産学連携推進センター
Profile Information
- Affiliation
- Office for Co-innovation, Fujita Health University
- Degree
- 薬学博士
- J-GLOBAL ID
- 201901010015875519
- researchmap Member ID
- 7000029395
Research Areas
4Research History
9-
Jan, 2025 - Present
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Apr, 2024 - Present
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Apr, 2019 - Present
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Feb, 2020 - Jun, 2024
Papers
30-
Heliyon, 6(9) e04929-e04929, Sep, 2020 Peer-reviewedBackground: Several immunochromatographic serological test kits have been developed to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies, but their relative performance and potential clinical utility is unclear. Methods: Three commercially available serological test kits were evaluated using 99 serum samples collected from 29 patients diagnosed with coronavirus disease 2019 (COVID-19) and 100 serum samples collected from 100 healthy volunteers in 2017 as negative controls. Results: The specificity of the IgM and IgG antibodies showed comparable results among the three immunochromatographic serological test kits. The specificity for IgM antibody was 98.0%, 98.0%, and 97.0%, and the specificity for IgG antibody was identical among the three kits (99.0%). The IgM antibody-positive rates of the three test kits for samples taken at the early stage of the disease (0-4 days after onset) were consistent with all three kits (18.2%); however, the IgM antibody-positive rates thereafter showed considerable differences among the kits, making it difficult to interpret the kinetics of IgM response against SARS-CoV-2. The IgG antibody-positive rates for samples taken after 13 days of onset were 100.0%, 97.6%, and 97.6%, respectively. Conclusion: There were large differences among the results of the three test kits. Only few cases showed positive results for IgM, suggesting that at least 2 of these kits used in this study were unsuitable for diagnosis of COVID-19. The IgG antibody was positive in almost all samples after 13 days of onset, suggesting that it may be useful for determining infections in the recent past.
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MOLECULAR IMMUNOLOGY, 64(1) 218-227, Mar, 2015 Peer-reviewedMacrophages are a major component of the innate immune system, and the cytokines they secrete are involved in antitumor responses. Z-100 is obtained from hot-water extract of human-type Mycobacterium tuberculosis strain Aoyama B and activates the innate immune response. However, while Z-100 is known to modulate macrophage activity, the mechanism behind this modulation is not fully understood. We evaluated the effects of Z-100 on the murine macrophage cell line RAW264.7. Tumor necrosis factor-alpha (TNF-alpha) production from RAW264.7 cells was strongly induced by Z-100 and interferon-gamma (IFN-gamma) stimulation but only weakly induced by Z-100 alone. Quantitative gene expression analysis showed that nucleotide-binding oligomerization domain containing 2 (Nod2) expression was up-regulated by IFN-gamma treatment in RAW264.7 cells while Z-100-induced TNF-alpha production was attenuated by Nod2 gene silencing. Further, componential analysis demonstrated that muramic acid and amino acids distinctive of muramyl dipeptide (MDP) were contained within Z-100 and Z-100Fr I, the low-molecular-weight fraction containing components <3 kDa in size. In addition, 2-100Fr I enhanced TNF-alpha production in RAW264.7 cells and promoted NOD2-dependent nuclear factor-kappa B (NF-kappa B) activation in murine NOD2-expressing SEAP reporter HEK293 (HEK-Blue-mN0D2) cells. Taken together, these results suggest that Z-100 contains MDP-like molecules and augments NF-kappa B signaling via the direct activation of Nod2 in macrophages, which might be one mechanism driving the innate immune responses induced by Z-100 in cancer immunotherapy. (C) 2014 Elsevier Ltd. All rights reserved.
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BIOLOGICAL & PHARMACEUTICAL BULLETIN, 37(4) 642-647, Apr, 2014 Peer-reviewedLymphatic metastasis is common in advanced-stage carcinoma and is associated with a poor prognosis. However, few effective treatments to inhibit it are available. Z-100 is an immunomodulatory extract of Mycobacterium tuberculosis strain Aoyama B that contains polysaccharides such as arabinomannan and mannan. Here, we investigated the inhibitory effect of Z-100 on spontaneous lymphatic metastasis. C57BL/6N mice injected subcutaneously with B16-BL6 melanoma cells in the right hind footpad were administered Z-100 subcutaneously in the right inguinal region on a daily basis. On day twenty-one after the injection, the right inguinal lymph nodes were excised, and the extent of metastasis, the number of immune cells, and the amount of granzyme B protein in the lymph nodes were examined. We also investigated the combined effect of Z-100 and irradiation in this model. Results showed that Z-100 reduced number of animals with metastasis, with respective metastasis rates of 85.7%, 42.9%, 7.1% and 0.0% in saline, 0.1 mg/kg Z-100, 1 mg/kg Z-100 and 10mg/kg Z-100 group. Further, mice that had been given Z-100 were found to have more immune cells and granzyme B protein in the lymph nodes than control mice. The combination of low dose Z-100 and irradiation also inhibited spontaneous lymph node metastases. These findings suggest that Z-100 may be beneficial in preventing lymphatic. metastasis by enhancing the immune response.
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LIFE SCIENCES, 89(17-18) 603-608, Oct, 2011 Peer-reviewedAims: As activation and overexpression of the cholecystokinin-2 (CCK-2)/gastrin receptor can lead to carcinogenesis, it has been explored as a therapeutic target in pancreatic cancer. We demonstrated that Z-360, a CCK-2/gastrin receptor antagonist, combined with gemcitabine prolonged survival and reduced gemcitabine-induced vascular endothelial growth factor (VEGF) expression in a pancreatic carcinoma orthotopic xenograft mouse. In this study, we investigated the role of the CCK-2/gastrin signaling pathway on gemcitabine-induced VEGF expression in PANC-1 human pancreatic carcinoma cells. Main methods: In PANC-1 cells treated with Z-360, anti-gastrin IgG or kinase inhibitors, the gene expression levels were analyzed by quantitative real-time RT-PCR, and the protein levels of Akt and phosphorylated Akt (p-Akt) in cellular extracts were measured by ELISA. Key findings: Gemcitabine-induced expression of VEGF and hypoxia-inducible factor-1 alpha (HIF-1 alpha) were suppressed by the treatment with an anti-gastrin antibody. In addition, VEGF and HIF-1 alpha gene expression was inhibited by treatment with an inhibitor of phosphatidylinositol 3-kinase (PI3K), which is involved in the downstream signaling pathway of the CCK-2/gastrin receptor, and was also suppressed by treatment with Z-360. Moreover, although Akt phosphorylation was increased by treatment with gemcitabine, this elevation was partially, but significantly, inhibited by an exposure of Z-360. Significance: Gemcitabine might induce gene expression of VEGF via the PI3K/Akt signaling pathway in the downstream of the CCK-2/gastrin receptor. The suppression of the CCK-2/gastrin signaling pathway by treatment with Z-360 could be a useful approach for potentiating prolonged survival of pancreatic cancer patients receiving gemcitabine therapy. (C) 2011 Elsevier Inc. All rights reserved.
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GASTROENTEROLOGY, 140(5) S603-S603, May, 2011 Peer-reviewed
Misc.
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ヒューマンサイエンス振興財団 日本医療研究開発機構研究費(創薬基盤推進研究事業)創薬技術調査報告書(Part 1), Mar, 2019
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ヒューマンサイエンス振興財団 日本医療研究開発機構研究費(創薬基盤推進研究事業) 創薬資源調査報告書(平成28年度), Mar, 2017
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ヒューマンサイエンス振興財団 日本医療研究開発機構研究費(創薬基盤推進研究事業) 創薬資源調査報告書(平成27年度), Mar, 2016
Teaching Experience
1-
Jun, 2020 - PresentIntroduction to Entrepreneurship (Fujita Health University)
Professional Memberships
6Research Projects
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Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science, Apr, 2023 - Mar, 2027
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Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science, Apr, 2020 - Mar, 2023