口腔颌面部恶性肿瘤患者血清中透明质酸含量的检测

目的　检测口腔颌面部恶性肿瘤患者血清中透明质酸(HA)的含量,探讨HA对口腔颌面部恶性肿瘤辅助诊断和治疗效果监测的价值。方法　选择住院治疗的口腔颌面部恶性肿瘤患者44例,健康人24例。肿瘤患者于手术前或化疗开始前采血,其中20例患者于手术后或化疗结束后再次采血;24例健康人于常规体检时采血。用放射免疫试验测定所有标本血清中的HA浓度。结果　治疗前口腔颌面部恶性肿瘤患者血清中HA含量显著高于健康人(P<0·05),口腔颌面部鳞癌患者血清中HA含量显著高于健康人(P<0·05),涎腺腺样囊性癌患者血清中HA 含量与健康人无显著差异(P>0·05)。口腔颌面部恶性肿瘤Ⅲ、Ⅳ期患者血清中HA含量显著高于Ⅰ、Ⅱ期患者和健康人(P<0·05)。口腔颌面部恶性肿瘤患者治疗后血清中HA含量低于治疗前,但差异不显著(P>0·05)。结论　HA含量测定对口腔颌面部恶性肿瘤可能有辅助诊断价值。血清中HA的含量变化可作为肿瘤分期和判断肿瘤预后的参考,但不能用于治疗效果的监测。     

Estimation of sCD14 levels in saliva obtained from patients with various periodontal conditions

Aim:  To assess the concentration of soluble CD14 receptor in saliva of people with periodontal disease and healthy patients and its relationship with periodontal status.
Subjects and Methods:  Unstimulated whole saliva samples from patients with chronic periodontitis ( n  =   34), aggressive periodontitis ( n  =   19) and healthy controls ( n  =   17) were obtained for the study. The periodontal status of each subject was assessed by criteria based on probing depth, clinical attachment loss and the extent of periodontal breakdown. The levels of sCD14 were measured in saliva samples with an enzyme-linked immunosorbent assay (ELISA).
Results:  Although no significant difference ( P  >   0.05) was found for salivary sCD14 levels between periodontitis groups, they were significantly greater ( P  <   0.05) than those detected for healthy controls. Furthermore, Spearman's correlation analysis showed statistically significant correlations ( P  <   0.01) between data from salivary sCD14 levels and clinical measurements.
Conclusion:  The findings of the present study re-emphasize the importance of whole saliva as sampling method in terms of immunological purposes in periodontal disease and suggest that the elevated sCD14 concentration may be one of the host-response components associated with the clinical manifestations of periodontal disease.     

Decreased expression of Ep-CAM protein is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan

Background:  The epithelial cell adhesion molecule (Ep-CAM) is involved in cell signaling, migration, proliferation, cell-cycle regulation, and cancer metastasis.
Methods:  This study used an immunohistochemical technique to examine the expression of Ep-CAM protein in 84 specimens of oral squamous cell carcinoma (OSCC), 98 specimens of oral epithelial dysplasia (OED, 31 mild, 41 moderate, and 26 severe OED cases), and 15 specimens of normal oral mucosa (NOM).
Results:  We found that the mean Ep-CAM labeling indices (LIs) decreased significantly from NOM (80 ± 18%) and mild OED (76 ± 14%) through moderate OED (66 ± 22%) and severe OED (55 ± 20%) to OSCC samples (46 ± 16%, P <  0.001). A significant correlation was found between the lower mean Ep-CAM LI and OSCCs with larger tumor size ( P =  0.003), positive lymph node metastasis ( P =  0.022), more advanced clinical stages ( P <  0.001), cancer recurrence ( P =  0.021), or extracapsular spread of lymph node ( P =  0.015). However, only Ep-CAM LI  <  50% ( P  < 0.0001) was identified as an independent unfavorable prognosis factor by multivariate analyses with Cox proportional hazard regression model. Kaplan–Meier curve showed that OSCC patients with an Ep-CAM LI < 50% had a significantly poorer cumulative survival than those with an Ep-CAM LI ≥ 50% ( P  < 0.00001, log-rank test).
Conclusions:  We conclude that the decreased expression of Ep-CAM protein is an early event in oral carcinogenesis. The Ep-CAM LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.     

CXCR-4 knockdown by small interfering RNA inhibits cell proliferation and invasion of oral squamous cell carcinoma cells

Background:  Oral squamous cell carcinomas (OSCCs) are characterized by a high degree of local invasion and a high rate of metastases to cervical lymph nodes. Downregulation of CXCR-4 by siRNA inhibits invasion and growth of breast and colon cancer cells. However, there have been no reports on the downregulation of CXCR-4 by small interfering RNA (siRNA) in oral cancer cells.
Methods:  We generated two stable CXCR-4-knockdown clones (KBsi and KOSCC-25Bsi) from the KB and KOSCC-25B OSCC cell lines by lentiviral delivery. In vitro invasion and cell proliferation assays were used to investigate the effect of CXCR-4 downregulation on cell proliferation and invasiveness in KBsi and KOSCC-25Bsi. Immunohistochemistry was performed to evaluate the correlation between CXCR-4 expression and proliferation in 26 OSCC tissue samples.
Results:  CXCR4-knockdown OSCC cells showed reduced invasiveness. The invasiveness of KBsi decreased to 29.5% of the vector-infected controls, and KOSCC-25Bsi decreased to 38.1% of the control vector-infected cells ( P  <   0.05). The CXCR4-knockdown OSCC cells grew significantly slower than the vector-infected control cells. KBsi and KOSCC-25Bsi cells proliferated at 69.5% and 71.7%, respectively, of the rate of control vector-infected cells ( P  <   0.05). CXCR-4-positive group had significantly higher PCNA labeling index than CXCR-4-negative group in OSCC tissue samples.
Conclusion:  These results suggest that the downregulation of CXCR-4 induces anti-proliferative and anti-invasive effects in OSCC and that CXCR-4 might be a useful target molecule for the treatment of OSCC.     

Prognostic significance of Bcl-2 and Bax protein expression in the patients with oral squamous cell carcinoma

Background:  The aim of this study was to investigate the expression of the apoptosis-inhibitory Bcl-2 protein and the apoptosis-promoting Bax protein and to identify their association with the clinical parameters and prognosis of the patients with oral squamous cell carcinoma (OSCC).
Methods:  The expression of Bcl-2 and Bax proteins was evaluated by immunohistochemical staining in specimens from 110 patients with OSCC. Every section was scored according to both the percentage of positive staining tumor cells and the staining intensity. The Kaplan-Meier test and Cox proportional hazards regression analysis were performed to assess the correlation between the protein levels and the long survival rate of patients. The association between Bax, Bcl-2 immunoexpression and clinicopathologic variables was analyzed with the chi-square test and non-parametric analysis. The Bcl-2 and Bax immunoexpression in 20 oral mucosa samples were also investigated as normal control.
Results:  The results showed that the 5-year survival rate was significantly higher in the patients with the ratio of Bcl-2/Bax ≤ 1 than in those with Bcl-2/Bax > 1 (76.79 ± 6.69% vs. 59.26 ± 6.69%, P  = 0.0489). Bax immunoreactivity was significantly correlated with histological grading and lymph node metastasis. Univariate analysis indicated that the ratio of Bcl-2/Bax and lymph node metastasis were two independent factors related to the prognosis.
Conclusion:  The ratio of Bcl-2/Bax could be used as an effective biomarker to predict the prognosis of OSCC.     

Role of TP53 in the progression of pre-malignant and malignant oral mucosal lesions. A follow-up study of 144 patients

Background:  Prediction of progression from pre-malignant oral mucosal lesions to malignancy, or recurrence of an existing oral squamous cell carcinoma (OSCC), is an important clinical problem in oral medicine.
Methods:  This study presents a follow-up of a study published in 2002. Samples from 54 patients with OSCC, 45 with oral lichen planus (OLP) and 45 with hyperkeratosis (clinically leukoplakia), diagnosed between 1987 and 1996, were analysed for TP53 protein expression and TP53 mutation. Follow-up was 11–17 years for OSCC (mean 13.3), 12–22 years for OLP (mean 15.9) and 12–17 years for hyperkeratosis (mean 14.5).
Results:  Of the 54 OSCC patients, 28 experienced recurrent disease, 21 died of OSCC, 22 died of other causes. Of the 14 OSCC patients with mutated TP53 ( n  = 11), the cancer recurred in eight (57%) and in 20/39 (51%) without mutation. Expression of TP53 protein was significantly associated with reduced overall survival. Among OLP patients, nine were TP53- mutated out of 31 tested. One TP53- mutated OLP patient developed OSCC in a different site. Of the hyperkeratosis patients, three were mutated of 22 tested. One hyperkeratosis patient (non-mutated) developed OSCC in the same site.
Conclusion:  TP53 mutations can exist in benign oral mucosal lesions for many years without progression to malignancy. No association was found between TP53 protein expression or TP53 mutation and recurrence of OSCC or disease-related survival. Overall survival was reduced in patients with positive TP53 protein expression.     

Progressive increase of human papillomavirus carriage rates in potentially malignant and malignant oral disorders with increasing malignant potential

Introduction:  We investigated the potential role of human papillomaviruses (HPVs) in potentially malignant oral disorders, oral leukoplakia (OL) and oral lichen planus (OLP), and in oral squamous cell cancer (OSCC) in an Eastern Hungarian population with a high incidence of OSCC.
Methods:  Excised tumor samples (65 OSCC patients) and exfoliated cells from potentially malignant lesions (from 44 and 119 patients with OL and OLP, respectively) as well as from healthy controls (72 individuals) were analysed. OLPs were classified based on clinical appearance, 61 patients had erosive–atrophic lesions (associated with higher malignancy risk, EA-OLP) and 58 had non-erosive non-atrophic lesions (with lower risk of becoming malignant, non-EA-OLP), respectively. Exfoliated cells collected from apparently healthy mucosa accompanied each lesion sample. HPV was detected by MY/GP polymerase chain reaction (PCR) and genotyped by restriction analysis of amplimers. Copy numbers in lesions were determined using real-time PCR. Prevalence rates, copy number distributions, and association with risk factors and diseases were analysed using chi-square test, t -test, and logistic regression, respectively.
Results:  We detected HPVs significantly more frequently in lesions than in controls ( P  ≤ 0.001 in all comparisons). HPV prevalence increased gradually with increasing severity of lesions (32.8, 40.9, and 47.7% in OLP, OL, and OSCC, respectively). Copy number distribution patterns roughly corresponded to prevalence rates, but OLP and OL were comparable. HPV prevalence differed significantly between EA-OLP and non-EA-OLP groups (42.6 vs. 22.4%); EA-OLP group showed a prevalence similar to that found in OL.
Conclusion:  HPVs may be involved in the development or progression of not only OSCC but also of potentially malignant oral lesions.     

Serum sCD14, polymorphism of CD14−260 and periodontal infection

Background and Aims:  CD14 is a co-receptor involved in the recognition of Gram-negative and positive bacteria. Infections are known to influence serum sCD14 levels, and CD14 gene promoter polymorphism (CD14 C−260T) has been reported to be associated with many infectious diseases. Our aim was to investigate whether serum sCD14 concentration is associated with periodontal infection and the CD14⁻²⁶⁰ genotype.
Subjects and Methods:  The periodontal status of 56 subjects with chronic periodontitis and 28 controls was clinically examined. Serum sCD14 concentration was analyzed using ELISA and CD14⁻²⁶⁰ genotype using polymerase chain reaction (PCR).
Results:  The mean concentration of sCD14 in serum was significantly higher in subjects with periodontitis than in control subjects (4.9  μ g ml⁻¹ vs 3.8  μ g ml⁻¹, P  < 0.001). Serum sCD14 concentration associated significantly with the extent of advanced periodontal disease. In a regression analysis including both subject groups, the CD14⁻²⁶⁰ genotype was a significant determinant for serum sCD14 concentration. After stratification by periodontal health status (periodontitis vs controls), the influence of the CD14⁻²⁶⁰ genotype on serum sCD14 concentration was seen only in the control group.
Conclusions:  Periodontal infection is associated with the serum concentration of sCD14. Moderate to severe periodontal infection overshadows the influence of the genotype on serum sCD14 concentration.     

Apoptosis-associated markers and clinical outcome in human oral squamous cell carcinomas

Background:  Apoptosis is a genetically regulated cell death involved in the deletion of cells in normal or malignant tissues. Proteins of the Bcl-2 family play a key role in the control of apoptosis and carry out both pro-apoptotic and anti-apoptotic functions. The present study evaluated the prognostic value of Bcl-2 and Bax expression at the invasive front of oral squamous cell carcinoma (OSCC), taking clinicopathological findings into account.
Methods:  Fifty-six specimens of OSCC were randomly selected, and Bcl-2 and Bax expression was evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded pre-treated specimens at the invasive front of OSCC. Clinicopathological data were gathered and patient survival was analysed.
Results:  No significant relationship was found between Bcl-2 or Bax expression and clinical variables. Patients with Bcl-2 expression had a worse prognosis than those without Bcl-2 expression, but the difference did not reach statistical significance. Patients with Bax expression had a significantly better prognosis than those without Bax expression ( P  <   0.05). In univariate analyses, T category, mode of cancer invasion and Bax expression showed significant correlations. Multivariate analysis revealed that the mode of cancer invasion and Bax expression were significant and independent variables. Bax expression was found to be the strongest independent prognostic parameter. Patients with negative Bcl-2 expression and positive Bax expression had a significantly better prognosis ( P  <   0.005).
Conclusion:  We suggest that Bax expression at the invasive front of OSCC is a significant predictor of prognosis and that it is therefore important to investigate the expression of Bcl-2 and Bax in this disease.     

鳞状细胞癌抗原(SCC-Ag)在口腔鳞癌患者血清中表达的临床意义

用化学发光法检测36例口腔鳞癌、11例口腔颌面部其他恶性肿瘤、45例口腔颌面部良性肿瘤患者以及70例正常人血清中鳞状细胞癌抗原(SCC-Ag)水平。鳞癌组SCC-Ag水平明显高于良性肿瘤组(P<0.01)、正常组(P<0.01)以及其他恶性肿瘤组(P<0.05)。SCC-Ag可作为口腔鳞癌患者辅助诊断指标。     

Alpha lipoic acid in burning mouth syndrome – a randomized double-blind placebo-controlled trial

The burning mouth syndrome (BMS) is a chronic condition characterized by oral burning pain in the absence of clinical abnormalities and without established therapy.
Objectives:  The purpose of this study was to evaluate the effectiveness of alpha lipoic acid (ALA) in the management of BMS symptoms through a randomized double-blind placebo-controlled trial.
Methods:  Thirty-eight patients (34 women and four men, median age 62.9 years, range 36–78) were included and 31 completed the study. The patients were randomized into two cycles of treatment: one with alpha lipoic acid and one with placebo both administered in identical capsules. These cycles were separated by a washout period of 20 days. The oral symptoms and the treatment response were assessed using a 100-mm visual analog scale before and after each cycle and the global perceived effect score, using a 5-point scale after each treatment cycle.
Results:  The level of reduction on burning was significant for both treatments (paired t -test: P <  0.05; rp = 0.011; ral < 0.001). Considering the two cycles together, 22 patients reported at least some improvement after ALA use and 23 patients after placebo.
Conclusions:  Comparison of the oral assessment scores of the two cycles failed to demonstrate the effectiveness of ALA over placebo ( t -test: P  > 0.05; r  = 0.75).     

An acute injection of Porphyromonas gingivalis lipopolysaccharide modulates the OPG/RANKL system and interleukin-6 in an ovariectomized mouse model

Background/aims:  In the present study, we attempted to develop a simulated model to explore the causal effects of periodontal pathogens on skeletal homeostasis in postmenopausal osteoporosis.
Methods:  Fifty-three female adult ICR mice were randomly assigned to an experimental group (ovariectomized) or a control group. A single injection of Porphyromonas gingivalis lipopolysaccharide ( P. gingivalis -LPS, ATCC 33277) or Escherichia coli lipopolysaccharide ( E. coli -LPS) was administered intraperitoneally 4 weeks after an ovariectomy. Concentrations of interleukin-6 (IL-6), osteoprotegerin (OPG), and the receptor activator of nuclear factor-κB ligand (RANKL) in serum were subsequently analyzed using an enzyme-linked immunosorbent assay (ELISA).
Results:  Under stimulation with P. gingivalis -LPS or E. coli -LPS, the concentration of OPG rose in both groups. The serum level of RANKL showed a decreasing trend 24 h after the injection in both groups. After injection of P. gingivalis -LPS in both the experimental and control animals, the OPG : RANKL ratio increased 24 h after the booster (22.26–620.99, P  < 0.05). The serum level of IL-6 in the experimental group significantly increased 1–6 h after administration of E. coli -LPS and 1–3 h after administration of P. gingivalis -LPS ( P  < 0.05).
Conclusions:  A single booster injection of P. gingivalis -LPS induced short-term changes in OPG, RANKL, and IL-6 serum levels in this ovariectomized mouse model.     

Overexpression of GLUT-1 in the invasion front is associated with depth of oral squamous cell carcinoma and prognosis

J Oral Pathol Med (2010) 39 : 74–78
Object:  Malignant cells show increased uptake, which is considered to be facilitated by glucose transporters (GLUTs). Increased GLUT-1 expression has been reported in many human cancers. We hypothesized that a oral squamous cell carcinoma, characterized by high frequency of lymph node metastasis, distant metastasis or local recurrences, was associated with GLUT-1 overexpression in invasion front.
Methods:  GLUT-1 immunostaining in invasion front was studied on 24 oral squamous cell carcinomas, and revealed the correlation with the clinical characteristics.
Result:  The analysis showed that all oral squamous cell carcinoma patients and GLUT-1 expression correlated the depth of the tumors ( P  =   0.023 < 0.05). Furthermore the survival of patients who had overexpression of invasion front was significant shorter than that of patients with GLUT-1 weakly positive ( P  =   0.046 < 0.05). No significant association was noted between GLUT-1 immunostaining and either age, gender, subsites, tumor size, or lymph node status.
Conclusion:  The present study shows that GLUT-1 served as a marker indicating that tumors with deep invasion tended to result in a worse prognosis in patients due to either lymph node metastasis, a recurrence of the primary lesion or distant metastasis.     

Relation of bone turnover markers to periodontal disease and jaw bone morphology in elderly Japanese subjects

Objective:  The purpose of this study was to evaluate the relation of bone turnover markers such as bone formation and resorption to periodontal disease and jaw bone morphology in elderly Japanese subjects.
Subjects and methods:  We selected 148 subjects for participation in this study. All subjects were aged 77 years. The periodontal examination included the assessment of clinical attachment level (CAL). Biochemical parameters of bone turnover measured included urinary deoxypyridinoline, serum osteocalcin (S-OC), and serum bone-specific alkaline phosphatase. In addition, to evaluate the jawbone, we used the mandibular inferior cortex classification (MIC).
Results:  Serum osteocalcin had significantly higher (males: P  =   0.038, females: P  =   0.041) tendency for MIC Class (ANOVA). Multiple linear regression results showed that the number of remaining teeth and S-OC were negatively associated with the percentage of sites with ≥6 mm CAL ( R ² = 0.322, P  < 0.001). Coefficients and betas were −0.71, −0.46 ( P  <   0.001) and −1.11, −0.28 ( P  =   0.002), respectively.
Conclusion:  In conclusion, this study suggests that there is a significant relation of bone turnover markers to periodontal disease and jaw bone morphology in elderly Japanese subjects.     

Enamel defects and salivary methylmalonate in methylmalonic acidemia

Introduction and objective:  To characterize enamel defects in patients with methylmalonic acidemia (MMA) and cobalamin (cbl) metabolic disorders and to examine salivary methylmalonate levels in MMA.
Subjects and methods:  Teeth from patients ( n  = 32) were evaluated for enamel defects and compared with age- and gender-matched controls ( n  = 55). Complementation class ( mut , cblA , cblB and cblC ) and serum methylmalonate levels were examined. Primary teeth from two patients were examined by light and scanning electron microscopy and salivary methylmalonate levels from two patients were analyzed.
Results:  Enamel defects were significantly more prevalent per tooth in the affected group than the control group, across complementation types ( P  <   0.0001). The mut MMA subgroup had a significantly higher prevalence per individual of severe enamel defects than controls ( P  =   0.021), and those with enamel defects exhibited higher serum methylmalonate levels than those without ( P  = 0.017). Salivary methylmalonate levels were extremely elevated and were significantly higher than controls ( P  =   0.002). Primary teeth were free of enamel defects except for two cblC patients who exhibited severe enamel hypoplasia. One primary tooth from a cblC patient manifested markedly altered crystal microstructure.
Conclusion:  Enamel anomalies represent a phenotypic manifestation of MMA and cbl metabolic disorders. These findings suggest an association between enamel developmental pathology and disordered metabolism.     

Use of Patient Self-Report Oral Health Outcome Measures in Assessment of Dental Treatment Outcomes

Objective: To assess the sensitivity of a newly developed brief measure of oral health-related quality of life (OQOL). Methods: Self-assessed oral health and OQOL were measured in three groups of patients who had presented for either prophylaxis ( n =  32), endodontic care ( n =  15), or for a denture ( n =  16) in a dental school setting before and after treatment. Main outcome measures included the single-item self-report of oral health (OH-1) and the 6- and 12-item versions of a new OQOL instrument. General linear modeling was used to compute means of self-reported oral health by treatment group. Results: Of the 63 patients who completed the baseline questionnaire, 44 (70 percent) returned questionnaires after treatment. The sample averaged 43  ±  15 years, 48 percent male and 55 percent with some college education. Ethnic representation included 35 percent White, 33 percent Black, and 32 percent other – mostly Latino. The mean self-reported number of teeth was 20.6. In terms of sensitivity, significant differences were observed between the treatment groups on the items assessing being upset ( P <  0.05), feeling depressed ( P <  0.05), and uncomfortable about the appearance of teeth or dentures ( P <  0.05). However, magnitude of change, as measured by an effect size, was characterized as minimal to small in the recall and endodontic groups and borderline moderate in the denture group. Conclusion: The measure was sensitive to differences within groups, with a small to borderline magnitude of change.     

CD44s、CD44v6在口腔鳞状细胞癌中的表达

目的　研究细胞粘附分子 CD4 4 s及 CD4 4 v6与口腔鳞状细胞癌 ( OSCC)的发生、淋巴结转移的关系。方法　采用免疫组织化学 S- P法对 2 6例口腔鳞癌及其 11例转移淋巴结进行 CD4 4 s、CD4 4 v6的检测。结果　CD4 4 s、CD4 4 v6在口腔鳞癌中的表达较正常鳞状上皮中显著下降 ( P<0 .0 5 ,P<0 .0 0 1) ;高度恶性口腔鳞癌中CD4 4 v6的表达水平较低度恶性者显著降低 ( P<0 .0 1) ;有淋巴结转移的原发灶较无淋巴结转移的原发灶的CD4 4 v6表达水平显著降低 ( P<0 .0 0 1)。结论　 CD4 4 s、CD4 4 v6表达下降在 OSCC的发生中有一定的作用 ;CD4 4 v6表达下降可作为预测 OSCC发生淋巴结转移可能性大小的一个指标。     

SAA and PLTP activity in plasma of periodontal patients before and after full-mouth tooth extraction

Objective:  To assess whether treatment of advanced periodontal disease affects plasma levels of serum amyloid A (SAA) and phospholipid transfer protein (PLTP) activity.
Design:  We measured the levels of SAA and PLTP activity in plasma of 66 patients with advanced periodontal disease before and after treatment by full-mouth tooth extraction (FME).
Results:  At baseline, median SAA levels in our study population were within the normal range (2.7 μg ml⁻¹) but SAA was elevated (>5 μg ml⁻¹) in 18% of periodontitis patients. Three months after FME, SAA levels were significantly reduced ( P  =   0.04). SAA did not correlate with any of the periodontal disease parameters. PLTP activity was elevated in patients with periodontitis, compared to the PLTP activity reference group (age-matched systemically healthy adults, n  =   29; 18 μmol ml⁻¹ h⁻¹ vs 13 μmol ml⁻¹ h⁻¹, respectively, P  =   0.002). PLTP activity inversely correlated with average periodontal pocket depth (PPD) per tooth ( r _s = −0.372; P  =   0.002). Three months after FME, median PLTP activity did not change significantly.
Conclusions:  Full-mouth tooth extraction significantly reduces SAA, a marker of inflammation, while it does not affect plasma PLTP activity. However, the inverse correlation between PLTP activity and average PPD suggests that increased PLTP activity may limit periodontal tissue damage.