Clinical Impact of Re-biopsy among Patients with Epidermal Growth Factor Receptor Mutant Lung Adenocarcinoma: Based on Real-world Clinical Data in South Korea

( Yunha Nam ),( Ho Cheol Kim ),( Young-chul Kim ),( Seung Hun Jang ),( Kye Young Lee ),( Shin Yup Lee ),( Sang Hoon Lee ),( Sung Yong Lee ),( Seong Hoon Yoon ),( Jeong-seon Ryu ),( Tae Won Jang ),( Yo 대한결핵 및 호흡기학회 2020 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.128 No.-

Objectives It is clinically important to identify T790M mutation in patients who are suspected to have acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). We therefore aimed to investigate the risk factors of acquired T790M mutation among patients with lung adenocarcinoma with EGFR mutation who were treated using EGFR-TKI, and to identify the clinical impact of re-biopsy. Materials and Methods This is a multicenter, retrospective cohort study in South Korea. From January 2007 to June 2017, patients with adenocarcinoma with EGFR mutation who received re-biopsy and were treated with EGFR-TKI were included in this study. Results A total of 352 patients were included in this study. T790M mutation was identified in 156 (41.9%) study patients at the time of re-biopsy; the median duration from initial biopsy to re-biopsy was 17 months. The univariate logistic analysis showed that exon 19 deletion (odds ratio [OR], 1.643; p = 0.026) and the absence of L858R (OR, 0.627; p = 0.042), and previous EGFR-TKI treatment duration (OR, 1.039; p < 0.001) were associated with T790M mutation. The univariate Cox proportional hazard model showed that brain metastasis at initial diagnosis (hazard ratio [HR], 1.439; p = 0.030) was associated with T790M mutation. Among the patients with T790M mutation at re-biopsy, the osimertinib user group (n = 90) had a better 1-year survival (68.7 vs. 58.3%, p = 0.048) than the osimertinib non-user group (n = 66). Conclusion Re-biopsy might affect the clinical course of patients with EGFR-mutant adenocarcinoma, especially patients with a history of long-term use of EGFR-TKI, exon 19 deletion mutation, and brain metastasis at initial diagnosis

Uvrag targeting by Mir125a and Mir351 modulates autophagy associated with Ewsr1 deficiency

Kim, Yunha,Kang, Young-Sook,Lee, Na-Young,Kim, Ki Yoon,Hwang, Yu Jin,Kim, Hyun-Wook,Rhyu, Im Joo,Her, Song,Jung, Min-Kyung,Kim, Sun,Lee, Chai-Jin,Ko, Seyoon,Kowall, Neil W,Lee, Sean Bong,Lee, Junghee LANDES BIOSCIENCE 2015 AUTOPHAGY Vol.11 No.5

Development of Nutritional Supplements for Diabetic Patients Who Need Blood Sugar Control

Yunha Lee 한국식품영양과학회 2022 한국식품영양과학회 학술대회발표집 Vol.2022 No.10

SIRT3 deregulation is linked to mitochondrial dysfunction in Alzheimer's disease

Lee, Junghee,Kim, Yunha,Liu, Tian,Hwang, Yu Jin,Hyeon, Seung Jae,Im, Hyeonjoo,Lee, Kyungeun,Alvarez, Victor E.,McKee, Ann C.,Um, Soo‐,Jong,Hur, Manwook,Mook‐,Jung, Inhee,Kowall, Neil W.,Ry John Wiley and Sons Inc. 2018 Aging cell Vol.17 No.1

<P><B>Summary</B></P><P>Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Despite decades of study, effective treatments for AD are lacking. Mitochondrial dysfunction has been closely linked to the pathogenesis of AD, but the relationship between mitochondrial pathology and neuronal damage is poorly understood. Sirtuins (SIRT, silent mating type information regulation 2 homolog in yeast) are NAD‐dependent histone deacetylases involved in aging and longevity. The objective of this study was to investigate the relationship between SIRT3 and mitochondrial function and neuronal activity in AD. SIRT3 mRNA and protein levels were significantly decreased in AD cerebral cortex, and Ac‐p53 K320 was significantly increased in AD mitochondria. SIRT3 prevented p53‐induced mitochondrial dysfunction and neuronal damage in a deacetylase activity‐dependent manner. Notably, mitochondrially targeted p53 (mito‐p53) directly reduced mitochondria DNA‐encoded ND2 and ND4 gene expression resulting in increased reactive oxygen species (ROS) and reduced mitochondrial oxygen consumption. ND2 and ND4 gene expressions were significantly decreased in patients with AD. p53‐ChIP analysis verified the presence of p53‐binding elements in the human mitochondrial genome and increased p53 occupancy of mitochondrial DNA in AD. SIRT3 overexpression restored the expression of ND2 and ND4 and improved mitochondrial oxygen consumption by repressing mito‐p53 activity. Our results indicate that SIRT3 dysfunction leads to p53‐mediated mitochondrial and neuronal damage in AD. Therapeutic modulation of SIRT3 activity may ameliorate mitochondrial pathology and neurodegeneration in AD.</P>

Remodeling of heterochromatin structure slows neuropathological progression and prolongs survival in an animal model of Huntington’s disease

Lee, Junghee,Hwang, Yu Jin,Kim, Yunha,Lee, Min Young,Hyeon, Seung Jae,Lee, Soojin,Kim, Dong Hyun,Jang, Sung Jae,Im, Hyoenjoo,Min, Sun-Joon,Choo, Hyunah,Pae, Ae Nim,Kim, Dong Jin,Cho, Kyung Sang,Kowall Springer Verlag 2017 Acta neuropathologica Vol.134 No.5

<P>Huntington's disease (HD) is an autosomal-dominant inherited neurological disorder caused by expanded CAG repeats in exon 1 of the Huntingtin (HTT) gene. Altered histone modifications and epigenetic mechanisms are closely associated with HD suggesting that transcriptional repression may play a pathogenic role. Epigenetic compounds have significant therapeutic effects in cellular and animal models of HD, but they have not been successful in clinical trials. Herein, we report that dSETDB1/ESET, a histone methyltransferase (HMT), is a mediator of mutant HTT-induced degeneration in a fly HD model. We found that nogalamycin, an anthracycline antibiotic and a chromatin remodeling drug, reduces trimethylated histone H3K9 (H3K9me3) levels and pericentromeric heterochromatin condensation by reducing the expression of Setdb1/Eset. H3K9me3-specific ChIP-on-ChIP analysis identified that the H3K9me3-enriched epigenome signatures of multiple neuronal pathways including Egr1, Fos, Ezh1, and Arc are deregulated in HD transgenic (R6/2) mice. Nogalamycin modulated the expression of the H3K9me3-landscaped epigenome in medium spiny neurons and reduced mutant HTT nuclear inclusion formation. Moreover, nogalamycin slowed neuropathological progression, preserved motor function, and extended the life span of R6/2 mice. Together, our results indicate that modulation of SETDB1/ESET and H3K9me3-dependent heterochromatin plasticity is responsible for the neuroprotective effects of nogalamycin in HD and that small compounds targeting dysfunctional histone modification and epigenetic modification by SETDB1/ESET may be a rational therapeutic strategy in HD.</P>

Conducting Properties of Polypyrrole Coated Imogolite

Yunha Lee,Bumjoong Kim,이휘건,Atsushi Takahara,Daewon Sohn* 대한화학회 2006 Bulletin of the Korean Chemical Society Vol.27 No.11

Imogolite which has chemical composition, (HO)3Al2O3SiOH, was synthesized with orthosilicate acid and aluminium chloride at low pH solution. It has extremely large aspect ratio with an external diameter of 2nm and the length of a few micrometers. The high aspect ratio of the imogolite could make the material as the filler for the high strength fiber and as the wire for the electronic applications. Here, Imogolite that derives considerable microporosity from a nanometer-sized tubular structure has been modified with a conducting polymer, polypyrrole. Its bonding and wiring structure were confirmed by IR and TEM. The measured conductivity after modification with polypyrrole increased with polypyrrole thickness at various voltage conditions.

Alternative Treatment for Infectious Arthritis in a Complicated Diabetes Mellitus Patient with Ankle Joint Instability

Lee Yunhae,Lee Myungchul 대한창상학회 2020 Journal of Wound Management and Research Vol.16 No.1

Treatment of diabetic foot infections requires attention to both local and systemic issues, as diabetes mellitus is accompanied by a high incidence of complications that delay wound healing and restrict treatment options. We present a patient with diabetes who had infectious arthritis of the ankle joint with a soft tissue defect involving the joint capsule. The comorbidities of the patient limited the options for treatment in reconstruction of the ankle joint defect. Therefore, nonabsorbable sutures bridging the periosteum of the fibula and calcaneus bones were applied to mimic the calcaneofibular ligament and secure the joint capsule. In addition, negative pressure wound therapy (NPWT) was administered to protect the joint space, absorb extra fluid, and promote wound healing. Acellular dermal matrix was used in combination with NPWT to enhance wound healing and tissue regeneration. Although methicillin-resistant Staphylococcus aureus was cultured from the wound several times, there were no signs that this treatment aggravated the infection. After 7 months of inpatient treatment, stable soft tissue coverage and ankle joint stabilization were achieved, allowing fair standing balance, gait and plantar flexion.

Relationship between mandible fractures and third molars

Lee, Yunhae,Kim, Jeenam,Lee, Myungchul,Shin, Donghyeok,Choi, Hyungon Korean Cleft Palate-Craniofacial Association 2019 Archives of Craniofacial Surgery Vol.20 No.6

Background: This study was conducted to determine the relationship between third molar (M3) and mandibular fracture. Methods: Patients with unilateral mandibular angle or condyle fractures between 2008 and 2018 were evaluated retrospectively. Medical records were reviewed regarding the location of fractures, and panoramic radiographs were reviewed to discern the presence and position of ipsilateral mandibular third molars (M3). We measured the bony area of the mandibular angle (area A) and the bony area occupied by the M3 (area B) to calculate the true mandibular angle bony area ratio (area A-B/area A×100). Results: The study consisted of 129 patients, of which 60 (46.5%) had angle fractures and 69 (53.5%) had condyle fractures. The risk of angle fracture was higher in the presence of M3 (odds ratio [OR], 2.2; p< 0.05) and the risk of condyle fracture was lower in the presence of M3 (OR, 0.45; p< 0.05), than in the absence of M3. The risk of angle fracture was higher in the presence of an impacted M3 (OR, 0.3; p< 0.001) and the risk of condyle fracture was lower in the presence of an impacted M3 (OR, 3.32; p< 0.001), than in the presence of a fully erupted M3. True mandibular angle bony area ratio was significantly lower in the angle fractures than in the condyle fractures (p= 0.003). Conclusion: Angle fractures had significantly lower true mandibular angle bony area ratios than condyle fractures. True mandibular angle bony area ratio, a simple and inexpensive method, could be an option to predict the mandibular fracture patterns.

Reconstructive rhinoplasty with costal cartilage grafting: A case report of relapsing polychondritis

Lee, Yunhae,Choi, Hyungon Korean Cleft Palate-Craniofacial Association 2019 Archives of Craniofacial Surgery Vol.20 No.5

Relapsing polychondritis (RP) is a rare autoimmune disorder of unknown etiology characterized by recurrent episodes of inflammation and the destruction of cartilaginous tissues, primarily involving the ear, nose, and the respiratory tract. Nasal chondritis is present in 24% of patients at the time of diagnosis and develops subsequently in 53% throughout the diseases progress. Progressive destruction of nasal cartilage leads to the characteristic flattening of the nasal bridge, resulting in the saddle nose deformity. In patients with RP, surgical management for saddle nose is carefully decided due to the disease relapsing characteristics. We present a RP patient with a saddle nose deformity who underwent reconstruction rhinoplasty with autologous costal cartilage grafting. At 6-month follow-up, the patient retained good esthetic results and showed neither complication nor relapse of RP.

고기술산업과 저기술산업의 제품혁신패턴 및 연구개발 결정요인 분석: Hurdle 모형과 Heckman 표본선택모형을 중심으로

이윤하(Yunha Lee),강승규(Kang, Seung-Gyu),박재민(Jaemin Park) 한국산학기술학회 2019 한국산학기술학회논문지 Vol.20 No.10

그간 진화경제학적 관점에서 산업 고유의 특성에 따라 발생하는 기술혁신 패턴을 고찰하고자 하는 시도가 있어왔다. 본 연구는 국내 제조업을 기술집약도에 따라 고기술산업과 저기술산업으로 구분하고 제품혁신 패턴 및 혁신 성과 결정요인의 산업별 차이를 확인하였다. 기존 연구들은 연구개발 수행에 대한 기업의 의사결정 과정에서 연구개발을 수행하도록 만드는 결정요인을 분석에 반영하지 못했다는 지적이 있다. 본 연구에서는 이러한 문제를 극복하기 위해서 Heckman 표본선택모형과 허들모형을 대안으로 제시하고, 「2014년 중소기업기술통계조사」 자료의 1,637개 기업에 대해 분석을 실시했다. 분석 결과 제조업의 중소기업이 수행하는 제품혁신 패턴과 제품혁신 성과에 영향을 미치는 결정요인들에 있어 고기술산업과 저기술산업 간 뚜렷한 차이가 있다는 것을 확인 할 수 있었다. 또한, 기존 연구의 한계점을 극복하기 위해 채택한 연구모형의 확장을 통해서 중소기업 연구개발 수행에 대한 의사결정 과정에서 표본선택편의 문제와 허들로 표현되는 문지방이 있다는 것을 발견할 수 있었다. 본 연구는 산업별 제품혁신 패턴의 특징과 제품혁신 성과결정요인을 다각적으로 살펴보았고, 중소기업의 연구개발 수행에 대한 의사결정 과정을 더 깊이 이해할 수 있었다는 점에서 학술적 의의가 있다. There have been many studies to examine the patterns in innovations reflecting industry-specific characteristics from an evolutionary economics perspective. The purpose of this study is to identify industry-specific differences in product innovation patterns and determinants of innovation performance. For this, Korean manufacturing is classified into high-tech industries and low-tech industries according to technology intensity. It is also pointed out that existing research does not reflect the decision-making process of firms" R&D implementations. In order to solve this problem, this study presents a Heckman sample selection model and a double-hurdle model as alternatives, and analyzes data from 1,637 firms in the 2014 Survey on Technology of SMEs. As a result, it was confirmed that the determinants and patterns of manufacturing in small and medium-size enterprise (SME) product innovation are significantly different between high-tech and low-tech industries. Also, through an extended empirical model, we found that there exist a sample selection bias and a hurdle-like threshold in the decision-making process. In this study, the industry-specific features and patterns of product innovation are examined from a multi-sided perspective, and it is meaningful that the decision-making process for manufacturing SMEs" R&D performance can be better understood.