zithromax and Brain-Neoplasms

Legionella species are a common cause of community-acquired pneumonia, infrequently complicated by cavitary disease. We describe Legionella pneumophila pneumonia and abscess formation in an immunosuppressed patient receiving corticosteroid therapy for metastatic breast carcinoma. The predisposing role of corticosteroids is discussed and the management of this complication is reviewed.

Topics: Adult; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Australia; Azithromycin; Brain Neoplasms; Breast Neoplasms; Ceftriaxone; Combined Modality Therapy; Cranial Irradiation; Dexamethasone; Diagnosis, Differential; Drainage; Female; Humans; Immunocompromised Host; Legionella pneumophila; Legionnaires' Disease; Lung Abscess; Lung Neoplasms; Metronidazole; Roxithromycin; Thoracic Surgery, Video-Assisted; Thoracostomy; Tomography, X-Ray Computed

The poor outcomes in glioblastoma (GBM) necessitate new treatments. As GBM is highly vascularized and its growth is largely dependent on angiogenesis, angiogenesis inhibitors have been hotly evaluated in clinical trials for GBM treatment for the last decade. In line with these efforts, our work reveals that azithromycin, a clinically available antibiotic, is a novel angiogenesis inhibitor. Azithromycin inhibits vessel structure formation on Matrigel of GBM-derived endothelial cell (ECs) and other types of ECs. Time course analysis shows that azithromycin interferes with the early stage of angiogenesis. Azithromycin also inhibits GBM-derived EC adhesion, growth and survival but not migration. The transgenic zebrafish Tg (fli1a: EGFP) model clearly shows that azithromycin inhibits angiogenesis in vivo. Of note, azithromycin at non-toxic dose inhibits GBM growth in mice and increases overall survival, and furthermore, this is associated with angiogenesis inhibition. Mechanism studies show that azithromycin decreases mitochondrial respiration by suppressing the activity of multiple complexes, leading to ATP reduction, oxidative stress and damage. In addition, oxidative stress induced by azithromycin is through thiol redox-mediated pathways. Our work demonstrates the anti-angiogenic activity of azithromycin via inducing mitochondrial dysfunction and oxidative stress. Our pre-clinical evidence provides a rationale for initiating clinical trials using azithromycin in combination with standard-of-care drugs for GBM patients.

Topics: Angiogenesis Inhibitors; Animals; Azithromycin; Brain Neoplasms; Cell Line, Tumor; Glioblastoma; Mice; Mitochondria; Neovascularization, Pathologic; Oxidative Stress; Zebrafish