1.Tumor Spheroids of an Aggressive Form of Central Neurocytoma Have Transit-Amplifying Progenitor Characteristics with Enhanced EGFR and Tumor Stem Cell Signaling
Hye Young SHIN ; Kyung-Seok HAN ; Hyung Woo PARK ; Yun Hwa HONG ; Yona KIM ; Hyo Eun MOON ; Kwang Woo PARK ; Hye Ran PARK ; C. Justin LEE ; Kiyoung LEE ; Sang Jeong KIM ; Man Seung HEO ; Sung-Hye PARK ; Dong Gyu KIM ; Sun Ha PAEK
Experimental Neurobiology 2021;30(2):120-143
Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as KLF4 and TPD5L1, when compared to their differentiated cells and human NSCs. Importantly, Gene Set Enrichment Analysis showed that gene sets of GBM-Spheroids, EGFR Signaling, and Packaging of Telomere Ends are enriched in CN-spheroids in comparison with their differentiated cells. We speculate that CN tumor stem cells have TAP and RGC characteristics, and upregulation of EGFR signaling as well as downregulation of eph-ephrin signaling have critical roles in tumorigenesis of CN. And their ephemeral nature of TAPs destined to neuroblasts, might reflect benign nature of CN.
2.Free-Breathing Motion-Corrected Single-Shot Phase-Sensitive Inversion Recovery Late-Gadolinium-Enhancement Imaging: A Prospective Study of Image Quality in Patients with Hypertrophic Cardiomyopathy
Min Jae CHA ; Iksung CHO ; Joonhwa HONG ; Sang-Wook KIM ; Seung Yong SHIN ; Mun Young PAEK ; Xiaoming BI ; Sung Mok KIM
Korean Journal of Radiology 2021;22(7):1044-1053
Objective:
Motion-corrected averaging with a single-shot technique was introduced for faster acquisition of late-gadoliniumenhancement (LGE) cardiovascular magnetic resonance (CMR) imaging while free-breathing. We aimed to evaluate the image quality (IQ) of free-breathing motion-corrected single-shot LGE (moco-ss-LGE) in patients with hypertrophic cardiomyopathy (HCM).
Materials and Methods:
Between April and December 2019, 30 patients (23 men; median age, 48.5; interquartile range [IQR], 36.5–61.3) with HCM were prospectively enrolled. Breath-held single-shot LGE (bh-ss-LGE) and free-breathing mocoss-LGE images were acquired in random order on a 3T MR system. Semi-quantitative IQ scores, contrast-to-noise ratios (CNRs), and quantitative size of myocardial scar were assessed on pairs of bh-ss-LGE and moco-ss-LGE. The mean ± standard deviation of the parameters was obtained. The results were compared using the Wilcoxon signed-rank test.
Results:
The moco-ss-LGE images had better IQ scores than the bh-ss-LGE images (4.55 ± 0.55 vs. 3.68 ± 0.45, p < 0.001). The CNR of the scar to the remote myocardium (34.46 ± 11.85 vs. 26.13 ± 10.04, p < 0.001), scar to left ventricle (LV) cavity (13.09 ± 7.95 vs. 9.84 ± 6.65, p = 0.030), and LV cavity to remote myocardium (33.12 ± 15.53 vs. 22.69 ± 11.27, p < 0.001) were consistently greater for moco-ss-LGE images than for bh-ss-LGE images. Measurements of scar size did not differ significantly between LGE pairs using the following three different quantification methods: 1) full width at half-maximum method; 23.84 ± 12.88% vs. 24.05 ± 12.81% (p = 0.820), 2) 6-standard deviation method, 15.14 ± 10.78% vs. 15.99 ± 10.99% (p = 0.186), and 3) 3-standard deviation method; 36.51 ± 17.60% vs. 37.50 ± 17.90% (p = 0.785).
Conclusion
Motion-corrected averaging may allow for superior IQ and CNRs with free-breathing in single-shot LGE imaging, with a herald of free-breathing moco-ss-LGE as the scar imaging technique of choice for clinical practice.
3.A Multicenter, Randomized, Controlled Trial for Assessing the Usefulness of Suppressing Thyroid Stimulating Hormone Target Levels after Thyroid Lobectomy in Low to Intermediate Risk Thyroid Cancer Patients (MASTER): A Study Protocol
Eun Kyung LEE ; Yea Eun KANG ; Young Joo PARK ; Bon Seok KOO ; Ki-Wook CHUNG ; Eu Jeong KU ; Ho-Ryun WON ; Won Sang YOO ; Eonju JEON ; Se Hyun PAEK ; Yong Sang LEE ; Dong Mee LIM ; Yong Joon SUH ; Ha Kyoung PARK ; Hyo-Jeong KIM ; Bo Hyun KIM ; Mijin KIM ; Sun Wook KIM ; Ka Hee YI ; Sue K. PARK ; Eun-Jae JUNG ; June Young CHOI ; Ja Seong BAE ; Joon Hwa HONG ; Kee-Hyun NAM ; Young Ki LEE ; Hyeong Won YU ; Sujeong GO ; Young Mi KANG ;
Endocrinology and Metabolism 2021;36(3):574-581
Background:
Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy.
Methods:
This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years.
Conclusion
The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.
4.Free-Breathing Motion-Corrected Single-Shot Phase-Sensitive Inversion Recovery Late-Gadolinium-Enhancement Imaging: A Prospective Study of Image Quality in Patients with Hypertrophic Cardiomyopathy
Min Jae CHA ; Iksung CHO ; Joonhwa HONG ; Sang-Wook KIM ; Seung Yong SHIN ; Mun Young PAEK ; Xiaoming BI ; Sung Mok KIM
Korean Journal of Radiology 2021;22(7):1044-1053
Objective:
Motion-corrected averaging with a single-shot technique was introduced for faster acquisition of late-gadoliniumenhancement (LGE) cardiovascular magnetic resonance (CMR) imaging while free-breathing. We aimed to evaluate the image quality (IQ) of free-breathing motion-corrected single-shot LGE (moco-ss-LGE) in patients with hypertrophic cardiomyopathy (HCM).
Materials and Methods:
Between April and December 2019, 30 patients (23 men; median age, 48.5; interquartile range [IQR], 36.5–61.3) with HCM were prospectively enrolled. Breath-held single-shot LGE (bh-ss-LGE) and free-breathing mocoss-LGE images were acquired in random order on a 3T MR system. Semi-quantitative IQ scores, contrast-to-noise ratios (CNRs), and quantitative size of myocardial scar were assessed on pairs of bh-ss-LGE and moco-ss-LGE. The mean ± standard deviation of the parameters was obtained. The results were compared using the Wilcoxon signed-rank test.
Results:
The moco-ss-LGE images had better IQ scores than the bh-ss-LGE images (4.55 ± 0.55 vs. 3.68 ± 0.45, p < 0.001). The CNR of the scar to the remote myocardium (34.46 ± 11.85 vs. 26.13 ± 10.04, p < 0.001), scar to left ventricle (LV) cavity (13.09 ± 7.95 vs. 9.84 ± 6.65, p = 0.030), and LV cavity to remote myocardium (33.12 ± 15.53 vs. 22.69 ± 11.27, p < 0.001) were consistently greater for moco-ss-LGE images than for bh-ss-LGE images. Measurements of scar size did not differ significantly between LGE pairs using the following three different quantification methods: 1) full width at half-maximum method; 23.84 ± 12.88% vs. 24.05 ± 12.81% (p = 0.820), 2) 6-standard deviation method, 15.14 ± 10.78% vs. 15.99 ± 10.99% (p = 0.186), and 3) 3-standard deviation method; 36.51 ± 17.60% vs. 37.50 ± 17.90% (p = 0.785).
Conclusion
Motion-corrected averaging may allow for superior IQ and CNRs with free-breathing in single-shot LGE imaging, with a herald of free-breathing moco-ss-LGE as the scar imaging technique of choice for clinical practice.
5.A Multicenter, Randomized, Controlled Trial for Assessing the Usefulness of Suppressing Thyroid Stimulating Hormone Target Levels after Thyroid Lobectomy in Low to Intermediate Risk Thyroid Cancer Patients (MASTER): A Study Protocol
Eun Kyung LEE ; Yea Eun KANG ; Young Joo PARK ; Bon Seok KOO ; Ki-Wook CHUNG ; Eu Jeong KU ; Ho-Ryun WON ; Won Sang YOO ; Eonju JEON ; Se Hyun PAEK ; Yong Sang LEE ; Dong Mee LIM ; Yong Joon SUH ; Ha Kyoung PARK ; Hyo-Jeong KIM ; Bo Hyun KIM ; Mijin KIM ; Sun Wook KIM ; Ka Hee YI ; Sue K. PARK ; Eun-Jae JUNG ; June Young CHOI ; Ja Seong BAE ; Joon Hwa HONG ; Kee-Hyun NAM ; Young Ki LEE ; Hyeong Won YU ; Sujeong GO ; Young Mi KANG ;
Endocrinology and Metabolism 2021;36(3):574-581
Background:
Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy.
Methods:
This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years.
Conclusion
The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.
6.Tumor Spheroids of an Aggressive Form of Central Neurocytoma Have Transit-Amplifying Progenitor Characteristics with Enhanced EGFR and Tumor Stem Cell Signaling
Hye Young SHIN ; Kyung-Seok HAN ; Hyung Woo PARK ; Yun Hwa HONG ; Yona KIM ; Hyo Eun MOON ; Kwang Woo PARK ; Hye Ran PARK ; C. Justin LEE ; Kiyoung LEE ; Sang Jeong KIM ; Man Seung HEO ; Sung-Hye PARK ; Dong Gyu KIM ; Sun Ha PAEK
Experimental Neurobiology 2021;30(2):120-143
Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as KLF4 and TPD5L1, when compared to their differentiated cells and human NSCs. Importantly, Gene Set Enrichment Analysis showed that gene sets of GBM-Spheroids, EGFR Signaling, and Packaging of Telomere Ends are enriched in CN-spheroids in comparison with their differentiated cells. We speculate that CN tumor stem cells have TAP and RGC characteristics, and upregulation of EGFR signaling as well as downregulation of eph-ephrin signaling have critical roles in tumorigenesis of CN. And their ephemeral nature of TAPs destined to neuroblasts, might reflect benign nature of CN.
7.Association between Physical Fitness and Cardiometabolic Risk of Children and Adolescents in Korea
Hyun Suk LEE ; Won Wook JEONG ; Yu Jeong CHOI ; Young Gyun SEO ; Hye Mi NOH ; Hong Ji SONG ; Yu Jin PAEK ; Yoon Myung KIM ; Hyun Jung LIM ; Hye Ja LEE ; Han Byul JANG ; Sang Ick PARK ; Kyung Hee PARK
Korean Journal of Family Medicine 2019;40(3):159-164
BACKGROUND: This study aimed to investigate the association between physical fitness and cardiometabolic health of Korean children and adolescents. METHODS: In total, 168 participants (89 boys and 79 girls) aged 10–16 years were recruited for the Intervention for Childhood and Adolescent Obesity via Activity and Nutrition Study in 2016. The subjects were categorized into two groups using the definition of metabolic syndrome by the International Diabetes Federation: metabolically unhealthy (with at least two of the five criteria) and healthy groups (with less than one criterion). Correlation analysis of the participants' general characteristics was performed. Odds ratios (ORs) of physical fitness for cardiometabolic risk were evaluated via logistic regression. RESULTS: Metabolically unhealthy children showed greater weight, height, and body mass index, higher Children's Depression Inventory score, and longer screen time than did the metabolically healthy children. Metabolically healthy children showed greater upper and lower extremity muscular strength than did the metabolically unhealthy children (P=0.04 and P<0.001, respectively). In the multiple logistic regression analysis, lower extremity muscle strength was inversely related to the clustered cardiometabolic risk of the children and adolescents with or without adjustment for confounders (OR, 4.32; 95% confidence interval [CI], 1.87–9.97; OR, 7.64; 95% CI, 1.55–37.74, respectively). CONCLUSION: Physical fitness, especially lower extremity muscle strength, is significantly inversely associated with individual and clustered cardiometabolic risks in Korean children and adolescents.
Adolescent
;
Body Mass Index
;
Child
;
Depression
;
Humans
;
Korea
;
Logistic Models
;
Lower Extremity
;
Muscle Strength
;
Odds Ratio
;
Pediatric Obesity
;
Physical Fitness
8.Practice guidelines for management of uterine corpus cancer in Korea: a Korean Society of Gynecologic Oncology Consensus Statement.
Shin Wha LEE ; Taek Sang LEE ; Dae Gy HONG ; Jae Hong NO ; Dong Choon PARK ; Jae Man BAE ; Seok Ju SEONG ; So Jin SHIN ; Woong JU ; Keun Ho LEE ; Yoo Kyung LEE ; Hanbyoul CHO ; Chulmin LEE ; Jiheum PAEK ; Hyun Jung KIM ; Jeong Won LEE ; Jae Weon KIM ; Duk Soo BAE
Journal of Gynecologic Oncology 2017;28(1):e12-
Clinical practice guidelines for gynecologic cancers have been developed by many organizations. Although these guidelines have much in common in terms of the practice of standard of care for uterine corpus cancer, practice guidelines that reflect the characteristics of patients and healthcare and insurance systems are needed for each country. The Korean Society of Gynecologic Oncology (KSGO) published the first edition of practice guidelines for gynecologic cancer treatment in late 2006; the second edition was released in July 2010 as an evidence-based recommendation. The Guidelines Revision Committee was established in 2015 and decided to produce the third edition of the guidelines as an advanced form based on evidence-based medicine, considering up-to-date clinical trials and abundant qualified Korean data. These guidelines cover screening, surgery, adjuvant treatment, and advanced and recurrent disease with respect to endometrial carcinoma and uterine sarcoma. The committee members and many gynecologic oncologists derived key questions from the discussion, and a number of relevant scientific literatures were reviewed in advance. Recommendations for each specific question were developed by the consensus conference, and they are summarized here, together with other details. The objective of these practice guidelines is to establish standard policies on issues in clinical areas related to the management of uterine corpus cancer based on the findings in published papers to date and the consensus of experts as a KSGO Consensus Statement.
Committee Membership
;
Consensus*
;
Delivery of Health Care
;
Drug Therapy
;
Endometrial Neoplasms
;
Evidence-Based Medicine
;
Female
;
Humans
;
Insurance
;
Korea*
;
Mass Screening
;
Sarcoma
;
Standard of Care
9.Inhalation Lung Injury Associated with Humidifier Disinfectants in Adults.
Jin Won HUH ; Sang Bum HONG ; Kyung Hyun DO ; Hyun Jung KOO ; Se Jin JANG ; Moo Song LEE ; Domyung PAEK ; Dong Uk PARK ; Chae Man LIM ; Younsuck KOH
Journal of Korean Medical Science 2016;31(12):1857-1862
We recently established a novel disease entity presented as progressive respiratory failure associated with the inhalation of humidifier disinfectants. In April 2011, we encountered a series of peripartum patients with complaints of respiratory distress of unknown etiology, which was an uncommon phenomenon. Accordingly, we created a multidisciplinary team comprising intensivists, radiologists, pathologists, epidemiologists, and the Korea Centers for Disease Control and Prevention (KCDC). Further, we defined the disease entity and performed a case-control study, epidemiologic investigation, and animal study to determine the etiology. The study findings indicated that the lung injury outbreak was related to the inhalation of humidifier disinfectants and showed that household chemical inhalation can cause severe respiratory failure. Following the withdrawal of humidifier disinfectants from the Korean market in 2012, no such cases were reported. This tragic event is a warning that appropriate safety regulations and monitoring for potential toxic household chemicals are critical to protect public health.
Adult*
;
Animals
;
Case-Control Studies
;
Centers for Disease Control and Prevention (U.S.)
;
Disinfectants*
;
Family Characteristics
;
Humans
;
Humidifiers*
;
Inhalation*
;
Korea
;
Lung Injury*
;
Lung*
;
Peripartum Period
;
Public Health
;
Respiratory Insufficiency
;
Social Control, Formal
10.Proposed Motor Scoring System in a Porcine Model of Parkinson's Disease induced by Chronic Subcutaneous Injection of MPTP.
Joon Ho MOON ; Ji Ho KIM ; Hyung Jun IM ; Dong Soo LEE ; Eun Jung PARK ; Kilyoung SONG ; Hyun Ju OH ; Su Bin HYUN ; Sang Chul KANG ; Hyunil KIM ; Hyo Eun MOON ; Hyung Woo PARK ; Hong Jae LEE ; Eun Ji KIM ; Seokjoong KIM ; Byeong Chun LEE ; Sun Ha PAEK
Experimental Neurobiology 2014;23(3):258-265
Destruction of dopaminergic neurons in the substantia nigra pars compacta (SNpc) is a common pathophysiology of Parkinson's disease (PD). Characteristics of PD patients include bradykinesia, muscle rigidity, tremor at rest and disturbances in balance. For about four decades, PD animal models have been produced by toxin-induced or gene-modified techniques. However, in mice, none of the gene-modified models showed all 4 major criteria of PD. Moreover, distinguishing between PD model pigs and normal pigs has not been well established. Therefore, we planned to produce a pig model for PD by chronic subcutaneous administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), neurotoxin. Changes in behavioral patterns of pigs were thoroughly evaluated and a new motor scoring system was established for this porcine model that was based on the Unified Parkinson's Disease Rating Scale (UPDRS) in human PD patients. In summary, this motor scoring system could be helpful to analyze the porcine PD model and to confirm the pathology prior to further examinations, such as positron emission tomography-computed tomography (PET-CT), which is expensive, and invasive immunohistochemistry (IHC) of the brain.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine*
;
Animals
;
Brain
;
Dopaminergic Neurons
;
Electrons
;
Humans
;
Hypokinesia
;
Immunohistochemistry
;
Injections, Subcutaneous*
;
Mice
;
Models, Animal
;
Muscle Rigidity
;
Parkinson Disease*
;
Pathology
;
Substantia Nigra
;
Swine
;
Tremor

Result Analysis
Print
Save
E-mail