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简介：瞄准：在老鼠把芙蓉sabdariffa(Roselle)和姜officinale(生姜)的保护的效果与导致cisplatin的繁殖毒性作比较并且学习位于这些效果下面的机制。方法：H.sabdariffa或Z.officinale(1g/kgx天)的乙醇摘录被给p.o到男白鼠26天，它在单个cisplatini.p注射(10mg/kg体重)前开始了21天。结果：H.sabdariffa和Z.officinale的摘录减少了导致cisplatin的精子反常的程度并且提高了精子活动性。两篇摘录恢复了malondialdehyde(MDA)的控制水平(类脂化合物每氧化标记)在对待cisplatin的睾丸。导致的cisplatin注射在超级氧化物的层次衰退歧化酶(草皮)，减少的谷胱甘肽(GSH)和过氧化氢酶(猫)显著地被颠倒在cisplatin被H.sabdariffa或Z.officinale的管理先于的组控制层次。结论：H.sabdariffa和Z.officinale处理增加了阴囊的抗氧化剂酶的活动并且恢复了对待cisplatin的老鼠的精子活动性。因此，测试植物的保护的效果被建议被他们的有势力抗氧化剂活动调停。

简介：Cisplatindamagescochlearhaircellsandspiralganglionneuronsthroughcelldeathsignalingpathwaysthatarenotfullyunderstood.Weusedfocusedapoptosisgenemicroarraystostudyearlychangesingeneexpres-sionincochlearculturesfromP3neonatalratstreatedwithcisplatin(0.2mM).After12hoursofcisplatintreat-ment,morethan50%ofthe96genesonthearrayshowedasignificantdecreaseinexpression,consistentwithwidespreadcelldeath.However,after3hoursofcisplatintreatment,10genesshowedsignificantincreaseinex-pressionintotalcochleartissue.Inexperimentswithsubsetsofcochleartissues,at3h,cisplatininducedincreasedexpressionof12genesinthecochlearsensoryepithelium(basilarmembrane)and11genesinthespiralganglion(tissueofRosenthal'scanal,containingthespiralganglion).Theseincludedpro-andanti-apoptoticgenesin-volvedinthep53signalingpathway,TNFreceptorfamily,NF-kappaBpathway,deathdomainfamily,deatheffec-tordomainfamily,Bcl-2family,CARDfamily,TRAFfamily,andGTPsignaltransduction.Althoughthechangesingeneexpressionshowedanoverlapbetweenbasilarmembraneandspiralganglion,otherchanges,whichmayreflecttheuniqueresponseofeachtissue,werealsoobserved.Pifithrin-αblockedcisplatin-inducedup-regulationofgenesinthep53signalingpathwaywhenassayedbybothsuperarrayandrealtimePCR.Thedataaddtoourunderstandingoftheinvolvementofp53incisplatin-inducedototoxicityandotoprotection,conferredbythep53inhibitorPifithrin-α.

简介：RecognitionofDNAdamageisacriticalstepforDNAdamage-mediatedcellularresponse.XPCisanimportantDNAdamagerecognitionproteininvolvedinnucleotideexcisionrepair(NER).WehavestudiedtheXPCproteinincisplatinDNAdamagingtreatment-mediatedcellularresponse.ComparisonofthemicroarraydatafrombothnormalandXPCdefectivehumanfibroblastsidentified861XPC-responsivegenesinthecisplatintreatment(withminimumfoldchange≥1.5).Thecellcycleandcellproliferation-relatedgenesarethemostaffectedgenesbytheXPCdefectinthetreatment.Manyothercellularfunctiongenes,especiallytheDNArepairandsignaltransduction-relatedgenes,werealsoaffectedbytheXPCdefectinthetreatment.Tovalidatethemicroarraydata,thetranscriptionlevelsofsomemicroarray-identifiedgeneswerealsodeterminedbyanRT-PCRbasedrealtimePCRassay.TherealtimePCRresultsareconsistentwiththemicroarraydataformostofthetestedgenes,indicatingthereliabilityofthemicroarraydata.Tofurthervalidatethemicroarraydata,thecisplatintreatment-mediatedcaspase-3activationwasalsodetermined.TheWesternblothybridizationresultsindicatethattheXPCdefectgreatlyattenuatesthecisplatintreatment-mediatedCaspase-3activation.Weelucidatedtheroleofp53proteinintheXPCproteinDNAdamagerecognition-mediatedsignalingprocess.TheXPCdefectreducesthecisplatintreatment-mediatedp53response.TheseresultssuggestthattheXPCproteinplaysanimportantroleinthecisplatintreatment-mediatedcellularresponse.Itmayalsosuggestapossiblemechanismofcancercelldrugresistance.

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.

简介：Cisplatinbelongstoplatinum-baseddrugsandiswidelyusedincancerchemotherapy.Ototoxicityisoneofthemajordoselimitingside-effectsofcisplatin.Fortoxicitytooccurcisplatinmustfirstbetransportedfromthebloodstreamintocochlearcells.Threecoppertransportersareconsideredpathwaysforregulatingtheuptakeandtranslocationofcisplatinintocells:Ctr1,ATP7AandATP7B.Ourrecentstudywithcochlearorganotypicculturesshowsthatcochlearhaircellscanbedestroyedbycisplatinatlowconcentrationsfrom10μmto100μn.However,highdosesofcisplatincannotdamagehaircells,maybeduetointrinsicfeedbackreactionsthatincreaseexportofplatinumbyATP7Bwhentheplatinumconcentrationishighinextracellularspace.Cimitidineisaspecificcoppertransporterinhibitorthatcanblocktheentranceofcopperandplatinum,andmaypreventcisplatin-inducedcochlearhaircellinjury.Toevaluatethishypothesis,wetreatedcochlearorganotypiccultureswithcisplatin(10μmor50μm)alone,orcisplatincombinedwithcimitidineatconcentrationsrangingfrom10-2000μmfor48hours.cisplatinat10μmdamagedabout20%haircells.Incontrast,whencimitidine(10μm,100μmand2000μm)wasaddedtotheculture,near100%cochlearhaircellsurvived.Athigherconcentration(50μm),cisplatindestroyedabout80%ofcochlearhaircells.However,100μmcimitidinerescuedabout50%haircellsfromcisplatindamage,and2000μmcimitidineprotectedabout80%haircells.ThedataofwesternblotshowedthatCTR1andATP7Bexpressionswereincreasedincisplatintreatedcochleartissue,butcimitidinesignificantlyreducedCTR1andATP7B.Inaddition,ATP7Aexpressionwasdepressedalittleaftercisplatintreatment.ConsideringthatCtr1isinvolvedincopperandplatinuminflux,buttheATP7AandATP7Barecopperexporttransporters,theresultssuggestthatcimitidinecaneffectivelyblocktheentrancebycoppertransportersandstoptheinfluxofcisplatin.

简介：Telomeraseactivitywasinhibitedinadoseandtime-dependentmannerwiththetreatmentofcisplatinfor24,48,or72hinaconcentrationrangedfrom0.8to50μMinBEL-7404humanhepatomacells.Therewerenochangesinexpressionpatternofthreetelomerasesubunits,itscatalyticreversetranscriptasesubunit(hTERT),itsRNAcomponent(hTR)ortheassociatedproteinsubunit(TP1),aftercisplatintreatedfor72hwithindicatedconcentrations.Meantelomerelengthsweredecreasedbythecisplatintreatment.CellgrowthinhibitionandcellcycleaccumulationinG2/Mphasewerefoundtobecorrelatedwithtelomeraseinhibitioninthepresentstudy,butpercentagesofcellapoptosisdidnotchangemarkedlyduringtheprocess.

简介：Cisplatin,awidelyusedanticancerdrug,damageshaircellsincochlearorganotypicculturesatlowdoses,butparadoxicallycauseslittledamageathighdosesresultinginaU-shapeddose-responsefunction.Todetermineifthecisplatindose-responsefunctionforvestibularhaircellsfollowsasimilarpattern,wetreatedvestibularorganotypiccultureswithdosesofcisplatinrangingfrom10to1000μM.Vestibularhaircelllesionsprogressivelyincreasedasthedoseofcisplatinincreasedwithmaximumdamageoccurringaround50–100μM,butthelesionsprogressivelydecreasedathigherdosesresultinginlittlehaircelllossat1000μM.TheU-shapeddoseresponsefunctionforcisplatin-treatedvestibularhaircellsincultureappearstoberegulatedbycoppertransporters,Ctr1,ATP7AandATP7B,thatdose-dependentlyregulatetheuptake,sequestrationandextrusionofcisplatin.

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简介：在病人作为首要或第二线的治疗评估paclitaxel，cisplatin和5-FU(PCF)的联合政体的功效和毒性与的目的进展胃并且在中国的esophagogastric连接(EGJ)腺癌。病人与paclitaxel被对待的方法d1上的150mg/m2；fractionatedcisplatin15mg/m2和连续注入5-FU600mg/(m2朠楬污映扩楲汬牡????????????М

简介：Cisplatinandotherplatinum-baseddrugsareusedfrequentlyfortreatmentoflungcancer.However,theirclinicalperformanceareusuallylimitedbydrugresistanceortoxiceffects.Carnosicacid,apolyphenolicditerpeneisolatedfromRosemary(Rosemarinusofficinalis),hasbeenreportedtohaveseveralpharmacologicalandbiologicalactivities.Inthepresentstudy,thecombinationeffectofcisplatinpluscarnosicacidonmouseLLC(Lewislungcancer)xenograftsandpossibleunderlyingmechanismofactionwereexamined.LLC-bearingmiceweretreatedwithintraperitonealinjectionwithcisplatin,oralgavagewithcarnosicacid,orcombinationwithcisplatinandcarnosicacid,respectively.Combinationofcarnosicacidandcisplatinyieldedsignificantlybetteranti-growthandpro-apoptoticeffectsonLLCxenograftsthandrugsalone.MechanisticstudyshowedthatcarnosicacidtreatmentboostedthefunctionofCD8~+TcellsasevidencedbyhigherIFN-γsecretionandhigherexpressionofFasL,perforinaswellasgranzymeB.Inthemeantime,theproportionofMDSC(myeloid-derivedsuppressorcells)intumortissueswerereducedbycarnosicacidtreatmentandthemRNAlevelsofiNOS2,Arg-1,andMMP9,whicharethefunctionalmarkersforMDSC,werereduced.Inconclusion,ourstudyprovedthatthefunctionalsuppressionofMDSCbycarnosicacidpromotedthelethalityofCD8~+Tcells,whichcontributedtotheenhancementofanti-lungcancereffectofcisplatin.

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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：瞄准：评估intra动脉的5氟尿嘧啶(5-FU)的时间依赖为先进肝细胞癌(aHCC)的治疗。方法：有aHCC和肝肝硬化的37个成年日本病人与联合intra动脉的5-FU，cisplatin(CDDP)，和甲酰四氢叶酸(LV)被对待。每个病人的日本综合阶段分数(JIS分数)是3或更多的。病人被划分成二个组，在组S的15个病人与6-h注入化疗在以后被对待(在12mg/h的LV，在10mg/h的CDDP，并且在250mg/m(2)的5-FU每4h)并且在组L的22个病人与24-h注入化疗(在12mg/h，在10mg/h的CDDP，和在每22h的250mg/m(2)的5-FU的LV)被对待。连续注入化疗经由合适的肝的动脉被执行为用一座植入的药水库的4wk的每5d。结果：有在化疗的4wk以后的部分回答的病人的百分比在组S是6.7%并且31.8%在组L。组L的幸存比组S的显著地好，与是的中部的生存时间在组L的496d和在组S的226d(P<0.05)。结论：连续24-hintra动脉的注入为aHCC是更有效的并且能显著地作为与6-h相比延长生存时间注入。

简介：客观：为了探索病理和临床的反应率的变化，为非小的房间肺癌症与MVP政体由neoadjuvant化疗对待。方法：这是在有阶段I-IIIa的病人的使随机化的研究。在他们之中，46个病人在neoadjuvant注册了1鈥对待的化疗吗？功课MVP政体。MMC被给6mg/M2由静脉内(I.V)day1上的注入，VDS2.5鈥吗？day1,8或day15上的mg/M2I.V，day1上的DDP90mg/M2I.V。治疗每28天被再循环。评估与的临床的RR标准。所有外科的样品与病理被分类。结果：在2功课化疗的全面反应率在1堂功课比那好(P<0.01)。有病理等级的病人的数字我在2功课化疗的鈥揑I比那高嗨1堂功课(P<0.01)。但是RR不能完全翻译了成病理等级我鈥揑I。病理等级我鈥揑I仔细与肿瘤参与(T)被联系(P<0.01)然而并非与地区性的淋巴节点转移(N)密切相关。和PCR使用RR判定化疗反应是合理的。NR病人不能作为化疗失败是问候。不服务毒性和外科的死亡被观察。结论：MVP政体是为I-IIIaNSCLC的有效neoadjuvant治疗政体。