• Communications for Statistical Applications and Methods
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• 제6권2호
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• pp.543-564
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• 1999

The principal aim of a sequential phase I clinical trial in which the toxicity reponses of a group of patient(s) determine the dose level of the next patient(s) group is to estimate the maximal tolerated dose(MTD) of a new drug, In this paper we compared with a simulation study the performance of the MTD estimates that are determined by a stopping rule in a design and also those that are determined by analyzing the data after a clinical trial is terminated. To the latter belong the mean median mode and maximum likelihood estimates. For the Standard Methods the stopping rule MTD is quite inefficient but the median MTD has a best efficiency and is robust with respect to the three different toxicity curves. The problem of non-convergence of MLE MTD is severe. A more improved MTD estimate is produced by combining the advantages of the various MTD estimates and its efficiency is better than the single median MTD estimate especially for the toxicity curve of an unlucky choice of dose levels. The simulation results suggest that simple types of phase I designs can be combined with relatively standard analytic techniques to provide a more efficient MTD estimate.

• 한국식품영양과학회지
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• 제30권2호
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• pp.234-238
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• 2001

In order to evaluate their possible subacute toxicity, groups of 40 male and female ICR mice were given to the diet with chickens irradiated up to 30 kGy for four weeks. During the experimental periods, appearance, behavior, mortality, food and water consumption of mice fed irradiated chickens were not affected compared to the control. In urine analysis, hematological as well as in serum biochemical findings, no significant differences were found between the control (non-irradiated) and the irradiated chickens. Although minor changes in biochemical parameters were observed, they were in the normal range and were not dose dependent. Spotty necrosis was found in the male liver administered with 30 kGy irradiated chicken. However, it seems not related with gamma irradiation, because it lacks either the dose dependency and the secondary changes accompanied. Our results indicate that the adverse effect of gamma irradiated chicken can be observed at more than 30 kGy level.

• 한국수정란이식학회지
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• 제30권1호
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• pp.1-6
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• 2015

The cold shock of spermatozoa is associated with oxidative stress induced by reactive oxygen species. This study was conducted to evaluate the toxicity of natural antioxidant green tea extract (GTE) in lactose-egg yolk (LEY) extender during boar sperm cooling prior to freezing. Spermatozoa were cooled to $5^{\circ}C$ for 3 h in LEY extender containing 0 (control), 1, 10, 100 or 1,000 mg/l of GTE, re-suspended with LEY-glycerol-Equex extender and cooled at $5^{\circ}C$ for 30 min. Sperm progressive motility, viability and phosphatidylserine (PS) translocation were evaluated. PS translocation was assayed by flow cytometry using Annexin V-FITC apoptosis detection kit. The sperm function including progressive motility, viability and PS translocation was not significantly different regardless of GTE concentrations (P>0.05). In conclusion, this study demonstrated non-toxicity of GTE supplement in LEY extender during sperm cooling.

• 한국임상약학회지
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• 제12권1호
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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.

• Molecules and Cells
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• 제41권12호
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• pp.1052-1060
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• 2018

Triclosan (TCS) is a phenolic antimicrobial chemical used in consumer products and medical devices. Evidence from in vitro and in vivo animal studies has linked TCS to numerous health problems, including allergic, cardiovascular, and neurodegenerative disease. Using Caenorhabditis elegans as a model system, we here show that short-term TCS treatment ($LC_{50}$: ~0.2 mM) significantly induced mortality in a dose-dependent manner. Notably, TCS-induced mortality was dramatically suppressed by co-treatment with non-ionic surfactants (NISs: e.g., Tween 20, Tween 80, NP-40, and Triton X-100), but not with anionic surfactants (e.g., sodium dodecyl sulfate). To identify the range of compounds susceptible to NIS inhibition, other structurally related chemical compounds were also examined. Of the compounds tested, only the toxicity of phenolic compounds (bisphenol A and benzyl 4-hydroxybenzoic acid) was significantly abrogated by NISs. Mechanistic analyses using TCS revealed that NISs appear to interfere with TCS-mediated mortality by micellar solubilization. Once internalized, the TCS-micelle complex is inefficiently exported in worms lacking PMP-3 (encoding an ATP-binding cassette (ABC) transporter) transmembrane protein, resulting in overt toxicity. Since many EDCs and surfactants are extensively used in commercial products, findings from this study provide valuable insights to devise safer pharmaceutical and nutritional preparations.

• Journal of Veterinary Science
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• 제23권2호
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• pp.26.1-26.12
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• 2022

Background: Glutamate is the main excitatory neurotransmitter. Excessive glutamate causes excitatory toxicity and increases intracellular calcium, leading to neuronal death. Parvalbumin is a calcium-binding protein that regulates calcium homeostasis. Quercetin is a polyphenol found in plant and has neuroprotective effects against neurodegenerative diseases. Objectives: We investigated whether quercetin regulates apoptosis by modulating parvalbumin expression in glutamate induced neuronal damage. Methods: Glutamate was treated in hippocampal-derived cell line, and quercetin or vehicle was treated 1 h before glutamate exposure. Cells were collected for experimental procedure 24 h after glutamate treatment and intracellular calcium concentration and parvalbumin expression were examined. Parvalbumin small interfering RNA (siRNA) transfection was performed to detect the relation between parvalbumin and apoptosis. Results: Glutamate reduced cell viability and increased intracellular calcium concentration, while quercetin preserved calcium concentration and neuronal damage. Moreover, glutamate reduced parvalbumin expression and quercetin alleviated this reduction. Glutamate increased caspase-3 expression, and quercetin attenuated this increase in both parvalbumin siRNA transfected and non-transfected cells. The alleviative effect of quercetin was statistically significant in non-transfected cells. Moreover, glutamate decreased bcl-2 and increased bax expressions, while quercetin alleviated these changes. The alleviative effect of quercetin in bcl-2 family protein expression was more remarkable in non-transfected cells. Conclusions: These results demonstrate that parvalbumin contributes to the maintainace of intracellular calcium concentration and the prevention of apoptosis, and quercetin modulates parvalbumin expression in glutamate-exposed cells. Thus, these findings suggest that quercetin performs neuroprotective function against glutamate toxicity by regulating parvalbumin expression.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4801-4804
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• 2013

Purpose: To investigate short-term response rate, quality of life and toxicities of mannan peptide combined with TP regimen in treating patients with non-small cell lung cancer (NSCLC). Patients and Methods: Forty one patients with NSCLC were divided into an experimental group treated with TP regimen combined with mannan peptide (21 patients) and a control group treated with TP alone (20 patients). Results: Response rates were 61.9% (13/21) for the experimental and 60% (12/20) for the control group (p>0.05). Regarding toxicity, white blood cell decreased more frequently in the control group (65%, 13/20) than in the experimental group (33.3%, 7/21) (p<0.05); nausea and vomiting also occurred more frequently in the control group (55%, 11/20 vs 23.8%, 5/21) (p<0.05). In terms of quality of life, this index was improved by 57.1% (12/21) and 25% (5/20) in experimental and control groups, respectively (p<0.05). Conclusions: Response rate of TP after combined with mannan peptide is mildly increased, while this combination alleviates bone marrow suppression as well as nausea and vomiting of TP, and improves quality of life when treating patients with NSCLC. However, this conclusion should be confirmed by randomized clinical trails.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3419-3424
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• 2014

Background: Our aim was to conduct a meta-analysis to compare the efficacy and safety of pemetrexed and docetaxel for non-small cell lung cancer (NSCLC). Materials and Methods: We systematically searched the Cochrane Library, PubMed, Embase, China Biology Medicine Database for randomized controlled trials (RCTs) comparing the efficacy and toxicities of pemetrexed versus docetaxel as a treatment for advanced NSCLC. We limited the languages to English and Chinese. Two reviewers independently screened articles to identify eligible trials according to the inclusion and exclusion criteria and assessed the methodological quality of included trials, and then extracted data. The meta-analysis was performed using STATA12.0. Results: Six RCTs involving 1,414 patients were identified. We found that there was no statistically significant differences in overall response rate, survival time, progression-free survival, disease control rate, and 1-2yr survival rate (p>0.050) but it is worthy of mention that patients in the pemetrexed arms had significantly higher 3-yr survival rate (P=0.002). With regard to the grade 3 or 4 hematological toxicity, compared with docetaxel, pemetrexed led to lower rate of grade 3-4 febrile neutropenia, neutropenia, and leukocyts toxicity (p<0.001). There was no significant difference in anemia between the two arms (p=0.08). In addition, pemetrexed led to higher rate of grade 3-4 thrombocytopenia toxicity (p=0.03). As for the non-hematological toxicities, compared with docetaxel, pemetrexed group had lower rate of grade 3-4 diarrhea and alopecia. Conclusions: Pemetrexed was almost as effective as docetaxel in patients with advanced NSCLC. At the same time, pemetrexed might increase the 3-yr survival rate. As for safety, pemetrexed led to lower rate of grade 3-4 febrile neutropenia, neutropenia, leukocytes, diarrhea and alopecia toxicity. However, it was associated with a higher rate of grade 3-4 thrombocytopenia.

• 한국환경보건학회지
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• 제30권4호
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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.

• 대한예방한의학회지
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• 제20권1호
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• pp.125-144
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• 2016

Objectives : About 13% of the medicines used by traditional korean medicines(TKM), are called animal medicines and are derived from non-herbal sources such as animals and insects. However, the clinical use of these preparations from animal medicines is often based on tradition and belief, rather than on evidence of toxicity and efficacy. As a result, animal medicines containing toxin have caused serious problems from injecting patients with venom. Here, various venoms frequently used as TKM were reviewed in terms of their instinct toxity and tried to estimate their safety classification. Methods : The estimation of safety classification was based on human equivalent dose(HED)-based MOS (margin of safety) and clinical dose applied for patients. Results and Conclusions : Except that of snake venom due to no clinical dose, they were evaluated as class 3 for bee venom, class 4 for cantharidin, toxin from blister beetle, and class 1 for venom from scolopendrid. In conclusion, animal medicines showed a wide range of safety classification from class 1 to class 4. This wide range is estimated to result from extremely limited applications of each venom for patients because of their strong toxicity. However, it should be cautious for application in clinics since animal medicines can produce anaphylactic reactions particularly after veinous administration even with a tiny amount of venom.