• Biomolecules & Therapeutics
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• v.32 no.5
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• pp.647-657
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• 2024

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat. This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression. Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.1
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• pp.28-39
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• 2017

Persistent organic pollutants (POPs) can affect epigenetic mechanisms and obesity development. Polybrominated diphenyl ethers (PBDEs)-widely used to make flames-are one of the important POPs. Prenatal exposure to endocrine disrupting chemicals (EDCs), such as POPs, may affect global DNA methylation in long interspersed nuclear elements (LINE-1), increasing the risk of obesity later in life. Therefore, pregnant Sprague-Dawley (SD) rats were used to elucidate whether BDE-47 and BDE-209 transferred through placenta and breast milk cause epigenetic changes in LINE-1 and increase genetic susceptibility to obesity as obesogen during the developmental periods. Global DNA methylation in LINE-1 and gene expression related to obesity were measured in dams and offspring, using a methylation-sensitive high resolution melting analysis (MS-HRM) and direct bisulfite sequencing and quantitative real time polymerase chain reaction (qPCR), respectively. The results of MS-HRM showed global DNA hypomethylation patterns in LINE-1 of exposed offspring (2 of total 4) at PND 4, but bisulfite sequencing showed no difference in both the exposed and non-exposed groups. Gene expression in dams related to ${\beta}$-oxidation pathway and those related to adipokines showed different patterns between the two groups. On the contrary, gene expressions of offspring showed a similar pattern. Gene expressions related to ${\beta}$-oxidation pathway and obesity were significantly increased when compared with 'at birth', but not $PPAR-{\alpha}$. In conclusion, this study demonstrated the possibility that co-exposure to BDE-47 and BDE-209-via the placenta and breast milk-may affect epigenetic changes and modulate gene expression levels related to obesity.

• Journal of Chest Surgery
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• v.31 no.8
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• pp.739-748
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• 1998

Background: It has been well documented that transient occlusion of the coronary artery causes myocardial ischemia and finally cell death when ischemia is sustained for more than 20 minutes. Extensive studies have revealed that ischemic myocardium cannot recover without reperfusion by adequate restoration of blood flow, however, reperfusion can cause long-lasting cardiac dysfunction and aggravation of structural damage. The author therefore attempted to examine the effect of postischemic reperfusion on myocardial ultrastructure and to determine the rationales for recanalization therapy to salvage ischemic myocardium. Materials and methods: Young Holstein-Friesian cows(130∼140 Kg body weight; n=40) of both sexes, maintained with nutritionally balanced diet and under constant conditions, were used. The left anterior descending coronary artery(LAD) was occluded by ligation with 4-0 silk snare for 20 minutes and recanalized by release of the ligation under continuous intravenous drip anesthesia with sodium pentobarbital(0.15 mg/Kg/min). Drill biopsies of the risk area (antero-lateral wall) were performed at just on reperfusion(5 minutes), 1-, 2-, 3-, 6-, 12-hours after recanalization, and at 1-hour assist(only with mechanical respiration and fluid replacement) after 12-hour recanalization. The materials were subdivided into subepicardial and subendocardial tissues. Tissue samples were examined with a transmission electron microscope (Philips EM 300) at the accelerating voltage of 60 KeV. Results: After a 20-minute ligation of the LAD, myocytes showed slight to moderate degree of ultrastructural changes including subsarcolemmal bleb formation, loss of nuclear matrix, clumping of chromatin and margination, mitochondrial destruction, and contracture of sarcomeres. However, microvascular structures were relatively well preserved. After 1-hour reperfusion, nuclear and mitochondrial matrices reappeared and intravascular plugging by polymorphonuclear leukocytes or platelets was observed. However, nucleoli and intramitochondrial granules reappeared within 3 hours of reperfusion and a large number of myocytes were recovered progressively within 6 hours of reperfusion. Recovery was apparent in the subepicardial myocytes and there were no distinct changes in the ultrastructure except narrowed lumen of the microvessels in the later period of reperfusion. Conclusions: It is likely that the ischemic myocardium could not be salvaged without adequate restoration of coronary flow and that the microvasculature is more resistant to reversible period of ischemia than subendocardium and subepicardium. Therefore, thrombolysis and/or angioplasty may be a rational method of therapy for coronarogenic myocardial ischemia. However, it may take a relatively longer period of time to recover from ischemic insult and reperfusion injury should be considered.

• Journal of Radiation Protection and Research
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• v.38 no.2
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• pp.106-118
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• 2013

In this paper, we analyzed the Cognition of irradiated food and its relation with self-efficacy. The most important variables described behaviors based on health choices compared with the choice to choose irradiated food items. According to the survey, 33.1% of respondents said that the reason why irradiated food is considered to be a health risk is because "radiation is dangerous". 27.9% of respondents answered that "eating irradiated food is like eating a radioactive substance", 21.1% said radiated food is comparable to a "genetic variation in food" while 10.1% said "food goes bad during the irradiation process". On this basis, it is reasonable to conclude that respondents have a misunderstanding of irradiated food without reference to the general theory of irradiated knowledge. In this respect, it would be helpful to provide education showing that irradiated food is not related to eating harmful or genetically modified food to help high school students create informed opinions of irradiated food. In terms of relevance with health-specific self-efficacy, experience of acquiring information about irradiated food was marked at r=0.148 (p<0.01), experience of purchasing irradiated food was marked at r=0.077 (p<0.05), experience of eating irradiated food was marked at r=0.113 (p<0.01) while knowledge of irradiated food, attitude towards irradiated food and behavior was marked at r=0.103 (p<0.01), r=0.076 (p<0.05) and r=0.105 (p<0.01) respectively. This shows that self-efficacy is high when one has experience of acquiring information about irradiated food, purchasing or eating irradiated food resulting in a high level of knowledge, attitude and behavior. Education which serves to improve the level of self-efficacy needs to be provided along with an educational program which will increase the public's understanding of irradiated food. It is expected that if this education which increases the level of self-efficacy is provided together with correct information of irradiated food, behavior to choose and eat irradiated food will also improve.

• Progress in Medical Physics
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• v.24 no.3
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• pp.154-161
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• 2013

This study assessed compared photon and proton treatment techniques, such as intensity modulated radiation therapy (IMRT), uniform scanning proton therapy (USPT), and intensity modulated proton therapy (IMPT), for a total of 10 prostate cancers. All treatment plans delivered 70 Gy to 95% of the planned target volume in 28 fractions. IMRT plans had 7 fields for the step and shoot technique, while USPT and IMPT plans employed two equally weighted, parallel-opposed lateral fields to deliver the prescribed dose to the planned target. Inverse planning was then incorporated to optimize IMPT. The homogeneity index (HI) and conformity index (CI) for the target and the normal tissue complication probability (NTCP) for organ at risk (OAR) were calculated. Although the mean HI and CI for target were not significantly different for each treatment techniques, the NTCP of the rectum was 2.233, 3.326, and 1.707 for IMRT, USPT, and IMPT, respectively. The NTCP of the bladder was 0.008, 0.003, and 0.002 respectively. The NTCP values at the rectum and bladder were significantly lower using IMPT. Our study shows that using proton therapy, particularly IMPT, to treat prostate cancer could be beneficial compared to 7-field IMRT with similar target coverage. Given these results, radiotherapy using protons, particularly optimized IMPT, is a worthwhile treatment option for prostate cancer.

• Korean Chemical Engineering Research
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• v.56 no.2
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• pp.169-175
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• 2018

This study deals with a process for the recovery of hydrogen isotopes from methane ($CQ_4$) and water ($Q_2O$) containing tritium in the nuclear fusion exhaust gas (Q is Hydrogen, Deuterium, Tritium). Steam Methane Reforming and Water Gas Shift reactions are used to convert $CQ_4$ and $Q_2O$ to $Q_2$ and the produced $Q_2$ is recovered by the subsequent Pd membrane. In this study, one circulation loop consisting of catalytic reactor, Pd membrane, and circulation pump was applied to recover H components from $CH_4$ and $H_2O$, one of $CQ_4$ and $Q_2O$. The conversion of $CH_4$ and $H_2O$ was measured by varying the catalytic reaction temperature and the circulating flow rate. $CH_4$ conversion was 99% or more at the catalytic reaction temperature of $650^{\circ}C$ and the circulating flow rate of 2.0 L/min. $H_2O$ conversion was 96% or more at the catalytic reaction temperature of $375^{\circ}C$ and the circulating flow rate of 1.8 L/min. In addition, the amount of $CQ_4$ generated by Korean Demonstration Fusion Power Plant (K-DEMO) in the future was predicted. Then, the treatment process for the $CQ_4$ was proposed and HAZOP (hazard and operability) analysis was conducted to identify the risk factors and operation problems of the process.

• Journal of The Korean Ophthalmological Society
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• v.59 no.11
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• pp.1049-1055
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• 2018

Purpose: To investigate the factors associated with glaucoma in patients with pseudoexfoliation syndrome by comparing features of the anterior segments and ocular biometry according to the presence or absence of open-angle glaucoma in pseudoexfoliation syndrome. Methods: We analyzed 96 patients (115 eyes) diagnosed as having pseudoexfoliation syndrome in this study. The patients were divided into two groups of simple pseudoexfoliation syndrome (64 patients, 76 eyes) and pseudoexfoliation glaucoma (32 patients, 39 eyes). We compared the age, sex, underlying disease, location of pseudoexfoliative material, iris change, degree of nuclear cataract, pupil dilatation, corneal endothelial cell counts, central corneal thickness, anterior chamber depth, axial length, corneal curvature, and intraocular pressure (IOP). Results: There were no significant differences between the two groups in terms of age (p = 0.694), sex (p = 0.161), diabetes (p = 0.440), hypertension (p = 0.238), pseudoexfoliative material observed in anterior capsule (p = 0.700), pupillary margin (p = 0.210), iris depigmentation (p = 0.526), pupillary ruff loss (p = 0.708), degree of nuclear cataract (p = 0.617), pupil dilatation (p = 0.526), central corneal thickness (p = 0.097), anterior chamber depth (p = 0.283), axial length (p = 0.095), or horizontal and vertical corneal curvature (p = 0.066 and 0.306, respectively). In pseudoexfoliation glaucoma, significantly higher IOP (p = 0.026), a high frequency of membrane formation (p = 0.047), and decreased corneal endothelial cell counts (p = 0.048) were observed. Conclusions: Pseudoexfoliation syndrome with open-angle glaucoma was shown to be associated with high IOP, decreased corneal endothelial cell counts, and a high frequency of membrane formation. Therefore, when such changes are observed in pseudoexfoliation syndrome patients, a higher risk of open-angle glaucoma should be recognized, and careful attentionis required accordingly.

• Radiation Oncology Journal
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• v.18 no.2
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• pp.157-166
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• 2000

Purpose : This investigation was peformed in order to improve the health care of radiation workers, to predict a risk, to minimize the radiation exposure hazard to them and for them to realize radiation exposure danger when they work in radiation area in hospital. Methods and Materials : The documentations checked regularly for personal radiation exposure in four university hospitals in Pusan city in Korea between January 1, 1993 and December 31, 1997 were analyzed. There were 458 persons in this documented but 111 persons who worked less then one year were excluded and only 347 persons were included in this study. Results : The average of yearly radiation exposure of 347 persons was 1.52$\pm$1.35 mSv. Though it was less than 50mSv, the limitaion of radiation in law but 125 (36%) people received higher radiation exposure than non-radiation workers. Radiation workers under 30 year old have received radiation exposure of mean 1.87$\pm$1.01 mSv/year, mean 1.22$\pm$0.69 mSv between 31 and 40 year old and mean 0.97$\pm$0.43 mSv/year over 41year old (p<0.001). Men received mean 1.67$\pm$1.54 mSv/year were higher than women who received mean 1.13$\pm$0.61 mSv/year (p<0.01). Radiation exposure in the department of nuclear modicine department in spite of low energy sources is higher than other departments that use radiations in hospital (p<0.05). And the workers who received mean 3.59$\pm$1.81 msv/year in parts of management of radiation sources and injection of sources to patient receive high radiation exposure in nuclear medicine department (p<0.01). In department of diagnostic radiology high radiation exposure is in barium enema rooms where workers received mean 3.74$\pm$1.74 mSv/year and other parts where they all use fluoroscopy such as angiography room of mean 1.17$\pm$0.35 mSv/year and upper gastrointestinal room of mean 1.74$\pm$1.34 mSv/year represented higher radiation exposure than average radiation exposure in diagnostic radiology (p<0.01). Doctors and radiation technologists received higher radiation exposure of each mean 1.75$\pm$1.17 mSv/year and mean 1.50$\pm$1.39 mSv/year than other people who work in radiation area in hospital (p<0.05). Especially young doctors and technologists have the high opportunity to receive higher radiation exposure. Conclusions : The training and education of radiation workers for radiation exposure risks are important and it is necessary to rotate worker in short period in high risk area. The hospital management has to concern health of radiation workers more and to put an effort to reduce radiation exposure as low as possible in radiation areas in hospital.

• Radiation Oncology Journal
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• v.22 no.2
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• pp.115-123
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• 2004

Purpose : This retrospective study was conducted to compare early preliminary results of breast conservation therapy (BCT) with mastectomy In early breast cancer. Materials and Methods : We evaluated 171 women with AJCC stage I and II breast cancer who had been treated at Kangnam St. Mary's Hospital from March 1989 to August 1996. Eighty-eight patients underwent mastectomy and 85 patients did conservative surgery with breast irradiation. in the BCT group, all patients received whole breast irradiation to a total dose of 45$\~$50 Gy/5$\~$6 wks, followed by a boost to the original tumor site at least 60 Gy. Chemotherapy was administered to 29 (34.1$\%$) patients in BCT and 40 (45.5$\%$) in mastectomy, with various sequencing of surgery and/or radiation. We compared survival rate, patterns of failure in each treatment group and the prognostic factors that had a significant effect on treatment failure. The median follow-up time was 63 months (19$\~$111 months). Log rank test was used to estimate the prognostic factors for treatment failure. Results : Overall survival, disease free survival, locoregional recurrence and distant metastasis rates were not significantly different between the two treatment groups. During the follow-up period, 11 patients (12.5$\%$)in the mastectomy group and 10 patients (11.8%$\%$ in the BCT group were failed. Six local recurrences occurred after mastectomy and 5 after BCT Five patients fatted at distant site in mastectomy and 4 in BCT. Of the local recurrence cases, five of 6 mastectomy patients and 3 of S BCT patients were alive with no evidence of disease after salvage surgery and/or chemoirradiation. Our results indicated that the major influence on survival was distant metastasis. Unfortunately, control of distant metastasisis was not frequently achieved. Even with salvage systemic therapy or radiotherapy, most of distant metastasis patients died or had uncontrolled disease in both treatment groups: only one of 4 BCT patients and none of mastectomy patients were alive without disease. There was no apparent difference in the incidence rate of contralateral breast cancer and non-breast 2$^{nd}$ primary tumor between the two treatment groups. Univariate Log-rank test identified the N stage and the involved axillary LN number as distinct prognostic factors that were highly predictive of treatment failure in both treatment groups. Additionally, marginal status in BCT and histologic nuclear grade In the mastectomy group were risk factors for treatment fallure (p < 0.05). Concousion : Although further careful follow-up is necessary to confirm the trends evident In this serles, it would appear that patterns of failure and survival rate following conservative surgery and radiotherapy in early breast cancer are similar to those following mastectomy. The great majority of patients with local recurrence had an exellent salvage rate in both treatment groups. Therefore, these preliminary short term results support BCT as an equally effective management for early breast cancer as an alternative to mastectomy.

• Tuberculosis and Respiratory Diseases
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• v.63 no.3
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• pp.251-260
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• 2007

Purpose: An imbalance of cell proliferation and cell apoptosis is an important mechanism in carcinogenesis. Capase 3, survivin and p53 have been identified as important members of the apoptotic related proteins. This study evaluated the proliferating cell nuclear antigen(PCNA), apoptosis, apoptotic related protein such as capase 3, survivin and p53 using urethane-induced mouse lung carcinogenesis, which provides reproducible steps from hyperplasia to adenocarcinoma. Methods: Urethane was administered to the ICR mice through an intra-peritoneal injection, The mice were sacrificed at 5, 15, and 25 weeks after urethane intervention. The sequential morphological changes and immunohistochemical expression of PCNA, apoptosis, capase 3, survivin, and p53 were examined during mouse lung carcinogenesis. Results: During carcinogenesis, the sequential histological changes were observed from hyperplasia of type II pneumocytes, to anadenoma, and ultimately to an overt adenocarcinoma. The PCNA Labeling index (LI) was 9.6% in hyperplasia, 23.2% in adenoma, and 55.7% in adenocarcinoma, respectively. The apoptotic LI was 0.24% in hyperplasia, 1.25% in adenoma, and 5.27% in adenocarcinoma. A good correlation was observed between the PCNA LI and apoptotic LI. The expression of caspase 3 was remarkable- i.e., 46.7% in adenocarcinoma, in contrast to 15% in hyperplasia and 16% in adenoma. Survivin was detected weakly in the alveolar hyperplasia and showed an increasing expressional pattern in adenoma and adenocarcinoma. p53 expression was detected only in the adenocarcinoma lesions with an expression rate of 13.3%. The level of caspase 3 expression correlated with the increase in the apoptotic index. The positive expression of caspase 3 was associated with an increased apoptotic index. Conclusions: These results suggest that the PCNA LI and apoptotic LI might be useful markers for evaluating the risk of a malignant transformation. In addition, caspase, survivin and p53 might play a role in the early and late steges of urethane-induced mouse lung carcinogenesis.