| Project/Area Number |
21591878
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Saitama Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ADACHI Junichi 埼玉医科大学, 医学部, 講師 (70291143)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Keywords | 中枢神経悪性リンパ腫 / temozolomide / methotrexate / MGMT / reduced folate carrier / 化学療法 / テモゾロミド / Methotrexate / 予後 / 脳・神経 / 癌 / Metotrexate |
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| Research Abstract |
High-dose methotrexate (HD-MTX)-based chemotherapy with whole brain irradiation improves the prognosis of PCNSL. However, up to 30% of patients are refractory to primary therapy and 60% relapse. Thus, novel treatment regimens for PCNSL are needed. Favorable responses to temozolomide chemotherapy have recently been reported in PCNSL patients who are refractory or relapsed to HD-MTX. The gene encoding the DNA repair enzyme O^6-methylguanine-DNA methyltransferase (MGMT) is transcriptionally silenced by promoter methylation in several human tumors, including gliomas and systemic lymphomas. MGMT promoter methylation is also a prognostic marker in glioblastoma patients treated with temozolomide. To validate temozolomide treatment in PCNSL, we applied methylation-sensitive high resolution melting analysis to quantitate MGMT methylation in PCNSL. MGMT promoter methylation was detected in tumors from 23 (51%) of 45 PCNSL patients,11 of which were considered to have high (more than 70.0%) methylation status. Of the five recurrent PCNSLs treated with temozolomide, four cases responded, with three achieving complete response and one, a partial response. All four responsive PCNSLs had methylated MGMT promoters, whereas the non-responsive recurrent PCNSL did not. Thus, the use of quantitative MS-HRM analysis for the detection of MGMT promoter methylation has been suggested in PCNSL for the first time. MGMT promoter methylation may become a useful marker for predicting the response of PCNSLs to temozolomide.
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