Dual metronomic chemotherapy with nab-paclitaxel and topotecan has potent anti-angiogenic activity in ovarian cancer

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1、Dualmetronomicchemotherapywithnab-paclitaxelandtopotecanhaspotentanti-angiogenicactivityinovariancancer1121RebeccaA.Previs*,GuillermoN.Armaiz-Pena*,YvonneG.Lin*,AshleyN.Davis,Sunila11111Pradeep,HeatherJ.Dalton,JeanM.Hansen,WilliamM.Merritt,AlpaM.Nick,RobertR.311,3,4Langley,Rob

2、ertL.Coleman,AnilK.Sood134DepartmentsofGynecologicOncology,CancerBiologyandtheCenterforRNAInterferenceandNon-CodingRNA,TheUniversityofTexasMDAndersonCancerCenter,Houston,770302DepartmentofObstetricsandGynecology,KeckSchoolofMedicine,UniversityofSouthernCalifornia,LosAngeles,CA9

3、0033*Theseauthorscontributedequallytothisproject.Currentaddress:SCOncologyAssociates,166StoneridgeDr,ColumbiaSC29210CorrespondingAuthor:Dr.AnilK.Sood,Professor,DepartmentsofGynecologicOncologyandCancerBiology,Unit1362,TheUniversityofTexasMDAndersonCancerCenter,1515HolcombeBlvd

4、,Houston,TX77030,USAtel:713-745-5266fax:713-792-7586email:asood@mdanderson.orgRunningTitle:Metronomicnab-paclitaxelandtopotecaninhibitangiogenesisKeyWords:nab-paclitaxel,topotecan,angiogenesis,metronomic,ovariancarcinomaDisclosureofPotentialConflictsofInterest:Theauthorsdeclare

5、thattherearenoconflictsofinterest.FinancialInformationFinancialsupportwasprovidedbytheNationalInstitutesofHealth(P50CA098258,CA109298,P50CA083639,U54CA151668,M.D.Anderson'sCancerCenterSupportGrantCA016672),theOvarianCancerResearchFund,Inc.(ProgramProjectDevelopmentGrant),theU.S

6、.DepartmentofDefense(OC073399,OC093146,BC085265),theAnnRifeCoxChairinGynecology,theBettyAnneAscheMurrayDistinguishedProfessorship,theRGKFoundation,andtheGilderFoundationtoA.K.Sood.R.A.Previs,J.M.HansenandH.J.DaltonweresupportedbyanNCI-DHHS-NIHT32TrainingGrant(T32CA101642).1Abst

7、ractThereisgrowingrecognitionoftheimportantroleofmetronomicchemotherapyincancertreatment.Onthebasisoftheiruniqueanti-angiogeniceffects,wetestedtheefficacyofnab-paclitaxel,whichstimulatesthrombospondin-1,andtopotecan,whichinhibitshypoxia-induciblefactor1-α,atmetronomicdosingfort

8、hetreatmentofovariancarcinoma.InvitroandinvivoSKOV3ip1