Oral submucous fibrosis

The Separation Anxiety Syndrome in Animals (SASA) and being more specific, in dogs, can be defined as a group of undesirable behaviors displayed by dogs when they are away from the attachment subject. The questionnaire was developed due to the need to identify this disorder and conduct an epidemiologic survey on SASA in dogs (QI-SASA). This instrument was developed based on reference data and was validated through two procedures. The first one was the comparison among evaluations of Brazilian ethologists on the appliance of 40 QI-SASA to dogs' owners. The second was the comparison between the previous evaluations, according to the criteria established in this research, with the results of the interviews to diagnose SASA. The QI-SASA seems to be a complete, safe and trustworthy tool to carry out epidemiologic surveys on SASA.

BACKGROUND: Very few reports have been published on the gender specificity of oral submucous fibrosis (OSF) in relation to habit patterns and the severity of disease in the world literature. The purpose of the study was to ascertain the gender specificity for different habits and severity of OSF. METHODS: A hospital-based cross-sectional study on various habit patterns associated with OSF was performed in Nagpur over a 5-year period. A total of 1000 OSF cases from 266 418 out patients comprised the study sample. RESULTS: The male-to-female ratio of OSF was 4.9:1. Occurrence of OSF was at a significant younger age group (<30 years) among men when compared with women (OR ¼ 4.62, 3.22-6.63, P ¼ 0.0001). Reduced mouth opening, altered salivation and altered taste sensation were found to be significantly more prevalent in women when compared with men. Exclusive areca nut chewing habit was significantly more prevalent in women (OR ¼ 44.5, 25.4-79.8, P ¼ 0.0001). Whereas significant increase for Gutkha (Areca quid with tobacco) (OR ¼ 2.33, 1.56-3.54, P ¼ 0.0001) and kharra/Mawa (crude combination of areca nut and tobacco) (OR ¼ 6.8, 4.36-11.06, P ¼ 0.0001) chewing was found in men when compared with women. CONCLUSIONS: There is a marked difference in literacy, socioeconomic status, areca nut chewing habits, symptoms and disease severity in women when compared with men in the central Indian population.

Those people are constantly chewing a fruit which they call areca, and which resembles a pear. They cut that fruit into four parts, and then wrap it in the leaves of their tree which they call betre…They mix it with a little lime, and when they have chewed it thoroughly, spit it out. It makes the mouth exceedingly red. All the people in those parts of the world use it, for it is very cooling to the heart, and if they ceased to use it they would die. Antonio Pigafetta, physician on Magellan's circumnavigation of the globe Limasawa, Leyte, Philippines, 1521 1 Betel is a compound of several natural substances chewed for its mild psychostimulating effects. Betel is composed of the fruit or nut of the areca palm (Areca catechu), the leaf of the betel pepper (Piper betle), and lime (calcium hydroxide, not the citrus fruit). Approximately 200 million persons chew betel regularly throughout the western Pacific basin and south Asia (Fig. 1). 2,3 Only three drugs-nicotine, ethanol, and caffeine-are consumed more widely than betel. 4 When arecanut, lime, and pepper leaf are chewed together, the compound produces a bloodred color and the desired psychoactive effects. The red juice can stain oral structures and after many years of use, the teeth may become nearly black (Fig. 2). Betel chewing is also associated with oral leukoplakia, submucous fibrosis, and squamous cell carcinoma. BOTANICAL ASPECTS The requisites for chewing area small piece of areca nut, a leaf of the Sirih or betel pepper, a little moistened lime, and, if people wish to be very luxurious, a paste made of spices.

OBJECTIVE: To investigate the prevalence and the associated risk factors of oral precancerous disorders in southern Taiwan. METHODS: We conducted a cross-sectional community survey interviewing 1075 adult subjects, 15 years of age and over, gathered from randomly selected 591 households, and spanning five villages in southern Taiwan. The study protocol included a visual oral soft tissue examination and a questionnaire-based interview. The chisquare test was used to test the differences in prevalence of oral precancerous lesions and conditions by different 'life styles' relating to current risk habits of current areca quid chewing, smoking, and alcohol drinking. To control for possible confounding, a logistic regression model was used to estimate the Odds Ratios (OR) for leukoplakia and oral submucous fibrosis (OSF). RESULTS: 136 precancerous lesions and conditions were detected among 1075 subjects (12.7%). The analysis of the spectrum of oral precancerous disorders detected, leukoplakia (n ¼ 80), OSF (n ¼ 17) and verrucous lesions (n ¼ 9), demonstrated an association with gender (P < 0.001). There were statistically significant associations among leukoplakia (P < 0.01), OSF (P < 0.0001), and verrucous lesions (P < 0.0001) and the life style of current areca quid chewing, smoking, and alcohol drinking. The synergistic effect of smoking and areca quid chewing habit on leukoplakia and OSF was demonstrated. CONCLUSION: This study reinforces the association of current areca quid chewing without tobacco, cigarette smoking, and alcohol drinking to leukoplakia, OSF, and verrucous lesions in Taiwan. J Oral Pathol Med (2005) 34: 460-6

Oral submucous fibrosis (OSF) is a well-recognisedpotentially malignant condition of the oral cavity associated with areca nut chewing. Areca nut has been shown to have a high copper content compared to other commonly eaten nuts, and chewing areca nut for 5-30 min significantly increases soluble copper in whole mouth fluids. Our aims were to determine if tissue and serum concentrations of copper were raised in patients with OSF as a result of chewing areca nut. A panel of buccal mucosal biopsies from patients with OSF from Nagpur, India, was used to measure the tissue concentrations of copper by mass absorption spectrometry (MAS). By MAS, the mean tissue copper level was 5.5∫2.9 mg/g in the OSF specimens (nϭ11) compared with 4∫1.9 mg/g in the non-areca chewing controls (nϭ7) (Pϭ0.2). Energy dispersive x-ray microanalysis (EDX) was used to identify the presence and distribution of the metal element. EDX showed distinct peaks corresponding to copper (K a , 8.04 keV; K b , 8.91 keV) in the epithelium (21/23) and in the connective tissue (17/23) of the OSF specimens compared to spectra obtained from control oral biopsies from non-areca chewing subjects (nϭ7). These findings were confirmed by secondary ion mass spectrometry (SIMS) analysis in a small number of samples. Serum copper (17.23∫1.80 mmol/l), caeruloplasmin (0.32∫0.04 g/l) levels and urinary copper (0.52∫0.26 mmol/l) in OSF patients (nϭ14) were within the laboratory reference ranges. The finding of copper in OSF tissue supports the hypothesis of copper as an initiating factor in OSF, playing a role in stimulating fibrogenesis by the upregulation of lysyl oxidase activity.

Oral submucous fibrosis (OSF) is a premalignant condition mainly associated with the practice of chewing betel quid containing areca nut, a habit common among South Asian people. It is characterized by inflammation, increased deposition of submucosal collagen and formation of fibrotic bands in the oral and paraoral tissues, which increasingly limit mouth opening. Recently, OSF has been reported among South Asian immigrants in Canada, the United Kingdom and Germany. Dentists in western countries should enhance their knowledge of this disease as it seems to be increasing with population migration. In this paper, we review the literature on OSF and present 3 cases representing different stages of the disease to help dentists make an early diagnosis and reduce the morbidity and mortality associated with this condition.

Smokeless tobacco consumption leads to oral submucous fibrosis (OSMF) condition, which is a long-lasting devastating condition of oral cavity having the potential of malignancy across the world. In this review, we mainly focus on smokeless tobacco such as paan and gutkha consumption, and their role in the induction of OSMF and finally oral cancer. The list of articles to be examined was established using citation discovery tools provided by PubMed, Scopus and Google Scholar. The continuous chewing of paan and swallowing of gutkha triggers the progressive fibrosis of sub-mucosal mucous tissue. Usually, the condition arises initiated from multifactorial risks especially smokeless tobacco, such as betel quid, areca nuts, and slaked lime used in paan and gutkha, which progressively lead to OSMF. The incidence of oral cancer is high in women as compared to men across the Southern Asian countries. The human oral epithelium cells are affected due to slake lime present in the betel quid and...

Oral submucous fibrosis (OSF) is a pre-malignant fibrotic lesion of the mouth in areca quid chewers. It is probably a consequence of disturbances in the hemeostatic equilibrium between synthesis and degradation of extracellular matrix molecules (ECM). To date, there has been little research about the role of tissue inhibitors of metalloproteinase (TIMPs) and matrix metalloproteinases (MMPs) in the pathogenesis of OSF. In the present study, we examined the activity of TIMPs from cells cultured from OSF and normal buccal mucosa. OSF specimens were found to have higher TIMP-1 expression than normal buccal mucosal fibroblasts (BMFs) by Western blots. To verify whether arecoline, a major areca nut alkaloid, could affect TIMP or MMP production by human BMFs, Western blots and gelatine zymography were used. Arecoline was found to elevate TIMP-1 expression at the concentration level under 20 mg/ml in a dose-dependent manner. The amount of TIMP-1 was about 2.7 fold at a concentration level of 10 mg/ml compared with control. From gelatin zymograms, the main gelatinolytic proteinase secreted by the human BMFs was MMP-2, and only minimal amounts of MMP-9 could be detectable from zymogram. In addition, arecoline was found to inhibit MMP-2 secretion and production at the concentration level of 40 mg/ml. The gelatinolytic activity of MMP-2 was about 54% at a concentration level of 80 mg/ml compared with control. Taken together, it was found that arecoline acted not only as an inhibitor on gelatinolytic activity of MMP-2, but also a stimulator for TIMP-1 activity. These synergistic effects may contribute to the ECM components accumulation in the areca quid associated OSF. #

Role of areca nut in the causation of oral submucous fibrosis: a casecontrol study in Pakistan. J Oral Pathol Med 1994; 23: 65-69. 3 Ma RH, Tsai CC, Shieh TY. Increased lysyl oxidase activity in fibroblasts cultured from oral submucous fibrosis associated with betel nut chewing in Taiwan. Esposito JJ. PCR strategy for identification and differentiation of smallpox and other orthopoxviruses. J Clin Microbiol 1995; 33: 2069-76. 4 Massung RF, Esposito JJ, Liu LI, et al. Potential virulence determinants in terminal regions of variola smallpox virus genome. Nature 1993; 366: 748-51. 5 Douglass N, Dumbell KR. Independent evolution of monkeypox and variola viruses.

Objective : Turmeric extract and turmeric oil have shown chemoprotective effect against chemicallyinduced malignancies in experimental animals. They can reverse precancerous changes in oral submucous fibrosis in humans. The use of turmeric or Curcuma longa Linn as a spice and household remedy has been known to be safe for centuries. In view of the long term administration required for cancer prevention a Phase I clinical trial of turmeric oil (TO) was designed to study the safety and tolerance of TO in volunteers for a period of 3 months. Material and Methods : Nine healthy volunteers between 20 and 33 years of age were tested for haemoglobin, blood counts, liver and kidney functions, bleeding and clotting time and serum electrolytes initially and at 1 and 3 months of treatment. They were administered 0.6 ml of TO three times a day for 1 month and 1 ml in 3 divided doses for 2 months. The acute tolerability study on Day 1 was conducted in a Clinical Pharmacology daycare Unit. Blood pressure and pulse were recorded frequently on Day 1 and at 24, 48, 72 and 96 hours and fortnightly till 12 weeks. Volunteers were daily supervised for TO intake as well as for any side effects throughout the study period. Results : Nine volunteers were enrolled for the study. One discontinued on 3rd day for allergic skin rashes which, on discontinuation of TO, gradually disappeared by two weeks. Another discontinued on 7th day for intercurrent fever requiring antibiotic treatment. Seven volunteers completed the study. There was no effect of TO, in two doses, on pulse and blood pressure and no side effects in acute tolerability study on Day 1. There was no effect of TO intake on weight, blood pressure, symptoms and signs upto 12 weeks. There was no clinical, haematological, renal or hepatic-toxicity of TO at 1 month and 3 months. Serum lipids did not show significant change except in one volunteer (reversible). Conclusions : In view of the potential for reversing oral submucous fibrosis, a precancerous condition for oral cancer, TO, can be recommended directly for a Phase II trial in patients.

Background and objective. Oral submucous fibrosis has been a scourge of southeastern Asia and its residents since time immemorial. Sscores of medicinal agents, singly and in combination, have been tried with not very encouraging results. In this study, therefore, we have restricted ourselves to different surgical modalities in the management of this condition and have tried to lay down indications of each surgical procedure. Study design. A total of 100 patients of oral submucous fibrosis were included in this study and randomly allocated to different surgical groups, 25 patients per group. After excision of fibrous bands, group I had buccal fat pad graft, group II had tongue flap, group III had nasolabial fold flap, and group IV had split skin graft for correction of mucosal defect created after incising the fibrous bands. Results. Mean preoperative mouth opening was 14.82 (SD 4.38) mm and ranged between 4.00 and 25.00 mm. Statistically there was no significant difference among the 4 groups (P ϭ .996). Mean postoperative mouth opening at 1 week was 35.79 (3.53) mm, ranging between 24.00 and 42.00 mm. Mean postoperative mouth opening at 1 month in group I was 36.36 (2.64) mm, in group II 35.36 (29) mm, in group III 35.64 (2.94) mm, and in group IV 35.80 (3.24) mm. Total score for pain, esthetics, and function at 1 month after surgery was highest (11.29) in group I, indicating better results. Conclusion. The results were very encouraging, and we were able to lay down specific indications for each procedure. However, we believe buccal fat pad rotation is superior to other procedures, because it offers ease of surgery, can be performed under local anesthesia as a day care procedure, shows little postoperative morbidity, and has good patient acceptance, and there appear to be no contraindications to its use. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;107:e1-e10)

Oral submucous fibrosis (OSF) is a premalignant, fibrosing disorder of the mouth, pharynx, and oesophagus, with a malignant transformation rate of 7-13%. OSF is strongly associated with areca (betel) nut chewing and worldwide, over 5 million people are affected. As αvβ6 integrin is capable of promoting both tissue fibrosis and carcinoma invasion, we examined its expression in fibroepithelial hyperplasia and OSF. αvβ6 was markedly up-regulated in OSF, with high expression detected in 22 of 41 cases (p < 0.001). We investigated the functional role of αvβ6 using oral keratinocyte-derived cells genetically modified to express high αvβ6 (VB6), and also NTERT-immortalized oral keratinocytes, which express low αvβ6 (OKF6/TERT-1). VB6 cells showed significant αvβ6-dependent activation of TGF-β1, which induced transdifferentiation of oral fibroblasts into myofibroblasts and resulted in up-regulation of genes associated with tissue fibrosis. These experimental in vitro findings were confirmed using human clinical samples, where we showed that the stroma of OSF contained myofibroblasts and that TGF-β1-dependent Smad signalling was detectable both in keratinocytes and in myofibroblasts. We also found that arecoline, the major alkaloid of areca nuts, up-regulated keratinocyte αvβ6 expression. This was modulated through the M 4 muscarinic acetylcholine receptor and was suppressed by the M 4 antagonist, tropicamide. Arecoline-dependent αvβ6 up-regulation promoted keratinocyte migration and induced invasion, raising the possibility that this mechanism may support malignant transformation. Over 80% of OSF-related oral cancers examined had moderate/high αvβ6 expression. These data suggest that the pathogenesis of OSF may be epithelial-driven and involve arecoline-dependent up-regulation of αvβ6 integrin. .thejournalofpathology.com 1-4 (1, focal staining confined to basal layer; 2, diffuse staining confined to basal layer; 3, diffuse staining of basal and suprabasal layers; and 4, diffuse staining of full thickness of epithelium). The score for intensity was added to the score for proportion to give a score in the range of 0-7 and grouped as negative (score = 0), low (score = 1-4), or high (score = 5-7). No strong expression was detected in hyperplastic oral mucosa; however, there was significantly higher expression in OSF, with high expression seen in 22 cases (54%; p < 0.001). . (A) TGF-β1 activation assay. Co-culture of VB6 cells with mink lung epithelial reporter cells (MLEC) promoted TGF-β1 activation, which was suppressed by antibody blockade of αvβ6 integrin (6.3G9). TGF-β1 activation was significantly higher in VB6 cells than in OKF6/TERT-1 and IC6pr cells. (B) HFFF2 cells and VB6 cells were co-cultured on glass coverslips and treated with control (7.2; i-iv) or anti-αvβ6 (6.3G9; v-viii) antibodies. Confocal micrograph shows cell nuclei (blue; i and v), αvβ6-positive VB6 cells (red; ii and vi), SMA-positive myofibroblasts (green; iii and vii), or the combined images (right; iv and viii). When co-cultured with VB6, HFFF2 cells up-regulated SMA indicating myofibroblastic transdifferentiation (i-iv). The transdifferentiation was suppressed by inhibiting αvβ6 (v-viii). Scale bar = 50 µM. (Ci) Western blotting showing that high-αvβ6-expressing VB6 cells induce myofibroblast transdifferentiation more effectively than IC6pr control cells, which are αvβ6-negative. VB6-dependent myofibroblastic transdifferentiation was suppressed by an αvβ6 inhibitory antibody (ii). Histograms represent the combined densitometric analyses from three sets of experiments. (D) Collagen gel contraction assay. Co-culture of VB6 cells and POF promoted myofibroblast-dependent gel contraction (i). This was αvβ6-dependent and suppressed by an αvβ6 inhibitory antibody (ii). Histograms represent the combined gel weights from four independent experiments. (E) SMA and Smad immunohistochemistry. SMA-positive myofibroblasts were not detectable in fibroepithelial hyperplasia (i), but were prominent within the lamina propria of OSF cases (ii, iii). pSmad2-and Smad4-positive nuclei (v and vi, respectively) were prominent in both keratinocytes and myofibroblasts in OSF, compared with fibroepithelial hyperplasia (iv), confirming activated TGF-β1 signalling.

Copper is implicated in the pathogenesis of several fibrotic disorders. Areca nut has been shown to have a high copper content and areca chewing is associated with oral submucous fibrosis (OSF). The effects of copper on human oral fibroblasts were investigated in vitro. Human oral fibroblasts were incubated with copper chloride (CuCl 2 ) at concentrations ranging from 0.01 mM to 500 mM for 24 h, and in vitro cell proliferation was assayed by incorporation of tritiated-thymidine; soluble and non-soluble collagen synthesis was assayed using tritiated-proline. Addition of copper chloride at concentrations ranging from 0.1 mM to 50 mM increased the collagen synthesis by the oral fibroblasts compared with growth without copper (PϽ0.05). The addition of copper chloride neither increased the synthesis of non-collagenous proteins by the fibroblasts nor influenced their proliferation rate. We conclude that copper upregulates collagen production in oral fibroblasts. This appears to be concentration dependent, with peak collagen synthesis at 50 mM CuCl 2 . These in vitro results taken together with the recent findings of copper in oral biopsies from OSF subjects support the hypothesis that copper in areca nut acts as a mediator of OSF.

Objective. The objective of this study was to evaluate the sensitivity and specificity of modified brush biopsy without computer-assisted analysis in the detection of oral premalignant and malignant lesions. Study design. Ninety-four patients attending outpatient clinics who exhibited oral lesions suspicious of premalignancy or malignancy were enrolled. All patients underwent an oral brush biopsy using a baby toothbrush followed by a scalpel biopsy. The specimens were analyzed manually in a double-blinded fashion. Sensitivity and specificity were used for the statistical analysis of the samples. Statistical significance was determined using the normal approximation to the binomial distribution of matched results, approximated by the Student t distribution mean test (paired t test). Results. Seventy-nine patients with adequate transepithelial brush biopsy samples were included in the study group. When compared to scalpel biopsy, the statistical sensitivity of the brush biopsy was greater than 76.8% (P Ͻ .05) while the statistical specificity was greater than 93.3% (P Ͻ .05). There were 4 false negative brush biopsy cases. The 4 false negative patients turned out to be dysplasia/ malignancy on histopathology. All 4 were patients with clinical oral submucous fibrosis. Conclusion. The oral brush biopsy without computer-assisted analysis was found to be a painless, noninvasive test for evaluating oral lesions. The toothbrush brush biopsy with manual analysis had marginally lower sensitivity and specificity than the commercially available oral brush biopsy with computer-assisted analysis. The results demonstrate that by using a toothbrush to obtain an oral brush biopsy sample, oral lesions can be easily evaluated in a resource challenged settings to rule out dysplasia and carcinoma.

Oral submucous fibrosis (OSF) is considered as a pre-cancerous condition of the oral mucosa and is highly associated with habitual areca quid
chewing. Arecoline is the major alkaloid in areca quid and is thought to be involved in the pathogenesis of OSF. Our previous studies have demonstrated
that arecoline could induce epithelial–mesenchymal transition (EMT)-related factors in primary human buccal mucosal fibroblasts
(BMFs). Therefore, we investigated the expression of zinc finger E-box binding homeobox 1 (ZEB1), which is a well-known transcriptional factor
in EMT, in OSF tissues and its role in arecoline-induced myofibroblast transdifferentiation from BMFs. The expression of ZEB1, as well as the
myofibroblast marker a-smooth muscle actin (a-SMA), was significantly increased in OSF tissues, respectively. With immunofluorescence
analysis, arecoline induced the formation of a-SMA-positive stress fibres in BMFs expressing nuclear ZEB1. Arecoline also induced collagen
contraction of BMFs in vitro. By chromatin immunoprecipitation, the binding of ZEB1 to the a-SMA promoter in BMFs was increased by arecoline.
The promoter activity of a-SMA in BMFs was also induced by arecoline, while knockdown of ZEB1 abolished arecoline-induced a-SMA promoter
activity and collagen contraction of BMFs. Long-term exposure of BMFs to arecoline induced the expression of fibrogenic genes and
ZEB1. Silencing of ZEB1 in fibrotic BMFs from an OSF patient also suppressed the expression of a-SMA and myofibroblast activity. Inhibition of
insulin-like growth factor receptor-1 could suppress arecoline-induced ZEB1 activation in BMFs. Our data suggest that ZEB1 may participate in
the pathogenesis of areca quid–associated OSF by activating the a-SMA promoter and inducing myofibroblast transdifferentiation from BMFs.

This study was conducted to assess the prevalence of various oral mucosal lesions (OML) among alcohol misusers attending a rehabilitation center in Chennai, south India. Materials and Methods: Qualified dental surgeons examined 500 consecutive alcohol misusers at Ragas Dental College and Hospital and TTK Hospital, India. Thorough history and oral findings were recorded in a pre-determined format. Data entry and statistical analysis were done using SPSS 10.0.5  . The variables for this study were OML, Oral Hygiene Index (OHI), age, smoking, and alcohol misuse (type and units consumed and duration of misuse). Results: Of the 500 patients, 77% were in the 25-44 years old age group and 84% were married. The mean age of initiation of alcohol misuse was 34 years. In addition to alcohol, 72% smoked tobacco and 96% used other psychoactive substances. The mean alcohol use duration was 12.6 years. A total of 25% of the study group had at least one OML. The common oral lesions were smoker's melanosis (10.2%), oral submucous fibrosis (8%), and leukoplakia (7.4%). Those who misused spirits had a higher incidence of OML than those who misused beer or both. Patients with fair oral hygiene had an odds ratio (OR) of 2.96 for OML compared with an OR of 2.08 for those who had OML with good oral hygiene. Conclusion: This study indicates that subjects who misuse alcohol have poor oral hygiene and are at risk for the development of periodontal disease and OML. This survey indicates that oral examination and treatment should be a part of the standard care for alcohol misusers at rehabilitation centers.

Mast cells (MCs) expressing serine proteases; tryptase and chymase, are associated with fibrosis in various diseases. However, little is known about their involvement in oral submucous fibrosis (OSF). Our goal was to evaluate the role of MC tryptase and chymase in the pathogenesis of OSF and its malignant transformation. Immunohistochemical expression of MC tryptase and chymase was evaluated in 20 cases of OSF, 10 cases of oral squamous cell carcinoma (OSCC) and 10 cases of healthy controls. Subepithelial zone of Stage 1 and 2 while deep zone of Stage 3 and 4 OSF demonstrated increased tryptase positive MCs. OSCC revealed a proportionate increase in tryptase and chymase positive MCs irrespective of areas of distribution. An altered balance in the subepithelial and deep distribution of tryptase and chymase positive MCs play an important role in the pathogenesis of OSF and its malignant transformation.

Background: Matrix metalloproteinases (MMPs) are enzymes that degrade all the components of extra cellular matrix and collagen. Various types of MMPs are known to be expressed and activated in patients with oral submucous fibrosis (OSMF) as well as head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to asses the association of the single nucleotide polymorphism (SNP) adenosine insertion/deletion polymorphism (-1171 5A->6A) in the MMP-3 promoter region in these lesions. Methods: MMP-3 SNP was genotyped by polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) analysis in a case control study consisting of 362 participants; 101 cases of OSMF, 135 of HNSCC and 126 controls, compared for age, sex and habits. ROC distribution was plotted to assess the contributions of genetic variation in MMP-3 genotypes with relation to age. Results: Analysis of MMP 3 (-1171 5A->6A) polymorphism revealed the frequency of 5A allele in OSMF, HNSCC and controls to be 0.15, 0.13 and 0.07, respectively. A significant difference was found in 5A genotype frequency between OSMF (5A genotype frequency = 0.15, p = 0.01, OR = 2.26, 95% CI = 1. 22-4.20) and in controls (5A genotype frequency 0.07) as well as HNSCC (5A genotype frequency 0.13, p = 0.03,95%CI = 1.06-3.51) and controls (5A genotype frequency = 0.07) In this study, 5A genotype had greater than two fold risk for developing OSMF (OR = 2.26) and nearly the same in case of HNSCC (OR = 1.94) as compared to controls. In patients with OSMF as well as HNSCC, the ROC analysis between the MMP-3 genotype and age, 6A/6A allele was found to be significant in patients both over and under 45 years of age; while the 5A/5A carrier alleles showed an association only in patients less than 45 years of age.

J Oral Pathol Med (2010) 39 141–148Background:  Cholesterol at either higher/lower level can be troublesome. Health issues related to higher than normal levels have received much public attention because of their relationship to incidence of heart disease, whereas implications of decreased cholesterol levels remain unclear. Present study tried to evaluate and correlate the decreased cholesterol levels in Oral cancer, Oral precancer and in tobacco abuse.Methods:  Total Cholesterol (TC), High Density Lipoproteins (HDL), Very Low Density Lipoproteins (VLDL), Low Density Lipoproteins (LDL) and Triglyceride (Tri) were estimated in 210 subjects. Out of these 210 subjects, 70 subjects were histopathologically confirmed Oral Cancer, 70 subjects were histopathologically confirmed Oral precancer (OPC) and 70, age and sex matched, healthy subjects who are not having Oral Cancer, Oral precancer and who had no history of any major illness in the past. These groups were subdivided into: Subjects with No Habit of Tobacco (NHT) and Subjects With Habit of Tobacco (WHT).Results:  There was significant decrease in TC, HDL, VLDL, and triglyceride in Oral Cancer group; and significant decrease in TC, and HDL in Oral precancer group as compared to Control. Mean serum lipid profile levels were not significantly different in subjects between NHT and WHT.Conclusions:  There is an inverse relationship between serum lipid profile and Oral Cancer and Oral precancer. There was no overall significant correlation of serum lipid profile with tobacco abuse.

s u m m a r y Background: Oral cancer (OC) is the leading cause of death from cancer in men between the ages of 25 and 44 in Taiwan. The survival rate for the last stage of OC is <20% while that for the earliest stage is >75%, which suggests the importance of the diagnosis of oral precancerous lesions (OPLs) in reducing OC mortality. The aim of this study was to analyze the time to OC event after OPL diagnosis, and to suggest the surveillance period necessary according to OPL type. Materials and methods: This was a retrospective cohort study based on 1.0 million people randomly selected from the Taiwan National Health Insurance Database, which provided data on 3058 adult male patients aged P20 years who were diagnosed with OPL for the first time between 1996 and 2009. The patient population was divided into two groups according to the type of lesion: oral submucous fibrosis (OSF) or oral leukoplakia (OLE). Age-standardized incidence rate (ASIR) and hazards rate (HR) were then estimated. Results: The ASIR for OPL showed an increasing trend over the study period, the main contributor to this being OSF. The OSF group demonstrated a higher OC incidence rate than the OLE group. Conclusion: Patients with both OLE and OSF carry a higher risk for OC than those with either OLE or OSF alone, and they may also experience malignant transformation at an earlier date (mostly within 5 years). The 5-and 10-year OC rate for both OLE and OSF was found to be 5% and around 10%, respectively. However, 10 years after the diagnosis of OPL, OSF carries a higher risk of developing into OC than OLE.

Background: Oral lichen planus (OLP) is a T cell-mediated inflammatory disease. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that has effects on cellular and humoral immunities. Previous studies have shown that keratinocytes and tissue-infiltrating mononuclear cells from OLP lesions can secrete IL-6. In some OLP patients, the high serum IL-6 levels are reduced after treatment, suggesting that IL-6 may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of OLP.Methods: In this study, we used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of IL-6 in a group of 180 patients with erosive OLP (EOLP), nonerosive OLP (NEOLP), erythema multiforme (EM), traumatic ulcers (TU), oral submucous fibrosis (OSF), pemphigus vulgaris (PV), or Sjögren's syndrome (SS), and in 77 normal control subjects. Some OLP patients were treated with levamisole plus Chinese medicinal herbs or levamisole only for 0.5–5.5 months and their serum IL-6 levels were measured after treatment.Results: We found that approximately 99% of the normal control subjects and the patients with EM, TU, or OSF had a normal serum IL-6 level less than 5.0 pg/ml. However, 15% (22/149) OLP patients, 15% (20/136) EOLP patients, 20% (5/25) major type EOLP patients, 14% (15/111) minor type EOLP patients, 15% (2/13) NEOLP patients, 14% (1/7) EM patients, 43% (3/7) PV patients, and 100% (6/6) SS patients had a serum IL-6 level greater than 5.0 pg/ml. The mean serum IL-6 level in patients with OLP (3.4 ± 3.1 pg/ml, P < 0.001), EOLP (3.4 ± 3.2 pg/ml, P < 0.001), major type EOLP (4.9 ± 3.5 pg/ml, P < 0.001), minor type EOLP (3.0 ± 3.0 pg/ml, P < 0.01), or NEOLP (4.2 ± 1.5 pg/ml, P < 0.001) was significantly higher than that in normal control subjects (2.0 ± 1.5 pg/ml). A significant difference in the mean serum IL-6 level was also found between major type and minor type EOLP patients (P < 0.01). The mean reduction of serum IL-6 level in OLP patients treated with levamisole plus Chinese medicinal herbs was significantly higher (7.4 ± 4.7 pg/ml) than that in OLP patients treated with levamisole only (3.8 ± 2.3 pg/ml, P < 0.05), suggesting that the combination therapy was superior to levamisole only.Conclusion: We conclude that levamisole and levamisole plus Chinese medicinal herbs can modulate the serum IL-6 level in OLP patients. IL-6 may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of OLP.

Background Oral malignancy is a major global health problem. Besides the main risk factors of tobacco, smoking and alcohol, infection by human papillomavirus (HPV) and genetic alterations are likely to play an important role in these lesions. The purpose of this study was to compare the efficacy of HC-II assay and PCR for the detection of specific HPV type (HPV 16 E6) in OSMF and OSCC cases as well as find out the prevalence of the high risk HPV (HR-HPV) in these lesions. Methods and materials Four hundred and thirty patients of the potentially malignant and malignant oral lesions were taken from the Department of Otorhinolaryngology, Moti Lal Nehru Medical College, Allahabad, India from Sept 2007-March 2010. Of which 208 cases were oral submucous fibrosis (OSMF) and 222 cases were oral squamous cell carcinoma (OSCC). The HC-II assay and PCR were used for the detection of HR-HPV DNA. Result The overall prevalence of HR-HPV 16 E6 DNA positivity was nearly 26% by PCR and 27.4% by the HC-II assay in case of potentially malignant disorder of the oral lesions such as OSMF. However, in case of malignant oral lesions such as OSCC, 32.4% HPV 16 E6 positive by PCR and 31.4% by the HC-II assay. In case of OSMF, the two test gave concordant result for 42 positive samples and 154 negative samples, with an overall level of agreement of 85.4% (Cohen's kappa = 66.83%, 95% CI 0.553-0.783). The sensitivity and specificity of the test were 73.7% and 92.05% (p < 0.00). In case of OSCC, the two test gave concordant result for 61 positive samples and 152 negative samples, with an overall level of agreement of 88.3% (Cohen's kappa = 79.29, 95% CI 0.769-0.939) and the sensitivity and specificity of the test were 87.14% and 92.76% (p < 0.00). Conclusion This study concluded that slight difference was found between the positivity rate of HR-HPV infection detected by the HC-II and PCR assay in OSMF and OSCC cases and the HC II assay seemed to have better sensitivity in case of OSCC.

In the field of quantitative microscopy, textural information plays a significant role very often in tissue characterization and diagnosis, in addition to morphology and intensity. The aim of this work is to improve the classification accuracy based on textural features for the development of a computer assisted screening of oral sub-mucous fibrosis (OSF). In fact, a systematic approach is introduced in order to grade the histopathological tissue sections into normal, OSF without dysplasia and OSF with dysplasia, which would help the oral onco-pathologists to screen the subjects rapidly. In totality, 71 textural features are extracted from epithelial region of the tissue sections using various wavelet families, Gabor-wavelet, local binary pattern, fractal dimension and Brownian motion curve, followed by preprocessing and segmentation. Wavelet families contribute a common set of 9 features, out of which 8 are significant and other 61 out of 62 obtained from the rest of the extractors are also statistically significant (p < 0.05) in discriminating the three stages. Based on mean distance criteria, the best wavelet family (i.e., biorthogonal3.1 (bior3.1)) is selected for classifier design. support vector machine (SVM) is trained by 146 samples based on 69 textural features and its classification accuracy is computed for each of the combinations of wavelet family and rest of the extractors. Finally, it has been investigated that bior3.1 wavelet coefficients leads to higher accuracy (88.38%) in combination with LBP and Gabor wavelet features through three-fold cross validation. Results are shown and discussed in detail. It is shown that combining more than one texture measure instead of using just one might improve the overall accuracy.

There are several factors like angiogenesis, lymphangiogenesis, genetic alterations, mutational factors that are involved in malignant transformation of potentially malignant oral lesions (PMOLs) to oral squamous cell carcinoma (OSCC). Fibroblast growth factor-2 (FGF-2) is one of the prototypes of the large family of growth factors that bind heparin. FGF-2 induces angiogenesis and its receptors may play a role in synthesis of collagen. FGFs are involved in transmission of signals between the epithelium and connective tissue, and influence growth and differentiation of a wide variety of tissue including epithelia. The present study was undertaken to analyze expression of FGF-2 and its receptors FGFR-2 and FGFR-3 in 72 PMOLs, 108 OSCC and 52 healthy controls, and their role in risk assessment for malignant transformation of Leukoplakia (LKP) and Oral submucous fibrosis (OSMF) to OSCC. Immunohistochemistry was performed using antibodies against FGF-2, FGFR-2 and FGFR-3. IHC results wer...

Bilateral full thickness naso-labial flaps have been used successfully in three patients to give long-term relief of the severe trismus caused by oral submucous fibrosis. The flaps are set into defects created by incision of the oral mucosa. The postoperative rehabilitation compared favourably with other methods and we now advocate the technique for all cases of submucous fibrosis requiring correction of severe trismus.

Circulating matrix metalloproteinase-9 (MMP-9) is a prognostic factor for gastric cancer and vascular diseases, and has been associated with head and neck cancers. The -1562 C-to-T polymorphism in MMP-9 promoter (abbreviated MMP-9 -1562 C&amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;T polymorphism) leads to differential transcription, and is associated with increased susceptibility to neoplastic and vascular diseases. Thus, our aim was to determine whether a functional MMP-9 polymorphism might also influence the risk or affect the progression of areca-associated oral cancers. Genomic DNAs were obtained from peripheral blood cells of male subjects with areca-associated oral squamous cell carcinoma (OSCC) (n = 192), oral submucosal fibrosis (OSF) (n = 73), and non-diseased areca users (n = 191). The PCR-based restriction fragment length polymorphism analysis was performed for MMP-9 genotyping. MMP-9 -1562 C&amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;T polymorphism was not associated with the risk of OSCC or OSF. However, when subjects were stratified by the median age, an association with the risk of OSCC was found in younger patients (P = 0.029). The T allele frequency was significantly higher in the subset of older patients with buccal mucosa OSCC than older patients with OSCC in counterpart locations. The joint MMP-9 -1562 C&amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;T and MMP-3 -1171 5A&amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;6A functional polymorphisms were not associated with OSCC risk or patient survival. Aberrant MMP-9 expression is closely related to tumor invasiveness and the prognosis of head and neck cancers. However, functional MMP-9 -1562 C&amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;T polymorphism is associated with OSCC risk only in younger areca chewers. The impact of aging or areca-related effect on this functional polymorphism should be elucidated.

Oral submucous fibrosis (OSMF) is a chronic, progressive, debilitating, scarring and crippling disorder of
the oral cavity. It is a potentially malignant oral disease which predominantly affects people of South and
Southeast Asia, especially Indian subcontinent, where chewing of areca nut and its commercial preparation
is rampant. However, due to increase in immigration of people from the Indian subcontinent, the health
professionals in many developed countries do come across this disease very often. Since decades, many
treatment modalities are suggested and studied using medicines, surgery and physiotherapy, with varying
degrees of benefit, but none have been able to cure this disease completely, and hence, it has become a
challenging condition. The present article emphasizes on various therapeutic interventions used till date
to curb the menace of this disease and the principal author with his vast academic research and clinical
experience in treating this disease has proposed the stage-wise treatment regimen for OSMF. The current
article is an attempt to compile the available treatment, its current status and future perspectives, so as to
assist early intervention of the disease with evidence-based approach. This article will ignite the research
minds of dental clinician, oral medicine specialist, otolaryngologist and general physician in treating OSMF.

In order to ascertain possible correlation between alterations in trace elemental profile and the progression or regression of two most common potentially malignant disorders affecting oral cavity, namely oral submucous fibrosis and leukoplakia, blood from 60 patients from each group of patients as well from 30 healthy individuals was analyzed for elemental profiling employing EDXRF technique. Out of the 16 detected elements (K, Si, Ca, V, Cr, Ni, Mn, Fe, Cu, Zn, Se, Br, Rb, Sr, Co, and Pb), Mn, Fe, Zn, Br, and Co showed remarkable alteration in their profile in both leukoplakia and oral submucous fibrosis patients with respect to the normal healthy individuals. While Zn, Br, and Fe reflected similar changes—showing gross depletion in both the diseased groups, Mn and Co depicted inverse pattern of alterations in their concentrations in the two types of precancerous disorders when compared to the control subjects.

The objective of the present study was to assess the oral-health-related quality of life (OHRQoL) of oral submucous fibrosis (OSMF) patients before and after standard treatment. A convenient sampling technique was used to recruit the clinically diagnosed patients of OSMF (n = 130). Based on the medical treatment, the patients were randomly divided into two study groups (group A and B). The group A patients received submucosal intralesional injections of dexamethasone (2 mL; 4 gm/mL), while group B patients received hyaluronidase (1500 IU). Both the group A and B patients received respective medical therapy biweekly for a period of five weeks. At the follow up visit (6 months), the impact of treatment on OHRQoL was assessed using the Oral Health Impact Profile-14 (OHIP-14). Data were analyzed by a chi-square test for quantitative variables and an independent t-test for qualitative variables. The comparison of all clinical parameters before and after treatment was performed by a paire...

Background: Betel quid chewing is a common habit widely practiced in Southern Asian populations. However, variations are seen in the content of a betel quid across the different countries. Factors associated with commencement and cessation of this habit has been numerously studied. Unfortunately, data on Malaysian population is non-existent. This study aims to determine the factors associated with the inception and also cessation of betel quid chewing behaviour among Malaysian adults. Method. This study is part of a nationwide survey on oral mucosal lesions carried out among 11,697 adults in all fourteen states in Malaysia. The questionnaire included sociodemographic information and details on betel quid chewing habit such as duration, type and frequency. The Kaplan-Meier estimates were calculated and plotted to compare the rates for the commencement and cessation of betel quid chewing behaviour. Cox proportional hazard regression models were used to calculate the hazard rate ratios for factors related to commencement or cessation of this habit. Results. Of the total subjects, 8.2% were found to be betel quid chewers. This habit was more prevalent among females and, in terms of ethnicity, among the Indians and the Indigenous people of Sabah and Sarawak. Cessation of this habit was more commonly seen among males and the Chinese. Females were found to be significantly more likely to start (p < 0.0001) and less likely to stop the quid chewing habit. Females, those over 40 years old, Indians and a history of smoking was found to significantly increase the likelihood of developing a quid chewing habit (p < 0.0001). However, those who had stopped smoking were found to be significantly more likely to promote stopping the habit (p = 0.0064). Cessation was also more likely to be seen among those who chewed less than 5 quids per day (p < 0.05) and less likely to be seen among those who included areca nut and tobacco in their quid (p < 0.0001). Conclusion. Factors that influence the development and cessation of this behaviour are gender, age, ethnicity, and also history of smoking habit while frequency and type of quid chewed are important factors for cessation of this habit

Oral submucous fibrosis (OSF) is characterized by abnormal collagen metabolism in the submucosal connective tissue. Its influence on the overlying epithelium is not known but about 14% of OSF cases undergo malignant transformation to squamous cell carcinoma indicating association with abnormality of the epithelium. Here, we have defined the keratin expression profile, by immunohistochemistry and quantitative image analysis, using a panel of 22 anti-keratin monoclonal antibodies on 28 OSF samples. We observed an increase of K1 and K10 in the suprabasal layers, induction of K6 in the basal layer and complete loss of K19 in the epithelium. Furthermore, there was increased K17 expression in the suprabasal layers, which correlated with disease severity. In a subset of the most severe OSF cases (14%), K17 expression was completely lost in the basal layer which might define them to be at most risk to undergo malignant transformation. There was no detectable expression of K8, K18, K7 and K9 and the expression of K4, K13, K14, K15 and K16 did not change in OSF. We propose that the altered keratin profiles could be useful as histological diagnostic markers and provide important insights into the pathogenesis of the disease and its predisposition to malignancy.

Oral submucous fibrosis (OSMF) is a disabling, potentially malignant condition of the oral cavity. The aetiology of OSMF is multifactorial but remains obscure. Although arecanut is considered to be the most important causative agent, responses observed in individuals using arecanut vary in relation to quantity and duration. It is considered that an immunological process is responsible for the pathogenesis of disease. We correlated salivary immunoglobulin A (IgA), salivary immunoglobulin G (IgG) and serum immunoglobulin A (IgA), serum immunoglobulin G (IgG), levels by turbidometric immunoassay. We estimated the levels of total serum protein (TSP) and haemoglobin (Hb) to determine the role of nutritional deficiency. The study population comprised 30 cases of OSMF and 10 controls. Five milliliters of blood and 2 ml of saliva were collected. Quantitative analysis of serum and salivary IgG, IgA was done by turbidometric immunoassay. TSP and Hb were estimated by Biuret and cyanmethaemoglobin methods, respectively. All patients showed significant (P < 0.01) increase in serum and salivary IgG, IgA levels as compared to controls. TSP patients showed significant (P < 0.01) decrease as compared to controls. Results of Hb in patients were not significant. The estimation of immunoglobulin levels is important to support the concept of autoimmune basis. Estimation of TSP and Hb suggests that nutrition has a definite role in OSMF.

Areca quid chewing is strongly correlated with oral submucous fibrosis (OSF) in Taiwan. The cytotoxicity of arecoline, a major areca nut alkaloid, on human oral fibroblasts has been extensively studied. To date, however, there has been little research exploring the possible effects of arecoline on cytoskeleton components. In this study, in addition to conducting a cytotoxicity assay, we examine the effect of arecoline on vimentin, an intermediate filament, and its expression in human buccal mucosal fibroblasts on exposure to various levels of arecoline (0-200 mg/ml) for 48 h. At a concentration above 50 mg/ml, arecoline demonstrated dosedependent cytotoxicity (P<0.05) for cultured fibroblasts. Using sodium dodecyl sulphate-polyacrylamide gel electrophoresis, we demonstrated dose-dependent elevation of 57 kDa cytoskeletal-protein levels for arecoline. Evidence from immunoblotting assay indicated this 57 kDa cytoskeletal protein was vimentin. The increase in vimentin with arecoline exposure corresponded to that noted for fibroblasts cultured from OSF patients. Immunohistochemical assay also revealed that vimentin expression was much higher for OSF specimens than for normal buccal mucosa. We suggest these results may advance understanding of the possible pathogenesis for submucous fibrosis through the transformation of normal buccal mucosa as a result of areca quid chewing.

Background Changes in lipid profile have long been associated with malignancies as lipids play a key role in maintenance of cell integrity. This study evaluated the alterations in extended lipid profile in untreated patients of oral submucous fibrosis (OSMF) and studied the correlation between lipid levels with tobacco consumption. Materials and methods In this hospital-based study, 65 clinically diagnosed and histopathologically proven patients of OSMF and 42 age and sex matched controls were studied. In these samples serum lipids including: (i) Total cholesterol, (ii) LDL cholesterol (LDLC), (iii) HDL cholesterol (HDLC) (iv) VLDL cholesterol (VLDLC) (v) triglycerides (vi) Apo-A1 (viii) Apo-B and (viii) LPa were analyzed. Results A significant decrease in plasma total cholesterol, HDLC and Apo-A1 was observed in patients with OSMF as compared to the controls. Thus an inverse relationship between plasma lipid levels and patients was found in OSMF. Conclusion The lower levels of plasma cholesterol and other lipid constituents in patients might be due to their increased utilization. The findings strongly warrant an in-depth study of alterations in plasma lipid profile in patients with oral precancerous conditions.

To learn about the use of various chewing substrates, such as areca nut and gutka, among subjects with oral submucosal fibrosis (OSMF) and controls with no oral mucosal lesions. In this hospital-based case-control study, 220 patients with OSMF were selected and compared with matched controls with regard to dietary habits, including spice use, smoking history, and preference for chewing substrates. Relative risk of various chewing habits was calculated using an odds ratio and logistic regression analysis to understand the influence of chewing habits, spices, and smoking on the development of OSMF. Discriminate analysis was employed to determine which risk factors were valid and reliable discriminators between individuals with or without OSMF. The relative risk of developing oral submucosal fibrosis was highest with gutka-chewing habit (relative risk, 1,142.4), which was significant (P &lt; .01) at 95% confidence interval. The next highest relative risk for development of oral submuco...

Fifty-five patients with oral submucosal fibrosis and an equal number of patients with no evidence of the disease were studied. All patients underwent upper gastrointestinal endoscopy and any abnormality was noted. Multiple oesophageal biopsies were obtained from the upper end of the oesophagus and from any endoscopically observed abnormality. The histological changes in the two groups were assessed blindly by an experienced histopathologist. Histological abnormalities were noted in the oesophageal mucosa in 2% of controls and 66% of patients with oral submucosal fibrosis (p < 0.0001). In the control group, acanthosis was seen in one patient, while in the patient group atrophy ofthe squamous epithelium was evident in 52%, hyperkeratosis in 52%, parakeratosis in 30%, dyskeratosis in 14%, acanthosis in 14%, and papillomatosis and mild dysplasia in 2% patients. Subepithelial collagenization was seen in 32 (64%) patients. The oesophageal abnormalities were seen more frequently in patients who had consumed Pan masala, Gutka, betel nut, tobacco or a combination of some or all of these, with or without betel leaf, for > 5 years compared to those consuming them for a shorter period of time (91% vs 46%, p< 0.001). It is concluded that oral submucosal fibrosis is not a disease confined to the oral cavity; the oesophagus may also be involved in about two-thirds of patients.

The aim of this study was to ascertain the prevalence of oral lesions among 500 psychoactive substance users in a hospital-based population. The study group consisted of 500 consecutive patients attending TTK Hospital, a non-governmental organisation involved in rehabilitation of substance users.

BACKGROUND: Oral submucous fibrosis (OSF) is associated with the betel quid chewing habit, and 86% of betel quid chewers in Taiwan are also smokers. Arecoline and safrole are major principles in the composition of betel quid, and nicotine is the main toxic ingredient of cigarettes. METHODS: To explore the pathogenesis of OSF, flow cytometry was used to compare collagen phagocytosis by fibroblasts from the normal and the OSF region of the same 15 OSF patients. RESULTS: The results indicated that heterogeneity of fibroblasts existed because collagen phagocytosis by fibroblasts from the normal region was higher than from the OSF region in the same patient. The percentage of phagocytic cells was significantly inhibited by 10, 25 and 50 lg/ml arecoline, safrole and nicotine in normal fibroblast cultures, respectively, and the percentage of phagocytic cells was significantly reduced by 25, 25 and 50 lg/ml arecoline, safrole and nicotine in OSF fibroblast cultures, respectively. Collagen phagocytosis by fibroblasts exhibited prominent dose-dependent inhibition as the concentration of arecoline, safrole, and nicotine increased. Besides, nicotine had a synergistic effect on arecoline-or safrole-inhibited collagen phagocytosis. CONCLUSIONS: The present study concludes that even in the same person, the collagen phagocytosis by fibroblasts is different between normal and OSF region. The deficiency in collagen phagocytosis by fibroblasts of the lesion might participate in the pathogenesis of OSF. Arecoline, safrole and nicotine, which are released in saliva during BQ chewing plus cigarette smoking, inhibit collagen phagocytosis by fibroblasts in a dose-dependent manner and may induce OSF formation in Taiwan's patients.

BACKGROUND: Our aim was to measure the relationship of FAS ()1377G>A and)670A>G), FASL ()844C>T) gene variants and risk of oral cancer. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to determine the FAS and FASL polymorphisms in 294 oral squamous cell carcinoma (OSCC), 53 oral submucous fibrosis (OSF), and 84 oral leukoplakia (OL) patients, as well as in 333 healthy controls. A standardized questionnaire was applied to collect demographic data, and potential confounding factors. JMP statistical software was used to analyze the association. RESULTS: FAS and FASL polymorphisms were not correlated with OSCC development or the malignant potential of OL by simple and multivariate logistic regression. However, a two-to fourfold difference in the risks of betel quid chewing, alcohol consumption, and smoking on OSCC development were observed between participants with different FAS polymorphisms. FAS polymorphisms were significantly correlated with the malignant potential of OSF. Multivariate logistic regression analysis indicated that FAS A-1377-G-670 vs. G-1377-A-670 haplotype (OR = 2.26, 95% CI = 1.16-4.41) was correlated with the malignant potential of OSF. CONCLUSIONS: We suggest that FAS and FASL polymorphisms are not significantly correlated with OSCC development or malignant potential of OL. The impact of substance usage on OSCC development could be differentiated by FAS polymorphisms. FAS A)1377-G)670 haplotype may play a role in the malignant potential of OSF.