiomarkers, TumorCell CommunicationCholangiocarcinomaCoculture TechniquesEpithelial-Mesenchymal TransitionFibroblastsFlow CytometryFluorescent Antibody TechniqueHumansImmunoenzyme TechniquesImmunomagnetic SeparationNeoplasm GradingStromal CellsTumor Cells, CulturedConceptsHuman biliary epithelial cellsTumor-stroma interactionsCancer-associated fibroblastsStromal cellsOrganotypic co-culture modelPrimary culturesTumor cell originMesenchymal cell markersBiliary epithelial cellsCCA cell linesRat cholangiocarcinomaCo-culture modelDevastating malignancySurgical resectionBile ductPresent studySurgical specimensDesmoplastic reactionCholangiocarcinomaCell originHuman cholangiocarcinomaCell markersFluorescent immunocytochemistryEpithelial cellsCK7