Three-dimensional High-Frequency Ultrasound Imaging for Longitudinal Evaluation of Liver Metastases in Preclinical Models

Graham, Kevin C.; Wirtzfeld, Lauren A.; MacKenzie, Lisa T.; Postenka, Carl O.; Groom, A. C.; Macdonald, Ian; Fenster, Aaron; Lacefield, James C.; Chambers, Ann F.

doi:10.1158/0008-5472.can-05-0440

Cited by 113 publications

(88 citation statements)

References 25 publications

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“…Tumor volume assessments were made by highresolution micro-ultrasound imaging as described previously (32,33). Micro-ultrasound imaging was performed with a VisualSonics Vevo 770 microimaging system.…”

Section: Methodsmentioning

confidence: 99%

MetMAb, the One-Armed 5D5 Anti-c-Met Antibody, Inhibits Orthotopic Pancreatic Tumor Growth and Improves Survival

Jin¹,

Yang²,

Zheng³

et al. 2008

Cancer Research

209

163

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The hepatocyte growth factor (HGF) and its receptor, c-Met, have been implicated in driving proliferation, invasion, and poor prognosis in pancreatic cancer. Here, we investigated the expression of HGF and c-Met in primary pancreatic cancers and described in vitro and in vivo models in which MetMAb, a monovalent antibody against c-Met, was evaluated. First, expression of HGF and MET mRNA was analyzed in 59 primary pancreatic cancers and 51 normal samples, showing that both factors are highly expressed in pancreatic cancer. We next examined HGF responsiveness in pancreatic cancer lines to select lines that proliferate in response to HGF. Based on these studies, two lines were selected for further in vivo model development: BxPC-3 (c-Met + , HGF À ) and KP4 (c-Met + , HGF + ) cells. As BxPC-3 cells are responsive to exogenous HGF, s.c. tumor xenografts were grown in a paracrine manner with purified human HGF provided by osmotic pumps, wherein MetMAb treatment significantly inhibited tumor growth. KP4 cells are autocrine for HGF and c-Met, and MetMAb strongly inhibited s.c. tumor growth. To better model pancreatic cancer and to enable long-term survival studies, an orthotopic model of KP4 was established. MetMAb significantly inhibited orthotopic KP4 tumor growth in 4-week studies monitored by ultrasound and also improved survival in 90-day studies. MetMAb significantly reduced c-Met phosphorylation in orthotopic KP4 tumors with a concomitant decrease in Ki-67 staining. These data suggest that the HGF/c-Met axis plays an important role in the progression of pancreatic cancer and that targeting c-Met therein may have therapeutic value.

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Section: Methodsmentioning

confidence: 99%

MetMAb, the One-Armed 5D5 Anti-c-Met Antibody, Inhibits Orthotopic Pancreatic Tumor Growth and Improves Survival

Jin¹,

Yang²,

Zheng³

et al. 2008

Cancer Research

209

163

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“…Our research team and collaborators have developed highfrequency (>20 MHz) three-dimensional ultrasound microimaging for measuring tumor progression in mouse cancer models (15)(16)(17) and showed the use of the technology in a GEM prostate cancer model (12,13). The sensitivity of high-frequency power Doppler to changes in tumor blood flow produced by an antivascular agent was first shown in an orthotopic melanoma in an athymic nude mouse model (18).…”

Section: Introductionmentioning

confidence: 99%

Functional Neoangiogenesis Imaging of Genetically Engineered Mouse Prostate Cancer Using Three-Dimensional Power Doppler Ultrasound

Xuan¹,

Bygrave

Jiang³

et al. 2007

Cancer Research

Self Cite

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We report the first application of high-frequency threedimensional power Doppler ultrasound imaging in a genetically engineered mouse (GEM) prostate cancer model. We show that the technology sensitively and specifically depicts functional neoangiogenic blood flow because little or no flow is measurable in normal prostate tissue or tumors smaller than 2-3 mm diameter, the neoangiogenesis ''switch-on'' size. Vascular structures depicted by power Doppler were verified using Microfil-enhanced micro-computed tomography (micro-CT) and by correlation with microvessel distributions measured by immunohistochemistry and enhanced vascularity visualized by confocal microscopy in two GEM models [transgenic adenocarcinoma of the mouse prostate (TRAMP) and PSP94 gene-directed transgenic mouse adenocarcinoma of the prostate (PSP-TGMAP)]. Four distinct phases of neoangiogenesis in cancer development were observed, specifically, (a) an early latent phase; (b) establishment of a peripheral capsular vascular structure as a neoangiogenesis initiation site; (c) a peak in tumor vascularity that occurs before aggressive tumor growth; and (d) rapid tumor growth accompanied by decreasing vascularity. Microsurgical interventions mimicking local delivery of antiangiogenesis drugs were done by ligating arteries upstream from feeder vessels branching to the prostate. Microsurgery produced an immediate reduction of tumor blood flow, and flow remained low from 1 h to 2 weeks or longer after treatment. Power Doppler, in conjunction with micro-CT, showed that the tumors recruit secondary blood supplies from nearby vessels, which likely accounts for the continued growth of the tumors after surgery. The microsurgical model represents an advanced angiogenic prostate cancer stage in GEM mice corresponding to clinically defined hormone-refractory prostate cancer. Three-dimensional power Doppler imaging is completely noninvasive and will facilitate basic and preclinical research on neoangiogenesis in live animal models. [Cancer Res 2007;67(6):2830-9]

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“…29,30 However, HFU and MRI only achieve a maximum resolution of 100 µm. 30,31 In contrast, current µ-CT scanners provide a resolution of 35 µm, thus making µ-CT nearly three times more accurate than HFU and MRI. 32 The algorithm used in this study to determine the surface topography includes a large number of neighboring voxels, resulting in topographic surface information with improved resolution.…”

Section: Discussionmentioning

confidence: 99%

Non-Invasive analysis of synthetic and decellularized scaffolds for heart valve tissue engineering

Akra¹,

Haller²,

Thierfelder³

et al. 2012

Thorac cardiovasc Surg

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Microcomputed tomography (µ-CT) is a nondestructive, highresolution, three-dimensional method of analyzing objects. The aim of this study was to evaluate the feasibility of using µ-CT as a noninvasive method of evaluation for tissue-engineering applications. The polyurethane aortic heart valve scaffold was produced using a spraying technique. Cryopreserved/thawed homograft and biological heart valve were decellularized using a detergent mixture. Human endothelial cells and fibroblasts were derived from saphenous vein segments and were verified by immunocytochemistry. Heart valves were initially seeded with fibroblasts followed by colonization with endothelial cells. Scaffolds were scanned by a µ-CT scanner before and after decellularization as well as after cell seeding. Successful colonization was additionally determined by scanning electron microscopy (SEM) and immunohistochemistry (IHC). Microcomputed tomography accurately visualized the complex geometry of heart valves. Moreover, an increase in the total volume and wall thickness as well as a decrease in total surface was demonstrated after seeding. A confluent cell distribution on the heart valves after seeding was confirmed by SEM and IHC. We conclude that µ-CT is a new promising noninvasive method for qualitative and quantitative analysis of tissueengineering processes. ASAIO Journal 2013;59:169-177.

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Three-dimensional High-Frequency Ultrasound Imaging for Longitudinal Evaluation of Liver Metastases in Preclinical Models

Cited by 113 publications

References 25 publications

MetMAb, the One-Armed 5D5 Anti-c-Met Antibody, Inhibits Orthotopic Pancreatic Tumor Growth and Improves Survival

MetMAb, the One-Armed 5D5 Anti-c-Met Antibody, Inhibits Orthotopic Pancreatic Tumor Growth and Improves Survival

Functional Neoangiogenesis Imaging of Genetically Engineered Mouse Prostate Cancer Using Three-Dimensional Power Doppler Ultrasound

Non-Invasive analysis of synthetic and decellularized scaffolds for heart valve tissue engineering

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