恶性脑肿瘤的化学治疗.pptVIP

BBBD治疗Osmoticopeningoftheblood-brainbarrier.Whenendothelialcellsthatlinecapillarywallsareexposedtoaconcentratedsugarsolution,thecellsshrink,thusopeningthetightjunctionsbetweenthem.(Adaptedfrom:SIRapoport,Blood-BrainBarrierinPhysiologyandMedicine.RavenPress,1976.)Blood-BrainBarrierDisruption(BBBD)治疗第30页，共69页，星期日，2025年，2月5日A/E:颈动脉灌注高渗溶液,迅速改变BBB通透性 20%甘露醇150-250ml,5-10ml/sec BBB血管内皮细胞收缩 胞间紧密联接增宽 ↓ 脑组织含水量增加1.0%-1.5% ↓ 4hr恢复正常 20世纪80年代用于临床 尚未Ⅲ期研究证实近年研究:BBB开放无选择性,内皮细胞破坏: 正常脑组织肿瘤,正常脑组织暴露化疗药物↑高渗性BBB开放第31页，共69页，星期日，2025年，2月5日第32页，共69页，星期日，2025年，2月5日Bloodbrainbarrierdisruption(BBBD)andintra-arterialmethotrexatebasedtherapyfornewlydiagnosedprimaryCNSlymphoma:TheBBBDConsortiumExperience.2007ASCOAnnualMeetingProceedingsPartI.Vol25,No.18S4institutions：1982-2005，177PCNSLBBBD/IAMTX；2,469proceduresPtsCRPRORRMOS(y)MPFS(y)PFS-5(y)1771014180.2%3.11.640%第33页，共69页，星期日，2025年，2月5日APhaseIITrialInvolvingPatientswithRecurrentPCNSLTreatedwithCarboplatin/BBBD,byAddingRituxan(Rituximab),anantiCD-20Antibody,totheTreatmentRegimenPhaseI/IIStudyofCarboplatin,MelphalanandEtoposidePhosphateinConjunctionwithOsmoticOpeningoftheBlood-BrainBarrierandDelayedIntravenousSodiumThiosulfateChemoprotection,inSubjectswithAnaplasticOligodendrogliomaorOligoastrocytomaPhaseIIClinicalTrialofPatientswithHigh-GradeGliomaTreatedwithIntra-arterialCarboplatin-basedChemotherapy,RandomizedtoTreatmentwithorwithoutDelayedIntravenousSodiumThiosulfateasaPotentialChemoprotectantagainstSevereThrombocytopeniaIntra-arterialMelphalan(L-phenylalaninemustard)AdministeredinConjunctionwithOsmoticBlood-BrainBarrierDisruptioninPatientswithBrainMalignancies:APhaseIStudyNeuro-OncologyBlood-BrainBarrierProgramOregonHealthScienceUniversity

BloodBrainBarrierandNeuro-OncologyPr