1、颅内淋巴瘤大剂量mtx化疗1 甲氨蝶呤(甲氨蝶呤(methotrexate,MTX)属抗代谢药,化学结构与叶酸相似,对二氢叶酸还原酶有强大而持久的抑制作用,干扰核酸的生物合成,特异性作用于S期,阻止肿瘤细胞的分裂繁殖,为细胞周期特异性药物。颅内淋巴瘤大剂量mtx化疗2还原性叶酸载体(reduced folate carrier,RFC)甲氨蝶呤聚谷氨酸合成酶(folylpolyglutamate synthetase,FPGS)MTX多聚谷氨酸(methotrexate polyglutamine,MTXPG)谷氨酸水解酶(gammaglutamylhydtrolase,GGH)胞外胞内颅内淋
2、巴瘤大剂量mtx化疗3,颅内淋巴瘤大剂量mtx化疗4颅内淋巴瘤大剂量mtx化疗5颅内淋巴瘤大剂量mtx化疗6颅内淋巴瘤大剂量mtx化疗7颅内淋巴瘤大剂量mtx化疗8颅内淋巴瘤大剂量mtx化疗9颅内淋巴瘤大剂量mtx化疗10MTXMTXMTXMTXR RF FC C MTX20umol/LMTX20umol/LMTXPGMTXPGGGHGGH还原性叶酸载体(reduced folate carrier,RFC)甲氨蝶呤聚谷氨酸合成酶(folylpolyglutamate synthetase,FPGS)MTX多聚谷氨酸(methotrexate polyglutamine,MTXPG)谷氨酸水解
3、酶(gammaglutamylhydtrolase,GGH)FPGSFPGSGluGlu (27)(27)颅内淋巴瘤大剂量mtx化疗11颅内淋巴瘤大剂量mtx化疗12MTXMTXMTXMTXR RF FC C MTX20umol/LMTX20umol/LMTXPGMTXPGGGHGGH还原性叶酸载体(reduced folate carrier,RFC)甲氨蝶呤聚谷氨酸合成酶(folylpolyglutamate synthetase,FPGS)MTX多聚谷氨酸(methotrexate polyglutamine,MTXPG)谷氨酸水解酶(gammaglutamylhydtrolase,GG
4、H)FPGSFPGSGluGlu (27)(27)颅内淋巴瘤大剂量mtx化疗13 J Clin Invest,1985,75(3):1008 1014 J Biol Chem,1985,260(117):9720 9726 J Clin Invest,1994,94:1996-2001颅内淋巴瘤大剂量mtx化疗14颅内淋巴瘤大剂量mtx化疗15 颅内淋巴瘤大剂量mtx化疗16 颅内淋巴瘤大剂量mtx化疗17颅内淋巴瘤大剂量mtx化疗18颅内淋巴瘤大剂量mtx化疗19颅内淋巴瘤大剂量mtx化疗20。颅内淋巴瘤大剂量mtx化疗21 颅内淋巴瘤大剂量mtx化疗22颅内淋巴瘤大剂量mtx化疗23颅内淋
5、巴瘤大剂量mtx化疗24颅内淋巴瘤大剂量mtx化疗25颅内淋巴瘤大剂量mtx化疗26颅内淋巴瘤大剂量mtx化疗27颅内淋巴瘤大剂量mtx化疗28 颅内淋巴瘤大剂量mtx化疗29MTXMTXMTXMTXR RF FC C MTX20umol/LMTX20umol/LMTXPGMTXPGGGHGGH还原性叶酸载体(reduced folate carrier,RFC)甲氨蝶呤聚谷氨酸合成酶(folylpolyglutamate synthetase,FPGS)MTX多聚谷氨酸(methotrexate polyglutamine,MTXPG)谷氨酸水解酶(gammaglutamylhydtrolase,GGH)FPGSFPGSGluGlu (27)(27)颅内淋巴瘤大剂量mtx化疗30 颅内淋巴瘤大剂量mtx化疗31颅内淋巴瘤大剂量mtx化疗32颅内淋巴瘤大剂量mtx化疗33颅内淋巴瘤大剂量mtx化疗34