| Project/Area Number |
21390408
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Nagoya University |
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Principal Investigator |
NATSUME Atsushi 名古屋大学, 大学院・医学系研究科, 准教授 (30362255)
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| Co-Investigator(Kenkyū-buntansha) |
WAKABAYASHI Toshihiko 名古屋大学, 大学院・医学系研究科, 教授 (50220835)
SUZUKI Masaaki 独立行政法人理化学研究所, 分子イメージング科学研究センター, 副センター長 (90093046)
KOYAMA Hiroko 岐阜大学, 大学院・医学系研究科, 助教 (50402160)
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| Co-Investigator(Renkei-kenkyūsha) |
KONDO Yutaka 愛知県がんセンター研究所, 室長 (00419897)
TAKEUCHI Ichiro 名古屋工業大学, 工学研究科, 准教授 (40335146)
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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 |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2010: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2009: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
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| Keywords | 創薬 / エピジェネティクス / 脳腫瘍 / 癌幹細胞 / エピジェネテュクス / ヒストン / メチル化 / 治療 |
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| Research Abstract |
Almost all cancer cells have multiple epigenetic abnormalities, which combine with genetic changes to affect many cellular processes, including cell proliferation and apoptosis, by silencing tumor-suppressor genes. In this study, we focused on the epigenetic mechanisms of DNA hypomethylation and CpG island hypermethylation in gliomas. Aberrant hypermethylation in promoter CpG islands has been recognized as a key mechanism involved in the silencing of cancer-associated genes and occurs at genes with diverse functions related to tumorigenesis and tumor progression. Such promoter hypermethylation can modulate the sensitivity of glioblastomas to drugs and radiotherapy. As an example, the methylation of the MGMT promoter is a specific predictive biomarker of tumor responsiveness to chemotherapy with alkylating agents. Finally, we also evaluated the potential of NY-ESO-1, the most immunogenic cancer/testis antigen(CTA) discovered thus far, as an immunotherapy target. The use of potent epigenetics-based therapy for cancer cells might restore the abnormally regulated epigenomes to a more normal state through epigenetic reprogramming. Thus, epigenetic therapy may be a promising and potent treatment for human neoplasia.
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