• 대한두경부종양학회지
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• 제33권2호
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• pp.9-15
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• 2017

The recently released the $8^{th}$ edition of the American Joint Committee on Cancer (AJCC) Staging Manual introduces significant modifications from the prior $7^{th}$ edition. In this paper, the contents of the new changes in the decision of cancer of the head and neck is summarized except changes in staging of skin and thyroid cancer. In addition to the 8th edition, 1) Addition of extracapsular involvement in metastatic lymph nodes (N category) 2) Oral cancer T classification change, 3) Staging of the pharyngeal cancer was divided into 3 chapters: high-risk human papilloma virus (HR-HPV) associated oropharyngeal cancer (OPC), non HR-HPV associated OPC and hypopharynx cancer (HPC), and nasopharynx cancer (NPC) 4) Changes in T and N classification in NPC, 5) In the case of cancer of unknown primary, P16-positive case is defined as HR-HPV related OPC, and EBV-positive case is defined as NPC. The process that led to these changes highlights the need to collect high-fidelity cancer registry-level data that can be used to confirm prognostic observations identified in institutional data sets. Clinicians will continue to use the latest information for patient care, including scientific content of the 8th Edition Manual. All newly diagnosed cases through December $31^{st}$ 2017 should be staged with the 7th edition. The time extension will allow all partners to develop and update protocols and guidelines and for software vendors to develop, test, and deploy their products in time for the data collection and implementation of the 8th edition in 2018. The 8th edition strikes a balance between a personalized, complex system and a more general, simpler one that maintains the user-friendliness and worldwide acceptability of the traditional TNM staging paradigm.

• International Journal of Oral Biology
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• 제45권4호
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• pp.152-161
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• 2020

D-pinitol is an analog of 3-methoxy-D-chiro-inositol found in beans and plants. D-pinitol has anti-inflammatory, antidiabetic, and anticancer effects. Additionally, D-pinitol induces apoptosis and inhibits metastasis in breast and prostate cancers. However, to date, no study has investigated the anticancer effects of D-pinitol in oral cancer. Therefore, in this study, whether the anticancer effects of D-pinitol induce apoptosis, inhibit the epithelial-to-mesenchymal transition (EMT), and arrest cell cycle was investigated in squamous epithelial cells. D-pinitol decreased the survival and cell proliferation rates of CAL-27 and Ca9-22 oral squamous carcinoma cells in a concentration- and time-dependent manner. Evidence of apoptosis, including nuclear condensation, poly (ADP-ribose) polymerase, and caspase-3 fragmentation, was also observed. D-pinitol inhibited the migration and invasion of both cell lines. In terms of EMT-related proteins, E-cadherin was increased, whereas N-cadherin, Snail, and Slug were decreased. D-pinitol also decreased the expression of cyclin D1, a protein involved in the cell cycle, but increased the expression of p21, a cyclin-dependent kinase inhibitor. Hence, D-pinitol induces apoptosis and cell cycle arrest in CAL-27 and Ca9-22 cells, demonstrating an anticancer effect by decreasing the EMT.

• 대한의생명과학회지
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• 제17권1호
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• pp.85-88
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• 2011

Tumor angiogenesis, which is essential for tumor growth and tumor metastasis, depends on angiogenic factors produced by tumor cells and/or infiltrating cells such as endothelial cells and immune cells in tumor tissue. Previously, we reported that licochalcone A (LicA), an important bioactive compound of Glycyrrhiza inflate, suppresses angiogenesis, tumor growth and metastasis. In this study, we evaluated the effect of LicA on angiogenin production in colon cancer cells because angiogenin is an essential factor to regulate angiogenesis and tumor progression. When we examined the angiogenin levels in three human colon cancer cells, HT-29, SW480 and Caco-2, LicA treatment significantly reduced the amounts of angiogenin among three cancer cell lines. In an in vivo study in which mice were implanted with HT-29 cells, oral administration of LicA reduced angiogenin in tumor tissues when compared with vehicle-administered mice. These results suggest that reduced angiogenin in response to LicA treatment may play essential role to inhibit tumor growth, angiogenesis as well as metastasis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4621-4625
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• 2013

The purpose of this study was to construct a protein-protein interaction (PPI) network related to oral squamous cell carcinoma (OSCC). Each protein was ranked and those most associated with OSCC were mined within the network. First, OSCC-related genes were retrieved from the Online Mendelian Inheritance in Man (OMIM) database. Then they were mapped to their protein identifiers and a seed set of proteins was built. The seed proteins were expanded using the nearest neighbor expansion method to construct a PPI network through the Online Predicated Human Interaction Database (OPHID). The network was verified to be statistically significant, the score of each protein was evaluated by algorithm, then the OSCC-related proteins were ranked. 38 OSCC related seed proteins were expanded to 750 protein pairs. A protein-protein interaction nerwork was then constructed and the 30 top-ranked proteins listed. The four highest-scoring seed proteins were SMAD4, CTNNB1, HRAS, NOTCH1, and four non-seed proteins P53, EP300, SMAD3, SRC were mined using the nearest neighbor expansion method. The methods shown here may facilitate the discovery of important OSCC proteins and guide medical researchers in further pertinent studies.

• Journal of Oral Medicine and Pain
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• 제24권2호
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• pp.145-161
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• 1999

The proto-oncogene bcl-2 confers a survival advantage to cells by blocking programmed cell death (apoptosis). Overexpression of bcl-2 probably plays a role in tumorigenesis, and the expression of the bcl-2 protein has been investigated in many kinds of tumors. An increased expression of nitric oxide synthetase(NOS) has been observed in human colon cancer cell lines as well as in human gynecological, breast, and CNS tumors. However there have been only a few reports on the expression of bcl-2 and $NOS_2$ in oral white lesions and cancer. The aim of this study was to investigate the relationship between the expression of Bcl-2 and $NOS_2$ and several pathological parameters such as histological types and layers. We reported desregulation of bcl-2 and $NOS_2$ expression during progression from oral white lesion, lichen planus and leukoplakia to squamous cell carcinoma. The obtained results were as follows: 1. Immunohistochemical analysis with monoclonal antibodies to bcl-2 oncoprotein and $NOS_2$ in formalin-fixed paraffin-embedded tissue sections revealed that bcl-2 expression is restricted to the basal cell layer and $NOS_2$ was mild expressed only in subepithelial inflammatory cells in normal human mucosa. There wasn't specific finding of those in lichen planus and leukoplakia. 2. Bcl-2 immunoreactivity in severe epithelial dysplasia or CIS occurs throughout the epithelium, $NOS_2$ reactivity in most superficial layer were noted. 3. In well-differentiated squamous cell carcinomas, mostly bcl-2 was overexpressed. In moderated and poor squamous cell carcinomas, the expression of $NOS_2$ was increased and that of bcl-2 was decreased. 4. The immunoreactivity of bcl-2 was 12.5% of normal mucosa, 30% of leukoplakia, 44% of lichen planus and 67% of carcinoma in situ. In carcinoma, those were 43%, 50% and 67% according to differentiation, respectively. 5. The immunoreactivity of $NOS_2$ was 25% of normal mucosa, 70% of leukoplakia, 78% of lichen planus and 100% of carcinoma in situ and epithelial dysplasia. In carcinoma, those were higher in moderated(100%) and poor(83%) squamous cell carcinomas than in well differentiated type(71%). 6. The expression of bcl-2 and $NOS_2$ by Western blot was increased highly in lichen planus and leukoplakia. Therefore, the expression of bcl-2 was increased in the white and precancerous lesions and that was decreased by differentiation of carcinoma. However, $NOS_2$ immunoreactivity in carcinoma in situ was lower than those in moderated and poor squamous cell. These findings suggest that the interaction of bcl-2 and $NOS_2$ may be roled importantly in growth and development of carcinoma.

• Journal of Periodontal and Implant Science
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• 제53권5호
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• pp.336-346
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• 2023

Purpose: The Korea Oral Biobank Network (KOBN) was established in 2021 as a branch of the Korea Biobank Network under the Korea Centers for Disease Control and Prevention to provide infrastructure for the collection, management, storage, and utilization of human bioresources from the oral cavity and associated clinical data for basic research and clinical studies. Methods: To address the need for the unification of the biobanking process, the KOBN organized the concept review for all the processes. Results: The KOBN established standard operating procedures for the collection, processing, and storage of oral samples. Conclusions: The importance of collecting high-quality bioresources to generate accurate and reproducible research results has always been emphasized. A standardized procedure is a basic prerequisite for implementing comprehensive quality management of biological resources and accurate data production.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제26권2호
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• pp.132-136
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• 2000

The cell surface glycoprotein CD44 is a kind of adhesion molecule, which binds hyaluronic acid, type I collagen and fibronectin. Although there have been numerous reports on the expression and the function of CD44 in lymphocytes and macrophages, very little is known about its distribution and definite role in epithelial tissue, especially in oral epithelial one. The present study was performed to investigate the distribution and expression of the CD44 in human gingiva and squamous cell carcinoma(SCC) arising in human gingiva. And the authors compared CD44 expression with histopathologic grade of SCC. The results were as follows: 1. The CD44 was strongly expressed in granular, spinous and basal layers of normal marginal and attached gingiva, in spinous and basal layers of normal sulcular gingiva, and in all epithelial layers of normal junctional gingiva. 2. In SCC of gingiva, the CD44 was expressed in all but one case. In most of the cases the CD44 was expressed at cell membrane and the degree of expression was relatively strong. 3. In low-grade SCC of gingiva, the CD44 was strongly expressed, especially at the basal and spinous layers of abundantly keratinized cancer nests. In high-grade SCC of gingiva, the CD44 expression tended to be weak but was strong at cells showing individual keratinization. This study suggest that the CD44 expression of normal and cancerous gingival epithelium is associated with the degree of proliferation and differentiation of epithelial cells.

• International Journal of Oral Biology
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• 제36권3호
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• pp.129-134
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• 2011

Eugenol is an essential oil found in cloves and cinnamon that is used widely in perfumes. However, the significant anesthetic and sedative effects of this compound have led to its use also in dental procedures. Recently, it was reported that eugenol induces apoptosis in several cancer cell types but the mechanism underlying this effect has remained unknown. In our current study, we examined whether the cytotoxic effects of eugenol upon human melanoma G361 cells are associated with cell cycle arrest and apoptosis using a range of methods including an XTT assay, Hoechst staining, immunocyto-chemistry, western blotting and flow cytometry. Eugenol treatment was found to decrease the viability of the G361 cells in both a time- and dose-dependent manner. The induction of apoptosis in eugenol-treated G361 cells was confirmed by the appearance of nuclear condensation, the release of both cytochrome c and AIF into the cytosol, the cleavage of PARP and DFF45, and the downregulation of procaspase-3 and -9. With regard to cell cycle arrest, a time-dependent decrease in cyclin A, cyclin D3, cyclin E, cdk2, cdk4, and cdc2 expression was observed in the cells after eugenol treatment. Flow cytometry using a FACScan further demonstrated that eugenol induces a cell cycle arrest at S phase. Our results thus suggest that the inhibition of G361 cell proliferation by eugenol is the result of an apoptotic response and an S phase arrest that is linked to the decreased expression of key cell cycle-related molecules.

• 생명과학회지
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• 제26권11호
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• pp.1289-1297
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• 2016

구강편평세포암종은 구강 내에서 발생하는 가장 흔한 암의 형태로서, 구강암의 90%이상을 차지한다. 구강암은 국소적인 침윤의 양상을 나타내며 또한 조기진단과 치료가 용이하여 암예방을 위한 유용한 모델로 인정되고 있다. 본 연구에서는 생강 유기용매 분획물의 항산화 활성, 트롬빈억제 및 PMA 또는 thrombin에 의해 유도된 MMP- 2 및 MMP-9활성 억제 효과를 조사하였다. 시료들은 생강 열수 추출물을 헥산(hexane), 클로로포름(chloroform), 에틸 아세테이트(Ethyl acetate), 부탄올(butanol) 및 물($H_2O$)과 같은 용매로 분획화하여 사용하였고, $H_2O$ 분획물의 수득율이 9.79%로 가장 높았다. 항산화 활성은 DPPH assay, 세포 생존율 측정은 MTS assay, 항염증 활성은 마우스 대식세포 Raw 264.7세포에서 NO 생성 그리고 MMP-2 및 MMP-9의 mRNA 발현 및 단백질 활성 억제는 인간구강편평세포암종 YD-10B 세포에서 RT-PCR과 zymography방법을 통해 측정하였다. 본 연구의 결과에 의하면 MMP-2/-9 활성은 PMA에 의해 YD-10B세포에서 증가하였고, thrombin 처리에 의해서는 MMP-9 활성이 유의한 증가를 보였다. YD-10B 세포에서, PMA 또는 thrombin처리 모두에서 hexane 분획물이 MMP-2/-9의 mRNA 발현 및 단백질 활성을 유의하게 억제하였다. 그리고 항산화 활성은 hexane과 $H_2O$ 분획물에서 92.38%와 92.96%로 높게 나타났다. 또한 $H_2O$ 분획물에서 65.86%로 가장 유의하게 트롬빈 억제 활성을 보였다. 그러므로 본 연구에서는 생강 hexane분획물이 구강암의 우수한 암 침윤 및 전이 억제제로서의 개발 가능성을 제시하고 있다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.5773-5777
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• 2015

Background: Oral squamous cell carcinoma (OSCC) is thought to develop from precancerous dysplastic lesions through multistep processes of carcinogenesis involving activation of oncogenes and loss of tumor suppressor genes. The human epidermal growth factor receptor 2 (Her-2/neu [erbB-2]), a cell membrane glycoprotein, is a growth factor receptor that has receptor tyrosine kinase activity. Her2/neu activation plays a central role in cell proliferation and survival. It has been shown that overexpression of Her2/neu increases the rate of cell division and growth, leading to precancerous changes. The aim of the present study was to compare the serum and salivary Her2/neu levels between cases with premalignant and malignant oral lesions. Materials and Methods: Fasting blood samples and unstimulated saliva by passive drooling were collected from three groups of healthy control (n=20), premalignant disorder (PMD) (n=20) and OSCC (n=25) subjects. The HER2 extracellular domain (HER2 ECD) levels were measured using ELISA. Results: The levels of serum Her2/neu showed no significant differences between any of the groups but on the other hand salivary Her2/neu levels were found to be significantly (p<0.05) higher when compared between control (median 68.7 pg/ml, range: 21.5 - 75.8) and OSCC (median 145.6 pg/ml, range: 45.1-191.1). A similar trend was observed when comparing between PMD (median 43.3, range: 22.1 -94.7) and OSCC with a statistical significance of p<0.05. Conclusions: Our study provided evidence of increased salivary Her2/neu in OSCC when compared to PMD and control which was not the case for serum levels. This suggests that probably Her2/neu is not highly amplified as in breast cancer so as to be reflected in serum. Since saliva is in local vicinity of the OSCC, even a mild increase might be mirrored. On the whole, this study proposes Her2/neu as marker for distinguishing premalignant and malignant conditions.