• International Journal of Oral Biology
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• v.49 no.1
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• pp.18-25
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• 2024

Despite advancements in therapeutic approaches, radiotherapy and cisplatin-based chemotherapy remain primary noninvasive treatments for patients with oral squamous cell carcinoma (OSCC). Moreover, the 5-year survival rate for patients with OSCC has remained almost unchanged for several decades, and many side effects of chemotherapy still exist. In this study, three-dimensional (3D) models of OSCC were established using fibroblasts, and the efficacy of various biological inhibitors was evaluated. A culture of epithelial cells with two types of fibroblasts (hTERT-hNOFs and cancer-associated fibroblasts) within a type I collagen matrix resulted in the formation of a continuous layer of tightly packed cells compared to models without fibroblasts. Furthermore, the effects of biological chemicals, including Y27632, latrunculin A, and verteporfin, on these models were investigated. The stratified formation of the epithelial layer and invasion in OSCC 3D-culture models were effectively inhibited by verteporfin, whereas invasion was weakly inhibited by Y27632 and latrunculin. Collectively, the developed OSCC 3D-culture models established with fibroblasts demonstrated the potential for drug screening, with verteporfin showing promising efficacy.

• The Journal of the Korean dental association
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• v.55 no.4
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• pp.276-283
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• 2017

Maxillary sinus squamous cell carcinoma is a relatively rare disease, comprising only 3% of malignant diseases of head and neck. As the growth rate is high and its prognosis is poor compared to others, the 5-year survival rate of maxillary sinus squamous cell carcinoma(MSSCC) is 23.4-49%. We introduce two rare clinical cases of squamous cell carcinoma originated from maxillary sinus of which symptoms include toothache and gingival swelling. On clinical examinations of both patients, deep periodontal pockets on upper right posterior teeth were detected. On panoramic images, the bony destruction of the maxillary sinus and its surrounding structures were not obvious and only alveolar bone loss was noted. It is difficult to diagnose MSSCC at an early stage due to symptoms of tooth pain and gingival swelling that are similar to that of periodontal diseases. However, if the symptoms do not improve after routine treatment of upper teeth, dentists should bear in mind of underlying malignant mass as differential diagnosis, thus early detection of the lethal disease. The aim of this study is to caution dental practitioners that malignancies have a potential to mimic periodontal diseases by introducing two cases of maxillary sinus squamous cell carcinoma presented as periodontitis.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.32 no.1
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• pp.1-8
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• 2010

Background and Purpose: Vascular endothelial growth factor (VEGF)-C and VEGF receptor (VEGFR)-3 are involved in tumor lymphangiogenesis. Oral mucosal squamous cell carcinoma (OMSCC) preferentially metastasizes to cervical lymph nodes, so we investigated the expression and distribution of VEGFR-3 signaling proteins in OMSCC. Materials and Methods: Tissue samples of 18 OMSCC, 10 oral mucosal leukoplakia, and 3 normal oral mucosa were evaluated for expression of VEGF-C, VEGF-D, and VEGFR-3 by immunohistochemical staining. The presence of lymphatic vessels was determined using D2-40 staining, by which we also measured lymphatic vessel density (LVD). Results: 72% (13/18) and 56% (10/18) of tissue samples showed VEGF-C and VEGF-D immunopositivity in tumor cells and tumor-associated endothelial cells. VEGFR-3 was also expressed in most of OMSCC, which was up-regulated when compared with normal mucosa or with leukoplakia. Furthermore, LVD was higher in OMSCC than in leukoplakia. Conclusion: Taken together, our results suggest that autocrine activation of lymphatic endothelial cell via VEGFR-3 by VEGF-C and/or VEGF-D could be involved in progression of OMSCC. Therefore, VEGF-C/VEGFR-3 signaling pathway can be a molecular target for anti-metastatic therapy in OMSCC.

• Biomolecules & Therapeutics
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• v.7 no.2
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• pp.153-157
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• 1999

The anticancer effect of medicinal plants against two oral carcinoma cells, A253 and SCC-25 were investigated in this study. Methanol extracts from 63 medicinal plants, which have anticancer activities against other cancers such as stomach, hepatocellular or colon carcinomas, were prepared and screened for their anti- oral cancer activity by using MTT assay. Thirty one samples showed anti-oral cancer activity against either cell line used, however, other 32 samples had no anti-oral cancer activity. Among these samples methanol extract of Caesalpinia sappan revealed the strongest anti-oral cancer activity. The $IC_{50}$/ values of this extract against A253 and SCC-25 cells were 16 and 25 $\mu$g/m1, respectively. Fractions of n-hexane, dichloromethane, ethylacetate, n-buthanol and water were prepared from methanol extracts of Caesalpinia sappan, Anthriscus sylvestris, Rhus japonica, Curcuma arowatica, Inula helenium, Sinoarnudinaria reticulata, and Polygonum cuspidatum, respectively. Among these 35 fractions the n-hexane fraction of Inula helenium showed the strongest anti-oral cancer activity, the $IC_{50}$/ value was 1.6$\pm$0.3 $\mu\textrm{g}$/ml. Ten other fractions showed $IC_{50}$/ values lower than 10 $\mu\textrm{g}$/ml.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.2
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• pp.94-100
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• 2006

Purpose: This study was done to confirm the role of NF-$\kappa$B in cisplatin-induced apoptosis of oral squamous cell carcinoma. Materials and Methods: Five cell lines originated from different oral cancer patients were tested for the apoptosis by the treatment of cisplatin. These cells showed different degree of cisplatin-resistance and the order is OSCC-2>OSCC-3>OSCC-5> OSCC-1>OSCC-4. OSCC-2 and OSCC-4 cells were assayed for the apoptosis by measuring DNA fragmentation and TUNEL staining after cisplatin treatment. While OSCC-4 cells showed apoptosis, OSCC-2 cells showed no or very slight apoptosis by cisplatin treatment. Next, It was determined whether NF-$\kappa$B activation is required in mediating cisplatin-induced apoptosis of OSCC-4. Result: The result was that elevated NF-$\kappa$B activity mediated cisplatin-induced apoptosis. Conclusion: In conclusion, these findings suggest that NF-$\kappa$B activation is essential to cisplatin-induced apoptosis and it may be involved in cisplatin resistance in OSCC cells.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.39 no.6
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• pp.283-288
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• 2013

As an uncommon, malignant salivary gland tumor with female predominance, hyalinizing clear cell carcinoma (HCCC) is regarded as an indolent tumor. The diagnosis of this rare tumor is challenging, and it depends on microscopic and immunohistochemical (IHC) studies. Although it is regarded as an indolent tumor, there are reports of unconventional forms with aggressive clinical courses. We report an atypical case of this rare tumor, HCCC, in a male patient who had a relatively large-sized mass ($3.8{\times}3.0$ cm) on the right mouth floor with ipsilateral neck node metastasis. The clinical, radiological, pathological, and IHC features together with the clinical course are described.

• Imaging Science in Dentistry
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• v.51 no.2
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• pp.203-208
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• 2021

Ghost cell odontogenic carcinoma (GCOC) is a rare malignant neoplasm characterized by the presence of ghost cells. It is considered to originate from either a calcifying odontogenic cyst(COC) or a dentinogenic ghost cell tumor(DGCT). Its clinical and radiographic characteristics are non-specific, including slow growth, locally aggressive behavior, and eventual metastasis. This case report describes a 43-year-old Thai man with plain radiographs and cone-beam computed tomographic images revealing a unilocular radiolucency with non-corticated borders surrounding an impacted left canine associated with radiopaque foci around the cusp tip. Based on the microscopic findings, the lesion was diagnosed as GCOC. Partial maxillectomy of the right maxilla was performed, and radiotherapy was administered. An obturator was made to support masticatory functions Three years later, the lesion showed complete bone remodeling and no signs of recurrence, and long-term follow-up was done regularly.

• International Journal of Oral Biology
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• v.46 no.1
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• pp.30-38
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• 2021

Cudraxanthone D (CD) is a natural xanthone compound derived from the root barks of Cudrania tricuspidata. However, the biological functions of CD in human metabolism have been rarely reported until now. Autophagy is the self-degradation process related to cancer cell metastasis. Here, we elucidated the effects of CD on human oral squamous cell carcinoma (OSCC) cells' metastatic ability. We confirmed that CD effectively decreased the proliferation and viability of SCC25 human OSCC cells in time- and dose-dependent manners. Also, the metastasis phenotype of the SCC25 cell (migration, invasion, and epithelial-mesenchymal transition [EMT]) was inhibited by CD. To further investigate the mechanism by which CD inhibited the metastatic capacity, we detected the relationship between EMT and autophagy in the SCC25 cells. The results revealed that CD inhibited the metastasis of the SCC25 cells by attenuating autophagy. Thus, our findings produced a potential novel agent for the treatment of human OSCC metastasis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.2
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• pp.141-150
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• 2008

We studied 1809 oral cancer patients who visited and were treated in 2002 at the 148 institutions certified as training facilities by the Japanese Society of Oral and Maxillofacial Surgeons, which is composed of 39 dental university hospitals, 44 medical university hospitals, 64 general hospitals, and 1 unknown institution. The patients consisted of 1071 (59.2%) males and 738 (40.8%) females (male:female ratio, 1.45:1), who had a mean age of 65.2 years old. The tongue (40.2%) was the most common site affected, followed by the gingiva (32.7%), buccal mucosa (10.1%), and oral floor (9.0%). There were 6 cases of intraoral multiple cancer. In histopathological examinations, squamous cell carcinoma (88.7%) was the most common type found, followed by adenoid cystic carcinoma (2.1%), and mucoepidermoid carcinoma (1.7%). In addition, non-epithelial tumors comprised 1.8%, among which malignant melanoma was the most common type. Cases classified as T2N0 were the most common (32.1%), followed by T1N0 (21.4%), T4N0 (8.0%), and T2N1 (7.6%). Distant metastasis occurred in 17 patients (1.0%). The sizes of the non-epithelial malignant tumors ranged from 1.0 to 7.0 cm, with a mean size of 3.7 cm.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.41
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• pp.56.1-56.6
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• 2019

Background: Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule that attenuates the immune response. PD-L1 contributes to failed antitumor immunity; thereby, blockade of PD-L1 with monoclonal antibody enhances the immune response. Recently, it was reported that PD-L1 was regulated by protein 53 (p53). Besides, cytokeratin 17 (CK17) is thought to be a diagnostic marker of oral squamous cell carcinoma (OSCC). Our aim was to evaluate the correlation between the immunohistochemical expression of PD-L1, p53 and CK17 with clinicopathological characteristics and disease-specific survival in patients with OSCC. Methods: A total of 48 patients with OSCC were included in this study. Immunohistochemical staining was performed to evaluate the correlation among the expressions of PD-L1, p53 and CK17, and furthermore the correlation among various clinicopathological factors, PD-L1, p53 and CK17. Results: The positive rate of p53, CK17, PD-L1 (tumor cells) and PD-L1 (tumor-infiltrating lymphocytes) was 63.2%, 91.7%, 48.9% and 57.1%. A statistically significant correlation between p53 expression and T stage and TNM stage (p = 0.049, p = 0.03, respectively) was observed. Also, a statistically significant correlation between p53 and PD-L1 (TCs) expression (p = 0.0009) was observed. Five-year disease-specific survival rate was not significantly correlated with gender, TNM stage, p53 expression, PD-L1 expression and CK17 expression. Conclusion: The expression of p53 and PD-L1 shows significantly positive correlation in oral squamous cell carcinoma in tumor cells. Also, a significant correlation between p53 expression and T stage and TNM stage was observed. No other significant correlation between PD-L1 staining or CK17 and clinical or pathologic characteristics was identified.