The development of effective therapy by the inhibition of cell proliferation and invasion in oral cancer
| Project/Area Number |
16390598
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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 | Meikai University |
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Principal Investigator |
FUKUDA Masakatsu Meikai University, Dentistry, Assistant Professor, 歯学部, 講師 (10311614)
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| Co-Investigator(Kenkyū-buntansha) |
KUSAMA Kaoru Meikai University, Dentistry, Professor, 歯学部, 教授 (20130479)
SAKASHITA Hideaki Meikai University, Dentistry, Professor, 歯学部, 教授 (10178551)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥11,600,000 (Direct Cost: ¥11,600,000)
Fiscal Year 2006: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥5,100,000 (Direct Cost: ¥5,100,000)
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| Keywords | oral cancer / CYLD / NF-κB / gene alteration / NCAM / apoptosis / perineural invasion / adenoid cystic carcinoma / 頭頚部悪性腫瘍 / NF-kB |
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| Research Abstract |
(1)Biopsy specimens were obtained from 17 patients with ACC treated in the Dept. of Oral and Maxillofac. Surg., Meikai Univ. Hospital, Japan. The positive reaction for MAb NCAM was observed on the cell membrane of cancer cells in 12 of 17 cases of ACC (70.6%). The immunohistochemical findings showed that NCAM immunoreactivity was sporadically and/or aggregately found in the cribriform and duct-like structure, especially perineural invasive cancer cells of ACC tissues. Although no significant association was found between expression of NCAM and clinicopathological variables, NCAM might be significantly associated with tumor development of ACC.
(2)CYLD and NF-κB were spontaneously expressed in HSG cells and both were increased by stimulation of TNF-α. Although the expression of NF-κB and NCAM was inhibited by cimetidine, CYLD expression was not decreased. Maximum NF-κB -dependent transcription was observed at 4 h. Luciferase activities in HSG cells were time-dependently decreased in respo
… More
nse to 10^<-4>M cimetidine from 4 h after stimulation.
(3)The adhesion of HSG cells to neural cells was inhibited by cimetidine in a dose-dependent manner.
(4)Mice were inoculated with HSG (1 × 10^6 cells) percutaneously. Cimetidine prevented the growth of HSG tumor mass in a dose-dependent manner.
(5)CYLD was clearly observed on the membrane and in the cytoplasm of cancer cells in 10 of 17 cases (58.8%) of ACC, whereas RelA was observed in the cytoplasm in 12 cases (70.6%). IκBα was observed in the nucleus in 13 cases (76.5%). IKKα was strongly observed in the cytoplasm of cancer cells in 14 cases (82.4%), and IKKβ was weakly observed in the cytoplasm in 4 cases. CYLD may be dysfunctional in ACC cases where CYLD is not detectable, or that NF-κB is activated despite the expression of CYLD. Up to date, although the analysis of CYLD gene alteration in 10 cases of ACC was finished, there was no alteration. These findings suggest that the growth, development and perineural/neural invasion of salivary gland tumor cells can be blocked by cimetidine administration through down-regulation of NCAM expression as well as by induction of apoptosis. Less
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Report
(4 results)
Research Products
(27 results)
