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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5528
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pubmed:dateCreated |
2001-7-13
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pubmed:abstractText |
Gastrointestinal (GI) tract damage by chemotherapy or radiation limits their efficacy in cancer treatment. Radiation has been postulated to target epithelial stem cells within the crypts of Lieberkühn to initiate the lethal GI syndrome. Here, we show in mouse models that microvascular endothelial apoptosis is the primary lesion leading to stem cell dysfunction. Radiation-induced crypt damage, organ failure, and death from the GI syndrome were prevented when endothelial apoptosis was inhibited pharmacologically by intravenous basic fibroblast growth factor (bFGF) or genetically by deletion of the acid sphingomyelinase gene. Endothelial, but not crypt, cells express FGF receptor transcripts, suggesting that the endothelial lesion occurs before crypt stem cell damage in the evolution of the GI syndrome. This study provides a basis for new approaches to prevent radiation damage to the bowel.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0036-8075
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
293
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
293-7
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11452123-Animals,
pubmed-meshheading:11452123-Annexin A5,
pubmed-meshheading:11452123-Apoptosis,
pubmed-meshheading:11452123-Bone Marrow,
pubmed-meshheading:11452123-Bone Marrow Transplantation,
pubmed-meshheading:11452123-Capillaries,
pubmed-meshheading:11452123-Endothelium, Vascular,
pubmed-meshheading:11452123-Fibroblast Growth Factors,
pubmed-meshheading:11452123-Humans,
pubmed-meshheading:11452123-In Situ Nick-End Labeling,
pubmed-meshheading:11452123-Intestinal Mucosa,
pubmed-meshheading:11452123-Intestines,
pubmed-meshheading:11452123-Mice,
pubmed-meshheading:11452123-Mice, Inbred C57BL,
pubmed-meshheading:11452123-Neoplasms,
pubmed-meshheading:11452123-Receptors, Fibroblast Growth Factor,
pubmed-meshheading:11452123-Sphingomyelin Phosphodiesterase,
pubmed-meshheading:11452123-Stem Cells,
pubmed-meshheading:11452123-Tumor Suppressor Protein p53,
pubmed-meshheading:11452123-Whole-Body Irradiation
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pubmed:year |
2001
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pubmed:articleTitle |
Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice.
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pubmed:affiliation |
Laboratory of Signal Transduction and, Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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