Shengmei Gu1,2, Jingyan Xue1,2, Yan Xi3, Rongbiao Tang4, Wei Jin1,2, Jia-Jian Chen1,2, Xi Zhang1,2, Zhi-Min Shao1,2, Jiong Wu1,2,5. 1. Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China. 2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. 3. School of Biomedical Engineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, China. 4. Department of Radiology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China. 5. Collaborative Innovation Center for Cancer Medicine, Shanghai 200032, China.
Abstract
BACKGROUND: The visualization of microvasculature is an essential step in understanding the mechanisms underlying early vessel disorders involved in breast cancer and for developing effective therapeutic strategies. However, generating detailed and reproducible data using immunohistochemistry analysis of breast cancer angiogenesis has been difficult. METHODS: To analyze the diversification of angiogenesis in the development of tumor growth and evaluate the anti-vascular effects of Avastin (bevacizumab), we used new X-ray microangiography and third-generation synchrotron radiation-based micro-computed tomography (SR micro-CT) technology. With these techniques, we were able to investigate the structures and density of microvessels in xenograft mouse models (n=24). Barium sulfate nanoparticles were injected into the left cardiac ventricle of the mice to allow the visualization of blood vessels. RESULTS: Three-dimensional structures of microvessels were displayed with a high spatial image resolution of 20-30 µm. The density of angiogenesis and the incidence of lung metastasis were significantly reduced in xenograft mouse models of breast cancer treated with Avastin compared with control groups. Also, the density of smaller vessels (diameter <50 µm) was significantly decreased in the Avastin-treated mice, while the density of larger vessels (diameter >100 µm) was not significantly changed. CONCLUSIONS: Avastin inhibited tumor growth and lung metastasis by reducing microvessels. Additionally, synchrotron radiation (SR) techniques are useful as an additional tool for more precise quantification of angiogenesis.
BACKGROUND: The visualization of microvasculature is an essential step in understanding the mechanisms underlying early vessel disorders involved in breast cancer and for developing effective therapeutic strategies. However, generating detailed and reproducible data using immunohistochemistry analysis of breast cancer angiogenesis has been difficult. METHODS: To analyze the diversification of angiogenesis in the development of tumor growth and evaluate the anti-vascular effects of Avastin (bevacizumab), we used new X-ray microangiography and third-generation synchrotron radiation-based micro-computed tomography (SR micro-CT) technology. With these techniques, we were able to investigate the structures and density of microvessels in xenograft mouse models (n=24). Barium sulfate nanoparticles were injected into the left cardiac ventricle of the mice to allow the visualization of blood vessels. RESULTS: Three-dimensional structures of microvessels were displayed with a high spatial image resolution of 20-30 µm. The density of angiogenesis and the incidence of lung metastasis were significantly reduced in xenograft mouse models of breast cancer treated with Avastin compared with control groups. Also, the density of smaller vessels (diameter <50 µm) was significantly decreased in the Avastin-treated mice, while the density of larger vessels (diameter >100 µm) was not significantly changed. CONCLUSIONS: Avastin inhibited tumor growth and lung metastasis by reducing microvessels. Additionally, synchrotron radiation (SR) techniques are useful as an additional tool for more precise quantification of angiogenesis.
Entities:
Keywords:
Avastin; Breast cancer; lung metastasis; microvessel density (MVD); synchrotron radiation (SR)
Authors: C N Chen; Y M Cheng; J T Liang; P H Lee; F J Hsieh; R H Yuan; S M Wang; M F Chang; K J Chang Journal: Cancer Res Date: 2000-06-01 Impact factor: 12.701
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