• 생약학회지
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• 제22권3호
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• pp.197-206
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• 1991

The water extract of Gamisamryungbaekchool-San increased the lifespan of mice implanted intraperitoneally with sarcoma 180. Significant depression of lethal toxicity of cis-platin $(45{\mu}M/kg,\;s.c)$ and renal toxicity (indicated by an increase in blood urea nitrogen value and creatinine value) of cis-platin $(35{\mu}M/kg,\;s.c)$ were observed in mice and rats treated with Gamisamryungbaekchool-San. RBC and WBC were significantly decreased in rats treated with cis-platin, and significant depression of hematologic toxicities of cis-platin $(35{\mu}M/kg,\;s.c)$ in rats treated with Gamisamryungbaekchool-San. After all, alleviative effect of the side actions of cis-platin was acknowledged by combined usage of Gamisamryungbaekchool-San and cis-platin.

• Applied Microscopy
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• 제30권1호
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• pp.45-59
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• 2000

항암제로 널리 사용되는 cis-platin은 백금(platinum) 원소에 염소기와 암모니아기가 수평면의 cis-위치에 결합되어 있는 금속화합물이다. Cis-platin은 인체의 종양에 상당한 항암효과가 있어 악성 난소종양, 두경부의 악성상피종양, 방광암 및 자궁경부암에 효과가 있다고 알려져 있으나 이 약제는 세포의 DNA합성을 억제하는 기능이 이미 밝혀져 있다. 저자는 cis-platin을 가임기의 여성에 투여되었을 때 난관상피 세포를 구성하는 섬모세포의 섬모형성에도 필연적으로 손상 및 억제적인 작용이 있을 것으로 생각되어 섬모의 주요 구성분인 미세소관의 $\alpha-tubulin$과 cis-platin과의 관계를 추구하고자 하였다. 실험동물로는 건강한 체중 $150\sim200gm$의 자성흰쥐를 사용하였으며 estradiol benzoate를 4일간 매일 투여함으로써 섬모세포를 난관내에서 지속적인 활성을 유지시킨 뒤 cis-platin을 실험군의 복강내로 주사한 후 1일, 3일, 5일 및 7일 경과시에 각각 실험동물의 난관에서 상피세포내 $\alpha-tubulin$의 발현을 관찰하기 위해 mouse antirat $\alpha-tubulin$ monoclonal antibody와 2차 항체로 bio-tinylated goat anti-rat IgG를 각각 사용하여 면역조직 화학법을 시행한 후 광학현미경으로 관찰하였다. 또 일부조직은 전자현미경 조직절편을 제작하여 1차 항체로 mouse anti rat $\alpha-tubulin$ monoclonal antibody와 2차 항체로 직경 15nm의 금과립을 결합시킨 goat anti-mouse IgG를 사용하여 면역조직 반응을 시행하고 투과전자현미경으로 관찰하여 다음과 같은 결과를 얻었다. 1. Estradiol benzoate를 4일간 매일 일정량을 투여한 흰쥐의 난관섬모세포내 $\alpha-tubulin$의 면역반응은 estradiol 투여후 1일, 3일 및 5일군에서 강한 반응을 나타내었다. 2. Estradiol beozoate를 4일간 투여한 후 cia-platin을 투여한 흰쥐 난관섬모세포내 $\alpha-tubulin$ 반응은 cis-platin 투여 1일군과 3일군에서 약한 반응을 나타내었으나 제 5일군에서는 강한 반응으로 회복되었다. 3. Cis-platin투여한 후 제 1일 및 3일군의 흰쥐 난관 섬모세포내 $\alpha-tubulin$반응은 첨부세포질에서는 감소되었고 기저체, 섬모등에서는 $\alpha-tubulin$반응이 대조군과 비교하면 변동이 없었다. 이상의 결과로 미루어 난관섬모세포내 $\alpha-tubulin$은 cis-platin투여에 의해 감소되는 것으로 결론 지을 수 있었다.

• Applied Microscopy
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• 제26권2호
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• pp.197-206
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• 1996

cis-Dichlorodiammineplatinum (II) (cis-Platin) inhibits the proliferation and growth of the tumor cells by way of inhibiting DNA and protein synthesis of the cancer cells. Although cis-Platin is very effective antitumor drug, it also produces many other side effects. Thus the author has studied the effects of cis-Platin on the proximal epiphyseal plate in the tibia of the rat. The results were as follows: In the chondrocyte of the proliferative zone, sacculated, and fragmented cisternae of rough endoplasmic reticulum, some mitochondria with disorganized mitochondrial cristae and distorted procollagens were observed, and in the matrix some large matrix granules and dispersed collagen fibrils were revealed on the 1st, 3rd day and 1st week group of cis-Platin treated rats. In the chondrocyte of the proliferative zone of cis-Platin treated rats on the 2nd and 3rd week group, parallely arranged rough endoplasmic reticulum and many procollagens were shown, and in the matrix a number of large matrix granules and many small matrical granules as well as collagen fibrils were revealed. Consequently it is suggested that though cis-Platin induces the degenerative changes of the chondrocyte resulting in components of the cartilagenous matrix, these toxic effects are regressed with time.

• Applied Microscopy
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• 제23권1호
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• pp.35-55
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• 1993

cis-Dichlorodiammineplatinum (II) (cis-Platin), a metallic compound, has widely been used as an effective anticancer chemotherapeutic agent. The precise mechanism of action of this agent is still unknown, but it is postulated that cis-Platin may act on the cancer cell like bifunctional alkylating agents. Although this agent is very beneficial to the patients with cervical cancer, germinoma of testis, neuroblastoma and others, it may also damage to the normal cell so that many side effects; severe hemorrhagic enterocolitis, bone marrow depression, renal damage and liver damage will develope. This experiment has been undertaken to pursue the cytotoxic effects of the cis-Platin on the ultrastructures of the interalveolar septum in the mouse lung. A total of 55 healthy male mice of ICR strain were used as experimental animals and divided into 5 mice of normal control group and 50 mice of cis-Platin treated group. The mice of cis-Platin treated group were sacrificed by carotid exsanguination at 6, 12, 24 hours, 3 days and 7 days after intraperitoneal injection of 6.0 mg of cis-Platin ($Abiplatin^R$ Abic Co. Ltd.) per kg of mouse body weight. The specimen obtained from the lower lobe of left lung were sliced into $1mm^3$ and prefixed with 2% glutaraldehyde -2.5% paraformaldehyde solution prepared with Millonig's phosphatae buffer solution (pH 7.4) at $4^{\circ}C$ for 3-4 hours. After postfixation with 1% osmium tetroxide solution all specimens were embedded in Epon 812. Ultrathin sections about $600-800{\AA}$ in thickness were stained with uranyl acetate and lead citrate and observed with Hitachi-600 electron microscope. The results obtained were as follows: 1. Local swellings with increase of electron density and number of pinocytic vesicles in the cytoplasms of the type I pneumocyte and endothelial cell of the blood air barrier in interalveolar septum of cis-platin treated mice were observed. 2. Cisternae of rough endoplasmic reticulum were dilated and sacculated in association with detachment of membrane bound ribosomes of the type II pneumocyte in interalveolar septum of cis-Platin treated mice. 3. Swollon mitochondria with uneven electron density of their matrix were observed in the type II pneumocyte of interalveolar septum in the cis-Platin treated mice. 4. The lamellae of lammelar bodies in type II pneumocyte of interalveolar septum in cis-Platin treated mice were devoided or transformed into homogeneous electron dense material. It is consequently suggested that cis-Platin would induce the cellular edema of type I pneumocyte and endothelial cell, and degenerative changes of cytoplasmic organelles of the type II pneumocyte in the interalveolar septum of the mouse lung.

• 생약학회지
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• 제23권2호
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• pp.89-95
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• 1992

The water extract of Gamidaebo-Tang depressed the lethal toxicity of cis-platin$(45{\mu}M/kg,\;s.c.)$, and mitomycin C (6mg/kg, s.c.). Significant depression of renal toxicity(indicated by an increased blood urea nitrogen value and creatinine value) of cis-platin $(35{\mu}M/kg)\;s.c.)$, was observed in mice treated with Gamidaebo-Tang. In rats treated with mitomycin C and Gamidaebo-Tang, the increased LDH activity and reduced total protein and albumin contents by mitomycin C were significantly depressed. The number of WBC was significantly increased in rats treated with mitomycin C but in the rats treated with mitomycin C and Gamidaebo-Tang, the number of WBC was increased and the hematocrit value and the number of RBC and Hgb were significantly increased in the dose-dependent manner. Therefore, bone marrow toxicity of mitomycin C in the rats treated with Gamidaebo-Tang was depressed. In the end, alleviative effects of the side actions of cis-platin and mitomycin C were acknowledged by combined usage of Gamidaebo-Tang and these anti-neoplastic drugs.

• 대한기관식도과학회지
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• 제5권2호
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• pp.164-173
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• 1999

Background : cis-Diamminedichloroplatinum(Ⅱ)(cis-platin) has been exhibited similar to bifunctional alkylating agents in the cell and known as an effective anticancer drug. Although this agent is very beneficial to the cancer patients, it may also damage to the normal cell. Many side effects were developed. Objectives : This experiments was undertaken to pursue the effect of cis-Platin on the mucous variation of the trachea. Materials and Methods : The male of Sprague-Dawley strain were used as and experimental animals. The experimental animals were killed at 1, 3 days and 1, 2 and 3 weeks after the third injection of cis-Platin was administered 1.5mg/kg to intraperitoneal injection at once a week for three weeks. The trachea was fixed to neutral formaline and stained with alcian blue(pH 1.0)-PAS, alcian blue(pH 2.5)-PAS double stains and these preparation observed with light microscope. Results : 1. In the trachea stained with alcian blue(pH 2.5)-PAS double stain, the epithelial cells were constricted in the 1 week, In the 1st day, 3rd day and 1st week, acidic mucopolysaccharide was increased but in the 2nd week, neutral mucopolysaccharide was increase. 2. In the trachea stained with alcian blue(pH 1.0)-PAS double stain, the 1st and 3rd day exhibited sulfa mucopolysaccharide with moderately or weakly positive reaction. In the 1st week the sulfa mucopolysaccharide with strongly positive reaction was increased. In the 2nd and 3rd week, the sulfa mucopolysaccharide with weakly positive and non-sulfa or neutral mucopolsaccharide with negative reaction were modified. Conclusion : It is consequently suggested that cis-Platin induces reversible toxic damage to tracheal cells including goblet cell.

• 생약학회지
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• 제29권2호
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• pp.93-103
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• 1998

In order to investigate the reducing effect of velvet antler water extract (VAWE) on the toxicity of anti-cancer drug, cis-platin (CDDP) and mitomycin C (MMC), we examined effects of co-administration with VAWE and anti-cancer drugs on their toxicities. We recognized that $LD_{50}$ of CDDP/MMC were increased by co-administration with VAWE and them in mice. It was found that co-administration of VAWE and MMC increased the survival rate in mice treated by lethal dose of MMC. Also, co-administration of VAWE and CDDP/MMC inhibited decrease of the body weight and organ weight in mice intoxificated by CDDP/MMC. The increase of serum blood urea and serum creatinine levels in rats intoxicated by CDDP were significantly inhibited by the co-administrationin with VAWE and CDDP. The decrease of RBC and WBC in rats intoxificated by MMC were significantly inhibited by the co-administration with VAWE and MMC. These results suggest that the combined usage of VAWE and CDDP/MMC drugs may be a new method for prevented or minimized the toxicity of them.

• 대한핵의학회:학술대회논문집
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• 대한핵의학회 1988년도 제27차 춘계학술대회
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• pp.134.1-134.1
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• 1988

• 혜화의학회지
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• 제4권2호
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• pp.255-272
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• 1996

소적백출산(消積白朮散)은 ${\ll}$화제국방(和劑局方)${\gg}$에 삼령백출산(蔘笭白朮散)에 정열해독약(淸熱解毒藥)인 와송(瓦松) 금은화(金銀花) 포공영(蒲公英)을 가미(加味)한 처방(處方)으로, 본방(本方)인 삼령백출산(蔘笭白朮散)은 비위허약(脾胃虛弱), 음식부진(飮食不振), 다곤소력(多困少力) 중만비대(中滿痺臺), 심정기천(心柾氣喘), 구토(嘔吐), 설사(泄瀉), 상한해수(傷寒咳嗽)를 치료목적(治療目的)으로 쓰여 온 이래(以來) 임상에서는 대편부실(大便不實), 구설(久泄), 옹달궤후(癰疸潰後) 불사식자(不思食者)를 치료(治療)하는데 다용(多用)되어 왔다. 종양(腫瘍)(Neoplasia)은 새로운 성장(成長)(New+ Glowth) 이라는 세포학적(細胞學的)으로 비정상세포(非正常細胞)의 과다증식(過多增殖)으로 인해 실질장기(實質臟器), 유강장기(有腔腸器), 및 골격(骨格), 피부조직(皮膚組織)에 비정상조직(非正常組織)을 형성(形成)하는 질환(疾患)이다. 현대적(現代的) 종양(腫瘍)과 유사(類似)한 한의학적(韓醫學的)인 병증(病症)은 ${\ll}$소문(素問)${\gg}$에서는 "궐산(厥疝), 복량(伏梁), 식적(息積)"으로 ${\ll}$영추(靈樞)${\gg}$에서는 "장담(腸覃), 석가"로 표시(表示)된 이후(以後)로 소원방(巢元方)은 징가, 식일, 석옹(石癰), 완저(緩疽), 석저(石疽) 등으로 표현(表現)하였다. 원인(原因)에 대(對)해서는 ${\ll}$내경(內經)${\gg}$에서는 허(虛)와 한기(寒氣), 한(寒) 열(熱)로 보았고, 그 외(外)의 학자(學者)들은 내허(內虛)와 기혈불순(氣血不順), 화(火), 한(寒), 기울(氣鬱), 음양불화(陰陽不和)등으로 보았다. 치료(治療)는 ${\ll}$내경(內經) 자법론(刺法論)${\gg}$에서 "정기재내(正氣在內) 사불가우(邪不可于)" 이라 하여 생명활동(生命活動)의 원동력(原動力)인 정기(正氣)의 역할(役割)을 강조(强調)하였고, ${\ll}$육원정기대론(六元正氣大論)${\gg}$에서는 "대적대취(大積大聚) 불가범야(不可犯也) 쇠기태반이지(衰其太半而止)"라 하여 공벌약(攻伐藥)을 과용(過用)하여 정기(正氣)를 손상(損傷)시켜서는 안된다고 하는 등 부정위주(扶正爲主), 거사위주(祛邪爲主) 혹은 부정거사(扶正祛邪) 겸용(兼用)의 방법(方法)이 혼용(混用)되고 있다. 현대(現代) 서양의학(西洋醫學)의 항암제(抗癌劑)는 치료효과(治療效果)는 우수(優秀)하지만 악심(惡心), 구토(嘔吐)를 비롯하여 골수억제효과(骨髓抑制效果)와 간(肝), 심(心), 신(腎), 폐(肺)의 손상(損傷)을 초래(招來)하는 등(等)의 부작용(副作用)을 나타내며, 빈번(頻繁)한 화학요법제(化學療法劑)의 투여(投與)로 인(因)한 암세포(癌細胞)의 약제저항성(藥劑抵抗性) 출현(出現)등이 항암제(抗癌劑)의 문제점(問題點)으로 제시(提示)되고 있다. 이에 저자(著者)는 비위기능(脾胃機能)을 강화(强化)시켜 정기형성(正氣形成)에 깊이 관여(關與)하는 삼령백출산(蔘笭白朮散)에 청열해독(淸熱解毒), 소종산결지제(消腫散結之劑)인 금은화(金銀花), 포공영(浦公英), 와송(瓦松)을 가미(加味)하여 암발생(癌發生) 백서(白鼠)에 투약(投藥)한 후(後) sarcoma 180암세포(癌細胞)에 대(對)한 생명연장효과(生命延長效果)와 항암제(劑)의 일종(一種)인 cis-platin을 이용(利用)하여 양방항암제(洋方抗癌劑)의 부작용(副作用)에 대(對)한 본(本) 방(方)의 효과(效果)를 실험(實驗)하여 관찰(觀察)하였던 바 다음과 같은 결론(結論)을 얻었다. 1. 소적백출산(消積白朮散)은 sarcoma 180 암세포(癌細胞) 이식종양(移植腫瘍)에 대(對)해 생명연장효과(生命延長效果)가 인정(認定)되었다. 2. 소적백출산(消積白朮散)은 치암제(治癌劑)인 cis-platin 치사독성(致死毒性)에 대(對)해 생존연장효과(生存延長效果)가 인정(認定)되었다. 3. 소적백출산(消積白朮散)은 cis-platin 현독성(腎毒性) 생쥐 및 흰쥐에 있어서 유의성(有意性) 있는 체중감소억제효과(體重減少抑制效果) 및 serum BUN 상승억제효과(上昇抑制效果)가 인정(認定)되었다. 4. 소적백출산(消積白朮散)은 cis-platin 현독성(賢毒性) 흰쥐에 대(對)해 유의성(有意性) 있는 serum creatinine 상승억제효과(上昇抑制效果)가 나타났으며, cis-platin의 혈액학적(血液學的) 부작용(副作用)인 RBC, WBC 감소(減少)에 대(對)해 감소억제효과(減少抑制效果)가 인정(認定)되었다. 5. 소적백출산(消積白朮散)은 cis-platin 현독성(腎毒性) 흰쥐에 대(對)해 뇨량감소억제(尿量減少抑制) 효과(效果) 및 ureanitrogen과 creatinine 배수감소억제효과가 관찰(觀察)되었다. 이상(以上)의 결과(結果)로부터 소적백출산(消積白朮散)은 악성종양치료(惡性腫瘍治療) 및 항암제(劑)의 부작용(副作用)을 경감(輕減)시키는 데 응용(應用)할 수 있을 것으로 사료(思料)된다.

• Journal of Nutrition and Health
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• 제31권4호
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• pp.739-746
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• 1998

This study was designed to investigated the antitumor effect and change chemosensitivity of chitosan in 2 kinds of humen lung cancer cell lines(NCI-H522, NCI-H596). To evaluate the antitumor effect and synergistic effectof chomosensitivity, MTT assay was used in vitro. then anticancer drugs used were 챤-platin , ectoposide, and adrimycin. The results of this study were as follows; Chitosan shwoed in antitumor effect on both NCI-H522 and NCI-H596. The lung cancer viability percent for NCI-H522 and NCL-H596 showed at the lowest levels of 5.31 and 5.33% when the concentration of chitosan was 25mg/$m\ell$ media and the exposure time of chitosan was 72 hours. ID50 value of chitosan on both NCI-H522 and NCI-H596 showed at the lowest levels of 14.07, 11.68 mg/$m\ell$ media when the exposure time of chitosan was 72 hours. the synergistic effect of chomosensitivity was better in NCI-H596 than in NCI0H522 . When the synergistic effect of chomosensitivity was shown according to the kind of the anticancer drugs, in case of NCI-H522 , in the concentration of 100$\mu\textrm{g}$/$m\ell$, ectoposide showed the highest synergistic effect of chomosensitivity and then was adrimycin In case of NCI-H596, in the concentration of 100$\mu\textrm{g}$/$m\ell$,, the order of the synergistic effect of chomosensitivity was ectoposide>adrimycin>cis-platin and in the concentration of 10$\mu\textrm{g}$/$m\ell$, ectoposide>cis-platin >adrimycin. It is concluded that chitosan is an active antitumor agent and is increased chomosensitivity though there is difference according to the kind and the concentration of anticancer drugs. But to be sued to lung cancer theraphy, further studies on toxicity, the mechanism of action, animal experiment are wanted.