• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.48-55
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• 2010

Neural progenitor cells (NPCs) differentiate into astrocytes, neurons and oligodendrocytes, which is controlled by various factors in brain. Recent evidences suggest that small molecules modulating the proliferation and differentiation of NPCs may have therapeutic value as well as the potential use as chemical probes. Phylligenin is a lignan with anti-inflammatory activity that is isolated from the fruits of Forsythia koreana. We investigated effects of phylligenin on proliferation and differentiation of NPCs. Treatment of phylligenin decreased the number of proliferating NPCs in culture without effects on the differentiation and survival of neural cells such as neurons and astrocytes. To examine the mechanism of the decreased NPCs number, we performed cell cycle analysis. Proliferation of NPCs was decreased via G1-S transition block by phylligenin treatment, and it was mediated by the increase of p21 level. However, phylligenin did not induce apoptosis of NPCs as determined by TUNEL assay and PARP cleavage. We also found that viability of glioma cell lines such as C6 and U87MG glioma cells, but not that of primary neuron and astrocyte, was inhibited by phylligenin. These results suggest that phylligenin selectively inhibits proliferation of rapidly growing cells such as neural stem cells and glioma cells. Given that the possible role of brain tumor stem cells in the pathology of brain cancers, the inhibitory effects of phylligenin might be useful in the development of new therapeutic agents against brain cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3219-3226
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• 2014

Chemotherapy continues to be a mainstay of cancer treatment, although drug resistance is a major obstacle. Lipid metabolism plays a critical role in cancer pathology, with elevated ether lipid levels. Recently, alkylglyceronephosphate synthase (AGPS), an enzyme that catalyzes the critical step in ether lipid synthesis, was shown to be up-regulated in multiple types of cancer cells and primary tumors. Here, we demonstrated that silencing of AGPS in chemotherapy resistance glioma U87MG/DDP and hepatic carcinoma HepG2/ADM cell lines resulted in reduced cell proliferation, increased drug sensitivity, cell cycle arrest and cell apoptosis through reducing the intracellular concentration of lysophosphatidic acid (LPA), lysophosphatidic acid-ether (LPAe) and prostaglandin E2 (PGE2), resulting in reduction of LPA receptor and EP receptors mediated PI3K/AKT signaling pathways and the expression of several multi-drug resistance genes, like MDR1, MRP1 and ABCG2. ${\beta}$-catenin, caspase-3/8, Bcl-2 and survivin were also found to be involved. In summary, our studies indicate that AGPS plays a role in cancer chemotherapy resistance by mediating signaling lipid metabolism in cancer cells.

• BMB Reports
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• v.55 no.12
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• pp.615-620
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• 2022

The murine leukemia virus-based semi-retroviral replicating vectors (MuLV-based sRRV) had been developed to improve safety and transgene capacity for cancer gene therapy. However, despite the apparent advantages of the sRRV, improvements in the in vivo transduction efficiency are still required to deliver therapeutic genes efficiently for clinical use. In this study, we established a gibbon ape leukemia virus (GaLV) envelope-pseudotyped semi-replication-competent retrovirus vector system (spRRV) which is composed of two transcomplementing replication-defective retroviral vectors termed MuLV-Gag-Pol and GaLV-Env. We found that the spRRV shows considerable improvement in efficiencies of gene transfer and spreading in both human glioblastoma cells and pre-established human glioblastoma mouse model compared with an sRRV system. When treated with ganciclovir after intratumoral injection of each vector system into pre-established U-87 MG glioblastomas, the group of mice injected with spRRV expressing the herpes simplex virus type 1-thymidine kinase (HSV1-tk) gene showed a survival rate of 100% for more than 150 days, but all control groups of mice (HSV1-tk/PBS-treated and GFP/GCV-treated groups) died within 45 days after tumor injection. In conclusion, these findings sug-gest that intratumoral delivery of the HSV1-tk gene by the spRRV system is worthy of development in clinical trials for the treatment of malignant solid tumors.

• Journal of Life Science
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• v.21 no.5
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• pp.631-646
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• 2011

Mesenchymal stem cells (MSC) are multipotent and can be isolated from diverse human tissues including bone marrow, fat, placenta, dental pulp, synovium, tonsil, and the thymus. They function as regulators of tissue homeostasis. Because of their various advantages such as plasticity, easy isolation and manipulation, chemotaxis to cancer, and immune regulatory function, MSCs have been considered to be a potent cell source for regenerative medicine, cancer treatment and other cell based therapy such as GVHD. However, relating to its supportive feature for surrounding cell and tissue, it has been frequently reported that MSCs accelerate tumor growth by modulating cancer microenvironment through promoting angiogenesis, secreting growth factors, and suppressing anti-tumorigenic immune reaction. Thus, clinical application of MSCs has been limited. To understand the underlying mechanism which modulates MSCs to function as tumor supportive cells, we co-cultured human adipose tissue derived mesenchymal stem cells (ASC) with cancer cell lines H460 and U87MG. Then, expression data of ASCs co-cultured with cancer cells and cultured alone were obtained via microarray. Comparative expression analysis was carried out using DAVID (Database for Annotation, Visualization and Integrated Discovery) and PANTHER (Protein ANalysis THrough Evolutionary Relationships) in divers aspects including biological process, molecular function, cellular component, protein class, disease, tissue expression, and signal pathway. We found that cancer cells alter the expression profile of MSCs to cancer associated fibroblast like cells by modulating its energy metabolism, stemness, cell structure components, and paracrine effect in a variety of levels. These findings will improve the clinical efficacy and safety of MSCs based cell therapy.

• Korean Journal of Organic Agriculture
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• v.13 no.4
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• pp.389-400
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• 2005

This study was conducted to investigate into the ecological environments and the soil microflora of purple-bracted plantain lily (Hosta longipes Matsumura) for wild vgetables. Native soil textures of purple-bracted plantain lily were in the order of sandy loam (SL) > loam (L) > clay loam (CL). pH in soil was relatively acid by 4.8, electric conductivity was 0.08mS/cm, and organic matter content was 0.08g/kg. CEC was measured by $100.8cmol^{(+)}kg^{-1}$ and available phosphate was 103.4mg/kg. Contents of exchangeable cations in terms of potassium, calcium, and magnesium were measured by $0.33cmol^{(+)}kg^{-1},\;2.26cmol^{(+)}kg^{-1},\;and\;0.87cmol^{(+)}kg^{-1}$, etc. Diurnal changes in the air temperature of the natives were 15 to $20^{\circ}C$, that temperature differential was relatively little compared with that in open field by 15 to $30^{\circ}C$. Relative humidity in the natives were much more humid by 60 to 80% compared with that in open feld by 35 to 85%. Light intensity in the natives and the open field at ten o'clock were $2,300{\mu}mol/m^2/sec.\;and\;1,750{\mu}mol/m^2/sec.$ Total number of soil microorganisms were $8.4{\times}10^7\;c.f.u./g$. Mycorrhizal spore densities over $500{\mu}m,\;355{\sim}500{\mu}m,\;251{\sim}354{\mu}m,\;107{\sim}250{\mu}m\;and\;45{\sim}106{\mu}m$ were 0.8, 1.3, 2.1, 38.1, and 110.0 respectively. Mycorrhizal root infections by vesicle and hyphae were 17% and 6%. However, arbuscules in the roots were not shown.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3495-3501
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• 2014

Melanoma-associated antigen (MAGE) family genes have been considered as potentially promising targets for anticancer immunotherapy. MAGED4 was originally identified as a glioma-specific antigen. Current knowledge about MAGED4 expression in glioma is only based on mRNA analysis and MAGED4 protein expression has not been elucidated. In the present study, we investigated this point and found that MAGED4 mRNA and protein were absent or very lowly expressed in various normal tissues and glioma cell line SHG44, but overexpressed in glioma cell lines A172,U251,U87-MG as well as glioma tissues, with significant heterogeneity. Furthermore, MAGED4 protein expression was positively correlated with the glioma type and grade. We also found that the expression of MAGED4 inversely correlated with the overall methylation status of the MAGED4 promoter CpG island. Furthermore, when SHG44 and A172 with higher methylation were treated with the DNA demethylating agent 5-aza-2'-deoxycytidine (5-AZA-CdR) reactivation of MAGED4 mRNA was mediated by significant demethylation in SHG44 instead of A172. However, 5-AZA-CdR treatment had no effect on MAGED4 protein in both SHG44 and A172 cells. In conclusion, MAGED4 is frequently and highly expressed in glioma and is partly regulated by DNA methylation. The results suggest that MAGED4 might be a promising target for glioma immunotherapy combined with 5-AZA-CdR to enhance its expression and eliminate intratumor heterogeneity.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.248-256
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• 2018

O-2-$^{18}F$-fluoroethyl-l-tyrosine ($[^{18}F]FET$) has been widely used for glioblastomas (GBM) in clinical practice, although evaluation of its applicability in non-clinical research is still lacking. The objective of this study was to examine the value of $[^{18}F]FET$ for treatment evaluation and prognosis prediction of anti-angiogenic drug in an orthotopic mouse model of GBM. Human U87MG cells were implanted into nude mice and then bevacizumab, a representative anti-angiogenic drug, was administered. We monitored the effect of anti-angiogenic agents using multiple imaging modalities, including bioluminescence imaging (BLI), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET/CT). Among these imaging methods analyzed, only $[^{18}F]FET$ uptake showed a statistically significant decrease in the treatment group compared to the control group (P=0.02 and P=0.03 at 5 and 20 mg/kg, respectively). This indicates that $[^{18}F]FET$ PET is a sensitive method to monitor the response of GBM bearing mice to anti-angiogenic drug. Moreover, $[^{18}F]FET$ uptake was confirmed to be a significant parameter for predicting the prognosis of anti-angiogenic drug (P=0.041 and P=0.007, on Days 7 and 12, respectively, on Pearson's correlation; P=0.048 and P=0.030, on Days 7 and 12, respectively, on Cox regression analysis). However, results of BLI or MRI were not significantly associated with survival time. In conclusion, this study suggests that $[^{18}F]FET$ PET imaging is a pertinent imaging modality for sensitive monitoring and accurate prediction of treatment response to anti-angiogenic agents in an orthotopic model of GBM.

• Nutrition Research and Practice
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• v.17 no.2
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• pp.241-256
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• 2023

BACKGROUND/OBJECTIVES: Diabetes-specific oral nutritional supplements (ONS) have anti-hyperglycemic effects, while D-allulose exerts anti-diabetic and anti-obesity effects. In this study, we investigated the efficacy and safety of diabetes-specific ONS, including allulose, on glycemic and weight changes in overweight or obese patients with type 2 diabetes mellitus (T2DM). SUBJECTS/METHODS: A single-arm, historical-control pilot clinical trial was conducted on 26 overweight or obese patients with T2DM (age range: 30-70 yrs). The participants were administered 2 packs of diabetes-specific ONS, including allulose (200 kcal/200 mL), every morning for 8 weeks. The glycemic profiles, obesity-related parameters, and lipid profiles were assessed to evaluate the efficacy of ONS. RESULTS: After 8 weeks, fasting blood glucose (FBG) level significantly decreased from 139.00 ± 29.66 mg/dL to 126.08 ± 32.00 mg/dL (P = 0.007) and glycosylated hemoglobin (HbA1c) improved (7.23 ± 0.82% vs. 7.03 ± 0.69%, P = 0.041). Moreover, the fasting insulin (δ: -1.81 ± 3.61 μU/mL, P = 0.017) and homeostasis model assessment for insulin resistance (HOMA-IR) (δ: -0.87 ± 1.57, P = 0.009) levels decreased at 8 weeks, and body weight significantly decreased from 67.20 ± 8.29 kg to 66.43 ± 8.12 kg (P = 0.008). Body mass index (BMI) also decreased in accordance with this (from 25.59 ± 1.82 kg/m² to 25.30 ± 1.86 kg/m², P = 0.009), as did waist circumference (δ: -1.31 ± 2.04 cm, P = 0.003). CONCLUSIONS: The consumption of diabetes-specific ONS with allulose in overweight or obese patients with T2DM improved glycemic profiles, such as FBG, HbA1c, and HOMA-IR, and reduced body weight and BMI.

• Korean Journal of Food Science and Technology
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• v.31 no.1
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• pp.238-245
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• 1999

Antioxidative effects of the water or ethanol extracts from Rhus verniciflua Stokes (RVS) were measured by protection against hydroxyl radicals in mouse brain tissue culture. In the water extracts from RVS, cell viabilities were estimated 60.0, 66.0, 72.0, 84.0 and 90.0% at addition of 1, 2, 4, 7 and $10{\mu}L$, respectively, compared with GO (20 mU/mL) alone. The cell viability in the ethanol extracts was similarly with water extracts. In the antitumor effects, the results showed that percentages of the HeLa cell death were approximately 24% for 12 hrs, 57% for 48 hrs at addition of 10%/well ethanol extracts respectively. To know inhibition of tumor growth, in vivo, mice (BALB/c) were inoculated with 0.25 mL CT-26 $(1{\times}10^6\;cells/mL)$ subcutaneously. After the generation of tumor, the results of RVS extracts (ethanol, water) injection showed generally that the tumor size in BALB/c was reduced. For physicochemical characterization of the RVS extracts, purified substances of water or ethanol extracts were analized with SDS-PAGE and ICP spectrometer. In electrophoresis, gel showed 2 bands (210, 230 KDa). The results of ICP verified that RVS extracts contain $Cu^{2+}$ in both samples. Conclusively, this substance might be a laccase which has a biological effective function, as a natural bioactive substance.

• Journal of Nutrition and Health
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• v.6 no.3
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• pp.47-63
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• 1973

This study concerns the nutritional status of food in a lunch-box and the school lunch program provided for Dong Duck Elementary School Pupils in Daegu. Two hundred andsix pupils were randomly selected as a sample. The nutrients contained in a lunch-box and school lunch menu were analyzed according to the Food Composition Table. Nutrients and cost of the Dong Duck Elementary School Lunch were compared to the average nutrient contents of food in a lunch-box of o pupil. In addition, comparisons between the Recommended Daily Allowances of nutrients for Korean children aged from 9 to 11 (4th, 5th, and 6th grade) and that of the contained nutrients in the average lunch-box were conducted. The average nutrients contained in the lunch-box compared with the Recommended Daily Allowances are: Calorie 77.41% (542.60ca1), Protein 73.60% (16.93gr), Fat 33.95% (3.95gr), Calcium 27.85% (111.39mg), Ferret 80.30% (2.65mg), Vitamin A 10.09% (100.93 I.U.), Vitamin Bl 70.27% (0.27mg), Vitamin B2 88.37% (0.38mg), Vitamin C 15.40% (3.45mg). All of the nutrients in the lunch-box fall far below the Recommended Daily Allowances for the 9-11 age group. The average nutrients of staple food in the lunch-box compared with the side-dishes were found to contain Calorie 90.80%, Protein 50.32%, Fat 58.27%, Calcium 37.07 %, Ferret 53.96%, Vitamin A 0.0028%, Vitamin B1 78.11%, Vitamin B2 21.09%. The nutrients of food contained in the Dong Duck Elementary School Lunch Program compared with the Recommended Daily Allowances were: 1. The Protein, Fat, Ferret, Vitamin B1 and Vitamin B2 content was generally satisfactory. 2. Calcuim, Vitamin A and Vitamin C were lower than the Recommended Daily Allowances. 3. The Calorie content was generally lower for the 9-11 age group. The per pupil cost of the lunch-box was 41.87 won which includes the cost of staple food 16.92 won and side-dishes 24.95 won, whereas the school lune Provided by Dong Duck Elementary School Costs 35 won per pupil. Questionnaires were sent to four hundred parents (through their children) to find out their attitude toward the school lunch program. 390(97.50%) of them were returned and 7 of them dia not answer at all. Therefore, these were eliminated from the samlpe. Among 185 parents whose children were eating the school lunch; 172 parents (92.97% ) would pay 40 won for the proposed new school lunch program whereas only 13 parents (7.03%) did not want it. Among 198 parents whose children were not having the school lunch, 58 parents (29.29%) would agree to have the lunch for their children at the cost of 35 won with the proposed new school lunch program equivalent to 40 won. 126 parents (63.63%) could not agree to have their children being the school lunch because of their financial difficulty (74 parents 58.72%). The rest of parents (52 parents 41.28%) raised other reasons which were minor problems. Among the tatal of 383 parents, 309 parents (80.68%) would agree to gave school lunch for their children if the cost of the proposed new school lunch program would be 35 won to 40 won and if minor problems concerning the school lunch program are solved. Sixty parents (15.66% ) raised questions about the school lunch program concerning sanitary problems, taste of bread, and the quantity of lunch. Among 383 parents, 358 parents answered and 25 parents did not. When school officer asked if the parents would help during the school lunch hour, 101 parents indicated they could not help at all, but 177 parents, replied they could help. Among 177 parents, 40 parents of them could share their time from one or two hours everyday except Saturday and 107 parents could serve 1 to 3 days per week. Through this study, it is evident that further investigation should be done of the school lunch program which can be provided 35 won with the proposed new school lunch program. The parents participation in the school lunch program would be improved the understanding between school and parents as well as insure better nutrition and sanitation for the children.