简介:Amajorproblemwhichispoorlyunderstoodinthemanagementofbladdercancerislowsensitivitytochemotherapyandhighrecurrenceaftertransurethralresection.Insulin-likegrowthfactor1receptor(IGF-1R)signalingplaysaveryimportantroleinprogression,invasionandmetastasisofbladdercancercells.Inthisstudy,weinvestigatedwhetherIGF-1Rwasinvolvedinthegrowthstimulatingactivityanddrugresistanceofbladdercancercells.Theresultsshowed:ThemRNAsofIGF-1,IGF-2andIGF-1Rwerestronglyexpressedinserum-freeculturedT24cellline,whereasnormalurothelialcellsdidnotexpressthesefactors/receptorsoronlyintracelevels;T24cellrespondedfarbettertogrowthstimulationbyIGF-1thandidnormalurothelialcells;blockageofIGF1Rbyantisenseoligodeoxynucleotide(ODN)significantlyinhibitedthegrowthofT24cellandenhancedsensitivityandapoptosisofT24cellstomitomycin(MMC).TheseresultssuggestedthatblockageofIGF-IRsignalingmightpotentiallycontributetothetreatmentofbladdercancercellswhichareinsensitivetochemotherapy.
简介:TheR(replicase)proteinistheuniquelydefinednon-structuralprotein(NSP)responsibleforRNAreplication,mutationrateorfidelity,regulationoftranscrip-tionincoronavirusesandmanyotherssRNAviruses.Basedonourcompletegenomesequencesoffourisolates(BJ01-BJ04)ofSARS-CoVfromBeijing,China,weanalyzedthestructureandpredictedfunctionsoftheRproteinincomparisonwith13otherisolatesofSARS-CoVand6othercoronaviruses.TheentireORF(open-readingframe)encodesfortwomajorenzymeactivities,RNA-dependentRNApolymerase(RdRp)andproteinaseactivities.TheRpolyproteinunder-goesacomplexproteolyticprocesstoproduce15function-relatedpeptides.Ahydrophobicdomain(HOD)andahydrophilicdomain(HID)arenewlyidentifiedwithinNSP1.ThesubstitutionrateoftheRproteinisclosetotheaverageoftheSARS-CoVgenome.ThefunctionaldomainsinallNSPsoftheRproteingivedifferentphylogeneticresultsthatsuggesttheirdifferentmutationrateunderselectivepressure.ElevenhighlyconservedregionsinRdRpandtwelvecleavagesitesby3CLP(chymotrypsin-likeprotein)havebeenidentifiedaspotentialdrugtargets.Findingssuggestthatitispossibletoobtaininformationaboutthephy-logenyofSARS-CoV,aswellaspotentialtoolsfordrugdesign,genotypinganddiagnosticsofSARS.