• International Journal of Oral Biology
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• v.32 no.4
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• pp.127-133
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• 2007

Oral squamous cell carcinoma (OSCC) is the most common malignancy and is a major cause of worldwide cancer mortality. The proto-oncogene c-myb plays an important role in regulation of cell growth and differentiation, and it is expressed at high levels in hematopoietic cells and many other types of cancers. However, the function of c-myb is not well known in OSCC. The present study aimed to reveal the function of c-myb and to test the alternation of cell growth and signaling by c-myb in OSCC. In this study, c-myb and dominant-negatibe myb(DNmyb) were expressed in an adenovirus-mediated gene delivery system to KB cells. The over-expressed c-myb brought increased cellular proliferation compared with control cells. However, DN-myb infected KB cells showed significant reduction of cell growth and enhanced induction of apoptosis to activate PARP and caspase 9. c-myb induced increase of IGF-I, -II and IGF-IR expressions while DN-myb down-regulated these expression. Activation of ERK and Akt/PKB pathway was shown only in c-myb transduced cells. These findings suggest that the role of c-myb in cell growth of oral cancer cells is partially mediated through the modulation of IGFs, ERK and Akt/PKB. From this results, DN-myb is strongly recommended as a curable gene for the treatment of c-myb dependent malignancies such as 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.31 no.1
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• pp.13-23
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• 2005

This study was performed to investigate mistletoe extract-induced apoptosis in oral squamous cell carcinoma. In vivo study, HN22 cells were xenografted in nude mice. After tumor was experimentally induced, mistletoe extract was directly injected on the tumor mass. The specimens were evaluated using light and transmission electron microscopes. In vitro study, HN22 cells were cultured and exposed to mistletoe extract. The cells were evaluated using transmissin electron microscope. To evaluate apoptotic cells, flow cytometric analysis was done. The results were obtained as follows: 1. Light microscopic view of tumor mass showed necrosis at 2-4 weeks. 2. Transmission electron micrographs of tumor mass showed apoptosis and necrosis. 3. In TEM view of cell lines, necrosis and apoptosis were shown with mistletoe extract at $300{\mu}g/ml$, apoptosis was shown with mistletoe extract at $100{\mu}g/ml$. 4. In flow cytometric analysis, early and late apoptosis was shown when using caspase-3Ab and annexin-V, but no significant change was noted when using mebstain and Apo2.7 Ab. In this study, mistletoe extract induced necrosis and apoptosis in the tumor mass was induced by HN22 cells, early and late apoptosis in vitro study. Mistletoe extract was likely to induce cell death in oral squamous cell carcinoma through apoptosis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.38 no.2
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• pp.101-109
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• 2012

Objectives: The inactivation of the tumor suppressor gene $p16^{INK4a}$ plays an important role in the development of malignant tumors, including oral squamous cell carcinoma. The p16 gene is involved in the p16/cyclin-dependent kinase/retinoblastoma (Rb) gene pathway of cell cycle control. The p16 protein is considered a negative regulator of this pathway. The p16 gene encodes an inhibitor of cyclin-dependent kinases 4 and 6 which regulate the phosphorylation of the retinoblastoma gene and G1 to S phase transition in the cell cycle. However, the p16 gene can lose its functionality through point mutations, loss of heterozygosity or methylation of its promoter region. Materials and Methods: In this study, the authors analyzed the correlation between various clinicopathological findings- patient age, gender and smoking, disease recurrence, tumor size, stage, and differentiation- and p16 protein expression or p16 promoter hypermethylation in 59 cases of head and neck squamous cell carcinoma. Results: The results revealed p16 protein expression and p16 promoter hypermethylation in 28 cases (47.5%) and 21 cases (35.6%), respectively, of head and neck squamous cell carcinoma. However, neither p16 protein expression nor p16 promoter hypermethylation had any statistical influence on clinicopathological findings or survival rate. Conclusion: This data, and a review of the literature, suggest that p16 promoter hypermethylation cannot yet be used as an independent prognostic factor influencing carcinogenesis, but must be considered as an important factor along with other genetic alterations affecting the pRb pathway.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.41 no.6
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• pp.299-305
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• 2015

Objectives: This article describes our experience with neck dissection in 10 patients with oral squamous cell carcinoma. Materials and Methods: Between January 2007 and October 2009, 10 patients underwent primary surgery for the treatment of squamous cell carcinoma of the oral cavity. For patients with $N_0$ disease on clinical exam, selective neck dissection (SND [I-III]) was performed. In patients with palpable cervical metastases (N+), modified radical neck dissections were performed, except in one patient in whom SND (I-III) was performed. The histopathologic reports were reviewed to assess the surgical margins, the presence of extra-capsular spread, perineural invasion, and lymphatic invasion. Results: On histopathologic examination, positive soft tissue margins were found in three patients, and regional lymph node metastases were present in five of the ten patients. Perineural invasion was noted in five patients, and extra nodal spread was found in four patients. Regional recurrence was seen in two patients and loco-regional recurrence plus distant metastasis to the tibia was observed in one patient. During the study period, three patients died. Seven patients remain free of disease to date. Conclusion: Histopathological evaluation provides important and reliable information for disease staging, treatment planning, and prognosis. The philosophy of neck dissection is evolving rapidly with regard to the selectivity with which at-risk lymph node groups are removed. The sample size in the present study is small, thus, caution should be employed when interpreting these results.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.19 no.4
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• pp.414-434
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• 1997

Though many genetic and epigenetic alterations have been identified in hamster oral carcinogenesis model, there is no information about the possible role of transforming growth factor related with oral cancer. The purpose of this paper was to find the expression patterns of transforming growth factor alpha and beta during the stages of complete oral carcinogenesis model in hamster. 0.5% 9, 10-dimethyl-1, 2-benzanthracene(DMBA) in mineral oil was topically applied to the buccal pouch of 75 hamster three times a week during the experimental periods. The experimental animals were subdivided into two groups of control and experiment. Only the mineral oil was applied to the control group. 0.5% DMBA in mineral oil was applied to the experimental groups of 6, 8, 10, 12, 14, 16, 18 and 20 weeks. The expression of the $TGF-{\alpha}$ and $TGF-{\beta}$ protein were evaluated by the distribution and intensity of positive cells during the carcinogenesis using the immunohistochemical study. The following results were obtained ; 1. The buccal pouch epithelium of hamster was histologically changed to the dysplasia at 6, 8, 10 weeks, carcinoma in situ at 12 weeks, and squamous cell carcinoma at 14 weeks. 2. The expression of the $TGF-{\alpha}$ was restricted to the parabasal and basal layers of the normal and dysplastic mucosa, but those positive cells were extended to the spinous layers of the epithelium in the carcinoma. 3. The degree of $TGF-{\alpha}$ expression was markedly decreased in the carcinoma at 16, 18, 20. The strong positive staining in the center of cancer islands and weak positive staining in periphery of tumor were seen at the stage of squamous cell carcinoma. 4. The positive index of the $TGF-{\alpha}$ had a tendency to increase with DMBA- applied time. There was a statistically significant difference between 12, 18, 20 experimental group and control group (p<0.05). 5. The expression of the $TGF-{\beta}$ was shown at the cytoplasm of all control and experimental groups, and the parabasal and basal layers of the normal and dyslastic mucosa, but it was shown at the basal layers of the epithelium in the carcinoma. 6. $TGF-{\beta}$ was expressed diffusely at 16, 18, 20 experimental group. The strong positive staining in the center of cancer islands and positive staining in periphery of tumor were seen at the stage of squamous cell carcinoma. From the above findings, the expression of $TGF-{\alpha}$ and ${\beta}$ in oral carcinogenesis model seems to have two formal stages, the first being an overexpression step as reaction to uncontrolled growth and the second being one in which external protein accumulate in the surrounding stroma and intracytoplasm. Overexpression of $TGF-{\alpha}$ and ${\beta}$ may have important cooperative roles for the promotion of cancer and factor of prognosis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.28 no.1
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• pp.7-15
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• 2002

The present study was carried out to evaluate the correlation of metastasis and prognostic factors in squamous cell carcinoma of head and neck. Examination was performed on a series of thirty-seven patients who were confirmed to squamous cell carcinoma and its lymphatic metastasis by pathologist. Correlations of metastasis and other factors such as angiogenesis, histologic grading, and p53 expression and ras oncogene were studied. The depth of tumors was around 1 to 27mm. Twenty cases were more than 10mm deep, of which seventeen cases were shown lymphatic metastasis. Total score of histologic grading including keratinization, nuclear atypia, growth pattern and intensity of inflammation was ranged from 5 to 10 points. Of these factors, nuclear atypia with intensity of inflammation, and nuclear atypia with growth pattern was correlated with nuclear atypia each. For angiogenesis, number of new-formed vessels were counted 13 to 58 each. Twenty-eight cases were shown to lymphatic metastasis. No correlation with histologic grading and lymphatic metastasis was found. The results of immunohistochemical staining for p53 and ras oncogene revealed that positive cases were 16 and 22, negative for 21 and 15 each. However, both were not correlated with histologic grading and lymphatic metastasis. These results were revealed that angiogenesis was not correlated with lymphatic metastasis of squamous cell carcinoma arising in head and neck. Nuclear atypia with intensity of inflammation and dysplasia with growth pattern were correlated with histologic grading, which suggested that more careful and adequate advice is needed for effective treatment.

• Journal of Oral Medicine and Pain
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• v.43 no.4
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• pp.136-141
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• 2018

Oral cancer is a malignant neoplasm of the lips or oral cavity. Surgery, radiotherapy and chemotherapy depending on the location and stage of the tumor can be considered as important treatment modalities of oral cancer. Unfortunately, all three treatments can have both acute and chronic complications. Among them, trismus and osteoradionecrosis (ORN), unique complications of radiotherapy in the orofacial region, are particularly difficult to treat once manifested. Therefore, these two complications of radiotherapy have devastating effects on the patient's oral health and furthermore, overall quality of life. In this study, we present a case of a patient showing trismus and ORN following radiotherapy for the treatment of maxillary squamous cell carcinoma and briefly discuss this matter of trismus and ORN in the perspective of a dentist.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.23 no.2
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• pp.174-179
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• 2001

The authors analyzed retrospectively the 19 patients with mucoepidermoid carcinoma of salivary glands who were treated at Department of Oral and Maxillofacial Surgery, Pusan National University Hospital from June, 1986 to September, 1998. The results obtained were as follows: 1. There were 4 males(21%) and 15 females(79%). Age distribution was wide and the mean age was 45.2. 2. Of all mucoepidermoid carcinomas of salivary gonads, 4 cases arose in the major salivary glands and 15 cases in the minor salivary glands. The incidence according to the anatomic primary site for minor salivary glands was 8 cases in the palate, 2 cases each arising in the tongue and floor of mouth and 1 case each arising in the mandible, buccal mucosa and the lower lip. 3. In histopathological classification of mucoepidermoid carcinoma, 5 cases were low grade. 9 cases, intermediate grade and 5 cases, high grade. 4. Perineural invasion was observed 40%(2/5) in high grade and 22%(2/9) in the intermediate grade of mucoepidermoid carcinoma. 5. The incidence of cervical lymph node metastasis according to histopathologic grade was 40% (2/5) in high grade and 11%(1/9) in intermediate grade of mucoepidermoid carcinoma. 6. The lung was the commonest site for metastasis comprising 3 cases among 3 cases of distant spread of which 2 cases in high grade and 1 case in intermediate grade of mucoepidermoid carcinoma.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.2
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• pp.95-110
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• 2006

The treatment for oral and maxillofacial carcinoma with chemotherapeutic agents is evaluated by many effective methods to reduce the tumor mass and cancer cell proliferation. However these chemotherapy have many serious side effects, such as bone marrow suppression, renal toxicity, G-I troubles. Therefore a possible approach to develop a clinically applicable chemotherapeutic agent is to screen anticancer activity of Taxol which is known to have very little side effect and have been used to breast cancer and ovarian carcinoma. Taxol is a new anti-microtubular anti-cancer agent extracted from the bark of the Pacific yew, Taxus brevifolia. Paclitaxel(Taxol) acts by promoting tubulin polymerization and over stabilizing microtubules agianst depolymerization. Despite the constant improvements of methods of the cancer treatment especially chemotherapy, the rate of cancer metastasis and recurrent are not decreased. Thus the investigation of new drug which have very little side effect and a possible clinically application continues to be a high priority. Considering that the Taxol have shown very effective chemotherapeutic agent with relatively low toxicity in many solid tumors, it deserves to evaluate its efficacy in oral squamous cell carcinoma. In this study, to investigate the in-vivo and in-vitro anti-cancer efficacy of Taxol in oral squamous cell carcinoma and lastly, the potency of Paclitaxel in the clinical application for oral cancer was evaluated. In vivo study, after HN22 cell line were xenografted in nude mice, the growth of tumor mass was observed, 3 mg/Kg taxol was injected intraperitoneally into nude mice containing tumor mass. The methods of these study were measurement of total volume of tumor mass, histopathologic study, immunohistochemical study, drug resistance assay, growth curve, MTT assay, flow cytometry, cDNA microarray in vivo and in vitro. The results were obtained as following. 1. The visual inspection of the experimental group showed that the volume of the tumor mass was slightly decreased but no significant difference with control group. 2. Ki-67 index was decreased at weeks 4 in experimental group. 3. Microscopic view of the xenografted tumor mass showed well differentiated squamous cell carcinoma and after Taxol injection, some necrotic tissue was seen weeks 4. 4. The growth curve of the tumor cells were decreased after 1day Taxol treatment. 5. According to the MTT assay, HN22 cell line showed relative drug resistancy above $5\;{\mu}g/ml$ concentrations of Taxol. 6. In drug resistance assay, the decrease of cell counts was seen relatively according to concentration. 7. In Flow cytometry, G2M phase cell arrests were seen in low concentration of the Taxol, while S phase cell arrests were seen in high concentration of the Taxol. 8. Using cDNA microarray technique, variable gene expression of ANGPTL4, TXNRD1, FAS, RRAGA, CTGF, CYCLINEA, P19, DUSP5, CEBPG, BTG1 were detacted in the oral squamous cell carcinoma cell after taxol treatment. In this study paclitaxel is effective against oral squamous cell carcinoma cell lines in vitro, but week effect was observed in vivo. So we need continuous study about anticancer effect of taxol in vivo in oral squamous cell carcinoma.