Mechanisms of bone exposure of jaw associated with chemotherapy-induced oral mucositis in oral cancer
| Project/Area Number |
20K10088
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 57060:Surgical dentistry-related
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| Research Institution | Hirosaki University |
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Principal Investigator |
Kubota Kosei 弘前大学, 医学部附属病院, 講師 (10529689)
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| Co-Investigator(Kenkyū-buntansha) |
松宮 朋穂 弘前大学, 医学研究科, 助教 (30344592)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 口腔癌 / 口腔粘膜炎 / 癌微小環境 / 遺伝子発現 / がん関連線維芽細胞 / 遺伝子 / 骨芽細胞 |
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| Outline of Research at the Start |
歯肉線維芽細胞と口腔がん細胞を共培養し、口腔癌由来がん関連線維芽細胞モデルを作成する。がん関連線維芽細胞モデルと骨芽細胞を共培養し、顎骨周囲の口腔癌微小環境モデルを作成する。顎骨周囲の口腔癌微小環境モデルに抗悪性腫瘍薬添加後にLPS（細菌感染）やpolyIC(ウイルス感染)を添加し、口腔粘膜炎顎骨露出モデルを作成する。このモデルを用いて化学療法誘発口腔粘膜炎に伴う顎骨露出の機序を解明する。
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| Outline of Final Research Achievements |
The role of interactions between gingival fibroblasts and cancer-associated fibroblasts in the tumor microenvironment in bone exposure in oral mucositis was investigated. TGF-beta signals were suggested to play an important role in inducing fibroblasts to become cancer-associated fibroblasts. In an oral mucositis model, expression of COX-2, VEGF, and MMP-1 and 9 mRNA were upregulated in gingival fibroblasts compared to gingival fibroblasts. The cDNA microarray of this condition showed that three chemokines were among the top 10 expressed genes.
This study suggests that gingival fibroblasts in the oral mucosa and tumor microenvironment play an important role in the mechanism causing severe oral mucositis and bone exposure.
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| Academic Significance and Societal Importance of the Research Achievements |
口腔粘膜炎での骨露出における歯肉線維芽細胞と腫瘍微小環境の癌関連線維芽細胞との相互作用の役割ついての基礎的研究を行い、癌関連線維芽細胞誘導における癌微小環境のTGF- beta シグナルと、癌微小環境と正常歯肉線維芽細胞での炎症機序が口腔粘膜炎増悪に関与していることが示唆された。本研究で得られた結果を基にさらに腫瘍免疫学的研究を行い、口腔粘膜炎増悪と顎骨露出の制御に向けた研究を進めたいと考えている。
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Report
(4 results)
Research Products
(5 results)
