• The Korean Journal of Physiology and Pharmacology
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• 제20권3호
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• pp.237-243
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• 2016

Oleanolic acid (OA) has a wide variety of bioactivities such as hepatoprotective, anti-inflammatory and anti-cancer activity and is used for medicinal purposes in many Asian countries. In the present study, the effect of OA on induction of autophagy in human hepatocellular carcinoma HepG2 and SMC7721 cells and the related mechanisms were investigated. MTT assay showed that OA significantly inhibited HepG2 and SMC7721 cells growth. OA treatment enhanced formation of autophagic vacuoles as revealed by monodansylcadaverine (MDC) staining. At the same time, increasing punctuate distribution of microtubule-associated protein 1 light chain 3 (LC3) and an increasing ratio of LC3-II to LC3-I were also triggered by OA incubation. In addition, OA-induced cell death was significantly inhibited by autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) pretreatment. And we found out that OA can suppress the PI3K/Akt1/mTOR signaling pathway. Furthermore, our data suggested that OA-triggered autophagy was ROS-dependent as demonstrated by elevated cellular ROS levels by OA treatment. When ROS was cleared by N-acetylcysteine (NAC), OA-induced LC3-II convertsion and cell death were all reversed. Taken together, our results suggest that OA exerts anticancer effect via autophagic cell death in hepatocellular carcinoma.

• 보건행정학회지
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• 제23권3호
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• pp.233-243
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• 2013

Background: This study was conducted to evaluate the individual and community level factors which were influencing the severe injury patients' death and transfer at discharge. Methods: Analysis data is based on Korean National Hospital Discharge In-depth Survey Data released by the Korea Center for Disease Control and Prevention from 2006 to 2008. Study subjects was 11,026 inpatients with of severe injury. For multi-level analysis, socio-demographic characteristics, injury related characteristics, hospitalization related characteristics were used as individual level factors, and socio-environmental characteristics and health care resource characteristics were used as community level factors. Results: As to community level factors affecting mortality of severe injury, the possibility of death was also high in cases of less numbers of surgeons per a population of 100,000 and more number of operation beds. As to community level factors affecting transfer of severe injury, vulnerable areas with higher social deprivation index and low population density had higher possibility of transfer. Conclusion: Both individual level factors and community level factors affected clinical outcomes of treatment for severe injury. In particular, since there happened higher death and transfer of severe injury in socioeconomic and medical vulnerable areas, special efforts for establishing preventive policy and care system for injury in national and area level should be directed toward such areas.

• Journal of Preventive Medicine and Public Health
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• 제54권1호
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• pp.55-62
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• 2021

Objectives: After heart disease, brain stroke (BS) is the second most common cause of death worldwide, underscoring the importance of understanding preventable and treatable risk factors for the outcomes of BS. This study aimed to model the survival of patients with BS in the presence of competing risks. Methods: This longitudinal study was conducted on 332 patients with a definitive diagnosis of BS. Demographic characteristics and risk factors were collected by a validated checklist. Patients' mortality status was investigated by telephone follow-up to identify deaths that may be have been caused by stroke or other factors (heart disease, diabetes, high cholesterol, etc.). Data were analyzed by the Lunn-McNeil approach at alpha=0.1. Results: Older age at diagnosis (59-68 years: adjusted hazard ratio [aHR], 2.19; 90% confidence interval [CI], 1.38 to 3.48; 69-75 years: aHR, 5.04; 90% CI, 3.25 to 7.80; ≥76 years: aHR, 5.30; 90% CI, 3.40 to 8.44), having heart disease (aHR, 1.65; 90% CI, 1.23 to 2.23), oral contraceptive pill use (women only) (aHR, 0.44; 90% CI, 0.24 to 0.78) and ischemic stroke (aHR, 0.52; 90% CI, 0.36 to 0.74) were directly related to death from BS. Older age at diagnosis (59-68 years: aHR, 21.42; 90% CI, 3.52 to 130.39; 75-69 years: aHR, 16.48; 90% CI, 2.75 to 98.69; ≥76 years: aHR, 26.03; 90% CI, 4.06 to 166.93) and rural residence (aHR, 2.30; 90% CI, 1.15 to 4.60) were directly related to death from other causes. Significant risk factors were found for both causes of death. Conclusions: BS-specific and non-BS-specific mortality had different risk factors. These findings could be utilized to prescribe optimal and specific treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6587-6590
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• 2014

Objective: To further observe the efficacy and safety of pemetrexed, combined with Irinotecan or oxaliplatin or cisplatin in treating patients with advanced gastric cancer as second-line or third-line chemotherapy. Methods: From September 2013 to February 2014 we recruited 50 patients with advanced gastric cancer, with stage IV disease or postoperative recurrence, or unresectable. Then treated with pemetrexed based chemotherapy. After two cycles of treatment, efficacy and toxicity were evaluated. Results: Pemetrexed based chemotherapy was used as second-line in 33 patients, RR(CR+PR) is 41.2%. And achieved 36.4% when used as third-line. Overall response rate of 50 patients treated with Pemetrexed based treatment was 38% (CR+PR). Treatment related side effects were bone marrow suppression, vomiting, hepatic dysfunction and malaise.No treatment related death occurred. Conclusions: Treatment with pemetrexed based chemotherapy is active and is well tolerated in patients with advanced gastric cancer.

• Journal of Acupuncture Research
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• 제31권2호
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• pp.87-98
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• 2014

Objectives : We investigated whether snake venom toxin(SVT) from Vipera lebetina turanica sensitizes HT29 human epithelial colorectal cancer cells to tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL) induced apoptosis in cancer cells. Methods : Cell viability assay was used to assess the inhibitory effect of TRAIL on cell growth of HT29 human colorectal cancer cells. And 6-diamidino-2-phenylindole(DAPI), terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay(TUNEL) staining assay were used to evaluate cell-apoptosis. Western blot analysis were conducted to observe apoptosis related proteins and death receptor. To assess whether the synergized inhibitory effect of SVT and TRAIL on reactive oxygen species(ROS) generation was reversed by strong anti-oxidative agent. Results : SVT with TRAIL inhibited HT29 cell growth different from TRAIL alone. Consistent with cell growth inhibition, the expression of TRAIL receptors; Expression of death receptor(DR)4 and DR5 was significantly increased and intrinsic pro-apoptotic cleaved caspase-3, -9 was subsequently increased together with increase of Bax/Bcl-2 ratio and extrinsic pro-apototic caspase-8 was also activated. In addition, the expression of anti-apoptotic survival proteins, a marker of TRAIL resistance(eg, cFLIP, survivin, X-linked inhibitor of apoptosis protein(XIAP) and Bcl-2) was suppressed by the combination treatment of SVT and TRAIL. Pretreatment with the ROS scavenger N-acetylcysteine abolished the SVT and TRAIL-induced upregulation of DR4 and DR5 expression and expression of the intrinsic pro-apoptotic caspase-3 and-9. Conclusion : The collective results suggest that SVT facilitates TRAIL-induced apoptosis in $HT_{29}$ human epithelial colorectal cancer cells through up-regulation of the TRAIL receptors; DR4 and DR5 and consecutive induction of bilateral apoptosis via regulating apoptosis related proteins.

• The Korean Journal of Pain
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• 제11권2호
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• pp.214-219
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• 1998

Pain is one of the most frequent and disturbing symptom of cancer patients. And almost of cancer patients are afraid of a attacks of pain related to cancer. Caring for the cancer patient can be divided into two phases. The phase of "active treatment" involves various interventions-surgical, chemical or radiological- that are designed to prolong the patient's life. "Terminal care" is the period from the end of active treatment until the patient's death. But in the majority of clinical settings, cancer pain is not being managed adequately results from a lack of education about how to treat the cancer pain management in the safest and most effective way during terminal phase. Althought organic factors represent the most important cause of their pain, it is also important to deal with the patient's psychological reactions and to take account of his or her social and family environment if treatment for chronic cancer pain is to prove adequate. Thus we try to evaluate a kinds of cancer related to pain, degree of pain, effectiveness of drugs, and patient's responses to management. In regard to the satisfaction for pain relief in pain clinics at Pusan National University Hospital(PNUH) are about 70% in patients and 90% in family. Average life expectancy in cancer patients are about 140 days (3 days- 5.7 years). Cancer patients are complained of several discomfortness (above 30 kinds) such as, pain associated with cancer (75%), nausea and vomitting (38%), sleeping disorder (38%), anorexia (38%), dyspnea (32%), constipation (31%), etc. Distributions of cancer associated with pain are stomach cancer (21%), lung cancer (16%), cervix cancer (10%), anorectal and colon cancer (8.6%), hepatoma (8%), pancreatic cancer (3%). About 1/3 of patients are suffer from incident pain in 3~5 times in a day especially in moving, coughing, and exercise. Methods for drug delivering system before death are transdermal fentanyl patch (42%), intravenous PCA (21%), oral intake of opioid (17%), epidural PCA (14%), etc.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3827-3833
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• 2015

Background: Positive para-aortic lymph node (PALN) at diagnosis in cervical cancer patients confers an unfavorable prognosis. This study reviewed the outcomes of extended field radiotherapy (EFRT) and concurrent chemotherapy with extended field RT (CCEFRT) in patients with positive PALN at diagnosis. Materials and Methods: Medical records of 407 cervical cancer patients between 1st January 2002 to 31st December 2012 were reviewed. Some 32 cases with positive PALN were identified to have received definitive extended field radiotherapy with or without chemotherapy. Treatment outcomes, clinicopathological factors affecting survival and radiotherapy related acute and late effects were analyzed. Results: Totals of 13 and 19 patients underwent EFRT and CCEFRT respectively during the period of review. The median follow-up was 70 months. The 5-year overall survival (OS) was 40% for patients who underwent CCEFRT as compared to 18% for patients who had EFRT alone, with median survival sof 29 months and 13 months, respectively. The 5-years progression free survival (PFS) for patients who underwent CCEFRT was 32% and 18% for those who had EFRT. Median PFS were 18 months and 12 months, respectively. Overall treatment time (OTT) less than 8 weeks reduced risk of death by 81% (HR=0.19). Acute side effects were documented in 69.7% and 89.5% of patients who underwent EFRT and CCEFRT, respectively. Four patients (12.5%) developed radiotherapy late toxicity and there was no treatment-related death observed. Conclusions: CCEFRT is associated with higher 5-years OS and median OS compared to EFRT and with tolerable level of acute and late toxicities in selected patients with cervical cancer and PALN metastasis.

• Asian-Australasian Journal of Animal Sciences
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• 제32권11호
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• pp.1789-1800
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• 2019

Objective: Although alveolar macrophages play a key role in the respiratory immunity of livestock, studies on the mechanism of differentiation and survival of alveolar macrophages are lacking. Therefore, we undertook to investigate changes in the lipid metabolism and survival rate, using 3D4/31 macrophages and Dudleya brittonii which has been used as a traditional asthma treatment. Methods: 3D4/31 macrophages were used as the in vitro porcine alveolar macrophages model. The cells were activated by exposure to phorbol 12-myristate 13-acetate (PMA). Dudleya brittonii extraction was performed with distilled water. For evaluating the cell survival rate, we performed the water-soluble tetrazolium salt cell viability assay and growth curve analysis. To confirm cell death, cell cycle and intracellular reactive oxygen species (ROS) levels were measured using flow cytometric analysis by applying fluorescence dye dichlorofluorescein diacetate and propidium iodide. Furthermore, we also evaluated cellular lipid accumulation with oil red O staining, and fatty acid synthesis related genes expression levels using quantitative polymerase chain reaction (qPCR) with SYBR green dye. Glycolysis, fatty acid oxidation, and tricarboxylic acid (TCA) cycle related gene expression levels were measured using qPCR after exposure to Dudleya brittonii extract (DB) for 12 h. Results: The ROS production and cell death were induced by PMA treatment, and exposure to DB reduced the PMA induced downregulation of cell survival. The PMA and DB treatments upregulated the lipid accumulation, with corresponding increase in the acetyl-CoA carboxylase alpha, fatty acid synthase mRNA expressions. DB-PMA co-treatment reduced the glycolysis genes expression, but increased the expressions of fatty acid oxidation and TCA cycle genes. Conclusion: This study provides new insights and directions for further research relating to the immunity of porcine respiratory system, by employing a model based on alveolar macrophages and natural materials.

• The Korean Journal of Physiology and Pharmacology
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• 제22권5호
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• pp.513-523
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• 2018

The tumor microenvironment greatly influences cancer cell characteristics, and acidic extracellular pH has been implicated as an essential factor in tumor malignancy and the induction of drug resistance. Here, we examined the characteristics of gastric carcinoma (GC) cells under conditions of extracellular acidity and attempted to identify a means of enhancing treatment efficacy. Acidic conditions caused several changes in GC cells adversely affecting chemotherapeutic treatment. Extracellular acidity did inhibit GC cell growth by inducing cell cycle arrest, but did not induce cell death at pH values down to 6.2, which was consistent with down-regulated cyclin D1 and up-regulated p21 mRNA expression. Additionally, an acidic environment altered the expression of atg5, HSPA1B, collagen XIII, collagen XXAI, slug, snail, and zeb1 genes which are related to regulation of cell resistance to cytotoxicity and malignancy, and as expected, resulted in increased resistance of cells to multiple chemotherapeutic drugs including etoposide, doxorubicin, daunorubicin, cisplatin, oxaliplatin and 5-FU. Interestingly, however, acidic environment dramatically sensitized GC cells to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Consistently, the acidity at pH 6.5 increased mRNA levels of DR4 and DR5 genes, and also elevated protein expression of both death receptors as detected by immunoblotting. Gene silencing analysis showed that of these two receptors, the major role in this effect was played by DR5. Therefore, these results suggest that extracellular acidity can sensitize TRAIL-mediated apoptosis at least partially via DR5 in GCs while it confers resistance to various type of chemotherapeutic drugs.

• 대한한방내과학회지
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• 제31권3호
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• pp.586-599
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• 2010

Objective : The water extract of Yukgunja-tang(YGJT) has been traditionally used in treatment of qi deficiency and phlegm in Oriental medicine. However, little is known about the mechanism by which YGJT protects neuronal cells from injury damages. Therefore, this study was designed to evaluate the protective effects of YGJT on C6 glial cells by glutamate-induced cell death. Methods : The present study describes glutamate, which is known as an excitatory neurotransmitter, related with oxidative damages, and YGJT, which shows protective effects against glutamate-induced C6 glial cell death. One of the main mediators of glutamate-induced cytotoxicity was known on the generation of reactive oxygen species(ROS) via activation of NADPH oxidase (NOX). The protective effects of antioxidant(NAC) and NOX inhibitor(apocynin) on the glutamate-induced C6 glial cells were determined by a MTT reduction assay. Result : YGJT inhibited glutamate-induced ROS generation via inhibition of NOX expression on glutamate-stimulated C6 glial cells. Furthermore, YGJT attenuated glutamate-induced caspase activation. These results suggest that YGJT could be a new potential candidate against glutamate-induced oxidative stress and cell death. Conclusion : These findings indicate that in C6 glial cells, ROS plays an important role of glutamate-induced cell death and that YGJT may prevent cell death from glutamate-induced cell death by inhibiting the ROS generation.