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Inhibition of Human Malignant Glioma Growth in Vivo by Human Recombinant Plasminogen Kringles 1-3
Joe, Young-Ae,Hong, Yong-Kil,Chung, Dong-Sup,Yang, Youn-Joo,Kang, Joon-Ki,Lee, Youn-Soo,Chang, Soo-Ik,You, Weon-Kyoo,Lee, Hyo-sil,Chung, Soo-Il 가톨릭대학교 2000 Bulletin of The Catholic Research Institutes of Me Vol.28 No.-
Human malignant gliomas are highly vascularized and aggressive tumors. Aniogenesis inhibitors have been shown to induce regression of a variety of primary and metastatic-tumors in vivo. However, their usefulness in treating brain tumors is not well understood. Aniostatin, a multiple krinlge (1-4 of 5)-containing fragment of plasminogen, is one of the highly effective natural cryptic angiogenesis inhibitors. In our study, the therapeutic efficacy of non-glycosylated and small molecular size recombinant kringles 1-3 (rPK1-3) was examined in the treatment of brain tumors generated by stereotactic intracerebral implantation of U-87 human glioma cells in nude mice. Mice bearing tumors 7 days post-implant were treated daily with rPK1-3 (100 mg/kg) s.c. for 21 days. Treated animals showed suppressed brain tumor growth by greater that 71.2% along with a 3-fold increase of apoptotic index and suppressed vascularization by 78.9%, without any observable signs of toxicity. Analysis of bFGF and VEGF expression in the tumors of treated animals using immunohistochemical methods showed near complete absence of growth factors. Our results indicate that the non-glycosylated, small molecular size rPK1-3 is an efficient tumoristatic agent for the treatment of intracranial human glioma xenografts in mice and might provide new strategies for the treatment of brain tumors. (International Journal of Cancer 82:694-699, 1999)
Isolation and Characterization of Plasmids from Streptomyces
Joe, Young Ae,Goo, Yang Mo 한국미생물 · 생명공학회 1994 Journal of microbiology and biotechnology Vol.4 No.4
Streptomyces spp. purchased from American Type Culture Collection and Institute for Fermentation in Osaka, and donated from Northern Regional Research Laboratory, and those isolated from soil samples were assayed to isolate many plasmids harboring streptomycetes. Among these organisms, 5 small size-plasmid carrying organisms SNUS 8810-597A, 8810-600, 8810-754, 8811-344, and 8811-347 were characterized and their plasmids pSJ597, pSJ600, pSJ754, pSJ344, and pSJ347 were isolated in a large scale. The plasmid harboring organisms were sensitive to neomycin, kanamycin, gentamicin, and thiostreptone, but some of them showed weak or strong resistance against streptomycin, chloramphenicol, ampicillin, and tetracycline. It was confirmed that pSJ597 and pSJ600 do not carry antibiotic biosynthetic genes. pSJ600 showed a pock-forming character.
Joe, Young-Ae,Goo, Yang-Mo,Lee, Youn-Young The Pharmaceutical Society of Korea 1989 Archives of Pharmacal Research Vol.12 No.2
Oxidation of isophorone by various fungi was examined. Aspergillus niger oxidized isophorone to 4-hydroxyisophorone, 3-hydroxymethyl-5,5-dimethyl-2-cyclohexen-1-one and 5-hydroxymethyl-3,5-dimethyl-2-cyclohexen-1-one. 4-Oxoisophorone obtained by chromic acid oxidation of 4-hydroxyisophorone was transformed to 2,3,5-trimethyl-p-benzoquinone by acid treatment.
( Young Ae Joe ),( Hyun Sun Lee ),( Eun Ju O ),( Kwang Sei Kim ) 한국응용약물학회 2010 Biomolecules & Therapeutics(구 응용약물학회지) Vol.18 No.4
Bone marrow-derived mesenchymal stem cells (BM-MSC) are a multipotent cell population that can differentiate into neuron-like cells. Previously it has been reported that murine BM-MSC can differentiate into neuron-like cells by co-treatment with a Rho-associated kinase (ROCK) inhibitor -Y27632 and CoCl2. In this study, we compared several ROCK inhibitors for the ability to induce human BM-MSCs to differentiate into neuron-like cells in the presence of CoCl2. Y27632 with high specificity for ROCK at 1-30 μM was best at inducing neuronal differentiation of MSCs. Compared to HA1077 and H1152, which also effectively induced morphological change into neuron-like cells, Y27632 showed less toxicity even at 100 μM, and resulted in longer multiple branching processes at a wide range of concentrations at 6 h and 72 h post-induction. H89, however, which has less specificity by inhibition of protein kinase A, S6 kinase 1 and MSK1 with similar or greater potency, was less effective at inducing neuronal differentiation of MSCs. Simvastatin, which can inhibit Rho, Ras, and Rac by blocking the synthesis of isoprenoid intermediates, showed little activity for inducing morphological changes of MSCs into neuron-like cells. Accordingly, the expression patterns for neuronal cell markers,including β-tubulin III, neuron-specific enolase, neurofilament, and microtubule-associated protein, were consistent with the pattern of the morphological changes. The data suggest that the ROCK inhibitors with higher specificity are more effective at inducing neuronal differentiation of MSCs.
Antiangiogenic and Antitumor Activities of the Cryptic Fragments with Kringle Architecture
( Young Ae Joe ),( Myung Rae Kim ),( Byoung Shik Shim ),( Dae Shik Oh ),( Sung Hee Hong ),( Yong Kil Hong ) 한국응용약물학회 2003 Biomolecules & Therapeutics(구 응용약물학회지) Vol.11 No.4
N/A Various angiogenesis inhibitors target vascular endothelid cells and block tumor angiogenesis. Angiostartin is a specific endogenous angiogenesis inhibitor in clinical trials, which contains only the first four triple loop structures, known as kringle domains. Its generated by proteolytic cleavage of its parent molecule plasminogen, which itself does not exhibit anti-angiogenic activity. Kringle domains from prothrombin, apolipoprotein, hepatocyte growth factor, urokinase and tissue-type plasminogen activator also elicit anti-angiogenic or antitumor activities in several model systems, albeit low amino acid sequence identity between angiostatin and each individual kringle. However, the differential effects of each kringle domain on endothelial cell proliferation, and migration observed in these kringle domains, suggest that the amino acid sequence of the primary structure is still important although kringle architecture is essential for anti-angiogenic activity. If it is further studied as to how amino acid sequence and kringle architecture contributes in anti-angiogenic activity, with studies on underlying mechanisms of anti-angiogenesis by kringle-based angiogenesis inhibitors, it will provide basis for the development of new potent anti-angiogenesis inhibitors and improvement of the efficacy of angiogenesis inhibitors.
Structural Features of Endostatin Required for Angiogenesis Inhibition
Joe, Young Ae 가톨릭 의과학연구원 1999 가톨릭 의과학연구원 국제학술대회 Vol.3 No.-
In the adult mammal, new blood vessels are formed by angiogenesis, the sprouting of new capillaries from existing vasculature (Bussolino et al., 1997; Risau, 1997).
Kanamycin Acetyltransferase Gene from Kanamycin-producing Streptomyces kanamyceticus IFO 13414
Joe, Young-Ae,Goo, Yang-Mo The Pharmaceutical Society of Korea 1998 Archives of Pharmacal Research Vol.21 No.4
A kanamycin producer, Streptomyces kanamyceticus IFO 13414 is highly resistant to kanamycin. Cloning of the kanamycin resistance genes in S. lividans 1326 with pIJ702 gave several kanamycin resistant transformants. Two transformants, S. lividans SNUS 90041 and S. lividan. SNUS 91051 showed similar resistance patterns to various aminoglycoside antibiotics. Gene mapping experiments revealed that plasmids pSJ5030 and pSJ2131 isolated from the transformants have common resistant gene fragments. Subcloning of pSJ5030 gave a 1.8 Kb gene fragment which showed resistance to kanamycin. Cell free extracts of S. lividans SNUS 90041, S. lividans SNUS 91051 and subclone a S. lividans SNUS 91064 showed kanamycin acetyltransferase activity. The detailed gene map is included.