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데옥시콜릭산에 의한 HT-29 대장상피세포의 신호전달 -NF-κB와 Interleukin-8의 역할-
이동기 ( Lee Dong Gi ),박선영 ( Park Seon Yeong ),백순구 ( Baeg Sun Gu ),권상옥 ( Kwon Sang Og ),정준모 ( Jeong Jun Mo ),오억수 ( O Eog Su ),김현수 ( Kim Hyeon Su ) 대한소화기학회 2004 대한소화기학회지 Vol.43 No.3
Background/Aims: Deoxycholic acid (DCA) has been appeared to be an endogenous colon tumor promoter. In this study, we investigated whether DCA induces nuclear factor-kappa B (NF-kB) activation and IL-8 expression, and tauroursodeoxycholic acid (TUDC) inhibits this signaling in HT-29 cells. Methods: After DCA treatments, time courses of NF-kB binding activity were determined by electrophoretic mobility shift assay (EMSA). Also, we performed Western blotting of IkBα to confirm NF-kB activation. Time and concentration courses of DCA-induced secretion of IL-8 were measured with ELISA in supernatants of cultured media from the cells. To evaluate the role of NF-kB, IL-8 levels were assessed after pretreatment with using phosphorothioate-modified anti-sense oligonucleotides (ODN). Moreover, DCA-induced secretions of IL-8 were measured after pretreatment with TUDC. Results: DCA dose-dependently induced prominent NF-kB binding complexes from 30 min to 8 hr and degradation of IkBα. The secretions of IL-8 were increased with DCA (50~200 μM) treatment in a time and dose-dependent manner. Pre-incubation of the cells with TUDC (0.1~10 μM) for 2 hours caused significant decreases in DCA induced IL-8 secretion. However, transient transfection using p50 or p65 AS-ODN showed no effect on IL-8 secretion. Conclusions: DCA may play as a colonic tumor promoter through anti-apoptotic effect of NF-kB activation and IL-8 expression, and DCA-induced NF-kB independent IL-8 expression is inhibited by TUDC. (Korean J Gastroenterol 2004;43:176-185)
대장암 세포주에서 데옥시콜릭산에 의한 세포 침습성과 전이의 조절
김현수 ( Kim Hyeon Su ),장화인 ( Jang Hwa In ),백순구 ( Baeg Sun Gu ),이동기 ( Lee Dong Gi ),권상옥 ( Kwon Sang Og ) 대한소화기학회 2003 대한소화기학회 추계학술대회 Vol.2003 No.-
<목적> 대장 내 DCA (deoxycholic acid) 농도의 증가는 인체역학연구와 동물모델에서 발암물질에 의한 대장종양발생을 촉진시키는 종양촉진인자로 알려져 있으나, 세포의 침습성이나 전이와 관련된 조절 기전에 대한 연구는 거의 없는 실정이다. 본 연구에서는 HT29 및 HCT116 대장암 세포주에서 DCA 자극 후 VEGF 및 HIF-1α, MMP (metalloproteinase)의 발현변화와 세포 이동성 등의 세포의 침습성 및 전이 관련 세포
지명관 ( Ji Myeong Gwan ),백순구 ( Baeg Sun Gu ),원찬식 ( Won Chan Sig ),변종원 ( Byeon Jong Won ),김현수 ( Kim Hyeon Su ),이동기 ( Lee Dong Gi ),권상옥 ( Kwon Sang Og ),김영주 ( Kim Yeong Ju ) 대한소화기학회 2003 대한소화기학회 추계학술대회 Vol.2003 No.-
<목적> 간경변환자는 문맥압 항진증과 동맥혈관 저항의 감소에 따른 혈역학적 변화를 갖는다. 본 연구는 간경변환자의 예후에 영향을 미치는 혈역학적 요인에 대해 알아보고자 하였다. <대상 및 방법> 총 103명의 간경변 환자를 대상으로 1999년 12월부터 2003년 6월까지 174주간의 추적연구를 통해 혈역학적 지표로 평균 혈압, 심박동수, 문맥압을 대변하는 간정맥 압력차(hepatic venous pressure gradient), 문맥 혈류량, 비장
위부분절제술 환자에서 미란성 식도염의 유병률 조사 환자-대조군 연구
석기태 ( Seog Gi Tae ),김현수 ( Kim Hyeon Su ),김정민 ( Kim Jeong Min ),최윤종 ( Choe Yun Jong ),백순구 ( Baeg Sun Gu ),이동기 ( Lee Dong Gi ),권상옥 ( Kwon Sang Og ),김대성 ( Kim Dae Seong ),김원중 ( Kim Won Jung ) 대한소화기학회 2003 대한소화기학회지 Vol.42 No.2
Background/Aims: Enterogastric bile reflux has been implicated as a definite causative factor for the development of postoperative bile reflux gastritis. However, little is known about the role of bile reflux into the stomach in gastro-esophageal reflux disease in patients with subtotal gastrectomy. In this study, we tried to prove that the bile reflux gastritis does increase the development of erosive esophagitis in patients who underwent subtotal gastrectomy. Methods: From January 1997 to December 2001, 222 patients with previous subtotal gastrectomy were enrolled. We also reviewd the endoscopic findings in 1,633 age and sex-matched healthy controls who had visited our hospital for routine check-up without significant gastrointestinal symptoms. Results: The prevalence of erosive esophagitis is 5% (LA A 2.7%, LA B 2.3%) in gastrectomized patients and 4.9% (LA A 3.2%, LA B 1.7%, LA C 0.0%) in healthy controls. There was no significant difference in the prevalence and the degree of esophagitis between the two groups. Conclusions: These results suggest that subtotal gastrectomy may not be a risk factor for developing the erosive reflux esophagitis. (Korean J Gastroenterol 2003;42:96-101)
대한간학회지 제8차 춘계학술대회 초록집 : 구연 ; 간경변 환자에서 Octreotide 정주가 문맥압에 미치는 영향
박동훈 ( Park Dong Hun ),백순구 ( Baeg Sun Gu ),김문영 ( Kim Mun Yeong ),최윤종 ( Choe Yun Jong ),김현수 ( Kim Hyeon Su ),이동기 ( Lee Dong Gi ),권상옥 ( Kwon Sang Og ),김영주 ( Kim Yeong Ju ) 대한간학회 2002 Clinical and Molecular Hepatology(대한간학회지) Vol.8 No.2(S)
경도-중등도의 역류성 식도염에서 저용량 오메프라졸과 표준 용량 라니티딘의 치료 효과
김재우 ( Kim Jae U ),김현수 ( Kim Hyeon Su ),이동기 ( Lee Dong Gi ),석기태 ( Seog Gi Tae ),김정민 ( Kim Jeong Min ),백순구 ( Baeg Sun Gu ),권상옥 ( Kwon Sang Og ),조미연 ( Jo Mi Yeon ) 대한소화기학회 2004 대한소화기학회지 Vol.43 No.3
Background/Aims: Proton pump inhibitors (PPI) and H2-receptor antagonists (H2RA) are commonly prescribed for the treatment of mild to moderate reflux esophagitis (MMRE). There remains great controversy in their usefulness as the first choice and the appropriateness. We prospectively compared the efficacy and safety of the 8-week low-dose PPI vs. standard-dose H2RA in MMRE. Methods: One hundred patients with MMRE were randomized to receive either low-dose of omeprazole (L-OMP: 10 mg, q.d.) or standard-dose of ranitidine (S-H2RA: 150 mg, b.i.d.) for 8 weeks. The H. pylori status using rapid urease test, histological examination and culture, reflux esophagitis (RE) grading, gastrointestinal symptoms using 4-point scale, adverse event and the standard laboratory examination were assessed at baseline and 8-week end point of therapy. Results: Improvement rate of RE [intention to treat (n=82)/per protocol (n=72)] were shown in 69.1%/63.9% for L-OMP and 65.0%/63.9% for S-H2RA group (p=0.697, p=1.000). Complete healing rates of RE were 54.7%/50.0% for L-OMP and 42.5%/41.7% for S-H2RA. No significant difference in healing rate, the rapidity of symptom resolution, adverse events, and laboratory monitoring was found between the two groups. Conclusions: The low-dose omeprazole therapy produced similar healing rates and safety in the treatment of MMRE. In addition, L-OMP is advantageous in its once-a-day dosing and might be an alternative to S-H2RA, especially in Korean patients with MMRE (Korean J Gastroenterol 2004;43:153-159)
위장관암 환자에서 혈청 CA 72-4, CA 19-9 및 CEA의 진단적 의의
장우익 ( Jang U Ig ),김철한 ( Kim Cheol Han ),김현수 ( Kim Hyeon Su ),이종인 ( Lee Jong In ),이동기 ( Lee Dong Gi ),권상옥 ( Kwon Sang Og ),심영학 ( Sim Yeong Hag ),김대성 ( Kim Dae Seong ),윤갑준 ( Yun Gab Jun ),장세진 ( Jang Se 대한내과학회 1992 대한내과학회지 Vol.42 No.6
연구배경 : 종양표지자는 암의 조기진단, 임상적 병기 구분 및 치료효과 판정에 사용될 수 있다. 위장관암에서 alpha-fetoprotein, carcinoembryonic antigen 및 CA 19-9가 중요한 종양표지자로 사용되고 있으나 위암에 대한 적당한 종양표지자가 없는 실정이다. 이에 저자등은 위암에 대한 새로운 종양표지자로 CA 72-4의 역할을 규명하고자 위암을 비롯한 각종 위장관암에서 CA 19-9 및 CEA를 동시 측정하여 비교하였다. 방법 : 대상은 위장관 악성종양환자 273예, 위장관 양성질환자 215예 및 정상대조군 93명이었으며, CA 72-4는 CIS ELSA CA 72-4 RIA kit, CA 19-9는 Abbott CA 19-9 RIA kit 그리고 CEA는 Abbott CEA RIA kit를 이용하여 측정하였으며, 각각의 정상 상한치는 4 U/ml, 37U/ml 그리고 5ng/ml로 하였고 다음과 같은 결과를 얻었다. 결과 : 1) CA 72-4, CA 19-9 및 CEA의 평균치는 악성종양군에서 정상대조군이나 양성질환군보다 높았다(p<0.05). 2) CA 72-4는 장기별 양성질환에서 95~100%의 높은 특이도를 보였으나 CA 19-9는 담도질환에서 54%, CEA는 간장질환에서 63%로 CA 72-4에 비해 낮은 특이도를 보였다. (p<0.05). 3) CA 72-4는 위암에서 민감도가 49%로 CEA(31%) 및 CA 19-9(31%)보다 높았다(p<0.05). 4) CA 72-4는 췌장암 및 담도암에서 민감도가 각각 43%, 44%로서 CA 19-9(각각 79%, 87%)보다 낮았으며 (p<0.05), 대장암에서도 35%로 CEA(74%)보다 매우 낮았다(p<0.05). 5) 8예의 조기위암환자 전예에서 CA 72-4를 비롯한 CA 19-9 및 CEA가 모두 음성이었다. 6) 위암에서 림프절 전이 유무에 따른 CA 72-4의 차이는 없었으나, 원격 전이가 없는 환자군(10%)에 비해 원격전이군(77%)에서 현저하게 높은 양성률을 보였다(p<0.05). 7) 위암의 병기별 CA 72-4의 분포는 4병기에서 83%로 1병기(7%), 2병기(8%) 및 3병기(13%)보다 현저히 높았다(P<0.05). 8) 근치적 위절제술을 시행한 5예의 위암환자에서 수술후 CA 72-4치가 정상 상한치 이하로 감소하였고 항암 약물요법에 반응을 보였던 4예의 진행성 위암환자에서도 약물치료후 현저한 감소가 있었다. 9) CA 72-4는 전이성 대장암 및 췌장암에서 국소 및 국소진행성 대장암 및 췌장암에 비해 현저히 높은 양성률을 보였다. 10) 위암환자에서 CA 72-4와 CA 19-9 또는 CA 72-4와 CEA사이의 상관관계는 없었다. 결론 : 이상과 같이 CA 72-4는 위암에서 CA 19-9 및 CEA 보다 높은 민감도를 보였으며 특히 4병기 위암에서 현저히 높은 민감도를 보이는바 CA 72-4가 양성인 경우 치료방침을 결정하는데 신중한 고려가 필요할 것으로 생각된다. 또한 CA 72-4는 위암에서 수술 혹은 항암 약물 요법의 치료 monitoring에 적절히 사용될 수 있는 종양 표지자로 생각된다. 또한 각종 위장관 질환에서 CA 72-4는 기존의 종양표지자에 비해 높은 특이도를 보이는바 CA 72-4가 양성인 경우 항상 악성종양의 가능성을 고려하여야 한다. Background: Detection of tumor markers could offer an accessible method for screening risk groups in order to achieve an early diagnosis of cancers, to contribute to an adequate staging, and to help evaluate effects of therapy. Alpha-fetoprotein, carcinoembryonic antigen and CA 19-9 are regarded as valuable tumor markers for gastrointestinal cancers. But in spite of the high incidence of gastric cancer in Korea, ideal tumor markers for gastric ancer have proved unrelible. So we investigated whether new tumor marker CA 72-4 is a reliable tumor marker for gastric cancer. And we compared CA 72-4 with CA 19-9 and CEA in the serodiagnosis of gastrointestinal cancers. Methods: Serum CA 72-4, CA 19-9 and CEA were determined radioimmunologically with monoclonal antibodies. A cut-off value of 4 U/ml, 37 U/ml and 5 ng/ml were used, respectively. Results: The results are summarized as follows. 1) The mean value of 72-4, CA 19-9 and CEA in malignant diseases were significantly higher than those of the benign digestive diseases (p<0.05). 2) CA 72-4 had high specificity ranged from 95%-100% in benign digestive disease groups but CA 19-9 (54%) had lower specificity in cholelithiasis(p<0.05) and CEA (63%) in benign liver diseases (p < 0.05). 3) In gastric carcinoma, the sensitivity of CA 72-4 (49%) was higher than that of CA 19-9 (31%, p<0.05) and CEA (31%, p<0.05). 4) The sensitivities of CA 72-4 was inferior to CA 19 -9 in pancreatic cancer (43% versus 79%, p<0.05) and in bile duct cancer (44% versus 87%, p<0.05) and to CEA in colon cancer (35% versus 749& p<0.05). 5) Eight of 45 resected gastric carcinoma patients had TI lesion (early gastric cancer), and CA 72-4, CA 19-9 and CEA were demonstrated all negative results for early gastric cancer. 6) In gastric carcinoma, there was no correlation between CA 72-4 positivity and occurrence of lymph node metastasis but significant difference of CA 72-4 positivity was observed between those with distant metastasis and those without metastasis(p<0.05). 7) The positive ratings in stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ gastric carcinoma were 7% (1 of 14 patients), 8% (1 of 12 patients), 13% (2 of 16 patients), and 83% (24 of 29 patients) respectively and significant higher CA 12-4 positivity was observed in stage IV gastric carcinoma (p<0.05). 8) Elevated levels of serum CA 72-4 decreased to below the cut-off value after radical gastric resection in five patients with resectable gastric carcinoma and decreased also after chemotherapy in four patients with chemo-responsive metastatic gastric carcinoma. 9) Comparing with local or locally advanced colon cancer and pancreatic cancer, high positivity of CA 72-4 was observed in metastatic colon cancer and pancreatic cancer. 10) No significant correlation was observed between CA 72-4 and CA 19-9 or between CA 72-4 and CEA in gastric carcinoma. Conclusion: In conclusion, our data indicates that CA 72-4 is a reliable new tumor marker of disease stages and activity in gastric carcinoma. And CA 72-4 had a very high specificity in benign digestive diseases, so that elevated serum levels of CA 72-4 should always be taken seriously.
간성상세포의 수축 및 성장에 대한 Angiotensin 2 수용체 길항제의 억제 효과
백순구 ( Baeg Sun Gu ),조호성 ( Jo Ho Seong ),석기태 ( Seog Gi Tae ),김정민 ( Kim Jeong Min ),이병준 ( Lee Byeong Jun ),최윤종 ( Choe Yun Jong ),김현수 ( Kim Hyeon Su ),이동기 ( Lee Dong Gi ),권상옥 ( Kwon Sang Og ),이건일 ( Lee G 대한소화기학회 2003 대한소화기학회지 Vol.42 No.2
Backgrounds/Aims: This study aimed to investigate the effects of angiotensin II (ANG II) and its receptor antagonist (losartan) on the contraction and growth of HSCs. Methods: HSCs were isolated from Sprague Dawley rat and cultured at various conditions as follows: control, pretreatment of 10(-5) M ANG II, pretreatment of 10(-5) M endothelin, and pretreatment of 10(-5) M ANG II and 10(-6) M losartan. We conducted morphologic analysis with cellular area and length by image analysis system to estimate cell growth in each group. In addition, we measured the change of intracellular calcium currents via electrophysiological methods to evaluate the contractile effect of ANG II and losartan on HSCs. Results: At the fifth day of incubation, the mean cellular area of ANG II-pretreated group and ANG II with losartan-pretreated group were 704.68±22.6 um2 and 332.90±32.6 um2, respectively. This difference was statistically significant (p<0.05). ANG II induced an increase in the intracellular calcium current by 22.0±3.0% compared with basal current level (p<0.05). However, when losartan was pretreated, ANG II did not cause a significant increase in calcium current (3.1±0.8%, p>0.05). Conclusion: ANG II accelerates the contraction and growth of HSCs, while its receptor blocker, losartan, inhibits the contraction and growth of HSCs (Korean J Gastroenterol 2003;42:134-141)