• Title/Summary/Keyword: Drug Toxicity

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Adoptive Cell Therapy of Melanoma with Cytokine-induced Killer Cells

  • Kim, Ji Sung;Kim, Yong Guk;Pyo, Minji;Lee, Hong Kyung;Hong, Jin Tae;Kim, Youngsoo;Han, Sang-Bae
    • IMMUNE NETWORK
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    • 제15권2호
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    • pp.58-65
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    • 2015
  • Melanoma is the most aggressive skin cancer and its incidence is gradually increasing worldwide. Patients with metastatic melanoma have a very poor prognosis (estimated 5-year survival rate of <16%). In the last few years, several drugs have been approved for malignant melanoma, such as tyrosine kinase inhibitors and immune checkpoint blockades. Although new therapeutic agents have improved progression-free and overall survival, their use is limited by drug resistance and drug-related toxicity. At the same time, adoptive cell therapy of metastatic melanoma with tumor-infiltrating lymphocytes has shown promising results in preclinical and clinical studies. In this review, we summarize the currently available drugs for treatment of malignant melanoma. In addition, we suggest cytokine-induced killer (CIK) cells as another candidate approach for adoptive cell therapy of melanoma. Our preclinical study and several previous studies have shown that CIK cells have potent anti-tumor activity against melanomas in vitro and in an in vivo human tumor xenograft model without any toxicity.

치매 치료제 염산 디히드로에보다이아민의 생식 및 발생 독성 (Reproduction and Development Toxicity of Anti-Alzheimer′s Drug Dehydroevodiamine-HCl)

  • 성이숙;정성윤;서영득;진미령;최봉웅;장병모;김대경
    • 약학회지
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    • 제46권6호
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    • pp.452-458
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    • 2002
  • Dehydroevodiamine-HCl (DHED), which is a component separated from Evodia rutaecarpa Bentham, has novel anticholinesterase and antiamnesic activities in a scopolamine-induced amnesia model. Several studies suggest that DHED might be an effective drug for Alzheimer's disease and a vascular type of dementia. DHED was at dose levels of 0, 50, 100 and 200 mg/kg/day administered intraperitoneally to Sprague-Dawley male rats for 60 days before mating and to females from 14 days before mating to 7 days after mating. Effects of the DHED on general symptom and reproductive performance of parent animals and embryonic development were examined. In male parents, whereas no death was observed, reduction in the increase rate of body weight was found at 200 mg/kg. In female parents, both of the mating performance and the fertility of parent animals were decreased at 200 mg/kg, but not significantly. In 200 mg/kg treated group, the fetal death rate was increased but total fetuses showed no changes compared to the control group. There were no malformed F1 fetuses in all groups.

새로운 반합성 Rifamucin 유도체 KTC-1의 랫트 수태능력 시험 (Fertility Study of KTC-1, a New Semisynthetic Rifamycin Derivative, in Rats.)

  • 김종춘;정문구;노정구
    • Toxicological Research
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    • 제12권1호
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    • pp.93-99
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    • 1996
  • The effect of KTC-1, a new semisynthetic rifamycin antituberculous drug, on general toxicity, reproductive capability and fetal development was investigated in Sprague-Dawley rats. Male rats were administered KTC-1 with mashed feed from 63 days before mating to the end of mating period, and female rats were given from 14 days before mating to day 7 of gestation at dose levels of 0, 375, 750, and 1,500 ppm. The females were sacrificed on day 21 of gestation for examination of their fetuses. At 1,500 ppm, a reduction in body weight gain and testis atrophy were observed in male rats. Histological examination revealed testicular atrophy, absence or decrease of germinal cells, and vacuolization of Sertoli cells in testis. A reduction in body weight gain, a decrease in food consumption were found in female rats. In addition, decreases in the number of corpora lutea, iraplantations, and the litter size of live fetuses were seen. Mating, fertility, and pregnancy performances were also affected. There were no external abnormalities observed by examination of fetuses. At 750 ppm, a reduction in the body weight gain of male and female rats and decreases in the number of implantations and litter size were found. At 375 ppm, no treatment-related effects were observed. The results suggest that the no-effect dose levels (NOELs) of KTC-1 are 375 ppm for males and females on general toxicity, 750 ppm for males and females on reproductive capability, and 375 ppm for fetuses on embryonic development.

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Genetic Toxicity Test of 1,2-Dibromoethane by Ames, Micronucleus, Comet Assays and Microarray Analysis

  • Kim, Ki-Y.;Kim, Ji-H.;Kwon, Kyoung-J.;Go, Seo-Y.;Min, Kyung-N.;Lee, Woo-S.;Park, Sue-N.;Shee, Yhun-Y.
    • Biomolecules & Therapeutics
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    • 제14권4호
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    • pp.246-252
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    • 2006
  • 1,2-Dibromoethane(DBE) has been widely used as a soil fumigant, an additive to leaded gasoline and an industrial solvent. In this study, we have carried out in vitro genetic toxicity test of 1,2-dibromoethane and microarray analysis of differentially expressed genes in response to 1,2-dibromoethane. 1,2-Dibromoethane showed mutations in base substitution strain TA1535 both with and without exogenous metabolic activation. 1,2-Dibromoethane showed mutations in frame shift TA98 both with and without exogenous metabolic activation. 1,2-Dibromoethane showed DNA damage based on single cell gel/comet assay in L5178Y cells both with and without exogenous metabolic activation. 1,2-Dibromoethane increased micronuclei in CRO cells both with and without exogenous metabolic activation. Microarray analysis of gene expression profiles in L5178Y cells in response to 1,2-dibromoethane selected differentially expressed 241 genes that would be candidate biomarkers of genetic toxic action of 1,2-dibromoethane.

비글개에서 신원방우황청심원의 급성 및 아급성독성시험 (Acute and Subacute Toxicity Studies of New Won-bangwoohwangchungsimwon in Beagle Dogs)

  • 성하정;권오경;방명주;곽형일;신대희;이진영;박대규;정규혁;윤효인
    • Toxicological Research
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    • 제14권2호
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    • pp.273-283
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    • 1998
  • Single and 4 weeks oral administration of New wonbangwoohwangchungsimwon (NSCH) which was used l-muscone as substitutive material qf musk, to beagle dogs of both sexes were per-formed to investigate both acute and subacute toxicity. Beagle dogs (3 males and 3 females) in acute experiments were administered orally with single dose of 2,000 mg/kg and groups of 9 male and 9 female beagle dogs in subacute experiments were given daily different dosage of NSCH, 160 mg/kg/day (low dosage group), 400 mg/kg/day (middle dosage group), 1,000 mg/kg/day (high dosage group) once a day for 4 weeks by oral route according to the Established Regulation of Korea Food and Drug Ad-ministration (l996. 4. 16). $LD_{50}$ value for beagle dogs was more than 2,000 mg/kg per oral for both male and females. In animals administered with NSCH, there were neither dead animals nor significant changes of body weights. In addition, no differences were found between control and treated groups in clinical sign, urinalysis, eye examination, hematology, serum chemistry, organ weight and other fingings. No histological lesions were observed in both control and treatment groups. Above data strongly suggset that NSCH in beagle dogs is considered to be safe.

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비글개에서 신우황청심원의 급성 및 아급성독성시험 (Acute and Subacute Toxicity of New Woohwangchungsimwon in Beagle Dogs)

  • 권오경;성하정;곽형일;방명주;신대희;이진영;박대규;정규혁;윤효인
    • Toxicological Research
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    • 제14권2호
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    • pp.249-260
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    • 1998
  • Single and 4 weeks oral administration of New Woohwangchungsimwon (NWCH) which was used l-muscone as substitutive material of musk, to beagle dogs of both sexes were performed to investigate both acute and subacute toxicity. Beagle dogs(3 males and 3 females) in acute experiments were administered orally with single dose of 2,000 mg/kg and groups of 9 male and 9 female beagle dogs in subacute experiments were given daily different dosage of NWCH, 160 mg/kg/day (low dosage group), 400 mg/kg/day (middle dosage group), 1,000 mg/kg/day (high dosage group) once a day for 4 weeks by oral route according to the Established Regulation of Korea Food and Drug Administration (1996. 4. 16). $LD_{50}$/ value for beagle dogs was more than 2,000 mg/kg per oral for both male and fe-males. In animals administered with NWCH, there were neither dead animals nor significant changes of body weights. In addition, no differences were found between control and treated groups in clinical sign, urinalysis, eye examination, hematology, serum chemistry, organ weight and other fingings. No histological lesions were observed in both control and treatment groups. Above data strongly suggset that NWCH in beagle dogs is considered to be safe.

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HPLC로 표준화한 가미홍화탕(KH-19)의 랫드와 Beagle견에 대한 단회경구투여독성시험 (Acute Oral Toxicity Study of Standardized Gami-Honghwa-Tang (KH-19) in Rats and Beagle Dogs)

  • 유영법;성현제;윤유식
    • Toxicological Research
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    • 제21권1호
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    • pp.63-70
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    • 2005
  • Gami-Honghwa-Tang (KH-19), a herbal prescription for reducing the side effect of radiotherapy, is composed of eight crude herbs such as Rehmanniae Radix Preparata, Angelicae Gigantis Radix, Cnidii Rhizoma, Paeoniae Radix, Corni Fructus, Moutan Cortex Radicis, Lycii Fructus, Carthami Flos, and Glycyrrhizae Radix. In this study, marker substances in KH-19 were analyzed by high performance liquid chromatography-diode array detector (HPLC-DAD) and safety evaluation of standardized KH-19 was evaluated by good laboratory practices (GLP) guideline of Korea Food and Drug Administration. HPLC-DAD was employed to determine the quantities and the qualities of several marker substances such as 5-hydroxymethyl-2-furaldehyde (5-HMF), paeonol, loganin, paeoniflorin, glycyrrhizin, and decursin in the KH-19. In acute oral toxicity study on rat, transient inhibition of body weight was shown, but change in general symptom was not detected. No dead animal was observed up to 5,000 mg/kg in both male and female animals. In acute oral toxicity study on Beagle dog, transient vomiting, diarrhea, anorexia, and body weight reduction were observed, However, no dead animal was observed up to 2,000 mg/kg in both male and female animals.