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이상길 ( Sang Kil Lee ),김효종 ( Hyo Jong Kim ),지성길 ( Sung Gil Chi ),장재영 ( Jae Young Jang ),남기덕 ( Ki Deok Nam ),김남훈 ( Nam Hoon Kim ),주광로 ( Kwang Ro Joo ),동석호 ( Seok Ho Dong ),김병호 ( Byung Ho Kim ),장영운 ( Youn 대한소화기학회 2005 대한소화기학회지 Vol.45 No.5
Background/Aims: Saccharomyces boulardii (S. boulardii) has been reported to be beneficial in the treatment of inflammatory bowel disease, however, little is known about its mechanism of action. Peroxisome proliferator- activated receptor-γ (PPAR-γ) is re
TNBS 유도 대장염에서의 Microarray 분석과 Saccharomyces boulardii의 역할에 관한 연구
이상길 ( Sang Kil Lee ),김효종 ( Hyo Jong Kim ),지성길 ( Sung Gil Chi ) 대한소화기학회 2010 대한소화기학회지 Vol.55 No.1
목적: Saccharomyces boulardii (S. boulardii)는 이미 여러 종류의 설사병에 사용되고 있으며 작용 기전이 정확히 알려져 있지는 않지만 염증성 장질환에서도 치료 효과가 보고되고 있다. 이에 저자들은 S. boulardii의 염증성 장질환에서의 효과와 작용 기전을 알아보기 위하여 2,4,6-trinitrobencene sulfonic acid (TNBS)로 유발한 대장염 동물모델을 이용하여 조직학적 분석과 microarray를 하였다. 대상 및 방법: BALB/c 흰쥐에게 경구 식이용 관을 이용하여 항문으로 TNBS (2mg)와 50% 에탄올 혼합물(0.1 mL)을 주입하였다. S. boulardii는 10 mg을 하루에 두 번 4일 동안 경구 투여시켰다. Microarray는 마크로젠의 DNA chip 기술 매뉴얼에 따라서 시행되었다. 결과: TNBS로 유발한 장염에서 S. boulardii의 처리는 조직학적 손상과 사망률을 감소시켰다(p<0.05). 총 33,013개의 유전자 중에서 TNBS와 S. boulardii에 의해서 유의한 수준인 2배 이상으로 변화한 것이 330개 있었다. 이 중에서 TNBS에 의해서 과발현된 유전자의 과발현폭을 S. boulardii가 감소시킨 것이 193개였다. 이들 유전자를 기능에 따라 분류하면 염증반응과 면역반응에 관여하는 유전자들이 많았다. 결론: S. boulardii의 항염증 효과가 염증반응과 면역 및 방어 반응에 관여하는 유전자의 발현변화를 통해서 나타날 가능성이 높고, 이에 대한 추가 연구가 필요하다. Background/Aims: Saccharomyces boulardii has been reported to be beneficial in the treatment of inflammatory bowel disease. The aim of this work was to evaluate the effect of S. boulardii in a mice model of 2,4,6-trinitrobencene sulfonic acid (TNBS) induced colitis and analyze the expression of genes in S. boulardii treated mice by microarray. Methods: BALB/c mice received TNBS or TNBS and S. boulardii treatment for 4 days. Microarray was performed on total mRNA form colon, and histologic evaluation was also performed. Results: In mice treated with S. boulardii, the histological appearance and mortality rate were significantly restored compared with rats receiving only TNBS. Among 330 genes which were altered by both S. boulardii and TNBS (>2 folds), 193 genes were down-regulated by S. boulardii in microarray. Most of genes which were down-regulated by S. bouardii were functionally classified as inflammatory and immune response related genes. Conclusions: S. boulardii may reduce colonic inflammation along with regulation of inflammatory and immune responsive genes in TNBS-induced colitis. (Korean J Gastroenterol 2010;55:33-45)
한국인 대장 선종성용종 환자에서의 MYH 유전자 변이에 대한 연구
김한수 ( Hansoo Kim ),김효종 ( Hyo Jong Kim ),지성길 ( Sung Gil Chi ),주광로 ( Gwang Ro Joo ),동석호 ( Seok Ho Dong ),김병호 ( Byung Ho Kim ),장영운 ( Young Woon Chang ),이정일 ( Jung Il Lee ),장린 ( Rin Chang ) 대한장연구학회 2005 Intestinal Research Vol.3 No.1
Background/Aims: Recently, germ-line mutation in the base-excision-repair gene MYH was identified to cause a novel autosomal recessive form of familial adenomatous polyposis (FAP). Interestingly, a striking evidence for MYH mutations within different ethnic groups has been demonstrated. We have screened 30 patients with multiple adenomatous polyps for MYH mutations to assess its prevalence and ethnic specificity in Korea. Methods: Thirty patients with multiple adenomatous polyps were examined for MYH mutations. Twenty-one men and 9 women presented at a median age of 62.3 years. The mean number of adenomas per patient was 10.0. Sixteen exonic regions and its intronic sequences were amplified by PCR and subjected to SSCP and DNA sequencing analyses. Results: None of the patients was identified to carry any truncating or sequence alterations in MYH. Our screening for the mutational regions, which were recognized from Caucasian patients or affected Indian families, also failed to detect sequence substitutions. Conclusions: Mutation in MYH may be rarely involved in the pathogenesis of multiple sporadic colorectal adenomas in Korea, although large-scale analysis will be required to clarify the presence of specific MYH variants in a subset of patients and its role for the predisposition of multiple colorectal adenomas in Korea. (Intest Res 2005;3:27-32)
이지은 ( Ji Eun Lee ),이선경 ( Seon Kyung Lee ),지성길 ( Sung Gil Chi ) 대한산부인과학회 2006 Obstetrics & Gynecology Science Vol.49 No.12
Objective: Vascular Endothelial Growth Factor (VEGF) is a potent stimulator of angiogenesis in solid tumors. Thrombospondin-1 (TSP-1) has inhibitory role in cancer cell proliferation and metastasis. To analyze the correlation with expression of VEGF and TSP-1 including microvessel density (MVD), the levels of VEGF/TSP-1 mRNA expression and microvessel count (MVC) were estimated in patients with invasive cervical carcinomas. Methods: From 1996 to 1999, 37 carcinomas and 7 normal cervical tissues were collected, frozen and stored at -70℃ until used. The levels of VEGF and TSP-1 mRNAs were determined by quantitative RT-PCR. MVD was assessed by immunostaining for factor VIII-related antigen. The results are expressed as the largest number of microvessels present within a single ×40 field, and counted at x 100 field. Results: Quantitative RT-PCR analysis demonstrated abnormally increased VEGF mRNA expression levels (>0.66) in 14 (37.8%) of 37 cervical carcinomas comparing to control groups (mean: 0.32±0.09) and abnormally low TSP-1 mRNA expression levels (<0.72) in 13 (35.1%) of 37 cervical carcinomas comparing to control groups (mean: 0.51±0.07). MVC was higher in tumors showing decreased expression of TSP-1 (but not statistically) (p<0.18) and overexpression of VEGF (p<0.05). When VEGF overexpression was accompanied with reduced TSP-1 expression, the microvessel density showed significantly increased pattern (p<0.05). Conclusion: Our study demonstrates that reduced expression of TSP-1 mRNAs and overexpression of VEGF mRNAs may be an important contributing factor in cervical carcinomas. Moreover, the inversed correlation of VEGF and TSP-1 mRNA expression can be an evidence of angiogenic role in cervical carcinomas.
부인암에서의 Telomerase 활성도와 자궁경부암 조직에서의 HPV E6 의 발현과 Telomerase 활성도의 상관관계
유용신(Yong Sin You),이선경(Seon Kyung Lee),김승보(Seung Bo Kim),지성길(Sung Gil Chi) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.8
Object : In this study, to evaluate the putative role of telomerase in gynecologic malignancies (cervical ca, ovarian ca, endometrial ca), we measured telomerase activity in malignant gynecologic tumor tissues and normal tussues, and compared it with prognostic factors in cervical cancer. To evaluate the correlation of telomerase activity and human papillomavirus (HPV) infection in cervical cancer, the analysis of HPV E6 gene was performed. Method : Specimens were obtained from 51 women who underwent gynecologic radical operation and 13 normal tissues (from December 1995 to December 1996) in the Department of Obstetrics and Gynecology, Kyung-Hee Univ. Medical Center. With Telomerase PCR ELISA (Boehring Mannheim), modified TRAP (Telomere Repeat Amplication Protocol), we examined telomerase activity of 32 cervical carcinomas, 11 ovarian carcinomas, 8 endometrial carcinomas, 5 normal cervical tissues, 4 normal ovarian tissues and 4 normal endometrial tissues. The analysis of HPV E6 gene was performed by PCR amplication. We compared the abnormally high telomerase activity with prognostic factors, also compared the telomerase activity with the expression of HPV E6 gene in cervical cancer tissues. Result : We detected the abnormally high telomerase activity in all cervical carcinomas, 10 of 11 (90.9%) ovarian carcinomas, 6 of 8 (75.0%) endometrial carcinomas, but couldn't detect in each normal tissues. There was statistically no significant difference of telomerase activity levels according to age, clinical stage, pathology, differentiation, LN involvement, depth of invasion and tumor size except lymphovascular space invasion in cervical carcinomas (p<0.05). According to the analysis of HPV E6 gene, 29 of 32 (90.6%) in 32 cervical cancer tissues showed HPV E6 positivity. So it was considered that telomerase activation was closely related with the expression of HPV E6 gene. Conclusion : Telomerase activation is associated with immortalization or malignant transformation of gynecologic cancers. The expression of HPV E6 gene is considered to activate telomerase in cervical cancer.
대장암에서 관찰되는 XAF1 과메틸화에 의한 유전자외 불활성 연구
장재영 ( Jae Young Jang ),김효종 ( Hyo Jong Kim ),지성길 ( Sung Gil Chi ),이길연 ( Kil Yeon Lee ),남기덕 ( Ki Deuk Nam ),김남훈 ( Nam Hoon Kim ),이상길 ( Sang Kil Lee ),주광로 ( Kwang Ro Joo ),동석호 ( Seok Ho Dong ),김병호 ( Byun 대한소화기학회 2005 대한소화기학회지 Vol.45 No.4
Background/Aims: X-linked inhibitor of apoptosis (XIAP) is the most potent member of the IAP family that exerts antiapoptotic effects. Recently, XIAP-associated factor 1 (XAF1) and two mitochondrial proteins, Smac/DIABLO and HtrA2, have been identified to
대뇌 핍지교종이 동반된 Turcot 증후군 1예의 유전학적 분석
김한수 ( Han Soo Kim ),박지영 ( Ji Young Park ),김효종 ( Hyo Jong Kim ),지성길 ( Sung Gil Chi ),김윤화 ( Yoon Hwa Kim ),이길연 ( Kil Yeon Lee ),정용희 ( Yong Hee Joung ),한요셉 ( Yo Seb Han ),동석호 ( Seok Ho Dong ),김병호 ( Byung 대한장연구학회 2003 Intestinal Research Vol.1 No.2
Turcot`s syndrome (TS) is a genetic disease characterized by primary brain tumor, colon cancer and/or multiple colorectal polyps. The mode of genetic transmission of the syndrome still remains unclear because TS is a rare disorder. The majority of central nervous system (CNS) neoplasms associated with TS are glioma, glioblstoma multiformes and medulloblastoma. Other types of CNS tumors related to TS have been noted in a few case reports, and there are only two reports of oligodendroglioma associated with TS. To the authors` knowledge, this is the first case of a patient with TS who had a cerebral oligodendroglioma and a colorectal adenocarcinoma in Korea. Therefore, the authors performed genetic analysis of this patient and her family to determine the genetic variants, including mutations in APC gene and mismatch repair gene, in Turcot`s syndrome. (Intestinal Research 2003;2:192-196)