2004 Fiscal Year Final Research Report Summary
Gene therapy for intractable gastrointestinal tumors with tumor promoter-mediated oncolyitc adenoviruses
| Project/Area Number |
15590706
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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 |
Gastroenterology
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| Research Institution | Chiba Cancer Center Research Institute |
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Principal Investigator |
KAWAMURA Kiyoko Chiba Cancer Center Res.Inst., Division of Pathology, Senior Researcher, 病理研究部, 主席研究員 (80260248)
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| Co-Investigator(Kenkyū-buntansha) |
TAGAWA Masatoshi Chiba Cancer Center Res.Inst., Division of Pathology, Head, 病理研究部, 部長 (20171572)
SAISHO Hiromitsu Graduate School of Medicine, Chiba University, Department of Medicine & Clinical Oncology, Professor, 大学院・医学研究院・腫瘍内科学, 教授 (10092058)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Gene Therapy / Tumor promoter / Transcription regulatory region / Oncolytic virus / Midkine / Survivin / E1A / SCID mouse |
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| Research Abstract |
We have constructed adenoviruses in which the E1A transcript was regulated with a 604 bp-regulatory region of the midkine gene (Ad/MK) ; the transcription of the gene is upregulated in a number of human gastrointestinal tumors but is restricted in normal adult tissues. Ad/MK induced greater E1A expression than wild-type Ad (Ad/WT) in human fibroblasts immortalized by the expression of dominant-negative p53 gene, but not in the parent normal fibroblasts. Ad/MK were cytotoxic to the immortalized fibroblasts compared with Ad/WT accordingly. Human hepatocellular carcinoma(HCC) cells were 500 times more susceptible to Ad/MK than normal fibroblasts, and replication of Ad/MK was 1000 times greater than that of Ad/WT in the HCC cells. Intratumoral injection of Ad/MK but not replication-defective Ad suppressed subsequent growth of solid HCC tumors developed in SCID mice. Histological examinations revealed massive necrosis of the tumors injected with Ad/MK. These data suggested that Ad/MK are oncolytic Ad that preferentially destroy tumors. We also examined the feasibility of oncolytic Ad with different a tumor promoter. Expression of the survivin gene is regulated with the cell cycle and is upregulated in tumors ; thereby the regulatory region is a candidate to control E1A expression. We identified a 500-bp region that mediated the preferential expression in tumors and is currently preparing oncolytic Ad with the promoter.
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Research Products
(24 results)
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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 E1 A 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] DNA polymerase θ is preferentially expressed in lymphoid tissues and upregulated in human cancers.2004
Author(s)
Kawamura, K., Bahar, R., Seimiya, M., Chiyo, M., Wada, A., Okada, S., Hatano, M., Tokuhisa, T., Kimura, H., Watanabe, S., Honda, I., Sakiyama, S., Tagawa, M., O-Wang, J.
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Journal Title
Int.J.Cancer 109
Pages: 9-16
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] Elevated expression of DNA polymerase κ expression in human lung cancer is associated with p53 inactivation : Negative regulation of POLK promoter 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] Expression of CD40 ligand in CD40-positive murine tumors activates transcription of the interleukin-23 subunit genes and produces antitumor responses.2004
Author(s)
Wada, A., Tada, Y., Shimozato, O., Takiguchi, Y., Tatsumi, K., Kuriyama, T., Tagawa, M.
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Journal Title
Anticancer Res. 24
Pages: 2713-2716
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] Stage-specific expression of Clast6/E3/LAPTM5 during B cell differentiation : elevated expression in human B lymphomas.2003
Author(s)
Seimiya, M., O-Wang, J., Bahar, R., Kawamura, K., Wang, Y., Saisho, H., Tagawa, M.
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Journal Title
Int.J.Oncol. 22
Pages: 301-304
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Fas ligand-expressing tumors induce tumor-specific protective mmunity in the inoculated hosts but vaccination with the apoptotic tumors suppresses antitumor immunity.2003
Author(s)
Tada, Y., O-Wang, J., Wada, A., Takiguchi, Y., Tatsumi, K., Kuriyama, T., Sakiyama, S., Tagawa, M.
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Journal Title
Cancer Gene Ther. 10
Pages: 134-140
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression of the interleukin-21 gene in murine colon carcinoma cells generates systemic immunity in the inoculated hosts.2003
Author(s)
Ugai, S., Shimozato, O., Kawamura, K., Wang, Y-Q., Yamaguchi, T., Saisho, H., Sakiyama, S, Tagawa, M.
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Journal Title
Cancer Gene Ther. 10
Pages: 187-192
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cell growth- and P53-dependent transcriptional activity of the midkine promoter confers suicide gene expression in tumor cells.2003
Author(s)
Yu, L., Ugai, S., O-Wang, J., Namba, M., Kadomatsu, K., Muramatsu, T., Matsubara, S., Sakiyama, S., Tagawa, M.
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Journal Title
Oncol.Rep. 10
Pages: 1301-1305
Description
「研究成果報告書概要(欧文)」より
