Project/Area Number |
05557084
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Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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Allocation Type | Single-year Grants |
Research Field |
病態科学系歯学(含放射線系歯学)
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Research Institution | The University of Tokushima |
Principal Investigator |
SATO Mitsunobu The University of Tokushima school of Dentistry, Second Department of Oral and Maxillofacial Surgery, Professor, 歯学部, 教授 (00028763)
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Co-Investigator(Kenkyū-buntansha) |
AZUMA Masayuki School of Dentistry, Second Department of Oral and Maxillofacial Surgery, Instru, 歯学部・付属病院, 講師 (20144983)
YOSHIDA Hideo School of Dentistry, Second Department of Oral and Maxillofacial Surgery, Associ, 歯学部, 助教授 (30116131)
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Project Period (FY) |
1993 – 1994
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Project Status |
Completed (Fiscal Year 1994)
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Budget Amount *help |
¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 1994: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1993: ¥8,000,000 (Direct Cost: ¥8,000,000)
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Keywords | Human salivary cancer cells / Cellular differentiation-inducing agents / Screening system / Salivary adenoid squamous carcinoma-forming cells / DNA hypomethylation / Apoptosis / Anti-tumor agents / 口腔小唾液腺由来腺様扁平上皮癌細胞 / 造腫瘍性ヒト腺房細胞癌細胞 / 分化誘導剤 |
Research Abstract |
1.Neuron-like cells (HSG-AZAll) with ample neurofilament bundles and endoplasmic reticulum as well as alpha-and beta-chain of tubulin were isolated from human salivary cancer cell line HSG treated with 5-azactidine. This HSG-AZAll cells were found to from neurites and express synaptophysin and neuron-specific enolase in response to dibutyryl cyclic AMP.This indicated that HSG-AZAll cells might be useful for searching cellular differentiation-inducing agents which work via cAMP signal transduction. 2.We have found that the treatment of HSG cells with 5-fluorodeoxyuridine monophosphate results in the differentiation into myoepithelial cells and induciton of apoptosis. 3.We have found that the cultivation of HSG-AZA3 cells with an acinar cell phenotype, which were induced by treatment of HSG cells with 5-azacytidine, in the presence of 3,4-dihydro-6-[3,4-dimethoxybenzoyl)-1-piperazinyl]-2 (1H) -quinolnone (vesnarinone) results in the differentiation into chondrocytes.In addition, it has b
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een found that the treatment of HSG-AZA3 cells with 22-oxa-1alpha, 25-dihydroxyvitamin D_3 causes the differentiation into osteoblasts. 4.We have found that the treatment of HSG cells with etoposide, an inhibitor of DNA topoisomerase II,results in the induction of cells with a smooth muscle cell phenotype, such as expression of alpha-smooth muscle actin and myofilaments, as well as in the induction of apoptosis. 5.When adenoid squamous carcinoma-forming cells (TYS) , derived from human minor salivary gland present in the oral cavity, was treated with 5-fluorouracil or vesnarinone, it has been found that the induction of apoptosis and differentiation into acinar cells occurs in the treated cells. 6.The treatment with 22-oxa-1alpha, 25 (OH) _2D_3 of HSG-AZA3 cells grown as xenografts in nude mice resulted in the marked growth inhibition of tumors, in which bone formation and bone remodeling were detected. 7.When TYS nude mouse tumors were treated with vesnarinone, significant suppression of tumor growth as well as differentiation into both keratinocytes and acinar cells were detected in the treated tumors. Less
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