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硒和抗癌医学宣教background•Selenium(Se),anessentialtracedietarynutrientwithanticarcinogenic（抑癌）potential•氧族元素，原子序

数34，相对分子量78.96•Infoodsanddietarysupplements:SeMetandSeCys,smalleramountsofmethylatedselenidesaredominantformsofSe2硒和抗癌医学宣教Fig.14硒和抗癌医学宣教mainpoi

ntsoftheSeleniummetabolism•absorbandretainSebetterfromSeMetandSeyeastthanfromtheinorganicSesalts•Selenid

ehasacentralroleinSemetabolism,beingthebranchpointoftwometabolicpathways:selenoproteinproductionandselenopr

oteinexcretion(排泄)•CH3SeHand[CH3]2SeH：excretedacrossthelungs（肺）•[CH3]3Se+andCH3Se-GalN,excretedacrossthekidney（肾）5硒和抗癌医学宣教mainpointsoftheSel

eniummetabolism•SAM是生物体内广泛存在的重要中间代谢物质，参与体内众多重要生化反应。作为生物体代谢的主要甲基供体•β-lyase是一种裂合酶6硒和抗癌医学宣教thediscoveryofsele

niumfunctionsSchwarz发现某些天然物质能够防止大鼠食饵性坏死Schwarz和Foltz均证明，硒是防止食饵性肝坏死的一种保护因子Roctrack和Hoekstra证明，硒是谷胱甘肽过氧化物酶的活性成分20世70年代初，中

国克山病研究工作者发现克山病与处于贫硒状态有关，采用硒盐之后，对克山病有预防作用世界卫生组织（WHO）1973年确认硒是人类生命必须14种微量元素的第一种微量元素，缺硒会严重影响人的身体健康7硒和抗癌医学宣教thed

iscoveryofseleniumfunctions•Itwasfirstsuggestedinthelate1960sthatSemightalsobeanticarcinogenic,basedo

naninverserelationshipofSestatusandrisksofsomekindsofcancer•Interestinthisareawasstimulatedbythelandmarkf

indingthatsupplementationoffree-livingpeoplewithSe-enrichedbrewer’syeast（啤酒发酵液）withpredominantlyselenomethioni

ne(SeMet)decreasedtheoverallcancermorbiditybynearly50%8硒和抗癌医学宣教thediscoveryofseleniumfunctions•ThatfindingcamefromtheNu

tritionalPreventionofCancer(NPC)trial,aprospective(有预计的),double-blinded（双盲的）,randomized（随机的）,placebo-controlled(有安

慰剂对照的)trialinvolving1312patientsrecruitedbecauseofhistoriesofnonmelanomaskincancers（非黑色素瘤性皮肤癌）•Tofollow-uponthatfinding,

theSeandVitaminEChemopreventionTrial(SELECT)waslaunchedinthefallof2001.Thisisarandomized,double-blind,d

esignedtodeterminewhetherSe(asSeMet)andvitaminE,aloneorincombination,canreducetheriskofprostatecanceramong32,400healthymen9硒

和抗癌医学宣教summary：seleniumfunctions•antioxidantprotection(viaselenoproteins),alteredcarcinogenmetabolism,enhancedimmunesurveillance,regul

ationofcellproliferationandtumorcellinvasionandinhibitionofneoangiogenesis(血管异生)•Inaddition,Sehasbeenshowntomedi

ateanumberofinsulinlike（类似胰岛素）actionsincludingthestimulationofglucoseuptakeandregulationofglycolysis(糖酵解),gluconeogenesis（糖异生）,fa

ttyacidsynthesisandthepentosephosphatepathway（磷酸戊糖途径）10硒和抗癌医学宣教Differentdose,differentfunctionAnyofthesef

ormscansupportthenutritionalrequirementsfortheelement;however,theirbioefficacydependsonbothdoseandchemicalform，speciallytheCH3SeH•0.1–0.2ppmasaness

entialmicronutrient•5ppmbecomestoxic•55ug/daydailyallowance•100–200ug/dayinhibitgeneticdamageandcancerdevelopmentinhumansubjects•400ug/d

ayuppersafelimit11硒和抗癌医学宣教Differentdose,differentfunction•Atlowdoses,SefunctionisanessentialcomponentofSeCysinseveralspecificselenoprotein

sandpromotecellproliferation,afactofparticularimportancetotheimmuneresponse.•Athigherdoses,butstillnontoxic,Secanredu

cecancerrisk.Thiseffectinvolvesthestimulationoftumorcellcyclearrestandapoptosisandtheinhibitionoftumorce

llmigrationandinvasion12硒和抗癌医学宣教Fig.213硒和抗癌医学宣教lowdoses：cellproliferation•WhenHL-60cellswereoptimizedinserum-freecultureconditionstomaximizetheeffec

tsofSeoncellgrowth,lowlevelsofSe(nmol/L)enhancedcellproliferationandup-regulatedtheexpressionofnumerouscel

lcycle-relatedgenes,includingasc-Myc,cyclinC,proliferatingcellnuclearantigen,cyclin-dependentkinase(CDK)1,CDK2,CDK4,cyclinBandcyclinD2mRNAandtota

lcellularphosphorylatedproteins14硒和抗癌医学宣教Furthermore,whenJurkatcellswereculturedinaserum-free(Sedeficient)medium,selenoen

zymeactivitiessuchasGPxandTrxRdecreasedsignificantlywithincellsandsubsequentlyinducedcelldeath.Interestingly,alipidsolubleradical-scav

engingantioxidant(vitaminE)butnotthewater-solubleantioxidants(ascorbicacid,N-acetylcysteineandglutathione),completelyblockedSedeficiency-induce

dcelldeath,althoughvitaminEcouldnorestoreSedependentenzymeactivity15硒和抗癌医学宣教•TheinsulinlikeactionsofS

eincludeincreasingglucoseuptakeandadenosinetriphosphategenerationthroughtheactivationofglycolysis,up-reg

ulationofantiapoptoticproteinBcl-2,maintenanceofmitochondrialmembranepotential,stimulationoffattyacidsynthesisandpentosephosphatepa

thwayactivity16硒和抗癌医学宣教SpecialabouttheCH3SeH•人体的正常血管是直线型，而肿瘤血管是螺旋形，血管内的血液流量变多，血液的压力变大，血液流速快，肿瘤吸收营养的速度自然也就加快

，瘤体因此迅速疯长。人体的正常血管生长周期是一年，而肿瘤血管的生长周期只有4天，也就是说，只需要4天的时间，肿瘤血管就能生长出来，破坏人体的正常组织，直接造成病人病灶部位的疼痛。癌细胞的转移，有两个渠道，一个是淋巴

道转移，只能转移到附近组织，所以危害相对较小；另外一个，危害巨大，那就是血管转移，事实上，90%的癌症患者，都是死于血道转移，这也是肿瘤血管造成的最大危害。•肿瘤血管，是癌细胞的营养通道和转移途径17硒和抗癌医学宣教Specialab

outtheCH3SeH•Methylselenolprecursorsexertrapid,inhibitoryeffectsontheexpressionofkeymoleculesinvolvedinangiogenesisregulation.•Forex

ample,itwasdemonstratedthatsubapoptoticdosesofMSeAinhibitedtheexpressionandsecretionofvascularendothelialgrowthfactor(VEGF,anangio

genicfactor),inseveralcancercelllinesandinhibitedMMP-2andVEGFexpressioninvascularendothelialcells18硒和抗癌医

学宣教