癌症生物学.ppt

癌症生物學1.授課老師:生命科學系胡承波教授辦公室:基礎科學實驗館206A電話:分機2479或2480手機0920734688e-mail:.tw2.課程目的:瞭解癌症生物學的內涵、機制、及發展。3.授課方式:a.以powerpoint講課b.提出問題，由同學發表意見及討論c.同學分組報告及討論,4.對同學的期許:a.準時上課，如無法出席，須以電話(留言)、e-mail、簡訊請假b.閱讀英文教科書c.主動參與討論，表達自己的想法及看法d.分組口頭報告(事先與老師討論)e.對同學的報告提出問題、討論及評量f.隨堂考試、期中考試、期末考試5.成績考核：由多方面考核；如準時出席、上課反應、小組參與、口頭報告、自發學習、隨堂考試、期中考及期末考6.教科書:Weinberg,R.A.TheBiologyofCancer.GarlandScience,Taylor&FrancisGroup,LLC,20077.隨時歡迎同學的口頭或書面建議,TheBiologyofCancerRobertA.WeinbergGarlandScience,Taylor&FrancisGroup,LLC,2007,RobertA.WeinbergWhiteheadInstituteforBiomedicalResearchMassachusettsInstituteofTechnology(MIT),RacingtotheBeginningoftheRoad:TheSearchfortheOriginofCancerR.A.Weinberg(1996)追獵癌症：癌症病因研究之路(天下文化)OneRenegadeCellR.A.Weinberg(1998)細胞反叛(天下文化)CuringCancerM.Waldholz(1997)致癌基因之謎(商業週刊),Chapter1TheBiologyandGeneticsofCellsandOrganisms-1.4-1.5-Mar1,2007,Figure1.11aTheBiologyofCancer(GarlandScience2007),HumanChromosomes(duringmetaphase),pcentromereq,ChromosomeBanding(1970s)-Identificationofchromosomesorthechromosomerearrangementincells-Theinteractionofcertainalkylating(adding-CH3)fluorochromes(e.g.,quinacrinemustard)andhistochemicalstains(e.g.,Giemsastain)withspecificregionsofchromosomesproduces“bands”alongthechromosomesthatcanbeusedtofingerprinteachchromosomepair.Thepatternsobtaineddependonthetreatmentused.,C-bandingstainscentromeres.R-bandingisthereverseofC-bandingandstainsnon-centromericregions.G-bandingisobtainedwithGiemsastain.Ityieldsaseriesoflightlyanddarklystainedbands.Q-bandingisafluorescentpatternobtainedusingquinacrineforstaining.ThepatternofbandsisverysimilartothatseeninG-banding.p:theshortarmabovethecentromere,e.g.,p13,p23q:thelongarmbelowthecentromere,e.g.,q22,q32,Figure1.11bTheBiologyofCancer(GarlandScience2007),TheDiploidKaryotypeofaNormalCell,1.4ChromosomesarealteredinmosttypesofcancercellsCancercellsoftenexhibit:a.presenceofextracopiesofchromosomeb.lossofentirechromosomesc.fusionofthearmofonechromosomewithpartofanotherd.aberrantlystructuredchromosomes,Figure1.11cTheBiologyofCancer(GarlandScience2007),Theaneuploidkaryotypeofahumanbreastcancercell,Sidebar1.3Cancercellsareoftenaneuploid,Euploidynormalconfiguration(numbers&pairs)ofchromosomesAneuploidychangesinchromosomenumberacquisitionofextracopiesofonechromosomeorthelossofanother,Chromosomesmayundergochangesinthestructure:A-1.translocationA-2.reciprocaltranslocation,Ph1,ThesmallerofthetworesultingabnormalchromosomesiscalledthePhiladelphiachromosome,afterthecitywheretheabnormalitywasfirstrecorded.,Figure1.12dTheBiologyofCancer(GarlandScience2007),B.deletionC.inversion,M-bandfluorescenceinsituhybridization(mFISH)reveals(B)adeletionand(C)aninsertionofaportionofchromosome5,Figure1.12aTheBiologyofCancer(GarlandScience2007),HSR,D.amplification1.HSR(homologouslystainingregion)2.DM(doubleminutes)-asegmentofachromosomeiscopied-asegmentiscleavedoutofamanytimesover,andtheresultingchromosome,replicateasanextracopiesmaybefusedhead-to-tailautonomous,extrachromosomalinlongarrayswithinachromosomalentity,andincreasetomanysegmentcopiespernucleus,resultingintheappearanceofsubchromosomalfragments,1.5Cancer-causingmutationsoccurinboththegermlineandthesomagermcells(生殖細胞)sperms&eggs-germlinetransmissionofmutationssoma(身體)theanimalorplantbodyasawholewiththeexceptionofthesexcells-somaticmutationsSomecancersarehereditary,butmostarecausedbysomaticmutations.,Youneedtofullyunderstandthefollowingtermshaploid,diplodkaryotypeallelehomozygous,heterozygousgenotype,phenotypedominant,recessiveincompletedominantco-dominance,haploiddescribingagenomeinwhichallchromosomesarepresentinasinglecopydiploiddescribingagenomeinwhichallchromosomesarepresentinpairs,oneofeachpairbeinginheritedfromafatherandtheotherfromamother,withtheexceptionofthesexchromosomes,whichinplacentalmammalsarepairedineithertheXXortheXYconfiguration.karyotypethearrayofchromosomescarriedbyacell,asdeterminedbydetailedexaminationofthesechromosomes,usuallyperformedwithcondensedchromosomesatmetaphase,alleleonealternativeamongdifferentversionsofagenethatmaybedefinedbythephenotypethatitcreates,bytheproteinthatitspecifies,orbyitsnucleotidesequencehomozygousreferringtotheconfigurationofageneticlocusinwhichthetwocopiesofthegenecarryidenticalversions(alleles)ofthegeneheterozygous-referringtotheconfigurationofageneticlocusinwhichthetwocopiesofthegenecarrydifferentversions(alleles)ofthegene,genotypegeneticconstitutionofanorganismphenotypeameasurableorobservabletraitofanorganismdomina