Linked Life Data

19001442

Source:http://linkedlifedata.com/resource/pubmed/id/19001442

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2008-11-12
pubmed:abstractText
Our aim was to assess the ability of convection-enhanced drug delivery (CED), a novel approach of direct delivery of drugs into brain tissue and brain tumors, to treat brain tumors using salirasib (farsnesyl thiosalicylic acid). CED was achieved by continuous infusion of drugs via intracranial catheters, thus enabling convective distribution of high drug concentrations over large volumes while avoiding systemic toxicity. Several phase II/III CED-based trials are currently in progress but have yet to overcome two major pitfalls of this methodology (the difficulty in attaining efficient CED and the significant nonspecific neurotoxicity caused by high drug doses in the brain). In this study, we addressed both issues by employing our previously described novel CED imaging and increased efficiency methodologies to exclusively target the activated form of the Ras oncogene in a 9L gliosarcoma rat model. The drug we used was salirasib, a highly specific Ras inhibitor shown to exert its suppressive effects on growth and migration of proliferating tumor cells in in vitro and in vivo models, including human glioblastoma, without affecting normal tissues. The results show a significant decrease in tumor growth rate in salirasib-treated rats relative to vehicle-treated rats as well as a significant correlation between CED efficacy and tumor growth rate with no observed toxicity despite drug concentrations an order of magnitude higher than previously detected in the brain. The results show that CED of salirasib is efficient and nontoxic for the treatment of glioblastoma in a rat model, thus suggesting that it may be considered for clinical application.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1535-7163
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3609-16
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Salirasib (farnesyl thiosalicylic acid) for brain tumor treatment: a convection-enhanced drug delivery study in rats.
pubmed:affiliation
Department of Neurobiochemistry, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel Aviv, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't