Linked Life Data

11801552

Source:http://linkedlifedata.com/resource/pubmed/id/11801552

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-1-21
pubmed:abstractText
More than one million new skin cancers are diagnosed yearly in the United States creating the need for effective primary and chemopreventive strategies to reduce the incidence, morbidity, and mortality associated with skin cancer. Skin chemoprevention trials often focus on subjects at high risk of nonmelanoma skin cancers and include biological endpoints like number of actinic keratoses (AK) and measures of cell proliferation, apoptosis, and p53 expression and/or mutation. Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, suppresses increased polyamine synthesis and inhibits tumors in models of skin carcinogenesis. Thus, DFMO is a good candidate chemopreventive agent in humans at increased risk of NMSC. We reported previously results of a randomized, placebo-controlled trial of topical DFMO in 48 participants with AK. In this study there was a significant reduction in the number of AK (23.5%; P = 0.001) and the polyamine, spermidine (26%, P = 0.04; Alberts, D. S. et al. Cancer Epidemiol. Biomark. Prev., 9: 1281-2186, 2000). In skin biopsies from the same study, we demonstrate that topical DFMO significantly reduces the percentage of p53-positive cells (22%; P = 0.04); however, there were no significant changes in proliferating cell nuclear antigen or apoptotic indices, or in the frequency of p53 mutations (25% at baseline, 21% after placebo, and 26% after DFMO). We conclude that inhibition of the premalignant AK lesions as well as a reduction in the expression of p53 and in spermidine concentrations may serve as surrogate endpoint biomarkers of DFMO and possibly other topically administered skin cancer chemopreventive agents.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
149-55
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11801552-Aged, pubmed-meshheading:11801552-Antineoplastic Agents, pubmed-meshheading:11801552-Apoptosis, pubmed-meshheading:11801552-Biopsy, pubmed-meshheading:11801552-Cell Division, pubmed-meshheading:11801552-Eflornithine, pubmed-meshheading:11801552-Enzyme Inhibitors, pubmed-meshheading:11801552-Female, pubmed-meshheading:11801552-Humans, pubmed-meshheading:11801552-Immunoenzyme Techniques, pubmed-meshheading:11801552-Keratosis, pubmed-meshheading:11801552-Male, pubmed-meshheading:11801552-Mutation, pubmed-meshheading:11801552-Ornithine Decarboxylase, pubmed-meshheading:11801552-Photosensitivity Disorders, pubmed-meshheading:11801552-Proliferating Cell Nuclear Antigen, pubmed-meshheading:11801552-Risk Factors, pubmed-meshheading:11801552-Skin Neoplasms, pubmed-meshheading:11801552-Spermidine, pubmed-meshheading:11801552-Tumor Markers, Biological, pubmed-meshheading:11801552-Tumor Suppressor Protein p53
pubmed:year
2002
pubmed:articleTitle
Modulation of biologic endpoints by topical difluoromethylornithine (DFMO), in subjects at high-risk for nonmelanoma skin cancer.
pubmed:affiliation
Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724, USA. jeinspahr@azcc.arizona.edu
pubmed:publicationType
Journal Article, Clinical Trial, Comparative Study, Research Support, U.S. Gov't, P.H.S., Randomized Controlled Trial