• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.155-161
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• 2001

Background and Objectives: Nitric oxide (NO) is generated in mammalian tissue by the conversion of L-arginine to L-citrulline. This reaction is catalyzed by nitric oxide synthase (NOS). NO is an important bioactive agent and a signalling molecule that mediates a variety of biologic actions such as vasodilation, neurotransmission, host defense, and iron metabolism but increased NO production may also contribute to the pathogenesis of a various of disorders, including cancer. Before now, the role of NO in thyroid gland is still investigated and it was supposed that NO mediate the angiogenesis in tumor growth. Others journal and works identified the expression of iNOS that involve by neutrophil and eNOS that involve in part in the vascular remodeling and to understand the role of NO in human thyroid gland. But authors revealed only eNOS in thyroid neoplasm. iNOS was identifed by inflammation in fault. Materials and Methods: Western blot analysis was performed, using a polyclonal antibody against eNOS (Rabbit polyclonal IgG). Using the same antibody, the distribution of eNOS was examined in 15 formalin-fixed paraffin embedded samples by immunohistochemistry. By NADPH consumption rate, NOS activity was estimated at nodular hyperplasia. Results: Western blot analysis exhibited that eNOS was significantly elevated in thyroid papillary carcinoma, compared to that in nodular hyperplasia and normal tissue. Immunohistochemistry showed that the immunoreacitivity was present more significantly in thyroid follicular epithelial cell layer than vascular endothelial cell. NOS activity increased in nodular hyperplasia. Conclusions: Thyroid papillary cancer without neutrophil invasion expressed only eNOS. The endothelial localization of eNOS may play an important role in pathogenensis of human thyroid nodular hyperplasia and the follicular localization of thyroid papillary carcinomas.

• Korean Journal of Head & Neck Oncology
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• v.14 no.1
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• pp.70-75
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• 1998

Tumor growth and metastasis depends on angiogenesis. Vascular endothelial growth factor (VEGF) is a potent mitogen for vascular endothelial cells in vitro and promotes neoangiogenesis in vivo. Objective: Follicular thyroid cancers(FTC) are a vascular tumor and traditionally metastasize via blood vessels. Likely other cancers, angiogenesis may playa important role in FTC. We, therefore, investigated the expression of VEGF and microvascular density by immunohistochemistry in FTC and follicular adenoma(FA). Materials and Methods: Findings of immunohistochemical stainings for VEGF and CD31 were measured by grading scale from +1 to 4+(strongest) and by counting the stained microvessels in 14 FTCs and 14 FAs. Results: 1) Expression of VEGF. a) FTCs have stronger expression than FAs in areas of tumor adjacent to capsule($mean{\pm}SD\:\;3.2{\pm}0.9\;vs\;2.0{\pm}0.9$, p<0.01) and in central area($2.3{\pm}0.7\;vs\;1.3{\pm}0.6$, p<0.01). b) The VEGF expression of capsular area in FTCs are higher than that of central area(p<0.05). 2) Microvascular density by CD31. a) FTCs have more microvessels than FAs in areas of adjacent to capsule($78.9{\pm}27.3\;vs\;38.7{\pm}15.6$, p<0.01) and in central area($75.5{\pm}23.3\;vs\;27.8{\pm}10.7$, p<0.01). b) In FTCs, the number of microvessels of capsular area are more than that of central tumor area, but not significant statistically(p>0.05). Conclusion: The higher expression of VEGF and microvascular density in FTC suggests angiogenesis plays an important role in progression of FTC.

• 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.

• 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.

• 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.

• Journal of Oral Medicine and Pain
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• v.43 no.3
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• pp.84-86
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• 2018

Salivary and lacrimal gland dysfunction is relatively frequent after radioiodine therapy. In most cases this is a transient side effect, but in some patients it may persist for a long period or appear late. Radioiodine ($^{131}I$) therapy is often administered to patients following total thyroidectomy to treat well-differentiated follicular cell-derived thyroid cancer. In addition to the thyroid, $^{131}I$ accumulates in the salivary glands, giving rise to transient or permanent salivary gland damage. Salivary gland dysfunction following radioiodine therapy can be caused by radiation damage. But, it also may be associated with $Sj{\ddot{o}}gren$ syndrome (SS) developed after radioiodine therapy. It would be recommended that the evaluation for SS including anti-SSA/Ro and anti-SSB/La should be considered before and after radioiodine therapy.

• Korean Journal of Head & Neck Oncology
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• v.22 no.2
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• pp.137-141
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• 2006

Purpose : It has been generally accepted that lobectomy is a standard surgical procedure in treatment of benign thyroid nodules. However lobectomy may cause postoperative hypothyroidism. Most of surgeons believe that nodulectomy has its limitation in treatment of thyroid nodules due to recurrence of nodules and presence of cancer. The current study attempts to determine whether nodulectomy is justified in aspects of preservation of thyroid function, risk of recurrence and complications. Methods: Data was collected retrospectively on 74 patients undergoing thyroidectomy(single nodulectomy, n=43;bilateral nodulectomies, n=9;lobectomy with nodulectomy, n=22) for benign thyroid nodules from 1999 to 2004. All patients were evaluated for complication, postoperative thyroid function, and recurrence of benign nodule and cancer were followed by regular ultrasonographic examination for 2-6 years. Results : The pathologic results of 74 patients were nodular hyperplasia(55 patients), Hashimoto's thyroiditis(8 patients), follicular adenoma(7 patients) and papillary carcinoma(4 patients). Average operation time was 30 minutes from skin incision to specimen out. In postoperative follow-up of 70 patients, six cases(8.5%) became mild hypothyroid, and ultrasonographically detected micronodule was also six cases(8.5%). There were no other complications. Conclusion : Thyroid nodulectomy appears to have advantages of relatively few complication and simple procedure with no access to laryngeal nerves. Therefore, it may be one of treatment options in selected cases of benign thyroid nodules.

• The Korean Journal of Nuclear Medicine
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• v.38 no.6
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• pp.511-515
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• 2004

Purpose: The sodium-iodide symporter (NIS) expression is an important factor in determining the sensitivity of radioiodine therapy in well-differentiated thyroid cancers. Several previous studies for the expression of NIS in thyroid tissues show diverse results. To investigate whether there is difference between methods in determining the expression of NIS in thyroid tissues of patients with thyroid nodules, we measured the expression ot NIS using two different methods (RT-PCR and immunoshistochemical staining) and compared the results. Materials & Methods: We measured the expression of NIS by reverse transcriptase-polymerase chain reaction (RT-PCR) and also by immunohistochemical staining using anti-NIS antibody in thyroid cancers and other benign thyroid diseases. We compared the results of each method. We included 19 papillary carcinomas, 1 follicular carcinoma, 7 medullary carcinoma, 4 adenomas and 7 nodular hyperplasias. Results: By RT-PCR analysis, 10 of 19 papillary carcinomas expressed NIS, but 1 follicular cancer didn't express NIS. By immunohistochemical staining, 15 of 19 papaillary carcinomas express NIS, but 1 follicular lancer didn't express NIS. There was a significant correlation between the semiquautitative results of RT-PCR and immunohistochemical staining of NIS expression. (p<0.01) Conclusion: Our data demonstrated that the expression of NIS in thyroid cancers and other benign diseases investigated by RT-PCR and immunohistochemical staining correlated well each other. However, by immunohistochemical staining, more NIS expression was found.

• The Korean Journal of Nuclear Medicine
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• v.38 no.2
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• pp.152-160
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• 2004

Radioiodide uptake in thyroid follicular epithelial cells, mediated by a plasma membrane transporter, sodium iodide symporter (NIS), provides a first step mechanism for thyroid cancer detection by radioiodide injection and effective radioiodide treatment for patients with invasive, recurrent, and/or metastatic thyroid cancers after total thyroidectomy. NIS gene transfer to tumor cells may significantly and specifically enhance internal radioactive accumulation of tumors following radioiodide administration, and result in better tumor control. NIS gene transfers have been successfully performed in a variety of tumor animal models by either plasmid-mediated transfection or virus (adenovirus or retrovirus)-mediated gene delivery. These animal models include nude mice xenografted with human melanoma, glioma, breast cancer or prostate cancer, rats with subcutaneous thyroid tumor implantation, as well as the rat intracranial glioma model. In these animal models, non-invasive imaging of in vivo tumors by gamma camera scintigraphy after radioiodide or technetium injection has been performed successfully, suggesting that the NIS can serve as an imaging reporter gene for gene therapy trials. In addition, the tumor killing effects of I-131, ReO4-188 and At-211 after NIS gene transfer have been demonstrated in in vitro clonogenic assays and in vivo radioiodide therapy studies, suggesting that NIS gene can also serve as a therapeutic agent when combined with radioiodide injection. Better NIS-mediated imaging and tumor treatment by radioiodide requires a more efficient and specific system of gene delivery with better retention of radioiodide in tumor. Results thus far are, however, promising, and suggest that NIS gene transfer followed by radioiodide treatment will allow non-invasive in vivo imaging to assess the outcome of gene therapy and provide a therapeutic strategy for a variety of human diseases.

• 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.