学科分类
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79 个结果
  • 简介:Objective:Chroniclymphocyticleukemia(CLL)andmantlecelllymphoma(MCL)cellsover-expressaguanineexchangefactor(GEF),Rasgrf-1.ThisGEFincreasesactiveRasasitcatalyzestheremovalofGDPfromRassothatGTPcanbindandactivateRas.ThisstudyaimstostudythemechanismofactionofRasgrf-1inB-cellmalignancies.Methods:N-terminustruncatedRasgrf-1variantshaveahigherGEFactivityascomparedtothefull-lengthtranscriptthereforeaMCLcelllinewithstableover-expressionoftruncatedRasgrf-1wasestablished.TheB-cellreceptor(BCR)andchemokinesignalingpathwayswerecomparedintheRasgrf-1over-expressingandacontroltransfectedcellline.Results:Cellsover-expressingtruncatedformofRasgrf-1haveahigherproliferativerateascomparedtocontroltransfectedcells.BCRwasactivatedbylowerconcentrationsofanti-IgMantibodyinRasgrf-1over-expressingcellsascomparedtocontrolcellsindicatingthatthesecellsaremoresensitivetoBCRsignaling.BCRsignalingalsophosphorylatesRasgrf-1thatfurtherincreasesitsGEFfunctionandamplifiesBCRsignaling.ThisactivationofRasgrf-1inover-expressingcellsresultedinahigherexpressionofphospho-ERK,AKT,BTKandPKC-alphaascomparedtocontrolcells.BesidesBCR,Rasgrf-1over-expressingcellswerealsomoresensitivetomicroenvironmentstimuliasdeterminedbyresistancetoapoptosis,chemotaxisandERKpathwayactivation.Conclusions:ThisGEFproteinsensitizesB-cellstoBCRandchemokinemediatedsignalingandalsoupregulatesanumberofothersignalingpathwayswhichpromotesgrowthandsurvivalofthesecells.

  • 标签: 细胞受体 环境信号 交换因子 恶性肿瘤 B细胞 鸟嘌呤
  • 简介:ThechronicinfectionofhepatitisBvirus(HBV)iscloselyrelatedtotheoccurrenceanddevelopmentofhepatocellularcarcinoma(HCC).AccumulatedevidencehasshownthatHBVXprotein(HBxprotein)isamultifunctionalregulatorwithacrucialroleinhepatocarcinogenesis.However,informationonthemechanismbywhichHBVinducesHCCislacking.ThisreviewfocusesonthepathologicalfunctionsofHBxinHBV-inducedhepatocarcinogenesis.Asatransactivator,HBxcanmodulatenuclearfactorkappa-light-chain-enhancerofactivatedBcells(NF-κB)andtranscriptionfactorAP-2.Moreover,HBxcanaffectregulatorynon-codingRNAs(ncRNAs)includingmicroRNAsandlongncRNAs(lncRNAs),suchasmiRNA-205andhighlyupregulatedinlivercancer(HULC),respectively.HBxisalsoinvolvedinepigeneticmodification,includingmethylationandacetylation.HBxinteractswithvarioussignal-transductionpathways,suchasproteinkinaseB/Akt,Wnt/β-catenin,signaltransducerandactivatoroftranscription,andNF-κBpathways.Moreover,HBxaffectscellularfatebyshiftingthebalancetowardcellsurvival.HBxmayleadtothelossofapoptoticfunctionsordirectlycontributestooncogenesisbyachievingtransformingfunctions,whichinducehepatocarcinogenesis.Additionally,HBxcanmodulateapoptosisandimmuneresponsebydirectorindirectinteractionwithhostfactors.WeconcludethatHBxhastensthedevelopmentofhepatoma.

  • 标签: 乙型肝炎病毒 蛋白质 肝癌 非编码RNA 信号转导途径 核因子KAPPA
  • 简介:根据世界癌症研究基金会(WCRF)资助的一项最新研究显示,人体血液中维生素B含量较高将有可能降低发生肺癌的风险,这个结果对吸烟、非吸烟以及曾经吸烟的人群是相同的。这项发现将有助于科学家了解肺癌发病的机理,并将对预防其发生提供线索。

  • 标签: 维生素B 肺癌 风险 非吸烟 人体血液 基金会
  • 简介:目的探讨心脏黏液瘤的临床治疗和预后。方法回顾性分析2000年1月至2009年12月126例心脏黏液瘤患者的临床资料。结果126例患者均接受手术治疗。围手术期死亡4例,死因分别为术后低心输出量综合征2例、应激性溃疡及大面积脑栓塞各1例,围术期病死率为3.17%。术后并发房性心律失常8例、心包积液4例、下肢栓塞1例。术后随访108例,随访率85.71%。2例分别在术后4年及8年复发,1例为多发性黏液瘤、1例为左房壁黏液瘤;2例分别死于亚急性感染性心内膜炎并发急性肾功能衰竭、慢性充血性心衰。结论心脏黏液瘤只要能够手术切除,预后是良好的,手术切除是治疗心脏黏液瘤首选的治疗方法。心脏黏液瘤手术后复发率低,远期复发可能与其起源部位有关。

  • 标签: 心脏黏液瘤 心脏外科手术
  • 简介:DuckhepatitisBvims(DHBV)DNAwasdetectedindifferenttumorousnodulesofduckswithhepaticmulticentriccancerorintrahepaticmetastasisbySouthernblottechnique.Among7duckswithhepatocellularcarcinomaofmultipletumornodules,thehybridizationpatternofIntegratedDHBVDNAIndifferenttumorousnoduleswasidenticalin3casesanddifferentin2cases.OnecaseshowedasimilarhybridizationpatternintwotumorousnodulesandotheronewasnegativetorDHBVDNA.IntegratedDHBVDNAwasalsoidentifiedinametastaticlungcancerofduckswithhepatocellularcarcinoma.Thehybridizationpatternofmetastasisoflungswasasthesomeasthatinprimaryhepatocellularcarcinoma.ThesamediscretehybridizationbandsInthedifferenttumorousnodulesindicatethatthesenodulesmightarisefromonetransformedcell.ThedifferenthybridizationpatternsInvarioustumorousnodulesshowthatthesetumorousnodulesmightarisefromvarioustransformedcells.Theresultssuggestthatthehyb

  • 标签: NODULES DNA DHBV transformed lungs metastasis
  • 简介:Objective:ToassesstheeffectofantiviraltherapyforhepatitisBvirus(HBV)-relatedhepatocellularcarcinoma(HCC)afterradicalhepatectomy.Methods:Atotalof478HBV-relatedHCCpatientstreatedbyradicalhepatectomywereretrospectivelycollected.Patientsinthetreatmentgroup(n=141)receivedpostoperativelamivudinetreatment(100mg/d),whereaspatientsinthecontrolgroup(n=337)didnot.Recurrence-freesurvival(RFS)rates,overallsurvival(OS)rates,treatmentsforrecurrentHCCandcauseofdeathwerecomparedbetweenthetwogroups.Propensityscorematching(PSM)analysiswasalsoconductedtoreduceconfoundingbiasbetweenthetwogroups.Results:The1-,3-,and5-yearRFSratesdidn’tsignificantlydifferbetweenthetwogroups(P=0.778);however,the1-,3-,and5-yearOSratesinthetreatmentgroupweresignificantlyhigherthanthoseinthecontrolgroup(P=0.002).Similarresultswereobservedinthematcheddata.SubgroupanalysisshowedthatantiviraltreatmentconferredasignificantsurvivalbenefitforBarcelonaClinicalLiverCancerstageA/Bpatients.FollowingHCCrecurrence,morepeopleinthetreatmentgroupwereabletochoosecurativetreatmentsthanthoseinthecontrolgroup(P=0.031).Forcauseofdeath,fewerpeopleinthetreatmentgroupdiedofliverfailurethanthoseinthecontrolgroup(P=0.041).Conclusion:PostoperativeantiviraltherapyincreaseschancesofreceivingcurativetreatmentsforrecurrentHCCandpreventsdeathbecauseofliverfailure,therebysignificantlyprolongingOS,especiallyinearly-orintermedian-stagetumors.

  • 标签: 抗病毒治疗 肝细胞癌 乙型肝炎病毒 切除术 肝功能衰竭 死亡原因
  • 简介:许多人类疾病的发生和发展可归因于一些基因的异常表达,从而导致疾病的发生。其中一部分基因是在核因子kappaB(nuclearfactor-kappaB,NF—κB)调控下进行的。NF—κ是广泛存在于哺乳动物中的转录因子,是由Sen等于1986年首先在B细胞中发现的一种核蛋白。因它能与B细胞免疫球蛋白上的K轻链基因增强子κB序列(GGGACTITCC)特异结合而得名。实际上它能与多种细胞基因的启动子和增强子序列位点发生特异性结合,并促进转录和表达,参与众多与免疫和炎症反应有关的基因转录的调控。它的异常激活或完全抑制与多种疾病的发生有关。在控制细胞增殖、凋亡、肿瘤的发生、发展和耐药问题上均起着重要的作用。因此深入探讨NF—κB在体内病理状态下的活化机制以及其与细胞、基因之间的调节作用具有重要的意义。现就NF—κB的组成、结构、激活途径以及与肿瘤的关系作一综述。

  • 标签: NF—κB 肿瘤 研究进展
  • 简介:Objective:Cancercellradioresistanceisastumblingblockinradiationtherapy.TheactivityinthenuclearfactorkappaB(NFκB)pathwaycorrelateswithanti-apoptoticmechanismsandincreasedradioresistance.TheIKKcomplexplaysamajorroleinNFκBactivationuponnumeroussignals.Inthisstudy,weexaminedtheinteractionbetweenionizingradiation(IR)anddifferentmembersoftheIKK-NFκBpathway,aswellasupstreamactivators,RAF1,ERK,andAKT1.Methods:Theeffectof4GyofIRontheexpressionoftheRAF1-ERK-IKK-NFκBpathwaywasexaminedinA549andH1299lungcancercelllinesusingWesternblotanalysisandconfocalmicroscopy.WeexaminedchangesinradiationsensitivityusinggenesilencingorpharmacologicalinhibitorsofERKandIKKβ.Results:IKKα,IKKγ,andIκBαincreaseduponexposuretoIR,therebyaffectingnuclearlevelsofNFκB(phospho-p65).ERKinhibitionorsiRNA-mediateddown-regulationofRAF1suppressedthepost-irradiationsurvivaloftheexaminedlungcancercelllines.AsimilareffectwasdetectedonsurvivaluponsilencingIKKα/IKKγorinhibitingIKKβ.Conclusions:ExposureoflungcancercellstoIRresultsinNFκBactivationviaIKK.ThegeneticorpharmacologicalblockageoftheRAF1-ERK-IKK-NFκBpathwaysensitizescellstotherapeuticdosesofradiation.Therefore,theIKKpathwayisapromisingtargetfortherapeuticinterventionincombinationwithradiotherapy.

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  • 简介:目的评价高频彩检查对腮腺肿块的诊断及鉴别诊断的价值。方法应用高频彩对58例腮腺肿块的患者进行检查,并结合病理检查结果分析、总结腮腺肿块的超声图像特征。结果高频彩检查对腮腺肿块的总检出率为100%,对腮腺良、恶性肿块的诊断符合率分别为87.2%、68.4%,其中腮腺囊肿诊断符合率为100%。二维超声检查中腮腺良、恶性肿块在形态、边界、边缘和内部回声方面的差异均有统计学意义(P〈0.05)。彩色多普勒血流显像对腮腺良、恶性肿块血流信号的检出率分别为82.1%、94.7%。以收缩期峰值流速≥23.8cm/s作为诊断腮腺恶性肿块阈值的标准,脉冲多普勒诊断的敏感度和特异度分别为73.7%和71.8%;以阻力指数≥0.68(除混合瘤外)作为诊断腮腺恶性肿块阈值的标准,其诊断敏感度和特异度分别为73.3%和85.0%。结论高频彩检查对腮腺肿块的检出率及诊断符合率均较高,对腮腺肿块的定性诊断有重要的临床应用价值。

  • 标签: 腮腺肿块 高频彩超 彩色多普勒血流显像 诊断
  • 简介:Objective:TodeterminewhetherInterferon-alpha-2b(IFN-α2b)canmodulatetheautophagicresponseinhepatocellularcarcinomacells.Methods:HepatocellularcarcinomacellsweretreatedwithIFN-α2b.Autophagywasassessedbyacridineorangestaining,GFP-LC3dottedassay,transmissionelectronmicroscopyandimmunoblotting.Results:AcridineorangestainingshowedthatIFN-α2btriggeredtheaccumulationofacidicvesicularandautolysosomesinHepG2cells.TheacridineorangeHepG2cellratioswere(4.3±1.0)%,(6.9±1.4)%,and(13.1±2.3)%,respectively,aftertreatmentwith100,1,000,and10,000IU/mLIFN-α2bfor48h.AmarkedlypunctatepatternwasobservedinHepG2cellstreatedwith10,000IU/mLIFN-α2bfor48h,butonlydiffuseandweaklyfluorescentGFP-LC3punctawasobservedincontrolcells.HepG2cellstreatedwith10,000IU/mLIFN-α2bfor48hdevelopedautophagosome-likecharacteristics,includingsingle-ordouble-membranevacuolescontainingintactanddegradedcellulardebris.TheBeclin1andLC3-IIproteinexpressionwasup-regulatedbyIFN-α2btreatment.Conclusion:Autophagycanbeinducedinadose-dependentmannerbytreatmentwithIFN-α2binHepG2cells,andtheBeclin1signalingpathwaywasstimulatedbyIFN-α2b.

  • 标签: 肝癌细胞 干扰素-Α 自噬 HepG2细胞 诱导 IFN-γ
  • 简介:Objective:Toinvestigatephospho-(-cateninexpressioninnon-smallcelllungcancer(NSCLC)andtostudytherelationshipbetweenphospho-(-cateninexpressionandsomeclinicalpathologicalfactors.Methods:Theexpressionofphospho-(-cateninin67primaryNSCLCcasesdetectedimmunohistochemically.Results:phospho-(-cateninwasnotexpressedinnormalbronchialmucouscellandshowedcytoplasmicandnuclearexpressioninNSCLCcell.Totalpositiveexpressionratereached62.7%,andpositiveexpressionrateofnucleuswas38.8%.Thepositiveexpressionrate(87.5%)andnuclearexpressionrateofadenocarcinoma(62.5%)wereapparentlyhigherthanthoseofsquamouscellcancer(40.0%and17.1%)(P<0.01).Expressionofphospho-(-cateninhadnorelationshiptodifferentiationdegreeandlymphaticmetastasis.Thepostoperativesurvivaltimeisnotrelatedtophospho-(-cateninexpression.(Log-ranktest,P=0.9198;P=0.6274).COXmodelanalysisshowedthattumorstageanddifferentiationareindependentriskfactorstoprognosis(P=0.001;P=0.020).Conclusion:NSCLCcellsshowpositiveexpressionofphospho-(-catenin,phospho-(-cateninnuclearexpressionisrelevanttohistologicaltypes.Thereisnodifferenceinpostoperativesurvivaltimebetweenpatientswithphospho-(-cateninpositiveexpressionandpatientswithnegativeexpression,expressionofphospho-(-cateninisnotindependentriskfactortoprognosis.

  • 标签: 非小细胞肺癌 磷酸化-β-catenin 细胞粘附调节因子 免疫组化 基因表达 信号通路
  • 简介:Objective:Toassesstheclinicalfeatures,survivalandprognosticfactorsofprimarytesticulardiffuselargeB-celllymphoma(DLBCL).Methods:Aretrospectivestudyof37patientswithprimarytesticularDLBCLwascarriedoutfromNovember2003toMay2012.Theirclinicalfeatures,survivalandprognosticfactorswereanalyzed.Results:Duringamedianfollow-upperiodof39.8months(5.4-93.0months),themedianprogression-freesurvival(PFS)was26.2months(95%CI:0-65months)andthe3-yearoverallsurvival(OS)ratewas78.4%.Withinthewholecohort,thefactorssignificantlyassociatedwithasuperiorPFSwerelimitedstage(stageI/II),lactatedehydrogenase(LDH)≤245U/L,internationalprognosticindex(IPI)≤1,primarytumordiameter<7.5cm,andpatientswhohadcompleteresponse(CR)andreceiveddoxorubicin-containedchemotherapy(P<0.05).Therewasatrendtowardsuperioroutcomeforpatientswhoreceivedcombinedtherapy(surgery/chemotherapy/radiotherapy)(P=0.055).PatientswhohadCR,primarytumordiameter<7.5cmandIPIscore≤1weresignificantlyassociatedwithlongerPFSatmultivariateanalysis.Conclusions:PrimarytesticularDLBCLhadpoorersurvival.CR,primarytumordiameterandIPIwereindependentprognosticfactors.Thecombinedtherapyoforchectomy,doxorubicin-containedchemotherapyandcontralateraltesticularradiotherapy(RT)seemedtoimprovesurvival.

  • 标签: B细胞淋巴瘤 临床特征 原发性 弥漫性 预后 睾丸
  • 简介:目的:评价前程加速分割治疗食管癌放疗疗效及放射反应.方法:对96例食管癌随机分为前程加速分割组(前组)和常规组,每组48例,全部经病理证实.男性63例,女性33例;年龄41岁~70岁,中位年龄57岁;病变部位胸上段21例,胸中段63例,胸下段12例.病变长度:<5cm29例,5.0cm~7.0cm57例,>10cm10例.全部采用6MVX线外照射,常规组1次/天,2.0Gy/次,5次/周,总剂量64Gy~68Gy,44~45天完成.前组2次/天,1.5Gy/次,间隔6小时以上,总剂量64~68Gy,35~37天完成.结果:随访率96.9%.1、3、5年生存率前组为81.15%、44.1%和26.8%,常规组为61.7%、25.1%和16.9%.前组1、3年生存率高于常规组(u值为2.97及2.64,P<0.01),5年生存率无显著意义(u=1.71,P>0.05).前组和常规组放射性食管炎发生率分别为27.16和16.7%(χ2=1.52,P=0.20);放射性气管炎发生率前组为18.8%,常规组为12.5%(χ2=0.71,P=0.40).结论:食管癌前程加速分割治疗的1年和3年生存率高于常规组,5年生存率无明显差异,患者对前组放疗副作用与常规组相比无明显增加.

  • 标签: 加速超分割 食管癌 生存率 放射治疗 常规 发生率