• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2523-2527
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• 2014

Background: Serum thyroglobulin detection plays an essential role during the follow-up of thyroid cancer patients treated with total/near total thyroidectomy and radioiodine ablation. The aim of this retrospective study was to evaluate the relationship between stimulated serum thyroglobulin (Tg) level at the time of high dose $^{131}I$ ablation and risk of recurrence, using a three-level classification in patients with differentiated thyroid cancer (DTC) according to the ATA guidelines. Also we investigated the relationship between postoperative stimulated Tg at the time of ablation and DxWBS results at 8-10 months thereafter. Materials and Methods: Patients with radioiodine accumulation were regarded as scan positive (scan+). If there was no relevant pathological radioiodine accumulation or minimal local accumulation in the thyroid bed region, this were regarded as scan negative (scan-) at the time of DxWBS. We classified patients in 3 groups as low, intermediate and high risk group for assessment of risk of recurrence according to the revised ATA guidelines. Also, we divided patients into 3 groups based on the stimulated serum Tg levels at the time of $^{131}I$ ablation therapy. Groups 1-3 consisted of patients who had Tg levels of ${\leq}2ng/ml$, 2-10 ng/ml, and ${\geq}10ng/ml$, respectively. Results: A total of 221 consecutive patients were included. In the high risk group according to the ATA guideline, while 45.5% of demonstrated Scan(+) Tg(+), 27.3% of patients demonstrated Scan(-) Tg(-); in the intermediate group, the figures were 2.3% and 90.0% while in the low risk group, they were 0.6% and 96.4%. In 9 of 11 patients with metastases (81.8%), stimulated serum Tg level at the time of radioiodine ablation therapy was over 10, however in 1 patient (9.1%) it was <2ng/mL and in one patient it was 2-10ng/mL (p=0.005). Aggressive subtypes of DTC were found in 8 of 221 patients and serum Tg levels were ${\leq}2ng/ml$ in 4 of these 8. Conclusions: We conclude that TSH-stimulated serum thyroglobulin level at the time of ablation may not determine risk of recurrence. Therefore, DxWBS should be performed at 8-12 months after ablation therapy.

• 대한두경부종양학회지
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• 제20권2호
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• pp.135-142
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• 2004

Objectives: The purpose of this study was to evaluate for prognostic significance of VEGF expression and tumor angiogenesis in papillary carcinomas of the thyroid. Materials and Methods: The materials were 79 cases of papillary thyroid carcinomas, and age, sex, tumor size, multiplicity of tumor, capsular invasion, lymph node metastasis, recurrence, TNM stage, DeGroot stage and AMES scale were evaluated. An immunohistochemical stains for CD 34 to estimate microvessel density (MVD), and VEGF were done. MVD was defined as an average count of vessels per ${\times}400$ power field in the most vascularized area. VEGF expression was interpreted as 1+ and 2+ according to staining intensity and percentages of positive cells. Results: Mean score of MVD was $39.7{\pm}16.9.$ MVD were significantly higher in cases with capsular invasion (p=0.0001), lymph node metastasis (p=0.0001), TNM stage III (p=0.0022), DeGroot stage III (p=0.0163) and high risk group by AMES scale (p=0.0001). VEGF 2+ expression rate was significantly increased in cases with capsular invasion and lymph node metastasis (p=0.0006, p=0.0013), and in cases with TNM stage III, DeGroot stage III and high risk group by AMES scale (p=0.0236, p=0.0003, p=0.0293). In VEGF 2 + expression group, MVD was significantly higher than in VEGF 1 + group (p=0.0008), and MVD showed positive relation to VEGF 2 + expression (r=0.4616). Conclusion: VEGF expression and high MVD were significantly correlated to capsular invasion, lymph node metastasis, TNM stage III, DeGroot stage III and high risk group by AMES scale. The expression of VEGF and high MVD could be considered to be one of prognostic factor in papillary thyroid carcinomas.

• 대한핵의학회지
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• 제17권1호
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• pp.17-23
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• 1983

In an attempt to evaluate the diagnostic singnificance of the serum thyroglobulin (TG) in various thyroid disease states, authors measured serum TG by radioimmunoassay technique in 20 cases of normal subject, 22 cases of hyperthyroidism, 12 cases of diffuse nontoxic goiter (DNG) and 96 cases of nodular nontoxic goiter(NNG). The results were as follows: 1. In 20 cases of normal subjects, serum TG level was $20.41{\pm}5.5ng/ml(M{\pm}S.D.)$. There was no significant difference between males ans females. 2. In 22 cases of hyperthyroidism, serum TG level was $60.23{\pm}34.56ng/ml$ and the range was from 22 to 175 ng/ml, which were significantly high levels comparing with normal controls (p<0.01). 3. In 12 cases of euthyroidism with DNG, serum TG was $37.28{\pm}27.36ng/ml$ and the range was from 14 to 89 ng/ml. In 96 cases of euthyroidism with NNG, serum TG was $70.43{\pm}78.18ng/ml$ and the range was from 12.8 to 440 ng/ml. Both groups showed significantly increased levels of TG than normal control (p<0.01). 4. 57 cases of NNG patients were analysed pathologically by operation or needle biopsy and the TG level of each disease group is as follows. Thyroid carcinoma (16 cases); $72.2{\pm}81.71ng/ml$, adenomatous goiter without cystic degeneration (15 cases); $74.86{\pm}45.64ng/ml(M{\pm}S.D.)$ and adenomatous goiter with cystic degeneration(23 cases); $73.56{\pm}64.78ng/ml(M{\pm}S.D.)$. There was no significant difference between each group. Also the TG levels of thyroiditis (5 cases) was $19.6{\pm}8.96ng/ml(M{\pm}S.D.)$. 5. There were no significant correlations between serum thyroid hormones and serum TG in each thyroid functional states.

• 대한두경부종양학회지
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• 제14권2호
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• pp.244-252
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• 1998

저자들은 1987년 1월부터 1997년 2월까지 만 10년간 경상대학교병원 외과학 교실에서 갑상선 결절 환자 298예에 대하여 임상적 검토를 실시하여 다음과 같은 성적을 얻었다. 1) 갑상선 결절 총 298예 중 양성 결절은 214예(71.8%), 악성 결절 84예(28.2%)이었고, 악성율은 진단방법의 발달과 수술 적응증의 강화로 증가 되었다. 양성 결절과 악성 결절은 30대에서 50대 사이에서 호발하였고 나이가 증가함에 따라 악성 빈도가 증가하였다. 남녀비는 양성 결절에서 1:5.88이었고, 악성 결절에서 1:11이었다. 2) 병리조직학적 소견상 양성 결절 214예중 여포선 종 136예 (63.5%), 선종성 선종 67예 (31.3%), 휘틀 세포 선종 4예(1.9%), 낭종 3예(1.4%), 기타 갑상선염 4예 (1.9%)이었고, 악성종양 84예중 유두암 728예 (85.72%). 여포암 8예(9.5%), 미분화암 2예(2.4%), 수양암 1예 (1.2%), 악성 림프종 1예 (1.2%)이었다. 3) 술전 시행한 세침 천자 흡인 세포 검사의 민감도는 52.8%, 특이도는 98.4%, 위음성율은 47.2%이었다. 4) 총 298예 중 단일 결절 85.6%, 다발성 결절 14.4%이었으며 이중 악성결절의 빈도는 단일 결절의 26.6%, 다발성 결절의 37.3%이었고, 고형 결절의 악성도는 83.3%로 낭성 결절의 16.7%보다 높았고, 갑상선 주사소견상 악성 결절에서 cold nodule이 22.7%였다. 5) 수술 방법은 양성결절 214예중 동측 전엽 절제술과 협부 절제술이 86%에서 시술 되었고, 악성 결절 84예 중 경부 곽청술을 동반한 갑상선 전절제술 27.3% 갑상선 전절제술 23.8%, 동측 전엽 절제술과 협부 절제술 23.8%에서 시술되었고, 술후 합병증은 전체 7.1% 중 양성 결절의 1.9%, 악성 결절의 20.2%에서 발생하여 악성 결절 수술시 유의하게 높았다. 영구 부갑상선 기능 저하증 2예(0.7%)에서 발생하였다. 악성 결절의 수술후 재발은 주로 유두상암의 임프절 재발이 다수였고 미분화암에서는 국소 재발 및 림프절 재발이 있었으나 원이부 전이는 없었다.

• 핵의학기술
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• 제21권1호
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• pp.39-43
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• 2017

Thyroglobulin (Tg)은 갑상선에서 특이적으로 생성되는 요오드단백질로써 분화갑상선 암(Differentiate Thyroid Carcinoma, DTC) 의 생물학적 표지자이다. 본 검사실의 Tg 검사법은 반응시간이 길어 진료과와 환자들의 결과보고 요청사항을 만족시키지 못하고 있는 상황이다. 이를 만족시키기 위해 Tg 검사의 반응시간을 단축하고자 현재 사용중인 B사 Kit와 타 병원에서 사용중인 C사 Kit의 반응시간을 단축시켜 실험을 진행하였다. 본원에 의뢰된 Tg 약 65명의 환자 검체를 대상으로 B사 Kit의 반응시간을 $37^{\circ}C$ shaking 2hr/2hr, 실온 shaking 3hr/2hr, $37^{\circ}C$ shaking 1hr/1hr으로, C사 Kit의 원법인 실온 shaking 3hr법과 반응시간을 단축한 실온 shaking 2hr, $37^{\circ}C$ shaking 2hr 방법으로 단축하여 기존에 시행하던 overnight법과 상관성검사를 실시하여 비교하였다. 그 결과 여섯가지 방법 모두 1.0 ng/mL 이상의 값에서는 높은 상관관계를 보였으나 1.0 ng/mL 이하의 값에서는 다소 흔들리는 경향이 있었다. 하지만 그 중 상대적으로 안정적이었던 B사 Kit $37^{\circ}C$ shaking 1hr/1hr 법과 C사 Kit 실온 shaking 2hr 법에 대해 다른 조건들을 재설정하여 적합한 방법을 찾는다면 진료과와 환자들의 요구 사항 충족은 물론, EIA법과의 경쟁력 면에서도 유용할 것이다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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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.

• Journal of Yeungnam Medical Science
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• 제33권2호
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• pp.155-158
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• 2016

Sorafenib (Nexavar) has been regarded as a treatment for unresectable hepatocellular carcinoma (HCC), with side effects that include hand-foot skin reaction, diarrhea, rash, fatigue, hypertension, nausea, anorexia, weight loss, and alopecia. Thyroid disorder, such as endocrine side effect, has also been reported. However no case involving adrenal insufficiency has been reported. Here, we report a case of adrenal insufficiency which occurred after taking sorafenib in a patient with HCC. A 56-year-old man visited our hospital due to right upper quadrant abdominal pain and he was diagnosed as multiple disseminated and unresectable HCCs with portal vein invasion; therefore transarterial chemoembolization was performed and sorafenib administration was started. Two months later, he was admitted to the hospital complaining of severe fatigue. The laboratory results showed cortisol of <$0.2{\mu}g/dL$ and adrenocorticotropic hormone of <1.00 pg/mL. The patient had no history of taking steroids or herbal medications. Secondary adrenal insufficiency was diagnosed and prednisolone 10 mg per day was started immediately; as a result, fatigue remarkably improved. This may be the first report indicating a possible association between sorafenib and adrenal insufficiency and it implies that the possibility of adrenal insufficiency should be considered in patients taking sorafenib who complain of severe fatigue.

• The Korean Journal of Physiology and Pharmacology
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• 제26권6호
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• pp.457-468
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• 2022

It has been demonstrated that APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) is involved in the regulation of several growth-related signaling pathways and thus closely associated with the development and progression of some cancers. Diallyl trisulfide (DAT), a garlic-derived bioactive compound, exerts selective cytotoxicity to various human cancer cells through interfering with pro-survival signaling pathways. However, whether and how DAT affects survival of human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we tested the hypothesis of the involvement of APPL1 in DAT-induced cytotoxicity in HCC HepG2 cells. We found that Lys 63 (K63)-linked polyubiquitination of APPL1 was significantly decreased whereas phosphorylation of APPL1 at serine residues remained unchanged in DAT-treated HepG2 cells. Compared with wild-type APPL1, overexpression of APPL1 K63R mutant dramatically increased cell apoptosis and mitigated cell survival, along with a reduction of phosphorylation of STAT3, Akt, and Erk1/2. In addition, DAT administration markedly reduced protein levels of intracellular TNF receptor-associated factor 6 (TRAF6). Genetic inhibition of TRAF6 decreased K63-linked polyubiquitination of APPL1. Moreover, the cytotoxicity impacts of DAT on HepG2 cells were greatly attenuated by overexpression of wild-type APPL1. Taken together, these results suggest that APPL1 polyubiquitination probably mediates the inhibitory effects of DAT on survival of HepG2 cells by modulating STAT3, Akt, and Erk1/2 pathways.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2447-2451
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• 2015

Background: Human papillary thyroid carcinoma (PTC) is often associated with Hashimoto's thyroiditis (HT); their coexistence improves PTC prognosis. Osteopontin, a secreted glycoprotein, plays a role in cell survival, immunity, and tumor progression, its expression being associated with a poor prognosis and metastasis in several malignancies. Osteopontin overexpression correlates with aggressive clinicopathological features in PTC. Lymph node metastases and large tumor size positively correlate with osteopontin positivity. This study aimed to: (1) confirm osteopontin overexpression in human PTC samples; (2) compare osteopontin expression levels in PTC cases with and without HT; and (3) identify correlations between tumor aggressiveness and osteopontin expression levels. Materials and Methods: Plasma osteopontin was assessed in 45 patients with PTC, 22 patients with PTC and HT, and 24 healthy controls by enzyme-linked immunosorbent assay. Thyroid tissue osteopontin mRNA and protein levels were analyzed by reverse transcription-polymerase chain reaction and Western blotting, respectively. Results: Plasma osteopontin levels were significantly higher in PTC patients than in healthy controls. Plasma osteopontin, tissue osteopontin mRNA, and tissue osteopontin protein levels were significantly lower in patients with PTC and HT than in those with PTC alone. In advanced disease stage cases, osteopontin mRNA and protein expression levels were lower in patients with PTC and HT than in those with PTC alone. However, the osteopontin expression level was not significantly associated with the TNM stage. Conclusions: Plasma osteopontin, tissue osteopontin mRNA, and tissue osteopontin protein levels were significantly lower in patients with PTC and HT than in those with PTC alone, suggesting that HT attenuates PTC aggressiveness through negative regulation of osteopontin expression.

• 대한두경부종양학회지
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• 제30권2호
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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.