Cooperative Subtype Switch of Thyroid Hormone Receptor and Nuclear Receptor Corepressor Related Epithelial–Mesenchymal Transition in Papillary Thyroid Cancer

정선향,이슬기,김현지,이기쁨,박선미,김인규,이잔디,조영석 대한갑상선학회 2021 International Journal of Thyroidology Vol.14 No.2

Background and Objectives: Although thyroid hormones affect human cancer progression, the regulatorymechanism of thyroid hormone receptors in carcinogenesis has not been elucidated. This study aimed to evaluatethe expression pattern of the thyroid hormone receptor (TR) and its corepressors, and to investigate the clinicaland biological functions of TR. Materials and Methods: Transcriptomic and clinical data for thyroid cancer weredownloaded from The Cancer Genome Atlas. Paraffin-embedded tissue sections from patients who underwentthyroidectomy were used for immunohistochemistry. BCPAP cells were treated with T3 to investigate the thyroidhormone target genes. Thyroid hormone receptor alpha (THRA) and Thyroid hormone receptor beta (THRB) wereknocked down by transient siRNA transfection. Results: THRA and THRB expression was lower in thyroid cancertissues than in normal tissues. However, strong focal staining of TRβ was observed in the invasive front. HighTHRB expression was associated with high Silencing Mediator for Retinoid or Thyroid hormone receptor (SMRT)expression, older age, a high MACIS (distant Metastasis, patient Age, Completeness of resection, local Invasion,and tumor Size) score, more aggressive histological subtypes, more frequent extra-thyroidal extension, andadvanced TNM stage. THRB expression was positively correlated with Hypoxia Inducible Factor 1 Subunit Alpha(HIF1A), L1 Cell Adhesion Molecule (L1CAM), and Lysyl Oxidase (LOX) expression. Thyroid hormone-inducedHIF1A, L1CAM, and LOX upregulation was abolished by siTHRB but not siTHRA in BCPAP cells. High SMRT andhigh THRB groups (SMRT/THRB) presented more aggressive clinical features and showed an upregulation of HIF1A,L1CAM, and LOX, as well as of epithelial-mesenchymal transition (EMT)-related genes, causing changes in thetumor microenvironment. Conclusion: Cooperative subtype switching from NCOR1/THRA to SMRT/THRB was thusrelated to aggressive clinical and molecular features, possibly related to EMT and EMT-related tumor microenvironment.

Liver X Receptor β Related to Tumor Progression and Ribosome Gene Expression in Papillary Thyroid Cancer

정선향,김인규,김현지,최문정,이잔디,조영석 대한내분비학회 2020 Endocrinology and metabolism Vol.35 No.3

Background: Intracellular lipid deposition has been reported in thyroid glands in obese animal and human. To understand the regulatory mechanism of lipid metabolism in thyroid cancer, we investigated the expression status of liver X receptor (LXR) and analyzed its clinicopathological characteristics and molecular biological features. Methods: Expression status of LXR and its transcriptional targets in human cancers were analyzed using The Cancer Genome Atlas(TCGA). The gene-sets related to high LXRβ expression was investigated by gene set enrichment analysis (GSEA) using Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways and gene ontology biologic process. Quantitative reverse transcription polymerase chain reaction was performed in thyroid cancer samples using our validation cohort. Results: In contrast to low expression of LXRα, LXRβ was highly expressed in thyroid cancer compared to the other types of humancancers. High LXRβ expression was correlated with the expression of LXRβ transcriptional targets genes, such as apolipoprotein C1(APOC1), APOC2, apolipoprotein E (APOE), ATP binding cassette subfamily G member 8 (ABCG8), sterol regulatory elementbinding protein 1c (SREBP1c), and SPOT14. Furthermore, High LXRβ expression group indicated poor clinicopathological characteristics and aggressive molecular biological features independently from the drive mutation status. Mechanistically, high LXRβ expression was coordinately related to ribosome-related gene sets. Conclusion: The mechanistic link between LXRβ and ribosomal activity will be addressed to develop new diagnostic and therapeutic targets in thyroid cancers.

IGF-1 Counteracts TGF-β-Mediated Enhancement of Fibronectin for in Vitro Human Lens Epithelial Cells

정소향,정선아,조영재,이준행,김응권 연세대학교의과대학 2007 Yonsei medical journal Vol.48 No.6

Purpose: To determine whether insulin-like growth factor (IGF-1) affects transforming growth factor (TGF-β)- mediated fibronectin accumulation in human lens epithelial cell line (HLE B-3) cells. Materials and Methods: HLE B-3 cells were incubated for 24 hours with TGF-β (10ng/ mL), IGF-1 (10ng/mL), or both. Expression of the fibronectin gene was determined using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Fibronectin levels were examined using western blot analysis and immunofluorescence staining. Results: Expression of the fibronectin gene was not different between the TGF-β/IGF-1 treated group and the TGF-β treated group (p= 0.116). However, western blot analysis demonstrated decreased fibronectin levels in human lens epithelial cells treated with TGF-β and IGF-1 compared to those treated with TGF-β only (p<0.01). Immunofluorescence staining disclosed inhibition of TGF-β-induced fibronectin in the presence of IGF-1. Conclusion: This study suggests that IGF-1 counteracts TGF-β-mediated fibronectin accumulation in human lens epithelial cells.

Comparative Analysis of Driver Mutations and Transcriptomes in Papillary Thyroid Cancer by Region of Residence in South Korea

이잔디,정선향,이화영,박선미,정미선,조영석 대한내분비학회 2023 Endocrinology and metabolism Vol.38 No.6

Background: Radiation exposure is a well-known risk factor for papillary thyroid cancer (PTC). South Korea has 24 nuclear reactors in operation; however, no molecular biological analysis has been performed on patients with PTC living near nuclear power plants. Methods: We retrospectively included patients with PTC (n=512) divided into three groups according to their place of residence at the time of operation: inland areas (n=300), coastal areas far from nuclear power plants (n=134), and nuclear power plant areas (n=78). After propensity score matching (1:1:1) by age, sex, and surgical procedure, the frequency of representative driver mutations and gene expression profiles were compared (n=50 per group). Epithelial-mesenchymal transition (EMT), BRAF, thyroid differentiation, and radiation scores were calculated and compared. Results: No significant difference was observed in clinicopathological characteristics, including radiation exposure history and the frequency of incidentally discovered thyroid cancer, among the three groups. BRAFV600E mutation was most frequently detected in the groups, with no difference among the three groups. Furthermore, gene expression profiles showed no statistically significant difference. EMT and BRAF scores were higher in our cohort than in cohorts from Chernobyl tissue bank and The Cancer Genome Atlas Thyroid Cancer; however, there was no difference according to the place of residence. Radiation scores were highest in the Chernobyl tissue bank but exhibited no difference according to the place of residence. Conclusion: Differences in clinicopathological characteristics, frequency of representative driver mutations, and gene expression profiles were not observed according to patients’ region of residence in South Korea.

한우 집단 폐사를 유발한 엔도설판 중독 사례

이보람,이현경,이경현,윤순식,김미경,박중원,정선향,이명헌,배유찬,Lee, Bo-Ram,Lee, Hyun-Kyoung,Lee, Kyung-Hyun,Yoon, Soon-Seek,Kim, Meekyung,Park, Jung-Won,Jeong, Seon-Hyang,Lee, Myoung-Heon,Bae, You-Chan 대한수의학회 2013 大韓獸醫學會誌 Vol.53 No.4

Here, we report the poisoning case of 10 cows. Several distinct clinical signs such as convulsion, excessive salivation, circling, lateral recumbency, and death were observed. Necropsy and histopathological examination did not reveal any significant abnormal findings. Moreover, no bacteria or viruses were detected in tissue, blood, and feeding food. However, endosulfan was detected from the stomach contents and microbials. Our results strongly suggest that death of cows may be closely associated with endosulfan poisoning.

듀이 철학에서 ‘놀이’의 의미: 놀이중심 교육과정 운영을 위한 교육철학적 탐구

권정선,이종향 한국교육철학학회 2024 교육철학연구 Vol.46 No.1

본 연구는 2019 개정 누리과정에서 추구하는 놀이중심 교육과정의 핵심을 이루고 있는 놀이 개념을 듀이의 논의를 바탕으로 탐구하는데 목적을 두었다. 듀이의 관점에서 놀이는 유목적적이고 능동적인 활동으로서, 유아교육에서 상상과 흥미, 사고를 유발하는 동시에 함양할 수 있도록 하는 효과적 매체이다. 놀이는 자연적인 발달을 존중하는 아동중심의 진보주의 교육과정의 취지와 맞닿아 유아의 삶으로부터 출발하여 본능적 요구를 충족시키면서 바람직한 상호작용을 이끌어내어 성장시킬 수 있는 유효한 조건과 가치가 상당하다. 이러한 놀이를 통한 교육이 현장에서 그 가치를 발하기 위해서는 상호작용과 계속성의 원리에 따라 새로운 놀이 경험이 이루어질 수 있도록 해야 하며, 이는 유아 교사들의 놀이 개념에 대한 이해와 교육적 경험에 대한 안목과 성찰, 유아의 경험에 대한 깊은 관심과 애정을 기반으로 이루어질 수 있다. The purpose of this study is to explore the concept of play, which forms the core of the play-centered curriculum pursued in the 2019 Nuri curriculum, based on Dewey's discussion. In Dewey's view, play is an effective medium of early childhood education that can be cultivated, as well as imagination, interest, and thought, as a purposeful and active activity. Play is in line with the purpose of the progressivism’s child-centered curriculum that respects natural development, and it has significant effective conditions and values ​​that can help children grow by satisfying their instinctive needs and eliciting desirable interactions starting from their lives. In order for such education through play to show its value in the field, it is necessary to ensure that new play experiences can be created according to the principles of interaction and continuity, and this can be done based on the understanding of the concept of play by early childhood teachers, their insight and reflection on educational experiences, and their deep interest and affection for the experiences of young children.