1998 Fiscal Year Final Research Report Summary
Application of midkine to diagnosis and treatment of tumors and growth of blood stem cells.
| Project/Area Number |
09557016
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
MURAMATSU Takashi School of Medicine, Nagoya University, Professor, 医学部, 教授 (00030891)
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| Co-Investigator(Kenkyū-buntansha) |
KUROSAWA Nobuyuki School of Medicine, Assistant Professor, 医学部, 助手 (50241253)
SAKUMA Sadatoshi Meiji Cell Technology Center, Director, 所長(研究職)
KADOMATSU Kenji School of Medicine, Associate Professor, 医学部, 助教授 (80204519)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Midkine / Enzyme-linked immunoassay / Tumor marker / Splicing / Lymphnode metastasis / Bone fracture / Gene therapy / Inflammation |
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| Research Abstract |
Large scale survey of serum midkine levels determined by enzyme-linked immunoassay revealed that in more than 80% cases of cancer patients, the serum midkine levels increased as compared to that of normal human subjects. Midkine levels may be used as a tumor marker. Tumor specificity of truncated midkine mRNA was further confirmed, and all cases of lymph node metastasis had truncated midkine mRNA.Thus, the truncated mRNA can be a marker to detect minor metastasis upon surgical operation by using PCR.We also found that midkine mRNA expression was increased in adenoma before development of colon carcinoma. Midkine was expressed in 8 cases among 14 cases of esophageal carcinoma, but not in the normal tissues. The 2.3 kb 5 upstream region of midkine gene contains a promoter sequence, which enabled expression of downstream genes in esophageal carcinoma cells. Thymidine kinase gene was placed under the promoter and transfected to the carcinoma cells, resulting in increased sensitivity to ganciclovir. Thus, a strategy of cancer therapy was proposed using the MK promoter. Midkine was expressed at the site of bone fracture. Introduction of midkine cDNA and overexpression induced differentiation of prechondrocytes. Midkine may be applied to cure of bone fracture. Midkine deficient mice were more susceptible to renal toxicity of cisplatin. Midkine may be useful in reducing toxicity of anti-cancer drugs. Midkine promoted migration of macrophages as well as neutrophils. In midkine deficient mice, macrophage migration and neointima formation did not occur upon balloon injury model. This finding implicated that midkine promoted migration of inflammatory cells and contributed to formation of pathological status.
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[Publications] Aridome, K., Takao, S., Kaname, T., Kadomatsu, K., Natsugoe, S., Kojima, F., Aikou, T.and Muramatsu, T.: "Truncated midkine as a marker of diagnosis and detection of nodal metastases in gastrointestinal carcinomas" Brit.J.Cancer. 78. 472-477 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Ye, C., Qi, M., Fan, Q.-W., Ito, K., Akiyama, S., Kasai, Y., Matsuyama, M., Muramatsu, T.and Kadomatsu, K.: "Expression of midkine in the early stage of carcinogenesis in hman colorectal cancer" Brit.J.Cancer. 79. 179-184 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Mochizuki, R., Takeda, A., Sato, N., Kimpara, T., Onodera, H., Itoyama, Y.and Muramatsu, T.: "Induction of midkine expression in reactive astrocytes following rat trasient forebrain ischemia." Exp.Neurol.149. 73-78 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Nakamura, E., Kadomatsu, K., Yuasa, S., Muramatsu, H., Mamiya, T., Nabeshima, T., Fan, Q.-W., Ishiguro, K., Igakura, T., Matsubara, S., Kaname, T., Horiba, M., Saito, H.and Muramatsu, T.: "Disruption of the midkine gene (Mdk) resulted in altered expression of a calcium binding protein in the hippocampus of infant mice and their abnormal behavior" Genes to Cells. 3. 811-822 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Yamakawa, T., Kurosawa, N., Kadomatsu, K., Matsui, T., Itoh, K., Maeda, N., Noda, M.and Muramatsu, T.: "Levels of expression of pleiotrophin and protein tyrosine phosphatase zeta are decreased in human colorectal cancer" Cancer Lett.(in press).
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「研究成果報告書概要(欧文)」より
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[Publications] Ohta, S., Muramatsu, H., Senda, T., Zou, K., Iwata, H.and Muramatsu, T.: "Midkine is expressed during repair of bone fracture and promotes chondrogenesis" J.Bone Miner.Res.(in press).
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「研究成果報告書概要(欧文)」より
