简介:Dermatofibrosarcomaprotuberans(DFSP),themostcommondermalsarcoma,isalow-grade,slowgrowingfibroblasticmalignantneoplasmthatmostfrequentlyaffectsmiddleagedadultsandischaracterizedbyahighlocalrecurrencerateandalowpropensityformetastasis.WidesurgicalresectionorMohsmicrographicsurgery(MMS)arethepreferredapproachesforlocalizeddisease,whileradiationtherapyiswarrantedforinoperablediseaseorforcaseswithpositivemarginswherere-excisionisnotpossible.DFSPisgenerallyregardedasrefractorytoconventionalchemotherapy.Treatmentoptionsforsystemicdiseasewerelimiteduntilthediscoveryofauniquetranslocation,t(17;22)(q22;q13)(COL1A1;PDGFB)foundinamajorityofcases.Inrecentyears,imatinib,aPDGFβR,ABLandKITinhibitor,hasrevolutionizedsystemictherapyinDFSP.Inthisreview,wesummarizetheepidemiological,clinical,histologicalandgeneticcharacteristicsofDFSPandupdatethereadersonitscurrentmanagement.
简介:Despitethefactthatironisoneofthemostabundantelementsoftheearth'scrust,irondeficienciesareseriousproblemsbothinhumannutrition[1]andinagriculture[2].Sixtoeightpercentoftheworld'spopulationispotentiallyaffectedbyirondeficiencyinducedanemia,aleadingcauseofmaternaldeathinAfricanandAsiancountrieswherepeoplerelymostlyonplantsfortheirdailyintakeofiron.Ironcanalsobealimitingfactorinthegrowthofeconomicallyimportantcropplantsbecauseofinadequatesoilchemistry,andsuchdeficienciescannoteasilybecorrectedbyamendingthesoil.Improvingtheplant'sabilitytoabsorbironinadverseconditionsandtoincreasetheiroverallcontentcouldoffersolutionstothesedramaticproblems.Thereforeunderstandingthemolecularmechanismsregulatingironuptakeandhomeostasisinplantshaspotentiallyimportantpracticalapplicationsbothinagricultureandhumanhealth[3].
简介:在脂肪和肌肉房间,刺激胰岛素的葡萄糖举起被葡萄糖transporter主要调停4(GLUT4),哪个到响应胰岛素刺激的房间表面的从细胞内部的分隔空间的translocates。AS160是Akt的底层之一并且在调整胰岛素的GLUT4translocation起重要作用。在这研究,(RUVBL2)象RuvB一样蛋白质2用与集体spectrometry相结合的哺乳动物的双人脚踏车亲密关系纯化(龙头)作为新AS160有约束力的蛋白质被识别。在3T3-L1adipocytes,RUVBL2高度被表示并且在cytosol主要是分布式的。在adipocytes的RUVBL2的弄空通过减少刺激胰岛素的AS160phosphorylation禁止刺激胰岛素的GLUT4translocation和葡萄糖举起。然而,人的RUVBL2的介绍能颠倒这禁止的效果。这些数据建议RUVBL2通过它和AS160的相互作用在刺激胰岛素的GLUT4translocation起一个重要作用。
简介:Wntsignalingplaysanimportantroleinembryogenesisandtumorgenesis.AlthoughthemechanismabouthowWntstransducetheirsignalingfromreceptorfrizzled(Fz)tocytosolhasnotbeenunderstood,dishevelled(Dvl)proteinwasconsideredastheintersectionofWntsignaltraffic.Inthisstudy,wecharacterizedthefunctionofthreedomains(DIX,PDZandDEP)ofDvl-1incanonicalWntsignaltransductionandDvl-1membranetranslocation.ItwasfoundbothDIXandDEPdomainweresufficienttoblockWnt-3a-inducedLEF-1transcriptionalactivityandfreecytosolβ-cateninaccumulation;whereasPDZdomainandafunctionalmutantformofDEPdomain(DEP-KM)hadnoeffectoncanonicalWntsignaling.Inaddition,whencotransfectedwithFz-7,DEPdomain,butnotDIX,PDZorDEP-KM,translocatedandco-localizedwithFz-7totheplasmamembrane,whichwassimilartoDvl-1.Furthermore,itwasDEPdomainthatcouldblockFz-7-inducedmembranetranslocationofDvl-1viaapossiblecompetitivemechanism.TheseresultsstronglysuggestthatDEPdomainisresponsibleforthemembranetranslocationofDvl-1proteinuponWntsignalstimulation.
简介:AIM:Toinvestigatetheanti-tumoreffectsofnuclearfactor-κB(NF-κB)inhibitorSN50andrelatedmechanismsofSGC7901humangastriccarcinomacells.METHODS:MTTassaywasusedtodeterminethecytotoxiceffectsofSN50ingastriccancercelllineSGC7901.Hoechst33258stainingwasusedtodetectapoptosismorphologicalchangesafterSN50treatment.Activationofautophagywasmonitoredwithmonodansylcadaverine(MDC)stainingafterSN50treatment.Immunofluorescencestainingwasusedtodetecttheexpressionoflightchain3(LC3).MitochondrialmembranepotentialwasmeasuredusingthefluorescentprobeJC-1.Westernblottinganalysiswereusedtodeterminetheexpressionofproteinsinvolvedinapoptosisandautophagyincludingp53,p53upregulatedmodulatorofapoptosis(PUMA),damage-regulatedautophagymodulator(DRAM),LC3andBeclin1.Wedetectedtheeffectsofp53-mediatedautophagyactivationontheapoptosisofSGC7901cellswiththep53inhibitorpifithrin-α.RESULTS:TheviabilityofSGC7901cellswasinhibitedafterSN50treatment.Inductionsintheexpressionofapoptoticproteinp53andPUMAaswellasautophagicproteinDRAM,LC3andBeclin1weredetectedwithWesternblottinganalysis.SN50-treatedcellsexhibitedpunctuatemicrotubule-associatedprotein1LC3inimmunoreactivityandMDC-labeledvesiclesincreasedaftertreatmentofSN50byMDCstaining.CollapseofmitochondrialmembranepotentialΔψweredetectedfor6to24hafterSN50treatment.SN50-inducedincreasesinPUMA,DRAM,LC3andBeclin1andcelldeathwereblockedbythep53specificinhibitorpifithrin-α.CONCLUSION:Theanti-tumoractivityofNF-κBinhibitorsisassociatedwithp53-mediatedactivationofautophagy.
简介:Resistancetocisplatin(DDP)-basedchemotherapyisamajorcauseoftreatmentfailureinhumangastriccancer(GC).Itisnecessarytoidentifythedrugstore-sensitizeGCcellstoDDP.Inourpreviousresearch,ZuoJinWanFormula(ZJW)hasbeenprovedcouldincreasethemitochondrialapoptosisviacofilin-1inaimmortalizedcellline,SGC-7901/DDP.Duetotheimmortalizedcellsmaystilldifficulthighlyrecapitulatetheimportantmoleculareventsinvivo,primaryGCcellsmodelderivedfromclinicalpatientwasconstructedinthepresentstudytofurtherevaluatetheeffectofZJWandtheunderlyingmolecularmechanism.ImmunofluorescentstainingwasusedtoindentifyprimaryculturedhumanGCcells.Westernblottingwascarriedouttodetecttheproteinexpression.CellCountingKit-8(CCK-8)wasusedtoevaluatecellproliferation.Flowcytometryanalysiswasperformedtoassesscellapoptosis.ZJWinhibitedproliferationandinducedapoptosisinprimaryDDP-resistantGCcells.Notably,theapoptosisinGCcellswasmediatedbyinducingcofilin-1mitochondrialtranslocation,down-regulatingBcl-2andup-regulatingBaxexpression.Surprisingly,thelevelofp-AKTproteinwashigherinDDP-resistantGCcellsthanthatoftheDDP-sensitiveGCcells,andtheactivationofAKTcouldattenuateZJW-inducedsensitivitytoDDP.ThesedatarevealedthatZJWcanincreasethechemosensitivityinDDP-resistantprimaryGCcellsbyinducingmitochondrialapoptosisandAKTinactivation.ThecombiningchemotherapywithZJWmaybeaneffectivetherapeuticstrategyforGCchemoresistancepatients.
简介:Theacquisitionofsecondarychromosomalaberrationsinchronicmyeloidleukemia(CML)patientswithPhiladelphiachromosome-positive(Ph+)karyotypesignifiesclonalevolutionassociatedwiththeprogressionofthediseasetoitsacceleratedorblasticphase.Therefore,theseaberrationshaveclinicalandbiologicalsignificance.T(3;12)(q26;p13),whichisarecurrentchromosomalaberrationobservedinmyeloidmalignancies,istypicallyassociatedwithdysplasiaofmegakaryocytes,multilineageinvolvement,shortdurationofanyblasticphase,andextremelypoorprognosis.Wehaveidentifiedarecurrentreciprocaltranslocationbetweenchromosomes3and12withdifferentbreakpointatbands3q21inthemalignantcellsfroma28-year-oldman.ThepatientwasinitiallydiagnosedashavingPh+CMLinthechronicphase.Thet(3;12)(q21;p13)translocationoccurred4yearsafterthepatientwasfirstdiagnosedwithCMLwhileundergoingtyrosinekinaseinhibitortherapy.Weconfirmedthet(3;12)(q21;p13)translocationviafluorescenceinsituhybridizationassaybyusingwhole-chromosomepaintprobesforchromosomes3and12.Ourfindingsdemonstratethat,similartootherrecurrenttranslocationsinvolving3q26suchast(3;3)andt(3;21),thet(3;12)(q21;p13)translocationisimplicatednotonlyinmyelodysplasticsyndromeandacutemyeloidleukemiabutalsointheprogressionofCML.Thesefindingsextendthediseasespectrumofthiscytogeneticaberration.
简介:AbstractBackground:Myocardial infarction occurs due to insufficient (ischemia) blood supply to heart for long time; plasmacytoma variant translocation 1 (PVT1) is a long non-coding RNAs (lncRNAs) involved in the pathogenesis of various diseases, including heart disease; However, few studies have explored its role. The present study evaluated the effects of lncRNA PVT1 on hypoxic rat H9c2 cells.Methods:Hypoxic injury was examined by measuring cell viability and apoptosis by using cell counting kit-8 activity and flow cytometry assays. Gene expressions after hypoxia were estimated by quantitative real time polymerase chain reaction and the signaling pathway were explored by Western blot analysis. RNA immunoprecipitation and luciferase reporter assays were applied to examine the interactions among genes. Data were analyzed using t-test with one-way or two-way analysis of variance.Results:The lncRNA PVT1 is up-regulated in hypoxia-stressed H9c2 cells and knockdown of PVT1 mitigates hypoxia-induced injury in H9c2 cells. PVT1 acts as a sponge for miR-135a-5p and knockdown of PVT1 attenuated the increased hypoxia-induced injury by up-regulating miR-135a-5p. Forkhead box O1 (FOXO1) was identified as a target of miR-135a-5p, and the expression was negatively regulated by miR-135a-5p. The exploration of the underlying mechanism demonstrated that knockdown of FOXO1 reversed PVT1/miR-135a-5p mediated hypoxia-induced injury in H9c2 cells.Conclusions:PVT1 plays a crucial role in hypoxia-injured H9c2 cells through sponging miR-135a-5p and then positively regulating FOXO1.