bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.