• Korean Journal of Medicinal Crop Science
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• v.25 no.5
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• pp.322-327
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• 2017

Background: Cynaroside is a flavone, a flavonoid-like compound, known by different names (luteoloside and cinaroside). It is commonly found in Lonicera japonica Thunb., Chrysanthemum moriflium, and Angelica keiskei. The process of cell death has been classified as necrosis and apoptosis. Necrosis refers to unregulated cell death induced by a chemotherapeutic agent. Doxorubicin is an anthracycline anti-cancer drug used to treat acute leukemia, cancer, and lymphoma. However, it induces nephrotoxicity including tubular damage. Therefore, we investigated the protective effect of cynaroside against doxorubicin-induced necrosis in HK-2 cells. Methods and Results: To confirm the beneficial effect of cynaroside on doxorubicin-induced necrosis, HK-2 cells, a human proximal tubule epithelial cell line were treated with $10{\mu}M$ doxorubicin and $80{\mu}M$ cynaroside. Doxorubicin treatment resulted in increased DNA fragmentation, caspase-3 activity and mitochondria hyperactivation during cell necrosis. However, pretreatment with $80{\mu}M$ cynaroside attenuated DNA fragmentation, caspase-3 activity and mitochondria hyperactivation induced by $10{\mu}M$ doxorubicin in HK-2 cells. Conclusions: These results indicated that pretreatment with cynaroside ameliorated doxorubicin-induced necrosis in HK-2 cells. Therefore, cynaroside be used as a therapeutic agent for improving doxorubicin-induced nephrotoxicity. However, further studies are required to evaluated the toxicity of cynaroside treatment in animals and to determine its protective effect against doxorubicin-induced nephrotoxicity in an animal model.

• Quality Improvement in Health Care
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• v.27 no.2
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• pp.18-29
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• 2021

Purpose: Patients with hematologic malignancy (HM) typically have a high mortality rate when their condition deteriorates. The chronic progressive course of the disease makes it difficult to assess the effect of intervention on acute events. We investigated the effectiveness of a rapid response team (RRT) on in-hospital mortality in patients with HM. Methods: We retrospectively analyzed the data of patients with HM who admitted to the medical intensive care unit between 2006 and 2015. Clinical outcomes before and after RRT implementation were evaluated. Results: A total of 228 patients in the pre-RRT period and 781 patients in the post-RRT period were included. The overall in-hospital mortality was 55.4%. Patients in the post-RRT period had improved survival; however, they required more vasopressor therapy, continuous renal replacement therapy, and extracorporeal membrane oxygenation. Multivariate analysis revealed that in-hospital mortality was associated with RRT activation (hazard ratio [HR], 0.634; 95% confidence interval [CI], 0.498-0.807; p < .001), neurological disease (HR, 2.007; 95% CI, 1.439-2.800; p < .001), sequential organ failure assessment score (HR, 1.085; 95% CI, 1.057-1.112; p < .001), need for continuous renal replacement therapy (HR, 1.608; 95% CI, 1.206-1.895; p< .001), mechanical ventilation (HR, 1.512; 95% CI, 1.206-1.895; p< .001), vasopressor (HR, 1.598; 95% CI, 1.105-2.311; p = .013), and extracorporeal membrane oxygenation (HR, 1.728; 95% CI, 1.105-2.311; p = .030). Conclusion: RRT activation may be associated with improved survival in patients with HM.

• Clinical and Experimental Pediatrics
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• v.45 no.8
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• pp.1000-1006
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• 2002

Purpose : In the course of treatment, patients with hematological or oncological disorders often develop pulmonary complication. The patients who develop a severe pulmonary complication have a poor outlook. The causes of pulmonary complication are either infectious or non-infectious in origin. We have analyzed the etiology and outcome of these patients admitted to the pediatric intensive care unit of Asan Medical Center. Methods : Medical records of 95 patients on Pediatric oncology service who were admitted to pediatric intensive care unit(PICU) of Asan Medical Center from Jan 1997 to May 2000 were retrospectively reviewed. Results : The mean age of the patients was 8.5 years(2 months-18 years). The underlying malignancies of these 95 patients were as following; acute lymphoblastic leukemia(31 cases), lymphoma (11 cases), acute myeloid leukemia(nine cases), brain tumor(eight cases) and other solid tumors(25 cases). Pulmonary complications included pneumonia, acute respiratory failure, pneumothorax and pleural effusion. The most common cause of pulmonary complication was infection(88%) in etiology. The overall mortality rate was 56.8%. Pulmonary complications in these patients carried high rates of mortality regardless of whether they were immune compromised(76%) or not(69%). Even without pulmonary complications, the hematological or oncological patients admitted to PICU had high mortality rates of 43%. Conclusion : Pulmonary complications are frequent finding in the hematological or oncological patients admitted to Intensive Care Unit. The main etiology of these pulmonary complications was infection, which carried a high mortality rate regardless of their immune status at the time when they were admitted to PICU.

• Journal of Life Science
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• v.20 no.7
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• pp.1054-1065
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• 2010

SH21B is a natural composition composed of seven herbs: Scutellaria baicalensis Georgi, Prunus armeniaca Maxim, Ephedra sinica Stapf, Acorus gramineus Soland, Typha orientalis Presl, Polygala tenuifolia Willd and Nelumbo nucifera Gaertner (Ratio 3:3:3:3:3:2:2). In our previous study, we reported that SH21B inhibited adipogenesis and fat accumulation in 3T3-L1 cells through modulation of various regulators in the adipogenesis pathway. The aim of this study was to analyze the transcriptome profiles for the anti-adipogenic effects of SH21B in 3T3-L1 cells. Total RNAs from SH21B-treated 3T3-L1 cells were reverse-transcribed into cDNAs and hybridized to Affymetrix Mouse Gene 1.0 ST array. From microarray analyses, we identified 2,568 genes of which expressions were changed more than two-fold by SH21B, and the clustering analyses of these genes resulted in 9 clusters. Three clusters among the 9 showed down-regulation by SH21B (cluster 4, cluster 6 and cluster 9), and two clusters showed up-regulation by SH21B (cluster 7 and cluster 8) during the adipogenesis of 3T3-L1 cells. It was found that many genes related to cell proliferation and adipogenesis were included in these clusters. Clusters 4, 6 and 9 included genes which were related with adipogenesis induction and cell cycle arrest. Clusters 7 and 8 included genes related to cell proliferation as well as adipogenesis inhibition. These results suggest that the mechanisms of the anti-adipogenic effects of SH21B may be the modulation of genes involved in cell proliferation and adipogenesis.

• Journal of Veterinary Clinics
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• v.24 no.4
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• pp.479-485
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• 2007

A retrospective study of 94 hypercalcemic dogs was performed to find out most common causes that lead to hypercalcemia through investigating dogs referred to the Veterinary Teaching Hospital of Konkuk University from 2002 to 2004. During the study period, hypercalcemia was found in 94 dogs of 19 breeds, and they were evaluated as case group. Control group was made up of 94 dogs of 18 breeds without hypercalcemia admitted for the same study period. For general signalments, there were no significant differences between case and control group with the exception of age distribution. Shih-tzu(17.02%) and Yorkshire terrier(26.60%) was the most common breed in case and control group, respectively. The most common diseases associated with hypercalcemia were chronic renal failure (18.09%), acute renal failure(14.89%), and renal calculi(6.38%). Malignant neoplasia(lymphoma, hemangiosarcoma, chronic lymphocytic leukemia, mammary gland tumor, and multiple myeloma) and endocrinopathies(hyperadrenocorticism, hyperthyroidism, hypoadrenocorticism, and hypothyroidism) occupied 8.5% and 6.4%, respectively. This report is a first retrospective study of hypercalcemic dogs in South Korea.

• KSBB Journal
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• v.22 no.1
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• pp.22-29
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• 2007

The water-soluble materials extracted from fruit bodies and mycelium of H. erinaceum were prepared. In-vitro anticancer activities on cancer cells and In-vivo proliferation effect on mouse peritoneal exudate cell and spleen cell of samples were investigated. Also, nitric oxide (NO) generation of peritoneal exudate cell, IL-2 production capacity of spleen cells and phagocytic activity of peritoneal macrophages were examined. The water extracts of H. erinaceum suppressed the proliferation of cancer cell (HeLa, Raw264.7, Jurkat, KATO3, EL4, LyD9) with concentration-dependent. The water extract from fruit body showed better suppression effect than that from mycelium in most of cancer cells used. The anticancer effect of water extract of fruits body in the range of 0.01 and 10 mg/ml for Raw 264.7 and EL4 cell lines were the same as the Taxol with one thousandth equivalent of fruit body concentration. Water extracts of fruit body and liquid-cultured products of H. erinaceum induced nitric oxide (NO) generation of peritoneal exudate cell and increased NO generation by stimulus of lipopolysaccharide. Water extracts alone did not induce the proliferation and IL-2 production capacity of spleen cells. However, spleen's proliferation and IL-2 production were induced significantly by the addition of lipopolysaccharide and Con A (concanavalin A) or Con A alone, and the effectiveness of mycelium extract with water were more active than those from fruit body.

• Tuberculosis and Respiratory Diseases
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• v.45 no.3
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• pp.565-573
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• 1998

Malignant pleural effusions are most commonly associated with lung cancers, however, it also can be resulted from breast cancers, ovarian cancers, stomach cancers and so on. According to the their histologic types, adenocarcinoma have been known as the most common cell type of malignant pleural effusions and squamous cell carcinoma is rare. We herein present incidences, clinical characteristics and survivals of malignant pleural effusions according to their cell types and primary diseases. The objects are 84 malignant pleural effusion patients diagnosed by pleural fluid cytologic examination or pleural biopsy from Jan. 1992 to May. 1997 in Seoul National University Hospital. A retrospective chart review on their histologic types, biochemical parameters and survivals is described. Among 84 patients, 52 were males and the other 32 were females with 1.6:1 of male and female ratio and their mean age was 57.6 years old. Common symptoms of them wele dyspnea, cough, sputum and pleuritic chest pain. The proportions of bloody nature of effusion, lymphocyte dominant pleural effusion, exudative effusions were 66%, 39% and 93%, respectively. They consisted of 54 cases of adenocarcinoma(33 cases of them were lung cancers), and 10 cases of squamous cell carcinoma (8 cases of them were lung cancers), 10 cases of malignant lymphoma, 8 cases of small cell lung cancer and a case of mesothelioma and leukemia. There was no differences in characteristics of effusions, clinical features and survivals between each histologic cell types. Analyzing them according to primary diseases, no difference except longer survivals in malignant pleural effusions from breast cancer than from other cancers was observed. In conclusion, considering the incidences of histologic types of lung cancers during same period (squamous cell carcinoma; 47%, adenocarcinoma; 33%, small cell lung cancer; 12% and large cell carcinoma; 2%), malignant pleural effusions more likely occurred in adenocarcinoma than other cell types of lung cancers and there was no significant difference of clinical characteristics between histologic types.

• Clinical and Experimental Pediatrics
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• v.46 no.6
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• pp.566-571
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• 2003

Purpose : Leukoencephalopathy(LE) is one of the most serious complications in children with hematologic malignancies during the course of treatment. Early recognition is important to reduce the impact and sequelae from LE. We therefore investigated the clinical features of LE following central nervous system(CNS) prophylaxis in children with hematologic malignancies and evaluated the significance of regular check-ups of brain MRI. Methods : We retrospectively reviewed children with hematologic malignancies who had CNS prophylaxis including intrathecal(IT) methotrexate(MTX) and/or cranial irradiation at the Department of Pediatrics, Kyungpook National University Hospital from Oct. 1995 to May 2002. Fifteen cases of acute leukemia and one case of lymphoma who experienced LE following CNS prophylaxis were included in the study. Clinical data were analyzed from the medical records and brain MRIs were reviewed by neuroradiologists. Results : The ages ranged from 1 to 13 years(median age=5.2 years), and the male to female ratio was 3 : 1. The time interval from the beginning of chemotherapy to the time of diagnosis of LE ranged from 2 to 17 months. They all had IT MTX two to 15 times and ten underwent cranial irradiation(1,800 rads). At the time of diagnosis, ten of them had neuropsychiatric symptoms including seizures, personality changes, headache, etc. After the change of treatment modality, four cases showed significant improvement on follow-up MRIs, six cases had no significant changes and two had worsening of LE. Four patients died of infection and bone marrow relapse. Conclusion : CNS prophylaxis with IT therapy and cranial irradiation may cause leukoencephalopathy during the course of treatment. As a result, regular brain MRI check-up is recommended for the early detection and reducing the incidence of LE, along with changes in the treatment modality.

• Radiation Oncology Journal
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• v.17 no.4
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• pp.321-328
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• 1999

Purpose : Total body irradiation (TBI) or whole body irradiation is used to acquire immune suppression, to treat malignant lymphoma and leukemia, and as an conditioning regimen for bone marrow transplantation. For these purposes, many methods were developed to obtain homogenous dose distribution. The objective of this study was to analyze and confirm the accuracy and the homogeneity of the treatment setup, the parallel opposed lateral technique, currently used in Seoul National University Hospital. Materials and Metheods : Surface dose data, measured with a thermoluminescent dosimeter, of 8 patients among 10 patients, who were given total body irradiation with the parallel opposed lateral technique between September 1996 to August 1998, at Seoul National University Hospital were analyzed. Surface doses were measured at the head, neck, axilla, thigh, and ankle level. Surface and midline doses were measured with similar set-up and technique in the Humanoid phantom. Results : Measured surface doses relative to prescribed dose for the head, neck, axilla, thight, and ankle leve were $91.3{\pm}7.8,{\;}98.3{\pm}7.5,{\;}95.1{\pm}6.3,{\;}98.3{\pm}5.5$, and $95.3{\pm} 6.3\%$, respectively. The midline doses of the head, neck, axilla, thigh, and ankle level estimated from the surface-to-midline ratios in the Humanoid Phantom were $103.4{\pm}9.0,{\;}107.8{\pm}10.5,{\;}91.1{\pm}6.1,{\pm} 93.8{\pm}4.5,{\;}and{\;}104.5{\pm}9.3\%$, respectively. Measured surface doses and estimated midline doses ranged from $-8.9\%$ to $+7.8\%$. Midline doses at the neck and the axilia level deviated more than $5\%$ from the prescribed doses. The difference of the estimated midline doses at the neck and the axilla level and the actual doses were attributed to the thickness differences between the Humanoid phantom and the patients. Conclusion Distribution of the midline doses as well as the suface doses were measured to be within $-8.7\~{\pm}7.8\%$ range. Actual dose distribution in the patient is expected to be better than the measured dose range mainly attributed to thickness difference between the patient and the Humanoid phantom.

• Tuberculosis and Respiratory Diseases
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• v.46 no.3
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• pp.327-337
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• 1999

Background: Reactive oxygen species are involved in multi-stage process of carcinogenesis. The moot of cancer cell lines and cancer cells in tumor tissue produce reactive oxygen species and on the other hand, the activities of catalase, Mn- and CuZn-superoxide dismutase in tumor cells are usually low. These persistent oxidative stress in tumor tissue facilitates tumor invasion and metastasis. 12-kDa thioredoxin, which regulates the intracellular redox potential with glutathione and glutaredoxin is involved in cell activation, proliferation, differentiation and redox-mediated apoptosis. It is also purified as 14-kDa and 10-kDa eooinophilic cytotoxic enhancing factor(ECEF) from human histiocytic cell(U937) and 10-kDa ECEF has more than 20 times eosinophilic stimulation activity than 14-kDa ECEF. It has been reported that adult T-cell leukemia, squamous cell carcinoma of uterine cervix, and hepatocellular carcinoma show increased amounts of human thioredoxin and thioredoxin mRNA is increased in lung cancer. In this study, we investigated the expression of conventional antioxidant enzymes such as catalase, CuZn-SOD, and glutathione peroxidase and thioredoxin in lung cancer tissue compared to adjacent normal lung tissue and the induction of thioredoxin in macrophage cells after treatment of oxidative stress and endotoxin Methods: We measured the amount of conventional antioxidant enzymes such as catalase, CuZn-SOD, and glutathione peroxidase and thioredoxin in lung cancer tissue compared to adjacent normal lung tissue by immunoblot analysis and the induction of thioredoxin in mouse monocyte-macrophage cells(RAW 264.7) by treatment of 5 ${\mu}M$ menadione and 1 ${\mu}g/ml$ endotoxin Results: On immunoblot analysis, the expression of 12-kDa thioredoxin was increased in lung cancer tissue compared to paired normal lung tissue. but the expression of catalase and CuZn-SOD were decreased in lung cancer tissue compared to paired normal tissue and the expression of glutathione peroxidase in lung cancer was variable. The expression of truncated thioredoxin was also increased in lung cancer. When mouse monocyte-macrophage cells were treated with 5 ${\mu}M$ menadione and 1 ${\mu}g/ml$ endotoxin, the expression of thioredoxin was peaked at 12 hrs and sustained to 48 hrs. Conclusion: In contrast with other conventional antioxidants, the expression of 12-kDa and truncated thioredoxin in lung cancer were increased and it is closely associated with persistent oxidative stress in tumor microenvironment. Considering especially the biological functions of truncated thioredoxin, the increased amount of truncated thioredoxin has significant role in tumor growth through cell proliferation.