涎腺放射损伤的发病机制与治疗

目前随着头颈部恶性肿瘤不断增加，放射治疗的应用也日益增加。放射治疗在减少局部复发、控制远处转移和提高患者生存率方面发挥了重要作用，但放射治疗后常造成涎腺尤其是腮腺的损伤，导致唾液分泌减少并引起口腔干燥症等一系列并发症的发生，影响患者生活质量。因此，涎腺放射损伤的机制与治疗一直都是困扰口腔颌面外科临床医生的难题，本文就涎腺放射性损伤机制及治疗方法作一综述。     

60Coγ射线照射大鼠涎腺组织后Mrell蛋白表达的初步研究

目的:检测Mre11基因及其蛋白在放疗后的大鼠腮腺和颌下腺组织中的表达变化。方法:选取近交系雄性Wistar大鼠60只,按单次照射0 Gy,3 Gy、6 Gy、9 Gy、12 Gy、15 Gy剂量分成6组,用60Coγ射线照射大鼠头颈部,2h后收集大鼠两侧腮腺和颌下腺组织。用透射电镜观察涎腺上皮细胞超微结构变化;用RT-PCR检测Mre11的基因表达情况;用免疫组化检测Mre11蛋白表达情况。结果:透射电镜显示:放射后大鼠腮腺腺泡细胞胞质和胞膜均出现不同程度的损坏,随着剂量的增加,这种损坏逐渐加剧,未见到再生、恢复的变化。颌下腺和导管变化不明显。RT-PCR检测Mre11mRNA表达无统计学差异。免疫组化检测Mre11蛋白表达有统计学差异。结论:治疗剂量的60Coγ照射对正常涎腺组织呈不可逆的损伤,损伤的程度具有剂量依赖性;大鼠涎腺细胞Mre11mRNA的表达无剂量依赖性;大鼠涎腺细胞Mre11蛋白的表达与辐射剂量以及组织类型有关,随剂量的增加先增强后减弱。     

涎腺粘液表皮样癌中Caveolin-1、PCNA的表达及意义

目的：研究Caveolin-1、增殖细胞核抗原（proliferating cell nuclear antigen,PCNA）在涎腺粘液表皮样癌中的表达,分析二者的关系及其与肿瘤生物学行为间的关系。方法：采用SP免疫组化技术检测75例涎腺粘液表皮样癌标本及20例正常涎腺组织中Caveolin-1、PCNA的表达,并行统计学分析。结果：Caveolin-1在20例正常涎腺组织中均呈阳性表达。Caveolin--1表达下调与病程短、病理级别及临床分期的增高有关,短病程组和长病程组间（42．1％VS67．6％）、低分化和高分化组问（38．5％VS63．3％）、Ⅲ＋IV期和I＋Ⅱ期组间（33．3％VS64．7％）比较差异有统计学意义（P〈O．05）。PCNA随着病理级别和临床分期的增高阳性表达率升高,低分化和高分化组间（33．38土11．98VS20．12士10．13）、HI＋IV期和I＋Ⅱ期组间（29．45土12．89VS22．49士11．73）比较差异有统计学意义（P〈O．05）。Caveolin--1与PCNA的表达呈负相关（rs－0．28,P－0．017）。Caveolin--1表达降低及PCNA表达增高与肿瘤复发显著相关（P〈O．05）。结论：Caveolin-1的表达对粘液表皮样癌细胞增殖起抑制作用,Caveolin--1是影响粘液表皮样癌发生发展的重要因素之一。     

损伤下颌下腺模型中涎腺干／祖细胞分离及特征的初步研究

目的:分离主导管结扎后损伤的下颌下腺中涎腺干/祖细胞,并对其特征进行研究.方法:结扎SD大鼠下颌下腺主导管,获得损伤模型;机械及酶消化法体外分离、培养腺体细胞,获得类上皮细胞集落;挑取集落后梯度稀释法纯化获得类上皮单克隆细胞(涎腺干/祖细胞, salivary gland progenitor cells,SGP);利用α6β1整合素、层粘蛋白、β1整合素、角蛋白19分别进行免疫细胞化学、免疫荧光染色鉴定.结果:SGP细胞α6β1整合素、层粘蛋白、β1整合素、角蛋白19抗体阳性.结论:主导管结扎后损伤的下颌下腺中能分离出具有组织干细胞特征的细胞.     

Id1在腺样囊性癌的表达及与肿瘤血管生成相关性研究

目的：研究即分化抑制因子-1（Id1）在腺样囊性癌的表达及其与腺样囊性癌临床病理特征、肿瘤血管生成的关系。方法：免疫组化EnvisionTM法检测46例腺样囊性癌组织和10例正常唾液腺组织Id1的表达,检测CD34的表达,对肿瘤组织微血管密度进行计数。应用SPSS16.0软件对实验数据进行统计学分析。结果：Id1在腺样囊性癌中表达阳性率为65.2%,显著高于正常唾液腺组（P〈0.01）。Id1表达与腺样囊性癌病理分型、临床分期、及肿瘤转移显著相关（P〈0.05）,与患者的性别和年龄无显著性相关（P〉0.05）。Id1在腺样囊性癌中的表达与CD34标记的肿瘤微血管密度密切相关。结论：Id1的表达与腺样囊性癌临床病理特征密切相关,Id1可能通过促进腺样囊性癌的血管生成而与肿瘤的发展和转移密切相关。     

人β-防御素-2在涎腺肿瘤及涎腺炎症中的表达及其意义

目的 研究涎腺良性肿瘤组织、恶性肿瘤组织和涎腺炎症中人β-防御素-2（HBD-2）mRNA和蛋白的表达特征。方法 对不同涎腺组织,采用聚合酶链反应（PCR）、实时聚合酶链反应（Real-Time PCR）和免疫组化检测HBD-2的表达,并分析HBD-2 mRNA和蛋白在涎腺良性肿瘤组织、恶性肿瘤组织、炎症组织和正常涎腺组织中的表达差异。结果 与涎腺正常组织比较,良性肿瘤组HBD-2 mRNA表达量为其6.468倍,显著高于涎腺正常组织组（P<0.05）;恶性肿瘤组为其0.334倍,显著低于涎腺正常组织组（P<0.05）;涎腺炎症组为其10.563倍,显著高于涎腺正常组织组（P<0.05）。HBD-2不仅在这些组织的细胞质中有表达,而且在恶性组织中的细胞核也有表达。结论 HBD-2在涎腺良性肿瘤组织及涎腺炎症组织中高表达,在涎腺恶性肿瘤组织中低表达,其蛋白发生核转移。     

基质金属蛋白酶-1在人涎腺腺样囊性癌细胞中的表达

目的:测定基质金属蛋白酶-1(MMP-1)在人涎腺腺样囊性癌不同转移力细胞系中的表达。方法:以人涎腺腺样囊性癌ACC-2细胞系及其高转移株ACC-M作为研究肿瘤转移分子机制的模型,采用免疫组化法和蛋白印迹(Western blot)法检测MMP-1的蛋白表达水平。结果:MMP-1在ACC-M细胞中的表达水平高于ACC-2细胞。结论:MMP-1在人涎腺腺样囊性癌的侵袭转移过程中可能发挥作用。     

The adhesion molecules NCAM, HCAM, PECAM-1 and ICAM-1 in normal salivary gland tissues and salivary gland malignancies

BACKGROUND: Some malignant salivary gland tumors are known for their propensity to exhibit perineural invasion and vascular metastases. It was hypothesized that alterations in the expression of cell adhesion molecules are involved in these processes. METHODS: The expression and distribution of neural cell adhesion molecule (NCAM), HCAM (CD44), platelet-endothelial cell adhesion molecule-1 (PECAM-1), and intercellular cell adhesion molecule-1 (ICAM-1) in normal salivary gland tissues and selected salivary gland malignancies, especially adenoid cystic carcinoma (AdCyCa) and polymorphous low-grade adenocarcinoma (PMLG), were determined immunohistochemically, and their influence on histologically demonstrated perineural invasion, vascular invasion, and tumor recurrence/patient death were investigated. RESULTS: NCAM, HCAM, and ICAM-1 were often found to be expressed by neoplastic cells, but no correlation to perineural invasion, tumor behavior, or patient prognosis was found. PECAM-1 was rarely and only focally expressed in three tumors, all of which were related to tumor metastases and patient death. CONCLUSIONS: Immunohistochemical demonstration of NCAM, HCAM, and ICAM-1 is not related to perineural invasion or tumor behavior. PECAM-1 expression was related to vascular invasion and poor patient prognosis in three cases.     

DDR1在唾液腺黏液表皮样癌中的表达及意义

目的:探讨盘状结构域受体1 (discoidin domain receptor 1,DDR1)在唾液腺黏液表皮样癌(mucoepidermoid carcinoma,MEC)中的表达及意义.方法:采用免疫组织化学和Western免疫印迹技术检测MEC细胞株M3SP2和MC3中DDR1的表达情况.应用免疫组织化学方法检测58例唾液腺MEC组织及20例正常唾液腺组织中DDR1的表达,采用SPSS13.0软件包对数据进行统计学分析.结果:DDR1在黏液表皮样癌组织中的阳性表达率为79.3％,显著高于正常唾液腺组织(10％,P＜0.01).DDR1的高表达与MEC的临床病理参数无显著相关性(P＞0.05).在黏液表皮癌细胞株M3SP2和MC3中,DDR1表达阳性.结论:DDR1在唾液腺MEC的发生、发展中可能发挥重要作用.     

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涎腺疾病包括涎腺肿瘤及非肿瘤性涎腺疾病.涎腺主要依靠其分泌液--唾液发挥功能.近些年来,涎腺疾病和唾液的研究方面取得了明显的进展,本文对其中部分进展作一概述.     

骨桥蛋白在涎腺良、恶性肿瘤中的表达及意义的研究

目的 探讨骨桥蛋白(OPN)在涎腺良、恶性肿瘤中的表达及意义。方法 采用免疫组化SP法检测OPN在68例涎腺肿瘤(多形性腺瘤20例、腺样囊性癌24例、Warthin瘤24例)和20例瘤旁正常涎腺组织中的表达。结果 OPN在多形性腺瘤和Warthin瘤中均较正常涎腺组织增高(P<0.05);在腺样囊性癌中较正常涎腺组织增高,但两组间比较差异无显著性(P>0.05)。结论 OPN在正常涎腺组织和腺样囊性癌中有弱表达,在多形性腺瘤和Warthin瘤中表达增高。     

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神经鞘磷脂(sphingomyelin,SM)是细胞膜的重要组成成分,是生成参与信号转导的神经酰胺(ceramide,CER)的主要来源。神经鞘磷脂酶(sphingomyelinase,SMase)是一种可催化神经鞘磷脂水解,生成CER和磷酸胆碱的酶。     

Prognostic significance of Ki-67 in salivary gland carcinomas

J Oral Pathol Med (2012) 41 : 598–602 Background: Salivary gland carcinomas are a heterogeneous group of tumors with varying malignant potential. In this study, we evaluated the proliferative marker Ki‐67 in salivary gland carcinomas and related the Ki‐67 index to clinical data. Methods: A total of 176 salivary gland carcinomas of 13 different subtypes were stained immunohistochemically for Ki‐67. The number of Ki‐67 positive cells was counted and the Ki‐67 index was calculated as the percentage of positive tumor cells. Results: The Ki‐67 median value was 26 (range 1–99). The median follow‐up time was 6.9 years (range 0–19 years). The 5‐ and 10‐year crude survival was 70% and 59%, respectively. In univariate analysis, Ki‐67 index, stage, vascular invasion and tumor grade were significantly related to crude survival, but in multivariate analysis only Ki‐67 index, age, and stage were independent prognostic factors. Conclusion: We showed that irrespective of subtyping, grading or morphological appearance of tumor, the Ki‐67 index is an important and independent prognosticator. Clinical and histo‐pathological data must be considered, when planning the treatment of the individual patient. We have shown that besides stage and age of the patient, Ki‐67 is a strong, independent prognostic factor.     

大鼠唾液腺细胞体外原代培养的一种新方法

目的 建立大鼠唾液腺上皮细胞体外原代培养模型,为体外研究唾液腺疾病提供种子细胞。方法 在无菌条件下取出生1~2 d的Wistar大鼠腮腺组织,手术显微镜下去除腺体包膜,以无血清培养基( kerotinocyte-SFM )为培养液,并添加表皮生长因子( rat epidermal growth factor, rEGF )、牛垂体提取物(bovine pituitary extract,BPE)、氢化可的松(hydrocortisone,HC)、转铁蛋白(transferrin,Tf)、胰岛素(insulin,INS)等因子,应用组织块培养法进行培养。用倒置相差显微镜观察培养细胞体外生长的形态特征。用H-E染色及细胞角蛋白、波形蛋白免疫组织化学染色对培养的细胞进行形态学检查和鉴定。结果 培养的腮腺上皮细胞为三角形、多边形、圆形、短梭形,细胞单层生长,连接疏松。H-E染色可见细胞多为圆形,核蓝染,细胞有突起、细胞间桥。细胞角蛋白染色阳性,证实所培养细胞为上皮来源;Vimentin、actin和calponin染色细胞大部分呈阳性,进一步确定细胞主要为肌上皮细胞。原代细胞在3~5 d内保持良好的生长状态,并存活1周左右。结论 组织块培养法可以简捷、快速地获得大鼠腮腺上皮细胞,成功建立Wistar大鼠腮腺上皮细胞的体外模型。     

Expression of hMSH2 and hMLH1 proteins of the human DNA mismatch repair system in salivary gland tumors

BACKGROUND: The human DNA mismatch repair (hMMR) system plays an important role in reducing mutation and maintaining genomic stability. The MMR system in human cells is composed of at least six genes (hMSH2, hMLH1, hMSH3, hPMS1, hPMS2 and GTBP/hMSH6). In particular, hMSH2 and hMLH1 are expressed in cells undergoing rapid renewal; their reduced expression has been reported in several tumors. METHODS: We examined the expression of hMSH2 and hMLH1 by immunohistochemistry in tumor specimens from 43 patients with primary tumors. RESULTS: All carcinomas (n = 20) expressed these proteins. In addition, when compared to pleomorphic adenomas, malignant tumors contained significantly (P < 0.01) higher proportions of hMSH2 (56.1 +/- 31.5 vs. 31.1 +/- 22.6) and hMLH1 (27.9 +/- 26.0 vs. 14.0 +/- 12.6) positive cells. Warthin's tumors showed no specific nuclear staining of tumor cells for both hMSH2 and hMLH1. CONCLUSIONS: These data suggest a minor, if any, role for a defect in the hMMR system in the pathogenesis of malignant salivary gland tumors.