• Korean Journal of Clinical Pharmacy
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• v.26 no.2
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• pp.150-162
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• 2016

Objective: First-in-human dose estimation is an essential approach for successful clinical trials for drug development. In this study, we systematically compared first-in-human dose and human pharmacokinetic parameter estimation approaches. Methods: First-in-human dose estimation approaches divided into similar drug comparison approaches, regulatory guidance based approaches, and pharmacokinetic based approaches. Human clearance, volume of distribution and bioavailability were classified for human pharmacokinetic parameter estimation approaches. Results: Similar drug comparison approaches is simple and appropriate me-too drug. Regulatory guidance based approaches is recommended from US Food and Drug Administration (FDA) and European Medicines Agency (EMA) regarding no-observed-adverse-effect level (NOAEL) or minimum anticipated biological effect level (MABEL). Pharmacokinetic based approaches are 8 approaches for human clearance estimation, 5 approaches for human volume of distribution, and 4 approaches for human bioavailability. Conclusion: This study introduced and compared all methods for first-in-human dose estimation. It would be useful practically to estimate first-in-human dose for drug development.

• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.648-658
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• 2017

7-O-Succinyl macrolactin A (SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anti-cancer activities. Recently, SMA has been extensively evaluated as an anti-cancer drug. Thus, the objectives of the present study were to characterise the pharmacokinetics of SMA via both non-compartmental and compartmental analysis in mice, rats, and dogs, and to derive an appropriate first-in-man dose based on allometric scaling of the animal data. The time courses of plasma SMA concentrations after intravenous administration to rats and dogs were analysed retrospectively, as were data collected after intraperitoneal SMA injection in mice. Pharmacokinetic parameters were estimated via both noncompartmental and compartmental analysis, and were correlated with body weight and/or the potential maximum life-span. The clearance and distribution volume of SMA in humans were predicted, and a first-in-man dose proposed. A two-compartment model best described the time courses of SMA plasma concentrations after a saturation elimination process was applied to fit the dataset obtained from rats. Incorporation of the maximum potential life-span during allometric scaling was required to improve the estimation of human clearance. The SMA clearance and the distribution volume in the steady state, in a 70-kg adult male, were estimated to be 30.6 L/h and 19.5 L, respectively. To meet the area under the curve (AUC) required for anti-tumour activity, a dose of 100 mg (~1.5 mg/kg) was finally proposed as the first dose for a 70-kg human. Although toxicological profiles derived from non-clinical studies must be considered before any final decision is made, our work will facilitate clinical studies on SMA.

• Nuclear Engineering and Technology
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• v.45 no.1
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• pp.1-12
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• 2013

This paper describes the radiation doses to human and non-human biota in the Republic of Korea, as a result of the Fukushima nuclear accident. By using the measured airborne activity and ground deposition, the effective and thyroid doses of five human age groups (infant, 5 years, 10 years, 15 years and adult) were estimated by the ECOSYS code, and the whole body absorbed dose rate of the eight Korean reference animals and plants (RAPs) was estimated by the K-BIOTA (the Korean computer code to assess the risk of radioactivity to wildlife). The first-year effective and thyroid human doses ranged from 5.7E-5 mSv in the infant group to 2.0E-4 mSv in the 5 years group, and from 5.0E-4 mSv in the infant group to 3.4E-3 mSv in the 5 years group, respectively. The life-time (70 years) effective and thyroid human doses ranged from 1.5E-4 mSv in the infant group to 3.0E-4 mSv in the 5 years group, and from 6.0E-4 mSv in the infant group to 3.5E-3 mSv in the 5 years group, respectively. The estimated maximum whole body absorbed dose rate to the Korean RAPs was 6.7E-7 mGy/d for a snake living in soil (terrestrial biota), and 2.0E-5 mGy/d for freshwater fish (aquatic biota), both of which were far less than the generic dose criteria to protect biota from ionizing radiation. Also, the screening level assessment for ERICA's (Environmental Risks from Ionizing Contaminants: Assessments and management) limiting organisms showed that the risk quotient (RQ) for the estimated maximum soil and water activity was significantly less than unity for both the terrestrial and freshwater organisms. Conclusively, the radiological risk of the radioactivity released into the environment by the Fukushima nuclear accident to the public and the non-human biota in the republic of Korea is considered negligible.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3175-3178
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• 2014

Background: Gastric cancer is a common malignant tumor. Our previous study demonstrated inhibitory effects of 3-bromopyruvate (3-BrPA) on pleural mesothelioma. Moreover, we found that 3-BrPA could inhibit human gastric cancer cell line SGC-7901 proliferation in vitro, but whether similar effects might be exerted in vivo have remained unclear. Aim: To investigate the effect of 3-BrPA to human gastric cancer implant tumors in nude mice. Materials and Methods: Animals were randomly divided into 6 groups: 3-BrPA low, medium and high dose groups, PBS negative control group 1 (PH7.4), control group 2 (PH 6.8-7.8) and positive control group receiving 5-FU. The TUNEL method was used to detect apoptosis, and cell morphology and structural changes of tumor tissue were observed under transmission electron microscopy (TEM). Results: 3-BrPA low, medium, high dose group, and 5-FU group, the tumor volume inhibition rates were 34.5%, 40.2%, 45.1%, 47.3%, tumor volume of experimental group compared with 2 PBS groups (p<0.05), with no significant difference between the high dose and 5-FU groups (p>0.05). TEM showed typical characteristics of apoptosis. TUNEL demonstrated apoptosis indices of 28.7%, 39.7%, 48.7% for the 3-BrPA low, medium, high dose groups, 42.2% for the 5-FU group and 5% and 4.3% for the PBS1 (PH7.4) and PBS2 (PH6.8-7.8) groups. Compared each experimental group with 2 negative control groups, there was significant difference (p<0.05); there was no significant difference between 5-FU group and medium dose group (p>0.05), but there was between the 5-FU and high dose groups (p<0.05). Conclusions: This study indicated that 3-BrPA in vivo has strong inhibitory effects on human gastric cancer implant tumors in nude mice.

• Journal of radiological science and technology
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• v.41 no.3
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• pp.215-221
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• 2018

Cone beam Computed Tomography(CBCT) is an increasing trend in clinical applications due to its ability to increase the accuracy of radiation therapy. However, this leaded to an increase in exposure dose. In this study, the simulation using Monte Carlo method is performed and the absorbed dose of CBCT is analyzed and standardized data is presented. First, after simulating the CBCT, the photon spectrum was analyzed to secure the reliability and the absorbed dose of the tissue in the human body was evaluated using the MIRD phantom. Compared with SRS-78, the photon spectrum of CBCT showed similar tendency, and the average absorbed dose of MIRD phantom was 8.12 ~ 25.88 mGy depending on the body site. This is about 1% of prescription dose, but dose management will be needed to minimize patient side effects and normal tissue damage.

• Journal of radiological science and technology
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• v.47 no.3
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• pp.167-173
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• 2024

This study purpose to establish an appropriate target exposure index(EIT) using dose area product(DAP) and exposure index(EI) based on chest radiography. First, the system response experiment was conducted with radiation quality of RQA5 to compare the dosimetry and dose area product of equipment. Next, EI and DAP were acquired and analyzed while varying the dose in the diagnostic at 70kVp using a human body model phantom. The signal to noise ratio(SNR) of the obtained results was analyzed in the diagnostic with in the diagnostic reference level(DRL) application range. The DRL at percentage 25% had a dose of 0.17 mGy and EI was 83, and at percentage 75% the dose was 0.68 mGy and EI was 344. As the dose increased, the SNR in the subdiaphragm increased. To set the EIT, calibration must first be performed using a dosimeter and set within the DRL range to reflect the needs of the medical institution.

• Journal of the Korean Society of Radiology
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• v.14 no.2
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• pp.169-178
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• 2020

The number of CT scans is increasing every year due to the improvement of the medical standards of the public, and thus the annual dose of medical radiation is also increasing. In this study, we evaluated the effective dose of the human body exposed to CT scans and estimated LAR. First, five region were selected from the CT diagnostic reference level guideline, and the effective dose of human body exposed to each examination was evaluated by clinical CT device. Second, the human organs and effective dose were calculated using the ALARA-CT program under the same conditions. Third, lifetime attributable risk (LAR) estimated by the effective dose exposed through the previous CT scan was estimated. As a result, the most effective dose was 21.18 mSv during the abdomen 4 phase scan, and the dose level was below DRL for all other tests except for the abdominal examination. As a result of evaluating effective dose using a dose calculation program under the same conditions, the results showed about 1.1 to 1.9 times higher results for each examination. In the case of organ dose, the closer the organ to the scan site, the higher the scattering ray. The lifetime attributable risk to CT radiation dose in adults was gradually decreased with age, and the results were somewhat different according to gender.

• Nuclear Engineering and Technology
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• v.3 no.3
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• pp.155-160
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• 1971

Average and effective energies for 239Pu-Be, 241Am-Li and 241Am-F neutron sources have been calculated from a number of published data for the neutron spectra and for the dose equivalent as a function of neutron energies by a numerical method. Also a calculation of the dose equivalent conversion factors, i. e., the first collision dose equivalent and the surface (or multicollision) dose equivalent that equals the product of surface-absorbed dose and a corresponding quality factor, per unit fluence of neutrons from these sources has been carried out in the same way as before. The results are as follows : 1. for average energies 4.07$\pm$0.33, 0.42 and 1.41 MeV； 2. for effective energies based on the concept of the first collision process in the human body 4.45$\pm$0.344, 0.51 and 1.47 MeV; 3. for effective energies based on the concept of the multi-collision process in the human body 4.50$\pm$0.36, 0.50 and 1.45 MeV； 4. for fluence-first collision dose equivalent conversion factors (2.74$\pm$0.07)10$^{-8}$ , 1.58$\times$ 10$^{-8}$ and 2.34$\times$10$^{-8}$ rems/(n/$\textrm{cm}^2$); and 5. for fluence-surface dose equivalent conversion factors (3.55$\pm$0.09)10$^{-8}$ , 2.19$\times$10$^{-8}$ and 2.82$\times$10$^{-8}$ rems/(n/$\textrm{cm}^2$) : respectively.

• Nuclear Engineering and Technology
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• v.38 no.3
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• pp.239-250
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• 2006

Computational anthropomorphic phantoms are computer models of human anatomy used in the calculation of radiation dose distribution in the human body upon exposure to a radiation source. Depending on the manner to represent human anatomy, they are categorized into two classes: stylized and tomographic phantoms. Stylized phantoms, which have mainly been developed at the Oak Ridge National Laboratory (ORNL), describe human anatomy by using simple mathematical equations of analytical geometry. Several improved stylized phantoms such as male and female adults, pediatric series, and enhanced organ models have been developed following the first hermaphrodite adult stylized phantom, Medical Internal Radiation Dose (MIRD)-5 phantom. Although stylized phantoms have significantly contributed to dosimetry calculation, they provide only approximations of the true anatomical features of the human body and the resulting organ dose distribution. An alternative class of computational phantom, the tomographic phantom, is based upon three-dimensional imaging techniques such as magnetic resonance (MR) imaging and computed tomography (CT). The tomographic phantoms represent the human anatomy with a large number of voxels that are assigned tissue type and organ identity. To date, a total of around 30 tomographic phantoms including male and female adults, pediatric phantoms, and even a pregnant female, have been developed and utilized for realistic radiation dosimetry calculation. They are based on MRI/CT images or sectional color photos from patients, volunteers or cadavers. Several investigators have compared tomographic phantoms with stylized phantoms, and demonstrated the superiority of tomographic phantoms in terms of realistic anatomy and dosimetry calculation. This paper summarizes the history and current status of both stylized and tomographic phantoms, including Korean computational phantoms. Advantages, limitations, and future prospects are also discussed.

• Food Science and Biotechnology
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• v.18 no.2
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• pp.552-555
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• 2009

This study investigated the proapoptotic effect of ethanol extracts obtained from dandelion (Taraxacum officinale) flower on human ovarian cancer SK-OV-3 cells. Cells were treated with dandelion flowers ethanol extract (DFE) ranging from 1.5625 to $100{\mu}g/mL$ for 24 hr. Significant antiproliferative effects of DFE were first observed from at $6.25{\mu}g/mL$ (p<0.05), and this inhibition showed in a dose-dependent manner. When cells were treated with more than $6.25{\mu}g/mL$ DFE, cell-cycle analysis showed that DFE caused an increase in the percentage of sub-G0/G1 cells and arrested at the S and G2/M phase in a dose-dependent manner. Moreover, apoptosis induction by DFE involved p53 activation and bax upregulation as well as downregulation of bcl-2. Our findings indicate that DFE resulted in apoptotic cell death, suggesting that DFE possesses potential anticancer properties.