• Proceedings of the Korean Society of Applied Pharmacology
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• 2007.11a
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• pp.11-15
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• 2007

Metabolomics is an emerging technology which makes it possible to evaluate change of biological system in response to the physiological, environmental alterations. It has advantages in the simplicity and sensitivity to analyze metabolites since the researcher can use cutting edge instrument, such as mass spectrometry and simple sample preparation method compared to genomics or proteomics. Nowadays this technology has been tried in pharmaceutical area to investigate toxicity and efficacy of drug candidates and drugs in preclinical test. The metabolomic applications on the pharmaceutics for early prediction on toxicity and efficacy are described in this presentation. The multivariate analysis to get metabolic fingerprinting and its relations with the physiological changes are investigated with several drugs. Feasibility of metabolomic application for pharmaceutical area would be suggested from those researches.

• Biomolecules & Therapeutics
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• v.8 no.2
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• pp.179-183
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• 2000

To determine biosafety of fluorosilicic acid as a source of fluoride, we carried out acute toxicity and general pharmacological studies using mouse. Fluorosilicic acid had little effects on general behavior, pain response, convulsion, skeletal muscle function and intestinal mobility as compared to controls. It had either little adverse effects on alkaline phosphatase and collagen levels in osteoblast cells. This study supports the safety of fluorosilicic acid in animals.

• Korean Journal of Clinical Pharmacy
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• v.12 no.1
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• pp.1-6
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• 2002

Central Cancer Registry of Korean National Cancer Center in 1999 reported that mortality from lung cancer is higher than mortality from stomach cancer or hepatocellular carcinoma in Korean male. Lung cancer is classified into small cell cancer and non-small cell lung cancer (NSCLC), and NSCLC patients account for $70\%$ of the whole lung cancer patients. The purpose of this study was to evaluate the efficacy and toxicity of docetaxel and cisplatin combination in Korean patients with NSCLC. All patients who had received the combination therapy of docetaxel and cisplatin for histologically confirmed NSCLC in Ajou University Hospital between 2000. $2\~2001$. 4 were retrospectively evaluated for the responses and toxicities of that combination therapy. Nineteen patients were treated with docetaxel 75 $mg/m^2$ on Day 1 and cisplatin 25 $mg/m^2$ on Day 1-3 every 4 weeks. The response for combination regimen was evaluated by CT scans after 2 or 3 cycles of treatments. Seventeen patients were evaluated for the responses and the 19 patients far the toxicities. Among the 19 patients (14 men and 5 women), there were one patient $(5.3\%)$ with stage I disease, 4 patients $(21.1\%)$ with stage III disease, and 14 patients $(73.1\%)$ with stage IV disease. Of the 17 patients who were evaluable for response, complete response (CR) was not observed in any patient while partial response (PR) was observed in 5 patients $(29.4\%)$. The overall response rate (CR+PR) was $29.4\%$. Stable disease (SD) was observed in 11 patients $(64.7\%)$ and progressive disease (PD) in 1 patient $(5.9\%)$. The toxicities were graded by NCI (National Cancer Institute) Common Toxicity Criteria for the evaluable 70 cycles. Grade 3 or 4 neutropenia occurred in 53 cycles $(76\%)$. Four patients were hospitalized due to febrile neutropenia. The combination chemotherapy of docetaxel and cisplatin was effective as NSCLC treatments, however, the regimen must be administered carefully due to its hematological side effects.

• Journal of Environmental Health Sciences
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• v.30 no.4
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• pp.347-351
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• 2004

A battery of sediment bioassays was performed for the sediments from the intertidal flat zone along the middle west coast of Korea to assess their potential toxicity. In the bioassays, three crustaceans, Daphnia magna, Nitocra spines, and Hyalella aztec a were exposed to $16\%$ sediments (wet weight) collected from 14 sites. Immobility($\%$) was checked as an endpoint after 24- and 48-h exposure of Daphnia magna and after 96-h exposure of Hyalella azteca and Nitocra spines. Among the three bioassays, the 48-h Daphnia bioassay showed the most distinct differential sensitivity in relation to sediment contamination, while the Nitocra and the Hyalella bioassays failed to show the differential sensitivity properly among the sites classified as polluted. Significantly different levels of immobility ($\%$) were obtained between the sites classified as chemical/nutrient polluted and the sites classified as non-polluted in the Daphnia bioassays, but not in the Nitocra bioassay and the Hyalella bioassay. Some differences of toxic response to the same sediments among bioassays were observed, suggesting that there may be a chemical specificity of response sensitivity to sediment toxicity, due to differences in bio-availability of sediment toxicants among test species.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1145-1148
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• 2014

Background: Single pegylated liposomal doxorubicin (PLD) is commonly used as a salvage treatment in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma (PPA) with a satisfactory outcome. However, the data for second generation PLD administered in this setting are still limited. We conducted a retrospective study to evaluate the outcome of patients who received single-agent second generation PLD (LIPO-DOX) after the development of clinical platinum resistance. The study period was between March 2008 and March 2013. LIPO-DOX was administered intravenously 40 $mg/m^2$ every 28 days until disease progression, but for not more than six cycles. The response rate was evaluated using the Gynecologic Cancer Intergroup (GCIG) criteria while the toxicity was evaluated according to WHO criteria. Twenty-nine patients met the inclusion criteria in the study period with an overall response rate of 13.8%. The median progression free survival and overall survival were three and eleven months, respectively. With the total of 96 cycles of chemotherapy, the patients developed grades 3 and 4 hematologic toxicity as follows: anemia, 0%, leukopenia, 9.6%, neutropenia, 32.3% and thrombocytopenia, 0%. In conclusion, the single agent second generation PLD demonstrated modest efficacy in patients with platinum-resistant ovarian cancer, fallopian tube cancer and PPA without serious toxicity.

• Archives of Pharmacal Research
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• v.14 no.2
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• pp.188-192
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• 1991

Single non-lethal doses of chloroform $(CHCL_3)$ dichlorobromomethane $(CHCL_2Br)$, dibromochloromethane $(CHCIBr_2)$, or bromoform $(CHBr_3)$ were administered to male rats. Routes of exposure including single intraperitional (ip) and subcutaneous (sc) injection were used in order to permit comparison of severity of THM effects and renal toxicity was assessed at varied times following treatment. On an equimolar basis, sc administration of $CHBr_3$ (either 12 or 3 mmoles/kg) is more effective at increasing KW/BW than ip $CHCI_3$ treatment. Plasma urea nitrogen (BUN) following ip THM injections are markedly increased with all four THM at 24 hours post treatment. BUN response to $CHCL_2Br$ and $CHCIBr_3$-effected BUN levels have essentially returned to those of vehicle control. THM sc treatment results in a BUN response similar to that seen following ip treatment, with only the time course being different. With the exception of $CHCL_3$, sc and ip-treatments appear to be equally effective in evoking absolute BUN elevations. These results suggest that THM administration induce renal toxicity dependent upon the route or exposure.

• Journal of Environmental Health Sciences
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• v.38 no.1
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• pp.1-7
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• 2012

Carbon nanotubes (CNTs) stand at the frontier of nanotechnology and are destined to stimulate the next industrial revolution. Rapid increase in their production and use in the technology industry have led to concerns over the effects of CNT on human health and the environment. The prominent use of CNTs in biomedical applications also increases the possibility of human exposure, while properties such as their high aspect ratio (fiber-like shape) and large surface area raise safety concerns for human health if exposure does occur. It is crucial to develop viable alternatives to in vivo tests in order to evaluate the toxicity of engineered CNTs and develop validated experimental models capable of identifying CNTs' toxic effects and predicting their level of toxicity in the human respiratory system. Human lung epithelial cells serve as a barrier at the interface between the surrounding air and lung tissues in response to exogenous particles such as air-pollutants, including CNTs. Monolayer culture of the key individual cell types has provided abundant fundamental information on the response of these cells to external perturbations. However, such systems are limited by the absence of cell-cell interactions and their dynamic nature, which are both present in vivo. In this review, we suggested two viable alternatives to in vivo tests to evaluate the health risk of human exposure to CNTs.

• Journal of Sensor Science and Technology
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• v.31 no.1
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• pp.6-11
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• 2022

To date, various techniques have been utilized to assess the contractility of cardiomyocytes and their response to drug-induced toxicity. However, these techniques are either invasive or involve complex fabrication methods and expertise. Here, we introduce the use of video-based analysis software to track the motion of cardiomyocytes and assess their contractility. The software, called "Tracker", is freely available and this is the first attempt at using it for cardiac contractility measurement. We used the software to measure the contractile properties of cells cultured on a rigid substrate and two flexible polydimethylsiloxane (PDMS) substrates having different elastic moduli day-wise up to eight days. Contractility was found to be highest in the most flexible substrate. Subsequently, the cardiotoxicity response of the cells on three different substrates was analyzed with verapamil. It was observed that the cells on rigid substrate were primarily affected by drug-induced toxicity, while the drug had a lesser impact on cells on the more flexible PDMS substrate. Evidently, the flexible substrate aided the maturation of cells and had lower drug toxicity, while the cells on PS could not fully mature. The assessment of cardiomyocytes using "Tracker" proved to be simple and reliable.

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.103-106
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• 2001

Bioluminescent bacteria fusing the stress promoter and lux gene have been developed as a toxicity biosensor. The light emitting bioluminescent bacteria have been used to measure the toxicity of many different chemicals. In this study, specially, DPD2540 (fabA::luxCDABE) was used to detect and classify phenolic toxicity to the cells membrane fatty acids, and then the relationship between phenolic toxicity and the distribution of various phenols in the cell was determined, with a model and equations provided. In addition, to show the possibility of detecting and classifying the toxicity of a chemical mixture, which may be present in wastewater, various bioluminescent bacteria having different stress promoters were used and their distinct response to the sample mixture was measured. To extend the applicable area of these bioluminescent bacteria to field, the portable biosensor using freeze-drying methods was developed and confirmed successfully.

• Environmental Analysis Health and Toxicology
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• v.30
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• pp.7.1-7.7
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• 2015

Objectives The widely promising applications of graphene nanomaterials raise considerable concerns regarding their environmental and human health risk assessment. The aim of the current study was to evaluate the toxicity profiling of graphene family nanano-materials (GFNs) in alternative in vitro and in vivo toxicity testing models. Methods The GFNs used in this study are graphene nanoplatelets ([GNPs]-pristine, carboxylate [COOH] and amide [$NH_2$]) and graphene oxides (single layer [SLGO] and few layers [FLGO]). The human bronchial epithelial cells (Beas2B cells) as in vitro system and the nematode Caenorhabditis elegans as in vivo system were used to profile the toxicity response of GFNs. Cytotoxicity assays, colony formation assay for cellular toxicity and reproduction potentiality in C. elegans were used as end points to evaluate the GFNs' toxicity. Results In general, GNPs exhibited higher toxicity than GOs in Beas2B cells, and among the GNPs the order of toxicity was pristine > $NH_2$ > COOH. Although the order of toxicity of the GNPs was maintained in C. elegans reproductive toxicity, but GOs were found to be more toxic in the worms than GNPs. In both systems, SLGO exhibited profoundly greater dose dependency than FLGO. The possible reason of their differential toxicity lay in their distinctive physicochemical characteristics and agglomeration behavior in the exposure media. Conclusions The present study revealed that the toxicity of GFNs is dependent on the graphene nanomaterial's physical forms, surface functionalizations, number of layers, dose, time of exposure and obviously, on the alternative model systems used for toxicity assessment.