• Molecules and Cells
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• v.41 no.9
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• pp.853-867
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• 2018

As the most common type of endocrine malignancy, papillary thyroid cancer (PTC) accounts for 85-90% of all thyroid cancers. In this study, we presented the hypothesis that SDC4 gene silencing could effectively attenuate epithelial mesenchymal transition (EMT), and promote cell apoptosis via the $Wnt/{\beta}-catenin$ signaling pathway in human PTC cells. Bioinformatics methods were employed to screen the determined differential expression levels of SDC4 in PTC and adjacent normal samples. PTC tissues and adjacent normal tissues were prepared and their respective levels of SDC4 protein positive expression, in addition to the mRNA and protein levels of SDC4, $Wnt/{\beta}-catenin$ signaling pathway, EMT and apoptosis related genes were all detected accordingly. Flow cytometry was applied in order to detect cell cycle entry and apoptosis. Finally, analyses of PTC migration and invasion abilities were assessed by using a Transwell assay and scratch test. In PTC tissues, activated $Wnt/{\beta}-catenin$ signaling pathway, increased EMT and repressed cell apoptosis were determined. Moreover, the PTC K1 and TPC-1 cell lines exhibiting the highest SDC4 expression were selected for further experiments. In vitro experiments revealed that SDC4 gene silencing could suppress cell migration, invasion and EMT, while acting to promote the apoptosis of PTC cells by inhibiting the activation of the $Wnt/{\beta}-catenin$ signaling pathway. Besides, $si-{\beta}-catenin$ was observed to inhibit the promotion of PTC cell migration and invasion caused by SDC4 overexpression. Our study revealed that SDC4 gene silencing represses EMT, and enhances cell apoptosis by suppressing the activation of the $Wnt/{\beta}-catenin$ signaling pathway in human PTC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5921-5926
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• 2014

A large proportion of patients with thyroid nodules in China undergo thyroidectomy in order to get confirmatory histology diagnosis. The financial impact of this modality remains to be investigated. To evaluate rationality of performing thyroidectomy without a routine FNA preoperatively from the economic perspective, we conducted a retrospective, observational study of all archival thyroidectomies with records of cost per stay (CPS), cost per day (CPD) and length of stay (LOS) from 2008 to 2013 in the First Affiliated Hospital of Nanjing Medical University. We compared all the parameters between cancer and non-cancer thyroidectomies. We recruited 6, 140 thyroidectomies with valid records of CPS, CPD and LOS in this period. The CPS of cancer thyroidectomy was significantly higher than non-cancer thyroidectomy. The percentage of cancer thyroidectomy increased from 26.5% to 41.6%. The percentage of annual cost of cancer thyroidectomies rose from 30.2% to 45.2%. The LOS for cancer and non-cancer thyroidectomy decreased while the CPD increased in the past six years. The estimated national cost in 2012 for all thyroidectomies would be USD 1.86 billion with USD 1.09 billion for non-cancer thyroidectomies. We have witnessed great improvement in the healthcare for patients with thyroid nodules in China. However, given limited healthcare resources, currently thyroid FNA for more precise preoperative diagnosis may help to curb the rapidly increasing demand in healthcare costs in the future for nodular thyroid disease in China.

• Korean Journal of Head & Neck Oncology
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• v.37 no.2
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• pp.105-109
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• 2021

Follicular thyroid carcinoma (FTC) is the second most common thyroid cancer, following papillary carcinoma. Metastasis to the orbital rim from FTC is very rare. We recently experienced a case of FTC with metastasis to the orbital rim in a 74-year-old woman, who initially presented with a huge thyroid mass and an asymptomatic solitary orbital rim lesion. The solitary orbital rim lesion was suspected to be a separate disease entity such as lymphoma from the preoperative imaging, but bone metastasis from FTC was finally confirmed after orbital rim resection and total thyroidectomy. During follow-up, the patient presented multiple bone metastasis, so the solitary orbital rim lesion was considered a clinical sign of systemic metastasis from FTC. Therefore, we present this unique case with a review of the literature.

• Korean Journal of Head & Neck Oncology
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• v.36 no.2
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• pp.9-15
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• 2020

Background/Objectives: To analyze the clinical characteristics of differentiated thyroid cancer (DTC) in children and adolescents. Materials & Methods: Medical records of 31 DTC cases that were diagnosed and treated at Korea Cancer Center Hospital between 2002 and 2018 were retrospectively reviewed. Results: Most cases were papillary carcinoma (n=26), with female predominance (n=25). Median age was 16.4 years (range, 11.9-18.6 years). Extrathyroidal extension was present in 24 cases. Twenty cases had tumor involvement at cervical lymph nodes and three had lung metastasis. Twenty-two patients received radioactive iodide treatment with a median cumulative dose of 300 mCi (range, 100-920 mCi). During a median follow-up of 68.2 months (range, 2.3-191.4 months), serum thyroglobulin level was elevated in 15 patients. Among them, two cases had remnant thyroid tissue, 4 had recurrence at cervical lymph nodes, and the remaining 9 did not have any detectable lesion. All were alive, and 5-year event-free survival (EFS) was 45.2±10.1%. Age £15 years, tumor size, lymph node status (N1b), and distant metastasis had negative effects on EFS. On multivariate analysis, age and tumor size had prognostic significance. Conclusion: For DTC of children and adolescents (£18 years old), age ≤15 years and tumor size were prognostic factor. Therefore, patients in this age group need meticulous follow-up. Further studies are necessary to answer the potential influence of age on the incidence and behavior of DTC.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.1
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• pp.9-15
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• 2006

Purpose: Previous studies have not showed consistent results for the level of expression of sodium/iodide symporter (NIS) in thyroid diseases, especially malignant tumor. We undertook this study to evaluate the distribution of NIS expression in malignant thyroid diseases and compare with that in benign thyroid disease. Materials and Methods: Total patients were 119 cases (Men 15, $48{\pm}13$ yrs). Total number of samples were 205 pieces. In malignant thyroid disease, there were 153 samples: 90 in papillary carcinoma, 4 in follicular carcinoma, 2 in medullary carcinoma and 57 in metastatic lymph node. In benign thyroid disease, there were 52 samples: 36 in goiter/cyst, 11 in thyroiditis and 5 in follicular adenoma. Using immunohistochemical methods, we probed 205 samples with monoclonal anti-NIS Ab. Grading of staining was stored as 0 (negative or absent), 1 (weakly positive), 2 (moderately positive) or 3 (strongly positive). Expression rate (ER) of NIS positivity in individual disease entity was expressed as percentage of total number divided by number in 2 plus 3 grade. Results: ERs of malignant thyroid diseases were 63% in papillary carcinoma, 81% in metastatic lymph node, 71% in follicular carcinoma and 100% in medullary carcinoma. ERs of benign thyroid disease were 53% in goiter/cyst, 64% in thyroiditis and 40% in follicular adenoma. ER of malignant thyroid diseases was higher than benign thyroid diseases (71% vs 54%). Grading of NIS expression in papillary carcinoma or goiter/cyst was heterogeneously distributed in considerable cases. Normal tissue also showed heterogeneous distribution of NIS expression, which was not correlated with that of primary lesion. Conclusion: In papillary thyroid carcinoma, distribution of NIS expression was heterogeneous and increased, and not different compared with that of benign thyroid disease.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2947-2951
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• 2015

Background: The phenomenon of occult carcinoma maybe observed in patients with clinically unilateral papillary thyroid microcarcinoma (PTMC). Although many studies have reported that the $BRAF^{T1799A}$ mutation is associated with aggressive PTMC, the relationship between $BRAF^{T1799A}$ mutation and occult carcinoma is unclear. The aim of this study was to investigate the risk factors, including $BRAF^{T1799A}$ mutation, for occult contralateral carcinoma in clinically unilateral PTMC accompanied by benign nodules in the contralateral lobe. Materials and Methods: From January 2011 to December 2013, we prospectively enrolled 89 consecutive PTMC patients with clinically unilateral carcinoma accompanied by benign nodules in the contralateral lobe who received a total thyroidectomy and cervical lymph node dissection. $BRAF^{T1799A}$ mutation was tested by pyrosequencing on postoperative paraffin specimens. The frequency and predictive factors for occult contralateral carcinoma were analyzed with respect to the following variables: age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or $BRAF^{T1799A}$ mutation. Results: A total of 36 patients (40.4%) had occult PTMC in the contralateral lobe. The median diameter of the occult tumors was $0.33{\pm}0.21cm$. The $BRAF^{T1799A}$ mutation was found in 38 cases (42.7%). According to the univariate analysis, there were no significant differences between the presence of occult contralateral carcinoma and age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or $BRAF^{T1799A}$ mutation. Conclusions: Using current methods, it is difficult to preoperatively identify patients with PTMC, and further research is needed to determine predictive factors for the presence of occult contralateral carcinoma in patients with unilateral PTMC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.935-940
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• 2013

Background: To evaluate the diagnostic utility of conventional ultrasonography and real time ultrasound elastography in differentiating degenerating cystic thyroid nodules mimicking malignancy from papillary thyroid carcinoma. Methods: We retrospectively analyzed conventional ultrasonographic and elastographic characteristics of 19 degenerating cystic thyroid nodules mimicking malignancy in 19 patients, with 30 surgically confirmed PTCs as controls. Based on size, the nodules had been grouped into less than 10mm (group A) and greater than 10 mm (group B). We evaluated conventional parameters and elasticity pattern. Color-scaled elastograms were graded as to stiffness of nodules using an elasticity pattern from I (soft) to IV (stiff). Results: Degenerating cystic thyroid nodules were similar to PTCs in conventional ultrasonographic findings, but the former frequently showed oval to round in shape (group A, 69.2% vs 18.8%, P=0.017; group B, 66.7% vs 7.14%, P=0.017) and punctuate hyperechoic foci (group A, 61.5% vs 0, P<0.001; group B, 50% vs 0, P<0.001). On real time ultrasound elastography, 7 of 13 degenerating cystic thyroid nodules in group A were pattern I, 5 were pattern II, 1 was pattern III. One degenerating cystic thyroid nodule in group B was pattern II, 5 were pattern III. The area under the curve for elastography was 0.98 in group A (sensitivity 92.3%, specificity 100%, P = 0.002), and 0.88 in group B (sensitivity 16.7%, specificity 100%, P = 0.014). Conclusions: As a dependable imaging technique, elastography helps increase the performance in differential diagnosis of degenerating cystic thyroid nodule and malignancy.

• Korean Journal of Head & Neck Oncology
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• v.13 no.2
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• pp.213-220
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• 1997

Background: Thyroid cancer is a relatively rare neoplasm and its incidence varies geographically and ethnically around the world. Thyroid cancer is the most common endocrine malignancy, but it has a wide spectrum of biologic behavior, histologic appearance, and management. Purpose: The purpose of the study was to analyse and evaluate all aspects of the clinical consideration in thyroid cancer. Method: Between 1986 and 1995, a retrospective analysis of 77 thyrod cancer patients admitted at the Department of Surgery, Hangang Sacred Heart Hospital, Hallym University was made to assess clinical entities. Result: By the pathological classification, the papillary carcinoma was the most common type(83.1%). Male to female ratio was 1 : 5.4 and most prevalent age group was noted from fourth decade to fifth decade(46.8%). The most common duration of illness between the appearance of the symptoms and the treatment was below 6 months(44.2%), and the most common symptom was the palpable mass at the anterior portion of the neck(96.1%). Most cases of the thyroid cancer were appeared as cold nodule in the $^{99m}$Tc-thyroid scan(95.7%). In the site of tumor location, the right and left lobe was distributed similarly. In the extent of tumor, incidence of intrathyroidal location was 41.6%, and that of the metastasis to the cervical lymph nodes was 44.2% and that of the direct capsular invasion was 27.3%, and incidence of both involved case was 13%. Surgical procedures were total thyroidectomy alone in 27 cases(35.1%) or with modified neck dissection in 6 cases(7.8%), or with radical neck dissection in 2 cases (2.6%), near total thyroidectomy alone in 22 cases(28.6%), ipsilateral lobectomy with isthmectomy alone in 12 cases(15.6%) or with modified neck dissection in 1 case(1.3%), and biopsy only in 7 cases(9.1%). The most common postoperative complications were transient hypoparathyroidism(5.2%) and transient unilateral recurrent laryngeal nerve paralysis(5.2%). Conclusion: The major problem of management of thyroid cancer include a wide spectrum of clinical behaviour of this tumor entity, the lack of reliable prognostic factors and lack of an objective assessment of the various treatment modalities. But because of showing the favorable prognosis for most thyroid cancer, appropriate and aggressive management should be recommended.

• 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.

• Archives of Plastic Surgery
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• v.39 no.1
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• pp.71-75
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• 2012

Recurrent laryngeal nerve paralysis is the most common and serious complication after thyroid cancer surgery. The objective of this study was to report the advantages of the vein wrapping technique for nerve reconstruction in patients with thyroid cancer invading the recurrent laryngeal nerve and its effects on postoperative phonatory function. The subjects were three patients who underwent resection of the recurrent laryngeal nerve during surgical extirpation of papillary thyroid cancer. Free ansa cervicalis nerve graft or direct neurorrhaphy with a vein wrapping technique was used to facilitate nerve regeneration, protect the anastomosed nerve site mechanically, and prevent neuroma formation. One-year postoperative laryngoscopic examination revealed good vocal cord mobility. Maximum phonation time ($19.5{\pm}0.3$ sec) was longer than a previously-reported value in conventional reconstruction patients ($18.8{\pm}6.6$ sec). The present phonation efficiency index ($7.88{\pm}0.78$) was higher than that previously calculated in conventional reconstruction ($7.59{\pm}2.82$). The mean value of the Voice Handicap Index-10 was 6, which was within the normal range. This study demonstrates improvement in phonation indices measured 1 year after recurrent laryngeal nerve reconstruction. Our results confirm that the vein wrapping technique has theoretical advantages and could be favored over conventional reconstruction techniques for invenerate nerve injuries.