| Project/Area Number |
18H03000
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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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 | University of East Asia (2020)
Hiroshima University (2018-2019) |
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Principal Investigator |
OKMOTO TETUJI 東亜大学, その他の研究科, 教授 (00169153)
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| Co-Investigator(Kenkyū-buntansha) |
吉岡 幸男 広島大学, 医系科学研究科(歯), 助教 (20335665)
工藤 保誠 徳島大学, 大学院医歯薬学研究部(歯学域), 教授 (50314753)
浜名 智昭 広島大学, 医系科学研究科(歯), 助教 (40397922)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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| Keywords | 無血清培養 / 癌幹細胞 / 放射線耐性細胞 / HBp17/FGFBP-1 / miRNA / exosome / krt13 / IGF2 / がん幹細胞 / sphere 形成 / HBp17/FGFBP1 / 放射線耐性 / エクソソーム / 腫瘍微小環境 / 口腔扁平上皮癌細胞 / ゲノム編集 / プロテオーム解析 / sphere形成能 / 口腔癌幹細胞 / CD133 / 低線量放射線 / 高線量放射線 / ケラチン13遺伝子 / sphere形成細胞 / 細胞増殖因子 / 無血清培地 / 口腔扁平上皮癌 / sphere形成 / regulatory chemical messenger (RCM) / 制御性ケミカルメッセンジャー / オーガノイド形成 |
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| Outline of Final Research Achievements |
Cancers consist of multiple cell populations, including highly proliferative cell populations and cells that have undergone some differentiation and maturation, and these consist of a small number of cancer stem cells (CSC). In this study, HBp17/FGFBP-1 (HBp17), which is highly expressed in OSCC and is closely involved in its growth and angiogenesis, is studied. In addition, surgical/radiation/chemo-therapy are effective in treating many cancers, and radiation therapy (RT) plays a major role in the treatment of OSCC. However, some tumors show radiation resistance. In addition, even if the case exhibited a clinically complete-response, there are cases where it recurs later. This is believed to be due to the presence of CSC. In order to elucidate the mechanism of Radiation resistance in OSCC, RR-SCC strains were isolated using two types of irradiation systems, HDR and LDR. The characteristics of the RR cells were clarified, and the genes involved in RR were clarified.
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| Academic Significance and Societal Importance of the Research Achievements |
VD3/ED-71はOSCC細胞に対してregulatory chemical messengerとしてexosomal miR-6887-5pの培養上清中への分泌を上昇させ腫瘍細胞及び周囲細胞に働きHBp17の発現を制御し増殖を抑制していた。ED-71の扁平上皮癌に対する治療薬としての有用性が示された。放射線耐性OSCC細胞ではIGF2やkrt13遺伝子が過剰発現され癌幹細胞の性質を持った細胞集団が蓄積し、腫瘍原性が亢進し、放射線・化学療法後の癌再発をもたらすと考えられた。RR-SCCモデルの確立は放射線耐性メカニズムを解明する強力なツールとなり、新規診断及び治療法の開発に有用と考えられた。
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