Idendification of DNA Methylation Marker for NSCLC and Adjacent Normal Lung Tissue using NotI-MseI Methylation Chip

( Mee Hye Kwon ),( Ko Eun Lee ),( Um Sub Kwak ),( Eu Gene Choi ),( Moon Jun Na ),( Hyun Min Cho ),( Young Jin Kim ),( Jung Uee Lee ),( Hye Jung Sul ),( Yoon Mee Kim ),( Bum Kyeong Kim ),( Ji Woong Son 대한결핵 및 호흡기학회 2006 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.103 No.-

Hpall- Mspl Methylation Microarray를 이용한 비소세포폐암의 DNA Methylation Marker 발굴

권미혜 ( Mi Hye Kwon ),이고은 ( Go Eun Lee ),권선중 ( Sun Jung Kwon ),최유진 ( Eu Gene Choi ),나문준 ( Moon Jun Na ),조현민 ( Hyun Min Cho ),김영진 ( Young Jin Kim ),설혜정 ( Hye Jung Sul ),조영준 ( Young Jun Cho ),손지웅 ( Ji Woo 대한결핵 및 호흡기학회 2008 Tuberculosis and Respiratory Diseases Vol.65 No.6

연구배경: 유전자의 후생적인 변화(epigenetic alteration)는 악성종양의 병인론에 있어서 유전자 변이와 동등한 위치를 점하고 있다. 특히 종양억제 유전자의 전사 촉진(promoter) 부위에 발생하는 비정상적인 메칠화(methylation)는 유전자의 발현을 침묵화(silencing)하고, 결과적으로 유전자의 기능 소실을 일으키게 된다. 저자들은 CpG island와 HpaII site를 가지고 있으며 암화 과정에 관여할 것으로 생각되는 유전자에 대하여 HpaII-MspI methylation microarray를 이용하여 새로운 종양억제 유전자를 발굴하고자 하였다. 방법: 2005년 건양대학교 병원에서 수술한 비 소세포성 폐암 환자 10명에서 폐암조직과 상응하는 암 주변의 정상조직을 얻었으며, HpaII-MspI methylation microarray (Methyl-Scan DNA chip(R), Genomic tree, Inc, South Korea)를 이용하여 21개의 유전자에 대하여 DNA methylation profile을 분석하였다. 각각의 유전자에서 메칠화된 정도를 두 그룹에서 비교하였고, 정상 대조군으로 두 명의 젊고 건강한 기흉 환자에서 수술한 폐 조직에 대하여 methylation profile을 분석하였다. 결과: 21개의 대상 유전자 중 10개의 유전자에서 폐암조직, 폐암 주변 정상 조직, 대조군에서 모두 공통적으로 과메칠화 되었고, 나머지 11개의 유전자 중 APC, AR, RAR-b, HTR1B, EPHA3, CFTR의 6개의 유전자에서 대조군에서 메칠화가 없으며, 폐암조직에서 폐암 주변 정상 조직에 비하여 더 빈번하게 과메칠화 되었다. 결론: HTR1B, EPHA3, CFTR은 비소세포 폐암에서 후생적 변화로 발생하는 새로운 종양억제 유전자의 후보유전자로서의 가능성이 있을 것으로 생각한다. (Tuberc Respir Dis 2008;65:495-503) Background: Epigenetic alterations in certain genes are now known as at least important as genetic mutation in pathogenesis of cancer. Especially abnormal hypermethylation in or near promoter region of tumor suppressor genes (TSGs) are known to result in gene silencing and loss of gene function eventually. The authors tried to search for new lung cancer-specific TSGs which have CpG islands and HpaII sites, and are thought to be involved in carcinogenesis by epigenetic mechanism. Methods: Tumor tissue and corresponding adjacent normal tissue were obtained from 10 patients who diagnosed with non small cell lung cancer (NSCLC) and underwent surgery in Konyang university hospital in 2005. Methylation profiles of promoter region of 21 genes in tumor tissue & non-tumor tissue were examined with HpaII-MspI methylation microarray (Methyl-Scan DNA chip(R), Genomic tree, Inc, South Korea). The rates of hypermethylation were compared in tumor and non-tumor group, and as a normal control, we obtained lung tissue from two young patients with pneumothorax during bullectomies, methylation profiles were examined in the same way. Results: Among the 21 genes, 10 genes were commonly methylated in tumor, non-tumor, and control group. The 6 genes of APC, AR, RAR-b, HTR1B, EPHA3, and CFTR, among the rest of 11 genes were not methyl-lated in control, and more frequently hypermethylated in tumor tissue than non-tumor tissue. Conclusion: In the present study, HTR1B, EPHA3, and CFTR are suggested as possible novel TSGs of NSCLC by epigenetic mechanism.

Establishment of PLS prediction modeling of function compounds contents using multivariate analysis of spectral data from soybean (Glycine max L) seeds

Seung Yeob Song,Sul Hye Hur,Byung Whan Min,In-Jung Kim,Suk Weon Kim 한국육종학회 2012 한국육종학회 심포지엄 Vol.2012 No.07

In this study we established the high throughput screening system of high functional soybean cultivars using PLS modeling from FT-IR spectral data of soybean(Glycine max L) seeds. Crude extract of 20% methanol from soybean seed powders (153 lines) were used for FT-IR spectroscopy. Total fatty acid, carotenoids, flavonoids and phenolic compounds contents from soybean seed powders were analyzed using UV-spectrum and GC analysis respectively. PCA analysis showed that 153 soybean lines formed a single clusters with a few outlier. PC score 1 and 2 represented 39.5, 16.4% of total variation, respectively. And than showed change patten from the middle to outside for PCA plot. We conducted PLS regression analysis between FT-IR spectral data and fatty acids data. Palmitic acid showed the highest regression coefficient (R=0.78). This result implied that the content of palmitic acid could be predicted from FT-IR spectral data from soybean seed powders with relatively high fidelity. PLS modeling of total carotenoids also showed regression coefficient of 0.69. Regression coefficient of total flavnoids and phenolic compounds were 0.44, 0.39, respectively. At present, we are trying to confirm the accuracy of PLS prediction modeling using targeted metabolite analysis (GC-MS, LC-MS) from predicted soybean lines. To increase the accuracy of PLS modeling, we also trying to standardization of spectroscopy and spectral data processing. Furthermore we are going to develop PLS modeling from GC-MS, LC-MS data. The PLS prediction modeling established in this study could be applied for high throughput screening of other leguminous plant.

Lipopolysaccharide (LPS)-Induced Autophagy Is Responsible for Enhanced Osteoclastogenesis

Sul, Ok-Joo,Park, Hyun-Jung,Son, Ho-Jung,Choi, Hye-Seon Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.11

We hypothesized that inflammation affects number and activity of osteoclasts (OCs) via enhancing autophagy. Lipopolysaccharide (LPS) induced autophagy, osteoclastogenesis, and cytoplasmic reactive oxygen species (ROS) in bone marrow-derived macrophages that were pre-stimulated with receptor activator of nuclear $factor-{\kappa}B$ ligand. An autophagy inhibitor, 3-methyladenine (3-MA) decreased LPS-induced OC formation and bone resorption, indicating that autophagy is responsible for increasing number and activity of OCs upon LPS stimulus. Knockdown of autophagy-related protein 7 attenuated the effect of LPS on OC-specific genes, supporting a role of LPS as an autophagy inducer in OC. Removal of ROS decreased LPS-induced OC formation as well as autophagy. However, 3-MA did not affect LPS-induced ROS levels, suggesting that ROS act upstream of phosphatidylinositol-4,5-bisphosphate 3-kinase in LPS-induced autophagy. Our results suggest the possible use of autophagy inhibitors targeting OCs to reduce inflammatory bone loss.

MicroRNA-29b Enhances Osteoclast Survival by Targeting BCL-2-Modifying Factor after Lipopolysaccharide Stimulation

Sul, Ok-Joo,Rajasekaran, Monisha,Park, Hyun-Jung,Suh, Jae-Hee,Choi, Hye-Seon Hindawi 2019 Oxidative medicine and cellular longevity Vol.2019 No.-

<P>Recent findings suggest that microRNAs (miRs) play a critical role in osteoclastogenesis, which regulates bone loss. We hypothesized that inflammation induces miR-29b, which increases the survival rate in osteoclasts (OCs), leading to bone loss. The expression level of miR-29b increased in OC stimulated by lipopolysaccharide (LPS) in an in vitro system which correlated with its increase in tibiae from mice that received LPS injections compared with those that received vehicle treatment. An miR-29b mimic increased OC survival rate without any change in OC differentiation, and furthermore, the inhibition of endogenous miR-29b induced by LPS decreased OC survival rate. Increased OC survival rate after overexpression of miR-29b was associated with antiapoptotic activity, as shown by staining annexin V-positive cells. We found that a target gene of miR-29b is BCL-2-modifying factor (<I>Bmf</I>), which acts as a proapoptotic factor, and that miR-29b binds to the 3′-UTR of <I>Bmf</I>. Our data demonstrate that LPS-induced miR-29b increases the number of OC by enhancing OC survival through decreased BMF.</P>

Altered expression of placental aging markers is associated with pathogenesis of preeclampsia

( Sul Lee ),( Min Jung Park ),( Eun Hye Jeon ),( Seung Chul Kim ) 대한산부인과학회 2020 대한산부인과학회 학술대회 Vol.106 No.-

Objective: Previous studies suggest, senescence of trophoblast is thought to be associated to the development of preeclampsia (PE). Therefore, this study aimed to confirm whether the expression of placental aging-related markers reveal a difference in a rat model of preeclampsia induced by reduced uterine perfusion pressure (RUPP). Methods: To confirm PE of RUPP rat models, the changes in blood pressure, urine protein, serum level of PE marker (VEGF, s-Flt) and fetal and placental weight were measured in rat model with RUPP. We also measured the differential expressions of placental aging-related markers (calprotectin and caveolin-1) in the placenta and serum of PE rat model by real-time PCR, ELISA, and immunohistochemistry. Results: 1) The tail blood pressure, urine protein, stillbirth rate, fetal and placental wight measured in the PE rat model were statistically changed compare to the Sham group(dpc18.5). 2) The expressions of calprotectin in the placenta and serum of RUPP models were increased. But, the level of caveolin-1 was decreased. Conclusion: These results suggest that altered expression of placental aging-related markers such as calprotectin and caveolin-1 might be involved in pathogenesis of PE. And additional experiment using human samples complicated of PE are warranted.

A comparison of survival outcome of open, total laparoscopic and laparoscopy-assisted vaginal radical hysterectomy in patients with early cervical cancer of stage IB2

( Sul Lee ),( Hyung Joon Yoon ),( Eun Hye Jeon ),( Juseok Yang ),( Yong Jung Song ),( Hyun Jin Roh ),( Sang Hun Lee ),( Byung Su Kwon ),( Ki Hyung Kim ),( Dong Soo Suh ) 대한산부인과학회 2019 대한산부인과학회 학술대회 Vol.105 No.-

Objective: The aim of this study is to evaluate oncologic outcomes of total abdominal radical hysterectomy (TARH), total laparoscopic radical hysterectomy (TLRH) and laparoscopic-assisted radical vaginal hysterectomy (LARVH) in early cervical cancer patients (stage IB2-3, tumor size≥2cm), analyzing the risk factors that may affect the clinical results. Methods: A total of 756 patients underwent radical hysterectomy between 2000 and 2019 from three university hospitals (Pusan National University Hospital, Yang-san Pusan National University Hospital, Ulsan University Hospital) were enrolled. Among them, 172 patients with stage IB2-3 were analyzed retrospectively. Results: Seventy-seven patients were treated with TARH, and 95 were managed via minimally invasive surgery (MIS), consisting of 35 with TLRH and 60 with LARVH. TARH group had better disease five-year disease free survival (DFS) and overall survival (OS) compared with MIS group (86.4% vs. 73.4 for DFS and 91.7 vs. 82.2 for OS), but not statistically significant in both (p=0.058 for DFS and p=0.119 for OS). When TARH and the LARVH group were compared, both five-year DFS and OS were not significant different (86.4 vs 82.2%; p=0.288 for DFS and 91.7 vs 84.4%; p=0.206 for OS). However, when TARH and the TLRH group were compared, TLRH group had significantly worse five-year DFS than TARH (86.4 vs 54.5%; p=0.008), but five-year OS was not significant different (91.7 vs 77.5%; p=0.127). Multivariate analysis showed that LN metastasis and TLRH surgical approaches were an independent prognostic factor for DFS in IB2-3 cervical cancers. Conclusion: Our findings provided the evidence that TLRH surgical approach was associated with worse DFS in IB2-3 cervical cancers but that of LARVH was not. Such results may have important implications of colpotomy method for MIS in cervical cancer.

Oral Bioavailability and Enterohepatic Recirculation of OtiloniumBromide in Rats

신범수,Jung Jun Kim,John Kim,Sul Ki Hu,Han Kyung Kim,Hye Suk Lee,Sun Dong Yoo 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.1

This study was conducted to examine the oral bioavailability and the possibility of enterohepatic recirculation of otilonium bromide in rats. A sensitive LC/MS/MS assay (LLOQ 0.5 ng/mL) was developed for the determination of otilonium and applied to i.v. and oral administration studies in bile duct cannulated (BDC) and non-BDC rats. After i.v. injection to BDC rats (1 mg/ kg as otilonium), average t1/2, CL, Vz and AUC were 7.9 ± 1.9 h, 8.7 ± 3.1 mL/min/kg, 5.7 ± 1.4 L/kg and 2,088 ± 676 ng·h/mL, respectively, and these values were comparable to those found in non-BDC rats. The percentages of i.v. dose excreted unchanged in bile and urine in BDC rats were 11.6 ± 3.0 and 3.1 ± 0.7%, respectively. Upon oral administration to non-BDC rats (20 mg/kg as otilonium), t1/2, Cmax, Tmax and AUC were 6.4 ± 1.3 h, 182.8 ± 44.6 ng/mL, 1.9 ± 1.6 h and 579 ± 113 ng·h/mL, respectively. The absolute oral bioavailability was low (1.1%), while the drug was preferentially distributed to gastrointestinal tissues. A secondary peak was observed in the serum concentration-time profiles in non-BDC rats following both i.v. and oral administration, indicating that otilonium bromide was subject to enterohepatic recirculation.

Research Collaborations for Better Predictions of Aviation Weather Hazards

Chun, Hye-Yeong,Kim, Jung-Hoon,Lee, Dan-Bi,Kim, Soo-Hyun,Strahan, Matt,Pettegrew, Brian,Gill, Philip,Williams, Paul D.,Schumann, Ulrich,Tenenbaum, Joel,Lee, Young-Gon,Choi, Hee-Wook,Song, In-Sul,Park, American Meteorological Society 2017 Bulletin of the American Meteorological Society Vol.98 No.5

인라인 스케이트 이용자들의 손상 유형과 위험 요인

서혜경,문지영,성주욱,김말영,이준호,박정이,차성화,백나영,이재민,김수민,임현술,정해관,배근량,정철 東國大學校醫學硏究所 2004 東國醫學 Vol.11 No.2

지난 몇 년 사이 인라인 스케이트는 젊은층을 중심으로 인기있는 스포츠가 되었으며 이러한 대중화와 더불어 인라인 스케이트와 관련된 사고 빈도도 증가하는 추세이다. 따라서 본 연구는 인라인 스케이트 이용에 따른 사고율과 이용습관 형태, 손상 유형 및 위험 요인을 알아보고자 시행되었다. 2003년 9월 14일부터 9월 24일까지 경주시 ○○초등학교 6학년, ○○중학교 1학년, ○○여자고등학교 1학년, ○○고등학교 1학년, 동국대학교 의과대학 의학과 학생, 경주황성·포항 해맞이 공원의 성인을 포함한 총설문 대상자 1,305명 중 인라인 스케이트 이용자 392명을 대상으로 단면 연구를 수행하였다. 조사에 앞서 병원 방문과 사전 조사를 시행 하였으며 자기 기입식 설문지를 통해 정보를 수집하였다. 초, 중, 고 인라인 스케이트 전체 이용률은 28.1% 사고율은 30.1%로 나왔으며 주로 젊은층에서 사고가 많았으며 나이가 증가할수록 빈도가 증가하였다. 보호 장비 착용률은 44.4%로 조사되었다. 손상 부위로는 무릎과 상지 부위가 많은 것으로 조사되었으며 손상 유형은 찰과상과 타박상이 많았다. 스케이트를 타기 시작한지 1개월 이내에서 사고를 가장 많이 당한 것으로 나타났다. 전체 부상자의 20%가 후유증이 있었던 것으로 나타났다. 본 연구에서 인라인 스케이트 이용자들의 사고율이 비교적 높음을 알 수 있었다. 손상 부위의 무릎 및 상지 집중 현상으로 인해 무릎과 상지 부위의 보호대 착용이 필요할 것으로 생각되며 또한 사고를 줄이기 위해 초기 기술 습득 단계부터 전문가를 통한 체계적 교육과 안전 의식 고양이 필요할 것으로 보인다. In the past several years, Inline skating has become a popular sport among young people. With popularization of Inline skating, the number of injuries has increased proportionately. The purpose of this study is to evaluate the prevalence of injuries, the behaviors of skating, the nature and risk factors of injuries. We conducted a questionnaire an 1,305 subjects from Sep. 14 to 24, 2003. The Inline skaters were 392. These participation were mainly students from ○○elementary school, ○○middle school, ○○women's high school, ○○high school, Dongguk medical school, and adult skaters in several parks. The prevalence of injuries were 30.1%. Injuries were predominant from younger age and frequencies were increased according to increasing age. The most common location of injuries were both knee and the upper extremities. Most of injury type were skin abrasion and contusion. Injuries were highest within one month after First skating. 20% of injuries experienced a sequela. The results of this study show the severity of Inline skating-related injuries. We expect that the knee and the upper extrimities protectors should be used adequatly. Also to reduce injuries, when the skills are obtainded, the specilized learning programs and safety awareness are needed.