| Project/Area Number |
14207090
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | The University of Tokushima |
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Principal Investigator |
SATO Mitsunobu The University of Tokushima, Graduate School, Institute of Health Bioscience, Professor, 大学院・ヘルスバイオサイエンス研究部, 教授 (00028763)
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| Co-Investigator(Kenkyū-buntansha) |
AZUMA Masayuki The University of Tokushima, Graduate School, Institute of Health Bioscience, Associate Professor, 医学部・歯学部附属病院, 講師 (20144983)
OKAMOTO Masato The University of Tokushima, Graduate School, Institute of Health Bioscience, Assistant Professor, 大学院・ヘルスバイオサイエンス研究部, 助手 (10243718)
HARADA Koji The University of Tokushima, Graduate School, Institute of Health Bioscience, Assistant Professor, 大学院・ヘルスバイオサイエンス研究部, 助手 (60253217)
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥50,440,000 (Direct Cost: ¥38,800,000、Indirect Cost: ¥11,640,000)
Fiscal Year 2005: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2004: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2003: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Fiscal Year 2002: ¥26,390,000 (Direct Cost: ¥20,300,000、Indirect Cost: ¥6,090,000)
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| Keywords | Oral cancer / Toll-like receptor 4 / MD-2 / OK-432 / UFT / Radiation / Lipoteichoic acid-related molecule / NF-κB / Toll-like receptor4 / 抗腫瘍免疫療法剤OK-432 / リポタイコ酸関連分子OK-PSA / Toll様受容体4 / テガフール / 樹状細胞(DC) / DC局所療法 / リポタイコ酸 / NF-kB |
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| Research Abstract |
Of 67 oral cancer patients who received OK-432,UFT in combination with radiation therapy (RT), complete remission (CR) was observed in 38 cases (56.7%), partial response in 29 cases (43.3%). Response rate was 100%. Of 14 patients received RT+UFT without OK-432,CR was observed only in 2 cases (14,3%). Therapeutic effect of this protocol was almost completely dependent on the expression of Toll-like receptor (TLR) 4 and MD-2 genes on peripheral blood mononuclear cells derived from the patients. We have isolated an active component from the OK-432, a lipoteichoic acid-related molecule designated OK-PSA. OK-PSA induced the maturation of human dendritic cells (DCs), and OK-PSA-treated DCs stimulated allogeneic T cells to produce IFN-γ, and to induce allo-antigen specific cytotoxic T cells. These activities of OK-PSA were also dependent on the gene expression of TLR4 and MD-2. Next, we encapsulated OK-PSA with poly (lactide-co-glycolide) micro-particles, and designated PLG-OK-PSA. In tumor-bearing mice, PLG-OK-PSA augmented the anti-cancer effect of RT and UFT far better than OK-PSA as well as OK-432,and CR was observed in most of the animals bearing tumors. Th1-type cytokines and nitric oxide were detected in the sera derived from the mice administered PLG-OK-PSA. The increased cytotoxic activities of the lymphocytes were also observed. These effects of OK-432,OK-PSA as well as PLG-OK-PSA were not observed in TLR4-mutant and in TLR4-deficient mice. It was greatly suggested that RT+UFT+OK-432 therapy is effective for the regulation of oral cancer, that TLR4 signaling is involved in anti-cancer effect of this therapy, and that PLG-OK-PSA may be useful tool for treating human cancer.
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