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pubmed-article:12075818pubmed:dateCreated2002-6-21lld:pubmed
pubmed-article:12075818pubmed:abstractTextRecently hydrophilic poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) was used for BS-RNase modification to prevent its degradation in bloodstream or fast elimination. Polymer-conjugated BS-RNase preparations proved to be cytotoxic after intravenous or intraperitoneal application, whereas native BS-RNase was ineffective. Here RNase A unimer was conjugated with two HPMA polymers (classic and star) and their antitumor effects both in vitro and in vivo were compared with those of BS-RNase polymers. Surprisingly, the antitumor effect of RNase A conjugates was also pronounced. The RNase A conjugates (classic and star) injected intravenously to mice bearing melanoma tumor caused a significant reduction in tumor volume following ten doses of 5 and 1 mg/kg, respectively. Despite the antitumor activity observed in vivo, the in vitro tested cytotoxic activity of RNase A did not differ from that caused by native RNase A while native BS-RNase (50 microg/ml) totally inhibited DNA synthesis in treated cells. The experiments with 125I-labeled preparations demonstrated concentration-dependent internalization of native BS-RNase by tumor cells within an hour, whereas the polymer conjugate (S-BS) was not internalized. On the contrary, the in vivo experiments showed that whereas 40% of S-BS conjugate persisted in bloodstream for 24h after administration, 98% of the native BS-RNase was already eliminated. Improved antitumor activities of PHPMA-modified RNases in vivo might be ascribed to their prolonged retention in bloodstream, better proteolytic stability and resistance to the action of the ribonuclease inhibitor.lld:pubmed
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pubmed-article:12075818pubmed:pagination175-83lld:pubmed
pubmed-article:12075818pubmed:dateRevised2006-11-15lld:pubmed
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pubmed-article:12075818pubmed:articleTitlePoly[N-(2-hydroxypropyl)methacrylamide] conjugates of bovine pancreatic ribonuclease (RNase A) inhibit growth of human melanoma in nude mice.lld:pubmed
pubmed-article:12075818pubmed:affiliationInstitute of Hematology and Blood Transfusion, Prague 2, Czech Republic.lld:pubmed
pubmed-article:12075818pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:12075818pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed