• Title/Summary/Keyword: regulatory factor

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Epidermal Growth Factor Receptor-Related DNA Repair and Radiation-Resistance Regulatory Mechanisms: A Mini-Review

  • Bai, Jing;Guo, Xiao-Guang;Bai, Xiao-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.4879-4881
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    • 2012
  • Epidermal growth factor receptor (EGFR) overexpression is associated with resistance to chemotherapy and radiotherapy. The EGFR modulates DNA repair after radiation-induced damage through an association with the catalytic subunit of DNA protein kinase. DNA double-strand breaks (DSBs) are the most lethal type of DNA damage induced by ionizing radiation, and non-homologous end joining is the predominant pathway for repair of radiation-induced DSBs. Some cell signaling pathways that respond to normal growth factors are abnormally activated in human cancer. These pathways also invoke the cell survival mechanisms that lead to resistance to radiation. The molecular connection between the EGFR and its control over DNA repair capacity appears to be mediated by one or more signaling pathways downstream of this receptor. The purpose of this mini-review was not only to highlight the relation of the EGFR signal as a regulatory mechanism to DNA repair and radiation resistance, but also to provide clues to improving existing radiation resistance through novel therapies based on the above-mentioned mechanism.

Overestimation of Radioactivity Concentration of Difficult-To-Measure Radionuclides in Scaling Factor Methodology

  • Park, Junghwan;Kim, Tae-Hyeong;Lee, Jeongmook;Kim, Junhyuck;Kim, Jong-Yun;Lim, Sang Ho
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.19 no.3
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    • pp.367-386
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    • 2021
  • The overestimation and underestimation of the radioactivity concentration of difficult-to-measure radionuclides can occur during the implementation of the scaling factor (SF) method because of the uncertainties associated with sampling, radiochemical analysis, and application of SFs. Strict regulations ensure that the SF method as an indirect method does not underestimate the radioactivity of nuclear wastes; however, there are no clear regulatory guidelines regarding the overestimation. This has been leading to the misuse of the SF methodology by stakeholders such as waste disposal licensees and regulatory bodies. Previous studies have reported instances of overestimation in statistical implementation of the SF methodology. The analysis of the two most popular linear models of the SF methodology showed that severe overestimation may occur and radioactivity concentration data must be dealt with care. Since one major source of overestimation is the use of minimum detectable activity (MDA) values as true activity values, a comparative study of instrumental techniques that could reduce the MDAs was also conducted. Thermal ionization mass spectrometry was recommended as a suitable candidate for the trace level analysis of long-lived beta-emitters such as iodine-129. Additionally, the current status of the United States and Korea was reviewed from the perspective of overestimation.

2-Methoxy-1,4-naphthoquinone (MNQ) regulates cancer key genes of MAPK, PI3K, and NF-κB pathways in Raji cells

  • Wong, Teck Yew;Menaga, Subramaniam;Huang, Chi-Ying F.;Ho, Siong Hock Anthony;Gan, Seng Chiew;Lim, Yang Mooi
    • Genomics & Informatics
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    • v.20 no.1
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    • pp.7.1-7.13
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    • 2022
  • 2-Methoxy-1,4-naphthoquinone (MNQ) has been shown to cause cytotoxic towards various cancer cell lines. This study is designed to investigate the regulatory effect of MNQ on the key cancer genes in mitogen-activated protein kinase, phosphoinositide 3-kinase, and nuclear factor κB signaling pathways. The expression levels of the genes were compared at different time point using polymerase chain reaction arrays and Ingenuity Pathway Analysis was performed to identify gene networks that are most significant to key cancer genes. A total of 43 differentially expressed genes were identified with 21 up-regulated and 22 down-regulated genes. Up-regulated genes were involved in apoptosis, cell cycle and act as tumor suppressor while down-regulated genes were involved in anti-apoptosis, angiogenesis, cell cycle and act as transcription factor as well as proto-oncogenes. MNQ exhibited multiple regulatory effects on the cancer key genes that targeting at cell proliferation, cell differentiation, cell transformation, apoptosis, reduce inflammatory responses, inhibits angiogenesis and metastasis.

The Annual Averaged Atmospheric Dispersion Factor and Deposition Factor According to Methods of Atmospheric Stability Classification

  • Jeong, Hae Sun;Jeong, Hyo Joon;Kim, Eun Han;Han, Moon Hee;Hwang, Won Tae
    • Journal of Radiation Protection and Research
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    • v.41 no.3
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    • pp.260-267
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    • 2016
  • Background: This study analyzes the differences in the annual averaged atmospheric dispersion factor and ground deposition factor produced using two classification methods of atmospheric stability, which are based on a vertical temperature difference and the standard deviation of horizontal wind direction fluctuation. Materials and Methods: Daedeok and Wolsong nuclear sites were chosen for an assessment, and the meteorological data at 10 m were applied to the evaluation of atmospheric stability. The XOQDOQ software program was used to calculate atmospheric dispersion factors and ground deposition factors. The calculated distances were chosen at 400 m, 800 m, 1,200 m, 1,600 m, 2,400 m, and 3,200 m away from the radioactive material release points. Results and Discussion: All of the atmospheric dispersion factors generated using the atmospheric stability based on the vertical temperature difference were shown to be higher than those from the standard deviation of horizontal wind direction fluctuation. On the other hand, the ground deposition factors were shown to be same regardless of the classification method, as they were based on the graph obtained from empirical data presented in the Nuclear Regulatory Commission's Regulatory Guide 1.111, which is unrelated to the atmospheric stability for the ground level release. Conclusion: These results are based on the meteorological data collected over the course of one year at the specified sites; however, the classification method of atmospheric stability using the vertical temperature difference is expected to be more conservative.

Identification of the Negative Regulatory Element on the Caprine $\beta$ Lactoglobulin Promoter (염소의 베타-락토글로불린 유전자 프로모터의 음성 조절 인자 규명)

  • 김재만;유명희
    • The Korean Journal of Zoology
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    • v.38 no.3
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    • pp.433-441
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    • 1995
  • Mammary tissue-specificity of the caprine $\beta$-lactoglobulin promoter appears to be secured by repression in non-expressing cells. In order to identify the mechanism of the negative regulation, the upstream promoter sequence of the caprine $\beta$-lactoglobulin gene was analyzed in detail. The repression was mediated by the upstream flanking sequence from -47O to -205. The sequence could repress the promoter activity of $\beta$-lactoglobulin in either orientation. The effect of the putative negative regulation element of caprine $\beta$-lactoglobulin on heterlogous promoters, however, varied: the promoter activity of herpes simplex virus thimidine kinase was either repressed or activated by the sequence depending on its orientation, while the SV4O early promoter was activated rather than repressed. The regulatory sequence involving the putative negative regulatory element was strongly shifted with the nuclear extract from non-mammary HeLa and CV-1 cells, while only weak shift was observed with that of mammary HC11 cells. Such correlation between repression and factor binding suggests that the protected regions in foot-printing assay may be the negative regulatory elements of $\beta$-lactoalobulin that serve tissue-specific repression.

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The synergistic regulatory effect of Runx2 and MEF transcription factors on osteoblast differentiation markers

  • Lee, Jae-Mok;Libermann, Towia A.;Cho, Je-Yoel
    • Journal of Periodontal and Implant Science
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    • v.40 no.1
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    • pp.39-44
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    • 2010
  • Purpose: Bone tissues for clinical application can be improved by studies on osteoblast differentiation. Runx2 is known to be an important transcription factor for osteoblast differentiation. However, bone morphogenetic protein (BMP)-2 treatment to stimulate Runx2 is not sufficient to acquire enough bone formation in osteoblasts. Therefore, it is necessary to find other regulatory factors which can improve the transcriptional activity of Runx2. The erythroblast transformation-specific (ETS) transcription factor family is reported to be involved in various aspects of cellular proliferation and differentiation. Methods: We have noticed that the promoters of osteoblast differentiation markers such as alkaline phosphatase (Alp), osteopontin (Opn), and osteocalcin (Oc) contain Ets binding sequences which are also close to Runx2 binding elements. Luciferase assays were performed to measure the promoter activities of these osteoblast differentiation markers after the transfection of Runx2, myeloid Elf-1-like factor (MEF), and Runxs+MEF. Reverse-transcription polymerase chain reaction was also done to check the mRNA levels of Opn after Runx2 and MEF transfection into rat osteoblast (ROS) cells. Results: We have found that MEF, an Ets transcription factor, increased the transcriptional activities of Alp, Opn, and Oc. The addition of Runx2 resulted in the 2- to 6-fold increase of the activities. This means that these two transcription factors have a synergistic effect on the osteoblast differentiation markers. Furthermore, early introduction of these two Runx2 and MEF factors significantly elevated the expression of the Opn mRNA levels in ROS cells. We also showed that Runx2 and MEF proteins physically interact with each other. Conclusions: Runx2 interacts with MEF proteins and binds to the promoters of the osteoblast markers such as Opn nearby MEF to increase its transcriptional activity. Our results also imply that osteoblast differentiation and bone formation can be increased by activating MEF to elicit the synergistic effect of Runx2 and MEF.