• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7497-7500
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• 2015

Background: Tumor markers, designated as a broad group of substances produced by malignancies, could be in the form of biochemical substances, immunological substances, cell surface changes and genetic alterations. Cancer, a disorder of cellular behavior is characterized by alteration of serum glycoproteins. L-fucose, a hexose, which is the terminal sugar in most of the plasma glycoproteins, may be useful as a tumor marker for the detection, monitoring and prognostic assessment of malignancies. The aim of the study was to ascertain the role of serum fucose as a biomarker for early detection of oral cancer and to compare serum fucose levels in healthy controls, leukoplakia and oral cancer patients. Materials and Methods: The study included 60 (100.0%) subjects, who were grouped as 20 (33.3%) control subjects, 20 (33.3%) squamous cell carcinoma patients and 20 (33.3%) leukoplakia patients. Fucose estimation was done using UV-visible spectrophotometry based on the method as adopted by Winzler using cysteine reagent. The results were analyzed statistically using ANOVA with Bonferroni post hoc tests. Results: Results showed a high significance in serum fucose in oral squamous cell carcinoma (OSCC) and leukoplakia subjects compared to normal controls. There was a gradual increase in the values noted from control to leukoplakia and to squamous cell carcinoma. Conclusions: Estimation of serum fucose may be a reliable marker and can be used as an effective diagnostic biomarker in oral squamous cell carcinoma patients.

• International Journal of Oral Biology
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• v.34 no.2
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• pp.73-79
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• 2009

Cytosolic $Ca^{2+}$ is an important regulator of tumor cell proliferation and metastasis. Recently, the strategy of blocking receptors and channels specific to certain cancer cell types has emerged as a potentially viable future treatment. Oral squamous cell carcinoma is an aggressive form of cancer with a high metastasis rate but the receptor-mechanisms involved in $Ca^{2+}$ signaling in these tumors have not yet been elucidated. In our present study, we report that bradykinin induces $Ca^{2+}$ signaling and its modulation in the human oral squamous carcinoma cell line, HSC-3. Bradykinin was found to increase the cytosolic $Ca^{2+}$ levels in a concentration-dependent manner. This increase was inhibited by pretreatment with the phospholipase C-${\beta}$ inhibitor, U73122, and also by 2-aminoethoxydiphenyl borate, an inhibitor of the inositol 1,4,5-trisphosphate receptor. Pretreatment with extracellular ATP also inhibited the peak bradykinin-induced $Ca^{2+}$ rise. In contrast, the ATP-induced rise in cytosolic $Ca^{2+}$ was not affected by pretreatment with bradykinin. Pretreatment of the cells with either forskolin or phorbol 12-myristate 13-acetate (activators of adenylyl cyclase and protein kinase C, respectively) prior to bradykinin application accelerated the recovery of cytosolic $Ca^{2+}$ to baseline levels. These data suggest that bradykinin receptors are functional in $Ca^{2+}$ signaling in HSC-3 cells and may therefore represent a future target in treatment strategies for human oral squamous cell carcinoma.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.43 no.6
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• pp.415-422
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• 2017

Calcifying cystic odontogenic tumor (CCOT) is defined as an odontogenic cyst-like benign neoplasm that characteristically contains several ghost cells, ameloblastoma-like epithelium, and occasional calcification. Ghost cell odontogenic carcinoma (GCOC), a malignant form of CCOT, is an exceptionally rare malignant tumor. In this report, we present a case of a 53-year-old man whose chief complaint was a solitary mass on the right mandible area. The mass was completely removed through an extraoral surgical approach and reconstructive surgery was performed in two phases.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.6
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• pp.474-481
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• 2004

Squamous cell carcinoma is the most prevalent oral cancer, which is characterized by its low survival rate, high malignancy, mortality with facial defects, and poor prognosis. Exact cause and pathogenesis of the squamous cell carcinoma is still unknown. Various routes including smoking, radiation, and viral infections predispose its genesis, and recent studies revealed that genetic defects which fail to prevent cancer proliferation play a role. Generally, a cancer develops from the decreased rate of apoptosis which is an active and voluntary cell death, and from the altered cell cycles. Anticancer effect can be obtained by recovering the apoptotic process, and by suppressing the cell cycles. Among the apoptosis related factors, bcl-2, caspase-9, and VDAC (voltage-dependent anion channel)are produced in mitochondria of the cell. Cyclosporin-A is known to induce apoptosis through its activation with VDAC. This study was to reveal the anticancer effect of Cyclosporin A to the oral squamous cell carcinoma. The inverted microscope was used to find alterations in the tissue, and sensitivity test to the anticancer cells was performed with MTT (Tetrazolium-based colorimetric) assay. Following cell line culture of primary and metastastic oral squamous cell carcinoma, electrophoresis was performed with extracted total RNA. Finally, semi-quantitative study was carried out through RT-PCR (Reverse Transcription-Polymerase Chain Reaction). The results of this study are as follows: 1. The inverted microscopic observation revealed a poorly defined cytoplasm at $2000ng{\sim}3000ng/ml$, indistinct nucleus, and apoptosis. 2. The Growth of cancer cells was decreased at 1000ng/ml of cyclosporin-A. No cancer cell growth was observed at over 2000ng/ml concentration of cyclosporin-A, and at one week, growth of cancer cells was ceased. 3. The MTT assays were decreased as cyclosporin-A concentration was increased. This means that the activation of succinyl dehydrogenase in mitochondria was decreased following administration of cyclosporin A. 4. A result of RT-PCR showed that amount of mRNA of VDAC-2 was decreased half times at a cyclosporine-A concentration of 2000ng/ml. In bcl-2, amount of mRNA was significantly decreased 1/5 times at 2000ng/ml. caspase-9, however, showed slight increase compared to the control group. From the results obtained in this study, administration of cyclosporin-A to the cell lines of oral squamous cell carcinoma induced alterations in morphology and growth of the cells as its concentration increased. Since apoptosis related factors such as VDAS-2, bcl-2, and caspase-9 also showed distinct alterations on their mRNAs, further research on cyclosporin A as an anti-cancer agent will be feasible.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.4
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• pp.271-281
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• 2004

Adenoid cystic carcinoma is malignant tumor in salivary gland, and its behavior is very invasive. Of all malignant tumor adenoid cystic carcinoma is occured in frequency of 4.4% in major salivary gland, and 1.29% in minor salivary gland. Histopathologically, adenoid cystic carcinoma is characterized by a cribriform appearance, and tubular form and solid nest type tumor can be seen. The tumor cell structure composed of modified myoepithelial cell, and basaloid cell. Extracellular matrix of this tumor cell contains variable ground substance with basement membrane component. Basement membrane matrix composed of collagen fibers, glycoproteins, proteoglycans, and its function is well known that it participate in differentiation, proliferation, and growth of tumor cell. Basement membrane molecule is essential for invasion of peripheral nerve, blood vessel, skeletal muscle in tumor cell of adenoid cystic carcinoma. In many studies, the tumor cell of adenoid cystic carcinoma containing modified myoepithelial cell participate in synthesis of proteoglycan. In this study, tissue sample of adenoid cystic carcinoma of human salivary gland were obtained from 15 surgical specimen, and all specimen were routinely fixed in 10% formalin and embedded. Serial $4-{\mu}m$ thick sections were cut from paraffin blocks. the histopathologic evaluation was done with light microscopy. And, the immunohistochemical staining, characteristics of glycosaminoglycan were observed. For biochemical analysis of glycosaminoglycan, isolation of crude glycosaminoglycan from tumor tissue and Western bolt analysis were carried out. With transmission electomicroscopy, tumor cell were observed. Biologic behavior of adenoid cystic carcinoma was observed with distribution and expression of basement membrane of glycosaminoglycan in tumor cells, The results obtained were as follows: 1. In immunohistochemical study, chondroitin sulfate is postively stained in tumor cell and interstitial space, dermatan sulfate is weakly stained in ductal cell. But keratan sulfate is negatively stained. 2. In immunohistochemical study, heparan sulfate is strong positive stained in tumor cell and basement membrane, especially in invasion area to peripheral nerve tissue. 3. In transmission electromicroscpic view, the tumor cells are composed modifed myoepithelial cells, and contains many microvilli and rough endoplasmic reticulum. 4. In Western blot analysis, the expression of glycosaminoglycan is expressed mostly in heparan sulfate. From the results obtained in this study, tumor cell of adenoid cystic carcinoma is composed modified myoepithelial cell, and glycosaminoglycan of basement membrane molecule of heparan sulfate and chondroitin sulfate mostly participate in the development and invasiveness of adenoid cystic carcinoma by immunohistochemical study and western blot analysis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.6
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• pp.483-490
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• 2001

There were many controversies in the cause and progress of tumorigenesis. Recently, studies on the mutation of genes related to the tumor have extensively been performed due to development of molecular biology. Structural and morphological changes of chromosomes, which are related to the abnormal activation of oncogenes or inactivation of tumor suppression genes, transform the normal cells into the tumor cells. p53 and Rb are well known tumor suppressor genes, while oncogenes include c-myc, bcl-2 and ras, etc. When exposed to cell damaging agents, p53 inhibits cell growth by inducing transcription of p21. Especially p73, which is homo-logy of p53, frequently deleted in melanoma, neuroblastoma, colon cancer, and breast cancer, when over produced, p73 activates the transcription of p21, bax-1 and inhibits cell growth by inducing apoptosis. For study on mRNA expression of p21 and p73, normal oral keratinocytes, and cell lines of primary and metastatic oral squamous cell carcinoma were cultured and then electrophoresis and RT-PCR(reverse transcription-polymerase chain reaction) were performed. 1. The mRNA of p21 and p73 in normal oral keratinocyte expressed lower than that of primary squamous cell carcinoma. 2. The mRNA of p21 in metastatic oral squamous carcinoma cell lines was expressed as various patterns compared with that of normal oral keratinocyte. 3. In the metastatic oral squamous cell lines, the mRNA of HN8 expressed higher than that of HN12 or HN19. 4. The mRNA of p73 in primary oral squamous cell lines expressed 4-5 times higher than that of normal keratinocyte. 5. In metastatic oral squamous cell lines, there was no significant expression of p73 mRNA compared with that of normal oral keratinocyte. From the results obtained in this study, mRNA expression of p73 in primary oral squamous cell lines was remarkable, while mRNA expression of p21 and p73 in metastatic oral squamous cell lines were statistically insignificant.

• International Journal of Oral Biology
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• v.35 no.2
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• pp.51-60
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• 2010

Few studies have evaluated the apoptosis-inducing efficacy of NaF on cancer cells in vitro but there has been no previous investigation of the apoptotic effects of NaF on human oral squamous cell carcinoma cells. In this study, we have investigated the mechanisms underlying the apoptotic response to NaF treatment in the YD9 human squamous cell carcinoma cell line. The viability of YD9 cells and their growth inhibition were assessed by MTT and clonogenic assays, respectively. Hoechst staining, DNA electrophoresis and TUNEL staining were conducted to detect apoptosis. YD9 cells were treated with NaF, and western blotting, immunocytochemistry, confocal microscopy, FACScan flow cytometry, and MMP and proteasome activity assays were performed sequentially. The NaF treatment resulted in a time- and dose-dependent decrease in YD9 cell viability, a dose-dependent inhibition of cell growth, and the induction of apoptotic cell death. The apoptotic response of these cells was manifested by nuclear condensation, DNA fragmentation, the reduction of MMP and proteasome activity, a decreased DNA content, the release of cytochrome c into the cytosol, the translocation of AIF and DFF40 (CAD) into the nucleus, a significant shift of the Bax/Bcl-2 ratio, and the activation of caspase-9, caspase-3, PARP, Lamin A/C and DFF45 (ICAD). Furthermore, NaF treatment resulted in the downregulation of G1 cell cyclerelated proteins, and upregulation of p53 and the Cdk inhibitor $p27^{KIP1}$. Taken collectively, our present findings demonstrate that NaF strongly inhibits YD9 cell proliferation by modulating the expression of G1 cell cycle-related proteins and inducing apoptosis via mitochondrial and caspase pathways.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1147-1150
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• 2013

Background: Cancer diagnostic biomarkers have a wide range of applications that include early detection of oral precancerous lesions and oral squamous cell carcinomas, and assessing the metastatic status of lesions. The interferon stimulated ISG15 gene encodes an ubiquitin-like protein, which conjugates to stabilize activation status of associated proteins. Hence a deregulated expression of ISG15 may promote carcinogenesis. Indeed overexpression of ISG15 has been observed in several cancers and hence it has been proposed as a strong candidate cancer diagnostic biomarker. Given the emerging relationship between malignant transformation and ISG15, we sought to examine the expression pattern of this gene in tumor biopsies of oral squamous cell carcinoma (OSCC) tissues collected from Indian patients. Materials and Methods: Total RNA isolated from thirty oral squamous cell carcinoma tissue biopsy samples were subjected to semi-quantitative RT-PCR with ISG15 specific primers to elucidate the expression level. Results: Of the thirty oral squamous cell carcinomas that were analyzed, ISG15 expression was found in twenty four samples (80%). Twelve samples expressed low level of ISG15, six of them expressed moderately, while the rest of them expressed very high level of ISG15. Conclusions: To the best of our knowledge, the results show for the first time an overexpression of ISG15 in up to 80% of oral squamous cell carcinoma tissues collected from Indian patients. Hence ISG15 may be explored for the possibility of use as a high confidence diagnostic biomarker in oral cancers.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.4
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• pp.213-220
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• 2009

Purpose: The present study was aimed to examine the usefulness of 18F-FDG PET/CT in the evaluation of cervical lymph node metastasis in patients with oral cancer. Materials and methods: Twenty-two patients who underwent neck dissection to treat oral cancer were subjected for examination. The cervical node metastasis was evaluated by means of clinical examination, CT scan, PET, and histologic examination. By comparing the results of each examination modality with those of histologic examination, it's sensitivity, specificity, positive predictive value, and negative predictive value were determined. Results: The oral cancer was more frequent in males with a ratio of 2.14:1. The sixth decade showed the highest incidence in age distribution with mean of $56{\pm}16$. Histologic findings showed that squamous cell carcinoma was the most common (15 patients), and mucoepidermoid carcinoma (3), malignant melanoma (2), and adenoid cystic carcinoma and ghost cell odontogenic carcinoma (1 each), in order. In most cases, wide surgical excision of the primary cancer and neck dissection was performed, followed by reconstruction with free flaps when necessary. When comparing the results of each examination modality with those of the histologic examination, clinical examination showed sensitivity, specificity, positive predictive value, and negative predictive value at 11%, 85%, 33%, and 58%, respectively. CT scans showed at 67%, 77%, 67%, and 77%, while $^{18}F$-FDG PET/CT at 78%, 77%, 70%, and 83%, respectively. Conclusions: These results suggest that PET is more useful, compared with clinical examination and CT scans, in the evaluation of cervical lymph node metastasis in patients with oral cancer.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.19 no.1
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• pp.79-86
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• 1997

Adenoid cystic carcinoma is characterized by sloe growth, multiple recurrence, a long clinical course and late metastasis. It is less than 1% of all head and neck malignancy, but most prevalent malignancy in salivary gland origin. During 14 years(from 1982 to 1995), 24 patients were diagnosed as adenoid cystic carcinoma in oral and maxillfacial area, in department of Oral and Maxillofacial Surgery, Korea Cancer Center Hospital. We studied clinically about their age and sex distribution, primary site distribution, TNM staging, treatment modalities, overall survival rates, survival rates according to stages. The age range were from 15 years to 79 years, average age weas 51 years. 15 were men and 9 Were women. Maxilla and palate were the most prevalent primary site. The most cases were in stage III(37%) and stage IV(46%). The 3 year and 5 year overall survival rate were 65.0% and 58.5%. The 5 year survival rate of the stage III cases was 66.7%, and that of the stage IV cases was 38.4%.