转化生长因子β1、基质金属蛋白酶2和9在唾液腺腺样囊性癌中的表达

目的 研究人唾液腺腺样囊性癌(SACC)组织中转化生长因子131(TGF-β1)、基质金属蛋白酶2(MMP-2)和MMP-9的表达情况,探讨它们的相关性及与临床病理特征的关系.方法 应用免疫组织化学SP二步法检测27例SACC组织标本(癌组)和15例正常唾液腺组织标本(对照组)中TGF-β1、MMP-2和MMP-9的表达情况.所有数据采用SPSS 17.0统计软件包进行统计学分析.结果 TGF-β1、MMP-2和MMP-9在SACC组中的阳性表达率(分别为77.78%、81.49%和77.78%)均明显高于在正常唾液腺对照组中的阳性表达率(分别为40%、26.67%和26.67%).差异有统计学意义(均为P＜0.01).SACC组织中TGr-β1、MMP-2和MMP-9在Ⅲ～Ⅳ期组的阳性表达率(均为94.44%)明显高于Ⅰ-Ⅱ期组(分别为44.44%、55.56%和44.44%),差异有统计学意义(分别为P＜0.01、P＜0.05和P＜0.01);而三者的表达与患者的性别、年龄、原发肿瘤部位、病理分型以及有无神经侵袭、复发和转移均无相关性(均为P＞0.05);TGF-β1与MMP-2和MMP-9的表达呈正相关(分别为r=0.771、P＜0.001和r=0.805,P＜0.001).结论 TGF-β1、MMP-2和MMP-9的高表达与SACC的临床进展密切相关.TGF-β1可能通过调控MMP-2和MMP-9共同参于SACC的发生、发展、侵袭及转移过程.     

转化生长因子β1、丝裂原活化蛋白激酶在唾液腺腺样囊性癌中的表达及临床意义

目的探讨人唾液腺腺样囊性癌(SACC)中转化生长因子β1(TGF-β1)、丝裂原活化蛋白激酶[MAPK(p-ERK1/2、p-p38及p-JNK1/2)]的表达、相关性及其与临床病理特征的关系。方法应用免疫组织化学SP二步法检测27例SACC组织和15例正常唾液腺组织标本中TGF-β1、MAPK的表达情况。所有数据采用SPSS17.0统计软件包进行统计学分析。结果 SACC中TGF-β1、MAPK的阳性表达率明显高于正常对照唾液腺(分别为P<0.01,P<0.01,P<0.01和P<0.05)。SACC组织中TGF-β1、p-ERK1/2和p-p38在Ⅲ～Ⅳ期组的阳性表达率明显高于Ⅰ～Ⅱ期组(分别为P<0.01,P<0.05和P<0.05),但p-JNK1/2的表达与临床分期无统计学关系(P>0.05),TGF-β1、MAPK的表达与患者的其他临床病理因素均无统计学关系(均为P>0.05);TGF-β1与MAPK的表达显著正相关(分别为r=0.819、P<0.001;r=0.728,P<0.001;r=0.640,P<0.05)。结论 TGF-β1、MAPK的高表达与腺样囊性癌的临床进展密切相关。TGF-β1可能通过激活MAPK信号通路调控腺样囊性癌的发生、发展、侵袭及转移过程。     

唾液腺腺样囊性癌组织中抑癌基因PTEN和蛋白激酶B的表达及其临床意义

目的:探讨唾液腺腺样囊性癌(SACC)组织中抑癌基因PTEN和蛋白激酶B(PKB)的表达及临床意义。方法:采用免疫组织化学方法(SP法)检测63例SACC组织中PTEN和PKB的表达,采用SPSS11.5软件进行χ2检验。结果:在带有癌旁非癌组织的38例中,唾液腺腺样囊性癌组织中PTEN表达阳性21例(55.26%),在癌旁非癌组织中PTEN表达阳性32例(84.21%),两者差异有显著性(P<0.05);唾液腺腺样囊性癌组织中PKB表达阳性31例(81.58%),在癌旁非癌组织中PKB表达阳性20例(52.63%),两者差异有显著性(P<0.01)。在临床诊断有转移的25例和无转移的38例病例中,PTEN表达阳性分别为9例(36%)和26例(68.42%),两者的差异有显著性(P<0.05);PKB表达阳性分别为24例(96%)和27例(71.05%),两者的差异有显著性(P<0.05)。而PTEN和PKB的表达在年龄、性别和病理分型上均无显著性差异。PTEN和PKB的表达呈负相关关系(P<0.01)。结论:SACC组织中PTEN的低表达和PKB的高表达与SACC的发生发展有一定关系,而且对SACC的转移也有一定影响。     

涎腺腺样囊性癌组织中ILK和E-cadherin的表达及意义

目的:探讨整合素连接激酶(integrin-linked kinase,ILK)和上皮型钙黏蛋白(E-cadherin)在涎腺腺样囊性癌(salivary adenoid cystic carcinoma,SACC)组织中的表达及其意义。方法:采用免疫组织化学SP法检测ILK和E-cadherin在SACC及正常涎腺组织中的表达。结果:ILK在SACC中表达,ILK的表达与SACC临床病理分型不相关(P>0.05),与TNM分期有关,在发生神经侵犯及远处转移的病例中,ILK的表达明显增加(P<0.05);与正常涎腺组织相比,E-cadherin在SACC中表达下降,差异有统计学意义(P<0.05),E-cadherin表达与不同组织病理学类型有关,且在实体型、发生神经侵犯及远处转移的病例中,E-cadherin表达下降更明显(P<0.05);ILK与E-cadherin的表达呈负相关(r=-0.768,P<0.001)。结论:SACC组织中ILK表达上调而E-cadherin表达降低,有望成为临床判断涎腺腺样囊性癌恶性程度、评估预后的潜在指标。     

BDNF、TrkB和E-cadherin在唾液腺腺样囊性癌中的表达及意义

目的 研究BDNF、TrkB和E-cadherin在唾液腺腺样囊性癌（salivary adenoid cystic carcinoma,SACC）中的表达及其与临床病理特点的关系。方法：采用免疫组织化学染色检测76例唾液腺腺样囊性癌和20例正常唾液腺组织中BDNF、TrkB和E-cadherin的表达情况,并分析其与临床病理特征之间的关系。采用SPSS17.0软件包对实验结果进行χ²检验、Wilcoxon秩和检验、Spearman相关系数检验。结果：与正常唾液腺组织相比,BDNF、TrkB在SACC组织中呈现高表达,阳性表达率分别为89.5%、92.1%;E-cadherin呈现中低表达,阳性表达率为46.1%。BDNF的表达与肿瘤临床分期、肿瘤转移显著相关（P<0.05）。TrkB的表达与肿瘤临床分期、神经侵袭、肿瘤转移显著相关（P<0.05）。 E-cadherin的表达与肿瘤病理分型、临床分期、神经侵袭、转移呈显著负相关（P<0.05）。在SACC中,BDNF表达与 E-cadherin表达无显著相关性（P>0.05）,而TrkB表达与E-cadherin表达呈显著负相关（P<0.05）。结论：BDNF、TrkB和E-cadherin的表达与SACC的临床病理特征密切相关,检测3者的表达对SACC的诊断和临床病理研究具有重要的参考价值。     

唾液腺腺样囊性癌中自噬相关基因beclin 1的表达

目的:研究自噬相关基因beclin 1在唾液腺腺样囊性癌(salivary adenoid cystic carcinoma,SACC)中的表达,探讨其与SACC的临床病理特征及患者预后的关系。方法:采用免疫组化法检测79例SACC和20例瘤旁腺体中beclin 1的蛋白表达,分析beclin 1表达与SACC临床病理特征之间的关系。采用SPSS16.0软件包对数据进行统计学分析。结果:Beclin 1在SACC肿瘤组织中的表达显著高于瘤旁腺体(P<0.05)。在SACC肿瘤组织中,Beclin 1表达的高低与组织学分级显著相关(P<0.05),在组织学3级中的表达高于1级和2级。结论:Beclin 1的表达与腺样囊性癌临床病理特征密切相关,对腺样囊性癌诊断和预后评估具有重要参考价值。     

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目的探讨肌动蛋白聚合蛋白-1(Fascin-1)在人涎腺腺样囊性癌(SACC)中的表达及临床意义。方法选择2007年11月至2009年12月哈尔滨医科大学附属口腔医院口腔颌面外科手术切除涎腺组织的患者63例,其中SACC患者46例,涎腺正常患者17例。应用免疫组化法检测SACC和正常涎腺组织中Fascin-1的表达水平,比较并分析其与患者其他因素的相关性。结果 Fascin-1在SACC组织中的表达率明显高于正常涎腺组织(P<0.01)。Fascin-1在SACC组织中的表达,与患者的年龄、性别、部位、肿瘤大小和病理类型无关(P>0.05)。临床分期Ⅲ～Ⅳ期的癌组织Fascin-1表达阳性率明显高于Ⅰ～Ⅱ期(P<0.05),有区域淋巴结转移患者Fascin-1表达阳性率明显高于无区域淋巴结转移者(P<0.05)。结论 Fascin-1表达与SACC患者的临床分期和淋巴结转移相关。     

唾液腺腺样囊性癌组织中ERK蛋白的表达及其临床意义

目的探讨唾液腺腺样囊性癌(SACC)组织中有丝分裂活化蛋白激酶(ERK)的表达及临床意义。方法采用免疫组化法(SP法)检测63例SACC组织中ERK的表达,数据采用χ2和t检验进行显著性比较。结果在带有癌旁非癌组织的38个病例中,所有唾液腺腺样囊性癌组织中均有ERK蛋白表达,在癌旁非癌组织中ERK表达阳性31例(52.63%),两者的差异有显著性(P<0.01);在25例有转移病例中ERK表达阳性24例(96%),在38例无转移病例中ERK表达阳性27例(71.05%),两者的差异有显著性(P<0.05);而ERK的表达在年龄、性别和病理分型上均无显著性差异(P>0.05)。结论ERK的高表达可能与唾液腺腺样囊性癌的发生发展密切相关,是患者预后的重要指标之一。     

整合素连接激酶和基质金属蛋白酶-9在涎腺腺样囊性癌中的表达及意义

目的: 探讨整合素连接激酶(ILK)和基质金属蛋白酶-9(MMP-9)在涎腺腺样囊性癌(SACC)中的表达及意义。方法: 选取59例SACC患者和42例非肿瘤患者正常涎腺组织,利用qRT-PCR技术检测ILK和MMP-9在SACC组织中表达。结果: SACC组织中ILK mRNA和MMP-9 mRNA相对表达量均高于对照组,差异均有统计学意义(P<0.05);ILK和MMP-9在SACC组织中表达均与组织类型、淋巴结转移、TNM分期有关(P<0.05),实体型和管状型SACC组织中ILK mRNA和MMP-9 mRNA相对表达量均高于筛状型(P<0.05);Pearson相关分析显示,SACC组织中ILK mRNA相对表达量与MMP-9 mRNA相对表达量呈正相关(r=0.586,P=0.000)。结论: ILK和MMP-9在SACC组织中呈高表达,可能共同协同参与了肿瘤细胞侵袭、转移过程。     

长非编码RNA lncRNA ADAMTS9-AS2促进唾液腺腺样囊性癌侵袭转移的研究

目的检测不同转移能力的唾液腺腺样囊性癌(salivary gland adenoid cystic carcinoma,SACC)细胞中差异表达的长非编码RNA(lncRNA),探讨lncRNA在唾液腺腺样囊性癌侵袭转移中的作用。方法以腺样囊性癌高转移细胞株SACC-LM为实验组,低转移细胞株SACC83为对照组,采用lncRNA芯片初步筛选差异表达的lncRNA,通过qRT-PCR进一步验证差异表达的lncRNA。通过侵袭迁移实验检测转染差异表达的lncRNA siRNAs前后腺样囊性癌细胞株侵袭迁移能力的变化。并对差异表达的lncRNA与SACC患者的临床病理特征和预后进行分析。结果芯片筛选出ADAMTS9-AS2在高转移细胞系(SACC-LM)中高表达,实时定量RT-PCR进一步验证了其在高转移细胞系(SACC-LM)显著上调,通过侵袭迁移实验发现在转染后下调ADAMTS9-AS2的表达水平后侵袭迁移能力明显降低(P<0.001)。临床病理资料分析表明,ADAMTS9-AS2在SACC组织中高度表达。高表达的ADAMTS9-AS2与SACC患者预后不良和肿瘤转移率高有关。结论高表达ADAMTS9-AS2促进SACC细胞迁移和侵袭,ADAMTS9-AS2在SACC组织中上调,并且与高转移率和不良预后相关。     

IGF-1基因转染对骨髓基质细胞分泌IGF-1、ON和Ⅰ型胶原的影响

目的:观察胰岛素样生长因子-1(IGF-1)基因转染的骨髓基质细胞(MSCs)合成IGF-1、骨粘连素(osteone-ctin,ON)和Ⅰ型胶原(Collagen-I)的变化,进一步了解基因转染骨髓基质细胞的生物学特性。方法:将含有IGF-1基因的真核质粒转染入大鼠骨髓基质细胞(MSCs)中,以正常培养的MSCs为对照组,分别于1、3、5、7d对MSCs进行IGF-1、ON和Collagen-I免疫组化观察。通过图像分析检测IGF-1基因转染对MSCs合成IGF-1、ON和Collagen-I的影响。结果:IGF-1基因转染后可促进MSCs合成IGF-1、ON和Collagen-(Ip<0.05),第3d合成IGF-1、ON和Collage-I作用最明显。结论:IGF-1基因转染的MSCs较未转染细胞合成IGF-1、ON和Collagen-I显著增加。     

Hypermethylation of carcinogen metabolism genes,CYP1A1, CYP2A13 and GSTM1 genes in head and neck cancer

Oral Diseases (2010) 16 , 668–673 Objectives: To investigate the role of aberrant hypermethylation of carcinogen metabolism pathway genes, CYP1A1, CYP2A13 and GSTM1 in head and neck cancer independently as well as its relation to tobacco and alcohol consumption and CYP1A1 and CYP2A13 polymorphisms in Indian population. Methods: Seventy‐three histologically confirmed head and neck cancer patients undergoing treatment in Postgraduate Institute of Medical Education and Research, Chandigarh, India were recruited. Non‐cancerous tissues were obtained from 19 trauma subjects undergoing maxillofacial surgery. Methylation‐specific PCR was performed to determine the methylation status of selected genes. Results: The aberrant hypermethylation of CYP1A1, CYP2A13 and GSTM1 genes was found in cancer tissues with frequency of about 39.7%, 27.4%, and 58.1%, respectively, and in normal healthy tissues with a frequency of about 10.5%, 15.8%, and 20.0%, respectively. Hypermethylation of CYP1A1 (P 0.027) and GSTM1 (P 0.010) showed significant association with head and neck cancer. We also observed significant interaction between smoking and methylation status of CYP1A1 (P 0.029) and CYP2A13 (P ‐0.034) in head and neck cancer. No association was observed between methylation status and alcohol consumption, clinical features and genetic polymorphisms of CYP1A1 and CYP2A13. Conclusions: Hypermethylation of carcinogen metabolism pathway genes independently and in interaction with smoking is associated with increased risk of head and neck cancer.     

Smoking and polymorphisms of the interleukin-1 gene cluster (IL-1alpha, IL-1beta, and IL-1RN) in patients with periodontal disease

BACKGROUND: Polymorphisms within the interleukin-1 cluster are known to be associated with adult periodontal disease. However, interactions of genetic with other risk factors, especially smoking, remain questionable. The aim of this cross-sectional study was to evaluate the genetic influence on periodontal variables in relation to environmental factors. METHODS: One-hundred fifty-four (154) Caucasian subjects were clinically and radiographically assessed for their periodontal status, their smoking history recorded, and their allelic pattern of IL-1alpha, IL-1beta, and IL-1RN polymorphisms determined by genotyping. RESULTS: In assessing periodontitis with mean probing depth, mean attachment loss, or mean bone loss, no differences were found in allele frequencies or combined allotypes between subjects with mild or moderate versus those with severe signs of periodontitis. However, the extent of attachment loss defined as percentage of sites >4 mm was significantly associated with the composite genotype of IL-1alpha/1beta in smokers (odds ratio [OR] = 4.00; 95% confidence interval [CI] 1.03 to 16.70; P= 0.02). No differences were found in genotype negative subjects irrespective of their smoking status. They had nearly identical attachment loss as genotype positive non-smokers. Similar non-significant results were found with respect to extent of bone loss. An increased risk of more extended attachment loss was observed also in individuals carrying mutations of the combined genotype IL-1alpha/IL-1RN, again showing enhanced risk only in genotype-positive and smoking subjects. CONCLUSIONS: The results provide evidence that the composite genotypes studied show interaction with smoking, the main exposition-related risk factor of periodontal disease. Non-smoking subjects are not at increased risk, even if they are genotype-positive.     

Periodontal manifestations of the heritable Mac-1, LFA-1, deficiency syndrome. Clinical, histopathologic and molecular characteristics

The clinical, histopathologic and functional consequences of the genetic deficiency of leukocyte Mac-1, LFA-1 and p150,95 were assessed among three affected patients, heterozygotes and unaffected individuals among two generations of a single kindred. Longitudinal assessments of this family afforded the unique opportunity to characterize the natural history of severe periodontal manifestations associated with this disorder. Features uniformly observed among each patient included recurrent, necrotic soft tissue infections, impaired pus formation, delayed wound healing, constant granulocytosis, severe abnormalities of adhesion-dependent granulocyte functions and a profound deficiency (3%-6% of normal) of Mac-1 glycoproteins on granulocyte surfaces. Characteristic features of generalized prepubertal periodontitis including rapidly progressive alveolar bone loss affecting the primary and permanent dentitions (leading to premature tooth loss), recession, clefting and migration in association with intense gingival inflammation were uniformly observed. Biopsies of inflamed periodontal tissues in these individuals demonstrated dense infiltrates of mononuclear leukocytes but a striking absence of extravascular neutrophil granulocytes. Heterozygous family members demonstrated approximately half normal Mac-1 protein expression but no susceptibility to systemic infections and normal, adhesion-dependent leukocyte functions. Prepubescent heterozygotes demonstrated no periodontal manifestations but a 31-year-old heterozygous female exhibited clinical and radiographic features typical of postjuvenile periodontitis. The profound periodontal manifestations recognized in this clinical-pathologic model emphasize the physiologic importance of leukocyte adhesion reactions in defense of the periodontium and further suggest a possible pathologic role for Mac-1 proteins in other forms of early-onset periodontitis.     

Immunohistochemical investigation of lysozyme, lactoferrin, alpha 1-antitrypsin, alpha 1-antichymotrypsin and ferritin in parotid gland tumors

Presence of lysozyme, lactoferrin, alpha 1-antitrypsin, alpha 1-antichymotrypsin and ferritin was examined by the immunoperoxidase method in 15 consecutive parotid gland tumors as well as in normal parotid gland tissue. Lysozyme and lactoferrin were detected in intercalated duct cells of normal tissue and in the epithelial component of pleomorphic adenomas. alpha 1-antitrypsin, alpha 1-antichymotrypsin and ferritin were found in both epithelial and mesenchymal components of pleomorphic adenomas but not in normal parotid tissue. In the epithelial component of adenolymphoma only alpha 1-antichymotrypsin and lactoferrin were observed. The results would support a tentative histogenetic link between the intercalated duct cell and the epithelial component of the pleomorphic adenoma.     

3D打印的数字化病例数据库在口腔颌面外科骨性疾病教学中的应用

目的:探讨基于3D打印技术建立临床病例教学数据库在口腔颌面外科骨性疾病临床教学中的应用价值。方法:选取80例口腔颌面部骨性疾病患者的3D打印模型和临床资料,建立临床病例教学数据库。选择2013级福建医科大学口腔医学专业学生34名,随机分为实验组和对照组,每组17名。对照组采取传统教学模式,实验组结合3D打印模型建立的临床病例教学数据库教学,授课结束后采用同一考核标准(百分制)从理论和技能2个方面对学生进行考核,并用调查问卷评估学习效果。采用SPSS19.0软件包对数据进行独立样本t检验。结果:实验组临床考核成绩为（78.82±3.70）分,对照组为（72.94±3.70）分;实验组调查问卷成绩为（22.88±0.70）分,对照组为（17.29±1.53）分,差异均有统计学意义（P<0.05）。结论:使用3D打印模型建立临床病例教学数据库,可以帮助学生扎实地掌握学习内容,培养临床思维和实践操作能力,激发学生的学习热情和自信,值得推广应用。