大剂量rmhtnf治疗恶性心包积液或恶性胸腔积液的临床研究

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1、第二军医大学硕+学位论文system，hematologicalsystem，nervoussystem，digestivesystemandrespiratorysystem，especiallyuesdinalloverthebody．Becausetheseadverseevents，theclinicalapplicationofTNF0【hasbeenlimited．From1990s，inordertOimprovethecurativeeffectanddecreasetoxicity,thestudyofmutatedTNFahasbeenextensi

2、velydevolped．RecombinantmutatedhumanTNFaisakindofmutaedTNFahavingimprovedanti—tumoractivityanddecreasedtoxicity，whichisinventedbyTheForthMiilitaryMedcineUnivercity(FMMU)．InAugust2003，thefirstmutatedTNFawhichcouldbeuesdinalloverthebodywaslicensed．WefoundthatrmhTNFainducedonlythoracalgiaan

3、dfebrile，seldomreactionofgastrointestinaltract，whenusedintherapyingnonsmall—celllungcancer(NSCLC)．IfwegaveantipyreticanalgesicbeforeTNF0twasused，theseadverseeventscouldberelieved．Becausethehalf-lifeofnaturalTNFaisonly10-15min，andithasnospecificaffinitytOtumor，theconcentrationofTNFacannot

4、beelevatedintumor．Inordertoimprovethecurativeeffect，manypeopleinjectnaturalTNFo【Eintotumororcavityandfindthatthecurativeeffectisimprovedandthetoxityisnotincreased．ThemalignantpleuralefusionstherapyingmechanismofrmhTNFaissimilartOnaturalTNFa，includingsupressingtheexpressionofoncogene，dire

5、ctlykillingtumorcells，inducingnecrosisoftumorandfinallyreducingtheproductionofmalignantpleuralefusions．ThehighconcentrationofrmhTNFacaninducestrongerinflammatoryreaction，andleadtothenecrosisandfibrosisoftumor．ItwasalsoprovedthathighconcentrationofrmhTNFacouldinhibittheangiogenesisoftumor

6、．SowepresumedthatrmhTNFacouldbeusedinntracavitaryinicetionandtheconcentrationcouldbeincreasedtoimprovethecurativeeffectmeanwhilethetoxitymightnotbeincreased．Ifthehypothesiscouldbeapproved，theclinicalindicationofrmhTNFacouldbeexpanded，andtherewouldbeanewmethodtocontrolmalignantpleuralefus

7、ions．Toapproveourhypothesis，wecarriedoutthisstudyafterliscencedbyEthicsCommittee．Methods：I．DataofpatientsMalignantpericardialefusions：56patientswithmalignantpericardialefusions，whichwerefinallydiagnosedthroughpathologyorcytology,wererandomlyseperatedintoAgroupandBgroup(28