bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of phosphorylated Akt in oral carcinogenesis and its induction by nicotine and alkaline stimulation
Authors: Wu Ho‐Tai , Ko Shun‐Yao , Fong Jenny Hwai‐Jen , Chang Kuo‐Wei , Liu Tsung‐Yun , Kao Shou‐Yen
Published: August 2010

Background:  In Taiwan, it is well documented that cigarette smoking and areca nut chewing contribute to the risk of oral squamous cell carcinoma (OSCC). The role of phosphorylated Akt (p‐Akt) in oral carcinogenesis induced by nicotine and alkaline environments was investigated.

Method:  Immunohistochemistry (IHC) was used to detect p‐Akt expression in cancerous (n = 30) precancerous (n = 30), and normal mucosa tissues (n = 10). Western blotting was used to detect time‐dependent induction of p‐Akt by 100 μM nicotine in normal human bronchial epithelial cell (NHBE), normal human oral keratinocytes (NHOK), immortalized human epithelial cells (HaCaT) and OEC‐M1 cells, dose‐dependent induction of p‐Akt in OEC‐M1 and HaCaT cells and pH effect of p‐Akt in OEC‐M1. The unpaired t‐test and the Fisher’s exact test were used to analyze the p‐Akt immunoreactivity in various groups and its association with clinicopathological parameters.

Results:  Higher p‐Akt expression in cancerous group than in normal mucosa (P = 0.0002) and precancerous (P = 0.0049) groups was observed. A time‐dependent increase in p‐Akt in the NHBE, NHOK, HaCaT and OEC‐M1 cell lines was observed with 100 μM nicotine treatment. The dose‐dependent increase in p‐Akt by nicotine treatment in HaCaT and OEC‐M1 cells was obviously observed. Higher p‐Akt expression in more alkaline environment (pH 8.0) was observed than at pH 7.4 in OEC‐M1 cells.

Conclusion:  A potential role for increased p‐Akt may relate to the dose and time of nicotine use. The potential role of an alkaline environment to enhance nicotine‐related oral carcinogenesis may exist.
The reported prevalence of oral lichen planus: a review and critique
Authors: McCartan B. E. , Healy C. M.
Published: August 2010

Objective:  To examine all studies reporting prevalences of oral lichen planus (OLP) for epidemiological validity and to extract prevalence data from the valid papers.

Design:  Computer based literature searches were carried out using the MeSH headings ‘lichen planus, oral and (prevalence or incidence)’ and were supplemented by manual searching.

Main Outcome Measures:  Each paper was examined for five criteria: clinic‐based or population study, adequate demographic description (by sex and age group) of the population, adequate demographic description of the sample (if the population was sampled), adequate demographic description of the OLP cases identified, and histological confirmation of the clinical diagnosis.

Results:  Forty‐five relevant papers were identified, 21 clinic‐based and 24 population studies. All but one of the population studies was deficient. One study, while having some defects, was probably sufficiently valid to permit the findings to be regarded as useful. An overall age‐standardized prevalence of 1.27% (0.96% in men and 1.57% in women) can be calculated from this study.

Conclusions:  There appears to be only one usable prevalence study of OLP. Other large‐scale studies are required in other populations. Such studies need to distinguish between OLP and lichenoid reactions.
Immune‐expression of HSP27 and IL‐10 in recurrent aphthous ulceration
Authors: Miyamoto Jr Nelson T. , Borra Ricardo Carneiro , Abreu Marilda , Weckx Luc Louis Maurice , Franco Marcello
Published: August 2010

Background:  Recently, abnormal cellular immune response has been considered responsible for the oral lesion in the recurrent aphthous ulceration (RAU). For reasons not yet defined, antigens of the oral microbiota would trigger abnormal Th1 immune response against epithelial cells. On the other hand, studies have demonstrated that heat shock proteins (HSP) can block the production of proinflammatory cytokine through inhibition of NF‐κB and mitogen‐activated protein kinase pathways or activate anti‐inflammatory cytokines and therefore control the magnitude of the immune response. HSP27 has been considered a powerful inductor of IL‐10, a major inhibitor of Th1 response.

Methods:  Using immunohistochemistry, we studied the expression and location of HSP27 and IL‐10 in ulcerated lesions clinically diagnosed as RAU (n = 27) and to compare it with that of oral clinically normal mucosa (CT; n = 6) and of other inflammatory chronic diseases such as oral fibrous inflammatory hyperplasia (FIH; n = 18), Crohn’s disease (CD; n = 10) and ulcerative colitis (UC; n = 9).

Results:  A lower proportion of HSP27‐positive epithelial cells in RAU and CD were observed when compared with CT and FIH (P < 0.001**; P = 0.013**). A lower proportion of IL‐10‐positive interstitial cells in RAU was observed when compared with FIH, UC, CT and CD (P < 0.001**; P < 0.001**; P < 0.001**; P = 0.034*).

Conclusion:  Altogether the data suggest that a reduced cellular expression of HSP27 and IL‐10 in RAU might be related with the aetiopathogenesis of the ulcerated oral lesions.
Fine deletion analysis of 1p36 chromosomal region in oral squamous cell carcinomas
Authors: Lefeuvre Mathieu , Gunduz Mehmet , Nagatsuka Hitoshi , Gunduz Esra , Al Sheikh Ali Mahmoud , Beder Levent , Fukushima Kunihiro , Yamanaka Noboru , Shimizu Kenji , Nagai Noriyuki
Published: August 2010

Background:  Squamous cell carcinoma is the most common cancer type of the oral cavity and approximately 50% of the patients succumb to the disease. Unfortunately, few are known about the molecular mechanisms involving in the formation of oral squamous cell carcinoma (OSCC). Recently, it has been reported that 1p36 chromosomal region is deleted in various cancer types and is suspected to harbor various tumor suppressor genes (TSGs). However, limited studies exist on genetics alteration on 1p36 in OSCC and the responsible TSG remained unidentified.

Methods:  To investigate area susceptible to harbor TSG(s) involved in OSCC on 1p36 region, paired normal and tumor tissues of 27 patients with diagnosis of OSCC have been analyzed for loss of heterozygosity (LOH) using nine microsatellite markers based on recent gene mapping.

Results:  LOH was found at least in one locus in 85% of the cases (23 of 27). Interestingly, microsatellite instability was also found in 7% (two of 27) of the cases analyzed. The higher LOH frequencies were found with the markers D1S243 (25%), D1S468 (22%), D1S450 (25%), D1S228 (38%), D1S199 (28%), and D1S1676 (23%).

Conclusions:  Three preferentially deleted regions have been identified in OSCC: region 1 (D1S468‐D1S243), region 2 (D1S450‐D1S228), and region 3 (D1S199‐D1S1676). Multiple candidate TSGs, such as RIZ1, p73, UBE4B, Rap1GAP, EPHB2, and RUNX3, are located in these three areas. The data obtained in this study can be used for further functional analysis of these genes involved in OSCC carcinogenesis.
Betel quid chewing, oral cancer and other oral mucosal diseases in Vietnam: a review
Authors: Reichart P. A. , Nguyen X. H.
Published: August 2010

Background:  Betel quid chewing (BQC) in Vietnam is still prevalent, however, no detailed information about its association with oral cancer and pre‐cancer are available in the English literature. Respective online searches (PubMed, Medline) were negative.

Methods:  Relevant publications in Vietnamese were collected by the authors and translated. Visits to cancer centres and institutes of odontology (Ho Chi Minh City, Hanoi) were made and seminars with respective scientists were held. Field excursions to local markets and interviews with betel quid vendors and individual BQ chewers gave further insights.

Results:  Generally, BQC is on the decline in Vietnam. 6.7% of the female population still seems to indulge in this habit. In an earlier study, a prevalence of 0.06% of oral cancer was reported. In a study of 1084 cases of oral cancer, the male:female ratio was 1.05:1 (1997). The age group between 60 and 75 years is most often affected by oral cancer. In BQ chewing women, the buccal mucosa (27.9%), tongue (23.1%) and lips (22.4%) are most often affected. Verrucous carcinoma is seen in the age group 70–79 years with women most often being affected (male:female ratio 1:3.4). The most important risk factor for oral cancer in women is BQC compared with men where smoking, alcohol drinking or combined smoking and drinking habits are the most common risk factors. Oral leukoplakia in BQ chewers is observed in 3.8%, oral submucous fibrosis in 13%.

Conclusions:  BQC in Vietnam is on the decline. Association between BQC and oral cancer in elderly women is still of importance. Eventually, the BQC habit will vanish and only play a role in socio‐ritual contexts.
Human papilloma virus types in the oral and cervical mucosa of HIV‐positive South African women prior to antiretroviral therapy
Authors: Richter Karin L. , Van Rensburg Estrelita Janse , Van Heerden Willie F. P. , Boy Sonja C.
Published: August 2010

Background:  To evaluate the prevalence of human papilloma virus (HPV) infection and types in the oral and cervix mucosa of treatment‐naïve HIV‐1‐positive women with CD4 counts less than 300 cells per ml with no HPV‐associated oral lesions.

Methods:  Oral epithelium was harvested from the buccal mucosa and lateral borders of the tongue and cervical samples were collected from the endocervical area of 30 women, 22–64 years old. Cytobrush Plus cell collectors were used for sampling both anatomical areas. Genital pathology, obstetric and gynaecological history, co‐morbid disease, hormone therapy, sexual behavior and smoking history were assessed via physical examination and clinical interviews. Special investigations included cervical Papanicolau smears, CD4 counts and HIV‐1 viral loads. The linear array HPV test was used to determine HPV genotypes present in the specimens.

Results:  Oral HPV were identified in 20% (n = 6) of the patients, of which two had infection with two HPV types. Genital HPV was found in 96.7% (n = 29) of the women, of which only 14 had cytological abnormalities on Papanicolau smear. Infection with multiple HPV types were present in 93.1% (n = 27) of the patients, with an average of four HPV types per individual.

Conclusions:  South African HIV‐positive women with CD4 counts less than 300 cells per ml have a significant risk of cervical HPV strains and multiple strain infection of the cervix. The prevalence of HPV in normal oral mucosa was low but high‐risk types were present. Limited correlation between oral HPV types and those identified in the cervical mucosa was found.
Minimum diagnostic criteria for plasmablastic lymphoma of oral/sinonasal region encountered in a tertiary cancer hospital of a developing country
Authors: Kane Shubhada , Khurana Aditi , Parulkar Gorakh , Shet Tanuja , Prabhash Kumar , Nair Reena , Gujral Sumeet
Published: August 2010

Background:  Haematolymphoid tumours other than plasmablastic lymphoma (PBL) may reveal plasmablastic differentiation with overlapping immunoreactivity causing diagnostic dilemma. Elaborate ancillary diagnostic techniques can make the process expensive, tedious and out of reach for pathology laboratory in a developing country.

Methods:  Out of 98 total cases of primary non‐Hodgkin’s lymphoma and plasmacytoma of oral‐sinonasal region recorded in our institute over 4 years, 39 cases showing varied plasmablastic differentiation were selected. Morphological and immunohistochemical criteria were applied to identify minimum diagnostic criteria for PBL. Human Immunodeficiency Virus (HIV) correlation and Epstein–Barr virus expressed RNA (EBER) in‐situ hybridisation studies were also performed.

Results:  Minimum morphological criteria required to diagnose PBL were: (1) predominant population of plasmablasts which are large monomorphic cells with high nuclear‐cytoplasmic ratio, moderate amount of amphophilic cytoplasm and round nucleus with prominent central nucleolus, (2) high mitotic and/or apoptotic index and (3) absence of neoplastic plasma cells in the background. Essential diagnostic immunophenotype consisted of CD20 negativity, LCA +/−, CD138/VS38c diffuse positivity, light chain restriction and high MIB‐1 index (>60 %). Twenty‐five of the total 32 PBL cases thus identified, involved oral cavity. Of these, 84% affected gingivo‐buccal complex. Twenty‐eight cases were HIV positive. EBER positivity confirmed the diagnosis in all the HIV‐negative cases.

Conclusions:  A triad of ‘rapidly growing lesion with predilection for oral mucosa, classical plasmablastic morphology and limited immunohistochemical panel’ can render a reliable diagnosis of PBL, irrespective of HIV and EBV status, especially in developing countries with limited resources.
Histomorphology of healthy oral mucosa in untreated celiac patients: unexpected association with spongiosis
Authors: Campisi G. , Compilato D. , Iacono G. , Maresi E. , Di Liberto C. , Di Marco V. , Di Fede G. , Craxì A. , Carroccio A.
Published: August 2010

Background:  The jejunal mucosa is the major site involved in celiac disease, but modifications have also been found in the gastric, rectal and esophageal mucosa. Few studies have focused on the histomorphological features of the oral mucosa in celiac disease patients. Our objectives were: (i) to assess the presence, quality and intensity of lymphocytic infiltrate in clinically healthy oral mucosa and its relation to celiac disease severity (villous height to crypt depth ratio); and (ii) to detect any other histological features connected to celiac disease.

Methods:  Twenty‐one untreated celiac disease patients (age range 13–68 years) with clinically healthy oral mucosa were enrolled and compared with 14 controls. Intestinal and oral biopsies were carried out and specimens were evaluated after staining with hematoxylin and eosin.

Results:  Intra‐epithelial lymphocyte B and T infiltrates of the oral mucosa were found to be similar in both groups; likewise, intensity of the lymphocytic infiltrate in the lamina propria was similar in both groups and was not related to intestinal damage; important signs of spongiosis were found to be more significantly present in celiac disease patients compared with controls (P = 0.0002).

Conclusions:  Our study showed that the healthy oral mucosa of untreated patients does not reflect the intestinal damage by celiac disease, but it is unexpectedly affected by spongiosis, as being detected for the first time in the literature. This latter feature could be related to gliadin ingestion and could contribute to explain the higher susceptibility of celiac disease patients to suffering from oral mucosa lesions.
Laser‐capture microdissection of oropharyngeal epithelium indicates restriction of Epstein–Barr virus receptor/CD21 mRNA to tonsil epithelial cells
Authors: Jiang Ru , Gu Xin , Nathan Cherie‐Ann , Hutt‐Fletcher Lindsey
Published: August 2010

Background:  Epstein–Barr virus colonizes the oropharynx of a majority of individuals. It infects B lymphocytes and epithelial cells and can contribute to the development of both lymphoid and epithelial tumors. The virus uses CD21 for attachment to B cells which constitutively express the protein. Infection of epithelial cells in vitro is also more efficient if CD21 is available. However, its potential contribution to infection in vivo has been difficult to evaluate as discrepant results with antibodies have made it difficult to determine which, if any, epithelial cells in the oropharynx express CD21.

Methods:  To reevaluate CD21 expression by an alternative method, epithelial cells were isolated by laser‐capture microdissection from formalin‐fixed sections of tissues from various parts of the oropharynx and mRNA was amplified with primers specific for the exons of CD21 which code for the Epstein–Barr virus binding site.

Results:  CD21 mRNA was expressed in tonsil epithelium, but not in epithelium from buccal mucosa, uvula, soft palate or tongue.

Conclusions:  CD21 does not contribute to infection of most normal epithelial tissues in the oropharynx, but may contribute to infection of epithelial cells in the tonsil, where virus has been demonstrated in healthy carriers.
Comparative evaluation of genetic assays to identify oral pre‐cancerous fields
Authors: Bremmer Jantine F. , Braakhuis Boudewijn J. M. , Brink Arjen , Broeckaert Mark A. M. , Beliën Jeroen A. M. , Meijer Gerrit A. , Kuik Dirk J. , René Leemans C. , Bloemena Elisabeth , Van Der Waal Isaäc , Brakenhoff Ruud H.
Published: August 2010

Background:  Oral squamous cell carcinomas often develop in a pre‐cancerous field, defined as mucosal epithelium with cancer‐related genetic alterations, and which may appear as a clinically visible lesion. The test characteristics of three genetic assays that were developed to detect pre‐cancerous fields were investigated and compared to histology.

Methods:  In total, 10 pre‐cancerous fields that were not visible at clinical inspection and gave rise to malignant transformation based on an identical TP53 mutation in tumor and mucosal epithelium in the surgical margin, as well as 10 normal oral mucosa specimens were analyzed for numerical chromosomal changes with multiplex ligation‐dependent probe amplification (MLPA), for loss of heterozygosity (LOH), with microsatellite PCR and for DNA index alterations with DNA image analysis.

Results:  No alterations were detected in normal tissue by either of the assays. Both MLPA and LOH assays detected all pre‐cancerous fields. DNA cytometry identified aneuploidy in four of 10 pre‐cancerous fields, while the corresponding tumors that developed in these fields were shown to be aneuploid.

Conclusions:  Both the MLPA and LOH assay seem suitable for screening pre‐cancerous fields in subjects at high risk for oral cancer even in the absence of clinically abnormal appearing oral mucosa. Measurements of DNA index might be valuable to determine the time to progression.
Correlation between enzyme production, germ tube formation and susceptibility to fluconazole in Candida species isolated from patients with denture‐related stomatitis and control individuals
Authors: Pinto Eugénia , Ribeiro Isabel Cristina , Ferreira Núria Joana , Fortes Cátia Eliana , Fonseca Patrícia Alexandra , Figueiral Maria Helena
Published: August 2010

Introduction:  Phospholipase and proteinase secretion in yeasts of the genus Candida has been described as a relevant virulence factor. Also, germ tube formation by Candida albicans is associated with its invasive capacity and is considered an important pathogenic mechanism.

Methods:  To link the production of hydrolytic enzymes with the capacity to produce infection, 232 clinical isolates of yeasts from the oral cavity of 140 individuals wearing removable maxillary protheses were studied. The sample was composed of 70 patients with denture‐related stomatitis (DRS) and 70 individuals with normal palatal mucosa. For strains identified as C. albicans, the correlation between germ tube formation and their capacity to cause infection was studied and the presence of Candida dubliniensis was investigated. Susceptibility to fluconazole was evaluated.

Results:  Candida albicans was the only species producing phospholipase and germ tube. We observed a higher level of production of phospholipase in cases of infection compared with commensals. Significant differences between the two groups of C. albicans isolates were observed as to germ tube production. Only, Candida glabrata showed lower susceptibility to fluconazole.

Conclusion:  The results reinforced the idea that C. albicans is the most frequent and can be the most pathogenic yeast in oral candidosis. However, the strains isolated from DRS patients and healthy individuals showed the same virulence factors. It seems that several virulence attributes are involved in the infective process but no single factor contributes to Candida virulence. Candida dubliniensis was absent in the oral cavity of individuals with and without DRS.
Prognostic significance of Bcl‐2 and Bax protein expression in the patients with oral squamous cell carcinoma
Authors: Zhang Mingbin , Zhang Ping , Zhang Chenping , Sun Jian , Wang Lizhen , Li Jiang , Tian Zhen , Chen Wantao
Published: August 2010

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.
Variant haplotypes atXRCC1and risk of oral leukoplakia in HPV non‐infected samples
Authors: Majumder Mousumi , Indra Dipanjana , Roy Puspita Das , Datta Sayantan , Ray Jay Gopal , Panda Chinmay K. , Roy Bidyut
Published: August 2010

Background: One of the mechanisms in human papillomavirus (HPV)‐related carcinogenesis is inhibition of DNA repair by HPV oncoprotein. In this study, we investigated whether polymorphisms atXRCC1, one of the DNA repair loci, could modulate the risk of tobacco‐related leukoplakia and cancer in HPV‐infected individuals.

Methods: Tissue DNA from 83 oral cancer, 91 leukoplakia and 100 healthy controls were screened for HPV 16/18 infection and polymorphisms atXRCC1by PCR–RFLP to estimate the risk of diseases independently and jointly.

Results: Human papillomavirus infection was significantly associated with increased risk of leukoplakia and cancer (OR = 2.8, 95% CI = 1.2–6.5 and OR = 5.5, 95% CI = 1.6–19, respectively). Independently, genotypes at three polymorphic sites onXRCC1did not modulate the risk of diseases but pooled variant haplotypes increased the risk of leukoplakia in overall and HPV non‐infected (OR = 1.8, 95% CI = 1.2–2.8; OR = 2.2, 95% CI = 1.2–4.0, respectively) samples but not that of cancer.

Conclusion: The association between variant haplotypes atXRCC1and risk of leukoplakia is pronounced in non‐infected individuals since HPV oncoprotein could inhibit directly the DNA repair activity of XRCC1. But more samples of leukoplakia and cancer are essential to validate these results.
Expression of β2‐adrenergic receptor in oral squamous cell carcinoma
Authors: Shang Zheng Jun , Liu Ke , Liang De Feng
Published: August 2010

Background:  It has been speculated that chemokines and neurotransmitters might be involved in the organ‐specific development of metastases because cancer metastasis is similar to the regulation of migratory activity in leukocytes. Here, we aimed to examine the expression of β2‐adrenergic receptor (β2‐AR) in oral squamous cell carcinoma (OSCC), and to investigate its correlation with tumor development and metastasis.

Methods:  Expression of β2‐AR was examined in 65 cases of OSCC specimens, 10 cases of normal oral mucosa, and two cell lines using immunohistochemistry, Western blot and RT‐PCR. The differences in β2‐AR expression between various groups were evaluated using SPSS 13.0 Statistical Software. Cell proliferation assays were assayed by β‐adrenergic receptors agonists (norepinephrine) and antagonists (propranolol). Norepinephrine‐mediated cell migration was assayed in Matrigel‐coated chemotaxis chamber.

Results:  β2‐AR was highly expressed on OSCC compared to normal controls. In OSCC, positive β2‐AR expression was significantly correlated with cervical lymph node metastasis (P = 0.001), age (P = 0.003), tumor size (P = 0.001) and clinical stage (P = 0.001), but not with gender. RT‐PCR and Western blot also confirmed positive β2‐AR expression in OSCC and TCa8113 cell line, and negative β2‐AR expression in normal oral mucosa and ACC cell line. β‐adrenoreceptor agonist (norepinephrine) was a potent mitogen for TCa8113 and ACC cell lines, and completely inhibited by the selective antagonist of β‐adrenergic receptors (propranolol). Norepinephrine induced migratory activity of OSCC cells in a dose‐dependent manner.

Conclusion:  Increased expression of β2‐AR may play an important role in the formation and metastasis of OSCC.
Association between lysyl oxidase polymorphisms and oral submucous fibrosis in older male areca chewers
Authors: Shieh Tzong‐Ming , Tu His‐Feng , Ku Ti‐Hsuan , Chang Shu‐Shin , Chang Kuo‐Wei , Liu Chung‐Ji
Published: August 2010

Objective:  Areca use is the major cause for oral squamous cell carcinoma and oral submucous fibrosis (OSF) in South Asians. Lysyl oxidase (LOX) is a copper‐activated enzyme critical for collagen cross‐linking and organization of extracellular matrix. The presence of a G to A polymorphism at nucleotide 473 caused a non‐conservative Arg158Gln change in the LOX amino acid sequence. OSF is a precancerous lesions characterized by the accumulation of collagen in oral submocousa. The aim of this study was to investigate the relationship between LOX Arg158Gln polymorphism and the risk of OSF.

Method:  PCR‐restriction fragment length polymorphisms and direct sequencing was utilized to compare LOX polymorphic allelotype in male areca‐chewing controls (n = 216) and OSF (n = 83) patients.

Results:  There was a borderline of statistically significant difference in Arg158Gln genotype lying between control and OSF patients. However, the G/A+A/A of LOX Arg158Gln in OSF patients older than 50 year was statistically significantly higher than controls older than 50 year (odd’s ratio: 4.48; 95% CI = 1.58–12.67).

Conclusion:  The elder OSF patients were increased in LOX Arg158Gln. Our findings may suggest a potential application in risk population selection using LOX polymorphism for preventive intervention of OSF genesis in a subset of areca chewers.
Signaling pathways for induction of platelet aggregation by SAS tongue cancer cells – a mechanism of hematogenous metastasis
Authors: Chang Mei‐Chi , Chan Chiu‐Po , Ho Yuan‐Soon , Lee Jang‐Jaer , Lin Po‐Shuen , Lin Bor‐Ru , Huang Ya‐Ling , Hahn Liang‐Jiunn , Yeh Hung‐Wei , Wang Ying‐Jan , Jeng Jiiang‐Huei
Published: August 2010

Background:  Tongue cancer metastasis is mainly through blood stream and possibly associated with tumor cell‐induced platelet aggregation (TCIPA).

Methods:  Platelet aggregation was induced by different amounts of SAS tongue cancer cells with/without inhibitors and the latent period for induction of platelet aggregation was recorded. Gene expression was analyzed by reverse transcriptase‐polymerase chain reaction.

Results:  SAS cells (4 × 104 to 1 × 106 cells/ml) induced platelet aggregation in a cell density‐dependent manner. The latent period for induction of platelet aggregation reduced from 11.3 min (2 × 105 cells/ml) to 0.9 min (5 × 105 cells/ml). The extent of platelet aggregation increased from 39% to 76% by 2 × 105 and 5 × 105 SAS cells. Pre‐treatment of SAS cells with aspirin showed little effect on its induction of platelet aggregation. SAS cells expressed tissue factor (TF) mRNA and the SAS cells‐induced TCIPA was inhibited by TF neutralization antibody (5–20 μg/ml), heparin (5–10 U/ml), Hirudin fragment 54–65 (50 μg/ml) and D‐Phenylalanyl‐L‐prolyl‐L‐arginine chloromethyl ketone. But areca nut (AN, a betel quid component known to generate reactive oxygen species (ROS)) extract showed little effect on TF expression in SAS cells. Pre‐treatment with U73122 and 2‐aminoethoxydiphenylborate inhibited SAS‐induced TCIPA. Interestingly, catalase suppressed SAS cells‐induced TCIPA, whereas AN extract enhanced this event.

Conclusions:  These results suggest that tongue cancer cells may induce TCIPA and enhance tumor metastasis. SAS‐induced TCIPA is related to TF secretion, thrombin generation and associated with Phospholipase C‐Inositol triphosphate signaling and ROS production. Betel quid chewing may potentially promote tongue cancer metastasis.
Oral lichen planus: a condition with more persistence and extra‐oral involvement than suspected?
Authors: Bidarra Marta , Buchanan John A. G. , Scully Crispian , Moles David R. , Porter Stephen R.
Published: August 2010

Background:  Lichen planus is a relatively common and often studied chronic mucocutaneous condition. Reports detailing certain aspects relevant to patients affected have been lacking or inconsistent.

Methods:  A questionnaire‐based survey was employed to assess the duration of oral lesions and the prevalence of self‐reported potential extra‐oral manifestations associated with oral lichen planus in 87 patients. All patients had recognized clinical features of oral lichen planus, and most had had histopathological confirmation following oral biopsy.

Results:  We report the findings of a preliminary survey which assessed the duration of oral lesions and the prevalence of extra‐oral lesions consistent with lichen planus in patients presenting with oral lesions. The study confirmed the chronic nature of oral lichen planus and the rarity of spontaneous resolution. Most subjects had experienced symptoms for one to ten years (66 patients; 75.8%). Approximately 40% (36 patients) of the sample reported clinical features suggestive of extra‐oral manifestations of lichen planus by the time that their oral lesions were apparent. The most commonly reported extra‐oral manifestations involved the nails (27.6%, 24 patients). 25.3% (22 patients) reported a persistently sore throat suggestive of oesophageal or pharyngeal involvement. Skin (17.2%, 11 patients), and genital (10.3%, 9 patients) involvement was relatively infrequently reported. Most patients reported extra‐oral lesions at only one site.

Conclusions:  The survey results suggest that in patients with oral lichen planus oral lesions persist for a prolonged period, and that extra‐oral lesions may be more common than suspected. However, further studies involving specialists to examine extra‐oral sites are required.
Oral cytology revisited
Authors: Mehrotra R. , Hullmann M. , Smeets R. , Reichert T. E. , Driemel O.
Published: August 2010

During the last decade, oral cytology has once again become the focus of scientific research. This new interest is due to the introduction of a cytobrush for cell collection as well as a computer‐assisted analysis (Oral CDx®). Although promising, the sensitivity and specificity of conventional oral brush cytology remains limited. To circumvent the problems and improve the accuracy, various adjunctive analytical methods have been attempted. DNA analysis, immunocytochemical and molecular analysis are suggested methodological cytology approaches to improve the validity of oral brush cytology. An increase in sensitivity (up to 100%) and specificity (up to 100%) of oral brush biopsy has been reported on localized pre‐malignant and malignant lesions. Oral brush biopsy probably will not replace histopathology in the definitive diagnosis of oral cancer, but it might be valuable for the prevention of misdiagnosis of clinically doubtful oral lesions and for the monitoring of lesions that might proceed on to oral cancer.
Expression of p16 in oral cancer and premalignant lesions
Authors: Buajeeb Waranun , Poomsawat Sopee , Punyasingh Jirapa , Sanguansin Sirima
Published: August 2010

Background:  Expression of p16 has been proposed as a marker for malignant transformation. This study aimed to evaluate p16 expression in oral squamous cell carcinoma (OSCC) and premalignant lesions including oral leukoplakia (OL) with and without dysplasia.

Methods:  Expression of p16 was investigated in 56 samples including OSCC, OL with and without dysplasia, and normal oral mucosa. Expression of p16 was identified by immunohistochemistry, using the CINtecTM p16INK4a Histology Kit. Both nuclear and/or cytoplasmic staining of the keratinocytes were considered to be positive and the percentage of positive cells was calculated.

Results:  Expression of p16 was detected in 3/16 (18.75%) cases of OSCC, in 4/15 (26.7%) cases of OL without dysplasia, and in none of OL with dysplasia and normal mucosa. No significant differences in p16 expression prevalence were found among OSCC, OL with and without dysplasia and normal mucosa. The percentages of positive cells in OSCC and OL without dysplasia were 0.89 and 0.17, respectively. No significant difference in the percentage of positive keratinocytes was found.

Conclusion:  As a marker, p16 is not reliable for oral mucosal dysplasia and malignant transformation.
Immunohistochemical analyses of survivin and heat shock protein 90 expression in patients with oral lichen planus
Authors: Chaiyarit Ponlatham , Jintakanon Darunee , Klanrit Poramaporn , Siritapetawee Mookhda , Thongprasom Kobkan
Published: August 2010

Background:  Survivin is an inhibitor of apoptosis protein. Heat shock protein 90 (Hsp90) is a molecular chaperone that is involved in protein folding and maturation. Alterations in the expression of survivin and Hsp90 have been reported in several chronic inflammatory diseases. No study has evaluated the expression of survivin and Hsp90 in the same lesion of oral lichen planus (OLP). The objective of this study was to investigate the expression of survivin and Hsp90 in biopsy specimens of patients with OLP and controls.

Method:  Formalin‐fixed and paraffin‐embedded biopsy specimens from 29 patients with OLP and 29 healthy subjects were used in this study. Immunohistochemical methods were used to detect the expression of survivin and Hsp90 in the oral epithelia of these two groups. The distributions of positively stained epithelial cells were evaluated with a semiquantitative method, using an immunostaining score system.

Results:  Expression of survivin and Hsp90 in oral epithelia of patients with OLP was significantly different in comparison with that in controls (P = 0.001 and P < 0.001 respectively). These differences were in the direction towards reduction in the expression of survivin and Hsp90 in the oral epithelia of patients with OLP .

Conclusion:  Our results provided additional evidence that alterations in the expression of survivin and Hsp90 in oral epithelia might be associated with pathological stress, such as chronic inflammation, in patients with OLP.
Methylation of P16, P21, P27, RB1 and P53 genes in odontogenic keratocysts
Authors: Moreira Paula Rocha , Guimarães Mariana Moreira , Guimarães André Luiz Sena , Diniz Marina Gonçalves , Gomes Carolina Cavaliéri , Brito João Artur Ricieri , Gomez Ricardo Santiago
Published: August 2010

Background:  Odontogenic keratocyst (OKC) is a benign neoplasm with an aggressive clinical behavior and a high recurrence rate. Although epigenetic alterations have been reported in different tumors, these events were not investigated in OKC yet. The aim of this study was to investigate the presence of methylation in P16, P21, P27, P53 and RB1 genes in OKC tumors.

Methods:  Methylation‐specific polymerase chain reaction (MSP) was used to evaluate the presence of methylation in 10 samples of OKCs, 10 samples of dental follicles and six samples of normal mucosa.

Results:  The methylation status of the P16 gene was similar among the three groups. In P21 gene, 30% of OKCs were methylated while no methylation could be detected in the other groups. High frequency of P27 methylation (90%) was observed in dental follicles, however, some OKC lesions (10%) and normal mucosa samples (33%) were also methylated. Concerning the RB1 gene, positive results were detected only in dental follicles (40%). No positive result was observed considering P53 gene.

Conclusions:  Our data show methylation of the promoter of P21 gene in OKCs. In addition, methylation of the P27 and RB1 genes are commonly found in dental follicles. Further studies are necessary to determine the functional relevance of these alterations.
Nitric oxide metabolism in cancerous and non‐cancerous oral gingivomucosal tissues: possible implications of nitric oxide in cancer process
Authors: Avci A. , Tüzüner‐Öncül A. M. , Gökcan M. K. , Namuslu M. , Öztürk A. , Durak İ.
Published: August 2010

Purpose:  Nitric oxide (NO) is a molecule that plays various roles in the body tissues. NO plays important roles in vasodilatation, platelet aggregation, cytokine stimulation, neurotransmission, immune function, etc. NO also exerts dual functions as an oxidant and antioxidant substance depending on its concentrations and environmental conditions. In this study, we aimed to examine possible correlation between NO levels and NO synthase (NOS) activity in the patients with oral cancer.

Materials and methods:  The study included 19 tissues from human subjects (11 malign and eight benign lesions).

Results:  NO level and NOS activity were found decreased in the malign lesions compared with those of the benign ones.

Conclusions:  In conclusion, two suggestions can be made; first, decreased NO synthesis may be an attempt to suppress angiogenesis, which is known to provide more essential nutrients to malign lesions and/or second, malign lesions may suppress NO production to be capable of creating more rapid proliferation as it has been known that NO is also a powerful free radical inducing apoptosis.
Granular cell tumor of the oral cavity: updated immunohistochemical profile
Authors: Vered Marilena , Carpenter William M. , Buchner Amos
Published: August 2010

Background:  Granular cell tumor (GCT) is a benign lesion that occurs at different body sites with preponderance to the oral cavity. It is generally believed to be of schwann cell/neural cell origin. We used a large panel of both traditional and recently developed antibodies in an attempt to trace the origin of GCTs on the basis of their immunoprofile.

Methods:  The patients’ demographic data and the cytological and architectural features of the lesions were analyzed in a large series of oral GCTs (n = 68). Forty‐two lesions were also submitted to a panel of immunohistochemical stains with antibodies against S‐100, CD‐68 (KP‐1 and PG‐M1), vimentin, calretinin, NKI/C3, PGP9.5, p75/NGFR and inhibin‐α.

Results:  The tongue was the most common location of oral GCTs (81%). The granular cells demonstrated a wide array of cytological features in terms of cell shape and position of the nucleus. In addition, the lesions showed different architectural patterns, including ‘infiltration’ with satellite nodules. Interestingly, no recurrences were reported, even in lesions that were not completely excised. Granular cells were usually found to be strongly and diffusely positive for p75, vimentin, calretinin and NKI/C3, inhibin‐α, PGP9.5, and S‐100.

Conclusions:  Immunoreactivity of the granular cells to a broad panel of antibodies that characterize different tissues does not confirm any particular cell type for the histogenetic origin of GCTs. Furthermore, GCTs could be regarded as lesions that reflect a local metabolic or reactive change rather than a true neoplasm.
Drooling
Authors: Scully Crispian , Limeres Jacobo , Gleeson Michael , Tomás Inmaculada , Diz Pedro
Published: August 2010

Introduction:  Drooling is the overflowing of saliva from the mouth. It is mainly due to neurological disturbance and less frequently to hypersalivation. Drooling can lead to functional and clinical consequences for patients, families, and caregivers. The aim of this review is to emphasize the clinical aspects of the assessing and management of drooling.

Methods:  All papers and clinical reviews of drooling in the electronic data bases (Medline, PubMed, Embase and the Cochrane Library) for the past 40 years in any languages have been evaluated.

Results:  The severity of drooling and the effects on the quality of life of the patient and family, help to establish a prognosis and to decide the therapeutic regimen. Treatment options range from conservative therapy to medication, radiation, or surgery, and often a combination is needed.

Conclusions:  Chronic drooling remains a problem that can be difficult to manage. Despite the acceptable results obtained with most of the treatments, none is free of undesirable effects.
Prognostic factors for keratocystic odontogenic tumor (odontogenic keratocyst): analysis of clinico‐pathologic and immunohistochemical findings in cysts treated by enucleation
Authors: Kuroyanagi Norio , Sakuma Hidenori , Miyabe Satoru , Machida Junichiro , Kaetsu Atsuo , Yokoi Motoo , Maeda Hatsuhiko , Warnakulasuriya Saman , Nagao Toru , Shimozato Kazuo
Published: August 2010

Background:  The purpose of this study was to determine prognostic factors for the recurrence of keratocystic odontogenic tumors (KCOTs) following simple enucleation by examining clinico‐pathologic and immunohistochemical findings.

Methods:  Following enucleation, the frequency of recurrence among 32 subjects diagnosed with KCOT was analyzed for tumor site, radiographic and histologic features, and immunopositivity for Ki‐67 and p53.

Results:  Keratocystic odontogenic tumors in four out of 32 subjects (12.5%) recurred during the follow‐up period (median: 33 months, range: 7–114 months). Three out of four subjects (75.0%) among recurrent group showed high expression of Ki‐67 (LI >10%) in basal layer and four (4/28; 14.3%) among non‐recurrence group (P = 0.025). Expression of p53 among non‐recurrent group was observed in 11 subjects (11/28; 39.3%), and in three subjects (3/4; 75.0%) among the recurrent group (P = 0.295). Hazard risk for the recurrence of KCOT was 4.02 (95% CI 1.42–18.14) for high Ki‐67 expression in the basal layer by the Cox proportional hazard model (P = 0.009). In our study, none of the other clinico‐pathologic variables were associated with the recurrence of KCOT.

Conclusion:  The results suggested that the evaluation of Ki‐67 expression in KCOT at the time of pathological diagnosis might be helpful for consideration of appropriate adjunctive surgical procedures to avoid a recurrence and may serve as a prognostic marker.
Systemic treatment of anti‐CD4+CD25+ T cell monoclonal antibody exacerbates sialoadenitis in submandibular glands during the early life in lupus‐prone female NZB × NZWF1 mice
Authors: Hayashi Toshiharu , Adachi Chie , Hasegawa Keiko
Published: August 2010

Background:  The maintenance mechanisms of peripheral tolerance by CD4+CD25+ T cells before the development of sialoadenitis in secondary Sjögren’s syndrome (sSS) are not well understood. The aim of the present study is to examine the effect of reduction of CD4+CD25+ T cells on the development of sialoadenitis during the early life in female NZB × NZWF1 (B/WF1) mice, a model for human sSS.

Methods:  Female B/WF1 mice at 3 days after birth were treated with either anti‐mouse CD4+CD25+ T cells rat IgG1 monoclonal antibody (mAb) or Rat IgG1(control). At 25 weeks of age, autoantibodies against nucleus and cytoplasm of ductal epithelial and myoepithelial cells, and histpathology of submandibular glands were examined in the mAb‐treated and control groups. Also the development of anti‐Ro/SS‐A antibodies was examined until 25 weeks of age in both groups.

Results:  The mAb‐treated group showed severe lesions with the development of autoantibodies compared to the control group.

Conclusions:  The present results suggest that peripheral CD4+CD25+ T cells may, at least in part, contribute to down‐regulate the development of sialoadenitis in submandibular glands of lupus‐prone female B/WF1 mice during their early life.
Apoptotic mechanism of paclitaxel‐induced cell death in human head and neck tumor cell lines
Authors: Hsiao J.‐R. , Leu S.‐F. , Huang B.‐M.
Published: August 2010

Background:  Paclitaxel (taxol) is clinically used to treat various human tumors. However, the cellular and molecular mechanism regarding apoptotic effect of paclitaxel on head and neck squamous cell carcinoma (HNSCC) remains elusive.

Methods:  The apoptotic effect and the mechanism of paclitaxel on FaDu hypopharyngeal cancer cell line, OEC‐M1 gingival cancer cell line, and OC3 betel quid chewing‐related buccal cancer cell lines were investigated by morphological observations, cell viability assay, flow cytometry assay and Western blotting methods.

Results:  Rounded‐up cell number increased with membrane blebbing as the treatment of paclitaxel (50–500 nM) increased from 24 to 48 h among these cell lines. In cell viability assay, cell surviving rate significantly decreased from 87 to 27% as the dosage and duration of paclitaxel treatment increased (P < 0.05). Flow‐cytometry analysis further demonstrated that 50 nM paclitaxel induced G2/M phase cell arrest among these cell lines within 8 h treatment, and then G2/M phase cell fraction significantly decreased as subG1 phase cell fraction significantly increased after 24 h treatment (P < 0.05), suggesting that cells underwent apoptosis. Furthermore, the activated caspases‐8, ‐9, ‐3, ‐6 and poly ADP‐ribose polymerase cleavage could all be significantly detected in FaDu, OEC‐M1 and OC3 cells (P < 0.05).

Conclusion:  Paclitaxel activated cell cycle arrest and caspase protein expressions to induce apoptosis in HNSCC cell lines.
Alpha lipoic acid in burning mouth syndrome – a randomized double‐blind placebo‐controlled trial
Authors: Cavalcanti Desirée Rosa , Da Silveira Fernando Ricardo Xavier
Published: August 2010

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).