简介:摘要目的研究FAS-670A/G基因多态与吉非替尼治疗敏感性及患者生存之间的关系。方法入组88例接受吉非替尼单药治疗的IIIA-IV期非小细胞肺癌患者,分析FAS-670A/G基因多态与吉非替尼治疗的临床获益率及患者生存的相关性。结果FAS-670A/G基因多态与全组患者临床获益率无关。AA、AG、GG患者的2年总生存率分别为49.2%、49.2%和28.7%,有显著差异(P=0.028);携带A等位基因的患者,2年总生存率高于GG基因型患者,分别为49.3%和28.7%,有统计学意义(P=0.007)。多因素预后分析显示病理类型(P=0.020,RR2.466,95%CI1.150-5.288)和FAS-670多态性(P=0.036,RR0.503,95%CI0.264-0.955)是独立的预后因素。结论促进肿瘤细胞凋亡是吉非替尼抗肿瘤作用的重要部分,FAS-670A/G基因多态可能成为吉非替尼治疗的进展期非小细胞肺癌患者生存的预测指标。
简介:ObjectivesToinvestigatetheassociationofsolubleFasligand(sFasL)andsolubleFasreceptor(sFas)withhumanchroniccongestiveheartfailure(CHF).MethodsTheserumlevelofsFasLandsFasin33patientswithCHF(13incardiacfunctionclassⅡ,17inclassⅢ,3inclassⅣ,NYHA)wasassessedwithenzyme-linkedimmunosorbentassay,andwascomparedwiththatof18age-,bloodpressure-matchedpatientswithcardiacfunctionclassⅠ(NYHA).ResultsTherewasnodifferenceinthelevelofsFasLbetweenthetwogroups[CHFgroup:231.50+/-84.50(cardiacfunctionclassⅡ216.50+/-96.00,classⅢ226.80+/-85.70,classⅣ244.00+/-73.00)vs.cardiacfunctionclassIgroup:217.50+/-89.00pg/mL,P>0.05].However,thelevelofsFaswassignificantlyhigherinthepatientswithCHFthanthoseofcardiacfunctionclassIgroup[CHFgroup:1353.30+/-507.71(cardiacfunctionclassⅡ1154.85+/-371.20,classⅢ1412.88+/-493.62,classⅣ1875.67+/-806.
简介:<正>Fasligand(FasL)wasfirstdescribedfunctionallyasaninduciblecellsurfacemoleculeusedbycytotoxicTcellstoinduceapoptoticcelldeathintumorcellsandactivatedlymphocytes.WiththeidentificationofFasastheIprgeneproduct,FasLbecamerecognizedasamoleculeinvolvedindown-regulationoftheimmunesystem.WhileFasLcanbeusedtoefficientlykillFas-expressingtumorcellsaswellasactivatedTandBlymphocytesinvitro,attemptstouseFasLtherapeuticallytotreatcancerortopreventtransplant
简介:ApoptosisproducedinBcellsthroughFas(APO-1,CD95)triggeringisregulatedbysignalsderivedfromothersurfacereceptors:CD40engagementproducesupregulationofFasexpressionandmarkedsusceptibilitytoFas-inducedcelldeath,whereasantigenreceptorengagement,orIL-4Rengagement,inhibitsFaskillingandinsodoinginducesastateofFas-resistance,eveninotherwisesensitive,CD40-stimulatedtargets.SurfaceimmunoglobulinandIL-4RutilizeatleastpartiallydistinctpathwaystoproduceFas-resistancethatdifferentiallydependonPKCandSTAT6,respectively.Further,surfaceimmunoglobulinsignalingforinducibleFas-resistancebypassesBtk,requiresNF-κB,andentailsnewmacromolecularsynthesis.TerminaleffectorsofBcellFas-resistanceincludetheknownanti-apoptoticgeneproducts,Bcl-XLandFLIP,andanovelanti-apoptoticgenethatencodesFAIM(FasApoptosisInhibitoryMolecule).faimwasidentifiedbydifferentialdisplayandexistsintwoalternativelysplicedforms;faim-Sisbroadlyexpressed,butfaim-Lexpressionistissue-specific.TheFAIMsequenceishighlyevolutionarilyconserved,suggestinganimportantroleforthismoleculethroughoutphylogeny.InducibleresistancetoFaskillingishypothesizedtoprotectforeignantigen-specificBcellsduringpotentiallyhazardousinteractionswithFasL-bearingTcells,whereasautoreactiveBcellsfailtobecomeFas-resistantandaredeletedviaFas-dependentcytotoxicity.InadvertentoraberrantacquisitionofFas-resistancemaypermitautoreactiveBcellstoescapeFasdeletion,andmalignantlymphocytestoimpedeanti-tumorimmunity.
简介:<正>ThesusceptibilityofprimaryBcellstoFas(APO-1,CD95)-mediatedapoptosisisregulatedbysignalsderivedfromadditionalsurfacereceptors.CD40engagementproducesupregulationofFasexpressionandinducesmarkedsensitivitytoFas-inducedcelldeath,whereasBcellantigenreceptor(BCR)engagementinhibitsFaskillingandtherebyproducesFas-resistance,eveninotherwisesusceptible,CD40-stimulatedtargets.BCRsignalingforinducibleFas-resistancedevelopsoveraperiodof12hoursanddependson
简介:摘要:阐述了MB670掘锚机电气设备系统的重要组成部分和各部件的功效,以及MB670掘锚机在使用中常见的电路故障及匹配处理方法。
简介:IncreasedexpressionofFasbyhematopoieticprogenitorsinaplasticanemia(AA)suggeststhatFas/Fasligand(FasL)systemplaysakeyroleintheformationofseverepancytopenia.Tofurtherconfirmtheabovehypothesis,Tcellsfrom8patientswithAAweresystematicallystudiedfortheirFasL'sdistributionpattern,releasingmannerandproapoptoticactivity,comparedwithnormalrestingTcellsandartificiallyactivatedTcellblasts.TheresultsdemonstratedthatAATcellsabnormallyexpressedlowlevelsofmembrane-boundFasLandcontainedhighlevelsofintracellularFasLwhichcouldbetriggeredtoreleasebyhigh-dosephytohemagglutinin(PHA)pulse-stimulation.ThesupernatantsfromthePHA-stimulatedAATcellshadapparentcytotoxicityagainstFasL-sensitiveJurkatcells,whichcouldbesignificantlyinhibitedbymonoclonalantibodyagainstFasLinadose-dependentmanner,ornearlycompletelyabrogatedbyultracentrifugation.TheabovephenomenaalsoappearedonartificiallyactivatedTcellblasts,butthiswasnotthecaseonnormalrestingTcells.TheseresultsindicatethatAATcellisatypeof'preactivated'Tlymphocyte,characterizedbyoverexpressionofFasL,especiallyintracellularFasLwhichcanbestimulatedtoreleaseinbioavtiveexosomesboundform.Takentogether,ourdataprovidefurtheranddirectevidenceforthehypothesisthatTcellsmightmediatethedestructionofhematopieticprogenitorinAAthroughFas/FasLsystem.
简介:摘要目的通过对670例Dravet综合征(DS)患儿进行随访,对其预后进行总结。方法收集2005年2月至2016年8月在北京大学第一医院儿科就诊的DS患儿,建立临床资料登记表,完善基因检查。通过门诊复诊及电话随访的方式对DS患儿的预后进行随访。结果670例DS患儿中,存在SCN1A突变者556例(556/670例,83.0%),随访608例(90.7%,608/670例),失访62例(失访率为9.3%,62/670例);末次随访中位年龄8岁5个月。82例(82/608例,13.5%)发作曾控制1年以上,中位随访年龄9岁2个月。其中38例再次出现发作(38/82例,46.3%),主要诱发因素为发热(34例)或漏服抗癫痫药物(2例)。分析发作曾控制1年以上的相关因素,发现携带SCN1A错义突变者、遗传性突变者、年龄相对较大者发作控制相对较好。随访的608例患儿中,死亡25例(25/608例,4.1%),发生死亡的中位年龄为4岁;12例因病程中出现长时间的癫痫持续状态,并多器官衰竭死亡。7例为可能的癫痫猝死,2例为呕吐窒息死亡,1例外伤后死亡,余3例死因不详。结论DS为难治性癫痫,但少数患儿发作可控制1年以上,携带SCN1A错义突变者、遗传性突变者、年龄相对较大者发作控制相对较好。DS病死率高,死亡原因主要为癫痫持续状态后多脏器衰竭和可能的癫痫猝死。