• 대한두경부종양학회지
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• 제17권2호
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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.

• 대한두경부종양학회지
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• 제14권1호
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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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• 제40권1호
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• pp.9-15
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• 2006

목적 : 기존의 연구는 갑상선 악성 종양에서 NIS 단백질 발현에 대해 충분한 증례에서 일관성 있는 결과를 보이지 못하고 있다. 이에 본 연구에서는 원발성 갑상선 악성 종양의 조직에서 NIS 발현율의 분포를 알아보고, 이를 양성 갑상선 질환에서의 NIS 발현율의 분포와 비교하였다. 대상 및 방법 : 악성 갑상선 종양이나 양성 갑상선 질환으로 수술을 시행한 환자들을 대상으로 후향적 분석을 하였다. 환자들은 총 119명(남자 15명)이며. 나이는 $48{\pm}3$세(범위 20-75세) 였다. 이들에게서 얻은 조직 표본은 총 205개 였다. 이 표본들은 악성 질환(총 153개)으로 유두상 종양이 90개, 여포상 종양이 4개, 수질상 종양이 2개, 전이성 임파절이 57개 였으며, 양성 질환(총 52개)으로 갑상선 종대가 36개, 갑상선염이 11개, 여포선종이 5개였다. 단클론 항체인 mouse anti-NIS Ab를 사용하였다. 염색된 조직을 현미경으로 관찰하여 양성 등급은 염색 강도에 따라 약하게 염색되면 등급 1, 중등도로 염색되면 등급 2, 강하게 염색되면 등급 3으로 나누었으며, 음성인 경우는 등급 0으로 표시하였다. 개개의 질환에 있어서 NIS의 발현율은 전체의 개수에 대하여 등급 2와 3이 차지하는 비율을 백분율로 표시하였다. 결과: 갑상선 악성 질환에서 NIS의 발현율은 유두상 종양의 원발성 종양에서 63%, 전이성 임파선에서 81%를 보였다. 여포상 종양과 수질상 종양의 NIS의 발현율은 각각 71, 100% 였다. 갑상선 양성 질환에서 NIS의 발현율은 갑상선 종대에서 53%, 갑상선염에서 64%, 여포선종에서 40%였다. NIS의 발현율은 악성 종양에서 양성 질환보다 더 높았다(71% vs 54%) 증례수가 많은 유두상 종양과 갑상선 종대의 경우에 한쪽 등급에만 치우침이 없이 모든 등급에 걸쳐 분포를 보이는 특징을 보였다. 갑상선 질환을 보이는 병변 조직의 주위에 있는 정상 조직의 염색 정도는 다양한 등급을 보여서 일관성을 보이지는 않았으며, 병변조직의 염색 정도와도 연관성을 보이지 않았다. 결론: 갑상선 유두상 종양에서 면역조직화학검사에 기초한 NIS의 발현율은 불균질성 분포를 나타내며 증가하는 양상을 보였고, 악성 질환과 양성 질환 사이에 NIS의 발현율이 큰 차이를 보이지 않았다.

• 대한두경부종양학회지
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• 제12권2호
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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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• 제29권5호
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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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• 제43권3호
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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.

• 대한두경부종양학회지
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• 제22권2호
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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.

• 대한핵의학회지
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• 제38권6호
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• pp.511-515
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• 2004

목적: 갑상선세포에서 요오드의 섭취는 갑상선호르몬 합성의 첫 단계이며, sodium iodide symporter (NIS)라는 세포막 단백질에 의해 이루어지는 것으로 알려져 있고 NIS 유전자가 클로닝됨으로써 NIS 발현을 직접 관찰하는 것이 가능해졌다. 하지만, 갑상선암을 비롯한 갑상선 결절과 정상 조직에서의 NIS 발현은 검사방법과 대상에 따라 아주 다양한 결과를 보이고 있다. 따라서 이 연구에서는 갑상선암을 비롯한 여러 갑상선질환에서 NIS의 발현여부와 정도를 두 가지 서로 다른 RT-PCR방법과 면역조직화학염색법으로 조사하여 비교하였다. 대상 및 방법: 갑상선절제술을 받은 32명의 조직을 이용하였다. 술후 병리학적 진단은 유두암 19명, 여포암 1명, 수질암 1명, 선종 4명, 선종양 갑상선종 7명이었다. RT-PCR방법을 이용하여 갑상선글로불린, NIS, 갑상선과산화효소의 발현을 관찰하였고, 항NIS 항체를 이용하여 면역조직화학염색을 시행하여 NIS 발현 정도를 반정량적으로 평가하고, 그 결과를 각각 비교하였다. 결과: RT-PCR의 결과에서 유두암 19명중 10예에서 NIS의 발현이 있었다. 여포암 1예와 수질암 1예는 NIS 발현이 없었다. 선종 4명중 2예, 선종양 갑상선종 7명중 4예에서 NIS의 발현이 있었다. 면역조직화학염색법으로는 유두암 19명중 15예에서 발현이 있었고, 여포암 1예는 발현이 없었다. 선종 4예중 3예, 선종양 갑상선종 7예중 6예에서 발현이 있었다. RT-PCR방법에 의한 NIS의 발현 정도와 면역조직화학염색의 정도를 반정량적으로 평가하여 비교한 결과 각 검사의 결과 사이에 유의한 양의 상관관계가 있었다(p<0.001). 결론: RT-PCR방법과 면역조직화학염색법으로 조사한 NIS의 발현 정도는 양의 상관관계가 있었으나, RT-PCR방법에 비해 면역조직화학염색법으로 NIS발현을 더 많이 찾을 수 있었다.

• 대한핵의학회지
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• 제38권2호
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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.

• 대한핵의학회지
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• 제20권1호
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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.