• Nuclear Medicine and Molecular Imaging
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• v.42 no.4
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• pp.307-313
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• 2008

Purpose: Vascular endothelial growth factor (VEGF) and its receptor, fetal liver kinase 1 (Flk-1), play an important role in vascular permeability and tumor angiogenesis. The aim of this study is to evaluate the therapeutic efficacy of $^{131}I$ labeled anti-Flk-1 monoclonal antibody (DC101) on the growth of melanoma tumor, which is known to be very aggressive in vivo. Materials and Methods: Balb/c nude mice were injected subcutaneously with melanoma cells in the right flank. Tumors were allowed to grow up to $200-250\;mm^3$ in volume. Gamma camera imaging and biodistribution studies were performed to identify an uptake of $^{131}I$-DC101 in various organs. Mice with tumor were randomly divided into five groups (10 mice per group) and injected intravenously; control PBS (group 1), $^{131}I$-DC101 $50\;{\mu}g/mouse$ (group 2), non-labeled DC101 $50\;{\mu}g/mouse$ (group 3), $^{131}I$-DC101 $30\;{\mu}g/mouse$ (group 4) and $15\;{\mu}g/mouse$ (group 5) every 3 or 4 days for 20 days. Tumor volume was measured with caliper twice a week. Results: In gamma camera images, the uptake of $^{131}I$-DC101 into tumor and thyroid was increased with time. Biodistribution results showed that the radioactivity of blood and other major organ was gradually decreased with time whereas tumor uptake was increased up to 48 hr and then decreased. After 4th injection of $^{131}I$-DC101, tumor volume of group 2 and 4 was significantly smaller than that group 1. After 5th injection, the tumor volume of group 5 also significantly reduced. Conclusion: These results indicated that delivery of $^{131}I$ to tumor using FlK-1 antibody, DC101, effectively blocks tumor growth in aggressive melanoma xenograft model.

• Journal of Sasang Constitutional Medicine
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• v.8 no.1
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• pp.295-317
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• 1996

It is researched to elucidate the effects of Taeumjowuitang(TE,太陰調胃湯), Sibimikwanjungtang(SE, 十二味寬中湯) and Yangkeogsanwhatang(SY,凉膈散火湯) on the obesity induced by gold thioglucose and the differentiation and growth of preadipocyte 3T3-L1 in the mouse. The result were as follows: 1. TE,SE and SY extracts improved the blood level of transaminase in the obese mouse induced by gold thioglucose. 2. TE,SE and SY extracts inhibited the increase of liver fat and body fat in the obese mouse induced by gold thioglucose. 3. TE,SE and SY extracts inhibited the increase of body weight in the obese mouse induced by gold thioglucose. 4. TE,SE and SY extracts inhibited the growth of undifferentiate preadipocyte 3T3-L1. 5. TE,SE and SY extracts showed inhibitory effect on the differentiation of preadipocyte 3T3-L1. The above results suggest that the TE,SE and SY extracts may be used on the obesity induced by the overgrowth and differentiation of adipocyte, and the accumulation of fat in liver and body.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.5
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• pp.383-393
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• 2008

Purpose: Cancer specific killing can be achieved by therapeutic gene activated by cancer specific promotor. Expression of sodium iodide symporter (NIS) gene causes transportation and concentration of iodide into the cell, therefore radioiodine treatment after NIS gene transfer to cancer cell could be a form of radionuclide gene therapy. luciferase (Luc) gene transfected cancer cell can be monitored by in vivo optical imaging after D-luciferin injection. Aims of the study are to make vector with both therapeutic NIS gene driven by AFP promoter and reporter Luc gene driven by CMV promoter, to perform hepatocellular carcinoma specific radiodiodine gene therapy by the vector, and assessment of the therapy effect by optical imaging using luciferase expression. Materials and Methods: A Vector with AFP promoter driven NIS gene and CMV promoter driven Luc gene (AFP-NIS-CMV-Luc) was constructed. Liver cancer cell (HepG2, Huh-7) and non liver cancer cell (HCT-15) were transfected with the vector using liposome. Expression of the NIS gene at mRNA level was elucidated by RT-PCR. Radioiodide uptake, perchlorate blockade, and washout tests were performed and bioluminescence also measured by luminometer in these cells. In vitro clonogenic assay with 1-131 was performed. In vivo nuclear imaging was obtained with gamma camera after 1-131 intraperitoneal injection. Results: A Vector with AFP-NIS-CMV-Luc was constructed and successfully transfected into HepG2, Huh-7 and HCT-15 cells. HepG2 and Huh-7 cells with AFP-NIS-CMV-Luc gene showed higher iodide uptake than non transfected cells and the higher iodide uptake was totally blocked by addition of perchlorate. HCT-15 cell did not showed any change of iodide uptake by the gene transfection. Transfected cells had higher light output than control cells. In vitro clonogenic assay, transfected HepG2 and Huh-7 cells showed lower colony count than non transfected HepG2 and Huh-7 cells, but transfected HCT-15 cell did not showed any difference than non transfected HCT-15 cell. Number of Huh-7 cells with AFP-NIS-CMV-Luc gene transfection was positively correlated with radioidine accumulation and luciferase activity. In vivo nuclear imaging with 1-131 was successful in AFP-NIS-CMV-Luc gene transfected Huh-7 cell xenograft on nude mouse. Conclusion: A Vector with AFP promoter driven NIS and CMV promoter driven Luc gene was constructed. Transfection of the vector showed liver cancer cell specific enhancement of 1-131 cytotoxicity by AFP promoter, and the effect of the radioiodine therapy can be successfully assessed by non-invasive luminescence measurement.

• Korean Journal of Veterinary Service
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• v.22 no.4
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• pp.325-347
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• 1999

This study was conducted to investigate the epidemiological, clinicopathological, microbiological, pathological observations and other tests from sudden death in feedlot cattle at the region of Sarari in Korea during the period from 1994 to 1999. Massive or sporadic occurrence of sudden death has been observed in 101 heads of 47 farmhouse. There were 20.8% in spring, 29.7% in summer, 16.8% in autumn, 32.7% in winter, and 62.3% in reproductive, 27.7% in growing, 5.0% in beef cattle, 5.0% in calf in prevalence of sudden death in cattle. Enterotoxemia(88.0%), pneumonia(3.5%), intestinal diarrhea(3.5%), liver abscess(1.5%) and indigestion(1.5%) were detected from 67 heads of sudden death cattle. In clinical observations, cattle were generally died of sudden recumbency with convulsions followed anorexia, depression, ataxia, muscular tremor, tachycardia and dyspnea without any premonitory symptoms. Epidemiological surveys showed no evidence that other factors such as pesticide, insecticide, fertilizer, chemical drug3 and those of others caused sudden death. Macroscopically, there were coagulation disorders of blood, congestion, edema and haemorrhage of lung, congestion and haemorrhages, watery and blood-tinged contents of small intestine. Histopathologically, we observed pulmonary congestion and haemorrhage, necrotic intestinal mucosa accompanied with haemorrhage and congestion, and also increased globule leukocytes between bronchial epithelia with mild pneumonia. Clinicopathologically, only elevation of blood glucose and aspartate aminotransferase(AST) was detected. Magnesium and calcium deficiency were not detected, but parasites were detected highly in normal and dead cattles. Microbiologically, Clostridium(Cl) pefringens were detected from small intestinal contents of 94% (63/67) of sudden death cattle and 51%(51/101) of slaughter cattle, and the population were $10^{6-8}$/cfu/$m\ell$ after 16~32 hours. Consequently, it was proved that the cause of death in cattle was enterotoxemia. Pathogenic test of mouse and goat inoculated with Cl perfringens type A toxin has been demonstrated as similar observation to natural cases. In antimicrobial susceptibility test, ampicillin, bacitracin, polymycin, cephalothin, penicillin, choramphenicol, erythromycin, tetracycline were highly susceptible, and amikacin, gentamicin, kanamycin, neomycin, streptomycin, sulfamethoxine, sulfamethazine were resistant. Cl perfringens were resisted for 4 hours in 3% formalin, 20 minutes in 4% phenol, 20 minutes in 0.5% mercuric chloride and 40 minutes in 0.1% sodium hydroxide, respectively. The useful method to prevent from occurrance of enterotoxemia in feedlot cattle was a dietary administration of antibiotics and miyari acid.

• Journal of Ginseng Research
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• v.25 no.4
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• pp.150-155
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• 2001

This study examined effects of the active ingredients from ginseng on paraquat(PQ) toxitity. Mice were given PQ(25mg/kg, ip) and then they were given total saponins (TS; 5mg/kg, orally), protopanaxadiol (PD; 5mg/kg, orally) and protopanaxatriol(PT; 5mg/kg, orally) per day for periods of 1,3 & 7 days. We measured the activities of superoxide dismutase (SOD), electrophoretic isozyme band, catalase (CAT) were compared in the liver of mouse that dose with PQ and/or TS, PD and PT. The activities of SOD, CAT were generally higher in PQ+PD group than others groups. Especially the activity of SOD was the highest in PQ+PD group than others groups. SOD isozyme separated into three bands by electrophoresis. One band was located to near the anode side and two bands were cathode side. As the results of treated with KCN, we were confiremed that the Cu, Zn-SOD was located to near the anode side but the Mn-SOD were cathode side. Our results suggested that an antioxidant effect of ginseng saponins elevated a protection ability to an oxidative damage by direct action of SOD, CAT and reinforced the synthetic ability of endogenous antioxidant material in living organism. Particularly, PD was a effective antioxidant compared with others.

• Journal of Life Science
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• v.25 no.8
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• pp.849-860
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• 2015

The anti-cancer activities of Rhus verniciflua Stokes (GC), Ulmus davidiana var. japonica Nakai (UGP) and arsenium sublimatum (SS) extracts, which have been used Oriental medicine therapy for various diseases, were investigated. The treatment of GC, UGP and SS alone, and combined treatment with GC, UGP and SS did not affect the cell viability in the mouse normal cell lines (RAW 264.7 macrophages and C2C12 myoblasts). However, co-treatment with GC, UGP and SS markedly induces apoptosis in human gastric cancer AGS cells, but not in other various cancer cell lines (human lung cancer A549, colon cancer HCT116, liver cancer Hep3B and bladder T24 cells) as evidenced by formation of apoptotic bodies, chromatin condensation, and accumulation of annexin-V positive cells. Co-treatment with GC, UGP and SS effectively induced the expression levels of Fas and Fas ligand, and inhibited the levels IAP family proteins such as XIAP, cIAP-1 and survivin, and anti-apoptotic Bcl-xL proteins compared with treatment with either agent alone. Combined treatment also significantly induced the loss of mitochondrial membrane potential, which was associated with the activation of caspases (-3, -8, and -9) and degradation of poly (ADP-ribose) polymerase. However, the cytotoxic effects induced by co-treatment with GC, UGP and SS were significantly attenuated by pan-caspases inhibitor, z-VAD-fmk, indicating an important role for caspases. These results indicated that the caspases were key regulators of apoptosis in response to co-treatment of GC, UGP and SS in human gastric cancer AGS cells and further studies will be needed to identify the active compounds.

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.867-870
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• 2001

All-trans-retinoic acid (RA) plays essential roles in the regulation of differentiation and proliferation. It has been proved that RA is effective in the treatments of epithelial and hematologic malignancies. However, in spite of its pronounced effects, the clinical applications of RA are limited due to the retinoid acute resistance. Although RA induces complete remission in a high proportion of the patients of acute promyelocytic leukemia (APL), the cancer was relapsed in many patients after a brief remission in spite of a continued RA treatment. Patients who relapsed from remission that was initially induced by RA had clinically resistant to further RA treatment. That is, specific cytochrome P450 enzymes in the liver were induced by the continuous oral administration of RA, thereby accelerating the metabolism of RA. To overcome this problem, biodegradable microspheres were proposed by us, previously. And, several microsphere formulations for RA delivery have been prepared and studied on their effectiveness. Recently, poly(D,L-lactide) (PDLLA) microsphere formulation was optimized, And, from the animal studies by using a mouse and a rat, it have appeared to be effective on both the inhibition of tumor growth and chemoprevention of a carcinogenesis. In this study, subacute toxicities of the PDLLA microsphere formulation have been investigated as a preclinical test. For the test, the microspheres was injected subcutaneously into the back site of rats, and body weight change, clinical signs, hematological changes, blood biochemistry were evaluated. As a result, severe toxicities such as mortality were observed at the dose of 100mg RA/kg, and toxicities were not observed at the dose of 50mg RA/kg, which is the effective dose against carcinogenesis. Bone fracture, observed at several rats, might be inhibited by treating them with anti-inflammatory drugs.

• Korean Journal of Medicinal Crop Science
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• v.8 no.1
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• pp.1-8
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• 2000

Achillea sibirica Ledeb. is widely distributed in Korea and has been often used as folk medicine in peptic and tonic. As one of our searches for bioactive (anti oxidation) compounds from medicinal plants, we studied Achillea sibirica Ledeb. (Compositae). Antioxidant activity of Achillea sibirica was determined by measuring lipid peroxide produced when a mouse liver homogenate was exposed at $90^{\circ}C$ using 2-thiobarbituric acid (TBA) and by evaluation the radical scavenging activity on 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical. Whole parts of Achillea sibirica was extracted with methanol and its extracts was fractionated with organic solvent; n-Hexane, methylene chloride, ethyl acetate, n-Butanol. EtOAc fraction exhibited antioxidant activity and From its, two flavonoid glycosides were isolated by silica gel and gel filtration colume chromatography and identified to kampferol 3-O-glucoside and luteolin 7-O-neo-hesperidoside, respectively, by physico-chemical and spectroscopical method. At antioxidant activity test for two compounds isolated, antioxidant activity was showed too. And from hexane fraction sterol was is isolated and identificated to mixture of campesterol, stigmasterol, and ${\beta}-sitosterol$.

• Journal of Acupuncture Research
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• v.24 no.3
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• pp.145-161
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• 2007

Objectives : The purpose of this study is to investigate the effect of electroacupuncture at Joksanmi($ST_{36}$) on Rat's aging by experimental methods. Methods : The author performed several experimental procedures to observe the effects of the EC-HAS at the arthritis. First, I measured the cell survival rate of the mice lung fibroblasts. Second, the incidence rate of arthritis and arthritis index of CIA were analyzed. Third, the levels of IL-6, $INF-{\gamma}$ , $INF-{\alpha}$ , $IL-1{\beta}$, IgG, IgM and anti-collagen II were measured in serum and the level of $INF-{\gamma}$, $INF-{\gamma}$/IL-4 ratio in the CIA mouse spleen cell culture. Fourth, histological analysis of the mice joint was performed. Fifth, the expression ratio of $CD3e^+$ cells to $CD19^+$ cells, $CD4^+$ cells to $CD8^+$ cells, $CD11a^+CD19^+$ cells, $CD4^+CD25^+$ cells, $CD3^+CD69^+$ cells, and $CD11b^+Gr-1^+$ cells were checked. Results: 1. The hematocrit was meaningfully (p<0.01, p<0.05) decreased in $ST_{36}$ group in comparison with the control and sham group. 2. The glucose, ALP were meaningfully (p<0.05, p<0.05) decreased in $ST_{36}$ group in comparison with the control group. 3. In the activation of hepatic antioxidase, the catalase was meaningfully (p<0.01) increased in $ST_{36}$ group in comparison with the control group. 4. In the liver, the NO formation was meaningfully (p<0.001) decreased in $ST_{36}$ group in comparison with the nomal, control and sham group. 5. In the activation of splenetic antioxidase, the GSH was meaningfully (p<0.01) increased in $ST_{36}$ group in comparison with the sham group, and the catalase was meaningfully (p<0.001) increased in $ST_{36}$ group in comparison with the control group. 6. In the spleen, the MDA formation was meaningfully (p<0.01, p<0.05) decreased in $ST_{36}$ group in comparison with the control and sham group. 7. In the spleen cell culture, the levels of IL-6 was meaningfully (p<0.05) decreased in comparison with the sham group, $INF-{\gamma}$( was meaningfully (p<0.05) increased in comparison with the control group. Conclusions: According to the results, it is considered that electroacupuncture at Joksamni($ST_{36}$) is effective in increasing the activities of antioxidative enzyme and inhibiting lipid peroxides, and has an immunomodulatory reaction. In conclusion, it han an significant anti-aging effect and need more experimental study.

• The Korean Journal of Food And Nutrition
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• v.25 no.4
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• pp.770-778
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• 2012

In this study, the effects of intake of Acer mono Max. seed oil, and Magnolia denudata seed oil on the lipid levels of mouse blood were compared to those of commercially available vegetable oils. Five ICR mice were each fed a corn oil, Acer mono Max. seed oil, and Magnolia denudata seed oil supplemented diet for a total of 8 weeks. The serum profiles of mice fed Acer mono Max. seed oil and Magnolia denudata seed oil were high in palmitic acid, oleic acid, and linoleic acid. The saturated fatty acid contents of mice fed Acer mono Max. seed oil and Magnolia denudata seed oil were 3.95% and 0.88%, whereas the unsaturated fatty acid contents were 8.71% and 4.60%, respectively. The liver and spleen weights of mice fed Acer mono Max. seed oil were higher than those fed corn oil (p<0.05). Total cholesterol level was highest in mice fed Acer mono Max. seed oil (p<0.05), whereas there were no significant changes in the cholesterol levels of mice fed Magnolia denudata seed oil and corn oil. The HDL-cholesterol levels in mice fed Acer mono Max. seed oil ($175.80{\pm}27.66mg/d{\ell}$) and in those fed Magnolia denudata seed oil ($145.20{\pm}19.10mg/d{\ell}$) were higher compared to those of mice fed corn oil (p<0.05). In conclusion, there were no significant differences in fatty acid composition between mice fed Acer mono Max. seed oil and Magnolia denudata seed oil. Future study on the antioxidant effects of seed oils should be carried out.