Understanding drug uptake and binding within targeted disease micro-environments in patients a new tool for translational medicine 英文参考文献.docVIP

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Understanding drug uptake and binding within targeted disease micro-environments in patients a new tool for translational medicine 英文参考文献.doc

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Understanding drug uptake and binding within targeted disease micro-environments in patients a new tool for translational medicine 英文参考文献

Marko-Vargaetal.ClinicalandTranslationalMedicine2012,1:8 /content/1/1/8 RESEARCH OpenAccess Understandingdruguptakeandbindingwithin targeteddiseasemicro-environmentsinpatients: anewtoolfortranslationalmedicine Gy?rgyMarko-Varga1,2*,ákosVégvári1,MelindaRezeli1,KaiuPrikk3,PeeterRoss3,MagnusDahlb?ck4, GouthamEdula4,RuthSepper3andThomasEFehniger1,3 Abstract Background:Formanycommonglobaldiseases,suchascancer,diabetes,neurodegenerativeandcardiovascular diseasesthereisanunmetneedfordiagnosingearlyindicationsofdiseasethatcouldenablemedicalintervention andearlytreatment.Thetreatmentofthesediseaseswillrequiredetailedknowledgeoftargetedpathwaysinvolved indiseasepathogenesisbutalsothemodeofdrugactionsatthebiologicallocationonthesetargets.Translational medicineisanewareaofresearchwhereexpertfromdifferentdisciplinesinvolvedinbasicscienceandclinical disciplinesmeetandjoinforces.Mode-of-drug-actionmechanismselucidationiskeyinthecharacterizationofdrugs thatcanrelatetobothefficacyandsafety. Methods:Matrixassistedlaserdesorption/ionizationmassspectrometryimaging(MALDI-MSI)wasusedproviding evidenceintothefate(destinationsanddistributions)ofadministereddrugswithintumorregionsoflung compartments. Results:Weherebypresentapulmonarystudyinwhichwehaveisolatedlungtissueafterinhaleddrug administrationandthenlocalizedthedrugwithinairwaywallcompartments.Thehistologyalsoprovidesevidence ofdrugbindingtosmoothmusclecellmicroenvironments.Wealsoidentifiedlungtissueregionswithtumorcell invasionintheseCOPDpatients. Conclusions:Theultimategoalistoidentifybridgingcomprehensionthatformsaknowledgebasethatcanbe usedbysocietytodevelopabettertreatmentandmedicineforpatients.Ourresultsdemonstratedthatrobust imagingdatacouldbegeneratedconfirmingdruglocalizationinpulmonaryregionsofCOPDpatientswithtumor pathology. Trialregistration:TallinnMedicalResearchEthicalCommitteedecision#1724,18.06.2009 Keywords:Clinicaldrugadministration,Ipratropiumbromide,Bronchialtissue,MALDI-MSImaging,MALDILTQ OrbitrapXL *Corresponde