简介：Colorectalcancer(CRC)isthesecondmostcommoncancerinwomenandthethirdmostcommoninmenglobally.CRCarisesfromoneoracombinationofchromosomalinstability,CpGislandmethylatorphenotype,andmicrosatelliteinstability.Geneticinstabilityisusuallycausedbyaneuploidyandlossofheterozygosity.Mutationsinthetumorsuppressororcellcyclegenesmayalsoleadtocellulartransformation.Similarly,epigeneticand/orgeneticalterationsresultinginimpairedcellularpathways,suchasDNArepairmechanism,mayleadtomicrosatelliteinstabilityandmutatorphenotype.Non-codingRNAs,moreimportantlymicroRNAsandlongnon-codingRNAshavealsobeenimplicatedatvariousCRCstages.Understandingthespecificmechanismsoftumorigenesisandtheunderlyinggeneticandepigenetictraitsiscriticalincomprehendingthediseasephenotype.Thispaperreviewsthesemechanismsalongwiththerolesofvariousnon-codingRNAsinCRCs.

简介：AbstractPatient-derived tumor organoids (PDOs) currently represent important modeling tools in pre-clinical investigation of malignancies. Organoid cultures conserve the genetic and phenotypic characteristics of the original tumor and maintain its heterogeneity, allowing their application in many research fields. PDOs derived from colorectal cancer (CRC) have been used for genetic modeling to investigate the function of driver genes. Some researchers have been exploring the value of CRC PDOs in chemotherapy, targeted therapy, and radiotherapy response prediction. The successful generation of PDOs derived from CRC could deepen our understanding of CRC biology and provide novel tools for cancer modeling, for realizing precision medicine by assessing specimens from individual patients ex vivo. The present review discusses recently reported advances in CRC PDOs and the challenges they face as pre-clinical models in CRC research.

简介：客观：复制错误(RER)与colorectal癌(CRC)的开始和开发有关。调查RER+和RER的不同生物行为？CRC。方法：染色PCR单个的海滨符合构造多型性(PCR-SSCP)和使中毒的polyacrylamide胶化电气泳动方法的银被用来在染色体2上在4loci检测microsatellite不稳定性(MSI)，5，17在60colorectal癌(CRC)和他们的配对的正常组织的嵌入石蜡的标本。如果，RER+被获得2或更多的loci作为获得额外的乐队表现了。结果：结果证明RER+在19/60CRC，7个案例在之中有家庭历史被发现。根据阿姆斯特丹的标准，4作为世袭nonpolyposiscolorectal癌症(HNPCC)被诊断，并且哪个3个案例是RER+。在HNPCC(75%)的比率RER+在分散的CRC(28.5%)之中比那显著地高。大多数RER+CRC有糟糕区分的腺癌的特征(P<0.01)，包含冒号的右边的趋势(P<0.05)，有家庭历史的一个更高的比例(P<0.05)，Ducke的A和B阶段(P<0.05)。结论：结果显示RER+是在CRC的一个相对普通的分子的事件。在RER+和RER之间有不同clinico病理学的特征和行为吗？CPC。

简介：Colorectalcarcinoma(CRC)isacommoncauseofmorbidityandmortalityworldwide.TwopathogenicpathwaysareinvolvedinthedevelopmentofadenomatoCRC.ThefirstpathwayinvolvesAPC/β-catenincharacterizedbychromosomalinstabilityresultingintheaccumulationofmutations.ThesecondpathwayischaracterizedbylesionsinDNAmismatchrepairgenes.AberrantDNAmethylationinselectedgenepromotershasemergedasanewepigeneticpathwayinCRCdevelopment.CRCscreeningisthemostefficientstrategytoreducedeath.SpecificDNAmethylationeventsoccurinmultistepcarcinogenesis.EpigeneticgenesilencingisacausativefactorofCRCdevelopment.DNAmethylationshavebeenextensivelyexaminedinstoolfromCRCandprecursorlesions.ManymethylatedgeneshavebeendescribedinCRCandadenoma,althoughnodefiniteDNAmethylationbiomarkerspanelhasbeenestablished.MultipleDNAmethylationbiomarkers,includingsecretedfrizzled-relatedprotein2,secretedfrizzled-relatedprotein1,tissuefactorpathwayinhibitor2,vimentin,andmethylguanineDNAmethyltransferase,havebeenfurtherinvestigated,andobservationshaverevealedthatDNAmethylationbiomarkersexhibitwithhighsensitivityandspecificity.ThesemarkersmayalsobeusedtodiagnoseCRCandadenomainearlystages.Realtimepolymerasechainreaction(qPCR)issensitive,scalable,specific,reliable,timesaving,andcosteffective.Stoolexfoliatedmarkersprovideadvantages,includingsensitivityandspecificity.AstoolqPCRmethylationtestmayalsobeanenhancedtoolforCRCandadenomascreening.

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简介：Coloncancersdevelopadaptivemechanismstosurviveunderextremeconditionsanddisplayhallmarksofunlimitedproliferationandresistancetocelldeath.Thederegulationofcelldeathisakeyfactorthatcontri-butestochemoresistanceintumors.Inaphysiologicalcontext,balancebetweencellproliferationanddeath,andprotectionagainstcelldamagearefundamentalprocessesformaintaininggutepithelialhomeostasis.Themechanismsunderlyinganti-deathcytoprotectionandtumorresistanceoftenbearcommonpathways,andalthoughdistinguishingthemwouldbeachallenge,itwouldalsoprovideanopportunitytodevelopadvancedanti-cancertherapeutics.Thisreviewwilloutlinecelldeathpathways(i.e.,apoptosis,necrosis,andnecroptosis),anddiscusscytoprotectivestrategiesinnormalintestinalepitheliumanddeathresistancemechanismsofcolontumor.Incolorectalcancers,theintracellularmechanismsofdeathresistanceincludethedirectalterationofapoptoticandnecroptoticmachineryandtheupstreameventsmodulatingdeatheffectorssuchastumorsuppressorgeneinactivationandpro-survivalsignalingpathways.Theautocrine,paracrineandexogenousfactorswithinatumormicroenvironmentcanalsoinstigateresistanceagainstapoptoticandnecroptoticcelldeathincoloncancersthroughchangesinreceptorsignalingortransporteruptake.Therolesofcyclooxygenase-2/prostaglandinE2,growthfactors,glucose,andbacteriallipopolysaccharidesincolorectalcancerwillbehighlighted.Targetinganti-deathpathwaysinthecoloncancertissuemightbeapromisingapproachoutsideofanti-proliferationandanti-angiogenesisstrategiesfordevelopingnoveldrugstotreatrefractorytumors.

简介：Colorectalcancer（CRC）isthethirdmostcommoncancerdiagnosedworldwideinhumanbeings.Surgery,chemotherapy,radiotherapyandtargetedtherapiesaretheconventionalfourapproacheswhicharecurrentlyusedforthetreatmentofCRC.Thesitespecificdeliveryofchemotherapeuticstotheirsiteofactionwouldincreaseeffectivenesswithreducingsideeffects.Targetedoraldrugdeliverysystemsbasedonpolysaccharidesarebeinginvestigatedtotargetanddeliverchemotherapeuticandchemopreventiveagentsdirectlytocolonandrectum.Site-specificdrugdeliverytocolonincreasesitsconcentrationatthetargetsite,andthusrequiresalowerdoseandhenceabridgedsideeffects.Somenoveltherapiesarealsobrieflydiscussedinarticlesuchasreceptor（epidermalgrowthfactorreceptor,folatereceptor,wheatgermagglutinin,VEGFreceptor,hyaluronicacidreceptor）basedtargetingtherapy;colontargetedproapoptoticanticancerdrugdeliverysystem,genetherapy.EventhoughgoodtreatmentoptionsareavailableforCRC,theultimatetherapeuticapproachistoaverttheincidenceofCRC.ItwasalsofoundthatCRCscouldbepreventedbydietandnutritionsuchascalcium,vitaminD,curcumin,quercetinandfishoilsupplements.ImmunotherapyandvaccinationareusednowadayswhichareshowingbetterresultsagainstCRC.

简介：EversinceHelicobacterpylori（H.pylori）wasrecognizedasaninfectiouscauseofgastriccancer,therehasbeenincreasinginterestinexaminingitspotentialroleincolorectalcarcinogenesis.Datafromcasecontrolandcross-sectionalstudies,mostlyrelyingonhospital-basedsamples,andseveralmeta-analyseshaveshownapositivestatisticalrelationshipbetweenH.pyloriinfectionandcolorectalneoplasia.However,thepossibilityexiststhattheresultshavebeeninfluencedbybias,includingtheimproperselectionofpatientsanddisparitieswithrespecttopotentialconfounders.Whiletheevidencefallsshortofadefinitivecausallink,itappearsthatinfectionwithH.pylori/H.pylori-relatedgastritisisassociatedwithanincreased,althoughmodest,riskofcolorectaladenomaandcancer.Thepathogenicmechanismsresponsibleforthisassociationremainuncertain.H.pylorihasbeendetectedincolorectalmalignanttissues;however,thepossibilitythatH.pyloriisadirectactivatorofcoloniccarcinogenesisremainspurelyhypothetical.Ontheotherhand,experimentaldatahaveindicatedaseriesofpotentialoncogenicinteractionsbetweenthesebacteriaandcolorectalmucosa,includinginductionandperpetuationofinflammatoryresponses,alterationofgutmicrofloraandreleaseoftoxinsand/orhormonalmediators,suchasgastrin,whichmaycontributetotumorformation.

简介：Objective:Toevaluatetheassociationbetweenobesityandtheriskofcolorectalcancer.Methods:331patientswithrectalcancerand175withcoloncancerwhoacceptedsurgicaloperationatBeijingCancerHospitalduring1995and2002wereenrolled.Datawerecollectedbyreviewingthepathologymaterialsandhospitalrecords.258healthypeoplewhoacceptedhealthexaminationatBeijingCancerHospitalduring2000and2002werealsoenrolledascontrol.Dataofheight,weightandgenderatthetimeofexaminationwerealsocollected.Obesitywasestimatedbybodymassindex(BMI),computedasweightinkilogramsdividedbyheightinmeterssquared(kg/m2).ThedegreeofobesitywascomparedbetweenthetwogroupsusingBMI(18.5,24-27.9and(28(kg/m2)asthecut-offpointsforunderweight,overweightandobesity.Associationswithobesitywereestimatedbyoddsratios(ORs)and95%confidenceintervals(CIs).AllORswereadjustedforageandsex.Results:Obesitywassignificantlyprevalentinfemalepatientswithrectalcancer.AllthepatientswithcoloncancershowedlowerlevelofBMIthancontrolsubjects.TheORsforrectalcancerrosewithincreasingBMIinwomen.Meanwhile,theORsforcoloncancerdroppedwithincreasingBMIinbothmenandwomen.Obesitywasanindependentriskfactorforrectalcancer,butnotanindependentriskfactorforcoloncancer.Conclusion:Rectalcancerandcoloncancermayhavedifferentbiologicalbehavior.Obesewomenhaverelativelyhighriskforrectalcancer.

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简介：Colorectalcancer(CRC)isasignificantcauseofmorbidityandmortalityworldwide.However,coloncancerincidenceandmortalityisdecliningoverthepastdecadeowingtoadoptionofeffectivescreeningprograms.Nevertheless,insomepartsoftheworld,CRCincidenceandmortalityremainontherise,likelyduetofactorsincluding'westernized'diet,lifestyle,andlackofhealth-careinfrastructureandresources.Participationandadherencetodifferentnationalscreeningprogramsremainobstacleslimitingtheachievementofscreeninggoals.Differentmodalitiesareavailablerangingfromstoolbasedteststoradiologyandendoscopywithvaryingsensitivityandspecificity.However,theavailabilityofthesetestsislimitedtoareaswithhigheconomicresources.Recently,FDAapprovedablood-basedtest(Epiprocolon?)forCRCscreening.Thisbloodbasedtestmayservetoincreasetheparticipationandadherencerates.Hence,leadingtoincreaseincoloncancerdetectionandprevention.ThisarticlewilldiscussvariousCRCscreeningtestswithaparticularfocusonthedataregardingthenewapprovedbloodtest.Finally,wewillproposeanalgorithmforasimplecost-effectiveCRCscreeningprogram.

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简介：Livermetastasessynchronouslyormetachronouslyoccurinapproximately50%ofcolorectalcancerpatients.Multimodalitycomprehensivetreatmentisthebesttherapeuticstrategyforthesepatients.However,theoptimalpatternofmultimodalitytherapyisstillcontroversial,anditraisesseveralsignificantconcerns.Liverresectionisthemostimportanttreatmentforcolorectallivermetastases.ThedefinitionofresectabilityhasshiftedtofocusonthecompletionofR0resectionandnormalliverfunctionmaintenance.Theroleofneoadjuvantandadjuvantchemotherapystillneedstobeclarified.Themanagementofeitherprogressionorcompleteremissionduringneoadjuvantchemotherapyischallenging.Theoptimalsequencingofsurgeryandchemotherapyinsynchronouscolorectallivermetastasespatientsisstillunclear.Conversionalchemotherapy,portalveinembolization,two-stageresection,andtumorablationareeffectiveapproachestoimproveresectabilityforinitiallyunresectablepatients.Severaltechnicalissuesandconcernsrelatedtothesemethodsneedtobefurtherexplored.Forpatientswithdefinitelyunresectableliverdisease,thenecessityofresectingtheprimarytumorisstilldebatable,andevaluatingandpredictingtheefficacyoftargetedtherapydeservefurtherinvestigation.Thisreviewdiscussesdifferentpatternsandimportantconcernsofmultidisciplinarytreatmentofcolorectallivermetastases.

简介：瞄准：学习颜色的协会有侵略的癌，本地复发，synchronicity和损害的元慢性的表面的锯齿状腺瘤(SA)。方法：从在一个八年的时期(1987-1995)上的1,096个病人的4,536息肉的一个总数回顾地被检验。显示出至少50%serrated建筑学的腺瘤被三称为SA考察病理学家。结果：(2%)91所有息肉被称为SA，它在46个病人被发现。侵略的癌从46在3被看见(6.4%)病人，一个人是家庭腺瘤息肉病(FAP)的一个盒子。男优势被注意，发育异常的温和的度的特征在多数被看见(n=75，83%)锯齿状腺瘤。后续变化了有5.75年的一吝啬的时间的1-12年。SA的复发在3被看见(6.4%)盒子，在16的同步SA(34.8%)在9的盒子和异时SA(19.6%)盒子。结论：侵略的癌在锯齿状腺瘤产生是稀罕的，为2的财务(4.3%)在这个系列的casesstudied。

简介：Objective:Signetringcellcarcinomaisararesubtypeofcolorectalcarcinoma(CRC)withanassociatedBRAFV600Emutation.WeinvestigatedfrequenciesofBRAFmutationin28CRCscontainingvariablesignetringcellcomponentandtheirrelationwithclinicopathologicparameters.Methods:Accordingtothepresenceofsignetringcellcomponent,tumorswerecategorizedintogroupsasfollows:0%–9%,10%–24%,25%–49%,and>50%.GenomicDNAwasisolatedandanalyzedforBRAFV600Egenemutationbypolymerasechainreaction-restrictionfragmentlengthpolymorphism.Elevenof28cases(39.3%)showedBRAFV600Emutation,whichwasalsoconfirmedbySangersequencing.Toelucidatetheimportanceofexistenceofsignetringcellcomponentatthemolecularlevel,weseparatedcasesintotwogroupswithcut-offlevelsof10%and50%,whichpertaintopercentagesofsignetringcells.Results:Sevenof19cases(36.8%)underthethresholdof50%andfourofninecases(44.4%)overthisthresholdvaluedemonstratedBRAFmutation.Threeof7cases(42.8%)featuring<10%signetringcellcomponentandeightoutof21cases(38.1%)showing>10%wereBRAFmutated.Conclusions:BRAFmutationmustbecloselyassociatedwiththepresenceofmalignantsignetringcellsregardlessoftheirpercentages.

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简介：AbstractAccumulating evidence suggests that intestinal bacteria play an important role in the pathogenesis of colorectal cancer (CRC). Due to the complexity of the intestinal microbiome, identification of the specific causative microbial agents in CRC remains challenging, and the search for the causative microbial agents is intense. However, whether bacteria or their products can induce inflammation that results in tumorigenesis or directly causes CRC in humans is still not clear. This review will mainly focus on the progress of bacterial infection and CRC, and introduce the microbial contribution to the hallmarks of cancer. This article uses Salmonella and its chronic infection as an example to investigate a single pathogen and its role in the development of CRC, based on laboratory and epidemiological evidence. The bacterial infection leads to an altered intestinal microbiome. The review also discusses the dysfunction of the microbiome and the mechanism of host-microbial interactions, for example, bacterial virulence factors, key signaling pathways in the host, and microbial post-translational modifications in the tumorigenesis. Colonic carcinogenesis involves a progressive accumulation of mutations in a genetically susceptible host leading to cellular autonomy. Moving forward, more human data are needed to confirm the direct roles of bacterial infection in CRC development. Insights into the inhibiting infection will help to prevent cancer and develop strategies to restore the balance between host and microorganisms.

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简介：Inthecomingyearslifeexpectancyisexpectedtoincreaseandwiththisthepercentageofthepopulationaboveage65willgrow.Patientsabove65makeupmorethantwothirdsofthosecurrentlydiagnosedwithgastrointestinalmalignancies.Availableevidencebasedmedicinedoesnotfocusontheaveragepatient,abovetheage70,encounteredineverydaypractice.Mostguidelinesandclinicaltrialsarenotdesignedtotakeintoaccountthespecialconsiderationsneededwhentreatingtheelderlysuchasfunctionalstatus,comorbidities,polypharmacy,lifeexpectancy,andsocialsupport.Themajorityofavailabledataisbasedonretrospectivereviewsorsubsetanalysesoflargerstudieswheretheelderlyrepresentafractionofthestudiedpopulation.Thisreviewfocusesonthetoxicitiesandtolerabilityofcurrentstandardtherapiesfornoncolorectalgastrointestinalmalignancies,includinggastroesophageal,pancreatic,bileductandhepatocellularcancersintheelderly.Withcarefulpatientselectionandgeriatricassessmenttheelderlycansafelybenefitfromstandardtherapiesofferedtoyoungerpatients.

简介：AIM:ToinvestigateFusobacteriumnucleatum（F.nucleatum）abundanceincolorectalcancer（CRC）tissuesanditsassociationwithCRCinvasivenessinChinesepatients.METHODS:Theresectedcancerandadjacentnormaltissues（10cmbeyondcancermargins）from101consecutivepatientswithCRCwerecollected.Fluorescentquantitativepolymerasechainreaction（FQ-PCR）wasappliedtodetectF.nucleatuminCRCandnormaltissues.ThedifferenceofF.nucleatumabundancebetweencancerandnormaltissuesandtherelationshipofF.nucleatumabundancewithclinicalvariableswereevaluated.Fluorescenceinsituhybridization（FISH）analysiswasperformedon22CRCtissueswiththehighestF.nucleatumabundancebyFQ-PCRtestingtoconfirmFQ-PCRresults.RESULTS:ThemedianabundanceofF.nucleatuminCRCtissues[0.242（0.178-0.276）]wassignificantlyhigherthanthatinnormalcontrols[0.050（0.023-0.067）]（P<0.001）.F.nucleatumwasover-representedin88/101（87.1%）CRCsamples.TheabundanceofF.nucleatumdeterminedby2-ΔCTwassignificantlygreaterintumorsamples[0.242（0.178,0.276）]thaninnormalcontrols[0.050（0.023,0.067）]（P<0.001）.Thefrequencyofpatientswithlymphnodemetastaseswashigherintheover-abundancegroup[52/88（59.1%）]thanintheunder-abundancegroup[0/13（0%）]（P<0.005）.NosignificantassociationofF.nucleatumwithotherclinico-pathologicalvariableswasobserved（P>0.05）.FISHanalysisalsofoundmoreF.nucleatuminCRCthaninnormaltissues(mediannumber6,25th3,75th10vs2,25th1,75th5)（P<0.01）.CONCLUSION:F.nucleatumwasenrichedinCRCtissuesandassociatedwithCRCdevelopmentandmetastasis.