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문은이(Eun Yi Moon),이진(Jin Lee),이원용(Won Yong Lee),최청하(Chung Ha Choi),이덕근(Dug Keun Lee),유제만(Jei Man Ryu),정용호(Yong Ho Chung),윤성준(Sung June Yoon),박경배(Kyung Bae Park) 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.3
DW-166HC (^(166)Holmium (^(166)Ho)-Chitosan complex) is a new radiopharmaceutic anticancer agent with a broad anti-tumorigenic spectrum, especially against human hepatic cancer. DW-166HC was evaluated for the appearance of micronucleus in polychromatic erythrocytes (PCEs) of mouse bone marrow cells after subcutaneous arid intravenous single administration. Bone marrow cells were prepared at 24 hr and 48 hr after DW-166HC-I (^(165)Ho-Chitosan complex : cold compound) administration and at 24 hr, 72 hr and 2 weeks after DW-166HC (^(166)Ho-Chitosan complex : hot compound) administration. The results showed there was no statistically significant increase of the numbers of PCEs with micronucleus in all DW-166HC-I administered groups compared with a negative control group but there was statistically significant increase of the numbers of PCEs with micronucleus at 24 hr arid 72 hr in all DW-166HC administered groups, which was recovered after 2 weeks from the drug administration. The results also showed the ratio of normochromatic erythrocytes (NCEs) to PCEs of all DW-166HC-I administered groups was not significantly different from that of a negative controi group but there was significant difference of this ratio at 24hr and 72 hr in all DW-166HC administered groups compared with that of negative group, which was also recovered after two weeks from the drug administration. These results suggested that DW-166HC-I may not cause any chromosomal damage but DW-166HC has in vivo mutagenic potential because of its radioactivity.
문은이(Eun Yi Moon),이진(Jin Lee),최정하(Chung Ha Choi),이치우(Chi Woo Lee),정용호(Yong Ho Chung),윤성준(Sung June Yoon),이덕근(Dug Keun Lee) 한국응용약물학회 1996 Biomolecules & Therapeutics(구 응용약물학회지) Vol.4 No.3
DW-116 {1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid hydrochloride} is a new quinolone antibiotic with a broad antibacterial spectrum against G(+) and G(-) bacteria. DW-116 was evaluated for the appearance of micronucleus in polychromatic erythrocytes (PCEs) of mouse bone marrow cells after intraperitoneal and oral single administration. We prepared the bone marrow cells at 30hr after drug administration and they were used for measuring PCE with micronucleus. The results showed there was no statistically significant increase in the numbers of PCEs with micronucleus in all DW-116 administered groups compared with a negative control group. The results also showed that the ratio of normochromatic erythrocytes(NCEs) to PCEs of all DW-l16 administered groups was not significantly different from that of a negative control group. These results suggested that DW-116 may not cause any chromosomal damage and it has no in vivo mutagenic potential under these experimental conditions.
문은이(Eun Yi Moon),최청하(Chung Ha Choi),성승규(Seung Kyoo Seong),이진(Jin Lee),유제만(Jei Man Ryu),이문선(Moon Sun Lee),정상헌(Sang Hun Jung),정용호(Yong Ho Chung),이덕근(Dug Keun Lee),윤성준(Sung June Yoon) 한국응용약물학회 1998 Biomolecules & Therapeutics(구 응용약물학회지) Vol.6 No.4
DW2282, (S)-(+)-4-phenyl-1-[N-(4-aminobenzoyl)-indolin-5-sulfonyl]-4,5-dihydro-2-imidazolone hydrochloride, is a novel anticancer agent thought to have an unique mechanism of action on the inhibition of tumor growth. In this study, we estimated in vivo antitumor activities and pharmacokinetics of DW2282 depending on various vehicles. The inhibition rate of tumor growth was increased by 50, 100 and 200 mg/kg of DW2282 in a dose-dependent manner. When DW2282 dissolved in 4 sorts of vehicles was orally single dosed to rats at 50 mg/kg, Cmax of DW2282 in 0.5% CMC.Na was a half as high as those in PG, PG+CP and PG+CP+DW. When DW2282 was orally administered to mice for 5 days, antitumor activity of 130 mg/kg suspended in 0.5% CMC.Na was as effective as that of 65 mg/kg dissolved in the rest of vehicles. Taken together, it is thought that antitumor activities of DW2282 are resulted from the absorption extent of it and related to the vehicle used.
이동권(Dong Kwon Rhee),문은이(Eun Yi Moon),표석능(Suhk Neung Pyo) 한국응용약물학회 1996 Biomolecules & Therapeutics(구 응용약물학회지) Vol.4 No.2
Aflatoxin B1 (AFB1) has been reported to directly suppress the immune responses. In the present study, the effect of AFB1 on immune functions was investigated. Splenic lymphocytes were treated with various doses of the mitogens (lipopolysaccharide, concanavalin A) in the presence of AFB1. AFB1 pretretment decreased the number of plague forming cells (PFC) in a dose-dependent manner. Antibody production of IgM and IgG class was significantly decreased in AFB1-treated splenic cells. In addition, when animals were exposed to AFB1, the susceptibility of bacterial infection as well as the growth of tumor cells was increased. These data suggest that AFB1 affected the immune function and humoral immunity impaired by AFB1 treatment contributed to pathological process.
마우스에서의 DW-166HC (Holmium-165-chitosan) 에 대한 급성독성
이원용(Won Yong Lee),이진(Jin Lee),문은이(Eun Yi Moon),남순철(Soon Chul Nam),이덕근(Dug Keun Lee),윤성준(Sung June Yoon) 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.1
DW-166HC (^(166)Holmium-chitosan) is a complex of ^(166)Ho, (β- and γ- ray emitter, and chitosan, a polymer of glucosamine, with radiotherapeutic potential. The current study was performed to determine the acute toxicities of ^(165)Ho-chitosan in mice by two different routes of administration. The both sex mice were given a single intravenous bolus injection of ^(165)Ho-chitosan complex at doses of 12, 10, 6, 5 and 4 mg/kg or subcutaneous administration at doses of 600, 500, 400 and 300 mg/kg. Chitosan was dosed to control animals as 16 and 800 mg/kg, intravenously and subcutaneously, respectively. The doses of ^(165)Ho-chitosan complex were expressed as ^(165)holmium nitrate pentahydrate and the ratio of ^(165)Ho(NO₃)₃, ·5H₂0 to chitosan was 3/4. Severe convulsion and respiratory failure were followed by death within 10 min after intravenous dosing. Transient unilateral hindlimb hypokinesias were found in two mice of 5 mg/kg dosing group during the study period. No abnormalities were observed during the necropsy of survived animals in intravenous dosing group. Only one male animal was found dead in 500 mg/kg subcutaneously dosed group. Alopecia with or without cutaneous ulcer were found in most mice including control animals. During necropsy, omental adhesion was observed in all dose ranges and enlarged spleen was found in several animals including control group. It is suggested that the acute intravenous LD_(50)s for male and female mice were 4.90 and 6.03 mg/kg, respectively. The lowest lethal dose in male was 500 mg/kg by subcutaneous administration.
대식세포에서 폐렴구균 협막 다당류에 의한 TNF-α 및 Nitric Oxide 생성
엄성희(Sung Hee Um),엄진섭(Jin Sub Um),인상환(Sang Hwan In),문은이(Eun Yi Moon),이동권(Dong Kwon Rhee),표석능(Suhk Neung Pyo) 한국응용약물학회 1998 Biomolecules & Therapeutics(구 응용약물학회지) Vol.6 No.1
Capsular polysaccharides (CPs) from Streptococcus pneumoniae were examined for the ability to induce secrefory responses in a pure population of peritoneal macrophages. The highly purified CPs were able to affect the macrophage, ie, secretion of tumor necrosis factor-alpha(TNF-α) and nitrite. As after stimulation with CPs, secretion of TNF-αinduced by these CPs reached its maximum within the first few hours of the interaction, while secretion of nitrite was increased with time. In addition, production of TNF-αand nitrite was increased in a dose-dependent manner. In the presence of indomethacin, CP-stimulated TNF-αproduction was not altered. In contrast, LPS with indomethacin stimulated 24.5% more TNF-αthan LPS alone, suggesting that the intracellular signaling processes for TNF production are differentially stimulated by CP and LPS. The results demonstrate that CPs are potent inducer of macrophage secretory activities.
문은이,이동권,표석능 성균관대학교 약학연구소 1996 成均藥硏論文集 Vol.8 No.1
Aflatoxin B1 (AFB1) has been reported to directly suppress the immune responses. In the present study, the effect of AFB1 on immune functions was investigated. Splenic lymphocytes were treated with various doses of the mitogens (lipopolysaccharide, concanavalin A) in the presence of AFB1. AFB1 pretretment decreased the number of plaque forming cells (PFC) in a dose-dependent manner. Antibody production of IgM and IgG class was significantly decreased in AFB1-treated splenic cells. In addition, when animals were exposed to AFB1, the susceptibility of bacterial infection as well as the growth of tumor cells was increased. These data suggest that AFB1 affected the immune function and humoral immunity impaired by AFB1 treatment contributed to pathological process.