简介：Objective:ThepresentstudyaimedtoinvestigatecircularRNA(circRNA)expressioninuvealmelanoma(UM).Methods:First,weusedmicroarraytocomparetheexpressionprofilesofcircRNAinfiveUMsamplesandfivenormaluveatissues.Next,bioinformaticsanalyses,includinggeneontology(GO)analysisandpathwayanalysis,wereappliedtostudythesedifferentiallyexpressedcircRNAstopredictpathogenicpathwaysthatmaybeinvolved.Quantitativereal-timepolymerasechainreaction(qRT-PCR)in20UMsamplesand20normaluveasampleswasusedtoconfirmthecircRNAexpressionprofilesobtainedfromthemicroarraydata.Finally,weanalyzedtheinteractionbetweenvalidatedcircRNAsandtheirpotentialcancer-associatedmiRNAtargets.Results:Intotal,50,579circRNAs[foldchange(FC)≥2.0;P<0.05],including20,654up-regulatedand29,925down-regulatedcircRNAs,wereidentifiedasdifferentiallyexpressedbetweenUMtissuesandnormaluveatissues.WeusedqRT-PCRtoverifysevendysregulatedcircRNAsindicatedbythemicroarraydata,includinghsacirc0119873,hsacirc0128533,hsacirc0047924,hsacirc0103232,hsa-circRNA10628-6,hsacirc0032148andhsacirc0133460,whichmaybepromisingcandidatestostudyfuturemolecularmechanisms.Conclusions:Thisstudyexplored,forthefirsttime,theabnormalexpressionofcircRNAsinUManddescribedtheexpressionprofileofcircRNAs,providinganewpotentialtargetforthemechanismofUMandfuturetreatmentofUM.

简介：Melanomaisthedeadliestformofskincancerandhasanincidencethatisrisingfasterthananyothersolidtumor.Metastaticmelanomatreatmenthasconsiderablyprogressedinthepastfiveyearswiththeintroductionoftargetedtherapy(BRAFandMEKinhibitors)andimmunecheckpointblockade(anti-CTLA4,anti-PD-1,andanti-PD-L1).However,eachtreatmentmodalityhaslimitations.Treatmentwithtargetedtherapyhasbeenassociatedwithahighresponserate,butwithshort-termresponses.Conversely,treatmentwithimmunecheckpointblockadehasalowerresponserate,butwithlongtermresponses.Targetedtherapyaffectsantitumorimmunity,andsynergymayexistwhentargetedtherapyiscombinedwithimmunotherapy.Thisarticlepresentsabriefreviewoftherationaleandevidenceforthepotentialsynergybetweentargetedtherapyandimmunecheckpointblockade.Challengesanddirectionsforfuturestudiesarealsoproposed.

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简介：Objective:VitaminDreceptor(VDR)mediatesvitaminDactivity.WeexaminedwhetherVDRexpressioninexcisedmelanomatissuesisassociatedwithVDRgene(VDR)polymorphisms.Methods:WeevaluatedVDRproteinexpression(bymonoclonalantibodyimmunostaining),melanomacharacteristics,andcarriageofVDR-FokI-rs2228570(C>T),VDR-BsmI-rs1544410(G>A),VDR-ApaI-rs7975232(T>G),andVDR-TaqI-rs731236(T>C)polymorphisms(byrestrictionfragmentlengthpolymorphism).Absenceorpresenceofrestrictionsitewasdenotedbyacapitalorlowerletter,respectively:'F'and'f'forFokI,'B'and'b'forBsmI,'A'and'a'forApaI,and'T'and't'forTaqIendonuclease.Seventy-fourItaliancutaneousprimarymelanomas(52.1±12.7yearsold)werestudied;51.4%werestageⅠ,21.6%stageⅡ,13.5%stageⅢ,and13.5%stageⅣmelanomas.VDRexpressionwascategorizedasfollows:100%positivevs.<100%;overthemedian20%(highVDRexpression)vs.≤20%(lowVDRexpression);absencevs.presenceofVDR-expressingcells.Results:StageImelanomas,Breslowthicknessof<1.00mm,levelIIClarkinvasion,Aaheterozygousgenotype,andAaTTcombinedgenotypeweremorefrequentinmelanomaswithhighvs.lowVDRexpression.CombinedgenotypesBbAA,bbAa,AATt,BbAATt,andbbAaTTweremorefrequentin100%vs.<100%VDR-expressingcells.CombinedgenotypeAATTwasmorefrequentinmelanomaslackingVDRexpression(oddsratio=14.5;P=0.025).VDRexpressionwasnotassociatedwithmetastasis,ulceration,mitosis>1,regression,tumor-infiltratinglymphocytes,tumoralinfiltrationofvasculartissues,additionalskinandnon-skincancers,andmelanomafamiliarity.Conclusions:WehighlightedthatVDRpolymorphismscanaffectVDRexpressioninexcisedmelanomacells.LowVDRexpressioninAATTcarriersisanewfindingthatmeritsfurtherstudy.VDRexpressionpossiblyposesimplicationsforvitaminDsupplementationagainstmelanoma.VDRexpressionandVDRgenotypemaybecomeprecisemedicinaltoolsformelanomainthefuture.

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简介：Objective:Fusogenicendogenousretroviralsyncytinplaysanimportantroleintheformationofsyncytiotrophoblastsinhumanplacenta.Apartfromitsexpressioninplacenta,brainandtestis,syncytinhasalsobeenfoundinmanycancers.Althoughsyncytinhasbeenproposedtoserveasapositiveprognosticmarkerinsomecancers,theunderlyingmechanismisunclear.Theaimofthisstudyistoevaluatetheeffectsofsyncytinexpressionontheinvasivephenotypeofmelanomacells.Methods:Theeukaryoticexpressionplasmidforsyncytin-EGFPwasconstructedandtransfectedintoB16F10melanomacells.TheeffectofsyncytinontheinvasionpotentialoftumorcellswasevaluatedinB16F10sublinecellsthatstablyexpressedsyncytin-EGFPfusionproteinorEGFPalone.Results:TheB16F10sublinesthatstablyexpressedsyncytin-EGFPorEGFPalonewereestablishedrespectivelyandconfirmedbyimmunofluorescentandimmunoblottingassay.SyncytinexpressioninB16F10cellswasassociatedwithdecreasedcellproliferation,migrationandinvasion.Multinucleatedgiantcellsthatcontainedasmanyasfivenucleiwereinducedinsyncytin-expressingcells.Inaddition,syncytinexpressiondidnotalterthesensitivityofB16F10cellstotrichosanthin,atoxinthatdamagessyncytiotrophoblastsmoreefficientlythanothertissues.Conclusions:Theseresultssuggestthatsyncytinexpressioninsomecancersmayconfinetheirinvasionpotentialandthusserveasapositiveprognosticfactor.更多还原

简介：Objective:ToinvestigatewhethervitaminDreceptorgene(VDR)BsmI-rs1544410andFokI-rs2228570polymorphisms,smokingduration,andbodymassindex(BMI)areriskfactorsforcutaneousmelanoma,especiallymetastaticmelanoma.Methods:Westudied120cutaneousmelanomacases[68stageIandIInon-metastaticmelanoma(NMetM)patients,plus52StageIIIandIVmetastaticmelanoma(MetM)patients],and120matchinghealthycontrolsfromnortheastItaly.VDRpolymorphismsweremeasuredbyrestrictionfragmentlengthpolymorphismanalysis.AbsenceorpresenceofBsmIandFokIrestrictionsiteswasdenotedby'B'and'F'orby'b'and'f,'respectively.Results:VDR-BsmIbbgenotypewasmorefrequentamongMetM(32.7%)thanamongNMetMcases(13.2%),withoddsratio(OR)=3.18.Comparisonofallmelanomapatientsvshealthycontrolsshowedthatthefollowingbiomarkerswereatrisk:≥20yearsofsmoking(OR=2.43);≥20yearsofsmokingcombinedwithbb(OR=4.78),Bb+bb(OR=2.30),Ff(OR=3.04),andFf+ff(OR=3.08);obesity(BMI>30Conclusions:RiskfactorsforcutaneousMetMincludetwoVDRpolymorphismscombinedwithsmokingdurationandobesity.Resultssuggestgene-environmentimplicationsinmelanomasusceptibilityandseverity.Futurestudiesinlargercohortsandinsubjectswithdifferentgeneticbackgroundarewarrantedtoextendourfindings.