Source:http://linkedlifedata.com/resource/pubmed/id/10676653
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2000-2-28
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pubmed:abstractText |
Substantial evidence suggests that loss of cellular p21WAF1/CIP1 results in increased apoptotic killing by ionizing radiation. We hypothesized that a p21 antisense (AS) oligodeoxynucleotide (ODN) could be used to sensitize cancer cells to radiotherapy. In vitro treatment of colon cancer cells (HCT116/p21+/+) with p21 AS ODN (200 nM) led to inhibition of radiation-induced p21 expression (>95% inhibition, 0-30 Gy), resulting in a loss of G1 arrest and an enhancement of apoptosis to comparable levels and with similar kinetics to HCT116/p21-/- cells (approximately 60% apoptotic cells at 96 h after 10 Gy). In vivo, p21 AS ODN in combination with radiation (i.p. ODN for 6 days at 20 mg/kg/day and 15 Gy) increased apoptosis in s.c. p21+/+ tumors in nude mice to levels similar to those of p21-/- tumors (2-fold at 24 h postirradiation) and improved radiocurability of p21+/+ tumors to levels comparable to those of p21-/- tumors (p21+/+, two of eight cures versus p21-/-, two of nine cures). Our findings suggest that p21 AS treatment may be a rational approach to improve conventional radiotherapy outcomes.
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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/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/Radiation-Sensitizing Agents
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
60
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
679-84
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:10676653-Animals,
pubmed-meshheading:10676653-Apoptosis,
pubmed-meshheading:10676653-Cell Division,
pubmed-meshheading:10676653-Colonic Neoplasms,
pubmed-meshheading:10676653-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:10676653-Cyclins,
pubmed-meshheading:10676653-Female,
pubmed-meshheading:10676653-G1 Phase,
pubmed-meshheading:10676653-Humans,
pubmed-meshheading:10676653-Mice,
pubmed-meshheading:10676653-Mice, Inbred BALB C,
pubmed-meshheading:10676653-Oligonucleotides, Antisense,
pubmed-meshheading:10676653-Radiation-Sensitizing Agents,
pubmed-meshheading:10676653-Tumor Cells, Cultured
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pubmed:year |
2000
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pubmed:articleTitle |
p21WAF1/CIP1 antisense therapy radiosensitizes human colon cancer by converting growth arrest to apoptosis.
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pubmed:affiliation |
Department of Radiation Medicine, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007-2197, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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