Primary oral squamous cell carcinoma (OSCC) associated with dental osseointegrated implants is very rare. We experienced two patients who had received dental implant surgery before they were diagnosed with OSCC. We report these cases to emphasize the importance of differential diagnosis of malignant lesions associated with dental implants. Additionally, we also suggest that bone graft materials around implants can serve as a potential inducer of invasiveness in cancer cells.

Several studies have shown that curcumin, which is derived from the rhizomes of turmeric, possesses antimicrobial, antioxidant and anti-inflammatory properties. The antitumor properties of curcumin have also now been demonstrated more recently in different cancers. This study was undertaken to investigate the modulation of cell cycle-related proteins and the mechanisms underlying apoptosis induction by curcumin in the SCC25 human tongue squamous cell carcinoma cell line. Curcumin treatment of the SCC25 cells resulted in a time- and dose-dependent reduction in cell viability and cell growth, and onset of apoptotic cell death. The curcumin-treated SCC25 cells showed several types of apoptotic manifestations, such as nuclear condensation, DNA fragmentation, reduced MMP and proteasome activity, and a decreased DNA content. In addition, the treated SCC25 cells showed a release of cytochrome c into the cytosol, translocation of AIF and DFF40/CAD into the nuclei, a significant shift in the Bax/Bcl-2 ratio, and the activation of caspase-9, caspase-7, caspase-6, caspase-3, PARP, lamin A/C, and DFF45/ICAD. Furthermore, curcumin exposure resulted in a downregulation of G1 cell cycle-related proteins and upregulation of p27KIP1. Taken together, our findings demonstrate that curcumin strongly inhibits cell proliferation by modulating the expression of G1 cell cycle-related proteins and inducing apoptosis via proteasomal, mitochondrial, and caspase cascades in SCC25 cells.

Development of squamous cell carcinoma around dental implants is an uncommon clinical manifestation with only a few cases described in the literature. Recently, we observed primary squamous cell carcinoma that developed from leukoplakia around dental implants. We report this case to emphasize the importance of careful oral examination, for implant surgery has to be preceded by thorough evaluation of oral mucosal conditions.

Chronic inflammation is widely considered to predispose individuals to cancer. Microorganisms facilitate recruitment and activation of inflammatory cells and thus allow release of inflammatory mediators. These molecules can then promote accumulation of mutations, leading to tumor development in the host. Porphyromonas gingivalis, a pathogen causing chronic periodontitis, is detected in oral squamous cell carcinoma (OSCC) tissues. Considering a strong link between chronic inflammation and tumor development, functional consequences of P. gingivalis infection may include malignant transformation of the host cells. In this study, we monitored transcriptional changes induced by invasion of P. gingivalis in OSCC cells using microarrays. Our preliminary results suggest changes in a wide range of genes involved in inflammation, apoptosis and autophagy, tumor progression, and carcinogenesis. Further studies on molecular mechanisms underlying these changes will lay a useful foundation to elucidate the role of microorganism-related inflammation and for the development of preventive and therapeutic agents for oral cancer.

A Warthin’s tumor of major salivary glands, in particular of parotid glands, is a common benign tumor that may occur synchronously or metachronously in the same or contralateral gland. Moreover, epithelial malignance associated with a Warthin’s tumor is extremely rare, and exists in three forms; epidermoid carcinoma, adenocarcinoma, and undifferentiated carcinoma. The reports, related with a case of squamous cell carcinoma arising in a Warthin’s tumor at the parotid gland were reported only additional 3 cases from 1999 to 2010; 30 cases reported up to 1999.[2,4,7] This case report was a extremely rare case where both a primary squamous cell carcinoma and a Warthin's tumor were coexisting in the same

Inflammation functions as a double-edged sword against external stimulus. For instance, inflammation can have anti-cancer effect and simultaneously can play cancer-promoting factors. Recent studies have shown that cytokine plays an important role in tumor biology by influencing tumor growth, invasion and metastasis. We classify these cytokines by cancer type and review current knowledge of cytokines in terms of carcinogenesis. Here, we also focus on whether cytokines can act as biomarkers for early detection of oral squamous cell carcinoma (OSCC). This review will provide basis for further approach to study the role of cytokines in carcinogenesis and evaluating the possibilities of cytokines as biomarkers for cancer detection

New therapeutic measure are needed to improve the outcome for patients with oral squamous cell carcinoma(OSCC) because OSCC continues to portend a relatively unfavorable prognosis. Recently RNA interference(RNAi) has emerged as an effective method to target specific genes for silencing. Although overexpression of urokinase-type plasminogen activator receptor(uPAR) has been implicated in progression and metastasis of OSCC, the transfection effect of RNAi- uPAR on OSCC has been rarely reported. The purpose of this study were to examine the efficient and specific inhibition of uPAR mRNA and protein expression by siRNA targeting of uPAR through RT-PCR and immunoslot blotting, and to study cell proliferation activity, adhesion, invasion and migration in vitro compared to the controls. In MTT assay, siRNA-uPAR transfected cells showed about 70-80% cell proliferation compared to OSCC cell lines after 2 days. In adhesion assay, siRNA-uPAR transfected cells showed about 20-30% adhesion activity compared to OSCC cell lines, but similar features to those of BSA coated wells. In migration assay, siRNA-uPAR transfected cells showed about 60% migration activity compared to OSCC cell lines, but higher 3.5 folds to those of BSA coated wells. In invasion assay, siRNA-uPAR transfected cells showed about 55% invasive activity compared to parental cell lines. mRNA expression of siRNA-uPAR transfected cells showed about 10-15 % compared to parental cell lines by RT-PCR. Protein expression of siRNA-uPAR transfected cells showed about 25% compared to parental cell lines by ELISA assay. It suggested that RNAi-uPAR tranfection might be used as a potent and specific therapeutic tool for the treatment of oral squamous cell carcinoma, especially in inhibiting invasion and metastasis.

Oral squamous cell carcinoma (OSCC) is one of the most common carcinomas in the head and neck area. Bitter melon extraction (Momordicacharantia, BME) has been used as a functional food to prevent and treat human health related issues. It has recently been reported that BME inhibits breast cancer cell growth by arresting cell cycle and promoting apoptosis. In this study, we aimed at proving the inhibitory action of BME on OSCC proliferation. We used two OSCC cell lines, SCC4 and Ca9-22. Both cell lines were treated with different concentrations (1%, 2%, and 5%) of BME. Cell viability was examined by MTT assay. DNA condensation was visualized by immunofluorescence microscope to determine the signs of the cell apoptosis. Cell numbers were significantly decreased in a dose-dependent manner by bitter melon at concentration of 1% of BME on Ca9-22 cell line (P=0.001) but no significant effect on SCC4 (P=0.124) at the same concentration. 2% BME treatment of the Ca9-22 cell line induces chromatin condensation and DNA fragmentation after 20 hours. It seems that BME inhibits the proliferation of Ca9-22 cell line by inducing apoptosis. Thus, BME may be used as a dietary supplement for prevention of OSCC.

Tumor cells, especially in a malignant form, proliferate rapidly that blood supply within the tumors becomes limited, leading to a condition of insufficient oxygen supply. Such hypoxic condition is known to impair the viability of cancer cells, but it can also be a factor to facilitate the appearance of cells with a higher degree of malignancy. Indeed, the hypoxic condition created within malignant tumors may contribute to promoting their aggressive behaviors, including tumor invasion and metastasis, and to the development of resistance to various therapeutic modalities such as chemotherapy. Recently, microRNAs, a group of short RNA fragments consisting of 18 to 20 nucleotides, have been shown to participate in regulating genes important for cell survival, differentiation and apoptosis. Since their discovery, modulation of these microRNAs has been a focus of intensive studies with regard to their significance on gene regulation and various aspects of cell biology. In this study, we investigated hypoxia-induced alterations in microRNAs in oral squamous cell carcinoma (OSCC) cells and discussed consequential gene modulation and relevant cellular responses.

Metastasis consists of complex cascades and a lot of factors are involved in each step of metastasis. In recent studies, the role of epithelial-mesenchymal transition (EMT) in metastasis is suggested. EMT has a feature of epithelial cells conversing into mesenchymal cells morphologically and phenotypically, is a characteristic of malignant and metastatic cells in most cancer. The mesenchymal cells usually show more malignant phenotype, including invasion and metastasis. EMT can play an important role in metastasis of oral squamous cell carcinoma (OSCC). Although the role of Snail, slug, other transcriptional factors and E-cadherin are well known in human cancers, there are a few studies on N-cadherin and Twist expression in OSCC. The present study was aimed to analyze the expression of N-cadherin and Twist protein in OSCC from Korean patients. The immunohistochemical stain was performed using 58 primary OSCCs and 6 metastatic OSCCs, and the correlation between the expression of these proteins and clinicopathological parameters of OSCC patients was analyzed. The expression rate of high expression of N-cadherin was observed in 70.4% and Twist in 87.3% of OSCC. The expression of N-cadherin in metastatic OSCC increased than in corresponding primary OSCC (p<0.05). The spearman correlation coefficiency between N-cadherin and Twist was calculated as 0.228. The clinical factors such as lymph node metastasis and survival showed statistically significant correlation between N-cadherin expression. The expression of Twist was correlated with recurrence. In conclusion, the authors suggest that N-cadherin may play an important role in malignant behaviour of OSCC and can be considered as prognostic indicator of OSCC.

Oral squamous cell carcinoma (OSCC) develops through multistep process, that is, from normal mucosa to hyperplastic area and progressed to dysplasia, carcinoma in situ, and finally to invasive carcinoma. The purpose of this study is to investigate the histological types of the transitional area from normal oral mucosa to invasive carcinoma for the baseline data to search intermediate end point markers for early detection of OSCC. For this purpose, we reviewed the 85 patients who were diagnosed as OSCC in the Department of Oral Pathology, Yonsei University College of Dentistry, from 2002 to 2008. We classified these histopathologic findings by light-microscopy, according to the histologic pattern of transitional areas. As results, stepwise transformation from normal oral mucosa, to dysplasia and to OSCC was shown in 47 patients. Intermittent lesions were seen in 16 patients, in which normal oral mucosa, dysplasia, and OSCC were alternately arranged. Twenty two patients showed abruptly transformed to OSCC from normal oral mucosa. These preliminary data will be used for searching biomarkers for early detection of OSCC.

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.

Recurrence-metastasis status of squamous cell carcinoma of tongue is a challenging oncologic problem. This study examined the expression of E-cadherin/β-catenin cell adhesion complex in squamous cell carcinoma of the tongue through an immunohistochemical study. Twenty samples from 15 patients with squamous cell carcinoma of the tongue, who were treated at the Department of Oral and Maxillofacial Surgery, consisted of primary or recurrent tumors along with matched metastatic lymph nodes were retrieved for immunohistochemical staining and grouped based on recurrence-metastasis status.Differences in stain localization were noted in E-cadherin, β–catenin and phospho β–catenin staining between different tumor groups based on the recurrence-metastasis status. The number of phospho β-catenin stain positive cells was found to have a significant role in survival. E-cadherin confirms its role as a powerful individual differentiation indicator and the role of β-catenin specially the phospho type elicts interest

A rare case of primary intraosseous squamous cell carcinoma(PISCC) arising from lining epithelium of a dentigerous cyst is described. The case occurred at the left mandibular 3rd molar region in a 56-year-old Japanese woman. Clinical observation revealed cyst formation with an impacted 3rd molar, a common finding in dentigerous cyst, in the left mandible. Histopathologically, the lining epithelium of the cyst demonstrated transition from epithelial dysplasia to invasive squamous cell carcinoma(SCC). This case was diagnosed as PISCC arising from lining epithelium of a dentigerous cyst.

Plasminogen activator(PA) system such as urokinase plasminogen activator(uPA), urokinase PA Receptor(uPAR), tissue, tissue PA, and PA inhibitor-1&2(PAI-1&2) play a role in tumor invasion, metastasis, and proliferation. It is interested that these factors in patients with primary oral squamous cell carcinoma(Oral SCC) will be evaluated and correlated with clinicopathologic variables. Recently, these expression of primary oral SCC has been restricted to clinical or immunohistochemical study such in vivo study. The purpose of this study were to investigate the mRNA expression and cytologic concentration of uPA, uPAr, tPA, and PAI-1,2 in oral SCC cell lines compared to NHOK and to apply these results to evaluate early detection biomarkers of oral SCC in future. All the cell lines(NHOK, HN 4 and SCC 25) were cultured under KBM bullet kit at 37℃ in a 5% CO2 incubator. We studied a possible association between mRNA expression and cytosolic concentrations of uPA, uPAR, tPA, and PAI-1,2 in oral SCC cell lines compared to NHOK using RT-PCR and an enzyme-linked immunoassay(ELISA) method. uPA mRNA expression was about 5-6 folds, while uPAR was a bout 3 f olds, and PAI-1 was about 1 .5-1.6 f olds. PAI-2 was a bout1.2 -1.3 f olds t han that o f NHOK, w hile t PA w as l ower t han that of NHOK. uPA cytosolic concentrations was about 15-19 folds, while uPAR was about 8 folds, and PAI-1 was about 3-4.5 folds. PAI-2 was about 2 folds than that of NHOK, while tPA was lower than that of NHOK. Both uPA, uPAR, and PAI-1,2 cytologic concentrations were correlated with mRNA expression of oral SCC cell lines. From the aboving results, high cytosolic concentrations of uPA, uPAR, and PAI-1 & 2 were correlated with mRNA expression. It suggested that these might be specific markers for oral SCC cell lines and these results would be contributed to evaluate early detection biomarkers for human oral squamous cell carcinoma.

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.

Human pituitary tumor transforming gene 1 (PTTG1), which is a newly identified proto-oncogene, is highly expressed in normal pituitary tissues containing proliferating cells and in several cancers. Also, PTTG1 has been known as a securin to involve in the regulation of c ell-cycle and in t he p rogression o f tumor. B u t the effect o f PTTG1 in o ral squamous cell carcinoma (oral SCC) h as not b een studied yet. The objective of this study is to analyze the expression of PTTG1 in oral SCC cell lines (YD-10B and YD-15) and to evaluate the effect of PTTG1 on oral SCC cell lines for the migration effect by PTTG1 siRNA treatment. Western blot, migration assay, and zymography were performed to evaluate the effects of PTTG1 on the expression of MMP-2/-9 and migration activity after PTTG1 siRNA treatment. PTTG1 was expressed in oral SCC cells lines, otherwise, significantly decreased after PTTG1 siRNA treatment. There is no difference in expression of MMP-2 regardless of PTTG1 siRNA treatment. However, the enzyme activity of MMP-9 was significantly decreased. In addition, the migration activities of oral SCC cells were significantly decreased after PTTG1 siRNA treatment (p<0.001). These results suggested that the down-regulated PTTG1 could inhibit the migration of human oral SCC cells through the low MMP-9 expressions. Therefore, these findings provide a useful guideline for the migration mechanism of oral SCC depend on PTTG1 expression.

Oral squamous cell carcinoma (OSCC) is the most common cancer of oral cancers. Recent data suggest that chemokines could be essential players in carcinogenesis and that tumor cells express chemokine receptors and use chemokines to metastasize to the target organ in many malignancies in humans. The aim of this study was to test the hypothesis that expression of SNPs in chemokine, CXCL1 and CXCL2 correlates with oral squamous cell carcinomas in Korean population. The CXCL1 and CXCL2 genotypes were determined in 21 subjects with oral squamous cell carcinoma and 90 control subjects without oral squamous cell carcinoma. The genotypes were determined by direct sequencing. The genotype distribution and allele frequency within the OSCC patients were not significantly different from those of control subjects. But among OSCC subjects, there was significant difference of CXCL1 gene in the degree of nuclear aberration. These findings suggest that CXCL1 -442C/T polymorphism and CXCL2 -264T/C polymorphism are not related to the development of OSCC but polymorphism of CXCL1 gene might have a relation with progression of OSCC in Korean population.

Malignant tumor cells outgrow new blood vessel formation and tend to be in hypoxic state. Hypoxic cancer cells adapt to hypoxic conditions by transforming its characteristics. On the other hand, one of the most important features of cancer cells is that carcinoma cells loses its inherent epithelial phenotype and acquires mesenchymal characteristics, called as epithelial-mesenchymal transition(EMT). It has been already well known that EMT contributes to tumor invasion and metastasis. The present study investigated whether hypoxia play a major role in induction of phenotypic changes of oral squamous cell carcinoma(OSCC). Furthermore, the mechanism of EMT in oral squamous cell carcinoma cells by hypoxia has been clarified. To mimic hypoxic condition, cobalt chloride and desferoxamine, well-known hypoxic mimetic agents, were used. This study shows that hypoxia suppresses the expression of E-cadherin(epithelial marker) and increases vimentin and N-cadherin( mesenchymal markers) in OSCC. In addition, α5 integrin protein, which is a receptor for fibronectin and an important molecule for tumor invasion, is prominently induced by hypoxia.

Tumor cell biological factors, such as urokinase plasminogen activator(uPA) and its inhibitor plasminogen activator inhibitor- 1(PAI-1) play a role in tumor invasion, metastasis, and proliferation. These factors in patients with primary oral squamous cell carcinoma(Oral SCC) will be evaluated and correlated with clinicopathologic variables. However, relatively rarely has been known in oral squamous cell carcinoma in vivo and in vitro study . The purpose of this study were to investigate the protein expression of uPA and PAI-1 in oral SCC cell lines cell line compared to NHOK and to study migration and adhesion assay. All the cell lines were cultured under KBM bullet kit at 37℃ in a 5% CO2 incubator. We studied a possible association between cytosolic uPA and PA-1 concentrations in oral SCC cell line compared to NHOK using an enzyme-linked immunoassay(ELISA). Cell adhesion and migration assay were done in all the cell l ines. In migration assay oral SCC cell lines were about 70 folds higher than NHOK. In adhesion assay oral SCC cell line were about 7-12 folds higher than NHOK. uPA cy tosolic concentrations was about 15-19 folds and PAI-1 was 3 to 4.5 folds than that of NHOK. Both uPA and PAI-1 concentrations were correlated with migration and adhesion assay. High cytosolic concentrations o f uPA and PAI-1 were correlated with migration and adhesion assay . It suggested that these markers might be specific for oral SCC cell line and these results would be contributed to treatment and prognosis of human oral squamous cell carcinoma.