• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.139-147
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• 2001

Objectives: The most important differential point of follicular carcinoma from adenoma is capsular invasion or angioinvasion of follicular cells. Serial sections for examination of levels of tumor margins are necessary to watch the invasion. However, the interpretation of capsular invasion or angioinvasion is sometimes not feasible on the routine staining of tumor tissue. The aim of this study is to evaluate the clinical significance of expressions of $p27^{KIP1}$, MIB-1, bcl-2 and p53 in differential diagnosis of follicular adenoma and carcinoma. Materials and Methods: 16 cases of follicular carcinoma and 26 cases of follicular adenoma were entered on study of immunohistochemical stains for $p27^{KIP1}$, MIB-1, bcl-2 and p53. In carcinoma cases, correlation between the above markers, patient's age, tumor size, infiltration pattern and metastasis was studied. Results: $p27^{KIP1}$ labelling index (LI) of follicular carcinoma and adenoma was $4.89{\pm}6.92$ and $14.52{\pm}9.17$, respectively, but there was no significant difference between adenoma and carcinoma (p=0.2560). MIB-1 LI of carcinoma and adenoma was $4.11{\pm}3.89$ and $0.80{\pm}0.75$, respectively, and MIB-1 LI was significantly higher in carcinoma (p=0.0000). bcl-2 expression was seen in 2(12.5%) of 16 carcinoma cases and 130(50.0%) of 26 adenoma cases, and bcl-2 expression rate was higher in adenoma than in carcinoma(p=0.014). In one adenoma and one carcinoma case, p53 expression was noted. In follicular adenoma with atypia compared to adenoma without atypia, lower $p27^{KIP1}$ LI, higher MIB-1 LI and lower bcl-2 expression rate were seen. In follicular carcinoma, MIB-1 LI was significantly higher in invasive carcinoma(p=0.045) and was relatively increased in tumors larger than 3.0cm, showing angioinvasion and distant metastasis. But $p27^{KIP1}$ LI was higher in cases over 40 years old(p=0.008) and with conspicuous capsular invasion. There were no positive correlations between expressions of MIB-1, bcl-2 and p53. Conclusion: MIB-1 labelling index and bcl-2 expression could be helpful for differential diagnosis of follicular adenoma and carcinoma, but p53 showed very low expression rate and no significance in differential diagnosis. $p27^{KIP1}$ labelling index reveals decreasing tendency in carcinoma compared with adenoma, MIB-1 LI was considered as a poor prognostic marker in follicular carcinoma, but $p27^{KIP1}$ LI was higher in carcinoma cases over 40 years old with showing conspicuous capsular invasion. Further study for the significance of $p27^{KIP1}$ labelling index in follicular neoplasms is necessary to evaluate diagnostic value of follicular carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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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.

• Korean Journal of Head & Neck Oncology
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• v.20 no.2
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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.

• The Korean Journal of Nuclear Medicine
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• v.17 no.1
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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.

• Korean Journal of Head & Neck Oncology
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• v.14 no.2
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• pp.244-252
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• 1998

The thyroid nodules are the most common endocrine disease requiring surgical management. We perfomed a clinical study of 298 cases with thyroid nodules, who were admitted to and operated at the Department of Surgery, College of Medicine, Gyeong sang National University from January 1987 to April 1997 and the results were summarized as follows: 1) Patients were composed of 214 cases(71.8%) of benign nodule and 84 cases(28.2%) of malignant nodule. Benign and malignant nodules were prevalent in fifth decade. 2) The sex distribution showed a preponderance of females with ratio of 5.88:1 in benign nodule and 11:1 in malignant nodule. 3) The nodules were located in the right lobe(134 cases, 44.9%), the left lobe(121 cases, 40.6%), both lobes(34 cases, 11.4%), and isthmus(8 cases, 2.7%). The possibility of malignancy was higher in the solid rather than cystic lesions. 4) Radioactive iodine scintiscans were perfomed in 273 cases and revealed cold nodules in 237 cases(86.8%), 58 of these cases(24.4%) were malignant. 5) According to the histopathologic classification, benign nodules included follicular adenomas 136 cases(63.5%), adenomatous goiters 67 cases(31.3%), Hurthle cell adenomas 4 cases(1.9%), cysts 3 cases(1.4%) and thyroiditis 4 cases(1.4%). In malignant nodules, papillary carcinomas 72 cases(85.7%), follicular carcinoma 8 cases(9.5%), undifferentiated carcinoma 2 cases(2.4%), medullary carcinoma 1 case(1.2%) and malignant lymphoma 1 case(1.2%). 6) The most commonly performed operative procedure was a lobectomy with isthmusectomy(85.5%) for bengn nodules and a total thyroidectomy(51.2%) for malignant nodules. 7) The rate of complications was higher in the cases with malignant nodules(20.2%) than in the benign cases(0.5%). The recurrence rate was 8.3%(7 cases).

• The Korean Journal of Nuclear Medicine Technology
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• v.21 no.1
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• pp.39-43
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• 2017

Purpose Thyroglobulin (Tg) is a biologic marker of differentiated thyroid carcinoma (DTC), produced by normal thyroid tissue or thyroid cancer tissue. Therefore, the Tg values of DTC patients is the most specific indicator for judging whether recurrence occur or whether the remaining thyroid cancer is present. Thyroid cancer is currently the most common cancer in Korea, of which 90% is differentiated thyroid cancer. The number of patients with thyroid disease of this application also increased, and an accurate and prompt results are required. However, the incubation time of the Tg commonly takes about 24 hours in our hospital, and the result reporting time is delayed, and We could not satisfied with the requirements of clinical departments and patients. In order to fulfill these requirements, experiments were conducted by shortening the incubation time between company B's Kit currently in use and company C's Kit used in other hospitals. Through these experiments, we could perform the correlation with the original method and shortening method, and could find the optimum reaction time to satisfy the needs of the departments and the patients, and we will improve the competitiveness with the EIA examination. Materials and Methods In September 2016, we tested 65 patients company B's kit and company C's kit by three incubation ways. First method $37^{\circ}C$ shaking 2hr/2hr, Second method RT shaking 3hr/2hr, Third method 1hr/1hr shaking at $37^{\circ}C$. Fourth method RT shaking 3hr method which is the original method of Company C's Kit. Fifth method, the incubation time was shortened under room temperature shaking 2hr, Sixth method $37^{\circ}C$ shaking 2hr. And we performed and compared the correlation and coefficient of each methods. Results As a result of performing shortening method on company B currently in use, when comparing the Original method of company B kit, First method $37^{\circ}C$ shaking 2hr/2hr was less than Tg 1.0 ng/mL and the ratio of $R^2=0.5906$, above 1.0 ng/mL In the value, $R^2=0.9597$. Second method RT shaking 3hr/2hr was $R^2=0.7262$ less than value of 1.0 ng/mL, $R^2=0.9566$ above than value of 1.0 ng/mL. Third method $37^{\circ}C$ shaking 1hr/1hr was $R^2=0.7728$ less than value of 1.0 ng/mL, $R^2=0.8904$ above than value of 1.0 ng/mL. Forth, Company C's The original method, RT shaking 3hr was $R^2=0.7542$ less than value of 1.0 ng/mL, and $R^2=0.9711$ above than value of 1.0 ng/mL. Fifth method RT shaking 2hr was $R^2=0.5477$ less than value of 1.0 ng/mL, $R^2=0.9231$ above than value of 1.0 ng/mL. Sixth method $37^{\circ}C$ shaking 2hr showed $R^2=0.2848$ less than value of 1.0 ng/mL, $R^2=0.9028$ above than value of 1.0 ng/mL. Conclusion Samples with both values of 1.0 ng/mL or higher in both of the six methods showed relatively high correlation, but the correlation was relatively low less than value of 1.0 ng/mL. Especially, the $37^{\circ}C$ shaking 2hr method of company C showed a sharp fluctuation from the low concentration value of 1.0 ng/mL or less. Therefore, we are planning to continuously test the time, equipment, incubation temperature and so on for the room temperature shaking 2hr method and $37^{\circ}C$ shaking 1hr/1hr of company C which showed a relatively high correlation. After that, we can search for an appropriate shortening method through additional experiments such as recovery test, dilution test, sensitivity test, and provide more accurate and prompt results to the department of medical treatment, It is competitive with EIA test.

• 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.

• Journal of Yeungnam Medical Science
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• v.33 no.2
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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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• v.26 no.6
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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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• v.16 no.6
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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.