Linked Life Data

18957164

Source:http://linkedlifedata.com/resource/pubmed/id/18957164

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pubmed-article:18957164pubmed:abstractTextPhor21-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.lld:pubmed
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pubmed-article:18957164pubmed:authorpubmed-author:FanJ SJSlld:pubmed
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pubmed-article:18957164pubmed:dateRevised2011-9-28lld:pubmed
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pubmed-article:18957164pubmed:year2008lld:pubmed
pubmed-article:18957164pubmed:articleTitlePharmacokinetics and pharmacodynamics of Phor21-betaCG(ala), a lytic peptide conjugate.lld:pubmed
pubmed-article:18957164pubmed:affiliationThe National Cancer Institute/NIH, Rockville, MD 20852, USA. jiale@mail.nih.govlld:pubmed
pubmed-article:18957164pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:18957164pubmed:publicationTypeResearch Support, U.S. Gov't, Non-P.H.S.lld:pubmed
pubmed-article:18957164pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed