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Development of an Orthotopic Intrasplenic Xenograft Mouse Model of Canine Histiocytic Sarcoma and Its Use in Evaluating the Efficacy of Treatment with Dasatinib

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Canine histiocytic sarcoma is a highly aggressive and metastatic hematopoietic neoplasm that responds poorly to currently available treatment regimens. Our goal was to establish a clinically relevant xenograft mouse model to assess the preclinical efficacy of novel cancer treatment protocols for histiocytic sarcoma. We developed an intrasplenic xenograft mouse model characterized by consistent tumor growth and development of metastasis to the liver and other abdominal organs. This model represents the metastatic or disseminated form of canine histiocytic sarcoma, which is considered the most clinically challenging form of the disease. Transfection of tumor cells with a luciferase vector supported the use of in vivo bioluminescence imaging to track tumor progression over time and to assess the response of this murine model to novel chemotherapeutic agents. Dasatinib treatment of the mice with intrasplenic xenografts decreased tumor growth and increased survival times, compared with mice treated with vehicle only. Our findings indicate the potential of dasatinib for the treatment of histiocytic sarcoma in dogs and for similar diseases in humans. These results warrant additional studies to clinically test the efficacy of dasatinib in dogs with histiocytic sarcoma.
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Document Type: Miscellaneous

Affiliations: 1: Comparative Medicine and Integrative Biology Program, Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 2: Comparative Medicine and Integrative Biology Program, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan 3: Department of Radiology, Comparative Medicine and Integrative Biology Program, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan 4: Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan 5: Research Technology Support Facility, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan 6: Comparative Medicine and Integrative Biology Program, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan;, Email: [email protected]

Publication date: February 1, 2019

This article was made available online on February 4, 2019 as a Fast Track article with title: "Development of an Orthotopic Intrasplenic Xenograft Mouse Model of Canine Histiocytic Sarcoma and Its Use in Evaluating the Efficacy of Treatment with Dasatinib".

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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