简介：Drugdevelopmentinoncologyisundergoingasubstantialshiftnowadays.Thedriversforthisaremulti-factorial.Ontheoneside,drugdevelopmentisperformedmorerationallythanever,profitingfromthescientificadvancesinmolecularbiologyingeneralandtheelucidationofthevarious'omes'fromgenometometabolomeinparticular.Ontheotherside,itisbasedonenormoustechnologicalprogress,e.g.,inthefieldofgenome

简介：Glioblastoma(GBM)isatypeoftumorthatishighlylethaldespitemaximaltherapy.Standardtherapeuticapproachesprovidemodestimprovementinprogression-freeandoverallsurvival,necessitatingtheinvestigationofnoveltherapies.Oncologictherapyhasrecentlyexperiencedarapidevolutiontoward'targetedtherapy',withdrugsdirectedagainstspecifictargetswhichplayessentialrolesintheproliferation,survival,andinvasivenessofGBMcells,includingnumerousmoleculesinvolvedinsignaltransductionpathways.Inhibitorsofthesemoleculeshavealreadyenteredorareundergoingclinicaltrials.However,significantchallengesintheirdevelopmentremainbecauseseveralpreclinicalandclinicalstudiespresentconflictingresults.Inthisarticle,wewillprovideanup-to-datereviewofthecurrenttargetedtherapiesinGBM.

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简介：ThechronicinfectionofhepatitisBvirus(HBV)iscloselyrelatedtotheoccurrenceanddevelopmentofhepatocellularcarcinoma(HCC).AccumulatedevidencehasshownthatHBVXprotein(HBxprotein)isamultifunctionalregulatorwithacrucialroleinhepatocarcinogenesis.However,informationonthemechanismbywhichHBVinducesHCCislacking.ThisreviewfocusesonthepathologicalfunctionsofHBxinHBV-inducedhepatocarcinogenesis.Asatransactivator,HBxcanmodulatenuclearfactorkappa-light-chain-enhancerofactivatedBcells(NF-κB)andtranscriptionfactorAP-2.Moreover,HBxcanaffectregulatorynon-codingRNAs(ncRNAs)includingmicroRNAsandlongncRNAs(lncRNAs),suchasmiRNA-205andhighlyupregulatedinlivercancer(HULC),respectively.HBxisalsoinvolvedinepigeneticmodification,includingmethylationandacetylation.HBxinteractswithvarioussignal-transductionpathways,suchasproteinkinaseB/Akt,Wnt/β-catenin,signaltransducerandactivatoroftranscription,andNF-κBpathways.Moreover,HBxaffectscellularfatebyshiftingthebalancetowardcellsurvival.HBxmayleadtothelossofapoptoticfunctionsordirectlycontributestooncogenesisbyachievingtransformingfunctions,whichinducehepatocarcinogenesis.Additionally,HBxcanmodulateapoptosisandimmuneresponsebydirectorindirectinteractionwithhostfactors.WeconcludethatHBxhastensthedevelopmentofhepatoma.

简介：在染色体9p21的Ink4地点编码P15Ink4b，P14Arf，P16Ink4a，MTAP，ncRNAANRIL/p15AS和p16AS，它在干细胞自强的规定起一个重要作用。这些基因的功能的损失通过绕过在房间周期的G1和S阶段之间的检查点支持房间增长。由在开始地点(TSS)的抄写附近的CpG岛的methylation的Transcriptional沉默是在carcinogenesis的早阶段的一个经常的事件。长期的发炎是为Ink4a基因的CpG岛的methylation的一个强壮的开始者。象Polycomb那样的transcriptionalsilencers的联合有基因特定的ncRNA的组(PcG)蛋白质能epigenetically第一在H3K27，然后在H3K9包括trimethylation导致histone修正。在抄写的长期的沉默的情况中，CpG地点的methylation在目标基因的完整的CpG岛以内日益增多地开始并且传播。就算它的宿主细胞与Ink4a活跃细胞被熔化，Ink4aCpG岛的methylation地位是很稳定的。

简介：Thymidinephosphorylase(TP)isakeyenzymethatcontributestothecompositionanddecompositionofpyrimidinenucleotides.TPseemshomologoustoplatelet-derivedendothelialcellgrowthfactor,anditseffectsoninducingvascularizationandanti-apoptosisarecloselyrelatedtogrowthandmetastasisofcolorectalcarcinoma.Inaddition,TPisakeyenzymethatcatalyzesthetransformationfrom5-fluorouracil(FU)prodrugsof5′-deoxy-5-fluorouridine(5′-DFUR)to5-FU.TheactivityofTPiscloselyrelatedtothesensitivityofcolorectalcarcinomacellstofluorouracildrugsandtargetedtherapy.GiventheimportantfunctionsofTPingrowth,metastasis,tumortreatment,andprognosis,determiningitsexpressionmechanismissignificant.ThisarticlesummarizestheresearchdevelopmentofTPexpressionincolorectalcarcinoma,tumorneovascularization,cytotoxicityactivationof5′-DFUR,andcolorectalcarcinomatherapy.

简介：Objective:IL-22-producingCD4+Thelpercells(Th22cells)havebeenidentifiedasmajorinducersoftissueinflammationandimmuneresponses.Currently,nopreviousstudyexploredtheroleofTh22cellsinthepathogenesisofhepatocellularcarcinoma(HCC).ThestudyaimedtodeterminethebiologicalfunctionofTh22cellsanditseffectorIL-22inHCCpatients.Methods:Forty-fiveHCCpatientsand19healthycontrolswererecruitedandtheirperipheralbloodwascollected.ThefreshHCCtissues,adjacentHCCtissuesandtennormallivertissueswerealsocollected.FlowcytometryanalysiswasusedtodeterminethefrequenciesofcirculatingTh22cellsandTh17cells.SerumIL-22levelsweretestedbyenzyme-linkedimmunosorbentassay(ELISA).Immunohistochemicalstainingandreal-timepolymerasechainreaction(PCR)wereusedtodetectIL-22proteinandmRNAintissuesspecimens,respectively.Results:CirculatingTh22cells,Th17cellsandserumIL-22levelsweresignificantlyelevatedinHCCpatientscomparedwiththoseofhealthycontrols(P<0.001).Th22cellswereshowedtobepositivelycorrelatedwithIL-22inHCCpatients(P<0.05),butnotinhealthycontrols.NosignificantdifferenceswerefoundinHCCpatientswithHBeAgpositivityornegativityintermofTh22cellsandserumIL-22levels.TheexpressionofIL-22proteinandmRNAwashighestinHCCtissues,followedbyadjacentHCCtissuesandnormallivertissues.Furthermore,Th22cells,serumIL-22levelsandIL-22mRNAwereelevatedatstageIII-IVcomparedwithstageI-IIofHCC(P<0.05).Conclusions:ElevationofcirculatingTh22cellsandIL-22maybeimplicatedinthepathogenesisofHCC,andpotentiallybecellulartargetsfortherapeuticintervention.

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