Molecular therapy for malignant brain tumors using microRNAs of drug-resistant genes
| Project/Area Number |
26293324
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurosurgery
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| Research Institution | Kagawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
三宅 啓介 香川大学, 医学部附属病院, 講師 (00398033)
岡田 真樹 香川大学, 医学部附属病院, 助教 (40457346)
小川 大輔 香川大学, 医学部附属病院, 助教 (70524057)
河井 信行 香川大学, 医学部, 准教授 (40294756)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
Fiscal Year 2016: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
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| Keywords | 薬剤耐性遺伝子 / MGMT / MicroRNA / 脳腫瘍 |
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| Outline of Final Research Achievements |
It is well known that O6-methylguanine-DNA methyltransferase (MGMT) is related to resistance of aggressive brain tumor glioblastoma (GBM) to DNA alkylating agent Temozolomide (TMZ) therapy. In this study, we searched for microRNA that modulate MGMT expression and give better sensitivity to TMZ. One out of 6 microRNAs (miR-655) down regulated more than 40% MGMT mRNA and protein level in both T98G glioma cell line and primary GBM cell line (GBM30). We will also show that microRNA expressing GBM30 transplanted in nude mice showed better survival with injection of TMZ in vivo. Thus, this endogenous mechanism of suppressing drug resistance gene MGMT will increase chemo-sensitivity to TMZ.This study will provide a new target to enhance efficacy of chemotherapy. In addition, The (pro) renin receptor ((P)RR) as a modular within Wnt receptor complex is essential for early CNS development by the activation of Wnt/β-catenin signaling pathway. Then we examined the role of (P)RR in gliomas.
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] Data on amyloid precursor protein accumulation, spontaneous physical activity, and motor learning after traumatic brain injury in the triple-transgenic mouse model of Alzheimers disease.2016
Author(s)
Kishimoto Y, Shishido H, Sawanishi M, Toyota Y, Ueno M, Kubota T, Kirino Y, Tamiya T, Kawai N
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Journal Title
Data Brief.
Volume: pub
Pages: 62-67
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] d-Allose Attenuates Overexpression of Inflammatory Cytokines after Cerebral Ischemia/Reperfusion Injury in Gerbil.2016
Author(s)
Shinohara N, Nakamura T, Abe Y, Hifumi T, Kawakita K, Shinomiya A, Tamiya T, Tokuda M, Keep RF, Yamamoto T, Kuroda Y.
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Journal Title
J Stroke Cerebrovasc Dis.
Volume: 25
Issue: 9
Pages: 2184-2188
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Histopathological investigation of glioblastomas resected under bevacizumab treatment.2016
Author(s)
Tamura R, Tanaka T, Miyake K, Tabei Y, Ohara K, Sampetrean O, Kono M, Mizutani K, Yamamoto Y, Murayama Y, Tamiya T, Yoshida K, Sasaki H.
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Journal Title
Oncotarget.
Volume: 7
Issue: 32
Pages: 52423-52435
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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