Gene therapy for a novel diffuse intrinsic pontine glioma model initiated in Olig2-expressing progenitors
| Project/Area Number |
20K17931
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56010:Neurosurgery-related
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| Research Institution | Okayama University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | Ad-SGE-REIC / びまん性橋膠腫モデル / 遺伝子治療 |
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| Outline of Research at the Start |
びまん性橋膠腫（DIPG）は、主に小児の橋に発生する稀な腫瘍である。現在標準治療は放射線治療のみで、診断からの生存期間中央値は約9か月と大変予後不良であり、新規治療の開発が強く望まれている。一方、癌抑制遺伝子REIC/Dkk-3は、あらゆる悪性腫瘍で発現が低下しており、REIC/Dkk-3遺伝子発現アデノウイルス（Ad-REIC）が岡山大学で開発され、前立腺がん、悪性中皮腫に対して臨床試験が行われている。そこで、細胞特異的遺伝子導入システムにより作成されたマウスDIPGモデルに対して、Ad-REICを腫瘍内投与することで生存期間が延長するかどうかを確かめることを本研究の目的としている。
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| Outline of Final Research Achievements |
We injected malignant glioma cell lines stereotactically into the brainstem to generate a mouse brain tumor model using U87ΔEGFR, a human malignant glioma cell line, and GL261, a mouse malignant glioma cell line. Regarding the Ad-REIC toxicity test, Ad-REIC was administered to the brainstem of immunodeficient mice (Balbc nu/nu) and immunocompetent mice (C57BL6). The dose of virus was initially 2.0x10^7 pfu, then increased to 2.0x10^8 pfu, and the mice were observed for 1 week. No obvious changes were observed in mice and these doses were considered non-toxic. Regarding experiments using Ad-SGE-REIC, we conducted basic experiments on the combination of Ad-SGE-REIC and bevacizumab in our laboratory, and a paper on those results were published. In addition, a paper on research related to a diffuse pontine glioma model initiated in Olig2-expressing progenitors, which was conducted by the primary researcher in the United States, was published.
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| Academic Significance and Societal Importance of the Research Achievements |
細胞特異的遺伝子導入システムであるRCAS/Tv-aシステムを用いた動物モデルは、発生機序など真のヒトびまん性橋膠腫（DIPG）に近い性質を有している。RCAS/Tv-aシステムで作成したマウスモデルでは、免疫能が正常であることも特徴の一つである。一方、Ad-REICを用いた遺伝子治療は、悪性神経膠腫に対して臨床試験が開始されたばかりで、将来性がある治療である。本研究は、細胞特異的遺伝子導入システムにより作成されたマウスDIPGモデルを用いることでさらにヒトDIPGの理解を深め、Ad-SGE-REICに関する基礎研究の成果は、今後の臨床応用に生かされると考えている。
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] A Novel Mouse Model of Diffuse Midline Glioma Initiated in Neonatal Oligodendrocyte Progenitor Cells Highlights Cell-of-origin Dependent Effects of H3K27M2022
Author(s)
Yusuke Tomita, Yosuke Shimazu, Agila Somasundaram, Yoshihiro Tanaka, Nozomu Takata, Yukitomo Ishi, Samantha Gadd, Rintaro Hashizume, Angelo Angione, Gonzalo Pinero, Dolores Hambardzumyan, Daniel J. Brat, Christine M. Hoeman, Oren J. Becher
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Journal Title
Glia
Volume: in press
Issue: 9
Pages: 1681-1698
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Genomic Profiling of a Case of Glioneuronal Tumor with Neuropil-like Islands2022
Author(s)
Tsuboi N , Ishida J , Shimazu Y , Edaki H , Uneda A , Otani Y , Fujii K , Kurozumi K , Ennishi D , Yanai H , Date I
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Journal Title
Acta Medica Okayama
Volume: 76
Issue: 4
Pages: 473-477
DOI
URL
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pyogenic Ventriculitis After Anterior Skull Base Surgery Treated With Endoscopic Ventricular Irrigation And Reconstruction Using a Vascularized Flap2021
Author(s)
Tomita Y , Shimazu Y , Kawakami M , Matsumoto H , Fujii K , Kameda M , Yasuhara T , Suruga Y , Ota T , Kimata Y , Kurozumi K , Date I
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Journal Title
Acta Medica Okayama
Volume: 75
Issue: 2
Pages: 243-248
DOI
NAID
URL
Related Report
Peer Reviewed / Open Access
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[Journal Article] Differentiated glioblastoma cells accelerate tumor progression by shaping the tumor microenvironment via CCN1-mediated macrophage infiltration2021
Author(s)
Uneda A, Kurozumi K, Fujimura A, Fujii K, Ishida J, Shimazu Y, Otani Y, Tomita Y, Hattori Y, Matsumoto Y, Tsuboi N, Makino K, Hirano S, Kamiya A, Date I.
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Journal Title
Acta Neuropathol Commun.
Volume: 9
Issue: 1
Pages: 29-29
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Detailed arterial anatomy and its anatomoses of the sphenoid ridge and olfactory groove meningiomas with special reference to the recurrent branches from the ophthalmic artery2020
Author(s)
Hiramatsu M , Sugiu K , Hishikawa T , Haruma J , Takahashi Y , Murai S , Nishi K , Yamaoka Y , Shimazu Y , Fujii K , Kameda M , Kurozumi K , Date I
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Journal Title
AJNR Americal Journal of Neuroradiology
Volume: 41(11)
Issue: 11
Pages: 2082-2087
DOI
Related Report
Peer Reviewed
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