Tumor necrosis factor-alpha enhances antitumor effects of radiation against glioma xenografts.
Long-term control of high-grade brain tumors is rarely achieved with current therapeutic regimens. The aim of this study was to determine if low doses of tumor necrosis factor-alpha (TNF-alpha) could augment the effects of radiation in a glioma xenograft model and to evaluate hematological and other parameters that might indicate treatment-related toxicity. Nude mice were injected subcutaneously with C6 rat glioma cells and randomized into groups. Two different time-dose protocols were employed using intravenous human recombinant TNF-alpha and radiation beginning within 24 h after tumor cell implantation. The administration of radiation as a single agent slowed tumor progression, whereas TNF-alpha alone had no effect. However, TNF-alpha, especially when given twice per week before radiation for a total of four doses each, significantly increased the efficacy of the radiation. Low leukocyte counts were associated with combination treatment, whereas transforming growth factor-beta 1 levels were depressed in all treated groups. TNF-alpha did not modulate radiation-induced inhibition of C6 cell proliferation in vitro. The data show that TNF-alpha at relatively nontoxic doses can significantly enhance the antitumor effects of radiation against a rapidly growing glioma. This effect was more than additive, because TNF-alpha alone did not slow tumor progression.
Gridley
D S
DS
Department of Microbiology & Molecular Genetics, Loma Linda University School of Medicine and Medical Center, CA 92350, USA.
Archambeau
J O
JO
Andres
M A
MA
Mao
X W
XW
Wright
K
K
Slater
J M
JM
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D051381:Rats; D011994:Recombinant Proteins; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000097:blood; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000494:pharmacology*
D004273:DNA, Neoplasm; D011838:Radiation-Sensitizing Agents; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha