幽门螺杆菌致胃癌发生机制-张微

:,E-mai:[e-mail]#张微,刘纯杰军事医学科学院生物工程研究所,北京100071=;MechanismsinvolvedinHelicobacterpylor-iinducedgastriccancer=KeywordsHelicobacterpylor;iGastriccancer=Firstauthor.snameandaddressZHANGWe,iBeijingIn-stituteofBiotechnology,Beijing100071,China:R735.2:A:2007-08-15:1006-5709(2008)03-0177-05(Helicobacterpylor,iH.pyloriHP),50%,,80%,H.pylori,,[1],,,,1994,[2],50,[3,4],85%~95%,H.pyloriH.pylori,1H.pyloriH.pylori,,1.1,,6%~10%9,UreA,UreB27H.pylori,,20%[4],,,(pH2)H.pylori,,,,/0,,H.pylori,H.pylori,,,H.pylori,,,pH,H.pylori,,,,,,VacAHela[6],VacA1.2(BabA)H.pylori,,,,babA(BabA),78KD,40%~95%H.pylori,Lewisb,H.pylori,H.pylori:BabA2,,Yu[7]104H.pyloriBabA2,CagAVacAs1,BabA+H.pylori#177#20083173ChinJGastroenterolHepato,lMar2008,Vo.l17,No.3IL-8BabA-,Lewisb1.3(VacA)vacA3888bp,136KD,87KD,vacAH.pylori,,H.pylori(Tox+),50%~60%H.pyloriTox+,VacAFox[8]386,89%Tox+,,Tox+58%VacA,80%Tox-,Tox+VacADNA,(M)(S)23,6s1/m1VacA,;s2/m2VacA,m1VacAH.pylori[9],,,s1/m1VacA[5]VacA,V,VacA,P450,,,,HCO-3,[10]VacA,VacAB,T[11],H.pylori,1.4CagACagA(Cy-totoxin-associatedproteinA,CagA),60%~70%H.pylori,VacACagA,:ÑcagA,CagAVacA,ÒcagA,CagAVacA,ÑÒ56%16%,28%CagAH.pylori,Konturek[12]:CagA4.1cagAH.pylori,3.3R1R2R3,ABCD4CagA,CCagA,CagA(CagPAI),CagA,31Ö[5]:CagAATPNTPÖ,CagA,CagA,,,(pedestal),,CagA+CagA,ÖCagA,CagA,CagA+CagANF-JBIL-8,[13]Mimnro[14]CagAGrb2,Ras/MEK/ERK,H.pylori,CagAH.pylori,Ali[15]CagPAIH.pylori,CagPAIH.pylori1.5H.pyloriHp26695J99HPAG13,,H.pylo-ri,H.pylori[16],DNA[16],,,HuynenH.pylori,60%H.pyloriH.pylori2H.pylori,,(SNP)H.pylori#178#20083173ChinJGastroenterolHepato,lMar2008,Vo.l17,No.32.1IL-1IL-1RNIL-1IL-1RN-1,,H.pyloriIL-1,H.pylori,H.pylori,,,H.pylori,,,IL-1B,H.pylori,,H.py-lori6~12,IL-1B,IL-1BH.pyloriIL-1BIL-1RN,,,IL-1B3(IL-1B-31T,IL-1B-511T,IL-1B+3954T)-511T-511C-31C-31T,H.pyloriIL-1B-511C/C(-31T/T)IL-1B-511T/T,[17],[18]IL-1B-511T/T-511C/C[19]-31T/T-511C/CH.pylori[20]Mansour[21]IL-1B-31IL-1B+3954T,[22]IL-1BIL-1RNIL-1B,,IL-1RN,IL-1RN*2/LIL-1B,,[21],CagAVacAs1/mL,IL-1BH.pylori,2.2(TNF)(TNF)TNF-AA(LT-A,TNF-B),HLA,TNF-A,(SNP),-238G/A-308G/A-857C/T-863C/A-1031T/C,TNF-A,,,H.pylori,TNF-AH.pylori[23]130:H.pylori+TNF-A-238G/AAH.pylori-,AH.pyloriH.pylori-4.5,TNF-A-238G/AH.pylori,AH.pyloriTNF-A-308H.pylori,Zambon[24]TNF-A-308AH.pylori,,EL-OmarTNF-A-308A,IL-10H.pylori,Ja[25][23]TNF-A-308AH.py-lori,,TNF-A,TNF-BH.pylori,Majestschak[26]TNF-B+252*ATNF-A,,,,,[27]TNF-B+252*AA,A3,H.pyloriTNF-B+252*AA,2.3IL-4,IL-6Th2,,IL-4,H.pylori,IL-6-174G/CSNPIL-6,IL-6[28],[23]IL-6-572C/C,IL-6-572C/C,E-lOmar[29]IL-10,TNF-AIL-10H.pylori,,,,,,,,H.pylori#179#20083173ChinJGastroenterolHepato,lMar2008,Vo.l17,No.33H.pylori3.1H.pylori,,,H.pylori,[30]:H.pylori90%,60%,,CagA,H.pylori3.2,,(N-),,,,H.pylori,,,,,,.:,[31],AC,A,C,H.pylori,Konturek[32],2g/dC,3375511571154:147,60%,40%,16%CH.pylori,AGSH.pyloriL-72h,C,[33]H.pyloriC10mg/d@7d,H.pylori[34]CH.pylori,[31],H.pylori,,H.pyloriH.pylori,H.pylori,,[1]CorreaP.Humangastriccarcinogenesis:amultistepandmultifactorialprocess-FirstAmeiricanCancerSocietyAwardLectureoncancerepide-miologyandprevention[J].CancerRes,1992,52(24):6735.[2]PeekRMJr,BlaserMJ.Helicobacterpyloriandgastrointestinaltractadenocarcinomas[J].NatRevCancer,2002,2(1):28-37.[3]ParkinDM.Internationalvariation[J].Oncogene,2004,23(38):6329-6340.[4]FerlayJ,AutierP,BoniolM,eta.lEstimatesofthecancerincidenceandmortalityinEuropein2006[J].AnnOnco,l2007,18(3):581-592.[5]PeekRMJr,CrabtreeJE.Helicobacterpyloriinfectionandgastricne-oplasia[J].JPatho,l2006,208(2):233-224.[6]RicciV,SommiP,FioccaR,eta.lHelicobacterpylorivacuolatingtoxinaccumulateswithintheendosoma-lvacuolarcompartmentofcu-lturedgastriccellsandpotentiatesthevacuolatingactivityoammonia[J].JPatho,l1997,183(4):453-459.[7]YuJ,LeungNK,GoMY,eta.lRelationshipbetweenHelicobacterpy-loribabA2statuswithgastricepithelialcellturnoverandpremaligmentgastriclesions[J].Gut,2002,51(4):480-484.[8]FoxJG,CorreaP,TaylorNS,eta.lHighprevalenceandpersistenceofcytot-oxin-positiveHelicobacterpyloristrainsinapopulationwithhighprevalenceofatrophicgastritis[J].AmJGastroentenro,l1992,87(11):1554.[9]RheadJL,LetleyDP,MohammadiM,eta.lAnewHelicobacterpylorivacuolatingcytotoxindeterminant,theintermediateregion,isassocia-tedwithgastriccancer[J].Gastroenterology,2007,133(3):926-936.[10]DebellisL,PapiniE,CaroppoR,eta.lHelicobacterpyloricytotoxinVacAincreasesalkalinesecretioningastricepithelialcell[J].AmJPhysiolGastrointestLiverPhysio,l2001,281(6):G1440-G1448.[11]TorresVJ,VancompernolleSE,SundrudMS,eta.lHelicobacterpy-lorivacuolatingcytotoxininhibitsactivation-inducedproliferationofHumanTandBlymphocytesubsets[J].JImmuno,l2007,179(8):5433-5440.[12]KonturekSJ,StarzynskaT,Marliczk,eta.lHelicobacterpylori(HP),CagAstatusandplasmagastrininthedevelopmentofgastriccancer[J].Gut,2000,47(Suppl1):A75.[13]ShibataW,HirataY,MaedaS,eta.lCagAproteinsecretedbytheintacttypeIVsecretionsystemleadstogastricepithelialinflammationintheMongoliangerbilmodel[J].JPatho,l2006,210(3):306-314.[14]MimuroH,SuznkiT,TanakaJ,eta.lGrb2isakeymediatorofcagAproteinactivities[J].MolCel,l2002,10(4):745-755.#180#20083173Ch