Center for Thyroid Cancer

Ilsan, South Korea

Center for Thyroid Cancer

Ilsan, South Korea
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Hwangbo Y.,Center for Thyroid Cancer | Lee E.K.,Center for Thyroid Cancer
Endocrinology and Metabolism | Year: 2017

Hyperglycemia during chemotherapy occurs in approximately 10% to 30% of patients. Glucocorticoids and L-asparaginase are well known to cause acute hyperglycemia during chemotherapy. Long-term hyperglycemia is also frequently observed, especially in patients with hematologic malignancies treated with L-asparaginase-based regimens and total body irradiation. Glucocorticoid-induced hyperglycemia often develops because of increased insulin resistance, diminished insulin secretion, and exaggerated hepatic glucose output. Screening strategies for this condition include random glucose testing, hemoglobin A1c testing, oral glucose loading, and fasting plasma glucose screens. The management of hyperglycemia starts with insulin or sulfonylurea, depending on the type, dose, and delivery of the glucocorticoid formulation. Mammalian target of rapamycin (mTOR) inhibitors are associated with a high incidence of hyperglycemia, ranging from 13% to 50%. Immunotherapy, such as anti-programmed death 1 (PD-1) antibody treatment, induces hyperglycemia with a prevalence of 0.1%. The proposed mechanism of immunotherapy-induced hyperglycemia is an autoimmune process (insulitis). Withdrawal of the PD-1 inhibitor is the primary treatment for severe hyperglycemia. The efficacy of glucocorticoid therapy is not fully established and the decision to resume PD-1 inhibitor therapy depends on the severity of the hyperglycemia. Diabetic patients should achieve optimized glycemic control before initiating treatment, and glucose levels should be monitored periodically in patients initiating mTOR inhibitor or PD-1 inhibitor therapy. With regard to hyperglycemia caused by anticancer therapy, frequent monitoring and proper management are important for promoting the efficacy of anti-cancer therapy and improving patients' quality of life. © 2017 Korean Endocrine Society.

Park Y.J.,Seoul National University | Lee E.K.,Seoul National University | Lee E.K.,Center for Thyroid Cancer | Lee Y.K.,Baylor College of Medicine | And 4 more authors.
Toxicology and Applied Pharmacology | Year: 2012

Clinical hypothyroidism affects various metabolic processes including drug metabolism. CYP2B and CYP3A are important cytochrome P450 drug metabolizing enzymes that are regulated by the xenobiotic receptors constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2). We evaluated the regulation of the hepatic expression of CYPs by CAR and PXR in the hypothyroid state induced by a low-iodine diet containing 0.15% propylthiouracil. Expression of Cyp3a11 was suppressed in hypothyroid C57BL/6 wild type (WT) mice and a further decrement was observed in hypothyroid CAR -/- mice, but not in hypothyroid PXR -/- mice. In contrast, expression of Cyp2b10 was induced in both WT and PXR -/- hypothyroid mice, and this induction was abolished in CAR -/- mice and in and CAR -/- PXR -/- double knockouts. CAR mRNA expression was increased by hypothyroidism, while PXR expression remained unchanged. Carbamazepine (CBZ) is a commonly used antiepileptic that is metabolized by CYP3A isoforms. After CBZ treatment of normal chow fed mice, serum CBZ levels were highest in CAR -/- mice and lowest in WT and PXR -/- mice. Hypothyroid WT or PXR -/- mice survived chronic CBZ treatment, but all hypothyroid CAR -/- and CAR -/- PXR -/- mice died, with CAR -/-PXR -/- mice surviving longer than CAR -/- mice (12.3±3.3days vs. 6.3±2.1days, p=0.04). All these findings suggest that hypothyroid status affects xenobiotic metabolism, with opposing responses of CAR and PXR and their CYP targets that can cancel each other out, decreasing serious metabolic derangement in response to a xenobiotic challenge. © 2012 Elsevier Inc.

Shin D.W.,Seoul National University | Cho J.,Sungkyunkwan University | Kim S.Y.,National Cancer Control Research Institute | Guallar E.,Johns Hopkins Medical Institutions | And 7 more authors.
Annals of Surgical Oncology | Year: 2013

Background: Surgery for cancer is often delayed due to variety of patient-, provider-, and health system-related factors. However, impact of delayed surgery is not clear, and may vary among cancer types. We aimed to determine the impact of the delay from cancer diagnosis to potentially curative surgery on survival. Methods: Cohort study based on representative sample of patients (n = 7,529) with colorectal, breast, lung and thyroid cancer with local or regional disease who underwent potentially curative surgery as their first therapeutic modality within 1 year of cancer diagnosis. They were diagnosed in 2006 and followed for mortality until April 2011, a median follow-up of 4.7 years. Results: For colorectal and breast cancers, the adjusted hazard ratios (95 % confidence intervals) for all-cause mortality comparing a surgical delay beyond 12 weeks to performing surgery within weeks 1-4 after diagnosis were 2.65 (1.50-4.70) and 1.91 (1.06-3.49), respectively. No clear pattern of increased risk was observed with delays between 4 and 12 weeks, or for any delay in lung and thyroid cancers. Concordance between the area of the patient's residence and the hospital performing surgery, and the patient's income status were associated with delayed surgery. Conclusions: Delays to curative surgery beyond 12 weeks were associated with increased mortality in colorectal and breast cancers, suggesting that health provision services should be organized to avoid unnecessary treatment delays. Health care systems should also aim to reduce socioeconomic and geographic disparities and to guarantee equitable access to high quality cancer care. © 2013 Society of Surgical Oncology.

Cho Y.Y.,Sungkyunkwan University | Lim J.,National Cancer Center | Oh C.-M.,National Cancer Center | Ryu J.,Center for Thyroid Cancer | And 4 more authors.
Cancer | Year: 2015

BACKGROUND: Thyroid cancer affects relatively young adults, and its overall survival is excellent. With long life expectancy, the development of subsequent cancers is an important concern for survivors of thyroid cancer. The objective of this study was to investigate the incidence and types of second primary malignancies in Korean patients with thyroid cancer. METHODS: The study cohort included 178,844 registrants with thyroid cancer from the Korea Central Cancer Registry (KCCR) database between 1993 and 2010. Standardized incidence ratios (SIRs) were calculated using a statistical software program (SEER∗Stat 8.0.4). RESULTS: Among 178,844 patients with thyroid cancer, 2895 (1.6%) were diagnosed with subsequent second primary malignancies. The overall risks of a second primary cancer were elevated by 6% in patients who had thyroid cancer compared with the general population during the same period. The elevated risks for developing second cancers were observed in all sites except the stomach and cervix. The elevated risk of second primary cancers was observed within the first 10 years of follow-up. Leukemia and cancers of the salivary gland, kidney, prostate, lung, and breast had the most significantly elevated risks as secondary cancers and presented as early as during the first 5 years after the initial diagnosis of thyroid cancer. CONCLUSIONS: This is the largest, standardized, population-based study to date using nationwide data from the entire Korean population. The risks of several cancers were elevated significantly during follow-up, thus alerting physicians to pay special attention in their care of patients with thyroid cancer and long-term survivors. © 2014 American Cancer Society.

Kim Y.-I.,Center for Gastric Cancer | Kim S.Y.,National Cancer Control Institute | Cho S.-J.,Center for Gastric Cancer | Park J.-H.,National Cancer Control Institute | And 7 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2014

Background Metformin use has been associated with a decreased incidence and mortality of various cancers. Aim To evaluate the association between metformin use and gastric cancer. Methods We randomly selected 100 000 type 2 diabetic patients from the 2004 Korean National Health Insurance claim database, and assessed gastric cancer incidence among 39 989 patients (aged 30-97 years) who were regularly treated with anti-diabetic drugs and followed-up from 2004 to 2010. In total, 26 690 patients had used metformin out of 32 978 diabetics who had not regularly used insulin (insulin non-users), and 5855 patients had used metformin out of 7011 regular insulin users. Results Patients who used metformin showed a lower incidence of gastric cancer than those who did not use metformin, in insulin non-users (P = 0.047, log-rank test). However, in patients on regular insulin, there was no difference of gastric cancer incidence according to metformin use. In insulin non-users, the adjusted hazard ratio (AHR) for metformin use was 0.73 (95% confidential interval [CI], 0.53-1.01) with borderline statistical significance (P = 0.059). Duration of metformin use was associated with the reduction in gastric cancer risk (AHR, 0.88; 95% CI 0.81-0.96, P = 0.003), especially in patients who used metformin for more than 3 years (AHR, 0.57; 95% CI, 0.37-0.87; P = 0.009). Conclusion Metformin use >3 years in type 2 diabetics who do not use insulin is associated with a significantly reduced gastric cancer risk. © 2014 John Wiley & Sons Ltd.

Jang J.Y.,Sungkyunkwan University | Park J.-O.,Sungkyunkwan University | Ryu J.,Center for Thyroid Cancer | Jeong H.-S.,Sungkyunkwan University
Clinical and Experimental Otorhinolaryngology | Year: 2014

Objectives. Advancements in medical endoscopy and techniques of rigid bronchoscopy for foreign body removal have enabled higher diagnostic accuracy, reduced morbidity and precise manipulation. However, in pediatric patients, endoscope-combined forceps may be too big to fit into the small sized airway. Here we present our method of endoscope assisted rigid bronchoscopy in pediatric patients and compare the clinical benefits with conventional naked-eye rigid bronchoscopy.Methods. We used a 2.7 mm, 0° straight endoscope and small caliber grasping forceps with 3.0 to 4.5 mm sized rigid bronchoscopy for very young (<3 years of age) patients of foreign body aspiration. As an assistant held the rigid bronchoscope in situ, the operator could manipulate the endoscope and forceps bimanually. With endoscopic guidance, the foreign body retrieval was performed carefully. The clinical advantages were compared between our endoscope-assisted method (n=29) and the conventional bronchoscopy method (n=33) in terms of operation time and recovery (hospital stay).Results. Bimanual endoscope-assisted rigid bronchoscopy method was technically feasible and safe. The operation time was less, compared to the conventional technique and the patients recovered more quickly. In all cases, our method completely removed the foreign body without need of a second bronchoscopy procedure.Conclusion. Bimanual endoscope-assisted retrieval of airway foreign body in very young age pediatric patients was superior to the conventional naked-eye method concerning accurate manipulation and safety. © 2014 by Korean Society of Otorhinolaryngology-Head and Neck Surgery.

PubMed | University of Houston, National Cancer Center, Baylor College of Medicine, Korea Atomic Energy Research Institute and 4 more.
Type: Journal Article | Journal: Oncotarget | Year: 2016

nc886 is a recently identified cellular non-coding RNA and its depletion leads to acute cell death via PKR (Protein Kinase RNA-activated) activation. nc886 expression is increased in some malignancies, but silenced in others. However, the precise role of nc886/PKR is controversial: is it a tumor suppressor or an oncogene? In this study, we have clarified the role of nc886 in thyroid cancer by sequentially generating PKR knockout (KO) and PKR/nc886 double KO cell lines from Nthy-ori 3-1, a partially transformed thyroid cell line. Compared to the wildtype, PKR KO alone does not exhibit any significant phenotypic changes. However, nc886 KO cells are less proliferative, migratory, and invasive than their parental PKR KO cells. Importantly, the requirement of nc886 in tumor phenotypes is totally independent of PKR. In our microarray data, nc886 KO suppresses some genes whose elevated expression is associated with poor survival confirmed by data from total of 505 thyroid cancer patients in the Caner Genome Atlas project. Also, the nc886 expression level tends to be elevated and in more aggressively metastatic tumor specimens from thyroid cancer patients. In summary, we have discovered nc886s tumor-promoting role in thyroid cancer which has been concealed by the PKR-mediated acute cell death.

Lee Y.-K.,Seoul National University | Lee Y.-J.,Center for Thyroid Cancer | Ha Y.-C.,Chung - Ang University | Koo K.-H.,Seoul National University
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context: Osteoporotic hip fracture is known to be associated with excess mortality. The 1-year mortality rate after hip fracture is known to reach up to ∼20%, similar to that of cancer. However, there was no study that compared cancer survival. Recently, relative survival has been used to present a prognosis for a particular disease. Objective: The purpose of this study was to compare the 5-year relative survival after osteoporotic hip fracture with those of general population and cancer patients. Design, Setting, and Patients: Were trospectively reviewed the medical records of 727 patients who were treated for osteoporotic hip fractures from 2003 to 2009. Intervention: Intervention was hip fracture surgery. Main Outcome Measure: Five-year relative survival after fracture was estimated and was compared with survival in the general population and in cancer patients. Relative survival of 100% would reflect no excess mortality associated with the hip fracture compared with the general population. Results: Cumulative mortality was 32.3% at 5 years, and 5-year absolute survival rate was 63.0% (95% confidence interval, 59.0%-66.9%). Five-year relative survival of hip fracture was 93.9% (95% confidence interval 87.5%-99.7%), which was comparable with those of thyroid or breast cancer (99.8% and 91.0%, respectively). Conclusions: Our results showed that 5-year relative survival after osteoporotic hip fracture was below those of the general populations and was comparable with some cancers such as thyroid and breast cancer. Therefore, osteoporotic hip fracture should not be overlooked. (J Clin Endocrinol Metab 99: 97-100, 2014). © Copyright 2014 by The Endocrine Society.

Cho S.W.,Seoul National University | Cho S.W.,National Medical Center | Kim Y.A.,Seoul National University | Sun H.J.,National Medical Center | And 9 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Results: In 27 PTC patients, 60% of patients showed β-catenin up-regulation and Dkk-1 downregulation in tumor vs normal tissues. Tissue microarray analysis showed that 14 of 148 PTC samples exhibited cytoplasmic-dominant β-catenin expression compared to membranous-dominant expression in normal tissues. Aberrant β-catenin expression was significantly correlated with higher rates of the loss of membranous E-cadherin expression and poor disease-free survival than that in the normal membranous expression group over a median follow-up period of 14 years. Implantation of Dkk-1-overexpressing BHP10-3SC cells revealed delayed tumor growth, resulting from the rescue of membranous β-catenin and E-cadherin expressions. Furthermore, tissue microarray analysis demonstrated that BRAFWT patients had higher rates of aberrant expressions of β-catenin andE-cadherin thanBRAFV600E patients. Indeed, the inhibitory effects of Dkk-1oncell survivalwere more sensitive in BRAFWT (BHP10-3SC and TPC-1) than in BRAFV600E (SNU-790 and BCPAP) cells. Overexpression of BRAFV600E in normal thyroid epithelial (H tori) cells also reduced the effects of Dkk-1 on cell survival.Background: Aberrant activation of the Wnt/β-catenin pathway is a common pathogenesis of various human cancers. We investigated the role of the Wnt inhibitor, Dkk-1, in papillary thyroid cancer (PTC). CopyrightMethods: Immunohistochemicalβ-catenin staining was performed in tissue microarray containing 148 PTCs and five normal thyroid tissues. In vivo effects of Dkk-1 were explored using ectopic tumors with BHP10-3SC cells.Conclusion: Asubset of PTC patients showed aberrant expression of β-catenin/E-cadherin signaling and poor disease-free survival. Dkk-1 might have a therapeutic role, particularly in BRAFWT patients. © 2014 by the Endocrine Society.

Kim S.-J.,Seoul National University | Park S.Y.,Center for Thyroid Cancer | Lee Y.J.,Center for Thyroid Cancer | Lee E.K.,Center for Thyroid Cancer | And 7 more authors.
Annals of Surgical Oncology | Year: 2014

Background: Lateral lymph node metastasis is an important prognostic factor and is predictive of tumor recurrence and cause-specific survival in patients with papillary thyroid cancer (PTC). However, the factors predicting recurrence and clinical outcomes after therapeutic lateral neck dissection are not well established. The aims of this study were to evaluate the incidence, pattern, and factors predictive of PTC recurrence after therapeutic lateral neck dissection. Materials and Methods: The records of 126 consecutive patients who underwent total thyroidectomy with therapeutic lateral neck dissection for primary PTC at the National Cancer Center were retrospectively reviewed. The factors predictive of recurrence were determined using both univariate and multivariate analyses considering several clinicopathologic variables. Results: The median follow-up period was 61.2 months, during which 22 patients (17.5 %) experienced recurrence with 1 death (0.8 %) due to disease. Locoregional recurrence and distant metastasis were found in 20 cases (15.9 %) and 2 cases (1.6 %), respectively. Male gender, aggressive histology, number of lymph node metastases, initial level of T4-off Tg per ng/mL, and ATA risk categories (high risk) were independent risk factors for recurrence. Of note, initial T4-off Tg levels greater than 4.2 ng/mL showed highest sensitivity and specificity in predicting recurrence. Conclusions: These results provide useful information regarding the clinical outcomes after therapeutic lateral neck dissection for primary PTC and can be used to identify at-risk patients who need aggressive treatment and intensive surveillance for postoperative recurrence. © 2014 Society of Surgical Oncology.

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