title: Analysis of the antitumoral mechanisms of lipopolysaccharide against glioblastoma multiforme.
abstract: Our objective was to analyze the lipopolysaccharide (LPS) antitumoral effect upon glioblastoma, including whether the lipid A subunit alone can elicit glioblastoma regression, whether dexamethasone suppresses this response to LPS, whether B and T lymphocytes factor in this response, and whether this antitumoral effect of LPS provides resistance against subsequent challenge with glioblastoma. Mice (BALB/c, nude or SCID) implanted with s.c. DBT glioblastomas were treated with LPS (with or without dexamethasone) or with lipid A. A subset of BALB/c mice in which s.c. DBT glioblastomas had previously been eradicated using LPS were re-implanted with s.c. or intracranial (i.c.) DBT cells. For mice with s.c. tumors, mean tumor masses (MTM) were compared between groups. Survival was compared for mice with i.c. tumors. Lipid A caused near complete tumor regression of DBT glioblastomas in BALB/c mice (p<0.0001). Dexamethasone did not alter the antitumoral effect of LPS (p=0.48). LPS reduced the MTM of s.c. glioblastomas in T lymphocyte-deficient nude mice, but not as effectively as in immunocompetent mice. The antitumoral response to LPS for T and B lymphocyte-deficient SCID mice bearing DBT glioblastomas was similar to that for nude mice. Eradication of s.c. DBT glioblastoma in BALB/c provided partial resistance to subsequent challenge with s.c. or i.c. glioblastoma. We conclude that the LPS-mediated antitumoral response against glioblastoma is dependent upon the lipid A subunit of LPS, partially dependent upon T lymphocytes, independent of B lymphocytes, unaffected by dexamethasone and provides partial protection against subsequent challenges with glioblastoma.
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Won
authors.forename: Michael C
authors.initials: MC
authors.lastname: Zahner
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Grant
authors.forename: Pankaj
authors.initials: P
authors.lastname: Gore
authors.forename: Michael R
authors.initials: MR
authors.lastname: Chicoine
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy*; D003907:Dexamethasone / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D008050:Lipid A / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D013045:Species Specificity
chemical_list: D018931:Antineoplastic Agents, Hormonal; D008050:Lipid A; D008070:Lipopolysaccharides; D003907:Dexamethasone