Roles of immune checkpoint and prostaglandin E in tumor metastasis.
Project/Area Number |
18H02571
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
|
Research Institution | Tokyo University of Agriculture and Technology |
Principal Investigator |
MIYAURA Chisato 東京農工大学, 工学(系)研究科(研究院), 教授 (20138382)
|
Co-Investigator(Kenkyū-buntansha) |
植松 智 大阪市立大学, 大学院医学研究科, 教授 (50379088)
稲田 全規 東京農工大学, 工学(系)研究科(研究院), 准教授 (80401454)
|
Project Period (FY) |
2018-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
|
Keywords | 骨代謝 / 破骨細胞 / 免疫チェックポイント / がん転移 / プロスタグランジンE / 質量分析イメージング |
Outline of Final Research Achievements |
It is known that tumor bone metastasis is difficult to cure. We examined the roles of prostaglandin E signal and immune checkpoint inhibitor, anti PD-1 (Programmed cell death 1) antibody in tumor bone metastasis. In this study, EP4 antagonist, which inhibit the signal of EP4, one of PGE receptor EP1-EP4, suppressed bone metastasis of B16 melanoma and bone loss associated with bone metastasis in mouse tumor metastasis model. In the presence of anti PD-1 antibody, EP4 antagonist nicely suppressed bone metastasis and bone loss in B16 model, and the co-operative effects of EP4 antagonist and anti PD-1 antibody are suggested. For the strategy of the resistance of anti PD-1 antibody, we suggest the possible roles of EP4 antagonist in the treatment of tumor metastasis.
|
Academic Significance and Societal Importance of the Research Achievements |
がん治療において、遠隔臓器への転移は予後を大きく左右することから、転移の克服は学術的かつ社会的課題である。特に、骨への転移は散在性に生じて完治が難しい。近年、免疫チェックポイント阻害の抗PD-1抗体が、がん免疫療法として注目されているが、一方で、応答性を示さない場合もあり、その治療効果の最大化が課題となっている。PGEシグナルの阻害は抗炎症・抗鎮痛作用として知られているが、EP4アンタゴニストは副作用が少なく、がんの増殖・転移への効果も期待できる。これら薬剤の併用によって、がん転移の根治への治療法を確立できれば、極めて大きな社会的意義を有する。
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Report
(4 results)
Research Products
(111 results)
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[Journal Article] Fecal Microbiome Composition in Healthy Adults in Ghana2021
Author(s)
Parbie Prince Kofi、Mizutani Taketoshi、Ishizaka Aya、Kawana-Tachikawa Ai、Runtuwene Lucky Ronald、Seki Sayuri、Abana Christopher Zaab-Yen、Kushitor Dennis、Bonney Evelyn Yayra、Ofori Sampson Badu、Uematsu Satoshi、Imoto Seiya、Kimura Yasumasa、Kiyono Hiroshi、Ishikawa Koichi、Ampofo William Kwabena、Matano Tetsuro
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Journal Title
Japanese Journal of Infectious Diseases
Volume: 74
Issue: 1
Pages: 42-47
DOI
NAID
ISSN
1344-6304, 1884-2836
Year and Date
2021-01-29
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[Journal Article] Orally desensitized mast cells form a regulatory network with Treg cells for the control of food allergy.2021
Author(s)
Takasato Y, Kurashima Y, Kiuchi M, Hirahara K, Murasaki S, Arai F, Izawa K, Kaitani A, Shimada k, Saito Y, Toyoshima S, Nakamura M, Fujisawa K, Okayama Y, Kunisawa J, Kubo M, Takemura N, Uematsu S, Akira S, Kitaura J, Takahashi T, Nakayama T, Kiyono H
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Journal Title
Mucosal Immunol
Volume: 14
Issue: 3
Pages: 640-651
DOI
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[Journal Article] Microsomal prostaglandin E synthase-1 promotes lung metastasis via SDF-1/CXCR4-mediated recruitment of CD11b+Gr1+MDSCs from bone marrow2020
Author(s)
Takahashi R, Amano H, Ito Y, Eshima K, Satoh T, Iwamura M, Nakamura M, Kitasato H, Uematsu S, Raouf J, Jakobsson PJ, Akira S, Majima M
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Journal Title
Biomedicine & Pharmacotherapy
Volume: 121
Pages: 109581-109581
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[Journal Article] Hypergravity and microgravity exhibited reversal effects on the bone and muscle mass in mice.2019
Author(s)
Tominari T, Ichimaru R, Taniguchi K, Yumoto A, Shirakawa M, Matsumoto C, Watanabe K, Hirata M, Itoh Y, Shiba D, Miyaura C, Inada M
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Journal Title
Sci Rep
Volume: 9(1)
Issue: 1
Pages: 6614-6614
DOI
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[Journal Article] Beta-cryptoxanthin inhibits lipopolysaccharide-induced osteoclast differentiation and bone resorption via the suppression of inhibitor of NF-κB kinase activity.2019
Author(s)
Hirata N , Ichimaru R , Tominari T , Matsumoto C, Watanabe K ,Taniguchi K , Hirata M , Ma S, Suzuki K , Grundler FM , Miyaura C, Inada M
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Journal Title
Nutrients
Volume: 11
Issue: 2
Pages: 368-368
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[Journal Article] Structure-activity relationship of anthocyanidins as an inhibitory effect on osteoclast differentiation.2018
Author(s)
Hirata N, Tominari T, Ichimaru R, Taniguchi K, Matsumoto C, Watanabe K, Hirata M, Ma S, Suzuki K, Grundler FM, Miyaura C, Inada M*
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Journal Title
BPB_Reports
Volume: 2
Pages: 1-6
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[Journal Article] Raloxifene reduces the risk of local alveolar bone destruction in a mouse model of periodontitis combined with systemic postmenopausal osteoporosis.2018
Author(s)
Ichimaru R, Tominari T, Yoshinouchi S, Matsumoto C, Watanabe K, Hirata M, Numabe Y, Murphy G, Nagase H, Miyaura C, Inada M*
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Journal Title
Arch. Oral Biol
Volume: 85
Pages: 98-103
DOI
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[Journal Article] Intestinal CD103(+)CD11b(+)cDC2 Conventional Dendritic Cells Are Required for Primary CD4(+) T and B Cell Responses to Soluble Flagellin.2018
Author(s)
Flores-Langarica A, Cook C, Muller Luda K, Persson EK, Marshall JL, Beristain-Covarrubias N, Yam-Puc JC, Dahlgren M, Persson JJ, Uematsu S, Akira S, Henderson IR, Lindbom BJ, Agace W, Cunningham AF.
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Journal Title
Front Immunol.
Volume: 9
Pages: 2409-2409
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[Journal Article] DUSP10 constrains innate IL-33-mediated cytokine production in ST2hi memory-type pathogenic Th2 cells2018
Author(s)
Yamamoto, T., Endo, Y., Onodera, A., Hirahara, K., Asou, H., Nakajima, T., Kanno, T., Ouchi, Y., Uematsu, S., Nishimasu, H., Nureki, O., Tumes, D. J., Shimojo, N., and Nakayama, T.
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Journal Title
Nature Communications
Volume: 9
Issue: 1
Pages: 4231-4231
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[Journal Article] Inhibition of microsomal prostaglandin E synthase-1 facilitates liver repair after hepatic injury in mice.2018
Author(s)
Nishizawa N, Ito Y, Eshima K, Ohkubo H, Kojo K, Inoue T, Raouf J, Jakobsson PJ, Uematsu S, Akira S, Narumiya S, Watanabe M, Majima M.
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Journal Title
J Hepatol.
Volume: S0168-8278(18)
Issue: 1
Pages: 30126-30130
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[Journal Article] Generation of tumor antigen-specific murine CD8+ T cells with enhanced anti-tumor activity via highly efficient CRISPR/Cas9 genome editing2018
Author(s)
Ouchi Y, Patil A, Tamura Y, Nishimasu H, Negishi A, Paul SK, Takemura N, Satoh T, Kimura Y, Kurachi M, Nureki O, Nakai K, Kiyono H, Uematsu S.
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Journal Title
International Immunology
Volume: 30
Issue: 4
Pages: 141-154
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