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简介:Objective:Toassessthesafetyandclinicalantiangiogeniceffectofrecombinantadenovirus-p53(rAd-p53)combinedwithhyperthermiaplusornotplusradiotherapyinadvancedcancer.Methods:ExpressionofVascularepithelialgrowthfactor(VEGF)afterintratumoralinjectionofrAd-p53wasassayedbyimmunohistochemistry(IHC)imaging.Forty-fourpatientswithadvancedcancerwereenrolledintothisclinicalstudy.ThepatientswereintratumorallyinjectedwithrAd-p53(Gendicine)atadoseof1×1012vponceaweek,withatotalof4-54(mean7.7)times.Totalof4-29(mean8.5)timesofhyperthermiawasgiventothepatients.Amongthe44patients,30patientswereconcurrentlyaddedwithradiotherapyofatotaldose30-76Gy/15-38f/3-8w(mean58Gy).Results:BeforeandafterintratumoralinjectionofrAd-p53,theVEGFIHCpositivecellscoreswere2.80and1.50,respectively(P=0.031).ThetreatmentofrAd-p53combinedwithhyperthermiaplusornotplusradiotherapyinadvancedcancerachievedCRrateof13.60%(6/44),andPRrateof29.6%(13/44),andthustheeffectiveratewas43.2%.Inadditionto6patientswithCR,19patients(19/38,50.0%)hadlowdensityarea(LDA)ofmorethan50%areaonCTimagewithintumorindicatingtumortissuenecrosis.Conclusions:OurdataindicatethatrAd-p53inhibitsVEGFexpressionandangiogenesis,andpromotestumornecrosisandshrinkageinducedbyhyperthermiaplusornotplusradiotherapyinadvancedcancer.
简介:microRNA是一种内源性非编码小RNA,通过与靶mRNA的序列互补配对的方式调节靶mRNA的翻译。microRNA多导致靶mRNA翻译受抑,甚至导致靶mRNA降解而失去功能,从而使相应的基因表达受影响。miR-409-3p在胃癌组织中呈低表达,并与胃癌的浸润深度和淋巴结转移成负相关。本篇综述重点阐述其在胃癌的增殖、侵袭、转移的过程中出现的变化和相应发挥的作用,以期为胃癌的诊断及治疗提供新思路。
简介:目的了解P16蛋白在外阴磷癌、外阴非瘤性上皮内病变、外阴上皮内瘤样病变及正常外阴皮肤中的表达,探讨P16与外阴癌变的关系。方法采用免疫组化SP法。结果正常外阴皮肤中P16的阳性率有高于其他三组的倾向,但无明显统计学差异(P>0.05)。外阴鳞癌组与其他三组相比有显著的差异(P<0.01)。而外阴非瘤性上皮内病变与外阴上皮内瘤样病变间比较无明显差异(P>0.05)。Ⅱ期肿瘤P16的阳性表达率明显低于Ⅰ期(P<0.05),中低分化组P16阳性表达率显著高于高分化组(P<0.05),结论P16在外阴磷癌组织中呈低表达;癌前病变和癌前疾病呈较高的表达;在正常组织中高表达。P16表达缺失与外阴癌变有关。
简介:Theexpressionofp53Protein,c-erbB-2oncoprotein,Proliferatingcennuclearantigen(usA)werestudiedbythestreptavidinperotidaseconjugated(S-P)immunohistochemicalmethodandDNAcontentinsituwastested,inordertoexplorethesignificanceofP53,c-erbB-2,PCNAinPrimallUng...
简介:Objective:Polycystickidneydisease(PKD)isthemajorcauseofkidneyfailureandmortalityinhumans.Ithasalwaysbeensuspectedthatthedevelopmentofcystickidneydiseasesharesfeatureswithtumorigenesis,althoughtheevidenceisunclear.Methods:Wecrossedp53mutantmice(p53N236S,p53S)withWernersyndromemiceandanalyzedthepathologicalphenotypes.TheRNA-seq,ssGSEAanalysis,andreal-timePCRwereperformedtodissectthegenesignaturesinvolvedinthedevelopmentofdiseasephenotypes.Results:Wefoundenlargedkidneyswithfluid-filledcystsinoffspringmicewithagenotypeofG3mTerc-/-WRN-/-p53S/S(G3TM).PathologyanalysisconfirmedtheoccurrenceofPKD,anditwashighlycorrelatedwiththeincidenceoftumorigenesis.RNA-seqdatarevealedthegenesignaturesinvolvedinPKDdevelopment,anddemonstratedthatPKDandtumorigenesissharedcommonpathways,includingcomplementpathways,lipidmetabolism,mitochondriaenergyhomeostasisandothers.Interestingly,thisG3TMPKDandtheclassicalPKD1/2deficientPKDsharedcommonpathways,possiblybecausethemutantp53ScouldregulatetheexpressionlevelsofPKD1/2,Pkhd1,andHnf1b.Conclusions:WeestablishedadualmousemodelforPKDandtumorigenesisderivedfromabnormalcellularproliferationandtelomeredysfunction.TheinnovativepointofourstudyistoreportPKDoccurringinconjunctionwithtumorigenesis.ThegenesignaturesrevealedmightshednewlightonthepathogenesisofPKD,andprovidenewmolecularbiomarkersforclinicaldiagnosisandprognosis.
简介:c-ras-P21andGamma-glutamyltransferase(G-GT)activityanditsisoenzymesinratliverextractsweremeasuredafterpartialhepatectomy.TherewereG-GTactivitypeaksat12thand36thhourafteroperation,whilenodistinctisoenzymepatternswerefound.P21proteinexpressionoccurredbetween48and96hoursafterpartialhepatectomy.TheseresultssuggestthatthetemporaryincreaseofG-GTandP21proteinlevelisinvolvedintheprereplica-tivestageofliverregeneration.
简介:目的:构建miR-15a-5p和miR-16-5p的荧光素酶报告载体,利用此载体分析并验证miR-15a-5p和miR-16-5p与CCND1基因3'-UTR区域的确切结合位点,探讨miR-15a-5p和miR-16-5p与CCND1基因的相互作用关系。方法:通过Pubmed和miRBase数据库分别寻找到CCND1基因3'-UTR区域碱基序列和miR-15a-5p、miR-16-5p的碱基序列。找出理论结合位点后,构建荧光素酶报告载体,并用荧光素酶报告基因方法验证miR-15a-5p和miR-16-5p与CCND1基因之间的作用关系。结果:通过基因测序表明,本实验成功构建了CCND1a/Ma和CCND1b/Mb荧光素酶报告基因表达载体。将上述载体应用于荧光素酶报告基因实验,结果发现CCND1b组的荧光素酶表达强度显著降低,差异有统计学意义(P〈0.05)。结论:miR-15a-5p和miR-16-5p与CCND1基因的3'-UTR区域存在结合位点,其具体结合位置在CCND1b区。这在理论上意味着miR-15a-5p和miR-16-5p可以抑制CCND1基因的表达。
简介:目的将在细胞生长,细胞周期和p21wap1/cip1和p27kip1的表情上调查triptolide(TPL)的效果。方法MTT试金被用来在人的多重骨髓瘤RPMI-8226房间在triptolide处理以后决定房间生存能力。房间周期分发上的效果被流动cytometry决定。半量的反向的transcription-PCR被用来检验p21wap1/cip1和p27kip1的mRNA表情。p21wap1/cip1和p27kip1的蛋白质表情被西方的污点决定。改变集中的结果Triptolide以剂量相关、时间相关的时尚导致了房间生存能力抑制并且在RPMI-8226房间引起了G0-G1房间周期前进的阶段拘捕。伴有p21wap1/cip1和p27kip1的表情的起来调整的这些效果。这些结果建议那triptolide的结论经由起来调整的p21wap1/cip1和p27kip1禁止房间增长和房间周期前进,triptolide可以通过这条小径施加它的反癌症活动。
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简介:目的:探讨Dixon手术直肠下端切缘p53基因突变情况及其与肿瘤预后的关系。方法:分析1990年以来Dixon直肠癌根治手术病人后三年以内死亡和生存五年以上两组病的临床情况,采用免疫组化的方法,检测两组不同生存期病人的直肠癌下段切缘p53基因突变率,结果:两病例在肿瘤们于直肠的位置和病理的淋志移率有显著差异,在两组直肠下端病理均未见癌的情况下,三年组p53突变检测分析3/19阳性,而五年组为2/24阳性,无显著性差异。结论:病理检查肿瘤切缘为正常细胞的部位,确实存在分子水平的、肿瘤相关异常基因细胞,表现为散在性点状,巢状分布,这应非一种孤立的、偶然的表现。
简介:目的:为了解P53蛋白异常表达与非小细胞肺癌(NSCLC)预后的关系。方法:采用S-P免疫组织化学法.检测90例手术切除的NSCLC组织石蜡包埋标本。结果:53.3%(48/90)的标本显示P53蛋白向染色阳性.肺鳞癌和腺癌的阴性率分别为64.3%(36/56)和35%(12/34)。统计学分析显示P53蛋白染色结果与病人年龄、性别及肿瘤分期无显著关系,但与肿瘤组织类型显著相关。P53蛋白染色阳性和阴性组病人中位生存月数分别是24个月和55个月。Kaplan-Meir图显示二组病人术后生存概率有明显差异。逐步回归多因素分析显示P53蛋白染色阳性与病人术后生存时间呈显著负相关。结论:P53蛋白异常表达是非小细胞肺癌预后不良的独立判断指标。
简介:DuckhepatitisBvims(DHBV)DNAwasdetectedindifferenttumorousnodulesofduckswithhepaticmulticentriccancerorintrahepaticmetastasisbySouthernblottechnique.Among7duckswithhepatocellularcarcinomaofmultipletumornodules,thehybridizationpatternofIntegratedDHBVDNAIndifferenttumorousnoduleswasidenticalin3casesanddifferentin2cases.OnecaseshowedasimilarhybridizationpatternintwotumorousnodulesandotheronewasnegativetorDHBVDNA.IntegratedDHBVDNAwasalsoidentifiedinametastaticlungcancerofduckswithhepatocellularcarcinoma.Thehybridizationpatternofmetastasisoflungswasasthesomeasthatinprimaryhepatocellularcarcinoma.ThesamediscretehybridizationbandsInthedifferenttumorousnodulesindicatethatthesenodulesmightarisefromonetransformedcell.ThedifferenthybridizationpatternsInvarioustumorousnodulesshowthatthesetumorousnodulesmightarisefromvarioustransformedcells.Theresultssuggestthatthehyb
简介:目的观察晚期肝癌患者动脉灌注人重组腺病毒p53介入治疗前后的生物学改变。方法采用流式细胞术、人体内微核实验检测介入治疗前后患者外周血中突变型p53表达及自发微核形成的改变。结果经p53基因动脉灌注介入治疗后,患者突变型p53平均表达率明显下降,和治疗前相比较(治疗前平均23.74%,治疗后平均11.81%)差异有统计学意义(P〈0.01);介入治疗后患者的平均微核率(MNF)与治疗前的比较(0.144%VS0.205%),差异有统计学意义(P〈0.05)。结论动脉灌注人重组腺病毒p53介入治疗晚期肝癌中的生物学研究对治疗剂量的选择、治疗效果的判断有积极的指导和监测作用。