Western Blot을 이용한 대장암과 대장선종의 Calreticulin 단백 발현 연구

금보라 ( Bora Keum ),진윤태 ( Yoon Tae Jeen ),박상훈 ( Sanghoon Park ),서연석 ( Yeon Seok Seo ),김용식 ( Yong Sik Kim ),전훈재 ( Hoon Jai Chun ),이홍식 ( Hong Sik Lee ),엄순호 ( Soon Ho Um ),이상우 ( Sang Woo Lee ),최재현 ( Jai Hy 대한장연구학회 2006 Intestinal Research Vol.4 No.1

목적: 대장암 발생에 여러 유전자 변이가 관여하여 이에 대한 표지자의 검색을 위해 유전자의 최종 발현산물인 단백질을 연구하여 유전자의 기능을 규명하고 암의 조기 진단 및 치료의 표지자를 찾는 연구가 진행되고 있다. Calreticulin은 대장암에서 정상 대장 점막에 비해 특이하게 발현하는 것으로 밝혀졌다. 본 연구에서는 calreticulin을 이용하여 정상조직과 대장선종 및 대장암에서의 발현을 비교 분석하고자 하였다. 대상 및 방법: 2004년 12월부터 2005년 3월까지 대장암 및 동시성 대장선종 각 예에서 선종, 대장암과 정상점막의 조직을 채취하였다. 채취한 조직에서 단백질을 분리하여 western blot을 시행하였고 항 calreticulin 항체를 사용하여 표지한 후 화학 발광 염색방법에 의해 확인하였다. 각 예에서 정상 대장 점막의 발현정도를 ‘1’로 하여 선종과 대장암의 발현을 비교하였다. 결과: Calreticulin의 발현 정도는 정상 대장 점막에 비해 대장선종이 평균 1.69±0.37, 대장암이 평균 2.78±1.12였다. 각 군 간의 차이를 비교하였을 때 정상점막과 대장암, 정상점막과 선종 간에는 유의한 차이를 보였다. 대장선종보다 대장암에서 calreticulin이 많이 발현되었으나 통계적으로 유의하지는 않았다. 결론: 대장암뿐만 아니라 전구 병변인 선종에서도 calreticulin이 정상조직에 비해 높게 발현되어 대장암 및 대장 선종을 예측하는 선별 검사 표지자 연구에서 calreticulin의 역할을 기대할 수 있을 것으로 생각한다. 향후 많은 환자를 대상으로 대장암 발생과 calreticulin의 연관성 및 검사 실용 가능성에 대한 연구가 필요할 것으로 생각된다. Background/Aims: Colon cancer has a multistep process of molecular changes on the way of carcinogenesis. The detection of gene mutations associated with those molecular changes is expected to be able to predict or diagnose colon cancer. Calreticulin is one of the protein which has being investigated as a biomarker of colorectal cancer. The Aims of this study was to demonstrate the expression of calreticulin in normal colon mucosa, colonic tubular adenoma and colorectal cancer of each patient, and analyze the differences among them. Methods: 8 patients who have colorectal adenocarcinoma and more than 10 mm sized tubular adenoma synchronously were enrolled. Colorectal adenocarcinoma, tubular adenoma and normal colon tissue were taken from each patient. After proteins isolation and separation, western blot assay were performed to demonstrate calreticulin. The results were analyzed by Wilcoxon Signed Rank Test. Results: Calreticulin was more expressed in colorectal adenocarcinoma and tubular adenoma significantly compared with normal mucosa. Also, calreticulin was more expressed in adenocarcinoma than in adenoma but there were no significant diffences. Conclusions: These results suggest that calreticulin may be available for an early diagnostic biomarker for colorectal cancer or advanced colon adenoma. (Intestinal Research 2006;4:7-11)

대장 근위부 진행성 선종 예측을 위한 원위부 용종의 임상적 의의: 전향적 다기관 대장 용종 연구

금보라 ( Bora Keum ),진윤태 ( Yoon Tae Jeen ),최재현 ( Jai Hyun Choi ),정성애 ( Sung Ae Jung ),김현수 ( Hyun Soo Kim ),김영호 ( Young Ho Kim ),김원호 ( Won Ho Kim ),김태일 ( Tae Il Kim ),김효종 ( Hyo Jong Kim ),양석균 ( Suk Kyun Y 대한장연구학회 2005 Intestinal Research Vol.3 No.2

목적: 대장암 선별 검사로 사용되는 S상결장경이 근위부 대장에 있는 진행성 병변의 상당부분을 간과할 수 있다는 것이 밝혀지면서 선별 검사로서 대장내시경의 사용과 대장 원위부 용종의 임상적 의미에 대한 연구들이 있었다. 본 연구는 국내에서 대장 근위부 진행성 선종을 예측하는 데 원위부 용종의 임상적 의미와 위험 인자를 알아보고자 하였다. 대상 및 방법: 전향적 다기관 대장 용종 연구에서 50세 이상 무증상 환자에서 대장 내시경을 시행하며 용종 절제를 시행받은 826명을 대상으로 용종의 크기, 모양, 조직형, 위치 등의 성상을 기록하였다. 비장 굴곡을 경계로 근위부와 원위부를 나누었고 용종의 성상에 따라 분류한 후 원위부 소견에 따른 근위부 소견, 근위부 진행성 선종에 대한 원위부 용종의 민감도, 양성 예측률과 위험 인자를 분석하였다. 결과: 근위부에 진행성 선종 환자는 98명이었고 이들에서 원위부 대장 용종이 없었던 경우가 45명(45.9%)이었다. 원위부 용종의 크기에 따라 5 mm 미만이었을 때 근위부 진행성 선종이 있었던 경우가 1.9%, 5-10 mm인 경우 26.4%, 10 mm 이상인 경우 71.7%였다(p<0.01). 크기와 함께 조직형을 고려하여 분석하였을 때에도 역시 원위부 용종이 진행성 선종일수록 근위부에도 진행성 선종이 증가하였다(p<0.01). 용종 크기로 근위부 진행성 선종에 대한 민감도를 구하였을 때 10 mm 이상, 5 mm 이상일 때 각각 38.7%, 53.2%였고 조직형을 합한 진행성 선종에서는 38.8%였으며 양성 예측률은 10 mm 이상, 5-9 mm일 때 각각 13.3%, 4.1%였고 진행성 선종은 14.4%였다. 근위부 진행성 선종을 예측하는 위험인자로 남자(OD 3.9, 95%CI 1.61-9.48), 원위부 용종 10 mm 이상(OD 7.8, 95%CI 1.04-58.95), 원위부 진행성 선종(OD5.4 95%CI 1.61-17.9)이 통계적으로 유의한 위험 인자였다. 결론: 원위부 용종 소견이 대장 내시경을 통한 선별 검사 시에도 근위부 병변 예측에 도움이 될 것으로 생각하나 원위부 병변없는 근위부 진행성 선종 환자를 반드시 고려해서 주의 깊게 검사해야 할 것으로 생각한다. Backgroud/Aims: Proximal lesion without distal finding is weak point in colon cancer screening. Clinical significance of distal finding for advanced proximal neoplasia (APN) is uncertain. Aims of this study were to assess distal finding for prediction of APN. Methods: Asymptomatic 826 adults (age≥50) were collected in KASID prospective study, who underwent colonoscopy and polypectomy. Polyps located distal to splenic flexure were defined as distal polyps. Age, gender, size, appearance, histology of distal polyps were analyzed as risk factor of APN (adenoma≥10 mm or villous histology or high grade dysplasia or invasive cancer). Sensitivity and positive predictive value of distal polyp on APN were assessed. Results: APN were found in 98 patients and 45 (45.9%) patients of them were not associated with any distal findings. Risk factors of APN were male, size of distal polyp and advanced distal polyp. Sensitivity of distal polyp size≥10 mm on APN was 38.8% and advanced distal polyp also 38.8%. Positive predictive value of distal polyp size≥10 mm and advanced distal polyp were 13.3%, 14.4% respectively. Conclusions: Although distal colon findings were helpful to predict APN in asymptomatic 50 years of age or order patients screening, more careful examination is required considering APN without distal polyps. (Intestinal Research 2005;3:121-126)

The Korean Society of Gastroenterology & SIDDS 2053 : Slide Session ;K-LG-24 : Lower GI Tract ; Ten Years Follow Up Risk of Colorectal Neoplasia after Initial Negative Colonoscopy

( Sang Yoon Chung ),( Ja Seol Koo ),( Seung Young Kim ),( Jong Jin Hyun ),( Sung Woo Jung ),( Bora Keum ),( Beom Jae Lee ),( Yoon Tae Jeen ),( Sang Woo Lee ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background/Aims: In Korea, the surveillance colonoscopy after initial negative colonoscopy is recommended 5 years after negative colonoscopy. We evaluated the risk factors for colorectal neoplasia after negative screening colonoscopy. Methods: Among the patients underwent screening colonoscopy at Korea University Ansan Hospital from Jan. 2002 to Dec. 2009, the subjects without adenomas wereenrolled in the study retrospectively. Baseline characteristics on index colonoscopy and surveillance colonoscopic fi ndings were reviewed. Advanced adenoma was de-fi ned as an adenoma that met more than one of the following criterias: a size =10 mm, the presence of a substantial villous component, the presence of high-grade dysplasia. The prevalence of any adenoma and advanced adenoma were identifi ed and the risk factors on surveillance colonoscopy after negative screening colonoscopy were evaluated by using Cox regression model. Results: Among total 3,516 patients with screening colonoscopy, 1,506 without any adenomas were enrolled. The median of follow up interval after screening colonoscopy was 47.3 months(range,12.0 ~ 124.8). The incidence of any adenoma within 5years after negative colonoscopy was 293(29.0%) and those of any adenoma from 5 to 10 years was 135(27.2%). The prevalences of same terms in advanced adenoma were23(2.5%) and 8(1.4%). In cox regression analysis, the prevalence of any adenoma on surveillance colonoscopy were significantly increased in male(P<0.001) and old age(P<0.001). However, male gender and age were not associated with risk of advanced adenoma. Conclusions: Among the subjects with no colorectal adenoma on initial screening colonoscopy, the incidence of advanced adenomas was 2.1% on 10 year follow up surveillance. Although gender and age is associated with metachronous colorectal adenoma on surveillance colonoscopy, those are not associated with advanced adenoma. Therefore, surveillance interval of colonoscopy can be prolonged to 10 years.

204 - Role of Interstitial Cells of Cajal on Gastric Slow Wave Patterns During Gastric Electrical Stimulation

Kim, Seung Han,Jeen, Yoon Tae,Min, Geeho,Choi, Seoung Ji,Kim, Woojung,Lee, Jung Min,Lee, Jae Min,Choi, Hyuk Soon,Kim, Eun Sun,Keum, Bora,Lee, Hongsik,Chun, Hoon Jai,Kim, Chang Duck Elsevier 2018 Gastroenterology Vol.154 No.6

The Korean Society of Gastroenterology & SIDDS 2027 : Slide Session ; S-UG-08 : Upper GI Tract ; The Therapeutic Effect of Irreversible Electroporation According to Tissue Properties of Upper Gastrointestinal Tract: Gene Expression Signature Analysis

( Hyuk Soon Choi ),( Bora Keum ),( Hong Bae Kim ),( Jae Min Lee ),( Seung Han Kim ),( Seung Joo Nam ),( Eun Sun Kim ),( Yeon Seok Seo ),( Yoon Tae Jeen ),( Hong Sik Lee ),( Hoon Jai Chun ),( Soon Ho U 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Irreversible electroporation (IRE) is a promising novel technique for the ablation of tumors. IRE has an advantage over other ablation technique in its mechanism to remove undesired cells by affecting the cell membrane without thermally destructing blood vessels, nerves and the surrounding tissues. This therapeutic modality has been considered to apply to Barrett`s dysplasia or epithelial neoplasm of upper gastrointestinal tract instead of previous radiofrequency ablation. Our purpose was to study effectiveness of IRE according to tissue properties in rat stomach. Methods: The Sprague-Dawley rats were used throughout this study. IRE ablation was applied in upper stomach (squamous cell epithelium) and lower stomach (columnar cell epithelium) with same energy parameters. The energy delivered for each ablation was 50/100 pulses of 1KV/cm ~ 3KV/cm. And we used DNA microarrays to measure the expression levels of large numbers of genes in rat stomach according to different electrical energy. And we measured several apoptotic gene expression using real time RT-PCR. Results: All animals survived for their designated times. H-E staining showed extensive cell death area at 10 hours after IRE ablation in upper (squamous cell epithelium) and lower (columnar cell epithelium) gastric tissue. We confi rmed apoptotic cell death by Tunnel assay. The number of signifi cantly up-regulated apoptotic genes was higher in 2KV, 100 pulse and 10hr than that of other electrical energy groups. The signifi cantly up-regulated genes related to apoptosis after IRE ablation in all IRE setting were s100a8/9, Ccl2, Timp1. Aif1, Lcn2, hspb1 genes. Conclusions: This study showed that IRE ablated stomach tissue through cellular apoptosis. This study suggests the potentiality of IRE application in the treatment of not only gastric neoplasm but also esophageal neoplasm including dysplasia of Barrett`s esophagus without metastasis.

Poster Session:PS 0220 ; Gastroenterology : Selenium Supplementation Alleviates intestinal Mucositis Associated with Chemotherapy: An Experimental Study in Rats

( Jae Min Lee ),( Bora Keum ),( In Kyung Yoo ),( Seung Joo Nam ),( Seung Han Kim ),( Hyuk Soon Choi ),( Eun Sun Kimm ),( Yoon Tae Jeen ),( Hong Sik Lee ),( Hoon Jai Chun ),( Chang Duck Kim ),( Ho Sang 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Mucositis is a serious complication in patients receiving chemotherapy, and is induced by pro-infl ammatory cytokines and reactive oxygen species. Selenium has several metabolic functions, including protection of membrane lipids and macromolecules from oxidative damage. Protection against intestinal mucositis during chemotherapy has not been investigated. This study aimed to investigate the protective effect of selenium against chemotherapy-induced mucositis in rats. Methods: Twenty-four female Wistar rats (body weight 200-220 g) were randomly allocated to four groups: control: selenium: 5-fl uorouracil (5-FU): 5-FU plus selenium. Mucositis was induced by an intraperitoneal injection of 5-FU (400 mg/kg). Selenium supplementation was administered by an intraperitoneal injection of sodium selenite (0.2 mg/kg). Results: Diarrhea and weight loss after 5-FU administration was attenuated by selenium treatment. The degree of damage to the intestinal villi in rats treated with 5-FU and selenium supplementation was lesser than that in rats treated with 5-FU without selenium(Fig.1). The mRNA expressions of IL-1ß and TNF-a were signifi cantly decreased in the group treated with 5-FU and selenium compared with those in the group treated with 5-FU alone(Fig.2). Conclusions: Selenium has a benefi cial effect in protecting the mucosa during chemotherapy. This protective effect is attributed to its anti-infl ammatory effects and the selenium-induced suppression of cytotoxic cytokines.

Case Report : Remission of Cap Polyposis Maintained for More Than Three Years after Infliximab Treatment

( Eun Sun Kim ),( Yoon Tae Jeen ),( Bora Keum ),( Yeon Seok Seo ),( Hoon Jai Chun ),( Soon Ho Um ),( Chang Duck Kim ),( Ho Sang Ryu ) The Editorial Office of Gut and Liver 2009 Gut and Liver Vol.3 No.4

Cap polyposis is a rare disorder with characteristic endoscopic and histological features; its etiology is still unknown, and no specific treatment has been established. We report a case of cap polyposis that improved remarkably after infliximab infusion and had no recurrence for 3 years. (Gut and Liver 2009;3: 325-328)

The Korean Society of Gastroenterology & SIDDS 2051 : Slide Session ;K-LG-22 : Lower GI Tract ; Effi cacy and Tolerability of Low Volume Methods for Colon Preparation: A Randomized Prospective Trial

( In Kyung Yoo ),( Yoon Tae Jeen ),( Jae Min Lee ),( Seung Han Kim ),( Seoung Joo Nam ),( Hyuk Soon Choi ),( Eun Sun Kim ),( Bora Keum ),( Hoon Jai Chun ),( Hong Sik Lee ),( Chang Duck Kim ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Low-volume bowel preparations provide equivalent cleansing with improved tolerability compared to standard 4 L polyethylene glycol. However, studiescomparing superiority between low-volume bowel preparations are rare, and results are controversial. This study aimed to compare the bowel cleansing quality and tolerability between split-dose methods of sodium picosulfate/magnesium citrate and polyethylene glycol with ascorbic acid. Methods: A randomized, observer-blinded study was performed. In total, 200 outpatientswere prospectively enrolled and received colonoscopy using the low-volume bowel preparation. The Boston Bowel Preparation Scale and Aronchick scale were used to evaluate the bowel cleansing, and bubble scoring was also performed to back up both results. To investigate the preference and tolerability, a questionnaire was administered before colonoscopy. Results: One hundred patients received SPMC and 100 patients received PEG-Asc.The SPMC group showed superior cleansing quality compared to the PEG-Asc group (8-9 Boston scale score: 40% versus 22.8%, excellent Aronchick grade: 28.5% versus 14.2%, p < 0.05). There were fewer gastrointestinal symptoms and solution taste was better in the SPMC group compared to the PEG-Asc group (p < 0.05). Conclusions: The SPMC group showed excellent cleansing quality and better tolerability, palatability compared to the PEG-Asc.

Risk Factors for Severe Diverticulitis in Computed Tomography-Confirmed Acute Diverticulitis in Korea

( Nark Soon Park ),( Yoon Tae Jeen ),( Hyuk Soon Choi ),( Eun Sun Kim ),( Young Jin Kim ),( Bora Keum ),( Yeon Seok Seo ),( Hoon Jai Chun ),( Hong Sik Lee ),( Soon Ho Um ),( Chang Duck Kim ),( Ho Sang 대한소화기학회 2013 Gut and Liver Vol.7 No.4

Background/Aims: Acute complicated diverticulitis can be subdivided into moderate diverticulitis and severe diverticulitis. Although there have been numerous studies on the risk factors for complicated diverticulitis, little research has focused on severe diverticulitis. This study was designed to identify the risk factors for severe diverticulitis in an acute diverticulitis attack using the modified Hinchey classification. Methods: Patients were included if they had any evidence of acute diverticulitis detected by computed tomography. The patients were subdivided into severe diverticulitis (Hinchey class Ib; abscesses or peritonitis) and moderate diverticulitis (Hinchey class Ia; pericolic inflammation) groups. Results: Of the 128 patients, 25 exhibited severe diverticulitis, and 103 exhibited moderate diverticulitis. In a multivariate analysis, age >50 years (odds ratio [OR], 5.27; p=0.017), smoking (OR, 3.61; p=0.044), comorbidity (OR, 4.98; p=0.045), leukocytosis (OR, 7.70; p=0.003), recurrence (OR, 4.95; p=0.032), and left-sided diverticulitis (OR, 6.92; p=0.006) were significantly associated with severe diverticulitis. Conclusions: This study suggests that the risk factors for severe diverticulitis are age >50 years, smoking, comorbidity, leukocytosis, recurrent episodes, and left-sided diverticulitis. (Gut Liver 2013; 7:443-449)

Polyethylene glycol plus ascorbic acid for bowel preparation in chronic kidney disease

Lee, Jae Min,Keum, Bora,Yoo, In Kyung,Kim, Seung Han,Choi, Hyuk Soon,Kim, Eun Sun,Seo, Yeon Seok,Jeen, Yoon Tae,Chun, Hoon Jai,Lee, Hong Sik,Um, Soon Ho,Kim, Chang Duck,Kim, Myung Gyu,Jo, Sang Kyung Williams & Wilkins Co 2016 Medicine Vol.95 No.36

<P>The safety of polyethylene glycol plus ascorbic acid has not been fully investigated in patients with renal insufficiency. High-dose ascorbic acid could induce hyperoxaluria, thereby causing tubule-interstitial nephritis and renal failure. This study aims to evaluate the safety and efficacy of polyethylene glycol plus ascorbic acid in patients with chronic kidney disease.We retrospectively reviewed prospectively collected data on colonoscopy in patients with impaired renal function. Patients were divided into 2 groups: 2 L polyethylene glycol plus ascorbic acid (n = 61) and 4 L polyethylene glycol (n = 80). The safety of the 2 groups was compared by assessing the differences in laboratory findings before and after bowel cleansing.The laboratory findings were not significantly different before and after the administration of 2 L polyethylene glycol plus ascorbic acid or 4 L polyethylene glycol. In both groups, the estimated glomerular filtration rate was not influenced by the administration of the bowel-cleansing agent. Patients' reports on tolerance and acceptability were better in the 2 L polyethylene glycol plus ascorbic acid group than in the 4 L polyethylene glycol group.The 2 L polyethylene glycol plus ascorbic acid solution is a safe choice for bowel preparation before colonoscopy in patients with impaired renal function.</P>