Zoledronic acid impairs myeloid differentiation to tumour-associated macrophages in mesothelioma

Background: Suppressive immune cells present in tumour microenvironments are known to augment tumour growth and hamper efficacy of antitumour therapies. The amino-bisphosphonate Zoledronic acid (ZA) is considered as an antitumour agent, as recent studies showed that ZA prolongs disease-free survival in cancer patients. The exact mechanism is a topic of debate; it has been suggested that ZA targets tumour-associated macrophages (TAMs). Methods: We investigate the role of ZA on the myeloid differentiation to TAMs in murine mesothelioma in vivo and in vitro. Mice were intraperitoneally inoculated with a lethal dose of mesothelioma tumour cells and treated with ZA to determine the effects on myeloid differentiation and survival. Results: We show that ZA impaired myeloid differentiation. Inhibition of myeloid differentiation led to a reduction in TAMs, but

Analysis of orthopedic surgery of bone metastases in breast cancer patients

<p>Abstract</p> <p>Background</p> <p>Breast cancer is the most common malignancy and the second leading cause of death in women. Because bone metastases are a common finding in patients with breast cancer, they are of major clinical concern.</p> <p>Methods</p> <p>In 115 consecutive patients with bone metastases secondary to breast cancer, 132 surgical procedures were performed. Medical records and imaging procedures were reviewed for age, treatment of the primary tumor, clinical symptoms, surgical treatment, complications, and survival.</p> <p>Results</p> <p>The overall survival of patients with metastatic breast cancer was dependent on the site and the amount of the metastases. Age was not a prognostic factor for survival. If the result of the orthopaedic surgery was a wide resection (R0) survival was significantly better than in the R1 (marginal resection – tumor resection in sane tissue) or R2 (intralesional resection) situation. Concerning the orthopaedic procedures there was no survival difference.</p> <p>Conclusion</p> <p>In conclusion a wide (R0) resection and the absence of pathological fracture and visceral metastases were predictive for longer survival in univariate analysis. Age and the type of orthopaedic surgery had no impact on survival in multivariate analysis. The resection margins lost significance. The standard of care for patients with metastatic breast cancer to the bone requires a multidisciplinary approach.</p