• Journal of Life Science
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• v.29 no.6
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• pp.679-687
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• 2019

Litsea populifolia, a plant species of the Lauraceae family, is widely distributed in the tropical and subtropical areas of Asia. The phylogenetic relationships and botanical characteristics of L. populifolia have been reported; however, its anti-oxidative and anti-cancer activities remain unclear. In this study, we evaluated the anti-oxidative and anti-cancer effects of ethanol extracts of L. populifolia (EELP) together with the molecular mechanism of its anti-cancer activity in human lung adenocarcinoma A549 cells. EELP showed significant anti-oxidative effects with a 50% inhibitory concentration at $11.71{\mu}g/ml$, which was measured by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. EELP exhibited cytotoxic activity and induced cell cycle arrest at the G1 phase in A549 cells in a dose-dependent manner, whereas EELP did not have the cytotoxic effect on the normal human lung cell line IMR90. Treatment with EELP also resulted in a decreased expression of G1/S transition-related molecules-including cyclin-dependent kinase (CDK) 2, CDK6, cyclin D1, and cyclin E-both for the transcription and translation levels. EELP-induced G1 arrest was associated with the phosphorylation of checkpoint kinase 2 (CHK2), p53, cell division cycle 25 homolog A (CDC25A), and the reduction of CDC25A expression in A549 cells. Collectively, these results suggest that EELP may exert an anti-cancer effect by cell cycle arrest at the G1 phase through both p53-dependent and p53-independent (ATM/CHK2/CDC25A/CDK2) pathways in A549 cells.

• Journal of Life Science
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• v.31 no.2
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• pp.199-208
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• 2021

Euonymus porphyreus, a species of plant in the Celastraceae family, is widely distributed in East Asia, especially in Southern China. The botanical characteristics of E. porphyreus have been reported, but its antioxidative and anticancer activities remain unclear. In this study, we evaluated the antioxidative and anticancer effects of ethanol extracts of E. porphyreus (EEEP) and the molecular mechanism of its anticancer activity in human lung adenocarcinoma A549 cells. The total polyphenol and flavonoid compound contents from EEEP were 115.42 mg/g and 23.07 mg/g, respectively. EEEP showed significant antioxidative effects with a concentration at 50% of the inhibition (IC50) value of 11.09 ㎍/ml, as measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. EEEP showed cytotoxic activity by increasing the SubG1 cell population of A549 cells in a dose-dependent manner. Apoptosis in A549 cells treated with EEEP was evident due to increased apoptotic cells and apoptotic bodies, as detected by Annexin V and 4,6-diamidino-2-phenylindole (DAPI) staining, respectively. EEEP-induced apoptosis resulted in increased expression of the First apoptosis signal (Fas), p53, and Bax, with decreased expression of Bcl-2 and subsequent activation of caspase-8, -9, and caspase-3, leading to cleavage of poly (ADP-ribose) polymerase (PARP). Collectively, these results suggest that EEEP may exert an anticancer effect by inducing apoptosis in A549 cells through both intrinsic and extrinsic pathways.

• Radiation Oncology Journal
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• v.10 no.1
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• pp.35-41
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• 1992

Forty eight patients with adenoid cystic carcinoma (ACC) in the head and neck treated between 1979 and 1990 were reviewed according to treatment modalities and clinical courses. The common site of origin was minor salivary gland ($69\%$), mostly hard palate and maxillary sinus. 11 patients received radiation therapy (RT) alone and 37 patients received combined surgery and radiation therapy. The follow-up period of the survivors ranged from 4 to 118 months (median 49.5 months). The 5 year local control rate was $69.3\%$, $67.3\%$ and 83.9$\%$ in RT alone, conservative operation (OP)+RT and radical OP+RT group, respectively (p>0.05). The control of local disease was best achieved with radical OP+RT. In postoperative RT, high dose ($\ge$60 Gy) and generous field size($\ge$64 cm$^2$) yielded a better local control rate. Actuarial overall survival rate was $79.0\%$, at 5 years and $19.2\%$ at 10 years. Distant metastases (DM) developed in $40\%$ of patients, mostly in the lung. Disease-free (NED) survival rate was $45.8\%$ at 5 years and significant differences did not exist according to primary sites and treatment options. Survival rate after the onset of DM was $19.5\%$ at 5 years. Occurrence of DM tends to lower survival significantly. In an effort to find the role of RT in the treatment of ACC, our data suggest that a well-planned postoperative RT employing a high dose and generous field size can produce high local control rate and remaining urgent problem of distant metastasis demands more effective chemotherapy for the purpose of improving survival of ACC patients.

• Journal of Preventive Medicine and Public Health
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• v.27 no.4 s.48
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• pp.711-734
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• 1994

Among chemical agents in herbicides, dioxin (2, 3, 7, 8-tetrachloro dibenzo-$\rho$-dioxin : TCDD), a chemical contaminant in herbicides sprayed during the Vietnam War has been known to be the major agent causing toxic effects. Approximately 320,000 korean soldiers participated the Vietnam War from 1964 to 1974. Although the potential hazards of the herbicides among Korean veterans exposed were implicated, the problem had not been a public issue until 1991 when Korean veterans were informed U.S. companies, the herbicides manufacturer payed fund, from which a trust fund for New Zealand and Australian Class members were established in 1985. After a series of appeals and demonstration by the Korean Veterans demanding medical care and compensation for their serious health damages, a bill of medical care and compensation for herbicides victims was promulgated in March 1993 and become effective from May 1993, This study was carried out with two major objectives : the first to understand the health problems caused from the herbicides by reviewing literatures published, and the second to examine the nature and extent of health impacts among Korean veterans exposed and to develop valid study methods for the major study by interviewing and reviewing records on a part of veterans (638 persons) registered and completed medical examination in Seoul Veterans Administration Hospital from June to October 1993. The results obtained are as followings: 1. The literature review of 107 papers revealed that 1) Dioxin is teratogenic, carcinogenic and affects almost all organs including nervous, endocrine, and reproductive systems in animal experiments. 2) The diseases showing evidence of causal association were Hodgkin's disease, non-Hodgkin's disease, lung cancer, lymphoma, soft tissue sarcoma, chloroacne and polyneuropathy when judged on the basis of consistency in study results and biological plausibility. 2. Interview and medical record review study on 638 veterans, though limited validity owing to lack of control group, crude estimates of dioxin exposure levels (no biomarkers measurable), and uncertainty of diagnosis, showed that: 1) Most of the study subject's were in their 40's of age and had been dispatched to Vietnam during the period from $1965{\sim}1970$ around one year. 2) Most frequently complained symptoms in medical examination were motor weakness (32%), sensory abnormalities in extremities (23%), skin diseases (22%), and pain in extremities (20%) whereas in Interview they were more frequent in order of skin problem (44%), motor weakness (38%), sensory abnormalities and pain in extremities(17% and 19% each). Kappa indices on the same category of complaints between two sources of information were variable and relatively low. 3) On medical examination, only a part of the 638 subjects had initial impression (442 pts) and final diagnosis (218 pts) suggesting decision making on diagnosis appeared to be difficult even with all available modern medical technologies: in initial impression disorders from peripheral and central neuropathy were predominant whereas in final diagnosis various types of skin disorder were most frequent 4) When dose-response relationship between several conditions (from questionnaire) and arbitrary exposure scores were examined by CMH linear trend test, spontaneous abortion, sexual problems and health problem of offsprings showed statistically significant linear trends. However, pregnancy, accident and suicidal attempts did not show any relationship in this study capacity. 5) Among complaints, psychosis and neurosis (anxiety, phobia) in interview study, and memory disorder and psychosis in medical record study revealed linear trend. 6) Skin disorder was the only condition showing linear trend in initial impression and none in final diagnosis on medical examination. Even though objective to select out dioxin-related disease or group of diseases from this study was not achieved the research experiences provided firm basis for developing various methodological approaches. 3. From this preliminary study we concluded that a larger scale major epidemiologic study on health impacts of herbicides among Korean veterans exposed is not only Indispensible but also well designed study with more valid exposure information and diagnosis may be able to establish causal relationship between certain groups of diseases and exposure to the herbicides among Korean veterans.

• Radiation Oncology Journal
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• v.18 no.1
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• pp.40-45
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• 2000

Purpose : To evaluate the histopathological prognostic factors, relapse pattern and survival in patients with endometrial carcinoma who were treated with surgery and postoperative adjuvant radiotherapy (RT). Methods and Materials : From September 1991 to December 1997, 27 patients with endometrial carcinoma treated with surgery and postoperative adjuvant RT at Asan Medical Center were entered in this study. Surgery was peformed with total abdominal hysterectomy in six, total abdominal hysterectomy with pelvic lymph node dissection in eight and radical hysterectomy in 13 patients. External RT of 50.4 Gy was done to all patients and among these, additional high dose rate vaginal vault irradiation of 20$\~$25 Gy with fractional dose of 4$\~$5 Gy was boosted In 16 patients. The patients were followed for 6$\~$95 months(median 30). Results : The number of patients according to FIGO stage were I 18 (67$\%$), II 1 ($4\%$) and III 7 ($26\%$). Patients with poor histologic grade, deep myometrial invasion, adnexal involvement, lymphovascular invasion showed more pelvic lymph node involvement, but no statistical significance was indicated. The 5 year overall and disease free survival were 100$\%$ and 76.8$\%$, respectively. Relapse sites were pelvic, para-aortic lymph node, and multiple metastases including lung, and no vaginal relapse was developed. Factors that were associated with disease free survival were FIGO stage (p=0.01), lymphovascular invasion (p=0.03), pelvic lymph node involvement (p=0.0001). There was only one Grade 1 rectal bleeding without moderate to severe complications. Conclusion : Postoperative adjuvant RT is considered to reduce the loco-regional failure, resulting the improvement of survival. The group of patients with the risk of vaginal failure without vaginal vault irradiation should be investigated according to stage and grade.

• The Korean Journal of Nuclear Medicine Technology
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• v.18 no.1
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• pp.19-25
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• 2014

Purpose: Integrated PET/MRI has been developed recently has become a lot of help to the point oncologic, neological, cardiological nuclear medicine. By using this PET/MRI, a ${\mu}-map$ is created some special MRI sequence which may be divided parts of the body for attenuation correction. However, because an MRI contrast agent is necessary in order to obtain an more MRI information, we will evaluate to see an effect of SUV on PET image that corrected attenuation by MRI with contrast agent. Materials and Methods: As PET/MRI machine, Biograph mMR (Siemens, Germany) was used. For phantom test, 1mCi $^{18}F-FDG$ was injected in cylinderical uniformity phantom, and then acquire PET data about 10 minutes with VIBE-DIXON, UTE MRI sequence image for attenuation correction. T1 weighted contrast media, 4 cc DOTAREM (GUERBET, FRANCE) was injected in a same phatnom, and then PET data, MRI data were acquired by same methodes. Using this PET, non-contrast MRI and contrast MRI, it was reconstructed attenuation correction PET image, in which we evanuated the difference of SUVs. Additionally, for let a high desity of contrast media, 500 cc 2 plastic bottles were used. We injected $^{18}F-FDG$ with 5 cc DOTAREM in first bottle. At second bottle, only $^{18}F-FDG$ was injected. and then we evaluated a SUVs reconstructed by same methods. For clinical patient study, rectal caner-pancreas cancer patients were selected. we evaluated SUVs of PET image corrected attenuastion by contrast weighted MRI and non-contrast MRI. Results: For a phantom study, although VIBE DIXON MRI signal with contrast media is 433% higher than non-contrast media MRI, the signals intensity of ${\mu}-map$, attenuation corrected PET are same together. In case of high contrast media density, image distortion is appeared on ${\mu}-map$ and PET images. For clinical a patient study, VIBE DIXON MRI signal on lesion portion is increased in 495% by using DOTAREM. But there are no significant differences at ${\mu}-map$, non AC PET, AC-PET image whether using contrast media or not. In case of whole body PET/MRI study, %diff between contras and non contrast MRAC at lung, liver, renal cortex, femoral head, myocardium, bladder, muscle are -4.32%, -2.48%, -8.05%, -3.14%, 2.30%, 1.53%, 6.49% at each other. Conclusion: In integrated PET/MRI, a segmentation ${\mu}-map$ method is used for correcting attenuation of PET signal. although MRI signal for attenuation correciton change by using contrast media, ${\mu}-map$ will not change, and then MRAC PET signal will not change too. Therefore, MRI contrast media dose not affect for attenuation correction PET. As well, not only When we make a flow of PET/MRI protocol, order of PET and MRI sequence dose not matter, but It's possible to compare PET images before and after contrast agent injection.

• Journal of Food Hygiene and Safety
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• v.28 no.4
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• pp.360-366
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• 2013

The objective of this study is to investigate the effect of multivitamin on macrophage activity in Raw 264.7 cell and repeated oral dose toxicity in Sprague-Dawely rat of multivitamin. Raw 264.7 cells were treated with 50 and $100{\mu}g/mL$ multivitamin for 24 h. To measure the activity of macrophages, NO and TNF-${\alpha}$ assays were performed in Raw 264.7 cells. Treatment with 50 and $100{\mu}g/mL$ multivitamin for 24 h significantly increased production of NO and TNF-${\alpha}$ compared with control groups, indicating activation of macrophages. The female rats were treated with multivitamin of control group, low group (0.24 g/kg), medium group (1 g/kg) and high group (2 g/kg) intragastrically for 4 weeks, respectively. We examined the body weight, the feed intake, the clinical signs and serum biochemical analysis. We also observed the histopathological changes of liver, ovary, brain, adrenal gland, spleen, kidney, heart and lung in rats. No significant differences in body weights, feed intake, biochemical analysis and histopathological observations between control and multivitamin treatment group were found. In conclusion, multivitamin is physiologically safe and improve macrophage activity.

• Radiation Oncology Journal
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• v.12 no.3
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• pp.377-386
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• 1994

Purpose: The role of radiotherapy in the management of patients with locoregional recurrent cervix cancer after radical surgery were retrospectively analyzed. Methods and materials: Twenty-eight patients treated with radiotherapy for locoregional recurrence after primary surgery for carcinoma of the cervix between 1989 and 1993 were analyzed. The median follow-up of survivors was 15 months (ranged 7-43 months). Eight patients had their disease confined to the vagina and 19 patients($68\%$) had pelvic mass as part of their locoregional recurrent disease. Within 24 months after the initial surgery, $82\%$ of recurrences manifested themselves. All patients had whole pelvic irradiation with or without intracavitary radiotherapy(ICR). Results: Complete response(CR) was achieved in 18 patients($54\%$). Five of eighteen patients($28\%$) with initial CR developed second locoregional recurrence. Response to radiotherapy correlated strongly with tumor volume, site of recurrence and total radiation dose. The overall 2 year survival rate was $43\%$ and the disease free survival was $31\%$. Survival rate was significantly influenced by the factors of interval from operation to recurrence, size and site of recurrent tumor, radiation dose, response of radiotherapy, lymph node status as initial presentation, The principal cause of death was lung metastasis($36\%$). Conclusion: Radiotherapy is an excellent modality for control of locoregional recurrent cervix cancer. To improve local control and survival rate, whole pelvic external radiotherapy in addition to ICR with more than 75.0Gy at the depth of 1.0cm from vaginal mucosa is needed and frequent follow up and early detection of recurrence is suggested as well.

• Tuberculosis and Respiratory Diseases
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• v.40 no.2
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• pp.123-134
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• 1993

Background: Tissue-type plasminogen activator is a physiologic activator, which has high affinity for fibrin and is activated by fibrin. Because of these properties, t-PA has the potential to induce effective thrombolysis without producing a systemic lytic state. In practice, however, therapeutically efficacious doses of t-PA has been associated with the development of a systemic lytic state. As experience with t-PA has accumulated, it has suggested that the fibrin selectivity is influenced by the dose and duration of t-PA infusion, and many studies have performed in an attempt to optimize the duration of t-PA regimen. Methods: This study was designed to assess the thrombolytic efficacy of t-PA and the differences of two dosing regimens of t-PA (infusion of 1 mg/kg t-PA over 15 or 180 minutes) in a canine model of pulmonary embolism, induced by injection of radioactive autologous blood clots. By continuously counting over both lung fields with a external gamma counter, we correlated rate and extent of pulmonary thrombolysis with corresponding pulmonary hemodynamics in addition to the gas analyses of arterial and mixed venous blood. Results: 1) While total clot lysis was similar ($36.2{\pm}3.3%$ and $39.6{\pm}2.3%$ respectively, p>0.05) when t-PA was infused over 15 or 180 minutes, the rate of lysis during infusion was markedly increased with the shorter infusion ($81.4{\pm}16.8%/hr$ vs $37.3{\pm}2.4%/hr$, p<0.05). 2) The duration of thrombolysis was $63.3{\pm}22.2$ minutes although t-PA was administered over 15 minutes, and it was only $148.5{\pm}14.0$ minutes in case of the infusion over 180 minutes (p<0.05). 3) The increased rate of thrombolysis with the shorter infusion was accompanied by a faster amelioration of cardiopulmonary impairment from pulmonary embolism (p<0.05). Conclusion: It is concluded that the shorter (15 minutes) infusion of t-PA is superior to the longer (180 minutes) infusion when the dose is equal, in consideration of the faster improvement in cardiopulmonary impairment from pulmonary embolism.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.441-446
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• 1998

Purpose : The incidence of esophageal carcinoma is increasing. Radical surgery is the treatment of choice, but large proportion of the esophageal cancer patients are with unresectable disease at the time of initial diagnosis, so radiation therapy has been the major treatment modality. We carried out retrospective analysis to see the outcome and prognostic factors of radiation therapy alone for esophageal carcinoma. Methods and Materials : From June of 1979 through December 1992, 289 patients with esophageal carcinoma were treated with radiation therapy alone at Department of Therapeutic Radiology, Seoul National University Hospital. Of these patients, 84 patients were excluded as they were ineligible for the current analyses. Twenty-two patients had distant metastasis other than supraclavicular lymph node metastasis, 52 patients received less than 45 Gy, and 10 patient were lost from follow-up. Therefore 205 patients constituted the base population of this study. According to AJCC s1aging system, there were 2 patients with stage 1, 104 with stage IIA, 26 with stage IIB, 48 with stage III, and 25 with stage IV Radiation dose ranged from 4500 cGy to 6980 cGy with median dose of 5940 cGy. Follow-up period of the alive patients ranged from 77 to 180 months. Results : The Median survival period of all the patients was II months and the 2-, 5-, and 10-year overall survival rates were 22.4$\%$, 10.2$\%$ and 5.3$\%$, respectively. Most of the failures were local recurrences. Of 169 failures, 134 had local failure as a component and 111 had local recurrence only. The Lymph node was most common distant metastatic site and the next was the lung. The stage, T-stage, N-stage, functional status, tumor size, and aim of treatment were statistically significant prognostic factors for survival by univariate analyses. But only tumor size and N-stage were significant by multivariate analyses. Conclusion : We could get 10.2$\%$ of 5 year survival rate and 5.3$\%$ of 10 year survival rate with radiation therapy alone. The size of tumor and N-stage were statistically significant prognostic factors for survival on multivariate analyses.