ABSTRACT
BACKGROUND: The purpose of this study was to examine the possible prognostics and clinicopathologic characteristics underlying the BRAFV600E mutation and papillary thyroid carcinoma (PTC) coexisting or in absence of chronic lymphocytic thyroiditis (CLT). METHODS: This study was conducted on 172 patients who had undergone total thyroidectomy or unilateral total thyroidectomy for PTC; the patients were then examined for the BRAFV600E mutation using specimens obtained after their surgery from January 2013 to August 2015. RESULTS: BRAF mutations were found in 130 of 172 patients (75.6%). CLT was present in 27.9% of patients (48/172). The incidence of the BRAFV600E mutation was significantly increased in the group with no CLT (P = 0.001). The findings of the multivariate analysis pertaining to the coexistence of CLT and PTC showed no significant correlation other than the BRAFV600E mutation. No significant difference was noted in the clinicopathologic factors between the two groups based on the coexistence of CLT in univariate and multivariate analyses. CONCLUSIONS: The BRAFV600E mutation is less frequent in PTC coexisting with CLT presumably because CLT and the BRAFV600E mutation operate independently in the formation and progression of thyroid cancer.
Subject(s)
Carcinoma, Papillary/genetics , Genetic Predisposition to Disease/epidemiology , Hashimoto Disease/genetics , Proto-Oncogene Proteins B-raf/genetics , Thyroid Neoplasms/genetics , Adult , Aged , Biopsy, Needle , Carcinoma, Papillary/complications , Carcinoma, Papillary/pathology , Carcinoma, Papillary/surgery , Cohort Studies , Female , Hashimoto Disease/complications , Hashimoto Disease/pathology , Hashimoto Disease/surgery , Humans , Immunohistochemistry , Incidence , Male , Middle Aged , Mutation/genetics , Prognosis , Retrospective Studies , Risk Assessment , Thyroid Cancer, Papillary , Thyroid Neoplasms/complications , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery , Thyroidectomy/methods , Treatment OutcomeABSTRACT
Thyroid cancer is the most common endocrine malignancy and can range in severity from relatively slow-growing occult differentiated thyroid cancer to uniformly aggressive and fatal anaplastic thyroid cancer. A subset of patients with papillary thyroid cancer present with aggressive disease that is refractory to conventional treatment. Myricetin is a flavonol compound found in a variety of berries as well as walnuts and herbs. Previous studies have demonstrated that myricetin exhibits anti-cancer activity against several tumor types. However, an anti-cancer effect of myricetin against human papillary thyroid cancer (HPTC) cells has not been established. The present investigation was undertaken to gain insights into the molecular mechanism of the anti-cancer activity of myricetin against HPTC cells. We examined the cytotoxicity, DNA damaging, and cell cycle arresting activities of myricetin using SNU-790 HPTC cells. We found that myricetin exhibited cytotoxicity and induced DNA condensation in SNU-790 HPTC cells in a dose-dependent manner. Moreover, myricetin up-regulated the activation of caspase cascades and the Bax:Bcl-2 expression ratio. In addition, myricetin induced the release of apoptosis-inducing factor (AIF) and altered the mitochondrial membrane potential. Our results suggest that myricetin induces the death of SNU-790 HPTC cells and thus may prove useful in the development of therapeutic agents for human thyroid cancers.
Subject(s)
Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Carcinoma, Papillary/drug therapy , Carcinoma, Papillary/pathology , Flavonoids/therapeutic use , Mitochondria/metabolism , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/pathology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis Inducing Factor/metabolism , Caspases/metabolism , Cell Cycle/drug effects , Cell Line, Tumor , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Flavonoids/chemistry , Flavonoids/pharmacology , Humans , Mitochondria/drug effects , Thyroid Cancer, Papillary , bcl-2-Associated X Protein/metabolismABSTRACT
AIM: Thyroid cancer is the most common endocrine malignancy, with an increasing incidence worldwide. Most thyroid cancers are well differentiated and have a favorable outcome. However, undifferentiated thyroid cancers are one of the most lethal human malignancies. Anaplastic thyroid cancer (ATC) accounts for 2% of all thyroid cancers, and its median survival rate is low. ATC is responsible for more than one-third of thyroid cancer-related deaths. Myricetin is a flavonol compound found in walnuts, herbs, and various berries and is known to induce apoptotic death of various types of cancer cells. However, an anticancer effect of myricetin against human anaplastic thyroid cancer (HATCs) cells has not been demonstrated. MATERIALS AND METHODS: In the present study, the anticancer effects and mechanism of action of myricetin were examined using SNU-80 HATC cells. SNU-80 HATC cells were treated with various concentrations of myricetin and compared with untreated controls. RESULTS: Myricetin significantly reduced HATC cell proliferation, by approximately 70%. A substantial proportion of dead cells exhibited arrest in the sub-G1 phase. Myricetin also exhibited cytotoxicity and induced DNA condensation in SNU-80 HATC cells in a dose-dependent manner. The mechanism of myricetin-induced cell death involved an increase in the activation of caspase cascades and the Bax:Bcl-2 ratio at a concentration of 100 µM. Myricetin also induced the release of apoptosis-inducing factor (AIF) from mitochondria into the cytosol and altered the mitochondrial membrane potential. CONCLUSION: Our results indicate that myricetin is a potent inducer of HATC cell death and may thus prove useful in the development of therapeutic agents for HATC.
Subject(s)
Apoptosis/drug effects , Flavonoids/pharmacology , Membrane Potential, Mitochondrial/drug effects , Mitochondria/pathology , Thyroid Carcinoma, Anaplastic/pathology , Thyroid Neoplasms/pathology , Caspases/metabolism , Cell Cycle/drug effects , Cell Proliferation/drug effects , Humans , Mitochondria/drug effects , Mitochondria/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Thyroid Carcinoma, Anaplastic/drug therapy , Thyroid Carcinoma, Anaplastic/metabolism , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/metabolism , Tumor Cells, Cultured , bcl-2-Associated X Protein/metabolismABSTRACT
OBJECTIVES: This study was to evaluate the performance of the newly developed information system (IS) implemented on July 1, 2014 at three public hospitals in Korea. METHODS: User satisfaction scores of twelve key performance indicators of six IS success factors based on the DeLone and McLean IS Success Model were utilized to evaluate IS performance before and after the newly developed system was introduced. RESULTS: All scores increased after system introduction except for the completeness of medical records and impact on the clinical environment. The relationships among six IS factors were also analyzed to identify the important factors influencing three IS success factors (Intention to Use, User Satisfaction, and Net Benefits). All relationships were significant except for the relationships among Service Quality, Intention to Use, and Net Benefits. CONCLUSIONS: The results suggest that hospitals should not only focus on systems and information quality; rather, they should also continuously improve service quality to improve user satisfaction and eventually reach full the potential of IS performance.
ABSTRACT
PURPOSE: Extrathyroidal extension (ETE) of papillary thyroid carcinoma (PTC) is a risk factor for tumor recurrence. By TNM Classification (7th edition), differentiated thyroid carcinoma with ETE is designated T3 (minimal invasion), T4a (extended invasion), or T4b (more extensive unresectable invasion), according to the degree of tumor involvement. We subsequently focused our investigation on minimal ETE (MEE), analyzing the clinicopathologic characteristics, recurrence rate, and recurrence-free survival (RFS) in this setting. METHODS: A retrospective study was conducted, based on 332 patients undergoing thyroidectomy for PTC between January 2005 and December 2006. RESULTS: The study population was stratified into two groups: PTC with MEE (103/332; 31.0%) and PTC without MEE (229/332; 69.0%). In patients with PTC, MEE correlated with gender, tumor size, multifocality, lymph node (LN) metastasis, underlying Hashimoto's thyroiditis, and the nature of the surgery. However, no significant intergroup differences were evident with respect to age, recurrence rate, and LN metastasis. In multivariate analysis, LN metastasis (odds ratio = 2.273; 95% confidence interval, 1.280-4.037) was recognized as an independent correlate of mETE (p = 0.005). However, recurrence-free survival did not differ significantly between the groups (p = 0.153), even when further stratified by the presence or absence of LN metastasis. CONCLUSION: In patients with PTC, MEE does not impact RFS. Thus, appropriate surgical intervention and postoperative follow up are mandatory in PTC, regardless of its extent.