2006 Fiscal Year Final Research Report Summary
Search of Molecular Targets for Oral Cancer by Proteome Analysis and Its Application for Order-Made Therapy
| Project/Area Number |
17390539
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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 | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Hiroshima University |
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Principal Investigator |
OKAMOTO Tetsuji Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (00169153)
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| Co-Investigator(Kenkyū-buntansha) |
TORATANI Shigeaki Hospital, Assistant Professor, 病院・講師 (90172220)
HAYASHIDO Yasutaka Hospital, Assistant Professor, 病院・講師 (70243251)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Oral Squamous Cell Carcinoma / MICA / Cell Therapy / HBp17 / FGFBP / Proteome Analysis / DNA microarray / Super-selective intra-arterial Catheter Therapy / Suscebility for Oral Cancer |
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| Research Abstract |
Evasion from NKG2D-mediated tumour immunosurveillance has been attributed to proteolytical shedding of MICA molecules. The binding of soluble MICA (sMICA) has been reported to induce the endocytosis and degradation of cell surface NKG2D, causing impairment of the responsiveness of tumor antigen-specific effector T cells. This systemic immune deficiency is associated with circulating tumour-derived sMICA encompassing the three extracellular domains which is released by tumor cells at high levels into the sera of oral cancer patients.
We have demonstrated that the release' of MICA from tumor cells is blocked by the inhibition of MMPs, resulting in the accumulation of MICA at the cell surface. Compared to normal tissue, their expression and activation is increased in almost all human cancers. Particularly MMP-2,-9 are highly expressed in oral carcinomas. This high expression of MMP-2,-9 in the OSCC cells has been found to depend on TGF-□ A novel aspect of TGF-□ as a central mediator of imm
… More
une evasion by OSCC cells is its influence on NKG2D-mediated antitumor responses. This is because the shedding of MICA from the surface of OSCC cells is mediated by MMPs which in turn are under the control of TGF-□ Inhibition via siRNA technology leads to an increase in MICA, and suppression in MMPs activity, leading to an increase in surface MICA levels. TGF-1/2 siRNA transfectants show that MICA have additive functions in triggering NKG2D, indicating that an anti-tumor immune response depends on the expression level of each NKG2DL at the cell surface of transformed or infected cells. These observations suggest a prominent role for the NKG2DL, MICA and in oral cancer immune surveillance, while the other ligands may exert their immune-stimulatory functions under different conditions.
These observations confirm that TGF-□ is central to the malignant progression of oral cancer and a principle target for the treatment of oral cancer. Anti-TGF-□ therapies may therefore not only relieve the immune dysfunction in human cancer patients, but also inhibit MMP-activity and restore MICA expression to the levels required for an effective anti-oral cancer immune response. Less
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Research Products
(16 results)
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[Journal Article] Zooxanthellamide D, a Polyhydroxy Polyene Amide from a Marine Dinoflagellate, and Chemotaxonomic Perspective of the Symbiodinium Polyols.2007
Author(s)
Fukatsu T, Onodera KI, Ohta Y, Oba Y, Nakamura H, Shintani T, Yoshioka Y, Okamoto T, Lohuis MT, Miller DJ, Kawachi M, Ojika M.
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Journal Title
J Nat Prod. Mar 23 70(3)
Pages: 407-411
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Leukemia inhibitory factor as an anti-apoptotic mitogen for pluripotent mouse embryonic stem cells in a serum-free medium without feeder cells2005
Author(s)
Furue, M., Okamoto, T., Hayashi, Y., Okochi, H., Fujimoto, M., Myoishi, Y., Abe, T., Ohnuma, K., Sato, G.H., Asashima, M., Sato, J.D.
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Journal Title
In Vitro Cell Dev Biol Anim. Jan-Feb;41(1-2)
Pages: 19-28
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Modulation of activin A-induced differentiation in vitro by vascular endothelial growth factor in Xenopus presumptive ectodermal cells.2005
Author(s)
Yoshida S., Furue M., Nagamine K., Abe T., Fukui Y., Myoishi Y., Fujii T., Okamoto T., Taketani Y., Asashima, M.
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Journal Title
In Vitro Cell Dev Biol Anim. Mar-Apr;41(3-4)
Pages: 104-10
Description
「研究成果報告書概要(欧文)」より
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