简介：Drugdevelopmentinoncologyisundergoingasubstantialshiftnowadays.Thedriversforthisaremulti-factorial.Ontheoneside,drugdevelopmentisperformedmorerationallythanever,profitingfromthescientificadvancesinmolecularbiologyingeneralandtheelucidationofthevarious'omes'fromgenometometabolomeinparticular.Ontheotherside,itisbasedonenormoustechnologicalprogress,e.g.,inthefieldofgenome

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简介：Thelymphaticsystemhasanimportantdefensiveroleinthehumanbody.Themetastasisofmosttumorsinitiallyspreadsthroughthesurroundinglymphatictissueandeventuallyformslymphaticmetastatictumors;thetumorcellsmayeventransfertootherorganstoformothertypesoftumors.Clinically,lymphaticmetastatictumorsdeveloprapidly.Giventhelimitationsofsurgicalresectionandtheloweffectivenessofradiotherapyandchemotherapy,thetreatmentoflymphaticmetastatictumorsremainsagreatchallenge.Lymphnodemetastasismayleadtothefurtherspreadoftumorsandmaybepredictiveoftheendpointevent.Underthesecircumstances,novelandeffectivelymphatictargeteddrugdeliverysystemshavebeenexploredtoimprovethespecificityofanticancerdrugstotumorcellsinlymphnodes.Inthisreview,wesummarizetheprinciplesoflymphatictargeteddrugdeliveryanddiscussrecentadvancesinthedevelopmentoflymphatictargetedcarriers.

简介：Objective:Toclonemultidrugresistance(MDR)relatedgenesinlungadenocarcinomacelllines.Methods:ThedifferentiallyexpressedcDNAfragmentsbetweenA549andA549DDPcellswereanalyzedbymRNAdifferentialdisplayPCR(DDRT-PCR).ThefragmentsthusobtainedwerefurtheranalyzedbyDNAsequencingandNorthernblotting.Results:ThreedifferentiallyexpressedcDNAfragmentswereobtainedandconfirmedbyNorthernblot.Sequenceanalysisrevealedthattwoofthemwerenovelandonewas100%identicalwithICEgene.Conclusion:AnalyzingdifferentiallyexpressedfragmentbetweenA549andA549DDPcellsmaybehelpfulforfindingnewMDRrelatedgenes.ThedrugresistanceofA549DDPcellsmayberelatedtotheinhibitionordown-regulationofICEgene.

简介：Platinum-basedanticanceragentsarewidelyusedasfirst-linedrugsincancerchemotherapyforvarioussolidtumors.However,greatsideeffectsandoccurrenceofresistanceremainasthemajordrawbacksforalmostalltheplatinumdrugsdeveloped.Toconquertheseproblems,newstrategiesshouldbeadoptedforplatinumdrugbasedchemotherapy.Modernnanotechnologyhasbeenwidelyemployedinthedeliveryofvarioustherapeuticsanddiagnostic.Itprovidesthepossibilityoftargeteddeliveryofacertainanticancerdrugtothetumorsite,whichcouldminimizetoxicityandoptimizethedrugefficacy.Here,inthisreview,wefocusedontherecentprogressinpolymerbaseddrugdeliverysystemsforplatinum-basedcombinationtherapy.

简介：Thedevelopmentofcancernanotherapeuticshasattractedgreatinterestintherecentdecade.Cancernanotherapeuticshaveovercomeseverallimitationsofconventionaltherapies,suchasnonspecificbiodistribution,poorwatersolubility,andlimitedbioavailability.Nanoparticleswithtunedsizeandsurfacecharacteristicsarethekeycomponentsofnanotherapeutics,andaredesignedtopassivelyoractivelydeliveranti-cancerdrugstotumorcells.Weprovideanoverviewofnanoparticle-baseddrugdeliverymethodsandcancertherapiesbasedontumor-targetingdeliverystrategiesthathavebeendevelopedinrecentyears.

简介：Risingworldwidecancerincidenceandresistancetocurrentanti-cancerdrugsnecessitatetheneedfornewpharmaceuticalcompoundsanddrugdeliverysystem.Malfunctionoftheimmunesystem,particularlyinthetumormicroenvironment,causestumorgrowthandenhancestumorprogression.Thus,cancerimmunotherapycanbeanappropriateapproachtoprovokethesystemicimmunesystemtocombattumorexpansion.Texosomes,whichareendogenousnanovesiclesreleasedbyalltumorcells,contributetocell-cellcommunicationandmodifythephenotypicfeaturesofrecipientcellsduetothetexosomes'abilitytotransportbiologicalcomponents.Forthisreason,texosome-baseddeliverysystemcanbeavaluablestrategyfortherapeuticpurposes.Toimprovethepharmaceuticalbehaviorofthissystemandtofacilitateitsuseinmedicalapplications,biotechnologyapproachesandmimetictechniqueshavebeenutilized.Inthisreview,wepresentthedevelopmenthistoryoftexosome-baseddeliverysystemsanddiscusstheadvantagesanddisadvantagesofeachsystem.

简介：Severaldrug-resistantvariantshavebeendevelopedbygrowingtheparentalMELcellsinpresenceofcolchicine,adriamycinandvincristinerespectivelywithstepwiseincreasingconcentration.Boththecolchicine-resistantSc9(ColO)andvincristine-resis-tantSc9(VCR5)cellsdisplayedanacceleratedHMBA-inducedcommitmenttoterminalcelldifferentiation,whereastheadriamycin-resistantSC9(A120)showednoaccelerationbutratherasubstantialdelayinHMBA-induceddifferentiation.ThestudiesprovidemorecluesaswellasexperimentalmodelsforfurtherstudyonthemechanismofinduceddifferentiationofMELcells.

简介：Glioblastoma(GBM)isoneofthemostlethalhumancancers.GenomicanalysesdefinethemoleculararchitectureofGBMandhighlightacentralfunctionformechanistictargetofrapamycin(mTOR)signaling.mTORkinaseexistsintwomultiproteincomplexes,namely,mTORC1andmTORC2.Thesecomplexesdifferintermsoffunction,regulationandrapamycinsensitivity.mTORC1iswellestablishedasacancerdrugtarget,whereasthefunctionsofmTORC2incancer,includingGBM,remainspoorlyunderstood.ThisstudyreviewstherecentfindingsthatdemonstrateacentralfunctionofmTORC2inregulatingtumorgrowth,metabolicreprogramming,andtargetedtherapyresistanceinGBM,whichmakesmTORC2asacriticalGBMdrugtarget.

简介：Inthefightagainstcancer,controlleddrugdeliverysystemshaveemergedtoenhancethetherapeuticefficacyandsafetyofanti-cancerdrugs.Amongthesesystems,mesoporoussilicananoparticles(MSNs)withafunctionalsurfacepossessobviousadvantagesandwerethusrapidlydevelopedforcancertreatment.Manystimuli-responsivematerials,suchasnanoparticles,polymers,andinorganicmaterials,havebeenappliedascapsandgatekeeperstocontroldrugreleasefromMSNs.ThisreviewpresentsanoverviewoftherecentprogressintheproductionofpH-responsiveMSNsbasedonthepHgradientbetweennormaltissuesandthetumormicroenvironment.Fourmaincategoriesofgatekeeperscanrespondtoacidicconditions.Thesecategorieswillbedescribedindetail.

简介：Objective:Toinvestigatetheeffectoftwoantisenseoligonucleotidesoncellsurviving,bcl-2expressionandapoptosisofleukemiacells.Methods:Theexperimentalassayswereperformedwithcellculture,immunochemistryandflowcytometry.Results:Thetwoantisenseoligodeoxynucleotides,combinedwithVp16orAra-corDNR,wereabletodeclinethesurvivalrateofmyeleukemiccells,downregulatebcl-2geneexpressionandinduceapoptosisofleukemiccellssignificantly,ascomparedwithVp16orAra-corDNRalone.Conclusion:Itispossibleforthetwonewbcl-2antisensestobedevelopedintoclinicaltrialsforleukemiaandtumorwithbcl-2geneoverexpression.

简介：Objective:TostudythedifferencesandsimilaritiesoftheantisensedrugswithdifferentstructuresonthebiologicalfunctionsofK562cells.Methods:Cytotoxiceffectsweremeasuredbyuseofacellviabilityassay.FlowcytometricanalysisandagarosegelelectrophoresisofDNAfragmentationwerealsoperformed.Theexpressionlevelofproteinwasassayedbyimmunofluorescenceusingfluoresceisothiocyanatelabel.Results:PNAtargetingthecodingregionoftheBcl-2messengerRNAcouldeffectivelyinhibitK562cellviability,down-regulatethesynthesisoftheBcl-2proteinandincreasecellapoptosis.By72haftertheBcl-2antisensePNAtreatment,K562cellsshowedmorereductioninthelevelofBcl-2proteincomparedwithcellstreatedwiththeantisenseODN.Aftertreatmentwith10μmol/LofBcl-2antisensePNAorantisenseODNfor72h,apoptoticratesofK562cellswere13.15±1.13and11.72±1.12,respectively.Furthermore,therewassignificantdifferenceinthepercentageofapoptoticcellsbetweenantisensePNAgroupandantisenseODNgroup.Conclusion:TheresultssuggestthatantisensePNAtargetingthecodingregionofBcl-2mRNAhasbetterantisenseeffectsthantheantisenseoligonucleotidesoninducingapoptosisofK562cells.

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简介：Objective:Toexplorethereversaleffectofmifepristoneonmultidrugresistance(MDR)indrug-resistanthumanbreastcancercelllineMCF7/ADRanditsmechanisms.Methods:ExpressionofMDR1andMDR-associatedprotein(MRP)mRNAinMCF7/ADRcellswasdetectedusingreversetranscription-polymerasechainreaction(RT-PCR).WesternblottingwasusedtoassaytheproteinlevelsofP-glycoprotein(P-gp)andMRP.Intracellularrhodamine123retentionand[3H]vincristine(VCR)accumulationweremeasuredbyflowcytometryandliquidscintillationcounter,respectively.MTTreductionassaywasusedtodeterminethesensitivityofcellstotheanticanceragent,adriamycin(ADR).Additionally,aMCF7/ADRcellxenograftmodelwasestablishedtoassessthereversaleffectofmifeprisoneonMDRinMCF7/ADRcellsinvivo.Results:Miferpristonedose-dependentlydown-regulatedtheexpressionofMDR1andMRPmRNAinMCF7/ADRcells,accompaniedbyasignificantdecreaseintheproteinlevelsofP-gpandMRP.Afterexposureto5,10,and20μmol/Lmifepristone,MCF7/ADRcellsshoweda3.87-,5.81-,and7.40-foldincreaseintheaccumulationofintracellularVCR(aknownsubstrateofMRP),anda2.14-,4.39-,and5.53-foldincreaseintheretentionofintracellularrhodamine123(anindicatorofP-gpfunction),respectively.MTTanalysisshowedthatthesensitivityofMCF7/ADRcellstoADRwasenhancedby7.23-,13.62-,and20.96-foldafterincubationwithmifepristoneasabove-mentioneddosesfor96h.Invivo,mifepristoneeffectivelyrestoredthechemosensitivityofMCF7/ADRcellstoADR.After8weeksofadministrationwithADR(2mg·kg-1·d-1)aloneorincombinationwithmifepristone(50mg·kg-1·d-1),thegrowthinhibitoryrateofxenograftedtumorsinnudemicewas8.08%and37.25%,respectively.Conclusion:MifepristoneexertspotentreversaleffectsonMDRinMCF7/ADRcellsinvitroandinvivothroughdown-regulationofMDR1/P-gpandMRPexpressionandinhibitionofP-gp-andMRP-dependentdrugefflux,thusincreasing

简介：客观：为了调查抵抗和颠倒的机制，在导致cisplatin的multidrug抵抗ligustrazine和cyclosporinA完成卵巢的癌症房间线3Ao/cDDP。方法：用每周期在30mgcisplatin从临床的化疗计算的相应剂量，我们建立了3Ao/cDDP，3Ao每次在10渭g/ml在常规间隔并且反复暴露了到cisplatin的高级集中24个小时。LRP，MRP，P-gp，GST蟺和TopoII的表情是与FCM检测的份量上。为药抵抗颠倒，没有cytotoxicity，cyclosporinA和ligustrazine在最大的剂量单身地或在联合被管理。抑制率被MTT试金决定。结果：3Ao/cDDP在4.5个月以后被建立，与抵抗因素1.6它类似于临床的抵抗度。MRP和P-gp的低表示层次在3Ao和3Ao/cDDP被发现(P>0.05)，并且在3Ao/cDDP的LRP和GST蟺表示层次比在3Ao的那些显著地高(P<0.005andP<0.05，分别地)，并且在3Ao/cDDP的TopoII显著地更低对3Ao(P<0.05)。cDDP的抑制率是20.807卤0.015%，加ligustrazine的cDDP27.421卤0.07%(P>0.05对cDDP)，加cyclosporinA的cDDP49.635卤0.021%(P<0.01对cDDP)，并且加ligustrazine和cyclosporinA的cDDP58.861卤0.014%(P<0.01对cDDP)。结论：3Ao/cDDP，由cisplatin导致了并且由为上皮的卵巢的癌症模仿临床的化疗的特征建立了，是为cisplatinresistanceinvitro的调查的一个理想的模型。在3Ao/cDDP的Cisplatin抵抗能被说明为由更高的LRP，GST蟺和更低的TopoII表示并且没与MRP或P-gp被联系。Ligustrazine没在A能颠倒的cisplatin抵抗，而是cyclosporin上有重要颠倒效果抵抗有效地。

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