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Zoledronic Acid Alters Hematopoiesis And Generates Breast Tumor-Suppressive Bone Marrow Cells., Jessalyn M. Ubellacker, Marie-Therese Haider, Molly J. Decristo, Gloria Allocca, Nicola J. Brown, Daniel P. Silver, Ingunn Holen, Sandra S. Mcallister
Zoledronic Acid Alters Hematopoiesis And Generates Breast Tumor-Suppressive Bone Marrow Cells., Jessalyn M. Ubellacker, Marie-Therese Haider, Molly J. Decristo, Gloria Allocca, Nicola J. Brown, Daniel P. Silver, Ingunn Holen, Sandra S. Mcallister
Department of Medical Oncology Faculty Papers
BACKGROUND: The bone-targeting agent zoledronic acid (ZOL) increases breast cancer survival in subsets of patients, but the underlying reasons for this protective effect are unknown. ZOL modulates the activity of osteoclasts and osteoblasts, which form hematopoietic stem cell niches, and therefore may affect hematopoietic cells that play a role in breast cancer progression.
METHOD: Immunocompetent and immunocompromised strains of mice commonly used for breast cancer research were injected with a single, clinically relevant dose of ZOL (100 μg/kg) or vehicle control. The effects of ZOL on the bone marrow microenvironment (bone volume, bone cell number/activity, extracellular matrix composition) were established …