Mechanism how scirrhous-type gastric cancer is formed
Project/Area Number |
15K06832
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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 |
Tumor biology
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
Fukamachi Hiroshi 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (70134450)
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Project Period (FY) |
2015-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | スキルス胃がん / がん幹細胞 / mTOR阻害剤 / 免疫チェックポイント阻害剤 / 初代培養 / PDX / 分子標的治療 / 胃がん / 分子標的薬 / R-spondin1 / Wnt3a |
Outline of Final Research Achievements |
We established patient-derived xenograft (PDX) lines from diffuse-type gastric cancer (GC), and searched for drugs that suppressed their growth. We found that mechanistic target of rapamycin (mTOR) inhibitor strongly suppressed the growth of PDX-derived diffuse-type GC-initiating cells. Diffuse-type GCs could be classified into two clusters, and we found that genomically stable subtype was major in cluster I while CIN and MSI subtypes were predominant in cluster II where PDX-derived cells were included. Further analysis showed that diffuse-type GCs in cluster II developed from intestinal-type GCs while those in cluster I from normal gastric epithelial cells We estimated that about 9% and 55% of the diffuse-type GCs in cluster II were responders to mTOR inhibitors and checkpoint inhibitors, respectively. We thus conclude that mTOR inhibitors and checkpoint inhibitors might be useful for the treatment of a subset of diffuse-type GCs which may develop from intestinal-type GCs.
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Academic Significance and Societal Importance of the Research Achievements |
本研究で我々は、mTOR阻害剤がスキルス胃がん幹細胞の増殖を特異的に抑制すること、スキルス胃がんの一部は分化型胃がんから派生し、多くの突然変異を持つことを明らかにした。これまで、スキルス胃がんは正常胃上皮細胞から形成され、突然変異は少ないと考えられてきた。突然変異が少ない腫瘍細胞は免疫チェックポイント阻害剤に反応しないので、スキルス胃がんの治療には免疫チェックポイント阻害剤は使われていない。我々の研究は、スキルス胃がんの一部は免疫チェックポイント阻害剤に反応性が高いことを示唆している。本研究で同定された薬剤が、スキルス胃がんの治療に著効を示すか否かは今後の検討課題である。
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Report
(5 results)
Research Products
(18 results)
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[Journal Article] Proteasome activity is required for the initiation of precancerous pancreatic lesions.2016
Author(s)
Furuyama, T., Tanaka, S., Shimada, S., Akiyama, Y., Matsumura, S., Mitsunori, Y., Aihara, A., Ban, D., Ochiai, T., Kudo, A., Fukamachi, H., Arii, S., Kawaguchi, Y., Tanabe, M.
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Journal Title
Sci. Rep.
Volume: 6
Issue: 5
Pages: 27044-27044
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] CD73 as a therapeutic target for pancreatic neuroendocrine tumor stem cells.2016
Author(s)
Katsuta, E., Tanaka, S., Mogushi, K., Shimada, S., Akiyama, Y., Aihara, A., Matsumura, S., Mitsunori, Y., Ban, D., Ochiai, T., Kudo, A., Fukamachi, H., Tanaka, H., Nakayama, K., Arii, S., Tanabe, M.
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Journal Title
Int. J. Oncol.
Volume: 48
Issue: 2
Pages: 657-669
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Diffuse-type gastric cancers are classified into two clusters, which may be formed via different carcinogenic pathways.2018
Author(s)
Fukamachi, H., Nishikawaji, T., Shimada, S., Akiyama, Y., Yuasa, Y., Tsuchiya, K., Tanaka, S.
Organizer
第77回日本癌学会学術総会
Related Report
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[Presentation] Diffuse-type gastric cancers are classified into two clusters, which may be formed via different carcinogenic pathways.2018
Author(s)
Fukamachi, H., Kim, S.-K., Koh, J., Lee, H. S., Nishikawaji T., Shimada, S., Akiyama, Y., Kim, Y. S., Kim, W. H., Yuasa, Y., Tanaka, S.
Organizer
INTERNATIONAL SYMPOSIUM Post-A3 Meeting 2018 Epigenetic Regulation of Cellular Stress Response
Related Report
Int'l Joint Research / Invited
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[Presentation] Identification of signal transduction pathway in PDX-derived diffuse-type gastric tumor-initiating cells.2017
Author(s)
Fukamachi, H., Nishikawaji, T., Shimada, S., Akiyama, Y., Yuasa, Y., Tsuchiya, K., Tanaka, S.
Organizer
The 76th Annual Meeting of the Japanese Cancer Association.
Related Report
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[Presentation] Identification of a signal transduction pathway working in the genesis and progression of diffuse type gastric cancers.2017
Author(s)
Fukamachi, H., Nishikawaji, T., Shimada, S., Akiyama, Y., Yuasa, Y., Tsuchiya, Kim, W. H., K., Tanaka, S.
Organizer
Post-A3 Meeting 2017 Epigenetic Signature of Carcinogenesis
Related Report
Int'l Joint Research
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[Presentation] Identification of MTDs that suppress the growth of PDX-derived diffuse-type gastric tumor-initiating cells.2016
Author(s)
Fukamachi, H., Nishikawaji, T., Shimada, S., Akiyama, Y., Yuasa, Y., Tsuchiya, K., Tanaka, S.
Organizer
第75回日本癌学会学術総会
Place of Presentation
横浜
Year and Date
2016-10-06
Related Report
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[Presentation] Characteristics of diffuse-type gastric cancer stem cells.2016
Author(s)
Fukamachi, H., Nishikawaji, T., Shimada, S., Akiyama, Y., Yuasa, Y., Tsuchiya, K., Tanaka, S
Organizer
26th Seoul Int. Cancer Symp. - Epigenetic Signature of Carcinogenesis
Place of Presentation
Seoul, Korea
Year and Date
2016-06-16
Related Report
Int'l Joint Research / Invited
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[Presentation] Features of poorly-differentiated gastric tumor-initiating cells from patient-derived tumor xenograft tissues.2015
Author(s)
Fukamachi, H., Shimada, S., Akiyama, Y., Yuasa, Y., Tsuchiya, K., Tanaka, S.
Organizer
第74回日本癌学会学術総会
Place of Presentation
名古屋国際会議場(愛知県名古屋市)
Year and Date
2015-10-08
Related Report
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