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简介：Lungcanceristhemostfrequentlydiagnosedcancerandaleadingcauseofcancermortalityworldwide,withadenocarcinomabeingthemostcommonhistologicalsubtype.Deeperunderstandingofthepathobiologyofnon-smallcelllungcancer(NSCLC)hasledtothedevelopmentofsmallmoleculesthattargetgeneticmutationsknowntoplaycriticalrolesinprogressiontometastaticdiseaseandtoinfluenceresponsetotargetedtherapies.Theprinciplegoalofprecisionmedicineistodefinethosepatientpopulationsmostlikelytorespondtotargetedtherapies.However,thecancergenomelandscapeiscomposedofrelativelyfew"mountains"[representingthemostcommonlymutatedgeneslikeKRAS,epidermalgrowthfactor(EGFR),andanaplasticlymphomakinase(ALK)]andavastnumberof"hills"(representinglowfrequencybutpotentiallyactionablemutations).Low-frequencylesionsthataffectadruggablegeneproductallowarelativelysmallpopulationofcancerpatientsfortargetedtherapytobeselected.

简介：Objective:Inthisstudy,weexaminetheeffectsofrecombinantadenovirus-p53(rAd-p53)onthepancreaticcarcinomacelllineSW1990.Specifically,wedetermineifexpressionofrAd-p53sensitizesthesecellstoradiation.Methods:FollowingtransfectionofSW1990cellswithrAd-p53,wemeasuredexpressionofP53,P21andBaxbyimmunocytochemistry.Bothtransfectedandcontrolcelllineswereirradiatedwitharangeofdoses,andthesurvivalfractions(SF)werecalculated.Dosesurvivalcurveswereconstructedandmodeledforcomparison.Results:TransfectionofSW1990cellswithrAd-p53resultedinincreasedexpressionofP53,P21andBaxinatime-dependentmanner.At96haftertransfection,89.92%ofcellsexpressedP53,56.8%expressedP21,and76.50%expressedBax.TheSFfollowingradiationwaslowerintherAd-p53transfectedcellscomparedtothecontrolcells,suggestingthatrAd-p53sensitizesSW1990cellstoradiation(D0fortheexperimentalandcontrolgroupswas2.199and2.462,respectively).Conclusions:UseoftheadenoviralvectorisaneffectivemeansoftransfectingSW1990cellswithwild-typeP53,andthissensitizesthecelllinetoirradiation.ThisworksuggeststhatcombiningrAd-p53withradiationtherapyinpancreaticcancermaybetherapeuticallybeneficial.

简介：Objective:ToinvestigatewhethertheBc1-2antisenseoligonucleotide(ASODN)mayenhanceradiation-inducedapoptosisinRajicellline.Methods:Cellsurvivingfractionwasdeterminedusingthetrypanbluedyeexclusionassay.Theexpressionlevelofbc1-2proteinwasassayedbyimmunofluorescenceusingfluoresceisothiocyanatelabel.ApoptosiswasdetectedbyGiemsastainingandflowcytomertriccellcycleanalysis.Results:ItwasfoundthatBc1-2ASODNcombinedwithradiationhadsignificantlyreducedthenumberofviablecells(P<0.05).TherewasnodifferenceoncellsurvivalbetweenmismatchBc1-2oligodeoxynucleotide/radiationcombinationandradiation-treatedcellsalone.Bc1-2ASODNcombinedwithradiationcouldsignificantlyinhibitexpressionofBc1-2proteininRajicells(P<0.05).CellstreatedwithBc1-2ASODNcombinedwithradiationat72hdisplayedclassicapoptoticchanges.ApoptosisratesofRajicellstreatedwithBc1-2oligodeoxynucleotide/radiationcombinationandradiation-treatedcellsalone,respectively.Conclusion:Bc1-2antisenseoligonucleotidecanenhanceradiation-inducedapoptosisinRajicellline.

简介：Objective:Toobservetheeffectofinhibitionoftelomeraseactivitybyseleniumdioxide(SeO2)onlungcarcinomacelllineGLC-82.Methods:TRAP-PCR-ELISAwasusedtostudythechangesoftelomeraseactivityinhumanpulmonaryadenocarcinomacelllineGLC-82treatedbySeO2atthedifferentconcentrations(3,10,30μmol/L)andfordifferenttimes(24,48,and72h).Results:SeO2inhibitedthetelomeraseactivityofGLC-82atthedifferentconcentrationsaftertreatmentof24,48and72h.Conclusion:SeO2inhibitsfromtelomeraseactivityofhumanlungcarcinomalineGLC-82.Theeffectofinhibitionisdose-dependantandtime-dependant.

简介：Objective:ToconstructamutantpEGFP-hTERTexpressionvector,toobserveitssteadyexpressionintransfectedhumanbladdercarcinomacelllineT24anditsroleinmolecularregulatorymechanismsoftelomerase,andtoprovideanewtargetgeneforbladdercancer.Methods:PCRamplificationwasperformedbyusingprimersbasedontheknowngenesequenceofhTERT.PCRproductionwasclonedintoplasmidpGEMT-TeasyandthesequenceofmutanthTERTgenewasanalyzed.ArecombinantmutanthTERTvector(pEGFP-hTERT)wasconstructedattheEcoRIandSalIsitesofthepEGFP-C1vector.AftertransfectingthefusiongeneintobladdercarcinomacelllineT24bycalciumphosphate-DNAcoprecipitation,thesteadyexpressionofGFP-hTERTfusionproteinwastestedbyfluorescentlightmicroscopy.TheproliferationchangesofbladdercarcinomacelllineT24weredetectedbylightmicroscopyandsenescencecorrelatedβ-galactosidasestaining.Results:IdentificationofpEGFP-hTERTbyenzymedigestionshowedthatmutanthTERTfragmenthadbeenclonedintoEcoRIandSalIsitesofthepEGFP-C1vector.ThesteadyexpressionofGFP-hTERTfusionproteinwaslocalizedinthenucleusoftransfectedcells.Expressionofsenescence-associatedβ-galactosidaseintransfectedcellsgraduallyincreasedwithextendedculturedtimeandcellgrowthwassuppressed.Conclusion:Themutant-typehTERTgenesuppressestheproliferationofbladdercarcinomacelllineT24bycompetitiveeffectontelomeraseactivity.ThissuggeststhathTERTgenemightbeasuitablegenetargetforbladdercancertherapy.

简介：Havingbeenpassedfor160generations,acelllinedesignatedasH22-F25/LwasestablishedfromamurinetumorlymphaticmetastatlcmodelH22-F25whichhadbeensetupinourcollege.Thecelllinewasinsuspensionculturewitharapidproliferationandstablegrowth.Thepeaktuneofcelldivisionandproliferationwas48and96hoursafterculture.Inaweek,thecellnumberwasIncreasedby25tunes.H22-F25/Lstillkeepsthefeaturesofapoorlydifferentiatedcancer.Itstumorinducingrate(invivo)was100%in615mice.Lymphnodemetastasisratewas50%andpulmonarymetastasisrate10%.H22-F25/LIsapopulationofheterogenetlctumorcellsIncluding2stemcelllines(themodelnumberofchromosomesbeing43in40%tumorcellsand86in32%)andsomesidelines.ThecommonmarkerchromosomesM1,M2,M3andM4werepresentinallstemandsidelines.

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简介：Objective:Toexploretheeffectsofdexamethasone(DXM)andvincristine(VCR)oncytosinearabinoside(Ara-C)inducedapoptosisandactivationofnuclearfactor-κ-genebinding(NF-κB)inleukemiccelllineHL60-n.Methods:ApoptosisofHL60-ncellswasanalysedbyTdT-mediatedX-dUTPnickandendlabeling(TUNEL)andDNAelectrophoresis.NF-κBactivityofHL60-ncellswasdetectedbyelectrophoreticmobilityshiftassay(EMSA).Results:TherewasslightactivationofNF-κBinHL60-ncellswithoutdruginduction.Ara-Cat1μmol/LsignificantlyenhancedtheactivationofNF-κBinHL60-ncells.ThelevelofNF-κBactivationinducedbyDXMat1μmol/LorVCRat0.1μmol/Lhadnosignificantdifferencecomparedwiththatofthecontrolgroup.However,inHL60-ncellspre-treatedwith1μmol/LofDXMor0.1μmol/LofVCR,theactivationofNF-κBinducedby1μmol/LofAra-Cwassignificantlysuppressedwithinhibitionratesof31.0%and47.0%,respectively.TheapoptosisratesofHL60-ncellsinducedby1.0μmol/L,10μmol/Land100μmot/LAra-Cwere45.00±3.16%,61.88±3.40%and77.62±4.75%,respectively.TheapoptoticratesofHL60-ncellsinducedbyDXMat1μmol/LorVCRat0.1μmol/Lweresimilartothatofthecontrolgroup.However,eitherDXMat1μmol/LorVCRat0.lμmol/LcouldenhancetheapoptosisofHL60-ncellsinducedbyAra-Cat1μmol/Lwithratesof39.1%and59.2%,respectively.Conclusion:Ara-CcaninduceapoptosisandactivationofNF-κBinHL60-ncells.ThemechanismofincreasedapoptosisofHL60-ncellsbyDXMorVCRmayberelatedtosuppressionofNF-κBactivation.

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：Objective:Panitumumabadministeredasmonotherapyincolorectalcancer(CRC)hasshownresponseanddiseasestabilizationratesofapproximately30%.Thecurrentstudyaimedtoevaluatetheprogression-freesurvival(PFS)andoverallsurvival(OS)ofpatientswithmetastaticcolorectalcancer(mCRC)treatedwithpanitumumabevery3weeksasasecondlinetreatment.Methods:Thisstudyisaretrospectiveanalysisof18patients,agedmorethan18years,withwild-typeKRASexon2mCRCtreatedwithpanitumumabasasecond-linesingleagentafterprogressiononfirst-linechemotherapy.Results:Themediannumberofcoursesreceivedwas10(range,4-29),andthemediandurationoftreatmentwas30weeks(range,12-96weeks).Afteramedianfollow-upperiodof13months,themedianPFSwas6months(range,4.3-7.7months)andthemedianOSwas11months(range,7.4-14.5months).ThemedianPFSwas4monthsforpatientswith

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。

简介：Objective:Tocomparetheefficacyandadverseeffectsofpaclitaxel-etoposide-carboplatin/cisplatin(TEP/TCE)regimenwiththoseofetoposide-carboplatin/cisplatin(EP/CE)regimenasfirst-linetreatmentforcombinedsmall-celllungcancer(CSCLC).Methods:Aretrospectivestudywasconductedon62CSCLCpatientswhoweretreatedatTianjinMedicalUniversityCancerInstituteandHospitalfromJuly2000toApril2013andadministeredwithTEP/TCEregimen(n=19)orEP/CEregimen(n=43)asfirst-lineCSCLCtreatment.Allpatientsreceivedmorethantwocyclesofchemotherapy,andtheresponsewasevaluatedeverytwocycles.Theprimaryendpointwasoverallsurvival(OS),andthesecondaryendpointswereprogression-freesurvival(PFS),objectiveresponserate(ORR),diseasecontrolrate(DCR),andadverseeffects.Results:ORRbetweentheTEP/TCEandEP/CEgroupsshowedastatisticaldifference(90%vs.53%,P=0.033).BothgroupsfailedtoreachastatisticaldifferenceinDCR(100%vs.86%,P=0.212).ThemedianPFSandOSoftheTEP/TCEgroupwereslightlylongerthanthoseoftheEP/CEgroup,althoughbothgroupsfailedtoreachastatisticaldifference(10.5vs.8.9months,P=0.484;24.0vs.17.5months,P=0.457).However,stratifiedanalysisindicatedthatthePFSofpatientswithstagesIIIandIVCSCLCshowedmarginallysignificantdifferencebetweentheTEP/TCEandEP/CEgroups(19.5vs.7.6months;P=0.071).BothratesofgradeIVbonemarrowdepressionandterminationofchemotherapyintheTEP/TCEgroupweresignificantlyhigherthanthoseintheEP/CEgroup(26.3%vs.7.0%,P=0.036;31.6%vs.14.7%,P=0.004).Conclusion:TheTEP/TCEregimenmaynotbepreferredforCSCLC,andthisthree-drugregimenrequiresfurtherexplorationandresearch.Todate,theEP/CEregimenremainsthestandardtreatmentforCSCLCpatients.

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