• 제목/요약/키워드: Lethal Factor

검색결과 79건 처리시간 0.052초

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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    • 제13권10호
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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.

혈관내피세포에서 Vascular Endothelial Growth Factor가 방사선에 의해 유도된 apoptosis에 미치는 영향 (Vascular Endothelial Growth Factor Inhibits irradiation-induced Apoptosis in Human Umbilical Vein Endothelial Cells)

  • 이송재;김동윤
    • 대한방사선치료학회지
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    • 제14권1호
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    • pp.165-174
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    • 2002
  • 혈관내피세포 성장 인자(Vascular endothelial growth factor, VEGF)는 혈관내피세포 특이하게 성장요인으로 작용하는 물질로 알려져 있다. 전리방사선에 대한 혈관내피세포의 효과는 정상조직에 대한 반응에 있어 아주 중요한 요소일 것으로 생각된다. 본 연구는 방사선 조사에 의해 배양시킨 혈관내피세포에서 apoptosis가 유도되는지, 유도가 된다면 VEGF에 의해 apoptosis가 억제되는지 그리고 apoptosis의 억제가 어떤 경로를 경유하는지를 실험하였다. 혈관내피세포에 방사선를 조사한 결과, 대조군에 비하여 선량이 증가함에 따라 apoptosis가 증가하였다. 같은 조건하에서 VEGF는 농도 의존적으로 apoptosis를 억제하였다. Antiapoptotic factor로서 VEGF가 어떤 신호 과정을 경유하는지를 밝히고자, 혈관내피세포에 방사선을 조사하여 apoptosis를 유도하면서 Flt-1과 Flk-1/KDR receptor를 처리하였다. 그결과 VEGF에 유도된 apoptosis 억제효과가 차단되었다. Phosphatidylinositol 3'-kinase(PI3-kinase) 특정 억제 물질인 Wortmanin과 LY294002를 방사선 조사한 혈관내피에 VEGF와 함께 처리했을 때 VEGF에 의해 유도된 apoptosis를 억제하였다. 이같은 결과는 VEGF가 방사선 조사로 일어나는 세포 치사를 억제하는 중요한 역할을 담당하며, In Vivo의 실험이 더 이루어져야 할 것으로 생각된다.

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An Animal Model to Evaluate the Protective Efficacy of Haemophilus influenzae Type b Conjugate Vaccines

  • Kim Hyun Sung;Yoo Tae Hyeon;Jang Yang Suk;Kim Hun;Park Jin Yong;Hur Byung Ki;Ryu Yeon Woo;Kim Jong Su
    • Biotechnology and Bioprocess Engineering:BBE
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    • 제9권6호
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    • pp.490-494
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    • 2004
  • An efficacy test of PRP (polyribosylribitol phosphate)-TT (Tetanus toxoid) conjugate vaccines was carried out using BALB/c mice as an animal model by inoculating Haemophilus in­fluenzae type b (Hib) with a virulence enhancement factor (VEF). Three administrations of the conjugate vaccines at 2-week intervals elicited a significantly high level of PRP antibodies (P>0.0001). The protective activity of the PRP immunization was challenged with either Hib with iron dextran (Hib/) or with a combination of mucin and hemoglobin (Hibmh) as a VEF. The me­dium lethal dose $(LD_{50})$ for Hibmh and Hibiwas measured as 10 CFU (Colony Forming Unit) and $2.5{\times}10^{8}$ CFU respectively. Each immunized animal was challenged with five or ten times the $LD_{50}$ level of bacteria with a VEF. A significant difference in mortality between the immunized and control mice (P> 0.01) was observed with the Hibmh challenge inoculation but not with the Hibi challenge inoculation. These results show that a combination of mucin and hemoglobin was able to enhance the virulence of Hib in BALB/c mice to cause a lethal infection, thus suggesting that BALB/c mice introduced to this method can be an effective model animal for testing the protective efficacy of H. influenzae conjugate vaccines.

연초의 형질전환을 위한 새로운 표지유전자로서 Mouse Adenosine Deaminase 유전자의 이용가능성 (Adenosine Deaminase Gene: Possible Selectable Marker for Tobacco Transformation)

  • 양덕춘;한성수;윤의수
    • 식물조직배양학회지
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    • 제22권4호
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    • pp.235-240
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    • 1995
  • 식물세포의 형질전환을 위한 새로운 표지유전자의 개발은 식물유전공학의 중요한 관건이 되고 있다. 본 실험은 독성 adenosine 유도체인 9-$\beta$-D-arabinofuranosyl adenine (Ara-A)과 cordycepin등에 저항을 나타내는 adenosine deaminase (ADA) 유전자를 새로운 식물세포의 형질전환용 표지유전자로 사용코자 수행하였다. 정상식물체에서는 치사하는 농도인 Ara-A 100 $\mu$M과 cordycepin 50 $\mu$M이 함유된 선발배지에서 ADA 유전자에 의하여 형질전환된 연초식물체는 생존이 가능하였으며 성공적으로 형질전환체를 선발할 수 있었다. 또한 형질전환된 연초식물체에서 획득한 종자도 동일한 선발배지에서 ADA 유전자가 유전된 종자와 유전되지 않은 종자를 쉽게 구별할 수 있었다. 이런 결과는 동물유전자인ADA 유전자를 연초조직의 새로운 형질전환용 표지유전자로 사용할 수 있음을 시사한다.

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Defective Self-Renewal and Differentiation of GBA-Deficient Neural Stem Cells Can Be Restored By Macrophage Colony-Stimulating Factor

  • Lee, Hyun;Bae, Jae-sung;Jin, Hee Kyung
    • Molecules and Cells
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    • 제38권9호
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    • pp.806-813
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    • 2015
  • Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the glucocerebrosidase gene (GBA), which encodes the lysosomal enzyme glucosylceramidase (GCase). Deficiency in GCase leads to characteristic visceral pathology and lethal neurological manifestations in some patients. Investigations into neurogenesis have suggested that neurodegenerative disorders, such as GD, could be overcome or at least ameliorated by the generation of new neurons. Bone marrowderived mesenchymal stem cells (BM-MSCs) are potential candidates for use in the treatment of neurodegenerative disorders because of their ability to promote neurogenesis. Our objective was to examine the mechanism of neurogenesis by BM-MSCs in GD. We found that neural stem cells (NSCs) derived from a neuronopathic GD model exhibited decreased ability for self-renewal and neuronal differentiation. Co-culture of GBA-deficient NSCs with BM-MSCs resulted in an enhanced capacity for self-renewal, and an increased ability for differentiation into neurons or oligodendrocytes. Enhanced proliferation and neuronal differentiation of GBA-deficient NSCs was associated with elevated release of macrophage colony-stimulating factor (M-CSF) from BM-MSCs. Our findings suggest that soluble M-CSF derived from BM-MSCs can modulate GBA-deficient NSCs, resulting in their improved proliferation and neuronal differentiation.

Screening of Peptides Bound to Anthrax Protective Antigen by Phage Display

  • Kim, Joung-Mok;Park, Hye-Yeon;Choi, Kyoung-Jae;Jung, Hoe-Il;Han, Sung-Hwan;Lee, Jae-Seong;Park, Joon-Shik;Yoon, Moon-Young
    • Journal of Microbiology and Biotechnology
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    • 제16권11호
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    • pp.1784-1790
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    • 2006
  • Bacillus anthracis is a causative agent of anthrax. Anthrax toxins are composed of a protective antigen (PA), lethal factor (LF), and edema factor (EF), in which the PA is a central mediator for the delivery of the two enzymatic moieties LF and EF. Therefore, the PA has been an attractive target in the prevention and vaccinization for anthrax toxin. Recently, it has been reported that the molecule consisting of multiple copies of PA-binding peptide, covalently linked to a flexible polymer backbone, blocked intoxification of anthrax toxin in an animal model. In the present study, we have screened novel diverse peptides that bind to PA with a high affinity (picomolar range) from an M13 peptide display library and characterized the binding regions of the peptides. Our works provide a basis to develop novel potent inhibitors or diagnostic probes with a diverse polyvalence.

산소자유기에 의해 저해된 배양 척수감각 신경절 세포에 대한 상피세포성장인자의 영향 (Effect of EGF against Oxygen Radical-Induced Neurotoxicity in Cultured Spinal Dorsal Root Ganglion Neurons of Mouse)

  • 박승택;김형룡;채한정
    • 약학회지
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    • 제41권1호
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    • pp.99-104
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    • 1997
  • In order to elucidate the cytotoxic effect of oxygen radicals on cultured spinal dorsal root ganglion(DRG) neurons derived from mouse. the neurotoxic effect of oxygen radicals w as examined after cultured DRG neurons were exposed to xanthine oxidase(XO) and hypoxanthine(HX)-oxygen radical generating system. In addition. neuroprotective effect of epidermal growth factor(EGF) against oxidant-induced neurotoxicity was also evaluated in these cultures. The results were, as follows: 1. Lethal concentration 50(LC$_{50}$) was 35mU/ml XO and 0.1mM HX in cultured DRG neurons. 2. Oxygen radicals induced the morphological changes such as the decrease of cell number and loss of neurites in these cultures. 3. EGF increased the cell viability and neurofilament in neurons damaged by oxygen radicals. From above the results, it is suggested that oxygen radicals have a cytotoxic effect on cultured DRG neurons of neonatal mouse and selective neurotrophic factors such as EGF are, effective, in blocking the neurotoxicity induced by oxygen radicals in cultured spinal DRG neurons.

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풍력을 포함한 마이크로그리드의 이윤극대 급전계획 연구 (A Probabilistic Analysis for Profit Maximization in a Microgrid Including Wind Power)

  • 조벽근;한종훈;장길수
    • 대한전기학회:학술대회논문집
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    • 대한전기학회 2011년도 제42회 하계학술대회
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    • pp.270-271
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    • 2011
  • Due to integration of wind power, its unpredictable uncertainty can be a very lethal factor in generation dispatch problem. To handle such uncertainty of wind power output, a profit maximization problem is formulated and random wind speed is modeled by Weibull distribution in this paper. A case study is calculated through profit maximization approach with random wind speed. The effect of case study results is evaluated on how the uncertain wind power integration into the power system affects on the generation dispatch.

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소규모 건설현장의 중대재해 저감 방안 도출을 위한 연구 (A Study of Decreasing Critical Disaterous Accidents in Small Construction Sites)

  • 백신원;김한중;최돈흥
    • 한국농공학회논문집
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    • 제54권6호
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    • pp.121-131
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    • 2012
  • Many of the falling which is the number one risk factor in lethal accidents in construction could have been prevented if the right activity or supervising had been taken in time. All other measures do not preventive the fall, but rather intercept the fallen itself or preventive severe injury. The most common and the bets measures on the preventive measures are guardrails which are to be worn on the site. Workers always exposed the risk of serious accidents induced by causal effects related with environments around construction sites. In order to represent how to decrease the risk of workers, this study was accomplished with a number of interview with experienced site director, cheief of instructors, workers. And the questionaire survey (2012. 5~2012. 10) were used to make proposed policies which are expected to reduce critical disastrous accidents and strength authorized limits of director's management automatically.

Heat Shock Responses for Understanding Diseases of Protein Denaturation

  • Kim, Hee-Jung;Hwang, Na Rae;Lee, Kong-Joo
    • Molecules and Cells
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    • 제23권2호
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    • pp.123-131
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    • 2007
  • Extracellular stresses induce heat shock response and render cells resistant to lethal stresses. Heat shock response involves induction of heat shock proteins (Hsps). Recently the roles of Hsps in neurodegenerative diseases and cancer are attracting increasing attention and have accelerated the study of heat shock response mechanism. This review focuses on the stress sensing steps, molecules involved in Hsps production, diseases related to Hsp malfunctions, and the potential of proteomics as a tool for understanding the complex signaling pathways relevant to these events.