• 한국환경보건학회지
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• 제45권5호
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• pp.457-464
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• 2019

Objectives: Quantitative structure-activity relationship (QSAR) is one of the effective alternatives to animal testing, but its credibility in terms of toxicity prediction has been questionable. Thus, this work aims to evaluate its predictive capacity and find ways of improving its credibility. Methods: Using $TOPKAT^{(R)}$, OECD toolbox, and $Derek^{(R)}$, all of which have been applied world-wide in the research, industrial, and regulatory fields, an analysis of prediction credibility markers including accuracy (A), sensitivity (S), specificity (SP), false negative (FN), and false positive (FP) was conducted. Results: The multi-application of QSARs elevated the precision credibility relative to individual applications of QSARs. Moreover, we found that the type of chemical structure affects the credibility of markers significantly. Conclusions: The credibility of individual QSAR is insufficient for both the prediction of chemical toxicity and regulation of hazardous chemicals. Thus, to increase the credibility, multi-QSAR application, and compensation of the prediction deviation by chemical structure are required.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.293-297
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• 2013

Background: : Chemotherapy-induced thrombocytopenia (CIT) is an important cause of morbitity in patients with cancer. Aim: To investigate the effect of the baseline plasma D-dimer level, an important marker for thrombotic activity, on chemotherapy-induced thrombocytopenia in patients with stage III colon cancer. Materials and Methods: A total of 43 (28 men) eligible patients were divided into two groups according to whether they exhibited chemotherapy-induced thrombocytopenia: Group 1 (n=21) and Group 2 (n=22). Comparison was made using demographic, histopathologic, and laboratory variables. Additionally, baseline plasma D-dimer levels underwent receiver operation characteristics curve analysis, and areas under the curve were calculated. Sensitivity, specificity, and positive and negative likelihood rates were then determined. Results: The incidence of chemotherapy-induced thrombocytopenia had a significant correlation with baseline platelet count (r=0.568, P=0.031) and baseline plasma D-dimer levels (r=0.617, P=0.036). When the cut-off point for the latter was set as 498 ng/mL, the area under the curve was 0.89 (95%CI: 0.74-0.93), the sensitivity was 91.4%, the specificity was 89.7%, the positive likelihood rate was 3.64 and the negative likelihood rate was 0.24 for chemotherapy-induced thrombocytopenia diagnosis. Conclusions: The baseline level of plasma D-dimer could help to differentiate high-risk patients for chemotherapy-induced thrombocytopenia.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.53-58
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• 2015

Background: The purpose of this study was to assess the the efficacy of oral glutamine (GLN) in prevention of acute radiation-induced esophagitis in patients with lung cancer and determine the predictive role of clinical and dosimetric parameters. Materials and Methods: Thirty-two patients diagnosed with lung cancer were studied prospectively. Sixteen patients (50%) received prophylactic powdered GLN orally in doses of 10g/8h. Patients were treated 2 Gy per fraction daily, 5 days a week. We evaluated the grading of esophagitis daily at the end of each fraction of each treatment day until a cumulative dose of 50 Gy was reached. The primary end point was radiation-induced esophagitis. Results: All patients tolerated GLN well. Toxicity grade, weight loss, serum cytokine levels and esophageal transit times exhibited statistically significant improvement in the GLN receiving group. GLN suppressed the inflammation related to the disease and treatment and reduced toxicity with statistical significance. Conclusions: This study suggests a benefical role of oral GLN use in prevention and/or delay of radiation-induced esophagitis, in terms of esophageal transit time and serum immunological parameters, as well as weight loss.

• 한국산업보건학회지
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• 제29권2호
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• pp.141-158
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• 2019

Objectives: An adverse outcome pathway is a biological pathway that disturbs homeostasis and causes toxicity. It is a conceptual framework for organizing existing biological knowledge and consists of the molecular initiating event, key event, and adverse output. The AOP concept provides intuitive risk identification that can be helpful in evaluating the carcinogenicity of chemicals and in the prevention of cancer through the assessment of chemical carcinogenicity predictions. Methods: We reviewed various papers and books related to the application of AOPs for the prevention of occupational cancer. We mainly used the internet to search for the necessary research data and information, such as via Google scholar(http://scholar.google.com), ScienceDirect(www.sciencedirect.com), Scopus(www.scopus. com), NDSL(http: //www.ndsl.kr/index.do) and PubMed(http://www.ncbi.nlm.nih.gov/pubmed). The key terms searched were "adverse outcome pathway," "toxicology," "risk assessment," "human exposure," "worker," "nanoparticle," "applications," and "occupational safety and health," among others. Results: Since it focused on the current state of AOP for the prediction of toxicity from chemical exposure at work and prospects for industrial health in the context of the AOP concept, respiratory and nanomaterial hazard assessments. AOP provides an intuitive understanding of the toxicity of chemicals as a conceptual means, and it works toward accurately predicting chemical toxicity. The AOP technique has emerged as a future-oriented alternative to the existing paradigm of chemical hazard and risk assessment. AOP can be applied to the assessment of chemical carcinogenicity along with efforts to understand the effects of chronic toxic chemicals in workplaces. Based on these predictive tools, it could be possible to bring about a breakthrough in the prevention of occupational and environmental cancer. Conclusions: The AOP tool has emerged as a future-oriented alternative to the existing paradigm of chemical hazard and risk assessment and has been widely used in the field of chemical risk assessment and the evaluation of carcinogenicity at work. It will be a useful tool for prediction, and it is possible that it can help bring about a breakthrough in the prevention of occupational and environmental cancer.

• 한국환경성돌연변이발암원학회지
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• 제21권2호
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• pp.118-121
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• 2001

The predictive screening of various molecular descriptors for predicting carcinogenic, mutagenic, teratogenic and alkylation activity of chlorinated disinfection byproducts (DBPs) has been investigated for the application of quantitative structure-activity relationships (QSAR). The toxicity index for 29 compounds were computed by the PASS program and active values were employed in this study. Studies show that different descriptors account for the model equation of each genotoxic endpoint and that thermodynamic descriptors significantly played a major role on prediction of endpoints of chlorinated aliphatic compounds.

• 한국식품영양과학회:학술대회논문집
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• 한국식품영양과학회 2003년도 정기총회 및 54차 학술발표회:건강기능식품의 유효성평가
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• pp.74-77
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• 2003

A new health paradigm may be evolving that would place emphasis on the positive aspects of diet, identifying components that are physiologically active and that contribute to the prevention of disease onset. It has been increasingly difficult to evaluate the impact of new bioactive materials and food products on the well being of society. Thus, testing systems for both health function and toxicity have become very elaborate, complex, and interrelated, making their interpretation difficult and open to controversy. To select the proper starting materials, to screen the appropriate health functionality and to determine the efficacy of product, a reliable, reproducible, sensitive and predictive assay is required. Particularly, in uitro assay is the first stage in preclinical test on physiologically active materials and have many advantages in terms of time, cost and convenience. However, several factors as well as some limitations should be considered in this assay system. This presentation, therefore, will address the use of in uitro assays for evaluating physiological functionality of foods coupled with general consideration.

• Molecular & Cellular Toxicology
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• 제2권3호
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• pp.216-221
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• 2006

The cholinesterase-inhibiting organophosphorous (OP) compounds known as nerve agents are highly toxic. The principal toxic mechanism of OP compounds is the inhibition of acethylcholine esterase (AChE) by phosphorylation of its catalytic site. The reversible competitive inhibition of AChE may prevent the subsequent OP intoxication. In this study, three-dimensional quantitative structure-activity relationship (3D-QSAR) was performed to investigate the relationship between the 29 compounds with structural diversity and their bioactivities against AChE. In particular, predictive models were constructed using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The results indicate reasonable model for CoMFA ($q^{2}=0.453,\;r^{2}=0.697$) and CoMSIA ($q^{2}=0.518,\;r^{2}=0.696$). The presence of steric and hydophobic group at naphtyl moiety of the model may lead to the design of improved competitive inhibitors for organophosphorous intoxication.

• Biomolecules & Therapeutics
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• 제14권4호
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• pp.183-188
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• 2006

The field of cytochrome P450 pharmacogenomics has progressed rapidly during the past 25 years. Recently, conjugating enzymes including sulfotransferase, acetyltransferase, glucuronosyltransferase and glutathione transferase have been also extensively studied. All the major human drug-metabolizing P450 enzymes and some conjugating enzymes have been identified and cloned, and the major gene variants that cause inter-individual variability in drug response and are related to adverse drug reactions have been identified. This information now provides the basis for the use of predictive pharmacogenomics to yield drug therapies that are more efficient and safer. Today, we understand which drugs warrant dosing based on pharmacogenomics to improve drug treatment. It is anticipated that genotyping could be used to personalize drug treatment for vast numbers of subjects, decreasing the cost of drug treatment and increasing the efficacy of drugs and health in general. It is assumed that such personalized P450 gene-based treatment which is so-called tailor(order)-made drug therapy would be relevant for 10-20% of all drug therapy in the future.

• 한국해양환경ㆍ에너지학회지
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• 제15권4호
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• pp.281-291
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• 2012

MPUV와 Plasma를 사용하여 선박의 평형수를 처리하는 ARA Plasma BWTS가 개발되었으며, 이로부터 방류되는 배출수가 해양생태계 미치는 영향을 파악하기 위하여 Skeletonema costatum, Tigriopus japonicus 및 Paralichthys olivaceus를 이용하여 배출수독성시험과 생성된 화학물질에 대한 환경위해성을 평가하였다. 34 psu 배출수는 P. olivaceus에 대하여 미약한 만성 독성영향을 보였다($7d-LC_{50}{\Rightarrow}100.00%$ 배출수, $7d-LC_{25}{\Rightarrow}85.15%$ 배출수). 34 psu 배출수에서 Bromobenzene, chlorobenzene과 4-chlorotoluene이 해수의 배경농도보다 높게 검출되었다. MAMPEC을 이용한 Bromobenzene, chlorobenzene과 4-chlorotoluene의 PEC 산출결과는 각각 3.34E-03, 2.10E-03 및 1.73E-03 ${\mu}g\;L^{-1}$이었고, PNEC는 1.6, 0.5 및 1.9 ${\mu}g\;L^{-1}$였다. 세 화학물질의 PEC/PNEC 비율은 1을 초과하지 않았고, PBT 특성을 보이지 않았다. 따라서 WET test 결과와 환경위해성평가결과는 ARA Plasma BWTS에 의하여 처리된 해수가 해양생태계에 수용 불가한 영향을 미치지 않을 것임을 시사하였다.

• 한국정보통신학회:학술대회논문집
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• 한국정보통신학회 2022년도 춘계학술대회
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• pp.276-278
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• 2022

모든 약물은 신체 내에서 특정한 작용을 하며, 많은 경우 합병증 또는 기존 약물치료 중 새롭게 발생하는 증상에 의해 약물이 혼용되는 경우가 발생한다. 이런 경우 신체 내에서 예상치 못한 상호작용이 발생할 수 있다. 따라서 약물 간 상호작용을 예측하는 것은 안전한 약물 사용을 위해 매우 중요한 과제이다. 본 연구에서는 다중 약물 사용 시 발생 가능한 약물 간 상호작용 예측을 위해 약물 정보 문서를 이용해 학습시키는 딥러닝 기반의 예측 모델을 제안한다. 약물 정보 문서는 DrugBank 데이터를 이용해 약물의 작용 기전, 독성, 표적 등 여러 속성을 결합해 생성되었으며, 두 약물 문서가 한 쌍으로 묶여 딥러닝 기반 예측 모델에 입력으로 사용되고 해당 모델은 두 약물 간 상호작용을 출력한다. 해당 연구는 임베딩 방법이나 데이터 전처리 방법 등 다양한 조건의 변화에 따른 실험 결과의 차이를 분석하여 차후 새로운 약물쌍 간 상호작용을 예측하는 데에 활용이 가능하다.