Linked Life Data

20520650

Source:http://linkedlifedata.com/resource/pubmed/id/20520650

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-11-11
pubmed:abstractText
Glioblastoma multiforme (GBM) is one of the most formidable brain tumors with a mean survival period of approximately 12 months. To date, a combination of radiotherapy and chemotherapy with an oral alkylating agent, temozolomide (TMZ), has been used as first-line therapy for glioma. However, the efficacy of chemotherapy for treating GBM is very limited; this is partly because of the high activity levels of the DNA repair protein O?-methylguanine-DNA methyltransferase (MGMT) in tumor cells, which creates a resistant phenotype by blunting the therapeutic effect of alkylating agents. Thus, MGMT may be an important determinant of treatment failure and should be considered as a suitable target for intervention, in an effort to improve the therapeutic efficacy of TMZ. In this study, we showed that small-interfering RNA (siRNA)-based downregulation of MGMT could enhance the chemosensitivity of malignant gliomas against TMZ. Notably, TMZ-resistant glioma-initiating cells with increased DNA repair and drug efflux capabilities could be efficiently transduced with MGMT-siRNA by using a novel liposome, LipoTrust. Accordingly, such transduced glioma-initiating cells could be sensitized to TMZ in both in vitro and in vivo tumor models. Taken together, this study provides an experimental basis for the clinical use of such therapeutic combinations.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1476-5462
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1363-71
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Efficient delivery of liposome-mediated MGMT-siRNA reinforces the cytotoxity of temozolomide in GBM-initiating cells.
pubmed:affiliation
Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan.
pubmed:publicationType
Journal Article