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Lee, Ahwon,Lee, Sung-Hak,Jung, Chan Kwon,Park, Gyungsin,Lee, Kyo Young,Choi, Hyun Joo,Min, Ki Ouk,Kim, Tae Jung,Lee, Eun Jung,Lee, Youn Soo Elsevier 2018 Pathology, research and practice Vol.214 No.5
<P><B>Abstract</B></P> <P>Targeted application of next-generation sequencing (NGS) technology allows detection of specific mutations that can provide treatment opportunities for cancer patients. We evaluated the applicability of the Ion AmpliSeq Cancer Hotspot Panel V2 (CHV2) using formalin-fixed, paraffin-embedded (FFPE) tissue of clinical specimens.</P> <P>Thirty-five FFPE tumour samples with known mutational status were collected from four different hospitals and sequenced with CHV2 using an Ion Chef System and Ion S5 XL system. Out of 35 cases, seven were sequenced with Oncomine focus Assay Panel for comparison. For the limit of detection test, we used an FFPE reference standard, a cell line that included an engineered 50% EGFR T790 M in an RKO cell line background. Coverage analysis results including number of mapped reads, on target percent, mean depth, and uniformity were not different according to hospitals. Sensitivity for mutation detection down to 3% was demonstrated. NGS results showed 100% concordance with the results from single molecular pathology tests Assay in 30 cases with 24 known positive mutations and 14 known negative mutations, and another NGS panel of the Oncomine focus in seven cases.</P> <P>The CHV2 NGS test for solid tumours using Ion chef system and S5 XL system in clinical molecular pathology laboratories for analysis of solid tumours could be routinely used and could replace some single molecular pathology tests after a stringent and thorough validation process.</P>
Lee, Ahwon,Kang, Jun,Lee, Hyoungnam,Lee, Youn Soo,Choi, Youn Jin,Lee, Keun Ho,Nistala, Goutam J,Scafe, Charles R.,Choi, Jongpill,Yoo, Jaeeun,Han M.D, Eunhee,Kim, Yonggoo,Kim, Myungshin Elsevier 2019 Pathology, research and practice Vol.215 No.11
<P><B>Abstract</B></P> <P><B>Introduction</B></P> <P>The detection of <I>BRCA1/2</I> mutations is important because PARP1 inhibitors are approved for germline and/or somatic <I>BRCA</I>-mutated advanced ovarian cancer. Next-generation sequencing (NGS) is increasingly used in clinical practice for <I>BRCA1</I>/2 mutations. The purpose of this study was to consider several conditions of NGS <I>BRCA1/2</I> assay applicable to clinical laboratory tests, in particular for using formalin fixed paraffin embedded (FFPE) ovarian tissues.</P> <P><B>Materials and methods</B></P> <P>We selected 64 ovarian cancer patients and performed Oncomine™ BRCA assay using FFPE tissue. Effect of FFPE sample quality was analyzed by NGS quality parameters including deamination metric. Somatic variants were selected by removing germline variants of peripheral blood and interpreted as pathogenic, variants of unknown significance, and false positive.</P> <P><B>Results</B></P> <P>We found a positive relationship between the number of variants over the deamination metric and FFPE age (<I>P</I> < 0.001) with a cutoff values of approximately 0.7 and 60 months, respectively. When comparing NGS results with Sanger sequencing, NGS misreported 3 of 15 variants using default parameters which were corrected after changing parameters. We detected somatic variants in eight patients and classified them into pathogenic (n = 3), VUS (n = 3) and false positive (n = 2).</P> <P><B>Conclusions</B></P> <P>This study is important for improving <I>BRCA1/2</I> mutation detection capabilities of NGS analytical pipelines and strategy to overcome their limitations using FFPE tissue in ovarian cancer patients.</P>
Lee, Hee Joong,Do, Jin Hwan,Bae, Sumi,Yang, Sanghwa,Zhang, Xianglon,Lee, Ahwon,Choi, Young Jin,Park, Dong Choon,Ahn, Woong Shick Science and Technology Letters 2011 MEDICAL ONCOLOGY -NORTHWOOD THEN BASINGSTOKE THEN Vol.28 No.1
<P>Glutathione peroxidase 3 (GPX3) is a member of glutathione peroxidase family, exerting one of the most important cellular defense mechanisms against stress signals, including oxidative damage. In this study, the expression of GPX3 mRNA and protein was analyzed for ovarian cancer tissues to test its applicability as a biomarker that can distinguish the four major histologic types of epithelial ovarian cancer. A public microarray dataset containing 99 ovarian cancer and 4 normal ovary samples was downloaded, and GPX3 mRNA expression was analyzed. The expression of GPX3 protein was measured by immunohistochemical staining in 40 epithelial ovarian cancer tissues, 10 for each of the serous, endometrioid, mucinous, and clear cell type. Histoscores were made from the immunohistostaining, and analysis of variance (ANOVA) was performed to quantitate the differences in protein level. Analysis of genomic dataset confirms a GPX3 overexpression in clear cell type ovarian adenocarcinoma compared with normal ovary and 3 other subtypes of epithelial ovarian cancer at mRNA level. GPX3 also shows the highest average antibody staining intensities in clear cell type ovarian adenocarcinomas over the other 3 types in immunostaining on tissue arrays. This is the first validation of GPX3 as a clear cell type-specific biomarker in ovarian cancer patients' tissues by immunostaining. GPX3 may serve as an important molecular marker for the diagnosis and molecular understanding of clear cell carcinoma of the ovary.</P>
Lee, Youn Joo,Youn, In Kyung,Kim, Sung Hun,Kang, Bong Joo,Park, Woo-chan,Lee, Ahwon Elsevier 2020 Magnetic resonance imaging Vol.66 No.-
<P><B>Abstract</B></P> <P><B>Purpose</B></P> <P>We aimed to investigate the magnetic resonance imaging (MRI) features and clinicopathologic factors with recurrence of triple-negative breast cancer (TNBC).</P> <P><B>Patients and methods</B></P> <P>We identified 281 patients with 288 surgically confirmed TNBC lesions who underwent pretreatment MRI between 2009 and 2015. The presence of intratumoral high signal on T2-weighted images, high-signal rim on diffusion-weighted images (DWI), and rim enhancement on the dynamic contrast-enhanced MRI and clinicopathological data were collected. Cox proportional analysis was performed.</P> <P><B>Results</B></P> <P>Of the 288 lesions, 36 (12.5%) recurred after a median follow-up of 18 months (range, 3.6–68.3 months). Rim enhancement (hazard ratio [HR] = 3.15; 95% confidence interval [CI] = 1.01, 9.88; <I>p</I> = .048), and lymphovascular invasion (HR = 2.73, 95% CI = 1.20, 6.23; <I>p</I> = .016) were independently associated with disease recurrence. While fibroglandular volume, background parenchymal enhancement, intratumoral T2 high signal, and high-signal rim on DWI, were not found to be risk factors for recurrence.</P> <P><B>Conclusion</B></P> <P>Pretreatment MRI features may help predict a high risk of recurrence in patients with TNBC.</P>
한아원 ( Ahwon Han ),조영권 ( Youngkwon Cho ),이희선 ( Heeseon Lee ),이흥수 ( Heungsoo Lee ),정세웅 ( Sewoong Jeong ),조영철 ( Youngcheol Cho ) 한국농공학회 2009 한국농공학회 학술대회초록집 Vol.2009 No.-
본 연구에서는 새만금호의 상류유역인 만경강과 동진강 유역의 하상 퇴적물이 내부오염원으로서 새만금 수질에 영향을 미칠 수 있는 가능성을 검토하기 위해 이들 지역에 퇴적물 중 유기물과 총질소, 총인을 분석하여 오염정도를 파악하였다. 퇴적물 시료는 2008년 8월부터 11월까지 3회에 걸쳐 두 강의 상류와 중류, 하류에서 각각 채취하였으며, 각 지점에서 좌안, 중앙, 우안으로 구분하여 시료를 채취하였다. 만경강과 동진강의 상류와 중류에서 채취한 퇴적물의 토성은 모두 “sand"로 분류되었다. 하류 일부 지점에서 silt 입자의 비율이 0.78~89%의 범위로 지점 또는 채취시점에 따른 변이가 컸으며, 토성도 “sand", "loamy sand", "sandy loam", "silt loam" 및 ”loam"으로 다양하게 나타났다. 만경강에서 채취된 퇴적물에서 강열감량은 상류와 중류에서 각각 평균 1.39±0.40, 1.30±0.62%로 측정되었으며, 하류에서는 평균 1.73±0.41%로 상류나 중류에 비해 약간 높은 값이 나타났다. 동진강의 경우 상류와 중류에서 일부 변이가 크게 나타나는 지점을 제외하고, 만경강과 거의 유사한 값을 나타내었으며, 하류에서는 평균 4.13±2.09%로, 만경강에 비해 높게 나타났다. 만경강 상류, 중류, 하류 퇴적물 중 COD 평균값은 각각 0.54±0.27, 0.64±0.51, 0.64±0.47 mg/g-sediment이었으며, 동진강의 경우 각각 0.64±0.77, 1.01±1.36, 1.77±1.15 mg/g-sediment로 측정되었다. 두 지역에서 측정된 강열감량과 COD 결과는 한강 하류와 팔당호, 대청호 퇴적물의 준설 기준에 비해 낮은 값을 나타내었다. 만경강 퇴적물에서 측정된 총질소의 양은 1.21~1.94 mg-N/g-sediment로 나타났으며, 중류의 좌안 퇴적물에서 이상적으로 높은 값이 측정되었고, 하류로 내려갈수록 농도가 상승하는 경향을 보였다. 동진강의 경우에는 상류, 중류 및 하류 지점에서 각각 평균 1.25, 1.83, 2.63 mg-N/g-sediment로 나타났다. 이는 팔당호 퇴적물 준설 기준보다 대부분 상회한 것이며, 일부 지점에서는 한강 하류 퇴적물 준설 기준보다 높게 측정되었다. 만경강 퇴적물에서 총인의 농도는 상류, 중류, 하류 지점에서 각각 평균 0.07, 0.11, 0.21mg-P/g-sediment로 하류로 갈수록 총인의 농도가 증가하였다. 동진강의 경우에는 상류, 중류, 하류 지점에서 각각 평균 0.15, 0.20, 0.21 mg-P/g-sediment로 만경강 퇴적물과 큰 차이가 없었다. 두 강의 총인의 농도는 팔당호 및 한강 하류 퇴적물 준설 기준에 비해 매우 낮았다. 만경강과 동진강의 하상 퇴적물의 오염도를 분석한 결과, 현재 오염이 심각하지 않은 것으로 판단되며, 만경강과 동진강의 하상퇴적물이 내부 오염원으로 새만금 수질에 영향을 미치지 않는 것으로 사료된다. 그러나 새만금 방조제 체절로 인한 오염 가능성이 존재하기 때문에, 만경강과 동진강 퇴적물의 지속적인 모니터링이 필요할 것으로 사료된다.
Bae, Young Kyung,Gong, Gyungyub,Kang, Jun,Lee, Ahwon,Cho, Eun Yoon,Lee, Ji Shin,Suh, Kwang-Sun,Lee, Dong Wha Lippincott Williams Wilkins, Inc. 2012 The American journal of surgical pathology Vol.36 No.12
Estrogen receptor (ER) and progesterone receptor (PR) are prognostic markers of breast cancer and predictive markers of response to endocrine therapy. To determine rates of ER and PR expression in invasive breast carcinoma among Korean women, the Breast Pathology Study Group of the Korean Society of Pathologists collected 1198 specimens of invasive breast carcinoma from 6 university hospitals. Immunohistochemical analysis was carried out using 1 antibody against PR and 3 antibodies against ER (1D5, 6F11, and SP1). Specimens were evaluated using the semiquantitative Allred score (scores >2 were considered positive). A total of 1077 cases were interpretable for all 3 anti-ER antibodies. ER expression was positive in 68.5% of cases using SP1, in 59.6% using 1D5, and in 58.9% using 6F11. Of 1073 interpretable cases, PR expression was positive in 51.7% of cases. The frequency distribution of Allred scores revealed a bimodal pattern (complete absence of staining or staining in most cells) for both ER and PR. Patients with discordant results for 2 different ER antibodies showed a median overall survival (between that of double-positive cancer and that of double-negative cancer). Our results showed that the rate of hormone receptor expression in breast carcinomas among Korean patients did not differ from that of western patients. In addition, SP1 was the most sensitive antibody for identifying ER expression in tumors. However, further evaluation is needed to determine which antibody is the best for selecting patients with discordant results who are likely to respond to endocrine therapy.
Jeeun Lee,Ahwon Kim,최석진,Eric Cho,Jaeyoung Seo,오성일,정진호,Ji-Sun Kim,성정준,Sharon Abrahams,홍윤호 대한신경과학회 2023 Journal of Clinical Neurology Vol.19 No.5
Background and Purpose Cognitive and behavioral changes are common in amyotrophic lateral sclerosis (ALS), with about 15% of patients presenting with overt frontotemporal dementia and 30%–50% with varying degrees of impairments. We aimed to develop and validate the Korean version of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS-K), a brief multidomain assessment tool developed for ALS patients with physical disability. Methods We developed the ECAS-K according to the translation guidelines, and administered it to 38 patients with ALS and 26 age- and education-level-matched controls. We also administered the Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB) to investigate convergent validity, and the Center for Neurologic Study-Liability Scale to assess the association between pseudobulbar affect and cognitive/behavioral changes. Results Internal consistency among the ECAS-K test items was found to be high, with a Cronbach’s alpha of 0.87. Significant differences were found between patients with ALS and the controls in language, fluency, and memory functions (p<0.05). Abnormal performance based on the ECAS total score was noted in 39.4% of patients, and 66.6% presented behavioral changes in at least one domain. Significant correlations were observed between the scores of the ECAS-K and those of other cognitive screening tools (MoCA and FAB, with correlation coefficients of 0.69 and 0.55, respectively; p<0.01). Conclusions We developed and validated the ECAS-K which could be used as an effective tool to screen the cognitive and behavioral impairments in Korean patients with ALS.