• Title/Summary/Keyword: Hepatobiliary

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Microarray and Next-Generation Sequencing to Analyse Gastric Cancer

  • Dang, Yuan;Wang, Ying-Chao;Huang, Qiao-Jia
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8035-8040
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    • 2014
  • Gastric cancer is the second after lung cause of cancer-related mortality in the world. Early detection and treatment can lead to a long survival time. Recently microarrays and next generation sequencing (NGS) have become very useful tools of comprehensive research into gastric cancer, facilitating the identification of treatment targets and personalized treatments. However, there are numerous challenges from cancer target discovery to practical clinical benefits. Although there are many biomarkers and target agents, only a minority of patients are tested and treated accordingly. Microarray technology with maturity was established more than 10 years ago, and has been widely used in the study of functional genomics, systems biology, and genomes in medicine. Second generation sequencing technology is more recent, but development is very fast, and it has been applied to the genome, including sequencing and epigenetics and many aspects of functional genomics. Here we review insights gained from these studies regarding the technology of microarray and NGS, how to elucidate the molecular basis of gastric cancer and identify potential therapeutic targets, and how to analyse candidate genes. We also discuss the challenges and future directions of such efforts.

Effect of Acute Ethanol Intoxication on Hepatic Rhodanese Activity in Rats with Extrahepatic Cholestasis

  • Park, Ki-Suk;Mun, Kyo-Cheol;Kim, You-Hee;Kwak, Chun-Sik
    • Biomedical Science Letters
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    • v.10 no.2
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    • pp.99-105
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    • 2004
  • Liver and serum rhodanese activities were determined in acute ethanol intoxicated rats with extrahepatic cholestasis induced by common bile duct ligation (CBD) to manifest the biochemical background of alcohol drinking hazard under the hepatobiliary disease. Liver cytosolic and microsomal rhodanese activities and these Vmax values in CBD ligated rats with acute ethanol intoxication were found to be decreased much more than that in CBD ligation alone. However, the difference of Km value on above hepatic enzyme was not found between the experimental groups. On the other hand, serum rhodanese activity in CBD ligated rats with acute ethanol intoxication was greater increased more than that in CBD ligation alone. These results indicate that the biosynthesis of the hepatic rhodanese decreases and the serum rhodanese activity increases in cholestasis combined with acute ethanol intoxication, reflecting damage of aggravated hapatocytic membrane. 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 Liver and Serum $\beta$-D-Mannosidase Activities in Ethanol Intoxicated Rats

  • Bae, Si-Woo;Kwak, Chun-Sik;Yoon, Chong-Guk
    • Biomedical Science Letters
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    • v.10 no.1
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    • pp.35-42
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    • 2004
  • Liver and serum $\beta$-D-mannosidase activities were determined in ethanol intoxicated rats with extrahepatic cholestasis induced by common bile duct ligation (CBD) to manifest the biochemical background of alcohol drinking hazard under the hepatobiliary disease. Liver $\beta$-D-mannosidase activity and its Vmax value in CBD ligated rats with chronic ethanol intoxication were found to be significantly decreased than that in CBD ligation alone. However, the difference of Km value on above hepatic enzyme was not found between the experimental groups. On the other hand, serum $\beta$-D-mannosidase activity in CBD ligated rats with chronic ethanol intoxication was increased more than that in CBD ligation alone. These results indicate that the biosynthesis of the hepatic $\beta$-D-mannosidase decreases and the serum $\beta$-D-mannosidase activity increases in cholestasis combined with chronic ehtanol intoxication, reflecting damage of aggravated hapatocytic membrane. Accordingly, the resulting data supported the fact that alcoholic drinks were enzymologically harmful to the hepatobiliary disease.

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Quantitative Evaluation of Liver Function Using $^{99m}Tc-DISIDA$ Cholescintigraphy ($^{99m}Tc-DISIDA$ 스캔에 의한 간기능의 정량적 평가)

  • Kim, Chahng-Guhn;Kim, Byung-Chan;Chung, Young-Sun;Won, Jong-Jin;Rhee, Jeong-Kyun
    • The Korean Journal of Nuclear Medicine
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    • v.22 no.2
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    • pp.181-185
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    • 1988
  • Since hepatocyte clearance, leading edge parencymal transit time and biliary excretion can be evaluated separately with hepatobiliary scan using $^{99m}Tc-DISIDA$, hepatobiliary scan may be useful in differentiating intrahepatic cholestasis from extrahepatic cholestasis. Excretory liver function was analysed in 13 healthy subjects and 11 patients with clinically suspected hepatocellular disease and 9 patients with extrahepatic biliary obstruction confirmed by surgery, radiological and clinical evidence. Indices of total liver activity (% TLA), liver parechymal uptake (% LPU), heart pool clearance (% HPC) and liver-heart rate (% LHR) were calculated from time activity curve over heart and liver. Compared with healthy subjects, significant reduction (p<0.05) in total liver activity (% TLA) and liver-heart rate (% LHR) was observed in all patients group. But no useful indices was demonstrated in differentiating hepatocellular disease from extrahepatic biliary obstruction.

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Imaging and Clinical Data Distinguish Lymphadenopathy-First-Presenting Kawasaki Disease from Bacterial Cervical Lymphadenitis

  • Park, Byung Sung;Bang, Myung Hoon;Kim, Sung Hye
    • Journal of Cardiovascular Imaging
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    • v.26 no.4
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    • pp.238-246
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    • 2018
  • BACKGROUND: Kawasaki disease (KD) sometimes presents with only fever and cervical lymphadenopathy before other clinical signs materialize. This lymphadenopathy-first-presenting Kawasaki disease (LKD) may be misdiagnosed as bacterial cervical lymphadenitis (BCL). We investigated characteristic imaging and clinical data for factors differentiating LKD from BCL. METHODS: We compared imaging, clinical, and laboratory data of patients with KD and BCL. We included patients admitted to a single tertiary center between January 2015 and July 2018. RESULTS: We evaluated data from 51 patients with LKD, 63 with BCL, and 218 with typical KD. Ultrasound imaging revealed multiple enlarged lymph nodes in both LKD and BCL patients. On the other hand, computed tomography (CT) showed more abscesses in patients with BCL. Patients with LKD were younger and showed higher systemic and hepatobiliary inflammatory markers and pyuria than BCL patients. In multivariable logistic regression, younger age and higher C-reactive protein (CRP) retained independent associations with LKD. A comparison of the echocardiographic findings in LKD and typical KD showed that patients with LKD did not have a higher incidence of coronary artery abnormalities (CAA). CONCLUSIONS: LKD patients tend to have no abscesses on CT and more elevated systemic hepatobiliary inflammatory markers and pyuria compared to BCL patients. The absence of abscess on CT, younger age, and elevated CRP were the most significant variables differentiating LKD from BCL. There was no difference in CAA between LKD and typical KD.

The Gastric-Bile Juice Reflux in Patients from Hepatobiliary Scan with Subtotal Gastrectomy (위 부분절제술 환자의 간담도 스캔에서 위-담즙역류)

  • Kwak, Dong-Woo;Kim, Ji-Hyeon;Kim, Kyung-Hun;Lee, Kyung-Jae;Park, Young-Jae;Lee, In-Won
    • The Korean Journal of Nuclear Medicine Technology
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    • v.14 no.2
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    • pp.17-20
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    • 2010
  • Purpose: The hepatobiliary scan is the examination which is the possibility of knowing the function of liver, gall bladder and closing of the biliary tract. Also, after subtotal gastrectomy, the increased gastric-bile reflux is known as the primary reason of reflux gastritis. In this study, according to changing the acquisition method, we tried to prove the reflux time and reflux index in patients who underwent subtotal gastrectomy. Materials and Methods: From Oct 2008 to Jan 2009, 72 patients with subtotal gastrectomy who took the hepatobiliary scan (man: 52, woman: 20, age range: 31-77, mean age: $60.5{\pm}7$) in our department. We used the radiopharmaceutical $^{99m}Tc$-mebrofenin 185 MBq/0.5 cc. After 5 minutes, we acquired 300,000 counts anterior image on supine, and then we acquired right lateral and $45^{\circ}$ LAO position by using the time setting method. We acquired 30 min, 60 min, 90 min, 120 min and fatty meal by the same method. We painted the ROI of liver, GB and CBD on 30 min anterior image and LAO image in patients had occurred the bile juice reflux. And then we painted the ROI of stomach on others image. We calculated the reflux index from those values. Results: According to this study, we found out 40 patients (55.6%) who had occurred the gastric-bile juice reflux (1 person from 30 min, 7 persons from 60 min, 4 persons from 90 min, 28 persons from after fatty meal). Hourly, the bile reflux highest level is 6 persons from 60 min, 2 persons from 90 min, 32 persons from fatty meal among those people. The reflux index of anterior is 0.85-23.36% (mean 6.53%). The reflux index of LAO is 1-29.13% (mean 8.89%). By visual assessment, we can distinguish that there were 26 of the 40 patients (65%) had occurred the reflux on LAO image more than anterior image. Conclusion: We find out that the patients with subtotal gastrectomy had occurred gastric-bile juice reflux more than 50% from hepatobiliary scan. And after eating fatty meal, we can know that it's the most possible to occur the gastric-bile juice reflux. When it happened, we have to change the acquisition method to reduce the overlap between colon and stomach. This study will be more valuable in diagnosis.

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Comparison of Tc-99m DISIDA Hepatobiliary Scintigraphy and Percutaneous Needle Biopsy in the Differential Diagnosis of Biliary Atresia and Intrahepatic Cholestasis (영아 담도폐쇄증 진단에서 Tc-99m DISIDA 간담도주사와 경피간침생검의 의의)

  • Kim, Woo-Suk;Park, Woo-Hyun;Choi, Soon-Ok;Kim, Sang-Pyo
    • Advances in pediatric surgery
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    • v.3 no.1
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    • pp.6-14
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    • 1997
  • To differentiate biliary atresia from intraheaptic cholestasis, Tc-99m DlSIDA hepatobiliary scintigraphies and percutaneous needle biopsies of 60 consecutive infants were evaluated retrospectively. Twenty three patients had biliary atresia and 37 patients intraheaptic cholestasis(neonatal hepatitis 34, TPN induced jaundice 2 and Dubin-Johnson syndrome 1). All sixty patients underwent Tc-99m DlSIDA hepatobiliary scintigraphy with phenobarbital pretreatment. Of 23 patients with biliary atresia, 22 were correctly interpreted showing 96% sensitivity while of 37 patients with intraheaptic cholestasis, only 12 had intestinal excretion of radionuclide showing 32% specificity. Among the forty needle biopsies, 17 of biliary atresia and 23 of intrahepatic cholestasis, 37 were correctly interpreted as either having biliary atresia or intrahepatic cholestasis. The overall diagnostic accuracy was 93%. Of 3 misdiagnosed cases, the histologic findings of two patients with biliary atresia(aged 43 days and 54 days at the first needle biopsy) were essentially the same as those of neonatal hepatitis. Follow-up biopsies, however, showed findings consistent with biliary atresia. The third one(VLBW premie with history of 8 weeks of TPN) showed mild ductal proliferation and portal fibrosis. This was interpreted as suspicious for biliary atresia. Jaundice resolved gradually. In summary, patients who have intestinal excretion of radionuclide on Tc-99m DlSIDA hepatobiliary scintigraphy, biliary atresia can be ruled out. But the patients who do not have intestinal excretion of radionuclide should have further investigation by needle biopsy. Judicious use of Tc-99m DISIDA hepatobiliary scintigraphy and percutaneous needle biopsy can give a diagnostic accuracy of 95% or more in cases of infantile cholestasis.

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Amphotericin B Aggregation Inhibition with Novel Nanoparticles Prepared with Poly(${\varepsilon}$-caprolactone)/Poly(N,N-dimethylamino-2-ethyl methacrylate) Diblock Copolymer

  • Shim, Yong-Ho;Kim, You-Chan;Lee, Hong-Joo;Bougard, Francois;Dubois, Philippe;Choi, Ki-Choon;Chung, Chung-Wook;Kang, Dae-Hwan;Jeong, Young-Il
    • Journal of Microbiology and Biotechnology
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    • v.21 no.1
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    • pp.28-36
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    • 2011
  • Diblock copolymers composed of poly(${\varepsilon}$-caprolactone) (PCL) and poly(N,N-dimethylamino-2-ethyl methacrylate) (PDMAEMA), or methoxy polyethylene glycol(PEG), were synthesized via a combination of ring-opening polymerization and atom-transfer radical polymerization in order to prepare polymeric nanoparticles as an antifungal drug carrier. Amphotericin B (AmB), a natural antibiotic, was incorporated into the polymeric nanoparticles. The physical properties of AmB-incorporated polymeric nanoparticles with PCL-b-PDMAEMA and PCL-b-PEG were studied in relation to morphology and particle size. In the aggregation state study, AmB-incorporated PCL-b- PDMAEMA nanoparticles exhibited a monomeric state pattern of free AmB, whereas AmB-incorporated PCL-b- PEG nanoparticles displayed an aggregated pattern. In in vitro hemolysis tests with human red blood cells, AmBincorporated PCL-b-PDMAEMA nanoparticles were seen to be 10 times less cytotoxic than free AmB (5 ${\mu}g$/ml). In addition, an improved antifungal activity of AmBincorporated polymeric nanoparticles was observed through antifungal activity tests using Candida albicans, whereas polymeric nanoparticles themselves were seen not to affect activity. Finally, in vitro AmB release studies were conducted, proving the potential of AmB-incorporated PCL-b-PDMAEMA nanoparticles as a new formulation candidate for AmB.

Biodistribution of 99mTc Labeled Integrin Antagonist

  • Jang, Beom-Su;Park, Seung-Hee;Shin, In Soo;Maeng, Jin-Soo;Paik, Chang H.
    • Toxicological Research
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    • v.29 no.1
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    • pp.21-25
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    • 2013
  • The selective targeting of an integrin ${\alpha}_v{\beta}_3$ receptor using radioligands may enable the assessment of angiogenesis and integrin ${\alpha}_v{\beta}_3$ receptor status in tumors. The aim of this research was to label a peptidomimetic integrin ${\alpha}_v{\beta}_3$ antagonist (PIA) with $^{99m}Tc(CO)_3$ and to test its receptor targeting properties in nude mice bearing receptor-positive tumors. PIA was reacted with tris-succinimidyl aminotriacetate (TSAT) (20 mM) as a PIA per TSAT. The product, PIA-aminodiacetic acid (ADA), was radiolabeled with $[^{99m}Tc(CO)_3(H_2O)_3]^{+1}$, and purified sequentially on a Sep-Pak C-18 cartridge followed by a Sep-Pak QMA anion exchange cartridge. Using gradient C-18 reverse-phase HPLC, the radiochemical purity of $^{99m}Tc(CO)_3$-ADA-PIA (retention time, 10.5 min) was confirmed to be > 95%. Biodistribution analysis was performed in nude mice (n = 5 per time point) bearing receptor-positive M21 human melanoma xenografts. The mice were administered $^{99m}Tc(CO)_3$-ADA-PIA intravenously. The animals were euthanized at 0.33, 1, and 2 hr after injection for the biodistribution study. A separate group of mice were also co-injected with 200 ${\mu}g$ of PIA and euthanized at 1 hr to quantify tumor uptake. $^{99m}Tc(CO)_3$-ADA-PIA was stable in phosphate buffer for 21 hr, but at 3 and 6 hr, 7.9 and 11.5% of the radioactivity was lost as histidine, respectively. In tumor bearing mice, $^{99m}Tc(CO)_3$-ADA-PIA accumulated rapidly in a receptor-positive tumor with a peak uptake at 20 min, and rapid clearance from blood occurring primarily through the hepatobiliary system. At 20 min, the tumor-to-blood ratio was 1.8. At 1 hr, the tumor uptake was 0.47% injected dose (ID)/g, but decreased to 0.12% ID/g when co-injected with an excess amount of PIA, indicating that accumulation was receptor mediated. These results demonstrate successful $^{99m}TC$ labeling of a peptidomimetic integrin antagonist that accumulated in a tumor via receptor-specific binding. However, tumor uptake was very low because of low blood concentrations that likely resulted from rapid uptake of the agent into the hepatobiliary system. This study suggests that for $^{99m}Tc(CO)_3$-ADA-PIA to be useful as a tumor detection agent, it will be necessary to improve receptor binding affinity and increase the hydrophilicity of the product to minimize rapid hepatobiliary uptake.