简介:Objective:Photoacoustic(PA)tomography(PAT)hasattractedextensiveinterestbecauseofitsopticalabsorptioncontrastandultrasonicdetection.ThisstudyaimstodevelopabiocompatibleandbiodegradablePAcontrastagentparticularlypromisingforclinicalapplicationsinhumanbody.Methods:Inthisstudy,wepresentedaPAcontrastagent:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)](DSPE-PEG)-coatedsuperparamagneticironoxide(SPIO)nanoparticles(NPs)loadedwithindocyaninegreen(ICG).WeusedICGandSPIONPsbecausebothdrugsareapprovedbytheU.S.FoodandDrugAdministration.Giventhestrongabsorptionofnear-infraredlaserpulses,SPIO@DSPE-PEG/ICGNPswithauniformdiameterof~28nmcouldsignificantlyenhancePAsignals.Results:WedemonstratedthecontrastenhancementoftheseNPsinphantomandanimalexperiments,inwhichtheinvivocirculationtimeofSPIO@DSPE-PEG/ICGNPswasconsiderablylongerthanthatoffreeICG.ThesenovelNPsalsodisplayedahighefficiencyoftumortargeting.Conclusions:SPIO@DSPE-PEG/ICGNPsarepromisingPATcontrastagentsforclinicalapplications.
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简介:Objective:Multiplemechanismsunderlyingthedevelopmentofportalveintumorthrombus(PVTT)inhepatocellularcarcinoma(HCC)havebeenreportedrecently.However,theoriginsofPVTTremainunknown.Increasingmulti-omicsdataonPVTTsinHCCshavemadeitpossibletoinvestigatewhetherPVTTsoriginatefromthecorrespondingprimarytumors(Ts).Methods:TheclonalrelationshipbetweenPVTTsandtheircorrespondingprimaryTswasinvestigatedusingdatasetsdepositedinpublicdatabases.OneDNAcopynumbervariationsdatasetandthreegeneexpressiondatasetsweredownloadedfortheanalyses.ClonalityanalysiswasperformedtoinvestigatetheclonalrelationshipbetweenPVTTsandTsfromanindividualpatient.DifferentialgeneexpressionanalysiswasappliedtoinvestigatethegeneexpressionprofilesofPVTTsandTs.Results:Oneoutof19PVTTshadnoclonalrelationshipwithitscorrespondingT,whereastheothersdid.ThePVTTswithindependentclonaloriginshoweddifferentgeneexpressionandenrichmentinbiologicalprocessesfromtheprimaryTs.Basedontheuniquegeneexpressionprofiles,agenesignatureincluding24geneswasusedtoidentifypairsofPVTTsandprimaryTswithoutanyclonalrelationship.ValidationinthreedatasetsshowedthatthesetypesofpairsofPVTTsandTscanbeidentifiedbythe24-genesignature.Conclusions:OurfindingsshowadirectevidenceforPVTToriginandconsolidatetheheterogeneityofPVTTsobservedinclinic.TheresultssuggestthatPVTTinvestigationatamolecularlevelisclinicallynecessaryfordiagnosisandtreatment.
简介:Objective:ToevaluatethefeasibilityofDNAimagecytometry(DNA-ICM)asaprimaryscreeningmethodforesophagealsquamouscellcancer(ESCC).Methods:Atotalof5,382localresidentsaged40–69yearsfromthreehigh-riskareasinChina(LinzhouinHenanprovince,FeichenginShandongprovinceandCixianinHebeiprovince)from2008to2011wererecruitedinthispopulation-basedscreeningstudy.And2,526subjectsdeclinedtoreceiveendoscopicbiopsyexaminationwithLugol'siodinestaining,while9and815subjectswereexcludedfromliquid-basedcytologyandDNA-ICMtestrespectivelyduetoslidequality.Finally,2,856,5,373and4,567subjectswereenrolledintheanalysisforendoscopicbiopsyexamination,liquid-basedcytologyandDNA-ICMtest,respectively.Sensitivity(SE),specificity(SP),negativepredictivevalues(NPV)andpositivepredictivevalues(PPV)aswellastheir95%confidenceintervals(95%CI)forDNA-ICM,liquid-basedcytologyandthecombinationofthetwomethodswerecalculated.Receiveroperatingcharacteristic(ROC)curveswereappliedtodeterminethecutoffpointofDNA-ICMforesophagealcancer.Results:DNA-ICMresultsweresignificantlycorrelativewithesophagealcancerandprecancerlesions(χ~2=18.016,P<0.001).Thecutoffpointswere5,802,5,803and8,002basedondissimilarpathologicaltypesoflowgradeintraepithelialneoplasia(LGIN),highgradeintraepithelialneoplasia(HGIN),andESCC,respectively,and5,803waschoseninthisstudyconsideringtheSEandSP.TheSE,SP,PPV,NPVofDNA-ICMtest(cutoffpoint5,803)combinedwithliquid-basedcytology[thresholdatypicalsquamouscellsofundeterminedsignificance(ASCUS)]wereseparately72.1%(95%CI:70.3%-73.9%),43.3%(95%CI:41.3%-45.3%),22.8%(95%CI:21.1%-24.5%)and87.0%(95%CI:85.7%-88.3%)forLGIN,85.7%(95%CI:84.3%-87.1%),41.3%(95%CI:39.3%-43.3%),4.6%(95%CI:3.8%-5.4%)and98.9%(95%CI:98.5%-99.3%)forHGIN,and96.0%(95%CI:95.2%-96.8%),40.8%(95%CI:38.8%-42.8%),1.7%(95%CI:1.2%-2.2%)and99.9%
简介:Objective:Toinvestigatetheinvitrocleavageabilityandeffectsonapoptosisandcellgrowthofthebcr-ablfusiongenespecificmulti-unitribozymes.Methods:Threefusionpointspecificribozymesweredesignedandthemulti-unitribozymes'invitrotranscriptionvectorandretroviralvectorwereconstructed.Theinvitrocleavageabilitywastested.TheretroviralvectorwastransfectedintoK562cellandtheeffectsonproliferation,apoptosis,cellcycleandcellstructurewereobserved.Results:Multi-unitribozymeshadinvitrocleavageefficiencyof70.8%,whichwasmoreefficientthansingle-unitanddouble-unitribozymes.TransfectionoftheretroviralvectoroftheribozymeintoK562cells,inducedinhibitionofcellgrowthandapoptosis.TheincorporationrateofDNAinribozymestransfectedK562cellswasgreatlydecreasedalongwithtimepassed,withaninhibitionrateofmorethan50%after96hoftransfection.UnderFCM,18.4%ofthecellsunderwentapoptosis72haftertransfectionandmorecellswereblockedinGphase,withtheratioinSphasegreatlydecreased(41.9%).Underelectronmicroscope,compactionofnuclearchromatinandapoptosisbodieswereobserved.Conclusion:Multi-unitribozymesspecifictobcr-ablfusiongenecanbeusedtotreatCMLandtopurgebonemarrowforself-grafting.
简介:以手术为主的综合治疗使胶质瘤的疗效有了明显提高,但由于胶质瘤具有侵袭性生长特性或位于脑重要功能区,即使神经导航显微手术也难以真正彻底切除肿瘤;又由于胶质瘤存在放疗抗拒和/或对化疗药物耐药,术后放/化疗尚不能全部杀灭残余的肿瘤细胞。近来胶质瘤的生物治疗发展迅速,已进入临床试验,可望对胶质瘤的治疗有巨大推动和突破。临床上,即使是相同病理类型和级别的胶质瘤,治疗效果存在很大差异。如低级别的胶质瘤(WHOI-Ⅱ级),多数病人治疗效果良好,但有部分患者易于恶变、复发;此外,同样是胶母细胞瘤,有部分患者可以达到5年以上生存。因此,在胶质瘤的临床治疗实践中,如何根据肿瘤的特征和患者的具体情况,合理地选择和制定个体化的治疗方案,提高疗效,是神经肿瘤医师必须考虑的现实问题。目