Source:http://linkedlifedata.com/resource/pubmed/id/12533670
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2003-1-20
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pubmed:abstractText |
Soluble copolymers of camptothecin (CPT), based on poly[N-(2-hydroxypropyl) methacrylamide] (pHPMA), were obtained by conjugation through the degradable spacers -Gly-Phe-Leu-Gly- or -Gly-6-aminohexanoyl-Gly-. We investigated to what extent passive accumulation and retention of hydroxypropyl methacrylamide copolymer of CPT (pHPMA-CPT) in tumors and modulation of the drug release influence efficacy. Release of CPT in vivo was detected by time-resolved phase-shift fluorescence imaging on tumor specimens, based on the evidence that free and bound drug had different fluorescence lifetimes in solution. HT-29 murine specimens, obtained at several times after treatment with (3)H-labeled free CPT, pHPMA-Gly-Phe-Leu-Gly-CPT, or pHPMA-Gly-6-aminohexanoyl-Gly-CPT, were either imaged for time-resolved phase-shift fluorescence or subjected to autoradiography. Phase shifts of CPT conjugates were equal or longer than those of free CPT, indicating the presence of both free and polymer-bound drug in the tumor, in agreement with autoradiograms. pHPMA-Gly-Phe-Leu-Gly-CPT underwent relevant intratumor hydrolysis during the first 24 h, whereas the hydrolysis of pHPMA-Gly-6-aminohexanoyl-Gly-CPT was slow. The latter showed antitumor activity at doses from 10 to 22.5 mg/kg/day against s.c. HT-29, A2780, M14, and A549 s.c. xenografts. Moreover, inhibition of tumor growth lasted for up to 73-88 days, and cures were observed on mice with orthotopic implanted HT-29; pHPMA-Gly-Phe-Leu-Gly-CPT was 2-fold more potent than pHPMA-Gly-6-aminohexanoyl-Gly-CPT but less tolerated. Our data suggest that the efficacy of pHPMA-CPT copolymers is related to their intratumor accumulation, and in vivo properties of releasing CPT by esterolytic and proteolytic degradation.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acrylamides,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Camptothecin,
http://linkedlifedata.com/resource/pubmed/chemical/Esters,
http://linkedlifedata.com/resource/pubmed/chemical/Methacrylates,
http://linkedlifedata.com/resource/pubmed/chemical/methacryloylglycylglycine-4-nitrophe...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1535-7163
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pubmed:author |
pubmed-author:CaiolfaValeria RVR,
pubmed-author:CastelliMaria GMG,
pubmed-author:D'ArgyRolandR,
pubmed-author:FaraoMariellaM,
pubmed-author:FiorinoAntonioA,
pubmed-author:FontanaErminiaE,
pubmed-author:GhiglieriAlbertoA,
pubmed-author:GrattonEnricoE,
pubmed-author:PesentiEnricoE,
pubmed-author:SuaratoAntoninoA,
pubmed-author:VandeVenMartinM,
pubmed-author:ZamaiMorenoM
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pubmed:issnType |
Print
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pubmed:volume |
2
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
29-40
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12533670-Acrylamides,
pubmed-meshheading:12533670-Animals,
pubmed-meshheading:12533670-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:12533670-Breast Neoplasms,
pubmed-meshheading:12533670-Camptothecin,
pubmed-meshheading:12533670-Esters,
pubmed-meshheading:12533670-Female,
pubmed-meshheading:12533670-Humans,
pubmed-meshheading:12533670-Lung Neoplasms,
pubmed-meshheading:12533670-Male,
pubmed-meshheading:12533670-Methacrylates,
pubmed-meshheading:12533670-Mice,
pubmed-meshheading:12533670-Mice, Nude,
pubmed-meshheading:12533670-Prostatic Neoplasms,
pubmed-meshheading:12533670-Spectrometry, Fluorescence,
pubmed-meshheading:12533670-Structure-Activity Relationship,
pubmed-meshheading:12533670-Tissue Distribution,
pubmed-meshheading:12533670-Transplantation, Heterologous
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pubmed:year |
2003
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pubmed:articleTitle |
Camptothecin poly[n-(2-hydroxypropyl) methacrylamide] copolymers in antitopoisomerase-I tumor therapy: intratumor release and antitumor efficacy.
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pubmed:affiliation |
Discovery Research Oncology, Pharmacia Corporation, 20014 Nerviano (MI), Italy. moreno.zamai@pharmacia.com
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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