Abstract
Aurora kinases play an important role in the cell cycle. These enzymes help establish mitotic spindles by directing centrosome duplication and separation and by regulating the spindle assembly checkpoint thereby helping control cytokinesis. An over-expression of aurora kinases has been reported in a variety of human tumors. In this study, we identified the expression of aurora-A and aurora-B kinases in canine malignant lymphoid cells. We also evaluated the effects of the aurora kinase inhibitor (ZM447439), and found that this inhibitor decreases cell viability, increases DNA content change, and leads to apoptosis in canine B- and T-cell lymphoid cell lines. The lymphotoxicity induced by ZM447439 in these canine lymphoid cell lines suggests that further in vivo evaluation of aurora kinase inhibitors as a potential treatment for canine malignant lymphoid tumors is warranted.
Highlights
Canine lymphoma, consisting of B and T cell lymphoma, is a very heterogeneous disease with both aggressive and indolent subtypes
We evaluated the effects of the aurora kinase inhibitor (ZM447439), and found that this inhibitor decreases cell viability, increases DNA content change, and leads to apoptosis in canine B- and T-cell lymphoid cell lines
There are no published data showing the effect of aurora kinase inhibitors in veterinary medicine at the time of this writing
Summary
Canine lymphoma, consisting of B and T cell lymphoma, is a very heterogeneous disease with both aggressive and indolent subtypes. Indolent subtypes of lymphoma have been reported in up to 29% of dogs [1]. Canine diffuse large B-cell lymphoma is typically an aggressive and high grade tumor in humans and dogs. The most common protocols for B-cell lymphoma are CHOP-based, which consist of cyclophosphamide, doxorubicin, vincristine and prednisone. Complete response rates range from approximately 80% - 90%, and median survival times range from approximately 12 - 14 months with standard CHOP-based protocols [2,3]. MOPP protocols (Mechlorethamine, vincristine, prednisone, and procarbazine) for T-cell lymphoma have been reported to produce 189 days of progression-free survival [4]. Even with high initial response rates with the CHOP based protocol, the majority of canine lymphoma patients die within 14 - 16 months
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