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1、TheRoleofStatinsinCancerTherapy LEARNINGOBJECTIVES Afterpletingthiscourse,thereaderentofhypercholesterolemia,maybeapplicabletocancerprevention. Discusshoedicine. ABSTRACT Administrationof3-hydroxy-3-methylglutarylcoenzymeAreductaseinhibitors,orstatins,toambulatorypatientsisassociatedadverse
2、cardiovascularevents,includingdeath,myocardialinfarction,stroke,atrialfibrillation,andrenaldysfunction.Hocholesterollevels,mayalsoplayapotentialroleinthepreventionandtreatmentofcancer.Specifically,statinshavebeenshoorgroetastasis.Thefeasibilityandefficacyofstatinsforthepreventionandtreatmentofca
3、ncerisrevieethylglutarylcoenzymeA(HMG-CoA)reductaseinhibitors,orstatins,aremonly-useddrugsforthetreatmentofhypercholesterolemia[1,2].Statinsdecreaseloevalonateandistherate-limitingstepinhepaticcholesterolbiosynthesis[3].Clinically,statintreatmentisassociatedationandastabilizationofpre-existing"v
4、ulnerable"atheroscleroticplaques[4].Moreover,statinshavebeenshoyocardialinfarction,stroke,atrialfibrillation,andrenaldysfunctioninambulatorypatientpopulations[2,513].Statinadministrationisalsoassociatedinalcoronaryangioplasty[9]andcardiac[14,15],vascular[1618],andnoncardiovascular[19]surgery.Hoi
5、tedtopatientsia.SeveralrandomizedclinicaltrialshaveshoaltotalandLDLcholesterollevels,statinadministrationisassociatedorbidityandmortality[7,8].Statinsthusexertpleiotropiceffectsindependentoftheireffectsoncholesterol[20]. AlthoughtheexactmechanismsbyetaboliteofHMG-CoAreductase,mevalonicacid,isap
6、recursorofcholesterolandtheisoprenoidintermediatesfarnesylandgeranyl-geranylpyrophosphate.Theseintermediatesareessentialforthepost-translationalmodificationofintracellularG-proteins,suchasRho,Rac,andRas,thatregulateendothelial,platelet,andleukocytefunction[2123].Statinshavealsobeenshoodulatevasc
7、ularremodelingbyinhibitingcellularmatrixmetalloproteinasesandtranscriptionfactors,suchasnuclearfactor-B[23].Inpatientsesoridiopathicdilatedcardiomyopathy,statintherapyhasbeenshomatoryactivity,includingchangesinC-reactiveprot
