Oral cancer: A multicenter study.

BACKGROUND: To determine the prevalence and clinicopathologic features of the oral cancer patients. MATERIAL AND METHODS: Biopsy records of the participating institutions were reviewed for oral cancer cases diagnosed from 2005 to 2014. Demographic data and site of the lesions were collected. Sites of the lesion were subdivided into lip, tongue, floor of the mouth, gingiva, alveolar mucosa, palate, buccal/labial mucosa, maxilla and mandible. Oral cancer was subdivided into 7 categories: epithelial tumors, salivary gland tumors, hematologic tumors, bone tumors, mesenchymal tumors, odontogenic tumors, and others. Data were analyzed by descriptive statistics using SPSS software version 17.0. RESULTS: Of the 474,851 accessioned cases, 6,151 cases (1.30%) were diagnosed in the category of oral cancer. The mean age of the patients was 58.37±15.77 years. A total of 4,238 cases (68.90%) were diagnosed in males, whereas 1911 cases (31.07%) were diagnosed in females. The male-to-female ratio was 2.22:1. The sites of predilection for oral cancer were tongue, labial/buccal mucosa, gingiva, palate, and alveolar mucosa, respectively. The three most common oral cancer in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. CONCLUSIONS: Although the prevalence of oral cancer is not high compared to other entities, oral cancer pose significant mortality and morbidity in the patients, especially when discovered late in the course of the disease. This study highlights some anatomical locations where oral cancers are frequently encountered. As a result, clinicians should pay attention to not only teeth, but oral mucosa especially in the high prevalence area as well since early detection of precancerous lesions or cancers in the early stage increase the chance of patient being cured and greatly reduce the mortality and morbidity. This study also shows some differences between pediatric and elderly oral cancer patients as well as between Asian and non-Asian oral cancer patients.

Miliarial gout: a rare presentation of extensive cutaneous tophi.

Gout is a systemic disorder characterized by hyperuricemia and recurrent arthritis, most involvement of ankles, midfoot joint and first metatarsophalangeal joint, with monosodium urate crystals deposition in synovial fluid and other tissues. We present a case of 53-year-old male, who had several nontender, white-yellow papules and plaques over his elbows, knees and arms with chalk-like substances and crust on inflammatory base wax and wane in the past 2 years. Upon histopathology examination of the skin lesions, it reported as intradermal urate tophi and miliarial gout was diagnosed. This case highlights the importance of considering unusual cutaneous tophi in the differential diagnosis of deposition disorders.

Do all the patients with gastric parietal cell antibodies have pernicious anemia?

OBJECTIVE: This study evaluated whether all the patients with serum gastric parietal cell antibody (GPCA) positivity had pernicious anemia (PA). MATERIALS AND METHODS: The blood hemoglobin (Hb), iron, and vitamin B12 concentrations, and mean corpuscular volume (MCV) in 124 GPCA-positive patients were measured and compared with the corresponding data in 124 age- and sex-matched healthy controls. PA was defined by World Health Organization (WHO) as having an Hb concentration < 13 g dl(-1) for men and < 12 g dl(-1) for women, an MCV ≥ 100 fl, and a serum vitamin B12 level < 200 pg ml(-1) . RESULTS: We found that 20, 25, and 20 GPCA-positive patients had deficiencies of Hb (men < 13 g dl(-1) , women < 12 g dl(-1) ), iron (<60 µg dl(-1) ), and vitamin B12 (<200 pg ml(-1) ), respectively. Moreover, 16 GPCA-positive patients had abnormally high MCV (≥ 100 fl). GPCA-positive patients had a significantly higher frequency of Hb, iron, or vitamin B12 deficiency and of abnormally high MCV (all P-values < 0.001) than healthy controls. However, only 12.9% of 124 GPCA-positive patients were diagnosed as having PA by the WHO definition. CONCLUSION: Only 12.9% of GPCA-positive patients are discovered to have PA by the WHO definition.

Arecoline-stimulated placenta growth factor production in gingival epithelial cells: modulation by curcumin.

OBJECTIVE: Placenta growth factor (PlGF) is associated with the progression and prognosis of oral cancer. MATERIALS AND METHODS: This study used ELISA, quantitative polymerase chain reaction, and Western blotting to study the arecoline-stimulated (PlGF) protein or mRNA expression in human gingival epithelial S-G cells. RESULTS: Arecoline, a major areca nut alkaloid and an oral carcinogen, could stimulate PlGF protein synthesis in S-G cells in a dose- and time-dependent manner. The levels of PlGF protein secretion increased about 3.1- and 3.8-fold after 24-h exposure to 0.4 and 0.8 mM arecoline, respectively. Pretreatment with antioxidant N-acetyl-l-cysteine (NAC) and ERK inhibitor PD98059, but not NF-κB inhibitor Bay 11-7082, JNK inhibitor SP600125, p38 MAPK inhibitor SB203580, and PI3-K inhibitor LY294002, significantly reduced arecoline-induced PlGF protein synthesis. ELISA analyses demonstrated that NAC and PD98059 reduced about 43% and 38% of the arecoline-induced PlGF protein secretion, respectively. However, combined treatment with NAC and PD98059 did not show additive effect. Moreover, 10 µM curcumin and 4 mM NAC significantly inhibited arecoline-induced ERK activation. Furthermore, 10 µM curcumin completely blocked arecoline-induced PlGF mRNA expression. CONCLUSION: Arecoline-induced PlGF synthesis is probably mediated by reactive oxygen species/ERK pathways, and curcumin may be an useful agent in controlling oral carcinogenesis.

Significant reduction of homocysteine level with multiple B vitamins in atrophic glossitis patients.

OBJECTIVE: This study evaluated whether supplementations of different vitamins and iron could reduce the serum homocysteine levels in 91 atrophic glossitis (AG) patients. MATERIALS AND METHODS: Atrophic glossitis (AG) patients with concomitant deficiencies of vitamin B12 only (n = 39, group I), folic acid only (n = 10, group II), iron only (n = 9, group III), or vitamin B12 plus iron (n = 19, group IV) were treated with vitamin BC capsules plus deficient hematinics. AG patients without definite hematinic deficiencies (n = 14, group V) were treated with vitamin BC capsules only. The blood homocysteine and hematinic levels at baseline and after treatment till all oral symptoms had disappeared were measured and compared by paired t-test. RESULTS: Supplementations with vitamin BC capsules plus corresponding deficient hematinics for groups I, II, III, IV patients and with vitamin BC capsules only for group V patients could reduce the high serum homocysteine levels to significantly lower levels after a mean treatment period of 8.3-11.6 months (all P-values < 0.05). CONCLUSION: Supplementations with vitamin BC capsules plus corresponding deficient hematinics or with vitamin BC capsules only can reduce the high serum homocysteine levels to significantly lower levels in AG patients.

Modulation of serum gastric parietal cell antibody level by levamisole and vitamin B12 in oral lichen planus.

OBJECTIVES: The objective of this study was to test the efficacy of three different treatment modalities on the reduction of serum anti-gastric parietal cell autoantibody (GPCA) level in GPCA-positive oral lichen planus (OLP) patients. MATERIALS AND METHODS: Of 147 GPCA-positive OLP patients, 100 were treated with levamisole plus vitamin B12, 10 with vitamin B12 only and 37 with levamisole only. The serum GPCA levels in 147 OLP patients were measured at baseline and after treatment. RESULTS: Treatment with levamisole plus vitamin B12 for a period of 2-50 months and treatment with vitamin B12 only for a period of 4-44 months could effectively reduce the high serum GPCA level to undetectable level in 100 and 10 OLP patients, respectively. However, treatment with levamisole only for a period of 2-50 months could not modulate the high mean serum GPCA titer to a significantly lower level in 37 OLP patients. A 92% GPCA recurrence rate was found in 25 OLP patients receiving no further vitamin B12 treatment during the GPCA-negative remission period. CONCLUSION: For GPCA-positive OLP patients, treatment modality containing vitamin B12 can effectively reduce the high serum GPCA level to undetectable level. OLP patients with underlying autoimmune atrophic gastritis trait should receive a maintenance vitamin B12 treatment for life.

Malignant amelanotic melanoma developing from an intradermal naevus in a patient with oculocutaneous albinism.

A 43-year-old Taiwanese man who had oculocutaneous albinism type 1 presented with a tumorous lesion over the pubic region. Within the tumour, there was a small pinkish plaque. Histopathologically, the tumour revealed benign naevus cells in the upper dermis and atypical malignant tumour cells in the deeper dermis. Immunohistochemistry using HMB-45 showed intensive positive staining in the deeper dermal tumour cells. Amelanotic malignant melanoma (MM) originating from a pre-existing intradermal naevus was diagnosed.

Non-calcifying variant of calcifying epithelial odontogenic tumor with Langerhans cells.

Calcifying epithelial odontogenic tumor (CEOT) is a rare type of odontogenic tumor. The most characteristic feature of the classical CEOT is the presence of amyloid globules and Liesegang ring calcification in the tumor tissue. Here, we present a non-calcifying variant of intraosseous CEOT with the presence of Langerhans cells within tumor epithelial nests in a 52-year-old Taiwanese woman. The patient was referred from a local dentist to our hospital for treatment of a unilocular radiolucent lesion at the right anterior region of the maxilla. The lesion was excised. Microscopically, the tumor was composed of small nests or strands of odontogenic epithelial cells and amorphous eosinophilic globules of amyloid-like materials in a loose fibrous connective tissue stroma. The tumor epithelial cells were positive for pan-cytokeratins (AE1 and AE3). Langerhans cells demonstrated by anti-CD1a staining were found in nests or strands of tumor epithelial cells. The eosinophilic globules were positive for Congo red and showed green birefringence when subjected to polarized light. Review of the English literature revealed two cases of non-calcifying variant of intraosseous CEOT with Langerhans cells in the anterior and premolar regions of the maxilla. Taken together, we suggest that the non-calcifying, Langerhan cell-rich variant of CEOT may have a distinct predilection for occurrence in the anterior and premolar region of the maxilla in contrast to the classical CEOTs that usually occur in the molar and ascending ramus area of the mandible.

Levamisole can reduce the high serum tumour necrosis factor-alpha level to a normal level in patients with erosive oral lichen planus.

In this study, we measured the baseline serum levels of tumour necrosis factor (TNF)-alpha in 158 patients with oral lichen planus (OLP) and in 54 normal control subjects. In total, 60 patients with erosive OLP (EOLP) with relatively high TNF-alpha levels were treated with levamisole and the serum TNF-alpha levels measured after treatment. We found that the mean +/- SD serum level of TNF-alpha in patients with either type of EOLP (12.0 +/- 1.7 pg/mL, P<0.005), major EOLP (15.5 +/- 4.4 pg/mL, P<0.001), minor EOLP (11.1 +/- 1.8 pg/mL, P<0.01), or nonerosive OLP (6.1 +/- 1.7 pg/mL, P<0.05) was significantly higher than that (3.8 +/- 0.2 pg/mL) of normal control subjects. Treatment with levamisole for a period of 0.5-7.5 months significantly reduced the mean serum TNF-alpha level from 22.6 +/- 3.4 pg/mL to 6.2 +/- 0.8 pg/mL (P<0.001) in 60 patients with EOLP. We conclude that levamisole can reduce high serum TNF-alpha levels to normal in patients with EOLP.

Cell-mediated immunity and head and neck cancer: with special emphasis on betel quid chewing habit.

Betel quid (BQ) chewing is popular in Taiwan, India, and many southeast-Asian countries. BQ chewing has strong association with the risk of oral leukoplakia (OL), oral submucous fibrosis (OSF), and oral cancer (OC). BQ components exhibit genotoxicity and may alter the structure of DNA, proteins and lipids, resulting in production of antigenicity. BQ ingredients are also shown to induce keratinocyte inflammation by stimulating the production of prostaglandins, TNF-alpha, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in keratinocytes. These events may provoke tissue inflammation, early cell-mediated immunity (CMI), and immune surveillance in BQ chewers. However, BQ components also directly affect the functional activities of immunocompotent cells, and moreover tumor cells may hypo-respond to the CMI via diverse mechanisms such as induction of apoptosis of lymphocytes, induction of production of suppressor T cells, downregulation of MHC molecules in tumor cells, etc. Clinically, an alteration in lymphocyte subsets, a decrease in total number of lymphocytes, and a reduction in functional activities of CMI have been observed in isolated peripheral blood mononuclear cells (PBMC) and tumor infiltrated lymphocytes (TIL) in patients with OSF, OL or OC. Adaptation of tumor cells to immune system may promote clonal selection of resistant tumor cells, leading to immune tolerance. Future studies on effects of BQ components on CMI and humoral immunity in vitro and in vivo can be helpful for chemoprevention of BQ-related oral mucosal diseases. To elucidate how virus infection, tobacco, alcohol and BQ consumption, and other environmental exposure affect the immune status of patients with oral premalignant lesions or OC will help us to understand the immunopathogenesis of OC and to develop immunotherapeutic strategies for OC.

Serum interleukin-8 level is a more sensitive marker than serum interleukin-6 level in monitoring the disease activity of oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a T-cell-mediated inflammatory disease. Interleukin (IL)-8 is a pro-inflammatory cytokine of host response to injury and inflammation. OBJECTIVES: To investigate whether serum IL-8 level was a more sensitive marker than serum IL-6 level in monitoring the disease activity of OLP and to assess whether IL-8 was a useful serum marker in evaluating the therapeutic effects of levamisole on OLP patients. METHODS: In this study, we used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of IL-6 and IL-8 in 158 patients with OLP, nine patients with traumatic ulcers (TU) and 54 normal control subjects. Some OLP patients with the serum IL-6 or IL-8 levels higher than the upper limit of normal serum concentration were treated with levamisole for 0.5-6.0 months and their serum IL-6 and IL-8 levels were measured after treatment. RESULTS: We found that 28% (44 of 158) OLP, 28% (40 of 142) erosive OLP (EOLP), and 25% (four of 16) nonerosive OLP (NEOLP) patients had a serum IL-6 level greater than the upper normal limit of 4.7 pg mL(-1). In contrast, 63% (99 of 158) OLP, 63% (90 of 142) EOLP and 56% (nine of 16) NEOLP patients had a serum IL-8 level greater than the upper normal limit of 8.7 pg mL(-1). In some OLP patients with the serum IL-6 or IL-8 levels higher than the upper limit of normal serum concentration, treatment with levamisole for a period of 0.5-6.0 months could significantly reduce the mean serum IL-6 level from 14.3 +/- 1.9 pg mL(-1) to 3.2 +/- 0.6 pg mL(-1) (P < 0.001) and could significantly reduce the mean serum IL-8 level from 95.8 +/- 17.1 pg mL(-1) to 14.8 +/- 5.8 pg mL(-1) (P < 0.001). CONCLUSIONS: Because measurement of the serum IL-8 level can detect more OLP patients with an abnormal serum level than measurement of the serum IL-6 level (63% vs. 28%), we conclude that serum IL-8 level is a more sensitive marker than serum IL-6 level in monitoring the disease activity of OLP. Levamisole can modulate both the serum IL-6 and IL-8 levels in OLP patients. IL-8, like IL-6, is also a useful serum marker in evaluating the therapeutic effects of levamisole on OLP patients.

Autofluorescence lifetime measurement on oral carcinogenesis.

Normal and cancerous tissues have distinct autofluorescence lifetime because of their biophysical and biochemical differences. Protoporphyrin IX (PplX) is a useful fluorophore, which generally accumulates more in cancerous cells than in normal cells due to heme synthesis pathway, is often employed in photodynamic detection and therapy. Under 410nm excitation, the main emission peak of PplX is at 630nm. Autofluorescence lifetime at 630nm emission would be elongated if PplX gathered more in cells. In this study, we tried to find if there exist significant differences of autofluorescence lifetime at 630nm (under 410nm excitation) between normal and cancerous tissues for in vivo measurement. The result shows that normal tissues in general have shorter lifetime (about 2.8 approximately 3.5 ns) than that of abnormal tissues. The measured data suggest that lifetime would get longer in accordance with the degree of carcinogenesis. For cancer tissues, the average autofluorescence lifetime was extended to be about 10ns. Furthermore, the efficiency of treatment could also be defined refer to the time-series of lifetime decline.

Oral cancer detection in fluorescent image by color image fusion.

Biopsy is the main diagnosis method for oral cancer, which is the fifth most prevalent cancer in male population in Taiwan. In order to increase the accuracy of diagnosis, it is required to reveal the distribution of malignancy prior to biopsy. Based on this purpose, we developed the fluorescent image system associated with color image fusion algorithm to indicate the cancer-susceptible area in the oral image. The system therefore can assist physicians to make appropriate biopsy.

High incidence of autoantibodies in Taiwanese patients with oral submucous fibrosis.

BACKGROUND: Previous study has shown a high incidence of autoantibodies including antinuclear (ANA), antismooth muscle (SMA), antigastric parietal cell (GPCA), antithyroid microsomal (TMA), and antireticulin antibodies in a small group of 26 patients with oral submucous fibrosis (OSF). The reasons why some of the OSF patients have high titers of autoantibodies in serum have not been completely explained and no further study on autoantibodies in OSF patients has been done in a large group of patients. METHODS: In this study, we determined the serum levels of ANA, SMA, GPCA, and TMA in a large group of 109 male Taiwanese patients with OSF by an indirect immunofluorescence technique (for ANA, SMA, and GPCA), and by a semiquantitative microtiter particle agglutination test (for TMA). The presence of serum autoantibodies in OSF patients was further correlated with patients' oral habits and the severity of OSF measured by maximum mouth opening (MMO) and sites of involvement. RESULTS: We found that the frequencies of presence of serum ANA (23.9%), SMA (23.9%), and GPCA (14.7%) in OSF patients were significantly higher than those (9.2, 7.3, and 5.5%, respectively) in healthy control subjects (P < 0.01, P < 0.005, and P < 0.05, respectively). Although the frequency of presence of TMA (5.5%) in OSF patients was also greater than that (2.8%) in healthy control subjects, the difference was not significant (P > 0.05). The presence of serum GPCA in OSF patients was significantly associated with daily areca quid (AQ) consumption (P < 0.05). The presence of serum ANA in OSF patients associated with daily AQ consumption was of borderline statistical significance (P = 0.066). However, no significant correlations were demonstrated between the presence of serum autoantibodies in OSF patients and other variables of oral habits, MMO, and sites of involvement. CONCLUSION: In this study, all the 109 OSF patients had AQ chewing habit and 73.4% of the OSF patients swallowed the 'juice' of AQ during the chewing process. The presence of serum GPCA and ANA in OSF patients was associated with daily consumption of AQs. AQ chewing caused mucosal microtrauma, and ulcerations facilitated the diffusion of genotoxic and cytotoxic AQ ingredients into the oral and gastric tissues. Altered autoantigens released from AQ ingredients-damaged cells may induce autoantibody production. Higher frequencies of specific HLA-DR antigens in OSF patients may also help autoantibody production. Therefore, we conclude that the high incidence of autoantibodies in OSF patients may be due to AQ chewing habit, toxic AQ ingredients, and genetic susceptibility of the OSF patients.

Quantitative analysis of immunocompetent cells in oral submucous fibrosis in Taiwan.

Previous studies have shown that the local and systemic upregulation of inflammatory and fibrogenic cytokines and downregulation of antifibrotic cytokines are central to the pathogenesis of oral submucous fibrosis (OSF). The immunocompetent cells, especially the macrophages and lymphocytes, are likely the main source of cytokine synthesis. Therefore, this study used an immunohistochemical method to quantify the T lymphocyte, B lymphocyte and macrophage densities in the epithelium and subepithelial connective tissue of 50 specimens of moderately advanced and advanced OSF and 10 specimens of normal oral mucosa (NOM). The mean T lymphocyte, B lymphocyte and macrophage densities in OSF specimens were 555.2+/-417.4, 63.4+/-44.3 and 66.9+/-76.4 cells/mm(2) in the subepithelial connective tissue and 308.1+/-261.1, 1.4+/-3.5 and 6.6+/-11.9 cells/mm(2) in the epithelium, respectively. These findings suggest that T lymphocytes were the major immunocompetent cells in both the subepithelial connective tissue and epithelium of OSF specimens. Macrophages and B lymphocytes are the minor immunocompetent cells in the subepithelial connective tissue and are only occasionally found in the epithelium of OSF specimens. Similar distribution of immunocompetent cells was also found in NOM specimens. However, the mean T lymphocyte, B lymphocyte and macrophage densities in the subepithelial connective tissue (271.2+/-107.0, 13.3+/-18.4 and 17.3+/-19.1 cells/mm(2), respectively) and the mean T lymphocyte density in the epithelium (97.7+/-51.4) of NOM specimens were significantly lower than the corresponding mean cell densities in OSF specimens. Using frozen tissue sections, we further quantified the CD4+ and CD8+ lymphocyte numbers in eight moderately advanced or advanced OSF specimens. It was found that the CD4+ and CD8+ lymphocyte densities were 213.3+/-140.7 and 101.5+/-72.8 cells/mm(2) in the subepithelial connective tissue of OSF specimens, respectively. The CD4+ to CD8+ lymphocyte ratio was 2.1:1. Our results showed a significant increase in the number of T lymphocytes and macrophages and a predominance of CD4+ lymphocytes over CD8+ lymphocytes in the subepithelial connective tissue of OSF specimens. We conclude that the cellular immune response may play an important role in the pathogenesis of OSF.

Oral administration of milk from cows immunized with human intestinal bacteria leads to significant improvements of symptoms and signs in patients with oral submucous fibrosis.

BACKGROUND: Previous studies have shown that the local and systemic upregulation of fibrogenic cytokines and downregulation of antifibrotic cytokine are central to the pathogenesis of oral submucous fibrosis (OSF). The milk from cows immunized with human intestinal bacteria (immune milk) contains an anti-inflammatory component that may suppress the inflammatory reaction and modulate cytokine production. Therefore, it was decided to test whether immune milk may have some beneficial effects on controlling the symptoms and signs in OSF patients. METHODS: In this preliminary study, 26 OSF patients who received immune milk treatment (45 g of immune milk powder twice a day) for 3 months and oral habit intervention were included in the experimental group. Another 20 OSF patients who received only oral habit intervention served as the control group. RESULTS: We found that the interincisor distance was significantly improved (> or =3 mm of the baseline measurement) in 18 of the 26 (69.2%) OSF patients in the experimental group at exit. However, in the control group none of the OSF patients had an increase in interincisor distance greater than 2 mm. In addition, disappearance or significant improvement of symptoms at exit was observed in 80% (16/20) of the patients with intolerance to spicy foods (P < 0.001) and 72.2% (13/18) of the patients with xerostomia (P < 0.005) in the experimental group, compared with 17.6% (3/17) of the patients with improvement of intolerance to spicy foods and 15.4% (2/13) of the patients with improvement of xerostomia in the control group. Partial regression of concomitant oral leukoplakia or erythroplakia (judged from the size reduction of the lesions) at exit was noted in 71.4% (5/7) of the patients in the experimental group (P < 0.05), compared with none (0/5) of the patients with improvement in the control group. CONCLUSION: We conclude that oral administration of immune milk leads to significant improvements of symptoms and signs in OSF patients.

Expression of transforming growth factor-alpha in adenoid cystic carcinoma of the salivary gland.

BACKGROUND: Transforming growth factor-alpha (TGF-alpha) is expressed in both normal and malignant epithelial cells. Although the expression of TGF-alpha has been extensively studied in some human epithelial neoplasms, its expression in adenoid cystic carcinomas (ACCs) of the salivary gland has not been reported. METHODS: This study used an immunohistochemical technique to assess the expression of TGF-alpha in 40 ACC specimens from the salivary glands, seven specimens from labial minor salivary glands adjacent to mucoceles, and five specimens from normal submandibular glands. RESULTS: In the normal submandibular gland specimens, positive TGF-alpha staining was found in all ductal segments as well as in serous and some mucous acinar cells. In labial minor salivary glands adjacent to mucoceles, positive TGF-alpha staining was found in ductal, serous acinar, serous demilune, and a few mucous acinar cells. Positive TGF-alpha immunostaining was observed in all five salivary gland ACC specimens with a solid histologic pattern, and 31 of the 35 salivary gland ACC specimens with a tubulo-cribriform histologic pattern. Overall, 36 of 40 ACCs of the salivary gland expressed TGF-alpha. Positive TGF-alpha staining was found in the salivary gland ACC specimens with solid, tubular, duct-like, and pseudocystic structures. No significant correlation was found between TGF-alpha expression in ACCs of the salivary gland and age, sex, primary cancer location, TNM status, clinical stage, prognosis, histologic type, perivascular or perineural invasion, focal necrosis of the tumor, or cellular atypia. CONCLUSIONS: This study demonstrated that ductal and acinar cells of the normal submandibular gland and of labial minor salivary glands adjacent to mucoceles are the major sites of TGF-alpha synthesis and secretion. Furthermore, TGF-alpha is biosynthesized in salivary gland ACC tumor cells, forming solid, tubular, duct-like, and pseudocystic structures. Our data suggest that TGF-alpha may play an important biologic role as a mitogen in the growth of salivary gland ACC.

Levamisole and/or Chinese medicinal herbs can modulate the serum level of squamous cell carcinoma associated antigen in patients with erosive oral lichen planus.

The serum levels of squamous cell carcinoma associated antigen (SCCA) were determined by a microparticle enzyme immunoassay in a group of patients with stage I oral squamous cell carcinoma (OSCC), major or minor type erosive oral lichen planus (EOLP), recurrent aphthous stomatitis (RAS), Behçet's disease (BD), oral leukoplakia (OL), or oral submucous fibrosis (OSF), and in normal control subjects. About 97% of the normal control subjects and the patients with minor type EOLP, RAS, BD, OL or OSF had a serum level of SCCA within the normal limit of 1.2 ng/ml. However, 6 of the 12 (50%) patients with stage I OSCC and 14 of the 31 (45.2%) patients with major type EOLP had a serum level of SCCA greater than 1.2 ng/ml. The mean serum level of SCCA in stage I OSCC patients (1.38+/-1.16 ng/ml) or in major type EOLP patients (1.32+/-1.23 ng/ml) was significantly higher than that in normal control subjects (P<0.001) and that in the patients with minor type EOLP (P<0.001), RAS (P<0.001), BD (P<0.05), OL (P<0.05), or OSF (P<0.05). Either major or minor type EOLP patients could obtain a significant mean reduction of the serum SCCA level of 0.34-0.63 ng/ml after treatment with levamisole and/or Chinese medicinal herbs for 1-30 months. Combination therapy with levamisole plus Chinese medicinal herbs could achieve a shorter duration of treatment to get complete remission than the single therapy with either levamisole only or Chinese medicinal herbs only. We conclude that levamisole and/or Chinese medicinal herbs can modulate the serum SCCA level in EOLP patients. SCCA may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of EOLP. For EOLP patients, the combination therapy is superior to the single therapy of levamisole or of Chinese medicinal herbs.

Induction of dental pulp fibroblast matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 gene expression by interleukin-1alpha and tumor necrosis factor-alpha through a prostaglandin-dependent pathway.

Matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) are involved in the degradation of extracellular matrix in many inflammatory diseases. Little is known regarding the expression of these mediators in dental pulp fibroblasts. The effects of proinflammatory cytokines (interleukin (IL)-1alpha and tumor necrosis factor-alpha (TNF-alpha)) and prostaglandin E2 (PGE2) on pulp fibroblast MMP-1 and TIMP-1 gene expression were investigated. Northern hybridization showed that IL-1alpha and TNF-alpha induced significant MMP-1 gene expression, with only little effect on TIMP-1 gene. Exogenous PGE2, however, upregulated TIMP-1 mRNA synthesis but not MMP-1. Concomitant addition of IL-1alpha and PGE2 or TNF-alpha and PGE2 suppressed MMP-1 mRNA production, compared with the groups treated with IL-1alpha or TNF-alpha alone. In contrast, PGE2 enhanced the upregulatory effects of TIMP-1 mRNA by IL-1alpha or TNF-alpha. Furthermore, cytokine stimulation of MMP-1 and TIMP-1 gene expressions can be enhanced or blocked by indomethacin, respectively, and reversed by exogenous PGE2. These results suggested that cytokine-stimulated MMP-1 and TIMP-1 gene expression in dental pulp fibroblasts was mediated, at least in part, by a prostaglandin-dependent pathway. The differential regulation of IL-1alpha or TNF-alpha-induced MMP-1 and TIMP-1 mRNA synthesis, as well as the direct upregulation of TIMP-1 gene expression by PGE2, also implied that prostaglandin may serve as a protective mechanism from excessive tissue breakdown during pulpitis.