• Korean Journal of Head & Neck Oncology
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• v.14 no.2
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• pp.220-227
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• 1998

The clinical and pathological features of 35 cases of anaplastic thyroid cancer were studied. These tumors occurred in 12 men and 23 women ranging in age from 19 to 83 years(mean age; 61.7 years). A rapidly enlarging thyroid mass was the most common presentation. The duration of the presence of mass varied from 20 days to 12 months with an average of 2.7 months. Systemic metastasis at the time of initial examination was found in 14 patients(40.0%) and the lung was the most common site of involvement. The overall rate of distant metastasis was about 65.7%. The tumors were subdivided morphologically into giant cell type of 10 cases, spindle cell type of 7 cases, epidermoid cell type of 1 cases, and mixed giant cell and spindle cell type of 5 cases. The mean survival period of 6 among 35 patients who had biopsy alone was 1.4 months. The 22 patients underwent the incomplete combined treatment modalities (palliative surgery with or without chemotherpy or radiation therapy) survived for a mean period of 3.0 months, among them, 7 patients who had surgery combined with chemotherapy and radiation therapy showed mean survival period of 3.7 months. The mean survival of 7 patients who had complete combined treatment modality(curative surgery combined with chemotherapy and hyperfractionated radiation therapy) was 6.6 months, only one patient survived for 21 months and one patient has been alive for 1 month after operation, and the others survived for a mean period of 4.8 months. So far, as of July 31, 1998, 34 patients among 35 were died(one has been survived for 1 month) despite the various treatment modalities, and the main cause of death were failure of local control and systemic metastasis. None of the various treatment modalities gave consistently favourable results. However, a combination of surgery, radiation therapy and chemotherapy seemed to have a slight positive effect on survival. Furthermore, the aggressive treatment modalities will be indicated only in the early diagnosed and minimal cases.

• Korean Journal of Head & Neck Oncology
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• v.30 no.2
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• pp.53-61
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• 2014

Background and Objectives : Anaplastic thyroid carcinoma(ATC) is a rare but highly aggressive thyroid malignancy that is associated with an extremely poor survival despite the best multidisciplinary care. BRAF(V600E) mutation is detected in about a quarter of ATC, but unlike its high treatment response to selective BRAF inhibitor (PLX4032) in metastatic melanoma, the treatment response of ATC is reported to be low. The purpose of this study is to investigate the innate resistance mechanism responsible for this low treatment response to BRAF inhibitor and its effect on epithelial-mesenchymal transition(EMT). Materials and Methods : Two ATP cell lines, 8505C and FRO were selected and treated with PLX4032 and its drug sensitivity and effects on cell migration and EMT were examined and compared. Further investigation on the changes in signals responsible for the different treatment response to PLX4032 was carried out and the same experiment was performed on both orthotopic and ectopic xenograft mouse models. Results : FRO cell line was more sensitive to PLX4032 treatment compared to 8505C cell line. The resistance to BRAF inhibition in 8505C was due to increased expression of EGFR. Effective inhibition of both EGFR and p-AKT was achieved after dual treatment with BRAF inhibitor(PLX4032) and EGFR inhibitor(Erlotinib). Similar results were confirmed on in vivo study. Conclusion : EGFR-mediated reactivation of the PI3K/AKT pathway and MAPK pathway contributes to the relative insensitivity of BRAF(V600E) mutant ATC cells to PLX4032. Dual inhibition of BRAF and EGFR leads to sustained treatment response including cell invasiveness.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.551-561
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• 2021

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

• Korean Journal of Head & Neck Oncology
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• v.21 no.2
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• pp.178-182
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• 2005

Insular carcinoma(poorly differentiated thyroid cancer) is defined as a aggressive, follicular-derived thyroid carcinoma with behavior intermediate between follicular/papillary and anaplastic carcinomas. It was described by Carcangiu in 1984, but its prognosis, classification and the origin is not yet clear. And preoperative fine needle aspiration cytology of insular carcinoma has not been satisfactory. We experienced a case of advanced thyroid insular carcinoma with invasion of the sternum. So we intend to present the case with a review of the related literatures.

• Korean Journal of Head & Neck Oncology
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• v.12 no.1
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• pp.8-15
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• 1996

When thyroid carcinoma invades the larynx or trachea, the proper treatment is needed because of significant morbidity and mortality due to airway obstruction. Hemoptysis and dyspnea are the result of intraluminal extension of the tumor and call for immediate investigation with endoscopic examination and CT. If the thyroid carcinoma with extracapsular spread invades only outer perichondrium of the tracheal or laryngeal cartilage, the shaving operation would be sufficient, but if the tumor invades the cartilage or if there is intraluminal invasion, it is mandatory to remove partial or total part of some aerodigestive tract structures. We retrospectively analyzed 14 surgical cases of the thyroid cancer with laryngotracheal invasion(12 papillary carcinomas and 2 anaplastic carcinomas) at the Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital. The analysis was focused on clinical manifestation, pathologic findings, types of management and results. Survival result was not adequately analyzed due to some recently operated cases.

• The Korean Journal of Nuclear Medicine
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• v.20 no.1
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• pp.59-65
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• 1986

Clinical features of 406 patients with histologically verified thyroid carcinomas were investigated from May, 1978 to April, 1985 at the Seoul National University Hospital with the following results. 1) The incidence of thyroid cancer according to their histological classification was 79.8% of papillary carcinoma, 14.5% of follicular carcinoma, 1.5% of medullary carcinoma, 2.2% of anaplastic carcinoma, 2 cases of squamous carcinoma and 3 cases of lymphoma. 2) The age distribution showed the peak incidence in the fourth decade (25.1%), followed by the fifth and the third decade. 3) The ratio of male to female patients was 1 : 6.1. The ratio is 1 : 5.9 in papillary carcinoma and 1 : 8.8 in follicular carcinoma. 4) The mean age was 40.2 year in papillary carcinoma, 37.4 year in follicular carcinoma. 36.5 year in medullary carcinoma, 60.3 year in anaplastic carcinoma, 62.0 year in squamous carcinoma, 59.7 year in lymphoma. 5) The diameter of the thyroid masses was smaller than 1.5cm in 19.9% of the patients, from 1.5cm to 5cm in 50.5%, from 5cm to 10cm in 25.4% and larger than 10cm in 25.4%. 6) Metastasis to the regional lymph nodes at diagnosis was noted in 44.2% of total patients, and distant metastasis was 5%, and local infiltration was 44.2%. 7) The clinical staging was revealed 42.1% of the patients in stage I, 9.1% in stage II, 35.7% in stage III, 5.2% in stage IV, and 7.9% in undetermined stage.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6059-6062
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• 2012

Regional cancer epidemiology is an important basis for determining the priorities for cancer control in different countries worldwide. There is no reliable information about the pattern of head and neck cancer in western Nepal and hence an attempt was here made to evaluate the situation based on hospital data, which provide the only source in the western region of Nepal. A clinicopathological analysis of head and neck cancers treated between 2003 and 2006 in Manipal Teaching Hospital affiliated to Manipal College of Medical Sciences, Pokhara, Western Development Region, Nepal was performed. A total of 105 head and neck cancer cases were identified with a male to female ratio of 1.8:1. The median ages of male and female patients were 62 and 64 years, respectively. Ninety-seven (92.4%) of the cancer patients were suffering from carcinoma, three (2.9%) had blastoma, three (2.9%) had sarcoma, and two (1.9%) had lymphoma. The majority (61.9%) of carcinoma cases were squamous cell carcinoma followed by anaplastic carcinoma (7.2%). Of the carcinoma cases, the most common site of primary lesion was larynx (19.6%), followed by the thyroid (14.4%), the tongue and hypopharynx with 10.3% cases each. Comparative analysis among males and females did not reveal any sex difference in type of head and neck cancers. The head and neck cancer pattern revealed by the present study provides valuable leads to cancer epidemiology in western Nepal and useful information for health planning and cancer control, and future research in western Nepal.