Angiogenesis Inhibitors in a Murine Neuroblastoma Model: Quantitative Assessment of Intratumoral Blood Flow with Contrast-enhanced Gray-Scale US

McCarville, M. Beth; Streck, Christian J.; Dickson, Paxton V.; Li, Chin‐Shang; Nathwani, Amit C.; Davidoff, Andrew M.

doi:10.1148/radiol.2401050709

Cited by 64 publications

(51 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously found that two variables were particularly useful for evaluating intratumoral perfusion using this technique: the change in contrast enhancement (in decibels) and the rate of this change (in decibels per second; ref. 20). Using this imaging modality, we determined that perfusion of retroperitoneal NB-1691 and subcutaneous U87 tumors was significantly greater and more homogeneous in AAV IFN-h -treated mice, as compared with mice given control vector ( Fig.…”

Section: Alterations Of the Intratumoral Vasculature With Aav Ifn-b Mmentioning

confidence: 95%

See 1 more Smart Citation

Continuous Delivery of IFN-β Promotes Sustained Maturation of Intratumoral Vasculature

Dickson¹,

Hamner²,

Streck³

et al. 2007

Molecular Cancer Research

Self Cite

View full text Add to dashboard Cite

IFNs have pleiotropic antitumor mechanisms of action. The purpose of this study was to further investigate the effects of IFN-B on the vasculature of human xenografts in immunodeficient mice. We found that continuous, systemic IFN-B delivery, established with liver-targeted adeno-associated virus vectors, led to sustained morphologic and functional changes of the tumor vasculature that were consistent with vessel maturation. These changes included increased smooth muscle cell coverage of tumor vessels, improved intratumoral blood flow, and decreased vessel permeability, tumor interstitial pressure, and intratumoral hypoxia. Although these changes in the tumor vasculature resulted in more efficient tumor perfusion, further tumor growth was restricted, as the mature vasculature seemed to be unable to expand to support further tumor growth. In addition, maturation of the intratumoral vasculature resulted in increased intratumoral penetration of systemically administered chemotherapy. Finally, molecular analysis revealed increased expression by treated tumors of angiopoietin-1, a cytokine known to promote vessel stabilization. Induction of angiopoietin-1 expression in response to IFN-B was broadly observed in different tumor lines but not in those with defects in IFN signaling. In addition, IFN-B -mediated vascular changes were prevented when angiopoietin signaling was blocked with a decoy receptor. Thus, we have identified an alternative approach for achieving sustained vascular remodeling-continuous delivery of IFN-B. In addition to restricting tumor growth by inhibiting further angiogenesis, maturation of the tumor vasculature also improved the efficiency of delivery of adjuvant therapy. These results have significant implications for the planning of combination anticancer therapy.

show abstract

Section: Alterations Of the Intratumoral Vasculature With Aav Ifn-b Mmentioning

confidence: 95%

“…Optison ultrasound contrast agent (Amersham Health, Inc.) was used to carry out contrast-enhanced ultrasonography, as described (20). Optison is a suspension of human serum albumin microspheres encapsulating octafluoropropane gas.…”

Section: Vascular Analysesmentioning

confidence: 99%

Continuous Delivery of IFN-β Promotes Sustained Maturation of Intratumoral Vasculature

Dickson¹,

Hamner²,

Streck³

et al. 2007

Molecular Cancer Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…There is a high demand for noninvasive imaging techniques to determine precisely the onset of tumor growth and to characterize growth over time, especially in spontaneous or induced murine tumor models such as WAP-T mice. Therefore, techniques have been applied that enable imaging and exact monitoring of tumor growth and progression in small animals, such as magnetic resonance imaging (MRI 7 ), ultrasound, [8][9][10] computed tomography (CT 11 ) and nuclear imaging. 12,13 Each modality possesses a unique combination of advantages and disadvantages that affect their selection for use in a particular study.…”

Section: Uiccmentioning

confidence: 99%

Detection of different tumor growth kinetics in single transgenic mice with oncogene‐induced mammary carcinomas by flat‐panel volume computed tomography

Jannasch

Dullin

Heinlein

et al. 2009

Intl Journal of Cancer

View full text Add to dashboard Cite

Transgenic mouse models offer an excellent opportunity for studying the molecular basis of cancer development and progression. Here we applied flat-panel volume computed tomography (fpVCT) to monitor tumor progression as well as the development of tumor vasculature in vivo in a transgenic mouse model for oncogene-induced mammary carcinogenesis (WAP-T mice). WAP-T mice develop multiple mammary carcinomas on oncogene induction within 3 to 5 months. Following induction, 3-dimensional fpVCT data sets were obtained by serial single scans of entire mice in combination with iodine containing contrast agents and served as basis for precise measurements of tumor volumes. Thereby, we were able to depict tumors within the mammary glands at a very early stage of the development. Tumors of small sizes (0.001 cm 3 ) were detected by fpVCT before being palpable or visible by inspection. The capability to determine early tumor onset combined with longitudinal noninvasive imaging identified diverse time points of tumor onset for each mammary carcinoma and different tumor growth kinetics for multiple breast carcinomas that developed in single mice. Furthermore, blood supply to the breast tumors, as well as blood vessels around and within the tumors, were clearly visible over time by fpVCT. Three-dimensional visualization of tumor vessels in high resolution was enhanced by the use of a novel blood pool contrast agent. Here, we demonstrate by longitudinal fpVCT imaging that mammary carcinomas develop at different time points in each WAP-T mouse, and thereafter show divergent growth rates and distinct vascularization patterns. ' UICCKey words: flat-panel volume computed tomography; in vivo imaging; murine transgenic tumor models; tumor angiogenesis Accompanying the rapid progress in deciphering the human and mouse genome, many transgenic mouse models have been generated. Weissleder and Mahmood already assumed in 2001 that more than 25 million transgenic and knockout mice would be raised that year for experimental studies, accounting for over 90% of all mammals in research.1 These mouse models offer the opportunity to study gene functions in their biological context in a much more physiological way than any other approach. Especially cancer research benefits from the advantages of these transgenic mice in elucidating the role of a specific gene in tumor growth and spread as well as angiogenesis. One promising model in addressing such questions is the WAP-T transgenic mouse. [2][3][4] In these mice, the SV40 early gene region is induced specifically in differentiating mammary epithelial cells upon activation of the WAPpromoter during late pregnancy and lactation, and drives mammary carcinogenesis in mammary epithelial cells re-expressing the transgene after involution of the mammary glands. The SV40 early region mainly serves to functionally eliminate the p53 and pRb tumor suppressors by binding to the SV40 large T-antigen 5 and to change the specificity of the phosphatase PP2A 6 by its interaction with SV40 small T-antigen, thereby...

show abstract

“…We have shown that CEUS is a reliable method for assessing tumor blood flow in murine pediatric tumor models treated with various antiangiogenic agents [22][23][24]. Most recently, we investigated temporal vascular changes induced by the anti-angiogenic agent bevacizumab in a murine neuroblastoma model by evaluating tumor perfusion at 24 h, 3 days, and 7 days after the administration of one dose of this agent.…”

Section: Assessing Tumor Response To Anti-angiogenic Agentsmentioning

confidence: 99%

Contrast-enhanced sonography in pediatrics

McCarville

2011

Pediatr Radiol

Self Cite

View full text Add to dashboard Cite

Microbubble US contrast agents are composed of an outer shell of protein, phospholipid or polymer that encase air or perfluorocarbon gas. These contrast agents have been widely used in adult cardiology patients to improve endocardial border delineation and have been proved safe and well tolerated in this patient population. There is also a growing body of literature elucidating the value of contrast-enhanced sonography to distinguish benign from malignant liver lesions in adults and to characterize non-hepatic adult malignancies. Because these agents have not been approved for pediatric use in many countries, less is known of the value of contrast-enhanced sonography in children. In this review I will discuss several proven and potential pediatric applications of contrast-enhanced sonography.

show abstract

Angiogenesis Inhibitors in a Murine Neuroblastoma Model: Quantitative Assessment of Intratumoral Blood Flow with Contrast-enhanced Gray-Scale US

Abstract: Quantification of intratumoral flow of a US contrast agent at gray-scale imaging shows promise for monitoring tumor vascular response to antiangiogenic therapy.

Cited by 64 publications

References 20 publications

Continuous Delivery of IFN-β Promotes Sustained Maturation of Intratumoral Vasculature

Continuous Delivery of IFN-β Promotes Sustained Maturation of Intratumoral Vasculature

Detection of different tumor growth kinetics in single transgenic mice with oncogene‐induced mammary carcinomas by flat‐panel volume computed tomography

Contrast-enhanced sonography in pediatrics

Contact Info

Product

Resources

About