1998 Fiscal Year Annual Research Report

ベスナリノンを用いた頭頸部癌の分化・アポトーシス誘導療法に関する研究

Research Project

Project/Area Number	10307051
Research Category	Grant-in-Aid for Scientific Research (A)
Research Institution	The University of Tokushima
Principal Investigator	佐藤光信徳島大学, 歯学部, 教授 (00028763)
Co-Investigator(Kenkyū-buntansha)	川又均徳島大学, 歯学部, 助手 (70224847) 由良義明徳島大学, 歯学部附属病院, 講師 (00136277) 吉田秀夫徳島大学, 歯学部, 助教授 (30116131)
Keywords	ベスナリノン / 細胞分化 / アポトーシス / TGF-β / p21^<WAF1> / TSC-22 / 唾液腺癌 / 口腔扁平上皮癌
Research Abstract	1.ヒト口腔扁平上皮癌細胞(BHY,HN)とヒト唾液腺癌細胞(HSG,HSG-AZA1,HSG-AZA3,TYS)をベスナリノン存在下で培養すると、総ての細胞に増殖抑制が生じ、G1 arrestの惹起されることをFACS解析により明らかにした。2.TYS細胞をベスナリノンで処理すると、細胞増殖の抑制に伴ってTGF-b1,p21^<WAF1>,TSC-22遺伝子がup-regulationされることを、Northern blottingにより明らかにした。また、TSC-22遺伝子をクローニングした。3.BHY,HN,HSG,HSG-AZA1,HSG-AZA3細胞は総て、p53遺伝子(Exon4-Exon9)が野生型であることを明らかにした。なお、TYS細胞においては、コドン281^<Asp-His>に点突然変異の存在を認めた。4.TYS細胞をヌードマウスに移植して、ベスナリノン(200mg/kg,35日間経口投与)で治療すると、有意な腫瘍増殖の抑制と、keratinocyte differentiation及びacinardifferentiationを認めた。加えて、アポトーシスの誘導とLe^Y抗原の発現を検出した。5.顎下腺より発生した腺様嚢胞癌症例にベスナリノン(60mg/day,per os,43日間)を投与して著効を認めた。すなわち、著明な腫瘍の縮小と高度分化型tubular typeへの腫瘍分化の出現及びLe^Y抗原とアポトーシスの発現を認めた。加えて、口腔扁平上皮癌症例においても、ベスナリノン投与(180mg/day,per os,56日間。その後60mg/day,per os,93日間)によりCRになった症例を認めた。本症例においては、p53遺伝子は野生型であり、Le^Y抗原の発現とDNA断裂を高頻度に認めた。

Research Products
(10 results)

All Other

All Publications (10 results)

[Publications] Hitoshi Kawamata: "Induction of TSC-22 by Treatment with a new anti-cancer drug vesnarincne in a human salirary gland cancer cell" Brit.g.Cancer. 77(1). 71-78 (1998)
[Publications] Kohichi Nakashiro: "Down-regulation of TSC-22(TGF-β stimutated clone-22)markedly Enhances the growth of a human salivary gland cancer cell line in vitro" Cancer Res.58(3). 549-555 (1998)
[Publications] Mohamed Obaque Hoque: "Significant correlation between matrix metalleproteinase activity and tumor necrosis factor-α in salrary extravasation mucoceles" J.Oral Pathel.Med.27(1). 30-33 (1998)
[Publications] Hitoshi Kawamata: "Active-MM2 in cancer cell nests of oral cancer patients:correlation with lymph nede metastasis" Int.J.Oncology. 13(3). 699-704 (1998)
[Publications] Masato Okamoto: "Lis-diammibedichloroplatinum and 5-fluorouracil are potent inducet of the cytekines and natrral killer cell activity in vivo and in vitro" Cancer Immunol.Immunother.47(4). 233-239 (1998)
[Publications] Kazuyoshi Kawai: "Enhancement of anticancer effects of radiation and conventional anticancer agents by a quinolinohe derivative vesnarinone:studies on human gastric cancer tissue xenografts in nude mice" Anticancer Res.18(1A). 405-412 (1998)
[Publications] Hitoshi Tsujimoto: "Effect of epidernal growth factor administration on the development of mouse salivary gland carcinomas." J.Oral Pathol.Med.28(1). 30-36 (1999)
[Publications] Hitoshi Kawamata: "Haematogenous cytokeratin 20 mRNA as a predictive markers for recurrence in oral cancer patients" Brit.J.Cancer. (in press). (1999)
[Publications] Masato Okamoto: "Cytokine-inducing activity and anti-tumor effect of liposome in corporated interferon-γ-inducing molecule derired from ok-432,a streptococcal preparation" J.Immunother.(in press). (1999)
[Publications] Mitsunobu Sato: "Human Cell Culture Vol.1 Chapter9 Salirary gland tumors" Kluwer Academic Publishers, 17 (1999)

1998 Fiscal Year Annual Research Report

ベスナリノンを用いた頭頸部癌の分化・アポトーシス誘導療法に関する研究

Principal Investigator

佐藤 光信 徳島大学, 歯学部, 教授 (00028763)

Research Products

[Publications] Hitoshi Kawamata: "Induction of TSC-22 by Treatment with a new anti-cancer drug vesnarincne in a human salirary gland cancer cell" Brit.g.Cancer. 77(1). 71-78 (1998)

[Publications] Kohichi Nakashiro: "Down-regulation of TSC-22(TGF-β stimutated clone-22)markedly Enhances the growth of a human salivary gland cancer cell line in vitro" Cancer Res.58(3). 549-555 (1998)

[Publications] Mohamed Obaque Hoque: "Significant correlation between matrix metalleproteinase activity and tumor necrosis factor-α in salrary extravasation mucoceles" J.Oral Pathel.Med.27(1). 30-33 (1998)

[Publications] Hitoshi Kawamata: "Active-MM2 in cancer cell nests of oral cancer patients:correlation with lymph nede metastasis" Int.J.Oncology. 13(3). 699-704 (1998)

[Publications] Masato Okamoto: "Lis-diammibedichloroplatinum and 5-fluorouracil are potent inducet of the cytekines and natrral killer cell activity in vivo and in vitro" Cancer Immunol.Immunother.47(4). 233-239 (1998)

[Publications] Kazuyoshi Kawai: "Enhancement of anticancer effects of radiation and conventional anticancer agents by a quinolinohe derivative vesnarinone:studies on human gastric cancer tissue xenografts in nude mice" Anticancer Res.18(1A). 405-412 (1998)

[Publications] Hitoshi Tsujimoto: "Effect of epidernal growth factor administration on the development of mouse salivary gland carcinomas." J.Oral Pathol.Med.28(1). 30-36 (1999)

[Publications] Hitoshi Kawamata: "Haematogenous cytokeratin 20 mRNA as a predictive markers for recurrence in oral cancer patients" Brit.J.Cancer. (in press). (1999)

[Publications] Masato Okamoto: "Cytokine-inducing activity and anti-tumor effect of liposome in corporated interferon-γ-inducing molecule derired from ok-432,a streptococcal preparation" J.Immunother.(in press). (1999)

[Publications] Mitsunobu Sato: "Human Cell Culture Vol.1 Chapter9 Salirary gland tumors" Kluwer Academic Publishers, 17 (1999)

佐藤光信徳島大学, 歯学部, 教授 (00028763)