Individual adjuvant therapy for malignant gliomas based on O6-methylguanine-DNA methyltransferase messenger RNA quantitation by real-time reverse-transcription polymerase chain-reaction.

Abstract

A new adjuvant therapy, individual adjuvant therapy (IAT), which is individualized according to the results of real-time reverse-transcription polymerase chain-reaction (RT-PCR) for O6-methylguanine-DNA methyltransferase (MGMT), was used to treat malignant gliomas. Immediately after the operation, mRNA expression for drug-resistance genes was investigated in frozen samples of malignant gliomas from 55 patients (30 glioblastoma multiformes, 20 anaplastic astrocytomas and 5 anaplastic oligodendroglial tumors) by real-time quantitative RT-PCR with specific primers for MGMT. Forty-two patients were treated with 1-(4-amino-2-methyl-5-pyrimidynyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU)-based chemotherapies since the relative quantitation value (RQV) of MGMT in real-time RT-PCR with SYBR-Green I was <1.0 or the absolute value of MGMT mRNA as measured by Taq Man probe methods normalized to the level of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was <6.0x10(3) copies/microg RNA. Thirteen patients, whose tumors had an RQV of >1.0 or who had an absolute value of MGMT of >6.0x10(3) copies/microg RNA, were treated by platinum-based chemotherapy using cisplatin or carboplatin. The response rate was 40.9% for glioblastoma multiformes, 60.0% for anaplastic astrocytomas and 80.0% for anaplastic oligodendroglial tumors. The median survival period of 30 patients with glioblastoma treated by IAT was 21.7 months. The 2-year survival rate of glioblastoma patients treated by IAT was 70.9%. Our IAT, based on the results of real-time RT-PCR, may lead to a beneficial glioma therapy.

• Authors: Satoshi Tanaka, Jiro Akimoto, Ikuo Kobayashi, Hidehiro Oka, Hiroshi Ujiie
• Journal: Oncology reports (Oncol Rep) Vol. 20 Issue 1 Pg. 165-71 (Jul 2008) ISSN: 1021-335X [Print] Greece
• PMID: 18575733 (Publication Type: Journal Article)

Chemical References

• RNA, Messenger
• Dacarbazine
• O(6)-Methylguanine-DNA Methyltransferase
• Temozolomide

Topics

• Adult
• Brain Neoplasms (mortality, therapy)
• Combined Modality Therapy
• Dacarbazine (analogs & derivatives, therapeutic use)
• Evidence-Based Medicine
• Female
• Glioma (mortality, therapy)
• Humans
• Male
• Middle Aged
• O(6)-Methylguanine-DNA Methyltransferase (genetics)
• RNA, Messenger (analysis)
• Reverse Transcriptase Polymerase Chain Reaction (methods)
• Survival Rate
• Temozolomide