Tmic-50. Delineating the Therapeutic Mechanism of Dexamethasone in Glioblastoma-related Cerebral Edema
Year: 2017
Type: conference-abstract
Abstract: Glioblastoma is the most common and aggressive primary brain tumor. During disease progression, nearly all patients will develop cerebral edema. Standard treatment for cerebral edema has been the corticosteroid dexamethasone for over 50 years. Although efficacious in decreasing edema, recent data from our lab and others indicates that dexamethasone administration is associated with reduced median survival when analyzing both stratified data from human patients as well as data generated with murine models. This has been attributed to interference of dexamethasone with standard radiation and chemotherapy. Therefore, it is necessary to develop a therapy for glioblastoma-related cerebral edema that is as effective as dexamethasone, but with decreased side effects. The inflammatory cytokine IL-1 has been referred to as the master regulator of neuroinflammation. It is primarily produced by macrophages; a cell population that can constitute up to 30-50% of the tumor in glioblastoma. This work demonstrates the ability of dexamethasone to inhibit IL-1 expression in primary, bone marrow-derived macrophages following stimulation with lipopolysaccharide and interferon gamma. Moreover, it illustrates the ability of dexamethasone to suppress induction of inflammation-related genes following stimulation with recombinant IL-1. Ongoing investigations utilizing RCAS/tv-a modeling of glioblastoma in IL-1-/- mice will elucidate the role of IL-1 in development of cerebral edema in vivo. Overall, this project demonstrates the role of IL-1 in the therapeutic efficacy of dexamethasone for treating cerebral edema and lays the groundwork for therapies that specifically target IL-1.
Source: Neuro-Oncology
Institution: Emory University
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2767541920