• International Journal of Oral Biology
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• v.46 no.4
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• pp.176-183
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• 2021

Oral squamous cell carcinoma (OSCC) metastasis is characterized by distant metastasis and local recurrence. Combined chemotherapy with cisplatin and 5-fluorouracil is routinely used to treat patients with OSCC, and the combined use of gefitinib with cytotoxic drugs has been reported to enhance the sensitivity of cancer cells in vitro. However, the development of drug resistance because of prolonged chemotherapy is inevitable, leading to a poor prognosis. Therefore, understanding alterations in signaling pathways and gene expression is crucial for overcoming the development of drug resistance. However, the altered characterization of Ca²⁺ signaling in drug-resistant OSCC cells remains unclear. In this study, we investigated alterations in intracellular Ca²⁺ ([Ca²⁺]_i) mobilization upon the development of gefitinib resistance in human tongue squamous carcinoma cell line (HSC)-3 and HSC-4 using ratiometric analysis. This study demonstrated the presence of altered epidermal growth factor- and purinergic agonist-mediated [Ca²⁺]_i mobilization in gefitinib-resistant OSCC cells. Moreover, Ca²⁺ content in the endoplasmic reticulum, store-operated calcium entry, and lysosomal Ca²⁺ release through the transient receptor potential mucolipin 1, were confirmed to be significantly reduced upon the development of apoptosis resistance. Consistent with [Ca²⁺]_i mobilization, we identified modified expression levels of Ca²⁺ signaling-related genes in gefitinib-resistant cells. Taken together, we propose that the regulation of [Ca²⁺]_i mobilization and related gene expression can be a new strategy to overcome drug resistance in patients with cancer.

• The Korean Journal of Cytopathology
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• v.4 no.2
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• pp.111-120
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• 1993

Fine needle aspiration cytology has become a frequently used technique for the diagnosis of lesions in the head and neck. Fine needle aspiration cytology of the salivary glands were performed on 66 patients. In 59 patients with satisfactory samples, cytologic diagnoses were as follows; there were 47 benign lesions, including pleomorphic adenoma(20), Warthin's tumor(3), benign cystic lesion(4), Inflammatory lesion(4), lymphoid lesion(3), myoepithelioma(1), unspecified benign neoplasm (5), and unclassified benign lesion(7). There were 6 cases of undetermined malignancy and 6 malignant lesions including mucoepidermoid carcinoma(3), adenoid cystic carcinoma(1), carcinoma ex pleomorphic adenoma(1), and metastatic carcinoma(1) in cytologic diagnosis. In 25 patients, the cytologic diagnosis was correlated with histologic findings. The sensitivity of the benign lesion was 96% and the specificity was 82%. There was no false-positive diagnosis. The sensitivity and the specificity of pleomorphic adenoma were 75% and 95%, respectively. Some of Warthin's tumors were confused with benign cystic lesion due to frequent cystic change of the tumor. The sensitivity and specificity of the malignant lesions were 56% and 88%, respectively. There were three false negative diagnoses. Two mucoepidermoid carcinomas were correctly diagnosed by cytology. Two of three adenoid cystic carcinomas were misdiagnosed as benign tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3961-3965
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• 2012

Objective: To compare the clinical effects of concurrent radiochemotherapy with those of radiotherapy in treating locally advanced nasopharyngeal carcinoma (Stage III~IVa). Methods: A total of 95 patients suffering from nasopharyngeal carcinoma (Stage III~IVa) were divided into two groups: concurrent radiochemotherapy (Group CCRT, n=49) and radiotherapy (Group RT, n=46). The two groups were both delivered conventional fractionated radiotherapy, while Group CCRT also received three cycles of PF (DDP+5-Fu) or PLF (DDP+5-Fu+CF) chemotherapy. Results: The complete remission rate and total remission rate of Group CCRT were higher than those of Group RT ($X^2$=4.72~7.19, P<0.05). The one-year overall survival (OS) rate calculated by the life table method, was also higher than that of Group RT ($X^2$=4.24, P<0.05) as well as the 3-year OS rate, nasopharyngeal control rate and cervical lymph nodes' control rate ($X^2$=4.28~4.40, P<0.05). In addition, the 5-year OS and metastasis-free rates of Group CCRT were higher than those of Group RT and the differences were of statistical importance ($X^2$=3.96~8.26, P<0.05). However, acute toxicity was also obviously higher, the difference in gastrointestinal reactions being statistically significant ($X^2$=11.70, P<0.05). Conclusion: This study demonstrated that concurrent radiochemotherapy could improve the remission rate, overall survival rate and locally control rate. The toxicity of concurrent radiochemotherapy could be tolerated by the patients.

• Korean Journal of Head & Neck Oncology
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• v.10 no.1
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• pp.13-24
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• 1994

Despite optimal local therapy such as surgery and/or radiotherapy, the long term outcome is poor for patients with advanced squamous cell carcinomma of head and neck, due to frequent loco-regional recurrence and distant metastases. We studied to determine whether the combination chemotherapy, especially as an adjuvant chemotherapy, would improve the survival of these patients. Between January, 1986 and December, 1992, 57 patients with previously untreated, locally advanced squamous cell arcinoma of head and neck were assigned to receive 2-3 cycles of induction chemotherapy consisting of 5-fluorouracil(F) and cisplatin(P) every 3 weeks and standard local therapy such as surgery and/or radiotherapy followed by adjuvant chemotherapy with the same FP regimens. Of the 57 enroled patients, 45 patients were evaluable. The obtained results were as following: 1) Among 45 evaluable patients, 18 patients finished all treatment protocol including adjuvant chemotherapy and 27 patients had no adjuvant chemotherapy. The difference of age, sex, performance status, disease stage, and tumor differentiation was not significant statistically between adjuvant chemotherapy group and no-adjuvant chemotherapy group. 2) After induction chemotherapy, 7/45(15.4%), 30/45(67%) achieved complete remission and partial remission respectively with 82.4% overall response rates in entire patients. 3) The 4year progression free survival was 43.3% in adjuvant chemotherapy group and 24.1% in no-adjuvant chemotherapy group(p>0.05). The 4year overall survival was 56.9% and 25.5% respectively(p>0.05). There was no significant different in the patterns of local recurrence and distant metastasis between the two groups. 4) Adverse reactions from combination chemotherapy included nausea, vomiting, mucositis, diarrhea and hematologic bone marrow depression. These were mild and tolerated by patients, and these was no episode of any life threatening toxicities. In conclusion, adjuvant chemotherapy after induction chemotherapy and local therapy did not show statistically significant survival improvement, but there was trend of prolongation of survival when compared to no adjuvant chemotherapy. Thus, large scale phase III randomized controlled studies are strongly recommended.

• Korean Journal of Head & Neck Oncology
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• v.9 no.1
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• pp.25-32
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• 1993

The nodular hyperplasia of the thyroid is a common thyriod disease. Nodular hyperplasia does rarely progress to thyroid cancer. The differentiation of a nodular hyperplasia from a neoplasm may be simple or difficult, both clinically and anatomically. The papillary carcinoma of the thyroid is the most common type of thyroid malignancies. There were few studies about cytogenetic observation in thyroid cancer. But only one case of banding observation in nodular hyperplasia have been reported. In order to compare the chromosomal changes in the thyroid cancer and the noncancerous thyroid disease, we performed cytogenetic analysis in two papillary carcinoma and two nodular hyperplasia after cell culture. The chromosomal pattern of the nodular hyperplasia found was very heterogenous but no clonal abnormaly in both cases was observed. Case I : A modal chromosomal number was in 42-46 range. Chromosome 8, 19, 21. 22 were commonly lost. 9 structural anomalities among 51 analysed cells were observed but they were not clonal. Case II: A modal chromosomal number was 43. Chromosome 17 and 19 were commonly lossed. Common cytogenetic characters of this two nodular hyperplasia are hypodiploidity and very heterogenous chromosomal pattern. The result about the papillary carcinoma are as follow. In one case some numerical and structural chromosomal changes were observed. But they were not clonal abnormality. In another case the chromosomal pattern found was very heterogenous with a clonal abnormality of del(11)(q23). The modal number was 46. The del(11)(q23) a chromosomal change in papillary carcinoma of the thyroid have previously been reported(Eva Olah et al. 1989). We suggest that 11q deletion may be important role to pathogenesis of papillary carcinoma of the thyroid. According to this results, we could not find out specific differences about chromosomal changes and any relationship between the papillary carcinoma and the nodular hyperplasia.

• Korean Journal of Head & Neck Oncology
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• v.14 no.1
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• pp.40-45
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• 1998

Backgroud and Objectives: Major salivary gland tumor is a rare disease with a largely unknown origin. And also corresponding to the diversity of histopathologic characteristics is an equally wide distribution of clinical behavior that makes treatment decisions difficult. The aim of this study is to analysis the clinical experience of our major salivary gland tumor and to suggest a guidline of management. Materials and Methods : We studied clinical manifestations and treatment results of 104 patients who were diagnosed as major salivary gland tumors. Tumor site, patient age and sex of the patients were analysed. Histopathologic diagnosis, treatment modality, lymph nodes metastasis, recurrence rate and 5-year survival rate were studied on malignant tumors. Results: 1) 48 patients were male and 56 patients were female. 2) Benign tumors were 79 cases. They consisted of 57 cases(72%) of parotid tumor, 22 cases(27%) of submandibular tumor. And pleomorphic adenoma was the most common benign tumor. 3) Malignant tumors were 25 cases and were consisted of 19 cases(76%) of parotid tumor, 4 cases(l6%) of submandibular tumor and 2 cases(8%) of sublingual gland tumor with high-grade mucoepidermoid carcinoma as the most common cause. 4) In the malignant tumors, the number of stage I, II tumors was 14 and that of stage III, IV tumors was 11. Neck node metastasis was noted in 8 cases. 5) 8 cases of malignant tumor were died and all of them had high-grade malignancy. And they were dead before 17 months from the time of diagnosis. 6) Mean survival duration in the malignant salivary gland tumor was 56 months. 7) High-grade malignancy had a 5-year survival rate of 57.9%. A 5-year survival rate of TI, T2 patients was 92.9% and that of T3, T4 patients was 36.4%. That of patients who had neck node metastasis was 37.5% and that of those who had tree neck was 82.4%. Conclusion: The results of this study suggest that the survival rate is dependent on the tumor size, lymph node matastasis and histologic grade. And also the early diagnosis and radical surgery result in the increased survival rate and are effective for prevention of the tumor recurrance.

• Korean Journal of Head & Neck Oncology
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• v.12 no.2
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• pp.153-160
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• 1996

Regardless of the prognostic factors in papillary thyroid cancer, such as sex, age, size of tumor, extent of disease, and distant metastasis, the prognosis of papillary thyroid cancer is sometimes difficult to predict from clinical and microscopic analysis alone and additional prognostic indicators are needed. Recent studies of thyroid cancer have indicated that DNA aneuploidy may be correlated to the biological behavior of malignancy and inversely correlated to the prognosis, but it still remains contraversal. We performed this study to assess DNA ploidy patterns in relation with the previously known prognostic factors in AMES scoring system and lateral neck node metastasis in papillary thyroid cancer. A series of 132 patients with papillary thyroid cancer and 80 patients with benign thyroid tumor(27 follicular adenomas and 53 adenomatous goiters) as a control group from October 1993 to Feburary 1995 were analyzed and their nuclear DNA content was measured with flow cytometry using fresh tissue specimens. DNA aneuploidy was found in 8(6.1%) in papillary cancer and 8(10%) in benign tumor. S-phase traction(SFP) and proliferative index(PI) were higher in thyroid cancers, being 2.18$\pm$4.24%, 6.34$\pm$4.94% in the papillary thyroid cancers and 1.97$\pm$2.93%, 4.44$\pm$3.80% in the benign tumors, respectively. However there was no significant difference of values between two groups(p>0.05). Among variable prognostic factors studied(age, sex, size of tun or, extent of disease, distant metastasis in AMES scoring system and lateral neck node metastasis), DNA aneuploidy was found to be common in distant metastasis(p<0.001) and in lateral neck node metastasis(p>0.035), but there was no significant difference between the high risk and low risk group according to the AMES scoring system(p<0.08). In our study, DNA aneuploidy was not valuable in determining the presence of malignancy and did not correlate to the AMES scoring system. However, follow-up study of more cases will be needed for accurate information about the DNA ploidy as a independent prognostic factor.

• Korean Journal of Head & Neck Oncology
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• v.15 no.2
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• pp.141-148
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• 1999

Objectives: The development of thyroid tumor has a relationship with carcinogen, oncogene and tumor suppressor gene. With aminotriazole, radioactive iodine and nitrosomethylurea as carcinogens in rat, authors investigate the incidence in type of the thyroid tumors, p21 and p53 protein expression pattern by immunohistochemical stain and the relationship between the tumors and p21-p53 protein expressions. Materials and Methods: 80 experimental animals were divided into four groups; group 1(control, no carcinogen, n=20), group 2(oral administration of aminotriazole for 36 weeks, n=20), group 3(intraperitoneal injection of 131I for one time and oral administration of aminotriazole for 36 weeks, n=20), group 4(oral administration of nitrosomethylurea for 3 days and aminotriazole for 36 weeks, n=20). After 40 weeks they were sacrificed with pathologic examination and we performed immunohistochemical staining with pan-ras monoclonal antibody for p21 protein and CMI polyclonal antibody for p53 protein with paraffin-embedded specimens. Results: 1) No tumors were observed in group I, but 38.3% of nodular goiters, 11.7% of adenomas and 50.0% of carcinomas were observed in carcinogen treated groups(group 2, 3, 4). 2) The incidence of nodular goiter, adenoma and carcinoma were 70%, 20% and 10% in group 2, 40%, 15% and 45% in group 3 and 5%, 0% and 95% in group 4. 3) p21 protein was not expressed in normal thyroid tissues but was expressed in 26.1% of nodular goiters, 42.9% of adenomas and 6.7% of carcinomas. On the other hands, p53 protein was not expressed in normal thyroid tissues, nodular goiters, adenomas and in well differentiated thyroid carcinomas by immunohistochemical stain. Conclusion: The authors suggest that aminotrizole, 131I, nitrosomethylurea can be etiologic agents in the development of thyroid tumor and the p21 protein can be expressed in the early stage and in benign condition of thyroid tumor but p53 protein is not expressed in all conditions of development in rats.

• Archives of Plastic Surgery
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• v.44 no.6
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• pp.530-538
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• 2017

Background A pharyngocutaneous fistula is a common and difficult-to-manage complication after head and neck reconstruction. It can lead to serious complications such as flap failure, carotid artery rupture, and pharyngeal stricture, and may require additional surgery. Previous radiotherapy, a low serum albumin level, and a higher T stage have been proposed as contributing factors. We aimed to clarify the risk factors for pharyngocutaneous fistula in patients who underwent flap reconstruction and to describe our experiences in treating pharyngocutaneous fistula. Methods Squamous cell carcinoma cases that underwent flap reconstruction after cancer resection from 1995 to 2013 were analyzed retrospectively. We investigated several significant clinical risk factors. The treatment modality was selected according to the size of the fistula and the state of the surrounding tissue, with options including conservative management, direct closure, flap surgery, and pharyngostoma formation. Results A total of 127 cases (18 with fistulae) were analyzed. A higher T stage (P=0.048) and tube-type reconstruction (P=0.007) increased fistula incidence; other factors did not show statistical significance (P>0.05). Two cases were treated with conservative management, 1 case with direct closure, 4 cases with immediate reconstruction using a pectoralis major musculocutaneous flap, and 11 cases with direct closure (4 cases) or additional flap surgery (7 cases) after pharyngostoma formation. Conclusions Pharyngocutaneous fistula requires global management from prevention to treatment. In cases of advanced-stage cancer and tube-type reconstruction, a more cautious approach should be employed. Once it occurs, an accurate diagnosis of the fistula and a thorough assessment of the surrounding tissue are necessary, and aggressive treatment should be implemented in order to ensure satisfactory long-term results.

• Korean Journal of Head & Neck Oncology
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• v.21 no.2
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• pp.121-125
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• 2005

Objectives: To investigate the role of MMP-2 and TIMP-2 in the invasion and metastasis of thyroid papillary microcarcinomas. Materials and Methods: We performed immunohistochemical study on MMP-2 and its tissue inhibitor (TIMP-2) using tissue microarrays containing 2 cores of 40 microPTC and 8 non-neoplastic thyroid tissue. The expression intensity was semiquantitatively scored as -, ${\pm}$, +1, +2, and +3. Results: Both MMP-2 and TIMP-2 expression was observed in all tumors(100%) and in 1 of 8 non-neoplastic tissue(12.5%), and the positive staining was restricted to the epithelial cells. In 17 and 23 tumors with or without extrathyroid invasion, respectively, 8(47%) and 10(43%) cases showed moderate to strong(+23) positivity for MMP-2. TIMP-2 expression was moderate to strong in 13 cases(76%) and 16 cases(70%) in each group. In multifocal and solitary tumors, 3 of 6(50%) and 11 of 21(52%) cases showed moderate to strong MMP-2 expression, and 5/6(83%) and 15/21(71%) showed moderate to strong TIMP-2 expression. Conclusion: There is no relationship between MMP-2 or TIMP-2 expression and extrathyroid invasion or tumor multifocality in papillary microcarcinoma of the thyroid gland.