Preclinical study of tumor-specific p53 gene therapy against refractory pancreatic cancer
Project/Area Number |
16K10596
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Digestive surgery
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Research Institution | Okayama University |
Principal Investigator |
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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Keywords | 膵臓癌 / p53 / KRAS / 腫瘍融解 / アデノウイルス / オートファジー / 免疫原性細胞死 / 神経関連因子 / マイクロRNA |
Outline of Final Research Achievements |
Pancreatic ductal adenocarcinoma (PDAC) frequently shows invasion and metastasis, leading to treatment resistance and poor prognosis. The development of novel antitumor strategy for PDAC is an urgent issue. Here, we show that a tumor-specific replication-competent oncolytic adenovirus expressing tumor suppressor p53, OBP-702, inhibits the migration and invasion abilities and tumor growth and induces the immunogenic cell death in human PDAC cells. In the future, the clinical application of a multiplidisciplinary therapy with OBP-702 is important.
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Academic Significance and Societal Importance of the Research Achievements |
本研究の成果は、高率にKRAS癌遺伝子やp53癌抑制遺伝子の異常を伴う膵臓癌に対して癌特異的増殖型ウイルスを用いたp53遺伝子治療がp53シグナルの活性化とKRAS-ERKシグナルの抑制を介して抗腫瘍効果を発揮する新たな治療戦略となる可能性を示唆している。予後不良な膵臓癌は有効な治療法の確立に未だ至っておらず、新規治療法の開発研究は膵臓癌患者の生命予後の改善につながるため社会的意義は大きい。
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Report
(4 results)
Research Products
(10 results)
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[Presentation] Overexpression of tumor suppressor p53 gene by oncolytic adenovirus boosts immune responses in human pancreatic ductal adenocarcinoma cells.2018
Author(s)
Araki H, Tazawa H, Ieda T, Fushimi T, Kuroda S, Yoshida R, Kishimoto H, Nishizaki M, Urata Y, Kagawa S, Fujiwara T.
Organizer
109th Annual Meeting of the American Association for Cancer Research
Related Report
Int'l Joint Research
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[Presentation] Oncolytic adenovirus-mediated p53 overexpression induces profound immunogenic cell death in human pancreatic ductal adenocarcinoma cells.2018
Author(s)
Araki H, Tazawa H, Ieda T, Fushimi T, Kuroda S, Yoshida R, Kishimoto H, Nishizaki M, Urata Y, Kagawa S, Fujiwara T.
Organizer
第24回日本遺伝子細胞治療学会
Related Report
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[Presentation] Virally enhanced p53 reactivation impairs KRAS-driven pancreatic cancer invasion2016
Author(s)
Koujima T, Tazawa H, Ieda T, Kuwada K, Tanimoto T, Kuroda S, Kishimoto H, Nishizaki M, Urata Y, Kagawa S, Fujiwara T
Organizer
107th Annual Meeting of the American Association for Cancer Research
Place of Presentation
New Orleans, USA
Year and Date
2016-04-16
Related Report
Int'l Joint Research
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