简介:N^6-methyladenosine(m^6A)isanessentialRNAmodificationthatregulateskeycellularprocesses,includingstemcellrenewal,cellulardifferentiation,andresponsetoDNAdamage.Unsurprisingly,aberrantm6Amethylationhasbeenimplicatedinthedevelopmentandmaintenanceofdiversehumancancers.Alteredm6AlevelsaffectRNAprocessing,mRNAdegradation,andtranslationofmRNAsintoproteins,therebydisruptinggeneexpressionregulationandpromotingtumorigenesis.Recentstudieshavereportedthattheabnormalexpressionofm6Aregulatoryenzymesaffectsm6Aabundanceandconsequentlydysregulatestheexpressionoftumorsuppressorgenesandoncogenes,includingMYC,SOCS2,ADAM19,andPTEN.Inthisreview,wediscussthespecificrolesofm6A“writers",“erasers”,and“readers”innormalphysiologyandhowtheiralteredexpressionpromotestumorigenesis.Wealsodescribethepotentialofexploitingtheaberrantexpressionoftheseenzymesforcancerdiagnosis,prognosis,andthedevelopmentofnoveltherapies.
简介:Glioblastoma(GBM)isoneofthedeadliesttumorsandhasamediansurvivalof3monthsifleftuntreated.Despiteadvancesinrationallytargetedpharmacologicalapproaches,theclinicalcareofGBMremainspalliativeinintent.Sincethemajorityofalteredsignalingcascadesinvolvedincancerestablishmentandprogressioneventuallyaffectcellcycleprogression,analternativeapproachforcancertherapyistodevelopinnovativecompoundsthatblocktheactivityofcrucialmoleculesneededbytumorcellstocompletecelldivision.Inthiscontext,wereviewpromisingongoingandfuturestrategiesforGBMtherapeuticsaimedtowardsG2/Minhibitionsuchasanti-microtubuleagentsandtargetedtherapyagainstG2/Mregulatorslikecyclin-dependentkinases,Aurorainhibitors,PLK1,BUB,1,andBUBR1,andsurvivin.Moreover,wealsoincludeinvestigationalagentsinthepreclinicalandearlyclinicalsettings.Althoughseveraldrugswereshowntobegliotoxic,mostofthemhavenotyetenteredtherapeutictrials.TheuseofeithersingleexposureoracombinationwithnovelcompoundsmayleadtotreatmentalternativesforGBMpatientsinthenearfuture.
简介:Gastrointestinal(GI)cancerisoneofthemostcommoncausesofcancer-relateddeathsworldwide.Tumormarkersarevaluableindetectingpost-surgicalrecurrenceorinmonitoringresponsetochemotherapy.PyruvatekinaseisoformM2(PKM2),aglycolyticenzymecatalyzingconversionofphosphoenolpyruvate(PEP)topyruvate,confersagrowthadvantagetothetumorcellsandenablesthemtoadapttothetumormicroenvironment.Inthisreview,wehavesummarizedcurrentresearchontheexpressionandregulationofPKM2intumorcells,anditspotentialroleinGIcarcinogenesisandprogression.Furthermore,wehavealsodiscussedthepotentialofPKM2asadiagnosticandscreeningmarker,andatherapeutictargetinGIcancer.
简介:目的:评价^99Tc^m-MIBI乳腺显像对乳腺肿瘤和腋窝淋巴结转移的诊断价值。方法:52例女性乳腺肿瘤患者,体检腋窝未扪及肿块。应用^99Tc^m-MIBI740MBq(20mCi)经肘静脉注射,行乳腺和腋窝显像,并用手术、病理加以对照。结果:48例乳腺肿瘤患者中,^99Tc^m-MIBI显像真阳性32例,灵敏度为84%(32/38例),特异性60%(6/10例),准确性79%,40例乳腺癌腋窝淋巴结的灵敏度为71%(10/14例),特异性88%(23/26例),准确性83%。结论:^99Tc^m-MIBI乳腺显像既可以显示乳腺肿瘤又能了解腋窝淋巴结的灵敏度为71%(10/14例),特异性88%(23/26例),准确性83%。结论:^99Tc^m-MIBI乳腺显像既可以显示乳腺肿瘤又能了解腋窝淋巴结,是核素乳腺显像的首选方法之一。
简介:Objective:Squamousesophagealcarcinomaishighlyprevalentindevelopingcountries,especiallyinChina.TuBeiMu(TBM),atraditionalfolkmedicine,hasbeenusedtotreatesophagealsquamouscellcarcinoma(ESCC)foralongterm.tubeimosideI(TBMS1)isthemaincomponentofTBM,exhibitinggreatanticancerpotential.Inthisstudy,weinvestigatedthemechanismofTBMS1cytotoxiceffectonEC109cells.Methods:Comparativenuclearproteomicapproachwasappliedinthecurrentstudyandweidentifiedseveralalteredproteinspots.Furtherbiochemicalstudieswerecarriedouttodetectthemitochondrialmembranepotential,cellcycleandcorrespondingproteins’expressionandlocation.Results:SubcellularproteomicstudyinthenucleusfromEC109cellsrevealedthatalteredproteinswereassociatedwithmitochondrialfunctionandcellproliferation.FurtherbiochemicalstudiesshowedthatTBMS1-inducedmoleculareventswererelatedtomitochondria-inducedintrinsicapoptosisandP21-cyclinB1/cdc2complex-relatedG2/Mcellcyclearrest.Conclusions:ConsideringtheconventionalapplicationofTBMinesophagealcancer,TBMS1thereforemayhaveagreatpotentialasachemotherapeuticdrugcandidateforESCC.
简介:Aseventyeightyearsoldmalepatientunderwentawholebody18F-FDGPET/CTimagingtodiagnosethelesionwhichwasshowedintherightlungbyachestXraytestandCTscanbefore.Besidestheintense18F-FDGuptakeofthelesionintherightlung,alesionintheleftparotidglandalsoshowedintense18F-FDGuptake.Toevaluatethepathologyofthelesionintheleftparotidgland,aparotidglandscintigraphyimagingwithTc-99mpertechnetatewasdoneandrevealedaWarthin'stumor.Laterafineneedleaspiration(FNA)confirmedthatitwasaWarthin'stumor.
简介:目的探讨全反式维甲酸(all-transretinoicacid,ATRA)提高人结肠癌细胞亚株SW480/M5对奥沙利铂(oxaliplatin,L-OHP)敏感性的可能机制.方法MTT法筛选ATRA和L-OHP实验浓度.流式细胞仪检测ATRA对肿瘤细胞周期影响.分别用ATRA、L-OHP、ATRA联合L-OHP作用SW480/M5细胞,MTT法检测药物对肿瘤细胞抑制率,流式细胞仪检测肿瘤细胞周期及凋亡率,原子光谱吸收仪检测肿瘤细胞DNA含铂(Pt)量.结果L-OHP抑制SW480/M5细胞增殖的GI50为58.0mg/L,主要阻滞肿瘤细胞在S和G2/M期.ATRA8.0μmol/L作用24小时后,G1期细胞减少,S期细胞增多;作用72小时后,S期和G2/M期细胞增加并明显抑制肿瘤细胞增殖.8.0μmol/LATRA作用至48小时后联合L-OHP,两药联合由相加作用转变为协同作用;联合用药后S期和G2/M期细胞明显增多,细胞DNA含Pt量显著增加,呈时效依赖性.相对于单独用药,联合用药并不上调肿瘤细胞凋亡率.结论ATRA通过改变SW480/M5细胞周期和提高细胞DNA含Pt量,明显增加肿瘤细胞对L-OHP敏感性.
简介:客观干扰素(IFN)和ribavirin(RBV)的联合是为丙肝的标准治疗病毒(HCV)感染。HCV遗传型2a对治疗证明了更顺从,但是它的功效是还有限的。这研究试图在HCV遗传型2a感染的一种情况中调查差的反应的机制。方法:我们从一个病人分析了HCVRNA的动态变化,与HCV遗传型2a感染了,显示出差的virological回答到是的IFN/RBV判定了12在由HCV的治疗的开始以后的星期克隆定序。然后,我们构造了subgenomic日语有人性化的Gaussia的暴发性的hepatitis-1(JFH1)replicon和不同妄想的replicons酶基因。妄想的replicons从subgenomicJFH1replicon,NS5A区域被病人顺序从pre/posttreatment在代替被导出,并且到IFN的妄想的replicons危险性被相对Gausia酶活动评估。预告的处理HCV定序的结果显得几乎一致,并且quasispecies变化是进一步的在12星期治疗以后简化的更多。而且,quasispecies变化似乎相对,在NS5A更多样化为IFN反应关键的一个区域,和每妄想的replicons展出了不同反应到IFN。结论在长期的感染的功课期间,HCV人口似乎被使适应病人免疫学的系统,并且推进被IFN/RBV治疗的联合选择,显示quasispecies可以完全与IFN的与那些不同的目标由另外的药的增加消除了。另外,到IFN的妄想的replicon的各不同的反应与氨基酸变化在或在在长期的感染和IFN/RBV治疗期间决定NS5A的区域(ISDR)的IFN敏感附近有关是最可能的。
简介:Objective:Noninvasivediffusion-weightedmagneticresonanceimaging(DWI)isawell-studiedMRimagingtechniqueforquantifyingwaterdiffusionespeciallyintumorarea.Thecorrelationbetweenapparentdiffusioncoefficient(ADC)valueandapoptosisorproliferationisnotclearbynow.ThisstudyaimedtoinvestigatewhetherDWI-ADCvaluecouldbeusedasanimagingmarkerrelatedwithpathologicindexesoftumors.Methods:Atotalof30Balb/cmicewithHT29colorectalcarcinomaweresubjectedtoDWIandhistologicanalysis.ThepercentageofADCchangesandtheapoptoticandproliferatingindexeswerecalculatedatpredefinedtimepoints.Kolmogorov-SmirnovdistanceswereconsideredtodeterminewhetherthepercentageofADCchanges,andtheapoptoticandproliferatingindexeswerenormallydistributed.Anindependent-samplest-testwasusedtoanalyzethedifferencebetweenapoptoticandproliferatingindexesinthetwogroups.Results:Therewasastatisticallysignificantdifferenceinproliferatingindexbetweentheradiotherapyandcontrolgroups(meanproliferatingindex:49.27%vs.83.09%),andtherewasastatisticallysignificantdifferenceinapoptoticindexbetweenthetwogroups(meanapoptoticindex:37.7%vs.2.71%).AsignificantpositivecorrelationwasfoundbetweenthepercentageofADCchangesoftheviabletissueandapoptoticindex.Pearson'scorrelationcoefficientwas0.655(P=0.015).AsignificantnegativecorrelationwasfoundbetweenthepercentageofADCchangesoftheviabletissueandki-67proliferationindex.Pearson'scorrelationcoefficientwas0.734(P<0.001).Conclusions:OurresultssuggestthatADCvaluemaybeusedinmeasurementofcellapoptoticandproliferatingindexesincolorectalcarcinoma.
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简介:神经胶质瘤是中枢神经系统(CNS)最常见的一类肿瘤,占了颅内原发肿瘤的35%-60%。2007年世界卫生组织(WH0)中枢神经系统肿瘤分类中将胶质瘤分为Ⅰ-Ⅳ级,其中Ⅲ、Ⅳ级为恶性胶质瘤,大约占所有胶质瘤的77.5%。目前对神经胶质瘤的临床治疗采取以手术治疗为主,结合放疗、化疗等疗法的综合治疗.虽然能延长患者生存时间,但存在高复发率、高致残率、高病死率等问题,总体预后仍然较差。自20世纪70年代以来.维生素C(VC)抗肿瘤作用的研究日益进展,国外的医疗工作者已将其作为肿瘤治疗的补充和替代疗法之一.并报道了静脉注射维生素C治疗神经胶质瘤、卵巢癌、肾细胞癌、乳腺癌、大肠癌、非霍奇金淋巴瘤、前列腺癌、膀胱癌等肿瘤的临床病例,认为其能改善患者的临床症状、提高生存质量、延长生存期。本文就维生素C对神经胶质瘤的治疗作用做一综述。