dc.contributor.author |
Bigner, DD |
|
dc.contributor.author |
Herndon, James Emmett II |
|
dc.contributor.author |
Kuan, Chien-Tsun |
|
dc.contributor.author |
Lipp, Eric S |
|
dc.contributor.author |
McLendon, Roger E |
|
dc.contributor.author |
Pegram, CN |
|
dc.contributor.author |
Rasheed, A |
|
dc.contributor.author |
Riggins, GJ |
|
dc.contributor.author |
Szafranski, SE |
|
dc.contributor.author |
Wakiya, K |
|
dc.contributor.author |
Wikstrand, CJ |
|
dc.coverage.spatial |
England |
|
dc.date.accessioned |
2011-06-21T17:29:38Z |
|
dc.date.issued |
2010-09-01 |
|
dc.identifier |
http://www.ncbi.nlm.nih.gov/pubmed/20809959 |
|
dc.identifier |
1471-2407-10-468 |
|
dc.identifier.uri |
https://hdl.handle.net/10161/4357 |
|
dc.description.abstract |
BACKGROUND: Glioblastoma multiforme (GBM) is refractory to conventional therapies.
To overcome the problem of heterogeneity, more brain tumor markers are required for
prognosis and targeted therapy. We have identified and validated a promising molecular
therapeutic target that is expressed by GBM: human multidrug-resistance protein 3
(MRP3). METHODS: We investigated MRP3 by genetic and immunohistochemical (IHC) analysis
of human gliomas to determine the incidence, distribution, and localization of MRP3
antigens in GBM and their potential correlation with survival. To determine MRP3 mRNA
transcript and protein expression levels, we performed quantitative RT-PCR, raising
MRP3-specific antibodies, and IHC analysis with biopsies of newly diagnosed GBM patients.
We used univariate and multivariate analyses to assess the correlation of RNA expression
and IHC of MRP3 with patient survival, with and without adjustment for age, extent
of resection, and KPS. RESULTS: Real-time PCR results from 67 GBM biopsies indicated
that 59/67 (88%) samples highly expressed MRP3 mRNA transcripts, in contrast with
minimal expression in normal brain samples. Rabbit polyvalent and murine monoclonal
antibodies generated against an extracellular span of MRP3 protein demonstrated reactivity
with defined MRP3-expressing cell lines and GBM patient biopsies by Western blotting
and FACS analyses, the latter establishing cell surface MRP3 protein expression. IHC
evaluation of 46 GBM biopsy samples with anti-MRP3 IgG revealed MRP3 in a primarily
membranous and cytoplasmic pattern in 42 (91%) of the 46 samples. Relative RNA expression
was a strong predictor of survival for newly diagnosed GBM patients. Hazard of death
for GBM patients with high levels of MRP3 RNA expression was 2.71 (95% CI: 1.54-4.80)
times that of patients with low/moderate levels (p = 0.002). CONCLUSIONS: Human GBMs
overexpress MRP3 at both mRNA and protein levels, and elevated MRP3 mRNA levels in
GBM biopsy samples correlated with a higher risk of death. These data suggest that
the tumor-associated antigen MRP3 has potential use for prognosis and as a target
for malignant glioma immunotherapy.
|
|
dc.language |
eng |
|
dc.language.iso |
en_US |
|
dc.relation.ispartof |
BMC Cancer |
|
dc.relation.isversionof |
10.1186/1471-2407-10-468 |
|
dc.relation.isreplacedby |
10161/16100 |
|
dc.relation.isreplacedby |
http://hdl.handle.net/10161/16100 |
|
dc.subject |
Animals |
|
dc.subject |
Antibodies, Monoclonal |
|
dc.subject |
Blotting, Western |
|
dc.subject |
Brain |
|
dc.subject |
Brain Neoplasms |
|
dc.subject |
Case-Control Studies |
|
dc.subject |
Cells, Cultured |
|
dc.subject |
Female |
|
dc.subject |
Glioblastoma |
|
dc.subject |
Humans |
|
dc.subject |
Immunoenzyme Techniques |
|
dc.subject |
Immunotherapy |
|
dc.subject |
Male |
|
dc.subject |
Mice |
|
dc.subject |
Mice, Inbred BALB C |
|
dc.subject |
Middle Aged |
|
dc.subject |
Multidrug Resistance-Associated Proteins |
|
dc.subject |
Neoplasm Staging |
|
dc.subject |
Prognosis |
|
dc.subject |
RNA, Messenger |
|
dc.subject |
Rabbits |
|
dc.subject |
Reverse Transcriptase Polymerase Chain Reaction |
|
dc.subject |
Survival Rate |
|
dc.subject |
Tumor Cells, Cultured |
|
dc.subject |
Xenograft Model Antitumor Assays |
|
dc.title |
MRP3: a molecular target for human glioblastoma multiforme immunotherapy. |
|
dc.title.alternative |
|
|
dc.type |
Journal article |
|
dc.description.version |
Version of Record |
|
duke.date.pubdate |
2010-9-1 |
|
duke.description.issue |
|
|
duke.description.volume |
10 |
|
dc.relation.journal |
Bmc Cancer |
|
pubs.author-url |
http://www.ncbi.nlm.nih.gov/pubmed/20809959 |
|
pubs.begin-page |
468 |
|
pubs.organisational-group |
Basic Science Departments |
|
pubs.organisational-group |
Biostatistics & Bioinformatics |
|
pubs.organisational-group |
Clinical Science Departments |
|
pubs.organisational-group |
Duke |
|
pubs.organisational-group |
Duke Cancer Institute |
|
pubs.organisational-group |
Faculty |
|
pubs.organisational-group |
Institutes and Centers |
|
pubs.organisational-group |
Neurosurgery |
|
pubs.organisational-group |
Pathology |
|
pubs.organisational-group |
School of Medicine |
|
pubs.organisational-group |
Surgery |
|
pubs.publication-status |
Published online |
|
pubs.volume |
10 |
|
dc.identifier.eissn |
1471-2407 |
|