title: The rationale of targeting neutrophils with dapsone during glioblastoma treatment.
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-Hansen's 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.
authors.affiliation: Department of Psychiatry, University of Vermont, Burlington, VT 05401, USA. rekast@email.com
authors.forename: Richard E
authors.initials: RE
authors.lastname: Kast
authors.forename: Angelika
authors.initials: A
authors.lastname: Scheuerle
authors.forename: Christian R
authors.initials: CR
authors.lastname: Wirtz
authors.forename: Georg
authors.initials: G
authors.lastname: Karpel-Massler
authors.forename: Marc-Eric
authors.initials: ME
authors.lastname: Halatsch
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003622:Dapsone / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D003622:Dapsone