简介：AlatticeBoltzmannnumericalmodelingmethodwasdevelopedtopredictskinconcentrationaftertopicalapplicationofadrugontheskin.ThemethodisbasedonD2Q9latticespacesassociatedwiththeBhatnagar-Gross-Krook(BGK)collisiontermtosolvetheconvection-diffusionequation(CDE).Asimulationwascarriedoutindifferentrangesofthevalueofbound,whichisrelatedtoskincapillaryclearanceandthevolumeofdiffusionduringapercutaneousabsorptionprocess.Whenatypicaldrugisusedontheskin,thevalueofcorrespondstotheamountofdrugabsorbedbythebloodandtheabsorptionofthedrugaddedtotheskin.Theeffectofwasstudiedforwhentheregionofskincontactisalinesegmentontheskinsurface.

简介：Wepresentherethedevelopmentofcholesterol(Chol)-modifieddendrimersystemfortargetedchemotherapyoffolate(FA)receptor-expressingcancercells.Inourstudy,poly(amidoamine)(PAMAM)dendrimersofgeneration5(G5)werefunctionalizedstepby-stepwithChol,fluoresceinisothiocyanate(FI),andFAviaapoly(ethyleneglycol)(PEG)spacer(PEG-FA),andthenacetamidetoshieldtheirremainingsurfaceamines.ThesynthesizedG5.NHAc-Chol-FI-PEG-FA(forshort,G5-CFPF)dendrimerswereutilizedtoencapsulate10-hydroxycamptothecin(HCP),ahydrophobicanticancerdrug.WefindthateachG5-CFPFdendrimercanencapsulate13.8HCPmolecules.ThecomplexesshowaslowerreleaseprofilesofHCPinapH-dependentmannerthanthecontrolcomplexesformedusingthesamedendrimerswithoutCholunderthesameconditions.ThankstothetargetingroleplayedbyFA,thecomplexesdisplayaspecificinhibitionefficacytoFAreceptor-expressingcervicalcancercells.ThedesignedChol-modifieddendrimersmaybeadoptedasapromisingcarrierforapplicationintargetedcancertherapy.

简介：Systemictoxicityandinsufficientdrugaccumulationatthetumours让earemainbarriersinchemotherapy.Thermosens让iveliposomes(TSL)combinedwithhighintensityfocusedultrasound(HIFU)hasemergedasapotentialsolutiontoovercomethesebarriersthroughtargeteddrugdeliveryandlocalisedrelease.Owingtothemultiplephysicalandbiochemicalprocessesinvolvedinthiscombinationtherapy,mathematicalmodellingbecomesanindispensabletoolfordetailedanalysisofthetransportprocessesandpredictionoftumourdruguptake.Tothisend,amultiphysicsmodelhasbeendevelopedtosimulatethetransportofchemotherapydrugsdeliveredthroughacombinedHIFU-TSLsystem.Allkeydeliveryprocessesareconsideredinthemodel;theseineludeinterstitialfluidflow,HIFUacoustics,bioheattransfer;drugreleaseandtransport,aswellastumourdruguptake.Thecapabilityofthemodelisdemonstratedthroughitsapplicationtoa2-Dprostatetumourmodelreconstructedfrommagneticresonanceimages.Ourresultsnotonlydemonstratethefeasibilityofthemodeltosimulatethiscombinationtherapy,butalsoconfirmtheadvantageofHIFU-TSLdrugdeliverysystemwithenhancementofdrugaccumulationintumourregionsandreductionofdrugavailabilityinnormaltissue.ThismultiphysicsmodellingframeworkcanserveasausefultooltoassistinthedesignofHIFU-TSLdrugdeliverysystemsandtreatmentregimenforimprovedanticancerefficacy.

简介：TherootbarkofMorusalbaL.orwhitemulberryiswidelyusedastraditionalmedicineinChina,JapanandKorea.Majorclassesandtypesofphenoliccompoundsisolatedfromtherootbarkareflavonoids(kuwanons,morusin,cyclomorusinandsanggenons),benzofurans(moracinsandmulberrofurans),andstilbenoids(mulberrosides).SomeoftheflavonoidsandbenzofuransareproductsofDiel-Aldertypeadducts.Otherclassesofcompoundsincludetriterpenes,phenolicacidsandcoumarins.Morusin,aprenylatedflavonoid,wasfirstisolatedfromtherootbarkofM.alba,andlaterfromtheleaf,stembarkandtwigoftheplant.Thepotentanti-cancerpropertiesofmorusinhaveattractedmuchattentionwithresearchon-goingandnewfindingsbeingpublished.Thecompoundinhibitsangiogenesis,tumourprogressionandtumourmigration,andtriggersapoptosis,cellcyclearrestandautophagyincolorectal,cervical,prostate,breast,hepatoma,pancreatic,glioblastoma,gastric,ovarianandlungcancercelllines.Theanti-canceractivitiesofmorusinareexecutedviavariousmoleculartargetsandsignallingpathways.Itisanticipatedthaton-goinginvitrostudieswillprogressgraduallytoinvivostudiesusinganimalmodelsbeforeeffortstowardsdrugdevelopmentcanbeinitiatedforclinicaltrials.

简介：Objective:SHR-1210isanewandpromisinganti-PD-1agentforsolidtumors.DuringthephaseIstudyofSHR-1210,weencounteredanovelbutprevalentimmune-relateddermatologictoxicity:reactivecapillaryhemangiomas(RCHs).ThuswetriedtosummarizethefeaturesofRCHsandestimatetheirrelationshipwithtumorresponse.Methods:Thisprospectiveobservationalstudysystematicallyenrolled98patientswithadvancedsolidtumorsfromApril27th,2016toJune8th,2017inthecontextofthephaseIclinicalstudyofSHR-1210.Thisreportfocusedontheskintoxicities.Patientsunderwententireskininspectioneverytwoweekswhiletakingmedication.TheclinicalcourseofRCHswasrecordedandtheirassociationwithtumorresponsewasestimated.Thedatacut-offdatewasNovember15th,2017.Results:Afteramedianfollow-upof242(range,29–567)days,RCHswereobservedin85.7%(84/98)ofpatientsoncutaneous/mucosalsurfaces;84.5%(71/84)oftheRCHswereevaluatedasgrade1adverseevents.Nograde3or4RCHswereobserved.ThetimeofonsetofRCHswasdosedependentandshortestinthe400mg-dosecohort(P<0.001).SpontaneousandcompleteregressionofRCHswasobservedbothduringandaftertreatment.TheobjectiveresponserateoftumorsforpatientswithRCHswas28.9%(24/83).However,noresponderswereobservedamongthepatientswithoutRCHs.Conclusions:RCHswereprevalentbutmanageableduringtreatmentwithSHR-1210.Itmightaddtotheexpandingliteratureregardingimmune-relateddermatologicadverseevents.