Linked Life Data

14521420

Source:http://linkedlifedata.com/resource/pubmed/id/14521420

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2003-10-2
pubmed:abstractText
Polyamine analogues 7, 10, 18, 27, and 32 containing cyclopropane rings were obtained by chemical synthesis. Their antineoplastic activities were assessed against the cultured human prostate tumor cell lines DU-145, DuPro, and PC-3. Decamines 32 and 27 exhibited variable levels of cytotoxicity against all three cell lines, while 7, 10, and 18 were efficacious against DU-145 and DuPro. Maximum tolerated doses (MTD) for all five compounds in a NCr-nu mouse model were determined at dosing schedules of q1d x 5 (ip) in two cycles with a break of 10 days between cycles. Their antitumor efficacies were then tested against DU-145 tumor xenografts in mice treated with all five agents at their respective MTDs. In addition, the efficacies of 7 and 10 against the same tumor xenograft were assessed at doses below their respective MTDs. In all experiments, administration began two weeks after tumor implantation. All compounds efficiently inhibited tumor growth for up to 50 days postimplantation, with negligible animal body weight loss. Tetramine 10 and hexamine 18 were the most efficient among the five analogues in arresting tumor growth. Tetramine 10 containing two cyclopropane rings had the lowest systemic toxicity as reflected in animal body weight loss. It was further assessed at a weekly administration regimen of (q1w x 4) in two cycles with a four-week break between the cycles. At this dosing schedule, 10 again efficiently arrested tumor growth with negligible effect on animal body weight. Tetramine 10 also arrested the growth of large tumors (ca. 2000 mm(3)) treated 66 days postimplantation. Studies on the metabolism of 10 showed that it accumulates in tumor within 6 h after the end of administration and reached a maximum level 72 h after cessation of dosing. Intracellular concentrations of 10 in liver and kidney were much smaller when compared to those in the tumor when measured 72 h after cessation of dosing. In liver and kidney, the deethyl metabolites of 10 accumulated over a 96 h period after cessation of dosing.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4586-600
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed-meshheading:14521420-Animals, pubmed-meshheading:14521420-Antineoplastic Agents, pubmed-meshheading:14521420-Body Weight, pubmed-meshheading:14521420-Cell Division, pubmed-meshheading:14521420-Cyclopropanes, pubmed-meshheading:14521420-Humans, pubmed-meshheading:14521420-Indicators and Reagents, pubmed-meshheading:14521420-Kidney, pubmed-meshheading:14521420-Liver, pubmed-meshheading:14521420-Magnetic Resonance Spectroscopy, pubmed-meshheading:14521420-Male, pubmed-meshheading:14521420-Mice, pubmed-meshheading:14521420-Mice, Nude, pubmed-meshheading:14521420-Neoplasm Transplantation, pubmed-meshheading:14521420-Polyamines, pubmed-meshheading:14521420-Prostatic Neoplasms, pubmed-meshheading:14521420-Stereoisomerism, pubmed-meshheading:14521420-Structure-Activity Relationship, pubmed-meshheading:14521420-Tumor Cells, Cultured
pubmed:year
2003
pubmed:articleTitle
Cyclopropane-containing polyamine analogues are efficient growth inhibitors of a human prostate tumor xenograft in nude mice.
pubmed:affiliation
SLIL Biomedical Corporation, 535 Science Drive, Suite C, Madison, WI 53711-1066, USA. bjfrydman@slil.com
pubmed:publicationType
Journal Article