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

Jin,Juyoun; Joo,Kyeung   Min; Nam,YoonHee; Kim,Dae   Hyun; Lee,Se   Jeong; Jo,Mi-young; Jin,Younggeon; Kim,Hyeong-Seok; Seo,Soo   Won; Kim,Seok   Jin; Nam,Do-Hyun; Kim,Won   Seog

doi:10.3892/etm.2010.143

November-December 2010 Volume 1 Issue 6

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November-December 2010 Volume 1 Issue 6

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Article

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

Authors:
- Juyoun Jin
- Kyeung Min Joo
- YoonHee Nam
- Dae Hyun Kim
- Se Jeong Lee
- Mi-young Jo
- Younggeon Jin
- Hyeong-Seok Kim
- Soo Won Seo
- Seok Jin Kim
- Do-Hyun Nam
- Won Seog Kim
View Affiliations / Copyright

Affiliations: Department of Neurosurgery, Samsung Medical Center and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Korea, Cancer Stem Cell Research Center, Samsung Medical Center and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Korea, Gwacheon Foreign Language High School, Gwacheon-si, Gyeonggi-do 427-805, Korea, Korean Minjok Leadership Academy, Anheung-myeon, Hoengseong-gun, Gangwon-do 225-823, Korea, Department of Biomedical Engineering, Samsung Medical Center and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Korea, Department of Hematology-Oncology, Samsung Medical Center and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Korea
Pages: 943-946
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Published online on: August 26, 2010

https://doi.org/10.3892/etm.2010.143
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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.

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