• Proceedings of the Korean Society of Life Science Conference
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• 2003.10a
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• pp.133-133
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• 2003

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.197-205
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• 1991

Local extravasation during intravenous administration of adriamycin (doxorubicin HCl) can cause severe skin ulceration and necrosis. To investigate the mechanism of adriamycin-induced skin toxicity, effects of adriamycin on reactive oxygen radical metabolism using cultured skin cells of fetal rat. Adriamycin produced significant release of lactic dehydrogenase from cultured skin cell preparations dose- and time-dependently. The production of superoxide anion in sonicated suspensions of cultured skin cells was significantly increased by adriamycin under the presence of NADPH and NADH. The drug also stimulated malondialdehyde (MDA) production, an index of lipid peroxidation, in NADPH- and NADH-supported cell preparations. The increased production of MDA was significantly inhibited by oxygen radical scavengers (superoxide dismutase, catalase, thiourea) and antioxidants (butylated hydroxytoluene, ${\alpha}-tocopherol$). Treatment of cultured skin cells with 1, 3,-bis (2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of glutathione reductase, enhanced the lipid peroxidation induced by adriamycin. The present study suggests that lipid peroxidation which is resulted from the stimulated production of reactive oxygen radical causes cellular damage in adriamycin-treated skin cells of rat.

• Archives of Pharmacal Research
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• v.20 no.4
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• pp.379-383
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• 1997

Cyclosporin A, an potent immunosuppressant, has been known to be one of the modulators of drug resistance as well as a cytostatic drug. Despite many attempts to basic or clinical application of cyclosporin A, there are few reports on the inhibition of brain tumor cells. In the present experiment, the possibility of cyclosporin A as synergic adjuvant was investigated by MTT assay, $[^{3}H]$ thymidine uptake and through flowcytometric anaysis. Sole treatment of cyclosporin A on the CRT and CH235-MG glioma cell line revealed dose dependent cytotoxicity within a range of tested dose. Combined treatment of cyclosporin A with ACNU, BCNU and hydroxyurea on various glioma cancer cell line led to a significant synergistic cytotoxicity as well as inhibition of DNA synthesis with dose-dependency. In addition, cyclosporin A alone or combined treatment caused discernible changes of cell cycle in the tested cells. These data provide that cyclosporin A could potentiate the effect of nitrosourea compounds in vitro on human glioma cells.

• Radiation Oncology Journal
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• v.7 no.1
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• pp.23-27
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• 1989

Forty-four patients with brain astrocytoma and glioblastoma were rested with surgical resection and postoperative radiation from January 1980 through May 1987, Four patients were lost to follow up, and in 40 patients survival time was evaluable. Three year actuarial survival rate was $66.7\%$ in Grade I and II astrocytoma, $30\%$ in Grade III, and $20.4\%$ in glioblastoma multiforme patients. The prognostic factors affecting survival rate were histologic grade in all cases, age, and total radiation dose in Grade III and glioblastoma.

• Archives of Pharmacal Research
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• v.6 no.2
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• pp.115-121
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• 1983

Cholesteryl p-[3-(2-chloroethyl_-3-nitrosoureido] phenylthioaccetate (2) was synthesized : an intermediate, p-[3(2-chloroethyl_-3-nitrosoureido] phenylthioacetic acid (1) is a congener of an antitumor chlorambucil which both the -CH$_{2}$CH$_{2}$-linkage and -N(CH$_{2}$CH$_{2}$Cl)$_{2}$ group of chlorambucil molecule is doubly modified into the respective -S-linkage and -NH-CO-NNO-CH$_{2}$CH$_{2}$CL group. The attackment of cholesterol moiety as a carrier group to p-[3-(2-chloroethyl-3nitrosoureido] phenylthioacetic acid was accomplished through the esterification of cholesterol with p-[3-(2-chloroethyl-3-nitrosoureido] phenylthioacetyl chloride which was obtained from the treatment of p-[3-(2-chloroethyl)-3-nitrosourei-do] phenylthioaceticacid with SOCL$_{2}$, p-[3-(2-chloroethyl)ureido]]-phenythioacetic acid was nitrosated with NaNO$_{2}$ IN 98-100% HCOOH to give exclusively p-[3-(2-chloroethyl_-3-nitrosoureido] phenylthioacetic acid. Antitumor evaluation of compounds, 1 and 2 on L 1210 leukemia did show significant activity (ED$_{40}$ : 1.14.mu./ml and 8.4.mu.g/ml, repectively). Further studies were subjected..

• Korean Journal of Pharmacognosy
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• v.18 no.2
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• pp.127-135
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• 1987

In vitro sensitivity testing was performed for 21 kinds putative anticancer drugs selected from references and information. Cellular damage of P815 mastocytoma cells following exposure to water extracts of drugs was evaluated by colony formation assay. Highly effective drugs with more than 50% inhibition of colony formation were seven (Houttuyniae Herba, Sanguisorbae Radix, Nepetae Herba, Manitis Squama, Lonicerae Flos, Amomi Semen, Polyporus), though not more effective than BCNU. According to the results of $^3H-thymidine$ incorporation assay for determination of selective cytotoxicity, 3 of these drugs (Houttuyniae Herba, Polyporus, Manitis Squama) were found to be low cytotoxic to normal mouse lymphoid cells. These findings suggest that the above 3 drugs may be used for effective anticancer drugs in vivo.

• Macromolecular Research
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• v.11 no.4
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• pp.207-223
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• 2003

For last five years, we are developing the novel local drug delivery devices using biodegradable polymers, especially polylactide (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) due to its relatively good biocompatibility, easily controlled biodegradability, good processability and only FDA approved synthetic degradable polymers. The relationship between various kinds of drug [water soluble small molecule drugs: gentamicin sulfate (GS), fentanyl citrate (FC), BCNU, azidothymidine (AZT), pamidronate (ADP), $1,25(OH)_2$ vitamin $D_3$, water insoluble small molecule drugs: fentanyl, ipriflavone (IP) and nifedipine, and water soluble large peptide molecule drug: nerve growth factor (NGF), and Japanese encephalitis virus (JEV)], different types of geometrical devices [microspheres (MSs), microcapsule, nanoparticle, wafers, pellet, beads, multiple-layered beads, implants, fiber, scaffolds, and films], and pharmacological activity are proposed and discussed for the application of pharmaceutics and tissue engineering. Also, local drug delivery devices proposed in this work are introduced in view of preparation method, drug release behavior, biocompatibility, pharmacological effect, and animal studies. In conclusion, we can control the drug release profiles varying with the preparation, formulation and geometrical parameters. Moreover, any types of drug were successfully applicable to achieve linear sustained release from short period ($1{\sim}3$ days) to long period (over 2 months). It is very important to design a suitable formulation for the wanting period of bioactive molecules loaded in biodegradable polymers for the local delivery of drug. The drug release is affected by many factors such as hydrophilicity of drug, electric charge of drug, drug loading amount, polymer molecular weight, the monomer composition, the size of implants, the applied fabrication techniques, and so on. It is well known that the commercialization of new drug needs a lot of cost of money (average: over 10 million US dollar per one drug) and time (average: above 9 years) whereas the development of DDS and high effective generic drug might be need relatively low investment with a short time period. Also, one core technology of DDS can be applicable to many drugs for the market needs. From these reasons, the DDS research on potent generic drugs might be suitable for less risk and high return.