2001 Fiscal Year Final Research Report Summary
Development of novel diagnostic device using lesion-orieinted biomagnetic probe
| Project/Area Number |
12557055
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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 |
Gastroenterology
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| Research Institution | Keio University |
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Principal Investigator |
HIBI Toshifumi Keio University, School of Medicine, Professor, 医学部, 教授 (50129623)
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| Co-Investigator(Kenkyū-buntansha) |
MAKABE Toshiaki Keio University, Dept of Science & Technology, Professor, 理工学部, 教授 (60095651)
SUEMATSU Makoto Keio University, School of Medicine, Professor, 医学部, 助教授 (00206385)
KITAJIMA Masaki Keio University, School of Medicine, Professor, 医学部, 教授 (90112672)
WATANABE Mamoru Tokyo Medical & Dental Univ. Dept. of Medicine, Professor, 医学部, 教授 (10175127)
NOMURA Tatsuji Central Laboratories for Experimental Animals, Director, 所長(研究職) (10072399)
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| Project Period (FY) |
2000 – 2001
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| Keywords | colon cancer / heme / liposome / biomagnetic probe / plasma / LHK antibody / in vivo tissue staining |
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| Research Abstract |
Current diagnostic approaches using monoclonal antibodies are performed by immunohistochemical staining of tissue samples taken invasively. A technology that we try to bring in practical use is visualization of tissue with certain antigen with ESR-CT or NMR-CT noninvasively following the administration of biomagnetic probe, i.e., monoclonal antibody aginst the antigen conjugated with liposome including heme-NO complex or Fe_2O_3. This in vivo staining using magnetic agent is novel diagnostic approach which have never performed and will be a epoch-making device of diagnosing numerous diseases.
In the present study, we focused on colon cancer as prototype target. To seek the specific antigen expressed on colon cancer cells, we immnized mice with colon cancer cell line colo205 and screened the antibodies raised. We obtained one monoclonal antibody, named LHK antibody, and this antibody induced apoptotic cell death to colon cancer cells. LHK antigen was also expressed by normal intestinal epithelial cell, pancreas and spleen. Further examination revealed that LHK antigen was distinct from Fas and TNF receptor, suggesting that LHK antigen regulated the homeostasis of epithelial cells by inducing apoptosis. We next sought most suitable material for biomagnetic probe. In this study, we demonstrated that heme could be methoxized in the presence of excess amount of NO and that it could form α-heme-NO complex by adjusting the concentration of NO. By including this conplex in the liposome, we will be able to send this biomagnetic probe to anywhere in the body, expecially to the site of inflammation or malignant tumor because the vascular permeability is increased in such disorders. These antigen-specific biomagnetic probe may provide the potential diagnostic tool as well as the therapeutic weapon against various diseases including cancer.
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[Publications] Kanai T, Watanabe M, Okazawa A, Sato T, Yamazaki M, Okamoto S, Ishii H, Totsuka T, liyama R, Okamoto R, Ikeda M, Kurimoto M, Takeda K, Akira S, Hibi T: "Macrophage-derived IL-18-mediated intestinal inflammation in'the murine model of Crohn's disease"Gastroenterology. 121. 875-88 (2001)
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