Linked Life Data

10353725

Source:http://linkedlifedata.com/resource/pubmed/id/10353725

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1999-7-30
pubmed:abstractText
D,L-alpha-difluoromethylornithine (DFMO) was synthesized over 20 years ago. It was hoped that this enzyme-activated, irreversible inhibitor of ornithine decarboxylase, the first enzyme in polyamine synthesis, would be effective as a chemotherapy for hyperproliferative diseases, including cancer and/or infectious processes. DFMO was generally found to exert cytostatic effects on mammalian cells and tissues, and its effectiveness as a therapeutic agent has been modest. DFMO was also found to cause treatment-limiting (but reversible) ototoxicity at high doses. This side effect, along with its minimal therapeutic activity, contributed to the loss of interest by many clinicians in further developing DFMO as a cancer therapeutic agent. However, DFMO was subsequently shown to inhibit carcinogen-induced cancer development in a number of rodent models, and interest in developing this compound as a preventive agent has increased. The rationale for the inhibition of ornithine decarboxylase as a cancer chemopreventive agent has been strengthened in recent years because this enzyme has been shown to be transactivated by the c-myc oncogene in certain cell/tissue types and to cooperate with the ras oncogene in malignant transformation of epithelial tissues. Recent clinical cancer chemoprevention trials, using dose de-escalation designs, indicate that DFMO can be given over long periods of time at low doses that suppress polyamine contents in gastrointestinal and other epithelial tissues but cause no detectable hearing loss or other side effects. Current clinical chemoprevention trials are investigating the efficacy of DFMO to suppress surrogate end point biomarkers (e.g., colon polyp recurrence) of carcinogenesis in patient populations at elevated risk for the development of specific epithelial cancers, including colon, esophageal, breast, cutaneous, and prostate malignancies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
945-51
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10353725-Animals, pubmed-meshheading:10353725-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:10353725-Anticarcinogenic Agents, pubmed-meshheading:10353725-Cell Division, pubmed-meshheading:10353725-Cell Transformation, Neoplastic, pubmed-meshheading:10353725-Clinical Trials, Phase I as Topic, pubmed-meshheading:10353725-Clinical Trials, Phase II as Topic, pubmed-meshheading:10353725-Colonic Neoplasms, pubmed-meshheading:10353725-Drug Screening Assays, Antitumor, pubmed-meshheading:10353725-Drug Synergism, pubmed-meshheading:10353725-Eflornithine, pubmed-meshheading:10353725-Hearing Loss, pubmed-meshheading:10353725-Hematologic Diseases, pubmed-meshheading:10353725-Humans, pubmed-meshheading:10353725-Neoplasm Proteins, pubmed-meshheading:10353725-Neoplasms, pubmed-meshheading:10353725-Neoplasms, Experimental, pubmed-meshheading:10353725-Ornithine Decarboxylase, pubmed-meshheading:10353725-Polyamines, pubmed-meshheading:10353725-Precancerous Conditions, pubmed-meshheading:10353725-Rodentia, pubmed-meshheading:10353725-Tumor Cells, Cultured
pubmed:year
1999
pubmed:articleTitle
Development of difluoromethylornithine (DFMO) as a chemoprevention agent.
pubmed:affiliation
Department of Medicine (Hematology/Oncology), and Chao Family Comprehensive Cancer Center, University of California, Irvine, Orange 92668-2675, USA. flmeyske@uci.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review