| Magnetic resonance imaging defines cervicovaginal anatomy, cancer, and VEGF trap antiangiogenic efficacy in estrogen-treated K14-HPV16 transgenic mice. | |
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MedLine Citation:
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PMID: 19789343 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Noninvasive detection of dysplasia provides a potential platform for monitoring the efficacy of chemopreventive therapy of premalignancy, imaging the tissue compartments comprising dysplasia: epithelium, microvasculature, and stromal inflammatory cells. Here, using respiratory-gated magnetic resonance imaging (MRI), the anatomy of premalignant and malignant stages of cervical carcinogenesis in estrogen-treated K14-HPV16 transgenic mice was noninvasively defined. Dynamic contrast enhanced (DCE)-MRI was used to quantify leakage across premalignant dysplastic microvasculature. Vascular permeability as measured by DCE-MRI, K(trans), was similar in transgenic (0.053 +/- 0.020 min(-1); n = 32 mice) and nontransgenic (0.056 +/- 0.029 min(-1); n = 17 mice) animals despite a 2-fold increase in microvascular area in the former compared with the latter. DCE-MRI did detect a significant decrease in vascular permeability accompanying diminution of dysplastic microvasculature by the antiangiogenic agent, vascular endothelial growth factor Trap (K(trans) = 0.052 +/- 0.013 min(-1) pretreatment; n = 6 mice versus K(trans) = 0.019 +/- 0.008 min(-1) post-treatment; n = 5 mice). Thus, we determined that the threshold of microvessel leakage associated with cervical dysplasia was <17 kDa and highlighted the potential of DCE-MRI to noninvasively monitor the efficacy of antiangiogenic drugs or chemoprevention regimens targeting the vasculature in premalignant cervical dysplasia. |
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Authors:
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Joel R Garbow; Andrea C Santeford; Jeff R Anderson; John A Engelbach; Jeffrey M Arbeit |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-09-29 |
Journal Detail:
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Title: Cancer research Volume: 69 ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-10-16 Completed Date: 2009-11-24 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 7945-52 Citation Subset: IM |
Affiliation:
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Department of Radiology, Alvin J Siteman Cancer Center, Washington University in St Louis, Missouri 63110, USA. garbow@wustl.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiogenesis Inhibitors
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therapeutic use Animals Capillary Permeability Carcinoma, Squamous Cell / blood supply*, drug therapy, virology Contrast Media / diagnostic use Estrogens / therapeutic use* Female Genitalia, Female / pathology* Humans Keratin-14 / genetics Magnetic Resonance Imaging* Mice Mice, Transgenic Neovascularization, Pathologic / diagnosis*, drug therapy Oncogene Proteins, Viral / genetics Papillomavirus E7 Proteins Recombinant Fusion Proteins / therapeutic use* Tumor Cells, Cultured Uterine Cervical Neoplasms / blood supply*, drug therapy, virology Vascular Endothelial Growth Factor A / antagonists & inhibitors |
| Grant Support | |
ID/Acronym/Agency:
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P30 CA091842-05/CA/NCI NIH HHS; P30 CA91842/CA/NCI NIH HHS; U24 CA083060-10/CA/NCI NIH HHS; U24 CA83060/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Angiogenesis Inhibitors; 0/Contrast Media; 0/Estrogens; 0/Keratin-14; 0/Oncogene Proteins, Viral; 0/Papillomavirus E7 Proteins; 0/Recombinant Fusion Proteins; 0/Vascular Endothelial Growth Factor A; 0/aflibercept; 0/oncogene protein E7, Human papillomavirus type 16 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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