Source:http://linkedlifedata.com/resource/pubmed/id/12880986
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1-2
|
| pubmed:dateCreated |
2003-7-25
|
| pubmed:abstractText |
Effective chemotherapy in neuroblastoma is limited by poor anti-tumor efficacy, systemic toxicity and the induction of drug resistance. Here, we provide further evidence that a hydrolytic activated prodrug design may overcome these problems. For this purpose, VP-16 was functionally blocked by a carbonate linker to generate two novel chemically stable prodrugs of VP-16, ProVP-16 I and II. We demonstrate profoundly different biological effects in vitro and in vivo of the prodrugs compared to parental VP-16. First, we established an up to >2 log higher in vitro toxicity of the two prodrugs compared to VP-16 on a panel of neuroblastoma cell lines. The highest increase of prodrug mediated cytotoxicity was observed in multi drug resistant cell lines. Second, in vivo studies showed a maximum tolerated dose (MTD) of ProVP-16 II (60 mg/kg), which was at least threefold higher than that of VP-16 (20 mg/kg). Tests of ProVP-16 II in a syngeneic NXS2 neuroblastoma model indicated that mice treated with this prodrug at 1/3 of the MTD was as effective as VP-16 parental compound used at the MTD in suppression of tumor growth. In summary, the etoposide prodrugs proved effective and less toxic and are therefore highly promising new anti-neuroblastoma compounds.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0304-3835
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
18
|
| pubmed:volume |
197
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
225-30
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:12880986-Animals,
pubmed-meshheading:12880986-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:12880986-Biotransformation,
pubmed-meshheading:12880986-Cell Survival,
pubmed-meshheading:12880986-DNA Primers,
pubmed-meshheading:12880986-Drug Design,
pubmed-meshheading:12880986-Drug Resistance, Multiple,
pubmed-meshheading:12880986-Drug Resistance, Neoplasm,
pubmed-meshheading:12880986-Drug Screening Assays, Antitumor,
pubmed-meshheading:12880986-Etoposide,
pubmed-meshheading:12880986-Female,
pubmed-meshheading:12880986-Humans,
pubmed-meshheading:12880986-Hydrolysis,
pubmed-meshheading:12880986-Maximum Tolerated Dose,
pubmed-meshheading:12880986-Mice,
pubmed-meshheading:12880986-Neuroblastoma,
pubmed-meshheading:12880986-Plasmids,
pubmed-meshheading:12880986-Prodrugs,
pubmed-meshheading:12880986-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:12880986-Tumor Cells, Cultured
|
| pubmed:year |
2003
|
| pubmed:articleTitle |
Rationally designed hydrolytically activated etoposide prodrugs, a novel strategy for the treatment of neuroblastoma.
|
| pubmed:affiliation |
Charité Children's Hospital, Experimental Oncology, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|