Expression of cancer stem cell markers ALDH1 and Bmi1 in oral erythroplakia and the risk of oral cancer.

BACKGROUND: Oral erythroplakia (OE) is a notoriously aggressive oral pre-malignant lesion with a high tendency to oral cancer development, but its biological behavior is largely unknown. The objective of this study was to determine the expression of cancer stem cell markers ALDH1 and Bmi1 in OE and their correlation with malignant transformation of OE. METHODS: In a retrospective case-control study, expression patterns of ALDH1 and Bmi1 were determined using immunohistochemistry in samples from 34 patients with OE, including patients with untransformed lesions (n=17) and patients with malignant transformed lesions (n=17). RESULTS: ALDH1 and Bmi1 expression was observed in 19 (55.9%) and 20 (58.8%) of 34 patients with OE, respectively. Multivariate analysis revealed that ALDH1 expression was significantly associated with increased risk of transformation (P<0.05), but Bmi1 expression was not a significant marker (P > 0.05). Notably, the coexpression of both ALDH1 and Bmi1 was a strong indicator associated with 8.56-fold (95% confidence interval [CI], 1.74-42.17; P<0.01) for malignant transformation. Point prevalence analysis revealed that 78.6% (95% CI, 54.0-100) of the patient with coexpression of both ALDH1 and Bmi1 developed oral cancer. CONCLUSION: Our data indicated that the expression patterns of ALDH1 and Bmi1 in OE were associated with malignant transformation, suggesting that they may be valuable predictors for evaluating the risk of oral cancer.

Two stem cell markers, ATP-binding cassette, G2 subfamily (ABCG2) and BMI-1, predict the transformation of oral leukoplakia to cancer: a long-term follow-up study.

BACKGROUND: Although oral leukoplakia (OL) is the best-known potentially malignant disorder, the risk of OL malignant transformation is difficult to assess. ATP-binding cassette, G2 subfamily (ABCG2) and BMI-1 are stem cell markers that have been found to be associated with head and neck tumorigenesis. The objective of the current study was to evaluate the usefulness of ABCG2 and BMI-1 in predicting OL transformation. METHODS: In a retrospective cohort of 135 patients with OL from the study institution who had a mean follow-up of 5.5 years, 32 developed cancer between 1985 and 2008. The expression of ABCG2 and BMI-1 was determined using immunohistochemistry in samples from these patients, and included untransformed OL (n = 103) and malignant-transformed OL (n = 32). The association between protein expression and clinicopathological parameters and transformation was analyzed. RESULTS: Expression of ABCG2 and BMI-1 was observed in 58 (43.0%) and 44 (32.6%) of 135 patients, respectively. The correlation between ABCG2 and BMI-1 expression was significant (P = .024). Kaplan-Meier analysis revealed that 37.9% of patients with ABCG2 positivity developed cancer compared with 13.0% of patients with ABCG2 negativity (P = .014, log-rank test). Approximately 40.9% of patients with BMI-1 positivity developed cancer compared with 15.4% of patients with BMI-1 negativity (P = .029, log-rank test). Multivariate analysis revealed that ABCG2 and BMI-1 expression was associated with a 3.24-fold (95% confidence interval [95% CI], 1.31-7.98; P = .011) and 4.03-fold (95% CI, 1.59-10.26; P = .003) increased the risk of transformation, respectively. CONCLUSIONS: ABCG2 and BMI-1 expression was found to be associated with the development of oral cancer in a large cohort of patients with OL for whom long-term follow-up was available, which suggests that ABCG2 and BMI-1 may be used as predictors of OL transformation.

A retrospective clinicopathological study on oral lichen planus and malignant transformation: analysis of 518 cases.

OBJECTIVE: To investigate the epidemiological and clinical characteristics of a relatively large cohort of patients with oral lichen planus (OLP) from eastern China. STUDY DESIGN: A total of 518 patients with histologically confirmed OLP in a long-term follow-up period (6 months-21.5 years) were retrospectively reviewed in our clinic. RESULTS: Of the 518 patients, 353 females and 165 males were identified. The average age at diagnosis was 46.3 years (range 9-81 years) with the buccal mucosa being the most common site (87.8%). At initial presentation, white lichen and red lichen was seen in 52.3% and 47.7% patients, respectively. Of these, 5 (0.96%) patients previously diagnosed clinically and histopathologically as OLP developed oral cancer. All of them were the females with no a history of smoking or alcohol use. CONCLUSIONS: Clinical features of eastern Chinese OLP patients were elucidated. Notably, approximately 1% of OLP developed into cancer, which provides further evidence of potentially malignant nature of OLP.

Metal-Protein Nanoparticles Facilitate Anti-VSV and H1N1 Viruses Through the Coordinative Actions on Innate Immune Responses and METTL14.

Host defense systems can invade viral infection through immune responses and cellular metabolism. Recently, many studies have shown that cellular metabolism can be reprogrammed through N6 -methyladenosine (m6 A) modifications during viral infection. Among of them, methyltransferase like-14 enzyme (METTL14) plays an important role in m6 A RNA modification, yet its antiviral function still remains unclear. In this work, it is uncovered that metal-protein nanoparticles designated GSTP1-MT3(Fe2+ ) (MPNP) can polarize macrophages toward the M1 phenotype and activate immune responses to induce Interferon-beta (IFN-ß) production in vesicular stomatitis virus (VSV)-infected macrophages. Further investigation elucidates that a high dose of IFN-ß can promote the expression of METTL14, which has a well anti-VSV capacity. Moreover, it is found that other negative-sense single-stranded RNA viruses, such as influenza viruses (H1N1(WSN)), can also be inhibited through either immune responses or METTL14. Collectively, these findings provide insights into the antiviral function of METTL14 and suggest that the manipulation of METTL14 may be a potential strategy to intervene with other negative-sense single-stranded RNA viruses infections.

Oral cancer development in patients with leukoplakia--clinicopathological factors affecting outcome.

BACKGROUND: Oral leukoplakia (OL) is the best-known potentially malignant disorder. The objective of the current study was to evaluate the clinicopathological factors predictive of outcome in a large cohort of patients with OL, and report our experience in the early detection of malignant events. METHODS: A total of 320 patients with biopsy-proven OL were retrospectively reviewed from the study institution who had a mean follow-up of 5.1 years. Data on patient and lesion at initial diagnosis and patient underwent sequential biopsies were reviewed. Multiple biopsies indicates > = 3 times sequential biopsies. Oral cancer-free survival rate (OCFS) was determined by the Kaplan-Meier method and significant factors were identified by Cox regression analysis. RESULTS: The 3-year and 5-year OCFS was 86.6% and 82.0%, respectively. A new binary system of grading oral dysplasia was performed and Kaplan-Meier analysis indicated that high-grade dysplasia had significantly higher malignant incidence than low-grade dysplasia (5-year OCFS, 90.5% vs 59.0%; P<0.001), especially during the first 2-3 years of follow-up. Multivariate analysis revealed that the 4 factors including patient aged >60 years, lesion located at lateral/ventral tongue, non-homogenous lesion, high-grade dysplasia were independent significant indicators for OL malignant transformation. In addition, significant positive correlation between the multiple biopsies and these 4 factors and malignant outcome was established. CONCLUSIONS: Elderly patients with OL located at lateral/ventral tongue and who had non-homogenous lesion with high-grade dysplasia correlated much higher risk of transformation. This high-risk subpopulation was suggested to undergo sequential biopsies and histologic examination contributing to early detection of malignant event.

Expression of podoplanin and ABCG2 in oral erythroplakia correlate with oral cancer development.

Oral erythroplakia (OE) is a notoriously aggressive oral premalignant lesion with a high tendency to oral cancer development, but it's biological behavior is largely unknown. The objective of the current study was to determine podoplanin and ABCG2 immunoexpression in OE and both correlation to malignant transformation of OE. In a retrospective follow-up study, the expression patterns of podoplanin and ABCG2 were determined using immunohistochemistry in samples from 34 patients with OE, including patients with untransformed lesions (n=17) and patients with malignant transformed lesions (n=17). Podoplanin and ABCG2 expression was observed in 15 (44.1%) and 21 (61.8%) of 34 patients, respectively. Multivariate analysis revealed that podoplanin and ABCG2 expression was associated with 6.31-fold (95% confidence interval [CI], 1.02-38.92; P=0.047) and 14.39-fold (95% CI, 2.02-102.29; P=0.008) increased the risk of transformation, respectively. Point prevalence analysis revealed that 90.9% (95% CI, 70.7-100) of the patient with both podoplanin and ABCG2 positivity developed oral cancer. Collectively, our data indicated that the expression patterns of podoplanin and ABCG2 in OE were associated with oral cancer development, suggesting that podoplanin and ABCG2 may be valuable predictors for evaluating oral cancer risk.

Squamous cell carcinoma development in previously diagnosed oral lichen planus: de novo or transformation?

OBJECTIVES: The objectives of this study were to investigate the incidence of oral squamous cell carcinoma (OSCC) developing in lesions that were previously diagnosed as oral lichen planus (OLP), and to evaluate potential contributing factors that might be associated with an increased risk for the development of OSCC in these patients. STUDY DESIGN: We retrospectively reviewed a relatively large cohort of 518 patients with OLP who received long-term follow-up (range, 6 months-21.5 years). RESULTS: There were 353 females and 165 males. Of these, 5 (0.96%) patients developed OSCC with a mean duration of 70 months. All were females with no history of smoking or alcohol use. Four of them received corticosteroid therapy. Notably, 1 of these patients received systemic corticosteroid therapy 13 months before transformation, and died of metastatic disease 46 months after transformation. CONCLUSIONS: The incidence of OSCC developing in lesions previously diagnosed as OLP is less than 1%, and females were more commonly affected. These cases appear to represent the transformation of OLP into OSCC, however it cannot be entirely ruled out that these cases may represent de novo OSCC.

[A 3-year retrospective assessment of deciduous teeth caries in 372 children aged 3 year-old in Shanghai].

PURPOSE: To observe the 3 years changes of deciduous teeth caries in 372 children aged 3 years old in Shanghai. METHODS: 372 samples of 3 year-old children from kindergartens in Shanghai were selected for clinical examination.The prevalence of dental caries,mean dmft score, caries severity index(CSI) and caries filling rate were calculated. The results were analyzed with SPSS13.0 software package for Chi(2) test, ANOVA and SNK. RESULTS: It was found that from 2005 to 2007,the prevalence of dental caries was 40.90%, 50.80% and 62.40%, respectively. The mean dmft was 2.17+/-3.38+/-2.56+/-3.61 and 3.15+/-3.87, respectively. The CSI was 6.38+/-11.16+/-7.67+/-12.04 and 8.73+/-13.03, respectively. The caries filling rate was 5.35%,13.46% and 18.15%,respectively. The prevalence of dental caries, mean dmft, CSI and caries filling rate increased gradually as the children grew up. There was significant difference among 3 years (Chi(2)=16.423,P<0.01;F=8.185,P<0.01;F=3.509,P<0.05;Chi(2)=16.423,P<0.05). SNK analysis showed that there was significant difference of dmft between 2005 and 2006 ,2005 and 2007 was found. Significant difference of CSI only between 2005 and 2007. No significant difference of incidence of caries between 2006 and 2007 was found. There was no significant difference between male and female in prevalence of dental caries,mean dmft,CSI and caries filling rate (P>0.05). CONCLUSION: The trend that the status of dental caries rapidly increases as the children grow up is decreasing in Shanghai;the filling rate is still very low, early prevention and treatment for deciduous caries are needed. Supported by Shanghai Municipal Health Bureau for Development of Science and Technology (Grant No.044034).