Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-2-28
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
679-84
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
p21WAF1/CIP1 antisense therapy radiosensitizes human colon cancer by converting growth arrest to apoptosis.
pubmed:affiliation
Department of Radiation Medicine, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007-2197, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.