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The Role of Fragile Histidine Triad As Tumor Suppressor in Pathogenesis of Hepatocellular Carcinoma
송일한 ( Song Il Han ),신정은 ( Sin Jeong Eun ),김홍자 ( Kim Hong Ja ),황일란 ( Hwang Il Lan ),류명수 ( Lyu Myeong Su ),( Kenneth H. Buetow ) 대한소화기학회 2003 대한소화기학회 추계학술대회 Vol.2003 No.-
<Aims> Fragile histidine triad (FHIT), located within chromosome 3p14.2, has been known to be one of molecular targets as the candidate tumor suppressor involved in the development of several human tumors. <Methods> In order to define the pathogenetic rol
선택적 cyclooxygenase-2 억제제에 의한 간암세포의 성장억제에서 surviving 유전자 발현의 하향조절
송일한 ( Il Han Song ),김동우 ( Dong Woo Kim ),신기철 ( Ki Chul Shin ),신현덕 ( Hyun Duk Shin ),윤세영 ( Se Young Yun ),김석배 ( Suk Bae Kim ),신정은 ( Jung Eun Shin ),김홍자 ( Hong Ja Kim ),김은영 ( Eun Young Kim ) 대한간학회 2008 Clinical and Molecular Hepatology(대한간학회지) Vol.14 No.3
송일한(Il Han Song),이영상(Young Sang Lee),정영화(Young hwa Chung),서동진(Dong Jin Suh),민영일(Young Il Min) 대한소화기학회 1995 대한소화기학회지 Vol.27 No.5
Mesenteric venous thrombosis(MVT) is a rare but distinct form of intestinal ischemia. Most patients with acute MVT usually present symptoms of acute abdominal pain, ileus, ascites, and mucoid or bloody diarrhea, and have rapidly deteriorating clinical courses. Portal vein thrombosis(PVT) can be frequent1y seen in patients with hepatocellular carcinoma(HCC), but MVT has rarely been reported. Because of rapid and complete compromise of venous drainage from the involved bowel and the rare chance of adequate collateral formation, MVT occurrence in patients with HCC could be one of fatal complications resulting in rapid deterioration and early death. We observed four cases of MVT in HCC, and analysed clinical data. Most of our patients had severe aMominal pain, nausea, vomiting, bloody diarrhea, uncontrolled ascites, and severe bowel edema. MVT could be verified by doppler ultrasonography, abdominal computerized tomography, and selective angiography. In spite of intensive medical care, they all died within 1 4 months, due to intractable gastrointestinal bleeding, hepatorenal syndrome, or sepsis. We present four cases of MVT in HCC patients with a review of the related literature. (Korean J Gastroenterol 1995;27: 595 - 601)
폐쇄성 황달을 동반한 간세포암 환자에서 담관조영소견의 분석
송일한(Il Han Song),고문수(Moon Soo Koh),최호순(Ho Soon Choi),이성구(Sung Koo Lee),정영화(Young Hwa Chung),김명환(Myung Hwan Kim),이영상(Yung Sang Lee),서동진(Dong Jin Suh),민영일(Young Il Min) 대한소화기학회 1996 대한소화기학회지 Vol.28 No.1
N/A Background/Aims: Jaundice is present in 19-44% of patients with hepatocellular carcinoma(HCC) at the time of diagnosis. The mechanisms of jaundice are associated with cirrhosis, tumor infiltration into the hepatic parenchyma, and bile duct obstruction. Causes of obstructive jaundice secondary to bile duct obstruction in HCC are bile duct invasion of tumor, tumor thrombi, blood clot of hemobilia, and direct bile duct compression of tumor or metastatic lymph n3e. Methods: To evaluate levels and causes of bile duct obstruction in HCC patients with obstructive jaundice and to assess its survival according to causes of obstructive jaundice, we performed retrospective study, from March 1992 to June 1994, with HCC patients with obstnictive jaundice who under- went endoscopic retrograde cholangogiraphy and/or percutaneous transhepatic cholangiography. Results: The commonest level of bile duct obstruction was common hepatic duct(35.3%), followed by common bile duct(23.5%). The causes of obstruction type were tumor invasion(58.8%), tumor thromhi(29.4%), blood clot with hemobilia(5.97o), and bile duct compression hy tumor (5.9%), in order. The level of bile duct obstruction in most cases of tumor invasion was common hepatic duct while in cases of tumor thrombi, common bile duct was the frequent site. There v:as no difference in levels and types of bile duct obstruction according to tumor types of HCC. The su.rvival period of patients with tumor thrombi was significantly longer than that of patients with bile duct invasion(p0.05). Conclusions; HCC involving bile duct will be found frequently with increased use of direct cholangiograpy. The commonest type of bile duct obstruction in HC'C was duct invasion, so aggressive and adequate treatment for HCC may be useful in management of bile duct obstruction. (Korean J Gastroenterol 1996;28: 101 - 110)
송일한 ( Song Il Han ) 대한소화기학회 2004 대한소화기학회지 Vol.43 No.1
Cancer metastasis, a complex and sequential network of cellular events involved in the migration and establishment of malignant cells from original site to distant foci, is an important and significant contributor to morbidity and mortality of cancer patients. Despite the clinical importance of cancer metastasis, its molecular and biochemical mechanism remains unclear. The identification of tumor suppressor gene confirmed that metastasis might involve the functional loss of genes that maintain the cellular differentiation optimally. Metastasis suppressor is defined by the ability to reduce the metastatic property of cancer cells without affecting its tumorigenesis. Since NM23 was first identified in 1988 as a metastasis suppressor, several metastasis suppressor genes have been identified and characterized. In this article, we review the complex and multi-step process of cancer metastasis and describe the recent progress of metastasis suppressors in the studies of identified. Consequently, we hope to introduce the new therapeutic target for the metastasis suppressors in cancer patients. (Korean J Gastroenterol 2004;43:1-7)
해설논문 : 진행성 간세포암종에 대한 분자생물학적 표적치료
송일한 ( Il Han Song ) 대한간학회 2009 Clinical and Molecular Hepatology(대한간학회지) Vol.15 No.3
간세포암종은 발생률에 있어서는 전세계적으로 지역적인 차이를 보이나 암 사망률에 있어서는 폐암종과 위암종에 이어 3위를 차지하는 악성 종양이다. 지난 수십 년 동안 근치적 치료가 불가능한 진행성 간세포암종 환자의 생존율을 향상시킬 수 있는 효과적인 전신항암치료법은 없었다. 그러나 최근 multikinase 억제제인 소라페닙(sorafenib)이 간세포암종 환자의 생존율을 유의하게 향상시키고 암종의 진행을 늦춘다는 연구 결과가 발표되면서 진행성 간세포암종에 대한 분자생물학적 표적치료가 주목을 받고 있다. 소라페닙은 세포 내 신호전달체계 중 Raf-1과 B-Raf serine-threonine kinase를 차단함으로써 암세포 증식을 억제하고, 세포막 수용체 중 혈관내피성장인자 수용체(vascular endothelial growth factor receptor, VEGFR)와 혈소판성장인자 수용체(platelet-derived growth factor receptor, PDGFR)를 차단함으로써 신생혈관형성(angiogenesis)을 막을 수 있는 약물이다. 그러나 지금까지 발표된 소라페닙 연구의 결과들을 보면 임상적으로 만족할 만한 수준에 도달하지는 않았으며, 또한 다양한 약물반응을 보이는 경우가 있어 일정 생물학적 반응과 연관을 보이는 표지자의 발굴을 통해 간세포암종을 분류하려는 시도가 진행되고 있다. 즉 같은 생물학적 동질성을 갖는 간세포암종의 분자생물학적 분류를 통해 궁극적으로 간세포암종 환자들의 개별화된 맞춤형 분자생물학적 표적치료를 최적화할 수 있을 것으로 생각된다. Hepatocellular carcinoma (HCC) is a major global health problem, which has a grave morbidity and mortality. Over the past few decades, no effective systemic therapeutic modalities have been established for patients with the unresectable HCC in advanced stage. Sorafenib is a small molecule that blocks cancer cell proliferation by targeting the intracellular signaling pathway at the level of Raf-1 and B-Raf serine-threonine kinases, and exerts an anti-angiogenic effect by targeting the vascular endothelial growth factor receptor-1, 2 and 3, and platelet-derived growth factor receptor-β tyrosine kinases. Recently, two clinical successful applications, SHARP and Asia-Pacific trial, of multikinase inhibitor sorafenib represent a significant advance in the treatment of advanced HCC patients without a curative chance. However, because the results of clinical trials show diverse responses in a subset of HCC patients, a molecular classification of HCC through the excavation of specific biomarkers related to its biological behavior is necessary for sorting HCC patients to each group with a biological homogeneity, ultimately leading to the most suitable individualization of molecular targeted therapy in HCC. (Korean J Hepatol 2009,15:299-308)