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25 ?g mL?1) or doxorubicin (0.2 ?g mL?1), respectively, and E(x,y) is the combined inhibition. Theoretical growth inhibition curves were derived utilizing this equation, and standard deviations were estimated by error propagation of experimental SD. Differences between treatment groups (Bliss theoretical versus experimental) were assessed using two-way ANOVA and Tukey's post-test. Statistical analyses were performed using Prism5 software (GraphPad, San Diego, CA, USA). Differences were considered statistically significant for P values less than 0.05. We conducted in vitro screens to determine whether aminobisphosphonates or nonaminobisphosphonate drugs increased the activity of 6 commonly used chemotherapy drugs against 3 different canine MH cell lines. The chemotherapy http://www.selleckchem.com/products/jq1.html drugs were administered in vitro at concentrations that elicited only 5�C20% cell killing to allow the detection of synergistic activity of the bisphosphonate�Cchemotherapy drug combinations. We found the following drugs had activity against canine MH cells at the following drug concentrations: dexamethasone (15 ?g mL?1), doxorubicin (0.2 ?g mL?1), lomustine (CCNU; 1.5 ?g mL?1) and vincristine (0.25 ?g mL?1) (Fig. 1). Next, these four chemotherapy drugs were evaluated for enhanced activity when combined with the following concentrations of clodronate (5 ?g mL?1) and zoledronate (0.2 ?g mL?1).41,58,59 The bisphosphonate drugs were also screened for activity alone against the MH cell lines (Figs 1 and 2). After incubation for 72 h, the cells were analysed for viability using the MTT assay. With clodronate, we detected a significant (P