• 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.

• Anatomy and Cell Biology
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• v.57 no.3
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• pp.408-418
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• 2024

Vitamin C is a well-known antioxidant with antiviral, anticancer, and anti-inflammatory properties based on its antioxidative function. Aptamin C, a complex of vitamin C with its specific aptamer, has been reported to maintain or even enhance the efficacy of vitamin C while increasing its stability. To investigate in vivo distribution of Aptamin C, Gulo knockout mice, which, like humans, cannot biosynthesize vitamin C, were administered Aptamin C orally for 2 and 4 weeks. The results showed higher vitamin C accumulation in all tissues when administered Aptamin C, especially in the spleen. Next, the activity of natural killer (NK) cells were conducted. CD69, a marker known for activating for NK cells, which had decreased due to vitamin C deficiency, did not recover with vitamin C treatment but showed an increasing with Aptamin C. Furthermore, the expression of CD107a, a cell surface marker that increases during the killing process of target cells, also did not recover with vitamin C but increased with Aptamin C. Based on these results, when cultured with tumor cells to measure the extent of tumor cell death, an increase in tumor cell death was observed. To investigate the signaling mechanisms and related molecules involved in the proliferation and activation of NK cells by Aptamin C showed that Aptamin C treatment led to an increase in intracellular STAT3 activation. In conclusion, Aptamin C has a higher capability to activate NK cells and induce tumor cell death compared to vitamin C and it is mediated through the activation of STAT3.

• Journal of agricultural medicine and community health
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• v.26 no.2
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• pp.147-159
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• 2001

A questionnaire survey of 568 women over the age of 30 in 11 dongs of Goryeong- gun was performed to identify the practice rate of breast self- examination and its related factors. It was found that the practice rate of breast self- examination was 28.2%, with 9.7% of those surveyed performing breast self- examinations more than once a month. The practice rate of breast self- examination showed significant differences according to factors, such as age, presence of spouse, educational level, occupation, economic status, smoking, regular exercise and chronic disease. According to age, the highest practice rate of breast self-examination was between the ages of 40-49 and the lowest over the age of 60. The practice rate increased with higher the educational level and presence of spouse. According to occupation, administrative and managerial occupations presented the highest practice rate of breast self- examination. Higher economic status, regular exercise and positive family history of breast cancer each presented high practice rates of breast self- examination. The practice rate revealed higher in those who did not smoke and who had no chronic diseases than others. The greatest reason for performing breast self- examination was decided by myself for health reasons, followed by effect of mass media and promotion by health center. The most common reasons for not performing breast self- examination were don't feel the need, followed by don't know how to perform the exam and don't know about the exam itself. Multiple logistic regression analysis showed that factors, such as over the age of 60, less education, and no experience with mammography all lowered the practice rate of self-breast examination. Inconclusion, the rates of breast self- examination and regular check-ups of people in rural areas, who are characteristically older and have low educational backgrounds, were 28.2% and 9.7%. These results show the immediate need for the education of the methods for breast self- examination to be carried out by health centers in these areas. Such efforts and programs could increase the practice rate of breast self- examination and thereby improve health and enhance the quality of life of women in rural areas.

• Journal of Yeungnam Medical Science
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• v.10 no.2
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• pp.432-444
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• 1993

Multidrug resistance(MDR) phenotype is frequently observed in animal and human cancer cell lines selected for in vitro resistance to a single chemotherapeutic agent. It is characterized by the diminished drug accumulation and is related to the drug efflux mechanism in resistant cells. In the present study, adriamycin resistant cells(L1210-$AdR_6$ : $10^{-6}M$ adriamycin, $-AdR_5$ : $10^{-5}M$) and vincristine resistant cells (L1210-$VcR_7$ : $10^{-7}M$ vincristine, $-VcR_6$ : $10^{-6}M$) were produced from mouse lymphoblastic leukemia cell line L1210. Growth profiles of survived cells were observed for 5 days with MTT(thiazolyl blue) assay and resistance was compared with $IC_{50}$(drug concentration of 50% survival reduction in absorbance). Resistant cells proliferated more slowly than sensitive cell. Doubling times were 29.7hr in L1210, 68.7hr in L1210-$AdR_5$ and 58.2hr in $-VcR_6$. MDRs expressed as resistance factor were as follows, L1210-$AdR_5$ was 76.4 times for vincristine, L1210-$VcR_6$ was 96.4 times for adriamycin. The cell membrane proteins with three different M.W. were recognized to be related resistance, 220, 158, and 88 kd in L1210-$AdR_5$, 158, 140 and 88 kd in L1210-$VcR_6$ by SDS-PAG electrophoresis. Cell surface membrane proteins were identified by radio-iodination and autoradiogram, their molecular weights were 158, 72.8, and 42.4 Kd in L1210-$VcR_6$.

• Radiation Oncology Journal
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• v.19 no.4
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• pp.319-326
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• 2001

Purpose : Planning target volume (PTV) for tumors in abdomen or thorax includes enough margin for breathing-related movement of tumor volumes during treatment. Depending on the location of the tumor, the magnitude of PTV margin extends from 10 mm to 30 mm, which increases substantial volume of the irradiated normal tissue hence, resulting in increase of normal tissue complication probability (NTCP). We developed a simple and handy method which can reduce PTV margins in patients with liver tumors, respiratory motion reduction device (RRD). Materials and methods : For 10 liver cancer patients, the data of internal organ motion were obtained by examining the diaphragm motion under fluoroscope. It was tested for both supine and prone position. A RRD was made using MeV-Green and Styrofoam panels and then applied to the patients. By analyzing the diaphragm movement from patients with RRD, the magnitude of PTV margin was determined and dose volume histogram (DVH) was computed using AcQ-Plan, a treatment planning software. Dose to normal tissue between patients with RRD and without RRD was analyzed by comparing the fraction of the normal liver receiving to $50\%$ of the isocenter dose. DVH and NTCP for normal liver and adjacent organs were also evaluated. Results : When patients breathed freely, average movement of diaphragm was $12{\pm}1.9\;mm$ in prone position in contrast to $16{\pm}1.9\;mm$ in supine position. In prone position, difference in diaphragm movement with and without RRD was $3{\pm}0.9\;mm$ and 12 mm, respectively, showing that PTV margins could be reduced to as much as 9 mm. With RRD, volume of the irradiated normal liver reduced up to $22.7\%$ in DVH analysis. Conclusion : Internal organ motion due to breathing can be reduced using RRD, which is simple and easy to use in clinical setting. It can reduce the organ motion-related PTV margin, thereby decrease volume of the irradiated normal tissue.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.123-129
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• 2002

Purpose : The purpose of this study 띤as to determine the potential role of three-dimensional conformal radiotherapy (3D-CRT) in the treatment of primary unresectable hepatocellular carcinoma. The preliminary results on the efficacy and the toxicity of 3D-CRT are reported. Materials and Methods : Seventeen patients were enrolled in this study, which was conducted prospectively from January 1995 to June 1997. The exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child-Pugh classification C, tumors occupying more than two thirds of the entire liver, and a performance status of more than 3 on the ECOG scale. Two patients were treated with radiotherapy only while the remaining 15 were treated with combined transcatheter arterial chemoembolization. Radiotherapy was given to the field including the tumor plus a 1.5 cm margin using a 3D-CRT technique. The radiation dose ranged from $36\~60\;Gy$ (median; 59.4 Gy). Tumor response was based on a radiological examination such as the CT scan, MR imaging, and hepatic artery angiography at $4\~8$ weeks following the completion of treatment. The acute and subacute toxicities were monitored. Results : An objective response was observed in 11 out of 17 patients, giving a response rate of $64.7\%$. The actuarial survival rate at 2 years was $21.2\%$ from the start of radiotherapy (median survival; 19 months). Six patients developed a distant metastasis consisting of a lung metastasis in 5 patients and bone metastasis in one. The complications related to 30-CRT were gastro-duodenitis $(\geq\;grade\;2)$ in 2 patients. There were no treatment related deaths and radiation induced hepatitis. Conclusion : The preliminary results show that 3D-CRT is a reliable and effective treatment modality for primary unresectable hepatocellular carcinoma compared to other conventional modalities. Further studies to evaluate the definitive role of the 3D-CRT technique in the treatment of primary unresectable hepatocellular carcinoma are needed.

• Journal of Chest Surgery
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• v.43 no.3
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• pp.280-284
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• 2010

Background: The postoperative management following lung transplantation has dramatically improved in the recent decade. However, some complications still remain as troublesome problems. We retrospectively reviewed the gastrointestinal complications and their management after lung transplantation. Material and Method: We performed a retrospective review of the medical records of 25 cases in 23 patients who underwent lung and heart-lung transplantations from July 1996 to March 2009. The definition of gastrointestinal complication was the gastrointestinal tract-related disease that occurred after lung transplantation. There were eight postoperative deaths (within postoperative 30 days) that were excluded from the analysis. Result: Twenty three gastrointestinal complications occurred in 11 (64.7%) of the 17 cases. The median follow-up period was 6.9 months (range: 2 months to 111 months), and chronic gastritis (23.5%, 4 of 17 cases) was the most common complication. Severe, prolonged (more than 2 weeks) diarrhea occurred in 3 cases. Three patients had gastric ulcer with one case requiring gastric primary closure for gastric ulcer perforation. This patient had gastric bleeding due to recurrent gastric ulcer 2 months after laparotomy. Cytomegalovirus gastritis and esophagitis occurred in 2 cases and 1 case, respectively, and esophageal ulcer occurred in 2 cases. There were esophageal strictures in 2 patients who underwent esophageal stent insertion. Other complications were one case each of ileus, early gastric cancer requiring endoscopic mucosal resection, gall bladder stone accompanied with jaundice, and pseudomembranous colitis. Conclusion: The incidence of gastrointestinal complication is relatively high in patients after they undergo lung transplantation. Since gastrointestinal complications can induce malnutrition, which might be related to considerable morbidity and mortality, close follow-up is necessary for the early detection and proper management of gastrointestinal complications.

• Journal of Home Health Care Nursing
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• v.10 no.1
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• pp.58-72
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• 2003

The purpose of this study was to describe the perceived burden of the terminally III patients's caregiver and to analyze relationship between the perceived burden and the various demographics, illness characteristics, family relationships, and economic factor of the family & patients. The sample of 132 caregivers who care for the terminally III patients Kyung-Gi province, Seoul, Korea. The period of this study was from August to September, 2002. The perceived burden of the family caregiver was measured by the burden scale(20 items, 4 point scale) developed by Montgomery et al. (1985). The Data was analyzed using SAS-program by t-test and ANOVA. The results were as follows; 1. The mean of the family caregiver's burden score was 3.02. The score showed that caregivers perceive severe the level of burden. The hight items of the family caregiver's burden were' I feel it is painful to watch patient's diseases'(3.77). 'I feel afraid for what the future holds for my patients'(3.66), 'I feel it reduced to amount of privacy time'(3.64). 2. The caregiver's burden was significantly related to patient's gender(F=3.17, p= 0.0020), patient's job(F=2.49, p=0.0476), caregiver's age(F=4.29, p=0.0030), and caregiver's job(F=2.49, p=0.0476). 3. The caregiver's burden according to illness characteristics showed no significant difference. 4. The caregiver's burden was significantly associated with patient's family relationship (F=4.05, p=0.0041), patient's care mean period in a day(F=47.18,

• Korean Journal of Psychosomatic Medicine
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• v.8 no.1
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• pp.65-71
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• 2000

Objects : Aimed to test the hypothesis that neonatal testosterone exposure in female mice influences the development of testosterone-related pain inhibitory system and that testosterone administered in adulthood decreases the pain sensitivity. Methods : Thirty androgenized(testosterone propionate $100{\mu}g$ ip within 24 hrs after birth) adult female and twenty five control(normal saline $100{\mu}g$ ip within 24 hrs after birth) adult female mice were injected with testosterone propionate 1mg/kg/day for 3 consecutive days from 84th experimental days. Nociceptive sensitivity was measured before and after treatment of testosterone by tail flick latency on 84th and 86th experimental days. Results : 1) On the 84th experimental day, basal nociceptive sensitivity was significantly higher in the androgenized group($2.7{\pm}0.4$ sec) as compared to the control group($3.3{\pm}1.1$ sec). 2) Testosterone treatment on the 84th experimental day significantly lowered nociceptive sensitivity in both androgenized($5.2{\pm}0.9$ sec) and control groups($4.6{\pm}1.8$ sec). However the effect was significantly greater in the androgenized group. 3) Nociceptive sensitivity on 86th experimental day before administration of testosterone was significantly lower in the androgenized group($4.8{\pm}1.9$ sec) as compared to the control group($3.9{\pm}1.2$ sec). 4) Testosterone treatment on the 86th experimental day significantly lowered the nociceptive sensitivity in both groups, but the androgenized group($5.9{\pm}0.9$ sec) showed significantly lower post-treatment nociceptive sensitivity as compared to the control group($4.9{\pm}1.5$ sec). 5) Nociceptive sensitivity was decreased significantly after injection of testosterone once a day for two consecutive days in the androgenized group(${\Delta}2.1{\pm}1.0$ sec), but not in the control group(${\Delta}0.5{\pm}1.3$ sec). Conclusions : There may be a testosterone-related pain inhibitory system, the development of which is enhanced by exposure to testosterone in the neonatal period, and the activity of which is also mediated by testosterone in the later life.

• Journal of agricultural medicine and community health
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• v.28 no.1
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• pp.67-77
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• 2003

Objectives: This study is designed to suggest the health service goals necessary for providing the more efficient services relevant to the requests of the community, through the evaluation on the operating status of the unified health subcenters. Methods: We visited total 5 unified health subcenters comprising 3 ones located in Gyeongsangbuk-do and 2 ones located in Gyeongsangnam-do from December 2000 to January 2001, and interviewed about the pre- and post-unified status related to manpower, facilities, equipment, medical service and health service quality, and the problems and improvement plans of the unified management. Results: According to the evaluation on the manpower before and after the unification of the health subcenters, the total employees increased by 2.8 persons on average from 6.8 to 9.6 persons in the investigated subjects. The numbers of doctors, dentists and nurses were almost the same as before. There were no clinical pathologic technician and radiological technician before but they were appointed to duty in 3 unified health subcenters later. The unification of the health subcenters has produced slight increases in the frequency of the medical service and dental treatment and considerable increases in that of the physical therapy and laboratory tests. In relating to the changes of the health service, the cases of visiting health care and ambulatory medical service, and the total number of health education participants were greatly increased after the unification. The number of cases undergoing the vaccination and cervical cancer screening was similar to that of the pre-unification while the patient number of the registration to hypertension or diabetes showed a tendency to increase a little. Since the unification of the health subcenters, the frequency of laboratory tests has been increased, but the quality of health service has not been improved yet. Nevertheless, the unification seems to be positive according to the result of the great improvement in visiting health care, ambulatory medical service and health education service. The problems of the unification of the health subcenters were indicated in indefiniteness of the service details between the workers; excessively large building hard to be effectively managed; insufficient medical instruments, inappropriation of working expenses, lack of professional training for the health education, etc. Conclusions: For further active functions of the unified health subcenters, the minimal allocation basis to appoint doctors, nurses and administrative workers to do the duty should be differentiated from the basis for a health subcenter, and the fundamental instruments needs to be expanded to improve the quality of the medical service and visiting health care service. Moreover, the unified health subcenter needs to have definite service details between the workers, and should improve the working efficiency through the development of service-related guidelines.