Title: The Rationale of Targeting Neutrophils with Dapsone during Glioblastoma Treatment
VOLUME: 11 ISSUE: 8
Author(s):Richard E. Kast, Angelika Scheuerle, Christian R. Wirtz, Georg Karpel-Massler and Marc-Eric Halatsch
Affiliation:Department of Psychiatry, University of Vermont, 22 Church Street, Burlington, VT 05401, USA.
Keywords:Angiogenesis, chemotaxis, chemotherapy, dapsone, glioblastoma, neutrophils, temozolomide, vascular endothelial growth factor, IL-8, azurophilic granules
Abstract: Data from past research is presented showing that neutrophils are active participants in new vessel formation in normal physiology, in proliferating human endometrium, in non-cancer pathologies as in the pannus of rheumatoid arthritis, and in various cancers, among them glioblastoma. These data show that interleukin-8 (IL-8) is a major chemokine attracting neutrophil infiltrates in these states. Since the old anti-Hansens disease drug dapsone inhibits neutrophil migration along an IL-8 gradient towards increasing concentrations, and is used therapeutically for this attribute to good effect in dermatitis herpetiformis, bullous pemphigoid and rheumatoid arthritis, we suggest dapsone may deprive glioblastoma of neutrophil-mediated growth promoting effects. We review past research showing that vascular endothelial growth factor, VEGF, is carried predominantly intracellularly within neutrophils- only 2% of circulating VEGF is found free in serum. Based on the available evidence summarized by the authors, dapsone has a strong theoretical potential to become a useful anti-VEGF, anti-angiogenic agent in glioblastoma treatment.
