簡(jiǎn)介：中文中文3070字出處出處SHIAOYH,DANIELABOVO?,GUIDOM,ETALMICROSATELLITEINSTABILITYAND/ORLOSSOFHETEROZYGOSITYINYOUNGGASTRICCANCERPATIENTSINITALYJINTERNATIONALJOURNALOFCANCER,1999,8215962青年胃癌患者的微衛(wèi)星不穩(wěn)定性和青年胃癌患者的微衛(wèi)星不穩(wěn)定性和/或雜和性缺失或雜和性缺失摘要胃癌在40歲前極少。比較40歲和大于40歲的患者，早期胃癌的分子機(jī)制可能是微衛(wèi)星不穩(wěn)定性MSI、錯(cuò)配修復(fù)和雜和性缺失（LOH）。從102例40歲胃癌患者的取出的標(biāo)本,用福爾馬林固定,石蠟包埋后,用PCR非放射篩查法檢測(cè)MSI和/或LOH。11/102患者中在1基因座發(fā)現(xiàn)MSI和/或LOH。MSI和/或LOH的發(fā)生率在D11S904基因座要高于D2S119、D2S123、D5S409和IFNA區(qū)域。在老年患者中未發(fā)現(xiàn)D11S904基因座上有優(yōu)先的基因改變。關(guān)于幾個(gè)臨床病理參數(shù)，相對(duì)于胃竇部和胃體的腫瘤，只有賁門(mén)的腫瘤上與MSI和/或LOH有顯著的統(tǒng)計(jì)學(xué)聯(lián)系。我們的研究提示，可能有獨(dú)特的機(jī)制增加了D11S904基因座對(duì)MSI和/或LOH的敏感性，特別是在年輕的賁門(mén)癌患者。40歲人群胃癌的早期啟動(dòng)與某些染色體基因座的基因改變，包括D11S904，有關(guān)。正文盡管胃癌的發(fā)病率在下降，但在90年代仍是全世界第二常見(jiàn)的和第二位致死腫瘤PARKINETAL,1993。由于胃癌自然的侵襲性，其總體5年生存率低于20％BREAUXETAL,1990。胃癌一般發(fā)病于大于50歲的患者，只有5％的胃癌患者小于40歲NEUGUTETAL,1996。小于40歲患者的胃癌比老年患者的胃癌更具侵襲性FUJIMOTOETAL,1994。將小于40歲患者的胃癌與老年患者的胃癌比較，可以發(fā)現(xiàn)有特殊的分子機(jī)制與腫瘤早期啟動(dòng)相關(guān)。微衛(wèi)星是短串連DNA重復(fù)序列，普遍存在于哺乳動(dòng)物的基因中。二、三、四個(gè)核酸重復(fù)序列存在于一半以上的人基因中BECKMANANDWEBER,1992。串連的DCDAN尤其豐富。每個(gè)位點(diǎn)重復(fù)的數(shù)目不同，如微衛(wèi)星不穩(wěn)定性（MSI），與人類(lèi)不同的疾病相關(guān)，包括腫瘤SPEICHER,1995。微衛(wèi)星序列的多態(tài)性也很明顯。由于重復(fù)數(shù)目不同引起的多態(tài)性對(duì)判斷基因的變化很有用，如雜和性缺失（LOH）。本研究中，我們檢測(cè)了5個(gè)染色體基因座，在一般人群的胃癌患者和小于40歲的胃癌患者中常在其中發(fā)現(xiàn)MSI和/或LOHRHYUETAL,1994CHONGETAL,1994NAGELETAL,1995TAMURAETAL,1995LINETAL,1995SERUCAETAL,1995BUONSANTIETAL，1997。并對(duì)MSI和/或LOH發(fā)生的頻率和其與其他臨床病理數(shù)據(jù)的聯(lián)系進(jìn)行了討論。材料和方法患者從具有可比性胃癌證據(jù)的多家意大利醫(yī)院中收集了102例小于40歲（平均年齡35歲；范圍16～40）的胃癌患者的福爾馬林固定，石蠟包埋的組織塊。通過(guò)協(xié)作研究得到人口統(tǒng)計(jì)學(xué)和病理學(xué)資料，包括年齡、性別、腫瘤的位置和腫瘤的TNM分期BEAHRSANDMYERS,1983。腫瘤的位置分為胃竇、胃體和賁門(mén)。沒(méi)有癌超出胃食管接合部。根據(jù)LAURéN分型（1965），胃癌分為腸型和彌漫型。當(dāng)兩種類(lèi)型都有的時(shí)候，則根據(jù)最具代表性的組織學(xué)表現(xiàn)。胃炎（非萎縮性和萎縮性/化生）的分類(lèi)根據(jù)HOUSTONUPDATEDSYDNEY系統(tǒng)DIXONETAL,1996。所有的病例均由兩個(gè)作者共同分析MCANDMR）。DNA的提取腫瘤和鄰近的非瘤組織用顯微切割的方法從未染色的福爾馬林固定，石蠟包埋的切片中分離，進(jìn)行去石蠟作用、蛋白激酶K消化和DNA純化SHIAOETAL,1994。顯微切割的瘤組織至少包含50％的腫瘤細(xì)胞?？赡軙r(shí)，淋巴結(jié)作為對(duì)照的非瘤細(xì)胞。PCR選擇5個(gè)帶有CAN二核苷酸重復(fù)D2S119,D2S123,D5S409,IFNAANDD11S904的染色101MSI1ND,NOTDETERMINED2,NODETECTABLEMSIAND/ORLOHTABLETABLEIIIICOMPARISONCOMPARISONOFOFTHETHEFREQUENCYFREQUENCYOFOFMSIMSIAND/ORAND/ORLOHLOHBETWEENBETWEENYOUNGYOUNGTHISTHISSTUDYSTUDYANDANDELDERLYELDERLYPATIENTSPATIENTSREFERENCEREFERENCED2S119D2S119D2S123D2S123D5S409D5S409IFNAIFNAD11S904D11S904THISSTUDY1/9610/8702/9921/10119/1009RHYUETAL199411/522115/5229NDND9/5217CHONGETAL1994ND117/7523NDNDNDNAGELETAL1995ND7/1937NDNDNDTAMURAETAL1995ND3/23137/23306/2326NDLINETAL1995ND16/5927NDNDNDSERUCAETAL1995NDNDNDND4/2417BUONSANTIETAL1997NDNDNDND2/8251ND,NOTDETERMINEDFIGUREFIGURE11ANALYSISOFMSIAND/ORLOHATTHED11S904LOCUSUSINGANONRADIOACTIVEMETHODN,NORMALC,CANCER

簡(jiǎn)介：CYTOKINEDRIVENREGULATIONOFNKCELLFUNCTIONSINTUMORIMMUNITYROLEOFTHEMICANKG2DSYSTEMNORBERTOWZWIRNER,MERCEDESBFUERTES,MARI′AVICTORIAGIRART,CAROLINAIDOMAICA,LUCASEROSSILABORATORIODEINMUNOGENE′TICA,HOSPITALDECLI′N(xiāo)ICAS‘‘JOSE′DESANMARTI′N(xiāo)’’,ANDDEPARTAMENTODEMICROBIOLOGI′A,FACULTADDEMEDICINA,UNIVERSIDADDEBUENOSAIRES,BUENOSAIRES,ARGENTINAAVAILABLEONLINE26FEBRUARY2007ABSTRACTNATURALKILLERNKCELLSARECRITICALPLAYERSDURINGTUMORGROWTHCONTROLINIMMUNOCOMPETENTHOSTSTHESECELLSALSOESTABLISHACROSSTALKWITHDENDRITICCELLSDCSANDPROMOTEATH1MEDIATEDIMMUNITYNKG2DISAPIVOTALRECEPTORTHATDIRECTSTHETUMORICIDALACTIVITYOFNKCELLSTHROUGHTHERECOGNITIONOFAGROUPOFLIGANDSSUCHASMICAWIDELYEXPRESSEDONDIFFERENTTUMORSHEREWEWILLREVIEWTHEMOSTIMPORTANTTUMORIMMUNEESCAPEMECHANISMSTHATCOMPROMISETHEFUNCTIONALITYOFNKG2DANDITSCOGNATELIGANDS,INCLUDINGTGFBSECRETION,TUMORSHEDDINGOFSOLUBLEMICA,ANDADDITIONALMECHANISMSTHATCOMPROMISETHETUMORICIDALACTIVITYOFNKG2DEXPRESSINGCELLSSUCHMECHANISMSMAYALSODAMPENTHECROSSTALKBETWEENNKCELLSANDDCSDURINGTHEANTITUMORIMMUNERESPONSESRECENTKNOWLEDGEMAYLEADTOINNOVATIVEAPPROACHESTOPROMOTEEFFICIENTNKCELLMEDIATEDANTITUMORIMMUNERESPONSES2007ELSEVIERLTDALLRIGHTSRESERVEDKEYWORDSMHCNKG2DNKCELLSMICATUMOR1INTRODUCTIONTUMORTRANSFORMATIONANDGROWTHISAMULTISTEPPROCESSTHATINVOLVESTHEACCUMULATIONOFMUTATIONSANDRESULTSINAGENETICINSTABILITY,LOSSOFCELLCYCLECONTROL,RESISTANCETOAPOPTOSIS,UNLIMITEDSELFRENEWALCAPACITYANDTHESELECTIONOFTUMORVARIANTSWITHTHEABILITYTOINVADELOCALANDDISTANTTISSUESHOWEVER,INIMMUNOCOMPETENTHOSTSTUMORSAREFORCEDTOGROWUNDERTHEPERMANENTPRESSUREOFANIMMUNESYSTEMTHATIMPOSESANIMMUNOLOGICALPRESSURETHISOBSERVATIONHASLEDTOTHEPOSTULATIONOFTHEIMMUNOSURVEILLANCEHYPOTHESISCURRENTLY,WEKNOWTHATMANYIMMUNEMEDIATEDCELLDESTRUCTIONMECHANISMSAREACTIVATEDTOELIMINATETUMORCELLSTHEPROGRESSMADEDURINGTHELASTTWODECADESINTHEAREAOFCELLULARANDMOLECULARIMMUNOLOGYANDONCOLOGYHASGREATLYCONTRIBUTEDTOADEEPERKNOWLEDGEABOUTTHETUMORHOSTRELATIONSHIPNEWIDEASHAVEBEENPROPOSEDTOEXPLAINTHECOMPLEXNATUREOFTHEEFFECTOFTHEIMMUNESYSTEMONTHETUMORCELLSANDTHEMECHANISMSDEVELOPEDBYTUMORSTOESCAPEDIFFERENTIMMUNEEFFECTORMECHANISMSALTHOUGHNOTMUTUALLYEXCLUSIVE,TWOMAINLINESOFTHINKINGWEREPOSTULATED1,2INTHEFIRSTCASE,ITWASPROPOSEDTHATTUMORGROWTHISACONSEQUENCEOFANIMMUNOEDITINGPROCESSACHIEVEDBYTHEIMMUNESYSTEMONTUMORCELLS1ACCORDINGLY,TUMORGROWTHANDMETASTASISINIMMUNOCOMPETENTHOSTSISACONSEQUENCEOFTHREESTAGESTHE‘‘THREEES’’OFIMMUNOEDITINGFIRST,THEIMMUNESYSTEMACHIEVESELIMINATIONOFSUSCEPTIBLETUMORCELLSIMMUNOSURVEILLANCESECONDLY,EQUILIBRIUMBETWEENTHEIMMUNESYSTEMANDTHESURVIVINGRESISTANTTUMORCELLSISREACHED,THUSSCULPTINGTHETUMORPHENOTYPEFINALLY,SURVIVINGTUMORCELLSENTERTHETUMORESCAPEPHASETHATISOFTENACCOMPANIEDBYTHEESTABLISHMENTOFMETASTASISOTHERAUTHORSHAVEPROPOSEDTHATTUMORSGROWWWWELSEVIERCOM/LOCATE/CYTOGFRCYTOKINEFAX541159508758EMAILADDRESSNWZSINECTISCOMARNWZWIRNER13596101/–SEEFRONTMATTER2007ELSEVIERLTDALLRIGHTSRESERVEDDOI101016/JCYTOGFR200701013THEABILITYOFNKG2DENGAGEMENTALONETOTRIGGERIFNGSECRETIONHASBEENQUESTIONEDBYTHEOBSERVATIONTHATENGAGEMENTOFTHISRECEPTORBYSOMESOLIDPHASEIMMOBILIZEDNKG2DSPECIFICMABSCOULDELICITCYTOTOXICGRANULERELEASEANDTARGETCELLKILLINGBUTNOTIFNGSECRETION13,16,19,23INSOMECASES,THISDIFFERENTIALRESPONSEHASBEENATTRIBUTEDTOADIFFERENTIALSPLICINGOFNKG2DINMOUSEBUTNOTHUMANNKCELLSANDTOADIFFERENTIALASSOCIATIONWITHTHEDAP10ANDDAP12ADAPTERPROTEINS24,25HOWEVER,RECENTEXPERIMENTALEVIDENCEINDICATESTHATMOUSENKG2DASSOCIATESWITHBOTHADAPTERPROTEINSINNKCELLSTOTRIGGERANACTIVATIONSIGNAL26INSOMECASES,THEDISCREPANCYINTHEABILITYOFNKG2DTOPROMOTEIFNGSECRETIONMIGHTBEDUETOTHEUSEOFSOLIDPHASEIMMOBILIZEDMABSAGAINSTNKG2DSINCEINTHESEEXPERIMENTS,IFNGSECRETIONWASINDUCEDBYENGAGEMENTOFNKG2DWITHSOLIDPHASEIMMOBILIZEDCHIMERICMOLECULESTHATRESEMBLENKG2DLS,SUCHASMICAFCANDULBP1FC16INADDITION,ITISLIKELYTHATINORDERTOTRIGGERIFNGSECRETIONTHROUGHNKG2D,NKCELLSREQUIRETHECOENGAGEMENTOFOTHERRECEPTORS12,13,23THEREFORE,INTERPRETATIONOFTHERESULTSOBTAINEDUPONSTIMULATIONOFNKCELLSTHROUGHNKG2DDURINGTHEINITIATIONOFCYTOTOXICITYANDCYTOKINEPRODUCTIONSHOULDBECAUTIOUSCONSIDERINGTHATTHEDISTINCTOUTCOMESDEPENDONTHECELLTYPE,ACTIVATIONSTATEOFTHECELLS,SPECIESANALYZEDHUMANORMOUSEANDTHESPECIFICLIGANDBEINGTESTEDTWOPOPULATIONSOFHUMANNKCELLSHAVEBEENIDENTIFIEDTHEMAJORPOPULATIONABOUT90ISCYTOTOXICANDSHOWSACD56DIMCD16PHENOTYPE,WHEREASTHEREMAINING10OFTHENKCELLSAREASOURCEOFIMMUNOREGULATORYCYTOKINESANDPRESENTACD56BRIGHTCD16DIMORCD56BRIGHTCD16?PHENOTYPE27ALTHOUGHNKG2DEXPRESSIONSEEMSTOBESLIGHTLYHIGHERINCD56DIMTHANINCD56BRIGHTNKCELLS,THESEDIFFERENCESDONOTAPPEARTOBEINVOLVEDINTHEDIFFERENTIALIFNGPRODUCTIONANDPROLIFERATIONOFTHESENKCELLSUBSETSUPONACTIVATIONBYDENDRITICCELLSDCS28INHUMANSANDMICE,NKG2DISPROMISCUOUSINTERMSOFLIGANDRECOGNITIONHUMANNKG2DLIGANDSNKG2DLSARETHEMHCCLASSIRELATEDCHAINGENESAANDBMICAANDMICB15,ANDAGROUPOFGLYCOSYLPHOSPHATIDYLINOSITOLGPIBOUNDSURFACEMOLECULESCALLEDUL16BINDINGPROTEINULBP1,2,3AND418,29MICEHAVEADIFFERENTSETOFNKG2DLS,WHICHCOMPRISETHERETINOICACIDEARLYINDUCIBLEGENERAE1FAMILYAGROUPOFGPIANCHORED,CELLSURFACEGLYCOPROTEIN,THEMINORHISTOCOMPATIBILITYANTIGENH60ANINTEGRALTRANSMEMBRANEPROTEINS,ANDTHEMURINEUL16BINDINGPROTEINLIKETRANSCRIPT1MULT1,ALLOFWHICHEXHIBITLOWSEQUENCEHOMOLOGYWITHTHEIRHUMANCOUNTERPARTS18,29HOWEVER,HUMANNKG2DBINDSMOUSENKG2DLSANDMOUSENKG2DCANRECOGNIZESOMEHUMANNKG2DLS,MOSTLIKELYREFLECTINGASELECTIVEADVANTAGEOFPRESERVINGTHENKG2DRECEPTORINBOTHSPECIESTHEMICAANDMICBGENESWEREDESCRIBEDIN1994ASAGROUPOFGENESTHATMAPWITHINTHEMHCCLASSIREGION,BUTEXHIBITALOWHOMOLOGYWITHTHECLASSICALMHCCLASSIGENES30,31EXPRESSIONOFMICAHASBEENOBSERVEDINHUMANEPITHELIALANDFIBROBLASTCELLLINES32,33,INPRIMARYCULTURESOFENDOTHELIALCELLSANDFIBROBLASTS34,TUMORSOFDIFFERENTHISTOTYPES12,35,THYMICMEDULLA36,ANDGASTROINTESTINALEPITHELIUM32EXPRESSIONOFMICAWASALSOOBSERVEDINCULTUREDHUMANKERATINOCYTES37,BUTTHISEXPRESSIONWASNOTOBSERVEDONTHECELLSURFACE34ALSO,ACTIVATEDCD4ANDCD8TCELLSWERESHOWNTOEXPRESSMICA38–40,ALTHOUGHLOWLEVELSOFTHISNKG2DLAREEXPRESSEDONTHECELLSURFACE41THEGENERALIZEDEXPRESSIONOFMICAOBSERVEDINMANYTUMORS35,42–46SUGGESTSTHATITSEXPRESSIONISACONSEQUENCEOFTHEMALIGNANTNEOTRANSFORMATIONHOWEVER,RECENTEVIDENCEINDICATESTHATEXPRESSIONOFMICAANDOTHERNKG2DLSISINDUCEDBYTHEDNADAMAGEPATHWAYINRESPONSETOGENOTOXICINSULTS,WHICHISACRITICALSTEPDURINGTHENEOTRANSFORMATION47HOWEVER,ALTHOUGHTHETUMORSUPPRESSORP53ANTIONCOGENHASBEENINVOLVEDINTHEPROTECTIONAGAINSTMALIGNTRANSFORMATION48,P53DOESNOTAPPEARTOBEINVOLVEDINUPREGULATIONOFMICAANDSUBSEQUENTACQUISITIONOFSUSCEPTIBILITYTONKG2DMEDIATEDCYTOTOXICITYALSO,EXPRESSIONOFMICAINACTIVATEDTCELLSINDICATESTHATTHISNKG2DLCANALSOBEINDUCEDBYCELLACTIVATIONCOINCIDENTALLY,CELLACTIVATIONANDNEOTRANSFORMATIONARETWOCELLULARPROCESSESREGULATEDBYNFKB49EXPERIMENTALEVIDENCEACCUMULATEDDURINGTHELASTYEARSINDICATESTHATTHEMICANKG2DSYSTEMPARTICIPATESINDIFFERENTASPECTSOFTHEIMMUNERESPONSE15,32,50–56,BUTTHATTHISINTERACTIONISPARTICULARLYIMPORTANTDURINGTUMORIMMUNITY42,43,57–60THEANTITUMOREFFECTORMECHANISMSUSEDBYNKCELLSCOMPRISETHECYTOTOXICITYAGAINSTSUSCEPTIBLETARGETCELLSANDTHESECRETIONOFIFNGANDOTHERPROINFLAMMATORYCYTOKINESTHEMECHANISMSOFNKCELLMEDIATEDCYTOTOXICITYHAVEBEENREVIEWEDELSEWHERE61,62INMOSTCASES,NKCELLSLYSESUSCEPTIBLETARGETCELLSSECRETINGCYTOTOXICGRANULESTHATCONTAINGRANZYMESANDPERFORINHOWEVER,STUDIESINPERFORIN,GRANZYMESORNKCELLDEFICIENTMICEANDSTUDIESWITHHUMANCELLSREVEALEDTHATNKCELLSCANALSOLYSETARGETCELLSBYDEATHRECEPTORMEDIATEDCYTOTOXICITYSUCHASTHEFASFASLSYSTEMANDTHETNFRELATEDAPOPTOSISINDUCINGLIGANDTRAIL63INMICE,NKCELLPERFORINMEDIATEDCYTOTOXICITY,BUTNOTPRODUCTIONOFIFNGWASCRITICALFORTHEREJECTIONOFRAE1BEXPRESSINGTUMORCELLSINVIVO22ANDFORTHEESTABLISHMENTOFTUMORMETASTASIS64,SUGGESTINGTHATPERFORINGRANZYMESECRETIONISTHEMAJOREFFECTORMECHANISMSOFTHENKG2DDEPENDENT,NKCELLMEDIATEDANTITUMORRESPONSETHEREFORE,CURRENTEVIDENCEINDICATESTHATTHEMECHANISMSTHROUGHWHICHNKG2DTRIGGERSNKCELLMEDIATEDCYTOTOXICITYRELIESONTHEGRANULESECRETIONPATHWAY,BUTITREMAINSANOPENQUESTIONWHETHERNKG2DENGAGEMENTCANALSOELICITFASANDTRAILMEDIATEDAPOPTOSISOFSUSCEPTIBLETARGETSTHEMOLECULARDISSECTIONOFRECEPTORSANDEFFECTORMOLECULESINVOLVEDINNKCELLMEDIATEDTUMORCELLDESTRUCTIONMAYLEADTOTHENWZWIRNERETAL/CYTOKINEGROWTHFACTORREVIEWS182007159–170161

簡(jiǎn)介：中文中文9169字出處出處ZWIRNERN,FUERTESM,GIRARTM,ETALCYTOKINEDRIVENREGULATIONOFNKCELLFUNCTIONSINTUMORIMMUNITYROLEOFTHEMICANKG2DSYSTEMJCYTOKINEGROWTHFACTORREVIEWS,2007,181215970腫瘤免疫中腫瘤免疫中NK細(xì)胞功能的細(xì)胞因子驅(qū)使調(diào)節(jié)細(xì)胞功能的細(xì)胞因子驅(qū)使調(diào)節(jié)MICANKG2D系統(tǒng)的作用系統(tǒng)的作用NZWIRNER，MFUERTES，MGIRART，CDOMAICA，LROSSI摘要NK細(xì)胞在免疫活性宿主的腫瘤生長(zhǎng)調(diào)控中起著關(guān)鍵作用。NK細(xì)胞還和樹(shù)突細(xì)胞相互，并且促進(jìn)了TH1介導(dǎo)的免疫活動(dòng)。NKG2D是指導(dǎo)NK細(xì)胞殺滅腫瘤作用的樞紐受體，它通過(guò)識(shí)別如MICA這樣的廣泛表達(dá)于不同腫瘤內(nèi)的一組配體發(fā)揮作用。這里我們將論述最重要的腫瘤免疫逃逸機(jī)制，即NKG2D的功能和它的相關(guān)配體，包括TGFB分泌物，腫瘤的可溶性MICA脫落物，及其他機(jī)制即NKG2D表達(dá)細(xì)胞的殺滅腫瘤作用。這些機(jī)制可能緩解了NK細(xì)胞和樹(shù)突細(xì)胞在抗腫瘤免疫反應(yīng)中的相互作用。最近的研究可能產(chǎn)生一種新的方法來(lái)促進(jìn)有效的NK細(xì)胞介導(dǎo)的抗腫瘤免疫反應(yīng)。關(guān)鍵詞MHC；NKG2D；NK細(xì)胞；MICA；腫瘤11序論序論腫瘤轉(zhuǎn)化和生長(zhǎng)是一個(gè)多步驟過(guò)程，包括突變的積累和導(dǎo)致遺傳不穩(wěn)定性，細(xì)胞周期調(diào)控的喪失，抗凋亡，無(wú)限自我增殖能力和具有入侵局部和遠(yuǎn)處組織能力的腫瘤突變體的選擇。盡管如此，在免疫活性宿主中，腫瘤一直在一個(gè)免疫系統(tǒng)給予的免疫壓力下生長(zhǎng)。這種觀點(diǎn)已經(jīng)引出免疫監(jiān)視假說(shuō)。如今，我們知道有許多免疫介導(dǎo)的細(xì)胞破壞機(jī)制被激活來(lái)消滅腫瘤細(xì)胞。在過(guò)去二十年中，細(xì)胞和分子免疫學(xué)及腫瘤學(xué)領(lǐng)域中的進(jìn)展已經(jīng)很大程度地促進(jìn)了腫瘤和宿主之間聯(lián)系的深入研究。已經(jīng)有新的觀點(diǎn)被提出來(lái)解釋免疫系統(tǒng)對(duì)腫瘤細(xì)胞的作用的復(fù)雜本質(zhì)以及腫瘤逃避不同免疫效應(yīng)機(jī)制的機(jī)理。盡管不是互相排斥，這種觀點(diǎn)的兩條主要思路依然是假說(shuō)。第一種思路提出腫瘤生長(zhǎng)是免疫系統(tǒng)對(duì)腫瘤細(xì)胞的一個(gè)免疫編輯過(guò)程的結(jié)果。而且，腫瘤在免疫活性宿主的生長(zhǎng)和轉(zhuǎn)移是三個(gè)步驟的結(jié)果。第一步，免疫系統(tǒng)實(shí)現(xiàn)對(duì)敏感腫瘤細(xì)胞的消除（免疫監(jiān)視）。第二步，免疫系統(tǒng)和存活腫瘤細(xì)胞之間達(dá)到平衡，從而腫瘤表型出現(xiàn)。最后，存活腫瘤細(xì)胞進(jìn)入腫瘤逃逸階段，該階段經(jīng)常伴隨有腫瘤轉(zhuǎn)移。其他專(zhuān)家也有提出腫瘤在活性免疫系統(tǒng)不斷給予的固定選擇壓力下生長(zhǎng)。這種觀點(diǎn)認(rèn)為，只有那些對(duì)免疫系統(tǒng)的免疫破壞和攻擊耐受的腫瘤細(xì)胞才會(huì)成為過(guò)度生長(zhǎng)的腫瘤細(xì)胞。這些特性共同賦予腫瘤不受控制生長(zhǎng)和轉(zhuǎn)移的潛力。盡管如此，腫瘤生長(zhǎng)其實(shí)是一個(gè)更為復(fù)雜的過(guò)程，因?yàn)樵谀[瘤生長(zhǎng)中，一系列血管生成和抗血管生成因子也參與形成腫瘤表型。；另外，細(xì)胞外基質(zhì)在腫瘤生長(zhǎng)中的重要作用最近也已經(jīng)被認(rèn)識(shí)到。不管有多少作用因素，無(wú)可爭(zhēng)議的是，免疫系統(tǒng)對(duì)腫瘤生長(zhǎng)的調(diào)控很關(guān)鍵。細(xì)胞毒性細(xì)胞，特別是NK細(xì)胞及致炎細(xì)胞因子促進(jìn)了免疫抗腫瘤作用。在這篇綜述中，我們將集中于腫瘤免疫中NK細(xì)胞功能的細(xì)胞因子驅(qū)使調(diào)節(jié)研究的新方面，特別是MICANKG2D系統(tǒng)在腫瘤逃逸中的作用。關(guān)于T淋巴細(xì)胞在腫瘤免疫中的作用以及細(xì)胞因子如何參與形成這些機(jī)制，將在另一篇優(yōu)秀的綜述中論述。2NK細(xì)胞，受體和配體細(xì)胞，受體和配體在過(guò)去幾十年的研究中已經(jīng)明確NK細(xì)胞呈現(xiàn)細(xì)胞毒性，分泌致炎細(xì)胞因子如IFNG,TNFA,TNFB,IL13,IL10ANDGMCSF與敏感腫瘤靶細(xì)胞接觸。例如，活體內(nèi)NK細(xì)胞缺失會(huì)導(dǎo)致腫瘤生長(zhǎng)的不受控制。而且，化學(xué)方法誘發(fā)的腫瘤在NK細(xì)胞缺陷的小鼠體內(nèi)被迅速排斥，而移植入NK細(xì)胞充分的小鼠體內(nèi)則腫瘤發(fā)展平衡。最近，NK細(xì)胞還被證明參與形成小鼠和人類(lèi)的適應(yīng)性免疫反應(yīng)。NK細(xì)胞對(duì)靶細(xì)胞的識(shí)別是通過(guò)種系密碼，細(xì)胞表面抑制和活化受體實(shí)現(xiàn)的。我們知和MICB，以及一組叫UL16結(jié)合蛋白1，2，3，4的糖基磷脂酰肌醇錨定表面分子。小鼠有一組不同的NKG2D配體，其中包含了維甲酸早期誘導(dǎo)基因I家族，次要組織相容性抗原H60，及小鼠UL16結(jié)合蛋白類(lèi)轉(zhuǎn)錄子。盡管如此，人類(lèi)NKG2D能結(jié)合小鼠的NKG2DLS，而小鼠的NKG2D也能識(shí)別一些人類(lèi)NKG2DLS，這一現(xiàn)象最有可能反映的是NKG2D受體在人類(lèi)和小鼠中的選擇性保存優(yōu)勢(shì)，MICA和MICB基因在1994年被描述為一組基因，定位于MHC類(lèi)別I區(qū)域，但和經(jīng)典MHC類(lèi)別I基因呈現(xiàn)低同源性。MICA的表達(dá)已經(jīng)在人類(lèi)上皮和成纖維細(xì)胞系中發(fā)現(xiàn)，首先是在上皮細(xì)胞和成纖維細(xì)胞，不同組織分型的腫瘤，胸腺髓質(zhì)，胃腸上皮組織的培養(yǎng)系中發(fā)現(xiàn)的。MICA的表達(dá)也在人工培養(yǎng)的人類(lèi)角質(zhì)化細(xì)胞中發(fā)現(xiàn)，但是這種表達(dá)不是發(fā)生在細(xì)胞表面。而且，活化的CD4和CD8T細(xì)胞也被證明表達(dá)MICA，盡管低水平的這種NKG2DL是表達(dá)在細(xì)胞表面。MICA在許多腫瘤上發(fā)現(xiàn)有表達(dá)，這表明它的表達(dá)是腫瘤惡性轉(zhuǎn)化的結(jié)果。盡管如此，最近的證據(jù)表明MICA和其他NKG2DLS的表達(dá)是適應(yīng)遺傳毒性損傷的DNA破壞途徑導(dǎo)致的，這是轉(zhuǎn)化中的關(guān)鍵步驟。雖然抑癌基因P53參與保護(hù)對(duì)抗惡性轉(zhuǎn)化，P53并不涉及MICA的上調(diào)及隨后NKG2D介導(dǎo)的細(xì)胞毒性敏感性的獲得。另外，MICA在活化T細(xì)胞的表達(dá)表明NKG2DL也能由細(xì)胞活化導(dǎo)致。同時(shí)，細(xì)胞活化和轉(zhuǎn)化是兩個(gè)受NFKB調(diào)控的細(xì)胞過(guò)程。去年的實(shí)驗(yàn)證據(jù)表明MICANKG2D系統(tǒng)參與免疫反應(yīng)的不同方面，但是這種相互作用在腫瘤免疫中尤其重要。NK細(xì)胞的抗腫瘤效應(yīng)物機(jī)制包含對(duì)可疑靶細(xì)胞的細(xì)胞毒性，IFN的分泌和其他致炎細(xì)胞因子。NK細(xì)胞介導(dǎo)的細(xì)胞毒性機(jī)制已經(jīng)在別處進(jìn)行了綜述。在大多數(shù)實(shí)驗(yàn)中，NK細(xì)胞溶解敏感靶細(xì)胞分泌細(xì)胞毒性顆粒，其中包含粒酶和穿孔素。盡管如此，對(duì)于穿孔素，粒酶或者NK細(xì)胞缺陷小鼠和人類(lèi)細(xì)胞的研究表明NK細(xì)胞也能通過(guò)死亡受體介導(dǎo)（TRAIL）的細(xì)胞毒性溶解靶細(xì)胞。在小鼠體內(nèi)，NK細(xì)胞穿孔素介導(dǎo)的細(xì)胞毒性，但不是IFN的產(chǎn)生對(duì)于體內(nèi)RAE1B表達(dá)的腫瘤細(xì)胞的排斥和腫瘤轉(zhuǎn)移的建議是置關(guān)重要的，這表明穿孔素粒酶分泌是NKG2D依賴(lài)性的，NK細(xì)胞介導(dǎo)的抗腫瘤反應(yīng)的主要效應(yīng)物機(jī)制。因此，當(dāng)前證據(jù)表明，NKG2D啟動(dòng)NK細(xì)胞介導(dǎo)的細(xì)胞毒性機(jī)制依賴(lài)于顆粒分泌途徑，但關(guān)于NKG2D配對(duì)是否也能引起FAS和TRAIL介導(dǎo)的可疑靶細(xì)胞的凋亡依然是個(gè)疑問(wèn)。對(duì)于受體和效應(yīng)分子的分子解析涉及NK細(xì)胞介導(dǎo)的腫瘤細(xì)胞破壞，可能促進(jìn)抑制腫瘤生長(zhǎng)和轉(zhuǎn)移的新方法的發(fā)展。3NK3NK細(xì)胞的細(xì)胞因子刺激及和樹(shù)突細(xì)胞的相互細(xì)胞的細(xì)胞因子刺激及和樹(shù)突細(xì)胞的相互NK細(xì)胞的分化和刺激是受巨噬細(xì)胞和樹(shù)突細(xì)胞如IL2，IL12，IL15，IL18，IL21，IL23和IFNA/B分泌的不同細(xì)胞因子的控制的。這些致炎細(xì)胞因子有差別地促進(jìn)NK細(xì)胞活化標(biāo)記的表達(dá)，IFN的分泌和/或啟動(dòng)NK細(xì)胞介導(dǎo)的細(xì)胞毒性，促進(jìn)他們的腫瘤殺傷功能。特別是，樹(shù)突細(xì)胞通過(guò)依賴(lài)于可溶性因子和細(xì)胞細(xì)胞連接的相互作用的建立，在活化NK細(xì)胞中發(fā)揮了關(guān)鍵的作用，在小鼠體內(nèi)引出了強(qiáng)烈的抗腫瘤免疫反應(yīng)。盡管一種類(lèi)似的相互作用也被證明發(fā)生在人類(lèi)DC和NK細(xì)胞之間，但可以觀察到的是不同的樹(shù)突細(xì)胞亞群促進(jìn)NK細(xì)胞活化，增殖，發(fā)揮細(xì)胞毒性的能力也不同。DC刺激NK細(xì)胞的能力不僅依賴(lài)于IL12，還依賴(lài)于其他細(xì)胞因子比如IFNA/BANDIL18,ANDCELL–CELL相互作用在人類(lèi)中，涉及DCNK細(xì)胞相互作用的主要的NK細(xì)胞受體是NKP30，該受體導(dǎo)致了不成熟DC的殺傷而不是成熟DC。這種差別抵抗的潛在機(jī)制并沒(méi)有被完全弄清楚，但它可能和成熟DC比非成熟DC表達(dá)更高水平的MHCI型分子有關(guān)。而且，一些證據(jù)表明NKP46和NKP44，NKG2D在DC和NK細(xì)胞相互作用中有少量參與，盡管其他也可能無(wú)法證明NKP46和NKG2D的涉及。NKG2D確實(shí)可能涉及這種相互作用，因?yàn)橐恍┛蒲腥藛T報(bào)道，MICA在DC的表達(dá)上調(diào)導(dǎo)致IL15或者IFN或者微生物組成的成熟。而且，因?yàn)镈C能被相關(guān)的有害復(fù)合物如TOLL類(lèi)受體或TLRS促效藥刺激，以及考慮到最近出現(xiàn)的證據(jù)表明甚至連NK細(xì)胞也表達(dá)功能性TLRS。在DC和NK細(xì)

簡(jiǎn)介：REVIEWARTICLETHEIMPACTOFGLYCAEMICCONTROLONOUTCOMESINPATIENTSWITHENDSTAGERENALDISEASEANDTYPE2DIABETESSOPHIAZOUNGAS,1,2PETERGKERR,3MICHELLELUI1ANDHELENAJTEEDE1,21DIABETESCLINICALSERVICESANDRESEARCHUNITAND3DEPARTMENTOFNEPHROLOGY,MONASHUNIVERSITY,MONASHMEDICALCENTRE,AND2JEANHAILESRESEARCHGROUP,MONASHINSTITUTEOFHEALTHSERVICESRESEARCH,MONASHMEDICALCENTRE,CLAYTON,VICTORIA,AUSTRALIASUMMARYINAUSTRALIAANDNEWZEALANDTHEPREVALENCEANDINCIDENCEOFENDSTAGERENALDISEASEESRDHASINCREASEDINAUSTRALIAALONETHEFINANCIALBURDENISESTIMATEDTOREACH500MILLIONBY2007DATAFROMTHENATIONALCHRONICKIDNEYDISEASESTRATEGYWORKSHOPREPORT2005THELEADINGCAUSEOFESRDINAUSTRALIAANDNEWZEALAND,ANDTHROUGHOUTTHEDEVELOPEDWORLD,ISTYPE2DIABETES,HAVINGOVERTAKENGLOMERULONEPHRITISIN20041TODATE,MANAGEMENTOFPATIENTSWITHDIABETESANDESRDHASBEEN,ACCORDINGTOGUIDELINES,GIVENFORPATIENTSWITHOUTESRDTHISCOMMENTARYRAISESTHREEIMPORTANTEMERGINGCONCERNSINTHECLINICALCAREOFTHESEPATIENTSITHELACKOFRELIABLETOOLSTOMEASUREGLYCAEMICCONTROLIILIMITATIONSOFTHECURRENTDATASETSUPPORTINGARELATIONSHIPBETWEENOUTCOMEANDGLYCAEMICCONTROLINESRDANDIIILACKOFSTUDIESEXAMININGTHEEFFECTOFINTENSIVEDIABETESCAREANDGLUCOSECONTROLINPATIENTSWITHESRDKEYWORDSENDSTAGERENALDISEASE,GLYCAEMICCONTROL,OUTCOMES,TYPE2DIABETESTHEEMERGINGPROBLEMOFTYPE2DIABETESANDESRDINAUSTRALIAANDNEWZEALAND,APPROXIMATELY740PEOPLEPERMILLIONPOPULATIONRECEIVERENALREPLACEMENTTHERAPYANDOFTHESE420PEOPLEPERMILLIONREQUIREDIALYSISTHERAPY2OVERTIMEASTEADYINCREASEINTHESEPREVALENCERATESHASBEENOBSERVEDFIG12OFTHOSEREQUIRINGRENALREPLACEMENTTHERAPY,ABOUTONETHIRDARENEWPATIENTSENTERINGADIALYSISPROGRAMMETHEMOSTCOMMONCAUSEOFESRDINAUSTRALIAANDNEWZEALANDISDIABETESIN2005,DIABETICNEPHROPATHYACCOUNTEDFOR32–41OFALLNEWPATIENTSENTERINGADIALYSISPROGRAMME1SIMILARLY,OFALLPATIENTSREQUIRINGRENALREPLACEMENTTHERAPY,42AND46HADDIABETES,RESPECTIVELYTHEMAJORITYOFTHESEPATIENTSAPPROXIMATELY90HAVETYPE2DIABETESFIG21OFTHOSEABOUTHALFARERECEIVINGINSULINTHERAPYSURVIVALOFTHEAVERAGEDIALYSISPATIENTISPOORTHEANNUALMORTALITYRATEFORTHEAUSTRALIANANDNEWZEALANDDIALYSISPOPULATIONIS145AND164DEATHSPER100PATIENTYEARS,RESPECTIVELY3ALARGEPROPORTIONOFTHIS,APPROXIMATELY65,ISATTRIBUTEDTOCARDIOVASCULARDISEASECVDANDINFECTIONANZDATAREGISTRYREPORTOF2005CAUSEOFDEATH,AUSTRALIA49CVDAND13INFECTIONNEWZEALAND49CVDAND15INFECTION3FURTHERMORE,THEDEATHRATEDUETOCVDIS10TO100FOLDGREATERTHANTHATFORAGEMATCHEDPOPULATIONSFIG33,4OVERTHELASTFIVEDECADES,MORTALITYDUETOCVDINTHEGENERALPOPULATIONHASDECLINEDBY505ANDINCIDENTCARDIOVASCULAREVENTSHAVEALSODECLINEDINPEOPLEWITHDIABETESNOTCOMPLICATEDBYESRD6ASREPORTEDBYANZDATA,3,7INTHEESRDPOPULATION,MORTALITYDUETOCVDREMAINSUNCHANGEDANDUNAFFECTEDBYMAJORADVANCESINMEDICALTHERAPYCVDMORTALITY1993AND2005485AND49,RESPECTIVELYINOUROWN5YEARPROSPECTIVESTUDYOFINCIDENTCARDIOVASCULAREVENTSINPATIENTSWITHESRD,THOSEWITHDIABETESHADATWOFOLDGREATERRISKOFEVENTSANDTHISRISKWASNOTABROGATEDBYADJUSTMENTFORAGE,GENDER,BLOODPRESSURE,PASTHISTORYOFCVD,SMOKINGSTATUSANDTREATMENTWITHLIPIDLOWERINGTHERAPYORASPIRINUNADJUSTEDHAZARDRATIO241,P0001,95CI183–318ADJUSTEDHAZARDRATIO186,P0001,95CI138–252UNPUBLISHEDDATA,FIG4CORRESPONDENCEDRSOPHIAZOUNGAS,DIABETESCLINICALSERVICESANDRESEARCHUNIT,SOUTHERNHEALTH,MONASHMEDICALCENTRE,246CLAYTONROAD,CLAYTON,VIC3168,AUSTRALIAEMAILSOPHIAZOUNGASMEDMONASHEDUAUACCEPTEDFORPUBLICATION15OCTOBER2007?2007THEAUTHORSJOURNALCOMPILATION?2007ASIANPACIFICSOCIETYOFNEPHROLOGYNEPHROLOGY200813,124–127DOI101111/J14401797200700901XANAEMIA,BLOODTRANSFUSIONANDRECOMBINANTERYTHROPOIETINUSEMAYALLIMPACTONTHEACCURACYOFTHEHBA1CMEASUREMENTTOTHISEND,AJAPANESESTUDYHASRECENTLYREPORTEDTHATGLYCATEDALBUMINMAYPROVIDEASIGNIFICANTLYBETTERMEASUREOFGLYCAEMICCONTROLINDIABETICHDPATIENTSCOMPAREDWITHHBA1CBECAUSEOFTHEEFFECTSOFANAEMIAANDERYTHROPOIETINUSE22MOREOVER,ITISUNCLEARASTOATWHATPOINTACROSSTHEVARIOUSSTAGESOFCHRONICKIDNEYDISEASETHESEMETHODOLOGICALISSUESBECOMECLINICALLYRELEVANTASMOSTOFTHEEFFECTSOFURAEMIAWOULDBEEXPECTEDTOLOWERHBA1CESTIMATIONS,ITMAYALSOBENECESSARYTODEFINEADIFFERENT‘NORMALRANGE’FORESRDULTIMATELY,AVAILABLE000025050075100KAPLAN–MEIERSURVIVALPROBABILITY7255280DIABETES2431711060NODIABETESNUMBERATRISK0246FOLLOWUPTIMEYEARSFIG4KAPLAN–MEIERCARDIOVASCULARDISEASEFREESURVIVALINPATIENTSWITHENDSTAGERENALDISEASEESRDASCOMPAREDWITHTHOSEWITHESRDANDDIABETESUNPUBLISHEDDATAP0001NODIABETES––––––DIABETES?ANZDATAREGISTRYCOMORBIDCONDITIONSATENTRYTOPROGRAM2005NUMBEROFPATIENTSPATIENTSCOUNTRYCHRONICLUNGDISEASECORONARYARTERYDISEASEPERIPHERALVASCULARDISEASECEREBROVASCULARDISEASESMOKINGAUSTRALIA2210YES27612731333921824011CURRENT25411TYPEI864SUSPECTED7313315671346603FORMER90241IIINSREQ37017NO187385132360168476191086NEVER105448IINONINS46421NO129058NEWZEALAND436YES6114111256415399CURRENT7016TYPEI143SUSPECTED2465112256123FORMER17841IIINSREQ9923NO35180274633477938588NEVER18843IINONINS8620NO23754DIABETESINCLUDINGDIABETICNEPHROPATHYNNFIG2COMORBIDCONDITIONSATENTRYTODIALYSISPROGRAMME1000120406080100AGEYEARS0010102040620406080100MORTALITYPERYEARFIG3AGESPECIFICMORTALITYRATESOFPATIENTSREQUIRINGRENALREPLACEMENTTHERAPYASCOMPAREDWITHTHEGENERALPOPULATION32004MORTALITYRATESDIALYSISTRANSPLANT–––––AUSTPOPULATIONSZOUNGASETAL126?2007THEAUTHORSJOURNALCOMPILATION?2007ASIANPACIFICSOCIETYOFNEPHROLOGY

簡(jiǎn)介：THEEXPRESSIONOFCSRCGENEINTHECARCINOGENESISPROCESSOFHUMANCARDIAADENOCARCINOMAWANGXIUJIA,YUANSHULAN,XIAOLIN,WANGXUHUAANDWANGCHAOJUNPOBOX2345,BEIJING100023,CHINAWJG,1999DECEMBER56488491FAX861085381893WORLDJOURNALOFGASTROENTEROLOGYEMAILWJGWJGNETCOMWWWWJGNETCOMCOPYRIGHT?1999BYTHEWJGPRESSISSN10079327SUBJECTHEADINGSCSRCGENEEXPRESSIONPRODUCTPP60CSRCCARDIAADENOCARCINOMACARCINOGENESISNEOPLASMMETASTASISIMMUNOHISTOCHEMISTRYABSTRACTAIMTOINVESTIGATETHEACTIVATION,EXPRESSIONOFCSRCGENEANDITSROLEINTHECARCINOGENETICPROCESSOFHUMANCARDIAADENOCARCINOMACAMETHODSFIFTYSIXCASESOFCA,34CASESOFNORMAL,36CASESOFPROTIFERATIVEEPITHELIAADJACENTTOCARCINOMA,AND20CASESOFLYMPHNODEMETASTASESOFCAWERESTUDIEDFORPP60CSRC,THEEXPRESSIONPRODUCTOFCSRCGENEIMMUNOHISTOCHEMICALLYBYUSINGTHESPECIFICMONOCLONALANTIBODY,MAB327RESULTSTHEPOSITIVERATESOFPP60CSRCINTHENORMALEPITHELIA,PROTIFERATIVEEPITHELIA,CAANDLYMPHNODEMETASTASESWERE29410/34,94434/36,71440/56AND60012/20,RESPECTIVELY,AMONGTHEM,THEDIFFERENCESOFTHEPOSITIVERATESWERESTATISTICALLYSIGNIFICANTP001THEEXPRESSIONLEVELSOFPP60CSRCINCAANDPROLIFERATIVEEPITHELIAWERESIGNIFICANTLYHIGHERTHANTHATINTHENORMALEPITHELIAP001THEPP60CSRCPOSITIVERATESINTHEPAPILLARY,TUBULAR,POORLYDIFFERENTIATEDANDMUCOUSADENOCARCINOMAWERE7506/8,81818/22,50010/20AND10006/6,RESPECTIVELY,WHEREASTHOSEOFTUBULARANDMUCOUSADENOCARCINOMASWERESIGNIFICANTLYHIGHERTHANTHOSEOFPAPILLARYANDPOORLYDIFFERENTIATEDADENOCARCINOMASP005,ANDTHEPP60CSRCEXPRESSIONLEVELSOFTUBULARANDMUCOUSADENOCARCINOMASWEREALSOSIGNIFICANTLYHIGHERTHANTHOSEOFPAPILLARYANDPOORLYDIFFERENTIATEDADENOCARCINOMASP001CONCLUSIONTHEACTIVATIONANDEXPRESSIONOFCSRCGENEAREASSOCIATEDWITHTHEINITIATIONANDDEVELOPMENTOFHUMANCATHEPROTEINAMOUNTOFPP60CSRCINCREASEDDURINGTHEPROCESSOFCARCINOGENESISANDPP60CSRCEXPRESSIONISALSORELATEDTOLYMPHNODEMETASTASESINTRODUCTIONTHEREISAGENERALTENDENCYINGASTRICCANCERTHATTHEINCIDENCERATEOFCARDIAADENOCARCINOMACAISINCREASINGSTEADLY,ANDCANCEROFTHEDISTALSTOMACHISDECREASINGPROPORTIONATELYTHEBIOLOGICALANDEPIDEMIOLOGICALFEATURESOFCAAREDISTINCTFROMTHOSEOFTHEDISTALSTOMACH,ANDTHEUNDERLYINGCAUSEREMAINEDUNELUCIDATED13PP60CSRCISTHEPRODUCTOFCSRCGENEPOSSESSINGTHEACTIVITYOFTYROSINEKINASEINCREASEDEXPRESSIONOFCSRCGENEHADBEENREPORTEDINSOMEHUMANSARCOMAANDCANCERSOFBREAST4,ESOPHAGUS5,STOMACH6ANDCOLON7,ANDTHEACTIVATIONANDEXPRESSIONOFCSRCGENEMIGHTBEASSOCIATEDWITHTHEINITIATIONANDDEVELOPMENTOFSOMECANCERSOURPREVIOUSSTUDYSHOWEDTHEACTIVATIONANDEXPRESSIONOFCSRCGENEWASASSOCIATEDWITHTHEDEVELOPMENTANDDIFFERENTIATIONOFESOPHAGEALSQUAMOUSCELLCARCINOMAS8,WEBELIEVEDTHATSIMILARCHANGESMIGHTOCCURINCANCEROFCARDIA,THEREFORE,THEFOLLOWINGSTUDYWASCARRIEDOUTMATERIALSANDMETHODSSAMPLECOLLECTIONANDPROCESSINGALL56CASESOFCASAMPLESWERECOLLECTEDFROMTHECAPATIENTSSURGICALLYTREATEDINYANTINGINSTITUTEOFCANCERPREVENTIONOFSICHUANPROVINCEALLTISSUESPECIMENSWEREROUTINELYPROCESSED,FORMALINFIXEDANDPARAFFINEMBEDDED,ATLEAST2SERIALPARAFFINSECTIONSOF4ΜM6ΜMTHICKNESSWEREMADE,ONEWASSTAINEDWITHHEMATOXYLINANDEOSINHEANDTHEOTHERWASUSEDFORPP60CSRCPROTEINDETECTIONBYIMMUNOHISTOCHEMICALSTAININGREAGENTSTHEMONOCLONALANTIBODYMAB327MOUSEIGGWASKINDLYGIVENBYTHEMOLECULARPATHOLOGYINSTITUTEOFCANCERRESEARCH,CANCERCENTER,THEFIRSTUNIVERSITYHOSPITALOFWESTCHINAUNIVERSITYOFMEDICALSCIENCES,CHENGDU610041,SICHUANPROVINCE,CHINAWANGXIUJIE,MALE,BORNON19570215INZIYANG,SICHUANPROVINCEANDGRADUATEDFROMWESTCHINAUNIVERSITYOFMEDICALSCIENCESIN1982,NOWASSOCIATEPROFESSOROFONCOLOGY,ENGAGEDINTHERESEARCHESOFETIOLOGYANDMECHANISMSOFCARCINOGENESISOFCANCERS,SCREENINGANDDEVELOPINGANTICANCERDRUGS,HAVING20PAPERSPUBLISHEDPROJECTSUPPORTEDBYTHEGRANTOFWESTCHINAUNIVERSITYOFMEDICALSCIENCES,NOL293015CORRESPONDENCETOWANGXIUJIE,INSTITUTEOFCANCERRESEARCH,CANCERCENTER,THEFIRSTUNIVERSITYHOSPITALOFWESTCHINAUNIVERSITYOFMEDICALSCIENCES,CHENGDU610041,SICHUANPROVINCE,CHINATEL86285501218,FAX86285583252RECEIVED19990721ACCEPTED19990922FIGURE1THEEXPRESSIONOFPP60CSRCINTHEPROLIFERATIVEEPITHELIAADJACENTTOCARCINOMALSAB200FIGURE2THEEXPRESSIONOFPP60CSRCINTUBULARADENOCARCINOMALSAB200FIGURE3THEEXPRESSIONOFPP60CSRCINTHEPOORLYDIFFERENTIATEDADENOCARCINOMALSAB200FIGURE4THEEXPRESSIONOFPP60CSRCINTHELYMPHNODEMETASTASISOFCALSAB200TABLE1THEEXPRESSIONOFPP60CSRCINCAANDRELATEDLESIONSSTAININGINTENSITYLESIONCASEPOSITIVERATENORMALEPITHELIA3424705102940010294PROLIFERATIVEEPITHELIA36256616728778D34944BCARDIAADENOCARCINOMA56162862035720357D40714BLYMPHNODEMETASTASES2084008400420012600BP001,INCOMPARISONOFTHEPOSITIVERATESINDIFFERENTLESIONSΧ23419VSNORMALEPITHELIADP001,INCOMPARISONOFTHEPOSITIVEINTENSITYINDIFFERENTLESIONSΧ22508VSNORMALEPITHELIATABLE2THEEXPRESSIONOFPP60CSRCINCAOFDIFFERENTHISTOLOGICALTYPESSTAININGINTENSITYLESIONCASEPOSITIVERATE0/10PAPILLARY822506750006750TUBULAR224182418214636B18818APOORLYDIFFERENTIATED2010500105000010500MUCOUS6000061000B61000ATOTAL5616286203572035740714AP005,INCOMPARISONOFTHEPOSITIVERATESOFTUBULARANDMUCOUSADENOCARCINOMASVSTHOSEOFPAPILLARYANDPOORLYDIFFERENTIATEDADENOCARCINOMASΧ2811BP001,INCOMPARISONOFTHEPOSITIVERATESOFTUBULARANDMUCOUSADENOCARCINOMASVSTHOSEOFPAPILLARYANDPOORLYDIFFERENTIATEDADENOCARCINOMASΧ22756DISCUSSIONPP60CSRCISAPHOSPHORYLATEDCYTOPLASMICPROTEINENCODEDBYCSRCGENE,HAVINGTHEACTIVITYOFTYROSINEKINASETHEEXPRESSIONOFPP60CSRCCANBEFOUNDINMANYNORMALCELLS,WHICHPLAYSIMPORTANTROLESINTHEREGULATIONOFCELLPROLIFERATION,DIFFERENTIATIONANDTRANSFORMATION4RECENTSTUDIESINDICATEDTHATTHEINCREASEINTHEAMOUNTOFPP60CSRCPROTEINANDKINASEACTIVITYWASASSOCIATEDWITHINITIATIONANDDEVELOPMENTOFSOMEHUMANNEOPLASMS,ANDTHEACTIVATIONANDINCREASEOFEXPRESSIONWEREONEOFTHEFACTORSFORCANCERINITIATION48INTHISSTUDY,THEEXPRESSIONSOFPP60CSRCINCA,PROLIFERATIVEEPITHELIAANDNORMALEPITHELIAWERE71440/56,94434/36AND29410/34,RESPECTIVELYANDTHEPOSITIVERATESOFPP60CSRCINCAANDPROLIFERATIVEEPITHELIAWEREMUCHHIGHERTHANTHATINTHENORMALEPITHELIAP001JANKOWISKIETALANALYZEDTHEEXPRESSIONPRODUCTOFCSRCGENEIN15CASESOFESOPHAGEALADENOCARCINOMAAND15CASESOFBARRETT’SESOPHAGEALEPITHELIAIMMUNOHISTOCHEMICALLY,THEPOSITIVERATESWERE203/15,SUGGESTINTHATTHEEXPRESSIONOFCSRCGENEISRELATEDTOTHEDEVELOPMENTOFESOPHAGEALADENOCARCINOMATHEREFORE,THERESULTSOFTHISSTUDYINDICATEDTHATTHEACTIVATIONANDEXPRESSIONOFCSRCGENEMIGHTBEASSOCIATEDWITHTHEINITIATIONANDDEVELOPMENTOFCAHOWEVER,THEHIGHEXPRESSIONOFPP60CSRCINTHEPROLIFERATIVEEPITHELIAMIGHTBEASSOCIATEDWITHTHEPROLIFERATIONOFGLANDULAREPITHELIALCELLS,OCCURRINGINTHEAGEDRATS9THELOWPP60CSRCEXPRESSIONINSOMENORMALEPITHELIAADJACENTTOCANCERMIGHTBEEXPLAINEDBYTHEFACTTHATTHEREHAD490ISSN10079327CN141219/RWJGDECEMBER1999VOLUME5NUMBER6

簡(jiǎn)介：點(diǎn)擊查看更多[雙語(yǔ)翻譯]--外文翻譯--基于移動(dòng)手機(jī)平臺(tái)的生物醫(yī)學(xué)傳感器技術(shù)精彩內(nèi)容。

簡(jiǎn)介：點(diǎn)擊查看更多[雙語(yǔ)翻譯]--外文翻譯--基于gpu的醫(yī)學(xué)圖像計(jì)算技術(shù)綜述精彩內(nèi)容。

簡(jiǎn)介：ORIGINALARTICLEALIMENTARYTRACTDOWNREGULATIONOFMIR141INGASTRICCANCERANDITSINVOLVEMENTINCELLGROWTHYINGDU?YANJUNXU?LINGDING?HAOMIYAO?HONGYU?TIANHUAZHOU?JIANMINSIRECEIVED18AUGUST2008/ACCEPTED28JANUARY2009/PUBLISHEDONLINE11APRIL2009?SPRINGER2009ABSTRACTPURPOSEHUMANMICRORNA141MIR141,AMEMBEROFTHEMIR200FAMILY,HASBEENREPORTEDTOBEASSOCIATEDWITHVARIOUSHUMANMALIGNANCIESHOWEVER,ITREMAINSUNKNOWNWHETHERMIR141ISINVOLVEDINTHEPATHOGENESISOFGASTRICCANCERTHEREFORE,WEEXAMINEDTHEEXPRESSIONOFMIR141INGASTRICCANCERTISSUESANDTHEEFFECTOFMIR141OVEREXPRESSIONONCANCERCELLPROLIFERATIONMETHODSTHEEXPRESSIONLEVELOFMIR141IN35PAIRMATCHEDGASTRICNEOPLASTICANDADJACENTNONNEOPLASTICTISSUES,ANDIN5GASTRICCANCERCELLLINESWEREEXAMINEDBYQUANTITATIVEREALTIMEPCRTHEGROWTHOFMGC803CELLSTRANSFECTEDWITHMIRNAPRECURSORWASEXAMINEDBYMTT34,5DIMETHYLTHIAZOL2YL2,5DIPHENYLTETRAZOLIUMBROMIDEASSAYRESULTSMIR141WASSIGNIFICANTLYDOWNREGULATEDIN8028/35OFPRIMARYGASTRICCANCERTISSUESCOMPAREDWITHPAIRMATCHEDADJACENTNONTUMORTISSUESP\001THEEXPRESSIONOFMIR141WASALSOFOUNDTOBESUBSTANTIALLYREDUCEDINSEVERALHUMANGASTRICCANCERCELLLINESSUCHASMGC803,HGC27,SGC7901ANDBGC823CELLSOVEREXPRESSIONOFMIR141WITHITSPRECURSORSSIGNIFICANTLYINHIBITEDTHEPROLIFERATIONOFGASTRICCANCERCELLSCONCLUSIONSTHESERESULTSSUGGESTTHATMIR141MAYBEINVOLVEDINTHEDEVELOPMENTOFGASTRICCANCERTHROUGHITSINHIBITORYEFFECTONCELLPROLIFERATIONKEYWORDSMIR141?GASTRICCANCER?MGC803CELL?CELLPROLIFERATIONINTRODUCTIONMICRORNASMIRNAS,ANEWCLASSOFENDOGENOUS,NONCODINGANDSINGLESTRANDEDRNAS,WERERECENTLYDISCOVEREDINBOTHANIMALSANDPLANTSTHEYTRIGGERTRANSLATIONALREPRESSIONAND/ORMRNADEGRADATIONMOSTLYTHROUGHCOMPLEMENTARYBINDINGTOTHE30UNTRANSLATEDREGIONSOFTARGETMRNASSTUDIESHAVESHOWNTHATMIRNASCANREGULATEAWIDEARRAYOFBIOLOGICALPROCESSESSUCHASCELLPROLIFERATION,DIFFERENTIATION,ANDAPOPTOSIS1ACCUMULATINGEVIDENCESUGGESTSTHATALTERATIONSOFMIRNASEXPRESSIONMAYPLAYVARIOUSROLESINTHEPATHOGENESISOFMANYHUMANCANCERS2,3SOMEMIRNASHASBEENSHOWNTOPOSSESSONCOGENICORTUMORSUPPRESSORACTIVITY4HIGHTHROUGHPUTTECHNIQUESHAVEBEENUSEDTOSCREENMIRNASDIFFERENTIALLYEXPRESSEDBETWEENHUMANNONMALIGNANTANDMALIGNANTSAMPLES,ANDANUMBEROFMIRNASDEREGULATEDINNUMEROUSHUMANTUMORSWEREFOUND,INCLUDINGLUNG,BREAST,LIVER,ESOPHAGEALANDPROSTATECANCERS5–9AMONGTHESEMIRNAS,MIR141,AMEMBEROFTHEMIR200FAMILY,ISOVEREXPRESSEDINOVARIANANDCOLORECTALCANCERS10,11ANDDOWNREGULATEDINPROSTATE,HEPATOCELLULAR,ANDRENALCELLCARCINOMA5,9,12,RAISINGACONTROVERSIALISSUEABOUTTHEROLEOFMIR141INCANCERPROGRESSIONELECTRONICSUPPLEMENTARYMATERIALTHEONLINEVERSIONOFTHISARTICLEDOI101007/S0053500900377CONTAINSSUPPLEMENTARYMATERIAL,WHICHISAVAILABLETOAUTHORIZEDUSERSYDU?HYU?JSIP\001SUBSTANTIALLYREDUCEDEXPRESSIONSOFMIR141WEREFOUNDINBOTHINTESTINALTYPE17FOLDN23FIG1BP\005ANDDIFFUSETYPEGASTRICCANCERS30FOLDN9FIG1CP\001THEEXPRESSIONOFMIR141INCELLLINESDERIVEDFROMGASTRICCANCERTOCONFIRMTHEASSOCIATIONBETWEENMIR141EXPRESSIONANDGASTRICCANCER,WEDETECTEDMIR141EXPRESSIONINFIG1THEEXPRESSIONOFMIR141INGASTRICCANCERQUANTIFICATIONOFMIR141WASMEASUREDBYTAQMANREALTIMEPCRALLDATAOFFOLDCHANGEWERETRANSFORMEDTOLOG2VALUESARELATIVEEXPRESSIONOFMIR141IN35PRIMARYGASTRICCANCERTISSUESCOMPAREDWITHTHEIRPAIRMATCHEDADJACENTNONTUMORTISSUESBRELATIVEEXPRESSIONOFMIR141IN23TISSUESWITHINTESTINALTYPEADENOCARCINOMARELATIVETOTHEIRPAIRMATCHEDADJACENTNONMALIGNANTTISSUESCRELATIVEEXPRESSIONOFMIR141IN9DIFFUSETYPEADENOCARCINOMATISSUESCOMPAREDWITHTHEIRPAIRMATCHEDADJACENTNONTUMORTISSUESTHEPATHOLOGICALFEATURESOFREPRESENTATIVEINTESTINALTYPEANDDIFFUSETYPEGASTRICCANCERWERESHOWNWITHHESTAININGSCALEBARS200LM558JGASTROENTEROL200944556–561123

簡(jiǎn)介：ULTRASENSITIVEELECTRICALBIOSENSINGOFPROTEINSANDDNACARBONNANOTUBEDERIVEDAMPLIFICATIONOFTHERECOGNITIONANDTRANSDUCTIONEVENTSJOSEPHWANG,GUODONGLIU,ANDMRASULJAN?DEPARTMENTOFCHEMISTRYANDBIOCHEMISTRY,NEWMEXICOSTATEUNIVERSITY,LASCRUCES,NEWMEXICO88003RECEIVEDDECEMBER15,2003EMAILJOEWANGNMSUEDUTHEDETECTIONOFDNAANDPROTEINSISOFCENTRALIMPORTANCETOTHEDIAGNOSISANDTREATMENTOFGENETICDISEASES,TOTHEDETECTIONOFINFECTIOUSAGENTS,DRUGDISCOVERY,ORWARNINGAGAINSTBIOWARFAREAGENTS14SUCHBIODETECTIONCOMMONLYRELIESONHYBRIDIZATIONORANTIGENANTIBODYAGABINTERACTIONS,ANDREQUIRESPROPERATTENTIONTOTHEACHIEVEMENTOFULTRASENSITIVEMEASUREMENTSELECTROCHEMICALTRANSDUCERSAREVERYATTRACTIVEFORSUCHBIOASSAYS,OWINGTOTHEIRHIGHSENSITIVITY,INHERENTSIMPLICITYANDMINIATURIZATION,ANDLOWCOSTANDPOWERREQUIREMENTSTHEUSEOFENZYMELABELSTOGENERATEELECTRICALSIGNALSHASBEENEXTREMELYUSEFULFORULTRASENSITIVEELECTROCHEMICALBIOAFFINITYASSAYSOFPROTEINSANDDNAHELLER’SGROUP5,6DEMONSTRATEDTHATAHIGHLYSENSITIVEAMPEROMETRICMONITORINGOFDNAHYBRIDIZATIONDOWNTO5ZMOLCOULDBEACHIEVEDINCONNECTIONWITHAHORSERADISHPEROXIDASEHRPLABELEDTARGETANDANELECTRONCONDUCTINGREDOXPOLYMERHRPLABELHASBEENCOMBINEDBYWILLNER’SGROUP7,8WITHABIOCATALYTICPRECIPITATIVEACCUMULATIONOFTHEENZYMEGENERATINGPRODUCTTOACHIEVEMULTIPLEAMPLIFICATIONSANDVERYLOW25AMOLDETECTIONLIMITSEFFORTSTOAMPLIFYENZYMELINKEDELECTRICALPROTEINASSAYSINCLUDEDDUALENZYMESUBSTRATERECYCLING9ORIONEXCHANGEACCUMULATIONOFTHEPRODUCT10YET,AMPLIFIEDTRANSDUCTIONOFBIOLOGICALRECOGNITIONEVENTSREMAINSAMAJORCHALLENGETOELECTRICALBIOASSAYSNEWSCHEMESBASEDONCOUPLINGTHEBIOCATALYTICAMPLIFICATIONOFENZYMETAGSWITHADDITIONALAMPLIFICATIONUNITSANDPROCESSESAREHIGHLYDESIREDFORMEETINGTHEHIGHSENSITIVITYDEMANDSOFELECTROCHEMICALDETECTIONOFPROTEINSANDNUCLEICACIDSHEREWEDEMONSTRATETHEUSEOFCARBONNANOTUBESCNTSFORDRAMATICALLYAMPLIFYINGENZYMEBASEDBIOAFFINITYELECTRICALSENSINGOFPROTEINSANDDNATHEUNIQUEELECTRONIC,CHEMICAL,ANDMECHANICALPROPERTIESOFCNTSMAKETHEMEXTREMELYATTRACTIVEFORELECTROCHEMICALSENSORS11,12MOSTCNTSENSINGWORKHASFOCUSEDONTHEABILITYOFSURFACECONFINEDCNTSTOPROMOTEELECTRONTRANSFERREACTIONSINVOLVEDINBIOCATALYTICDEVICES13,14INOURNEWBIOAFFINITYASSAYSFIGURE1,CNTSPLAYADUALAMPLIFICATIONROLEINBOTHTHERECOGNITIONANDTRANSDUCTIONEVENTS,NAMELYASCARRIERSFORNUMEROUSENZYMETAGSANDFORACCUMULATINGTHEPRODUCTOFTHEENZYMATICREACTIONTHESENOVELSUPPORTANDPRECONCENTRATIONFUNCTIONSOFCNTSREFLECTTHEIRLARGESPECIFICSURFACEAREA15ANDAREILLUSTRATEDUSINGTHEALKALINEPHOSPHATASEALPENZYMETRACERSUCHCOUPLINGOFSEVERALCNTDERIVEDAMPLIFICATIONPROCESSESLEADSTOTHELOWESTDETECTIONLIMITREPORTEDTHUSFARFORELECTRICALDNADETECTIONTHENEWCNTBASEDAMPLIFIEDBIOELECTRONICPROTOCOLFIGURE1INVOLVESTHESANDWICHHYBRIDIZATIONAORANTIGENANTIBODYBBINDINGALONGWITHMAGNETICSEPARATIONOFTHEANALYTELINKEDMAGNETICBEAD/CNTASSEMBLYA,FOLLOWEDBYENZYMATICAMPLIFICATIONB,ANDCHRONOPOTENTIOMETRICSTRIPPINGDETECTIONOFTHEPRODUCTATTHECNTMODIFIEDELECTRODECOURTEMOBSERVATIONSEG,FIGURE2INDICATETHATTHEHYBRIDIZATIONEVENTLEADSTOCROSSLINKINGOFTHEALPLOADEDCNTSANDTHEMAGNETICBEADSWITHTHEDNADUPLEXACTINGAS“GLUE”TOOURKNOWLEDGE,THISISTHEFIRSTEXAMPLEOFUSINGDNAFORLINKINGPARTICLESTOCNTSNOSUCHAGGREGATIONWASOBSERVEDINTHEPRESENCEOFNONCOMPLEMENTARYOLIGONUCLEOTIDESBAPPARENTLY,WITHOUTTHERECOGNITIONEVENT,THEALPTAGGEDCNTSAREREMOVEDBYTHEMAGNETICSEPARATION,LEAVINGTHEMAGNETICBEADSBEHINDALPWASIMMOBILIZEDONCNTSUSINGA1ETHYL33DIMETHYLAMINOPROPYLCARBODIIMIDELINKERSEEFIGURE1INSUPPORTINGINFORMATIONACOVERAGEOFAROUND9600ENZYMEMOLECULESPERACNTIE,BINDINGEVENTWASESTIMATEDFROMASEPARATEELECTROCHEMICALEXPERIMENTCOMPARINGTHERNAPHTHOLRESPONSEOFKNOWNAMOUNTSOFALPLOADEDCNTSANDALPASSUMINGSIMILARACTIVITIESFORTHEFREEANDBOUNDALPTHEDRAMATICSIGNALENHANCEMENTASSOCIATEDWITHTHECNTBASEDDUALAMPLIFICATIONROUTEISDEMONSTRATEDINFIGURE3FORDNAHYBRIDIZATIONAANDAGABBBIOASSAYSTHECONVENTIONALPROTOCOLS,BASEDONTHESINGLEENZYMETAGANDAGLASSYCARBONTRANSDUCER,ARENOTRESPONDINGTOEITHER10PGML1DNATARGETA,AOR80PGML1IGGB,ATHEFIRSTAMPLIFICATIONSTEPBASEDONTHEALPLOADEDCNTSBOFFERSCONVENIENTDETECTIONOFTHESELOWANALYTECONCENTRATIONSTHESINGLEALPPROTOCOLSDISPLAYEDA?PERMANENTADDRESSDEPARTMENTOFCHEMISTRY,UNIVERSITYOFPESHAWAR,PAKISTANFIGURE1SCHEMATICREPRESENTATIONOFTHEANALYTICALPROTOCOLACAPTUREOFTHEALPLOADEDCNTTAGSTOTHESTREPTAVIDINMODIFIEDMAGNETICBEADSBYASANDWICHDNAHYBRIDIZATIONAORABAGABINTERACTIONBBENZYMATICREACTIONCELECTROCHEMICALDETECTIONOFTHEPRODUCTOFTHEENZYMATICREACTIONATTHECNTMODIFIEDGLASSYCARBONELECTRODEMB,MAGNETICBEADSP,DNAPROBE1T,DNATARGETP2,DNAPROBE2AB1,FIRSTANTIBODYAG,ANTIGENAB2,SECONDARYANTIBODYSANDP,SUBSTRATEANDPRODUCT,RESPECTIVELY,OFTHEENZYMATICREACTIONGC,GLASSYCARBONELECTRODECNT,CARBONNANOTUBELAYERFIGURE2TEMIMAGESOFTHEMAGNETICBEADSDNACNTASSEMBLYPRODUCEDFOLLOWINGA20MINHYBRIDIZATIONWITHTHE10AAND0BPGML1TARGETSAMPLETHEMICROGRAPHSWERETAKENWITHAHITACHIH7000INSTRUMENTOPERATEDAT75KVPUBLISHEDONWEB02/18/200430109JAMCHEMSOC2004,126,30103011101021/JA031723WCCC2750?2004AMERICANCHEMICALSOCIETYLOWERSIGNALFORASIGNIFICANTLY1000FOLDHIGHERTARGETCONCENTRATIONNOTSHOWNTHENEARLY104IMPROVEMENTINTHESENSITIVITYISINGOODAGREEMENTWITHTHEESTIMATEDALPLOADINGPERCNTONLY～50FOLDSENSITIVITYENHANCEMENTWASOBSERVEDBYUSINGASTREPTAVIDINCOATEDPOLYSTYRENECARRIERBEADINSTEADOFTHECNTSUPPORTFURTHERENHANCEMENTSOFTHEDNAANDPROTEINSIGNALSBY～30FOLDAREOBSERVEDINTHESECONDAMPLIFICATIONPATH,EMPLOYINGTHECNTMODIFIEDTRANSDUCERCTHELATTERREFLECTTHESTRONGADSORPTIVEACCUMULATIONOFTHELIBERATEDRNAPHTHOLONTHECNTLAYERTHEPRECONCENTRATIONFEATUREOFTHECNTLAYERWASINDICATEDFROMTHEUSEOFDIFFERENTACCUMULATIONTIMESTHATLEDTOASHARPINCREASEINTHERNAPHTHOLSIGNALCOMPAREDTOTHETIMEINDEPENDENTSIGNALOBSERVEDATTHEBAREELECTRODESEEFIGURE2INSUPPORTINGINFORMATIONFIGURE4ADISPLAYSTYPICALCHRONOPOTENTIOGRAMSFOREXTREMELYLOWTARGETDNACONCENTRATIONS001100PGML1AEWELLDEFINEDRNAPHTHOLSIGNALSAREOBSERVEDFORTHESELOWDNACONCENTRATIONSINCONNECTIONWITH20MINHYBRIDIZATIONTHERESULTINGPLOTOFRESPONSEVSLOGTARGETSHOWNASINSETISLINEARANDSUITABLEFORQUANTITATIVEWORKTHEFAVORABLERESPONSEOFTHE5FGML1DNATARGETBINDICATESAREMARKABLYLOWDETECTIONLIMITOFAROUND1FGML154AM,IE,820COPIESOR13ZMOLINTHE25ΜLSAMPLESUCHALOWDETECTIONLIMITCOMPARESFAVORABLYWITHTHELOWESTVALUESOF5ZMOL3000COPIESAND25AMOLREPORTEDFORELECTRICALDNADETECTION6,8SIMILARLY,IGGWASDETERMINEDWITHADETECTIONLIMITOF500FGML1160ZMOLIN25ΜLSAMPLESANDEXHIBITSAWELLDEFINEDLOGARITHMICCONCENTRATIONDEPENDENCETHESMALLERSIGNALOBSERVEDINACONTROLEXPERIMENTFORAHUGE～106EXCESSOFANONCOMPLEMENTARYOLIGONUCLEOTIDEFIGURE4,CVSBREFLECTSTHEHIGHSELECTIVITYASSOCIATEDWITHTHEEFFECTIVEMAGNETICSEPARATIONTHEAMPLIFIEDELECTRICALSIGNALISCOUPLEDTOAGOODREPRODUCIBILITYTWOSERIESOFSIXREPETITIVEMEASUREMENTSOF1PGML1DNATARGETOR08NGML1IGGYIELDEDREPRODUCIBLESIGNALSWITHRELATIVESTANDARDDEVIATIONSOF56AND89,RESPECTIVELYINCONCLUSION,WEHAVEDEMONSTRATEDACNTBASEDDUALAMPLIFICATIONROUTEFORULTRASENSITIVEELECTRICALBIOASSAYSOFPROTEINSANDDNATHEUSEOFCNTAMPLIFIERSLOADEDWITHNUMEROUSALPTAGSHASBEENCOMBINEDWITHTHEPRECONCENTRATIONFEATUREOFCNTTRANSDUCERSTOYIELDADRAMATICENHANCEMENTOFTHESENSITIVITYSUCHCOUPLINGOFSEVERALCNTDERIVEDAMPLIFICATIONPROCESSESRESULTSINHIGHLYSENSITIVEDETECTIONOFPROTEINSANDDNAANDHENCEINDICATESGREATPROMISEFORPCRFREEDNAASSAYSFURTHERIMPROVEMENTSINTHESENSITIVITYAREEXPECTEDEITHERTHROUGHREDUCINGTHEELECTRODESIZEANDSAMPLEVOLUME6ORBYSUBSTRATERECYCLING9THENEWCNTDERIVEDAMPLIFICATIONBIOASSAYSAREEXPECTEDTOOPENNEWOPPORTUNITIESFORMEDICALDIAGNOSTICSANDPROTEINANALYSISTHEFINDINGTHATDNAHYBRIDIZATIONCANBEUSEDFORLINKINGCNTSTOPARTICLESHOLDSPROMISEFORASSEMBLINGCONTROLLABLENANOSCALESYSTEMSACKNOWLEDGMENTFINANCIALSUPPORTFROMTHENATIONALSCIENCEFOUNDATIONGRANTCHE0209707ANDNATIONALINSTITUTESOFHEALTHAWARDR01A105604701ISGRATEFULLYACKNOWLEDGEDSUPPORTINGINFORMATIONAVAILABLERELATEDEXPERIMENTALCONDITIONSINSTRUMENTATION,REAGENTS,SEQUENCES,ANDPROCEDURESALONGWITHADDITIONALDATAPDFTHISMATERIALISAVAILABLEFREEOFCHARGEVIATHEINTERNETATHTTP//PUBSACSORGREFERENCES1PALECEK,EFOJTA,MANALCHEM2001,73,75A2DRUMMOND,TGHILL,MGBARTON,JKNATBIOTECHNOL2003,21,11923WANG,JCHEMEURJ1999,5,16814GOODING,JJELECTROANALYSIS2002,14,11495CARUANA,DJHELLER,AJAMCHEMSOC1999,121,7696ZHANG,YKIM,HHELLER,AANALCHEM2003,75,32677PATOLSKY,FKATZ,EBARDEA,AWILLNER,ILANGMUIR1996,12,37038PATOLSKY,FLITCHENSTEIN,AWILLNER,IANGEWCHEM,INTED2000,39,9409BAUER,CEREMENKO,AEHRENTREICHFOSTER,EBIER,FMAKOWER,AHALSALL,HBHEINEMAN,WRSCHELLER,FWANALCHEM1996,68,245310LIMOGES,BDEGRAND,CANALCHEM1996,68,414111BAUGHMAN,RHZAKHIDOV,ADEHEER,WASCIENCE2002,297,78712ZHAO,QGAN,ZZHUANG,QELECTROANALYSIS2002,14,160913WANG,JMUSAMEH,MLIN,YJAMCHEMSOC2003,125,240814RUBIANES,MDRIVAS,GAELECTROCHEMCOMMUN2003,5,68915PEIGNEY,ALAURENT,CFLAHAUT,EBASCA,RROUSSET,ACARBON2001,39,507JA031723WFIGURE3CHRONOPOTENTIOMETRICSIGNALSFOR10PGML1TARGETOLIGONUCLEOTIDEAAND80PGML1IGGBUSINGTHEGLASSYCARBONGCTRANSDUCERANDAASINGLEALPTAGANDBCNTLOADEDWITHMULTIPLEALPTAGSCSAMEASBBUTUSINGTHECNTMODIFIEDGCELECTRODEAMOUNTOFMAGNETICBEADS,50ΜGSANDWICHASSAYWITH20AND30MINFOREACHHYBRIDIZATIONEVENTANDAG/ABASSOCIATION,RESPECTIVELYSAMPLEVOLUME,50ΜLDETECTION,ADDITIONOF50ΜLRNAPHTHYLPHOSPHATE50MMSOLUTIONWITHA20MINENZYMATICREACTIONMEASUREMENTSOFTHERNAPHTHOLPRODUCTWEREPERFORMEDATTHEBAREORMODIFIEDGCELECTRODES,USINGA2MINACCUMULATIONAT02VINASTIRREDPHOSPHATEBUFFERSOLUTION005M,PH741ML,FOLLOWEDBYA10SRESTPERIODWITHOUTSTIRRINGANDAPPLICATIONOFANANODICCURRENTOF50ΜASEESUPPORTINGINFORMATIONFORTHECONCENTRATIONSOFTHEOLIGONUCLEOTIDEPROBESANDANTIBODY,ANDSEQUENCEOFOLIGONUCLEOTIDEPROBES,LEVELSANDPREPARATIONOFTHEALPDNACNTANDALPSTREPTAVIDINCNTCONJUGATESFIGURE4CHRONOPOTENTIOMETRICSIGNALSFORINCREASINGLEVELSOFTHEDNATARGETA001,B01,C1,D50,E100PGML1ALSOSHOWNINSETISTHERESULTINGCALIBRATIONPLOTA,ANDTHERESPONSEFOR5FGML1TARGETDNABAND10NGML1NONCOMPLEMENTARYNCOLIGONUCLEOTIDECSAMPLEVOLUME,25ΜLBAND50ΜLCOTHERCONDITIONS,ASINFIGURE3A,CBASEDONPROTOCOLOFFIGURE1AACCOMMUNICATIONSJAMCHEMSOC9VOL126,NO10,20043011

簡(jiǎn)介：點(diǎn)擊查看更多[雙語(yǔ)翻譯]--醫(yī)學(xué)外文翻譯--血糖控制對(duì)2型糖尿病合并esrd患者預(yù)后的影響精彩內(nèi)容。

簡(jiǎn)介：點(diǎn)擊查看更多[雙語(yǔ)翻譯]--醫(yī)學(xué)外文翻譯--己糖激酶-1在被hiv-1感染的巨噬細(xì)胞的生存過(guò)程中的作用精彩內(nèi)容。

簡(jiǎn)介：點(diǎn)擊查看更多[雙語(yǔ)翻譯]--醫(yī)學(xué)外文翻譯--表觀擴(kuò)散系數(shù)對(duì)肝臟良惡性腫塊的鑒別精彩內(nèi)容。

簡(jiǎn)介：點(diǎn)擊查看更多[雙語(yǔ)翻譯]--醫(yī)學(xué)外文翻譯--人賁門(mén)癌癌變進(jìn)程中c-src基因的表達(dá)精彩內(nèi)容。

簡(jiǎn)介：點(diǎn)擊查看更多[雙語(yǔ)翻譯]--醫(yī)學(xué)外文翻譯--心臟衰竭末期的心肌細(xì)胞再生精彩內(nèi)容。

簡(jiǎn)介：點(diǎn)擊查看更多[雙語(yǔ)翻譯]--醫(yī)學(xué)外文翻譯--mir-141在胃癌和它相關(guān)細(xì)胞生長(zhǎng)中的下調(diào)精彩內(nèi)容。