• Biomolecules & Therapeutics
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• 제28권2호
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• pp.202-210
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• 2020

Fluoxetine is used widely as an antidepressant for the treatment of cancer-related depression, but has been reported to also have anti-cancer activity. In this study, we investigated the cytotoxicity of fluoxetine to human gastric adenocarcinoma cells; as shown by the MTT assay, fluoxetine induced cell death. Subsequently, cells were treated with 10 or 20 µM fluoxetine for 24 h and analyzed. Apoptosis was confirmed by the increased number of early apoptotic cells, shown by Annexin V- propidium iodide staining. Nuclear condensation was visualized by DAPI staining. A significant increase in the expression of cleaved PARP was observed by western blotting. The pan-caspase inhibitor Z-VAD-FMK was used to detect the extent of caspase-dependent cell death. The induction of autophagy was determined by the formation of acidic vesicular organelles (AVOs), which was visualized by acridine orange staining, and the increased expression of autophagy markers, such as LC3B, Beclin 1, and p62/SQSTM 1, observed by western blotting. The expression of upstream proteins, such as p-Akt and p-mTOR, were decreased. Autophagic degradation was evaluated by using bafilomycin, an inhibitor of late-stage autophagy. Bafilomycin did not significantly enhance LC3B expression induced by fluoxetine, which suggested autophagic degradation was impaired. In addition, the co-administration of the autophagy inhibitor 3-methyladenine and fluoxetine significantly increased fluoxetine-induced apoptosis, with decreased p-Akt and markedly increased death receptor 4 and 5 expression. Our results suggested that fluoxetine simultaneously induced both protective autophagy and apoptosis and that the inhibition of autophagy enhanced fluoxetine-induced apoptosis through increased death receptor expression.

• BMB Reports
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• 제49권7호
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• pp.382-387
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• 2016

Reactive oxygen species generated under oxidative stress are involved in neuronal diseases, including ischemia. Glutathione S-transferase pi (GSTpi) is a member of the GST family and is known to play important roles in cell survival. We investigated the effect of GSTpi against oxidative stress-induced hippocampal HT-22 cell death, and its effects in an animal model of ischemic injury, using a cell-permeable PEP-1-GSTpi protein. PEP-1-GSTpi was transduced into HT-22 cells and significantly protected against H2O2-treated cell death by reducing the intracellular toxicity and regulating the signal pathways, including MAPK, Akt, Bax, and Bcl-2. PEP-1-GSTpi transduced into the hippocampus in animal brains, and markedly protected against neuronal cell death in an ischemic injury animal model. These results indicate that PEP-1-GSTpi acts as a regulator or an antioxidant to protect against oxidative stress-induced cell death. Our study suggests that PEP-1-GSTpi may have potential as a therapeutic agent for the treatment of ischemia and a variety of oxidative stress-related neuronal diseases.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4567-4570
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• 2014

Background: This systemic analysis was conducted to evaluate the efficacy and safety of pemetrexed based chemotherapy in treating patients with metastatic breast cancer as first or second line chemotherapy. Methods: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for patients with breast cancer were identified using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: In first line pemetrexed based regimens, 10 clinical studies which including 513 patients with advanced breast cancer were considered eligible for inclusion. For second line pemetrexed based chemotherapy, 5 clinical studies which including 281 patients with advanced breast cancer were considered eligible. Systemic analysis suggested that, in all patients, pooled RR was 32.6% (167/513) in pemetrexed based first line regimens, and 13.9 % (39/281) in pemetrexed based second line regimens. Major adverse effects were neutropenia, leukopenia, fatigue, and anemia in pemetrexed based first line treatment; and lymphopenia, neutropenia, leukopenia, as well as anemia in second line chemotherapy. One treatment related death occurred with pemetrexed based second line treatment. Conclusion: This systemic analysis suggests that pemetrexed based first line regimens are associated with a reasonable response rate and acceptable toxicity, however with low response rate for treating patients with metastatic breast cancer when is used in the second line.

• 대한약리학회지
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• 제17권1호
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• pp.41-46
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• 1981

Eighty of Sarcoma 180 bearing mice, averaging 30 gm of body weight, were divided into eight groups of animals receiving Saline as the control, Corynebacterium parvum, Tubercin-3 and Cyclophosphamide alone and Cyclophosphamide combined with C. parvum, with Tubercin-3 and with both C. parvum and Tubercin-3 and Tubercin-3 combined with C. parvum respectively. Treatment was initiated 4.8 hours after tumor implantation and repeated three times once a day. Doses were suspended or dissolved in 0.2 ml of Saline: 1.4 mg of C. parvum: 0.5 micrograms of Tubercin-3; and 2.7 mg of Cyclophosphamide either in alone or in combination. All the agents given were administered subcutaneously but Cyclophosphamide was given intraperitoneally. The observation on the general conditions of animal took place twice a day following the treatment until the time of death after tumor implantation was determined. Average survival days in each group were as follows: In Control, Saline (11.2 days), C. parvum (14.8 days), Tubercin-3 (16.7 days), Cyclophosphamide(18.7 days). In combination therapy, Cyclophosphamide with C. parvum(22.8 days) with Tubercin-3 (26.9 days). Cyclophosphamide with both C. parvum an Tubercin-3, however, was somewhat longer than in Cyclophosphamide alone but shorter than in combined with either one of C. parvum or Tubercin-3. Finally, in combination with immunotherapeutic agents, Tubercin-3 and C. parvum each other it (8.2 days) was shorter even than Control. Life span of host is, in generally, inversely related to the number of malignant cells and conclusively, the therapeutic potentiation was reflected to be extended survival in combined treatment of a chemotherapeutic Cyclophosphamide with either one of immunotherapeutics, Tubercin-3 or C. parvum. Tubercin-3 and C. parvum in combination, however, appeared to be antagonistic each other.

• Biomolecules & Therapeutics
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• 제6권1호
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• pp.95-110
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• 1998

A 13-week dermal toxicity test was conducted to assess the toxicity of DA-5018, a capsaicin derivative. Three groups of Sprague-Dawley rats (10-15 males and 10-15 females) were treated with DA-5018 cream daily by dermal application at concentrations of 0.1%, 0.3% or 0.9% as 500 mg/kg for 13 weeks. One further group of rats (15 males and 15 females) received cream base at 500 mg/kg/day and acted as controls. One male receiving 0.3% DA-5018 cream died during the treatment period. But the animal did not show any signs of treatment-related toxicity until death. There were no local skin reaction of application site and systemic reaction to the treatment of DA-5018 creams in all experimental groups throughout treatment and recovery period. Weight gain and food consumption in animals that received DA-5018 creams appeared to be comparable to that of the controls. Laboratory analyses (hematology, urinalysis and opthalmoscopic examination) did not revealed pathological values. In biochemical investigations, an increase of glucose level associated with increased food consumption and some other significant changes were noted in the animals of both sexes received DA-5018 creams. But these changes were not considered to be of toxicological importance. Postmortem examination did not show macroscopic or histological alterations attributable to the DA-5018 treatments. Based on these results, NOAEL(no-observable-adverse-effect level) of DA-5018 cream if estimated to be over 500 mg/tg/day as 0.9% cream.

• 한국약용작물학회지
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• 제22권1호
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• pp.46-52
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• 2014

In traditional Korean and Chinese medicine, safflower (Carthamus tinctorius L.) for the treatment of central nervous system-related symptoms such as tremor, seizure, stroke and epilepsy. We investigated the effects of safflower could influence cerebral ischemia-induced neuronal and cognitive impairments. Administration of safflower for 1 day (200 mg/kg body weight, p.o.) increased the survival of hippocampal CA1 pyramidal neurons after transient global brain ischemia. And neurological functions measured as short term memory. Post-treatment with safflower for 2 times decreased the induction/reduction - induced production of neuronal cell loss from global cerebral ischemia. Safflower markedly decreased neuronal cell death and also caused a decrease in the content of thiobarbituric acid-reacting substances (TBARS) ($55.2{\pm}9.4{\mu}mol\;mg^{-1}$) and significant improvement of activities of glutathione (GSH) ($27.2{\pm}5.0{\mu}mol\;mg^{-1}$) in hippocampus. We conclude that treatment with safflower attenuated learning and memory deficits, and neuronal cell loss induced by global cerebral ischemia. These results suggest that safflower may be a potential candidate for the treatment of vascular dementia.

• 대한한의학방제학회지
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• 제29권4호
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• pp.167-179
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• 2021

Objectives : Oxidative stress is a important cause of liver disease, and regulation of oxidative stress is essential to maintain the normal metabolic function of the liver. Until a recent date, there has been no studies on the hepatoprotective effect of Ikwiseungyang-tang (IWSYT). Therefore, this study aims to demonstrate the hepatoprotective effect of IWSYT and its related molecular mechanisms on arachidonic acid (AA) + iron induced oxidative stress model in HepG2 cells. Methods : To determine the cytoprotective effect of IWSYT against AA + iron-induced oxidative stress, cell viability, apoptosis-related proteins, intracellular reactive oxygen species (ROS), GSH, and mitochondrial membrane potential (MMP) were measured. Nuclear factor erythroid 2-related factor 2 (Nrf2) activation was analyzed by immunoblot analysis. In addition, Nrf2 transcription activation through ARE binding was measured by reporter gene assays, and the expression of the Nrf2 target antioxidant genes were confirmed by immunoblot analysis. Results : IWSYT increased cell viability from cell death induced by AA + Iron, and inhibited apoptosis by regulating apoptosis-related proteins. Furthermore, IWSYT protected cells by inhibiting intracellular ROS production, GSH depletion, and MMP degradation. Nrf2 activation was increased by IWSYT, and Nrf2 target genes were activated by IWSYT too. Conclusions : These results suggest that IWSYT can protect hepatocytes from oxidative stress through Nrf2 activation and can be potentially applied in the prevention and treatment of liver damage.

• 대한본초학회지
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• 제29권5호
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• pp.91-95
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• 2014

Objectives : This study was carried out to evaluate whether the water extract from cause the cellular damage in HepG2 cell line. It was reported that Dictamnus dasycarpus Turcz(DDT) intake induce poisoning symptoms in human population. These symptoms was closely related to liver toxicity, however, mechanisms for liver toxicity caused by DDT have not been elucidated exactly. Here, hepatotoxicity caused by DDT was evaluated using HepG2 cell line. Methods : Water extract of DDT was treated into HepG2 cell with various doses such as 0, 0.1, 0.5, 1.0 and $5.0mg/m{\ell}$. In order to cell viability, both MTT and LDH assay were carried out. Also, apoptosis array kit was used to identify whether cell death caused by DDT is due to apoptosis or not. In addition, reactive oxygen species (ROS) was measured after treatment of water extract. Results : We found out significant changes in the apoptosis related factors of hepatocyte. The cell viability of HepG2 treated with DDT water extract was decreased in dose-dependent. Also most of the apoptosis related factors were significantly increased. We found out that Caspase 3, Cytochrome C and ROS had increased in dose-dependent. In addition, other apoptosis related factors Bcl 2 and Bax, which were also constant changes. However, there was no significance. Conclusions : These results suggest that water soluble extract of DDT is expected to have oral toxicity, including hepatocellular damage Therefore, it is suggested that DDT could cause various side effects and toxicity of clinical conditions.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제25권2호
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• pp.65-72
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• 2014

Objectives : The objective of this study was to evaluate the treatment duration and adherence of osmotic-controlled release oral delivery system (OROS) methylphenidate for treatment of attention-deficit hyperactivity disorder (ADHD). Methods : A total of 843 children with ADHD were recruited : 213 children (25.3%) who had previously taken medications for ADHD and 630 drug-na$\ddot{i}$ve children (74.7%) were recruited. The dosage was adjusted according to the clinician's judgment. The primary efficacy endpoint of this study was treatment retention rate, which was estimated at Week 12 and Week 20 using the Kaplan-Meier curve. The Swanson, Nolan and Pelham-IV (SNAP-IV), Clinical Global Impression-Severity (CGI-S), Clinical Global Impression-Improvement, and the side effect rating scale were measured at every visit. Remission rates were presented based on SNAP-IV and CGI-S, respectively. Results : The treatment retention rate at 12 weeks and at 20 weeks was 76.2% and 66.8%, respectively. Divided according to 6-8, 9-11, 12-14 and 15-18 years of age, younger children tended to show a statistically higher treatment retention rate (p=.02). Based on SNAP-IV and CGI scores, children with better response to medication showed tendencies of statistically higher treatment retention rate. The most common adverse events included loss of appetite (7.1%) and insomnia (3.3%). There was no serious adverse event related to the treatment, such as death. Conclusion : The use of OROS methylphenidate for treatment of ADHD was safe and tolerable for children. In this study, lower age and better treatment response showed a statistically significant relationship with higher treatment adherence. Boys showed a trend of high treatment adherence. The treatment adherence at 20 weeks was satisfactory, however, the treatment adherence after 20 weeks showed a sharp decrease. Therefore, treatment persistence for six months after the beginning of ADHD treatment is important. In addition, the positive role of psycho-education for children and parents is necessary for increasing treatment adherence.

• 디지털융복합연구
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• 제14권2호
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• pp.489-499
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• 2016

본 연구는 65세 이상 노인들의 연명치료 선호도에 영향을 미치는 요인들을 규명하는 것을 주목적으로 한다. 분석을 위해 한국보건사회연구원의 "2014년도 전국 노인생활실태 및 복지욕구조사"의 데이타베이스를 활용하였고 분석표본은 10,451건이었다. 응답자의 86.4 퍼센트가 무의미한 연명치료를 원하지 않는 것으로 나타났다. 다중회귀 분석결과, 여성일 경우(${\beta}=-.045$, p<.001), 연령이 낮을수록(${\beta}=-.024$, p<.05), 교육수준이 높을수록(${\beta}=.027$, p<.05), 연명치료를 원하지 않은 것으로 나타났다. 자아통합적 특성과 연명치료 선호도 간 구체적 영향관계는 삶의 만족도가 높을수록(${\beta}=.022$, p<.05), 본인의 죽음에 대해 생각해본 적이 있는 경우(${\beta}=.032$, p<.01), 연명치료 선호도가 낮은 것으로 나타났다. 반면 경로당이용을 통해 사회적 소속감을 느끼는 경우(${\beta}=-.038$, p<.01), 연명치료 선호도가 높은 것으로 나타났다. 노인의 자아통합 발달이 무의미한 연명치료를 본인에게 해야 할 상황에 처했을 때 연명치료 반대결정에 영향을 준다는 본 연구결과는 자아통합을 이룰 수 있도록 촉매역할을 하는 노인복지 프로그램의 제공을 통해 무의미한 연명치료를 줄일 수 있는 가능성을 시사한다.