2020
Abnormal Liver Function Tests in Patients With COVID‐19: Relevance and Potential Pathogenesis
Bertolini A, van de Peppel I, Bodewes FAJA, Moshage H, Fantin A, Farinati F, Fiorotto R, Jonker JW, Strazzabosco M, Verkade HJ, Peserico G. Abnormal Liver Function Tests in Patients With COVID‐19: Relevance and Potential Pathogenesis. Hepatology 2020, 72: 1864-1872. PMID: 32702162, PMCID: PMC7404414, DOI: 10.1002/hep.31480.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAbnormal liver function testsLiver function testsCOVID-19 patientsAspartate aminotransferaseFunction testsHospitalized coronavirus disease 2019 (COVID-19) patientsSevere COVID-19 diseaseCoronavirus disease 2019 (COVID-19) patientsElevated liver function testsPre-existing liver diseaseDrug-induced liver injuryCOVID-19Hyper-inflammatory statusAlanine aminotransferase levelsLopinavir/ritonavirOvert liver failureStart of treatmentUse of acetaminophenCause of deathPlasma aspartate aminotransferaseUpper reference limitSARS-CoV-2COVID-19 diseaseAlkaline phosphataseALT elevation
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 inhibitor
2017
Notch signaling and progenitor/ductular reaction in steatohepatitis
Morell CM, Fiorotto R, Meroni M, Raizner A, Torsello B, Cadamuro M, Spagnuolo G, Kaffe E, Sutti S, Albano E, Strazzabosco M. Notch signaling and progenitor/ductular reaction in steatohepatitis. PLOS ONE 2017, 12: e0187384. PMID: 29140985, PMCID: PMC5687773, DOI: 10.1371/journal.pone.0187384.Peer-Reviewed Original ResearchConceptsHepatic stellate cellsDuctular reactionRole of NotchMCD diet-fed miceMethionine-choline deficient (MCD) dietHepatic progenitor cell activationPrimary hepatic stellate cellsChronic liver diseaseDiet-fed miceTGF-β1 expressionAlternative therapeutic targetsTGF-β1 treatmentProgenitor cell activationNotch-1 activationLiver injuryMCD dietLiver diseaseFibrosis progressionNotch signalingDR responseLiver repairBSEP expressionHepatocyte cell lineLiver cancerAAV8-TBG
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 markers
2009
Diferentially expressed adenylyl cyclase isoforms mediate secretory functions in cholangiocyte subpopulation
Strazzabosco M, Fiorotto R, Melero S, Glaser S, Francis H, Spirli C, Alpini G. Diferentially expressed adenylyl cyclase isoforms mediate secretory functions in cholangiocyte subpopulation. Hepatology 2009, 50: 244-252. PMID: 19444869, PMCID: PMC2738985, DOI: 10.1002/hep.22926.Peer-Reviewed Original ResearchConceptsSoluble adenylyl cyclaseAdenylyl cyclasesGene expressionAC isoformsCyclic adenosine monophosphateAC gene expressionDifferent tissue specificitiesGroup of enzymesAdenylyl cyclase isoformsTissue specificityCholangiocyte secretionCyclase isoformsIsoformsSAC inhibitorIsohydric changesAdenylyl cyclaseIsoform expressionSACS geneReal-time polymerase chain reactionGenesAdenosine monophosphateAC8ExpressionCAMP levelsCAMP productionSide chain structure determines unique physiologic and therapeutic properties of norursodeoxycholic acid in Mdr2−/− mice
Halilbasic E, Fiorotto R, Fickert P, Marschall H, Moustafa T, Spirli C, Fuchsbichler A, Gumhold J, Silbert D, Zatloukal K, Langner C, Maitra U, Denk H, Hofmann AF, Strazzabosco M, Trauner M. Side chain structure determines unique physiologic and therapeutic properties of norursodeoxycholic acid in Mdr2−/− mice. Hepatology 2009, 49: 1972-1981. PMID: 19475687, PMCID: PMC3569724, DOI: 10.1002/hep.22891.Peer-Reviewed Original ResearchConceptsNorursodeoxycholic acidBile duct unitsUnique physiologicSerum bile acid levelsDuct unitsBile acid levelsCholestatic liver diseaseDramatic therapeutic effectsTherapeutic propertiesRelative resistanceCholehepatic shuntingCholestatic injuryPharmacologic featuresLiver histologyLiver diseaseRole of CFTRBile compositionPharmacologic propertiesCholeretic effectNorUDCATherapeutic effectExpression of MRP4Standard dietSerum biochemistryExperimental cholestasis
2007
Analysis of Liver Repair Mechanisms in Alagille Syndrome and Biliary Atresia Reveals a Role for Notch Signaling
Fabris L, Cadamuro M, Guido M, Spirli C, Fiorotto R, Colledan M, Torre G, Alberti D, Sonzogni A, Okolicsanyi L, Strazzabosco M. Analysis of Liver Repair Mechanisms in Alagille Syndrome and Biliary Atresia Reveals a Role for Notch Signaling. American Journal Of Pathology 2007, 171: 641-653. PMID: 17600123, PMCID: PMC1934520, DOI: 10.2353/ajpath.2007.070073.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAlagille SyndromeBiliary AtresiaChildChild, PreschoolCyclin-Dependent Kinase Inhibitor p21FemaleHepatocyte Nuclear Factor 1-betaHepatocytesHumansImmunohistochemistryInfantKeratin-19Keratin-7Ki-67 AntigenLiverLiver CirrhosisLiver RegenerationLiver TransplantationMaleMiddle AgedReceptors, NotchSeverity of Illness IndexSignal TransductionConceptsReactive ductular cellsHepatic progenitor cellsAlagille syndromeLiver repair mechanismsHepatobiliary cellsDuctular cellsBiliary cirrhosisProgenitor cellsIntermediate hepatobiliary cellsComputer-assisted morphometryCholestatic cholangiopathiesSevere ductopeniaBiliary atresiaSevere cholestasisNotch signalingDuctular reactionRapid progressionSeptum thicknessRole of NotchReparative mechanismsBiliary phenotypeEpithelial componentPostnatal lifeRepair mechanismsCirrhosis
2001
Proinflammatory Cytokines Inhibit Secretion in Rat Bile Duct Epithelium
Spirlı̀ C, Nathanson M, Fiorotto R, Duner E, Denson L, Sanz J, Di Virgilio F, Okolicsanyi L, Casagrande F, Strazzabosco M. Proinflammatory Cytokines Inhibit Secretion in Rat Bile Duct Epithelium. Gastroenterology 2001, 121: 156-169. PMID: 11438505, DOI: 10.1053/gast.2001.25516.Peer-Reviewed Original ResearchConceptsProinflammatory cytokinesFluorescein-labeled dextranIL-1Interferon gammaCAMP-dependent fluid secretionCystic fibrosis transmembrane conductance regulatorBile duct epitheliumRat bile duct epitheliaTumor necrosis factorCyclic adenosine monophosphate levelsSecretin receptorAdenosine monophosphate levelsBile duct unitsDuctular cholestasisPortal inflammationCholestatic disordersIL-6Inflammatory cytokinesTNF-alphaBiliary epitheliumNecrosis factorCellular cyclic adenosine monophosphate (cAMP) levelsDuct epitheliumPurinergic agonistsSR expression