简介：AIM:Toanalyzethemismatchrepair(MMR)statusandtheARID1Aexpressionaswellastheirclinicopathologicalsignificanceingastricadenocarcinomas.METHODS:WeexaminedtheexpressionsofMMRproteinsandARID1Abyimmunohistochemistryinconsecutive489primarygastricadenocarcinomas.Theresultswerefurthercorrelatedwithclinicopathologicalvariables.RESULTS:ThelossofanyMMRproteinexpression,indicativeofMMRdeficiency,wasobservedin38cases(7.8%)andwassignificantlyassociatedwithanolderage(68.6±9.2vs60.4±11.7,P<0.001),afemalesex(55.3%vs31.3%,P=0.004),anantrallocation(44.7%vs25.7%,P=0.021),andadifferentiatedhistology(57.9%vs39.7%,P=0.023).AbnormalARID1Aexpression,includingreducedorlossofARID1Aexpression,wasobservedin109cases(22.3%)andwassignificantlycorrelatedwithlymphaticinvasion(80.7%vs69.5%,P=0.022)andlymphnodemetastasis(83.5%vs73.7%,P=0.042).ThetumorswithabnormalARID1AexpressionmorefrequentlyindicatedMMRdeficiency(47.4%vs20.2%,P<0.001).AmultivariateanalysisidentifiedabnormalARID1Aexpressionasanindependentpoorprognosticfactor(HR=1.36,95%CI:1.01-1.84;P=0.040).CONCLUSION:OurobservationssuggestthattheAIRD1Ainactivationisassociatedwithlymphaticinvasion,lymphnodemetastasis,poorprognosis,andMMRdeficiencyingastricadenocarcinomas.

简介：Wehavereviewedthegenetherapyingastrointestinaldiseases^[1].GastriccanceriscommoninChina^(2-20),anditsearlydiagnosisandtreatmentarestilldifficultuptonow^(13-36).Theex-pressionofanexogenousgeneintroducedbygenetherapyintopa-tientswithgliomascanbemonitorednon-invasivelybypositron-emissiontornography^[4].

简介：胆囊疾病在发达国家是很普通的。复杂胆石疾病代表外科定期为被倡导的胆汁的混乱最经常。关于，胆囊炎代表普通腹的外科的干预；它能作为选任的干预或紧急情况外科被执行，在坏疽，穿孔，腹膜炎或败血的情况中。现在，laparoscopic途径被喜欢甚于开的剖腹术。全球性，众多的胆囊炎每天被执行；然而，小证据都不关于对跟随这些干预的生活(QOL)的surgical以后质量的评价存在。为了估计胆囊炎以后的QOL，事实上，高质量的照顾的文档服从于报导病人的结果满足的扩大讨论，和使用因为优秀改进被倡导几年了。然而，几乎没有很少研究，关于跟随胆囊炎的QOL结果出版；另外，许多当前的文学在以病人为中心的结果上缺乏系统的数据。然后，尽管几个工具被用来在胆囊炎以后测量QOL，困难留在选择有意义的参数以便获得可再现的数据反映手术后的QOL。这研究的目的是在QOL上为胆囊疾病考察外科的影响。这评论在QOL后面的胆囊炎上包括当前的文学的Medline搜索。大多数研究证明征兆的病人比收到选任的干预的病人从外科更获利。因此，在没有症状的外科，和病人少些获利或可以甚至在QOL有减小以前，在QOL的获得取决于一般条件。

简介：AIM:Toconductasystematicreviewofthepublishedepidemiologicalstudiesinvestigatingtheassociationoftheinteractionsbetweengenevariantsanddietaryintakewithgastriccancerrisk.METHODS:AliteraturesearchwasconductedinPubMed,EMBASE,andMEDLINEforarticlespublishedbetweenJanuary2000andJuly2013,and38studieswereidentified.Previousstudiesincludedvariousdietaryfactors(e.g.,fruitsandvegetables,soybeanproducts,salt,meat,andalcohol)andgeneticvariantsthatareinvolvedinvariousmetabolicpathways.RESULTS:Studiessuggestthatindividualswhocarryhigh-riskgeneticvariantsanddemonstrateparticulardietaryhabitsmayhaveanincreasedriskofgastriccancercomparedwiththosewhodonotcarryhigh-riskgeneticvariants.Distinctivedietarypatternsandvariationsinthefrequencyofgeneticvariantsmayexplainthehigherincidenceofgastriccancerinaparticularregion.However,mostpreviousstudieshavelimitations,suchasasmallsamplesizeandaretrospectivecasecontroldesign.Inaddition,paststudieshavebeenunabletoelucidatethespecificmechanismingene-dietinteractionassociatedwithgastriccarcinogenesis.CONCLUSION:Additionallargeprospectiveepidemiologicalandexperimentalstudiesarerequiredtoidentifythegene-dietmetabolicpathwaysrelatedtogastriccancersusceptibility.

简介：瞄准：为了由学习在IFN-gamma基因多型性，包括的IFN-gamma+874A/T单个核苷酸多型性(SNP)和CA之间的关系探索孩子的危险性到子宫内的HBV感染，重复微卫星多型性和子宫内的HBV感染。方法：在IFN-gamma+874A/T单个核苷酸多型性的TaqMan荧光聚合酶链反应在子宫内的HBV感染组被测试(组我)并且孩子们组织的正常免疫者(组II)。毛状的电气泳动在上述二个组被执行到试金IFN-gammaCA重复微卫星多型性。结果：AA的频率，在并且TT遗传型在感染组织的子宫内的HBV是67.4%，19.6%和13.0%，并且45.2%，30.1%和24.7%分别地在正常有免疫力的孩子组织。有效差量在在二个组之间的IFN-gamma+874遗传型的频率分发被发现(chi2=5.102，P=0.02389)。在子宫内的HBV感染组，AA遗传型比在正常免疫者组织是更普通的。IFN-gamma+874A等位基因的频率在子宫内的HBV感染组是77.17%，并且60.27%在正常有免疫力的孩子组织。在子宫内的HBV感染组，IFN-gamma+874A等位基因比在正常免疫者组织是更普通的。有效差量在在二个组之间的频率分发被发现(chi2=7.238，P=0.02389，或=2.228，95%CI=1.244-3.992)。(CA12)IFN-gammaCA微卫星多型性的+/(CA12)+在子宫内的HBV感染组是11.90%，26.47%在正常有免疫力的孩子组织。有效差量在在二个组之间的频率分发被发现(chi2=5.64，P=0.0176)。IFN-gammaCA重复的频率在子宫内的HBV感染组是25%，43.38%在正常有免疫力的孩子组织。IFN-gammaCA重复的频率比在正常免疫者组织是在子宫内的HBV感染组的更少。有效差量在在二个组之间的频率分发被发现(chi2=7.548，P=0.0060)。结论：在IFN-gamma+874A/TSNP和子宫内的HBV感染之间以及在IFN-gammaCA微卫星多型性和子宫内的HBV感染之间有一种关系。IFN-gamma基因多型性可能在决定个人的危险�

简介：Gastrointestinaltoxicities(GIT),includingoralmucositis,nauseaandvomiting,anddiarrhea,arecommonsideeffectsofchemotherapyandtargetedagentsinpatientswithadvancedcolorectalcancerandpancreaticcancer.Beingoftenunderreported,itisstilldifficulttopreciselyestablishtheirburdenintermsofbothpatient’squalityoflifeandcancercarecosts.Moreover,withtheuseofmoreintensiveupfrontcombinationregimens,thefrequencyofthesetoxicitiesisrapidlygrowingwithapotentialnegativeeffectalsoonpatient’soutcome,asaresultofdosereductions,delaysorevendiscontinuationofactivetreatments.Thus,identifyingpatientsathigherriskofdevelopingGITaswellasanoptimalmanagementareparamountinordertoimprovepatient’scomplianceandoutcome.Afterthedescriptionofthemaintreatment-inducedGIT,wediscussthecurrentknowledgeonthepathophysiologyofthesesideeffectsandcommentthescalescommonlyusedtoassessandgradethem.WethenprovideacriticalupdateonGITincidencebasedontheresultsofkeyrandomizedtrialsconductedinpatientswithmetastaticcolorectalcancerandadvancedpancreaticcancer.

简介：AIM:ToinvestigatetheeffectofhepatitisBvirus(HBV)XgeneonapoptosisandexpressionsofapoptosisfactorsinXgene-transfectedHepG2cells.METHODS:TheHBVXgeneeukaryonexpressionvectorpcDNVA3-XwastransientlytransfectedintoHepG2cellsbylipid-mediatransfection.UntransfectedHepG2andHepG2transfectedwithpcDNA3wereusedascontrols.ExpressionofHBxinHepG2wasidentifiedbyPT-PCR.MTTandTUNELwereemployedtomeasureproliferationandapoptosisofcellsin.threegroups.Semi-quantifiedRT-PCRwasusedtoevaluatetheexpressionlevelsofFas/FasL,Bax/Bcl-xL,andc-mycineachgroup.RESULTS:HBVXgenewastransfectedintoHepG2cellssuccessfully.RT-PCRshowedthatHBxwasonlyexpressedinHepG2/pcDNA3-Xcells,butnotexpressedinHepG2andHepG2/pcDNA3cells.AnalyzedbyMTT,cellproliferationcapacitywasobviouslylowerinHepG2/pcDNA3-Xcells(0.08910±0.003164)thaninHepG2(0.14410±0.004927)andHepG2/pcDNA3cells(0.12150±0.007159)(P＜0.05andP＜0.01).AnalyzedbyTUNEL,cellapoptosiswasmuchmoreinHepG2/pcDNA3-Xcells(980/2000)thanHepG2(420/2000),HepG2/pcDNA3cells(520/2000)(P＜0.05andP＜0.01).Evaluatedbysemi-quantifiedRT-PCR,theexpressionlevelofFas/FasLwassignificantlyhigherinHepG2cellstransfectedwithHBxthaninHepG2andHepG2/pcDNA3cells(P＜0.05andP＜0.01).Bax/Bcl-xLexpressionlevelwasalsoelevatedinHepG2/pcDNA3-Xcells(P＜0.05andP＜0.01).Expressionofc-mycwasmarkedlyhigherinHepG2/pcDNA3-XcellsthaninHepG2andHepG2/pcDNA3cells(P＜0.05andP＜0.01).CONCLUSION:HBVXgenecanimpaircellproliferationcapacity,improvecellapoptosis,andupregulateexpressionofapoptosisfactors.TheinterventionofHBVXgeneontheexpressionofapoptosisfactorsmaybeapossiblemechanismresponsibleforthechangeincellapoptosisandproliferation.

简介：AIMTocompareKAI1incancerofpapillaofVaterandpancreastoevaluatewhethertherearedifferencesinbiologicbehaviorwhichmightaccountforprognosis.METHODSWecomparedtheexpressionin24papillayand29pancreaticcancersusingNorthernblotanalysis,immunochemicalassayandinsituhybridization,andinvestigatedwhetherearlydiagnosisormoleculardifferencespredicttheoutcomeinthesetumorentities.RESULTSByNorthernblotanalysisthereisnostatisticaldifferenceofKAI1levelsinnormalandcancerouspapilla.NoassociationbetweenKAI1mRNAexpressionandtumorstageortumordifferentiationwasfoundinthetumors.Byimmunohistochemicalassay,KAI1stainingincytoplasmofpapillarycancercellswassimilartothatofnormalpapillarycells.Byinsituhybridization,theresultsofKAI1mRNAexpressioninnormalandcancerouspapillaweresimilartothosewithimmunohistochemicalassay.Thenormalandcancerouspancreastissueswerealsoanalyzedbythemethodsusedinpapillarysamples.CONCLUSIONAlthoughthebiologicrolesofKAI1havenotbeenclarified,ourresultssuggestthatKAI1mayrestricttheprogressionofmalignantpapillarycancer,butitsexpressionmightnothaveanyeffectonthecharacteristicsofpapillarytumor,whereasbytheanalysisofKAl1gene,itsreducedexpressioniscloselyrelatedtotheprogressionandmetastasesofpancreaticcancer.

简介：AIM:Toinvestigatethediversecharacteristicsofdifferentpathologicalgradingsofgastricadenocarcinoma(GA)usingtumor-relatedgenes.METHODS:GAtissuesindifferentpathologicalgradingsandnormaltissuesweresubjectedtotissuearrays.Expressionsof15majortumor-relatedgenesweredetectedbyRNAinsituhybridizationalongwith3’terminaldigoxin-labeledanti-sensesinglestrandedoligonucleotideandlockednucleicacidmodifyingprobewithinthetissuearray.Thedataobtainedwereprocessedbysupportvectormachinesbyfourdifferentfeatureselectionmethodstodiscovertherespectivecriticalgene/genesubsetscontributingtotheGAactivitiesofdifferentpathologicalgradings.RESULTS:IncomparisonofpoorlydifferentiatedGAwithnormaltissues,tumor-relatedgeneTP53playsakeyrole,althoughothersixtumor-relatedgenescouldalsoachievetheAreaUnderCurve(AUC)ofthereceiveroperatingcharacteristicindependentlybymorethan80%.ComparingthewelldifferentiatedGAwithnormaltissues,wefoundthat11tumor-relatedgenescouldindependentlyobtaintheAUCbymorethan80%,butonlythegenesubsets,TP53,RBandPTEN,playakeyrole.Onlythegenesubsets,Bcl10,UVRAG,APC,Beclin1,NM23,PTENandRBcoulddistinguishbetweenthepoorlydifferentiatedandwelldifferentiatedGA.Noneofasinglegenecouldobtainavaliddistinction.CONCLUSION:Differentfromthetraditionalpointofview,thewelldifferentiatedcancertissueshavemorealterationsofimportanttumor-relatedgenesthanthepoorlydifferentiatedcancertissues.

简介：AIM:ToelucidatethemolecularmechanismsunderlyinghepatitisBvirus(HBV)occultinfectionofgenotypeC.METHODS:Atotalof10typesofhepatitisBsurfaceantigen(HBsAg)variantsfromaKoreanoccultcohortwereused.AfteracompleteHBVgenomeplasmidmutatedsuchthatitdoesnotexpressHBsAgandplasmidencoding,eachHBsAgvariantwastransientlyco-transfectedintoHuH-7cells.ThesecretioncapacityandintracellularexpressionoftheHBVvirionsandHBsAgsintheirrespectivevariantswereanalyzedusingreal-timequantitativepolymerasechainreactionassaysandcommercialHBsAgenzyme-linkedimmunosorbentassays,respectively.RESULTS:AllvariantsexhibitedlowerlevelsofHBsAgsecretionintothemediumcomparedwiththewildtype.Inparticular,ineightofthetenvariants,verylowlevelsofHBsAgsecretionthatweresimilartothenegativecontrolweredetected.Incontrast,mostvariants(9/10)exhibitednormalvirionsecretioncapacitiescomparablewith,orevenhigherthan,thewildtype.ThisprovidednewinsightintotheintrinsicnatureofoccultHBVinfection,whichleadstoHBsAgsero-negativenessbuthashorizontalinfectivity.Furthermore,mostvariantsgeneratedhigherreactiveoxidativespeciesproductionthanthewildtype.ThisfindingprovidespotentiallinksbetweenoccultHBVinfectionandliverdiseaseprogression.CONCLUSION:ThepresentlyobtaineddataindicatethatdeficiencyinthesecretioncapacityofHBsAgvariantsmayhaveapivotalfunctionintheoccultinfectionsofHBVgenotypeC.

简介：AIM:Toinvestigatethemutationsofthe5'noncodingregionofBCL-6geneinChinesepatientswithprimarygastriclymphomas.METHODS:PCRanddirectDNAsequencingwereusedtoidentifyBCL-6genemutationsinthe5'noncodingregionin29casesofgastricdiffuselargeB-celllymphoma(DLBCL)and18casesofgastricmucosa-associatedlymphoidtissue(MALT)lymphomaaswellas10casesofreactivehyperplasiaoflymphnode(LRH).RESULTS:Sixof29gastricDLBCLs(20.7%),4of18gastricMALTlymphomas(22.2%)and1of10LRHs(10%)werefoundtohavemutations.Allmutationsweresingle-basesubstitutionsandthefrequencyofsingle-basechangeswas0.20x10-2-1.02x10-2perbp.CONCLUSION:Pointmutationsinthe5'noncodingregionofBCL-6genearefoundinChinesepatientswithprimarygastricDLBCLsandMALTlymphomas,suggestingthattheymay,insomeextent,participateinthepathogenesisofprimarygastricDLBCLsandMALTlymphomas.

简介：AIM:Toinvestigatewhethergenemethylationintheperitonealfluid(PF)predictsperitonealrecurrenceingastriccancerpatients.METHODS:ThegenemethylationofCHFR(checkpointwithforkheadandringfingerdomains),p16,RUNX3(runt-relatedtranscriptionfactor3),E-cadherin,hMLH1(mutLhomolog1),ABCG2(ATP-bindingcassette,sub-familyG,member2)andBNIP3(BCL2/adenovirusE1B19kDainteractingprotein3)wereanalyzedin80specimensofPFbyquantitativemethylation-specificpolymerasechainr...

简介：瞄准：评估在人的肝细胞癌的房间增长和apoptosis上的基因衬里的人的易碎的组氨酸三个一组(FHIT)的禁止的效果Hep3B在试管内。方法：包括FHIT基因的功能的区域的recombinantpcDNA3.1(+)/FHIT被构造并且转了进人的肝细胞癌房间在试管内。mRNA和在transfected房间的FHIT基因的蛋白质表示被RT-PCR和西方的污点分别地检测。增长上的FHIT的效果被MTT试金检测。在房间周期和apoptosis的变化是由流动血细胞计数的assayed。五只老鼠收到了Hep3B-FHIT的下的移植；5只老鼠作为控制收到了正常Hep3B和Hep3B-C的下的移植。裸体老鼠和肿瘤生长的体重被测量。结果：RT-PCR和西方的污点分析证明FHIT-mRNA和FHIT蛋白质的表示水平在在有pcDNA3.1(+)/FHIT的感染以后的Hep3B房间是更高的。与pcDNA3.1(+)/FHIT对待的Hep3B细胞的生长显著地被禁止。pcDNA3.1(+)/FHIT-transfectedHep3B房间在G0-G1阶段显示出显著地更高的房间率并且与控制比较增加了apoptosis(P<0.05)。移植肿瘤的生长被FHIT显著地禁止。从Hep3B-FHIT房间产生的肿瘤比那些从Hep3B和Hep3B-C房间产生晚很发生了。Hep3B-FHIT房间的生长是慢的，肿瘤体积是低的。结论：FHIT基因的转导变异禁止人的肝细胞癌细胞的生长并且导致细胞apoptosis在活体内和在试管内。

简介：AIM:Todeterminethebowelsymptomsassociatedwithdiabetesanddiabetes-relatedfactorsafterexcludinggastrointestinal(GI)organicdiseases.METHODS:Participantswere4738(603diabeticand4135non-diabetic)patientswhounderwentcolonoscopyandcompletedaquestionnaire.Onthedayofpre-colonoscopy,9symptoms(borborygmus,abdominaldistension,increasedflatus,constipation,diarrhea,loosestools,hardstools,fecalurgency,andincompleteevacuation)wereprospectivelyevaluatedona7-pointLikertscale.Thetest-retestreliabilityofthebowelsymptomscoresfromthebaselineandsecondquestionnaireswasanalyzedusingkappastatistics.Associationsbetweenbowelsymptomscoresanddiabetesordiabetes-relatedfactorswereanalyzedbyarank-orderedlogisticmodeladjustedforrelatedconfounders,andoddsratios(ORs)wereestimated.RESULTS:Inmultivariateanalysis,constipation[adjustedoddsratio(AOR)=1.57,CI:1.33-1.85,P<0.01]andhardstools(AOR=1.56,CI:1.33-1.84,P<0.01)wereassociatedwithdiabetes,andfecalurgency(AOR=1.16,CI:0.99-1.37,P=0.07)andincompleteevacuation(AOR=1.16,CI:1.00-1.36,P=0.06)weremarginallyassociatedwithdiabetes.ThesesymptomsremainedassociatedevenafterexcludingorganicGIdiseasesoncolonoscopy.Test-retestreliabilityofsymptomscorewithameandurationof3.2mowasgood(meankappa,0.69).Associationsofsymptomswithdiabetes-relatedfactorswerefound;constipationwithHbA1c≥8.0%(AOR=2.11,CI:1.19-3.73),bodymassindex(BMI)<25(AOR=2.11,CI:1.22-3.66),andinsulinuse(AOR=1.90,CI:1.08-3.36);hardstoolswithdiabetesduration(AOR=1.03,CI:1.00-1.07);fecalurgencywithBMI<25(AOR=1.73,CI:1.00-2.98);andincompleteevacuationwithBMI<25(AOR=2.60,CI:1.52-4.43),serumcreatininelevel(AOR=1.27,CI:1.10-1.47),andinsulinuse(AOR=1.92,CI:1.09-3.38).CONCLUSION:Diabetesisassociatedwithconstipation,hardstools,fecalurgency,andincompleteevacuation,andpoorglycemiccontrol,duration,leanness,andnephropathyaffecttheriskofthesesymptoms.

简介：瞄准：调查影响他我有教养的老鼠小岛的生存能力和功能上的oxygenase-1(HO-1)基因转移在试管内。方法：小岛被管内胶原酶消化从Sprague-Dawley老鼠的胰孤立，并且由不连续的Ficoll密度坡度远心沉淀净化了。净化的老鼠小岛是有包含人的HO-1基因(Ad-HO-1)的adenoviral向量的transfected或提高了绿荧光灯的蛋白质基因(Ad-EGFP)，然后为七天有教养。Transfection被萤光显微镜检查和西方的污点证实。小岛生存能力被氮蒽orange/propidium碘化物评估荧光灯的染色。刺激葡萄糖的胰岛素版本用胰岛素放射性免疫测定工具包被检测并且被用来估计小岛的功能。刺激索引(SI)被在低葡萄糖刺激之上由胰岛素版本在高葡萄糖刺激之上划分胰岛素版本计算。结果：在七种天文化以后，有教养的老鼠小岛的生存能力显著地减少了(92%+/-6%对52%+/-13%，P<0.05)，并且刺激葡萄糖的胰岛素版本也显著地减少了(6.47+/-0.55mIU/L/30IEQ对4.57+/-0.40mIU/L/30IEQ，14.93+/-1.17mIU/L/30IEQ对9.63+/-0.71mIU/L/30IEQ，P<0.05)。有在20的MOI的adenoviral向量的老鼠小岛的Transfection是有效的，并且没损害小岛功能。在7dpost-transfection，Ad-HO-1transfected小岛的生存能力比控制小岛的高(71%+/-15%对52%+/-13%，P<0.05)。在Ad-HO-1transfected组之中在在低葡萄糖刺激(2.8mmol/L)之上的胰岛素版本没有有效差量，Ad-EGFPtransfected组织，并且控制组织P>0.05)，当时当由高葡萄糖(16.7mmol/L)刺激了时答案，在Ad-HO-1transfected组的胰岛素版本比在Ad-EGFP，transfected组织并且控制组显著地高，分别地(12.50+/-2.17mIU/L/30IEQ对8.87+/-0.65mIU/L/30IEQ；12.50+/-2.17mIU/L/30IEQ对9.63+/-0.71mIU/L/30IEQ，P<0.05)。Ad-HO-1transfected组的SI比Ad-EGFP，transfected组织并且控制组也显著地高，分

简介：瞄准：为了在病人调查胰岛素抵抗和糖尿病的临床的参数的流行，由长期的丙肝(CHC)或长期的肝炎B(CHB)影响了。方法：我们回顾地评估了经历了肝活体检视的852个连续病人(726CHC和126CHB)。我们记录了年龄，性别，中高音，类型2糖尿病或新陈代谢的症候群(MS)，身体团索引(BMI)，和明显的疾病持续时间(增加)。结果：年龄，增加，BMI，在有温和/中等的肝纤维变性的病人的MS和糖尿病的流行在CHC是显著地更高的。然而，脂肪变性的度和在肝活体检视评估的肝纤维变性没在CHC和CHB病人之间不同。在多变量分析，年龄，性别，BMI，中高音和糖尿病是为在CHC的肝纤维变性的独立风险因素，而仅仅年龄与在CHB的肝纤维变性有关。我们也评估了在重要脂肪变性之间的协会(>30%)并且年龄，性别，BMI，糖尿病，MS和肝纤维变性。糖尿病，BMI和肝纤维变性与脂肪变性>被联系30%在CHC，而仅仅年龄和BMI与在CHB的脂肪变性有关。结论：这些数据可以显示丙肝病毒感染是为胰岛素抵抗的一个风险因素。

简介：AIMTocharacterizepunctualmutationsin23SrRNAgeneofclarithromycin-resistantHelicobacterpylori(H.pylori)anddeterminetheirassociationwiththerapeuticfailure.METHODSPCRproductsof23SrRNAgeneVdomainof74H.pyloriisolates;34resistanttoclarithromycin(29fromalow-riskgastriccancer(GC)population:Tumaco-Colombia,and5fromahigh-riskpopulation:Tuquerres-Colombia)and40fromasusceptiblepopulation(28fromTumacoand12fromTúquerres)weresequencedusingcapillaryelectrophoresis.TheconcordancebetweenmutationsofVdomain23SrRNAgeneofH.pyloriandtherapeuticfailurewasdeterminedusingtheKappacoefficientandMcNemar’stestwasperformedtodeterminetherelationshipbetweenH.pylorimutationsandclarithromycinresistance.RESULTS23SrRNAgenefromH.pyloriwasamplifiedin56/74isolates,ofwhich25wereresistanttoclarithromycin(20fromTumacoand5fromTúquerres,respectively).In17resistantisolates(13fromTumacoand4fromTúquerres)thefollowingmutationswerefound:A1593T1,A1653G2,C1770T,C1954T1,andG1827CinisolatesfromTumaco,andA2144GfromTúquerres.ThemutationsT2183C,A2144GandC2196TinH.pyloriisolatesresistanttoclarithromycinfromColombiaarereportedforthefirsttime.NoassociationbetweentheH.pylorimutationsandinvitroclarithromycinresistancewasfound.However,therapeuticfailureoferadicationtreatmentwasassociatedwithmutationsof23SrRNAgeneinclarithromycin-resistantH.pylori(κ=0.71).CONCLUSIONThetherapeuticfailureoferadicationtreatmentinthetwopopulationsfromColombiawasassociatedwithmutationsofthe23SrRNAgeneinclarithromycinresistantH.pylori.

简介：AIM:Toinvestigatetheanti-tumoreffectsofnuclearfactor-κB(NF-κB)inhibitorSN50andrelatedmechanismsofSGC7901humangastriccarcinomacells.METHODS:MTTassaywasusedtodeterminethecytotoxiceffectsofSN50ingastriccancercelllineSGC7901.Hoechst33258stainingwasusedtodetectapoptosismorphologicalchangesafterSN50treatment.Activationofautophagywasmonitoredwithmonodansylcadaverine(MDC)stainingafterSN50treatment.Immunofluorescencestainingwasusedtodetecttheexpressionoflightchain3(LC3).MitochondrialmembranepotentialwasmeasuredusingthefluorescentprobeJC-1.Westernblottinganalysiswereusedtodeterminetheexpressionofproteinsinvolvedinapoptosisandautophagyincludingp53,p53upregulatedmodulatorofapoptosis(PUMA),damage-regulatedautophagymodulator(DRAM),LC3andBeclin1.Wedetectedtheeffectsofp53-mediatedautophagyactivationontheapoptosisofSGC7901cellswiththep53inhibitorpifithrin-α.RESULTS:TheviabilityofSGC7901cellswasinhibitedafterSN50treatment.Inductionsintheexpressionofapoptoticproteinp53andPUMAaswellasautophagicproteinDRAM,LC3andBeclin1weredetectedwithWesternblottinganalysis.SN50-treatedcellsexhibitedpunctuatemicrotubule-associatedprotein1LC3inimmunoreactivityandMDC-labeledvesiclesincreasedaftertreatmentofSN50byMDCstaining.CollapseofmitochondrialmembranepotentialΔψweredetectedfor6to24hafterSN50treatment.SN50-inducedincreasesinPUMA,DRAM,LC3andBeclin1andcelldeathwereblockedbythep53specificinhibitorpifithrin-α.CONCLUSION:Theanti-tumoractivityofNF-κBinhibitorsisassociatedwithp53-mediatedactivationofautophagy.

简介：AIM:TOexplorethefeasibilityofenhancingapoptosis-inducingeffectsofchemotherapeuticdrugsonhumangastriccancercellsbystabletransfectionofextrinsicSmacgene.METHODS:AfterSmacgenewastransferredintogastriccancercelllineMKN-45,subclonecellswereobtainedbypersistentG418selection.CellularSmacgeneexpressionwasdeterminedbyRT-PCRandWesternblotting.Aftertreatmentwithmitomycin(MMC)asanapoptoticinducer,invitrocellgrowthactivitieswereinvestigatedbytrypanblue-stainingmethodandMI-Icolorimetry.Cellapoptosisanditsratesweredeterminedbyelectronicmicroscopy,annexinV-FITCandpropidiumiodidestainingflowcytometry.Cellularcaspase-3proteinexpressionanditsactivitieswereassayedbyWesternblottingandcolorimetry.RESULTS:WhencomparedwithMKN-45cells,theselectedsubclonecelllineMKN-45/SmachadsignificantlyhigherSmacmRNA(3.12±0.21vs0.82:1:0.14,t=7.52,P<0.01)andproteinlevels(4.02±0.24vs0.98:1:0.11,t=8.32,P<0.01).Aftertreatmentwith10μg/mLMMCfor6-24h,growthinhibitionrateofMKN-45/Smac(15.8±1.2-54.8±2.9%)wassignificantlyhigherthanthatofMKN-45(5.8±0.4-24.0±1.5%,t=6.42,P<0.01).PartialMKN-45/Smaccancercellspresentedcharacteristicmorphologicalchangesofapoptosisundertheelectronicmicroscopewithanapoptosisrateof36.4=1=2.1%,whichwassignificantlyhigherthanthatofMKN-45(15.2±0.8%,t=9.25,P<0,01).ComparedwithMKN-45,caspase-3expressionlevelsinMKN-45/Smacwereimprovedsignificantly(3.39±0.42vs0.96:1:0.14,t=8.63,P<0.01),whileitsactivitieswere3.25timesasmanyasthoseofMKN-45(0.364±0.010vs0.112:1:0.007,t=6.34,P<0.01).CONCLUSION:StabletransfectionofextrinsicSmacgeneanditsover-expressioningasbiccancercelllinecansignificantlyenhancecellularcaspase-3expressionandactivities,ameliorateapoptosis-inducingeffectsofmitomycinConcancercells,whichisanovelstrategytoimprovechemotherapeuticeffectsongastriccancer.

简介：AIM:Toinvestigatetheassociationbetweenendogenousgeneexpressionandgrowthregulationincludingproliferationandapoptosisinducedbytransforminggrowthfactor-β1(TGF-β1)inhumangastriccancer(GC)cells.METHODS:Reversetranscriptionpolymerasechainreaction(RT-PCR)wasperformedtodetectthemaincomponentsoftheTGF-β1/SmadssignalpathwayinhumanpoorlydifferentiatedGCcelllineBGC-823.LocalizationofSmadproteinswasalsodeterminedusingimmunofluorescence.Then,theBGC-823cellswereculturedinthepresenceorabsenceofTGF-β1(10ng/mL)for24and48h,andtheeffectsofTGF-β1onproliferationandapoptosisweremeasuredbycellgrowthcurveandflowcytometry(FCM)analysis.TheultrastructuralfeaturesofBGC-823cellswithorwithoutTGF-β1treatmentwereobservedundertransmissionelectronmicroscope.Theapoptoticcellswerevisualizedbymeansoftheterminaldeoxynucleotidyltransferase(TdT)-mediateddTUPinsitunickend-labeling(TUNEL)method.Meanwhile,theexpressionlevelsofendogenousp15,p21andSmad7mRNAandthecorrespondingproteinsinthecellsweredetectedat1,2and3haftercultureinthepresenceorabsenceofTGF-β1(10ng/mL)bysemi-quantitativeRT-PCRandWesternblot,respectively.RESULTS:TheTGF-β1/SmadsignalingwasfoundtobeintactandfunctionalinBGC-823cells.ThegrowthcurverevealedthemostevidentinhibitionofcellproliferationbyTGF-β1at48h,andFCMassayshowedG1arrestaccompaniedwithapoptosisinducedbyTGF-β1.ThetypicalmorphologicalchangesofapoptosiswereobservedincellsexposedtoTGF-β1.Theapoptosisindex(AI)inTGF-β1-treatedcellswassignificantlyhigherthanthatintheuntreatedcontrols(10.7±1.3%vs0.32±0.06%,P＜0.01).Thelevelsofp15,p21andSmad7mRNAandcorrespondingproteinsincellsweresignificantlyup-regulatedat1h,butgraduallyreturnedtobasallevelsat3hfollowingTGF-β1(10ng/mL)treatment.CONCLUSION:TGF-β1affectsbothproliferationandapoptosisofGCcellsth