• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4703-4706
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• 2012

Objective: To compare efficacy and safety profile of vinorelbine, ifosfamide and cisplatin (NIP) with etoposide and cisplatin (EP) in the treatment of advanced combined small cell lung cancer (c-SCLC). Methods: From January 2006 to December 2010, 176 patients with advanced c-SCLC were enrolled. The primary endpoint was overall survival (OS) and the secondary endpoints were progression free survival (PFS), response rate (RR) and toxicity. Results: Overall RR was 30.0% in the NIP and 38.5% in the EP group; there was no significant difference (P=0.236). The PFS in the EP group was little longer than that of NIP group, with 6.5 months for EP and 6.0 months for NIP group, but the difference was statistically non-significant (P=0.163). The median OS and one year survival rates were 10.4 months and 36.3% for NIP group, and 10.8 months and 49.0% for EP respectively, EP showing a survival benefit, although this was not statistically significant. Both groups well tolerated the adverse effects. The incidence of grade I-II leucopenia and alopecia in the NIP group was significantly higher than that of EP group (32.5% vs. 10.4% (P<0.001, 35.0% vs. 12.5%, P<0.001). Conclusion: the ORR, PFS and OS in NIP were slightly inferior to traditional regimen EP. The toxicity of NIP can be considered tolerable. The usage of three drugs combination in the treatment of mixed SCLC remains uncertain. Nevertheless, the results need to be further confirmed by large, prospective clinical trials.

• Journal of Ecology and Environment
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• v.41 no.11
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• pp.318-327
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• 2017

Background: A typical sewage treatment plant is designed for organic and nutrient removal from municipal sewage water and not targeted to eliminate micropollutants such as pesticides, pharmaceuticals, and nano-sized metals which become a big concern for sustainable human and ecological system and are mainly discharged from sewage treatment plant. Therefore, despite contaminant removal by wastewater treatment processes, there are still remaining environmental risks by untreated pollutants in STP (sewage treatment plant) effluents. This study performed aquatic toxicity tests of raw wastewater and treated effluents in two sewage treatment plants to evaluate toxicity reduction by wastewater treatment process and analyze concentration of contaminants to reveal potential toxic factors in STP effluents. Methods: Water samples were collected from each treatment steps of two STPs, and acute and chronic toxicity tests were conducted following USEPA (United States Environmental Protection Agency) and OECD (Organization for Economic Cooperation and Development) guidelines. Endpoints were immobility for mortality and reproduction effect for estrogenicity. Results: Acute $EC_{50}s$ (median effective concentration) of influents for Seungki (SK) and Jungnang (JN) STPs are $54.13{\pm}32.64%$ and $30.38{\pm}24.96%$, respectively, and reduced to $96.49{\pm}7.84%$ and 100%. Acute toxicity reduction was clearly correlated with SS (suspended solids) concentration because of filter feeding characteristics of test organisms. Chronic toxicity tests revealed that lethal effect was reduced and low concentration of influents showed higher number of neonates. However, toxicity reduction was not related to nutrient removal. Fecundity effect positively increased in treated wastewater compared to that in raw wastewater, and no significant differences were observed compared to the control group in JN final effluent implying potential effects of estrogenic compounds in the STP effluents. Conclusions: Conventional wastewater treatment process reduced some organics and nutritional compounds from wastewater, and it results in toxicity reduction in lethal effect and positive reproductive effect but not showing correlation. Unknown estrogenic compounds could be a reason causing the increase of brood size. This study suggests that pharmaceutical residues and nanoparticles in STP effluents are one of the major micropollutants and underline as one of estrogenic effect factors.

• Environmental Mutagens and Carcinogens
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• v.21 no.2
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• pp.77-81
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• 2001

Kamijadowhan (KMD), an oriental herbal medicine used for anti-angiogenic effect, was extracted with 80% ethanol from mixture of source materials and lyophilized. KMD was orally administered to plugpositive pregnant rats from gestational days 12 to 20, dividing into three groups including vehicle-treated control, 0.5 g/kg or 3 g/kg KMD-treated groups. Dam weight during gestation and post-gestation, weight of pre- and post-weaning offsprings in male and female, and reproductive and developmental endpoints including incisor eruption, eye opening and testes descent were measured. No significant alterations in development of physical landmarks in offspring, maternal weight gain during gestation and post-gestation, and offspring weight were observed in KMD-treated group. The measurement of organ weight at post-gestational days 21 was not changed in dams. In 0.5 g/kg KMD-treated rats, kidney weights in male and female offsprings were significantly increased, and the body weight in male offspring was also increased. Liver and brain weights were not changed. Taken together, these data suggest that KMD may not significantly cross the placenta and produce no reproductive and developmental toxicity at maternally non-toxic dosages.

• Korean Journal of Clinical Pharmacy
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• v.15 no.1
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• pp.1-8
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• 2005

Clopidogrel is used to reduce the risk of cardiovascular events in patients with atherosclerosis documented by recent ischemic stroke, recent myocardial infarction (MI), or established peripheral arterial disease (secondary prevention). Clopidogrel is metabolized by CYP3A4, and the active metabolites inhibit platelet aggregation. The purpose of this study was to assess clopidogrel only versus clopidogrel + others (aspirin, CYP3A4 inhibitor, and CYPBA4 inducer) in terms of cardiovasculalr events and bleeding complications. We reviewed the charts of patients who visited between August 1, 2002 and August 31, 2003, retrospectively. Total 72 patients were included and they consisted of 5 groups; clopidogrel group (n=36), clopidogrel + aspirin group (n=11), clopidogrel + CYP3A4 inhibitor group (n=15), clopidogrel + aspirin + CYP3A4 inhibitor group (n=6), clopidorel + CYP3A4 inducer group (n=4). The primary endpoints at 6 months, 12 months were the composite of cardiovascular (CV) events. The secondary end-point was the incidence of bleeding events at 6months, and 12months. At 12months, the primary endpoint was not significantly different among the five groups (p=0.056). In comparison of two groups as clopidogrel only versus clopidogrel + others (aspirin, CYP3A4 inhibitor and CYP3A4 inducer), the primary endpoint was significantly different (p=0.02). The CV events were increased in the clopidogrel + others group. The secondary end point was not significantly different among the five groups (p=0.52). However, time to bleeding events was 230.8 in the clopidogrel group and 74.7 in the clopidogrel + others group (p = 0.046). In conclusion, clopidogrel interaction with aspirin, CYP3A4 inhibitor, and CYP3A4 inducer affected cardiovascular events and bleeding events. Drug interaction of clopidogrel with concurrent medications should be considered cautiously.

• Journal of Food Hygiene and Safety
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• v.31 no.5
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• pp.356-364
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• 2016

In vivo genotoxic potential of isoquercetin, a plant common flavonoid, in comparison with quercetin was investigated for the DNA breakage and the clastogenicity endpoints. Male ICR mice were administered by oral gavage for 3 days with $3{\times}0.5%$ carboxymethyl cellulose (CMC), 3 ${\times}$ isoquercetin (250, 500 mg/kg/day), 3 ${\times}$ quercetin (250, 500 mg/kg/day) and 2 ${\times}$ ethyl methanesulfonate (EMS, 200 mg/kg/day). Tissues were collected 48 hours after the first treatment and within 3 hours after the last treatment. The DNA damages were evaluated using Comet assay in liver and stomach, while the clastogenicities were determined using micronucleus test in bone marrow of same animals. The treatment of isoquercetin as well as quercetin did not cause the DNA damages in liver and stomach, and not induce the frequencies of micronucleus polychromatic erythrocytes in bone marrow. In conclusion, isoquercetin as well as quercetin did not cause the DNA breakages and the chromosomal damages in vivo system in these study conditions.

• Toxicological Research
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• v.28 no.2
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• pp.81-91
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• 2012

Many risk factors exist for chemotherapy-induced nausea and vomiting (CINV). This study utilized a multivariate projection technique to identify which risk factors were predictive of CINV in clinical practice. A single-centre, prospective, observational study was conducted from January 2007~July 2010 in Singapore. Patients were on highly (HECs) and moderately emetogenic chemotherapies with/without radiotherapy. Patient demographics and CINV risk factors were documented. Daily recording of CINV events was done using a standardized diary. Principal component (PC) analysis was performed to identify which risk factors could differentiate patients with and without CINV. A total of 710 patients were recruited. Majority were females (67%) and Chinese (84%). Five risk factors were potential CINV predictors: histories of alcohol drinking, chemotherapy-induced nausea, chemotherapy-induced vomiting, fatigue and gender. Period (ex-/current drinkers) and frequency of drinking (social/chronic drinkers) differentiated the CINV endpoints in patients on HECs and anthracycline-based, and XELOX regimens, respectively. Fatigue interference and severity were predictive of CINV in anthracycline-based populations, while the former was predictive in HEC and XELOX populations. PC analysis is a potential technique in analyzing clinical population data, and can provide clinicians with an insight as to what predictors to look out for in the clinical assessment of CINV. We hope that our results will increase the awareness among clinician-scientists regarding the usefulness of this technique in the analysis of clinical data, so that appropriate preventive measures can be taken to improve patients' quality of life.

• YAKHAK HOEJI
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• v.40 no.2
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• pp.218-224
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• 1996

This laboratory has recently reported the synthesis and in vitro antitumor activity of PT(II) complexes containing ethylenediamine and diphosphine. In view of the reports of others, cisplatin is toxic to the kidney since the kidney's vulnerability to PT(II) complexes may originate in its ability to accumulate and retain platinum to a greater degree than other organs. The in vitro cytotoxicity of these synthetic PT(II) complexes on the primary cultured proximal tubular cells of rabbit kidney and renal cortical cells of human kidney was investigated. Three endpoints for cytotoxicity tests were evaluated:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), $^3H$-thymidine uptake and the glucose consumption tests. The rank order of sensitivity exhibited $^3H$-thymidine uptake>MTT>glucose consumption test. The agents with diphosphine leaving group were significantly less cytotoxic than cisplatin. Moreover, 1,2-bis(diphenylphosphino)ethane (DPPE) exhibited less cytotoxicity than 1.3-bis (diphenylphosphino)propane (DPPP) against on rabbit and human cultured kidney cells. Based on these results, the decreased nephrotoxicity of these new complexes over cisplatin appeared to be partially attributable to a leaving group of DPPP and DPPE. This novel class of platinum compound represents a valuable lead in the development of a "third-generation" agent.

• Journal of the Korea Institute of Information Security & Cryptology
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• v.28 no.2
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• pp.457-469
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• 2018

This study aimed to investigate the fundamental reasons for the presence of multi-homed host and the risks associated with such risky system. Furthermore, multi-homed host detection methods that have been researched and developed so far were compared and analyzed to determine areas for improvement. Based on the results, we propose the model of an improved automatic detection system and we implemented it. The experimental environment was configured to simulate the actual network configuration and endpoints of an organization employing network segmentation. And the functionality and performance of the detection system were finally measured while generating multi-homed hosts by category, after the developed detection system had been installed in the experiment environment. We confirmed that the system work correctly without false-positive, false-negative in the scope of this study. To the best of our knowledge, the presented detection system is the first academic work targeting multi-homed host under agent-based.

• The KIPS Transactions:PartC
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• v.17C no.3
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• pp.299-306
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• 2010

IPTV and VoIP services are considered as killer applications over Mobile WiMAX network, which provideshigh mobility and data rate. Among those which affect the quality of voice in those services, the jitter buffer or playout buffer can compensate the poor voice quality caused by the packet drop due to frequent route change or differences among routes between service endpoints. In this paper, we analyze the correlation between the sleep interval length and jitter buffer size in order to guarantee a predefined level of voice quality. For this purpose, we present an end-to-end delay model considering additional delay incurred by the WiMAX PSC-II sleep mode and a VoIP service quality requirement based on the delay constraints. Through extensive simulation experiments, we also show that the increase of jitter buffer size may degrade the voice quality since it can introduce additional packet drop in the jitter buffer under WiMAX power saving mode.

• Biomolecules & Therapeutics
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• v.26 no.4
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• pp.417-423
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• 2018

Extracellular interleukin 1 alpha (IL-$1{\alpha}$) released from keratinocytes is one of the endpoints for in vitro assessments of skin irritancy. Although cells dying via primary skin irritation undergo apoptosis as well as necrosis, IL-$1{\alpha}$ is not released in apoptotic cells. On the other hand, active secretion has been identified in interleukin-1 receptor antagonist (IL-1ra), which was discovered to be a common, upregulated, differentially-expressed gene in a microarray analysis performed with keratinocytes treated using cytotoxic doses of chemicals. This study examined whether and how IL-1ra, particularly extracellularly released IL-1ra, was involved in chemically-induced keratinocyte cytotoxicity and skin irritation. Primary cultured normal adult skin keratinocytes were treated with cytotoxic doses of chemicals (hydroquinone, retinoic acid, sodium lauryl sulfate, or urshiol) with or without recombinant IL-1ra treatment. Mouse skin was administered irritant concentrations of hydroquinone or retinoic acid. IL-1ra (mRNA and/or intracellular/extracellularly released protein) levels increased in the chemically treated cultured keratinocytes with IL-$1{\alpha}$ and IL-$1{\beta}$ mRNAs and in the chemically exposed epidermis of the mouse skin. Recombinant IL-1ra treatment significantly reduced the chemically-induced apoptotic death and intracellular/extracellularly released IL-$1{\alpha}$ and IL-$1{\beta}$ in keratinocytes. Collectively, extracellular IL-1ra released from keratinocytes could be a compensatory mechanism to reduce the chemically-induced keratinocyte apoptosis by antagonism to IL-$1{\alpha}$ and IL-$1{\beta}$, suggesting potential applications to predict skin irritation.