Convection-enhanced delivery of tumor necrosis factor-related apoptosis-inducing ligand with systemic administration of temozolomide prolongs survival in an intracranial glioblastoma xenograft model

Ryuta Saito; John R Bringas; Amith Panner; Matyas Tamas; Russell O Pieper; Mitchel S Berger; Krystof S Bankiewicz

doi:10.1158/0008-5472.CAN-04-1683

Convection-enhanced delivery of tumor necrosis factor-related apoptosis-inducing ligand with systemic administration of temozolomide prolongs survival in an intracranial glioblastoma xenograft model

Cancer Res. 2004 Oct 1;64(19):6858-62. doi: 10.1158/0008-5472.CAN-04-1683.

Authors

Ryuta Saito¹, John R Bringas, Amith Panner, Matyas Tamas, Russell O Pieper, Mitchel S Berger, Krystof S Bankiewicz

Affiliation

¹ Brain Tumor Research Center, Department of Neurological Surgery, University of California at San Francisco, San Francisco, California 94103, USA.

PMID: 15466173
DOI: 10.1158/0008-5472.CAN-04-1683

Abstract

Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent activator of cell death, preferentially killing neoplastic cells over normal cells, the efficacy of TRAIL for the treatment of glioma might be limited due to cellular resistance and, importantly, poor distribution after systemic administration. TRAIL and temozolomide (TMZ) were recently shown to have a synergistic antitumor effect against U87MG glioma cells in vitro. Convection-enhanced delivery (CED) can effectively distribute TRAIL protein throughout a brain tumor mass. In this study, we evaluated CED of TRAIL, alone and in conjunction with systemic TMZ administration, for antitumor efficacy. CED of TRAIL demonstrated safe and effective distribution in both normal brain and a U87MG intracranial xenograft model. Individually, both CED of TRAIL and systemic TMZ administration prolonged survival in tumor-bearing rats. However, the combination of these two treatments was significantly more effective than either treatment alone. CED of TRAIL in conjunction with systemic TMZ treatment is a promising strategy for the treatment of malignant gliomas.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
Apoptosis / drug effects
Apoptosis Regulatory Proteins
Brain Neoplasms / drug therapy*
Brain Neoplasms / metabolism
Brain Neoplasms / pathology
Cell Line, Tumor
Convection
Dacarbazine / administration & dosage
Dacarbazine / analogs & derivatives*
Drug Delivery Systems / methods*
Drug Synergism
Glioblastoma / drug therapy*
Glioblastoma / metabolism
Glioblastoma / pathology
Humans
Male
Membrane Glycoproteins / administration & dosage
Membrane Glycoproteins / pharmacokinetics
Rats
Rats, Nude
Recombinant Proteins / administration & dosage
TNF-Related Apoptosis-Inducing Ligand
Temozolomide
Tumor Necrosis Factor-alpha / administration & dosage
Tumor Necrosis Factor-alpha / pharmacokinetics
Xenograft Model Antitumor Assays

Substances

Apoptosis Regulatory Proteins
Membrane Glycoproteins
Recombinant Proteins
TNF-Related Apoptosis-Inducing Ligand
TNFSF10 protein, human
Tnfsf10 protein, rat
Tumor Necrosis Factor-alpha
Dacarbazine
Temozolomide