Aurora A 專一性抑制劑MLN8237造成細胞中Aurora A表現增加 ...

論文名稱(外文):, A selective Aurora A inhibitor, MLN8237, induces cellular Aurora A expression increase and centrosomal abnormality. 指導教授: 林赫. 資料載入處理中... 跳到主要內容 臺灣博碩士論文加值系統 ::: 網站導覽| 首頁| 關於本站| 聯絡我們| 國圖首頁| 常見問題| 操作說明 English |FB專頁 |Mobile 免費會員 登入| 註冊 功能切換導覽列 (188.166.176.73)您好！臺灣時間：2022/06/1804:26 字體大小：       ::: 詳目顯示 recordfocus 第1筆/ 共1筆  /1頁 論文基本資料 摘要 外文摘要 目次 參考文獻 電子全文 QRCode 本論文永久網址: 複製永久網址Twitter研究生:張智瑩研究生(外文):Chih-YingChang論文名稱:AuroraA專一性抑制劑MLN8237造成細胞中AuroraA表現增加及中心粒異常論文名稱(外文):AselectiveAuroraAinhibitor,MLN8237,inducescellularAuroraAexpressionincreaseandcentrosomalabnormality.指導教授:林赫指導教授(外文):HoLin口試委員:余長澤、吳俊錡口試委員(外文):Chang-TzeRickyYu、Chun-ChiWu口試日期:2018-07-11學位類別:碩士校院名稱:國立中興大學系所名稱:生命科學系所學門:生命科學學門學類:生物學類論文種類:學術論文論文出版年:2018畢業學年度:106語文別:中文論文頁數:67中文關鍵詞:AuroraA、MLN8237(Alisertib)、中心粒、p53外文關鍵詞:AuroraA、MLN8237(Alisertib)、centrosome、p53相關次數: 被引用:0點閱:138評分:下載:0書目收藏:0 在過去文獻中細胞週期中G1期→S期→G2期→M期四期，而有絲分裂(M期)則是在細胞週期扮演非常重要的一環，並且受到細胞外因子或是細胞內訊息傳遞所調控，且在不同的文獻中也提到當癌症發生時AuroraA會有過度表現的現象，因此也被當作是治療癌症指標之一。

而在不同年份中的文獻中也指出AurorakinaseA(AuroraA)是絲氨酸/蘇氨酸激酶(Serine/Threoninekinases)是Aurorakinase家族成員之一，主要參與在調控有絲分裂(Mitoticprogression)和減數分裂(Meiosisprogression)的過程，其中包含了中心體(Centrosome)的形成、使雙極紡錘體(Spindle)伸長、DNA解聚(Decondensation)和後期核膜重建，以及細胞移動(Celllocomotion)以及細胞極性化作用(Cellpolarity)上扮演重要角色。

Alisertib(MLN8237)是一種AuroraA選擇性小分子抑制劑，是從先前分子Alisertib開發的用於治療晚期惡性腫瘤的選擇性小分子AAK(AuroraAkinase)抑製劑，並在許多癌症治療中作為單一藥物開發中，並會和其他藥物做合併使用。

當我們將MLN8237用於生長快速的胚胎腎元細胞(HEK293)，我們發現到了各式蛋白質的表現量上升如：CyclinB1、CyclinD1，表示了在MLN8237處理下，細胞週期的進展受到了影響，細胞週期停留在G2/M期，但在偶然情況下將藥物處理於非小細胞肺癌(H1299)發現了AuroraA的蛋白質表現量隨著劑量的上升有顯著性上升的趨勢，也觀察了AuroraA的mRNA(AurkA)表現量隨之上升，並且在免疫螢光染色方面證實了加入MLN8237藥物會使的染色體、中心粒的異常，並會使的AuroraA明顯的累積性增加，也在HeLa細胞中發現了AuroraA蛋白質的增加以及p53蛋白質的減少，很有可能MLN8237藥物會透過AuroraA和p53之間負向調控而影響AuroraA的增加，本次研究所發現的結果在臨床應用具有一定程度的貢獻，且對治療時提供了一些應注意的事項。

AuroraAisaserine/threoninekinasewhichprimarilylocalizesinthecentrosomeandmitoticspindleandrespondsforcentrosomematuration,separation,spindleformationandmitoticentry.Therefore,AuroraAplaysanimportantregulatortomitosisandmeiosisaswellastheregulationofcellproliferation.TheoncogenicroleofAuroraAhasalsobeenexploredinrecentyearsanditsinhibitionbecomesarelevantissueincancertherapy.MLN8237(Alisertib)isaspecificinhibitorofAuroraAwhichhasbeencurrentlyunderevaluationofcancerclinicaltrial.Inourpresentresultstreatingthefast-growingcellline,HEK293,withMLN8237(0-500nM),wefoundtheproteinlevelsofCyclinB1andCyclinD1wereincreased,suggestingtheprogressofG2/Mphaseincellcyclewasaffected.ItreflectsthereasonwhyMLN8237canbeusedtotreatcancer.Accidentally,theproteinlevelsofAuroraAwassignificantlyincreasedafterMLN8237treatment.Severallinesofevidencealsoaddresssimilarfindingswithoutdetailedmechanismanddiscussion.Inadditiontoproteinlevels,therealtimeQ-PCRdataindicatedthatAuroraAmRNA(AurkA)wasalsoincreasedafterMLN8237treatment.Andp53proteinlevelsandQ-PCRdatawasalsodecreasedafterMLN8237treatment.Insummary,MLN8237isapotentialdrugforfuturecancertherapy;however,thetreatmentmightleadtotheincreasinggeneexpressionofitself.Thephysiologicalnegativefeedbackmightbeoneofthereasonstoexplainthephenomenon.Meanwhile,thecombinationtreatmentagainstAuroraAexpressionwithitskinaseinhibitormightbebeneficialtocomprehensivelyblockAuroraAactionsincellproliferationinhibition,polyploidy,mitoticcatastropheandmultiplecentrosome. 目次第一章、前言-1-一、背景-1-(一)、本次實驗使用之細胞介紹-1-(二)、細胞週期與細胞週期調控蛋白-4-(三)、AurorakinaseA與中心體介紹-7-(四)、AurorakinaseA與肺癌-9-(五)、MLN8237(Alisertib)藥物-10-二、研究動機-11-第二章、材料與方法-12-一、細胞之培養(CellCulture)-12-二、蛋白質萃取與定量分析-13-(一)、蛋白質萃取(Proteinextraction)-13-(二)、蛋白質濃度測定(BradfordAssay)-13-三、西方墨點法(Westernblotting)-14-(一)、聚丙烯醯胺膠體電泳(SDS-polyacrylamidegelelectrophoresis,SDS-PAGE)-14-(二)、蛋白質轉印法(Transfer)-15-(三)、抗體偵測呈色-15-四、細胞生長測定(Trypanblueassay&MTTassay)-16-五、細胞核質蛋白分離(Nuclear/CytosolProteinFractionation)-17-六、免疫沈澱法(Immunoprecipitation,IP)-18-七、基因體轉染技術(Transfection)-18-八、免疫螢光雜交染色(Immunocytochemistry,ICC)-19-九、mRNA表現量分析-20-(一)、TotalRNA純化抽取(TotalRNApurification)-20-(二)、反轉錄聚合酶連鎖反應(RT-PCR,ReverseTranscriptionpolymerasechainreaction)-21-(三)、定量即時聚合酶連鎖反應(QuantitativeRT-PCR)-21-十、報導基因分析(ReporterAssay)-22-十一、量化統計分析-23-十二、附錄-24-(一)、抗體產品型號-24-第三章、實驗結果-25-一、觀察MLN8237藥物使細胞生長停滯-25-(一)、對於HEK293、H1299、MRC-5細胞型態影響-25-(二)、對於HEK293、H1299、MRC-5細胞生長影響-25-二、觀察MLN8237藥物對於細胞內蛋白質表現量影響-26-(一)、對於HEK293、H1299、MRC-5、HeLa相關蛋白的表現-26-(二)、對於H1299的AuroraA蛋白質隨著時間而增加-28-三、觀察MLN8237藥物影響基因層面表現量-28-(一)、MLN8237藥物使得AuroraAmRNA(AurkA)的表現量增加-28-(二)、MLN8237藥物使得p53mRNA(TP53)的表現量增加-29-四、觀察MLN8237藥物影響AuroraA在細胞內表現分佈-29-(一)、觀察在正常情況下AuroraA與中心粒的分佈情形-29-(二)、MLN8237藥物使得AuroraA在細胞內增加比例-30-(三)、MLN8237藥物使得細胞內中心粒異常表現-30-(四)、MLN8237藥物使得細胞內中染色體異常表現-31-第四章、討論-32-(一)、MLN8237藥物使得細胞生長及形態變化-32-(二)、MLN8237藥物使得AuroraA蛋白質上升p53蛋白質減少-32-(三)、MLN8237增加了AuroraAmRNA表現量-33-(四)、MLN8237影響p53mRNA表現量-33-(五)、MLN8237藥物使得AuroraA表現量增加影響中心粒及染色體異常-34-第五章、結論-35-第六章、參考文獻-36-第七章、實驗結果圖-44- 1.Jacobs,J.P.,Jones,C.M.,andBaille,J.P.(1970)CharacteristicsofahumandiploidcelldesignatedMRC-5.Nature227,168-1702.Mao,Y.,Yang,D.,He,J.,andKrasna,M.J.(2016)EpidemiologyofLungCancer.SurgicaloncologyclinicsofNorthAmerica25,439-4453.North,C.M.,andChristiani,D.C.(2013)Womenandlungcancer:whatisnew?Seminarsinthoracicandcardiovascularsurgery25,87-944.Rivera,G.A.,andWakelee,H.(2016)LungCancerinNeverSmokers.Advancesinexperimentalmedicineandbiology893,43-575.Haddadin,S.,andPerry,M.C.(2011)Historyofsmall-celllungcancer.Clinicallungcancer12,87-936.Sampsonas,F.,Ryan,D.,McPhillips,D.,andBreen,D.P.(2014)Moleculartestingandpersonalizedtreatmentoflungcancer.Currentmolecularpharmacology7,22-327.Sculier,J.P.(2013)Nonsmallcelllungcancer.Europeanrespiratoryreview:anofficialjournaloftheEuropeanRespiratorySociety22,33-368.Semenova,E.A.,Nagel,R.,andBerns,A.(2015)Origins,geneticlandscape,andemergingtherapiesofsmallcelllungcancer.Genes&development29,1447-14629.Sesti,J.,andDonington,J.S.(2014)Managinglungcancerinhigh-riskpatients:whattoconsider.Expertreviewofrespiratorymedicine8,443-45210.Sibille,A.,Paulus,A.,Martin,M.,Bourhaba,M.,Barthelemy,N.,Radermecker,M.,Corhay,J.L.,Louis,R.,andDuysinx,B.(2015)[MANAGEMENTOFNON-SMALLCELLLUNGCANCER].RevuemedicaledeLiege70,432-44111.Sundar,R.,Soong,R.,Cho,B.C.,Brahmer,J.R.,andSoo,R.A.(2014)Immunotherapyinthetreatmentofnon-smallcelllungcancer.Lungcancer(Amsterdam,Netherlands)85,101-10912.Wakelee,H.,Kelly,K.,andEdelman,M.J.(2014)50Yearsofprogressinthesystemictherapyofnon-smallcelllungcancer.AmericanSocietyofClinicalOncologyeducationalbook.AmericanSocietyofClinicalOncology.Meeting,177-18913.Byron,E.,andPinder-Schenck,M.(2014)Systemicandtargetedtherapiesforearly-stagelungcancer.Cancercontrol:journaloftheMoffittCancerCenter21,21-3114.Biswas,T.,Sharma,N.,andMachtay,M.(2014)ControversiesinthemanagementofstageIIInon-small-celllungcancer.Expertreviewofanticancertherapy14,333-34715.Bolca,C.,Danaila,O.,Paleru,C.,andCordos,I.(2013)[Roleofsurgeryinsmallcelllungcancer].Pneumologia(Bucharest,Romania)62,236-23816.Gadgeel,S.M.(2016)PersonalizedTherapyofNon-smallCellLungCancer(NSCLC).Advancesinexperimentalmedicineandbiology890,203-22217.Li,X.,andZhu,G.(2014)[ClinicaldevelopmentsfortheEGFR-TKIcombinedwithradiotherapyinadvancednon-smallcelllungcancer].Zhongguofeiaizazhi=Chinesejournaloflungcancer17,357-36218.Sadiq,A.A.,andSalgia,R.(2013)METasapossibletargetfornon-small-celllungcancer.Journalofclinicaloncology:officialjournaloftheAmericanSocietyofClinicalOncology31,1089-109619.Hensing,T.,Chawla,A.,Batra,R.,andSalgia,R.(2014)Apersonalizedtreatmentforlungcancer:molecularpathways,targetedtherapies,andgenomiccharacterization.Advancesinexperimentalmedicineandbiology799,85-11720.Chen,K.N.(2016)[SmallCellLungCancerandTNMStaging].Zhongguofeiaizazhi=Chinesejournaloflungcancer19,409-41221.Abe,Y.,andTanaka,N.(2016)TheHedgehogSignalingNetworksinLungCancer:TheMechanismsandRolesinTumorProgressionandImplicationsforCancerTherapy.BioMedresearchinternational2016,796928622.Arcaro,A.(2015)Targetedtherapiesforsmallcelllungcancer:Wheredowestand?Criticalreviewsinoncology/hematology95,154-16423.Cagle,P.T.,Allen,T.C.,andOlsen,R.J.(2013)Lungcancerbiomarkers:presentstatusandfuturedevelopments.Archivesofpathology&laboratorymedicine137,1191-119824.Czarnecka-Kujawa,K.,andYasufuku,K.(2014)Molecularalterationsinnon-small-celllungcancer:perspectivefortargetedtherapyandspecimenmanagementforthebronchoscopist.Respirology(Carlton,Vic.)19,1117-112525.Garon,E.B.,Abarca,P.A.,Strunck,J.L.,Nameth,D.,Neumann,C.,Wolf,B.,Kim,K.Y.,Marx,C.,andElashoff,R.M.(2015)ClinicalTrialsinNon-SmallCellLungCancerwithBiomarker-DrivenTreatmentAllocation:ReadyorNot,HereWeCome.Criticalreviewsinoncogenesis20,339-34726.Mar,N.,Vredenburgh,J.J.,andWasser,J.S.(2015)TargetingHER2inthetreatmentofnon-smallcelllungcancer.Lungcancer(Amsterdam,Netherlands)87,220-22527.Evans,M.(2013)Lungcancer:needsassessment,treatmentandtherapies.Britishjournalofnursing(MarkAllenPublishing)22,S15-16,s18,s20-1228.Gerber,D.E.,Paik,P.K.,andDowlati,A.(2015)Beyondadenocarcinoma:currenttreatmentsandfuturedirectionsforsquamous,smallcell,andrarelungcancerhistologies.AmericanSocietyofClinicalOncologyeducationalbook.AmericanSocietyofClinicalOncology.Meeting,147-16229.Jiang,S.,andLi,P.(2015)[ProgressinPalliativeCareBenefitofElderlyPatientswithNon-smallCellLungCancer].Zhongguofeiaizazhi=Chinesejournaloflungcancer18,462-46830.Lu,Y.,andFan,Y.(2015)[ResearchProgressionofMaintenanceTherapyinSmallCellLungCancer].Zhongguofeiaizazhi=Chinesejournaloflungcancer18,559-56431.Zheng,G.,andYu,H.(2015)Regulationofsisterchromatidcohesionduringthemitoticcellcycle.ScienceChina.Lifesciences58,1089-109832.Williams,G.H.,andStoeber,K.(2012)Thecellcycleandcancer.TheJournalofpathology226,352-36433.Vermeulen,K.,Berneman,Z.N.,andVanBockstaele,D.R.(2003)Cellcycleandapoptosis.Cellproliferation36,165-17534.Swanton,C.(2004)Cell-cycletargetedtherapies.TheLancet.Oncology5,27-3635.Smith,J.A.,andMartin,L.(1973)Docellscycle?ProceedingsoftheNationalAcademyofSciencesoftheUnitedStatesofAmerica70,1263-126736.Salomoni,P.,andCalegari,F.(2010)Cellcyclecontrolofmammalianneuralstemcells:puttingaspeedlimitonG1.Trendsincellbiology20,233-24337.Pines,J.(2011)Cubismandthecellcycle:themanyfacesoftheAPC/C.Naturereviews.Molecularcellbiology12,427-43838.Pietenpol,J.A.,andStewart,Z.A.(2002)Cellcyclecheckpointsignaling:cellcyclearrestversusapoptosis.Toxicology181-182,475-48139.Levy,A.,Albiges-Sauvin,L.,Massard,C.,Soria,J.C.,andDeutsch,E.(2011)[Cellcycle,mitosisandtherapeuticapplications].Bulletinducancer98,1037-104540.Imoto,Y.,Yoshida,Y.,Yagisawa,F.,Kuroiwa,H.,andKuroiwa,T.(2011)Thecellcycle,includingthemitoticcycleandorganelledivisioncycles,asrevealedbycytologicalobservations.Journalofelectronmicroscopy60Suppl1,S117-13641.Heber-Katz,E.,Zhang,Y.,Bedelbaeva,K.,Song,F.,Chen,X.,andStocum,D.L.(2013)Cellcycleregulationandregeneration.Currenttopicsinmicrobiologyandimmunology367,253-27642.Harper,J.V.,andBrooks,G.(2005)Themammaliancellcycle:anoverview.Methodsinmolecularbiology(Clifton,N.J.)296,113-15343.Ford,H.L.,andPardee,A.B.(1999)Cancerandthecellcycle.JournalofcellularbiochemistrySuppl32-33,166-17244.DeSouza,C.P.,andOsmani,S.A.(2007)Mitosis,notjustopenorclosed.Eukaryoticcell6,1521-152745.Dalton,S.(2015)LinkingtheCellCycletoCellFateDecisions.Trendsincellbiology25,592-60046.Bertoli,C.,Skotheim,J.M.,anddeBruin,R.A.(2013)ControlofcellcycletranscriptionduringG1andSphases.Naturereviews.Molecularcellbiology14,518-52847.Bendris,N.,Lemmers,B.,andBlanchard,J.M.(2015)Cellcycle,cytoskeletondynamicsandbeyond:themanyfunctionsofcyclinsandCDKinhibitors.Cellcycle(Georgetown,Tex.)14,1786-179848.Ubersax,J.A.,Woodbury,E.L.,Quang,P.N.,Paraz,M.,Blethrow,J.D.,Shah,K.,Shokat,K.M.,andMorgan,D.O.(2003)Targetsofthecyclin-dependentkinaseCdk1.Nature425,859-86449.Qiao,X.,Zhang,L.,Gamper,A.M.,Fujita,T.,andWan,Y.(2010)APC/C-Cdh1:fromcellcycletocellulardifferentiationandgenomicintegrity.Cellcycle(Georgetown,Tex.)9,3904-391250.Pines,J.,andHunter,T.(1992)CyclinsAandB1inthehumancellcycle.CibaFoundationsymposium170,187-196;discussion196-20451.Vermeulen,K.,VanBockstaele,D.R.,andBerneman,Z.N.(2003)Thecellcycle:areviewofregulation,deregulationandtherapeutictargetsincancer.Cellproliferation36,131-14952.Stacey,D.W.(2003)CyclinD1servesasacellcycleregulatoryswitchinactivelyproliferatingcells.Currentopinionincellbiology15,158-16353.Sanchez,I.,andDynlacht,B.D.(2005)Newinsightsintocyclins,CDKs,andcellcyclecontrol.Seminarsincell&developmentalbiology16,311-32154.Nigg,E.A.(1995)Cyclin-dependentproteinkinases:keyregulatorsoftheeukaryoticcellcycle.BioEssays:newsandreviewsinmolecular,cellularanddevelopmentalbiology17,471-48055.Morgan,D.O.(1992)Cellcyclecontrolinnormalandneoplasticcells.Currentopinioningenetics&development2,33-3756.Mombach,J.C.,Bugs,C.A.,andChaouiya,C.(2014)ModellingtheonsetofsenescenceattheG1/Scellcyclecheckpoint.BMCgenomics15Suppl7,S757.Lopez-Mejia,I.C.,andFajas,L.(2015)Cellcycleregulationofmitochondrialfunction.Currentopinionincellbiology33,19-2558.Lim,S.,andKaldis,P.(2013)Cdks,cyclinsandCKIs:rolesbeyondcellcycleregulation.Development(Cambridge,England)140,3079-309359.Johnson,D.G.,andWalker,C.L.(1999)Cyclinsandcellcyclecheckpoints.Annualreviewofpharmacologyandtoxicology39,295-31260.Hermeking,H.,andBenzinger,A.(2006)14-3-3proteinsincellcycleregulation.Seminarsincancerbiology16,183-19261.Dillon,M.T.,Good,J.S.,andHarrington,K.J.(2014)SelectivetargetingoftheG2/Mcellcyclecheckpointtoimprovethetherapeuticindexofradiotherapy.Clinicaloncology(RoyalCollegeofRadiologists(GreatBritain))26,257-26562.Barnum,K.J.,andO''Connell,M.J.(2014)Cellcycleregulationbycheckpoints.Methodsinmolecularbiology(Clifton,N.J.)1170,29-4063.Arellano,M.,andMoreno,S.(1997)RegulationofCDK/cyclincomplexesduringthecellcycle.Theinternationaljournalofbiochemistry&cellbiology29,559-57364.Katsha,A.,Belkhiri,A.,Goff,L.,andEl-Rifai,W.(2015)AurorakinaseAingastrointestinalcancers:timetotarget.Molecularcancer14,10665.Fu,J.,Bian,M.,Jiang,Q.,andZhang,C.(2007)RolesofAurorakinasesinmitosisandtumorigenesis.Molecularcancerresearch:MCR5,1-1066.Damodaran,A.P.,Vaufrey,L.,Gavard,O.,andPrigent,C.(2017)AuroraAKinaseIsaPriorityPharmaceuticalTargetfortheTreatmentofCancers.Trendsinpharmacologicalsciences38,687-70067.D''Assoro,A.B.,Haddad,T.,andGalanis,E.(2015)Aurora-AKinaseasaPromisingTherapeuticTargetinCancer.Frontiersinoncology5,29568.Carvajal,R.D.,Tse,A.,andSchwartz,G.K.(2006)Aurorakinases:newtargetsforcancertherapy.Clinicalcancerresearch:anofficialjournaloftheAmericanAssociationforCancerResearch12,6869-687569.Bolanos-Garcia,V.M.(2005)Aurorakinases.Theinternationaljournalofbiochemistry&cellbiology37,1572-157770.Nikonova,A.S.,Astsaturov,I.,Serebriiskii,I.G.,Dunbrack,R.L.,Jr.,andGolemis,E.A.(2013)AuroraAkinase(AURKA)innormalandpathologicalcelldivision.Cellularandmolecularlifesciences:CMLS70,661-68771.Crane,R.,Gadea,B.,Littlepage,L.,Wu,H.,andRuderman,J.V.(2004)AuroraA,meiosisandmitosis.Biologyofthecell96,215-22972.Hong,Y.R.,Chen,C.H.,Chang,J.H.,Wang,S.,Sy,W.D.,Chou,C.K.,andHowng,S.L.(2000)Cloningandcharacterizationofanovelhumannineinproteinthatinteractswiththeglycogensynthasekinase3beta.Biochimicaetbiophysicaacta1492,513-51673.Hong,Y.R.,Chen,C.H.,Chuo,M.H.,Liou,S.Y.,andHowng,S.L.(2000)Genomicorganizationandmolecularcharacterizationofthehumannineingene.Biochemicalandbiophysicalresearchcommunications279,989-99574.Wu,J.M.,Chen,C.T.,Coumar,M.S.,Lin,W.H.,Chen,Z.J.,Hsu,J.T.,Peng,Y.H.,Shiao,H.Y.,Lin,W.H.,Chu,C.Y.,Wu,J.S.,Lin,C.T.,Chen,C.P.,Hsueh,C.C.,Chang,K.Y.,Kao,L.P.,Huang,C.Y.,Chao,Y.S.,Wu,S.Y.,Hsieh,H.P.,andChi,Y.H.(2013)AurorakinaseinhibitorsrevealmechanismsofHURPinnucleationofcentrosomalandkinetochoremicrotubules.ProceedingsoftheNationalAcademyofSciencesoftheUnitedStatesofAmerica110,E1779-178775.Wong,J.,Lerrigo,R.,Jang,C.Y.,andFang,G.(2008)AuroraAregulatestheactivityofHURPbycontrollingtheaccessibilityofitsmicrotubule-bindingdomain.Molecularbiologyofthecell19,2083-209176.Wang,G.F.,Dong,Q.,Bai,Y.,Yuan,J.,Xu,Q.,Cao,C.,andLiu,X.(2017)OxidativestressinducesmitoticarrestbyinhibitingAuroraA-involvedmitoticspindleformation.Freeradicalbiology&medicine103,177-18777.Schneider,M.A.,Christopoulos,P.,Muley,T.,Warth,A.,Klingmueller,U.,Thomas,M.,Herth,F.J.,Dienemann,H.,Mueller,N.S.,Theis,F.,andMeister,M.(2017)AURKA,DLGAP5,TPX2,KIF11andCKAP5:Fivespecificmitosis-associatedgenescorrelatewithpoorprognosisfornon-smallcelllungcancerpatients.Internationaljournalofoncology50,365-37278.deGroot,C.O.,Hsia,J.E.,Anzola,J.V.,Motamedi,A.,Yoon,M.,Wong,Y.L.,Jenkins,D.,Lee,H.J.,Martinez,M.B.,Davis,R.L.,Gahman,T.C.,Desai,A.,andShiau,A.K.(2015)ACellBiologist''sFieldGuidetoAuroraKinaseInhibitors.Frontiersinoncology5,28579.Afonso,O.,Figueiredo,A.C.,andMaiato,H.(2017)LatemitoticfunctionsofAurorakinases.Chromosoma126,93-10380.Kobayashi,A.,Hashizume,C.,Dowaki,T.,andWong,R.W.(2015)TherapeuticpotentialofmitoticinteractionbetweenthenucleoporinTprandaurorakinaseA.Cellcycle(Georgetown,Tex.)14,1447-145881.Pihan,G.A.(2013)Centrosomedysfunctioncontributestochromosomeinstability,chromoanagenesis,andgenomereprogramingincancer.Frontiersinoncology3,27782.Giet,R.,andPrigent,C.(1999)Aurora/Ipl1p-relatedkinases,anewoncogenicfamilyofmitoticserine-threoninekinases.Journalofcellscience112(Pt21),3591-360183.Agnese,V.,Bazan,V.,Fiorentino,F.P.,Fanale,D.,Badalamenti,G.,Colucci,G.,Adamo,V.,Santini,D.,andRusso,A.(2007)TheroleofAurora-Ainhibitorsincancertherapy.Annalsofoncology:officialjournaloftheEuropeanSocietyforMedicalOncology18Suppl6,vi47-5284.Yan,M.,Wang,C.,He,B.,Yang,M.,Tong,M.,Long,Z.,Liu,B.,Peng,F.,Xu,L.,Zhang,Y.,Liang,D.,Lei,H.,Subrata,S.,Kelley,K.W.,Lam,E.W.,Jin,B.,andLiu,Q.(2016)Aurora-AKinase:APotentOncogeneandTargetforCancerTherapy.Medicinalresearchreviews36,1036-107985.Tang,A.,Gao,K.,Chu,L.,Zhang,R.,Yang,J.,andZheng,J.(2017)Aurorakinases:noveltherapytargetsincancers.Oncotarget8,23937-2395486.Zou,L.J.,Li,G.Q.,Gong,L.L.,Wang,Y.,Jin,W.,Zhao,J.Y.,Ma,H.Y.,Yang,P.M.,andShao,S.J.(2005)[Expressionofaurora-AkinaseinhumanlungcancercelllinesPG,A549,andNCI-H460].Aizheng=Aizheng=Chinesejournalofcancer24,792-79587.Xu,H.T.,Ma,L.,Qi,F.J.,Liu,Y.,Yu,J.H.,Dai,S.D.,Zhu,J.J.,andWang,E.H.(2006)Expressionofserinethreoninekinase15isassociatedwithpoordifferentiationinlungsquamouscellcarcinomaandadenocarcinoma.Pathologyinternational56,375-38088.Smith,S.L.,Bowers,N.L.,Betticher,D.C.,Gautschi,O.,Ratschiller,D.,Hoban,P.R.,Booton,R.,Santibanez-Koref,M.F.,andHeighway,J.(2005)OverexpressionofauroraBkinase(AURKB)inprimarynon-smallcelllungcarcinomaisfrequent,generallydrivenfromoneallele,andcorrelateswiththelevelofgeneticinstability.Britishjournalofcancer93,719-72989.Linardopoulos,S.(2007)Aurora-AkinaseregulatesNF-kappaBactivity:lessonsfromcombinationstudies.JournalofB.U.ON.:officialjournaloftheBalkanUnionofOncology12Suppl1,S67-7090.Sun,C.,Chan,F.,Briassouli,P.,andLinardopoulos,S.(2007)AurorakinaseinhibitiondownregulatesNF-kappaBandsensitisestumourcellstochemotherapeuticagents.Biochemicalandbiophysicalresearchcommunications352,220-22591.Ogawa,E.,Takenaka,K.,Katakura,H.,Adachi,M.,Otake,Y.,Toda,Y.,Kotani,H.,Manabe,T.,Wada,H.,andTanaka,F.(2008)PerimembraneAurora-Aexpressionisasignificantprognosticfactorincorrelationwithproliferativeactivityinnon-small-celllungcancer(NSCLC).Annalsofsurgicaloncology15,547-55492.Zhang,X.H.,Rao,M.,Loprieato,J.A.,Hong,J.A.,Zhao,M.,Chen,G.Z.,Humphries,A.E.,Nguyen,D.M.,Trepel,J.B.,Yu,X.,andSchrump,D.S.(2008)AuroraA,AuroraBandsurvivinarenoveltargetsoftranscriptionalregulationbyhistonedeacetylaseinhibitorsinnon-smallcelllungcancer.Cancerbiology&therapy7,1388-139793.Adams,N.D.,Adams,J.L.,Burgess,J.L.,Chaudhari,A.M.,Copeland,R.A.,Donatelli,C.A.,Drewry,D.H.,Fisher,K.E.,Hamajima,T.,Hardwicke,M.A.,Huffman,W.F.,Koretke-Brown,K.K.,Lai,Z.V.,McDonald,O.B.,Nakamura,H.,Newlander,K.A.,Oleykowski,C.A.,Parrish,C.A.,Patrick,D.R.,Plant,R.,Sarpong,M.A.,Sasaki,K.,Schmidt,S.J.,Silva,D.J.,Sutton,D.,Tang,J.,Thompson,C.S.,Tummino,P.J.,Wang,J.C.,Xiang,H.,Yang,J.,andDhanak,D.(2010)DiscoveryofGSK1070916,apotentandselectiveinhibitorofAuroraB/Ckinase.Journalofmedicinalchemistry53,3973-400194.Biran,A.,Brownstein,M.,Haklai,R.,andKloog,Y.(2011)DownregulationofsurvivinandauroraAbyhistonedeacetylaseandRASinhibitors:anewdrugcombinationforcancertherapy.Internationaljournalofcancer128,691-70195.Wu,C.C.,Yu,C.T.,Chang,G.C.,Lai,J.M.,andHsu,S.L.(2011)Aurora-ApromotesgefitinibresistanceviaaNF-kappaBsignalingpathwayinp53knockdownlungcancercells.Biochemicalandbiophysicalresearchcommunications405,168-17296.Ke,C.S.,Liu,H.S.,Yen,C.H.,Huang,G.C.,Cheng,H.C.,Huang,C.Y.,andSu,C.L.(2014)Curcumin-inducedAurora-Asuppressionnotonlycausesmitoticdefectandcellcyclearrestbutalsoalterschemosensitivitytoanticancerdrugs.TheJournalofnutritionalbiochemistry25,526-53997.Tsai,A.C.,Pai,H.C.,Wang,C.Y.,Liou,J.P.,Teng,C.M.,Wang,J.C.,andPan,S.L.(2014)Invitroandinvivoanti-tumoureffectsofMPT0B014,anovelderivativearoylquinoline,andincombinationwitherlotinibinhumannon-small-celllungcancercells.Britishjournalofpharmacology171,122-13398.Hook,K.E.,Garza,S.J.,Lira,M.E.,Ching,K.A.,Lee,N.V.,Cao,J.,Yuan,J.,Ye,J.,Ozeck,M.,Shi,S.T.,Zheng,X.,Rejto,P.A.,Kan,J.L.,Christensen,J.G.,andPavlicek,A.(2012)AnintegratedgenomicapproachtoidentifypredictivebiomarkersofresponsetotheaurorakinaseinhibitorPF-03814735.Molecularcancertherapeutics11,710-71999.Niu,H.,Manfredi,M.,andEcsedy,J.A.(2015)ScientificRationaleSupportingtheClinicalDevelopmentStrategyfortheInvestigationalAuroraAKinaseInhibitorAlisertibinCancer.Frontiersinoncology5,189100.Xu,J.,Yue,C.F.,Zhou,W.H.,Qian,Y.M.,Zhang,Y.,Wang,S.W.,Liu,A.W.,andLiu,Q.(2014)Aurora-Acontributestocisplatinresistanceandlymphaticmetastasisinnon-smallcelllungcancerandpredictspoorprognosis.Journaloftranslationalmedicine12,200101.Zeng,B.,Lei,Y.,Zhu,H.,Luo,S.,Zhuang,M.,Su,C.,Zou,J.,Yang,L.,andLuo,H.(2014)Aurora-Aisanovelpredictorofpoorprognosisinpatientswithresectedlungadenocarcinoma.Chinesejournalofcancerresearch=Chung-kuoyenchengyenchiu26,166-173102.Xia,L.P.,Zhou,F.F.,Yang,M.T.,andLiu,Q.(2009)[RolesofAurora-Aintumorigenesisandprognosisofbreastcancer].Aizheng=Aizheng=Chinesejournalofcancer28,668-672103.Mehra,R.,Serebriiskii,I.G.,Burtness,B.,Astsaturov,I.,andGolemis,E.A.(2013)Aurorakinasesinheadandneckcancer.TheLancet.Oncology14,e425-435104.Lok,W.,Klein,R.Q.,andSaif,M.W.(2010)Aurorakinaseinhibitorsasanti-cancertherapy.Anti-cancerdrugs21,339-350105.Libertini,S.,Abagnale,A.,Passaro,C.,Botta,G.,andPortella,G.(2010)AuroraAandBkinases--targetsofnovelanticancerdrugs.Recentpatentsonanti-cancerdrugdiscovery5,219-241106.Li,M.,Gao,K.,Chu,L.,Zheng,J.,andYang,J.(2018)TheroleofAurora-Aincancerstemcells.Theinternationaljournalofbiochemistry&cellbiology98,89-92107.Katayama,H.,andSen,S.(2010)Aurorakinaseinhibitorsasanticancermolecules.Biochimicaetbiophysicaacta1799,829-839108.Karthigeyan,D.,Prasad,S.B.,Shandilya,J.,Agrawal,S.,andKundu,T.K.(2011)BiologyofAuroraAkinase:implicationsincancermanifestationandtherapy.Medicinalresearchreviews31,757-793109.Jones,D.,Noble,M.,Wedge,S.R.,Robson,C.N.,andGaughan,L.(2017)AuroraAregulatesexpressionofAR-V7inmodelsofcastrateresistantprostatecancer.Scientificreports7,40957110.Gabrielli,B.,Bokhari,F.,Ranall,M.V.,Oo,Z.Y.,Stevenson,A.J.,Wang,W.,Murrell,M.,Shaikh,M.,Fallaha,S.,Clarke,D.,Kelly,M.,Sedelies,K.,Christensen,M.,McKee,S.,Leggatt,G.,Leo,P.,Skalamera,D.,Soyer,H.P.,Gonda,T.J.,andMcMillan,N.A.(2015)AuroraAIsCriticalforSurvivalinHPV-TransformedCervicalCancer.Molecularcancertherapeutics14,2753-2761111.Dominguez-Brauer,C.,Thu,K.L.,Mason,J.M.,Blaser,H.,Bray,M.R.,andMak,T.W.(2015)TargetingMitosisinCancer:EmergingStrategies.Molecularcell60,524-536112.Zhu,X.,Mei,J.,andWang,Z.(2014)Aurora-Akinase:potentialtumormarkerofosteosarcoma.Journalofcancerresearchandtherapeutics10Suppl,C102-107113.Muscal,J.A.,Scorsone,K.A.,Zhang,L.,Ecsedy,J.A.,andBerg,S.L.(2013)AdditiveeffectsofvorinostatandMLN8237inpediatricleukemia,medulloblastoma,andneuroblastomacelllines.Investigationalnewdrugs31,39-45114.Dees,E.C.,Cohen,R.B.,vonMehren,M.,Stinchcombe,T.E.,Liu,H.,Venkatakrishnan,K.,Manfredi,M.,Fingert,H.,Burris,H.A.,3rd,andInfante,J.R.(2012)PhaseIstudyofauroraAkinaseinhibitorMLN8237inadvancedsolidtumors:safety,pharmacokinetics,pharmacodynamics,andbioavailabilityoftwooralformulations.Clinicalcancerresearch:anofficialjournaloftheAmericanAssociationforCancerResearch18,4775-4784115.Zhou,N.,Singh,K.,Mir,M.C.,Parker,Y.,Lindner,D.,Dreicer,R.,Ecsedy,J.A.,Zhang,Z.,Teh,B.T.,Almasan,A.,andHansel,D.E.(2013)TheinvestigationalAurorakinaseAinhibitorMLN8237inducesdefectsincellviabilityandcell-cycleprogressioninmalignantbladdercancercellsinvitroandinvivo.Clinicalcancerresearch:anofficialjournaloftheAmericanAssociationforCancerResearch19,1717-1728116.Kelly,K.R.,Shea,T.C.,Goy,A.,Berdeja,J.G.,Reeder,C.B.,McDonagh,K.T.,Zhou,X.,Danaee,H.,Liu,H.,Ecsedy,J.A.,Niu,H.,Benaim,E.,andIyer,S.P.(2014)PhaseIstudyofMLN8237--investigationalAuroraAkinaseinhibitor--inrelapsed/refractorymultiplemyeloma,non-Hodgkinlymphomaandchroniclymphocyticleukemia.Investigationalnewdrugs32,489-499117.Cervantes,A.,Elez,E.,Roda,D.,Ecsedy,J.,Macarulla,T.,Venkatakrishnan,K.,Rosello,S.,Andreu,J.,Jung,J.,Sanchis-Garcia,J.M.,Piera,A.,Blasco,I.,Manos,L.,Perez-Fidalgo,J.A.,Fingert,H.,Baselga,J.,andTabernero,J.(2012)PhaseIpharmacokinetic/pharmacodynamicstudyofMLN8237,aninvestigational,oral,selectiveauroraakinaseinhibitor,inpatientswithadvancedsolidtumors.Clinicalcancerresearch:anofficialjournaloftheAmericanAssociationforCancerResearch18,4764-4774118.Broccoli,A.,Argnani,L.,andZinzani,P.L.(2017)PeripheralT-celllymphomas:Focusingonnovelagentsinrelapsedandrefractorydisease.Cancertreatmentreviews60,120-129119.Kanagal-Shamanna,R.,Lehman,N.L.,O''Donnell,J.P.,Lim,M.S.,Schultz,D.S.,Chitale,D.A.,Bueso-Ramos,C.E.,Medeiros,L.J.,andInamdar,K.V.(2013)Differentialexpressionofaurora-AkinaseinT-celllymphomas.Modernpathology:anofficialjournaloftheUnitedStatesandCanadianAcademyofPathology,Inc26,640-647120.Friedberg,J.W.,Mahadevan,D.,Cebula,E.,Persky,D.,Lossos,I.,Agarwal,A.B.,Jung,J.,Burack,R.,Zhou,X.,Leonard,E.J.,Fingert,H.,Danaee,H.,andBernstein,S.H.(2014)PhaseIIstudyofalisertib,aselectiveAuroraAkinaseinhibitor,inrelapsedandrefractoryaggressiveB-andT-cellnon-Hodgkinlymphomas.Journalofclinicaloncology:officialjournaloftheAmericanSocietyofClinicalOncology32,44-50121.Dardenne,E.,Beltran,H.,Benelli,M.,Gayvert,K.,Berger,A.,Puca,L.,Cyrta,J.,Sboner,A.,Noorzad,Z.,MacDonald,T.,Cheung,C.,Yuen,K.S.,Gao,D.,Chen,Y.,Eilers,M.,Mosquera,J.M.,Robinson,B.D.,Elemento,O.,Rubin,M.A.,Demichelis,F.,andRickman,D.S.(2016)N-MycInducesanEZH2-MediatedTranscriptionalProgramDrivingNeuroendocrineProstateCancer.Cancercell30,563-577122.Graff,J.N.,Higano,C.S.,Hahn,N.M.,Taylor,M.H.,Zhang,B.,Zhou,X.,Venkatakrishnan,K.,Leonard,E.J.,andSarantopoulos,J.(2016)Open-label,multicenter,phase1studyofalisertib(MLN8237),anauroraAkinaseinhibitor,withdocetaxelinpatientswithsolidtumors.Cancer122,2524-2533123.Lee,J.K.,Phillips,J.W.,Smith,B.A.,Park,J.W.,Stoyanova,T.,McCaffrey,E.F.,Baertsch,R.,Sokolov,A.,Meyerowitz,J.G.,Mathis,C.,Cheng,D.,Stuart,J.M.,Shokat,K.M.,Gustafson,W.C.,Huang,J.,andWitte,O.N.(2016)N-MycDrivesNeuroendocrineProstateCancerInitiatedfromHumanProstateEpithelialCells.Cancercell29,536-547124.Fathi,A.T.,Wander,S.A.,Blonquist,T.M.,Brunner,A.M.,Amrein,P.C.,Supko,J.,Hermance,N.M.,Manning,A.L.,Sadrzadeh,H.,Ballen,K.K.,Attar,E.C.,Graubert,T.A.,Hobbs,G.,Joseph,C.,Perry,A.M.,Burke,M.,Silver,R.,Foster,J.,Bergeron,M.,Ramos,A.Y.,Som,T.T.,Fishman,K.M.,McGregor,K.L.,Connolly,C.,Neuberg,D.S.,andChen,Y.B.(2017)PhaseIstudyoftheauroraAkinaseinhibitoralisertibwithinductionchemotherapyinpatientswithacutemyeloidleukemia.Haematologica102,719-727125.Dickson,M.A.,Mahoney,M.R.,Tap,W.D.,D''Angelo,S.P.,Keohan,M.L.,VanTine,B.A.,Agulnik,M.,Horvath,L.E.,Nair,J.S.,andSchwartz,G.K.(2016)PhaseIIstudyofMLN8237(Alisertib)inadvanced/metastaticsarcoma.Annalsofoncology:officialjournaloftheEuropeanSocietyforMedicalOncology27,1855-1860126.Goldberg,S.L.,Fenaux,P.,Craig,M.D.,Gyan,E.,Lister,J.,Kassis,J.,Pigneux,A.,Schiller,G.J.,Jung,J.,JaneLeonard,E.,Fingert,H.,andWestervelt,P.(2014)Anexploratoryphase2studyofinvestigationalAuroraAkinaseinhibitoralisertib(MLN8237)inacutemyelogenousleukemiaandmyelodysplasticsyndromes.Leukemiaresearchreports3,58-61127.Barr,P.M.,Li,H.,Spier,C.,Mahadevan,D.,LeBlanc,M.,UlHaq,M.,Huber,B.D.,Flowers,C.R.,Wagner-Johnston,N.D.,Horwitz,S.M.,Fisher,R.I.,Cheson,B.D.,Smith,S.M.,Kahl,B.S.,Bartlett,N.L.,andFriedberg,J.W.(2015)PhaseIIIntergroupTrialofAlisertibinRelapsedandRefractoryPeripheralT-CellLymphomaandTransformedMycosisFungoides:SWOG1108.Journalofclinicaloncology:officialjournaloftheAmericanSocietyofClinicalOncology33,2399-2404128.Wang,F.,Li,H.,Yan,X.G.,Zhou,Z.W.,Yi,Z.G.,He,Z.X.,Pan,S.T.,Yang,Y.X.,Wang,Z.Z.,Zhang,X.,Yang,T.,Qiu,J.X.,andZhou,S.F.(2015)Alisertibinducescellcyclearrestandautophagyandsuppressesepithelial-to-mesenchymaltransitioninvolvingPI3K/Akt/mTORandsirtuin1-mediatedsignalingpathwaysinhumanpancreaticcancercells.Drugdesign,developmentandtherapy9,575-601129.Fu,Y.,Zhang,Y.,Gao,M.,Quan,L.,Gui,R.,andLiu,J.(2016)AlisertibinducesapoptosisandautophagythroughtargetingtheAKT/mTOR/AMPK/p38pathwayinleukemiccells.Molecularmedicinereports14,394-398130.Wu,C.C.,Yang,T.Y.,Yu,C.T.,Phan,L.,Ivan,C.,Sood,A.K.,Hsu,S.L.,andLee,M.H.(2012)p53negativelyregulatesAuroraAviabothtranscriptionalandposttranslationalregulation.Cellcycle(Georgetown,Tex.)11,3433-3442131.Yang,T.Y.,Teng,C.J.,Lin,T.C.,Chen,K.C.,Hsu,S.L.,andWu,C.C.(2018)TranscriptionalrepressionofAurora-Agenebywild-typep53throughdirectlybindingtoitspromoterwithhistonedeacetylase1andmSin3a.Internationaljournalofcancer142,92-108  電子全文(本篇電子全文限研究生所屬學校校內系統及IP範圍內開放) 推文 網路書籤 推薦 評分 引用網址 轉寄                                                                                                                                                                                                                    top 相關論文 相關期刊 熱門點閱論文 1. 探討解螺旋酶DDX3調控抑癌基因p53之機轉及其對細胞分裂之影響 2. 探討粒線體上GSK3beta-Drp1及中心體上Ninein-AIBp-AuroraA/Plk1蛋白質交互作用的分子調控機制 3. AuroraA與Haspin激酶在人類大腸癌中調控p53及腫瘤生長的角色 4. 探討p53與AuroraA在bortezomib誘發大腸癌細胞之G2/M期停滯與細胞凋亡的角色   無相關期刊   1. 新型CDK抑制劑對於攝護腺癌LNCaP細胞內AuroraA蛋白量的影響 2. CDK5穩定過度表現之攝護腺癌細胞株22Rv1中特定基因表現之分析 3. 於CDK5穩定過度表現之攝護腺癌細胞株22Rv1中探討細胞增生與移動的相關訊息傳遞 4. 探討紫外線對攝護腺癌LNCaP細胞內AuroraA及p53蛋白調控的影響 5. 豬β2整合素基因轉殖小鼠對胸膜肺炎放線桿菌之感受性探討 6. Metformin與Emodin對於雄性激素受體蛋白及攝護腺癌LNCaP細胞增殖的協同抑制作用 7. 畜禽彎曲桿菌檢測方法學之比較 8. 豬肺炎黴漿菌疫苗所誘發之抗體與巨噬細胞吞噬能力之關係 9. 探討Aurora-A對Maf1活性的調控機制和功能作用 10. 利用MMR、PD-L1免疫組織化學染色以及TIL等生物指標，來做轉移性大腸直腸癌患者臨床病理特徵以及預後因子的探討 11. 菸草去氧-D-木酮醣-5-磷酸還原異構酶參與竹嵌紋病毒複製之研究 12. 睡眠姿勢對阻塞性睡眠呼吸中止症的影響 13. 具白斑與否之水鴨腳秋海棠葉特徵、生殖特性與被取食的比較探討 14. 低溫處理對不同時期冰花葉片抗氧化機制的影響 15. 無菌冰花小苗最適生長條件與外源性肌醇對小苗鹽耐受性之影響     簡易查詢 | 進階查詢 | 熱門排行 | 我的研究室