Analysis of mechanism of intravesical BCG therapy for bladder cancer
Project/Area Number |
22591780
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Urology
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Research Institution | Nippon Medical School |
Principal Investigator |
TAKAHASHI Hidemi 日本医科大学, 大学院・医学研究科, 教授 (40221361)
|
Project Period (FY) |
2010 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | 樹状細胞(DC) / BCG / DEC-205陽性DC / 共刺激分子 / NKT細胞 / γδ型T細胞 / ランゲルハンス細胞(LC) / γδ型T細胞 / LAM / MHC / 共刺激分子群 / γσ型T細胞 / CD1 |
Research Abstract |
Intravesical bacillus Calmette-Guerin (BCG) therapy is considered the most successful immunotherapy against solid tumor of human bladder carcinoma, but the precise anti-tumor mechanism is still unknown. BCG-susceptible dendritic cells (DCs) have been thought as key cells to induce tumor-specific immunity. However, because these DCs will not be tumorcells generally and thus, they can present antigenic molecule obtained from external tumors via class II MHC molecules, by which tumor-specific class-I MHC molecule-restricted CD8-positive cytotoxoc T lymphocytes (CTLs) will not be generated. Nevertheless, recent findings demonstrated that DC-subpopulation expressing DEC-205 can present captured antigenic molecules associated with their class I MHC by “cross-presentation”. In this study, we found that we could selectively activate DEC-205-expressing DCs when they were stimulated with viable BCG. Because such viable BCG seems to be toxic to DCs, we have currently examined the non-toxic components of BCG such as micolic acid or lipoaravinomannan (LAM) and found that these BCG-derived components have a potency to stimulate DEC-205-positive DCs. Based on the observation, we are trying to provide a new safer immunotherapy for human bladder carcinoma.
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Report
(4 results)
Research Products
(82 results)
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[Journal Article] E-cadherin interactions are required forLangerhans cell differentiation.2013
Author(s)
Mayumi, N., Watanabe, E., Norose, Y., Watari, E., Kawana, S., Geijtenbeek, T.B., and Takahashi, H
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Journal Title
Eur.J. Immunol
Volume: 43(1)
Pages: 270-280
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[Journal Article] Marrow stromal cells induce B7-H1 expression on myeloma cells, generating aggressive characteristics in multiple myeloma2013
Author(s)
Tamura, H., Ishibashi, M., Tonosaku, S., Okuyama, N., Kondo, A., Hyodo, H., Shinya, E., Takahashi, H., Dong, H., Tamada, K., Chen, L., Dan, K., and Ogata, K
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Journal Title
Leukemia
Volume: 27(2)
Pages: 464-472
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[Journal Article] Induction ofapoptosis-resistant andTGF-β-insensitive murine CD8+ CTLs specific for HIV-1 gp160.2013
Author(s)
Takaku, S., Nakagawa, Y., Owaki, A., Shimizu, M., Takahashi, M., and Takahashi, H.
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Journal Title
Cell. Immunol
Volume: 280(2)
Pages: 138-147
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[Journal Article] C. Ribavirin downmodulates inducible costimulator on CD4+ T cells and their interleukin-10 secretion to assist in hepatitis C virus clearance.2012
Author(s)
Atsukwa, M., Nakatsuka, K., Kobayashi, T., Shimizu, M., Tamura, H., Harimoto, H., Takahashi, H.and Sakamoto
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Journal Title
J. Gastroenterol. Hepatol
Volume: 27(4)
Pages: 823-831
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[Journal Article] Disruption of maternal immune balance maintained by innate DC subsets results in spontaneous pregnancy loss in mice.2012
Author(s)
Negishi, Y., Wakabayashi, A., Shimizu, M., Ichikawa, T., Kumagai, Y., Takeshita, T., and Takahashi, H
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Journal Title
Immunobiology
Volume: 217(10)
Pages: 951-961
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[Journal Article] C. Ribavirin modulates the conversion of human CD4(+) CD25(-) T cell to CD4(+) CD25(+) FOXP3(+) T cell2012
Author(s)
Kobayashi, T., Nakatsuka, K., Shimizu, M., Tamura, H., Shinya, E., Atsukawa, M., Harimoto, H., Takahashi, H. and Sakamoto
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Journal Title
Immunology
Volume: 137(3)
Pages: 259-270
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[Journal Article] Disruption of maternal immune balance maintained by innate DC subsets results in spontaneous pregnancy loss in mice2012
Author(s)
Negishi, Y., Wakabayashi, A., Shimizu, M., Ichikawa, T., Kumagai, Y., Takeshita, T., Takahashi, H.
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Journal Title
Immunobiology
Volume: 217(Jan 13, 2012 on line published)
Issue: 10
Pages: 951-961
DOI
Related Report
Peer Reviewed
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[Journal Article] Production of Auto-antibodies by Murine B-1a Cells Stimulated with Helicobacter pylori Urease through TLR2 Signaling2011
Author(s)
Kobayashi, F., Watanabe, E., Nakagawa, Y., Yamanishi, S., Norose, Y., Fukunaga, Y., and Takahashi, H
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Journal Title
Infect. Immun
Volume: 79
Pages: 4791-4801
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[Journal Article] Characterization of recombinant Streptococcus mitis-derived human platelet aggregation factor.2011
Author(s)
Ohkuni, H., Nagamune, H., Ozaki, N., ,Tabata, A., Todome, Y., Watanabe,Y., Takahashi, H., Ohkura, K., Kourai, H., Ohtsuka, H., Fischetti, V.A., and Zabriskie, J.B.
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Journal Title
APMIS
Volume: 120
Pages: 56-71
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[Journal Article] Ribavirin down-modulate ICOS on CD4+ T-cells and the interleukin-10 secretion to assist clearance of hepatitis C virus2011
Author(s)
Atsukawa, M., Nakatsuka, K., Kobayashi, T., Shimizu, M., Harimoto, H., Takahashi, H., Sakamoto, C.
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Journal Title
J.Gastroenterol.Hepatol.
Volume: 26
Issue: 4
Pages: 823-831
DOI
Related Report
Peer Reviewed
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[Journal Article] Production of auto-antibodies by murine B-1a cells stimulated with Helicobacter pylori urease through TLR2 signaling2011
Author(s)
Kobayashi, F., Watanabe, E., Nakagawa, Y., Yamanishi, S., Norose, Y., Fukunaga, Y., Takahashi, H.
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Journal Title
Infect Immun.
Volume: 79
Pages: 4791-4801
Related Report
Peer Reviewed
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[Journal Article] Characterization of recombinant Streptococcus mitius-derived human platelet aggregation factor2011
Author(s)
Ohkuni, H., Nagaume, H., Ozaki, N., Tabata, A., Todome, Y., Watanabe, Y., Takahashi, H., Fischetti H., Zabriskie, J.B.
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Journal Title
APMIS
Volume: 120
Pages: 56-71
Related Report
Peer Reviewed
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[Journal Article] Transformation of breast milk macrophages by HTLV-I: implications for HTLV-I transmission via breastfeeding.2010
Author(s)
Takeuchi, H., Takahashi, M., Norose, Y.,Takeshita, T., Fukunaga, Y., K., Takahashi, H.
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Journal Title
Biomedical Res.
Volume: 31
Pages: 53-61
NAID
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[Journal Article] Small intestine CD4+ cell reduction and enteropathy in SHIV-KS661-infected rhesus macaques in presence of low viral load.2010
Author(s)
Inaba, K., Fukazawa, Y., Matsuda, K., Himeno, A., Matsuyama, M., Ibuki, K., Miura, Y., Koyanagi, Y., Nakajima, A., Blumberg, R. S., Takahashi, H., Hayami, M., Igarashi, T., Miura, T.
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Journal Title
J. Gen. Virol
Volume: 91
Pages: 773-781
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[Journal Article] Effect of probiotic bacterial strains of Lactobacillus, Bifidobacterium and Enterococcus on enteroaggregative Echerichia coli.2010
Author(s)
Miyazaki, Y, Kamiya, S., Hanawa, T., Fukuda, M., Kawakami, H., Takahashi, H., Yokota, H.
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Journal Title
J. Infect. Chemother
Volume: 16
Pages: 10-18
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[Journal Article] Inhibition ofDC-SIGN-mediated transmission ofHIV-1 by TLR3 signaling in breast milk macrophages2010
Author(s)
Yagi, Y., Watanabe, E., Watari, E., Shinya, E., Satomi, M., Takeshita, T., Takahashi, H.
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Journal Title
Immunology
Volume: 130
Pages: 597-607
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[Journal Article] Induction of tumor-specific acquired immunity against already established tumors by selective stimulation of innate DEC-205(+) dendritic cells.2010
Author(s)
Moriya, K., Wakabayashi, A., Shimizu, M., Tamiura, H., Dan, K., Takahashi, H.
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Journal Title
Cancer Immunol. Immunother
Volume: 59
Pages: 1083-1095
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[Journal Article] Interferon- gamma and tumor necrosis factor-alpha induce an immunoinhibitory molecule, B7-H1, via nuclear factor-kappaB activation in blasts in myelodysplastic syndromes2010
Author(s)
Kondo, A, Yamashita, T., Tamura, H., Zhao, W., Tsuji, T., Shimizu, M., Shinya, E., Takahashi, H., Tamada, K., Chen, L., Dan, K., Ogata, K
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Journal Title
Blood
Volume: 116
Pages: 1124-1131
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[Journal Article] Transformation of breast milk macrophages by HTLV-I : implications for HTLV-I trans-mission via breastfeeding.2010
Author(s)
Takeuchi, H., Takahashi, M., Norose, Y., Takeshita, T., Fukunaga, Y., K., Takahashi, H.
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Journal Title
Biomedical Res.
Volume: 31
Pages: 53-61
Related Report
Peer Reviewed
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[Journal Article] Small intestine CD4+ cell reduction and enteropathy in SHIV-KS661-infected rhesus macaques in presence of low viral load.2010
Author(s)
Inaba, K., Fukazawa, Y., Matsuda, K., Himeno, A., Matsuyama, M., Ibuki, K., Miura, Y., Koyanagi, Y., Nakajima, A., Blumberg, R.S., Takahashi, H., Hayami, M., Igarashi, T., Miura, T
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Journal Title
J.Gen Virol.
Volume: 91
Pages: 773-781
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Peer Reviewed
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[Journal Article] Inhibition of DC-SIGN-mediated transmission of HIV-1 by TLR3 signaling in breast milk macrophages.2010
Author(s)
Yagi, Y., Watanabe, E., Watari, E., Shinya, E., Satomi, M., Takeshita, T., Takahashi, H.
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Journal Title
Immunology
Volume: 130
Pages: 597-607
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Peer Reviewed
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[Journal Article] Induction of tumor-specific acquired immunity against already established tumors by selective stimulation of innate DEC-205(+)dendritic cells.2010
Author(s)
Moriya, K., Wakabayashi, A., Shimizu, M., Tamiura, H., Dan, K., Takahashi, H.
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Journal Title
Cancer Immunol Immunother.
Volume: 59
Pages: 1083-1195
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Peer Reviewed
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[Journal Article] Interferon- gamma and tumor necrosis factor-alpha induce an immunoinhibitory molecule, B7-H1, via nuclear factor-kappaB activation in blasts in myelodysplastic syndromes.2010
Author(s)
Kondo, A, Yamashita, T., Tamura, H., Zhao, W., Tsuji, T., Shimizu, M., Shinya, E., Takahashi, H., Tamada, K., chen, L., Dan, K., Ogata, K.
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Journal Title
Blood
Volume: 116
Pages: 1124-1131
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Peer Reviewed
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[Book] 微生物学2012
Author(s)
高橋秀実
Total Pages
664
Publisher
メディカル・サイエンス・インターナショナル社
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