Establishment of new target therapy depending on the origin of lung cancer stem cell
| Project/Area Number |
17K09631
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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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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Kansai Medical University |
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Principal Investigator |
KUMANO Keiki 関西医科大学, 医学部, 准教授 (90396721)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 肺がん / Bmi1 / Notch / 幹細胞 / Kras / BASC / がん幹細胞 / 系譜追跡 |
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| Outline of Final Research Achievements |
We investigated the effect of supression of Notch signaling in Bmi1 (+) cells. Bmi1(+) AT2 cells supontineously differentiated to the AT1 cells.Bronchio-Alveolar stem cell (BASC) also expressed Bmi1 and differentiated to the neuroedncrine cells by the inhibition of Notch signaling.
Using active Kras mutation, Bmi1(+) cells clonally expanded and developed lung adenocarcinoma.Although by the ihibition of Notch signaling, the initial step of lung cancer formation was not affected, clonal lung cancer formation was suppressed after 12 weeks. Bmi1(+) BASC developed the neuroendocrine tumor by Kras activation and Notch inhibition.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究ではがんの起源細胞の違いが、がんの種類を決定するという仮設のもとに、肺がんの起源細胞や発症メカニズムを明らかにすることで、難治性であり予後不良である肺がんの治療法の確立を目指すことを目的とする。肺がんの起源細胞としてBmi1陽性細胞を同定した。Bmi1陽性細胞はfacultative stem cellである1型肺胞上皮細胞とBASCからなり、それらはNotchの抑制により異なる挙動を示した。
発がん過程を経時的に観察することにより、臨床検体ではほとんど見つかることのない前がん病変の検出も可能となり、前がん病変の新たなバイオマーカーの発見や発がんへ至る分子メカニズムの同定が可能となる。
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Report
(4 results)
Research Products
(5 results)
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[Journal Article] Using patient-derived iPSCs to develop humanized mouse models for chronic myelomonocytic leukemia and therapeutic drug identification, including liposomal clodronate.2018
Author(s)
1.Taoka K, Arai S, Kataoka K, Hosoi M, Miyauchi M, Yamazaki S, Honda A, Aixinjueluo W, Kobayashi T, Kumano K, Yoshimi A, Otsu M, Niwa A, Nakahata T, Nakauchi H, Kurokawa M.
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Journal Title
Scientific Reports
Volume: 8
Issue: 1
Pages: 15855-15867
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Intestinal stem cells contribute to the maturation of the neonatal small intestine and colon independently of digestive activity.2017
Author(s)
Yanai H, Atsumi N, Tanaka T, Nakamura N, Komai Y, Omachi T, Tanaka K, Ishigaki K, Saiga K, Ohsugi H, Tokuyama Y, Imahashi Y, Ohe S, Hisha H, Yoshida N, Kumano K, Kon M, Ueno H.
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Journal Title
Scientific Reports
Volume: 7
Issue: 1
Pages: 9891-9901
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Intestinal cancer stem cells marked by Bmi1 or Lgr5 expression contribute to tumor propagation via clonal expansion.2017
Author(s)
Hirotsugu Yanai, Naho Atsumi, Toshihiro Tanaka, Naohiro Nakamura, Yoshihiro Komai, Taichi Omachi, Kiyomichi Tanaka, Kazuhiko Ishigaki, Kazuho Saiga, Haruyuki Ohsugi, Yoko Tokuyama, Yuki Imahashi, Shuichi Ohe, Hiroko Hisha, Naoko Yoshida, Keiki Kumano, Masanori Kon and Ueno H.
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Journal Title
Scientific Reports
Volume: 7
Issue: 1
Pages: 41838-41847
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
