简介：Sincetheapprovalofrituximabin1997,monoclonalantibodies(mAbs)havebecomeanincreasinglyimportantcomponentoftherapeuticregimensinoncology.ThesuccessofmAbsasatherapeuticclassisaresultofgreatstridesthathavebeenmadeinmolecularbiologyandinbiotechnologyoverthepastseveraldecades.Currently,thereare14approvedmAbproductsforoncologyindications,andtherearetenadditionalmAbsinlatestagesofclinicaltrials.Comparedtotraditionalchemotherapeuticagents,mAbshaveseveraladvantages,includingalongcirculatinghalf-lifeandhightargetspecificity.Antibodiescanserveascytotoxicagentswhenadministeredalone,exertingapharmacologiceffectthroughseveralmechanismsinvolvingtheantigenbinding(Fab)and/orFcdomainsofthemolecule,andmAbsmayalsobeutilizedasdrugcarriers,targetingatoxicpayloadtocancercells.TheextremelyhighaffinityofmAbsfortheirtargets,whichisdesirablewithrespecttopharmacodynamics(i.e.,contributingtothehightherapeuticselectivityofmAb),oftenleadstocomplex,non-linear,target-mediatedpharmacokinetics.Inthisreport,wesummarizethepharmacokineticandpharmacodynamicsofmAbsthathavebeenapprovedandofmAbsthatarenearingapprovalforoncologyindications,withparticularfocusonthemolecularandcellularmechanismsresponsiblefortheirdispositionandefficacy.

简介：Acompetitiveenzyme-linkedimmunosorbentassay(ELISA)wasdevelopedtodetermineruscogenin(RUS)byusingthemonoclonalantibody(McAb).ThemonoclonalantibodyagainstRUS,secretedfromtheestablishedhybridomacelllines,wasidentifiedasbeingoftheIgG1isotype.TheMcAbexhibitedhighspecificitytoRUS,showingaveryslightcrossreactivitywithdiosgenin(15.7%),andnocross-reactivitytosarsasapogenin,diammoniumglycyrrhizinate,oleanolicacidandnotoginsenosideR1.TheestablishedELISA,atanIC50valueof157.55ng.mL-1andadetectionlimit(IC20)of20.57ng.mL-1,wascomparedwithHPLCanalyses,andagoodcorrelationbetweenELISAandHPLC-ELSDanalysesofRUSintheextractofRadixOphiopogoniswasobtained.TheexperimentaldataindicatedthattheELISAmethodexhibitsmoreadvantagesoverHPLC-ELSD,suchaslowdetectionlimit,highspecificity,lowbackground,andnorequirementforsamplepre-treatment,andismoresuitableforthedeterminationofnaturalcomponentsinChinesetraditionalmedicinesandinbiologicalsamplesforpharmacokineticstudies.

简介：Objective:Theepidermalgrowthfactorreceptor(EGFR)inhibitorsmonoclonalantibodies(MoAbs)havealreadyshownthetherapeuticeffectivenessinpatientswithmetastaticcolorectalcancer(mCRC).Butmanypatientsresisttothetreatment.Theaimofthismeta-analysiswastoassessEGFRgenecopynumber(GCN)asacandidatepredictivebiomarkerforresistancetoanti-EGFRMoAbsinmCRCtreatment.Methods:SystematiccomputerizedsearchesofthePubMed,EMBaseandCochraneLibrarywereperformed.Theprimaryendpointwasobjectiveresponserate(ORR).Thesecondendpointsincludedprogression-freesurvival(PFS),andoverallsurvival(OS).Thepooledoddratio(OR)andpooledsensitivity,specificity,andsummaryreceiveroperatorcharacteristic(SROC)forORRwereestimated.Thepooledhazardratios(HR)forPFSandOSwerealsocalculated.Results:Fourteenstudieswith1,021patientswereincluded.IncreasedEGFRGCNwasassociatedwithincreasedORR(OR=6.905;95%CI:4.489-10.620).Itwasalsofoundinwild-typeKRASmCRCpatients,withthepooledORof8.133(95%CI:4.316-15.326).GCNhasmediumvalueforpredictingORR,withthepooledsensitivityof0.79(95%CI:0.73-0.84),thepooledspecificityof0.59(95%CI:0.55-0.62).InwildtypeKRASmCRCpatients,thesensitivityandthespecificitywere0.80(95%CI:0.70-0.87)and0.60(95%CI:0.53-0.66),respectively.IncreasedEGFRGCNwasassociatedwithincreasedPFS(HR=0.557;95%CI:0.382-0.732)andOS(HR=0.579;95%CI:0.422-0.737).Conclusions:Thismeta-analysissuggeststhatEGFRGCNrepresentsapredictivebiomarkerfortumorresponseinmCRCpatientstreatedwithMoAbsregardlessofKRASmutation.mCRCpatientswithincreasedEGFRGCNaremorelikelytohaveabetterresponse,PFS,andOSwhentreatedwithcetuximaborpanitumumab.