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04) reduced. We next sought to determine whether the interactions between bisphosphonates and cytotoxic chemotherapy drugs reflected truly synergistic interactions. To determine synergy, two different statistical analyses were used. First, the effects on MH cell viability of increasing concentrations of doxorubicin, with or without the addition of zoledronate (0.2 ?g mL?1), were evaluated. http://www.selleckchem.com/products/Everolimus(RAD001).html The results of the first analysis demonstrated a significant reduction (P revealed a synergistic interaction between doxorubicin and zoledronate in combination (P of synergistic interactions between these drugs. Experiments were conducted next to elucidate the mechanism(s) by which bisphosphonate drugs increased killing of MH cells when combined with vincristine or doxorubicin. Canine DH82 MH cells were treated with clodronate alone (5 ?g mL?1) or vincristine alone (0.25 ?g mL?1) or both drugs together, and the effects on induction of apoptosis were assessed using Annexin V and propidium iodine staining and flow cytometry. Treatment with the combination of vincristine and clodronate induced a significant increase (P