Source:http://linkedlifedata.com/resource/pubmed/id/21157378
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2011-2-23
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pubmed:abstractText |
Whereas carcinogenesis requires the acquisition of driver mutations in progenitor cells, tumor growth and progression are heavily influenced by the local microenvironment. Previous studies from our laboratory have used Neurofibromatosis-1 (NF1) genetically engineered mice to characterize the role of stromal cells and signals to optic glioma formation and growth. Previously, we have shown that Nf1+/- microglia in the tumor microenvironment are critical cellular determinants of optic glioma proliferation. To define the role of microglia in tumor formation and maintenance further, we used CD11b-TK mice, in which resident brain microglia (CD11b+, CD68+, Iba1+, CD45low cells) can be ablated at specific times after ganciclovir administration. Ganciclovir-mediated microglia reduction reduced Nf1 optic glioma proliferation during both tumor maintenance and tumor development. We identified the developmental window during which microglia are increased in the Nf1+/- optic nerve and demonstrated that this accumulation reflected delayed microglia dispersion. The increase in microglia in the Nf1+/- optic nerve was associated with reduced expression of the chemokine receptor, CX3CR1, such that reduced Cx3cr1 expression in Cx3cr1-GFP heterozygous knockout mice led to a similar increase in optic nerve microglia. These results establish a critical role for microglia in the development and maintenance of Nf1 optic glioma.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0022-3069
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
70
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
51-62
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:21157378-Animals,
pubmed-meshheading:21157378-Antigens, CD11,
pubmed-meshheading:21157378-Cell Proliferation,
pubmed-meshheading:21157378-Down-Regulation,
pubmed-meshheading:21157378-Heterozygote Detection,
pubmed-meshheading:21157378-Humans,
pubmed-meshheading:21157378-Mice,
pubmed-meshheading:21157378-Mice, Inbred C57BL,
pubmed-meshheading:21157378-Mice, Knockout,
pubmed-meshheading:21157378-Mice, Transgenic,
pubmed-meshheading:21157378-Microglia,
pubmed-meshheading:21157378-Neurofibromatosis 1,
pubmed-meshheading:21157378-Optic Nerve Glioma,
pubmed-meshheading:21157378-Receptors, Chemokine,
pubmed-meshheading:21157378-Time Factors,
pubmed-meshheading:21157378-Up-Regulation
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pubmed:year |
2011
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pubmed:articleTitle |
Neurofibromatosis-1 heterozygosity increases microglia in a spatially and temporally restricted pattern relevant to mouse optic glioma formation and growth.
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pubmed:affiliation |
Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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