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The use of
MRI in patients with glioblastoma multiforme to identify regions of vascular
permeability for genomic analysis
Samira Guccione, Yishan
Yang, Ron Homer, Steven Chang, Griff Harsh, Scott Atlas, Mark Bednarski
Stanford University, Palo
Alto, CA
Glioblastoma multiforme
(GBM) is a primary brain tumor with poor prognosis with the overall 5-yr
survival rate of less than 6%.
Similar to most solid tumors, GBM is morphologically heterogeneous adding to the
difficulties associated with tissue sampling for genomic analysis.
Additionally, each patient has a unique temporal dependence in the course of
tumor progression.
Contrast enhanced MRI using Gd(DTPA) can reveal imaging features associated with
increased vascular permeability, vessel density, and areas of fluid accumulation
and necrosis.
We hypothesized that contrast enhanced MRI can be used to guide sample
acquisition for gene array analysis.
Specifically, we have found that the contrast enhancing areas (CE) of GBM
relative to areas that do not take up contrast (non-enhancing areas, NE) within
the same tumor can reveal important molecular targets for the development of new
diagnostic and therapeutic agents.
Patients presenting with glioblastoma multiforme, without any prior surgical,
chemotherapy, or radiation interventions were recruited for tissue sampling at
the time of their surgical resection.
All patient were scanned on a clinical 1.5T GE MRI scanner using standard T1 and
T2-weighted sequences, with Magnevist (Berlex) as contrast agent.
Samples from CE and NE areas were obtained from each patient and used for
genomic profiling using oligonucleotide microarray analysis.
Results from 6 patients indicate that aFGF, laminin receptor, IGFBP-2, IGFBP-3,
IGFBP-5, galectin-3, CD44 (HCAM), NCAM were all upregulated in the CE areas of
the tumor relative to the NE regions.
In addition using this approach, we have avoided sampling regions of necrosis
that can complicate gene array analysis.
Immunohistologiocal staining was used to confirm the upregulation of the protein
products of these genomic targets.
Since these proteins are being produced in regions with high vascular
permeability, we are currently evaluating their presence in the blood, urine,
and CSF of GBM patients.
The Evaluation of genomic data using imaging to sample areas of vascular
permeability to identify targets for the detection of blood markers and
development of therapeutics is a new approach for the use of genomic data for
target identification.
Copyright © 2003 American
Association for Cancer Research. All rights reserved
Source: http://aacr03.agora.com/planner/displayabstract.asp?presentationid=192
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