• Korean Journal of Clinical Laboratory Science
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• v.50 no.3
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• pp.337-344
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• 2018

Hepatocellular carcinoma (HCC), a major type of hepatoma, is associated with high recurrence and mortality because of its uncontrolled metastatic feature. Silymarin is a polyphenolic flavonoid from Silybum marianun (milk thistle) and exhibits anti-carcinogenic activity through modulation of the epithelial-mesenchymal transition (EMT) in several cancer cells. In this study, the inhibitory mechanism of silymarin against migration and invasion was investigated in the Huh7 HCC cell line. Wound healing and in vitro invasion assays were conducted to examine the effects of silymarin on migration and invasion. Western blot analysis was also applied to evaluate the inhibitory effects of silymarin on the EMT-related genes and their upstream signaling molecules. Silymarin inhibited the migratory and invasive activities of Huh7 cells. In addition, silymarin attenuated the protein expression levels of vimentin and matrix metalloproteinase (MMP)-9 as well as their transcription factors, Snail, and nuclear factor $(NF)-{\kappa}B$, while the expression of E-cadherin was increased by the silymarin treatment. Among the upstream signaling molecules, the phosphorylation of Akt was inhibited by the silymarin treatment, which was confirmed by the selective inhibitor, LY294002. Consequently, silymarin inhibited the invasive and migratory activities in Huh7 cells through the modulation of EMT-related gene expression by the PI3K/Akt signaling pathway, which may have potential as a chemopreventive agent against HCC metastasis.

• The Journal of Korean Society for Radiation Therapy
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• v.24 no.2
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• pp.157-165
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• 2012

Purpose: We evaluated usefulness of abdominal compressor for stereotactic body radiotherapy (SBRT) with unresectable hepatocellular carcinoma (HCC) patients and hepato-biliary cancer and metastatic liver cancer patients. Materials and Methods: From November 2011 to March 2012, we selected HCC patients who gained reduction of diaphragm movement >1 cm through abdominal compressor (diaphragm control, elekta, sweden) for HT (Hi-Art Tomotherapy, USA). We got planning computed tomography (CT) images and 4 dimensional (4D) images through 4D CT (somatom sensation, siemens, germany). The gross tumor volume (GTV) included a gross tumor and margins considering tumor movement. The planning target volume (PTV) included a 5 to 7 mm safety margin around GTV. We classified patients into two groups according to distance between tumor and organs at risk (OAR, stomach, duodenum, bowel). Patients with the distance more than 1 cm are classified as the 1st group and they received SBRT of 4 or 5 fractions. Patients with the distance less than 1 cm are classified as the 2nd group and they received tomotherapy of 20 fractions. Megavoltage computed tomography (MVCT) were performed 4 or 10 fractions. When we verify a MVCT fusion considering priority to liver than bone-technique. We sent MVCT images to Mim_vista (Mimsoftware, ver .5.4. USA) and we re-delineated stomach, duodenum and bowel to bowel_organ and delineated liver. First, we analyzed MVCT images to check the setup variation. Second we compared dose difference between tumor and OAR based on adaptive dose through adaptive planning station and Mim_vista. Results: Average setup variation from MVCT was $-0.66{\pm}1.53$ mm (left-right) $0.39{\pm}4.17$ mm (superior-inferior), $0.71{\pm}1.74$ mm (anterior-posterior), $-0.18{\pm}0.30$ degrees (roll). 1st group ($d{\geq}1$) and 2nd group (d<1) were similar to setup variation. 1st group ($d{\geq}1$) of $V_{diff3%}$ (volume of 3% difference of dose) of GTV through adaptive planing station was $0.78{\pm}0.05%$, PTV was $9.97{\pm}3.62%$, $V_{diff5%}$ was GTV 0.0%, PTV was $2.9{\pm}0.95%$, maximum dose difference rate of bowel_organ was $-6.85{\pm}1.11%$. 2nd Group (d<1) GTV of $V_{diff3%}$ was $1.62{\pm}0.55%$, PTV was $8.61{\pm}2.01%$, $V_{diff5%}$ of GTV was 0.0%, PTV was $5.33{\pm}2.32%$, maximum dose difference rate of bowel_organ was $28.33{\pm}24.41%$. Conclusion: Despite we saw diaphragm movement more than 5 mm with flouroscopy after use an abdominal compressor, average setup_variation from MVCT was less than 5 mm. Therefore, we could estimate the range of setup_error within a 5 mm. Target's dose difference rate of 1st group ($d{\geq}1$) and 2nd group (d<1) were similar, while 1st group ($d{\geq}1$) and 2nd group (d<1)'s bowel_organ's maximum dose difference rate's maximum difference was more than 35%, 1st group ($d{\geq}1$)'s bowel_organ's maximum dose difference rate was smaller than 2nd group (d<1). When applicating SBRT to HCC, abdominal compressor is useful to control diaphragm movement in selected patients with more than 1 cm bowel_organ distance.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3879-3884
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• 2014

Background: In chronic hepatitis B (CHB), the presence of hepatic steatosis (HS) seems to be associated with known host and viral factors which may influence the long-term prognosis of chronic hepatitis B (CHB), probably leading to cirrhosis and hepatocellular carcinoma (HCC). Different from chronic hepatitis C (CHC), factors associated with HS in CHB are not clearly explored. Materials and Methods: 160 CHB patients were divided into two groups depending on the results of liver biopsy. Group I consisted of 71 patients with confirmed steatosis. Group II comprised 89 patients without steatosis. The groups were compared in terms of basal characteristics, body mass index (BMI), liver enzymes (ALT, AST, ALP), serum fasting blood sugar (FBS) and lipids, hepatitis B e antigen (HBeAg), viral load, and histological findings. Results: In terms of host factors, male gender, older age, BMI, high serum FBS and lipid levels were associated with HS. On the other hand, ALT levels, the HAI scores of necroinflammation and stage of fibrosis did not associate with HS. On multivariate analysis, parameters of sex, BMI, cholesterol and FBS levels were independently associated with HS. Regarding viral factors, HBeAg negativity was significantly associated with HS (81.7%, p value 0.006), but not HBV DNA level (p value 0.520). Conclusions: HS in CHB appears to be unrelated to the status of HBV replication. However, fibrosis progression in CHB is related to variable host factors. HS may be enhanced through these factors in HBV chronic patients.

• The Journal of Internal Korean Medicine
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• v.36 no.1
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• pp.58-68
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• 2015

Objectives : To evaluate the long-term survival effects of traditional Korean medicine (TKM) on refractory metastatic lung cancer and small cell lung cancer (SCLC), which have historically poor survival rates. Methods : A retrospective study was conducted using the medical records of two patients in Daejeon University hospital. The first patient, with SCLC, was treated from January 2000 to December 2009 and the other, with metastatic pulmonary cancer from primary hepatocellular carcinoma (HCC), was treated from September 2004 to February 2014. The patients were treated with herbal medicines at one-month intervals. During hospitalization, acupuncture and indirect moxibustion were performed concurrent with the administration of Western therapy. Treatment efficacy was assessed monthly using chest radiography, chest computed tomography, and laboratory examination data, and by measuring patient performance status. Results : Both patients exhibited a stable disease course for more than 9 years after the initial diagnosis of intractable lung cancer, suggesting that their disease status was controlled by TKM. Conclusions : We suggest that a combination of TKM with conventional Western therapy for refractory lung cancer patients is effective in controlling various symptoms related to lung cancer and improving quality of life, and may potentially prolong overall survival.

• The Journal of Korean Society for Radiation Therapy
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• v.26 no.1
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• pp.1-9
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• 2014

Purpose : To analyze tumor's movement and volume change from changing position in order to minimize movement caused by breathing. Materials and Methods : We conducted survey of 14 patients with HCC(Hepatocellular carcinoma). Patient immobilization device was made in two ways(Supine position, prone position) and from image acquisition, tumor's movement, volume and dose are analyzed. Results : The mean movement of target(LR, Left-right) in supine position and prone position was $2.76{\pm}1.25mm$, $2.21{\pm}0.93mm$. AP(Anterior-posterior) and SI(Superior-inferior) was $4.02{\pm}1.63mm$, $11.56{\pm}3.08mm$, $3.36{\pm}1.17mm$, $7.45{\pm}1.96mm$. Treatment volume was decreased and normal liver volume was increased in prone position. Conclusion : We could reduce the margin of the treatment volume by minimizing the movement of liver caused by breathing. Especially in prone position, it is considered to be able to decrease the movement of the liver and increase normal liver volume.

• Radiation Oncology Journal
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• v.7 no.2
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• pp.247-257
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• 1989

Thirty patients with nonresectable hepatocellular carcinoma (HCC) due to either locally advanced lesion or association with liver cirrhosis, treated with combined radiotherapy and hyperthermia between April 1988 and July 1988, at Dept. of Radiation Oncology, Yonsei university College of medicine, were analysed. External radiotherapy of a total dose of 3060cGy/3.5 wks was given. Hyperthermia was given twice a week with a total of 6 treatment sessions using 8MHz radiofrequency capacitive type heating device, i.e., Thermotron RF-8 and Cancermia. In all cases hyperthermia was given within 30 minutes after radiotherapy for 30~60min. Temperature was measured by inserting thermocouple into the tumor mass under the ultrasonographic guidance only for those who had not bleeding tendency. As a result, partial response (PR) was achieved in 12 patients (40%), and symptomatic improvement was observed in 22 patients (78.6%) among 28 patients who had suffered from abdominal pain. The most significant factor affecting the tumor response rate was the type of tumor (single massive: 10/14, 71.4%; diffuse infiltrative: 2/10, 20%; multinodular:0/6, 0%; p<0.005). There were not any significant side effects relating to combined treatment. The overall 1 year survival rate was 34%, with 50% in the PR group and 22% in the no response group (NR), respectively. Median survival was 6.5 months and longer for those of PR than of NR (11 mos. vs 5, p<0.05). In conclusion, combined radiotherapy and hyperthermia appeared to be effective in local control and symptomatic palliation of HCC. Further study including a larger number of the patients to confirm its effect in survival and detrimental side effect should be urged.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2006.02a
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• pp.83-89
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• 2006

Cellular functions are carried out by a concerted action of biochemical pathways whose components have genetic interactions. Abnormalities in the activity of the genes that constitute or modulate these pathways frequently have oncogenic implications. Therefore, identifying the upstream regulatory genes for major biochemical pathways and defining their roles in carcinogenesis can have important consequences in establishing an effective target-oriented antitumor strategy We have analyzed the gene expression profiles of human liver cancer samples using cDNA microarray chips enriched in liver and/or stomach-expressed cDNA elements, and identified groups of genes that can tell tumors from non-tumors or normal liver, or classify tumors according to clinical parameters such as tumor grade, age, and inflammation grade. We also set up a high-throughput cell-based assay system (cell chip) that can monitor the activity of major biochemical pathways through a reporter assay. Then, we applied the cell chip platform for the analysis of the HCC-associated genes discovered from transcriptome profiling, and found a number of cancer marker genes having a potential of modulating the activity of cancer-related biochemical pathways such as E2F, TCF, p53, Stat, Smad, AP-1, c-Myc, HIF and NF-kB. Some of these marker genes were previously blown to modulate these pathways, while most of the others not. Upon a fast-track phenotype analysis, a subset of the genes showed increased colony forming abilities in soft agar and altered cell morphology or adherence characteristics in the presence of purified matrix proteins. We are currently analyzing these selected marker genes in more detail for their effects on various biological Processes and for Possible clinical roles in liver cancer development.

• Korean Journal of Radiology
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• v.22 no.10
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• pp.1658-1670
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• 2021

Objective: To assess the two-year treatment outcomes of chemoembolization with drug-eluting embolics (DEE) for nodular hepatocellular carcinoma (HCC). Materials and Methods: This study was a prospective, multicenter, registry-based, single-arm trial conducted at five university hospitals in Korea. Patients were recruited between May 2011 and April 2013, with a target population of 200. A DC Bead loaded with doxorubicin was used as the DEE agent. Patients were followed up for two years. Per-patient and per-lesion tumor response analysis, per-patient overall survival (OS) and progression-free survival (PFS) analysis, and per-lesion tumor control analysis were performed. Results: The final study population included 152 patients, with 207 target lesions for the per-lesion analysis. At one-month, six-month, one-year, and two-year per-patient assessments, complete response (CR) rates were 40.1%, 43.0%, 33.3%, and 19.6%, respectively. The objective response (OR) rates were 91.4%, 55.4%, 35.1%, and 19.6%, respectively. The cumulative two-year OS rate was 79.7%. The cumulative two-year PFS rate was 22.4% and the median survival was 9.3 months. In multivariable analysis, the Child-Pugh score (p = 0.019) was an independent predictor of OS, and tumor multiplicity (p < 0.001), tumor size (p = 0.020), and Child-Pugh score (p = 0.006) were independent predictors of PFS. In per-lesion analysis, one-month, six-month, one-year and two-year CR rates were 57.5%, 58.5%, 45.2%, and 33.3%, respectively, and the OR rates were 84.1%, 65.2%, 46.6%, and 33.3%, respectively. The cumulative two-year per-lesion tumor control rate was 36.2%, and the median time was 14.1 months. The Child-Pugh score (p < 0.001) was the only independent predictor of tumor control. Serious adverse events were reported in 11 patients (7.2%). Conclusion: DEE chemoembolization for nodular HCCs in the Korean population showed acceptable survival, tumor response, and safety profiles after a two-year follow-up. Good liver function (Child-Pugh score A5) was a key predictor of per-patient OS, PFS, and per-lesion tumor control.