• Title/Summary/Keyword: Hepatobiliary

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Upregulation of Carbonyl Reductase 1 by Nrf2 as a Potential Therapeutic Intervention for Ischemia/Reperfusion Injury during Liver Transplantation

  • Kwon, Jae Hyun;Lee, Jooyoung;Kim, Jiye;Kirchner, Varvara A.;Jo, Yong Hwa;Miura, Takeshi;Kim, Nayoung;Song, Gi-Won;Hwang, Shin;Lee, Sung-Gyu;Yoon, Young-In;Tak, Eunyoung
    • Molecules and Cells
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    • v.42 no.9
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    • pp.672-685
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    • 2019
  • Currently, liver transplantation is the only available remedy for patients with end-stage liver disease. Conservation of transplanted liver graft is the most important issue as it directly related to patient survival. Carbonyl reductase 1 (CBR1) protects cells against oxidative stress and cell death by inactivating cellular membrane-derived lipid aldehydes. Ischemia-reperfusion (I/R) injury during living-donor liver transplantation is known to form reactive oxygen species. Thus, the objective of this study was to investigate whether CBR1 transcription might be increased during liver I/R injury and whether such increase might protect liver against I/R injury. Our results revealed that transcription factor Nrf2 could induce CBR1 transcription in liver of mice during I/R. Pre-treatment with sulforaphane, an activator of Nrf2, increased CBR1 expression, decreased liver enzymes such as aspartate aminotransferase and alanine transaminase, and reduced I/R-related pathological changes. Using oxygen-glucose deprivation and recovery model of human normal liver cell line, it was found that oxidative stress markers and lipid peroxidation products were significantly lowered in cells overexpressing CBR1. Conversely, CBR1 knockdown cells expressed elevated levels of oxidative stress proteins compared to the parental cell line. We also observed that Nrf2 and CBR1 were overexpressed during liver transplantation in clinical samples. These results suggest that CBR1 expression during liver I/R injury is regulated by transcription factor Nrf2. In addition, CBR1 can reduce free radicals and prevent lipid peroxidation. Taken together, CBR1 induction might be a therapeutic strategy for relieving liver I/R injury during liver transplantation.

[ $^{99m}Tc-DISIDA$ ] Scintigraphic Diagnosis Of Extrahepatic Hepatocellular Carcinoma Metastasis : Comparison with Primary Hepatocellular Carcinoma ($^{99m}Tc-DISIDA$ 신티그래피를 이용한 간세포암 간외 전이의 진단 : 원발 간세포암과의 비교)

  • Chung, Soo-Kyo;Kim, Sung-Hoon;Baik, Joon-Hyun;Kim, Young-Joo;Chun, Kyung-Ah;Park, Seog-Hee;Bahk, Yong-Whee;Shin, Kyung-Sub
    • The Korean Journal of Nuclear Medicine
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    • v.29 no.4
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    • pp.484-491
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    • 1995
  • It is well known that hepatobiliary agent are taken up by metastatic hepatocellular carcinoma(HCC) as well as primary HCC. But the reported cases of the extrahepatic metastasis of HCC diagnosed by hepatobiliary scintigraphy are for the most part hematogenous ones. The relation of the uptake pattern of hepatobiliary agent in the primary and metastatic HCC is also still remains unknown. So we undertook this study to evaluate the relation of the hepatobiliary scintigraphic patterns of primary and metastatic HCC with different metastatic routes. Nine patients with primary HCC and twelve cases of metastatic HCC including four lung metastases, one bone metastasis, one right atrial metastasis, one peritoneal wall metastasis, and five lymph node metastases were studied with $^{99m}Tc-DISIDA$ scintigraphy. The images were taken on 10, 30 minutes, 1, 2, 4-6 hours. The overall detection rates of hematogenous metastases(lung and bone) is 60%(3 of 5), direct metastasis(right atrium and peritoneal wall), 100%(2 of 2) and lymphatic metastases, 0%(0 of 5). In four of five metastatic cases demonstrated with hepatobiliary scintigraphy, biliary agent is also taken up by primary HCC lesions. And the appearing time of the radioactivity in the direct metastatic HCC lesioin is same as that of primary HCC and in the cases of hematogenous metastasis, earlier than that of primary HCC. Hepatobiliary scintigraphy is more useful in the diagnosis of the metastatic HCC than primary HCC, in the cases of hematogenous and direct metastasis.

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Efficient of Hepatobiliary Scintigraphy both Decubitus Position in Biliary Leakage Patients (간담도 스캔 시 담즙 누출(Biliary Leakage)환자에서의 양측와위 자세(Both Decubitus Position)의 유용성)

  • Bahn, Young-Kag;Roh, Dong-Ook;Kang, Chun-Koo;Kim, Jae-Sam;Lee, Chang-Ho
    • The Korean Journal of Nuclear Medicine Technology
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    • v.12 no.3
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    • pp.229-234
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    • 2008
  • Hepatobiliary scintigraphy is very sensitivity of hepatic cell and gallbladder, biliary track atresia and biliary leakage. however, Hepatobiliary scan of biliary leakage diagnosis was separated determine biliary leakage and bowl drainage bile-juice. The object of this study will determine biliary leakage and bowl drainage bile-juice to hepatobiliary scintigraphy both decubitus position in bile leakage patients. Material & Methode: 31 patients (meal 14, Femeal 17), $51.1{\pm}14.4$ years. dynamic scan acquisition 60 farme for 60 minute on supine position. and delay scan was 2 hrs, 4 hrs, 24 hrs for 5 minute on supine, both decubitus position. Both decubitus position scan was kept for 5 minutes. Efficient of Hepatobiliary Scintigraphy both decubitus position in bile leakage patients was compared leakage size, density, image of supine position and both decubitus position. Results: 23 patients for 31 bile leakage patients was checked up function image or delay image, and 8 patients was checked up bile leakage on both decubitus. anatomical leakage location was supine position very well, but both decubitus position was separated bile leakage and moving bile-juice in bowl. also, uptake (counts/pixel) average of roi and bkg was supine 5.02, left decubitus 2.08, right decubitus 2.68. No. pixels of supine ROI counted 1.91 times than left decubitus, 1.05 times than right decubitus. Conclusion: 31 patient both decubitus position, but decubitus position was separated bile juice movement in bowl leakage location. also, It was compared ROI/BKG ratio and ROI No. pixels of supine, both decubitus in 38.5% patients. And No. pixels of supine position was large 19%, 5% than left decubitus, right decubitus, And density was in low 60%, 50% than left decubitus, right decubitus. It was mean bile leakage of ROI. so, If Hepatobiliary Scintigraphy was additional both decubitus position scan in bile leakage patients, this study will be more valuable in diagnosis of bile leakage.

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Early Exclusive Diagnosis of Biliary Atresia among Infants with Cholestasis (영아기 담즙정체성 황달 질환 중 담도폐쇄증의 조기 배제 진단)

  • Choe, Byung-Ho
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.14 no.2
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    • pp.122-129
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    • 2011
  • The persistence of jaundice beyond the first 2 weeks of life require further investigation and this can be determined if the conjugated bilirubin levels are greater than 1.5 mg/dL or greater than 20% of the total bilirubin level. There is a diverse differential diagnosis for the cause of neonatal cholestasis due to hepatobiliary disease including biliary atresia, which eventually leads to liver cirrhosis if uncorrected before 60~80 days of life. Long-established initial studies include abdominal ultrasonography, hepatobiliary scintigraphy and liver biopsy, but better diagnostic methods are needed. Promising new options are described including MRCP (magnetic resonance cholangiography), ERCP (endoscopic retrograde cholangiography), and PCC (percutaneous cholecysto-cholangiography). Though no single test can differentiate biliary atresia from other neonatal cholestasis with confidence, a combination of diagnostic methods is usually consistently beneficial. By excluding biliary atresia as early as possible, the risk of unnecessary explolaparotomy with intraoperative cholangiography is decreased. Further evaluation would be required for the diagnosis of neonatal cholestasis after excluding biliary atresia.

Expression and Role of ICAM-1 in the Occurrence and Development of Hepatocellular Carcinoma

  • Zhu, Xi-Wen;Gong, Jian-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.3
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    • pp.1579-1583
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    • 2013
  • Intercellular adhesion molecule-1 (ICAM-1) is a member of the immunoglobulin superfamily, its main function being to participate in recognition and adhesion between cells. ICAM-1 is considered closely related to occurrence, development, metastasis and invasion process of hepatocellular carcinoma (HCC). A variety of inflammatory cytokines and stimulus affect its expression through the nuclear factor-kappa B (NF-${\kappa}B$) signal transduction pathway. In the initial stage of inflammation, hepatocirrhosis and tumor development, ICAM-1 is expressed differently, and has varied effects on different cells to promote occurrence of malignancy and metastasis. ICAM-1 has diagnostic significance for AFP-negative or suspected HCC, and may be a prognositic significance. It is thus widely used in studies as a biomarker which reflects cancer cells metastasis as well as curative effect of drugs. Many new treatments of HCC may be based on the effects of ICAM-1 on different levels of function.

Metformin Inhibits Growth of Hepatocellular Carcinoma Cells by Inducing Apoptosis Via Mitochondrion-mediated Pathway

  • Xiong, Yu;Lu, Qing-Jun;Zhao, Jing;Wu, Guo-Yang
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3275-3279
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    • 2012
  • Recently, population-based studies of type 2 diabetes patients have provided evidence that metformin treatment is associated with a reduced cancer incidence and mortality, but its mode of action remains unclear. Here we report effects of metformin on hepatocellular carcinoma (HCC) Hep-G2 cells and details of molecular mechanisms of metformin activity. Our research indicates that metformin displays anticancer activity against HCC through inhibition of the mTOR translational pathway in an AMPK-independent manner, leading to G1 arrest in the cell-cycle and subsequent cell apoptosis through the mitochondrion-dependent pathway. Furthermore, we showed that metformin strongly attenuated colony formation and dramatically inhibited Hep-G2 tumor growth in vivo. In conclusion, our studies suggested that metformin might have potential as a cytotoxic drug in the prevention and treatment of HCC.

The Effects of Extrahepatic Cholestasis on Serum $\alpha$-D-Mannosidase Isozyme Activities in Ethanol Intoxicated Rats

  • Si-Woo Bae;Chun-Sik Kwak;Chong-Guk Yoon
    • Biomedical Science Letters
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    • v.8 no.4
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    • pp.203-209
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    • 2002
  • Serum $\alpha$-D-mannosidase isozyme activities were measured in rats with ethanol intoxication combined with extrahepatic cholestasis induced by common bile duct ligation for the manifestation of the biochemical background of drinking hazards under the hepatobiliary disease. When chronic ethanol intoxication was combine with extraheparlc cholestasis, the activities of the rat's serum cytosolic, Iysosomal and Golgi $\alpha$-D-mannosidase isozymes increased at a more significant rate than those of the cholestasis alone. However, when acute ethanol intoxication was combined with extrahepatic cholestasis, the activities of the above isozymes were seen in the cholestasis alone. The results suggested that the elevated activities of these isozymes in chronic ethanol intoxication with cholestasis rather than in cholestasis alone were indications of increased hepatic damages, which caused these isozymes to leak into the blood in great quantity. Accordingly, the resulting data supported the fact that alcoholic drinks were enzymologically harmful to the hepatobiliary disease.

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Effects of Extrahepatic Cholestasis on Hepatic $\alpha$-D-Mannosidase Activity in Chronic Ethanol Intoxicated Rats

  • Si-Woo Bae;Chun-Sik Kwak;Chong-Guk Yoon
    • Biomedical Science Letters
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    • v.9 no.1
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    • pp.21-27
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    • 2003
  • Hepatic subcellular $\alpha$-D-mannosidases activities and its Km and Vmax values were determined in chronic ethanol intoxicated rats with extrahepatic cholestasis induced by common bile duct ligation to manifest the biochemical background of alcohol drinking hazard under the hepatobiliary disease. In case of extrahepatic cholestasis, chronic ethanol intoxication in animals led to the increased activities of liver Golgi and microsomal $\alpha$-D-mannosidase as well as the Vmax values of these enzymes. However, the difference of Km values on hepatic subcellular enzymes were not found between the experimental groups. Therefore, the results indicate that the liver Golgi and microsomal $\alpha$-D-mannosidase may be more induced in chronic ethanol intoxication animals in case of cholestasis. Accordingly, the resulting data supported the fact that alcoholic drinks may led to enhancement of the hepatobiliary liver damage.

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