Preclinical Liver Metastases: Three-Dimensional High-Frequency Ultrasound Imaging
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Metastasis, the spread of a primary cancer to distant organs, continues to be the most significant cause of cancer mortality. Isolated primary tumors can often be treated surgically with a relatively high success rate. However, if the primary tumor has invaded the surrounding tissue and metastasized to secondary sites in the body, treatment options are often limited to systemic chemotherapies with much lower success rates and greater toxicity. Thus, it is imperative that a greater understanding of the biology of the metastatic process be acquired in order to achieve a significant reduction in the morbidity and mortality associated with cancer diagnosis.
The process of metastasis consists of multiple biological steps governed by a wide range of molecular processes (Chambers et al., 2002). The cells in a developing primary tumor must invade the surrounding tissue and gain access to a blood or lymphatic vessel to facilitate dissemination. Once the metastatic cell has arrived at a secondary site, the cell must arrest in the vascular system, survive, undergo cell division in the new microenvironment, and eventually recruit new blood vessels to allow for continued development. Although many cells initiate this sequence of events by gaining access to the vascular system, < 1% of these cells are able to complete all of the steps to form overt metastases (Chambers et al., 2002). The multi-step nature and biological and molecular complexity of the metastatic process have necessitated that a variety of research tools be used to effectively model this process. In vitro models have allowed for a greater understanding of how tumor cells circumvent normal cell growth and survival regulations. In vitro models are essential to isolate the contribution of specific molecular pathways to the development of a metastatic cell, but fail to capture the complexity of the entire metastatic process that exists in the in vivo situation. Thus, in order to study the complete metastatic process it is necessary to develop and utilize animal models. Animal models are used to study the interactions of a tumor cell with a changing micro-environment as it progresses through the metastatic process, and are often used to evaluate novel therapeutics and treatment strategies.
KeywordsContrast Agent Liver Metastasis Metastatic Process Compute Tomogra Metastasis Model
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