细胞外基质金属蛋白酶诱导因子与恶性肿瘤

细胞外基质金属蛋白酶诱导因子广泛地存在于人体各种肿瘤组织中诱导基质金属蛋白酶的产生,从而促进肿瘤的侵袭并在恶性肿瘤的生长、浸润、转移和诱导肿瘤组织的恶性潜能等方面起重要作用.下面就细胞外基质金属蛋白酶诱导因子的作用机制、调节以及与口腔颌面部肿瘤的关系作一.     

细胞外基质金属蛋白酶诱导因子与牙周炎的关系

细胞外基质金属蛋白酶诱导因子广泛地存在于人类各种肿瘤细胞和一些正常细胞中，能刺激基质金属蛋白酶的合成，促进细胞外基质的降解，在恶性肿瘤的浸润和转移、风湿性关节炎、心血管疾病、糖尿病和牙周炎的发生和发展中起着重要的作用。本文将就细胞外基质金属蛋白酶诱导因子及其与牙周炎关系的最新研究进展作一综述。     

细胞外基质金属蛋白酶诱导因子与牙周炎的关系

细胞外基质金属蛋白酶诱导因子广泛地存在于人类各种肿瘤细胞和一些正常细胞中,能刺激基质金属蛋白酶的合成,促进细胞外基质的降解,在恶性肿瘤的浸润和转移、风湿性关节炎、心血管疾病、糖尿病和牙周炎的发生和发展中起着重要的作用。本文将就细胞外基质金属蛋白酶诱导因子及其与牙周炎关系的最新研究进展作一综述。     

血清亲环素A浓度在环孢素诱导牙龈增生中的临床意义

目的:探讨环孢素诱导的牙龈增生(CIGO)与血清亲环素A(CyPA)之间的关系。方法 :本研究以73例用环孢素A(CsA)为主要免疫抑制剂抗排异患者为研究对象,经牙龈增生指数(GOI)评价后将患者分为牙龈增生组(GO+)和无牙龈增生组(GO-)。比较两组患者各临床相关因素之间的差异,重点观察血清CyPA浓度与CIGO发生及严重程度的关系。应用SPSS 17.0软件包进行统计检验,P<0.05表示差异有统计学意义。结果:与正常成人相比,肾移植术后服用CsA的患者,血清CyPA浓度显著降低(P=0.003)。其中,GO+组[(0.30±0.16)ng/mL]明显低于GO-组[(0.44±0.34)ng/Ml](P=0.036),且与牙龈增生的严重程度呈负相关(r=-0.233,P=0.047),但与CsA服药剂量和血清浓度无关(r=0.001,P=0.999;r=0.006,P=0.963)。结论:血清CyPA与CIGO发生密切相关,血清CsA/CyPA比值有望作为CIGO发生风险因素,帮助临床预判牙龈增生的发生。     

细胞外基质金属蛋白酶诱导因子表达与唾液腺肿瘤侵袭性的关系

目的:检测唾液腺肿瘤组织中细胞外基质金属蛋白酶诱导因子(EMMPRIN)的表达和定位,探讨其与唾液腺肿瘤侵袭性生物学行为的关系。方法:采用免疫组织化学方法,检测9例唾液腺正常组织、28例多形性腺瘤(PA)、25例黏液表皮样癌(MC)、33例腺样囊性癌(ACC)中EMMPRIN的表达和定位。采用SPSS10.0软件包进行多个样本率间的χ2检验或确切概率分析。结果:EMMPRIN在正常唾液腺组织、多形性腺瘤、黏液表皮样癌、腺样囊性癌的表达阳性率分别为11.11%、53.71%、84.00%和90.91%(P<0.05)。在正常唾液腺组织的表达主要见于导管上皮细胞的细胞膜;EMMPRIN蛋白在多形性腺瘤、黏液表皮样癌、腺样囊性癌的表达见于肿瘤细胞的胞膜或胞质。腺样囊性癌嗜神经现象组中,EMMPRIN表达的阳性率高于无嗜神经现象组,但差异无统计学意义。结论:EMMPRIN的表达与唾液腺肿瘤侵袭性生物学行为密切相关。     

舌鳞癌组织细胞外基质金属蛋白酶诱导因子的表达及其与预后的关系

目的：研究舌鳞癌组织中细胞外基质金属蛋白酶诱导因子（EMMPRIN）的表达及其与舌癌患者临床病理特征和生存期之间的相关性。方法：应用SP免疫组织化学法,检测68例舌鳞癌组织及相应的癌旁组织中EMMPRIN的表达情况,并对68例舌鳞癌患者进行随访观察。应用非参数秩和检验检测两个独立样本的EMMPRIN的表达差异,应用SPSS 13.0软件包进行生存分析;应用Cox比例风险模型分析预后。结果：EMMPRIN在舌鳞癌组织中的表达阳性率高于相应的癌旁组织（P〈0.05）。舌鳞癌组织中EMMPRIN的表达与肿瘤大小和临床分期密切相关,与性别、年龄、淋巴结转移和肿瘤病理分化程度不相关。Cox比例风险模型多因素预后分析显示,EMMPRIN表达是影响舌鳞癌患者预后的独立因素。结论：EMMPRIN可以作为舌鳞癌预后判断的参考指标,并有望成为口腔癌生物治疗的潜在靶点。     

RORγT在人根尖肉芽肿和根尖囊肿中的表达及意义

目的:通过免疫组织化学方法对Th17细胞的特异性标记维A酸相关孤核受体γT(RORγT)进行检测,以阐明Th17细胞在人慢性根尖周病损中的表达及意义。方法:收集安徽医科大学口腔医学院口腔颌面外科经根尖手术切除的根尖囊肿18例,根尖肉芽肿22例作为实验组。收集埋伏阻生智牙拔除时需凿骨患者的健康牙槽骨5例作为正常对照组。对样本中RORγT蛋白表达水平进行免疫组织化学检测,同时检测白细胞介素(interleukin,IL) 17的蛋白表达水平。根据病变类型 (根尖肉芽肿、根尖囊肿、正常对照组) 和炎症浸润程度(轻度、中度、重度、正常对照组),分析RORγT和IL-17的蛋白表达水平。采用SPSS 17.0软件包对数据进行统计学分析。结果:RORγT表达于所有根尖周炎病损组织中,并显著高于正常对照组 (P<0.05),正常对照组中未检测到RORγT的表达;RORγT在轻度、中度和重度炎症细胞浸润中的表达水平均显著高于正常对照组 (P<0.05);RORγT和IL-17的蛋白表达水平在根尖肉芽肿(r=0.935,P<0.05)和根尖囊肿(r=0.803,P<0.05)中呈正相关。结论:RORγT在根尖肉芽肿和根尖囊肿中的表达量显著高于正常对照组,表明Th17细胞可能存在于根尖周病变中。     

基质金属蛋白酶与根尖周病

基质金属蛋白酶（matrix metalloproteinases,MMPs）属于锌依赖性蛋白水解酶的一种,是由多种蛋白酶组成的多功能内肽酶,主要降解细胞外基质（extracellularmatrix,ECM）。在正常稳定状态组织中MMP表达量极少,而在炎性细胞因子、激素、生长因子刺激下和细胞转化过程其表达上升。病理上根尖周病通常分为根尖周炎和根尖囊肿,根尖周炎多是由根管内微生物感染引起的局部炎症性疾病,常累及邻近牙槽骨和根尖部的牙骨质,使其吸收破坏。     

基质金属蛋白酶-8和基质金属蛋白酶-13在人根尖周病组织肥大细胞上的表达

目的:观察基质金属蛋白酶-8(matrixmetalloproteinase-8,MMP-8)和基质金属蛋白酶-13(matrixmetalloproteinase-13,MMP-13)在人慢性根尖周炎组织肥大细胞(mastcells,MCs)上的表达情况,探讨肥大细胞在根尖周病发病机制中的作用。方法:将90例样本分为3组:1)根尖肉芽肿组30例;2)根尖囊肿组30例;3)正常牙周膜组30例。组织标本置于10%中性福尔马林固定液中浸泡48h以上,制作连续组织切片。HE染色,光学显微镜下观察各组的组织学变化;免疫荧光双染色(doubleimmunofluorescence,DIF),荧光显微镜下观察MMP-8和MMP-13在根尖周组织MCs上表达的情况。结果:与正常对照组相比,两组慢性根尖周炎组织中MMP-8和MMP-13双阳性MCs数目均显著增多(P<0.01);根尖囊肿组与根尖肉芽肿组MMP-8和MMP-13双阳性MCs密度无显著性差异。结论:慢性根尖周炎病变组织中MCs数目明显增多,同时MMP-8和MMP-13双阳性MCs密度显著增高,提示MMP-8和MMP-13阳性MCs可能在慢性根尖周炎的致病机制中发挥作用。     

Comparative Expression of CD34, Intercellular Adhesion Molecule-1, and Podoplanin and the Presence of Mast Cells in Periapical Granulomas,Cysts, and Residual Cysts

Introduction

The aim of the present study was to compare the immunoexpression of CD34, intercellular adhesion molecule-1 (ICAM-1), and podoplanin and the presence of mast cells with clinical, demographic, radiologic, and histologic features from periapical granulomas, periapical cysts, and residual cysts.

Immunohistochemical Analysis of Galectins-1, -3, and -7 in Periapical Granulomas,Radicular Cysts,and Residual Radicular Cysts

Introduction

Galectins play important roles in immunoinflammatory responses, but their participation in the development of periapical lesions remains unclear. This study aimed to evaluate the expressions of galectins-1, -3, and -7 in periapical lesions, correlating them with the intensity of the inflammatory infiltrate and the pattern of the cystic epithelium.

Differences in Inflammation and Bone Resorption between Apical Granulomas,Radicular Cysts,and Dentigerous Cysts

IntroductionDental cysts can be of inflammatory (radicular cysts) or noninflammatory (dentigerous cysts) origin. Apical periodontitis is a necrosis of the pulp and infection of the root canal causing the development of apical granulomas or radicular cysts. The immunology of granuloma and cyst formation is important because modern root filling materials are immunologically active and can contribute to the resolution of apical granulomas. In contrast, radicular cysts often require apicectomy. A better understanding of the pathophysiology of inflammation and bone resorption in apical periodontitis could be the basis for developing new root filling materials with superior immunomodulatory properties.MethodsForty-one apical granulomas, 23 radicular cysts, and 23 dentigerous cysts were analyzed in this study. A tissue microarray of the 87 consecutive specimens was created, and human leukocyte antigen–DR isotype (HLA-DR)-, CD83-, receptor activator of nuclear factor kappa B ligand–, macrophage colony-stimulating factor (MCSF)-, galectin-3 (Gal3)-, CD4-, and CD8-positive cells were detected by immunohistochemistry. Tissue microarrays were digitized, and the expression of markers was quantitatively assessed.ResultsHLA-DR, CD83, MCSF, and Gal3 expression was significantly (P < .05) higher in radicular cysts compared with apical granulomas. HLA-DR, CD83, MCSF, receptor activator of nuclear factor kappa B ligand, and Gal3 expression in dentigerous cysts was significantly (P < .05) lower than in both periapical lesions (apical granulomas and radicular cysts). CD4 and CD8 infiltration was not statistically different between apical granulomas and radicular cysts. Dentigerous cysts showed a significantly (P < .05) lower T-cell infiltration than apical periodontitis. The CD4/CD8 ratio was not significantly different between the analyzed groups.ConclusionsThe development of radicular cysts in apical periodontitis is associated with an increased expression of myeloid inflammatory markers and bone resorption parameters. Antigen-presenting cells and myeloid cells might be more relevant for the pathogenesis of apical periodontitis than T cells. Increased inflammation might promote the formation of radicular cysts and more pronounced bone resorption.     

Evaluation of the Reliability and Accuracy of Using Cone-beam Computed Tomography for Diagnosing Periapical Cysts from Granulomas

Introduction

The purpose of this study was to evaluate the reliability and accuracy of cone-beam computed tomographic (CBCT) imaging against the histopathologic diagnosis for the differential diagnosis of periapical cysts (cavitated lesions) from (solid) granulomas.

Methods

Thirty-six periapical lesions were imaged using CBCT scans. Apicoectomy surgeries were conducted for histopathological examination. Evaluator 1 examined each CBCT scan for the presence of 6 radiologic characteristics of a cyst (ie, location, periphery, shape, internal structure, effects on surrounding structure, and perforation of the cortical plate). Not every cyst showed all radiologic features (eg, not all cysts perforate the cortical plate). For the purpose of finding the minimum number of diagnostic criteria present in a scan to diagnose a lesion as a cyst, we conducted 6 receiver operating characteristic curve analyses comparing CBCT diagnoses with the histopathologic diagnosis. Two other independent evaluators examined the CBCT lesions. Statistical tests were conducted to examine the accuracy, inter-rater reliability, and intrarater reliability of CBCT images.

Results

Findings showed that a score of ≥4 positive findings was the optimal scoring system. The accuracies of differential diagnoses of 3 evaluators were moderate (area under the curve = 0.76, 0.70, and 0.69 for evaluators 1, 2, and 3, respectively). The inter-rater agreement of the 3 evaluators was excellent (α = 0.87). The intrarater agreement was good to excellent (κ = 0.71, 0.76, and 0.77).

Conclusions

CBCT images can provide a moderately accurate diagnosis between cysts and granulomas.     

MMP-9、CD147在涎腺腺样囊性癌中的表达及临床意义

目的:联合检测人涎腺腺样囊性癌组织中MMP-9、CD147的表达并分析其相关性,探讨其与临床病理参数间的关系,为腺样囊性癌的临床治疗和预后判断提供理论依据。方法:选择山西医科大学第一医院病理科存档的腺样囊性癌组织标本21例(癌组),正常涎腺组织6例(对照组)。21例腺样囊性癌分别依据临床分期、有无侵犯神经进行分组。运用免疫组织化学PV-9000二步法检测MMP-9、CD147,结果用SPSS 13.0软件分析。结果:MMP-9及CD147在腺样囊性癌组中的阳性表达率(分别为76.2%和81.0%)明显高于在对照组中的阳性表达率(分别为16.7%和16.7%),差异有统计学意义(分别为P<0.05和P<0.01)。Ⅲ+Ⅳ期腺样囊性癌病例MMP-9及CD147的阳性表达率(均为100.0%),明显高于Ⅰ+Ⅱ期病例(分别为44.4%和55.6%),差异有统计学意义(分别为P<0.01和P<0.05)。有无侵犯神经的病例组间比较,MMP-9及CD147的表达差异没有统计学意义(P>0.05)。MMP-9和CD147在腺样囊性癌组织中均呈阴性、弱阳性、阳性、强阳性表达者分别为4、5、7和3例,表达一致率为90.5%,Kappa值为0.870。结论:MMP-9和CD147均可作为反映腺样囊性癌细胞生物学行为的客观参考指标,其表达与临床分期密切相关,且二者之间的表达有正相关。     

CD147在唾液腺腺样囊性癌中的表达及临床意义

目的：研究CD147在唾液腺腺样囊性癌（adenoid cystic carcinoma,ACC）中的表达及与腺样囊性癌临床病理特征、患者预后的关系。方法：采用免疫组化Envision^TM法检测72例唾液腺腺样囊性癌组织和20例正常唾液腺组织CD147的表达,应用SPSS16．0软件包对实验数据进行统计学分析。结果：CD147在腺样囊性癌中表达阳性率为62．5％,显著高于正常唾液腺组（25．0％）,P〈0．01。CD147表达与腺样囊性癌大小、病理分型、临床分期、神经侵袭、血管侵袭及肿瘤转移显著相关（P〈0．05）,与患者性别、年龄及肿瘤复发无显著性相关忪0．05）。单因素分析显示．CD147表达强阳性组累积生存率显著低于弱阳性及阴性表达组（P〈0.0001）。多因素分析显示,CD147表达及肿瘤病理分型、血管侵袭、肿瘤转移是影响腺样囊性癌患者总生存期的独立预后因素（P〈0．05）。结论：CD147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有重要参考价值。     

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。     

CD147和MMP-2、VEGF在腺样囊性癌侵袭转移中的作用

目的:研究CD147和基质金属蛋白酶-2(MMP-2)、血管内皮生长因子(VEGF)在腺样囊性癌(adenoid cystic carcinoma,ACC)组织中的表达和意义.方法:采用免疫组化EnvisionTM法检测72例ACC组织中CD147和MMP-2、VEGF的表达情况,结合临床病理资料进行统计分析.结果:CD147和MMP-2、VEGF在ACC组织中高表达,阳性表达率分别为62.5%、65.3%、73.6%;三者的表达均与肿瘤病理分型和临床分期有关(P<0.05),而与患者的性别、年龄无明显关联(P>0.05);神经侵袭组的CD147和MMP-2表达明显强于无神经侵袭组(P<0.05),VEGF在有无神经侵袭组间的表达无统计学差异(P>0.05);血管侵袭组和肿瘤发生转移组的CD147和MMP-2、VEGF的表达均明显强于对应组(P<0.05);CD147的表达与MMP-2和VEGF的表达具有显著相关性(P<0.001).结论:CD147和MMP-2、VEGF的表达与ACC的侵袭转移密切相关,检测三者的表达有助于对ACC进行临床病理研究及转移潜势预测.     

T lymphocyte activation and cytokine expression in periapical granulomas and radicular cysts

Introduction

Radicular cysts (RCs) are periapical lesions resulting in jaw bone destruction. The inflammatory dental periapical granuloma (PG) is considered to be the origin of RC formation; however the mechanism of RC development remains unclear.

Methods

Cell suspension from the surgically extirpated tissue of 27 RCs and 25 PGs was obtained. Bacteriological analysis of the PG tissue samples was performed in order to define two major groups of PG according to the prevailing causative bacterial infection: the streptococcal PG (PG-S, n = 10) and the anaerobe PG (PG-A, n = 9) group. The inflammatory response of tissue infiltrating lymphocytes was assessed by following T lymphocyte activation (HLA-DR expression) as well as interferon γ (IFN-γ) and interleukin 4 (IL-4) production which were evaluated by the flow cytometry.

Results

In comparison to RC both types of PG contained a higher proportion of activated T cells (HLA-DR) and lower proportion of IL-4 producing cells. PG-A tissue contained increased percentage of CD3 cells and increased percentage of T helper 1 (Th1) cells in comparison with PG-S. In RC the IFN-γ production is higher than in streptococcal PG-S but similar as in PG-A.

Discussion

Tissue infiltration by Th2 cells and IL-4 production is likely to play an etiopathogenic role in RC formation.