• Journal of Life Science
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• v.23 no.5
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• pp.710-720
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• 2013

Radiotherapy is commonly used in treating many kinds of cancers which cannot be cured by other therapeutic strategies. However, radiotherapy also induces the damages on the normal tissues. Radiation-induced fibrosis is frequently observed in the patients undergoing radiotherapy, and becomes a major obstacle in the treatment of intrahepatic cancer. Hedgehog (Hh) that is an essential in the liver formation during embryogenesis is not detected in the healthy liver, but activated and modulates the repair process in damaged livers in adult. The expression of Hh increases with the degree of liver damage, regulating the proliferation of hepatic progenitors and hepatic stellate cells (HSC). In addition, Hh induces epithelial-to-mesencymal transition (EMT) and activation of myofibroblasts. In the irradiated livers, up-regulated expression of Hh signaling was associated with proliferation of progenitors, EMT induction, and increased fibrosis. Female-specific expression of Hh leaded to the expansion of progenitors and the accumulation of collagen in the irradiated livers of female mice, indicating that gender disparity in Hh expression may be related with radiation-susceptibility in female. Hence, Hh signaling becomes a novel object of studies for fibrogenesis induced by radiation. However, the absence of the established experimental animal models showing the similar physiopathology with human liver diseases and fibrosis-favorable microenvironment hamper the studies for the radiation-induced fibrosis, providing a few descriptive results. Therefore, further research on the association of Hh with radiation-induced fibrosis can identify the cell and tissue-specific effects of Hh and provides the basic knowledge for underlying mechanisms, contributing to developing therapies for preventing the radiation-induced fibrosis.

• Journal of Life Science
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• v.26 no.7
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• pp.764-771
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• 2016

Extracts from Artemisia annua Linné (AAE) have been known to possess various functions, including anti-bacterial, anti-virus, and anti-oxidant effects. However, the mechanism of those effects of AAE is not well-known. The aim of this study was to analyze the inhibitory effects of AAE on cell proliferation of the human hepatoma cell line (Hep3B) and to examine its effects on apoptosis. Activation by phosphorylation of Akt is cell proliferation through the phosphorylation of TSC2, mTOR, and GSK-3β. We suggested that AAE may exert cancer cell apoptosis through Akt/mTOR/GSK-3β signal pathways and mitochondria-mediated apoptotic proteins. For this, we examined the effects of extracts of AAE on cell proliferation according to treatment concentration. Treatment with AAE not only reduced cell viability, but also resulted in the induced release of lactate dehydrogenase (LDH). These results were determined with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and a lactate dehydrogenase (LDH) assay. Furthermore, we determined the effects of apoptosis through Hoechst 33342 staining, annexinⅤ-propidium iodide (PI) staining, 5,5′, 6,6′-tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1) staining, and Western blotting. Our study showed that the treatment of liver cancer cells with AAE resulted in the inhibition of Akt, TSC2, GSK-3β-phosphorylated, Bcl-2, and pro-caspase 3 and the activation of Bim, Bax, Bak, and cleaved PARP expressions. These results indicate that AAE induced apoptosis by means of a mitochondrial event through the regulate of Akt/mTOR/GSK-3β signaling pathways.

• Journal of Korean Medical Science
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• v.33 no.51
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• pp.325.1-325.10
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• 2018

Background: To evaluate survival outcomes and prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) who received sunitinib (SU) and pazopanib (PZ) as first-line therapy in real-world Korean clinical practice. Methods: Data of 554 patients with mRCC who received SU or PZ at eight institutions between 2012 and 2016 were retrospectively reviewed. Based on the targeted therapy, the patients were divided into SU (n = 293) or PZ (n = 261) groups, and the clinicopathological variables and survival rates of the two groups were compared. A multivariable Cox proportional hazard model was used to determine the prognostic factors for OS. Results: The median follow-up was 16.4 months (interquartile range, 8.3-31.3). Patients in the PZ group were older, and no significant difference was observed in the performance status (PS) between the two groups. In the SU group, the dose reduction rate was higher and the incidence of grade 3 toxicity was more frequent. The objective response rates were comparable between the two groups (SU, 32.1% vs. PZ, 36.4%). OS did not differ significantly between the two groups (SU, 36.5 months vs. PZ, 40.2 months; log-rank, P = 0.955). Body mass index, Eastern Cooperative Oncology Group PS > 2, synchronous metastasis, poor Heng risk criteria, and liver and bone metastases were associated with a shorter OS. Conclusion: Our real-world data of Korean patients with mRCC suggested that SU and PZ had similar efficacies as first-line therapy for mRCC. However, PZ was better tolerated than SU in Korean patients.

• Advances in Traditional Medicine
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• v.5 no.4
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• pp.322-330
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• 2005

The plant Bryonia laciniosa (Family: Cucurbitaceae) has been indicated for the treatment of various diseases one among which is cancer. The purpose of this study was investigating experimentally the possible anti-tumor effect and antioxidant role of Bryonia laciniosa leaves in animal model. The methanol extract of Bryonia laciniosa (MEBL) administered at the doses of 62.5, 125 and 250 mg/kg in mice for 14 days after 24 h of tumor inoculation. The effect of MEBL on the growth of transplantable murine tumor, life span of EAC bearing mice, hematological profile and liver biochemical parameters (lipid peroxidation, antioxidant enzymes) were estimated. Treatment with MEBL decreased the tumor volume and viable cell count thereby increasing the life span of EAC bearing mice and brought back the hematological parameter more or less normal level. The effect of MEBL also decreases the levels of lipid peroxidation and increased the levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). The present work indicates that the methanol extract of Bryonia laciniosa exhibited significant antitumor and antioxidant activity in vivo.

• Journal of Pharmaceutical Investigation
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• v.33 no.4
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• pp.287-292
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• 2003

A novel antitumor agent, antibody-endostatin fusion protein $(anti-HER2/neu\;IgG3C_H3-Endostatin,\;AEFP)$ formed by genetic engineering procedure from antibody (Ab) which specifically targets to tumor cells ad angiogenesis inhibitor, endostatin (Endo) that has excellent antitumor effect, minimizes the toxicity of normal cells and selectively kills only tumor cells. The purpose of this study is to evaluate the phamacokinetic parameters and to analyze the localization of AEFP. After an intravenous injection of $150\;{\mu}l\;(5\;{\mu}Ci)\;[^{125}I]Ab,\;[^{125}I]AEFP$ to mice, blood was collected though retroorbital plexus from 15 min to 2880 min. Following the jugular vein injetion of $150\;{\mu}l\;(10\;{\mu}Ci)\;[^{125}I]Endo$, blood was collected by the use of carotid artery cannulation from 0.25 min to 30 min. Consequently, Endo was very rapidly removed from plasma compartment within 30 min. On the other hand, AEFP similar to Ab was slowly cleared from plasma. Also, Endo was metabolized about 40% within 30 min. However, AEFP was shown to metabolize less than 10% within 2880 min. The organ distribution of Endo was in order kidney, lung, spleen. Both Ab and AEFP were localized in order spleen, kidney, liver. Futhermore the tumor/blood distribution ratio of AEFP at 96 hours after injection is about 20 times higher than it of Endo at one hour after injection. In conclusion, these studies demonstrate that the anti-cancer or suppression of angiogenesis effect of Endo may be improved by the use of AEFP because the longer half life and stability of AEFP is able to selectively target antigens expressed on tumors.

• BMB Reports
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• v.51 no.10
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• pp.520-525
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• 2018

Cardiovascular diseases arising from atherosclerosis are the leading causes of mortality and morbidity worldwide. Lipid-lowering agents have been developed in order to treat hypercholesterolemia, a major risk factor for atherosclerosis. However, the prevalence of cardiovascular diseases is increasing, indicating a need to identify novel therapeutic targets and develop new treatment agents. Adenosine receptors (ARs) are emerging as therapeutic targets in asthma, rheumatoid arthritis, cancer, ischemia, and inflammatory diseases. This study assessed whether LJ-1888, a selective antagonist for $A_3$ AR, can inhibit the development of atherosclerosis in apolipoprotein E knock-out ($ApoE^{-/-}$) mice who are fed a western diet. Plaque formation was significantly lower in $ApoE^{-/-}$ mice administered LJ-1888 than in mice not administered LJ-1888, without any associated liver damage. LJ-1888 treatment of $ApoE^{-/-}$ mice prevented western diet-induced hypercholesterolemia by markedly reducing low-density lipoprotein cholesterol levels and significantly increasing high-density lipoprotein cholesterol concentrations. Reduced hypercholesterolemia in $ApoE^{-/-}$ mice administered LJ-1888 was associated with the enhanced expression of genes involved in bile acid biosynthesis. These findings indicate that LJ-1888, a selective antagonist for $A_3$ AR, may be a novel candidate for the treatment of atherosclerosis and hypercholesterolemia.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.45 no.6
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• pp.553-560
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• 2012

Hizikia fusiformis, a brown alga that is widely consumed in Korea, Japan, and China, possesses a number of potentially beneficial compounds, including antioxidants and anticoagulants. However, the molecular mechanisms of H. fusiformis in hepatoma cells have not been elucidated. This study investigated the antiproliferative effect and mechanism of action of a glycoprotein from H. fusiformis (HFGP) in HepG2 human hepatoma cells. In an MTS assay, 25 ${\mu}g/mL$ HFGP inhibited the proliferation of HepG2 cells by $52.36{\pm}2.37%$. HFGP caused the dose-dependent growth inhibition of HepG2 cells by inducing apoptosis and a sub-G1 phase arrest. The antiproliferative activity of HFGP was confirmed based on the expression of several apoptosis-related proteins, which was assessed by Western blot analysis. The expressions of Fas, Fas-associated death domain protein, Bax, and Bad was significantly up-regulated in HFGP-treated cells, and HFGP induced the translocation of Bax to mitochondria and the release of cytochrome c into the cytosol. Therefore, HFGP might be useful in the treatment of liver cancer.

• Journal of Nutrition and Health
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• v.55 no.2
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• pp.211-226
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• 2022

Choline, an essential nutrient for humans, is required for the structural integrity of the cell membranes, methyl-group metabolism, synthesis of the neurotransmitter acetylcholine, synthesis of the membrane phospholipid components of the cell membranes, and the transport of lipids and cholesterol. Choline can be synthesized in the body, but it is insufficient to meet the daily requirements and hence it must be obtained through the diet. In the United States/Canada, Australia/New Zealand, Europe, China, and Taiwan, the adequate intake (AI) and tolerable upper intake level (UL) of choline have been established, while the establishment of the 2020 Dietary Reference Intakes for Koreans (KDRI) for choline was postponed due to the lack of a choline database for Korean foods and studies on the choline intake of Koreans. However, as part of the preparation work for the 2020 DRI revision and finalization, choline intake and the possibility of disease occurrence were verified through analysis of published data. The groundwork for the subsequent establishment of a choline DRI was laid through a literature search, evaluation, and review of the literature reported from 1949 up to 2019. This can be regarded as the culmination of this project. According to the results of randomized controlled trials (RCTs), cohort studies, case-control studies, and cross-sectional observational studies in humans, approximately 400-500 mg/day of choline intake was effective in preventing liver function damage (fatty liver), neural tube damage, cardiovascular disease, breast cancer, and cognitive function improvement. The same amount of choline intake, however, also correlated with the risk of prostate and colorectal cancer. At present, there is limited information available on choline intake and health outcomes, particularly for the Korean population. More human studies, including clinical trials on the requirements and the physiological benefits associated with dietary intake, are needed to establish the KDRI for choline.

• Korean Journal of Poultry Science
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• v.33 no.2
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• pp.97-103
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• 2006

Telomeres are essential for chromosome stability and are related with cell senescence, apoptosis and cancer. Even though telomere length and telomerase activity have been studied extensively, very little is known to analyze the telomere dynamics in chicken cells. This study was carried out to analyze the telomere distribution and telomerase activity of Korean Native Chicken cells along with aging. The cells were collected from brain, heart, liver, kidney and germinal tissues during physiological stages. Telomere distribution was analyzed by Quantitative-Fluorescence in situ Hybridization (Q-FISH) techniques using the chicken telomeric DNA probe. Telomerase activity was performed by Telomeric Repeat Amplification Protocol (TRAP) assay. In results, the telomeres of chicken were found at the ends of all chromosomes with the interstitial telomeres on chromosomes 1, 2 and 3. The amount of telomeres on chicken cells was decreased along with aging in most tissues. Furthermore, the telomere quantity was significantly different among tissues. The relative amount of telomeres in proliferous cells such as testis cells had much more than those of liver, brain, heart, blood and kidney cells. The telomerase activity was down-regulated in cells of brain, heart and liver tissues. Whereas gonadal cells showed a constitutive activity of telomerase during all stage of life. In conclusions, the telomere quantity and telomerase activity in chicken are closely relate to cell proliferation and tissue specificity during developmental stages and aging. There is also closely correlated between the amounts of telomeric DNA and telomerase activity in chicken tissues.

• The Korean Journal of Nuclear Medicine
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• v.35 no.3
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• pp.185-191
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• 2001

Objectives: Recently, $[methyl-^{11}C]-({\beta}$-Hydroxyethyl)trimethylammonium ($[^{11}C]$choline) Has been discovered to be a very effective tracer in imaging various human tumors using positron omission tomography. Because of the short half-life of C-11, it is very difficult to use in a routine imaging procedure and needs a frequent synthesis of $[^{11}C]$choline. This can be supplemented by the substitution of $[^{11}C]$choline with $[methyl-^{18}F]$fluorocholine. Here, we would like to report ceil uptake and biodistribution of $[^{11}C]$choline and $[^{18}F]$fluorocholine as a basic study. Methods: $[^{11}C]$Choline was prepared by the treatment of $[^{11}C]CH_3I$ with N,N-dimethylaminoethanol and $[^{18}F]$fluorocholine was synthesized from reaction of $CH_2Br[^{18}F]F$ with N,N-dimethylaminoethanol. The radiochemical purity was checked by high performance liquid chromatography (HPLC). The blodistribution of $[^{11}C]$choline and $[^{18}F]$fluorocholine was determined in balb/c mouse at 5 min, 20 min, 40 min and 80 min. The cell uptake was measured using glioma (9L) and colon adenocarcinoma (SW620). Results: The radiochemical purity was more than 98% after purification. In the liver, uptake did not change over time; the uptake was 20%ID/g for $[^{11}C]$choline and 13%ID/g for $[^{18}F]$fluorocholine. In the kidney, radioactivity decreased over time; the uptake was 15%ID/g for $[^{11}C]$choline and 20%ID/g for $[^{18}F]$fluorocholine, 80 min post-injection. The cell uptake of $[^{11}C]$choline was 4.93% for glioma (9L) and 18.69% for colon adenocarcinoma (SW620). For $[^{18}F]$fluorocholine, 1.77% for glioma (9L) and 2.77% for colon adenocarcinoma (SW620). Conclusion: $[^{11}C]$Choline and $[^{18}F]$fluorocholine showed a different cell uptake tendency, depending on cancer cell line.