Cyclic guanosine monophosphate phosphodiesterase activity in human gingival carcinoma

BACKGROUND: Cyclic guanosine monophosphate (cGMP) is an essential second messenger metabolized by phosphodiesterases (PDEs). OBJECTIVES: We looked for a possible correlation of PDE activities in human oral squamous cell carcinoma (OSCC) with and without lymph node metastases. MATERIALS AND METHODS: The analysis of phosphodiesterase activity and the cGMP assay were done by reverse-phase HPLC on samples of fresh or frozen gingival tissues. Analysis of cGMP was confirmed with the enzyme-linked immunoabsorption assay. RESULTS AND CONCLUSIONS: cGMP PDE activity was 34.92 +/- 7.17 SD, 12.89 +/- 4.43 SD, and 35.88 +/- 8.76 SD (nmols/mg of protein), respectively, in controls, samples without lymph node involvement (N-), and specimens with lymph node metastases (N+). cGMP values were 1.97 +/- 0.63 SD, 3.30 +/- 1.47 SD, and 3.49 +/- 1.47 SD (nmols/mg of protein). Our data support the hypothesis of a role for cGMP and PDE in the progression of OSCC.     

The cellular and molecular mechanisms of bone invasion by oral squamous cell carcinoma

Oral squamous cell carcinomas (SCCs) are malignant tumours that frequently invade the mandibular bone and bone invasion is a common clinical problem. Recent studies have revealed that bone resorption by osteoclasts is an important step in the process of bone invasion by oral SCCs. However, the cellular and molecular mechanisms of bone invasion by oral SCCs remain unclear. Oral SCCs invade the mandibular bone through an erosive, mixed or infiltrative pattern that correlates with clinical behaviours. The expressions of interleukin (IL)-6, IL-11, tumour necrosis factor (TNF) α and parathyroid hormone-related protein (PTHrP) were higher in the infiltrative pattern than in the erosive pattern. These cytokines lead to receptor activator of NF-κB ligand (RANKL) expression or osteoprotegerin (OPG) suppression not only in oral SCC cells but also in cancer stromal cells to induce osteoclastogenesis. Taken together, oral SCCs provide a suitable microenvironment for osteoclastogenesis to regulate the balance of RANKL and OPG. In this review, we introduce recent advances in the knowledge of the cellular and molecular mechanisms, by which oral SCC invades mandibular bone based on the recent findings of our lab and others.     

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目的研究鸟氨酸脱羧酶（ODC）与口腔白斑的发生、发展乃至癌变潜能的关系。方法选取2009—2010年大连医科大学附属第一医院口腔科收治且经病理确诊的口腔白斑患者22例,以其病变黏膜组织为研究对象,同时以11例正常口腔黏膜、22例口腔扁平苔藓组织和22例口腔鳞癌组织为对照。采用免疫组化法检测ODC在各种组织中的表达,并对阳性率进行比较分析。结果在口腔正常黏膜、扁平苔藓、白斑和鳞癌组织中ODC的阳性率依次增加;ODC在口腔扁平苔藓中的阳性率高于正常黏膜,但差异无统计学意义（P〉0.05）,ODC在口腔白斑中的阳性率与正常黏膜和扁平苔藓的差异均有统计学意义（P〈0.05）,口腔鳞癌组织中ODC的阳性率显著高于其余组（P〈0.05）。结论 ODC表达程度可用于判断口腔白斑的恶变倾向及口腔鳞癌的恶性程度。     

Differential infiltration of CD8+ and NK cells in lip and oral cavity squamous cell carcinoma

J Oral Pathol Med (2010) 39 162–167 Background: CD8⁺ and natural killer (NK) cells have been considered the most effective cells in the combat of cancer, contributing to better prognosis and longer survival. Methods: The aim of this study was to evaluate the population of CD8⁺ and NK cells, by immunohistochemistry, in samples of oral cavity squamous cell carcinoma (OCSCC) and lip squamous cell carcinoma (LSCC), leukoplakia, actinic cheilitis, and healthy oral mucosa (control). The relationship of CD8⁺ and NK cells with survival data, lymph node metastasis, tumor size, and proliferative index was also evaluated. Results: The number of peritumoral and intratumoral CD8⁺ and NK cells was significantly higher in LSCC, when compared with control, pre‐malignant lesions, and OCSCC. A higher proportion of peritumoral CD8⁺ cells demonstrated correlation with a lower neoplastic proliferative index. Moreover, patients with OCSCC with a high density of peritumoral CD8⁺ cells showed a tendency towards a longer survival time. Conclusions: The differential CD8⁺ and NK cells infiltration in oral SCC might reflect a distinctive tumor microenvironment with a favorable local cytotoxic immune response against neoplastic cells.     

口腔黏膜癌变过程中中心体的扩增及其意义

目的　了解口腔黏膜癌变过程中中心体的状况,探讨中心体的异常在口腔鳞状细胞癌(OSCC)发生发展中的作用及其在口腔黏膜癌变过程中的意义。方法　选取正常口腔黏膜(12例)、轻度上皮异常增生(2例)、中度上皮异常增生(8例)、重度上皮异常增生(12例),口腔高分化鳞癌(10例)、中分化鳞癌(15例)、低分化鳞癌(7例)的石蜡包埋组织,采用间接免疫荧光双重染色(γ-微管蛋白单克隆抗体及细胞角蛋白多克隆抗体)显示上皮细胞中的中心体,分析其在口腔黏膜癌变过程中的变化趋势及在各组间的差异。结果　正常口腔黏膜上皮表现为大小数目正常的中心体,但在72·73%(16/22)的上皮异常增生及84·38%(27/32)OSCC组织中观察到部分上皮或肿瘤细胞中出现异常中心体,表现为中心体直径的增加或数目的增多。具有异常中心体的细胞数目随上皮异常增生程度的增加及肿瘤分化程度的降低而增加,二者存在明显的正相关关系(P<0·01)。结论　中心体的扩增是口腔黏膜癌变过程中的早期事件并与口腔癌发生发展进程有关,口腔黏膜癌变过程中的细胞形态学改变与中心体扩增之间可能存在直接机制上的联系。从调控中心体循环入手治疗口腔癌前病损及OSCC,有可能成为口腔癌预防和治疗的新途径。     

X-性染色体连锁凋亡抑制蛋白与口腔鳞癌细胞Tca8113化疗耐药的关系

目的研究X-性染色体连锁凋亡抑制蛋白（XIAP）在口腔鳞癌细胞Tca8113中的表达水平,并探讨XIAP表达与Tca8113细胞对化疗药物耐药性之间的关系。方法用平阳霉素（PYM）间歇性加药,逐步递增剂量,采用甲基噻唑基四唑（MTT）法检测药物处理前后细胞对PYM的敏感性,逆转录聚合酶链反应（RT-PCR）分别检测XIAP在药物处理前后的各Tca8113细胞组中的表达变化,并探讨XIAP与细胞耐药性的关系。结果Tca8113细胞在PYM间断作用下产生耐受,Tca8113-1-10组、Tca8113-10-10组耐药细胞对PYM的半数有效浓度（IC50）分别为（12.758±0.030）、（18.986±0.150）μg·mL-1。Tca8113-1-20、Tca8113-10-20组耐药细胞对PYM的IC50分别为（26.302±0.072）、（35.294±0.115）μg·mL-1。XAIP的表达水平与细胞对PYM的耐药有相关性（P<0.01）。结论XIAP在口腔鳞癌中的表达水平升高,可能与鳞癌的化疗耐药性有关,这可作为口腔鳞癌基因治疗的一个新靶点。     

nm23-H1基因在口腔鳞癌颈淋巴结转移不同阶段的调控作用

目的　探讨nm23-H1基因在口腔鳞癌区域淋巴结转移不同阶段的调控作用及影响。方法　利用免疫组化和Western Blot技术,结合淋巴结转移和原发灶浸润分型的资料,分组对照研究nm23-H1基因在200例口腔鳞癌颈淋巴结转移不同阶段的表达情况。结果　淋巴结转移组nm23-H1基因阴性表达率明显高于无淋巴结转移组(P<0·01)。N1期、转移仅累及1个淋巴结、Ⅳc型浸润,以及低分化肿瘤的患者,均有比其它患者明显增高的 nm23-H1基因的阴性表达率(P<0·01);转移至颌下或颌下-颈深上淋巴结平面者的阴性表达率,也高于转移到其它平面者(P<0·05)。结论　nm23-H1基因主要是通过干扰肿瘤实体内高转移细胞亚群的形成和初始转移的发生来调控口腔鳞癌患者的颈淋巴结转移。     

头颈部鳞状细胞癌干细胞的研究进展

肿瘤干细胞假说认为,只有一小部分细胞可维持肿瘤的生长,这一小部分细胞被称为“肿瘤干细胞”,其他的大部分细胞只有有限的或根本没有生长潜能。在头颈部鳞状细胞癌在内的多种肿瘤中已经初步鉴定和分离出了肿瘤干细胞。本文就CD44阳性细胞、醛脱氢酶阳性细胞、侧群细胞和八聚体4／nanog／CD133阳性细胞等与头颈部鳞状细胞癌干细胞相关的研究现状作一综述。     

OSCC中ER-α、RAR-β、MGMT。及P16INK4a基因启动子甲基化的临床研究

目的：探讨肿瘤相关基因ER-α、RAR-β、MGMT及P16INK4a启动子在口腔鳞状细胞癌（OSCC）组织中的甲基化状态。方法：20例病理确诊为OSCC的组织切片,经酶消化法提取组织DNA后双硫法检测ER-αL、RAR-β、MGMT及P16INK4a基因启动子的甲基化状态,比较分析4种基因启动子甲基化状态和临床病理参数的相关性。结果：20例中,P16INK4a、MGMT启动子甲基化发生率均为10％,RAR-B启动子甲基化发生率为40％,ER-d启动子甲基化发生率为55％,两株OSCC细胞系中,ER-α、RAR-β启动子均出现甲基化,而MGMT及P16INK4a启动子均未见甲基化。结论：RAR-β、ER-α基因启动子的甲基化较P16INK4a、MGMT＇g更为常见,提示前两者可能在OSCC的发生中具有更重要的作用。     

无创检测口腔白斑及鳞癌中人乳头瘤病毒及其分型

[摘要] 目的 探讨口腔白斑（oral leukoplakia,OLK）和口腔鳞状细胞癌（oral squamous cell carcinoma,OSCC）中人乳头瘤病毒（human papillomavirus,HPV）及其分型和临床意义。方法 采用无创方法收集30例正常人,103例OLK,30例OSCC的口腔黏膜脱落细胞,采用聚合酶链反应（Polymerase chain reaction,PCR）结合导流杂交技术进行37种HPV基因型别的检测,对受检者进行相关资料分析。结果 正常人检出HPV阳性1例,检出率为3.33%（1/30）,OLK检出HPV阳性5例,检出率为4.85%（5/103）,OSCC检出HPV阳性1例,检出率为3.33%（1/30）,各组间差异无统计学意义（χ2=0.22,P=0.90＞0.05）。其中OLK中有4例为HPV单一型阳性,1例为HPV三重型别阳性。结论 PCR导流杂交检测技术能无创检测口腔HPV分型情况,可应用于临床。HPV在OLK、OSCC中检出率较低,可能与OLK、OSCC的发病关联性不强。     

Salvage surgery for recurrent carcinoma of the oral cavity: assessment of prognostic factors

Salvage surgery is the most acceptable therapeutic option for disease control of loco-regional recurrences in oral cancers. Prognostic factors need to be assessed to select patients for salvage surgery who would benefit the most. This was a single-centre retrospective observational study conducted between 2015 and 2018. A total of 168 patients with recurrent oral cavity carcinoma who underwent salvage surgery were included for analysis. The primary endpoints of the study were to evaluate overall survival (rOS) after salvage surgery and prognostic factors affecting survival. In this study, the median rOS was 18 months and the median disease-free survival (rDFS) was 14 months. Advanced stage (hazard ratio (HR) 2.387, 95% confidence interval (CI) 1.496–3.808; P = 0.001) and multimodality treatment (HR 1.642, 95% CI 1.139–2.367; P = 0.008) in the initial disease, as well as nodal spread (HR 3.794, 95% CI 1.580–9.111; P = 0.008) and perineural invasion (HR 2.167, 95% CI 1.358–3.455; P = 0.001) in the recurrent disease, were found to adversely affect survival after salvage surgery. With thorough assessment of the prognostic factors and appropriate patient selection, survival may be favourable after salvage surgery for recurrent oral cavity carcinoma.     

口腔鳞状细胞癌及白斑人乳头瘤病毒16型感染的临床研究

目的:探讨口腔鳞状细胞癌(OSCC)和白斑(LK)患者人乳头瘤病毒16型(HPV-16)感染和临床病理参数之间的相关性。方法:收集30例OSCC和5例LK患者的组织切片,所有病例均经病理学确诊,提取组织DNA,通过巢式PCR检测HPV-16感染情况。结果:HPV-16与TNM分级之间未见相关性,60岁以下女性患者的HPV-16感染率高于60岁以上女性患者(P=0.024),而男性患者未见HPV-16感染和年龄存在相关性(P=0.649)。结论:60岁以下女性OSCC及LK患者中出现较高的HPV-16感染率,提示这可能是新的致癌危险因子。     

E‐cadherin downregulation and Twist overexpression since early stages of oral carcinogenesis

There is some evidence of Twist participation in oral carcinogenesis; however, little is known about its interaction with E‐cadherin in oral squamous cell carcinoma (OSCC) development. This experimental study included an immunohistochemical analysis of Twist and E‐cadherin proteins in paraffin‐embedded specimens of oral leukoplakia (OL), OSCC, and normal oral mucosa. In addition, it was also performed a Western blot and double‐immunofluorescence analysis of Twist and E‐cadherin expression in OSCC cell lines. Significant differences in Twist and E‐cadherin immunoexpression were observed between normal oral mucosa and OL, with an inverse relation since the earliest stages of oral dysplasia (r = ?0,512; P < 0.001). Western blot and double‐immunofluorescence analysis showed differences in Twist and E‐cadherin expression among human oral keratinocytes and OSCC cell lines suggesting that downregulation of E‐cadherin occurs in a dependent manner of Twist in OSCC. Our results showed a possible value of Twist and E‐cadherin in the prediction of risk of oral epithelium malignant transformation.     

The Influences of Periodontal Status and Periodontal Pathogen Quantity on Salivary 8‐Hydroxydeoxyguanosine and Interleukin‐17 Levels

Background: Periodontitis is a biofilm‐initiated disease that is characterized by elevated inflammatory status. 8‐Hydroxydeoxyguanosine (8‐OHdG) and interleukin (IL)‐17 are highly associated with inflammation and bone resorption and therefore are regarded as potential biomarkers for periodontitis. In this study, the associations between salivary 8‐OHdG and IL‐17 levels and clinical and microbial parameters before and after non‐surgical treatment are investigated. Methods: Forty‐five patients with chronic periodontitis (CP) and 47 periodontally healthy volunteers were recruited for the study. Clinical parameters, including the probing depth (PD), clinical attachment level (CAL), sulcular bleeding index, and simplified oral hygiene index (OHI‐S), were examined for each participant. Microbial parameters including the quantities of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola in the subgingival plaque and saliva were determined by real‐time polymerase chain reaction at baseline and 1 and 3 months after the non‐surgical treatment. Salivary 8‐OHdG and IL‐17 levels were detected by enzyme‐linked immunosorbent assays. Results: Compared with healthy volunteers, CP group patients had significantly higher salivary 8‐OHdG and IL‐17 levels at baseline. Baseline salivary 8‐OHdG and IL‐17 levels were positively correlated with all clinical parameters as well as the quantities of T. forsythia and T. denticola. After non‐surgical treatment, baseline levels of salivary 8‐OHdG and IL‐17 were reduced significantly at both the 1‐ and 3‐month follow‐ups. The hierarchical linear model revealed that variations in the PD, CAL, and OHI‐S had significant positive effects on variation in the salivary 8‐OHdG level. However, variations in the PD; quantity of T. forsythia in the subgingival plaque; and quantities of P. gingivalis, T. forsythia, and T. denticola in saliva were associated significantly with variation in the salivary IL‐17 levels. Conclusions: There was a strong association between salivary 8‐OHdG and IL‐17 levels and periodontitis. Variation in the salivary 8‐OHdG level was correlated with variations in the clinical parameters, whereas variation in the IL‐17 level was correlated with variation in the microbial parameters.