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Novel Methylation Biomarker for Non-invasive Diagnostics in Lung Cancer
오태정,( Chang Hun Lee2 ),( Min Ki Lee ),( Yeul Hong Kim ),( Sang Yull Lee ),( Hyo Sung Jeon ),( Shin Yup Lee ),( Seung Soo Yoo ),( Jae Yong Park ),( Sung Whan An ) 대한결핵 및 호흡기학회 2012 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.114 No.-
To identify aberrantly hypermethylated DNA in lung cancer cells we established a genome-wide analysis for hypermethylation sites, namely Methyl DNA Isolation and Amplification (MeDIA) coupled-CpG microarray analysis. In the comprehensive methyaltion profiling analysis between human lung cancer, A549 cells and normal NHBE cells, we observed that several clusters of genes show a significant level of aberrancy in CpG island methylation pattern in cancer cells compared to normal cells. We further identified PCDHGA12 gene as a new marker of non-invasive diagnostics for lung cancer based on followings. 1) Transcription of PCDHGA12 gene is reactivated after treatment of A549 cells with demethylating agent. 2) Bisulfide clonal-sequencing reveals that CpG island of PCDHGA12 shows a distinctive differential methylation between two cell lines. 3) Pyrosequencing-based quantitative methylation assay for such region in tumor and non-tumorous tissues from lung cancer patients shows aberrant hypermethylation in 37 (92%) of the 40 tumor tissues. In clinical validation by pyrosequencingin induced-sputum of lung cancer patients (n=87) and healthy controls (n=51), we observed aberrant hypermethylation incident at significantly elevated level in samples derived from lung cancer patients. According to the optimal threshold calculated by ROC curve analysis, sensitivity and specificity of PCDHGA12 was 86.2% and 82.4%, respectively. PCDHGA12 methylation status could be a potential methylation biomarker alone or combined with others for the screen and the detection of relapse of lung cancer.
( Hong Yeul Lee ),( Jaeyoung Cho ),( Nakwon Kwak ),( Sun Mi Choi ),( Jinwoo Lee ),( Young Sik Park ),( Chang-hoon Lee ),( Chul-gyu Yoo ),( Young Whan Kim ),( Sang-min Lee ) 대한결핵 및 호흡기학회 2019 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.127 No.0
Background: Prone position ventilation improves oxygenation and reduces the mortality of patients with severe acute respiratory distress syndrome (ARDS). However, there has been some debate on the relationship between the improvement of oxygenation and survival. Herein, we analyze whether the improvement of oxygenation would predict survival in patients receiving prone positioning for ARDS. Methods: We retrospectively reviewed adult patients receiving prone positioning for ARDS in medical intensive care unit (ICU) at Seoul National University Hospital between 2017 and 2019. Demographic variables, laboratory examinations, ventilator setting and clinical outcomes were collected for analysis. Arterial blood gases were analyzed before, during, and after prone positioning session. The primary outcomes were ICU and 28-day mortality. A multivariate Cox regression was used to identify independent predictors of survival. Results: A total of 63 patients receiving prone positioning were included, of whom 22 (34.9%) were ICU survivor. Male were 46 (73%) and median age was 68 years (IQR 59-74). Although there was no difference in PaO2/FiO2 (P/F) ratio prior to turning prone between survivors and non-survivors (92.5 ± 30.6 vs. 95.4 ± 31.7, p=0.730), subjects who survived had a higher P/F ratio after 8 hours of prone positioning (170.2 ± 69.5 vs. 110.0 ± 47.6, p=0.001). The area under the receiver operating characteristic (ROC) curve for delta-P/F ratio to predict ICU mortality was 0.863 (sensitivity 76.9% /specificity 85.7%) with an optimal cut-off value of an increase in P/F ratio of 31.6%. Prone responders were defined as an increase in P/F ratio of ≥31.6%. In the multivariate Cox regression analysis, prone responders (HR=0.236, 95% CI, 0.118-0.470, p<0.001) and SOFA score (HR=1.196, 95% CI, 1.070-1.336, p=0.001) were independent factors in predicting 28- day mortality. Conclusions: Improvement of oxygenation after 8hr of prone positioning may be good predictor for survival in the patients receiving prone positioning for ARDS.
Effect of a rapid response system on code rates and in-hospital mortality in medical wards
Hong Yeul Lee,이진우,Sang-Min Lee,Sulhee Kim,양은진,Hyun Joo Lee,Hannah Lee,류호걸,Seung-Young Oh,Eun Jin Ha,Sang-Bae Ko,조재영 대한중환자의학회 2019 Acute and Critical Care Vol.34 No.4
Background: To determine the effects of implementing a rapid response system (RRS) on code rates and in-hospital mortality in medical wards. Methods: This retrospective study included adult patients admitted to medical wards at Seoul National University Hospital between July 12, 2016 and March 12, 2018; the sample comprised 4,224 patients admitted 10 months before RRS implementation and 4,168 patients admitted 10 months following RRS implementation. Our RRS only worked during the daytime (7 AM to 7 PM) on weekdays. We compared code rates and in-hospital mortality rates between the preintervention and postintervention groups. Results: There were 62.3 RRS activations per 1,000 admissions. The most common reasons for RRS activation were tachypnea or hypopnea (44%), hypoxia (31%), and tachycardia or brady cardia (21%). Code rates from medical wards during RRS operating times significantly decreased from 3.55 to 0.96 per 1,000 admissions (adjusted odds ratio [aOR], 0.29; 95% confidence interval [CI], 0.10 to 0.87; P=0.028) after RRS implementation. However, code rates from medical wards during RRS nonoperating times did not differ between the preintervention and postintervention groups (2.60 vs. 3.12 per 1,000 admissions; aOR, 1.23; 95% CI, 0.55 to 2.76; P=0.614). In-hospital mortality significantly decreased from 56.3 to 42.7 per 1,000 admissions after RRS implementation (aOR, 0.79; 95% CI, 0.64 to 0.97; P=0.024). Conclusions: Implementation of an RRS was associated with significant reductions in code rates during RRS operating times and in-hospital mortality in medical wards.
( Hong Jun Kim ),( In Keun Choi ),( Se Ryeon Lee ),( Seung Tae Kim ),( Hwa Jung Sung ),( Kyong Hwa Park,),( Sang Cheul Oh ),( Jae Hong Seo ),( Sang Won Shin ),( Yeul Hong Kim ),( Jun Suk Kim ) 대한내과학회 2013 대한내과학회 추계학술대회 Vol.2013 No.1
Introduction: Recent study reported that 38 percent of new patients with soft tissue sarcoma were aged more than 65 years. However, few studies reported clinical outcomes after chemotherapy in elderly patients with recurrent or advanced soft tissue sarcoma. Elderly patients hesitate to receive chemotherapy. But, an equal response to chemotherapy is expected in elderly patients as in young patients. Hence, we aimed to study the clinical results of chemotherapy in elderly patients with recurrent or advanced soft tissue sarcoma. Patients and Methods: 97 patients were admitted for chemotherapy at the Korea University Anam, Guro, and Ansan Hospital s between 2003.3 and 2012.4. Patients were treated with an appropriate chemotherapy regimen. Results: The median age of the patients in the entire group was 52 years. Patients received a median of 4 cycles of chemotherapy. The median overall survival for the entire group was 61 months (95% CI: 29.3-92.7 months). 33 patients were identified as elderly patients aged 60 years or older. In the elderly group, the most common type of soft tissue sarcoma was leiomyosarcoma (21.2%). The median number of chemotherapy cycles was three and median survival was 15 months in the elderly group. In the elderly group, one patient had a complete response. There were four partial responses. 14 patients had progressive disease. In the subgroup analysis, 51 of 64 patients (79.75%) in the non-elderly group were responders, while 19 of 33 patients (57.6%) in elderly group responders were responders (Chi-square test p=0.03). However, there was no statistically significant difference in survival between the elderly and non-elderly groups (p=0.11, log-rank test). Disease burden and response to chemotherapy were predictive of survival in elderly patients with recurrent or advanced soft tissue sarcoma. Conclusions: Taking only an age-based decision for systemic chemotherapy seems not to be reasonable in elderly patients with recurrent or advanced soft tissue sarcoma. A judicious decision needs to be taken for selecting the candidate for chemotherapy in elderly patients with recurrent or advanced soft tissue sarcoma after considering the benefit and toxicity of chemotherapy.
Improvement of diabetes and hypertension after gastrectomy: a nationwide cohort study.
Lee, Eun Kyung,Kim, So Young,Lee, You Jin,Kwak, Mi Hyang,Kim, Hak Jin,Choi, Il Ju,Cho, Soo-Jeong,Kim, Young Woo,Lee, Jong Yeul,Kim, Chan Gyoo,Yoon, Hong Man,Eom, Bang Wool,Kong, Sun-Young,Yoo, Min Kyo WJG Press 2015 WORLD JOURNAL OF GASTROENTEROLOGY Vol.21 No.4
<P>To evaluate the effect of gastrectomy on diabetes mellitus (DM) and hypertension (HTN) in non-obese gastric cancer patients.</P>
Lee, Sang Wook,Ryu, Chae-Min,Shin, Jung-Hyun,Choi, Daeheon,Kim, Aram,Yu, Hwan Yeul,Han, Ju-Young,Lee, Hye-Yeon,Lim, Jisun,Kim, Yong Hwan,Heo, Jinbeom,Lee, Seungun,Ju, Hyein,Kim, Sujin,Hong, Ki-Sung,Ha Korean Continence Society 2018 International Neurourology Journal Vol.22 No.S1
<P><B>Purpose</B></P><P>To evaluate the therapeutic effect of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (M-MSCs) on ketamine-induced cystitis (KC) in rats.</P><P><B>Methods</B></P><P>To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS) was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×10<SUP>6</SUP> cells) of M-MSCs (KC+M-MSC group) or PBS vehicle (KC group) were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×10<SUP>5</SUP> cells) to that of an identical dose of adult bone marrow (BM)-derived MSCs.</P><P><B>Results</B></P><P>Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×10<SUP>5</SUP>) of cells, at which point BM-derived MSCs did not substantially improve bladder function.</P><P><B>Conclusions</B></P><P>This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic damage.</P>