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Schedule-dependent synergistic effect of rituximab on methotrexate chemotherapy against lymphoma of the central nervous system

Cited 3 time in Web of Science Cited 3 time in Scopus
Authors
Jin, Juyoun; Joo, Kyeung Min; Nam, Yoonhee; Kim, Dae Hyun; Jo, Mi-Young; Kim, Hyeong-Seok; Kim, Seok Jin; Kim, Won Seog; Nam, Do-Hyun; Seo, Soo Won; Jin, Younggeon; Lee, Se Jeong
Issue Date
2010-12
Publisher
SPANDIDOS PUBL LTD
Citation
EXPERIMENTAL AND THERAPEUTIC MEDICINE; Vol.1, No.6; 943-946
Keywords
central nervous system lymphomarituximabmethotrexatecombination therapymouse model
Abstract
We hypothesized that methotrexate (MTX) normalizes the increased permeability of the blood-tumor barrier and thus reduces the accessibility of rituximab (RTX) to central nervous system (CNS) lymphoma. Here, we evaluated the combinational treatment capability of RTX and MTX using an alternative treatment schedule against CNS lymphoma. We developed a CNS lymphoma animal model that closely mimics the morphological and molecular characteristics of human CNS lymphoma by injecting Raji human Burkitt lymphoma cells into the brains of immune-compromised mice and tested a novel combinational treatment schedule by which penetration of RTX was not influenced by MTX administration. RTX was conjugated with Alexa Fluor 680, and its distribution in the brain was analyzed by in vivo imaging. When MTX treatment was followed by a 3-day post RTX administration, RTX was scarcely distributed in the brain, and there were only modest statistically insignificant therapeutic effects compared with the control mice which received sham injections. In contrast, RTX administration followed by a 3-day post MTX treatment showed significantly increased distribution of RTX and significantly reduced tumor volume in the brain. Collectively, our data demonstrate that RTX can be successfully combined with MTX using an alternative treatment schedule that allows increased distribution of RTX in CNS lymphoma.
ISSN
1792-0981
Language
English
URI
http://hdl.handle.net/10371/78664
DOI
https://doi.org/10.3892/etm.2010.143
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College of Medicine/School of Medicine (의과대학/대학원)Anatomy (해부학전공)Journal Papers (저널논문_해부학전공)
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