Combinatory use of replication-competent adenoviruses and chemotherapeutic agents produces anti-tumor effects on human esophageal carcinoma cells
Project/Area Number |
23591951
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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 |
Digestive surgery
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Research Institution | Chiba Cancer Center (Research Institute) |
Principal Investigator |
TAGAWA Masatoshi 千葉県がんセンター(研究所), がん治療開発グループ, 部長 (20171572)
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Co-Investigator(Kenkyū-buntansha) |
SHIMADA Hideaki 東邦大学, 医学部, 教授 (20292691)
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Project Period (FY) |
2011 – 2013
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Project Status |
Completed (Fiscal Year 2013)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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Keywords | 遺伝子 / ウイルス / 癌 / 受容体 / 化学療法 / CD46 / 抗腫瘍効果 / 食道がん / アデノウイルス / 細胞死 / p53 / 食道癌 / CD46分子 / 細胞周期 |
Research Abstract |
We examined a novel therapeutic strategy for intractable cancer in particular esophageal carcinoma. We replaced a transcriptional regulatory region of the E1 region-encoded genes in adenoviruses (Ad) with a 5' region of a gene that was highly expressed in human tumors but not in normal tissues such as midkine, survivin and cyclooxygenase-2. We also changed the fiber region of conventional type 5 Ad, which played a key role in infecting target cells, with a type 35-derived fiber region. The modification increased the viral infectivity since an expression level of the CAR molecules, which were a cellular receptor of type 5 Ad, were often down-regulated in human tumors. In contract, the expression of CD46 molecules, which are the major receptor of type 35 Ad, is rather up-regulated in human tumors. The fiber replacement greatly enhanced Ad infectivity in CAR-low tumors and subsequently enhanced the Ad-mediated cytotoxicity, and produced combinatory effects with anti-cancer agents.
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Report
(4 results)
Research Products
(44 results)
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[Journal Article] Combination of adenoviruses expressing melanoma differentiation-associated gene-7 and chemotherapeutic agents produces enhanced cytotoxicity on esophageal carcinoma.2014
Author(s)
Ma, G., Kawamura, K., Yang, S., Okamoto, S., Li, Q., Namba, M., Shingyoji, M., Tada, Y., Tatsumi, K., Hiroshima, K., Shimada, H. and Tagawa, M.
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Journal Title
Cancer Gene Ther.
Volume: 21
Issue: 1
Pages: 31-37
DOI
Related Report
Peer Reviewed
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[Journal Article] Enhanced antitumor efficacy of fiber-modified, midkine promoter-regulated oncolytic adenovirus in human malignant mesothelioma2013
Author(s)
Takagi-Kimura, M., Yamano, T., Tamamoto, A., Okamura, N., Okamura, H., Hashimoto-Tamaoki, T., Tagawa, M., Kasahara, N. and Kubo, S.
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Journal Title
Cancer Sci.
Volume: 104
Issue: 11
Pages: 1433-1439
DOI
Related Report
Peer Reviewed
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[Journal Article] Fiber-substituted conditionally replicating adenovirus for oncolysis of human renal carcinoma cells2012
Author(s)
Nagaya, H., Tagawa, M., Hiwasa, K., Terao, S., Kanno, T., Nishizaki, T. and Gotoh, A.
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Journal Title
Anticancer Res.
Volume: 32
Pages: 2985-2990
URL
Related Report
Peer Reviewed
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[Journal Article] Upregulated p53 expression activates apoptotic pathways in wild-type p53-bearing mesothelioma and enhances cytotoxicity of cisplatin and pemetrexed2012
Author(s)
Li, Q., Kawamura, K., Okamoto, S., Yamanaka, M., Yang, S., Yamauchi, S., Fukamachi, T., Kobayashi, H., Tada, Y., Takiguchi, Y., Tatsumi, K., Shimada, H., Hiroshima, K. and Tagawa, M.
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Journal Title
Cancer Gene Ther
Volume: 19
Issue: 3
Pages: 218-228
DOI
Related Report
Peer Reviewed
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[Journal Article] Fiber-substituted conditionally replicating adenovirus for oncolysis of human renal carcinoma cells.2012
Author(s)
Nagaya, H., Tagawa, M., Hiwasa, K., Terao, S., Kanno, T., Nishizaki, T. and Gotoh, A.
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Journal Title
Anticancer Res.
Volume: 32
Pages: 2985-2990
Related Report
Peer Reviewed
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[Journal Article] A possible anti-cancer agent, type III interferon, activates cell death pathways and produces anti-tumor effects2011
Author(s)
Tagawa, M., Kawamura, K., Li, Q., Tada, Y., Hiroshima, K. and Shimada, H.
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Journal Title
Clin. Dev. Immunol
Volume: 2011
Pages: 1-6
DOI
Related Report
Peer Reviewed
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[Journal Article] Antitumor activity of type III interferon alone or in combination with type I interferon against human non-small-cell lung cancer2011
Author(s)
Fujie, H., Tanaka, T., Tagawa, M., Kaijun, N., Watanabe, M., Suzuki, T., Nakayama, K. and Numasaki, M.
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Journal Title
Cancer Sci.
Volume: 102
Pages: 1977-1990
NAID
Related Report
Peer Reviewed
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[Journal Article] Adenoviruses-mediated transduction of human esophageal carcinoma cells with the interferon-lambda genes produced anti-tumor effects2011
Author(s)
Li, Q., Kawamura, K., Okamoto, S., Fujie, H., Numasaki, M., Namba, M., Nagata, M., Shimada, H., Kobayashi, H. and Tagawa, M.
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Journal Title
Br. J. Cancer
Volume: 105
Issue: 9
Pages: 1302-1312
DOI
Related Report
Peer Reviewed
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[Presentation] Gene therapy for malignant mesothelioma with restored p53 functions.2012
Author(s)
Masatoshi Tagawa, Kiyoko Kawamura, Shan Yang, Yuanyuan Jiang, Kuan Chai, Naoto Yamaguchi, Yuji Tada, Yuichi Takiguchi, Koichiro Tatsumi, Hideaki Shimada, Kenzo Hiroshima.
Organizer
Internatinal Socieity for Cell and Gene Therapy of Cancer 2012
Place of Presentation
シンガポール
Related Report
Invited
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[Book] Mesotheliomas-synonyms and definition, epidemiology, etiology, pathogenesis, cyto-histopathological features, clinic, diagnosis, treatment, prognosis.2012
Author(s)
Fukamachi, T., Saito, H., Tagawa, M. and Kobayashi, H.
Total Pages
244
Publisher
InTech
Related Report
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[Book] Midkine: From embryogenesis to pathogenesis and therapy.2012
Author(s)
Tagawa, M., Kawamura, K., Yu, L., Tada, Y., Hiroshima, K. and Shimada, H.
Total Pages
319
Publisher
Springer-Verlag Gmbh
Related Report
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