Novel anti-cancer therapy with cyclic sulfide compounds regulating macrophage activation
Project/Area Number |
16K09247
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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 |
General internal medicine(including psychosomatic medicine)
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Research Institution | Kumamoto University |
Principal Investigator |
Fujiwara Yukio 熊本大学, 大学院生命科学研究部(医), 講師 (70452886)
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Co-Investigator(Kenkyū-buntansha) |
哈 斯塔 (Horlad Hasita) 熊本大学, 大学院生命科学研究部(医), 研究員 (00644840)
白石 大偉輔 熊本大学, 医学部附属病院, 非常勤診療医師 (70769512)
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Research Collaborator |
Komohara Yoshihiro
Ohnishi Koji
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | マクロファージクロファージ / ガン / 代替医療 / マクロファージ / 環状スルフィド化合物 / ガン免疫 / スルフィド化合物 |
Outline of Final Research Achievements |
It is well known that regulating macrophages activation (regulation from M2-like phenotype into M1-like phenotype) in tumor microenvironment is novel strategy for tumor therapy. In the present study, we identified cyclic sulfide compounds regulating macrophage activation and those compounds suppressed tumor proliferation under co-culture with macrophages and tumor cells. Furthermore, administration of those compounds significantly suppressed tumor development in tumor-bearing mice, thus indicating that cyclic sulfide compounds may be potentially new strategy for tumor prevention and therapy.
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Academic Significance and Societal Importance of the Research Achievements |
近年、遺伝子改変動物等を用いた国内外での研究により、Mφ活性化調節が病態の改善に有効であると知られている。また、腫瘍内にはM2Mφなどの免疫抑制的に働く細胞が多数浸潤しており、腫瘍免疫を抑制することで腫瘍増殖に関与している。ゆえに、既存の癌治療が著効しない症例ではM2Mφによる免疫抑制が原因であると考えられている。本研究で同定した環状スルフィド化合物はMφの活性化制御という既存の治療薬とは異なるメカニズムで腫瘍進展を抑制し、ガン治療に応用できる可能が示唆された。つまり本研究成果は、将来的に新たな分子標的薬を開発するための基礎的知見として学術的・社会的にも意義ある研究成果であると考えられる。
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Report
(4 results)
Research Products
(61 results)
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[Journal Article] Inhibition of local macrophage growth ameliorates focal inflammation and suppresses atherosclerosis.2018
Author(s)
Yamada S, Senokuchi T, Matsumura T, Morita Y, Ishii N, Fukuda K, Murakami S, Nishida S, Kawasaki S, Motoshima H, Furukawa N, Komohara Y, Fujiwara Y, Koga T, Yamagata K, Takeya M, Araki E
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Journal Title
Arteriosclerosis, Thrombosis, and Vascular Biology
Volume: 印刷中
Issue: 5
Pages: 994-1006
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] CD163 is required for protumoral activation of macrophages in human and murine sarcoma.2018
Author(s)
Shiraishi D, Fujiwara Y, Horlad H, Saito Y, Iriki T, Tsuboki J, Cheng P, Nakagata N, Mizuta H, Bekki H, Nakashima Y, Oda Y, Takeya M, Komohara Y.
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Journal Title
Cancer Res
Volume: in press
Issue: 12
Pages: 3255-3266
DOI
Related Report
Peer Reviewed
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[Journal Article] Genetic Fusion of Type-I Interferon to a Recombinant Albumin Mutant with polymannosylated N-linked oligosaccharide attached is a Novel and Superior Kupffer Cell Targeting Agent for the Treatment of Hepatitis.2018
Author(s)
Minayoshi Y, Maeda H, Yanagisawa H, Hamasaki K, Mizuta Y, Nishida K, Kinoshita R, Enoki Y, Imafuku T, Chuang VTG, Koga T, Fujiwara Y, Takeya M, Sonoda K, Wakayama T, Taguchi K, Ishima Y, Ishida T, Iwakiri Y, Tanaka M, Sasaki Y, Watanabe H, Otagiri M, Maruyama T.
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Journal Title
Drug Delivery
Volume: 25
Issue: 1
Pages: 1067-1077
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Phlenumdines D and E, new Lycopodium alkaloids from Phlegmariurus nummulariifolius, and their regulatory effects on macrophage differentiation during tumor development2018
Author(s)
Nakayama W, Fujiwara Y, Kosuge Y, Monthakantirat O, Fujikawa K, Watthana S, Kitanaka S, Makino T, Ishiuchia K.
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Journal Title
Phytochemistry Letters
Volume: 29
Pages: 98-103
DOI
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Peer Reviewed / Int'l Joint Research
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[Journal Article] Stat3 inhibitor abrogates the expression of PD-1 ligands on lymphoma cell lines2017
Author(s)
Ma C, Horlad H, Pan C, Yano H, Ohnishi K, Fujiwara Y, Matsuoka M, Lee A, Niidome T, Yamanaka R, Takeya M, Komohara Y
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Journal Title
Journal of Clinical and Experimental Hematopathology
Volume: 57
Issue: 1
Pages: 21-25
DOI
NAID
ISSN
1346-4280, 1880-9952
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Cell adhesion molecule-1 (CADM1) expressed on adult T-cell leukemia/lymphoma cells is not involved in the interaction with macrophages.2017
Author(s)
Komohara Y, Ma C, Yano H, Pan C, Horlad H, Saito Y, Ohnishi K, Fujiwara Y, Okuno Y, Nosaka K, Shimosaki S, Morishita K, Matsuoka M, Wakayama T, Takeya M
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Journal Title
Journal of Clinical and Experimental Hematopathology
Volume: 57
Issue: 1
Pages: 15-20
DOI
NAID
ISSN
1346-4280, 1880-9952
Related Report
Peer Reviewed / Open Access
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[Journal Article] Antitumor <i>Allium</i> Sulfides2017
Author(s)
Nohara T, Fujiwara Y, El-Aasr M, Ikeda T, Ono M, Nakano D, Kinjo J.
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Journal Title
Chemical and Pharmaceutical Bulletin
Volume: 65
Issue: 3
Pages: 209-217
DOI
NAID
ISSN
0009-2363, 1347-5223
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Atypical Cyclic Sulfides, Garlicnins G, I, and J, Extracted from <i>Allium sativum</i>2017
Author(s)
Ono M, Fujiwara Y, Ikeda T, Pan C, El-Aasr M, Lee JH, Nakano D, Kinjo J, Nohara T.
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Journal Title
Chemical and Pharmaceutical Bulletin
Volume: 65
Issue: 1
Pages: 102-106
DOI
NAID
ISSN
0009-2363, 1347-5223
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] An IL-27/Stat3 axis induces expression of programmed cell death 1 ligands (PD-L1/2) on infiltrating macrophages in lymphoma.2016
Author(s)
Horlad H, Ma C, Yano H, Pan C, Ohnishi K, Fujiwara Y, Endo S, Kikukawa Y, Okuno Y, Matsuoka M, Takeya M, Komohara Y.
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Journal Title
Cancer Sci.
Volume: 107
Issue: 11
Pages: 1696-1704
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Onionin A inhibits ovarian cancer progression by suppressing cancer cell proliferation and the protumour function of macrophages.2016
Author(s)
Tsuboki J, Fujiwara Y, Horlad H, Shiraishi D, Nohara T, Tayama S, Motohara T, Saito Y, Ikeda T, Takaishi K, Tashiro H, Yonemoto Y, Katabuchi H, Takeya M, Komohara Y.
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Journal Title
Sci Rep
Volume: 6
Issue: 1
Pages: 29588-29588
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Onionin A, a sulfur-containing compound isolated from onions, impairs tumor development and lung metastasis by inhibiting the protumoral and immunosuppressive functions of myeloid cells2016
Author(s)
Fujiwara Yukio, Horlad Hasita, Shiraishi Daisuke, Tsuboki Junko, Kudo Rino, Ikeda Tsuyoshi, Nohara Toshihiro, Takeya Motohiro, Komohara Yoshihiro
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Journal Title
Molecular Nutrition & Food Research
Volume: 60(11)
Issue: 11
Pages: 2467-2480
DOI
Related Report
Peer Reviewed
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[Journal Article] Infiltration of tumor-associated macrophages is involved in CD44 expression in clear cell renal cell carcinoma.2016
Author(s)
Ma C, Komohara Y, Ohnishi K, Shimoji T, Kuwahara N, Sakumura Y, Matsuishi K, Fujiwara Y, Motoshima T, Takahashi W, Yamada S, Kitada S, Fujimoto N, Nakayama T, Eto M, Takeya M.
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Journal Title
Cancer Sci.
Volume: Epub
Issue: 5
Pages: 700-707
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Two new bicyclic sulfoxides from Welsh onion2016
Author(s)
Nohara, Toshihiro; Fujiwara, Yukio; Ikeda, Tsuyoshi; Murakami, Kotaro; Ono, Masateru; El-Aasr, Mona; Nakano, Daisuke; Kinjo, Junei
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Journal Title
Journal of Natural Medicines Volume
Volume: 70 (2)
Issue: 2
Pages: 260-265
DOI
NAID
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] Onionin A, a sulfur-containing compound isolated from onions, impairs tumor progression by inhibiting the protumoral functions of macrophages2017
Author(s)
Yukio Fujiwara, Junko Tsuboki, Hasita Horlad, Daisuke Shiraishi, Toshihiro Nohara, Yoshihiro Komohara, Motohiro Takeya
Organizer
Keystone Symposia, Mononuclear Phagocytes in Health, Immune Defense and Disease (D3)
Related Report
Int'l Joint Research
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