• Journal of Microbiology and Biotechnology
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• v.32 no.9
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• pp.1103-1109
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• 2022

Deoxypodophyllotoxin (DPT), a naturally occurring flavonolignan, possesses several pharmacological properties, including anticancer property. However, the mechanisms underlying DPT mode of action in oral squamous cell carcinoma (OSCC) remain unknown. This study aimed to investigate the anticancer effects of DPT on OSCC and the underlying mechanisms. Results of the MTT assay revealed that DPT significantly reduced the cell viability in a time- and dose-dependent manner. Flow cytometry analysis revealed that DPT induces apoptosis in OSCC cells in a dose-dependent manner. Moreover, DPT enhanced the production of mitochondrial reactive oxygen species (ROS) in OSCC cells. Mechanistically, DPT induced apoptosis in OSCC cells by suppressing the PI3K/AKT signaling pathway while activating the p38 MAPK signaling to regulate the expression of apoptotic proteins. Treatment with SC79, an AKT activator, reversed the effects of DPT on AKT signaling in OSCC cells. Taken together, these results provide the basis for the use of DPT in combination with conventional chemotherapy for the treatment of oral cancer.

• Genomics & Informatics
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• v.8 no.4
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• pp.212-218
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• 2010

An accurate system for predicting the survival of patients with oral squamous cell carcinoma (OSCC) will be useful for selecting appropriate therapies. A nomogram for predicting survival was constructed from 96 patients with primary OSCC who underwent surgical resection between January 1994 and June 2003 at the Yonsei Dental Hospital in Seoul, Korea. We performed univariate and multivariate Cox regression to identify survival prognostic factors. For the early stage patients group, the nomogram was able to predict the 5 and 10 year survival from OSCC with a concordance index of 0.72. The total point assigned by the nomogram was a significant factor for predicting survival. This nomogram was able to accurately predict the survival after treatment of an individual patient with OSCC and may have practical utility for deciding adjuvant treatment.

• 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.

• 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.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.36 no.3
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• pp.85-93
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• 2014

Purpose: Nodal metastasis is the main prognostic factor in the patients with oral squamous cell carcinoma (OSCC). We investigated the association between tumor-associated lymphatics and OSCC characteristics. Methods: Thirty-four specimens were used for the immunohistochemical staining with the antibody for vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, phosphorylated VEGFR-3, D2-40, and matrix metallproteinases (MMPs). We observed the distribution of the lymphangiogenic factors and quantified the degree of expression. We determined lymphatic vessel density (LVD) and lymphatic vessel dilatation with D2-40 immunostaining. We assessed the association of LVD or lymphatic vessel dilatation with tumor progression or tumor differentiation. Results: OSCC cells expressed lymphangiogenic ligands. Lymphangiogenic receptor, VEGFR-3, was expressed and activated in some tumor cells as well as in tumor-associated endothelial cells. LVD was not associated with tumor size or nodal status, but lymphatic vessel dilatation was higher in tumors with nodal metastasis, and also higher in poorly differentiated tumors. In stromal area of OSCC, MMP-1 and MMP-10 were up-regulated and the basement membrane of tumor-associated endothelial cells was destroyed by these collagenases. Conclusion: In the primary tumors with nodal metastasis, especially in poorly differentiated OSCC, tumor cells invaded the dilated lymphatic vessels via ruptured sites. MMP-1 and MMP-10 are important in the lysis of the glycocalyx inside the tumor-associated lymphatic endothelial cells.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5811-5815
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• 2012

Background: Non-invasive oral verrucous carcinoma (OVC) and invasive well-differentiated oral squamous cell carcinoma (OSCC) have similar histopathologic findings but different biological behavior. These two malignancies must be correctly differentiated by pathologists. The aim of this study was to determine immunohistochemical (IHC) expression of Ki67 in OVC and well-differentiated OSCC. Methods: Expression of Ki67 was evaluated by IHC in 15 cases of epithelial hyperplasia with no dysplasia (A group), 15 cases of OVC (B group), 12 cases of microinvasive OSCC(C group) and 15 cases of well-differentiated OSCC (D group). Results: There was a significant difference in Ki67 expression based on pattern distribution of immunostaining positive cells, with quantitative and semi-quantitative analyses, among the four groups ; also, between A group and each of the other three groups (P=0.0001). But there was no significant difference between B and C, C and D, and B and D groups (P>0.05). Conclusions: The three evaluation methods of Ki67 expression showed Ki67 (Mib-1) is not a good immunohistochemical marker to assess invasion status and differentiate OVC from well-differentiated OSCC; also, it cannot be used as a diagnostic tool to distinguish between variants of OSCC with similar grade.

• BMB Reports
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• v.37 no.6
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• pp.671-675
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• 2004

The expression and clinicopathological significance of Quox-1 gene was studied in oral squamous cell carcinoma (OSCC). Immunocytochemistry and western blot analysis were used to examine the different expressions of Quox-1 protein in 114 OSCC specimens, 34 oral epithelial dysplasia specimens, and 16 normal oral mucosa specimens. RT-PCR and virtual Northern Blot were also used to examine the expression of Quox-1 mRNA. It was found that Quox-1 was not expressed in normal epithelium. However, as dysplastic lesions progressed Quox-1 expression increased (p < 0.01), and Quox-1 expression was not significantly different between severe dysplasia and highly differentiated OSCCs (p > 0.05). As the degree of differentiation decreased, Quox-1 positivity increased in OSCC (p < 0.01), and the rate of Quox-1 (81.58%) positivity in OSCC was higher than that in normal oral mucosa (p < 0.01). Our findings imply that the positive expression of Quox-1 is correlated with the histological classification of OSCCs. Thus, the expression of Quox-1 in OSCC may serve as a significant predicting factor of proliferative status and malignant degree, and it may also be a biological detection marker of oral mucosas initial cancer and of OSCC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6755-6760
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• 2014

Background: Oral cancer is a common form of cancer in India, particularly among men. About 95% are squamous cell carcinomas. Tobacco along with alcohol are regarded as the major risk factors. Objectives: (i) To determine associations of oral squamous cell carcinoma (OSCC) with respect to gender, age group, socioeconomic status and risk habits; (ii) To observe the distribution of affected oral anatomical sites and clinico-pathological profile in OSCC patients. Materials and Methods: This is an unmatched case-control study during period January 2012 to December 2013. Total of 471 confirmed OSCC patients and 556 control subjects were enrolled. Data on socio-demography, risk habits with duration and medical history were recorded. Results: There were significant associations between OSCC with middle age (41-50years; unadjusted OR=1.63, 95%CI=1.05-2.52, p=0.02) (51-60 years; unadjusted OR=1.79, 95%CI=1.15-2.79, p=0.009) and male subjects (unadjusted OR=2.49, 95%CI=1.89-3.27, p=0.0001). Cases with both habits of tobacco chewing and smoking were at a higher risk for OSCC than tobacco chewing alone (unadjusted OR=0.52, 95%CI=0.38-0.72, p=0.0001), duration of risk habits also emerged as a responsible factor for the development of carcinoma. The majority of patients were presented in well-differentiated carcinomas (39.9%). Prevalence of advance stages (TNM stage III, IV) was 23.4% and 18.3% respectively. The buccal mucosa was the most common (35.5%) affected oral site. Conclusions: In most Asian countries, especially India, there is an important need to initiate the national level public awareness programs to control and prevent oral cancer by screening for early diagnosis and support a tobacco free environment.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.1
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• pp.1-10
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• 2008

Oral squamous cell carcinoma (OSCC) is the most frequent form of oral cancer and holds the eighth position in the cancer incidence ranking. OSCC patients are treated by classical therapeutic modalities consisting of surgery, radiotherapy, and/or chemotherapy. But OSCC still shows significant mortality rates. Thus, new therapeutic approaches have been investigated and the most promising one is naturally acquired agents with known anti-cancer effects. Genistein is a compound extracted from soy bean. Its anti-cancer effect on breast cancer is well established now and it is investigated whether it has similar effect on OSCC. It inhibited the growth and invasive-ness of OSCC cells in vitro, but these effects did not work in living animals in vivo. Catechin is a compound from green tea and its anti-cancer effect on OSCC is known better than other agents. Catechin showed its anti-cancer effect in vitro via induction of apoptosis, cell cycle arrest, inhibition of growth, and down-regulation of invasion/metastasis. These effects were confirmed in vivo with mouse model. Cordycepin is one of major pharmacologically important components in Cordyceps Militaris and may exert its anti-cancer effect as an adenosine receptor agonist. In recent study, it inhibited the proliferation of OSCC cells via A3 adenosine receptor. But because there is very scarce evidence on this effect, more researches are needed on this theme.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.91-96
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• 2015

A lipopeptide extract of Bacillus amyloliquefaciens BACY1 (BLE) was found to induce cell death in human oral squamous cell carcinoma (OSCC) cell lines, SCC4 and SCC25, in this study. The results of MTT assay showed that BLE inhibited OSCC cell proliferation in a dose-dependent manner. BLE was also effective in increasing the sub-G1 phases. Furthermore, when membrane damage in SCC4 cells treated with BLE was monitored by LDH assay, release of LDH was significantly increased. The protein and mRNA levels of pro-apoptotic Bax, and caspase-3 were up-regulated by BLE. Taken together, these results suggest that BLE induces apoptosis and then inhibits the cell proliferation of human OSCC cells.