| Microarray gene expression analysis of murine tumor heterogeneity defined by dynamic contrast-enhanced MRI. | |
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MedLine Citation:
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PMID: 12920855 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Current methods of studying angiogenesis are limited in their ability to serially evaluate in vivo function throughout a target tissue. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and pharmacokinetic modeling provide a useful method for evaluating tissue vasculature based on contrast accumulation and washout. While it is often assumed that areas of high contrast enhancement and washout comprise areas of increased angiogenesis and tumor activity, the actual molecular pathways that are active in such areas are poorly understood. Using DCE-MRI in a murine subcutaneous tumor model, we were able to perform pharmacokinetic functional analysis of a tumor, coregistration of MRI images with histological cross-sections, immunohistochemistry, laser capture microdissection, and genetic profiling of tumor heterogeneity based on pharmacokinetic parameters. Using imaging as a template for biologic investigation, we have not found evidence of increased expression of proangiogenic modulators at the transcriptional level in either distinct pharmacokinetic region. Furthermore, these regions show no difference on histology and CD31 immunohistochemistry. However, the expression of ribosomal proteins was greatly increased in high enhancement and washout regions, implying increased protein translation and consequent increased cellular activity. Together, these findings point to the potential importance of posttranscriptional regulation in angiogenesis and the need for the development of angiogenesis-specific contrast agents to evaluate in vivo angiogenesis at a molecular level. |
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Authors:
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Nick G Costouros; Dominique Lorang; Yantian Zhang; Marshall S Miller; Felix E Diehn; Stephen M Hewitt; Michael V Knopp; King C P Li; Peter L Choyke; H Richard Alexander; Steven K Libutti |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Molecular imaging Volume: 1 ISSN: 1535-3508 ISO Abbreviation: Mol Imaging Publication Date: 2002 Jul |
Date Detail:
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Created Date: 2003-08-18 Completed Date: 2003-10-23 Revised Date: 2011-04-07 |
Medline Journal Info:
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Nlm Unique ID: 101120118 Medline TA: Mol Imaging Country: United States |
Other Details:
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Languages: eng Pagination: 301-8 Citation Subset: IM |
Affiliation:
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National Cancer Institute, Bethesda, MD, USA. Steven_Libutti@nih.gov |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Base Sequence Contrast Media DNA Primers / genetics Gene Expression Profiling / methods* Magnetic Resonance Imaging / methods* Mice Mice, Inbred C57BL Neoplasms, Experimental / blood supply, genetics*, pathology Neovascularization, Pathologic Oligonucleotide Array Sequence Analysis / methods* |
| Chemical | |
Reg. No./Substance:
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0/Contrast Media; 0/DNA Primers |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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