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8 个结果
  • 简介:Cisplatindamagescochlearhaircellsandspiralganglionneuronsthroughcelldeathsignalingpathwaysthatarenotfullyunderstood.Weusedfocusedapoptosisgenemicroarraystostudyearlychangesingeneexpres-sionincochlearculturesfromP3neonatalratstreatedwithcisplatin(0.2mM).After12hoursofcisplatintreat-ment,morethan50%ofthe96genesonthearrayshowedasignificantdecreaseinexpression,consistentwithwidespreadcelldeath.However,after3hoursofcisplatintreatment,10genesshowedsignificantincreaseinex-pressionintotalcochleartissue.Inexperimentswithsubsetsofcochleartissues,at3h,cisplatininducedincreasedexpressionof12genesinthecochlearsensoryepithelium(basilarmembrane)and11genesinthespiralganglion(tissueofRosenthal'scanal,containingthespiralganglion).Theseincludedpro-andanti-apoptoticgenesin-volvedinthep53signalingpathway,TNFreceptorfamily,NF-kappaBpathway,deathdomainfamily,deatheffec-tordomainfamily,Bcl-2family,CARDfamily,TRAFfamily,andGTPsignaltransduction.Althoughthechangesingeneexpressionshowedanoverlapbetweenbasilarmembraneandspiralganglion,otherchanges,whichmayreflecttheuniqueresponseofeachtissue,werealsoobserved.Pifithrin-αblockedcisplatin-inducedup-regulationofgenesinthep53signalingpathwaywhenassayedbybothsuperarrayandrealtimePCR.Thedataaddtoourunderstandingoftheinvolvementofp53incisplatin-inducedototoxicityandotoprotection,conferredbythep53inhibitorPifithrin-α.

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  • 简介:NuclearfactorkappaB(NF-κB)isoneofthebest-characterizedtranscriptionfactorsplayingimportantrolesinmanycellularresponsestoalargevarietyofstimuli,includinginflammatorycytokines,phorbolesters,growthfactors,andbacterialandviralproducts.TheaimofthisstudyistodemonstrateNF-κBexpressioninthemousecochleaanditsenhancementinresponsetolipopolysaccharides(LPS)andkanamycin(KA)treatment.MethodsKAtreatmentconsistedofsubcutaneousKAinjectionsat700mg/kgtwiceadaywithaneight-hourintervalbetweenthetwoinjectionsfor3or7days.ForanimalsintheLPStreatmentgroup,asingledoseof0.3mgLPSdissolvedin0.2mlsterilesalinewereinjectedintobothbullaethroughthetympanicmembraneandkepttherefor3hours.Animalsinthecontrolgroupreceivedsubcutaneoussalineinjectionfor7days.Followingimmmunohistochemichalprocessingwithrabbitpolyclonalanti-NF-κBp65antibodies,cryosectionsofthecochleawereexaminedforexpressionofNF-κBp65invariousstructuresinthecochlea.ResultsNF-κBp65expression,identifiedbypresenceofbrownreactionproductscharacteristicofDABimmunohistochemistry,wasvisibleinthespiralligament,spiralprominence,tectorialmembrane(TM),spiralganglionandnervefibers.RelativelyweakNF-κBp65expressionwasalsovisualizedintheorganofCorti.WithintheorganofCorti,theinnerhaircells(IHC),outerhaircells(OHC),innerpillarcells(IP),outerpillarcells(OP),Deiter'scells(DC),andBoettcher'scellsexhibitedstrongerstainingthantheinnersulcuscells,Hensen'scells(HC)andClaudius'cells.NoNF-κBp65expressionwasseeninthenucleusoftheIHCandOHC.NF-κBp65expressionwasincreasedinanimalsexposedtoLPSorKA,demonstratingsignificantdifferencesinthestainingbetweencontrolanimalsandLPS/KA-treatedanimals.NF-κBp65expressionwasnotsignificantlydifferentbetweenLPStreatedandKAtreatedanimalsorbetween3and7daysinKA-treatedanimals.Conclusio

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  • 简介:ObjectiveAlongwithchangesintheecologysystemandundertheinfluenceofvariousenvironmentalfactors,theincidenceoftumorhasbeenincreasingyearafteryear.Thereisatrendincancertherapytomovetocombinedtherapiesinvolvingsurgery,radiationchemotherapyandgenetherapy.Cancergenetherapyinrecentyearshasbroughtnewopportunitiesfortreatmentoftumor.Itsadvantagesincludelowrateoftolerance,insensitivitytocellcycles,highspecificityandcoverageforbothprimaryandmetastatictumors1,2.However,thisisanewfieldofclinicalresearch.RegardingthecorrelationamongtheSTAT3,CyclinD1andP21genesandtumors,researchhasfocusedontheirexpressionandregulation.Thisarticleprovidesasummaryofrelatedresearch.

  • 标签: 细胞周期蛋白D1 肿瘤治疗 STAT3 P21基因 肿瘤基因治疗 环境因素
  • 简介:Background:Currently,thereisasignificantlackofdataconcerninglong-termoutcomesfollowingpaediatriccochlearimplantationintermsofqualityoflife.Thereisaneedforalong-term,prospectivestudyinthisregard.Thisstudyaimsathighlightingthepreliminaryresults,oneyearpostsurgeryofafiveyearprospectivestudy.Methods:TheCochlearTMPaediatricImplantedRecipientObservationalStudy(P-IROS)isaprospective,patientoutcomesregistryforroutinelyimplantedchildren.Thestudycollectsdatausingquestionnairespost-surgeryandatregularintervalsuptofiveyears.Results:AtourCentre,159cochlearimplantsurgeryprocedureswerecarriedoutbetweenJanuary2014andDecember2014.CategoryofAuditoryPerformanceIIscoreincreasedfrom‘0’to‘3’atsixmonthsandto‘5’at12monthsforchildrenaged0—3years,althoughthiswasnotstatisticallysignificant.However,thesametrendwasstatisticallysignificantfortheage3—6yearandage6—10yearbrackets.Thequalityoflifeofthechildimprovedsignificantly.Analysisofcommunicationmoderevealedastatisticallysignificantoverallshifttotheauditory-oralmodefromtotalcommunication.Conclusion:Cochlearimplantationisalife-changingintervention.Theevidenceinsupportofwhatitcanachievesafelyisclear.However,thecostsassociatedwithitraisethequestionifitwillremainaneffectiveoptionforlifeinallchildren.TheCochlearP-IROSisanattempttoanswerthesameoverafiveyearperiod.OurstudyinNewDelhi,sofarconcludesthatcochlearimplantationinapopulationwithlimitedaccesstofundsisveryeffective,oneyearaftersurgery.

  • 标签: 人工耳蜗 新德里 移植 儿科 生活质量 印度
  • 简介:目的研究10号染色体缺失张力蛋白磷酸酶(phosphataseandtensinhomologuedeletedonchromosometen,PTFEN)、磷酸化Akt(P—Akt)及核转录因子-KB(NF—KB)在中耳胆脂瘤上皮中的表达,探讨P13K(phos—phatidylinositol-3-kinase,磷脂酰肌醇-3激酶)-Akt信号通路在中耳胆脂瘤上皮细胞过度增殖机制中的可能作用。方法采用免疫组织化学SP法(辣根酶标记链霉卵白素连接法,streptavidin—peroxidaseconjugatedmethod)检测30例中耳胆脂瘤组织标本与15例正常外耳道皮肤标本中PTEN、P—Akt及NF—KB蛋白的表达。结果PTEN蛋白阳性表达主要定位于上皮细胞核,其在中耳胆脂瘤上皮中阳性表达率为36.7%,明显低于正常外耳道皮肤组的9313%(P〈0.01);P—Akt蛋白阳性表达主要定位于上皮细胞胞质,其在中耳胆脂瘤上皮中阳性表达率为70.0%.明显高于正常外耳道皮肤组的26.7%(P〈0.01);NF—KB蛋白阳性表达定位于上皮细胞核.其在中耳胆脂瘤上皮中阳性表达率为63-3%,明显高于正常外耳道皮肤组的20.0%(P〈0.01)。在30例中耳胆脂瘤上皮组织中,PTEN分别与P—Akt、NF—KB蛋白的表达之间呈显著负相关(P〈0.01),而P—Akt和NF—KB蛋白的表达呈显著正相关(P〈0.01)。结论PTEN、P-Akt和NF—KB在中耳胆脂瘤上皮的异常表达可能在胆脂瘤的发生、发展过程中起重要作用。胆脂瘤上皮中P13K—Akt信号通路的激活可能参与了胆脂瘤上皮细胞过度增殖机制。

  • 标签: 胆脂瘤 中耳 PTEN P-AKT 核转录因子-κB 免疫组织化学