• The Korean Journal of Nuclear Medicine
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• v.16 no.2
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• pp.71-80
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• 1982

In the present communication, the results will be reported on a clinical study of how well scintigraphic visualization of the hepatobiliary elements and several commonly used clinical liver function tests correlate each other in various diseases oft hepatobiliary system. The demonstrability of the biliary tract, gallbladder (GB) and duodenum was rather closely paralleled to serum bilirubin level and less closely to alkaline phosphatase and rather poorly to SGOT and SGPT. The biliary tree could not be visualized scintigraphically when bilirubin exceeded 10.5mg/dl. The usefulness of Tc-99m EHIDA [N-(2,6-diethylacetanilido) iminodiacetic acid, made by Amersham, England] hepatobiliary scintigraphy (Tc EHIDA HBS) in settling diagnostic controversy and ambiguity raised by oral cholecystography, intravenous cholangiography and ultrasonography in many hepatobiliary diseases is well known. The purpose of this investigation was to semiquantitatively evaluate the scintigraphic demonstrability of the hepatobiliary tract, GB and duodenum following intravenous injection of Tc-99m EHIDA in normal subjects and in patients with a disturbed liver function from various hepatobiliary diseases. The hepatobiliary scintigraphy was performed in 10 normal subjects and 39 patients with various hepatobiliary diseases (Table 1) at the Dept. of Radiology, St. Mary's Hospital Catholic Medical College, Seoul, Korea during 2 years period from September 1979. Scintigraphic examination was started at end of 3 minutes after intravenous injection of Tc-99m EHIDA in the amount of $50{\mu}Ci/kg$ and was continued until after 30 minutes at 5 minutes interval. The imaging was usually terminated when the tracer could be seen in the duodenum. Late scintigrams were obatained at 1 1/2, 3, 4 and 6 hours when reeded. Scintigrams were analyzed in terms of promptness and clarity of visualization of the biliary tree, GB and duodenum and demonstrability of these anatomical landmarks was correlated with the values of liver function tests. The demonstrability of the common hepatic duct, common bile duct, GB and duodenum was closely paralleled to the level of serum bilirubin when it is less than 10.5 mg/dl as shown in figure 1. However when the bilirubin exceeded 10.5 mg/dl the time of visualization between protracted reaching a flat curve or plateau around 10.5 mg/dl. The biliary tract could not be visualized when the bilirubin was higher than 10.5 mg/dl. The correlability between scintigraphic demonstration and serum alkaline phosphatase was less strong and between scintigraphic demonstration and SGOT and SGPT was rather poor. The present clinical study confirmed the usefulness and limitation of Tc-99m EHIDA hepatobiliary scintigraphy in visulizing and diagnosing the biliary system and duodenum when radiogrpahy and ultrasonography failed to provide useful informations. Scintigraphy was very helpful in the diagnosis of neonatal hepatitis, biliary atresia, cholecystitis and extrahepatic biliary obstruction. The hepatobiliary system and duodenum were visualized when serum bilirubin level was less than 10.5 mg/dl, SGOT 135 units, SGPT 114 units and alkaline phosphatase 52.2 KAU.

• Journal of Veterinary Clinics
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• v.24 no.4
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• pp.593-596
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• 2007

The purpose of this study is to investigate normal hepatobiliary functions in healthy miniature pigs. $^{99m}Tc-DISIDA$ hepatobiliary scintigraphy(HBS) was used for it. Five mCi dose of $^{99m}Tc-DISIDA$ was injected intravenously into 3 healthy adult miniature pigs, and dynamic images were obtained during 1 hour. $^{99m}Tc-DISIDA$ HBS in a miniature pig was evaluated for 6 variables. A cardiac washout occurred within 1 min in all miniature pigs and radioactivities in the gallbladder were not detected in two miniature pigs. Thus, the initial radioactivity and Tmax of the gallbladder were non-available to identify. Mean Tmax of liver was $8.67{\pm}2.08$ min and initial small intestinal radioactivity was seen at $9.67{\pm}2.52$ min after $^{99m}Tc-DISIDA$ injection. Mean hepatic washout time was not detected in 60 min dynamic images. Therefore, $^{99m}Tc-DISIDA$ HBS is the effective diagnostic method to evaluate the function of hepatocyte and bile flow rate. However, it was not a proper method to evaluate the function of gallbladder, which indicates that an additional study is needed to further specify the reasons for the absence of radioactivities in gallbladder of two miniature pigs.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.483-486
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• 2012

Background: The hepatocellular carcinoma is very common in China. Our aim in this report was to investigate clinical and pathological factors based on the current decade data that could influence prognosis of HCC patients after hepatectomy. Methods: Between 2002 and 2009, all patients undergoing hepatectomy for HCC were followed up and reviewed retrospectively. Prognostic factors were studied by univariate and multivariate analysis, with Kaplan-Meier and Cox multivariate survival analyses. Results: Complete clinicopathologic and follow-up data were available for 114 patients. The estimated cumulative survival rates at 1, 3, and 5 yr were 84.6%, 60.2% and 51.8%, respectively. On univariate analysis, key prognostic factors were AFP level, GGT level, tumor size, number of tumors, portal vein invasion, liver cirrhosis status and TNM stage. In the multivariate analysis, tumor size, GGT level, liver cirrhosis status and portal vein invasion were significantly associated with patients' prognosis. Conclusion: Through follow-up of a relatively large cohort of Chinese patients, tumor size, GGT level, liver cirrhosis status, portal vein invasion were revealed as important factors for long-term survival after hepatectomy. Early diagnosis for tumor and the improvement of liver function before surgery are important ways to improve the prognosis.

• Molecules and Cells
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• v.39 no.8
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• pp.639-644
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• 2016

Discovery of non-invasive diagnostic and predictive biomarkers for acute rejection in liver transplant patients would help to ensure the preservation of liver function in the graft, eventually contributing to improved graft and patient survival. We evaluated selected cytokines and chemokines in the sera from liver transplant patients as potential biomarkers for acute rejection, and found that the combined detection of IL-10, IL-17, and CXCL10 at 1-2 weeks post-operation could predict acute rejection following adult liver transplantation with 97% specificity and 94% sensitivity.

• BMB Reports
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• v.45 no.11
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• pp.629-634
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• 2012

The human glycoprotein, stanniocalcin 2 (STC2) plays multiple roles in several tumor types, however, its function and clinical significance in hepatocellular carcinoma (HCC) remain unclear. In this study, we detected STC2 expression by quantitative real-time PCR and found STC2 was upregulated in HCC tissues, correlated with tumor size and multiplicity of HCC. Ectopic expression of STC2 markedly promoted HCC cell proliferation and colony formation, while silencing of endogenous STC2 resulted in a reduced cell growth by cell cycle delay in G0/G1 phase. Western blot analysis demonstrated that STC2 could regulate the expression of cyclin D1 and activate extracellular signal-regulated kinase 1/2 (ERK1/2) in a dominant-positive manner. Transwell chamber assay also indicated altered patterns of STC2 expression had an important effect on cell migration. Our findings suggest that STC2 functions as a potential oncoprotein in the development and progression of HCC as well as a promising molecular target for HCC therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6393-6398
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• 2013

In this research, we used $GdCl_3$ (gadolinium chloride) to restrain the function of Kupffer cells and assessed effects on hepatocarcinogenesis and metastasis in the Kunming mouse. A 0.25% $GdCl_3$ solution (10 mg/kg b.w.) was infused via the vena caudalis of each mouse 1 week before inoculation of H22 cells and was continued once per three days. Then we observed the follow indexes 3 weeks after injection of H22 cells: tumor weight, histologic characteristics of tumor tissue by light microscopy, ultramicrostructure of Kupffer cells under the electron microscope, distribution and number of Kupffer cells by histochemical staining, and TNF-${\alpha}$ and IFN-${\gamma}$ levels in blood-serum and liver tissue by ELISA and RT-PCR. MMP-2 protein expression was tested by immunohistochemistry. The $GdCl_3$ pretreatment had no effect on the quantity of Kupffer cells, but clearly restrained their functions, with decrease of TNF-${\alpha}$ and IFN-${\gamma}$ levels and elevation of MMP2. Tumor immunity functions were markedly suppressed and tumor growth was accelerated with appearance of metastasis. Furthermore, survival time of trial mice was shortened.

• Nuclear Engineering and Technology
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• v.37 no.4
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• pp.391-394
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• 2005

N-(3-bromo-2,4,6-trimethylacetanilide)iminodiacetic acid (BrTIDA) was synthesized using nitrilotriacetic anhydride prepared in situ, and lyophilized vials were prepared which contained 20 mg of BrTIDA and 0.4 mg of $SnCl_2$. To evaluate the clinical efficacy of the in-house prepared lyophilized kit, a technetium-99m complex of BrTIDA was prepared; its in vivo pharmacokinetic behavior was evaluated via animal studies to assess the hepatocytic function and the functional status of the cystic duct and the gallbladder. Serial static image scans of rabbits and the biodistribution in mice injected with $^{99m}Tc-BrTIDA$ revealed that none of the tissues except for the hepatobiliary system showed radioactivity concentrations, and a rapid clearance from the organs was observed. In conclusion, a lyophilized kit and its prepared $^{99m}Tc-BrTIDA$ can be applied as a hepatobiliary imaging agent for the evaluation of the functional status of the hepatocytes and the patency of the biliary duct.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1917-1921
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• 2012

Background: Colorectal cancer is one of the leading causes of mortality worldwide. Genome wide analysis studies have identified sequence mutations causing loss-of-function that are associated with disease occurrence and severity. Epigenetic modifications, such DNA methylation, have also been implicated in many cancers but have yet to be examined in the East Asian population of colorectal cancer patients. Methods: Biopsies of tumors and matched non-cancerous tissue types were obtained and genomic DNA was isolated and subjected to the bisulphite conversion method for comparative DNA methylation analysis on the Illumina Infinium HumanMethylation27 BeadChip. Results: Totals of 258 and 74 genes were found to be hyper- and hypo-methylated as compared to the individual's matched control tissue. Interestingly, three genes that exhibited hypermethylation in their promoter regions, CMTM2, ECRG4, and SH3GL3, were shown to be significantly associated with colorectal cancer in previous studies. Using heatmap cluster analysis, eight hypermethylated and 10 hypomethylated genes were identified as significantly differentially methylated genes in the tumour tissues. Conclusions: Genome-wide methylation profiling facilitates rapid and simultaneous analysis of cancerous cells which may help to identify methylation markers with high sensitivity and specificity for diagnosis and prognosis. Our results show the promise of the microarray technology in identification of potential methylation biomarkers for colorectal cancers.

• The Korean Journal of Nuclear Medicine
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• v.31 no.1
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• pp.102-107
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• 1997

Laparoscopic cholecystectorny can be performed safely in most patients with symptomatic cholelithiasis. Preoperative evaluation should assess the potential problems that affect the performance of laparoscopic cholecystectomy. Hepatobiliary scintigraphy or oral cholecystography can assess the gallbladder function and nonvisualization of gallbladder usually indicates acute or severe chronic cholecystitis. The purpose of this study was to evaluate the role of preoperative hepatobiliary scintigraphy or oral cholecystography in predicting the performance of laparoscopic cholecystectorny. The study group consists of 176 patients who underwent both hepatobiliary scintigraphy with Tc-99m DISIDA and oral cholecystography within one month before laparoscopic cholecystectomy. Nonvisualization of gallbladder was defined as persistent nonvisualization of gallbladder until 4 hours on hepatobiliary scintigraphy or 12 hours on oral cholecystography. Among 176 patients, gallbladder was not visualized in 38 patients on hepatobiliary scintigraphy and 41 patients on oral cholecystography. Concordance rate between hepatobiliary scintigraphy and oral cholecystography was 89.2%. The conversion rate to open cholocystectomy was significantly higher in patients with nonvisualization of gallbladder than in patients with gallbladder visualization(15.8% vs 2.9% on hepatobiliary scintigraphy, 12.2% vs 3.7% on oral cholecystography p<0.01 and p<0.05 respectively). The operative complication rate was also significantly higher in patients with nonvisualization of gallbladder (13.2% vs 2.9% on hepatobiliary scintigraphy, 14.6% vs 2.2% on oral cholecystography p<0.01 and p<0.001, respectively). Similarly, operation time was significantly prolonged in patients with nonvisualization of gallbladder ($88.8{\pm}41.9min$ vs $62.5{\pm}23.6min$ on hepatobiliary scintigraphy : p<0.001, $89.4{\pm}41.3$ min vs $61.8{\pm}22.8$ min on oral cholecystography : p<0.001). It is concluded that nonvisualization of gallbladder on hepatobiliary scintigraphy or oral cholecystography is a valuable preoperative clinical risk factor in predicting increased conversion rate to open cholecystectomy, increased operative complication and prolonged operation time.