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Imageable Clinically Relevant Mouse Models of Metastasis

In the past 10 years, we have developed a new approach to the development of a clinically accurate rodent model for human cancer based on our invention of surgical orthotopic implantation (SOI). The SOI models have been described in approx. 70 publications and in 4 patents.*SOI allows human tumors of a ...

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Imaging Metastatic Cell Trafficking at the Cellular Level In Vivo with Fluorescent Proteins

Fluorescent proteins have revolutionized biology, allowing what was formerly invisible to be clearly seen. The Nobel Prize in Chemistry was awarded in 2008 for the discovery and early use of green fluorescent protein (GFP) as a genetic reporter. Our laboratory pioneered the use of GFP for in vivo ...

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Ultrasound Techniques for the Detection of Tumors and Metastases in Small Animals

Small animals are widely used for the identification of new therapeutic targets and the evaluation of potential anticancer therapies. To study tumors and metastasis in longitudinal studies of tumor progression, fast noninvasive and easy-to-handle imaging modalities are requir ...

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The PFP/RAG2 Double-Knockout Mouse in Metastasis Research: Small-Cell Lung Cancer and Prostate Cancer

Patients with small-cell lung cancer (SCLC) and prostate cancer (PCa) as well as other solid tumors may have micro- or macro-metastatic spread at an early stage of the disease. SCLC and PCa xenograft transfer models in immunodeficient mice fail to model this metastatic spread in vivo. In both tumor t ...

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Ultrasound-Guided Intracardial Injection and In Vivo Magnetic Resonance Imaging of Single Cells in Mice as a Paradigm for Hematogenous Metastases

Magnetic resonance imaging (MRI) has become an important technique for noninvasive cell tracking in preclinical research. Following appropriate cell labeling MRI can be used to detect larger cell cohorts and also single cells in vivo in mice. Cell distribution to different organs such as ...

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Spontaneous and Experimental Metastasis Models: Nude Mice

Immunodeficient mice are widely used for cancer research as they can provide an in vivo system in which to study the tumorigenicity and metastatic potential of human cancer cells. The athymic or “nude” mouse has been employed for a variety of experimental analyses of tumor growth, invasion, and me ...

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Magnetic Resonance Imaging of Metastases in Xenograft Mouse Models of Cancer

Magnetic resonance imaging (MRI) of small animals has emerged as a valuable tool to noninvasively monitor tumor growth in mouse models of cancer. However, imaging of metastases in mouse models is difficult due to the need for high spatial resolution. We have demonstrated MRI of metastases in the l ...

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Identifying the Origin and Phenotype of Cells in Tumor Xenografts

The growth of human tumor cells transplanted into immunodeficient mice is frequently studied to gain understanding about the way potential drug treatments interfere with growth in vivo. A wide range of methods is available for learning about specific aspects of tumor cell behavior, for ex ...

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Single Cell and Spheroid Collagen Type I Invasion Assay

Tumor invasion is the outcome of a complex interplay between cancer cells and the stromal environment and requires the infiltration of a dense, cross-linked meshwork of collagen type I extracellular matrix. We use a membrane-free single-cell and spheroid-based complementary model to s ...

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In Vitro Invasion Assay Using Matrigel: A Reconstituted Basement Membrane Preparation

Basement membranes, specialized extracellular matrices composed of collagens, laminins, and proteoglycans, form thin, continuous sheetlike structures that separate epithelial tissues from adjacent connective tissues. The crossing of basement membranes by cancer cel ...

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Rocking Adhesion Assay System to Study Adhesion and Transendothelial Migration of Cancer Cells

Adhesion of metastatic cancer cells to the vascular endothelium of the target organs and their subsequent transendothelial migration is one of the critical, yet poorly understood, steps of the metastatic cascade. Conventionally, the mechanisms of this complex process have been stud ...

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Small-Cell Lung Cancer (SCLC) Cell Adhesion on E- and P-Selectin Under Physiological Flow Conditions

Hematogenous metastasis is still a poorly understood phenomenon. The rate-limiting step within the metastatic cascade is not yet clear although it may be estimated that the extravasation of circulating tumor cells is a step of crucial importance, as most tumor cells that are shed into circu ...

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Metabolic Monitoring of Chemosensitivity with 18FDG PET

Accurate and early evaluation of tumor response to chemotherapy is a growing clinical need for optimal management of oncology patients. This is even more warranted by the lack of appropriate response evaluation criteria to new molecularly targeted anticancer therapies. In the two last d ...

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Magnetic Resonance Imaging of Tumor Response to Chemotherapy

The breadth and substance of anatomic (structural) and novel physiological (functional) imaging methods to noninvasively monitor and assess anticancer therapies continues to grow. Current techniques span several imaging disciplines including magnetic resonance (MR) im ...

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99mTc-Annexin A5 Uptake and Imaging to Monitor Chemosensitivity

Most anticancer agents act by inducing apoptosis in sensitive tumor cells. Hence, in many types of cancers, significant increase of tumor apoptosis after chemotherapy correlates with tumor chemosensitivity. Theoretically, a reliable evaluation of apoptotic changes, postche ...

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Evaluation of Chemosensitivity of Micrometastases with Green Fluorescent Protein Gene-Tagged Tumor Models in Mice

The chemosensitivity of micrometastasis is an important factor in therapeutic approaches to micrometastasis. The protocol in this chapter presents procedures capable of examining the drug sensitivity of micrometastases to anticancer agents, especially those in the perito ...

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Assessing Growth and Response to Therapy in Murine Tumor Models

Rodent models provide an important means of assessing antitumor activity vs toxicity for new cancer therapies. Tumors are often grown subcutaneously on the flank or back of animals, allowing accurate serial determination of tumor volume with calipers by measuring the tumors in three dim ...

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Preclinical Testing of Antileukemic Drugs Using an In Vivo Model of Systemic Disease

Acute lymphoblastic leukemia (ALL) is predominantly a disease of the bone marrow that disseminates to multiple organ sites throughout the body and, without aggressive treatment, eventually results in multiorgan failure and death. Experimental models that mimic the disseminati ...

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Orthotopic Metastatic (MetaMouse) Models for Discovery and Development of Novel Chemotherapy

Currently-used rodent tumor models, including transgenic tumor models, or subcutaneously growing human tumors in immunodeficient mice, do not sufficiently represent clinical-cancer, especially with regard to metastasis and drug sensitivity. In order to obtain clinically ...

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Clinically Relevant Metastatic Breast Cancer Models to Study Chemosensitivity

Metastatic disease, notably to the lungs, liver, bone, and brain, is the most common cause of death from breast cancer, despite advances in surgical and clinical management. Two basic principles govern the process of metastasis: first, that tumors are heterogeneous populations of cells; and s ...

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