A total of 481,414 Korean participants aged 40-79 years at enrollment were examined. The hazard ratios for all-cause, all-cancer, and head and neck cancer mortality were analyzed using Cox proportional hazards models, which were adjusted for potential confounding factors. In the overall study population, the highest AST/ALT ratio level was significantly associated with risk of all-cause, all-cancer, and head and neck cancer mortality (p < 0.01). After excluding participants who died of all-cause, all-cancer, and head and neck cancer within five years of enrollment, the main results remained similar to those of the analysis of all deaths in the study population. These findings indicate that serum AST/ALT ratio is positively associated with an increased mortality risk in all-cause, all-cancer, and head and neck cancer.

Background: The purpose of this study was to determine the bidirectional association between burning mouth syndrome (BMS) and depression disorders. Methods: A total of 854 pairs of BMS and 58 999 pairs of depression disorders matched 1:1 for age and sex were analyzed using conditional logistic regression models, which were adjusted for potential confounding factors. Results: Bidirectional analysis found that BMS was associated with depression disorders (odds ratio=4.64, P < 0.001) and depression disorders was also significantly associated with BMS (odds ratio=2.97, P < 0.001). Conclusion: These findings indicate a significant bidirectional association between BMS and depression disorders. The odds ratios suggest that BMS is a stronger predictor for incidence of depression disorders than depression disorders predicting incidence of BMS. Given this retrospective cohort design, the mechanisms underlying the association between BMS and depression disorders are not directly analyzed. Therefore, further investigation are needed to analyze the causality between BMS and depression disorders.

Mucinous adenocarcinoma (MAC) refers to a malignant neoplasm that belongs to a subtype of adenocarcinoma which produces mucin. The World Health Organization has classified MAC as a tumor of salivary gland origin and it is extremely rare. Therefore, its characteristics are not well-known. This study reports a case of MAC of minor salivary gland origin, which occurred in the oral commissure of an 82-year-old female patient, and a systematic review on existing cases of MAC of salivary origin. Based on the study’s findings, it is safe to assume that the occurrence of lymph node metastasis is an important factor in determining the prognosis of patients with MAC.

The case of an intraosseous leiomyoma in a 22-year-old man is presented. The tumor was incidentally discovered during dental radiographic examination for endodontic treatment of mandibular first molar. Radiographic examination revealed a well-defined unilocular radiolucency between the roots of mandibular left canine-first premolar, measuring approximately 1.9 x 1.8 cm and perforation of the buccal cortical plate. Histological and immunohistochemical examination was diagnostic of intraosseous solid leiomyoma. Here, we report a rare case of leiomyoma of the mandible, together with conventional histopathologic and immunohistochemical findings.

Lycorine, a natural alkaloid extracted from the Amaryllidaceae plant family, was reported to various physiological and pharmacological effects including anti-cancer activity. Nevertheless, there is no report of the anticancer effect of lycorine in oral cancer cells. The effects of lycorine on cell proliferation and apoptosis were examined through trypan blue exclusion assay, 4’-6-diamidino-2-phenylindole (DAPI) stain, Live/Dead assay, Western blot analysis and RT-PCR. Lycorine suppressed cell viability and induced apoptosis in MC3 and HSC-3 cell lines. Lycorine decreased survivin protein but did not affect its mRNA. It regulated survivin through accelerating protein degradation in a time-dependent manner although neither proteasome nor lysosome was not associated with lycorine-mediated protein degradation. Collectively, our results suggest that lycorine may be a potential therapeutic anti-cancer drug candidate for the treatment of human oral cancer.

Background: Cisplatin is a well-known platinum-containing anti-cancer drug against bladder, ovarian, lung and testicular cancer. However, the potential effects and molecular targets of cisplatin in human mucoepidermoid carcinoma (MEC) are not fully understood. Here, we investigated the apoptotic effect and underlying mechanism of cisplatin in human MEC cells. Methods: The potential effects of cisplatin were evaluated by trypan blue exclusion assay, Western blotting, 4’-6-diamidino-2-phenylindole (DAPI) staining, live/dead assay and immunocytochemistry. Results: Cisplatin suppressed cell growth and enhanced expression of cleaved PAPR in MC3 and YD15 cells. Cisplatin caused morphological change of nuclei and increased the number of ethidium homodimer-1-stained cells. In addition, cisplatin commonly increased Bax activation in both cells, while other Bcl-2 family proteins were not affected. Conclusions: These results suggest that cisplatin might induce apoptosis by activating Bax protein, which would provide baseline data for development of effective treatment strategy against MEC.

Terfenadine (TFN) was a second generation histamine receptor antagonist. Although several studies have reported the regulatory effect of H1-histamine receptor antagonists in human cancer cell lines, its effect in oral cancer remains unclear. In this study, we focused on addressing the anti-cancer activity of TFN in human oral cancer cell lines. The anti-cancer activities of TFN were performed by tryphan blue exclusion assay, 4'-6-diamidino-2-phenylindole (DAPI) staining, live/dead assay and Western blot analysis. TFN induced a significant reduction of the growth in three different human oral cancer cell lines (MC3, HSC4 and Ca9.22). TFN markedly induced apoptosis through DNA damage and increase in cytotoxicity. It also accumulated cleaved PARP and caspase 3. This process was due to cleavage of caspase 8 and Bid protein. The results from this study strongly demonstrated that the cleavages of caspase 8 and Bid are required for the apoptotic activity of TFN in human oral cancer cells. Taken together, these findings suggest TFN as a potent anticancer drug candidate for the treatment of oral cancer.

Caffeic acid phenethyl ester (CAPE), a component of propolis, was reported to possess anti-inflammatory, anti-bacterial, anti-viral, and anti-tumor activities. Our aim was to investigate the effect of CAPE on apoptosis in cultured human mucoepidermoid carcinoma (MEC) cell line, MC-3. Apoptotic effects of CAPE were measured by cell viability assays, Western blotting, 4’-6-diamidino-2-phenylindole (DAPI) staining and Live/Dead assay. The result of cell viability assay showed that CAPE displayed a strong growth-inhibitory effect in a concentration-dependent manner against MC-3 cells. Consumption of CAPE resulted in pronounced increase in the cleavage of caspase-3 and PARP, induced nuclear condensation and fragmentation and clearly increased the number of dead cells in MC-3 cells. CAPE also caused the increase in truncated Bid (t-Bid) and the cleavage of caspase-8 and this phenomenon was regulated by death receptor 5 (DR5). In addition, Phosphorylation of AKT and ERK were downregulated by CAPE. Taken together, these results suggest that CAPE is a potent apoptosis-inducing agent in MC-3 cells.

Background. Vitamin K (VK) is a fat-soluble vitamin and is known to have anticancer activity in various cancer cell lines. However, there is no report on the anticancer effect of VK2 in mucoepidermoid carcinoma cells. Methods. The effects of VK2 on anti-proliferative and apoptotic activity were recognized by the trypan blue exclusion assay, 4'-6-diamidino-2-phenylindole (DAPI) staining and Western blot analysis. Results. The results showed that VK2 decreased cell viability and induced apoptotic programmed cell death in MC3 cells evidenced by the cleavages of caspase3 and PARP. VK2 treatment clearly increased Bak and truncated Bid (t-Bid) compared with the control treatment whereas it did not alter other Bcl-2 family members. Conclusions. Overall, our results suggest that VK2 can be a good apoptotic inducer accompanied by the increase in Bak and Bid protein. VK2 may be a potent target of anticancer drug candidate for the treatment of oral cancer.

Dibenzylideneacetone (DBA), an analogue of curcumin has been shown to have anti-cancer activity in a variety of tumor cell lines. However, the anti-cancer activity of DBA and its molecular mechanism in HN22 oral cancer cell line have not been fully explored. The effects of DBA on anti-proliferative and apoptotic activity were evaluated by the trypan blue exclusion assay, 4’-6-diamidino-2-phenylindole (DAPI) staining, Western blot analysis, and reverse transcriptase-polymerase chain Reaction (RT-PCR). Our data showed that the treatment of DBA to HN22 cells exerted anti-proliferative and apoptotic activities and the activity was accompanied by a decrease in Sp1 protein, Sp1 mRNA and its promoter activity. DBA also reduced the expression level of Sp1 protein and caused apoptotic cell death in HN22 cells simultaneouly. Phosphorylation of ERK and JNK were regulated by DBA whereas phosphorylation of p38 was not altered. Overall, our results suggest that the regulation of Sp1 activities and ERK/JNK are involved in DBA-induced apoptosis and DBA can be a promising anticancer drug candidate for the treatment of oral cancer.

Cruciferous vegetables including diindolylmethane (DIM) have been shown to have anticancer activity. Especially, DIM-pPhBr and DIM-pPhF used in this study was reported to have more effective and less toxic effects than DIM. However, there is no report presenting their anti-tumorigenic activity in oral cancer. In the present study, we examined the effects of DIM-pPhBr and DIM-pPhF on the cell proliferation and apoptosis in KB human oral cancer cells. DIM-pPhBr and DIM-pPhF decreased cell proliferation and induced apoptosis evidenced by western blot analysis, DAPI staining and sub-G1 population. This provides the first evidence that DIM-pPhBr and DIM-pPhF originating from cruciferous vegetables induce apoptotic cell death in human oral cancer cells to inhibit cancer cell proliferation.

β-phenylethyl isothiocyanate(PEITC) is a component derived from cruciferous vegetables and has been demonstrated to fight many types of cancers through various molecular pathways. In the present study, we focused on its effect on the induction of apoptotic cell death to inhibit cell growth and its molecular mechanism in HSC-4 human oral cancer cells. A colorimetric MTS assay was used to examine cell viability. The apoptotic effect and was investigated using DAPI staining and the molecular target and mechanism of PEITC-mediated apoptosis were determined by Western blotting. The result showed that PEITC inhibited oral cancer cell growth and induced apoptosis via extrinsic signaling pathway evidenced by the activation of caspase 8, truncation of bid protein and induction of death receptor(DR) 5. DR5 protein level was increased through the activation of p38 and c-Jun N-terminal kinase(JNK). These results from this study strongly suggest that DR5 is a potential molecular target for PEITC-induced apoptosis in oral cancer via p38 and JNK.

Runt-related transcription factor (RUNX) 3 is well known as a developmental regulators, as well as candidate tumor suppressor gene in human breast cancer, gastric cancer, esophageal cancer, and so on. The present study was aimed to analyze the expression of RUNX3 protein in oral squamous cell carcinoma (OSCC) from Korean patients. The immunohistochemical stain was performed with 14 normal oral mucosa (NOM) and 25 OSCCs, and statistical analysis was carried out to find out the correlation between the expression of RUNX and clinicopathological parameters of OSCC patients. In OSCC, the expression of RUNX3 protein was found to increase more than in NOM. Moreover, in the univariate correlation analysis, the gender, regional lymph node metastasis, and histopathologic differentiation of OSCC patients were positively correlated with the expression of RUNX3 (p<0.05). These results indicate that RUNX3 can play a role as an oncogene in OSCC, in contrast to some reports on RUNX3 in other human cancers. In addition, RUNX3 may be considered as new malignant biomarker of OSCC.

Emodin is a bioactive compound isolated from the root and rhizomes of Rheum plamatum L. (polygenaceae), which is known as a traditional Chinese and Japanese medicine. In the present study, the effect of emodin on YD-15 mucoepidermoid carcinoma cells and its molecular mechanism were investigated. This study shows that emodin significantly inhibits the growth of YD-15 cells. Activation of caspase-3 and PARP is triggered by emodin and it increases sub-G1 population and the number of YD-15 cells with nuclear condensation and fragmentation. In addition, we found that emodin significantly decreases myeloid cell leukemia 1(MCL-1). These results suggest that MCl-1 is an important molecule for emodin-induced apoptosis. Taken together, emodin inhibits cell viability and induces apoptosis via down-regulation of MCL-1 and it can be a new potent anticancer drug candidate for the treatment of mucoepidermoid carcinoma

Because of the irreversible nature of periodontal disease, early diagnosis is an important aspect of management of patients with periodontal disease. Human saliva is an attractive medium for disease diagnosis because its collection is noninvasive and simple. Analysis of saliva may be especially beneficial in the determination of current periodontal status and serve as means for the screening of periodontal disease. In the present study, we investigated potential biochemical markers in whole saliva samples for the screening of periodontal disease using proteomics technique. We enrolled five subjects each from four different groups on the basis of measures of periodontal health (healthy group, gingivitis group, chronic periodontitis group and aggressive periodontitis group). Eleven proteins in whole saliva samples were identified as differentially expressed proteins between the healthy and periodontal disease groups using 2-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight / time-of-flight mass spectrophotometry (MADLI-TOF/TOF MS) approaches. Although the diagnostic value of oral fluid has been recognized for some time and potential biomarkers of periodontal disease have been identified in saliva, this, to our knowledge, is one of the first studies to examine large-scale proteomic profiling to identify the extent of periodontal destruction. Thus, this work provides an important framework for future efforts aimed at understanding salivary responses to periodontal destruction and predicting the future disease progression.

The human embryonic-lethal abnormal vision-like protein, HuR, stabilizes mRNA containing adenine- and uridine- rich elements in their 3’untranslated region. Because cyclooxygenase-2 (COX-2) mRNA is a cellular transcript that contains an adenine- and uridine-rich element, it can be regulated by the HuR protein. In this study, we examined the relationship between COX-2, HuR, MVD, and the clinicopathological parameters. Nineteen out of 43 cases of HNSCC showed high level of COX-2expression, and 68% of these patients showed high COX-2 immuno-reactivity indicating the strong expression of the cytoplasmic HuR protein. Also, MVD expression in the cases with high COX-2 expression was higher than in the cases with low COX-2 expression. These results suggest a strong correlation between the overexpression of cytoplasmic HuR and COX-2 expression in HNSCC, and that COX-2 is associated with MVD in HNSCC. In conclusion, COX-2 regulated by cytoplasmic HuR may be a good tumor angiogenic factor in HNSCC.

The human ELAV(embryonic lethal abnormal vision)-like protein HuR stabilizes a certain group of cellul ar mHNAs that contain AU- rich elements in their 3’ - untranslated region , To test the significance of HuR in carcinogenesis of head and neck squamous cell carcinomas(HNSCCs), we have investigated HuH expression from 32 benign epithelial lesions , 14 prema lignant epitheli al lesions and 80 HNSCCs, There were two different staining patterns of HuR in HNSCCs : nuclear expression was seen in 78 7% (63 of 80) 01' cases; and an additional cyto plasmic expression was seen in 28, 7%(23 of 80) 01 cases, Nuclear expression of HuR was s ignificantly increased in premalignant lesions and HNSCCs, whereas increased cytoplasπli c expression of HuR was only observed in HNSCCs Cytoplasmic HuR expression was significantly increased in pa tients of HNSCC younger than 60 yea rs , Al though there was no significant correlation between a natomic s ites of HNSCCs and HuR express ion , cyto plasmic HuR expression was highly increased in HNSCCs of larynx, There was no significant co rrela tion between HuR expression and other clinicopathological parameters such as histological type‘ tumor s ize‘ 0 1' n odal s tatus , ln conclusion, this study s uggests that overexpression of HuR in HNSCCs may be part of a regula tory pathway tha t co ntro ls the mHNA stability 0 1' several important targets in carcinogenesis of HNSCCs

Human saliva conta ins a la rge number of proteins and peptides whose composition may alter as a conseq uence of disease. '1'0 date‘ however. the proteins and peptides that routinely populate t his oral fluid are largely unknown, '1'0 provid e a ca ta logue 이， sali va protei ns. we have surveyed the unstimulated human whole saliva by using shotgun proteomics. F'or the shotgun a pproach‘ whole sali va proteins were digested into peptides with ChemDigestD and the res ulting pe ptide fragments were sepa rated by RP- HPLC, followed by each fraction was tryptic di gestion ChemDiges tD- Trypsin diges ted pe pt ides were analyzed by tandem mass spectrometry (MS!MS) using a nano-LC equi pped quadru po le-time of fli ght rnass spect rometer, and the obtained spectra were searched against human protein sequence da tabase us ing MASCOT Shotgun proteomics a llowed a total of 291 human proteins to be confidently assigned. The largest gro u p (17 , 2%) of the identifi ed proteins sorted into functional categories was included in the s ignal transducti on function except for the hypothet ical or unknown functio n, This work provides a valuable starting point for the ana lys is of human sa l i va ry protei ns a nd theil‘ biological functions and candidates from human whole saliva that may prove to be of diagn ost ic and t herapeutic s ignif‘ Ica nce

The tumor suppressor gene, phosphate and tensin homologue(PTEN) has been shown to dephosphorylate the phosphatidylinositol 3-kinase(PI 3-K)-generated phosphatidylinositol(3-5)-triphosphate in vivo, thus interfering with the potentially oncogenic signals emanating from PI 3-K. Promoter hypermethylation of CpG islands has recently been shown to be an epigenetic change resulting in loss of function in some genes involved in cell cycle regulation and DNA repair. Immunohistochemal staining for monoclonal antibody 6H2.1 was performed from paraffin embedded blocks of 20 benign epithelial lesions and 40 head and neck squamous cell carcinomas(HNSCCs). Immunoreactivity was graded semiquantitatively by considering the percentage and intensity of the staining of the tumor cells. Also, this study tried to identify PTEN methylation in benign epithelial lesions(24 cases) and HNSCCs(44 cases of paraffin embedded blocks, 4 cases of frozen tissues) using methylation-specific PCR(MSP). In HNSCCs, immunoreactive scores of stage 1 and 2(12 cases, average score 85.2) were higher than those of stage 3 and 4(15 cases, 41.9) and statistically significant(P=0.017). Immunoreactive scores of moderate and poorly differentiated carcinomas(22 cases, 61.6) are more or less lower than those of well differentiated carcinoma(15 cases, 87.0) but not significant(P=0.361). Among 24 cases of benign epithelial lesions, 12 cases showed unmethylated PTEN but none methylated. In HNSCCs, 22 of 44 paraffin embedded blocks showed unmethylated PTEN but none methylated, and all 4 frozen tissue revealed unmethylated PTEN, one of which(25%) methylated. We consider that the loss of PTEN protein expression may be associated with the progression of HNSCCs and the other alteration rather than methylation may be important in the inactivation of PTEN in HNSCCs.