bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral lesions in HIV and HCV co‐infected individuals in HAART era
Authors: Giuliani Michele , Lajolo Carlo , Sartorio Alessandra , Ammassari Adriana , Lacaita Maria Grazia , Scivetti Michele , Tamburrini Enrica , Tumbarello Mario 
Published: August 2010

Background:  During recent years, a new population of HIV and HCV co‐infected subjects has emerged presenting particular oral problems. The aim of our study was to determine the prevalence of oral lesions in HIV+ subjects and HIV and HCV co‐infected subjects, to assess whether co‐infection is a risk factor for the presence of oral lesions.Methods:  200 HIV+ subjects were consecutively enrolled, divided into two groups: Group 1 (130 HIV+ subjects) and Group 2 (70 HIV–HCV co‐infected subjects) and visited by two oral medicine specialists. Epidemiological, laboratory and clinical parameters were gathered to determine the possible risk factors for oral lesions.Results:  52 on 200 subjects (26%) presented oral lesions: in Group 1, 25 on 130 subjects (19.23%) presented oral lesions, whereas in Group 2, 27 on 70 subjects (38.57%) presented oral lesions. Multivariate analysis showed that the following variables are statistically associated with the presence of oral lesions: HIV–HCV co‐infection (OR = 2.32; 95% CI = 1.01–5.33: P < 0.05) and the use of drugs for the treatment of systemic diseases not associated with HIV (OR = 4.34; 95% CI = 1.78–5.33: P = 0.005).Conclusions:  It is possible to assess, on the basis of our results, that co‐infected patients are more prone than HIV mono‐infected patients to develop oral lesions and thus should undergo strict oral medicine monitoring.
The effect of betel quid and cigarette on multistate progression of oral pre‐malignancy
Authors: Yen Amy Ming‐Fang , Chen Shao‐Ching , Chang Shu‐Hui , Chen Tony Hsiu‐Hsi 
Published: August 2010

Background:  Although the effect of betel quid chewing and smoking on oral cancer has been well documented, both influences, dose and duration during life time, on multistate progression of oral pre‐malignancy are hardly addressed.Methods:  By recruiting a group of male chewers from different occupation groups, we modeled the effects of both duration and quantity of betel quid chewing and smoking on annual incidence rate of developing leukoplakia and average dwelling times (ADTs) staying in leukoplakia and erythroleukoplakia.Results:  The annual incidence rate (per year) of leukoplakia was estimated as 0.35% (95% CI: 0.22–0.48%). The ADTs were 24 years for leukoplakia and 7 years for erythroleukoplakia. Annual incidence rate of leukoplakia with high consumption and long duration of betel quid and smoking was higher. Both quantity and duration of smoking and betel quid chewing play minor roles in the influence of ADT. The risks of developing oral cancer after 20 years of follow‐up were 42.2% for leukoplakia and 95.0% for erythroleukoplakia.Conclusion:  The effects of betel quid chewing and smoking on multistate progressions between oral pre‐malignancies were elucidated. These results can be applied to predict long‐term risk of malignant transformation varying with different duration and quantity of betel quid and cigarette.
Head and neck squamous cell carcinoma in non‐smoking and non‐drinking patients with multiple tumors: etiologic significance of p53 and Ki‐67 in non‐tumorous epithelium
Authors: Farshadpour F. , Hordijk G. J. , Koole R. , Slootweg P. J. 
Published: August 2010

Background:  Non‐smoking and non‐drinking patients with head and neck squamous cell carcinoma have different clinical characteristics than their smoking and drinking counterparts. They are predominantly older female patients with oral cavity tumors, however, both groups show the same percentage of second primary tumors. Expression of tumor suppressor gene p53 and proliferation marker Ki‐67 in mucosal epithelial cells was analyzed to study whether biomarker expression is associated with a history of smoking and drinking and with single and multiple tumors.Methods:  Non‐smoking and non‐drinking patients with multiple (n = 18) and single tumors (n = 15), smoking and drinking patients with multiple (n = 15) and single tumors (n = 14) were selected. For all groups, p53 and Ki‐67 expression patterns in non‐tumorous (tumor‐adjacent) mucosa including positivity of dispersed single cells and clusters for p53 and for suprabasal expression of Ki‐67 were immunohistochemically analyzed and compared.Results:  p53 expression was significantly higher in users of tobacco and alcohol than in non‐users. Ki‐67 expression was not affected by tobacco and alcohol usage. Both Ki‐67 and p53 were similarly expressed in the groups with single and multiple tumors and hence not significantly related to the number of tumors.Conclusions:  Non‐smoking and non‐drinking patients with squamous cell carcinoma have the same risk for developing multiple tumors as their smoking and drinking counterparts. As this occurs without an increased expression of p53 or Ki‐67, the significance of these proteins as biomarkers indicating pre‐malignant mucosal alterations is doubtful. Further research is needed to clarify this predisposition for developing multiple head and neck cancer.
Decreased expression of Ep‐CAM protein is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan
Authors: Hwang Emily Ya‐Chi , Yu Chuan‐Hang , Cheng Shih‐Jung , Chang Julia Yu‐Fong , Chen Hsin‐Ming , Chiang Chun‐Pin 
Published: August 2010

Background:  The epithelial cell adhesion molecule (Ep‐CAM) is involved in cell signaling, migration, proliferation, cell‐cycle regulation, and cancer metastasis.Methods:  This study used an immunohistochemical technique to examine the expression of Ep‐CAM protein in 84 specimens of oral squamous cell carcinoma (OSCC), 98 specimens of oral epithelial dysplasia (OED, 31 mild, 41 moderate, and 26 severe OED cases), and 15 specimens of normal oral mucosa (NOM).Results:  We found that the mean Ep‐CAM labeling indices (LIs) decreased significantly from NOM (80 ± 18%) and mild OED (76 ± 14%) through moderate OED (66 ± 22%) and severe OED (55 ± 20%) to OSCC samples (46 ± 16%, P < 0.001). A significant correlation was found between the lower mean Ep‐CAM LI and OSCCs with larger tumor size (P = 0.003), positive lymph node metastasis (P = 0.022), more advanced clinical stages (P < 0.001), cancer recurrence (P = 0.021), or extracapsular spread of lymph node (P = 0.015). However, only Ep‐CAM LI < 50% (P < 0.0001) was identified as an independent unfavorable prognosis factor by multivariate analyses with Cox proportional hazard regression model. Kaplan–Meier curve showed that OSCC patients with an Ep‐CAM LI < 50% had a significantly poorer cumulative survival than those with an Ep‐CAM LI ≥ 50% (P < 0.00001, log‐rank test).Conclusions:  We conclude that the decreased expression of Ep‐CAM protein is an early event in oral carcinogenesis. The Ep‐CAM LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.
Immunohistochemical analysis of interleukin‐1α, its type I receptor and antagonist in keratocystic odontogenic tumors
Authors: Suyama Yoko , Kubota Yasutaka , Ninomiya Tomohiro , Shirasuna Kanemitsu 
Published: August 2010

Background:  Interleukin‐1α (IL‐1α) is thought to play a crucial role in the growth of keratocystic odontogenic tumors (KCOTs) in the jaw. The function of IL‐1α is regulated by the local levels of IL‐1α, its receptor and receptor antagonist (IL‐1Ra) in tissues. In this study, the expression of these proteins was investigated both before and after marsupialization in KCOTs.Methods:  The expression of IL‐1α, IL‐1 receptor type I (IL‐1RI) and IL‐1Ra was detected immunohistochemically in 10 specimens of KCOTs.Results:  IL‐1α was intensively expressed throughout the epithelium in all cases, while mild expression of IL‐1α was detected in the subepithelial layer endothelial cells and fibroblasts. Mild or intensive immunoreactivity for IL‐1RI was also observed in the epithelial cells in all cases, and in the endothelial cells and fibroblasts in five cases respectively. The expression of IL‐1Ra was detected in the epithelial cells in five cases, and in the endothelial cells and fibroblasts in three cases. After marsupialization, the immunoreactivity for IL‐1α and IL‐1RI in the epithelial cells decreased, while the immunoreactivity for IL‐1Ra in the epithelial cells increased. However, the immunoreactivity for IL‐1RI and IL‐1Ra in endothelial cells and fibroblasts did not change significantly.Conclusion:  The effects of IL‐1α on the epithelial cells might be downregulated after marsupialization by changing the expression levels of IL‐1α, IL‐1RI and IL‐1Ra in the epithelium of KCOTs.
CXCR‐4 knockdown by small interfering RNA inhibits cell proliferation and invasion of oral squamous cell carcinoma cells
Authors: Hong Ji‐Soo , Pai Hyun‐Kyung , Hong Kyoung‐Ok , Kim Mi‐Ae , Kim Ji‐Hong , Lee Jae‐Il , Hong Sam‐Pyo , Hong Seong‐Doo 
Published: August 2010

Background:  Oral squamous cell carcinomas (OSCCs) are characterized by a high degree of local invasion and a high rate of metastases to cervical lymph nodes. Downregulation of CXCR‐4 by siRNA inhibits invasion and growth of breast and colon cancer cells. However, there have been no reports on the downregulation of CXCR‐4 by small interfering RNA (siRNA) in oral cancer cells.Methods:  We generated two stable CXCR‐4‐knockdown clones (KBsi and KOSCC‐25Bsi) from the KB and KOSCC‐25B OSCC cell lines by lentiviral delivery. In vitro invasion and cell proliferation assays were used to investigate the effect of CXCR‐4 downregulation on cell proliferation and invasiveness in KBsi and KOSCC‐25Bsi. Immunohistochemistry was performed to evaluate the correlation between CXCR‐4 expression and proliferation in 26 OSCC tissue samples.Results:  CXCR4‐knockdown OSCC cells showed reduced invasiveness. The invasiveness of KBsi decreased to 29.5% of the vector‐infected controls, and KOSCC‐25Bsi decreased to 38.1% of the control vector‐infected cells (P < 0.05). The CXCR4‐knockdown OSCC cells grew significantly slower than the vector‐infected control cells. KBsi and KOSCC‐25Bsi cells proliferated at 69.5% and 71.7%, respectively, of the rate of control vector‐infected cells (P < 0.05). CXCR‐4‐positive group had significantly higher PCNA labeling index than CXCR‐4‐negative group in OSCC tissue samples.Conclusion:  These results suggest that the downregulation of CXCR‐4 induces anti‐proliferative and anti‐invasive effects in OSCC and that CXCR‐4 might be a useful target molecule for the treatment of OSCC.
Follicular dendritic cells confirm lymphoid organization in the minor salivary glands of primary Sjögren’s syndrome
Authors: Jonsson Malin V. , Skarstein Kathrine 
Published: August 2010

Background:  Sjögren’s syndrome (SS) is an autoimmune chronic inflammatory disorder affecting the salivary and lacrimal glands. The aim of this study was to explore immunophenotypic features of chronic inflammatory reactions in the minor salivary glands in patients with primary SS (pSS).Methods:  Formalin‐fixed, paraffin‐embedded labial minor salivary gland tissue sections from randomly selected patients with pSS (n = 60) were investigated for the expression of CD21, CD23, CD35 and IgD by immunohistochemistry.Results:  Based on the distribution and staining pattern of CD21, CD23, CD35 and IgD in lymphoid aggregates, several stages of chronic inflammatory reactions were observed. In 12/60 (20%) patients, lymphoid infiltrates with germinal centre (GC)‐like features such as extensive networks of CD21‐, CD23‐ and CD35‐positive cells were observed in the minor salivary gland tissue. Smaller networks and /or focal infiltrates with scattered CD21+, CD23+ and CD35+ cells were observed in the remaining 48/60 (80 %) cases. When dividing patients according to the presence (GC+) or the absence (GC−) of GC in the minor salivary glands, the mean focus score was significantly higher in the GC+ patients (P < 0.05). Double staining of the minor salivary glands revealed focal infiltrates with follicular dentritic cell networks and B cells resembling normal GCs in tonsillar tissue.Conclusion:  A particular cellular profile was demonstrated in a sub‐group of patients with pSS and could be linked to serological aberrations. These findings warrant further prospective studies.
Endoplasmic reticulum stress is involved in hydrogen peroxide induced apoptosis in immortalized and malignant human oral keratinocytes
Authors: Min Seung‐Ki , Lee Sun‐Kyung , Park Jae‐Sang , Lee Jun , Paeng Jun‐Young , Lee Sang‐Im , Lee Hwa‐Jeong , Kim Youngho , Pae Hyun‐Ock , Lee Suk‐Keun , Kim Eun‐Cheol 
Published: August 2010

Background:  Although hydrogen peroxide may play an important role in the development of cancer, it can be an efficient inducer of apoptosis in cancer cells; the exact mechanism by which this action occurs is not completely understood in oral cancer cells.Method:  In this study, the mechanisms by which H2O2 inhibited growth and induced apoptosis were differentially investigated using HPV‐immortalized human oral keratinocytes (IHOK) and oral cancer cells (HN4).Results:  H2O2 treatment sensitively and dose‐dependently induced growth inhibition and typical apoptosis in IHOK and HN4 cells, as demonstrated by a decreased level of cell viability, an increased population of cells in the sub‐G0/G1 phase, ladder formation of the genomic DNA, chromatin condensation and accumulation of Annexin V+/PI+ cells. Furthermore, the expression of Bax, p53 and p21WAF1/CIP1 increased, whereas the expression of Bcl‐2 decreased in immortalized and malignant keratinocytes that were treated with H2O2. In addition, cytochrome‐c from the mitochondria was observed in H2O2‐treated IHOK and oral cancer cells, and this was accompanied by the activation of caspase‐3 and ‐9. Additionally, H2O2 treatment induced upregulation of CHOP, GRP78 and several representative endoplasmic reticulum (ER) stress‐responsive proteins, including heme oxygenase‐1.Conclusion:  Overall, these results suggest that H2O2 triggers apoptosis via the mitochondrial and ER stress pathway in IHOK and HN4 cells, and that increasing the cellular levels of H2O2 sufficiently may lead to selective killing of oral cancer cells and therefore be therapeutically useful.
Graph models for phenotype and genotype association between oral mucosa and submandibular gland tumorigenesis in rat
Authors: Brunotto Mabel , Zarate Ana M , Barra José Luis , Malberti Alicia 
Published: August 2010

Background:  In recent years, success of statistics in field of genetics has been the identification of genes that affect the process of disease. Experimental models using animals enable early stages of tumor development to be studied. The aim of this study was to apply graph models to assess the association between the observed phenotypic changes in rat oral mucosa and induced tumorigenesis in the submandibular gland (SMG).Materials and methods:  We studied changes in oncogenes TP53 and bcl‐2, histopathological and immunomarker variables in samples of oral mucosa and SMG of Wistar male rats, 60 days old and 180 g in weight, in which tumorigenesis was induced in their SMG by a 0.5% solution of 9,10‐dimethyl‐1,2‐benzanthracene in acetone. A set of linear structural equations were defined, with each formula indicating the response variables and the direct influences. In graph models, saliva was considered as a latent variable. The association was analyzed using Graphical Gaussian Markov models and odd ratios.Results:  About 40% of animals treated with 9, 10‐dimethyl‐1, 2‐benzanthracene showed histological alterations in the epithelial basal strata of their oral mucosa only at 150 days. Statistical models indicated a relationship between gene alteration in gene bcl‐2 in the SMG and histological changes observed in the oral mucosa (P = 0.04).Conclusion:  Graph statistical model with one latent variable allows to conclude that these results associated with other clinical parameters may be useful in detecting early changes in SMG tumorigenesis. Furthermore, the design of randomized sampling of oral mucosa allows to validate these results and establish a reliable methodology for presumptive diagnosis or screening in the future.
Minor salivary gland immunohistology in the diagnosis of primary Sjögren’s syndrome
Authors: Salomonsson Stina , Rozell Barbro Lundh , Heimburger Mikael , Wahren‐Herlenius Marie 
Published: August 2010

Background:  Focal lymphocytic infiltrates of minor salivary glands are considered target‐organ related signs of Sjögren’s syndrome. The percentages of plasma cells expressing IgA, IgG and IgM in minor salivary gland biopsies have also been suggested as useful in establishing a diagnosis of Sjögren’s syndrome, and this study aimed at evaluating this method.Methods:  All biopsies from patients under investigation for Sjögren’s syndrome (n = 210) at our department during 4 years were analyzed for IgA, IgG and IgM producing cells by immunohistochemistry, and related to Sjögren classification parameters.Results:  A focus score ≥1 was observed in 67/210 patients and the frequency of IgA producing cells was <70% in 42/210 patients. Sufficient clinical data for classification of disease were available for 57/210 patients. Patients were classified as having primary Sjögren’s syndrome (pSS) (n = 9), secondary Sjögren’s syndrome (sSS) (n = 12) or non‐Sjögren’s syndrome (non‐SS) (n = 36). IgA expressing cells were significantly decreased (P < 0.01) and IgG expressing cells significantly increased (P < 0.02) in patients with pSS compared to non‐SS. Also, increased numbers of salivary gland IgG producing plasma cells correlated with increased IgG serum levels (P < 0.001). However, there was no significant difference between sSS and non‐SS with regard to IgA, IgG or IgM expressing cells in the glands.Conclusions:  Our results support previous reports indicating the relevance of quantitative evaluation of Ig isotype expression in plasma cells in the clinical investigation of Sjögren’s syndrome and further indicate a difference in plasma cell populations between pSS and sSS.
Maspin, p53, p63, and Ki‐67 in epithelial lesions of the tongue: from hyperplasia through dysplasia to carcinoma
Authors: Vered Marilena , Allon Irit , Dayan Dan 
Published: August 2010

Background:  The pattern of changes in the expression of mammary serine protease inhibitor (maspin) tumor suppressor protein in tongue epithelial lesions [hyperplasia (HP), mild dysplasia (MD), moderate‐to‐severe dysplasia (MSD) and squamous cell carcinoma (SCC)] was investigated and correlated to the expression of maspin‐regulating factors p53 and p63, and the proliferation marker Ki‐67.Methods:  Cases of HP (n = 16), MD (n = 12), MSD (n = 11), and SCC (n = 22) were immunostained for maspin, p53, p63, and Ki‐67. Maspin expression was scored separately for the basal, middle, and upper thirds of the epithelial width, and as the total sum of all ‘thirds’ (maspin‐total). p53, p63, and Ki‐67 were immuno‐morphometrically assessed for the entire epithelial width.Results:  Maspin expression was differential and progressive extending to higher epithelial layers as dysplastic changes aggravated and culminated in carcinoma. Strong expression was related to MSD in the middle third and to carcinoma in the upper third. It was frequently lost at the invasion front, where the tumor was less differentiated. The changes in mean scores of maspin‐total in the different study groups were positively correlated to the mean scores of p63 (r = 0.5, P < 0.001), p53 (r = 0.4, P = 0.004), and Ki‐67 (r = 0.5, P < 0.001).Conclusions:  Strong expression of maspin in the middle third of the epithelium may be considered a diagnostic sign of mild‐to‐moderate dysplasia and an indication of carcinoma in the upper third. The correlations between maspin and controlling factors (e.g. p63 and p53) may be events with key roles in the development of tongue carcinoma.
Activation of innate immune responses through Toll‐like receptor 3 causes a rapid loss of salivary gland function
Authors: Deshmukh Umesh S. , Nandula Seshagiri Rao , Thimmalapura Pushpa‐Rekha , Scindia Yogesh M , Bagavant Harini 
Published: August 2010

Background:  Recent studies have demonstrated the expression of Toll‐like receptor 3 (TLR3) in salivary glands and epithelial cell lines derived from Sjögren’s syndrome (SS) patients. As viral infections are considered to be a trigger for SS, in this study we investigated whether in vivo engagement of TLR3 affects salivary gland function.Methods:  Female New Zealand Black/WF1 mice were repeatedly injected with polyinosinic:polycytidylic acid [poly(I:C)]. TLR3 expression within submandibular glands was studied using immunohistochemistry. RNA levels of inflammatory cytokines in the submandibular glands were determined by real time polymerase chain reaction. Pilocarpine induced saliva volume was used as an index of glandular function.Results:  Immunohistochemical analysis of submandibular glands showed TLR3 expression in epithelium of serous and mucous acini, granular convoluted tubules, and ducts. Poly(I:C) treatment rapidly up‐regulated the mRNA levels of type I interferon (IFN) and inflammatory cytokines in the submandibular glands. One week after treatment, the saliva volumes in poly(I:C) treated mice were significantly reduced in comparison with the phosphate‐buffered saline (PBS) treated mice. Hematoxylin and eosin staining showed that salivary gland histology was normal and lymphocytic foci were not detected. Glandular function recovered after poly(I:C) treatment was stopped.Conclusions:  Our results demonstrate that engagement of TLR3 within the salivary glands results in a rapid loss of glandular function. This phenomenon is associated with the production of type I IFN and inflammatory cytokines in the salivary glands. Restoration of glandular function suggests that for viral etiology of SS, a chronic infection of salivary glands might be necessary.
DNA damage and apoptosis induced by Pteridium aquilinum aqueous extract in the oral cell lines HSG and OSCC‐3
Authors: Pereira Luciana Oliveira , Bicalho Leandro Santos , Campos‐da‐Paz Lopes Mariana , De Sousa Thiago Machado Mello , Báo Sônia Nair , De Fátima Menezes Almeida Santos Maria , Fonseca Marcio José Poças 
Published: August 2010

Background:  Bracken fern (Pteridium aquilinum) has been consumed by humans and animals for centuries. However, its consumption is associated with a high incidence of cancer in the upper digestory tract of different species. Although the oral cavity is the first site of contact with ingested toxic substances, the interaction of bracken fern composites with oral cell lines has not yet been studied.Methods:  In order to study the biological responses of oral cells exposed to bracken fern, we evaluated the genotoxic and cytotoxic effects of a bracken fern aqueous extract in oral cell lines. Human submandibular gland (HSG) and human oral epithelium cells (OSCC‐3) cells were treated with three different concentrations of the extract. DNA damage was determined by the comet assay, and cellular morphology was examined by light microscopy. Apoptotic changes were evaluated by transmission electron microscopy and TUNEL assay.Results:  The comet assay revealed that the extract was genotoxic for both cell lines but the results were not dose‐dependent. The morphological and ultrastructural analyses showed that the extract caused conspicuous alterations in both cell types: uncommon chromatin condensation, nuclear picnosis, cellular volume decrease, nuclear envelope disruption, formation of numerous vacuoles of different sizes and apoptotic bodies. The TUNEL assay confirmed apoptosis induction.Conclusions:  These results demonstrate that the extract was cytotoxic to HSG and OSCC‐3 cells, and that cellular degeneration occurred mainly by apoptosis. We believe that oral cells could trigger apoptosis after bracken fern induced DNA damage, in order to avoid the malignant transformation.