癌前病变口腔上皮中细胞粘附分子CD44v3和CD44v6表达的改变

目的　研究细胞粘附分子CD44v3和CD44v6在口腔癌前病变中的表达特点及其与癌变的关系。方法　用SP免疫组织化学染色法检查 85例正常、单纯及异常增生的口腔上皮和口腔鳞癌中CD44v3和CD44v6的表达。结果　正常及单纯增生口腔上皮细胞膜有CD44v3和v6的强表达 ,上皮染成网状。上皮轻度异常增生变化不明显。随上皮异常增生程度加重 ,上皮深层细胞出现CD44v3和v6低表达 ,染色变浅或无染色 ,12例重度异常增生者均出现低表达。同一标本中既有上皮单纯增生又有上皮中、重度异常增生的 9例中 ,8例有CD44v3和v6的低表达。鳞状细胞癌的浸润缘有上述低表达 ,部分转移灶较原发灶染色浅。结论　上皮中、重度异常增生时 ,CD44v3和v6表达下降。这种低表达可能与异常增生时细胞粘附力下降及癌变时发生基底膜浸润有关。     

Smad4、Smad7和Caveolin-1在Wistar大鼠口腔黏膜癌变中的表达和意义

目的:研究母亲DPP同源物4 (mothers against decapentaplegic homolog 4,Smad4)、母亲DPP同源物7(mothers against decapentaplegic homolog 7,Smad7)和小窝蛋白1 (Caveolin-1)在Wistar大鼠口腔黏膜癌变过程中的表达,了解TGF-β/Smad信号传导通路和小窝蛋白Caveolin-1在口腔癌前病变中的作用.方法:采用郑州大学口腔医学院存档的Wistar大鼠口腔腭部黏膜癌变标本,包括正常黏膜5例,单纯增生黏膜10例,轻度异常增生黏膜6例,中度异常增生黏膜7例,重度异常增生黏膜13例,口腔癌变组织28例.应用免疫组织化学SP法检测Smad4、Smad7和Caveolin-1蛋白的表达,采用SPSS 15.0软件包对数据进行统计学分析.结果:Smad4蛋白在正常和单纯增生黏膜、上皮异常增生黏膜和口腔癌黏膜中表达依次降低,3组间差异显著(P＜0.05);Smad7和Caveolin-1蛋白在正常和单纯增生黏膜、上皮异常增生黏膜和口腔癌黏膜中表达均依次升高,3组间差异显著(P＜0.05).经Spearman相关分析,Smad4与Smad7蛋白表达呈负相关,Smad4与Caveolin-1蛋白表达呈负相关,Smad7与Caveolin-1蛋白表达呈正相关(P＜0.05).结论:Smad4、Smad7和Caveolin-1蛋白在口腔黏膜癌变过程中可能存在协同作用.     

口腔癌及癌前病变中PTEN与CXCR4的蛋白表达及相关性研究

目的通过检测抑癌基因PTEN与趋化因子CXCR4在口腔癌及癌前病变中的蛋白表达情况,并分析其相关性。方法收集口腔癌及癌前病变标本共111例,其中正常口腔黏膜15例、单纯上皮增生22例、上皮异常增生16例、口腔鳞癌58例,应用免疫组化SP法检测这些标本中PTEN与CXCR4蛋白表达水平,并对结果进行统计学分析。结果 PTEN在口腔鳞癌中阴性和弱阳性表达占74%(43/58),显著低于正常黏膜、单纯上皮增生、上皮异常增生组(P<0.05);CXCR4在单纯增生、异常增生和口腔鳞癌中阳性或强阳性表达分别占40.91%、43.75%和66.13%,显著高于正常组的表达(P<0.05)。经直线相关分析和Spearman等级相关分析,PTEN与CXCR4之间存在负相关关系(r=-1.000,P<0.001)。结论口腔鳞癌的发生和发展过程中PTEN和CXCR4均起着一定的作用;口腔癌中PTEN与CXCR4的蛋白表达存在负相关的关系。     

整联蛋白连接激酶在口腔白斑及早期浸润癌中的表达

目的 研究整联蛋白连接激酶(integrin-linked kinase,ILK)在口腔自斑及早期浸润癌中的表达特点及演变规律,以期为口腔癌前病变的诊断、治疗及口腔癌的预防提供依据.方法 联合应用免疫组织化学及过碘酸希夫反应(periodic acid Schiff reaction,PAS)方法研究ILK在19例正常口腔黏膜(正常黏膜组)、43例白斑伴上皮单纯增生(单纯增生组)、84例白斑伴上皮异常增生[异常增生组,包括轻、中度异常增生44例(轻中度异常增生组),重度异常增生和原位癌40例(重度异常增牛组)]及54例早期浸润癌(浸润癌组)中的表达情况及分布规律.结果 ILK在正常口腔黏膜中呈阴性表达,在其他3组中的阳性表达率可高达90%(163/181),并且ILK在间质的表达随病变程度的加重而增加(χ2=41.585,P<0.001).白斑从单纯增生至癌变,ILK的表达呈现从上皮浅层向基底层下移的趋势,基底细胞由阴性转为阳性着色,并且伴随从胞质向胞膜的分布改变.重度异常增生组基底层和间质表达之间差异有统计学意义(P=0.029).ILK在早期浸润癌的癌巢表达较癌旁上皮浅,间质阳性的病例[76%(41/54)]较重度异常增生[45%(18/40)]增多.结论 ILK在口腔白斑的癌变中可能起莺要作用,确切机制需进一步研究.     

口腔黏膜癌变过程中Slit蛋白的表达及其与血管生成的关系

目的:研究Slit蛋白在口腔黏膜癌变过程中的表达及其与肿瘤血管形成的关系。方法:采用免疫组织化学Envision法检测40例人口腔鳞状细胞癌、18例上皮单纯增生、20例上皮异常增生、20例原位癌及19例正常口腔黏膜标本Slit、VEGF的表达和MVD。结果:口腔鳞癌组中有34例Slit表达阳性,与正常黏膜组及癌前病变组相比有显著性差异(P<0.01),而19例正常口腔黏膜仅有1例表达为弱阳性,与原位癌组及上皮异常增生组之间有显著性差异(P<0.01,P<0.05)。VEGF的表达趋势与Slit蛋白一致,Slit蛋白和VEGF表达均与MVD呈显著正相关(P<0.01)结论:口腔鳞癌癌变过程中Slit蛋白阳性表达与其恶性程度呈正相关,Slit在口腔鳞癌中有促血管形成的作用,并可能对口腔鳞癌的发展过程起重要作用。     

CD147和Ki-67在口腔黏膜白斑和鳞癌组织中的表达及意义

目的：观察CD147和ki-67在口腔正常黏膜、白斑和鳞癌组织中表达的变化,阐明CD147在口腔癌发病机制中的作用。方法：采用免疫组织化学法检测10例正常口腔黏膜、20例白斑伴上皮异常增生上皮和40例鳞癌组织中CD147及Ki-67的表达变化。结果：CD147在正常黏膜阴性表达,白斑和鳞癌组上皮均显著表达CD147;正常组Ki-67表达主要位于上皮棘层,鳞癌组织中Ki-67阳性细胞分布广泛,有大部分侵入固有层中。结论：口腔黏膜发生癌前病变时,即出现CD147表达阳性,随着Ki-67阳性细胞数的增多,癌变细胞增殖不断加强,两者共同作用促进鳞癌的发展。     

Prx1 overexpression in human oral leukoplakia

目的 检测抗氧化蛋白Prx1和DNA氧化损伤标记物8-OHdG在口腔黏膜白斑中的表达,探讨Prx1在口腔黏膜白斑中的作用.方法 选择40例口腔黏膜白斑,包括单纯增生10例,白斑伴上皮轻度异常增生15例,白斑伴上皮中度异常增生15例,正常口腔黏膜10例.采用免疫组织化学染色方法,分别检测Prx1、8-OHdG在黏膜中的表达.结果 口腔黏膜白斑伴上皮中度异常增生组Prx1和8-OHdG染色的MOD值均高于正常组、白斑单纯增生组、白斑伴上皮轻度异常增生组,且差异有统计学意义(P<0.01).结论 Prx1与口腔黏膜白斑的发病有关,口腔黏膜白斑的发生可能与氧化损伤有关.     

骨桥蛋白及其受体CD44v6在口腔鳞状细胞癌中的定量表达及意义

目的探讨骨桥蛋白（OPN）及其受体CD44v6在口腔鳞状细胞癌（OSCC）中的蛋白定量表达、临床意义及二者之间的关系。方法应用EnVisionTM法检测正常口腔黏膜（n=12）和OSCC患者（n=59）肿瘤组织中OPN和CD44v6的表达,结合图像分析系统进行定量分析,统计不同临床、病理指标下OSCC肿瘤组织中OPN的表达情况以及两种蛋白表达的相互关系。结果OPN在OSCC肿瘤组织中的表达显著高于正常口腔黏膜（P<0.05）。OPN的表达与OSCC不同临床分期、颈淋巴结转移有相关性,在OSCC高分化和中低分化者间差异无统计学意义。CD44v6在OSCC与正常口腔黏膜中差异无统计学意义,且其表达与临床病理指标关系不密切。在OSCC中,OPN与CD44v6表达无显著相关性。结论OPN在OSCC存在过度表达,其表达水平与肿瘤临床分期以及有无淋巴结转移存在一定的相关性,CD44v6与肿瘤临床病理特征无关,而且与OPN表达无相关性。     

p16,p53,Ki67在口腔癌前病变表达及4年临床随访

目的 :研究 p16,p5 3 ,Ki-67蛋白表达与口腔癌前病变的关系。 方法 :采用免疫组织化学LsAB法对43例上皮异常增生 ( 2 0例轻度上皮异常增生 ,2 3例重度上皮异常增生 )和 2 0例正常口腔黏膜 p16,P5 3和Ki -67蛋白的表达进行研究 ,并对上皮异常增生患者实际癌变率做了 4年追踪。结果 :正常黏膜组 ,p5 3不表达 ,Ki -67少量表达 ,p16的阳性表达为 10 0 %。轻度上皮异常增生 ,p5 3 ,Ki-67少数表达 ,p16表达率为 86.96%。重度上皮异常增生 ,p5 3和Ki-67过度表达 ,p16表达明显下降 ,与正常黏膜 ,轻度上皮异常增生相比差异显著 (P <0 .0 5 )。p5 3和Ki-67蛋白过度表达而 p16呈低表达与实际口腔癌前病变癌变率有一定相关性。 结论 :口腔黏膜癌变是一个由量变到质变的过程 ,它们的调控基因 p16,p5 3 ,Ki -6发生了显著的变化 ,可能起着重要的调控作用。     

口腔黏膜良性淋巴组织增生病的免疫组化研究

目的　研究口腔黏膜良性淋巴组织增生病与口腔癌的细胞增殖能力、血管密度和细胞凋亡的变化。方法　采用免疫组化SP法检测 15例黏膜良性淋巴组织增生病、9例黏膜良性淋巴组织增生病伴上皮异常增生、15例口腔癌及 10例正常黏膜组织中Ki 6 7的表达、细胞凋亡及微血管密度。结果　口腔黏膜良性淋巴组织增生病伴异常增生及鳞状细胞癌中Ki 6 7的表达明显高于不伴异常增生的口腔黏膜良性淋巴组织增生病及正常黏膜 (P <0 0 5 ) ,在所有的口腔黏膜良性淋巴组织增生病及鳞状细胞癌中微血管密度均明显高于正常组 (P <0 0 5 )。口腔黏膜良性淋巴组织增生病中细胞凋亡明显高于正常黏膜及口腔癌 (P <0 0 5 )。结论　在伴有上皮异常增生的口腔黏膜良性淋巴组织增生病中Ki 6 7表达及微血管密度均介于正常组织和口腔癌之间 ,凋亡细胞数也明显多于正常组织。研究结果提示 :口腔黏膜良性淋巴组织增生病是一种具有癌变潜能的疾患     

Expression of CD14, CD16 and CD45RA on monocytes from periodontitis patients

BACKGROUND AND OBJECTIVE: Peripheral blood monocytes are a heterogeneous population, with phenotypes that change on activation or differentiation. Most of the monocytes express lipopolysaccharide (LPS) receptor, CD14 intensely, and do not express Fc gamma receptor III, CD16 (CD14++CD16- monocytes). But monocytes expressing CD16 with reduced CD14 (CD14+CD16+ monocytes) increase in inflammatory diseases as well as sepsis and bacteremia in hemodialysis patients. CD45RA is expressed on activated monocytes, and is regarded as an activation marker of peripheral blood monocytes. The purpose of this study was to determine the phenotypic and functional alteration of monocytes in periodontitis patients. METHODS: Peripheral blood was collected from 33 aggressive periodontitis patients (22 females, 11 males), 55 chronic periodontitis patients (35 females, 20 males) and 30 healthy subjects (16 females, 14 males), and the expression of CD14, CD16 and CD45RA on monocytes was determined using flow cytometry. The production of interleukin-6 (IL-6) by CD16+ and CD16- monocytes stimulated with LPS from Escherichia coli and Actinobacillus actinomycetemcomitans was also examined using flow cytometry. RESULTS: The percentage of CD14+CD16+ monocytes was significantly increased in chronic periodontitis patients. Percentage of monocytes expressing CD45RA was significantly increased in aggressive periodontitis patients compared to healthy subjects. CD16+ and CD16- monocytes produced IL-6 in response to LPS from E. coli and A. actinomycetemcomitans, and the percentage of IL-6 producing cells was higher in CD16+ monocytes than CD16- monocytes, suggesting that CD14+CD16+ monocytes represent a hyper-reactive phenotype. CONCLUSIONS: The present study demonstrated that CD14+CD16+ monocytes and CD45RA+ monocytes were increased in chronic and aggressive periodontitis, respectively. These findings suggest that alteration of monocytes in periodontitis patients could be evaluated by monitoring the surface expression of CD14, CD16 and CD45RA on monocytes.     

炎症组织中CD40/CD40L与白细胞介素-8和单核细胞趋化蛋白-1的相关性

CD40/CD40L相互作用可促进多种细胞前炎症细胞因子和趋化因子的产生,如白细胞介素(IL)-8和单核细胞趋化蛋白(MCP)-1,而IL-8和MCP-1可趋化炎症细胞向炎症部位聚集,从而调节炎症的发生和发展.下面就CD40/CD40L与IL-8和MCP-1在炎症组织中的相关性以及CD40/CD40L诱导IL-8和MCP-1的调节因素等作一.     

CD44在口腔鳞癌中的表达

目的初步探讨CD44分子在口腔鳞癌中的表达情况。方法以免疫组织化学方法对22例口腔不同部位的鳞癌及其周边扩大切除的组织进行了观察研究,并和癌组织的病理分级进行对比分析。结果 CD44表达在正常口腔粘膜表皮的基底细胞和部分棘层细胞的细胞膜上,同时在淋巴细胞上强表达。在鳞癌上皮组织中CD44的表达模式发生紊乱,表达水平与细胞分化程度有关,病理分化度较差的癌组织中CD44的表达逐渐减弱。结论 CD44可以作为评价口腔鳞癌恶性度的一个指标。     

CD44v3及CD44v6在舌鳞癌组织中的表达及意义

目的探讨CD44v3及CD44v6在舌鳞癌组织中的表达及其与临床病理因素的关系。方法免疫组织化学方法检测中山大学附属第二医院口腔颌面头颈外科1996年1月至2006年12月单纯接受手术治疗的71例舌鳞癌石蜡标本中CD44v3及CD44v6的表达．用SPSS13．0统计软件分析CD44v3及CD44v6的表达与舌鳞癌患者的年龄、性别、临床分期、肿瘤分化程度、淋巴结转移等临床病理因素的关系。结果（1）舌鳞癌组织中CD44v3及CD44v6阳性百分数均高于癌旁组织中CD44v3及CD44v6阳性百分数（P〈0．001）。（2）舌鳞癌组织中CD44v3及CD44v6阳性百分数有统计学相关（Speamlan相关系数为0．494．P〈0．001）。（3）淋巴结转移与无淋巴结转移组间舌鳞癌CD44v3及CD44v6阳性强度差异均有统计学意义（P值分别为0．023及0．019）。结论舌鳞癌CD44v3及CD44v6表达与淋巴结转移有关。检测它们有助于判断患者的预后。     

复发性阿弗它溃疡患者外周血中CD4+/CD45RA+细胞亚群的表达及意义

目的探索复发性阿弗它溃疡(recurrent aphthous ulcer,RAU)患者T淋巴细胞亚群CD4+/CD45RA+细胞的数量变化.方法应用流式细胞术检测RAU患者及正常对照人群CD4+/CD45RA+亚群细胞的数量.结果 RAU患者的CD4+/CD45RA+细胞数约占CD4+细胞总数的14.24%,正常对照约占总数的21.56%,两者有显著性差异(P＜0.01).结论 RAU患者外周血T淋巴细胞亚群中CD4+/CD45RA+细胞量减少,提示CD4+/CD45RA+细胞可能与RAU的发病有关.     

CD44与CD33在77例口腔黏膜良性淋巴组织增生病中的表达及临床意义

目的：探讨CD44与CD33在口腔黏膜良性淋巴组织增生病（benign lymphoadenosis of oral mucosa,BLOM）中的表达及临床意义。方法：选择2017年1月—2020年3月青岛市中医医院病理科77例BLOM蜡块作为实验组，另取同时间段63例正常口腔黏膜组织蜡块作为对照组。采用免疫组织化学法检测2组CD44、CD33阳性表达情况，采用Spearman分析BLOM患者病变组织中CD33与CD44阳性表达的相关性。收集患者一般资料，分析BLOM患者病变组织中CD33、CD44表达与临床病理特征的关系。采用SPSS 21.0软件包对数据进行统计学分析。结果：对照组、实验组CD33阳性表达率分别为95.24%、63.64%，差异有统计学意义（P<0.05）;CD44阳性表达率分别为93.65%、67.53%，差异有统计学意义（P<0.05）。Spearman分析结果显示，BLOM患者病变组织中CD33与CD44阳性表达呈正相关（r=0.834,P=0.002）;CD33、CD44表达与临床分型、炎症程度、有无淋巴滤泡、淋巴细胞浸润有关（P<0.05...     

CD29 expression on CD4+ gingival lymphocytes supports migration of activated memory T lymphocytes to diseased periodontal tissue

The cell surface phenotypes of CD4⁺ cells extracted from inflammatory periodontal disease tissues were analyzed using two- and three-color immunofluorescence and flow cytometry. Cells extracted from both adult periodontal and localized juvenile periodontitis lesions showed a depressed CD4/CD8 ratio (1.0±0.1 adult periodontitis and 1.1 ±0.1 localized juvenile periodontitis) compared with cells recovered from normal/marginal gingivitis tissue (1.8 ±0.2) or with normal peripheral blood cells (2.1 ±0.1) or periodontal disease blood cells (2.1±0.1 and 1.7±0.1 for adult periodontitis and juvenile periodontitis, respectively). The monoclonal antibodies anti-2H4 and anti-4B4 were used to identify the CD45RA and CD29 antigens respectively on CD4⁺ T cells from the periodontal disease lesions. In peripheral blood, CD29⁺ cells accounted for 66–77% of the CD4⁺ population, and CD45RA⁺ cells accounted for 22–27% of the CD4⁺ subset. No differences in expression were found between peripheral blood lymphocytes from normal subjects and from periodontal disease patients. Two-color analyses of lymphocytes from periodontal diseased tissues showed that 87–89% of the CD4⁺ population were CD29⁺ and that 70–79% of the CD4⁺ cells were CD45RA⁺. Normal tissues contained significantly fewer CD4⁺CD29⁺ cells (56±4%) and CD4⁺CD45RA⁺ cells (40±4%) on average, and few, if any double-labelled cells could be accounted for. These data implied that a significant percentage of the CD4⁺ cells from the diseased tissues were both CD29⁺ and CD45RA⁺ and that these populations are found in quite different proportions in diseased periodontal tissue than in peripheral blood or nondiseased tissue. In further analyses using three-color cytometry the mean percentage of CD4⁺CD29⁺CD45RA⁺ lymphocytes extracted from periodontal disease lesions was 43±9% of the CD4⁺ population. These results suggest that CD4⁺ T lymphocytes in periodontal disease not only demonstrate varying levels of maturity but also that the accumulation of CD4⁺ T cells within the periodontal tissues maybe a result of increased adhesion and transendothelial migration.     

Cell surface markers CD44 and CD166 localized specific populations of salivary acinar cells

Oral Diseases (2012) 18 , 162–168 Objective: Experimental approaches tested to date for functional restoration of salivary glands (SGs) are tissue engineering, gene transfer, and cell therapy. To further develop these therapies, identifying specific cell surface markers for the isolation of salivary acinar cells is needed. To test a panel of cell surface markers [used in the isolation of mesenchymal stem cells, (MSCs)] for the localization of salivary acinar cells. Materials: Human submandibular and parotid glands were immunostained with a panel of MSC markers and co‐localized with salivary acinar cell differentiation markers [α‐amylase, Na‐K‐2Cl cotransporter‐1, aquaporin‐5 (AQP5)]. Additional cell markers were also used, such as α‐smooth muscle actin (to identify myoepithelial cells), cytokeratin‐5 (basal ductal cells), and c‐Kit (progenitor cells). Results: CD44 identified serous acini, while CD166 identified mucous acini. Cytokeratin‐5 identified basal duct cells and 50% of myoepithelial cells. None of the remaining cell surface markers (Stro‐1, CD90, CD106, CD105, CD146, CD19, CD45, and c‐Kit) were expressed in any human salivary cell. Conclusions: CD44 and CD166 localized human salivary serous and mucous acinar cells, respectively. These two cell surface markers will be useful in the isolation of specific populations of salivary acinar cells.     

Expression of MHC Class II, CD70, CD80, CD86 and pro-inflammatory cytokines is differentially regulated in oral epithelial cells following bacterial challenge

Oral epithelium may play a regulatory role in local immune responses when interacting with bacteria. The present study was undertaken to investigate the effects of selected bacterial pathogens found in periodontal and endodontic infections on oral epithelial cells. Expression of cell surface molecules (major histocompatibility complex (MHC) Class II, CD54, CD70, CD80 and CD86) and secretion of inflammatory cytokines (interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha) in response to selected bacterial challenge were examined on an immortalized oral epithelial cell line, HOK-18A and a skin epithelial cell line, HaCaT. Actinomyces viscosus, Actinomyces israelii, Fusobacterium nucleatum lipopolysaccharide (LPS) or primary human periradicular exudate from a granuloma were co-cultured with epithelial cells for 4 or 24 h. Subsequently, cell surface expression of MHC Class II, CD54, CD70, CD80 and CD86, along with pro-inflammatory cytokine levels were determined using flow cytometry, ELISA and RT-PCR. Results indicated that the selected oral bacteria have greater effects on oral versus skin epithelial cells. F. nucleatum increased MHC Class II and CD54 (ICAM-1) cell surface expression on HOK-18A and HaCaT cells. A. israelii also had enhancing effects on the expression of CD54 and MHC Class II. A. israelii and LPS induced a 2.8-fold (P < 0.001) and 4.4-fold (P < 0.005) TNF-alpha secretion, respectively, while F. nucleatum and LPS induced a 10-fold (P < 0.0004) and 6-fold (P < 0.01) IL-1beta secretion, respectively by HOK-18A. Interestingly, CD70, CD80, and CD86 were generally decreased upon bacteria and LPS challenge on HOK-18A. The effects of increased MHC Class II and decreased CD70 were also evident with challenge of human periradicular exudate on HOK-18A. The implications of the study are unique in that oral epithelial cells may play both activating and inhibitory roles in the host immune response towards infection by oral bacteria. We introduce a concept of 'dormancy' where the differential expression of key cell surface antigens on oral epithelial cells may keep the recruited immune effector cells in a state of unresponsiveness, thus contributing to the long term quiescent period observed in many periodontal and endodontic lesions.