• IMMUNE NETWORK
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• v.11 no.3
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• pp.182-189
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• 2011

Background: Cytotoxic T lymphocytes (CTLs) appear to play an important role in the control and prevention of human cytomegalovirus (HCMV) infection. The pp65 antigen is a structural protein, which has been defined as a potential target for effective immunity against HCMV infection. Incorporation of an 11 amino acid region of the HIV TAT protein transduction domain (Tat) into protein facilitates rapid, efficient entry into cells. Methods: To establish a strategy for the generation of HCMV-specific CTLs in vitro, recombinant truncated N- and C-terminal pp65 protein (pp65 N&C) and N- and C-terminal pp65 protein fused with Tat (Tat/pp65 N&C) was produced in E.coli system. Peripheral blood mononuclear cells were stimulated with dendritic cells (DCs) pulsed with pp65 N&C or Tat/pp65 N&C protein and immune responses induced was examined using IFN-${\gamma}$ ELISPOT assay, cytotoxicity assay and tetramer staining. Results: DCs pulsed with Tat/pp65N&C protein could induce higher T-cell responses in vitro compared with pp65N&C. Moreover, the DCs pulsed with Tat/pp65 N&C could stimulate both of $CD8^+$ and $CD4^+$ T-cell responses. The T cells induced by DCs pulsed with Tat/pp65 N&C showed higher cytotoxicity than that of pp65-pulsed DCs against autologous lymphoblastoid B-cell line (LCL) expressing the HCMV-pp65 antigen. Conclusion: Our results suggest that DCs pulsed with Tat/pp65 N&C protein effectively induced pp65-specific CTL in vitro. Tat fusion recombinant protein may be useful for the development of adoptive T-cell immunotherapy and DC-based vaccines.

• Biomolecules & Therapeutics
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• v.20 no.5
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• pp.492-498
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• 2012

Phytochemicals have been known to exhibit potent antioxidant activity. This study examined cytoprotective effects of phytochemicals including quercetin, catechin, caffeic acid, and phytic acid against oxidative damage in SK-Hep-1 cells induced by the oxidative and non-oxidative metabolism of ethanol. Exposure of the cells to excess ethanol resulted in a significant increase in cytotoxicity, reactive oxygen species (ROS) production, lipid hydroperoxide (LPO), and antioxidant enzyme activity. Excess ethanol also caused a reduction in mitochondrial membrane potential (MMP) and the quantity of reduced glutathione (GSH). Co-treatment of cells with ethanol and quercetin, catechin, caffeic acid and phytic acid significantly inhibited oxidative ethanol metabolism-induced cytotoxicity by blocking ROS production. When the cells were treated with ethanol after pretreatment of 4-methylpyrazole (4-MP), increased cytotoxicity, ROS production, antioxidant enzyme activity, and loss of MMP were observed. The addition of quercetin, catechin, caffeic acid and phytic acid to these cells showed suppression of non-oxidative ethanol metabolism-induced cytotoxicity, similar to oxidative ethanol metabolism. These results suggest that quercetin, catechin, caffeic acid and phytic acid have protective effects against ethanol metabolism-induced oxidative insult in SK-Hep-1 cells by blocking ROS production and elevating antioxidant potentials.

• Toxicological Research
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• v.16 no.1
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• pp.17-25
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• 2000

Chitosan cross-linked collagen-glycosaminoglyan (CCGM) is an artificial skin substitute made to form a sponge like dimensional matrix. It can be used to facilitate reconstruction of dermal tissue when applied on large wounds such as severe burns. In order to study the toxicological effects of CCGM the cytotoxicity, local irritation and skin sensitization test were carried out according to the standards of ISO 10993. In the cytotoxicity test utilizing LDH and MTT test, both the CCGM and its extract had no toxicity of Balb/c 3T3 cells. The local irritatioin test on rabbit skin demonstrated that CCGM did not promote any harmful when directly applied on skin. In addition, it did not elicit any allergic reaction in the guinea pig maximization test. Based on these results, it is suggested that CCGM is a material without cytotoxicity, local irritation and allergenicity.

• Korean Journal of Pharmacognosy
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• v.25 no.4 s.99
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• pp.388-394
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• 1994

80% Methanol extracts of 44 traditional drugs used for the treatment of liver diseases or tonic effects were screened for anti-hepatotoxic activity by in vitro assay using $CCl_4-induced$ cytotoxicity in primary cultured rat hepatocytes. $CCl_4-induced$ cytotoxicity was evaluated by determination of LDH, GOT or GPT activity in the medium. Rehmaniae Radix Preparata and Gelantina nigra inhibited the release of LDH, GOT or GPT from $CCl_4-treated$ hepatocytes. Gibotii Rhizoma and Eucommiae Cortex showed inhibitory effect on release of LDH from normal hepatocytes as well as $CCl_4-treated$ hepatocytes. Eucommiae Cortex and Lili Bulbus decreased release of GOT and LDH from normal hepatocytes, respectively. Astragali Radix inhibited release of GPT in $CCl_4-treated$ hepatocytes. Phlomidis Radix, Imperatae Rhizoma, Cistanchis Herba, Broussonetiae Fructus, Asparagi Tuber, Trigonellae Semen and Polgonati Rhizoma inhibited release of LDH from $CCl_4-treated$ hepatocytes. Among 44 traditional drugs, most of them released LDH, GOT or GPT at the dose of 1 mg/ml in normal hepatocytes, and Drynariae Rhizoma, Acanthopanacis Cortex, Longanae Arillus, Atratylodis Rhizoma and Ecliptae Herba increased $CCl_4-induced$ cytotoxicity.

• Environmental Analysis Health and Toxicology
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• v.27
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• pp.11.1-11.8
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• 2012

Objectives: Hepatotoxicity of acetaminophen has been widely studied. However, the adverse effects on the heart have not been sufficiently evaluated. This study was performed to investigate cytotoxicity and alterations of gene expression in cultured cardiomyocytes ($H_9C_2$ cells) after exposure to acetaminophen. Methods: $H_9C_2$ cells were incubated in a 10 mM concentration of acetaminophen for the designated times (6, 12, and 24 hours), and cytotoxicity was determined by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Alteration of gene expression was observed by microarray analysis, and RT-PCR was performed for the three representative oxidative stress-related genes at 24 hours after treatment. Results: It revealed that acetaminophen was toxic to cardiomyocytes, and numerous critical genes were affected. Induced genes included those associated with oxidative stress, DNA damage, and apoptosis. Repressed genes included those associated with cell proliferation, myocardial contraction, and cell shape control. Conclusions: These findings provide the evidences of acetaminophen-induced cytotoxicity and changes in gene expression in cultured cardiomyocytes of $H_9C_2$ cells.

• Journal of Biomedical Engineering Research
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• v.17 no.1
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• pp.11-18
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• 1996

The toxic metal ion release behaviour and the cytotoxicity of a super stainless steel (S.S.S, 22cr-20Ni -6Mo-0.25N) were investigated The measurement of the amount of static and wear- induced trace metal ion released from the steels was conducted in Hank's balanced salt solution using an electrothermal atomic absdrption spectrometry equiped with Uaphite furnace. And the in vitro cytotoxicity of the materials was assesed in cell culture. The static dissolution rates of Fe and Cr ions from the S.S.S were significantly lower than those of 316L SS. However, the Ni ion release from the S.S.S during the first 4 weeks was yester than that from 316L 55 by 15-45%. Also, the wear-in- duces dissolution rates from the steels were not correlated either with their elemental composition rates or with the static metal ion release rates. The S.S.S did not deteriorate the osteoblasts viability. And no toxic response was observed from the macrophages cultured for 7 days in RFMI 1640 medium immersed with the S.S.S specimens.

• Natural Product Sciences
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• v.8 no.4
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• pp.165-169
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• 2002

One-hundred and twenty plant extracts were prepared from 29 Indonesian plants and were primarily tested in vitro cytotoxicity in cultured human lung (A549), colon (Col2), and stomach (SNU-638) cancer cells. As a result, the 23 extracts were found to be active in the criteria of $ED_{50}$<$20\;{\mu}g/ml$. Remarkable cytotoxicity was observed for chloroform and n-butanol extracts of Calotropis gigantea, with $ED_{50}$ values ranging from 0.25 to $0.46\;{\mu}g/ml$. Five extracts derived from Eclipta alba and Excoecaria cochinchinensis displayed potent cell-line selective cytotoxicity, while the rest of 15 extracts showed modest cytotoxic activity against all of three cancer cells. In addition, the cytotoxic potential of subfractions of Zingiber cassumunar against a panel of human cancer cell lines is presented.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.288-301
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• 2000

A series of 2-alkyl, 2-aryl, and 2-piperazinyl benzimidazole-4,7-dione derivatives (7a-h) and 16m-o) were prepared, and their cytotoxicities were tested against three cancer cell lines (mouse lymphocytic leukemia cell line P388, and human gastric carcinoma cell lines SNU-1 and SNU-16). These compounds showed potent cytotoxicity against all of three cell lines tested, and especially SNU-16 was sensitive to them. 2-Aryl (7g,h) and 2-piperazinyl benzimidazole-4,7-dione derivative (I6 m) were more potent than mitomycin C against P388 and SNU-16. Among benzimidazole-4,7-dione derivatives with alkyl group at position 2, 7a had the most potent cytotoxicity against all of the cell lines tested.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.845-848
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• 2006

Three new sesquiterpene hydroperoxides, 1-[3-(2-hydroperoxy-3-methylbut-3-en)-4-hydroxyphenyl]ethanone (2), $7{\beta}-hydroperoxy-eudesma-11-en-4-ol$ (3), and $7{\alpha}-hydroperoxymanool$ (4), together with three known compounds, germacrone (1), ent-germacra-4(15),5,10(14)-trien-$1{\alpha}$-ol (5) and teucdiol A (6) were isolated from the aerial parts of Aster spathulifolius (Compositae). Their structures were characterized using chemical and spectroscopic methods. The isolated compounds were tested for their cytotoxicity against five human tumor cell lines in vitro using a SRB method. The two new compounds, 3 and 4, showed moderate cytotoxicity against human cancer cells with $ED_{50}$ values ranging from 0.24 to $13.27\;{\mu}g/mL$.

• Archives of Pharmacal Research
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• v.18 no.2
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• pp.118-120
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• 1995

The cytotoxicity-directed fractionation of MeOH extract of Terminalia chebula fruits led to the isolation of three hydrolyzed tannins and a related compound, gallic acid(1), $1,2,3,4,6-penta-O-galloy-{\beta}-_D/-glucopyranose(II)$,. chebulagic acid (III) and chebulinic acid(IV), as active principles. They were shoen to exhibit moderate cytotoxicity against cultured human tumor cell lines including A-549, SK-OV-3, Sk-MEL-2, XF-498 and HCT-15 in vitro.