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Magnetic resonance imaging defines cervicovaginal anatomy, cancer, and VEGF trap antiangiogenic efficacy in estrogen-treated K14-HPV16 transgenic mice.
- Source :
-
Cancer research [Cancer Res] 2009 Oct 15; Vol. 69 (20), pp. 7945-52. Date of Electronic Publication: 2009 Sep 29. - Publication Year :
- 2009
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Abstract
- 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.
- Subjects :
- Angiogenesis Inhibitors therapeutic use
Animals
Capillary Permeability
Carcinoma, Squamous Cell drug therapy
Carcinoma, Squamous Cell virology
Contrast Media
Female
Humans
Keratin-14 genetics
Mice
Mice, Transgenic
Neovascularization, Pathologic drug therapy
Oncogene Proteins, Viral genetics
Papillomavirus E7 Proteins
Receptors, Vascular Endothelial Growth Factor
Tumor Cells, Cultured
Uterine Cervical Neoplasms drug therapy
Uterine Cervical Neoplasms virology
Vascular Endothelial Growth Factor A antagonists & inhibitors
Carcinoma, Squamous Cell blood supply
Estrogens therapeutic use
Genitalia, Female pathology
Magnetic Resonance Imaging
Neovascularization, Pathologic diagnosis
Recombinant Fusion Proteins therapeutic use
Uterine Cervical Neoplasms blood supply
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 69
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 19789343
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-09-1271