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In Vivo Antitumor Efficacy of Cw252053, A Folate-based Thymidylate Synthase Inhibitor

  • Oh, Se-Woong;Ha, Jong-Ryul;Baek, Du-Jong
    • Archives of Pharmacal Research
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    • v.24 no.4
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    • pp.323-326
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    • 2001
  • Previous studies have demonstrated that CW252053, a quinazoline antifolate, exhibits potent inhibitory activity against thymidylate synthase (TS) as well as cytotoxic activity against tumor cell lines in vitro. In this studys, we evaluated the in vivo antitumor efficacy of CW252053 in the mouse tumor model. Female B6D2F$_1$ mice were injected with LY3.7. 2C TK-/- (thymidine kinase deficient mouse Iymphoma) cells into the gastrocnemius muscle. Then, CW252053 was administered twice daily by intraperitoneal injection for 10 days, and tumor growth was monitored daily by leg diameter measurement. All animals in the vehicle, 5-FU, and low dose (30mgmg/kg CW252053 treated groups died between days 12 and 23 because of the tumor burden. In contrast, dosing with 60 mg/kg of CW252053 produced a cure rat against tumor growth of 37.5% and a survival rate of 50%. Even more significantly, a higher dose of CW252053 (120 mg/kg) elicited both a 100% cure rate and a 100% survival rate at the termination of the study, confirming that this compound has very potent in vivo antitumor activity against tumor growth. During the experimental period of this study no signs of toxicity were observed even at the high CW252053 dosage rate of 120 mg/kg.

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The Ecology Tetranychus viennensis Zacher and its Chemical Control Effects (벚나무응애의 생태적 특성 및 약제방제효과)

  • 최경희;권용정;이순원;류언하
    • Korean journal of applied entomology
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    • v.36 no.1
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    • pp.111-117
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    • 1997
  • Occurrence status of Tetranychus viennensis Zacher was investigated in Kyonghuk province. Its ecological studies were carried out and chemical control efficacy against females and eggs was examined. And the results ohtained are as follows. T. viennensis occurred from mid April through mid November with the peak time in June on cherry tree. Population level of T. viennensis was varied from 0 to 160 individuals per 100 peach leaves in different peach orchards, and its occurrence rate was 35% out of 20 ochards. However no T. viennensis was observed from 25 apple orchards in 5 districts of Kyongbuk province. Overwintering stage of T. viennensis females appeared in mid October, and most of them moved into under the rough hark in early November. The overwintered adult females moved out from the rough bark to leaves in early April. Mortality during overwintering was about 55%. Under four constant temperatures of 16, 19, 22, 25$^{\circ}$C. egg periods were 14. 3, 9.2, 6.8, and 4.0 days ; larva -nymph periods were 20.2, 13.9, 8.7, and 6.6 days. Female longevity was 67. 7, 60.7, 46.4, and 34.0 days : mean tota: fecundities per female were 21.2, 44.3, 54.4, and 64.7 eggs. Some acaricides, azocyclotin, pyridaben, propargite, tehufenpyrad and fenpyroximate were highly effective against females, while hexythiazox and clofentezine showed very low control effect from 3.6 to 14.4%. Whereas, all of 7 acaricides tested highly effective against the eggs.

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CoMFA and CoMSIA Analysis on the Selective Fungicidal Activity of N-phenyl-D-phenylthionocarbamate Analogues against Resistant and Sensitive Gray Mold (Botrytis cinerea) (저항성 및 감수성 잿빛곰팡이병균(Botrytis cinerea)에 대한 N-Phenyl-O-phenylthionocarbamate 유도체들의 선택적인 살균활성에 관한 CoMFA 및 CoMSIA 분석)

  • Soung, Min-Gyu;Sung, Nack-Do
    • The Korean Journal of Pesticide Science
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    • v.11 no.3
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    • pp.138-143
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    • 2007
  • The relationships between three dimensional quantitative structure and activity relationships (3D-QSARs) for the selective fungicidal function between N-phenyl substituents of N-phenyl-O-phenyl-thionocarbamate derivatives analogues and their the fungicidal activities against resistant (RBC) and sensitive (SBC) gray mold (Botrytis cinerea) were studied quantitatively using CoMFA and CoMSIA methods. The statistical values of optimized CoMSIA (M7) model were better ($r^2$ & $q^2=CoMSIA{\gg}CoMFA$) than that of CoMFA (M5) model. And the factor influencing of the selective between the fungicidal activity against RBC and SBC was dependent on electrostatic field of CoMFA (M5) model. Therefore, it is predicted that, from the CoMSIA contour maps of CoMSIA (M7) model, the selectivity will be improved by the H-bond donor that is with negatively charged favored group at meta-position on the N-phenyl ring.

Active Immunization Study of Colon Cancer Derived 1-8D Peptide in HHD Mice

  • Jung, Hun-Soon;Ahn, In-Sook;Do, Hyung-Ki;Lemonnier, Francois A.;Song, Kuk-Hyun;Do, Myoung-Sool
    • IMMUNE NETWORK
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    • v.5 no.3
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    • pp.157-162
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    • 2005
  • Background: 1-8D gene is a member of human 1-8 interferon inducible gene family and was shown to be overexpressed in fresh colon cancer tissues. Three peptides 1-6, 3-5 and 3-7 derived from human 1-8D gene were shown to have immunogenicity against colon cancer. Methods: To study tumor immunotherapy, of three peptides we established an active immunization model using HHD mice. $D^{b-/-}{\times}{\beta}2$ microglobulin $({\beta}2m)$ null mice transgenic for a chimeric HLA-$A2.1/D^{b-}\;{\beta}2m$ single chain (HHD mice) were challenged with B16/HHD/1-8D tumor cells and were immunized with irradiated peptide-loaded RMA- S/HHD/B7.1 transfectants. In therapy model tumor growth was retarded in HHD mice that were injected with 3-5 peptide-loaded RMA-S/HHD/B7.1. In survival test vaccination with 1-8D-derived peptide protects HHD mice from tumor progression after tumor challenge. Results: These studies show that peptide 3-5 derived from 1-8D gene can be the most effective candidate for the vaccine of immunotherapy against colon cancer and highlight 1-8D gene as putative colon carcinoma associated antigens. Conclusion: We demonstrated that RMA-S/HHD/ B7.1 loaded with 1-8D peptides, especially 3-5, immunization generates potent antitumor immunity against tumor cells in HHD mice and designed active immunization as proper immunotherapeutic protocols.

Development of New Quinolone Antibacterials with Dextran-bond (Dextran에 결합된 새로운 Quinolone계 항균제의 개발)

  • Kim, Sun-Il;Na, Jae-Woon
    • Applied Chemistry for Engineering
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    • v.5 no.3
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    • pp.501-508
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    • 1994
  • 1-Ethyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazinyl)quinolinea-3-car-boxylic acid-dextran was synthesized by the reaction of 1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazinyl )quinoline-3-acryloyl chloride with dextran. Polymeric drug was tested for antimicrobial activity in vitro against ten species of microorganisms. Polymeric drug revealed good antibacterial activity against Bacillus subtillis ATCC 6633, Staphyloccus aureus ATCC 25923, Mycrobactertum phlei IFO 3158, Salmonella typhimurium KCTC 1925, Escherichia coli KCTC 1039, Escherichia coli ESS, Klebsiella puemouiae KCTC 1560 and Pseudomonas aeruginosa IFO 13130. Polymeric drug have no antimicrobial against Candida albicans ATCC 10231, but moderately active Micrococcus luteus ATCC 9341.

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Algicidal Activity of a Dibenzofuran-Degrader Rhodococcus sp.

  • Wang, Meng-Hui;Peng, Peng;Liu, Yu-Mei;Jia, Rui-Bao;Li, Li
    • Journal of Microbiology and Biotechnology
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    • v.23 no.2
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    • pp.260-266
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    • 2013
  • Rhodococcus sp. strain p52, a previously isolated dibenzofuran degrader, could effectively inhibit the growth of cyanobacteria, including species of Microcystis, Anabaena, and Nodularia. When strain p52 was inoculated at the concentration of $7.7{\times}10^7$ CFU/ml, 93.5% of exponentially growing Microcystis aeruginosa ($7.3{\times}10^6$ cells/ml initially) was inhibited after 4 day. The threshold concentration for its algicidal activity against M. aeruginosa was $7.7{\times}10^6$ CFU/ml. Strain p52 exerted algicidal effect by synthesizing extracellular substances, which were identified as trans-3-indoleacrylic acid, DL-pipecolic acid, and L-pyroglutamic acid. The effective concentrations of trans-3-indoleacrylic acid and DL-pipecolic acid against M. aeruginosa were tested to be 0.5 mg/l and 5 mg/l, respectively.

Antimicrobial Effect of Ethanol Extracts of Quercus spp. against Foodborne Pathogens (병원성 식중독 미생물에 대한 참나무과 식물 부위별 에탄올 추출물의 항균효과)

  • 윤재원;유미영;박부길;이명구;오덕환
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.3
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    • pp.463-468
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    • 2004
  • This study was conducted to determine the antimicrobial effect of leaf, bark and xylem of 6 kinds of Quercus spp. against food borne disease bacteria. All of the samples tested showed the antimicrobial effect against food borne disease bacteria. Bacillus cereus, Listeria monocytogenes, and Staphylococcus aureus was more sensitive than gram negative bacteria such as Salmonella typhimurium and Escerichia coli O157:H7, but no antimicrobial activity was observed against yeast and molds. Based on antimicrobial activity for kinds of Quercus spp., the antimicrobial activities of Quercus aliena Blume, Quercus mongolica Fisch, and Quercus dentata Thunb were stronger than those of Quercus variebilis Blume, Quercus serrata Thunb, and Quercus acutissima Carruth. In the meantime, the ethanol extract of Quercus spp. leaves showed the strongest antimicrobial activity compared to that of bark and xylem. Especially, the ethanol extract of Quercus aliena Blume leaf showed the strongest antimicrobial effect against foodborne disease bacteria among 6 kinds of Quercus spp.

Studies on the production and characterization of monoclonal antibodies against bovine rotaviruses isolated in Korea (소 로타바이러스(국내분리주)에 대한 단크론항체 생산 및 특성에 관한 연구)

  • Ahn, Jae-moon;Cho, Sun-hee;Kang, Shien-young
    • Korean Journal of Veterinary Research
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    • v.36 no.2
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    • pp.395-403
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    • 1996
  • Monoclonal antibodies(MAbs) against field isolates of the bovine rotavirus A strain(G6), V strain(G10) and reference I-801 strain(G8) were produced and characterized. Six MAbs(4C2, 4D9, 5E1, 5E7, 5D5, 3E4) against A strain had neutralizing activity and reacted only with the G6 bovine rotaviruses determined by fluorescence focus neutralization (FFN) test. Otherwise, five neutralizing MAbs(1G2, 2G6, 5E2, 5E12, 5H7) against I-801 strain neutralized the G6 and G8 bovine rotaviruses. Five non-neutralizing MAbs(5F12, 7F12, 5E11, 2A11, 2B12) were VP6-specific and cross-reacted with all bovine and porcine rotaviruses examined by fluorescence antibody(FA) test. None of the MAbs reacted with bovie viral diarrhea virus(BVDV) and bovine coronavirus(BCV) determined by FA and FFN test.

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Studies on the immunization against field strain after live Newcastle disease virus vaccination (뉴캣슬병 생독백신 접종 후 야외 분리 바이러스에 대한 면역성 조사)

  • 김순태;박인화;김성국;김영환;조광현;손재권
    • Korean Journal of Veterinary Service
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    • v.24 no.2
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    • pp.147-159
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    • 2001
  • This Study was conducted to determine vaccination programs for the control of Newcastle Disease(ND) in chickens and investigate protective effect against Newcastle disease virus (NDV) after live ND vaccination. Maternal HI antibody titer level of chickens according to day(age) 1, 7, 14, 21, 28 and 35 were decreased gradually as 7.10$\pm$0.74, 6.57$\pm$0.74, 3.71$\pm$1.25, 2.20$\pm$1.03, 1.20$\pm$1.23 and 0.50$\pm$0.71. As a result of HI test and ELISA, both chickens vaccinated with VG/GA strain live vaccine at 1-day-old and chickens not vaccinated do not have antibody titer for protection against NDV at 14-day-old. Except for LaSota strain vaccine, in case of vaccination with VG/GA spray and VG/GA, B1 and LaSota strain drinking water at 14-day-old, the protective effect was 100% in chickens inoculated NDV($10^{7.2}$ $EID_{50}$/50${\mu}\ell$, eye drop) at 21-day-old, but not 10~50% at 28-day-old. These data suggest that live NDV vaccination should be given at 10-day-old 20-25day-old for protect against NDV at periodic outbreaks of ND caused by velogenic viscerotropic NDV in the environment of a farm.

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Chemical Constituents from the Leaf and Twig of Acer okamotoanum Nakai and their Cytotoxicity

  • Jin, Wen-Yi;Min, Byung-Sun;Youn, Ui-Jung;Hung, Tran-Manh;Song, Kyung-Sik;Seong, Yeon-Hee;Bae, Ki-Hwan
    • Korean Journal of Medicinal Crop Science
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    • v.14 no.2
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    • pp.77-81
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    • 2006
  • As a result of cytotoxic compounds against cancer cell lines from natural sources, senven compounds were isolated from the leaf and twig of Acer okamotoanum Nakai. The compounds (1-7) were identified as ethyl gallate (1), methyl gallate (2), gallic acid (3), trans $resveratrol-3-O-{\beta}-D-glucopyranoside$ (4), acertannin (5), nikoenoside (6), and fraxin (7) by physicochemical and spectroscopic data (including mp, UV, IR, MS, $^1H-NMR,\;^{13}C-NMR$, DEPT, and HMBC) in comparison with those of published papers. All the compounds were tested for their cytotoxic activity against L1210, HL-60, K562, and B16F10 cancer cell lines in vitro by MTT assay method. Compounds 1-3 and 5 showed cytotoxic activity against all tested cell lines with $IC_{50}$ values ranged from 12.5 to $72.2\;{\mu}M$. Of the compounds, methyl gallate (2) exhibited the most potent cytotoxic activity against L1210, HL-60, K562, and B16F10 tumor cells with $IC_{50}$ values of 12.5, 48.3, 22.8, and $22.8\;{\mu}M$, respectively. Other compounds did not show any cytotoxic activity against four cancer cell lines.