pubmed-article:15142883 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:15142883 | lifeskim:mentions | umls-concept:C0023449 | lld:lifeskim |
pubmed-article:15142883 | lifeskim:mentions | umls-concept:C0037083 | lld:lifeskim |
pubmed-article:15142883 | lifeskim:mentions | umls-concept:C0079904 | lld:lifeskim |
pubmed-article:15142883 | lifeskim:mentions | umls-concept:C0038952 | lld:lifeskim |
pubmed-article:15142883 | lifeskim:mentions | umls-concept:C0034538 | lld:lifeskim |
pubmed-article:15142883 | lifeskim:mentions | umls-concept:C0205217 | lld:lifeskim |
pubmed-article:15142883 | lifeskim:mentions | umls-concept:C1710082 | lld:lifeskim |
pubmed-article:15142883 | lifeskim:mentions | umls-concept:C1704259 | lld:lifeskim |
pubmed-article:15142883 | lifeskim:mentions | umls-concept:C0683598 | lld:lifeskim |
pubmed-article:15142883 | lifeskim:mentions | umls-concept:C1521725 | lld:lifeskim |
pubmed-article:15142883 | lifeskim:mentions | umls-concept:C1705987 | lld:lifeskim |
pubmed-article:15142883 | lifeskim:mentions | umls-concept:C1314939 | lld:lifeskim |
pubmed-article:15142883 | lifeskim:mentions | umls-concept:C1516044 | lld:lifeskim |
pubmed-article:15142883 | lifeskim:mentions | umls-concept:C0332183 | lld:lifeskim |
pubmed-article:15142883 | pubmed:issue | 5 | lld:pubmed |
pubmed-article:15142883 | pubmed:dateCreated | 2004-8-19 | lld:pubmed |
pubmed-article:15142883 | pubmed:abstractText | To investigate possible causes of the variable response to treatment in pediatric B-precursor acute lymphoblastic leukemia (ALL) and to establish potential novel therapeutic targets, we used ionizing radiation (IR) exposure as a model of DNA damage formation to identify tumors with resistance to p53-dependent apoptosis. Twenty-one of 40 ALL tumors responded normally to IR, exhibiting accumulation of p53 and p21 proteins and cleavage of caspases 3, 7, and 9 and of PARP1. Nineteen tumors exhibited apoptotic resistance and lacked PARP1 and caspase cleavage; although 15 of these tumors had normal accumulation of p53 and p21 proteins, examples exhibited abnormal expression of TRAF5, TRAF6, and cIAP1 after IR, suggesting increased NF-kappaB prosurvival signaling as the mechanism of apoptotic resistance. The presence of a hyperactive PARP1 mutation in one tumor was consistent with such increased NF-kappaB activity. PARP1 inhibition restored p53-dependent apoptosis after IR in these leukemias by reducing NF-kappaB DNA binding and transcriptional activity. In the remaining 4 ALL tumors, apoptotic resistance was associated with a TP53 mutation or with defective activation of p53. We conclude that increased NF-kappaB prosurvival signaling is a frequent mechanism by which B-precursor ALL tumors develop apoptotic resistance to IR and that PARP1 inhibition may improve the DNA damage response of these leukemias. | lld:pubmed |
pubmed-article:15142883 | pubmed:language | eng | lld:pubmed |
pubmed-article:15142883 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15142883 | pubmed:citationSubset | AIM | lld:pubmed |
pubmed-article:15142883 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15142883 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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pubmed-article:15142883 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15142883 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15142883 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:15142883 | pubmed:month | Sep | lld:pubmed |
pubmed-article:15142883 | pubmed:issn | 0006-4971 | lld:pubmed |
pubmed-article:15142883 | pubmed:author | pubmed-author:YeoG NGN | lld:pubmed |
pubmed-article:15142883 | pubmed:author | pubmed-author:StankovicTatj... | lld:pubmed |
pubmed-article:15142883 | pubmed:author | pubmed-author:MossPaul A... | lld:pubmed |
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pubmed-article:15142883 | pubmed:author | pubmed-author:MarstonEliotE | lld:pubmed |
pubmed-article:15142883 | pubmed:author | pubmed-author:LawsonSarahS | lld:pubmed |
pubmed-article:15142883 | pubmed:author | pubmed-author:HillFrankF | lld:pubmed |
pubmed-article:15142883 | pubmed:author | pubmed-author:MannJill RJR | lld:pubmed |
pubmed-article:15142883 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:15142883 | pubmed:day | 1 | lld:pubmed |
pubmed-article:15142883 | pubmed:volume | 104 | lld:pubmed |
pubmed-article:15142883 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:15142883 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:15142883 | pubmed:pagination | 1465-73 | lld:pubmed |
pubmed-article:15142883 | pubmed:dateRevised | 2007-11-15 | lld:pubmed |
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pubmed-article:15142883 | pubmed:year | 2004 | lld:pubmed |
pubmed-article:15142883 | pubmed:articleTitle | Apoptotic resistance to ionizing radiation in pediatric B-precursor acute lymphoblastic leukemia frequently involves increased NF-kappaB survival pathway signaling. | lld:pubmed |
pubmed-article:15142883 | pubmed:affiliation | Cancer Research UK Institute for Cancer Studies, Birmingham University, Edgbaston, Birmingham, B15 2TT, United Kingdom. victoriaw@cancer.bham.ac.uk | lld:pubmed |
pubmed-article:15142883 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:15142883 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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