MGMT与肿瘤的预见性化疗.doc

;O6-DNA(O6-methylguanine DNA-transferaseMGMT)DNAO6-DNA(AGAT)(alkylating agents)DNADNA6MGMTMerMerMerMerMGMTMerO6-BGMerMGMT 1 MGMT 1/4DNADNADNA12DNAO6-DNAO6-DNADNA13MGMTMGMTMGMTMGMTMGMTMGMTMGMTMGMTMGMT(ACNU)MGMTMGMTMGMT 19871420MGMTMGMTMGMT()()MGMTMGMTMGMT!-empirenews.page- 20442221HeLa S3(Mer+)HeLa MR(Mer-)MGMTACNUBCNU203SHG-44BGC-823BEL-7402SMMC-772120MGMT210%ScudieroMGMT20%(19/93)4Ikenaga15%(6/40)5MGMT20SHG-44HeLa MRMGMTBGC-823BEL-7402SMMC-7721HeLa S310%(D10)D10MGMTMGMTMGMT(1)MGMT MGMTWatataniMGMTMNNGMGMTMGMT61107MGMTHeLa MRSHG-44MGMTHeLa S3SMMC-772125gACNU14ACNU50g/2HeLa MRSHG-441ACNUMGMTHeLa S3SMMC-7721(2)MGMTACNUMGMT1 MGMTACNU1.HeLa MR/HeLa S3(ACNU 0);2.HeLa MR/HeLa S3(ACNU 25g/g4);9.HeLa MR/HeLa MR(ACNU 50g/g2);2 ACNU MGMTMGMT!-empirenews.page- MGMTMGMT(DTIC)(TMZ)7MGMTSCEMGMTMGMT8MGMT9MGMT MGMTMGMT74MGMT9524142MGMT>>>>>>>>MGMT746MGMT318.1%Isowa21MGMT9.5%10Frosina27MGMT7.4%11MGMTMGMTMGMTMGMT123 MGMT MGMT cDNAneopSV2MGMT-neoMGMTHeLa MRMGMT cDNAMer-MGMT cDNA54MGMTMGMT mRNAACNUMNNGMGMTMGMT mRNAMGMT 2 MGMT mRNAMGMTMGMTMGMTMGMT3Mer+(HeLa S3SMMC-7721Cc801)3MGMTACNUBCNU(StreptozotocinSTZ)Mer+3Mer+371hMGMTSTZ1.5mmol/LHeLa S3MGMT1.10pmol/mg0.59pmol/mgSTZ1.0mmol/LSMMC-7721MGMT0.770.39STZ0.5mmol/LCc801MGMT0.390.143MGMTACNUD10HeLa S3114g/ml68g/mlSMMC-772177g/ml47g/mlCc80139g/ml23g/mlSTZ3.0mmol/L2.0mmol/L1.0mmol/LHeLa S3SMMC-7721Cc801MGMT0.01pmol/mgMer-HeLa MR3Mer+ACNUD10HeLa MRD10=10g/ml3Mer+ACNUSTZ3.0mmol/L2.0mmol/L1.0mmol/LHeLa S3SMMC-7721Cc801BCNUD10HeLa MRBCNU100g/g STZ25g/g ACNUACNUHeLa S3Mer+STZACNUO6-(O6-benzylguanineO6-BG)Mer+HeLa S3SMMC-7721Cc801MGMTMer+!-empirenews.page- MGMTSTZACNU8(1)(2)CTACNU(3)(4)12(5)ACNU6(6)WBC>4109/L>100109/LSTZACNUSTZ(2g/m2)1hACNU(23mg/kg)12CT8ACNU1CR()2PR(50%)4NC(<50%)1PD(>25%)CRPR37.5%(3/8)STZACNUSTZACNU MGMTMGMTMGMT 3 MGMT MGMT(APAAP)MGMT(IgG)FabFabAPAAPAPAAPMGMT 3.1 MGMT DNA starMGMT33820KLH 3.2 MGMT (1)MGMT14Fmoc-HBTU-HOBT-RinkMGMT14(2)(keyhole limpet hemocyaninKLH)MBSKLH 3.3 68BALB/cELISA 3.4 MGMT (1)(2)SP20HAT(3)MGMT 3.5 !-empirenews.page- 3.6 MGMT (1)MGMT710(2)MGMT33%(3)MGMTPharmacia Biotech.AKTA FPLCHiTrapq Protein G-Sepharose 3.7 MGMT IgGMGMTIgG180%98%MGMT140 3.8 MGMT 11 MGMT MGMT MGMT(ACNU)MGMT(STZ)MGMT 16123 MGMTMGMTMGMT 4 MGMT 4.1 C pG(CpG island)5200bpGCCpGMGMTCpGMGMTMGMTCpG 45DTICTMZMSP(methylation specific PCR)19DTICTMZ9(9/1947%)MGMTCpG97(7/978%)MGMT26DTICTMZ265(5/2619%)MGMTCpG51(1/520%)MGMTMGMTCpGDTICTMZMSP!-empirenews.page- 4.2 (TemozolomideTemodar)343451d1235-8Schering-plough19998FDA()-DNAO6-MeG 4.3 MerMGMTO6-PatersonTrinity CollegePaTrinTM6(4-bromo-2-thenyl)methoxypurin-2-aminePaTrin-2 O6-(4-bromothenyl)guaninePaTrin2TMZM