bluuebunny/crossref_metadata_2025 huggingface dataset:
Epithelial salivary gland tumors of children and adolescents in west China population: a clinicopathologic study of 79 cases
Authors: Laikui Liu , Hongwei Li , Hongbing Jiang , Zhixiu He
Published: August 2010

Objective:  Determine the clinical and histopathologic features of epithelial salivary gland tumors of children and adolescents.

Methods:  A total of 79 cases of epithelial salivary gland tumors of children and adolescents were retrieved from the files. Information about demographic, clinical, histopathologic characteristics, and follow‐up status were analyzed.

Results:  Sixty tumors (75.9%) were benign and 19 (24.1%) malignant. The most common tumor overall was pleomorphic adenoma (PA). The parotid was the most frequently involved site (43.0%). PA was the most common type of benign tumor. The most common malignant tumor was mucoepidermoid carcinoma. Five patients with parotid PA and two cases with palate myoepithelioma showed local recurrences. One patient with mucoepidermoid carcinoma showed local recurrences and died from the tumor 3 years after the initial treatment. One patient with adenocarcinoma presented local and neck recurrences, and died 4 years after initial treatment.

Conclusions:  Our data showed that the salivary gland tumors in children and adolescents may be the higher incidence of benign tumors, especially of PA; the slightly higher tendency for female predominance; the higher incidence of parotid glands. Mucoepidermoid carcinoma was the most common malignant tumor, with majority of low grade. Initial treatment should be planned to excise the tumor completely with satisfactory margins. The neck dissections or postoperative radiotherapy were performed in patients with low differentiation malignancies, or patients who present nodal metastasis or with clinically suspicious regional metastasis.
NGF and its receptors TrkA and p75NTR in the epithelium of oral lichen
Authors: Hayashi Katsuhiko , Karatsaidis Andreas , Schreurs Olav , Bjørnland Tore , Sugisaki Masashi , Schenck Karl
Published: August 2010

Background:  Nerve growth factor (NGF) can through its receptors TrkA and p75NTR convey signals for cell survival, differentiation and death. The aim of this study was to examine whether NGF can play a role in the pathology of oral lichen (OL).

Methods:  Sections from biopsies taken from patients with erythematous (ERY) OL and from volunteers with normal oral mucosa (NOM) were immunostained with antibodies against NGF, proNGF, TrkA, phosphorylated Trk, p75NTR and phosphorylated Akt (pAkt) and expression of RNA coding for proNGF/NGF was investigated by in situ hybridization.

Results:  Both in ERY OL and NOM, cytoplasmic staining for NGF was seen in granular and upper spinous cell layers of the epithelium, whereas proNGF staining was seen in all epithelial cell layers. In situ hybridization showed that the proNGF protein was produced in the same cell layers. In OL, strong cytoplasmic stainings for TrkA and activated Trk (pTrk) were observed in all epithelial cell layers while these stainings were only weak in NOM. Basal keratinocytes in OL showed no or only weak cytoplasmic staining for p75NTR, but in NOM there was a clear cell membrane staining. In OL, strong cytoplasmic and intermittent nuclear staining for pAkt was observed in spinous, granular and superficial layers, while basal and parabasal keratinocytes were negative. This staining was weak or absent in the entire epithelium of NOM.

Conclusions:  TrkA upregulation and activation in OL is one of the pathways that can activate pAkt and thereby rescue epithelial cells from untimely cell death.
Quantitative histological changes of repeated antigen‐induced arthritis in the temporomandibular joints of rabbits treated with intra‐articular corticosteroid
Authors: Kristensen Kasper Dahl , Stoustrup Peter , Küseler Annelise , Pedersen Thomas Klit , Nyengaard Jens Randel , Hauge Ellen‐Margrethe , Herlin Troels
Published: August 2010

Background:  To compare the inflammatory changes of antigen‐induced temporomandibular joint (TMJ) arthritis in rabbits by different histological methods and to evaluate the immunomodulatory effect of intra‐articular corticosteroid injections histologically.

Methods:  35 rabbits (10 weeks old) pre‐sensibilized with ovalbumin were divided into three groups: a placebo group of five (saline), an arthritis group of 15 (ovalbumin) and a steroid‐treated group of 15 (ovalbumin + corticosteroid). Additionally, a group of seven rabbits receiving no sensibilization with ovalbumin and no intra‐articular injections served as controls. Histomorphometry of the inflammatory changes in the subsynovial connective tissue (SSCT) of the TMJ included: (i) semi‐quantitative (S‐Q) scoring of inflammation and synovial proliferation, (ii) thickness measurements and fractional surface and (iii) stereological quantitative assessment of volume and plasma cells in thick sections of the SSCT by an optical fractionator.

Results:  The histomorphometry showed synovial proliferation in both the arthritis and the steroid groups. The plasma cell count obtained by the optical fractionator was significantly reduced when treating the TMJ with corticosteroids. However, the thickness of the synovial lining and volume of the SSCT as well as S‐Q scoring of inflammation showed no difference between the arthritis and the steroid‐treated groups. The optical fractionator proved a superior tool compared to S‐Q assessments.

Conclusion:  Counting of plasma cells in the SSCT showed that corticosteroids reduced the inflammation, but did not eliminate it. Semiquantitative scoring of synovial proliferation and inflammation demonstrated low sensitivity regarding changes in immunomodulation in antigen‐induced arthritis compared to stereological quantitative estimations using an optical fractionator.
Oral aphthous‐like lesions, PFAPA syndrome: a review
Authors: Femiano Felice , Lanza Alessandro , Buonaiuto Curzio , Gombos Fernando , Cirillo Nicola
Published: August 2010

Aphthous ulcers are the most common oral mucosal lesions in the general population. Several precipitating factors for aphthous ulcers are suggested to operate on subjects with genetic predisposition. Sometimes aphthous ulcers can be the sign of systemic diseases. Therefore, it is essential to establish a correct diagnosis to determine suitable therapy. There are several diseases potentially responsible for oral ulcers. Sometimes appearance of periodic oral ulcers coincides with periodic fever and other symptoms leading to the diagnosis of a rare childhood disease: PFAPA (periodic fever, aphthous stomatitis, pharyngitis and adenopathy) syndrome. PFAPA or Marshall’s syndrome is characterized by abrupt onset of periodic episodes of high fever accompanied by aphthous stomatitis, pharyngitis and cervical adenitis, often associated with headache and / or abdominal or joint pain. Owing to the periodic onset of oral symptoms, often an oral physician or pediatric dentist may be the first healthcare worker to evaluate a child with clinical signs compatible with PFAPA syndrome. Children diagnosed with this condition require systematic oral follow‐up to monitor for signs of ulceration.
Mood and malignancy: head and neck cancer and depression
Authors: Archer Jo , Hutchison Iain , Korszun Ania
Published: August 2010

Head and neck cancer patients have been reported to show high rates of depression. However, it is important to differentiate between depressive symptoms and a depressive disorder. This review critically examines the relationship between head and neck cancer and depression. There appears to be little evidence for depression leading to an increased risk of developing cancer and although depressive symptoms in head and neck cancer patients are common, very few studies have investigated depressive disorders. The studies that investigated the incidence of a comorbid depressive disorder report a prevalence very close to that of the general population, implying that major depression is not a normal response to cancer. Finally, the evidence suggests that comorbidity of depression with cancer has a negative impact on morbidity and mortality. Both psychosocial and biological factors could account for this. Dysregulation of the stress hormone axis and increased inflammation are common in depressive disorders and have been suggested as underlying pathological mechanisms and are both markers of poor prognosis in cancer. This evidence suggests that a relatively small number of patients develop a depressive disorder following a diagnosis of cancer, but for those that do it may have a substantial impact on their prognosis.
Human laminin‐332 degradation by Candida proteinases
Authors: Pärnänen P. , Kari K. , Virtanen I. , Sorsa T. , Meurman J. H.
Published: August 2010

Background:  Human laminin‐332 (Lm‐332) degradation by 12 Candida strains and effects of synthetic proteinase inhibitors [Ilomastat (ILM), EDTA, chemically modified tetracycline‐3(CMT‐3), CMT‐308, synthetic peptide CTT‐2, and Pefabloc] were studied.

Materials and methods:  Laminin‐332 was incubated with sonicated cell fractions and 10 times concentrated cell‐free fractions of reference and clinical strains of C. albicans, C. dubliniensis, C. guilliermondii, C. glabrata, C. krusei, and C. tropicalis. Proteolysis, pH effects, and inhibitors were analyzed by fluorography and zymography.

Results:  Cell fractions of all species except C. guilliermondii and cell‐free fractions of C. albicans, and C. dubliniensis showed 20–70 kDa gelatinases at pH 5.0 and 6.0. At pH 7.6, C. glabrata, C. krusei, and C. tropicalis cell fractions and C. tropicalis cell‐free fractions showed 55–70 kDa gelatinases. CMT‐3, CMT‐308, and CTT‐2 inhibited Candida gelatinases slightly better than Pefabloc, ILM, and EDTA. No Candida fractions degraded Lm‐332 at pH 7.6, but at pH 5.0, 100 kDa bands were generated by cell fractions of C. dubliniensis and C. tropicalis; C. albicans and C. glabrata clinical strains; and C. guilliermondii reference strain. C. krusei reference strain yielded three 100–130 kDa bands. C. albicans, C. dubliniensis, and C. tropicalis reference and clinical strain’s cell‐free fractions generated 100 kDa band.

Conclusions:  Laminin‐332 degradation is pH‐dependent and differences exist between studied Candida strains. Lm‐332 degradation can exert functional disturbances on basement membrane integrity, possibly aiding Candida cell invasion into tissues. Certain synthetic matrix metalloproteinase inhibitors (CMTs, CTT) can inhibit Candida proteinases and may be therapeutically useful in future.
Microsatellite GTn‐repeat polymorphism in the promoter of heme oxygenase‐1 gene is an independent predictor of tumor recurrence in male oral squamous cell carcinoma patients
Authors: Vashist Y. K. , Blessmann M. , Trump F. , Kalinin V. , Kutup A. , Schneider C. , Gawad K. , Kaifi J. T. , Schmelzle R. , Izbicki J. R. , Yekebas E. F.
Published: August 2010

Background:  Transcriptional activity of the heme oxygenase‐1 gene (HMOX‐1) is modulated by a GTn‐repeat promoter polymorphism. The long GTn‐repeat allele has been previously reported to be associated with increased risk of oral squamous cell carcinoma (OSCC) in male areca chewer and short GTn‐repeat allele has been proposed to have protective properties in OSCC patients. The aim of the present study was to correlate the GTn‐repeat genotypes with clinicopathological characteristics along with clinical outcome of non‐areca chewer OSCC patients.

Methods:  DNA of 99 patients that underwent complete surgical resection of OSCC was analyzed for GTn‐repeat polymorphism in the HMOX‐1 promoter by polymerase chain reaction, capillary electrophoresis and DNA sequencing.

Results:  Seven SS (7.1%), 51 SL (51.5%) and 41 LL (41.4%) genotypes were found. In a total of 14 (14.1%) patients, tumor recurrence (TR) was observed. There was no TR in the SS allele carriers. In SL carriers three and in LL 11 TR occurred (P = 0.009, chi‐squared test). Mean relapse‐free survival was 109.2 months in SL allele carriers compared with 72.3 months in LL allele carriers (P = 0.01, log‐rank test). Multivariate Cox regression modeling identified GTn‐repeat genotype as an independent prognostic factor (P = 0.03; relative risk (RR) 4.1; 95% CI 1.1–14.6).

Conclusion:  Presence of S allele was associated with a lower TR rate and better relapse‐free survival in OSCC patients. HMOX‐1 promoter polymorphism might be considered as a potential prognostic marker in OSCC patients.
Areca chewing in Xiangtan, Hunan province, China: interviews with chewers
Authors: Zhang Xiaolin , Li Chengjie , Liao Qizhi , Reichart Peter A.
Published: August 2010

Background:  To report on Areca chewing (AC) in Xiangtan, Hunan province, China, and to test the knowledge of chewers related to side effects of the habit.

Methods:  Interviews with 276 individuals were performed. A questionnaire including general data, chewing habits, educational level and knowledge about side effects were used. Data were analysed using spss. Chi‐square test was used at a significance level of P < 0.05.

Results:  Around 257 individuals were chewers (male: 54.1%; female: 45.9%) and 19 were former chewers (male: 31.6%; female: 68.4%). Mean age of chewers was 36.1 years. Around 42.4% of chewers smoked; 58.0% had a drinking habit. Average period of chewing was 11.2 years. Around 88.3% of chewers did not include the nut (seed). Around 79.0% considered AC habits negative for general health and 85.2% for oral health.

Conclusions:  Most respondents did not know that AC may induce oral submucous fibrosis and oral cancer. The ‘betel quid’ chewed in Xiangtan usually does not contain Areca ‘nut’ (seed, endosperm), but consists of the husk. As no studies on the chemical composition of the Areca husk have been published such investigations are urgently needed.
Oral manifestations in patients with gastro‐oesophageal reflux disease: a single‐center case–control study
Authors: Di Fede Olga , Di Liberto Chiara , Occhipinti Giuseppe , Vigneri Sergio , Lo Russo Lucio , Fedele Stefano , Lo Muzio Lorenzo , Campisi Giuseppina
Published: August 2010

Objective:  To assess the occurrence of oral pathological changes and symptoms in patients affected by gastro‐oesophageal reflux disease (GERD).

Patients and methods:  200 patients with GERD and 100 matched healthy controls were studied. Thorough visual examination of the dental and oral mucosal tissues was performed and medical history relevant to oral symptoms was collected. The primary outcome was defined as a statistically significant difference, between the study group and controls, in the presence of the following indicators: soft/hard palate and uvula erythema, tooth wear, xerostomia, oral acid/burning sensation, subjective halitosis and dental sensitivity. Statistical analysis included chi‐squared test, and crude odds ratio with 95% CI.

Results:  Univariate analysis showed that xerostomia, oral acid/burning sensation, subjective halitosis, and soft and hard palate mucosa and uvula erythema were more common in patients with GERD than matched controls (P < 0.05).

Conclusions:  This study failed to find any significant association between GERD and dental erosions, whereas some symptoms and other objective oral mucosal changes were found to be significantly associated with GERD.
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.
Oral malignant melanoma: a review of the literature
Authors: Femiano Felice , Lanza Alessandro , Buonaiuto Curzio , Gombos Fernando , Di Spirito Federica , Cirillo Nicola
Published: August 2010

Primary oral melanoma (POM) is an uncommon malignant tumor that originates from the proliferation of melanocytes. Such tumors can be present at any location in the oral cavity; however, it affects more frequently the hard palate and the maxillary alveolar mucosa. POM is usually asymptomatic in the early stages and it presents normally as a pigmented patch or as a mass with a rapid growth rate. In the advanced stages, it can show ulceration, swelling, bleeding, rapid enlargement and loosening of teeth. Melanoma of the mouth is rare, most commonly occurring in the upper jaw of patients more than 65 years. Because of a frequent delay in diagnosis, the tumors are often diagnosed when they are deeper than the average cutaneous melanoma. The prognosis is extremely poor, especially in advanced stages. Therefore, pigmented lesions of undetermined origin should be routinely subjected to a biopsy examination. In this study, we aimed to present a review on primary malignancy.
Hypericum perforatum extract in burning mouth syndrome: a randomized placebo‐controlled study
Authors: Sardella Andrea , Lodi Giovanni , Demarosi Federica , Tarozzi Marco , Canegallo Lorenza , Carrassi Antonio
Published: August 2010

Burning mouth syndrome (BMS) or stomatodynia is characterized by a spontaneous burning pain in the oral mucosa without known cause or recognized treatment. This double‐blind, randomized, placebo‐controlled, single‐center study evaluated the effects of systemic Hypericum perforatum extract in patients with BMS. Forty‐three patients participated, of whom 39 (35 women, four men, aged 64.9 ± 4.7 years) completed the study. The patients took indistinguishable 300‐mg capsules containing either H. perforatum extract (hypericin 0.31% and hyperforin 3.0%) or placebo three times a day for 12 weeks. The intensity of burning pain was evaluated using a 10‐cm visual analog scale (VAS) before the first dose and at visits after 4, 8, and 12 weeks. Furthermore, we also recorded the number of oral mucosa sites with reported burning symptoms and the self‐reported descriptions of the patient’s condition before and after the treatment. Pain, measured using the VAS, was similar at the beginning of the study and even though a slightly better performance in the test group, the difference was not statistically significant (P = 0.2216). The results failed to demonstrate that 300 mg of H. perforatum extract taken three times a day for 12 weeks improved the pain of BMS patients, although the general reduction in the number of sites with reported burning sensation, a less accurate and objective score, was significant.
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.
IL‐1β and PGE2 levels are increased in the saliva of children with Langerhans cell histiocytosis
Authors: Preliasco Virginia F. , Benchuya Carolina , Pavan Veronica , De La Cal Carolina , Ganzinelli Sabrina , Sterin‐Borda Leonor
Published: August 2010

Langerhans cell histiocytosis (LCH) is a rare disorder mainly of children, whose pathogenesis is still unknown. Some studies have demonstrated that LCH lesions produce different cytokines abnormally that may be relevant to the pathogenesis of the disease. The purpose of this study was to investigate interleukin‐1β (IL‐1β) and prostaglandin E2 (PGE2) levels in saliva from children with different clinical subtypes of LCH. We studied 29 children with LCH: seven unifocal (Group I), seven multifocal (Group II), 15 multisystemic (Group III) and 12 healthy volunteers (Group IV). Salivary IL‐1β and PGE2 levels were significantly higher in LCH than in normal children. A multi‐comparison test showed significantly (P < 0.001) higher levels of both IL‐1β and PGE2 in saliva from Group III compared with Groups II and I. A significant correlation (r = 0.05) between IL‐1β and PGE2 concentrations in saliva from each group was determined. Our findings demonstrated an association between high concentrations of salivary IL‐1β and PGE2 and advanced stages of the disease. This allows us to suggest that the abnormal amount of these factors in saliva may serve as a risk marker for disease progression.
New insights into the nature of Warthin’s tumour
Authors: O’Neill Iain David
Published: August 2010

Warthin’s tumour is considered heterogeneous as to its pathogenesis with some data supporting a polyclonal origin for the epithelium, implying a non‐neoplastic nature. After inconsistent reports, current information from molecular studies suggests that a recurrent t(11;19) and associated CRTC1‐MAML2 fusion oncogene characterizes a subset of Warthin’s tumours and supports a clonal origin in such cases. CRTC1‐MAML2 is also a frequent feature of mucoepidermoid carcinoma. These findings, and the recent reports of Warthin’s tumour and co‐existent mucoepidermoid carcinoma with common CRTC1‐MAML2 expression, provide a morphological and molecular framework for future studies as a basis for a fresh appraisal of the pathogenesis of Warthin’s tumour. The underlying molecular basis and the pivotal studies defining such events are discussed.
Decreased expression of Annexin A1 correlates with pathologic differentiation grade in oral squamous cell carcinoma
Authors: Zhang Lei , Yang Xiao , Zhong Lai‐ping , Zhou Xiao‐jian , Pan Hong‐ya , Wei Kui‐jie , Li Jiang , Chen Wan‐tao , Zhang Zhi‐yuan
Published: August 2010

Previously, we established an in vitro cellular carcinogenesis model of oral squamous cell carcinoma (OSCC), including the human immortalized oral epithelia cells (HIOECs) and its derived cancerous HB96 cells. In this study, comparative proteomic analysis identified that Annexin A1 was one of the significantly down‐regulated genes in the cancerous HB96 cells. To investigate Annexin A1 down‐regulation and its potential usefulness as a molecular marker in OSCC, we further screened Annexin A1 expressions with a panel of OSCC lines, and clinical samples of cancerous and the paired adjacent normal tissues from primary OSCC patients. By Western blot analysis and real‐time PCR, we showed that both Annexin A1 mRNA and protein expressions decreased in OSCC cell lines except in two cell lines for the mRNA levels. Immunohistochemistry and real‐time PCR also showed that both Annexin A1 mRNA and protein expressions decreased in the cancerous tissues from OSCC patients compared with those in the paired adjacent non‐malignant epithelia. More importantly, both Annexin A1 mRNA and protein expressions negatively correlated with the pathologic differentiation grades of cancerous tissues. The lower Annexin A1 mRNA or protein expressions correlated with the poorer pathologic differentiation grades. These results suggest that decreased expression of Annexin A1 contributes to the cancerous progression of OSCC, and Annexin A1 may be a potential biomarker for pathologic differentiation grade of OSCC.
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.
Inhibition of CD146 gene expression via RNA interference reduces in vitro perineural invasion on ACC‐M cell
Authors: Chen W. , Zhang H. L. , Jiang Y. G. , Li J. H. , Liu B. L. , Sun M. Y.
Published: August 2010

Background:  Overexpression of melanoma cell adhesion molecule (MCAM or CD146), a novel member of the immunoglobulin gene superfamily, promotes invasion, metastasis, growth and survival of malignant cells.

Materials and methods:  Here, we used a human U6 promoter‐driven DNA template approach to induce short hairpin RNA (shRNA)‐triggered RNA interference to block CD146 gene expression in the human high‐metastatic adenoid cystic carcinoma (ACC) cell line ACC‐M. reverse transcription‐polymerase chain reaction, Western blot, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide assay, flow cytometry analysis and in vitro perineural invasion (PNI) assay were used to investigate the effects of CD146 on cell growth, cell cycle distribution and cell PNI activity in ACC‐M cells.

Results:  We have demonstrated that different shRNAs can specifically knockdown the transcription of CD146, resulting in the inhibition of cell proliferation, and G0/G1 to S phase arrest in ACC‐M cells. Knockdown of CD146 by shRNA resulted in decrease of the ACC‐M PNI activity in vitro.

Conclusion:  These findings suggested that CD146 was an ACC‐related gene and CD146 may play an important role in the carcinogenesis, progression and PNI activity of ACC.