Linked Life Data

17361317

Source:http://linkedlifedata.com/resource/pubmed/id/17361317

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-3-15
pubmed:abstractText
Mouse models for colon cancer that harbor a germ line mutation in the tumor suppressor gene Adenomatous polyposis coli (Apc) exhibit a primary genetic defect that predisposes to a high incidence of adenomatous polyps in the small intestine rather than in the colon. Colon cell culture models expressing quantifiable markers for carcinogenic risk may represent an alternative approach to reduce, refine or replace long-term animal experimentation. The newly developed colon epithelial cell lines 1638N COL-Cl(1) (clonal derivative of the parental Apc mutant cell line 1638N COL) and 1638N COL-Pr(1) (tumor derivative of the clone), established from an Apc1638N [+/-] mutant mouse, exhibit aberrant cell cycle progression, downregulated apoptosis, enhanced carcinogenic risk and tumor formation, indicating that aberrantly proliferative preneoplastic1638N COL-Cl(1) cells exhibit a quantifiable risk for carcinogenesis. Treatment of these preneoplastic Apc mutant cells with a combination of celecoxib and 5-fluorouracil at clinically achievable low concentrations produced a 2.1 fold to 5.5 fold higher efficacy for cytostatic growth arrest and a 40.2% to 52.4% higher efficacy for inhibition of carcinogenic risk, relative to that obtained by these agents used individually. Thus, a low dose combination of mechanistically distinct agents resulted in enhanced efficacy. These data validate a novel cell culture model and a rapid mechanism-based approach to prioritize efficacious drug combinations for animal studies and clinical trials on cancer prevention and, thereby, support the 3R concept by refining and/or reducing the use of animals in biomedical research relevant to prevention/therapy of colon cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1868-596X
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
16-21
pubmed:dateRevised
2010-6-22
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Cell culture model for colon cancer prevention and therapy: an alternative approach to animal experimentation.
pubmed:affiliation
Strang Cancer Prevention Center, New York 10021, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural