bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative analysis of c‐erbB‐2 (HER‐2/neu) in squamous cell carcinoma of the tongue: does over‐expression exist? And what is its correlation with traditional diagnostic parameters?
Authors: Angiero Francesca , Sordo Rachele Del , Dessy Enrico , Rossi Elisa , Berenzi Angiola , Stefani Michele , Sidoni Angelo
Published: August 2010

Objectives:  Over‐expression of the proto‐oncogene c‐erbB‐2 (HER‐2/neu) has been shown to be a prognostic marker in many kinds of cancer, whereas conflicting data exist about the prevalence of HER‐2/neu over‐expression in squamous cell carcinoma (SCC) of the tongue. The status of Her‐2/neu was evaluated in a series of SCC of the tongue to verify the frequency of over‐expression of HER‐2/neu and evaluate the correlation with traditional diagnostic parameters of this neoplasm.

Method:  Fourty patients with SCC of the tongue were investigated for over‐expression of the protein through immunohistochemistry using CB11 antibody, the Hercep Test® kit and FISH.

Results:  Data obtained using the Hercep Test® differ from published reports concerning the over‐expression of Her‐2/neu and there was no correlation between levels of expression of Her‐2/neu and other clinico‐pathological and/or prognostic parameters. Of the 40 specimens, using CB11 we obtained results in line with published reports; however, with the Hercep Test® we found only 1 positive case (2.5%) (score 3+).

Conclusion:  These data, confirmed by FISH, suggest that Her‐2/neu is not a suitable marker that could play a primary role in the clinical‐therapeutic management of SCC of the tongue.
P21/ WAF1 and cyclin D1 variants and oral squamous cell carcinoma
Authors: Gomes Carolina C. , Drummond Sergio N. , Guimarães André L. S. , Andrade Carlos I. , Mesquita Ricardo A. , Gomez Ricardo S.
Published: August 2010

Background:  Genetic factors are known to be involved in oral squamous cell carcinoma (OSCC) development.

Method:  We evaluated a possible association between CCND1 A870G and P21/WAF1 C98A polymorphisms and OSCC, as well as the impact of the genotypes on protein immunoexpression. The study group consisted of 80 individuals with histopathological diagnosis of OSCC and the control group consisted of 80 healthy individuals without oral lesions and matched by age, sex and tobacco usage. The genotypes were studied by the polymerase chain reaction and restriction fragment length polymorphic analysis. Paraffin‐embedded sections were used for immunohistochemical analysis.

Results:  No statistical association between CCND1 and/or P21/WAF1 genotypes and OSCC was demonstrated, although we found that people harbouring the combined presence of at least one variant allele of both genes showed a 1.8 times more chance of developing OSCC compared to the referent genotype. OSCC tumours from individuals with P21 heterozygous genotype showed a significantly higher immunopositivity than tumours from wild‐type individuals.

Conclusion:  The present study did not demonstrate a significant association between CCND1 and / or P21 / WAF1 genotypes and OSCC. However, P21 protein expression in OSCC tumours is affected by P21 / WAF1 genotype.
Demonstration of ethanol‐induced protein adducts in oral leukoplakia (pre‐cancer) and cancer
Authors: Warnakulasuriya Saman , Parkkila Seppo , Nagao Toru , Preedy Victor R. , Pasanen Markku , Koivisto Heidi , Niemelä Onni
Published: August 2010

Background:  Excessive alcohol consumption is a common cause for upper gastrointestinal tract cancers. However, the primary mechanisms of alcohol‐induced carcinogenesis have remained poorly defined.

Method:  We examined the generation and subcellular distribution of protein adducts with acetaldehyde (AA), the first metabolite of ethanol, and end products of lipid peroxidation, malondialdehyde (MDA) and 4‐hydroxynonenal (HNE), from oral biopsy specimens obtained from 36 subjects (11 British, 25 Japanese) reporting alcohol misuse. All patients had been diagnosed with oral pre‐cancer (leukoplakia, n = 7) or squamous cell carcinoma (SCC; n = 29). Automated immunostaining for AA, MDA and HNE adducts was performed using monospecific antibodies.

Results:  Positive staining for AA, MDA and HNE adducts was observed in the dysplastic or malignant epithelial cells, HNE being relatively the most abundant adduct species. The subgroup of Japanese patients had higher levels of AA and MDA, although not HNE, than the British sample. When the material was divided to those with SCC or leukoplakia, MDA adducts but not the other antigens were more prominent in the former group. Significant correlations were found between the different adducts (AA vs. MDA, r = 0.68, P < 0.001; AA vs. HNE, r = 0.47, P < 0.01 and MDA vs. HNE, r = 0.59, P < 0.001). In addition, cytochrome P450 2E1 staining was found in these samples, correlating with both AA and MDA adducts.

Conclusion:  The data indicates that AA‐ and lipid peroxidation‐derived adducts are formed in oral tissues of alcohol misusers with oral leukoplakia and cancer. The findings also support a pathogenic role of AA and excessive oxidative stress in carcinogenesis.
Tissue microarray – a high‐throughput molecular analysis in head and neck cancer
Authors: Radhakrishnan Raghu , Solomon Monica , Satyamoorthy Kapaettu , Martin Leslie E. , Lingen Mark W.
Published: August 2010

With the identification of a number of novel markers having diagnostic, prognostic, and therapeutic significance, the application of tissue microarray (TMA) has become a valuable tool for validating candidate markers in cancer research. The TMA is a high‐throughput technique, which allows large‐scale analyses of hundreds of archival clinical tissue samples using the ‘array’ approach. This paper highlights briefly its robust technology, technical aspects of its construction, and the validity of the TMA results for oral pathology diagnostics by reviewing data from recent literature particularly with reference to head and neck cancer.
Ameloblastoma, calcifying epithelial odontogenic tumor, and glandular odontogenic cyst show a distinctive immunophenotype with some myoepithelial antigen expression
Authors: Gratzinger Dita , Salama Mohamed E. , Poh Catherine F. , Rouse Robert V.
Published: August 2010

Background:  Odontogenic neoplasms have some morphologic overlap with salivary gland neoplasms, many of which show myoepithelial differentiation. In the 1980s, an ultrastructural study identified a population of myoepithelial‐like cells in calcifying epithelial odontogenic tumor. Myoepithelial derived tumors have since been shown to have distinct immunohistochemical profiles.

Methods:  We examined a series of odontogenic neoplasms, including 11 ameloblastomas, four calcifying epithelial odontogenic tumors, five glandular odontogenic cysts (GOCs), and five keratocystic odontogenic tumors with a panel of myoepithelial‐associated immunohistochemical stains. We also assessed representative control examples of oral mucosa, odontogenic rests, and dentigerous cysts.

Results:  All of the neoplastic and non‐neoplastic oral epithelium‐derived entities share a p63‐positive, high molecular weight cytokeratin (CK5/6)‐positive immunophenotype. Calponin reactivity was at least focally present in two of four calcifying epithelial odontogenic tumors, three of five GOCs, and 10 of 11 ameloblastomas; the sole completely non‐reactive ameloblastoma represents a lung metastasis. One case of calcifying epithelial odontogenic tumor was focally positive for glial fibrillary acidic protein. However, other more definitive markers of myoepithelial differentiation, including S‐100 and smooth muscle actin, were negative. Two of three calcifying epithelial odontogenic tumors and five of five GOCs were also positive for a low molecular weight cytokeratin (CK7).

Conclusions:  Ameloblastomas, GOCs, and calcifying epithelial odontogenic tumors show a distinctive immunophenotype which overlaps with that of myoepithelial‐derived salivary gland neoplasms but does not provide definitive support for myoepithelial differentiation.
Two unusual vascular lesions: epithelioid angiomatous nodule and spindle cell hemangiomatosis
Authors: Ide F. , Tanaka A. , Kusama K.
Published: August 2010

This report outlines the pathologic findings of epithelioid angiomatous nodule and spindle cell hemangiomatosis and briefly discusses the list of differential diagnoses. Although prevalent in the skin, both the above acquired vascular lesions are rarely described in the oral cavity. It should be realized that their microscopic features often raise concern for malignancy.
Perlecan‐rich epithelial linings as a background of proliferative potentials of keratocystic odontogenic tumor
Authors: Tsuneki Masayuki , Cheng Jun , Maruyama Satoshi , Ida‐Yonemochi Hiroko , Nakajima Motowo , Saku Takashi
Published: August 2010

Background:  The intraepithelial deposit of perlecan, a basement membrane‐type heparan sulfate (HS) proteoglycan, has been demonstrated in neoplastic conditions such as salivary gland tumors, odontogenic tumors, and oral carcinoma in situ. Our aim was to determine whether perlecan turnover was enhanced in the lining cells of keratocystic odontogenic tumor (KCOT), which had been recently renamed from odontogenic keratocyst because of its accumulated evidence of neoplasm, as a possible background for neoplastic proliferation.

Methods:  Ten surgical specimens from each of KCOT, dentigerous cyst, and radicular cyst were examined for the expressions of perlecan core protein, HS chains, heparanase, and Ki‐67 by immunohistochemistry and in situ hybridization.

Results:  In KCOT, perlecan core protein and HS chains were localized on the cell border from the parabasal to subkeratinized layers of the lining epithelium. Heparanase was localized in a similar fashion to those for perlecan and HS chains but was within the cytoplasm. mRNA signals for perlecan core protein and heparanase were mostly compatible with their protein signals. Ki‐67‐positive cells were localized mainly in the second basal cell layers with definitely higher labeling indices (approximately 31.3%, second layer). In contrast to KCOT, dentigerous cysts and radicular cysts had no perlecan, HS chains, and heparanase deposition in their linings with extremely lower Ki‐67 indices (0.4–0.8%).

Conclusion:  The result suggests that the characteristic intra‐lining‐epithelial deposit of perlecan in KCOT, which has never been seen in other cystic jaw lesions, is a new evidence supporting the neoplastic nature of KCOT.
Deglycosylated bleomycin triggers apoptosis in laryngeal carcinoma cells in a caspase and reactive oxygen species independent manner
Authors: Brahim Souhir , Bettaieb Ali , Kenani Abderraouf
Published: August 2010

Background:  Bleomycin‐A2, a member of a family of glycopeptide antibiotics, has potent antitumor activity against a range of lymphomas, head and neck cancer and germ cell tumors. However, little is known about the biologic activity of the carbohydrate moiety in Bleomycin‐A2‐induced cytotoxicity.

Methods:  We compared the capacity of Bleomycin‐A2 and its deglycosylated form (deglycoBleomycin‐A2) to induce cell death. Apoptosis was analyzed by cell nuclear staining with Hoechst 33342 dye and DNA fragmentation. The signal transduction pathway was measured through Western blotting and production of reactive oxygen species (ROS).

Results:  When tested on HEp‐2 laryngeal carcinoma cells, Bleomycin‐A2, and deglycoBleomycin‐A2 decreased cell viability and clonogenic survival, but Bleomycin‐A2 was more toxic than its deglycosylated form. The cell death occurred by apoptosis as identified by condensed chromatin and the formation of apoptotic bodies. While Bleomycin‐A2‐induced apoptosis was dependent on caspase activation and ROS production, deglycoBleomycin‐A2‐triggered apoptosis did not require caspase activation and ROS production.

Conclusions:  The deglycosylation of Bleomycin‐A2 suppresses the ability of the drug to induce ROS formation without hampering its toxic effect. These observations indicate that deglycoBleomycin‐A2 may demonstrate a less toxic profile than BLM in the clinic.
International collaborative study on ghost cell odontogenic tumours: calcifying cystic odontogenic tumour, dentinogenic ghost cell tumour and ghost cell odontogenic carcinoma
Authors: Ledesma‐Montes Constantino , Gorlin Robert J. , Shear Mervyn , Præ´torius Finn , Mosqueda‐Taylor Adalberto , Altini Mario , Unni Krishnan , Paes de Almeida Oslei , Carlos‐Bregni Román , Romero de León Elías , Phillips Vince , Delgado‐Azañero Wilson , Meneses‐García Abelardo
Published: August 2010

Background:  Calcifying odontogenic cyst was described first by Gorlin et al. in 1962; since then several hundreds of cases had been reported. In 1981, Prætorius et al. proposed a widely used classification. Afterwards, several authors proposed different classifications and discussed its neoplastic potential. The 2005 WHO Classification of Odontogenic Tumours re‐named this entity as calcifying cystic odontogenic tumour (CCOT) and defined the clinico‐pathological features of the ghost cell odontogenic tumours, the CCOT, the dentinogenic ghost cell tumour (DGCT) and the ghost cell odontogenic carcinoma (GCOC).

Methods:  The aim of this paper was to review the clinical‐pathological features of 122 CCOT, DGCT and GCOC cases retrieved from the files of the oral pathology laboratories from 14 institutions in Mexico, South Africa, Denmark, the USA, Brazil, Guatemala and Peru. It attempts to clarify and to group the clinico‐pathological features of the analysed cases and to propose an objective, comprehensive and useful classification under the 2005 WHO classification guidelines.

Results:  CCOT cases were divided into four sub‐types: (i) simple cystic; (ii) odontoma associated; (iii) ameloblastomatous proliferating; and (iv) CCOT associated with benign odontogenic tumours other than odontomas. DGCT was separated into a central aggressive DGCT and a peripheral non‐aggressive counterpart. For GCOC, three variants were identified. The first reported cases of a recurrent peripheral CCOT and a multiple synchronous, CCOT are included.

Conclusions:  Our results suggest that ghost cell odontogenic tumours comprise a heterogeneous group of neoplasms which need further studies to define more precisely their biological behaviour.
Upregulation of HIF‐1α in malignant transformation of oral submucous fibrosis
Authors: Tilakaratne W. M. , Iqbal Z. , Teh M. T. , Ariyawardana A. , Pitiyage G. , Cruchley A. , Stewart J. E. , Hagi‐Pavli E. , Lalli A. , Waseem A. , Parkinson E. K. , Fortune F.
Published: August 2010

Background:  Oral submucous fibrosis (OSF) is a precancerous condition showing extensive fibrosis of the submucosa and affects most parts of the oral cavity, including pharynx and upper third of the oesophagus. The molecules involved in the biological pathways of the fibrotic process appeared to be either down‐ or upregulated at different stages of the disease. Despite the precancerous nature, malignant transformation of the epithelium in the background of fibrosis has not been studied in detail. HIF‐1α is a known transcription factor that is induced by hypoxia.

Aims:  To test the hypothesis that hypoxia plays a role in malignant transformation and progression of OSF.

Materials and methods:  We used both formalin‐fixed and frozen samples of OSF and normal mucosa to investigate the relationship between HIF‐1α and epithelial dysplasia using immunohistochemistry and RT‐PCR.

Conclusions:  Our data indicate that HIF‐1α is upregulated at both protein and mRNA levels in OSF and the correlation with epithelial dysplasia is statistically significant (P < 0.001). We propose that HIF‐1α may play a role in malignant transformation of OSF. Further, over‐expression of HIF‐1α may contribute to the progression of fibrosis. It may be possible to use HIF‐1α as a marker for malignant transformation of OSF.
The upregulation of heat shock protein 47 expression in human buccal fibroblasts stimulated with arecoline
Authors: Yang Shun‐Fa , Tsai Chung‐Hung , Chang Yu‐Chao
Published: August 2010

Background:  Heat shock protein (HSP) 47, a collagen‐specific molecular chaperone, is involved in the processing and/or secretion of procollagen. HSP47 is consistently and dramatically upregulated in a variety of fibrotic diseases. The aim of this study was to compare HSP47 expression in normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further to explore the potential mechanisms that may lead to induce HSP47 expression.

Methods:  The mRNA levels of HSP47 from fibroblasts cultured from 20 OSF and 10 normal buccal mucosal fibroblasts (BMFs) were evaluated by reverse transcription polymerase chain reaction. The effect of arecoline, the major areca nut alkaloid, was added to explore the potential mechanisms that may lead to induce HSP47 expression. Furthermore, mitogen‐activated protein kinase kinase (MEK) inhibitor U0126, phosphatidylinositol 3‐kinase (PI3K) inhibitor LY294002, p38 inhibitor SB203580, cyclo‐oxygenase‐2 (COX‐2) inhibitor NS‐398, and glutathione precursor N‐acetyl‐l‐cysteine were added to find the possible mechanisms.

Results:  OSF demonstrated significantly higher HSP47 mRNA expression than BMFs (P < 0.001). Arecoline was also found to elevate HSP47 mRNA expression in a dose‐dependent manner (P < 0.05). The amount of HSP47 was about 3.7‐fold at a concentration level of 80 μg/ml arecoline when compared with control (P < 0.05). In addition, pre‐treatment with pharmacologic agents markedly inhibited the arecoline‐induced HSP47 mRNA expression (P < 0.05).

Conclusions:  Taken together, HSP47 is significantly upregulated in OSF from areca quid chewers and HSP47 expression induced by arecoline in fibroblasts may be mediated by MEK, PI3K, and COX‐2 signal transduction pathways.
Increased number of CD25+ FoxP3+ regulatory T cells in oral squamous cell carcinomas detected by chromogenic immunohistochemical double staining
Authors: Schwarz Stephan , Butz Martin , Morsczeck Christian , Reichert Torsten E. , Driemel Oliver
Published: August 2010

Background:  The role of tumor‐infiltrating regulatory T cells (Treg) compromising antitumor effects of immune cells in oral squamous cell carcinoma (OSCC) is largely unknown.

Purpose:  The presence of CD25+ FoxP3+ Treg as well as of CD3+ FoxP3+ and of CD8+ FoxP3+ tumor‐infiltrating lymphocytes (TIL) was verified in OSCC and compared with non‐cancerous lymphoepithelial tissue.

Method:  Three double stainings (CD3/FoxP3, CD8/FoxP3 and CD25/FoxP3) were performed on tissue sections of 15 OSCC and compared with 15 human tonsils.

Results:  OSCC biopsy samples provide evidence for a strong infiltration of TIL, in particular, naturally occurring CD25+ FoxP3+ Treg. Whereas a comparison of OSCC and control tissue did not show significant changes in the number of CD3+ FoxP3+ TIL and of CD8+ FoxP3+ TIL, a significantly higher frequency of CD25+ FoxP3+ TIL (Treg) could be observed in OSCC (P < 0.001, two‐sided t‐test). Given the small number of specimens, a significant correlation with tumor stage could not be verified.

Conclusion:  Chromogenic double staining of CD4/FoxP3 is a promising tool for the detection of Treg in paraffin‐embedded tissue of OSCC.
Fingerprinting genomic instability in oral submucous fibrosis
Authors: Teh M. T. , Tilakaratne W. M. , Chaplin T. , Young B. D. , Ariyawardana A. , Pitiyage G. , Lalli A. , Stewart J. E. , Hagi‐Pavli E. , Cruchley A. , Waseem A. , Fortune F.
Published: August 2010

Background:  Oral submucous fibrosis (OSF) is a high‐risk pre‐cancerous condition where 7–13% of these patients develop head and neck squamous cell carcinoma (HNSCC). To date there is no cancer predictive markers for OSF patients. Genomic instability hallmarks early genetic events during malignant transformation causing loss of heterozygosity (LOH) and chromosomal copy number abnormality. However, to date there is no study on genomic instability in OSF. Although this condition is known as a high‐risk pre‐cancerous condition, there is no data regarding the genomic status of this disease in terms of genetic susceptibility to malignant transformation.

Methods:  In this study, we investigated the existence of genetic signatures for carcinogenesis in OSF. We employed the high‐resolution genome‐wide Affymetrix Mapping single nucleotide polymorphism microarray technique to ‘fingerprint’ global genomic instability in the form of LOH in 15 patient‐matched OSF–blood genomic DNA samples.

Results:  This rapid high‐resolution mapping technique has revealed for the first time that a small number of discrete hot‐spot LOH loci appeared in 47–53% of the OSF tissues studied. Many of these LOH loci were previously identified regions of genomic instability associated with carcinogenesis of the HNSCC.

Conclusion:  To our knowledge, this is the first evidence that genomic instability in the form of LOH is present in OSF. We hypothesize that the genomic instability detected in OSF may play an important role in malignant transformation. Further functional association studies on these putative genes may reveal potential predictive oral cancer markers for OSF patients.
Mutational analysis of Wnt signaling molecules in ameloblastoma with aberrant nuclear expression of β‐catenin
Authors: Tanahashi Jin , Daa Tsutomu , Yada Naomi , Kashima Kenji , Kondoh Yoshiyuki , Yokoyama Shigeo
Published: August 2010

Background:  To clarify the genetic background of ameloblastoma, expression of β‐catenin, and mutational status of genes involved in Wnt signaling pathway were investigated.

Methods:  We analyzed β‐catenin and cyclin D1 in 18 cases of ameloblastoma by immunohistochemical staining, and searched for mutations in CTNNB1 (gene for β‐catenin), APC, AXIN1, and AXIN2 by polymerase chain reaction (PCR) and direct sequencing method.

Result:  We detected membranous and occasionally cytoplasmic expression of β‐catenin in 16 of 18 cases (89%), and nuclear expression of β‐catenin principally in the peripheral columnar cells in 11 of 18 cases (61%). In nine of the 18 cases (50%), we detected the expression of cyclin D1 principally in the peripheral columnar cells. However, there was no correlation between nuclear expressions of β‐catenin and cyclin D1. No missense mutations were found in CTNNB1, APC, AXIN1, and AXIN2 in all cases except for silent mutation and already‐known single nucleotide polymorphism.

Conclusion:  Mutations in CTNNB1, APC, AXIN1, and AXIN2 are not implicated in nuclear accumulation of β‐catenin, and that the expression of cyclin D1 is accelerated independently of β‐catenin in ameloblastomas. Other Wnt signaling members or alternative pathways involved in the degradation of β‐catenin should be subject of further investigation.
The role of basic fibroblast growth factor in oral submucous fibrosis pathogenesis
Authors: Bishen Kundendu Arya , Radhakrishnan Raghu , Satyamoorthy Kapaettu
Published: August 2010

Background:  Oral submucous fibrosis (OSF) is a chronic fibrotic disease of oral mucosa and oropharynx, induced by betel quid chewing often resulting in restricted mouth opening. The principal cells implicated as a source of extracellular matrix in areas of fibrosis are fibroblasts. Accumulation of connective tissue matrix is secondary to factors such as cytokines and growth factors. The contribution of basic fibroblast growth factor (bFGF) in disease progression and the consequent stromal changes with increase in the severity of OSF was studied.

Methods:  A case series analysis of 30 cases of OSF was carried out for bFGF expression using immunohistochemistry. Connective tissue changes in these cases were corroborated using aldehyde fuchsin and Verhoeff’s hematoxylin special stains.

Results:  bFGF immunoreactivity was found to be increased in fibroblasts and in endothelial cells in early OSF cases, while the expression of bFGF in stroma increased notably in advanced fibrosis.

Conclusion:  Increased bFGF expression in early stages of the disease was explainable to an initial injury phase because of areca consumption, followed by cellular activation by chemotactic cytokines and other growth factors with eventual fibrosis occurring as a result of molecular alteration at the cellular level.
Morphology of the sella turcica in Axenfeld–Rieger syndrome with PITX2 mutation
Authors: Meyer‐Marcotty P. , Weisschuh N. , Dressler P. , Hartmann J. , Stellzig‐Eisenhauer A.
Published: August 2010

Background:  Axenfeld–Rieger syndrome (ARS) is a rare autosomal dominant disorder with an incidence of 1:200 000. Genotype and phenotype are heterogeneous and clinical morphology impresses with variable expressivity. Additionally to the typical craniofacial and dental aberrations anomalies in the morphology of sella turcica are discussed.

Method:  In a multidisciplinary genetic and clinical study four patients of a family with ARS were screened by direct DNA sequencing. Radiographic analysis of the patients was performed for evaluating cranial and dental structures. Additionally, a specific analysis of the morphology of the sella turcica was made on the radiographs.

Results:  Screening for PITX2 and FOXC1 mutations revealed a P64L missense mutation in PITX2 in all four patients. The cephalometric analysis showed a midface hypoplasia associated with a skeletal Class III. All patients showed a sella turcica bridge combined with a prominent posterior clinoid process followed by a steep clivus and an elongated sella turcica.

Conclusion:  The incidence of a sella turcica bridge in combination with a PITX2 mutation would suspect that sella turcica anomalies are typical symptoms of the syndrome. Sella turcica anomalies in association with craniofacial and dental aberrations, such as maxillary retrognathia, skeletal Class III relationship and hypoplasia of teeth, might be important indicators for ARS caused by PITX2 mutation.
The management of oral mucous membrane pemphigoid with dapsone and topical corticosteroid
Authors: Arash Azizi , Shirin Lawaf
Published: August 2010

Statement of problem:  Mucous membrane pemphigoid (MMP) is a chronic autoimmune subepithelial disease that primarily affects the mucous membranes of patients over the age of 50 years, resulting in mucosal ulceration and subsequent scarring.

Purpose:  The purpose of this study was to investigate the efficacy of dapsone in combination with topical corticosteroids to treat the oral lesions of MMP.

Materials and methods:  Twenty‐two patients who had been diagnosed with MMP were selected. The oral features were graded according to severity of disease from 1 to 3. Each patient was assigned to one of four groups according to his or her response to therapy.

Results:  Five patients with mild to moderate disease were treated with topical corticosteroids alone for the duration of the study; 15 patients with moderate to severe disease were treated by topical corticosteroid with dapsone therapy. All of 15 patients had significant benefits.

Conclusions:  The use of dapsone in combination with topical corticosteroids is one of the most useful methods for the treatment of MMP.
Isolation and characterization of dental pulp stem cells from a supernumerary tooth
Authors: Huang Anderson Hsien‐Cheng , Chen Yuk‐Kwan , Lin Lin‐Min , Shieh Tien‐Yue , Chan Anthony Wing‐Sang
Published: August 2010

Background:  Dental pulp stem cells (DPSCs) were primarily derived from the pulp tissues of primary incisors and permanent third molar teeth, whereas no report to our knowledge has yet been documented on deriving DPSCs from the other tooth types. The aim of this study is to present a novel approach of harvesting stem cells from a supernumerary tooth (a mesiodens).

Materials and methods:  The pulp tissues from a mesiodens of a 20‐year‐old healthy male patient and the left lower deciduous canine of a healthy 10‐year‐old boy (the positive control) were extracted and cultured for DPSCs, which were examined with stem cells (Oct‐4, Nanog and Rex‐1) and differentiation (Osteonectin and Nestin) markers. Furthermore, DPSCs were directionally differentiated to osteogenic and adipogenic cell lineages.

Results:  Dental pulp stem cells derived from the mesiodens were capable of differentiating into adipogenic and osteogenic lineages. The mesioden’s DPSCs also expressed stem cell and differentiation markers, which suggested their stem cell origin and differentiation capability. All the aforementioned results for the mesiodens were consistent with those of the DPSCs derived from the positive control.

Conclusion:  We have demonstrated the feasibility of deriving DPSCs from a usually discarded tissue such as a supernumerary tooth.
Influences of tumor stroma on the malignant phenotype
Authors: Nielsen Jørgen Dau , Moeslund Mette , Wandall Hans H. , Dabelsteen Sally
Published: August 2010

Background:  The microenvironment makes a significant contribution to the progression of oral carcinomas. Many different stromal events, such as vascularization, fibroblast activation, myofibroblast differentiation, and the presence of specific stromal proteins, such as proteolytic enzymes, fibronectin and laminin 5 are all characteristics of the tumor stroma. Less is, however, known of the significance of the biophysical properties of the tumor stroma. The purpose of the present study was to investigate how cellular and mechanical properties of the three‐dimensional collagen matrix may influence cell proliferation and invasion of oral carcinoma cell lines.

Method:  Oral cancer cells were cultured in an organotypic culture system on different collagen concentrations, and invasion was measured. Furthermore, the presence of cancer associated proteins such as glycosylated oncofetal fibronectin and laminin 5 was investigated.

Results:  We found that expression of glycosylated oncofetal fibronectin was increased in the invasive phenotype of oral carcinoma cell lines. Furthermore we demonstrated that certain concentrations of collagen in the connective tissue equivalent, appears to stimulate invasiveness of oral carcinoma cells.
Immunoexpression of hMSH2 and hMLH1 in oral squamous cell carcinoma and its relationship to histological grades of malignancy
Authors: Fernandes Anacelia Mendes , Ramos‐Jorge Maria Letícia , Cardoso Sergio Vitorino , Loyola Adriano Mota , Mesquita Ricardo Alves , Aguiar Maria Cássia Ferreira
Published: August 2010

Background:  The aim of this study was to describe the human mutS homolog 2 (hMSH2) and human mutL homolog 1 (hMLH1) immunoexpression in different areas of oral squamous cell carcinoma (OSCC) – central/superficial (C/S) and invasive tumor front (ITF) – in an attempt to verify if the histological grade of malignancy interferes in this expression.

Methods:  Forty‐six samples of OSCC were analyzed histologically. Twenty‐six cases (56.5%) presented ITF. Histological grades of malignancy were evaluated in all samples, and immunohistochemistry was applied using specific antibodies against hMSH2 and hMLH1 proteins. Immunoexpression was semiquantitatively scored, and results were correlated with their histological grades of malignancy.

Results:  The hMSH2 immunoexpression in both C/S and ITF was not correlated with histological grades of malignancy, whereas hMLH1 overexpression was correlated (P = 0.043) and associated (P = 0.041) with well‐differentiated tumors. In addition, hMHL1 reduction or negative expression was detected in poorly differentiated tumors. Moreover, negative expression for hMSH2 and hMLH1 proteins was demonstrated in some cases of OSCC.

Conclusions:  The findings of the present study indicate that the histological grade of malignancy interferes in hMLH1 immunoexpression. The negativity for both hMSH2 and hMLH1 proteins in some cases suggests a possible association between OSCC and hereditary non‐polyposis colorectal cancer. Further investigation from future studies is needed to elucidate this supposition.
Dysfunction of CD4+CD25high T regulatory cells in patients with recurrent aphthous stomatitis
Authors: Lewkowicz Natalia , Lewkowicz Przemyslaw , Dzitko Katarzyna , Kur Barabara , Tarkowski Maciej , Kurnatowska Anna , Tchórzewski Henryk
Published: August 2010

Background:  Recurrent aphthous stomatitis (RAS) is a chronic inflammatory disease of unknown etiology characterized by recurring formation of painful oral ulcers. RAS may result from oral epithelium damage caused by T‐cell‐mediated immune response. CD4+CD25+ T regulatory (Treg) cells suppress proliferation and effector functions of other immune cells, and therefore are crucial in regulating the immune response.

Methods:  We tested the function of peripheral CD4+CD25high Treg cells in active RAS through their ability to inhibit proliferation and cytokine production of conventional CD4+ T cells. We also attempted to detect the presence of FOXP3 and indoleamine 2,3‐dioxygenase (IDO) mRNA in the lesional and non‐lesional oral mucosa of RAS patients and healthy individuals using real‐time PCR assay.

Results:  Treg cells derived from RAS patients were less efficient in the suppression of cytokine production of CD4+ T effector cells than Treg cells from healthy individuals. Moreover, in RAS, Treg cells were nearly twice less potent in the inhibition of CD4+CD25− T cell proliferation than in healthy donors. Furthermore, we have demonstrated the decreased proportion of CD4+CD25+FOXP3+ Treg cells in peripheral blood of RAS patients compared with controls. We failed to detect FOXP3 mRNA, while IDO mRNA expression was decreased in non‐lesional mucosa biopsies from RAS patients compared with ulcer biopsies or normal mucosa from healthy donors.

Conclusions:  These findings suggest that CD4+CD25high Treg cells are both functionally and quantitatively compromised in RAS and that decreased constitutive expression of IDO in oral mucosa in RAS may lead to the loss of local immune tolerance.
Serum cytokine and T regulatory cell levels in patients with burning mouth syndrome
Authors: Pekiner Filiz Namdar , Demirel Gülderen Yanıkkaya , Gümrü Birsay , Özbayrak Semih
Published: August 2010

Background:  Burning mouth syndrome is a disorder usually associated with an unexplained, prolonged sensation of burning inside the oral cavity. Although the etiology is unknown, neural and psychologic factors and cytokines may be implicated in the pathogenesis of burning mouth syndrome. The aim of this study was to investigate the relationship between serum cytokine and T regulatory cell levels in patients with burning mouth syndrome with regard to depression and anxiety.

Methods:  Thirty patients with burning mouth syndrome and 30 matched controls participated in the study. Serum cytokine levels were measured with cytometric bead array and T regulatory cells were defined as CD4+CD25+Foxp‐3+ cells by flow cytometry. The level of anxiety and depression were analyzed by means of the Speilberger State‐Trait Anxiety Inventory and Zung Self‐Rating Depression Scale. Visual analogue scale was used in the quantification of burning levels of patients.

Results:  Serum IL‐2 and TNF‐α levels were significantly decreased in patients with burning mouth syndrome compared with controls [mean 16.79 ± 8.70 vs. 37.73 ± 41.05 pg / ml (P < 0.05) and mean 39.09 ± 29.40 vs. 70.83 ± 42.44 pg / ml (P < 0.01) respectively].

Conclusions:  IL‐2 and TNF‐α might play a role in burning mouth syndrome. Burning mouth syndrome may occur as a sign of predisposition to autoimmunity. Presence of low levels of CD28+ supports the provision that BMS might be a pre‐otoimmune disease.
Quality of life in patients with burning mouth syndrome
Authors: López‐Jornet Pía , Camacho‐Alonso Fabio , Lucero‐Berdugo Mayra
Published: August 2010

Objective:  To study the quality of life in patients with burning mouth syndrome (BMS), our primary aim was to compare BMS patients with healthy controls and the secondary aim was to compare subgroups of BMS patients on the type of therapy received; using the Medical Outcome Short Form Health Survey Questionnaire (SF‐36) and the Oral Health Impact Profile (OHIP‐49) as measurement instruments.

Method:  Sixty consecutive patients (10 males and 50 females) with BMS were studied in the Department of Oral Medicine (Faculty of Medicine and Dentistry, University of Murcia, Spain), while 60 healthy patients were used as controls. The Spanish version of the SF‐36 was used to evaluate general quality of life, together with the OHIP‐49 in its Spanish version.

Results:  Regarding general quality of life as assessed with the SF‐36, and on comparing the BMS vs. the control groups, lower scores were obtained in the former in all domains (P < 0.001). The OHIP‐49 in turn yielded significant differences in each of the domains vs. the controls. No significant differences were found between the patients with BMS in any domain regarding parafunctional habits and the presence of dentures. In relation to the different treatments, significant differences were recorded in functional limitation (P = 0.02) and physical pain (P = 0.033).

Conclusion:  Patients with BMS yield poorer scores on all scales vs. the healthy controls when applying the SF‐36 and OHIP‐49.
An immunohistochemical study of XIAP expression in pleomorphic adenoma and carcinoma ex pleomorphic adenoma
Authors: Hoch Benjamin L. , Wu Maoxin , Lewis Michael , Gan Li , Burstein David E.
Published: August 2010

Background:  X‐linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitor of apoptosis proteins family of caspase inhibitors. Expression of XIAP in various neoplasms has been associated with aggressive behavior. The biological progression from pleomorphic adenoma (PA) to carcinoma ex pleomorphic adenoma (CXPA) has been poorly understood. We studied XIAP expression by immunohistochemistry in PA and CXPA.

Materials and methods:  Formalin‐fixed, paraffin‐embedded representative sections of 14 cases of PA and seven cases of CXPA (four invasive and three intracapsular) were stained with anti‐XIAP (# 610763; BD Biosciences, San Jose, CA, USA) following citrate‐based antigen retrieval. Granular cytoplasmic staining was considered positive and intensity was assessed from weak (1+) to strong (3+). PAs were morphologically evaluated for cellularity, cytological atypia and mitotic activity.

Results:  Of the seven PAs composed mostly of myxohyaline stroma with scattered ductal elements, two tumors showed no staining and five showed rare (<1%) 1+ positive cells. Of seven more cellular PAs, five had sheets of tumor cells comprising more than 50% of the tumor and two had sheets comprising more than 80% of the tumor (cellular PA), focal to diffuse 2+ to 3+ staining was observed. Tumor cells with strong staining often exhibited cytological atypia in the form of nuclear enlargement and contour irregularity, prominent nucleoli and eosinophilic cytoplasm. Mitotic activity was occasionally seen in cellular areas expressing XIAP. All cases of CXPA demonstrated diffuse 3+ staining in the carcinomatous component and 1+ to focally 3+ staining in cellular areas of the underlying PA.

Conclusion:  Increased expression of XIAP from PA to cellular PA to CXPA and in atypical cells within cellular areas of PA adds to our growing understanding of defective apoptotic pathways in malignant transformation in this group of salivary gland tumors and suggests an adenoma to adenocarcinoma model of progression. Further correlation with other oncogene expression may provide insight into the multiple molecular pathways that are affected in these tumors. Targeted therapy of XIAP may play a future role in the management of CXPA.
Expression profile of the S100 gene family members in oral squamous cell carcinomas
Authors: Sapkota Dipak , Bruland Ove , Bøe Olav E. , Bakeer Hala , Elgindi Osman A. A. , Vasstrand Endre N. , Ibrahim Salah O.
Published: August 2010

Background:  Several of the S100 gene members have been reported to be differentially expressed in many human pathological conditions, in particular, the malignancies. Identification and quantification of the differentially expressed S100 gene members in oral squamous cell carcinoma (OSCC) might facilitate their use as potential diagnostic and/or prognostic markers or targets for therapy.

Methods:  we examined the expression profile of 16 members of the S100 gene family at the mRNA level by semiquantitative reverse transcription‐polymerase chain reaction (sRT‐PCR) in 27 cases of OSCCs/their pair‐wised normal controls obtained from Sudanese patients, and confirmed the sRT‐PCR results by performing quantitative real time‐polymerase chain reaction (qRT‐PCR) for 6 of the 16 genes examined.

Results:  With sRT‐PCR, 4 (25%; S100A4, S100A6, S100A8, S100A14) out of the 16 S100 gene members examined were found to be significantly down‐regulated (P < 0.05) in the tumors compared to the normal controls. None of the S100 gene members examined were found to be significantly up‐regulated in the tumors. qRT‐PCR results confirmed the significant down‐regulation of the S100A4, S100A6, and S100A14 genes in the tumors examined.

Conclusion:  S100 gene family members might play an important role in the pathogenesis of the OSCCs examined. Findings of the present work warrant in‐depth studies of the S100 gene family members, in particular, the S100A4, S100A6, S100A8, and S100A14 to further understand their possible role(s) in OSCC tumorigenesis.
Prevalence of oral herpes simplex virus reactivation in cancer patients: a comparison of different techniques of viral detection
Authors: Djuric Milanko , Jankovic Ljiljana , Jovanovic Tanja , Pavlica Dusan , Brkic Snezana , Knezevic Aleksandra , Markovic Dubravka , Milasin Jelena
Published: August 2010

Background:  Oral reactivation of latent Herpes simplex virus (HSV) infection may easily occur in cancer patients. Virus reactivation can cause oral mucosa damage, worsen already existing lesions caused by stomatotoxic effect of cancer therapy and, whether symptomatic or asymptomatic, ample spreading and promote viral transmission.

Methods:  Polymerase chain reaction (PCR), cell‐culture and direct immunofluorescence have been used to determine the frequency of oral HSV reactivation in 60 patients undergoing chemotherapy for different malignancies.

Results:  By means of PCR, the presence of viral DNA was detected in 71.7% of patients prior to chemotherapy and in 85.0% after chemotherapy. 33.3% of patients before and 40.0% after chemotherapy were viral‐culture positive, while 3.3% of patients before and 11.7% after chemotherapy were positive as shown by direct immunofluorescence. No significant difference in HSV‐1 reactivation was found before and after chemotherapy. In addition, no significant difference was found when comparing HSV‐1 reactivation in patients with and without mucositis. HSV‐2 was not detected in any of the patients.

Conclusions:  Reactivation of latent HSV is exceptionally frequent in cancer patients. The results of this study suggest that virus reactivation occurs independently of cancer chemotherapy. The potential role of HSV reactivation in oral mucosa damage remains unclear.
Significantly higher frequencies of presence of serum autoantibodies in Chinese patients with oral lichen planus
Authors: Chang Julia Yu‐Fong , Chiang Chun‐Pin , Hsiao Chuhsing Kate , Sun Andy
Published: August 2010

Background:  Previous studies have shown the presence of serum anti‐nuclear (ANA), anti‐smooth muscle (SMA), anti‐mitochondrial (AMA), anti‐gastric parietal cell (GPCA), anti‐thyroglobulin (TGA) and anti‐thyroid microsomal autoantibodies (TMA) in small groups of patients with oral lichen planus (OLP).

Methods:  In this study, the serum levels of ANA, SMA, AMA, GPCA, TGA and TMA were measured in a group of 320 Chinese OLP patients and 53 healthy control subjects to assess whether Chinese OLP patients had significantly higher frequencies of serum autoantibodies than healthy control subjects and to assess which risk factors had a significant influence on the possession of a specific serum autoantibody in OLP patients.

Results:  We found that autoantibodies were present in 195 (60.9%) of the 320 OLP patients. The frequencies of presence of serum ANA (28.1%), GPCA (26.3%), TGA (21.3%) and TMA (24.4%) in OLP patients were significantly higher than those (5.7%, 1.9%, 1.9% and 1.9%, respectively) in healthy control subjects (all P‐values were < 0.005). Forty‐one (12.8%) OLP patients also had anti‐hepatitis C virus antibody (HCVA) in their sera. The multivariate logistic regression found that major erosive OLP (EOLP) [odds ratio (OR) = 1.786], TGA/TMA‐positivity (OR = 2.517), and HCVA‐positivity (OR = 2.214) were significant risk factors to influence ANA‐positivity in OLP patients. Moreover, only major EOLP (OR = 1.879) and ANA‐positivity (OR = 2.581) were significant risk factors to influence TGA/TMA‐positivity in OLP patients.

Conclusions:  There are significantly higher frequencies of presence of ANA, GPCA, TGA and TMA in Chinese OLP patients than in healthy control subjects.
Topical clobetasol in the treatment of atrophic‐erosive oral lichen planus: a randomized controlled trial to compare two preparations with different concentrations
Authors: Carbone M. , Arduino P. G. , Carrozzo M. , Caiazzo G. , Broccoletti R. , Conrotto D. , Bezzo C. , Gandolfo S.
Published: August 2010

Oral lichen planus (OLP) is a chronic inflammatory disease that can be painful, mainly in the atrophic and erosive forms. Numerous drugs have been used with dissimilar results, but most treatments are empirical and do not have adequate control groups or correct study designs. However, to date, the most commonly employed and useful agents for the treatment of LP are topical corticosteroids. A randomized, double‐blind, placebo‐controlled trial has been designed to compare the efficacy and safety of two different formulations of clobetasol, a very potent topical steroid, in the topical management of OLP and to evaluate which gives the longest remission from signs and symptoms. Thirty‐five consecutive patients were divided into two groups: the first received clobetasol propionate 0.025% and the second was given clobetasol propionate 0.05%. Both drugs were placed in 4% hydroxyethyl cellulose bioadhesive gel. Anti‐mycotic prophylaxis was also added. After the end of therapy, patients received a 2‐month follow‐up. In all, 14 of the 15 clobetasol 0.025% patients (93%) and 13 of the 15 clobetasol 0.05% patients (87%), had symptoms improvement after 2 months of therapy (P = 0.001 in both groups). Also, 13 of the 15 clobetasol 0.025% patients (87%) and 11 of the 15 clobetasol 0.05% patients (73%) had clinical improvement after 2 months of therapy (P < 0.05 in both groups). No statistical differences were found in comparing the two different formulations. A larger concentration of the active molecules cannot further improve the therapeutic findings or optimize the obtained results in a significant manner.
Off‐label use of biologicals in the management of inflammatory oral mucosal disease
Authors: O’Neill Iain David
Published: August 2010

The recent development of novel biologic immunomodulators effective in the treatment of immune‐mediated inflammatory conditions has led to their widespread use in rheumatology and dermatology. These include the tumour necrosis factor‐α antagonists, infliximab, etanercept and adalimumab and the T‐cell modulator modifiers efalizumab and alefacept. In dermatology, although these agents are licensed only for psoriasis, increasingly off‐label use has extended to a number of conditions in which oral mucosal disease is a significant component. These include Behçet’s disease, recurrent apthous stomatitis, benign mucous membrane pemphigoid and lichen planus. This article provides a review of the current literature on such off‐label use in oral mucosal disease.