The Use of Three-Dimensional Ultrasound Micro-Imaging to Monitor Prostate Tumor Development in a Transgenic Prostate Cancer Mouse Model

Wu, Guojun; Wang, Liguo; Yu, Long-Chuan; Wang, He; Xuan, Jim W.

doi:10.1620/tjem.207.181

Cited by 15 publications

(8 citation statements)

References 20 publications

(23 reference statements)

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“…Ultrasound imaging technology was used to detect prostate tumors in the TGMAP mouse model (39,40). However, these techniques have not been used in complex models that recapitulate human disease (such as Pten null mice).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Tumor Growth Progression by Antiandrogens and mTOR Inhibitor in aPten-Deficient Mouse Model of Prostate Cancer

Zhang¹,

Zhu²,

Efferson³

et al. 2009

Cancer Research

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Androgen receptors have been shown to play a critical role in prostate cancer. We used ultrasound imaging techniques to track tumor response to antiandrogen and rapamycin treatment in a prostate-specific Pten-deleted mouse model of cancer. Depletion of androgens by either surgical or chemical castration significantly inhibited tumor growth progression without altering the activation of Akt and mammalian target of rapamycin (mTOR). We also showed for the first time that targeting mTOR along with antiandrogen treatment exhibited additive antitumor effects in vivo when compared with single agents. Our preclinical data suggest that combination of antiandrogens with mTOR inhibitors might be more effective in treating androgen-dependent prostate cancer patients. [Cancer Res 2009;69(18):7466-72]

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Section: Discussionmentioning

confidence: 99%

Inhibition of Tumor Growth Progression by Antiandrogens and mTOR Inhibitor in aPten-Deficient Mouse Model of Prostate Cancer

Zhang¹,

Zhu²,

Efferson³

et al. 2009

Cancer Research

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“…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

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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...

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“…Cheung et al [79] originally described the use of microultrasound in the assessment of xenograft growth analysis. It is now routinely used in serial two-dimensional and three-dimensional volumetric quantification of tumour sizing in vivo in a variety of rodent and nonrodent cancer models [25,26,[80][81][82][83][84][85]. Micro-ultrasound has been shown to more accurately track tumour volume than external callipers [86].…”

Section: Tumour Sizing and Quantification In Two And Three Dimensionsmentioning

confidence: 99%

Micro-ultrasound for preclinical imaging

2011

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Over the past decade, non-invasive preclinical imaging has emerged as an important tool to facilitate biomedical discovery. Not only have the markets for these tools accelerated, but the numbers of peer-reviewed papers in which imaging end points and biomarkers have been used have grown dramatically. High frequency 'micro-ultrasound' has steadily evolved in the post-genomic era as a rapid, comparatively inexpensive imaging tool for studying normal development and models of human disease in small animals. One of the fundamental barriers to this development was the technological hurdle associated with high-frequency array transducers. Recently, new approaches have enabled the upper limits of linear and phased arrays to be pushed from about 20 to over 50 MHz enabling a broad range of new applications. The innovations leading to the new transducer technology and scanner architecture are reviewed. Applications of preclinical micro-ultrasound are explored for developmental biology, cancer, and cardiovascular disease. With respect to the future, the latest developments in high-frequency ultrasound imaging are described.

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The Use of Three-Dimensional Ultrasound Micro-Imaging to Monitor Prostate Tumor Development in a Transgenic Prostate Cancer Mouse Model

Cited by 15 publications

References 20 publications

Inhibition of Tumor Growth Progression by Antiandrogens and mTOR Inhibitor in aPten-Deficient Mouse Model of Prostate Cancer

Inhibition of Tumor Growth Progression by Antiandrogens and mTOR Inhibitor in aPten-Deficient Mouse Model of Prostate Cancer

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

Micro-ultrasound for preclinical imaging

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