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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2008-10-29
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pubmed:abstractText |
Phor21-betaCG(ala), a 36-amino acid peptide comprised of a lytic peptide (Phor21) conjugated to a modified 15-amino acid segment of the beta-chain of chorionic gonadotropin (betaCG(ala)), selectively kills cancer cells that over-express luteinizing hormone/chorionic gonadotropin (LH/CG) receptors by disrupting cellular membrane structure. These studies were designed to further characterize its in-vitro inhibition and in-vivo destruction of prostate cancer cells, biostability and pharmacokinetics to determine its pharmacokinetic and pharmacodynamic profile. Inhibitory effects of Phor21-betaCG(ala) were tested in PC-3 and Caco-2 cells as well as in nude mice bearing PC-3 cells transfected with the luciferase gene (PC-3.luc). Plasma stability, protease hydrolysis and pharmacokinetics of Phor21-betaCG(ala) were measured by using liquid chromatography mass spectrometry (LC/MS/MS). Phor21-betaCG(ala) selectively inhibited proliferation in-vitro and in-vivo metastases of PC-3 cells. Phor21-betaCG(ala) was relatively stable in mouse, rat, dog and human plasma. Its degradation was partially due to protease hydrolysis and thermodynamic catalysis. Intravenous administration of Phor21-betaCG(ala) showed its blood C(max) and AUC(0-->infinity) around the in-vitro effective levels. In the tested rodents, Phor21-betaCG(ala) displayed a moderate volume of distribution at steady state (Vd(ss)) and slow clearance (Cl) in the rodents. In conclusion, Phor21-betaCG(ala) displayed promising in-vitro and in-vivo anti-cancer activity with favourable pharmacokinetics, and may offer a novel approach to metastatic cancer chemotherapy.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-10881023,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-10901303,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-11170139,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-11925119,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-12486692,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-12568441,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-12611453,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-12779076,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-12784188,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-12858351,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-14666172,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-15279610,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-15644871,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-16033998,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-16085758,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-17101210,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-17356822,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-17382461,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-17868966,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-18220562,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-18220563,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18957164-9800957
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-3573
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
60
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1441-8
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pubmed:dateRevised |
2011-9-28
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pubmed:meshHeading |
pubmed-meshheading:18957164-Animals,
pubmed-meshheading:18957164-Antineoplastic Agents,
pubmed-meshheading:18957164-Area Under Curve,
pubmed-meshheading:18957164-Caco-2 Cells,
pubmed-meshheading:18957164-Cell Line, Tumor,
pubmed-meshheading:18957164-Cell Proliferation,
pubmed-meshheading:18957164-Chromatography, Liquid,
pubmed-meshheading:18957164-Dogs,
pubmed-meshheading:18957164-Humans,
pubmed-meshheading:18957164-Luciferases,
pubmed-meshheading:18957164-Male,
pubmed-meshheading:18957164-Mice,
pubmed-meshheading:18957164-Mice, Inbred BALB C,
pubmed-meshheading:18957164-Mice, Inbred C57BL,
pubmed-meshheading:18957164-Mice, Nude,
pubmed-meshheading:18957164-Neoplasm Metastasis,
pubmed-meshheading:18957164-Peptides,
pubmed-meshheading:18957164-Prostatic Neoplasms,
pubmed-meshheading:18957164-Rats,
pubmed-meshheading:18957164-Rats, Inbred F344,
pubmed-meshheading:18957164-Species Specificity,
pubmed-meshheading:18957164-Tandem Mass Spectrometry,
pubmed-meshheading:18957164-Tissue Distribution,
pubmed-meshheading:18957164-Transfection
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pubmed:year |
2008
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pubmed:articleTitle |
Pharmacokinetics and pharmacodynamics of Phor21-betaCG(ala), a lytic peptide conjugate.
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pubmed:affiliation |
The National Cancer Institute/NIH, Rockville, MD 20852, USA. jiale@mail.nih.gov
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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