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Induction of Indoleamine 2,3-dioxygenase (IDO) Enzymatic Activity Contributes to Interferon-Gamma Induced Apoptosis and Death Receptor 5 Expression in Human Non-small Cell Lung Cancer Cells

  • Chung, Ting Wen;Tan, Kok-Tong;Chan, Hong-Lin;Lai, Ming-Derg;Yen, Meng-Chi;Li, Yi-Ron;Lin, Sheng Hao;Lin, Chi-Chen
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.18
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    • pp.7995-8001
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    • 2014
  • Interferon-gamma (IFN-${\gamma}$) has been used to treat various malignant tumors. However, the molecular mechanisms underlying the direct anti-proliferative activity of IFN-${\gamma}$ are poorly understood. In the present study, we examined the in vitro antitumor activity of IFN-${\gamma}$ on two human non-small-cell lung carcinoma (NSCLC) cell lines, H322M and H226. Our findings indicated that IFN-${\gamma}$ treatment caused a time-dependent reduction in cell viability and induced apoptosis through a FADD-mediated caspase-8/tBid/mitochondria-dependent pathway in both cell lines. Notably, we also postulated that IFN-${\gamma}$ increased indoleamine 2,3-dioxygenase (IDO) expression and enzymatic activity in H322M and H226 cells. In addition, inhibition of IDO activity by the IDO inhibitor 1-MT or tryptophan significantly reduced IFN-${\gamma}$-induced apoptosis and death receptor 5 (DR5) expression, which suggests that IDO enzymatic activity plays an important role in the anti-NSCLC cancer effect of IFN-${\gamma}$. These results provide new mechanistic insights into interferon-${\gamma}$ antitumor activity and further support IFN-${\gamma}$ as a potential therapeutic adjuvant for the treatment of NCSLC.

Transformation of Arabidopsis gamma-Tocopherol Methyltransferase into Lettuce (Lactuca sativa L.) (애기장대 gamma-Tocopherol Methyltransferase 유전자를 이용한 상추의 형질전환)

  • 김명준;백소현;유남희;윤성중
    • Korean Journal of Plant Tissue Culture
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    • v.27 no.6
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    • pp.435-439
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    • 2000
  • Explants of lettuce (Lactuca sativa L.) were cocultured with A. tumefaciens LBA 4404 harboring ${\gamma}$-tocopherol methyltransferase (${\gamma}$-TMT) gene from Arabidopsis thaliana. These explants were transferred to MS medium supplemented with 50 mg/L kanamycin, 500 mg/L carbenicillin, 0.1 mg/L NAA and 0.5 mg/L BA. After 4 weeks, kanamycin resistant shoots were obtained from the explants on the selection medium. The putative transgenic shoots were transferred to rooting MS medium supplemented with 50 mg/L kanamycin and 250 mg/L carbenicillin. Stable incorporation of the Arabidopsis ${\gamma}$-TMT cDNA into lettuce genomic DNA was confirmed by PCR and Southern analysis. HPLC analysis showed that $\alpha$- to ${\gamma}$-tocopherol ratio increased over four fold in a transgenic lettuce line indicating successful expression of the transgenic Arabidopsis ${\gamma}$-TMT in lettuce.

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Coalescence behavior of dispersed domains in binary immiscible fluid mixtures having bimodal size distributions under steady shear flow

  • Takahashi Yoshiaki;Kato Tsuyoshi
    • Korea-Australia Rheology Journal
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    • v.17 no.3
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    • pp.125-130
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    • 2005
  • Coalescence process of binary immiscible fluid mixtures having bimodal size distributions, prepared by mixing two pre-sheared samples at different shear rates, ${\gamma}_{pre1}\;and\;{\gamma}_{pre2}$, under shear flow at a final shear rate, ${\gamma}_f$, are examined by transient shear stress measurements and microscopic observations in comparison with the results for simply pre-sheared samples having narrow size distributions (unimodal distribution samples). Component fluids are a silicone oil (PDMS) and a hydrocarbon-formaldehyde resin (Genelite) and their viscosities are 14.1 and 21.0 $pa{\cdot}sec$ at room temperature $(ca.\;20^{\circ}C)$, respectively. The weight ratio of PDMS: Genelite was 7:3. Three cases, $({\gamma}_{pre1}=7.2sec^{-1},\;{\gamma}_{pre2}=12.0sec^{-1}\;and\;{\gamma}_f=2.4sec^{-1}),\;({\gamma}_{pre1}=0.8sec^{-1},\;{\gamma}_{pre2}=4.0sec^{-1}\;and\;{\gamma}_f=2.4sec^{-1}),\;and\;({\gamma}_{pre1}=7.2sec^{-1},\;{\gamma}_{pre2}=12.0^sec^{-1}\;and\;{\gamma}_f=7.2sec^{-1})$ the first case, transient shear stress did not show any significant difference but domains larger than the initial state are observed at short times. In the latter cases, there exist undershoot of shear stress, reflecting existence of deformed large domains, which is confirmed by the direct observation. It is concluded that coalescence between large and small domains more frequently occur than coalescence between the domains with similar size in the bimodal distribution samples.

Studies on the Properties of E. coli ${\gamma}-Glutamylcysteine$ Synthetase in Relation to the Enzymatic Synthesis of Glutathione (글루타치온의 효소적 생합성에 관계되는 E.coli ${\gamma}-Glutamylcysteine$ Synthetase의 특성 연구)

  • Nam, Yong-Suk;Kwak, Joon-Hyeok;Lee, Se-Yong
    • Applied Biological Chemistry
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    • v.40 no.6
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    • pp.478-483
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    • 1997
  • ${\gamma}-Glutamylcysteine$ synthetase was purified from E. coli K-12 strain and its properties related to the in vitro synthesis of glutathione by enzymatic method were investigated. The activity of purified ${\gamma}-glutamylcysteine$ synthetase was increased with increasing concentration of L-glutamate up to 60 mM, while it was decreased by about 50% and 40% under 60 mM of L-cysteine and 45 mM of glycine, respectively. The enzyme activity was reduced not only by ADP, one of the reaction products, but also by the reduced form of glutathione. Therefore, because the reduced glutathione as well as glycine which is the substrate for glutathione synthetase inhibit the activity of ${\gamma}-glutamylcysteine$ synthetase, it is recommended to design a bioreactor system with two separate reactions for glutathione synthesis : one with ${\gamma}-glutamylcysteine$ synthetase reaction and the other glutathione synthetase reaction. In addition since ADP, resulted from these reactions, reduces the activity of ${\gamma}-glutamylcysteine$ synthetase, it is necessary to introduce an ATP regeneration system for glutathione synthesis.

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Effect of Interleukin-10 on Lipopolysaccahride/Interferon-γ-Induced Chemokine Mig Gene Expression

  • Jin, Hee;Jin, Jung-Sook;Park, Ho-Sun;Kim, Sung-Kwang;Lee, Jai Youl;Kim, Hee-Sun
    • IMMUNE NETWORK
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    • v.2 no.1
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    • pp.12-18
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    • 2002
  • Interferon-${\gamma}$ (IFN-${\gamma}$) is well known as a potent inducer in monokine induced by IFN-${\gamma}$ (Mig) mRNA expression. Although lipopolysaccharide (LPS) alone is weakly effective on Mig mRNA expression. the stimulation of LPS and IFN-${\gamma}$ (LPS/IFN-${\gamma}$ simultaneously has been shown to synergize to produce a high level of Mig mRNA in mouse peritoneal macrophages. In this study, interleukin-10 (IL-10) was found to suppress the LPS/IFN-${\gamma}$-induced Mig mRNA expression in cell type- and mouse strain-specific fashion, but IFN-${\gamma}$ alone-induced Mig mRNA was unaffected by IL-10 under identical experimental conditions. The IL-10-mediated suppression of LPS/IFN-${\gamma}$-stimulated Mig mRNA expression was dependent on the concentration of IL-10, and was prevented when the agent was added 2 hours after LPS/IFN-${\gamma}$ treatment. The suppressive action of IL-10 was dependent on a protein synthesis. However, IL-10 did not reduce the stability of LPS/IFN-${\gamma}$-induced Mig mRNA. These data may have important implications for a previously unrecognized role for IL-10 as a regulator of synergistic effect of LPS on the IFN-${\gamma}$-induced expression of the Mig gene in macrophages.

Dosimetrical Analysis of Reactor Leakage Gamma-rays by Means of Scintillation Spectrometry

  • Jun, Jae-Shik
    • Nuclear Engineering and Technology
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    • v.5 no.4
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    • pp.291-309
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    • 1973
  • Exposure rates due to leakage gamma-rays from operating reactors TRIGA Mark II and III were measured in a horizontal plane by means of scintillation spectrometry using a 3"$\times$3" cylindrical Nal(T1) detector associated with a 400 channel pulse height analyzer under varied conditions of reactor operation. In determining exposure rate due to the leakage gamma-rays at each point of measurement, Moriuchi's spectrum-exposure rate conversion theory was applied instead of using conventional responce matrix method which necessitates very complicated procedures to convert a spectrum into exposure rate. The results show that a basic pattern of "typical" spectrum of the reactor leakage gamma-rays is neither affected by thermal output of the reactor, nor influenced by overall attenuation in radiation intensity. It was indicated that he attenuation of the leakage gamma-rays in air in terms of exposure rate as a whole follows an exponential law, and the total exposure rate due to the leakage gamma-rays at a certain point is nearly proportional to thermal output of the reactor. The complexity in spectrum measured for a movable core reactor, TRIGA Mark III, was analyzed through spectrum resolution, and proper judgement of the leakage gamma-rays in a complex spectrum was discussed.ctrum was discussed.

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Inhibition of hypoxia-induced cyclooxygenase-2 by Korean Red Ginseng is dependent on peroxisome proliferator-activated receptor gamma

  • Song, Heewon;Lee, Young Joo
    • Journal of Ginseng Research
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    • v.41 no.3
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    • pp.240-246
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    • 2017
  • Background: Korean Red Ginseng (KRG) is a traditional herbal medicine made by steaming and drying fresh ginseng. It strengthens the endocrine and immune systems to ameliorate various inflammatory responses. The cyclooxygenase-2 (COX-2)/prostaglandin E2 pathway has important implications for inflammation responses and tumorigenesis. Peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) is a transcription factor that regulates not only adipogenesis and lipid homeostasis, but also angiogenesis and inflammatory responses. Methods: The effects of the KRG on inhibition of hypoxia-induced COX-2 via $PPAR{\gamma}$ in A549 cells were determined by luciferase assay, Western blot, and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The antimigration and invasive effects of KRG were evaluated on A549 cells using migration and matrigel invasion assays. Results and conclusion: We previously reported that hypoxia-induced COX-2 protein and mRNA levels were suppressed by KRG. This study examines the possibility of $PPAR{\gamma}$ as a cellular target of KRG for the suppression of hypoxia-induced COX-2. $PPAR{\gamma}$ protein levels and $PPAR{\gamma}$-responsive element (PPRE)-driven reporter activities were increased by KRG. Reduction of hypoxia-induced COX-2 by KRG was abolished by the $PPAR{\gamma}$ inhibitor GW9662. In addition, the inhibition of $PPAR{\gamma}$ abolished the effect of KRG on hypoxia-induced cell migration and invasion. Discussion: Our results show that KRG inhibition of hypoxia-induced COX-2 expression and cell invasion is dependent on $PPAR{\gamma}$ activation, supporting the therapeutic potential for suppression of inflammation under hypoxia. Further studies are required to demonstrate whether KRG activates directly $PPAR{\gamma}$ and to identify the constituents responsible for this activity.

Development of Neutron Induced Prompt γ-ray Spectroscopy System Using 252Cf (252Cf 선원을 이용한 즉발감마선 계측시스템 구성)

  • Park, Yong-Joon;Song, Byung-Chul;Jee, Kwang-Yong
    • Analytical Science and Technology
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    • v.16 no.1
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    • pp.12-24
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    • 2003
  • For the design and set-up of neutron induced prompt ${\gamma}$-ray spectroscopy system using $^{252}Cf$ neutron source, the effects of shielding and moderator materials have been examined. The $^{252}Cf$ source being used for TLD badge calibration in Korea Atomic Energy Research Institute was utilized for this preliminary experiment. The ${\gamma}$-ray background and prompt ${\gamma}$-ray spectrum of the sample containing Cl were measured using HPGe (GMX 60% relative efficiency) located at the inside of the system connected to notebook PC at the outside of the system (about 20 meter distance). The background activities of neutron and ${\gamma}$-rays were measured with neutron survey meter as well as ${\gamma}$-ray survey meters, respectively and the system was designed to minimize the activities. Prompt ${\gamma}$-ray spectrum was measured using ${\gamma}$-${\gamma}$ coincident system for reduce the background and the continuum spectrum. The optimum system was designed and set up using the experimental data obtained.

The development of th gamma-ray imaging and operation algorithm for the gamma-ray detection system (감마선 탐지장치의 감마선 영상화 및 운용 알고리즘 개발)

  • Song, Kun-young;Hwang, Young-gwan;Lee, Nam-ho;Yuk, Young-ho
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2016.10a
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    • pp.942-943
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    • 2016
  • Stereo gamma ray detection system generates a two-dimensional image of the gamma ray by using the position values and the gamma ray signal. And the device will overlap with the visible light image shows the actual distribution of the gamma-ray space. The gamma ray detection device is a stereo configuration to a motion controller for controlling the signal measurement unit and the position detection portion for detecting the detection portion and the gamma-ray signal comprising a gamma-ray detection sensor. In this paper, we developed a system operation management algorithm for each module individually configured efficiently. We confirmed the imaged and distribution information output for the gamma rays from gamma-ray irradiation test site by using these results.

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Improvement of Statistics in Proton Beam Range Measurement by Merging Prompt Gamma Distributions: A Preliminary Study

  • Kim, Sung Hun;Park, Jong Hoon;Ku, Youngmo;Lee, Hyun Su;Kim, Young-su;Kim, Chan Hyeong;Jeong, Jong Hwi
    • Journal of Radiation Protection and Research
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    • v.44 no.1
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    • pp.1-7
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    • 2019
  • Background: To monitor proton beam in proton therapy, prompt gamma imaging systems are being developed by several research groups, and these systems are expected to improve the quality of the treatment and the patient safety. To apply the prompt gamma imaging systems into spot scanning proton therapy, the systems should be able to monitor the proton beam range of a spot with a small number of protons ( <$10^8$ protons), which is quite often not the case due to insufficient prompt gamma statistics. Materials and Methods: In the present study, we propose to improve prompt gamma statistics by merging the prompt gamma distributions of several individual spots into a new distribution. This proposal was tested by Geant4 Monte Carlo simulations for a multi-slit prompt gamma camera which has been developed to measure the proton beam range in the patient. Results and Discussion: The results show that the proposed method clearly enhance the statistical precision of beam range measurement. The accuracy of beam range verification is improved, within ~1.4 mm error, which is not achievable before applying the developed method. Conclusion: In this study, we tried to improve the statistics of the prompt gamma statistics by merging the prompt gamma distributions of multiple spots, and it was found that the merged distribution provided sufficient prompt gamma statistics and the proton beam range was determined accurately.