血管新生抑制因子之临床运用课件

血管新生抑制因子之临床运用血管新生抑制因子之临床运用血管新生抑制因子之临床运用Angiogenesistheprocessofgrowingnewbloodvessels

playsanimportantroleinphysiologicalprocesssuchasfetaldevelopment,woundhealing,andmenstrualcycleparticipatesinpathologicalconditionssuchastumorigenesis,retinopathy,andarthritis.血管新生抑制因子之临床运用Tumordevelopmentstages血管新生抑制因子之临床运用Clinicalapplicationof

angiogenesisinhibitorscancer/metastasiscorneaangiogenesischoroidalneovascularizationrheumatoidarthritis血管新生抑制因子之临床运用Dr.Folkman'sWaronCancer

PioneeronangiogenesisandtumorsuppressionTreatcanceraschronicdisease!血管新生抑制因子之临床运用NPCcalreticulin1--4171--18020-6xHis-vasostatinExpressionandpurificationofvasostatinABkDa30-vasostatin血管新生抑制因子之临床运用Vasostatininducedendothelialapoptosis血管新生抑制因子之临床运用Vasostatinperturbedtubeformation血管新生抑制因子之临床运用InhibitionofneovascularizationinCAMPBSVS血管新生抑制因子之临床运用Summary(I)VasostatinspecificallyinducesapoptosisinendothelialcellsVasostatininhibitsangiogenesisinvitroandinvivo血管新生抑制因子之临床运用Topicalapplicationofvasostatinfortreatmentofneovascularizationineyes血管新生抑制因子之临床运用Angiogenesiscausesproblemsineyes**血管新生抑制因子之临床运用Modelsfor

eyeneovascularization

corneaangiogenesis

implantationofbFGF-containingpolymerintocornea

choroidalneovascularization

laser-inducedphotocoagulation血管新生抑制因子之临床运用Excellentstabilityofvasostatin血管新生抑制因子之临床运用ExperimentalSchemeVSeyedropeyedrop血管新生抑制因子之临床运用TopicalapplicationofVSeyedropreducedcorneaangiogenesis血管新生抑制因子之临床运用TopicalapplicationofVSeyedropreducedcorneaangiogenesisMolecularVision2005;11:28-35血管新生抑制因子之临床运用Corneaiseasy.Howaboutretina?**血管新生抑制因子之临床运用Choroidalneovascularization

/MaculardegenerationChoroidalneovascularization(CNV)istheprimarycauseforvisionlossinpatientswithmaculardegeneration血管新生抑制因子之临床运用InductionofchoroidalneovscularizationphotoreceptorsandRPEdamagelaserfreeradicalproduction3-6weeksFluoresceinangiography血管新生抑制因子之临床运用ExperimentalScheme0 7 14 21 28 35 42(day)Eyedrops(n=12,threetimesdaily)LaserFAGanalysis血管新生抑制因子之临床运用PBSeyedropControlVSeyedropTopicalapplicationofVSreducedtheincidenceofCNV血管新生抑制因子之临床运用VSeyedropreducedtheareaofCNV血管新生抑制因子之临床运用Summary(II)RepeatedinjectionofvasostatinretardedthetumorgrowthandenhancedsurvivalEyedropcontainingvasostatineffectivelyinhibitedneovascularizationineyeswithoutsignificantadverseeffects血管新生抑制因子之临床运用Proteinworksgreat,buttediousandlabor-intensive

Howaboutgenedelivery?Whatnon-viralpolymertobeused?血管新生抑制因子之临床运用vasostatinAAAACMVHAGenedeliveryschemePVPpolymerpoly-(N-vinylpyrrolidone)DNA-PVPcomplexIMinjection血管新生抑制因子之临床运用kDa453121PBSpCMV3pCMV3-VS

-tubulinHA21HAPBSpCMV3pCMV3-VSkDaCellextractsCulturedsupernatantsVSgenedeliveryinmusclecells血管新生抑制因子之临床运用kDa-21.5PVP-vectorPVP-VSABHAcalreticulinIMinjectionofvasostatinPVPpolymercomplexledtosystemicvasostatinexpressionExperimentalEyeResearch81(2005)673–679血管新生抑制因子之临床运用IntramuscularVSgenedeliveryreducedtheincidenceofCNVsalinePVP-VSPVP-vectorExperimentalEyeResearch81(2005)673–679血管新生抑制因子之临床运用****IntramuscularVSgenedeliveryreducedtheextentofCNV血管新生抑制因子之临床运用HistologicalanalysisofCNVafterintramuscularVSgenedeliveryABPVP+vectorPVP+VS血管新生抑制因子之临床运用Summary(III)IntramuscularvasostatingenedeliveryincreasedcirculatingvasostatinlevelsandsuppressedtumorgrowthSystemicvasostatingenedeliverypotentlyinhibitedneovascularizationineyeswithoutsignificantadverseeffects血管新生抑制因子之临床运用Systemicanti-angiogenictherapyworkswell,butmayhaveadverseeffectonphysiologicalprocesses

Canweachievenon-invasive,localgenedeliveryineyes?血管新生抑制因子之临床运用LTUE1AE1BE2E3E4E3deletionAd5genomevasostatinCMVpromoterAATAAASV40polyAAdenovirusGeneDeliverySystemPurificationbyCsClgradientultracentrifugation1x1012pfu/mlluciferase血管新生抑制因子之临床运用day1day7day14day21day28day35Durationofadenovirus-mediatedluciferaseexpressionaftersubconjunctivalinjection血管新生抑制因子之临床运用ExperimentalScheme0 7 14 21 28 35 42(day)Subconjuntivalinjection(1x109pfu)LaserFAG&ERGanalysis血管新生抑制因子之临床运用SuppressionofCNVby

subconjunctivalinjectionofAd-VSControlAd-GFPAd-VS血管新生抑制因子之临床运用SuppressionofCNVby

subconjunctivalinjectionofAd-VS血管新生抑制因子之临床运用Summary(IV)Subconjunctivalinjectionofadenovirusvectorsleadstosustainedtransgeneexpressioninconjunctivaregionfor28daysSubconjunctivalinjectionofAd-VSeff