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Application of midkine to diagnosis and treatment of tumors and growth of blood stem cells.

Research Project

Project/Area Number 09557016
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Pathological medical chemistry
Research InstitutionNagoya University

Principal Investigator

MURAMATSU Takashi  School of Medicine, Nagoya University, Professor, 医学部, 教授 (00030891)

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)
村松 寿子  名古屋大学, 医学部, 助手 (50182134)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1998: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1997: ¥8,100,000 (Direct Cost: ¥8,100,000)
KeywordsMidkine / Enzyme-linked immunoassay / Tumor marker / Splicing / Lymphnode metastasis / Bone fracture / Gene therapy / Inflammation / ヘパリン / 肺癌 / 腎透析 / 成長因子
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.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Kuniaki Aridome: "Truncated midkine as a marker of diagnosis and detection of nodal metastases in gastrointestinal carcinomas" Brit.J.Cancer. 78. 472-477 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] C.Ye: "Expression of midkine in the early stage of carcinogenesis in hman colorectal cancer" Brit.J.Cancer. 79. 179-184 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Rumiko Mochizuki: "Induction of midkine expression in reactive astrocytes following rat trasient forebrain ischemia." Exp.Neurol.149. 73-78 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Eishin Nakamura: "Disruption of the midkine gene (Mdk) resulted in altered expression of a calcium binding protein in the hippocampus of infant mice and their abnormal behaviour" Genes to Cells. 3. 811-822 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Taishi Yawakawa: "Levels of expression of pleiotrophin and protein tyrosine phosphatase ζ are decreased in human colorectal cancers," Cancer Lett.印刷中. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Susumu Ohta: "Midkine is expressed during repair of bone fracture and promotes chondrogenesis" J.Bone Miner.Res.印刷中. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [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).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [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).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuniaki Aridome: "Truncated midkine as a marker of diagnosis and detection of nodal metastases in gastrointestinal carcinomas" Brit.J.Cancer. 78. 472-477 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] C.Ye: "Expression of midkine in the early stage of carcinogenesis in hman colorectal cancer" Brit.J.Cancer. 79. 179-184 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Rumiko Mochizuki: "Induction of midkine expression in reactive astrocytes following rat trasient forebrain ischemia." Exp.Neurol.149. 73-78 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Eishin Nakamura: "Disruption of the midkine gene (Mdk) resulted in altered expression of a calcium binding protein in the hippocampus of infant mice and their abnormal behaviour" Genes to Cells. 3. 811-822 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Taishi Yawakawa: "Levels of expression of pleiotrophin and protein tyrosine phosphatase ζ are decreased in human colorectal cancers," Cancer Lett.(印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Susumu Ohta: "Midkine is expressed during repair of bone fracture and promotes chondrogenesis" J.Bone Miner.Res.(印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Song, X-J. ら: "The serum level of midkine, a heparin-binding growth fuctor, as a tumor marker." Biomed. Res.18. 375-381 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mishima, K., ら: "Increased expression of midkine during the progression of human astrocytomas." Neurosci. Lett.233. 29-32 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Aridome, K. ら: "Truncated midkine as a marker of diagnosis and detection of nodal metastases in gastrointestinal carcinomas." British J. Cancer. (印刷中). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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