2000 Fiscal Year Final Research Report Summary
Therapeutic effects of cytokine gene therapy and suicide gene therapy for gastrointestinal tumors
| Project/Area Number |
11670556
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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 Research Institute, Division of Pathology, Research Fellow, 研究局・病理研究部, 主任研究員 (80260248)
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| Co-Investigator(Kenkyū-buntansha) |
SAISHO Hiromitsu Chiba University, School of Medicine, Professor, 医学部・内科学第一講座, 教授 (10092058)
TAGAWA Masatoshi Chiba Cancer Center Research Institute, Division of Pathology, Head, 研究局・病理研究部, 部長 (20171572)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Gene therapy / Cyotokine / Suicide gene / Transcriptional regulation / IL-12 / IL-15 / IL-18 / HSV-TK |
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| Research Abstract |
(1)We explored possibility of gene therapy for gastrointestinal tumors using cytokine genes that direct Th-1 type T cells. Three cytokine genes, IL-12, IL-15 and IL-18 gene, were cloned with a RT-PCR method. These cytokines induces the differentiation of immature T cells into Th-1 type cells or are secreted from Th-1 type cells. Human pancreatic and murine colon carcinoma cells were retrovirally transduced with the cytokine genes and were inoculated into immunocompetent or immunocompromized mice. Syngeneic mice rejected the cytokine producers and the mice developed tumor-specific, T cell-dependent protective immunity. Anti-tumor effects were also produced in immunocompromized hosts and a number of mechanisms such as anti-angiogenesis were involved in the anti-tumor activity. (2)We took another approarch to express a suicide gene specifically in tumor cells. The promoter region of the midkine gene, whose expression was predominantly observed in a number of gastrointestinal tissues but not in normal tissues, should enable the tumor-specific gene expression. In fact we detected the midkine gene expression in 14 out 15 hepatocellular specimens and identified a 0.5-kb promoter region within the regulatory sequences, which was responsible for preferential expression of a fused foreign gene in tumor cells. Human pancreatic carcinoma cells transduced with the promoter-linked herpes simplex virus-thymidine kinase gene became sensitive to ganciclovir compared with untransduced parent cells.
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Research Products
(20 results)
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[Publications] Miyauchi, M., Shimada, H., Kadomatsu, K., Muramatsu, T., Matsubara, S., Ikematsu, S., Takenaga, K., Asano, T., Ochiai, T., Sakiyama, S.and Tagawa, M.: "Frequent expression of midkine gene in esophageal cancer suggests a potential usage of its promoter for suicide gene therapy"Jpn. J.Cancer Res.. 90. 469-475 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kimura, M., Yoshida, Y., Narita, M., Takenaga, K., Takenouchi, T., Yamaguchi, T., Saisho H., Sakiyama, S.and Tagawa, M.: "Acquired immunity in nude mice induced by expression of the IL-2 or IL-4 gene in human pancreatic carcinoma cells and anti-tumor effect generated by in vivo gene transfer using retrovirus"Int. J.Cancer. 82. 549-555 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yoshida, H., Tanabe, M., Miyauchi, M., Kawamura.K., Takenaga, K., Ohnuma, N., Sakiyama, S.and Tagawa. M.: "Induced immunity by expression of interleukin-2 or GM-CSF gene in murine neuroblastoma cells can generate antitumor response to established tumors."Cancer Gene Ther. 6. 395-401 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Tasaki, K., Yoshida. Y., Maeda, T., Miyauchi, M., Kawamura, K., Takenaga, K., Yamamoto, H., Kouzu, T., Asano, T., Ochiai, T., Sakiyama, S.and Tagawa, M.: "Protective immunity is induced in murine colon carcinoma cells by the expression of interleukin-12 or interleukin-18, which activate type 1 helper T cells."Cancer Gene Ther.. 7. 247-254 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yoshida, Y., Tasaki, K., Miyauchi, M., Narita, M., Takenaga, K., Yamamoto, H., Yamaguchi, T., Saisho, H., Sakiyama, S.and Tagawa, M.: "Impaired tumorigenicity of human pancreatic cancer cells retrovially tranduced with interleukin-12 or interleukin-15 gene"Cancer Gene Ther. 7. 324-331 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kawamura, K., Tasaki, K., Hamada, H., Takenaga, K., Sakiyama, S.and Tagawa, M.: "Expression of Escherichia coli uracil phosphoribosyltransferase g0ene in murine colon carcinoma cells augments the antitumoral effect of 5-fuluorouracil and induces protective immunity."Cancer Gene Ther.. 7. 637-643 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kawamura, K., Namba, H., Bahar, R., Miyauchi, M., Maeda, T., Hamada, H., Sakiyama, S.and Tagawa, M.: "Transduction of the human deoxycytidine kinase gene in rodent tumor cells induces in vivo growth retardation in syngeneic hosts."Cancer Lett. 156. 151-157 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kawamura, K., O-Wang, J., Bahar, R., Koshikawa, N., Shishikura, T.Nakagawara, A., Sakiyama, S., Kajiwara, K., Kimura, M.and Tagawa, M.: "The error-prone DNA polymerase z catalytic subunit(Rev3) gene is ubiquitously expressed in normal and malignant human tissues."Int. J.Oncol.. 18. 97-103 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kawamura, K., H., Bahar, R., Namba, H., Seimiya, M., Takenaga, K., Hamada, H., Sakiyama, S.and Tagawa, M.: "Bystander effect in uracil phosphoribosyltransferase/5-fluorouracil-mediated suicide gene therapy is correlated with the level of intercellular communication"Int. J.Oncol. 18. 117-120 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Miyauchi, M., Yoshida, Y., Tada, Y., Narita, M., Maeda, T., Bahar, R., Kadomatsu, K., Muramatsu, T., Matsubara, S., Nakagawara, A., Sakiyama, S.and Tagawa, M.: "Expression of herpes simplex virus-thymidine kinase gene controlled by a promoter region of the midkine gene confers selective cytotoxicity to ganciclovir in human carcinoma cells."Int. J.Cancer. 91. 723-727 (2001)
Description
「研究成果報告書概要(欧文)」より
