SOCS3, a suppressor of cytokine signaling 3, is known as a negative regulator of various cytokines and a tumor suppressor gene in human tumors. This study aimed to investigate the role of SOCS3 in oral squamous cell carcinoma (OSCC) and its impact on epithelial-mesenchymal transition (EMT) in OSCC cells. Although SOCS3 is recognized as a negative regulator of various cytokines and a tumor suppressor gene in human tumors, its specific effects on OSCC remain poorly understood. For the assessment of SOCS3 expression in OSCC, the UALCAN website and TCGA data were used to evaluate its expression in head and neck cancer. Additionally, immunohistochemical staining was conducted to determine the SOCS3 expression specifically in OSCC. The findings indicated a significant decrease in SOCS3 expression in tumor tissue compared to that in normal tissues. To investigate the enhancement of SOCS3 expression in OSCC cancer cell lines, IL6 treatment was administered to MC3 cells. However, no significant differences were observed in cell viability, wound healing assay, and invasion assay. Conversely, the transfection of SOCS3 siRNA into OSCC cells led to a notable increase in cell viability and statistically significant increases in wound healing and invasion assays. These results suggest that SOCS3 plays a crucial role in cell viability and EMT in OSCC, thereby contributing to oral carcinogenesis. Further research is necessary to elucidate the precise role of SOCS3 in OSCC.

Taxillus yadoriki (Siebold) Dancer is a parasitic plant that grows on camellia trees and is common on Jeju Island. The branches of T. yadoriki have long been used to treat various diseases, including hypertension, diabetes mellitus, viral infections, and arthritis. Although recent studies reported that T. yadoriki has anticancer effects in various human cancer cell lines, including lung cancer, the exact molecular mechanisms supporting its anticancer effects are not well understood. This study aims to assess the anticancer effect of the methanol extract of T. yadoriki branches (METY) on mucoepidermoid carcinoma (MEC) cell lines (MC3 cells and YD15 cells) and explore its mechanism of action. Inhibitory activity of MEC cell proliferation was assessed using the CCK-8 assay. The mechanism of the anticancer effect on METY-treated MC3 cells and YD15 cells was evaluated with Hoechst 33342 stain and Western blot. After treating MC3 cells and YD15 cells with METY for 48 hours, the cytotoxicity of MC3 and YD15 cells increased, and nuclear fragmentation increased in both METY-treated MEC cells. Caspase-3 and cleaved PARP activation demonstrated apoptosis of METY-treated MEC cells. Cell proliferation inhibition with METY was alleviated in METY-treated MEC cells pretreated with zVAD-FMK, supporting the cell proliferation inhibition effect by apoptosis. METY-induced apoptosis in MEC cells occurs through MAP kinase pathways such as p38 and pAkt. MEC cell. METY-induced apoptosis of MEC cells occurs via the p38 and pAkt MAPK pathways. Therefore, METY may be a promising anticancer candidate for the MEC therapeutic strategy.

Mucosal malignant melanoma is an uncommon tumor of the head and neck, and patient cannot easily recognize the lesion. Most patients are diagnosed with advanced lesions, and the 5-year survival rate is very low. Therefore, intraoral pigmented lesions require an incisional biopsy for differential diagnosis from malignant melanoma. As the size of the tumor increases, lesion showing vertical growth and lymph node metastasis increases, and the prognosis becomes poor. In this study, we report a case of mucosal malignant melanoma in the oral cavity that shows radial growth and no lymph node metastasis despite its relatively large size.

Human melatonin receptors consist of melatonin receptor 1A (MT1) and melatonin receptor 1B (MT2), and possess various biological activations, which include the control of circadian rhythm and immune regulation. Recently, it have been found that melatonin receptors inhibit cell proliferation and have oncostatic properties, which is being researched in the treatment strategies of breast cancer, prostate cancer, and Non-Small Cell Lung Cancer. Also, interest in the effect of melatonin receptor’s correlation to head and neck carcinogenesis and application possibilities on head and neck cancer has been found. However, in head and neck cancer, how melatonin receptor relates and functions with epithelial-mesenchymal transition (EMT), which plays a major role in human carcinogenesis, is yet unknown. In this research, in HSC5 cell and YD15 cell, the head and neck cancer cell lines, a selective melatonin receptor antagonist, Luzindole, was utilized to examine the effect of melatonin receptors on EMT. After treating Luzindole on HSC5 cells and YD15 cells, the authors evaluated cell viability rate with CCK 8 assay, and performing colony forming assay, invasion assay and western blot analysis, to confirm melatonin receptor’s effect on EMT. When Luzindole was treated on HSC5 cells and YD15 cells in low concentration of 100nM, no significant difference in cell viability was found, whereas Luzindole-treated cells had a significantly increase in the invasion assay. As a result of colony forming assay, in YD15 cells, the number of colony formation decreased slightly, whereas in HSC3 cells, the number of colony formation increased. According to the western blotting, no difference in E-cadherin, Slug, and vimentin protein expression was shown. This result of research indicates the possibility of melatonin receptor being related to EMT and new chemotherapeutic target in the carcinogenesis of head and neck cancer.

Autophagy is a cell survival mechanism that works for the survival of cells under various physiological and pathological conditions. ATG5 is a key protein in the process of autophagy propagation and is involved in tumor development and progression. Chemotherapeutic agents targeting ATG5 enhance the host's immune response in various human cancers and intensify the effectiveness of chemotherapy. However, the physiological role of ATG5 protein in oral squamous cell carcinoma (OSCC) has not been fully recognized. The purpose of this study was to examine the correlation between clinico-pathological factors of OSCC patients and ATG5 immunoexpression through immunohistochemistry (IHC) in the tissues of OSCC patients treated at our hospital, and to analyze the regarding influences and their mechanisms. The authors analyzed 20 OSCC patients from National University Dental Hospital, at Pusan National University from January 2002 to December 2007, which were eligible for the study. Data were obtained by reviewing the medical records of the OSCC patients, and ATG5 immunoexpression was obtained using IHC staining in the tissue samples of the OSCC patients. In the tissue sample of OSCC patients, the immunoexpression of ATG5 elevated, in comparison to the normal oral mucosa, and there was a significant correlation with Drinking, Pathological Stage. In regards to Cox regression analysis, Clinical stage, Tumor size, Histopathologic grade, Cervical nodal metastasis, Loco-regional recurrence, and ATG5 expression have statistically significant correlations. These results imply that the changes in the expression of ATG5 proteins in OSCC can be a prominent factor in the OSCC progression and the prognosis of OSCC patients.

Basaloid squamous cell carcinoma (BSCC) is a rare and aggressive variant of squamous cell carcinoma arising in various anatomical sites. This article describes a case history of BSCC of the floor of mouth with mandibular involvement, and further discusses the appropriate management of such case with reference to the literature review. A 52-year-old male patient was referred to our clinic from another university hospital. Segmental mandibulectomy with supraomohyoid neck dissection and mandible reconstruction with left fibular free flap under general anesthesia was performed, followed by radiotherapy. Histopathological examination on the tumor lesion revealed features of squamous cell carcinoma with comedo-type necrosis. A diagnosis of BSCC was given by the oral pathology specialist. Basaloid squamous cell carcinoma (BSCC) is a biphasic variant of SCC with both basaloid and squamous cell histology. A recent report showed that there is no significant difference in the prognosis. Due to the lack of accumulated research, close follow-up and continuous research are deemed necessary. Treatment that focuses on the stage of the tumor is appropriate. A periodic follow-up observation is also very important due to the occurrence of distant metastasis to the lungs.

Nerve injury induced protein 1 (Ninjurin1) was originally described in neuroscience in which the expression of Ninjurin1 was regulated by Schwann cells and dorsal root ganglion neuronal cells of damaged nerve tissues. After the first discovery of Ninjurin1, the widespread expression of Ninjurin1 in adult and embryonic tissues have been observed including bone marrow, peripheral blood lymphocytes, thymus, and heart. Currently, the Ninjurin1 mediated positive regulation of pre-osteoclasts fusion and osteoclast development was reported. The bone homeostasis is dynamically balanced by bone-resorbing activity of osteoclast and bone-forming activity of osteoblast. Until now, the role of Ninjurin1 was never been described in osteoblastogenesis. Therefore, in this study, we have evaluated the expression and function of Ninjurin1 in osteoblast. The ample expression of Ninjurin1 was observed in bone marrow of mouse tibia sections but it was barely expressed in osteocytes. And also the expression levels of Ninjurin1 were gradually increased during osteoblast differentiation of calvarial pre-osteoblast, C2C12, and MC3T3-E1 cells. Importantly, the expression of Ninjurin1 was increased in the absence of osteogenic stimulus, BMP2, which suggests the cell density-dependent regulation of Ninjurin1. The controlled expression of Ninjurin1 by cell-density was evidently shown in not only pre-osteogenic osteoblast lineage cells but also in non-osteogenic cancer cells such as HeLa and A549 cells. In addition, the isoform-specific knockdown of Ninjurin1 remarkably reduced the alkaline phosphatase (ALP)-positive osteoblast differentiation. Thus, our results suggest a previously unappreciated mechanism of Ninjurin1 expression and also suggest its role on osteoblastogenesis.

The vascular origin diseases occurring in the oral and maxillofacial region can be divided into hemangiomas and vascular malformation. They are rare and early lesions are not easy to diagnosis, so they may be misdiagnosed as clinicians, or the method and timing of treatment may be inappropriate. For 10 years, from August 2005 to August 2015, we analyzed the clinical records, diagnosis, treatment, and prognosis of 23 patients with hemangioma or vascular malformation confirmed by clinical, histopathological or radiological examination of maxillofacial lesions at department of oral and maxillofacial surgery, Pusan National University Hospital and Pusan National University Dental Hospital. Chief complants of patients were mainly swelling, mass, and spot-like lesion on various intraoral sites. Treatments were performed with excision, embolization, sclerotherapy, depending on each lesions condition. Arteriovenous malformation cases were more frequently recurred than other lesions. Prognosis of lesions were relatively good but close observation should be needed.

Odontogenic keratocyst (OKC), also known as keratocystic odontogenic tumor (KCOT), is an emerging odontogenic tumor originating from the dental lamina. It is an aggressive lesion with a squamous epithelium and a recurrence rate of 15-35%.1 Radiologically, there is a clear, smooth, or shell-like border showing a unilocular or multifocal, polycystic radiographic picture. Hard tissue formation in OKC is a very rare phenomenon and occurs in the form of dystrophic calcification, cartilaginous tissue or dentinoid.2 In this article, we report the case of OKC with calcification. OKC with radiopaque lesion is very rare, these are considered as dystrophic calcification, dentinoid formation, ossification. The incidence of dystrophic calcification in recurrent OKC is low, so it can be inferred that the recurrence rate of OKC with dystrophic calcification is lower than that of conventional OKC.

Background: Mucoepidermoid carcinoma (MEC) is the most common malignant epithelial tumor of the salivary gland in the oral cavity. In South Korea, it occurs most frequently in the palate, retromolar area, floor of the mouth, buccal mucosa, and other areas of the oral cavity. MEC is rare in children and adolescents under 20 years of age, but it is the most common malignant salivary gland tumor in this group. Reconstructive surgery is often required due to cystic lesions or resection of malignancy in the oral cavity. Buccal fat pad (BFP) is a flap that is reliable and suitable for reconstructing oral defects because it has a low complication rate and small volume change over time. Case Presentation: We report the case of a 12-year-old female patient with low-grade MEC on light soft palate with no neck metastasis. After tumor resection the palatal mucosal defect was reconstructed with a BFP flap. Conclusion: The purpose of this article is to discuss the features and treatment methods of MEC that is rarely occurring in children, and the usefulness of BFP for reconstruction. Therefore, we will make a precise diagnosis and treatment as we examine the clinical feature and review the literature.

Autophagy is recently receiving the spotlight as the development strategy for promising anticancer drugs. In particular, the majority of anticancer drugs originating from natural products are known to induce autophagy. Saururus chinensis has been used for treating various inflammatory diseases. Recent research has revealed that the extract of Saururus chinensis possess cytotoxicity for various types of human cancer cells. However, the exact action mechanism of Saururus chinensis extract for oral squamous cell carcinoma (OSCC) has not been studied yet. Therefore, the authors of this research aim to study the effect of methanol extract of S. chinensis (MESC) on OSCC cells. To observe the cell proliferation inhibitory effect of MESC on HSC3 cells, the authors conducted the trypan blue exclusion assay. Also, the action mechanism of MESC was studied by conducting the cell cycle analysis, acidic vesicular organelle (AVO) staining and flow cytometry analysis, monodansylcadaverine (MDC) staining, propidium iodide staining, and Western blotting on MESC-treated HSC3 cells. When HSC3 cells were treated in MESC, the cell proliferation was suppressed in time-dependent and dose-dependent manners. Also, the number of sub-G1 arrested cells increased in a dose-dependent manner. MDC punctate and AVO puncta significantly increased respectively. Western blot analysis demonstrated the expression of autophagy-related proteins increased, but apoptotic proteins were not observed. Also, the pAkt protein was reduced, while the p-p38 protein and pERK protein increased. According to our results, MESC induced autophagy and accompanied changes in the cell cycle in HSC3 cells. Also, the alteration in Akt, ERK, and p38 pathways were confirmed. This result suggested the possibility of MESC as the new promising adjuvant for treating OSCC patients.

Natural products are vastly utilized as a source of chemotherapeutic agents for human cancers. Kochia scopraia is traditionally used for the cure of urological and dermatological diseases. Recently, methanol extract of Kochia scoparia (MEKS) has been shown to have anti-cancer activity to various human cancers. However, there is no report demonstrating the anti-cancer activity of MEKS in human mucoepidermoid carcinoma (MEC) cells. In this study, the authors studied the effects of MEKS on the cell proliferation and underlying mechanism in YD15 human MEC cells. MEKS decreased YD15 cell proliferation proven by trypan blue exclusion assay and induced apoptosis, evidenced by cell cycle analysis and western blotting. Autophagy induction by MEKS was verified by western blotting. In addition, MEKS regulated the expression of phosphorylated Akt, phosphorylated p38 and Nrf2 protein. This results can imply that MEKS might be a potential candidate for the treatment of human MEC cells.

The Hippo pathway was originally discovered in Drosophila by genetic screening and it has been shown to be conserved in various organisms including human. Until now, the essential roles of Hippo pathway in regulating cell proliferation, apoptosis, tumorigenesis, and organ size control is extensively studied. Currently, Mats1/2 (Mob1a/1b), one of the important components in Hippo pathway, mutant mice were generated which has abnormal phenotype such as resistance to apoptosis and spontaneous tumorigenesis. Of note, Mats1/2 mutant mice also showed dental malocclusion. Therefore, in this study, we have evaluated the bone phenotype of Mats1/2 mutant mice. Although the mRNA expressions of Mats1 or Mats2 were observed in both osteoclastogenesis and osteoblastogenesis, the increase of Mats1 level was most prominent during osteoblastogenesis. The RANKL-induced osteoclast differentiation from bone marrow-derived macrophages (BMMs) was unaltered upon Mats1/2 mutation; however, the osteoblast differentiation using calvarial pre-osteoblasts was significantly reduced in Mats1/2 mutant mice compare to that of wild type mice. In accordance with in vitro results, Mats1/2 mutant mice showed decreased bone volume as well as increased trabecular separation in μCT analyses. These results may provide novel prospect of the probable linkage between Hippo pathway and bone homeostasis.

Connective tissue growth factor (CTGF, CCN2) is one of the multi-functional secreted proteins which belong to CCN family of cysteine-rich growth factors. CTGF is known to have pivotal roles in embryonic endochondral ossification but its role in relevance to periodontitis is never been determined. To identify new molecular mediators associated with periodontitis-induced bone resorption, we have analyzed publicly available GEO database and found the markedly augmented CTGF mRNA expression in periodontitis gingival tissues. The existence of CTGF significantly enhanced mature osteoclasts survival which accompanied by reduction in TUNEL-positive nuclei and PARP cleavage. These results may provide another line of evidence the CTGF mediated prolonged osteoclast survival and subsequent increased bone resorption in the periodontitis patients.

The fruit of Kochia scoparia Scharder is traditionally used as a medicinal ingredient to treat allergic skin diseases and inflammatory diseases in China, Japan and Korea. Recently, several studies reported that K. scoparia had potential for the cytotoxicity of human cancer cells. To investigate the anti-cancer effect of K. scoparia on oral cancer and to determine the specific type of cell death induced by MEKS treatment. We investigated the anti-cancer effects of K. scoparia, methanol extract (MEKS) in HSC4 human oral cancer cells. We examined the effects of MEKS on the proliferation rate, cell cycle arrest, 7-AAD-ANNEXIN V double stain, reactive oxygen species (ROS) generation and activation of apoptosis and necroptosis-associated proteins in HSC4 cells. MTT assay results demonstrated that MEKS decreased the proliferation rates of HSC4 cells in a dose-dependent manner with an IC50 value of 45.3 μg/ml. MEKS at 50 μg/ml significantly increased the sub-G1 DNA contents of HSC4 cells to 84.8%, versus untreated cells. However, the activation of apoptosis-associated proteins such as cleaved caspase 3, cleaved caspase 8, cleaved caspase 9 and cleaved Poly (ADP-ribose) polymerase (PARP) did not detect. The level of Bax protein markedly increased in MEKS-treated HSC4 cells. In addition, the cell viability of the DPQ pre-treated HSC4 cells with MEKS treatment was significantly greater than that of MEKS treated-cells. These results suggest that MEKS inhibits cell proliferation and induces necroptosis in oral cancer cells and that MEKS may have potential chemotherapeutic value for the treatment of human oral cancer.

Visfatin is a pro-inflammatory cytokine, which is thought to play a central role in systemic inflammation and the pathogenesis of obesity related diseases. Only a few studies investigated the effect of visfatin on human cancers. Furthermore, there have been no studies on the association between the expression of visfatin in OSCC tissue and its effect on OSCC patients. Hence, the present study analyzed the expression of visfatin in OSCC from Korean patients. Immunohistochemistry for visfatin was performed using 12 normal oral mucosas (NOM), 16 oral leukoplakias (with/without dysplasia), and 58 OSCC patients samples. Immunoreactivity was semi-quantitatively scored and the correlation between the expression of visfatin and clinicopathological parameters of OSCC patients was analyzed. The immunohistochemical analysis demonstrated that the expression level of visfatin increased in OSCC alone (p<0.05). Moreover, the immunoexpression score of visfatin was significantly correlated with TNM stage of OSCC patients. Our findings suggested that visfatin can play a certain role in the pathogenesis of OSCC. In addition, visfatin was associated with the tumor progression of OSCC patients and may act as independent biomarker of OSCC.

Oral squamous cell carcinoma (OSCC), is the most common malignancy of oral cavity, and the sixth most frequently diagnosed cancer worldwide. This tumor type is associated with poor prognosis, and most OSCC patients are diagnosed after the cancer has reached an advanced stage. The over expression of NF-κB p65 has been associated with OSCC progression and lymph node metastasis. Hence, the present study analyzed the expression of NF-κB p65 in OSCC from Korean patients. Immunohistochemistry for NF-κB p65 was performed using 12 normal oral mucosas (NOM), 16 oral leukoplakia (with/without dysplasia), and 58 OSCC patients samples. Immunoreactivity was semi-quantitatively scored and the correlation between the expression of NF-κB p65 and clinicopathological parameters of OSCC patients was analyzed. Immunohistochemical staining revealed that NF-κB p65 expression level increased in oral leukoplakia with dysplasia and OSCC. Moreover, the immunoexpression of NF-κB p65 appeared to be associated with age, recurrence, TNM stage, and lymph node metastasis in OSCC patients (p<0.05). These results indicated that NF-κB p65 can play a role as oncogene in OSCC. Moreover, NF-κB p65 may play an important role in both oral carcinogenesis and OSCC patient outcome. It may be considered as another new malignant biomarker of OSCC.

Neuromedin B (NMB) acts as a growth factor or a morphogen and plays a role in cancer progression. Indeed, the NMB receptor (NMB-R) is overexpressed in different types of tumors. In our current study, we investigated the involvement of NMB-R in the proliferation of oral cancer cells. Human oral squamous cell carcinoma (SCC) and human oral cancer cells, SCC-25 cells were found to be NMB-R-positive. The NMB-R antagonist PD168368 inhibited the proliferation of SCC-25 cells and reduced their colony formation capacity. We also found that PD168368 induced the cell cycle arrest and apoptosis of SCC-25 cells in a dose-/time-dependent manner. Overall, this antitumor activity of PD168368 in human oral cancer cells suggests that NMB-R is a potential target for the future prevention and treatment of human cancers.

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.

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.