简介:Currentlytheclinicalmanagementofbreastcancerreliesonrelativelyfewprognostic/predictiveclinicalmarkers(estrogenreceptor,progesteronereceptor,HER2),basedonprimarytumorbiology.Circulatingbiomarkers,suchascirculatingtumorDNA(ctDNA)orcirculatingtumorcells(CTCs)mayenhanceourtreatmentoptionsbyfocusingontheverycellsthatarethedirectprecursorsofdistantmetastaticdisease,andprobablyinherentlydifferentthantheprimarytumor'sbiology.Toshiftthecurrentclinicalparadigm,assessingtumorbiologyinrealtimebymolecularlyprofilingCTCsorctDNAmayservetodiscovertherapeutictargets,detectminimalresidualdiseaseandpredictresponsetotreatment.Thisreviewservestoelucidatethedetection,characterization,andclinicalapplicationofCTCsandctDNAwiththegoalofprecisiontreatmentofbreastcancer.
简介:Objective:Survivalandtreatmentofpatientswithmicroinvasivebreastcancer(MIBC)remaincontroversial.Inthispaper,weevaluatedwhetheradjuvantchemotherapyisnecessaryforpatientswithMIBCtoidentifyriskfactorsinfluencingitsprognosisanddecidetheindicationforadjuvantchemotherapy.Methods:Inthisretrospectivestudy,108patientswithMIBCwererecruitedaccordingtoseventheditionofthestagingmanualoftheAmericanJointCommitteeonCancer(AJCC).Thesubjectsweredividedintochemotherapyandnon-chemotherapygroups.Wecomparedthe5-yeardisease-freesurvival(DFS)andoverallsurvival(OS)ratesbetweengroups.Furthermore,weanalyzedthefactorsrelatedtoprognosisforpatientswithMIBCusingunivariateandmultivariateanalyses.Wealsoevaluatedtheimpactofadjuvantchemotherapyontheprognosticfactorsbysubgroupanalysisaftermedianfollow-uptimeof33months(13-104months).Results:The5-yearDFSandOSratesforthechemotherapygroupwere93.7%and97.5%,whereasthoseforthenonchemotherapygroupwere89.7%and100%.Resultsindicatethat5-yearDFSwassuperior,butOSwasinferior,intheformergroupcomparedwiththelattergroup.However,nostatisticalsignificancewasobservedinthe5-yearDFS(P=0.223)orOS(P=0.530)rateofthetwogroups.Mostrelevantpoor-prognosticfactorswereKi-67overexpressionandnegativehormonalreceptors.Cumulativesurvivalwas98.2%vs.86.5%betweenlowKi-67(≤20%)andhighKi-67(>20%).ThehazardratioofpatientswithhighKi-67was16.585[95%confidenceinterval(CI),1.969-139.724;P=0.010].Meanwhile,ER(-)/PR(-)patientswithMIBChadcumulativesurvivalof79.3%comparedwith97.5%forER(+)orPR(+)patientswithMIBC.ThehazardratioforER(-)/PR(-)patientswithMIBCwas19.149(95%CI,3.702-99.057;P<0.001).SubgroupanalysisshowedthatchemotherapycouldimprovetheoutcomesofER(-)/PR(-)patients(P=0.014),butnotthosewhooverexpressKi-67(P=0.105).Conclusions:PatientswithMIBCwhooverexpressKi-67and
简介:Sarcoidosisisabenignsystematicgranulomatousdisorderofunknownetiologyandisassociatedwithvariousmalignancies.However,granulomatousandmetastaticlymphnodelesionsaredifficulttodistinguishevenwhenusingpreciseandmoderndiagnosticmethods,suchaspositronemissiontomography.Thus,histologicalverificationistheonlymethodthatcanbeusedtoaccuratelydescribethenatureofthisdisease.Inthisarticle,wereportacaseofnon-luminalHER-2/neu-positivebreastcancerinapatientwithouthistoryofsarcoidosisandsuspectedtohavemetastaticdisease.
简介:Theimplementationofmolecularprofilingtechnologiesinoncologydeepensourknowledgeforthemolecularlandscapesofcancerdiagnoses,identifyingaberrationsthatcouldbelinkedwithspecifictherapeuticvulnerabilities.Inparticular,thereisanincreasinglistofmolecularlytargetedanticanceragentsundergoingclinicaldevelopmentthataimtoblockspecificmolecularaberrations.Thisleadstoaparadigmshift,withanincreasinglistofspecificaberrationsdictatingthetreatmentofpatientswithcancer.Thisparadigmshiftimpactsthefieldofclinicaltrials,sincetheclassicalapproachofhavingclinico-pathologicaldiseasecharacteristicsdictatingthepatients'enrolmentinoncologytrialsshiftstowardstheimplementationofmolecularprofilingasprescreeningstep.Inordertofacilitatethesuccessfulclinicaldevelopmentofthesenewanticancerdrugswithinspecificmolecularnichesofcancerdiagnoses,therehavebeendevelopednew,innovativetrialdesignsthatcouldbeclassifiedasfollows:i)longitudinalcohortstudiesthatimplement(ornot)'nested'downstreamtrials,2)studiesthatassesstheclinicalutilityofmolecularprofiling,3)'master'protocoltrials,iv)'basket'trials,v)trialsfollowinganadaptivedesign.Inthepresentarticle,wereviewtheseinnovativestudydesigns,providingrepresentativeexamplesfromeachcategoryandwediscussthechallengesthatstillneedtobeaddressedinthiseraofnewgenerationoncologytrialsimplementingmolecularprofiling.Emphasisisputonthefieldofbreastcancerclinicaltrials.
简介:MicroRNAs(miRNAs)areasetofnon-codingsmallRNAmoleculesthatplayacriticalroleinregulationofproteincodinggenesincells.MiRNAshavebeenextensivelystudiedasnovelbiomarkers,therapeutictargets,andnewdrugsinvarioushumandiseases.Breastcancerisaoneoftheleadingtumortypessignificantlyaffectingwomenhealthworldwide.Overthepastdecade,anumberofnaturalagents,suchaspaclitaxelandcurcumin,havebeenappliedfortreatmentandpreventionofbreastcancerduetotheirrelativelylowtoxicity.However,themechanismsofactionhavenotbeencompletelyunderstood.InvestigationonmiRNAsisabletopotentiallyprovideanovelinsightintobetterunderstandingtheanticanceractivitiesofthesenaturalproducts.GiventhatasinglemiRNAcantargetmultiplegenes,theoretically,thosegenesinvolvedinacertainphenotypecanbeclusteredwithoneorafewmiRNAs.Therefore,pleiotropicactivitiesofnaturalagentsshouldbeinterpretedbyinteractionsbetweenselectedmiRNAsandtheirtargets.Inthisreview,wesummarizethelatestpublicationsrelatedtothealterationsofmiRNAsbytwonaturalagents(paclitaxelandcurcumin)thatarecurrentlyusedininterventionofbreastcancer,andconcludethatthemechanisminvolvingtheregulationofmiRNAexpressionisoneofthekeystounderstandpleiotropicactivitiesofnaturalagents.
简介:与女乳癌相比,男乳癌是稀罕疾病,并且在临床/病理学的特征和预后之间的关系争论,或甚至大部分未知。在这研究,我们从合用的男乳癌病人在天津医药大学癌症研究所和医院从1996年1月对待到2011年12月的109nonmetastatic用临床、病理学的数据执行了回顾的分析。木头等级测试证明那降低肿瘤舞台,没有淋巴节点参与,和积极雌激素/孕酮受体地位是没有疾病的幸存和外套的好预言者univariate分析上的幸存。然而,hormonotherapy仅仅是没有疾病的幸存,并且不全面幸存的一个好预兆的因素。另外,基于考克斯,比例的危险回归模型,仅仅淋巴节点参与,和雌激素/孕酮受体地位是multivariate分析上的统计上重要的预兆的因素。我们的结果证明尽管辅助全身的治疗在男乳癌广泛地被使用,病人和预后在最后几十年,淋巴节点参与,和雌激素/孕酮受体地位改善了仍然是最重要的预示的因素。有一种更大的样品尺寸的未来的多中心研究着急地被需要进一步理解男乳癌。
简介:Objective:Ki-67playsanimportantfunctionincelldivision,butitsexactroleisstillunknown.Moreover,fewworksregardingitsoverallfunctionwerepublished.ThepresentstudyevaluatedtheclinicalsignificanceofKi-67indexasaprognosticmarkerandpredictorofrecurrenceindifferentmolecularsubtypesofbreastcancer.TherelationshipofKi-67indexwithdifferentclinicopathologicalfactorswasalsoanalyzed.Methods:Ki-67indexwasmeasuredin107casesofprimarybreastcancerfrom2010-2012.Thesepatientswereevaluatedforestrogenreceptor,progesteronereceptor,andHER2.Ki-67wasdividedaccordingtopercentagelevels:<15%and>15%.Followuprangedfrom32monthsupto6years.Results:Approximately44,23,15,and25casesweregroupedasluminalA,luminalB,HER2subtype,andtriple-negative(TN),respectively.NoluminalApatientsshowedKi-67levelhigherthan15%,andtheirrecurrencewas20%.InluminalBgroup,Ki-67levelhigherthan15%wasobservedin69%ofpatients,andrecurrencewas39%.InHER2subtype,Ki-67washigherthan15%in34%ofcases,andrecurrencewas40%.Intriple-negativecases,Ki-67washigherthan15%in60%ofcases,andrecurrencewasdetectedin32%ofpatients.PatientswithKi-67lessthan15%displayedbetteroverallsurvivalthanthosewithKi-67higherthan15%(P=0.01).PatientswithKi-67higherthan15%exhibitedhigherincidenceofmetastasisandrecurrencethanthosewithKi-67lessthan15%(P=0.000).Conclusions:Ki-67maybeconsideredasavaluablebiomarkerinbreastcancerpatients.
简介:Objective:Theelevatedincidenceofobesityhasbeenparalleledwithhigherrisksofbreastcancer.Highadiposityincreasesleptinsecretionfromadiposetissue,whichinturnincreasescancercellproliferation.Theinterplaybetweenleptinandestrogenisoneofthemechanismsthroughwhichleptininfluencesbreastcarcinogenesis.Anunbalancedestrogenmetabolismincreasestheformationsofcatecholestrogenquinones,DNAadducts,andcancermutations.ThisstudyaimstoinvestigatetheeffectofleptinonsomeestrogenmetabolicenzymesandDNAadductioninbreastcancercells.Methods:Highperformanceliquidchromatography(HPLC)wasperformedtoanalyzetheDNAadducts4-OHE1[E2]-1-N3adenineand4-OHE1[E2]-1-N7guanine.Reportergeneassay,realtimereversetranscriptionpolymerasechainreaction(realtimeRT-PCR),andWesternblotwereusedtoassesstheexpressionofestrogenmetabolizinggenesandenzymes:CytochromeP-4501B1(CYP1B1),Nicotinamideadeninedinucleotidephosphate-quinoneoxidoreductase1(NQO1),andCatechol-O-methyltransferase(COMT).Results:LeptinsignificantlyincreasedtheDNAadducts4-OHE1[E2]-1-N3adenineand4-OHE1[E2]-1-N7guanine.Furthermore,leptinsignificantlyupregulatedCYP1B1promoteractivityandproteinexpression.TheluciferasepromoteractivitiesofNQO1andmRNAlevelsweresignificantlyreduced.Moreover,leptingreatlyreducedthereporteractivitiesoftheCOMT-P1andCOMT-P2promotersanddiminishedtheproteinexpressionofCOMT.Conclusions:LeptinincreasesDNAadductlevelsinbreastcancercellspartlybyaffectingkeygenesandenzymesinvolvedinestrogenmetabolism.Thus,increasedfocusshouldbedirectedtowardleptinanditseffectsontheestrogenmetabolicpathwayasaneffectiveapproachagainstbreastcancer.
简介:在这份报纸,许多三维(3D)数字胸模型基于临床的磁性的回声图象(MRI)被开发。一个混合轮廓察觉方法被用来创造轮廓,并且内部空间充满不同的胸纸巾,与相应于MRI象素紧张的指定间隔的各个。发达模型解剖地在乳房描述复杂织物结构和绝缘的性质。而且,他们与finite-difference-time-domain(FDTD)兼容格子房间。Convolutional完成式匹配的层(CPML)与FDTD一起被使用在模型外面模仿开的边界。在测试阶段,微波乳癌察觉模拟与改变X光线照相术的密度在四个模型被执行。然后,共焦的算法被利用重建肿瘤图象。成像结果证明肿瘤voxels能在每种情况中被认出,与在二个低密度盒子中的2公里地点错误和在二个高密度盒子中的7个mm8公里地点错误,证明导出MRI的模型能描绘病人乳房之间的单个差别。
简介:Objective:Panitumumabadministeredasmonotherapyincolorectalcancer(CRC)hasshownresponseanddiseasestabilizationratesofapproximately30%.Thecurrentstudyaimedtoevaluatetheprogression-freesurvival(PFS)andoverallsurvival(OS)ofpatientswithmetastaticcolorectalcancer(mCRC)treatedwithpanitumumabevery3weeksasasecondlinetreatment.Methods:Thisstudyisaretrospectiveanalysisof18patients,agedmorethan18years,withwild-typeKRASexon2mCRCtreatedwithpanitumumabasasecond-linesingleagentafterprogressiononfirst-linechemotherapy.Results:Themediannumberofcoursesreceivedwas10(range,4-29),andthemediandurationoftreatmentwas30weeks(range,12-96weeks).Afteramedianfollow-upperiodof13months,themedianPFSwas6months(range,4.3-7.7months)andthemedianOSwas11months(range,7.4-14.5months).ThemedianPFSwas4monthsforpatientswith
简介:Cancertreatmentfailure,drugresistance,ormetastaticrecurrencearethoughttobecausedmainlybytheexistenceofaverysmallnumberofcancerstemcells(CSCs).Thecharacteristicsofthissubgroupofcellsincludeself-renewal,tumorigenesis,multipledifferentiationandhighinvasiveness,metastasis,anddrugresistancepotential.ManystudieshavedemonstratedthatCSCsplayimportantrolesintumorgrowth,spreadandmetastaticrelapseaftertreatment,andarecloselyrelatedtotheprognosisofpatients.Fromatherapeuticviewpoint,deepinsightsintotheCSCsbiology,developmentofspecifictherapeuticstrategiesfortargetingCSCs,andcharacterizationoftheirmicroenvironmentcouldbeanidealwaytocombatcancer.
简介:Objective:Apreviousstudydemonstratedthatnon-anthracycline-containingdocetaxelpluscyclophosphamide(TC)regimenwasinferiortodocetaxel,anthracyclineandcyclophosphamide(TAC)inneoadjuvanttreatmentoftriple-negativebreastcancer(TNBC)andhumanepidermalgrowthfactorreceptor-2-(HER2)-positivebreastcancerinashort-termfollow-up.Herein,long-termfollow-upsurvivaloutcomeshavebeeninvestigated.Methods:TNBCorHER2-positivepatientswererandomizedtoreceive6cyclesofTCorTACneoadjuvanttreatment.Theprimaryendpointwaspathologicalcompleteremission(pCR).Secondaryendpointsincludedclinicalresponserate,event-freesurvival(EFS),andoverallsurvival(OS).Results:Acohortof96patientsconsistedof45inTCand51inTACarm.Withamedianfollow-upperiodof53(range,8–76)months,thepatientsachievingpCRpostneoadjuvantchemotherapyexhibitedsuperiorEFSandOSthanpatientswithoutpCR(P<0.05).TACtreatmentresultedinconsistentlybetterEFSthanTCtreatment:theestimated5-yearEFSwas66.1%vs.29.8%(P=0.002).Moreover,theestimated5-yearOSwasalsoinfavorofTAC:88.4%vs.51.6%(P<0.001).Multivariableanalysisdemonstratedthatthetreatmentregimenwasanindependentprognosticfactor,andpatientstreatedwithTAChadasuperiorEFS[hazardratio(HR),0.48;95%confidenceinterval(95%CI),0.26–0.90;P=0.021]andOS(HR,0.20;95%CI,0.08–0.60;P=0.003).Conclusions:Theupdatedlong-termfollow-updatademonstratedasustainedbenefitinEFSandOSfromanthracycline-containingTACtreatment,indicatingthatanthracyclineisanessentialandeffectivedruginthisclinicaltrial.
简介:AccordingtoGLOBOCAN2012,livercanceristhesixthmostcommoncancerintheworld.Therewere782,000newcasesdiagnosedin2012,with50%inChinaalone.Livercanceristhesecondmostcommoncauseofcancerdeathworldwideanditsprognosisisverypoor.TheWorldHealthOrganization(WHO)declared745,517deathscausedbylivercancerin2012,withmorethanhalffromChina~1.
简介:Humanendogenousretroviruses(HERVs)areretrovirusesthatinfectedhumangenomemillionsofyearsagoandhavepersistedthroughouthumanevolution.About8%ofourgenomeiscomposedofHERVs,mostofwhicharenonfunctionalbecauseofepigeneticcontrolordeactivatingmutations.However,acorrelationbetweenHERVsandhumancancerhasbeendescribedandmanytumors,suchasmelanoma,breastcancer,germcelltumors,renalcancerorovariancancer,expressHERVproteins,mainlyHERV-K(HML6)andHERV-K(HML2).AlthoughthecausativeroleofHERVsincanceriscontroversial,datafromanimalmodelsdemonstratedthatendogenousretrovirusesarepotentiallyoncogenic.HERVproteinexpressioninhumancellsgeneratesanimmuneresponsebyactivatinginnateandadaptiveimmunities.SomeHERV-derivedpeptideshaveantigenicproperties.Forexample,HERV-K(HML-6)encodestheHER-KMELpeptiderecognizedbyCD8+lymphocytes.Inaddition,HERVsaretwoedgedimmunomodulators.HERVsshowimmunosuppressiveactivity.Thepresenceofgenomicretroviralelementsinhost-cellcytosolmayactivateaninterferontypeIresponse.Therefore,targetingHERVsthroughcellularvaccinesorimmunomodulatorydrugscombinedwithcheckpointinhibitorsisattractinginterestbecausetheycouldbeactiveinhumantumors.
简介:AsreadersofCancerBiologyandMedicinewellknow,therehasbeenaseismicshiftinhumanmolecularbiologyoverthepastfewyears,asmomentousinitsownwayasthediscoveryofthedouble-helicalstructureofDNAbyWatsonandCrick60yearsago,theelucidationofthegeneticcodeshortlythereafter,theadventofrecombinantDNAandgenecloning
简介:Colorectalcancer(CRC)isthesecondmostcommoncancerinwomenandthethirdmostcommoninmenglobally.CRCarisesfromoneoracombinationofchromosomalinstability,CpGislandmethylatorphenotype,andmicrosatelliteinstability.Geneticinstabilityisusuallycausedbyaneuploidyandlossofheterozygosity.Mutationsinthetumorsuppressororcellcyclegenesmayalsoleadtocellulartransformation.Similarly,epigeneticand/orgeneticalterationsresultinginimpairedcellularpathways,suchasDNArepairmechanism,mayleadtomicrosatelliteinstabilityandmutatorphenotype.Non-codingRNAs,moreimportantlymicroRNAsandlongnon-codingRNAshavealsobeenimplicatedatvariousCRCstages.Understandingthespecificmechanismsoftumorigenesisandtheunderlyinggeneticandepigenetictraitsiscriticalincomprehendingthediseasephenotype.Thispaperreviewsthesemechanismsalongwiththerolesofvariousnon-codingRNAsinCRCs.
简介:Epithelialovariancancerrepresentsthemostlethalgynecologicalmalignancyinthedevelopedworld,andcanbedividedintofivemainhistologicalsubtypes:highgradeserous,endometrioid,clearcell,mucinousandlowgradeserous.Thesesubtypesrepresentdistinctdiseaseentities,bothclinicallyandatthemolecularlevel.Molecularanalysishasrevealedsignificantgeneticheterogeneityinovariancancer,particularlywithinthehighgradeseroussubtype.Assuch,thissubtypehasbeenthefocusofmuchresearchefforttodate,revealingmolecularsubgroupsatboththegenomicandtranscriptomiclevelthathaveclinicalimplications.However,stratificationofovariancancerpatientsbasedontheunderlyingbiologyoftheirdiseaseremainsinitsinfancy.Here,wesummarizethemolecularchangesthatcharacterizethefivemainovariancancersubtypes,highlightpotentialopportunitiesfortargetedtherapeuticinterventionandoutlineprioritiesforfutureresearch.
简介:Natureisarichsourceofmedicinalplantsandtheirproductsthatareusefulfortreatmentofvariousdiseasesanddisorders.Momordicacharantia,commonlyknownasbittermelonorbittergourd,isoneofsuchplantsknownforitsbiologicalactivitiesusedintraditionalsystemofmedicines.Thisplantiscultivatedinallovertheworld,includingtropicalareasofAsia,Amazon,eastAfrica,andtheCaribbeanandusedasavegetableaswellasfolkmedicine.Allpartsoftheplant,includingthefruit,arecommonlyconsumedandcookedwithdifferentvegetables,stir-fried,stuffedorusedinsmallquantitiesinsoupsorbeanstogiveaslightlybitterflavorandtaste.Theplantisreportedtopossessanti-oxidant,anti-inflammatory,anti-cancer,anti-diabetic,anti-bacterial,anti-obesity,andimmunomodulatoryactivities.Theplantextractinhibitscancercellgrowthbyinducingapoptosis,cellcyclearrest,autophagyandinhibitingcancerstemcells.Theplantisrichinbioactivechemicalconstituentslikecucurbitanetypetriterpenoids,triterpeneglycosides,phenolicacids,flavonoids,essentialoils,saponins,fattyacids,andproteins.Someoftheisolatedcompounds(KuguacinJ,KaravilosideXI,KuguaglycosideC,MomordicosideQ-U,Charantin,α-eleostearicacid)andproteins(α-Momorcharin,RNaseMC2,MAP30)possesspotentbiologicalactivity.Inthepresentreview,wearesummarizingtheanti-oxidant,anti-inflammatory,andanti-canceractivitiesofMomordicacharantiaalongwithashortaccountofimportantchemicalconstituents,providingabasisforestablishingdetailbiologicalactivitiesoftheplantanddevelopingnoveldrugmoleculesbasedontheactivechemicalconstituents.
简介:Objective:Population-basedcancerregistrationdatain2012fromallavailablecancerregistriesinHenanprovincewerecollectedbyHenanOfficeforCancerResearchandControl.ThenumbersofnewcancercasesandcancerdeathsinHenanprovincewithcompiledcancerincidenceandmortalityrateswereestimated.Methods:In2015,allregistries'datainHenanprovincewerequalifiedforthenationalcancerregistryannualreportin2012.Thepooleddatawerestratifiedbyarea(urban/rural),gender,agegroup(0,1-4,5-9,10-14,…,85+)andcancertype.Newcancercasesanddeathswereestimatedusingage-specificratesandcorrespondingpopulationofHenanprovincein2012.TheChinesecensusdatain2000andSegi'spopulationwereappliedforage-standardizedrates.Alltherateswereexpressedper100,000person-years.Results:Qualified19cancerregistries(4urbanand15ruralregistries)covered16,082,688populationsofHenanprovincein2012.Thepercentageofcaseswithmorphologicallyverified(MV%)anddeathcertificateonlycases(DCO%)were69.84%and2.30%,respectively,andthemortalitytoincidencerateratio(M/I)was0.64.Itwasestimatedthattherewere248,510newcancercasesand158,630cancerdeathsinHenanprovincein2012.Theincidenceratewas266.17/100,000(288.61/100,000inmalesand241.86/100,000infemales),theage-standardizedincidenceratesbyChinesestandardpopulation(ASIRC)andbyworldstandardpopulation(ASIRW)were208.95/100,000and206.41/100,000withthecumulativeincidencerate(0-74yearsold)of24.30%.Thecrudeincidencerateinurbanareaswashigherthanthatinruralareas.However,afteradjustedbyage,thecancerincidencerateinruralwashigherthanthatinurbanareas.ThecrudemortalityofallcancersinHenanprovincewas169.90/100,000(201.23/100,000inmalesand135.95/100,000infemales).Theage-standardizedmortalityratesbyChinesestandardpopulation(ASMRC)andbyworldstandardpopulation(ASMRW)were131.20/100,000and130.80/100,000,respect