• Communications for Statistical Applications and Methods
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• 제18권2호
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• pp.179-187
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• 2011

제 1상 입상시험의 주된 목적은 신약의 최대허용용량(Maximum tolerated dose; MTD)의 추정이다. 본 논문에서는 실험으로 얻어진 Dose-toxicity data를 S자 모형에 적합 시켜 MTD를 추정하는 방법을 제안하였다. 멈춤 규칙(stopping rule)에 의해 MTD가 결정되는 방법과 미리 정해진 표본수에서 실험을 종료하고 MTD를 추정하는 기존의 추정방법을 본 논문에서 제안한 방법과 모의실험을 통하여 비교하였다.

• 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.

• 대한암한의학회지
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• 제20권1호
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• pp.11-21
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• 2015

Objectives : The cancer incidence and cancer burden is increasing. In addition, the use of botanical agents in cancer care is increasing. This article aims to review a research strategy for botanical agents. Methods : The clinical studies of anticancer botanical agents and the papers about clinical research methodology of botanical agents were reviewed. Results : In phase I study, safety confirmation, optimal dose determination and drug interaction study are important. Most botanical agents have low toxicity and some have non-monotone dose response. Therefore, dose-response curve must be evaluated separately from the dose-toxicity curve to determine optimal dose. Although anticancer botanical agents can't shrink tumor size rapidly, they do extend survival. So, in phase II study, response should be evaluated by the survival. Conclusions : Clinical research of botanical agents in cancer is different from traditional methods and strategies. Considering the characteristics of botanical agents and experimental mechanism is necessary in conducting botanical based clinical trials.

• 한국방사선학회논문지
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• 제6권6호
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• pp.507-513
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• 2012

본 연구는 초상자성 산화철 나노입자 (SPIONs)의 세포독성평가 및 SPIONs를 uptake한 뇌신경교종 (glioblastoma multiforme, GBM) 세포의 방사선 세포생존곡선을 구하기 위해 수행되었으며, 본 연구의 결과는 양성자선과 SPIONs 이용한 GBM의 양성자선 치료선량 정보 등 양성자선 치료효과를 개선하기 위한 기초자료로 활용될 수 있을 것이다. SPIONs의 세포독성을 평가는 in vitro 실험 후 MTT 분석법을 이용하여 수행하였다. 독성평가 결과 $1{\sim}100{\mu}g/ml$의 농도에서는 세포생존율의 유의한 차이가 나타나지 않았다. 하지만 $200{\mu}g/ml$의 농도에서는 세포생존율이 74.2%로 감소하며 세포독성을 나타냈다. SPIONs가 uptake 된 U373MG세포와 uptake 되지 않은 U373MG세포에 0~5 Gy의 양성자선을 조사하여 각각에 대한 세포생존곡선을 측정한 결과를 분석하여 SPIONs가 uptake된 U373MG세포의 세포생존율이 더 급격히 감소함을 알 수 있었다. 결론적으로 SPIONs가 uptake 된 세포에서는 보다 적은 선량으로도 세포사멸을 유도할 수 있음을 알 수 있었다. 따라서 GBM에 SPIONs를 타겟팅하면 양성자선을 이용한 뇌신경교종 치료효과를 개선할 수 있음을 보였다.

• The Korean Journal of Physiology
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• 제7권2호
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• pp.67-70
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• 1973

This experiment was carried out to investigate the influence of adrenergic receptor blockade. on digitalis intoxication. The effects of adrenergic alpha and beta receptor blockade on the lethal dose of digitonin were evaluated. $LD_{50}$ and dose mortality curve of digitonin in mice pretreated with dibenzylin or propranolol hydrochloride (Inderal) were obtained. All drugs were injected subcutaneously. Digitonin toxicity was significantly decreased in mice pretreated with beta·blockade compare with alpha-blockade and control groups.

• 한국환경보건학회지
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• 제43권4호
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• pp.247-256
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• 2017

Objectives: The deaths of Korean victims exposed to the disinfectant CMIT/MIT have remained unresolved. This is mainly due to a lack of concordance between the few available toxicity tests and the abundant epidemiological data, making it difficult to establish a cause-and-effect relationship. Therefore, this study was carried out to investigate any potential associations between CMIT/MIT exposure and death. Methods: Groups of experimental and control C57BL/6 mice were instilled (in the trachea) with chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a visual instillobot. CMIT/MIT was instilled over a period of three days and eight weeks, respectively, to achieve acute and chronic exposures. A threshold dose-response model was applied for estimating the threshold level as one line of evidence for a causal association between CMIT/MIT and death. Results: An acute exposure of 1.2 mg ai/kg/day of CMIT/MIT was estimated to reflect the threshold for death. The dose-response curve with this threshold showed a very steep slope and a narrow range of CMIT/MIT exposures. The narrow range of CMIT/MIT exposures, in particular, indicated an evident boundary between survival and death, thus implicating a strong causal association. A similar threshold dose-response relationship observed following acute exposure was also seen following chronic exposure to CMIT/MIT. Airborne disinfectant exposure was visible as minimal or mild lung damage with no fibrosis, as shown by histopathological tests. However, many observations are considered to be functional respiratory tract or lung failure due to death, as observed in necropsies of the mice that died due to CMIT/MIT exposures. Conclusions: There are two strong lines of evidence for a causal association between death and CMIT/MIT exposure: 1) The threshold dose-response curve, with a very steep slope and a narrow range of CMIT/MIT exposures showing a visible boundary between survival and death; and 2) many cases of functional respiratory or lung failure.

• ALGAE
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• 제32권2호
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• pp.131-137
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• 2017

Although green algae of the genus Closterium are considered ideal models for testing toxicity in aquatic ecosystems, little data about the effects of toxicity on these algal species is currently available. Here, Closterium ehrenbergii was used to assess the acute toxicity of copper (Cu). The median effective concentration ($EC_{50}$) of copper sulfate based on a dose response curve was $0.202mg\;L^{-1}$, and reductions in photosynthetic efficiency ($F_v/F_m$ ratio) of cells were observed in cultures exposed to Cu for 6 h, with efficiency significantly reduced after 48 h (p < 0.01). In addition, production of reactive oxygen species significantly increased over time (p < 0.01), leading to damage to intracellular organelles. Our results indicate that Cu induces oxidative stress in cellular metabolic processes and causes severe physiological damage within C. ehrenbergii cells, and even cell death; moreover, they clearly suggest that C. ehrenbergii represents a potentially powerful test model for use in aquatic toxicity assessments.

• 대한약침학회지
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• 제25권3호
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• pp.290-300
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• 2022

Objectives: This study was conducted to evaluate the safety of SU-Eohyeol pharmacopuncture (SUEP) by assessing its potential to cause chromosomal abnormalities in Chinese hamster lung cells (CHL/IC). Methods: A dose-curve was conducted to determine the highest dose of SUEP. Doses of 10, 5, 2.5, 1.25, 0.625, and 0.313% were used, and no cytotoxicity or SUEP precipitation was observed. SUEP doses of 10, 5, and 2.5%, with positive and negative controls, were used in a chromosome aberration test. Results: In this study, the frequency of abnormal chromosomal cells in the SUEP group did not show a statistically significant difference from that of the negative control group in short-term treatments with and without metabolic activation and the continuous treatment without metabolic activation. Compared with the negative control group, the positive control group had a significantly higher frequency of cells with structural chromosomal abnormalities. This test's results satisfied all conditions for determining the results. Conclusion: SUEP did not induce chromosomal aberrations under the conditions of this study. Other toxicity evaluations, safety studies in humans, and various clinical trials are required to evaluate the safety and efficacy of SUEP.

• 대한약리학회지
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• 제4권1호
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• pp.33-36
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• 1968

The effect on schedule controlled behavior and toxicity of Atractylis alkaloid was investigated in the pigeons which were trained on a multiple fixed-ratio fixed-interval schedule of food presentation. Atractylis alkaloid decreased the rate of responding during both the fixed-interval and fixed ratio component of the schedule at 10 mg/kg. Further depression occurred at 30 mg/kg. This 'flat dose-response curve for depression of conditioned behavior was typical of tranquilizers. Conclusively it was suspected that Atractylis alkaloid had major tranquilizing activity.

• 한국토양비료학회지
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• 제45권6호
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• pp.1114-1119
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• 2012

$Ag^+$ 이온을 주성분으로 하는 $Ag^+N$과 $Ag^0$ 나노입자를 주성분으로 하는 $Ag^0NP$의 미생물학적 독성을 Microtox 생물검정법을 이용하여 수용액과 토양에서 용량-반응관계를 이용하여 비교, 평가하였다. 수용액 실험에서 Vibrio fisheri의 50% 발광 저해율을 보여주는 $EC_{50}$ 값은 $Ag^+N$이 $Ag^0NP$ 보다 현저히 낮게 나타나, 이온상태의 $Ag^+N$이 독성이 훨씬 높음을 알 수 있었다. 노출시간이 15분에서 30분으로 증가하면 독성 또한 증가했다. 반대로 토양 추출액 실험에서는 $Ag^+N$의 $ED_{50}$ 값이 $Ag^0NP$의 값 보다 높아, $Ag^+N$의 독성이 더 낮게 나타났다. 이것은 $Ag^+N$의 $Ag^+$가 토양 입자 또는 부식산에 강하게 흡착 되거나, Microtox 희석제 NaCl과 반응하여 난용해성 AgCl 침전물을 형성하여, 토양 추출액 중의 활성 Ag 농도가 감소한 것에 기인하는 것으로 판단되었다. Microtox 분석에 의한 Ag 나노용액의 생물학적 독성은 Ag의 존재형태 ($Ag^+$, $Ag^0$), 반응매질 (수용액, 토양), 노출시간에 따라 서로 상이한 결과를 보여 주었다.