Preliminary individual adjuvant therapy for gliomas based on the results of molecular biological analyses for drug-resistance genes.
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-pi (GST-pi). 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-pyrimidynyl) methyl-3-(2-chloroethyl)-3-nitrosourea 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.
Tanaka
S
S
Department of Neurosurgery, Kitasato University School of Medicine, Sagamihara, Japan. s1422.tanaka@nifty.ne.jp
Kamitani
H
H
Amin
M R
MR
Watanabe
T
T
Oka
H
H
Fujii
K
K
Nagashima
T
T
Hori
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015376:Nimustine / Q000627:therapeutic use; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015376:Nimustine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D012333:RNA, Messenger