• Title, Summary, Keyword: ATP

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Mechanism of Resistance and Epithelial to Mesenchymal Transition of BRAF(V600E) Mutation Thyroid Anaplastic Cancer to BRAF(V600E) Inhibition Through Feedback Activation of EGFR (BRAF(V600E) 돌연변이 갑상선 역형성암에서 BRAF(V600E) 억제에 의한 EGFR 발현 증가가 표적치료에 대한 저항성발현과 상피-간질세포이행과정에 미치는 영향분석)

  • Byeon, Hyung Kwon;Na, Hwi Jung;Yang, Yeon Ju;Park, Jae Hong;Kwon, Hyeong Ju;Chang, Jae Won;Ban, Myung Jin;Kim, Won Shik;Shin, Dong Yeob;Lee, Eun Jig;Koh, Yoon Woo;Choi, Eun Chang
    • Korean Journal of Head & Neck Oncology
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    • v.30 no.2
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    • pp.53-61
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    • 2014
  • Background and Objectives : Anaplastic thyroid carcinoma(ATC) is a rare but highly aggressive thyroid malignancy that is associated with an extremely poor survival despite the best multidisciplinary care. BRAF(V600E) mutation is detected in about a quarter of ATC, but unlike its high treatment response to selective BRAF inhibitor (PLX4032) in metastatic melanoma, the treatment response of ATC is reported to be low. The purpose of this study is to investigate the innate resistance mechanism responsible for this low treatment response to BRAF inhibitor and its effect on epithelial-mesenchymal transition(EMT). Materials and Methods : Two ATP cell lines, 8505C and FRO were selected and treated with PLX4032 and its drug sensitivity and effects on cell migration and EMT were examined and compared. Further investigation on the changes in signals responsible for the different treatment response to PLX4032 was carried out and the same experiment was performed on both orthotopic and ectopic xenograft mouse models. Results : FRO cell line was more sensitive to PLX4032 treatment compared to 8505C cell line. The resistance to BRAF inhibition in 8505C was due to increased expression of EGFR. Effective inhibition of both EGFR and p-AKT was achieved after dual treatment with BRAF inhibitor(PLX4032) and EGFR inhibitor(Erlotinib). Similar results were confirmed on in vivo study. Conclusion : EGFR-mediated reactivation of the PI3K/AKT pathway and MAPK pathway contributes to the relative insensitivity of BRAF(V600E) mutant ATC cells to PLX4032. Dual inhibition of BRAF and EGFR leads to sustained treatment response including cell invasiveness.

Effects of Unripe Black Raspberry Water Extract on Lipid Metabolism and Oxidative Stress in Mice (복분자 미숙과 물 추출물이 마우스의 지질대사 및 산화적 스트레스에 미치는 영향)

  • Choi, Hye Ran;Lee, Jung-Hyun;Lee, Su Jung;Lee, Min Jung;Jeong, Jong Tae;Lee, Tae-Bum
    • Korean Journal of Food Science and Technology
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    • v.46 no.4
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    • pp.489-497
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    • 2014
  • We examined the effects of unripe black raspberry water extract (UBR-W) on lipid metabolism and oxidative stress in mice. C57BL/6J mice were divided into 4 groups: those administered a control diet (CTL), high-fat diet (HFD), UBR-W and simvastatin for 12 weeks. In the HFD group, LDL cholesterol were significantly higher than in the CTL group. However, the UBR-W treated group showed dose-dependent reduction of plasma LDL levels. Hepatic total lipid, TC, and malondialdehyde were significantly increased in hyperlipidemic mice. However, supplementation with either UBR-W or simvastatin effectively reduced these lipid profiles and lipid peroxidation. UBR-W increased mRNA expression of the LDL receptor, sterol regulatory element binding protein 2 (SREBP2), 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase and ATP-binding cassette transporter A1 (ABCA1) compared to that observed in the HFD group. In addition, UBR-W and simvastatin showed significantly reduced oxidized LDL uptake by the scavenger receptor CD36. These results suggest that UBR-W is useful for treatment and prevention of hyperlipidemia and lipid peroxidation.

Non-ribosomal Ribosome Assembly Factors in Escherichia coli (Escherichia coli 에서 리보솜 조립과정에 관여하는 단백질들)

  • Choi, Eunsil;Hwang, Jihwan
    • Journal of Life Science
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    • v.24 no.8
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    • pp.915-926
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    • 2014
  • The ribosome is a protein synthesizing machinery and a ribonucleoprotein complex that consists of three ribosomal RNAs (23S, 16S and 5S) and 54 ribosomal proteins in bacteria. In the course of ribosome assembly, ribosomal proteins (r-protein) and rRNAs are modified, the r-proteins bind to rRNAs to form ribonucleoprotein complexes which are folded into mature ribosomal subunits. In this process, a number of non-ribosomal trans-acting factors organize the assembly process of the components. Those factors include GTP- and ATP-binding proteins, rRNA and r-protein modification enzymes, chaperones, and RNA helicases. During ribosome biogenesis, they participate in the modifications of ribosomal proteins and RNAs, and the assemblies of ribosomal proteins with rRNAs. Ribosomes can be assembled from a discrete set of components in vitro, and it is notable that in vivo ribosome assembly is much faster than in vitro ribosome assembly. This suggests that non-ribosomal ribosome assembly factors help to overcome several kinetic traps in ribosome biogenesis process. In spite of accumulation of genetic, structural, and biochemical data, not only the entire procedure of bacterial ribosome synthesis but also most of roles of ribosome assembly factors remain elusive. Here, we review ribosome assembly factors involved in the ribosome maturation of Escherichia coli, and summarize the contributions of several ribosome assembly factors which associate with 50S and 30S ribosomal subunits, respectively.

Removal of Organic Matter and Pharmaceuticals in Wastewater Effluent through Managed Aquifer Recharge (하수처리수를 이용한 대수층 함양관리 기술(Managed Aquifer Recharge)에서 유기물과 의약화합물 제거)

  • Im, Huncheol;Yeo, Inseol;Maeng, Sung-Kyu;Choi, Heechul
    • Journal of Korean Society of Environmental Engineers
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    • v.37 no.3
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    • pp.182-190
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    • 2015
  • This study was conducted to evaluate the removal efficiencies of organic matter and pharmaceuticals and to identify the removal mechanism of pharmaceuticals using sand obtained from Hwangryong River in Jangsung. Batch and column studies were used to simulate managed aquifer recharge (MAR) systems. All experiments were performed using field effluent containing pharmaceuticals from Damyang Wastewater Treatment Plant as an influent. Based on the removal results of organic matter and pharmaceuticals from the batch and column experiments, soil organic matter (SOM) and microbial activity were found to effectively remove target contaminants. The removal of organic matter was found to increase under biotic conditions. Neutral and cation pharmaceuticals (iopromide, estrone, and trimethoprim) exhibited removal efficiencies higher than 70% from natural sand and baked sand media in batch and column studies. Carbamazepine persisted in the sand batch and column studies. Anion pharmaceuticals (ketoprofen, ibuprofen, and diclofenac) can be removed under conditions featuring high SOM and adenosine triphosphate (ATP) concentrations in the sand surface. Based on the experimental Batch and column results, biodegradation and sorption were found to be important mechanisms for the removal of pharmaceuticals within the simulated MAR systems.

A Clinical Study on Relevance between Classified Dampness-Phlegm Pattern of Metabolic Syndrome and Heart Rate Variability (대사증후군의 습담 변증군과 심박변이도의 관련성에 관한 고찰)

  • Lee, Jae-Wook;Shin, Yoon-Ri;Bae, Su-Hyun;Park, Seon-Young;Choi, Sang-Ok;Kim, Kyoung-Min;Kim, Young-Kyun
    • The Journal of Internal Korean Medicine
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    • v.33 no.3
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    • pp.284-297
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    • 2012
  • Objectives : This study was performed to investigate characteristic indice of heart rate variability (HRV) according to presence of metabolic syndrome (MS), pattern identification. Methods : We analyzed 167 subjects who participated in a stroke check-up. We classified the subjects into two groups as MS (n=48) and non-MS (n=119) based on NCEP ATP III. First, we investigated pattern identification of all subjects based on Korean Standard Pattern Identifications for Stroke-III. Second, we surveyed significance of HRV indices between MS and non-MS groups. Third, we investigated significance of HRV indices between classified DP of MS and classified DP of non-MS. Fourth, we investigated significance of HRV indices between classified DP of MS and non-MS. Fifth, we investigated significance between components of MS and HRV indices. Results : 1. SDNN, RMS-SD, HF, Ln(HF), and HF (NORM) were significantly lower in the MS than non-MS group. LN (TP), LF/HF were significantly higher in the MS than non-MS. 2. Ln (HF), Ln (TP), and LF/HF were statistically significant in the classified DP of MS group. 3. RMS-SD, and Ln (HF) were significantly lower in the abdominal obesity group than in the non-abdominal obesity group. SDNN, RMS-SD, TP, Ln (TP), VLF, Ln (VLF), and Ln (LF) were significantly lower in the hypertension group than in the non-hypertension group. RMS-SD was significantly lower in the diabetes group than in the non-diabetes group. Mean HRT,LF/HF were significantly higher in the hypertriglyceridemia than non-hypertriglyceridemia group, but Ln (HF), RMS-SD, and HF (NORM) were significantly lower in the hypertriglyceridemia than non-hypertriglyceridemia group. Conclusions : We found a few significant relationships between classified DP of MS and HRV indices. The resluts demonstrate that MS has potentially negative effects on the cardiovascular system, and these effects could be detected by HRV.

Correlation between Metabolic Syndrome and Plasma Homocysteine Level in Patients with Silent Lacunar Infarction (무증상성 열공성 뇌경색 환자에서 호모시스테인과 대사증후군의 상관관계에 대한 연구)

  • Shin, Yoon-Ri;Lee, Jae-Wook;Lee, Seung-Yeon;Yun, Yong-Jae;Jeong, Hyun-Yun;Kim, Kyoung-Min;Kim, Young-Kyun
    • The Journal of Internal Korean Medicine
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    • v.33 no.3
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    • pp.243-256
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    • 2012
  • Objectives : This clinical study was done to examine metabolic syndrome (MS) and plasma homocysteine (HCY) level in patients with silent lacunar infarction (SLI) and in normal controls. Methods : A total of 154 patients, who were over 20 years of age and visited the stroke prevention check-up center of a university hospital from December 2006 to December 2010, were examined by brain CT or brain MRI, and classified into two groups. We compared the components of MS and HCY levels between patients with SLI (n=74) and normal controls (n=80). Modified ATP III definition was used for diagnosis of MS while Korean standard for waist circumference was used. Results : Prevalence of MS was significantly higher in the SLI group than the normal group. HCY was also significantly higher in the SLI group than the noraml, and the odds ratio (OR) for SLI, comparing high HCY level (${\geq}10{\mu}mol/L$) with low HCY level ($<10{\mu}mol/L$), was 3.64 (95% confidence interval (CI); 1.81-7.29, p<.0001). However, there was no correlation between MS and HCY in the SLI group. Prevalence of diabetes and hypertension (HT) was higher in the SLI group than the normal group, but there was no significant difference in blood lipids level between the SLI and normal groups. Of note, HT itself was enough to be an independent risk factor for SLI (OR; 4.58, 95% CI; 1.91-11.01, p=0.001). Body mass index, waist circumference, waist-hip ratio and visceral fat area were significantly higher in the SLI than normal group, and visceral fat area was enough to be an independent risk factor for SLI (OR; 2.41, 95% CI; 1.04-5.59, p=0.040). Conclusions : SLI is shown to have significant correlation with HCY and prevalence of MS, however there is no relationship between HCY and prevalence of MS in patients with SLI.

Analysis on infection control of general hospital radiology (종합병원 영상의학과의 감염관리 대한 분석)

  • Shin, Jung-Sub;Park, Cheol-Woo;Jeon, Byeong-Kyou
    • Journal of the Korean Society of Radiology
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    • v.6 no.5
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    • pp.335-342
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    • 2012
  • This study aims to find a way to control infection of community radiology effectively by calculating the degree of contamination, culture and identifying the flora in radiology of five general hospitals in Gyeongsangbuk-do. Staphylococcus, Micrococcus, Pseudomonas stutzeri, Pseudomonas oryzihabitans were identified as surface flora. These are know to be pathogens of hospital acquired infection and there was no radiology-specific flora. Research subject hospitals were conducting similar infection control education but degree of contamination of each hospital showed significant difference. Difference in degree of contamination according to contact sources were analyzed by Contact sources were classified into technologist-using, patients-using and common-using materials. Analysis of each hospital's degree of contamination showed that patient-using materials were significantly more contaminated than technologist-using and common-using materials (p<0.001). Devices which are similar to each other in monthly average frequency of use showed no significant difference in degree of contamination, but general X-ray devices and chest boards which are used most frequently showed higher degree of contamination than others. In addition, hospital A, B and C which have heavier monthly average caseload showed relatively high degree of contamination on irradiation devices which are used by technologists only or by technologists and patients commonly, office desks and doorpulls. Hence it is considered that intensity of infection control education should be different according to the degree of monthly average caseload. This study provided an opportunity to aware that technologists' feeling of contamination is crucial for infection control of radiology, and the Accupoint ATP public hygiene monitoring system which was used in this study for measuring the degree of contamination was proved to be an effective measuring device for hospital acquired infection management.

Development of Standard Specification of Korea Radio based Train Control System(KRTCS-2) for Conventional & High Speed Railway (일반·고속철도용 무선기반 열차제어시스템(KRTCS-2) 표준사양 개발)

  • Kim, Chan-ho;Park, Jong-won;Lee, Kang-gyoo;Sung, Dong-il;Yun, Hak-sun
    • Journal of the Korean Society for Railway
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    • v.19 no.6
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    • pp.736-743
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    • 2016
  • In accordance with the trend of higher speed and automation, the Train Control System is building on the technology of control methods using radio in the technology of exchanging information by wire, toward a wireless communication method that will be applied using LTE-R radio communication technology with $4^{th}$ generation LTE mobile communication a $2^{nd}$ generation GSM-R. Therefore, a standard specification suitable for the Korea Radio based Train Control System-2(below KRTCS-2) for the 350km/h class using wireless communication is created; a prototype based on the standard specification is installed on a high-speed train and is installed on a test section(Ik san-Jeong eup) on the Honam high speed line to ensure the reliability and safety of the standard specifications, which are verified through various performance tests. In the future, the standard specification that has been established as a national railway standard, and the standard specifications will be commercialized by applying the train control system to conventional and High speed railway lines.

Predictors of Metabolic Syndrome in Chronic Schizophrenic Patients Followed for 5 Years(2011-2016) (5년 동안 추적한 만성 조현병 환자에서 대사증후군의 예측인자)

  • Joe, Jae-Gil;Yoon, Bo-Hyun;Jeon, Bong-Hee;Park, Su-Hee;Song, Je-Heon;Jeong, Ha-Ran;Hong, Kye Hyun
    • Korean Journal of Psychosomatic Medicine
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    • v.24 no.2
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    • pp.217-226
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    • 2016
  • Objectives : To investigate changes in, and predictors of, metabolic syndrome(MetS) status over a 5-year period in chronic schizophrenic patients and to identify factors associated with the prevention of or recovery from MetS. Methods : In total, 107 patients, all of whom provided written informed consent, were followed from 2011 to 2016 at Naju National Hospital for this study. MetS was defined according to the revised National Cholesterol Education Program-Adult Treatment Panel III guidelines. Results : During follow-up period, 22(20.5%) patients were newly diagnosed to MetS, 14(13.1%) were disappeared, 77(66.4%) were not changed[MetS : 34(31.8%), No MetS 37(34.6%)]. Common significant factors in the two changed groups were triglyceride and waist circumference, not dose and type of antipsychotic medication. Multiple logistic regression analysis revealed that female gender(odds ratio[OR]=2.846, 95% confidence interval[CI] : 1.020-7.942), attending two or more outpatient visits per month(OR=3.155, 95% CI : 1.188-8.379) and taking antidepressant medication(OR=3.991, 95% CI : 1.048-15.205) were significantly associated with MetS after controlling for other confounding variables. Type and dose of antipsychotic medication were not significantly associated with MetS. Conclusions : Triglyceride and waist circumference were important manageable indicator of MetS. Adoption of a healthy lifestyle is more important than adjusting the dose or type of antipsychotic medication in the treatment of chronic schizophrenia patients with MetS.

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Valproic Acid Reduces Reactive Oxygen Species in Fibroblast of X-linked Adrenoleukodystrophy (부신백질형성장애증 섬유모세포에서 발프로산의 항산화능)

  • Kang, Joon Won;Quan, Zhejiu;Jang, Jiho;Kang, Hoon-Chul
    • Journal of the Korean Child Neurology Society
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    • v.23 no.2
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    • pp.45-50
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    • 2015
  • Purpose: X-linked adrenoleukodystrophy (X-ALD) is a fatal, axonal demyelinating, neurodegenerative disease, and is caused by mutations the in ABCD1 (ATP-binding cassette transporter subfamily D member 1). Oxidative damage of proteins caused by very long chain fatty acid accumulating in X-ALD, is an early event in the neurodegenerative cascade. We evaluated valproic acid (VPA) as a possible option for oxidative damage in X-ALD. Method: We generated fibroblast of the childhood cerebral ALD from patient. We evaluated mRNA (ribonucleic acid) level of ABCD2 by real-time polymerase chain reaction, and reactive oxygen species (ROS) levels by flow cytometry. Results: VPA increased expression of ABCD2 in both control and ALD fibroblast. ABCD2 gene mRNA expression was increased 1.76 fold in normal fibroblasts, and 2.22 fold in the X-ALD fibroblasts. ROS levels were decreased in VPA treated X-ALD fibroblast, especially in treated with 1 mM of VPA. ROS levels revealed 13.7 in control fibroblast, on the other hand, 5.83 in X-ALD fibroblast treated with 1 mM of VPA. Conclusion: We propose VPA as a promising novel therapeutic approach in oxidant damage that warrants further clinical investigation in X-ALD.