PURPOSE: Thyroid cancer is the most common malignancy in Korean females and can be treated with good prognosis. However, drugs to treat aggressive types of thyroid cancer such as poorly differentiated or anaplastic thyroid cancer have not yet been established. To that end, we analyzed the effects of berberine on human thyroid cancer cell lines to determine whether this compound is useful in the treatment of aggressive thyroid cancer. MATERIALS AND METHODS: The two thyroid cancer cell lines 8505C and TPC1, under adherent culture conditions, were treated with berberine and analyzed for changes in cell growth, cell cycle duration, and degree of apoptosis. RESULTS: Following berberine treatment, both cell lines showed a dose-dependent reduction in growth rate. 8505C cells showed significantly increased levels of apoptosis following berberine treatment, whereas TPC1 cells showed cell cycle arrest at the G0/G1 phase. Immunobloting of p-27 expression following berberine treatment showed that berberine induced a little up-regulation of p-27 in 8505c cells but relatively high up-regulation of p-27 in TPC1 cells. CONCLUSION: These results suggest that berberine treatment of thyroid cancer can inhibit proliferation through apoptosis and/or cell cycle arrest. Thus, berberine may be a novel anticancer drug for the treatment of poorly differentiated or anaplastic thyroid cancer.
Antineoplastic Agents/*pharmacology ; Apoptosis/drug effects ; Berberine/*pharmacology ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Humans ; Thyroid Neoplasms/*metabolism

Various energy devices had been used in thyroid surgery. Aim of study is to develop canine model for recurrent laryngeal nerve injury by harmonic scalpel and to evaluate feasibility of using this model for evaluating the safety use of harmonic scalpel during thyroid surgery. Nine dogs were divided into 3 groups according to distance between harmonic scalpel application and recurrent laryngeal nerve; group 1 (1 mm), 2 (2 mm), and 3 (3 mm). Vocal cord function was assessed pre- and postoperatively using video laryngoscopy. Harmonic scalpel was applied adjacent to left recurrent laryngeal nerve and, two weeks later, right recurrent laryngeal nerve at assigned distances. Recurrent laryngeal nerves were evaluated for subacute and acute morphologic changes. Laryngoscopy demonstrated 3 abnormal vocal cords in group 1, 1 in group 2, and no in group 3 (P=0.020). Subacute histologic changes were observed in nerves with abnormal function. Acute histologic changes were observed 5/8 (62.5%) in group 1, 1/7 (14.3%) in group 2, and not in group 3. We developed canine model for recurrent laryngeal injury. The functional outcomes matched with the histologic changes. These warrant further study to determine the safety margin for energy device in vicinity of recurrent laryngeal nerve.
Animals ; Dogs ; Laryngoscopy ; Recurrent Laryngeal Nerve ; Recurrent Laryngeal Nerve Injuries ; Thyroid Gland ; Vocal Cords

Background: Cross-talk between mitogen-activated protein kinase and estrogen has been reported; however, the role of BRAFV600E in the estrogen responsiveness of thyroid cancer is unknown. We elucidated the effect of BRAFV600E on the estrogen-induced increase in metastatic potential in thyroid cancer. Methods: Using a pair of cell lines, human thyroid cell lines which harbor wild type BRAF gene (Nthy/WT) and Nthy/BRAFV600E (Nthy/V600E), the expression of estrogen receptors (ERs) and estrogen-induced metastatic phenotypes were evaluated. Susceptibility to ERα- and ERβ-selective agents was evaluated to confirm differential ER expression. ESR expression was analyzed according to BRAFV600E status and age (≤50 years vs. >50 years) using The Cancer Genome Atlas (TCGA) data. Results: Estradiol increased the ERα/ERβ expression ratio in Nthy/V600E, whereas the decreased ERα/ERβ expression ratio was found in Nthy/WT. BRAFV600E-mutated cell lines showed a higher E2-induced increase in metastatic potential, including migration, invasion, and anchorage-independent growth compared with Nthy/WT. An ERα antagonist significantly inhibited migration in Nthy/V600E cells, whereas an ERβ agonist was more effective in Nthy/WT. In the BRAFV600E group, ESR1/ESR2 ratio was significantly higher in younger age group (≤50 years) compared with older age group (>50 years) by TCGA data analysis. Conclusion Our data show that BRAFV600E mutation plays a crucial role in the estrogen responsiveness of thyroid cancer by regulating ER expression. Therefore, BRAFV600E might be used as a biomarker when deciding future hormone therapies based on estrogen signaling in thyroid cancer patients.

Objectives: . The BRAFV600E mutation is a major driver mutation in papillary thyroid cancer. The aim of this study was to elucidate the correlation between DNA methylation and gene expression changes induced by the BRAFV600E mutation in thyroid cells. Methods: . We used Nthy/BRAF cell lines generated by transfection of Nthy/ori cells with the wild-type BRAF gene (Nthy/WT cells) and the V600E mutant-type BRAF gene (Nthy/V600E cells). We performed gene expression microarray and DNA methylation array analyses for Nthy/WT and Nthy/V600E cells. Two types of array data were integrated to identify inverse correlations between methylation and gene expression. The results were verified in silico using data from The Cancer Genome Atlas (TCGA) and in vivo through pyrosequencing and quantitative real-time polymerase chain reaction (qRT-PCR). Results: . In the Nthy/V600E cells, 199,821 probes were significantly hypermethylated, and 697 genes showed a “hypermethylation-downregulation” pattern in Nthy/V600E. Tumor suppressor genes and apoptosis-related genes were included. In total, 66,446 probes were significantly hypomethylated, and 227 genes showed a “hypomethylation-upregulation” pattern in Nthy/V600E cells. Protooncogenes and developmental protein-coding genes were included. In the TCGA analysis, 491/697 (70.44%) genes showed a hypermethylation-downregulation pattern, and 153/227 (67.40%) genes showed a hypomethylation-upregulation pattern. Ten selected genes showed a similar methylation-gene expression pattern in pyrosequencing and qRT-PCR. Conclusion . Induction of the BRAFV600E mutation in thyroid cells led to frequent hypermethylation. Anticancer genes, such as those involved in tumor suppression or apoptosis, were downregulated by upstream hypermethylation, whereas carcinogenic genes, such as protooncogenes, were upregulated by hypomethylation. Our results suggest that the BRAFV600E mutation in thyroid cells modulates DNA methylation and results in cancer-related gene expression.

Cushing's syndrome results from prolonged exposure to high levels of glucocorticoid hormones. ACTH-dependent Cushing's syndrome accounts for about 85% of endogenous causes. Autonomous pituitary ACTH secretion, called Cushing's disease, is responsible for 80% of these causes, whereas ectopic ACTH secretion is responsible for 20% of them. Appropriate therapy of patients with Cushing's syndrome depends on accurate diagnosis and classification of the disorder. In addition to the history and clinical evaluation, the laboratory evaluation of a patient with Cushingoid appearance is necessary to establish the diagnosis and determine the cause of hypercortisolism. A major problem in the differential diagnosis of ACTH-dependent Cushing's syndrome is distinguishing Cushing's disease from the ectopic ACTH syndrome. Both entities can have similar clinical and laboratory features. In addition, both pituitary microadenoma and ectopic ACTH-secreting tumors may be radiologically occult. Bilateral inferior petrosal sinus and peripheral vein catheterization with simultaneous collection of samples for measurement of ACTH is one of the most specific tests available to localize the source of ACTH production. We report two cases of Cushing's syndrome diagnosed by inferior petrosal sinus sampling associated with normal or low ACTH levels on routine basal hormone assay.
ACTH Syndrome, Ectopic ; Adrenocorticotropic Hormone* ; Catheterization ; Catheters ; Classification ; Cushing Syndrome* ; Diagnosis ; Diagnosis, Differential ; Humans ; Petrosal Sinus Sampling ; Plasma* ; Veins