Takada Marilia, Smyth Lauren A, Hix Jeremy Ml, Corner Sarah M, Kiupel Matti, Yuzbasiyan-Gurkan Vilma
Comparative Medicine and Integrative Biology Program, Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin.
Comparative Medicine and Integrative Biology Program, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan.
Comp Med. 2019 Feb 1;69(1):22-28. doi: 10.30802/AALAS-CM-18-000065. Epub 2019 Feb 4.
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.
犬组织细胞肉瘤是一种侵袭性很强且具有转移性的造血肿瘤，对目前可用的治疗方案反应不佳。我们的目标是建立一种临床相关的异种移植小鼠模型，以评估针对组织细胞肉瘤的新型癌症治疗方案的临床前疗效。我们开发了一种脾内异种移植小鼠模型，其特点是肿瘤生长一致，并发生向肝脏和其他腹部器官的转移。该模型代表了犬组织细胞肉瘤的转移性或播散性形式，这被认为是该疾病临床上最具挑战性的形式。用荧光素酶载体转染肿瘤细胞有助于利用体内生物发光成像来跟踪肿瘤随时间的进展，并评估该小鼠模型对新型化疗药物的反应。与仅用赋形剂处理的小鼠相比，用达沙替尼治疗脾内异种移植小鼠可减少肿瘤生长并延长存活时间。我们的研究结果表明达沙替尼在治疗犬组织细胞肉瘤及人类类似疾病方面具有潜力。这些结果值得进行更多研究，以临床测试达沙替尼对患有组织细胞肉瘤的犬的疗效。
