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Preliminary Individual Adjuvant Therapy for Gliomas Based on the Results of Molecular Biological Analyses for Drug-resistance Genes

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Abstract

New adjuvant therapy individualized by the results of reverse transcription-polymerase chain reaction (RT-PCR) for drug-resistance genes has been used to treat malignant gliomas. Protocol studies for malignant gliomas were not so encouraging in their therapeutic results because of heterogeneity and the various drug-sensitivities of the tumors. Individualization of glioma therapy is recommended. Drug-resistance genes messenger ribonucleic acid (mRNA) expressions were investigated in drug-resistant human glioma cell lines derived from U87MG and 46 frozen samples of retrospectively examined neuroepithelial tumors (12 low grade neuroepithelial tumors, 16 Grade III gliomas, 11 glioblastomas, and 7 other malignant neuroepithelial tumors such as medulloblastomas and primitive neuroectodermal tumors) by RT-PCR with the specific primers for O6-methylguanine DNA methyltransferase (MGMT), multidrug-resistance gene 1 (MDR1), multidrug-resistance-associated protein (MRP), and glutathione-S-transferase-π(GST-π). Thirty-seven preliminary individual adjuvant therapies (IAT) based on RT-PCR results, mainly in MGMT expression, were performed on 30 consecutive patients with neuroepithelial tumors. In the retrospectively examined series, the initial response to 1-(4-amino-2-methyl-5-pyri-midynyl) methyl-3-(2-chloro-ethyl)-3-nitro-sourea hydrochloride (ACNU) was correlated most significantly to the MGMT mRNA expression among 11 independent prognostic factors (p=0.0037) in multivariate logistic regression analysis. In the preliminary IAT, 17 of 32 evaluable therapies had a partial or complete response (53.1% response rate). Our IAT based on RT-PCR seemed to be more effective than conventional therapies for malignant gliomas.

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Authors and Affiliations

  1. Department of Neurosurgery, Kitasato University School of Medicine, Sagamihara, Japan

    Satoshi Tanaka, Hidehiro Oka & Kiyotaka Fujii

  2. Division of Neurosurgery, Institute of Neurological Sciences, Faculty of Medicine, Tottori University School of Medicine, Yonago, Japan

    Hideki Kamitani, Md Ruhul Amin & Takashi Watanabe

  3. Department of Neurosurgery, Ichihara Hospital, Teikyo University School of Medicine, Chiba, Japan

    Tadashi Nagashima

  4. Department of Neurosurgery, Neurological Institute, Tokyo Women's Medical University, Tokyo, Japan

    Tomokatsu Hori

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  1. Satoshi Tanaka
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Tanaka, S., Kamitani, H., Amin, M.R. et al. Preliminary Individual Adjuvant Therapy for Gliomas Based on the Results of Molecular Biological Analyses for Drug-resistance Genes. J Neurooncol 46, 157–171 (2000). https://doi.org/10.1023/A:1006399903635

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