• Title/Summary/Keyword: 표적화

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The Role of Heme Oxygenase-1 in Lung Cancer Cells (폐암세포주에서 Heme Oxygenase-1의 역할)

  • Jung, Jong-Hoon;Kim, Hak-Ryul;Kim, Eun-Jung;Hwang, Ki-Eun;Kim, So-Young;Park, Jung-Hyun;Kim, Hwi-Jung;Yang, Sei-Hoon;Jeong, Eun-Taek
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.3
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    • pp.304-313
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    • 2006
  • Background : Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes the oxidative degradation of heme to form biliverdin, carbon monoxide (CO), and free iron. The current evidence has indicated a critical role of HO-1 in cytoprotection and also in other, more diverse biological functions. It is known that the high expression of HO-1 occurs in various tumors, and that HO-1 has an important role in rapid tumor growth because of its antioxidative and antiapoptotic effects. Therefore, the role of HO-1 was analyzed in human lung cancer cell lines, and especially in the A549 cell line. Material and Methods : Human lung cancer cell lines, i.e., A549, NCI-H23, NCI-H157 and NCI-H460, were used for this study. The expression of HO-1 in the untreated state was defined by Western blotting. ZnPP, which is the specific HO inhibitor we used, and the viability of cells were tested for by conducting MTT assaysy. The HO enzymatic activity, as determined via the bilirubin level, was also indirectly measured. Moreover, the generation of intracellular hydrogen peroxide (H2O2) was monitored fluorimetrically with using a scopoletin-horse radish peroxidase (HRP) assay and 2',7'-dichlorofluorescein diacetate (DCFH-DA). We have also transfected small HO-1 interfering RNA (siRNA) into A549 cells, and the apoptotic effects were evaluated by flow cytometric analysis and Western blotting. Results : The A549 cells had a greater expression of HO-1 than the other cell lines, whereas ZnPP significantly decreased the viability of the A549 cells more than the viability of the other lung cancer cells in a dose-dependant fashion. Consistent with the viability, the HO enzymatic activity also was decreased. Moreover, intracellular H2O2 generation via ZnPP was induced in a dose-dependent manner. Apoptotic events were, then induced in the HO-1 siRNA transfected A549 cells. Conclusion : HO-1 provides new important insights into the possible molecular mechanism of the antitumor therapy in lung cancer.

The Study of Normal Tissue Complication Probability(NTCP) for Radiation Pneumonitis by Effective Volume Method (유효체적 방법과 임상분석을 통한 방사선에 의한 정상 폐조직의 부작용 확률에 관한 연구)

  • Ahn Seung Do;Choi Eun Kyung;Yi Byong Yong;Chang Hyesook
    • Radiation Oncology Journal
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    • v.15 no.3
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    • pp.243-249
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    • 1997
  • Purpose : In radiation therapy, NTCF is very importart indicator of selecting the optimal treatment plan. In our study, we tried to find out usefullness of NTCP in lung cancer by comparng the incidence of radiation pneumonitis with NTCP. Materials and Methods : From August 1993 to December 1994, thirty six patients with locally advanced non=small cell lung cancer were treated by concurrent chemoradiation therapy. Total dose of radiation therapy was 6480cGy (120cGy, bid) and chemotherapeutlc agents were mitomycin C. vinblastion, cisplatin (2 cycles, 4 weeks interval). We evaluated the development of raniation pneumonitis by CT scan, chest x-rar and clinical symptoms. We used grading system of South Western Oncology Group (SWOG) for radiation pneumanitis. Dose Volume Histograms (DVH) were analyzed for ipsilateral and whole lung, Non uniform DVH was translated to uniform DVH by effective volume method. With these data, we calculated NTCP for ipsilateral and whole lung. Finally we compared the clinical results to NTCP. Results : Eight of thrity six patients developed radiation pneumonitis. Of these 8 patients , 6 had grade I severity and 2 had grade II. The average NTCP value cf the patients who showed radiation pneumonitis was significantly higher than that uf the patients without pneumonitis $(66\%\;vs.\;26.4\%)$. But the results of pulmonary function test was not correlated with NTCP. Conclusion : NTCP of lung is very good indicator for selecting rival treatment planning in lung cancer. According to the results of NTCP, it may be possible to adjust target volume and optimize target dose. In the near future, we are going to anaiyze the effect of hyperfractionation and concurrent chemotherapy in addition to NTCP.

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Study on the Photoneutrons Produced in 15 MV Medical Linear Accelerators : Comparison of Three-Dimensional Conformal Radiotherapy and Intensity-Modulated Radiotherapy (15 MV 의료용 선형가속기에서 발생되는 광중성자의 선량 평가 - 3차원입체조형방사선치료와 세기조절방사선치료의 비교 -)

  • Yang, Oh-Nam;Lim, Cheong-Hwan
    • Journal of radiological science and technology
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    • v.35 no.4
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    • pp.335-343
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    • 2012
  • Intensity-modulated radiotherapy(IMRT) have the ability to provide better dose conformity and sparing of critical normal tissues than three-dimensional radiotherapy(3DCRT). Especially, with the benefit of health insurance in 2011, its use now increasingly in many modern radiotherapy departments. Also the use of linear accelerator with high-energy photon beams over 10 MV is increasing. As is well known, these linacs have the capacity to produce photonueutrons due to photonuclear reactions in materials with a large atomic number such as the target, flattening filters, collimators, and multi-leaf collimators(MLC). MLC-based IMRT treatments increase the monitor units and the probability of production of photoneutrons from photon-induced nuclear reactions. The purpose of this study is to quantitatively evaluate the dose of photoneutrons produced from 3DCRT and IMRT technique for Rando phantom in cervical cancer. We performed the treatment plans with 3DCRT and IMRT technique using Rando phantom for treatment of cervical cancer. An Rando phantom placed on the couch in the supine position was irradiated using 15 MV photon beams. Optically stimulated luminescence dosimeters(OSLD) were attached to 4 different locations (abdomen, chest, head and neck, eyes) and from center of field size and measured 5 times each of locations. Measured neutron dose from IMRT technique increased by 9.0, 8.6, 8.8, and 14 times than 3DCRT technique for abdomen, chest, head and neck, and eyes, respectively. When using IMRT with 15 MV photonbeams, the photoneutrons contributed a significant portion on out-of-field. It is difficult to prevent high energy photon beams to produce the phtoneutrons due to physical properties, if necessary, It is difficult to prevent high energy photon beams to produce the phtoneutrons due to physical properties, if necessary, it is need to provide the additional safe shielding on a linear accelerator and should therefore reduce the out-of-field dose.

Inhibitory Effects of Asparagus cochinchinensis in LPS-Stimulated BV-2 Microglial Cells through Regulation of Neuroinflammatory Mediators, the MAP Kinase Pathway, and the Cell Cycle (Lipopolysaccharide로 자극된 BV-2 미세교세포에서 신경염증 매개체, MAP kinase경로, 세포주기의 조절에 의한 천문동(Asparagus cochinchinensis)의 저해효과)

  • Lee, Hyun Ah;Kim, Ji Eun;Choi, Jun Young;Sung, Ji Eun;Youn, Woo Bin;Son, Hong Joo;Lee, Hee Seob;Kang, Hyun-Gu;Hwang, Dae Youn
    • Journal of Life Science
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    • v.30 no.4
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    • pp.331-342
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    • 2020
  • The suppression of neuroinflammatory responses in microglial cells can be considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Asparagus cochinchinensis has traditionally been used as a medicine to treat fever, cough, kidney disease, breast cancer, inflammatory diseases, and brain diseases. In this study, we investigated the neuroprotective mechanism of an aqueous extract from A. cochinchinensis root (AEAC), particularly its anti-inflammatory effects on lipopolysaccharide (LPS)-activated BV-2 microglial cells. BV-2 cells were treated with four different concentrations of AEAC. No significant toxicity was detected in BV-2 cells treated with AEAC. Nitric oxide (NO), cyclooxygenase-2 (COX-2) mRNA, and inducible nitric oxide synthase (iNOS) mRNA levels were 21% lower in the AEAC+LPS group than in the Vehicle+LPS group. Lower proinflammatory (TNF-α and IL-1β) and anti-inflammatory cytokine (IL-6 and IL-10) levels were also detected in the AEAC+LPS group than in the Vehicle+LPS group, albeit at varying rates. Moreover, the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group compared to the Vehicle+LPS group, enhancement of the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group, while cell cycle arrest at the G2/M phase caused by LPS treatment was less severe in the AEAC+LPS group. The increase in reactive oxygen species (ROS) generation induced by LPS treatment was also lower in the AEAC-pretreated group than in the Vehicle+LPS group. This is the first study to show that AEAC exerts anti-neuroinflammatory activity against LPS stimulation by regulating the MAPK signaling pathway, the cell cycle, and ROS production.

MicroRNA Expression Profiling in Cell and Mouse Models of Fabry Disease to Identify Biomarkers for Fabry Disease Nephropathy (파브리병의 바이오마커 발굴을 위한 파브리 마우스와 세포모델에서의 microRNA 발현 분석)

  • Jung, Namhee;Park, Saeyoung;Jeon, Yeo Jin;Choi, Yoonyoung;Jung, Sung-Chul
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.15 no.3
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    • pp.127-137
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    • 2015
  • Purpose: The main aim of this study was to compare and analyze expression profiles of microRNAs (miRNAs) to establish miRNA signature of Fabry nephropathy related epithelial mesenchymal transition (EMT). Methods: Expression profiles of miRNAs in kidney tissue samples and cell lines from normal and Fabry disease mouse model were examined by miRNA expression microarray analysis followed by quantitative real-time polymerase chain reaction analysis (qRT-PCR). Results: In the miRNA expression microarray analysis of Fabry mouse kidney tissues compared to wild type mouse, 5 and 3 miRNAs among 1,247 miRNAs examined were up- and down-regulated, respectively. Among them, miR-149-5p was down-regulated about 2-fold in Fabry kidney samples. The down-regulations of miR-149-5p were observed in kidney tissues of under 35 week-old-Fabry mice. However, this down-regulation was not observed in kidney tissues of 42 week-old Fabry mice. In SV40 MES 13 cells, mouse mesangial cells, treated with globotriaosylsphingosine (lyso-Gb3), miR-149-5p was also downregulated. The down-regulation of miR-149-5p induced up-regulation of its target genes related to EMT. Conclusion: The miRNA expression array and qRT-PCR results show that miR-149-5p expression was decreased in kidney tissues of Fabry mice compared to wild type mice under 35 weeks of age. Along with the observation of miR-149-5p expression in Fabry disease cell models, these results indicate that the down-regulated miR-149-5p were related to the biological response of mesangial cells to lyso-Gb3 and also have influence to the transcriptional up-regulation of its target genes. These results suggest miR-149-5p might play important roles in the Fabry nephropathy.

Trends in Rapid Detection Methods for Marine Organism-derived Toxins (해양 생물 유래 독소의 나노 기술 기반 신속 진단법 개발 동향)

  • Park, Chan Yeong;Kweon, So Yeon;Moon, Sunhee;Kim, Min Woo;Ha, Sang-Do;Park, Jong Pil;Park, Tae Jung
    • Journal of Food Hygiene and Safety
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    • v.35 no.4
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    • pp.291-303
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    • 2020
  • Marine organism-derived toxins have negative effects not only on human health but also in aquaculture, fisheries, and marine ecosystems. However, traditional analytical methods are insufficient in preventing this threat. In this paper, we reviewed new rapid methods of toxin detection, which have been improved by adopting diverse types of nanomaterials and technologies. Moreover, we herein describe the main strategies for toxin detection and their related sensing performance. Notably, to popularize and commercialize these newly developed technologies, simplifying the process of pre-treating real samples real samples is very important. As part of these efforts, numerous studies have reported pretreatment methods based on the antibody-immobilized magnetic nanoparticles, and some cases have applied nanoparticles to enhance the sensing performance by utilizing the intrinsic catalytic activity. Furthermore, some reports have introduced fluorescent nanoparticles, such as quantum dots, to represent the lower detection limits of conventional enzyme-based colorimetric methods and lateral flow assays. Some studies using electrochemical measurements based on aptamer-nanoparticle complexes have also been announced. In addition, as the response to new toxins generated by changes in the marine environment is still lacking, further research on diagnostic and detection is also greatly needed for these kinds of marine toxins and their derivatives.

Microarray Analysis of Gene Expression in Rat Glioma after Ethanol Treatment (에탄올 처리에 의한 흰쥐 신경아교종(Glioma) 세포에서의 유전자 발현 - DNA 칩을 이용한 분석 -)

  • Lee, So Hee;Oh, Dong-Yul;Han, Jin-Hee;Choi, Ihn-Geun;Jeon, Yang-Whan;Lee, Joon-Noh;Lee, Tae Kyung;Jeong, Jong-Hyun;Jung, Kyung Hwa;Chai, Young-Gyu
    • Korean Journal of Biological Psychiatry
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    • v.14 no.2
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    • pp.115-121
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    • 2007
  • Objetives : Identification of target genes for ethanol in neurons is important for understanding its molecular and cellular mechanism of action and the neuropathological changes seen in alcoholics. The purpose of this study is to identify of altered gene expression after acute treatmet of ethanol in rat gliom cells. Methods : We used high density cDNA microarray chip to measure the expression patterns of multiple genes in cultured rat glioma cells. DNA microarrays allow for the simultaneous measurement of the expression of several hundreds of genes. Results : After comparing hybridized signals between control and ethanol treated groups, we found that treatment with ethanol increased the expression of 15 genes and decreased the expression of 12 genes. Upregulated genes included Orthodenticle(Drosophila) homolog 1, procollagen type II, adenosine A2a receptor, GATA bindning protein 2. Downregulated genes included diacylglycerol kinase beta, PRKC, Protein phosphatase 1, clathrin-associated protein 17, nucleoporin p58, proteasome. Conclusion : The gene changes noted were those related to the regulation of transcription, signal transduction, second messenger systems. modulation of ischemic brain injury, and neurodengeneration. Although some of the genes were previously known to be ethanol responsive, we have for the most part identified novel genes involved in the brain response to ethanol.

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Computer Assisted EPID Analysis of Breast Intrafractional and Interfractional Positioning Error (유방암 방사선치료에 있어 치료도중 및 분할치료 간 위치오차에 대한 전자포탈영상의 컴퓨터를 이용한 자동 분석)

  • Sohn Jason W.;Mansur David B.;Monroe James I.;Drzymala Robert E.;Jin Ho-Sang;Suh Tae-Suk;Dempsey James F.;Klein Eric E.
    • Progress in Medical Physics
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    • v.17 no.1
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    • pp.24-31
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    • 2006
  • Automated analysis software was developed to measure the magnitude of the intrafractional and interfractional errors during breast radiation treatments. Error analysis results are important for determining suitable planning target volumes (PTV) prior to Implementing breast-conserving 3-D conformal radiation treatment (CRT). The electrical portal imaging device (EPID) used for this study was a Portal Vision LC250 liquid-filled ionization detector (fast frame-averaging mode, 1.4 frames per second, 256X256 pixels). Twelve patients were imaged for a minimum of 7 treatment days. During each treatment day, an average of 8 to 9 images per field were acquired (dose rate of 400 MU/minute). We developed automated image analysis software to quantitatively analyze 2,931 images (encompassing 720 measurements). Standard deviations ($\sigma$) of intrafractional (breathing motion) and intefractional (setup uncertainty) errors were calculated. The PTV margin to include the clinical target volume (CTV) with 95% confidence level was calculated as $2\;(1.96\;{\sigma})$. To compensate for intra-fractional error (mainly due to breathing motion) the required PTV margin ranged from 2 mm to 4 mm. However, PTV margins compensating for intefractional error ranged from 7 mm to 31 mm. The total average error observed for 12 patients was 17 mm. The intefractional setup error ranged from 2 to 15 times larger than intrafractional errors associated with breathing motion. Prior to 3-D conformal radiation treatment or IMRT breast treatment, the magnitude of setup errors must be measured and properly incorporated into the PTV. To reduce large PTVs for breast IMRT or 3-D CRT, an image-guided system would be extremely valuable, if not required. EPID systems should incorporate automated analysis software as described in this report to process and take advantage of the large numbers of EPID images available for error analysis which will help Individual clinics arrive at an appropriate PTV for their practice. Such systems can also provide valuable patient monitoring information with minimal effort.

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A Study on Customer Loyalty and Word-of-Mouth Effect according to Character Trait of Patient in Dental Clinics (치과내원환자의 성격특성에 따른 고객충성도 및 구전효과 연구)

  • Yang, Hae-Young
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.12 no.12
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    • pp.5819-5826
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    • 2011
  • Recently in the dental world, competition in the medical industry has been intensified due to the prolonged economic stagnation, the quantitative expansion of medical institutions, the enhancement of medical consumers'awareness of rights, and the diversity of medical consumer needs. Dental institution management of the difficulties is the requirement for dental institution to ensure competitiveness. So Word-of-Mouth marketing, which creates high marketing effectiveness with low cost, needs to be actively utilized as a new alternative to mass communication marketing. This research is to accurately grasp the target group of dental medical marketing activities through research on the degree of customer loyalty and Word-of-Mouth effects according to character trait of the patients visiting dental clinics, and to present the basic data for Word-of-Mouth marketing strategies from a viewpoint of practical business through presenting Word-of-Mouth promotion factors. To achieve this, questionnaire survey was conducted on 10 dental clinics located in Daegu for 4 weeks from April 11, 2011 to May 6, 2011 and 612 copies of responses to the questionnaires for final data for analysis were obtained. The results of the analysis are as follows. There were no significant differences in the degree of customer loyalty according to character trait of the subjects between the introverts and the extroverts, and the subjects with high market mavens propensity were found to show high degree of customer loyalty (F=5.243, p=.006). In the differences in Word-of-Mouth effectiveness according to character trait, there were greater differences in Word-of-Mouth experiences in the extrovert subjects ($x^2$=6.738, p=.006) and the subjects with high market mavens propensity ($x^2$=17.251, p=.000). The results of this research clarifies the degree of customer loyalty according to character trait of the patients visiting dental clinics and the differentiated influences of Word-of-Mouth effectiveness, and through this, they will become basic data for presenting ways to establish strategies from the viewpoint of practical business that should be considered in establishing dental medical marketing strategies.

Molecular Characterization and Expression Analysis of Clathrin-Associated Adaptor Protein 3-δ Subunit 2 (AP3S2) in Chicken

  • Oh, Jae-Don;Bigirwa, Godfrey;Lee, Seokhyun;Song, Ki-Duk
    • Korean Journal of Poultry Science
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    • v.46 no.1
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    • pp.31-37
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    • 2019
  • A chicken clathrin-associated adaptor protein $3-{\delta}$ subunit 2 (AP3S2) is a subunit of AP3, which is involved in cargo protein trafficking to target membrane with clathrin-coated vesicles. AP3S2 may play a role in virus entry into host cells through clathrin-dependent endocytosis. AP3S2 is also known to participate in metabolic disease developments of progressions, such as liver fibrosis with hepatitis C virus infection and type 2 diabetes mellitus. Chicken AP3S2 (chAP3S2) gene was originally identified as one of the differentially expressed genes (DEGs) in chicken kidney which was fed with different calcium doses. This study aims to characterize the molecular characteristics, gene expression patterns, and transcriptional regulation of chAP3S2 in response to the stimulation of Toll-like receptor 3 (TLR3) to understand the involvement of chAP3S2 in metabolic disease in chicken. As a result, the structure prediction of chAP3S2 gene revealed that the gene is highly conserved among AP3S2 orthologs from other species. Evolutionarily, it was suggested that chAP3S2 is relatively closely related to zebrafish, and fairly far from mammal AP3S2. The transcriptional profile revealed that chAP3S2 gene was highly expressed in chicken lung and spleen tissues, and under the stimulation of poly (I:C), the chAP3S2 expression was down-regulated in DF-1 cells (P<0.05). However, the presence of the transcriptional inhibitors, BAY 11-7085 (Bay) as an inhibitor for nuclear factor ${\kappa}B$ ($NF{\kappa}B$) or Tanshinone IIA (Tan-II) as an inhibitor for activated protein 1 (AP-1), did not affect the expressional level of chAP3S2, suggesting that these transcription factors might be dispensable for TLR3 mediated repression. These results suggest that chAP3S2 gene may play a significant role against viral infection and be involved in TLR3 signaling pathway. Further study about the transcriptional regulation of chAP3S2 in TLR3 pathways and the mechanism of chAP3S2 upon virus entry shall be needed.