Research of transcriptional control and drug sensitivity by antisense MGMT congenic
| Project/Area Number |
15592112
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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 |
Surgical dentistry
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| Research Institution | Okayama University |
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Principal Investigator |
ASAUMI Junichi Okayama University, Medicine and Dentistry Hospital, Assistant Professor, 医学部・歯学部附属病院, 講師 (60184131)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Tetsuyoshi Okayama University, Graduate School of Medicine and Dentistry, Assistant Professor, 大学院・医歯学総合研究科, 助手 (20223258)
MURAKAMI Jun Okayama University, Medicine and Dentistry Hospital, Assistant Professor, 医学部・歯学部附属病院, 助手 (40362983)
KAWAI Noriko Okayama University, Graduate School of Medicine and Dentistry, Assistant Professor, 大学院・医歯学総合研究科, 助手 (60284072)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | MGMT / CpG methylation / Morpholino / antisense oligonucleotide / アンチセンスオリゴ導入 / アルキル化剤 / 口腔癌 |
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| Research Abstract |
1.Confirmation of MGMT inhibitory effect by MGMT antisense oligo introduction
The MGMT inhibition antisense oligo made in 2003 was introduced into the MGMT high level expression cell lines, and the MGMT expression suppression condition was examined by western blotting.
The MGMT protein expression decreased after introduction of the antisense oligo in all cell lines.
However, because the cytotoxicity by introduction of the antisense oligo was strong, the introduction of the antisense oligo was discontinued inadequately in the clinical application. and the MGMT inhibitory effect combined with O6-benzylguanine, MGMT inhibitor, was examined.
2.Examination of influence on drug sensitivity by inhibition of MGMT combined with O6-benzylguanine, an MGMT inhibitor.
5-FU or cisplatin was combine with O6-benzylguanine, and the influence against their sensitivity of the O6-benzylguanine was examined by MTT assay in oral squamous cell carcinoma cell lines.
As a result, the sensitivity of 5-FU and cisplatin by combination with O6-benzylguanine was markedly enhanced in all cell lines.
In addition, because the cytotoxicity by O6-benzylguanine was not seen, the combination therapy of 5-FU or cisplatin with O6-benzylguanine may apply clinically.
The paper of the combined effect of 5-FU or cisplatin with O6-benzylguanine is under submission.
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Report
(3 results)
Research Products
(15 results)
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[Journal Article] Influence of CpG island methylation status in 06-methylguanine-DNA methyltransferase expression of oral cancer cell lines2004
Author(s)
Murakami J, Asaumi J, Maki Y, Tsujigiwa H, Nagatsuka H, Kokeguchi S, Inoue T, Kawasaki S, Tanaka N, MacPhee D, Matsubara N, Kishi K.
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Journal Title
Oncology Reports 12・2
Pages: 339-345
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Influence of CpG island methylation status in O6-methylguanine-DNA methyltransferase expression of oral cancer cell lines2004
Author(s)
Murakami J, Asaumi J, Maki Y, Tsujigiwa H, Nagatsuka H, Kokeguchi S, Inoue T, Kawasaki S, Tanaka N, MacPhee D, Matsubara N, Kishi K.
-
Journal Title
Oncology Reports 12-2
Pages: 339-345
Description
「研究成果報告書概要(欧文)」より
Related Report
-
[Journal Article] Influence of CpG island methylation status in O6-methylguanine-DNA methyltransferase expression of oral cancer cell lines2004
Author(s)
Murakami J, Asaumi J, Maki Y, Tsujigiwa H, Nagatsuka H, Kokeguchi S, Inoue T, Kawasaki S, Tanaka N, MacPhee D, Matsubara N, Kishi K
-
Journal Title
Oncology Reports 12・2
Pages: 339-345
Related Report
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