• Korean Journal of Pharmacognosy
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• v.22 no.3
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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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• v.30 no.1
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• pp.45-59
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• 2000

Cis-platin is a widely used anticancer drug against certain solid tumors such as malignant ovarian tumor, malignant carcinoma of head and neck, bladder cancer and cervical cancer of uterus, and its major mechanism of action is inhibition of DNA synthesis of the tumor cell. To investigate the inhibitory effects of cis-platin on the ciliogensis of the ciliated cells in the mucosa of oviduct, the author pursued the alterations of $\alpha-tubulin$, which is the main constituent of the microtubles in cilia, after cis-platin treatment. To eliminate the possible variations due to ovarian cycle, female Spargue-Dawley rats ($150\sim200gm$ in B.W.) were pretreated with estradiol benzoate (20 mg/kg, once a day, for 4 consecutive days). Animals were administrated with cis-platin (6 mg/kg, i.p.) and sacrificed at 1day, 3days, 5days and 7days after treatment, respectively. Immunohistochemistry for $\alpha-tubulin$ using mouse anti-rat $\alpha-tubulin$ monoclonal antibody as primary antibody was done. Immunogold electronmicroscopy for intracellular distributions of $\alpha-tubulin$ was also performed with same primary antibody and Goat anti- mouse IgM which is preconjugated with gold particles of 15 nm as secondary antibody. The results obtained were as follows; 1. Strong immunoreactivity of $\alpha-tubulin$ was observed in ciliated cells of oviducts at 1, 3 and 5 days after estradiol pretreatment. 2. Weak immunoreactivity of $\alpha-tubulin$ was observed in ciliated cells of oviducts at 1 and 3 days after cis-platin treatment but it was recovered to strong immunoreactivity in 5 days 3. In immunogold electronmicroscopy, density of gold particles for $\alpha-tubulin$ reactions was decreased in apical cytoplasm, but few changes were observed in basal body or cilia at 1 and 3 days after cis-platin treatment. From these above results, it is indicated that synthesis of $\alpha-tubulin$ in ciliated cells of rat oviduct is inhibited by cis-platin treatment.

• Applied Microscopy
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• v.26 no.2
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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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• v.23 no.1
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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.

• Korean Journal of Pharmacognosy
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• v.23 no.2
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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.

• Korean Journal of Bronchoesophagology
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• v.5 no.2
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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.

• Korean Journal of Pharmacognosy
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• v.29 no.2
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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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• 1988.05a
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• pp.134.1-134.1
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• 1988

• Journal of Haehwa Medicine
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• v.4 no.2
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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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• v.31 no.4
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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.