HPV-associated oropharyngeal carcinogenesis by super-enhancer-mediated gene regulation.
| Project/Area Number |
19K09895
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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 56050:Otorhinolaryngology-related
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| Research Institution | Yokohama City University |
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Principal Investigator |
SANO Daisuke 横浜市立大学, 医学部, 准教授 (10620990)
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| Co-Investigator(Kenkyū-buntansha) |
波多野 孝 横浜市立大学, 附属病院, 助教 (40807583)
折舘 伸彦 横浜市立大学, 医学研究科, 教授 (90312355)
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| Project Period (FY) |
2019-04-01 – 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 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | HPV関連中咽頭癌 / ヒトパピローマウイルス / 中咽頭癌 / スーパーエンハンサー / オルガノイド / PDXモデル / オルガノイド培養 / 唾液腺癌 / 遺伝子発現制御 |
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| Outline of Research at the Start |
本研究は，HPV関連中咽頭発癌機構における，スーパーエンハンサーを介した遺伝子発現 制御の詳細を明らかにするために以下の研究を行う。
1. ChIP-seqによるHPV関連中咽頭癌細胞におけるスーパーエンハンサーの同定
2. スーパーエンハンサーにより発現制御される遺伝子の機能解析
3. スーパーエンハンサー阻害剤，ならびにスーパーエンハンサー領域を欠失させた際の影響
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| Outline of Final Research Achievements |
To analyse the relationship between the progression of HPV-related oropharyngeal carcinoma and the tumour microenvironment, an organoid culture method reflecting an environment similar to that of in vivo tissue was used. To establish this culture technique, we attempted to establish organoids using resected specimens from patients with salivary gland cancer and a PDX model. We succeeded in establishing a PDX model/PDXO short-term culture of salivary adenoid cystic carcinoma, a PDX model/PDO/PDXO of salivary duct carcinoma, a PDX model/PDO/PDXO of mucoepidermoid carcinoma and a PDX model of myoepithelial carcinoma. Each model reproduced the original histological features and retained genetic features such as transcriptional profiles, genetic mutations and the presence of fusion genes.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究を介して頭頸部癌研究においても従来の二次元培養に比べてより生体内組織に近い環境を反映することが可能であり，癌周囲の微小環境が解析可能となる三次元培養法によりオルガノイド株樹立が可能であることを示した。
このような生体内組織に近い環境を反映可能なモデルが今後の頭頸部癌研究で使用可能となることは，頭頸部癌の発癌機序解明や，頭頸部癌の個別化治療開発に大きく貢献すると考える。
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Report
(5 results)
Research Products
(22 results)
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[Journal Article] FosL1 Regulates Regional Metastasis of Head and Neck Squamous Cell Carcinoma by Promoting Cell Migration, Invasion, and Proliferation2021
Author(s)
Hiroshi Hyakusoku, Kae Sawakuma, Daisuke Sano, Hideaki Takahashi, Takashi Hatano, Kaname Sato, Yasuhiro Isono, Shoko Shimada, Kentaro Takada, Tatsu Kuwahara, Yoshihiro Aizawa, Nobuhiko Oridate
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Journal Title
Anticancer research
Volume: 41
Issue: 7
Pages: 3317-3326
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Addition of S-1 to radiotherapy for treatment of T2N0 glottic cancer: Results of the multiple-center retrospective cohort study in Japan with a propensity score analysis2019
Author(s)
Sano D, Tanabe T, Kubota A, Miyamoto S, Tanigaki Y, Okami K, Komatsu M, Ikoma R, Suzuki K, Akazawa Y, Kobayashi S, Yamada Y, Oridate N
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Journal Title
Oral Oncology
Volume: 99
Pages: 104454-104454
Related Report
Peer Reviewed
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