Source:http://linkedlifedata.com/resource/pubmed/id/11474496
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2001-7-27
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pubmed:abstractText |
Intraesophageal administration of manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) prior to single fraction radiation has been shown to protect mice from lethal esophagitis. In our study, C3H/HeNsd mice received fractionated radiation in two protocols: (i) 18 Gy daily for four days with MnSOD-PL administration 24 hr prior to the first and third fraction, or (ii) 12 Gy daily for six days with MnSOD-PL 24 hr prior to the first, third, and fifth fraction. Control radiated mice received either no liposomes only or LacZ (bacterial beta-galactosidase gene)-plasmid/liposome (LacZ-PL) by the same schedules. We measured thiol depletion and lipid peroxidation (LP) in whole esophagus and tested the effectiveness of a new plasmid, hemagglutinin (HA) epitope-tagged MnSOD (HA-MnSOD). In fractionation protocols, mice receiving MnSOD-PL, but not LacZ-PL (200 microl of plasmid/liposomes containing 200 microg of plasmid DNA), showed a significant reduction in morbidity, decreased weight loss, and improved survival. Four and seven days after 37 Gy single fraction radiation, the esophagus demonstrated a significant increase in peroxidized lipids and reduction in overall antioxidant levels, reduced thiols, and decreased glutathione (GSH). These reductions were modulated by MnSOD-PL administration. The HA-MnSOD plasmid product was detected in the basal layers of the esophageal epithelium 24 hr after administration and provided significant radiation protection compared to glutathione peroxidase-plasmid/liposome (GPX-PL), or liposomes containing MnSOD protein, vitamin E, co-enzyme Q10, or 21-aminosteroid. Thus, MnSOD-PL administration significantly improved tolerance to fractionated radiation and modulated radiation effects on levels of GSH and lipid peroxidation (LP). These studies provide further support for translation of MnSOD-PL treatment into human esophageal radiation protection.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprost,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Unsaturated,
http://linkedlifedata.com/resource/pubmed/chemical/Hemagglutinins,
http://linkedlifedata.com/resource/pubmed/chemical/Liposomes,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/parinaric acid
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0020-7136
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2001 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
20
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pubmed:volume |
96
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
221-31
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11474496-Animals,
pubmed-meshheading:11474496-Biological Markers,
pubmed-meshheading:11474496-Cells, Cultured,
pubmed-meshheading:11474496-Chromatography, High Pressure Liquid,
pubmed-meshheading:11474496-Dinoprost,
pubmed-meshheading:11474496-Dose-Response Relationship, Drug,
pubmed-meshheading:11474496-Epitopes,
pubmed-meshheading:11474496-Esophagitis,
pubmed-meshheading:11474496-Fatty Acids, Unsaturated,
pubmed-meshheading:11474496-Female,
pubmed-meshheading:11474496-Hemagglutinins,
pubmed-meshheading:11474496-Lac Operon,
pubmed-meshheading:11474496-Lipid Metabolism,
pubmed-meshheading:11474496-Lipid Peroxidation,
pubmed-meshheading:11474496-Liposomes,
pubmed-meshheading:11474496-Mice,
pubmed-meshheading:11474496-Mice, Inbred C3H,
pubmed-meshheading:11474496-Mice, Inbred C57BL,
pubmed-meshheading:11474496-Plasmids,
pubmed-meshheading:11474496-Radiotherapy,
pubmed-meshheading:11474496-Superoxide Dismutase,
pubmed-meshheading:11474496-Time Factors
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pubmed:year |
2001
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pubmed:articleTitle |
Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) administration protects mice from esophagitis associated with fractionated radiation.
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pubmed:affiliation |
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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