1997 Fiscal Year Annual Research Report

タポタイコ酸:頭頸部癌における放射線、5-フルオロウラシルの治療効果の増強

Research Project

Project/Area Number	09557170
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)	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	リポタイコ酸 / 頭頸部癌 / 放射線 / 5-フルオロウラシル / サイトカイン / キラー活性 / 分化誘導 / アポトーシス
Research Abstract	1.溶連菌製剤OK-432のブタノール抽出物より、生理活性物質であるリポタイコ酸を分離・精製した。すなわち、OK-432のIFN-_γ誘導を部位を認識するマウス単クローン抗体(TS-2)をリガンドとしたアフィニティー・クロマトグラフィーを調製し、OK-432のブタノール抽出物よりTS-2抗体と反応する抗原を分離し、更に高速液体クロマトグラフィーにより精製した。 2.OK-432より抽出したリポタイコ酸標品(OK-LTA)は、ヒト末梢血単核球と反応して、IFN-α,β,γ,TNF-α,β,IL-1β,IL-12等のサイトカインを誘導し、更にNK,LAK活性を誘導することを明らかにした。 3.ヌードマウスにヒト頭頸部癌細胞(口腔扁平上皮癌細胞と唾液腺癌細胞)を移植して、X線(10Gy),5-Fu(40mg/Kg),OK-LTA(10-100μg/body)をそれぞれ単独及び併用投与して、抗腫瘍効果を検討した。その結果、放射線、5-Fuの抗腫瘍効果は、OK-LTAにより増強されることが示唆された。 4.OK-LTAをリポソームに封入した標品を調製した。このリポソームに封入したOK-LTAでヒト末梢血単核球を刺激すると、リポソームに封入していないOK-LTAの場合と比較して、IFN-α,β,γ,TNF-α,β,IL-1β,IL-12等のサイトカインの産生は有意に増強した。 5.口腔粘膜癌を放射線、テガフ-ル、OK-432にて同時併用治療を行うと非常に有効であること、この場合の治療効果は、口腔扁平上皮癌細胞の分化とアポトーシスとに関連していることが示唆された。

Research Products

(11 results)

All Other

All Publications (11 results)

[Publications] Mitsunobu Sato: "Therapy for oral squamous cell carcinoma by tegafur and Stroptococcal agent OK-432 in combination with radiotherapy : Association of the themapentic effect with differentiation and apoptosis in the cancer cells" Apoptosis. 2(2). 227-238 (1997)
[Publications] Mitsunobu Sato: "Indaction of tumour differentiation and apoptosis and Let antigen expression in treatmetn with differentiation-inducing agent,resharinone,of a patient with salivary adenoid cystic carcinoma" Apoptosis. 2(1). 106-113 (1997)
[Publications] Mitsunobu Sato: "The treatment with differentiation- and apoptosis- inducing agent vesnarinone,of a patient with oral squamous cell carcinoma" Apoptosis. 2(3). 313-318 (1997)
[Publications] Mitsunobu Sato: "Induction of cyclin-dependent kinase inhibitor P21 ^<WAFI>,by treatment with 3,4-dihydro-6-〔4-(3,4)-dimethoxybenzoyl)-1-,piporazinylt-2(1H)-quino linone (vesnarinone)in a human salivary cancer cell line with mutant P53 gene" Cancer Letters. 112(4). 181-189 (1997)
[Publications] Mitsunobu Sato: "Emergence of osteoblast-like cells in a neoplastic human salivary cancer cell line ofter treatment with 22-oxa-1α,25-dihydroxyvitamin" Cancer Letters. 115(4). 149-160 (1997)
[Publications] Hitoshi Kawamata: "Possible contribution of active MMP2 to lymph-node metastasis and secreted cathepsin L to bone invasion of newly established human oral squamons cancer cell lines" Int.J.Cancer. 70(3). 120-127 (1997)
[Publications] Masayuki Azuma: "Enhancement of bFGF export associated with malignant progressio of human salivary gland cell clones" Int.J.Cancer. 71(2). 891-896 (1997)
[Publications] Hitoshi kawamata: "Induction of TSC-22 by treatment with a new anti-cancer drug,vesnarinone,in a human salivary gland cancer cell" Brit.J.Cancer. 77(1). 71-78 (1998)
[Publications] Koh-ichi Nakashiro: "Down-regulation of TSC-22 (Transforming growth factor β-stimulu clore 22) markedly enhances the growth of a human salivary gland cancer cell line in vitro and in vivo" Cancer Res.58(3). 549-555 (1998)
[Publications] Hoque MO: "Significant correlation between matrix metalloproteinase activity and tumor necrosis factor -α in salivary extravasation mucoceles" J.Oral Pathol Med. 27(1). 30-33 (1998)
[Publications] Kazuyoshi Kawai: "Enhancement of anticancer effects of radiation and conventional anticancer agents by a quinolinone derivative,vesnarinone:stulies on human gastric cancer tissue xenografts in nade mice" Anticancer Res. (in press). (1998)

1997 Fiscal Year Annual Research Report

タポタイコ酸:頭頸部癌における放射線、5-フルオロウラシルの治療効果の増強

Principal Investigator

佐藤 光信 徳島大学, 歯学部, 教授 (00028763)

Research Products

[Publications] Mitsunobu Sato: "Therapy for oral squamous cell carcinoma by tegafur and Stroptococcal agent OK-432 in combination with radiotherapy : Association of the themapentic effect with differentiation and apoptosis in the cancer cells" Apoptosis. 2(2). 227-238 (1997)

[Publications] Mitsunobu Sato: "Indaction of tumour differentiation and apoptosis and Let antigen expression in treatmetn with differentiation-inducing agent,resharinone,of a patient with salivary adenoid cystic carcinoma" Apoptosis. 2(1). 106-113 (1997)

[Publications] Mitsunobu Sato: "The treatment with differentiation- and apoptosis- inducing agent vesnarinone,of a patient with oral squamous cell carcinoma" Apoptosis. 2(3). 313-318 (1997)

[Publications] Mitsunobu Sato: "Induction of cyclin-dependent kinase inhibitor P21 ^<WAFI>,by treatment with 3,4-dihydro-6-〔4-(3,4)-dimethoxybenzoyl)-1-,piporazinylt-2(1H)-quino linone (vesnarinone)in a human salivary cancer cell line with mutant P53 gene" Cancer Letters. 112(4). 181-189 (1997)

[Publications] Mitsunobu Sato: "Emergence of osteoblast-like cells in a neoplastic human salivary cancer cell line ofter treatment with 22-oxa-1α,25-dihydroxyvitamin" Cancer Letters. 115(4). 149-160 (1997)

[Publications] Hitoshi Kawamata: "Possible contribution of active MMP2 to lymph-node metastasis and secreted cathepsin L to bone invasion of newly established human oral squamons cancer cell lines" Int.J.Cancer. 70(3). 120-127 (1997)

[Publications] Masayuki Azuma: "Enhancement of bFGF export associated with malignant progressio of human salivary gland cell clones" Int.J.Cancer. 71(2). 891-896 (1997)

[Publications] Hitoshi kawamata: "Induction of TSC-22 by treatment with a new anti-cancer drug,vesnarinone,in a human salivary gland cancer cell" Brit.J.Cancer. 77(1). 71-78 (1998)

[Publications] Koh-ichi Nakashiro: "Down-regulation of TSC-22 (Transforming growth factor β-stimulu clore 22) markedly enhances the growth of a human salivary gland cancer cell line in vitro and in vivo" Cancer Res.58(3). 549-555 (1998)

[Publications] Hoque MO: "Significant correlation between matrix metalloproteinase activity and tumor necrosis factor -α in salivary extravasation mucoceles" J.Oral Pathol Med. 27(1). 30-33 (1998)

[Publications] Kazuyoshi Kawai: "Enhancement of anticancer effects of radiation and conventional anticancer agents by a quinolinone derivative,vesnarinone:stulies on human gastric cancer tissue xenografts in nade mice" Anticancer Res. (in press). (1998)

佐藤光信徳島大学, 歯学部, 教授 (00028763)