1999 年度実績報告書

リポタイコ酸: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

研究課題

研究課題/領域番号	09557170
研究機関	徳島大学
研究代表者	佐藤光信徳島大学, 歯学部, 教授 (00028763)
研究分担者	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)
キーワード	リポタイコ酸 / OK-432 / 放射線 / 5-フルオロウラシル / 頭頸部癌 / サイトカイン / リポソーム / キラー細胞
研究概要	1.インターフェロン(IFN)-γ誘導分子(OK-LTA)を、IFN-γ誘導活性を中和する単クローン抗体TS-2を結合させたCNBr-activated Sepharose4Bを用いたアフィニティ・クロマトグラフィにより、A群溶血性レンサ球菌製剤OK-432より精製した。OK-LTAはin vivo及びin vitroの実験系において著明な抗腫瘍活性を保有していた。2.OK-LTAのエフェクター細胞への移送と治療効果を増強するために、リポソームを使用した。リポソームに封入したOK-LTA(Lipo-OK-LTA)は、OK-LTA単独の1/100量以下で、ヒト末梢血単核球及びマウス脾細胞において、IFN-γ,tumor necrosis factor(TNF)-α,β,interleukin(IL)-1β,natural killer(NK)及びlymphokine-activated killer(LAK)活性を誘導した。Lipo-OK-LTAにより誘導されたこれらの活性の総ては、抗アシアロGM1抗体と補体により、ほぼ完全に中和された(p<0.001)。3.in vivo実験系において、Lipo-OK-LTAは同系Meth-A腫瘍或いはcolon-26担癌BALB/cマウス並びにヒト唾液腺癌(HSG)担癌ヌードマウスに対してOK-LTAよりも著明な抗腫瘍活性を惹起した。更に、NK及びLAK活性の高レベル並びにアシアロ-GM1,IFN-γ,TNF-α或いはIL-1β陽性細胞の有意の増加が、Lipo-OK-LTAの投与を受けたマウス脾細胞に検出された。これらの所見は、明確にOK-LTAがOK-432の抗腫瘍活性に重要な役割を演じていること、またLipo-OK-LTAはアシアロ-GM1陽性細胞を介した抗腫瘍効果を促進することを示唆している。

研究成果
(24件)

すべてその他

すべて文献書誌 (24件)

[文献書誌] Sato M: "Induction of cyclin-dependent kinase inhibitor,p21WAF1,by treatmentwith 3,4-dihydro-6-[4(3,4)dimethoxybenzoyl-1-piperazinyl]-2(1H)-quinolinone (vesnarinone) in a human salivary cancer cell line with mutant p53 gene"Cancer lett,. 112(2). 181-189 (1997)
[文献書誌] Kawamata H: "Possible contribution of active MMP2 to lymph-node metastasis and secreted cathepsin L to bone invasion of newly established human oral-squamous-cancer cell lines."Int J Cancer. 70(1). 120-127 (1997)
[文献書誌] Sato M: "Induction of tumor differentiation and apoptosis,and LeY antigen expression in treatment with differentiation Inducing agent,vesnarinone,of a patient with salivary adenoid cystic carcinoma."Apoptosis. 2(1). 106-113 (1997)
[文献書誌] Sato M: "Emergence of osteoblast-like cells in a neoplastic human salivary cancer cell line after treatment with 22-oxa-1 α,25-dihydroxyvitamin D3"Cancer letter.. 115(2). 149-160 (1997)
[文献書誌] Azuma M: "Enhancement of bFGF export associated with malignant progression of human salivary gland cell clones."Int J Cancer. 891-896 (1997)
[文献書誌] Sato M: "Therapy for oral squamous cell carcinoma by tegafur and streptococcal agent OK-432 in combination with radiotherapy: Association of the therapeutic effect with differentiation and apoptosis in the cancer cells."Apoptosis. 2(2). 227-238 (1997)
[文献書誌] Azuma M: "Role of cytokines in the destruction of acinar structure in Sjogren's syndrome salivary glands"Laboratory Investigation. 77(3). 269-280 (1997)
[文献書誌] Sato M: "The treatment with differentiation- and apoptosis inducing agent,vesnarinone of a patient with oral squamous cell cartinoma."Apoptosis. 2(3). 313-318 (1997)
[文献書誌] 由良義明: "プロテインキナーゼC阻害剤と活性化剤のヘルペスウイルス感染に及ぼす影響"口腔組織培養研究会誌. 6(1). 35-48 (1997)
[文献書誌] Yura Y: "Effects of protein tyrosine kinase inhibitors on the replication of herpes simplex virus and the phosphorylation of viral proteins."Intervirology. 40(2). 7-14 (1997)
[文献書誌] Kawamata H: "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)
[文献書誌] Nakashiro K: "Down-regulation of TSC-22(TGF-β stimulated clone-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)
[文献書誌] Hoque MO: "Significant correlation between matrix metalloproteinase activity and tumor necrosis factor-α in salivary extravasation mucoceles."J Oral Pathol Med. 77(3). 269-280 (1997)
[文献書誌] Kawamata H: "Active-MMP2 in cancer cell nests of oral cancer patients: Correlation with lymph node metastasis."Int J Oncology. 13. 699-704 (1998)
[文献書誌] Okamoto M: "Cis-diamminedichloroplatinum and 5-fluorouracil are potent inducer of the cytokines and natural killer cell activity in vivo and in vitro."Cancer Immunol Immunother.,. 47(3). 233-241 (1998)
[文献書誌] Tujimoto H: "Effect of epidermal growth factor administration on the development of mouse salivary gland carcinomas."J Oral Pathol Med.. 28(1). 30-36 (1999)
[文献書誌] Kawamata H: "Haematogenous cytokeratin 20 mRNA as a predictive marker for recurrence in oral cancer patients."Brit.J Cancer. 80(3/4). 448-452 (1999)
[文献書誌] Azuma M: "TGF-β1 inhibits NF-kB activity through induction of IkB-α expression in human salivary gland cells: A possible mschanism of growth suppression by TGF-β1"Exp.Cell Res.. 250(1). 213-222 (1999)
[文献書誌] Kawamata H: "Significant correlation between matrix metalloproteinase activity and tumor necrosis factor-α in salivary extravasation mucoceles."Int J Oncology. 15(3). 661-667 (1999)
[文献書誌] 佐藤光信: "口腔扁平上皮癌に対するRT+UFT+OK-432併用療法。"Therapeutic Research. 20(8). 76(2264)-84(2272) (1999)
[文献書誌] 岡本正人: "OK-432より分離したリポタイコ酸標品のTh1-typeサイトカイン誘導活性。"Biotherapy. 13(5). 504-508 (1999)
[文献書誌] 佐藤光信: "口腔癌におけるUFT+OK-432+RT同時併用療法。"Tumor Dormancy Therapy. 1(4). 17-22 (1999)
[文献書誌] Okamoto M: "Liposome-incorporated interfeon-γ-inducing molecule dereived from OK-432,a streptococcal reparation."J Immunuther.. (in press).
[文献書誌] Mitsunobu Sato: "Human Cell Culture Vol.1"Kluwer Academic Publisher,Lancaster,UK. 18 (1998)

1999 年度 実績報告書

リポタイコ酸: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

研究代表者

佐藤 光信 徳島大学, 歯学部, 教授 (00028763)

研究成果

[文献書誌] Sato M: "Induction of cyclin-dependent kinase inhibitor,p21WAF1,by treatmentwith 3,4-dihydro-6-[4(3,4)dimethoxybenzoyl-1-piperazinyl]-2(1H)-quinolinone (vesnarinone) in a human salivary cancer cell line with mutant p53 gene"Cancer lett,. 112(2). 181-189 (1997)

[文献書誌] Kawamata H: "Possible contribution of active MMP2 to lymph-node metastasis and secreted cathepsin L to bone invasion of newly established human oral-squamous-cancer cell lines."Int J Cancer. 70(1). 120-127 (1997)

[文献書誌] Sato M: "Induction of tumor differentiation and apoptosis,and LeY antigen expression in treatment with differentiation Inducing agent,vesnarinone,of a patient with salivary adenoid cystic carcinoma."Apoptosis. 2(1). 106-113 (1997)

[文献書誌] Sato M: "Emergence of osteoblast-like cells in a neoplastic human salivary cancer cell line after treatment with 22-oxa-1 α,25-dihydroxyvitamin D3"Cancer letter.. 115(2). 149-160 (1997)

[文献書誌] Azuma M: "Enhancement of bFGF export associated with malignant progression of human salivary gland cell clones."Int J Cancer. 891-896 (1997)

[文献書誌] Sato M: "Therapy for oral squamous cell carcinoma by tegafur and streptococcal agent OK-432 in combination with radiotherapy: Association of the therapeutic effect with differentiation and apoptosis in the cancer cells."Apoptosis. 2(2). 227-238 (1997)

[文献書誌] Azuma M: "Role of cytokines in the destruction of acinar structure in Sjogren's syndrome salivary glands"Laboratory Investigation. 77(3). 269-280 (1997)

[文献書誌] Sato M: "The treatment with differentiation- and apoptosis inducing agent,vesnarinone of a patient with oral squamous cell cartinoma."Apoptosis. 2(3). 313-318 (1997)

[文献書誌] 由良義明: "プロテインキナーゼC阻害剤と活性化剤のヘルペスウイルス感染に及ぼす影響"口腔組織培養研究会誌. 6(1). 35-48 (1997)

[文献書誌] Yura Y: "Effects of protein tyrosine kinase inhibitors on the replication of herpes simplex virus and the phosphorylation of viral proteins."Intervirology. 40(2). 7-14 (1997)

[文献書誌] Kawamata H: "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)

[文献書誌] Nakashiro K: "Down-regulation of TSC-22(TGF-β stimulated clone-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)

[文献書誌] Hoque MO: "Significant correlation between matrix metalloproteinase activity and tumor necrosis factor-α in salivary extravasation mucoceles."J Oral Pathol Med. 77(3). 269-280 (1997)

[文献書誌] Kawamata H: "Active-MMP2 in cancer cell nests of oral cancer patients: Correlation with lymph node metastasis."Int J Oncology. 13. 699-704 (1998)

[文献書誌] Okamoto M: "Cis-diamminedichloroplatinum and 5-fluorouracil are potent inducer of the cytokines and natural killer cell activity in vivo and in vitro."Cancer Immunol Immunother.,. 47(3). 233-241 (1998)

[文献書誌] Tujimoto H: "Effect of epidermal growth factor administration on the development of mouse salivary gland carcinomas."J Oral Pathol Med.. 28(1). 30-36 (1999)

[文献書誌] Kawamata H: "Haematogenous cytokeratin 20 mRNA as a predictive marker for recurrence in oral cancer patients."Brit.J Cancer. 80(3/4). 448-452 (1999)

[文献書誌] Azuma M: "TGF-β1 inhibits NF-kB activity through induction of IkB-α expression in human salivary gland cells: A possible mschanism of growth suppression by TGF-β1"Exp.Cell Res.. 250(1). 213-222 (1999)

[文献書誌] Kawamata H: "Significant correlation between matrix metalloproteinase activity and tumor necrosis factor-α in salivary extravasation mucoceles."Int J Oncology. 15(3). 661-667 (1999)

[文献書誌] 佐藤光信: "口腔扁平上皮癌に対するRT+UFT+OK-432併用療法。"Therapeutic Research. 20(8). 76(2264)-84(2272) (1999)

[文献書誌] 岡本正人: "OK-432より分離したリポタイコ酸標品のTh1-typeサイトカイン誘導活性。"Biotherapy. 13(5). 504-508 (1999)

[文献書誌] 佐藤光信: "口腔癌におけるUFT+OK-432+RT同時併用療法。"Tumor Dormancy Therapy. 1(4). 17-22 (1999)

[文献書誌] Okamoto M: "Liposome-incorporated interfeon-γ-inducing molecule dereived from OK-432,a streptococcal reparation."J Immunuther.. (in press).

[文献書誌] Mitsunobu Sato: "Human Cell Culture Vol.1"Kluwer Academic Publisher,Lancaster,UK. 18 (1998)

1999 年度実績報告書

佐藤光信徳島大学, 歯学部, 教授 (00028763)