Linked Life Data

12075818

Source:http://linkedlifedata.com/resource/pubmed/id/12075818

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-6-21
pubmed:abstractText
Recently 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1061-186X
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
175-83
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12075818-Animals, pubmed-meshheading:12075818-Antineoplastic Agents, pubmed-meshheading:12075818-Binding Sites, pubmed-meshheading:12075818-Cattle, pubmed-meshheading:12075818-Dose-Response Relationship, Drug, pubmed-meshheading:12075818-Drug Administration Routes, pubmed-meshheading:12075818-Drug Carriers, pubmed-meshheading:12075818-Endoribonucleases, pubmed-meshheading:12075818-Female, pubmed-meshheading:12075818-Humans, pubmed-meshheading:12075818-Injections, Intraperitoneal, pubmed-meshheading:12075818-Injections, Intravenous, pubmed-meshheading:12075818-Iodine Radioisotopes, pubmed-meshheading:12075818-Lymphocytes, pubmed-meshheading:12075818-Melanoma, Experimental, pubmed-meshheading:12075818-Mice, pubmed-meshheading:12075818-Mice, Nude, pubmed-meshheading:12075818-Molecular Structure, pubmed-meshheading:12075818-Polymethacrylic Acids, pubmed-meshheading:12075818-Protein Conformation, pubmed-meshheading:12075818-Ribonuclease, Pancreatic, pubmed-meshheading:12075818-Tumor Cells, Cultured, pubmed-meshheading:12075818-Xenograft Model Antitumor Assays
pubmed:year
2002
pubmed:articleTitle
Poly[N-(2-hydroxypropyl)methacrylamide] conjugates of bovine pancreatic ribonuclease (RNase A) inhibit growth of human melanoma in nude mice.
pubmed:affiliation
Institute of Hematology and Blood Transfusion, Prague 2, Czech Republic.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't