Anti-tumour effects of the hepatitis drug propagermanium on breast cancer via immunostimulation.
Project/Area Number |
20K17556
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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Research Institution | Kyushu University |
Principal Investigator |
Ando Yuki 九州大学, 大学病院, 医員 (50869568)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 乳がん / ドラッグリポジショニング / プロパゲルマニウム / 免疫賦活化 / CCL2 / 免疫能賦活化 / CD8 |
Outline of Research at the Start |
近年ドラッグリポジショニングが薬剤開発期間の短縮や医療費抑制の点で注目されている。慢性B型肝炎治療薬であるプロパゲルマニウム(PG)がCCL2/CCR2経路を阻害し前転移ニッチ形成を抑制することで転移を抑制することが見出され(J Clin Invest 2015)、臨床応用を見据えた進行胃癌での臨床試験(論文投稿中)や乳癌患者を対象とした安全性評価のための医師主導型治験(UMIN000022494)により、腫瘍組織への直接的な抗腫瘍効果を認め、探索的解析により免疫能賦活化作用の可能性が示唆された。本研究では、PGの直接的抗腫瘍効果のメカニズムを免疫賦活化作用に注目して解明することを目的とする。
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Outline of Final Research Achievements |
In this study, blood samples and tumour tissue from the clinical trial were analysed. Multi-cytokine chemokines were measured in blood samples and cytokines that showed changes in the PG-treated group were identified. RNA sequencing analysis of tumour tissue showed increased CD8 expression in the PG-treated group, which was also confirmed by immunohistochemical staining. Breast cancer cells were transplanted into mice and validated in mouse experiments, and similar results were obtained by immunohistochemical staining. The mechanism of immunostimulation by PG in tumour tissue is thought to be the activation of CD8-positive T cells under the influence of cytokine chemokines, which were found to change in the PG-treated group, and will be investigated in the future.
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Academic Significance and Societal Importance of the Research Achievements |
本邦において悪性腫瘍は3大死因の一つである。近年、ある疾患に有効な治療薬から、別の疾患に有効な薬効を見つけ出すドラッグリポジショニングが開発期間の短縮や医療費の抑制の点で注目されている。今回肝炎治療薬であるプロパゲルマニウムを乳がんに対する抗腫瘍効果およびメカニズムを検討した。今後乳がんでの臨床応用が期待される。
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Dynamic Changes in Peripheral Systemic Immunity Markers During Chemotherapy in HER2-negative Advanced Breast Cancer2023
Author(s)
Takaaki Masuda, Hiroaki Ueo, Yuta Okumura, Yuichiro Kai, Yuki Ando, Ken Masuguchi, Miwa Kitagawa , Akihiro Kitagawa, Naoki Hayashi, Yusuke Tsuruda, Yuichi Hisamatsu, Shuji Suehiro, Hirofumi Ohmura, Kenji Fujiyoshi, Fumiaki Tanaka, Koshi Mimori
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Journal Title
Cancer Genomics Proteomics
Volume: 2
Issue: 2
Pages: 182-194
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] Development of risk assessment of distant metastasis in ductal carcinoma in situ of the breast2022
Author(s)
Yuki Ando, Takaaki Masuda, Miwa Kitagawa, Takanari Tatsumi, Chihiro Matsumoto, Shohei Shibuta, Yuya Ono, Yuki Miyata, Kiyotaka Hosoda, Yoshiki Hiraki, Katsushi Dairaku , Yusuke Nakano, Masahiro Hashimoto, Tadashi Abe , Yushi Motomura ,Yuichi Hisamatsu , Takeo Toshima , Yusuke Yonemura and Koshi Mimori
Organizer
第60回日本癌治療学会学術集会
Related Report
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[Presentation] Genomic characterizations of Japanese breast cancer2022
Author(s)
Yuki Ando, Takaaki Masuda, Kiyotaka Hosoda, Yoshiki Hiraki, Katsushi Dairaku, Yusuke Nakano, Masahiro Hashimoto, Tadashi Abe, Yushi Motomura, Yuichi Hisamatsu, Takeo Toshima, Yusuke Yonemura, Koshi Mimori
Organizer
第81回日本癌学会学術総会
Related Report
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[Presentation] Clinical significance of SETBP1 expression in breast cancer.2021
Author(s)
Yuki Ando, Takaaki Masuda, Naoki Hayashi, Kenichi Mochizuki, Tadashi Abe, Hideyuki Saito,Yuki Ozato, Takafumi Nakano, Kensuke Koike, Yushi Motomura, Takahashi Junichi,Takeo Toshima, Yuichi Hisamatsu, Yusuke Yonemura, Koshi Mimori
Organizer
第80回日本癌学会学術総会
Related Report
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