2005 Fiscal Year Final Research Report Summary
Oncolytic adenovirus modified to increase its infectivity for gastrointestinal cancer
| Project/Area Number |
16591381
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Chiba Cancer Research Institute |
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Principal Investigator |
TAGAWA Masatoshi Chiba Cancer Ctr.Res.Inst., Div. of Path., Head, 病理研究部, 部長 (20171572)
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| Co-Investigator(Kenkyū-buntansha) |
OCHIAI Takenori Graduate School of Chiba Univ., Dept. of Academic Surg., Professor, 大学院・医学研究院・先端応用外科, 教授 (80114255)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Gastrointestival tumors / Gene therapy / Transcriptional control region / E1A / E1B region / Oncolytic adenovirus / Fiber region / Suvivin / Shuttle vector |
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| Research Abstract |
Adenovirus (Ad) has a strong cytotoxic activity and the E1A protein, one of the early transcriptional products, has a pivotal role in viral replication in the infected cells. Ad modified to control the E1A gene expression with a putative tumor promoter can thereby be oncolytic. We examined the regulatory regions of the genes which were predominantly expressed in tumors with the luciferase assay and found that a 500 bp and a 600 bp upstream regions of the survivin and midkine genes, respectively, were responsible for the transcriptional control. The cellular receptors of the Ad type 5 is CAR (Coxsackievirus and Adenovirus Receptor) and the expression is often downregulated in gastrointestinal tumors. In contrast, the expression of CD46, which is a receptor of Ad type 35, is rather upregulated in the tumors and consequently, the Ad bearing CD46 binding sites can increase the infectivity to the tumors. We thereby constructed a vector system consisting of vector DNA that could activate the E1A and E1B genes with an exogenous regulatory region and another vector that contained the rest of the whole Ad sequences, in which the fiber-knob region was replaced with the Ad type 35-derived one. In vitro ligation of the vectors enables the construction of the Ad bearing the type 35 fiber-knob structure in the E3 region. The oncolytic Ad with the type 35 fiber-knob can be produced with easy compared with conventional methods that required in vivo recombination. The chimeric oncolytic Ad prepared with our vector system was more cytotoxic to CAR-low human tumors than conventional type 5 oncolytic Ad and was as cytotoxic as the type 5 Ad to CAR-high tumors.
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Research Products
(34 results)
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[Journal Article] Vaccination of apoptotic Fas ligand-expressing tumors decreased antitumor responses by enhanced production of immunosuppressive cytokines.2005
Author(s)
Wada, A., Tada, Y., Shimozato, 0., Takiguchi, Y., Tatsumi, K., Kuriyama, T., Tagawa, M.
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Journal Title
Anticancer Res. 25
Pages: 299-304
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression of IL-27 in murine carcinoma cells produces antitumor effects and induces protective immunity in inoculated host animals.2005
Author(s)
Chiyo, M., Shimozato, O., Yu, L., Kawamura, K., Iizasa, T., Fujisawa, T., Tagawa, M.
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Journal Title
Int.J.Cancer 115
Pages: 437-442
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Recombinant Sendai virus vector induces complete remission of established brain tumors through efficient interleukin -2 gene transfer in vaccinated rats.2005
Author(s)
Iwadate, Y., Inoue, M., Saegusa, T., Tokusumi, Y., Kinoh, H., Hasegawa, M., Tagawa, M., Yamaura, A., Shimada, H.
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Journal Title
Clin.Cancer Res. 11
Pages: 3821-3827
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Increased infectivity of adenovirus type 5 bearing type 11 or type 35 fibers to human esophageal and oral carcinoma cells.2005
Author(s)
Yu, L., Takenobu, H., Shimozato, O., Kawamura, K., Nimura, Y., Seki, N., Ugai, K., Tanzawa, H., Shimada, H., Ochiai, T., Tagawa, M
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Journal Title
Oncol.Rep. 14
Pages: 831-835
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression of the fetal-oncogenic fibroblast growth factor-8/17/18 subfamily in human hematopoietic tumors.2005
Author(s)
Nezu, M., Tomonaga, T., Sakai, C., Ishii, A., Itoga, S., Nishimura, M., Matsuo, Y., Tagawa, M., Nomura, F.
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Journal Title
Biochem.Biophys.Res.Commun. 335
Pages: 843-849
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Up-regulation of the error-prone DNA polymerase x promotes pleiotropic genetic- alterations and tumorigenesis.2005
Author(s)
Bavoux, C., Leopoldino, A.M., Bergoglio, V., O-Wang, J., Ogi, T., Bieth, A., Pena, S.D.J., Poupon, M., Helleday, T., Tagawa, M., Machado, C.R., Hoffmann, J., Cazaux, C.
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Journal Title
Cancer Res. 65
Pages: 325-330
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Insertion of an exogenous promoter in the E1A regulatory region of adenovirus does not disturb viral replication despite reduced E1A transcription.2004
Author(s)
Yu, L., Hamada, K., Namba, M., Kadomatsu, K., Muramatsu, T., Matsubara, S., Tagawa, M.
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Journal Title
Cancer Lett. 203
Pages: 51-57
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Midkine promoter can mediate transcriptional activation of a fused suicide gene in a broader range of human breast cancer compared with c-erbB-2 promoter.2004
Author(s)
Yu, L., Yamamoto, N., Kadomatsu, K., Muramatsu, T., Matsubara, S., Sakiyama S., Tagawa, M.
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Journal Title
Oncology 66
Pages: 143-146
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Elevated expression of DNA polymerase x expression in human lung cancer is associated with p53 inactivation: Negative regulation of POLKpromoter activity by p53.2004
Author(s)
Wang, Y.Q., Seimiya, M., Kawamura, K., Yu, L., Ogi, T., Takenaga, K., Shishikura, T., Nakagawara, A., Sakiyama, S., Tagawa, M., O-Wang, J.
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Journal Title
Int.J.Oncol. 25
Pages: 161-165
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Impaired lymphocyte development and function in Clast5/Stra13/DEC1 transgenic mice.2004
Author(s)
Seimiya, M., Wada, A., Kawamura, K., Sakamoto, A., Ohkubo, Y., Okada, S., Hatano, M., Tokuhisa, T., Watanabe, T., Saisho, H., Tagawa, M., O-Wang, J.
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Journal Title
Eur.J.Immunol. 34
Pages: 1322-1332
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Midkine promoter-driven suicide gene expression and -mediated adenovirus replication produced cytotoxic effects to immortalized and tumour cells.2004
Author(s)
Yu, L., Hamada, K., Namba, M., Kadomatsu, K., Muramatsu, T., Matsubara, S., Tagawa, M.
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Journal Title
Eur.J.Cancer 40
Pages: 1787-1794
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Correlation between interleukin 6 production and tumor proliferation in non-small cell lung cancer.2004
Author(s)
Yamaji, H., Iizasa, T., Koh, E., Suzuki, M., Otsuji, M., Chang, H., Motohashi, S., Yokoi, S., Hiroshima, K., Tagawa, M., Nakayama, T., Fujisawa T.
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Journal Title
Cancer Immunol.Immunother. 53
Pages: 786-792
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A Cox-2 promoter-based replication-selective adenoviral vector to target the Cox-2-expressing human bladder cancer cells.2004
Author(s)
Shirakawa, T., Hamada, K., Zhang, Z., Okada, H., Tagawa, M., Kamidono, S., Kawabata, M., Gotoh, A.
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Journal Title
Cancer Res. 10
Pages: 4342-4348
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Midkine promoter-based conditionally replicative adenovirus for malignant glioma therapy.2004
Author(s)
Kohno, S., Nakagawa, K., Hamada, K., Harada, H., Yamasaki, K., Hashimoto, K., Tagawa, M., Nagato, S., Furukawa, K., Ohnishi, T.
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Journal Title
Oncol Rep. 12
Pages: 73-78
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression of interleukin-22 in murine carcinoma cells did not influence tumor growth in vivo but did improve the survival of inoculated hosts.2004
Author(s)
Nagakawa, H., Shimozato, O., Yu, L., Takiguchi, Y., Tatsumi, K., Kuriyama, T., Tagawa, M.
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Journal Title
Scand.J.Immunol. 60
Pages: 449-454
Description
「研究成果報告書概要(欧文)」より
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