2005 Fiscal Year Final Research Report Summary
Development of a novel combined chemotherapy in head and neck cancer-combination of a DNA demethylating agent and an anticancer agent-
| Project/Area Number |
15390617
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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 | The University of Tokushima |
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Principal Investigator |
AZUMA Masayuki The University of Tokushima, University Medical and Dental Hospital, Assistant Professor, 医学部・歯学部附属病院, 講師 (20144983)
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| Co-Investigator(Kenkyū-buntansha) |
TAMATANI Tetsuya The University of Tokushima, University Medical and Dental Hospital, Assistant Professor, 医学部・歯学部附属病院, 助手 (30274236)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Head and Neck Cancer / Demethylating Agent / Anti-cancer Agents / Transcription Factor NF-κB / CpG Island / Gene Promoter |
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| Research Abstract |
1.Cisplatin treatment affected neither NF-κB activity nor the expression levels of antiapoptotic proteins, including TRAF-1,TRAF-2, and cFLIP, in oral cancer cells. However, two apoptosome molecules, cytochrome c and Apaf-1, were significantly augmented in the cytoplasm by cisplatin treatment. Thus, cisplatin exerts its apoptotic action by the mitochondria-mediated activation of caspases but not by the activation of caspases due to the inhibition of NF-κB activity.
2.Introduction into human oral squamous carcinoma cells of a super-repressor form of IκB-α cDNA causes a drastic decrease in tumorigenicity in nude mice due to down-regulation of the expression of IL-1α,IL-6,IL-8,VEGF, and MMP-9.
3.Irradiation- and 5-FU-induced production of IL-6 and IL-8 was significantly suppressed in IκB-α cDNA-transfected cell clones, leading to a marked inhibition of the tumorigenic ability in IκB-α cDNA-transfectedcell clones as compared to that in parental cellc or empty vector-transfected cell clones.
4.Cepharanthin suppressed the NF-κB activity in oral squamous carcinoma cells and concomitantly enhanced radiosensitization in vitro and in vivo, therefore, leading to the possibility that combination of radiotherapy with cepharanthin could lead to the enhancement of radiosensitization in the treatment of oral cancer.
5.Immortalized normal human salivary gland ductal cells, expressing aquaporin (AQP)-3 but not AQP5, acquired the ability to express AQP-5 and secrete fluid in response 5-aza-2'-deoxycytidine. Demethylation at CG sites, both in the second consensus Sp1-binding site and outside of the third consensus Sp1-binding site of the AQP-5 promoter region, directly activated the transcription of the AQP-5 gene in ductal cells.
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Research Products
(12 results)
