2000 Fiscal Year Final Research Report Summary
Suicide gene therapy for gastrointestinal tumors using tumor-specific promoters
| Project/Area Number |
11671298
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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 Center Research Institute |
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Principal Investigator |
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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| Co-Investigator(Kenkyū-buntansha) |
OCHIAI Takenori Chiba University, School of Medicine, Surgery(II), Professor, 医学部・外科学第二講座, 教授 (80114255)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Gene therapy / Promoter / Suicide gene / Transcriptional regulation / c-erbB-2 / Midkine / VEGF |
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| Research Abstract |
Tumor-specific gene expression is important for improved safely and enhanced efficacy of gene therapy for cancer. We then examined promoter regions of the midkine gene which was expressed in tumors but not in normal surrounding tissues or that of the c-erbB-2 and vascular endothelial growth factor gene whose expressions were predominantly found in the tumors of upper gastrointesinal tract and a number of solid tumors, respectively. Our results were as follows. (1)The midkine gene was expressed in 8 out of 14 human esophageal specimens and 14 out of 15 hepatocellular carcinoma specimnens, whereas none of non-tumorous regions of the same patients were negative for the expression. (2)Reporter assays using deletion mutants of the promoter region of the midkine gene showed that the 550-bp fragment was responsible for tumor-specific transcriptional activation. (3)The 250-bp fragment of 5'-upstream region of the c-erbB-2 gene strongly drove the transcription of the fused reporter gene in tumors but not in normal fibroblasts. (4)The 1.2-kb promoter region of the vascular endothelial growth factor gene had a cis-acting element for hypoxic responsiveness. (5)Forced expression of the herpes simplex virus-thymine kinase gene using these linked promoters conferred increased sensitivity of the transfected vells to ganciclovir. (6)The deoxycytidine kinase/ara-C and the uracil phosphoribosyl transferase/5-FU systems were useful for cell killing together with an appropriate promoter.
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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] Matsubara, H., Kimura, M., Sugaya, M., Koide, Y., Gunji, Y., Takegana, K., Asano, A., Ochiai, T., Isono, K., Sakiyama, S.and Tagawa, M.: "Expression of wild-type p53 gene confers increased sensitivity to radiation and chemotherapeutic agents in human esophageal carcinoma cells."Int. J.Oncol. 14. 1081-1085 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Maeda, T., Matsubara, H., Sugaya, M., Miyazawa, Y., Gunji, Y., Ochiai, T., Sakiyama, S.and Tagawa, M.: "Loss of tumorigenicity of human breast cancer cells engineered to produce IL-2, IL-4 or GM-CSF in nude mice."Int. J.Oncol.. 15. 943-947 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Matsubara, H., Kawamura, K., Sugaya, M., Koide, Y., Gunji, Y., Takenaga, K., Asano, T., Ochiai, T., Sakiyama, S.and Tagawa, M.: "Differential efficacy of suicide gene therapy by herpes simplex virus-thymidine kinase gene reflects the status of p53 gene in human esophageal cancer cells."Anticancer Res.. 19. 4157-4160 (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] Tasaki, K., Yoshida, Y., Miyauchi, M., Maeda, T., Takenaga, K., Kouzu, T., Asano, T., Ochiai, T., Sakiyamna, S.and Tagawa, M.: "Transduction of murine colon carcinoma cells with interleukin-15 gene induces antitumor effects in immunocompetent and immunocompromised hosts."Cancer Gene Ther.. 7. 255-261 (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 deoxycytidinekinase 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] 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 congers 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
