頭頸部扁平上皮癌培養細胞に対するEpidermal Growth Factorの影響

頭頸部扁平上皮癌培養細胞に対する上皮成長因子 (Epidermal Growth Factor;EGF) の作用, またこれらの細胞のEGFリセプター (EGFR) 発現, 抗EGFR抗体の作用, 化学療法の感受性に対する影響などを検討した。培養上清のEGF産生量はすべて検出限界値以下であった。EGFRは全ての細胞に発現し, 過剰発現する細胞もみられた。サイトカイン (IFNα, β, TNFα) によってEGFR発現は増強し, EGFとの併用で増殖能も上昇した。EGFによって増殖促進される細胞にはセルサイクルの変化すなわちS+G2M期への集積がみられ, この増殖促進効果は抗EGFR抗体添加に...

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Published in耳鼻咽喉科展望 Vol. 40; no. 2; pp. 156 - 164
Main Authors 周, 莉新, 新井, 泰弘, 三上, 康和, 持松, いづみ, 松田, 秀樹, 加賀, 潤, 佃, 守, 湯山, 誠一郎
Format Journal Article
LanguageJapanese
Published 耳鼻咽喉科展望会 15.04.1997
Online AccessGet full text
ISSN0386-9687
1883-6429
DOI10.11453/orltokyo1958.40.156

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Abstract 頭頸部扁平上皮癌培養細胞に対する上皮成長因子 (Epidermal Growth Factor;EGF) の作用, またこれらの細胞のEGFリセプター (EGFR) 発現, 抗EGFR抗体の作用, 化学療法の感受性に対する影響などを検討した。培養上清のEGF産生量はすべて検出限界値以下であった。EGFRは全ての細胞に発現し, 過剰発現する細胞もみられた。サイトカイン (IFNα, β, TNFα) によってEGFR発現は増強し, EGFとの併用で増殖能も上昇した。EGFによって増殖促進される細胞にはセルサイクルの変化すなわちS+G2M期への集積がみられ, この増殖促進効果は抗EGFR抗体添加により抑制された。EGF添加によりcisplatinの腫瘍に対するinhibition rateは高まり, 抗腫瘍効果においてcisplatinと抗EGFR抗体の相乗効果がみられた。
AbstractList 頭頸部扁平上皮癌培養細胞に対する上皮成長因子 (Epidermal Growth Factor;EGF) の作用, またこれらの細胞のEGFリセプター (EGFR) 発現, 抗EGFR抗体の作用, 化学療法の感受性に対する影響などを検討した。培養上清のEGF産生量はすべて検出限界値以下であった。EGFRは全ての細胞に発現し, 過剰発現する細胞もみられた。サイトカイン (IFNα, β, TNFα) によってEGFR発現は増強し, EGFとの併用で増殖能も上昇した。EGFによって増殖促進される細胞にはセルサイクルの変化すなわちS+G2M期への集積がみられ, この増殖促進効果は抗EGFR抗体添加により抑制された。EGF添加によりcisplatinの腫瘍に対するinhibition rateは高まり, 抗腫瘍効果においてcisplatinと抗EGFR抗体の相乗効果がみられた。
Author 加賀, 潤
周, 莉新
三上, 康和
佃, 守
新井, 泰弘
湯山, 誠一郎
持松, いづみ
松田, 秀樹
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References 15) Ozawa S, Ueda M, Ando N, et al : High incidence of EGF receptor hyperproduction in esophageal squamous cell carcinomas. Int J Cancer 39 : 333-337, 1987.
21) Maurizi M, Scambia G, Beneditti PP, et al : EGF receptor expression in primary laryngeal cancer : correlation with clinicopathological feature and prognostic significance. Int J Cancer 52 : 862-866, 1992.
13) Sporn M, Roberts A : Autocrine growth factors and cancer. Nature 313 : 745-747, 1985.
10) Shoyab M, Plowman GD, McDonald VL, et al : Structure and function of human amphiregulin : a member of the epidermal growth factor family. Science 243 : 1074-1076, 1989.
35) Jose B, Larry N, Hideo M, et al : Antitumor effects of doxorubicin in combination with anti-epidermal growth factor receptor monoclonal antibodies. J Natl Cancer Inst 85 : 1327-1333, 1993.
32) Haas I, Koldovsky P, Bier H : Immunohistochemical studies of advanced laryngeal and hypopharyngeal carcinomas 3 days after administration of monoclonal antibody against epidermal growth factor receptor. Laryngorhinootologie 73 : 626-630, 1994.
26) Osaku M, Ueda M, Ando N, et al : Targeted killing of squamous carcinoma cells by a monoclonal antibody-pepleomycin conjugate which recognizes the EGF receptor. Anticancer Res 11 : 1951-1956, 1991.
36) 小澤壮治, 池田佳史, 篠崎浩治, 他 : 遺伝子異常からみた食道癌の臨床特性. 日気食会報46 : 115-120, 1995.
19) Dassonville O, Formento JL, Francoual M, et al : Expression of epidermal growth factor receptor and survival in upper aerodigestive tract cancer. J Clin Oncol 11 : 1873-1878, 1993.
33) Modjtahedi H, Hickish T, Nicolson M, et al : Phase I trial and tumor localization of the anti-EGFR monoclonal antibody ICR 62 in head and neck or lung cancer. Br J Cancer 73 : 228-235, 1996.
23) 新井泰弘, 佃守, 久保田彰, 他 : 頭頸部扁平上皮癌の新鮮凍結組織を用いたDNA ploidyの解析.日耳鼻97 : 254-259, 1994.
34) Perez-Soler R, Donato NJ, Shin DM, et al Tumor epidermal growth factor receptor studies in patients with non-small cell lung cancer or head and neck cancer treated with monoclonal antibody RG 83852. J Clin Oncol 12 : 730-739, 1994.
5) 佃, 守 : 頭頸部癌における染色体, 遺伝子異常研究の現況.耳喉頭頸68 : 751-766, 1996
17) Stanton P, Richards S, Reeves J, et al : Epidermal growth factor expreesion by human squamous cell carcinomas of the head and neck, cell lines and xenografts. Br J Cancer 70 : 427-433, 1994.
22) Irish JC, Bernstein A : Oncogenes in head and neck cancer. Laryngoscope 103 : 42-52, 1993.
2) Gregory H : In vivo aspects of urogastroneepidermal growth factor. J Cell Sci Suppl 3 : 11-17, 1985.
3) Carpenter G : aeapidermal growth factor, its receptor, and related proteins. Exp Cell Res 164 : 1-10, 1986.
9) Ullrich A, Coussens L, Hayflik J, et al : Human epidermal growth factor receptor cDNA sequence and abberant expression of the amplified gene in A 431 epidermoid carcinoma cells. Nature 309 : 418-425, 1984.
11) Higashiyama S, Lau K, Besner GE, et al : Structure of heparin-binding EGF-like growth factor : multiple forms, primary structure, and glycosylation of the mature protein. J Biol Chem 267 : 6205-6212, 1992.
14) Ozawa S, Ueda M, Ando N, et al : Epidermal growth factor receptors in cancer tissues of esophagus, lung, pancreas, colorectum, breast and stomach. Jpn J Cancer Res 79 : 1201-1207, 1988.
12) Kimura H, Fischer WH, Schubert D : Structure, expression and function of a schwannoma-derived growth factor. Nature 348 : 257-260, 1990.
6) 三上康和 : 頭頸部扁平上皮癌細胞のBasic Fibroblast Growth Factor産生と血管新生.耳展36 : 685-695, 1993.
4) Carpenter G : Receptors for epidermal growth factor and other polypeptide mitogens. Ann Rev Biochem 56 : 881-914, 1987.
8) 蒲生忍, 清水信義 : 増殖因子レセプター.ホルモンと臨床42 : 71-80, 1995.
30) Kroning R, Jones JA, Hom DK, et al : Enhancement of drug sensitivity of human malignancies by epidermal growth factor. Br J Cancer 72 : 615-619, 1995.
16) Ozanne B, Schum A, Richards CS, et al : Evidence for increased EGF receptor in epidermal malignancies. Cancer Cells 3 : 41-49, 1985.
31) Bonner JA, Maihle NJ, Folven BR : The inteaction of epidermal growth factor and radiation in human head and neck squamous cell carcinoma cell lines with vastly different radiosensitivities. Int J Radiat Oncol Biol Phys 29 : 243-247, 1994.
1) Cohen S : Isoration of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem 237 : 1555-4562, 1962.
25) Modjtahedi H, Eccles S, Scandle J : Differentiation or immune destruction : two pathways for therapy of squamous cell carcinomas with antibodies to the epidermal growth factor receptor. Canser Res 54 : 1695-1701, 1994.
18) Ohi K, Suzuki M, Koike S, et al : Expression of epidermal growth factor receptor in squamous cell carcinoma of the head and neck. J Otolaryngol Jpn 96 : 2039-2043, 1993.
20) Starkey RH, Orth DN : Radioimmunoassay of human epidermal growth factor (urogastrone). J Clin Endocr Metab 45 : 1144-1153, 1987.
24) 清河信敬, 藤本純一郎, Mien-Chie H : 受容体型チロシンキナーゼEGFRの細胞周期依存性機能調節機構日本癌学会総会記事55 : 90, 1996.
28) Giovanni S, Pierluigi BP, Gabriella F : Effect of recombinant human interferon-alpha/2 b on epidermal-growth-factor-, estrogen-and progesterone-receptor exprression in primary cervical cancer. Int J Cancer 58 : 769-773, 1994.
27) Michele C, Annalisa L, Stefania C : α-interferon potentiates epidermal growth factor receptor mediated effects on human epidermoid carcinoma KB cells. Int J Cancer 61 : 342-347, 1995.
7) 蒲生 忍, 清水信義 : 上皮増殖因子とそのレセプター.日本臨床50 : 193-200, 1992.
29) Mochimatsu M, Tsukuda M, Furukawa S, et al : The sensitivity of head and neck squamous cell carcinomas to tumor necrosis factor-α. Biotherapy 6 : 239-244, 1994.
References_xml – reference: 14) Ozawa S, Ueda M, Ando N, et al : Epidermal growth factor receptors in cancer tissues of esophagus, lung, pancreas, colorectum, breast and stomach. Jpn J Cancer Res 79 : 1201-1207, 1988.
– reference: 24) 清河信敬, 藤本純一郎, Mien-Chie H : 受容体型チロシンキナーゼEGFRの細胞周期依存性機能調節機構日本癌学会総会記事55 : 90, 1996.
– reference: 36) 小澤壮治, 池田佳史, 篠崎浩治, 他 : 遺伝子異常からみた食道癌の臨床特性. 日気食会報46 : 115-120, 1995.
– reference: 21) Maurizi M, Scambia G, Beneditti PP, et al : EGF receptor expression in primary laryngeal cancer : correlation with clinicopathological feature and prognostic significance. Int J Cancer 52 : 862-866, 1992.
– reference: 15) Ozawa S, Ueda M, Ando N, et al : High incidence of EGF receptor hyperproduction in esophageal squamous cell carcinomas. Int J Cancer 39 : 333-337, 1987.
– reference: 33) Modjtahedi H, Hickish T, Nicolson M, et al : Phase I trial and tumor localization of the anti-EGFR monoclonal antibody ICR 62 in head and neck or lung cancer. Br J Cancer 73 : 228-235, 1996.
– reference: 13) Sporn M, Roberts A : Autocrine growth factors and cancer. Nature 313 : 745-747, 1985.
– reference: 26) Osaku M, Ueda M, Ando N, et al : Targeted killing of squamous carcinoma cells by a monoclonal antibody-pepleomycin conjugate which recognizes the EGF receptor. Anticancer Res 11 : 1951-1956, 1991.
– reference: 28) Giovanni S, Pierluigi BP, Gabriella F : Effect of recombinant human interferon-alpha/2 b on epidermal-growth-factor-, estrogen-and progesterone-receptor exprression in primary cervical cancer. Int J Cancer 58 : 769-773, 1994.
– reference: 12) Kimura H, Fischer WH, Schubert D : Structure, expression and function of a schwannoma-derived growth factor. Nature 348 : 257-260, 1990.
– reference: 32) Haas I, Koldovsky P, Bier H : Immunohistochemical studies of advanced laryngeal and hypopharyngeal carcinomas 3 days after administration of monoclonal antibody against epidermal growth factor receptor. Laryngorhinootologie 73 : 626-630, 1994.
– reference: 3) Carpenter G : aeapidermal growth factor, its receptor, and related proteins. Exp Cell Res 164 : 1-10, 1986.
– reference: 27) Michele C, Annalisa L, Stefania C : α-interferon potentiates epidermal growth factor receptor mediated effects on human epidermoid carcinoma KB cells. Int J Cancer 61 : 342-347, 1995.
– reference: 6) 三上康和 : 頭頸部扁平上皮癌細胞のBasic Fibroblast Growth Factor産生と血管新生.耳展36 : 685-695, 1993.
– reference: 30) Kroning R, Jones JA, Hom DK, et al : Enhancement of drug sensitivity of human malignancies by epidermal growth factor. Br J Cancer 72 : 615-619, 1995.
– reference: 5) 佃, 守 : 頭頸部癌における染色体, 遺伝子異常研究の現況.耳喉頭頸68 : 751-766, 1996
– reference: 11) Higashiyama S, Lau K, Besner GE, et al : Structure of heparin-binding EGF-like growth factor : multiple forms, primary structure, and glycosylation of the mature protein. J Biol Chem 267 : 6205-6212, 1992.
– reference: 23) 新井泰弘, 佃守, 久保田彰, 他 : 頭頸部扁平上皮癌の新鮮凍結組織を用いたDNA ploidyの解析.日耳鼻97 : 254-259, 1994.
– reference: 2) Gregory H : In vivo aspects of urogastroneepidermal growth factor. J Cell Sci Suppl 3 : 11-17, 1985.
– reference: 9) Ullrich A, Coussens L, Hayflik J, et al : Human epidermal growth factor receptor cDNA sequence and abberant expression of the amplified gene in A 431 epidermoid carcinoma cells. Nature 309 : 418-425, 1984.
– reference: 8) 蒲生忍, 清水信義 : 増殖因子レセプター.ホルモンと臨床42 : 71-80, 1995.
– reference: 25) Modjtahedi H, Eccles S, Scandle J : Differentiation or immune destruction : two pathways for therapy of squamous cell carcinomas with antibodies to the epidermal growth factor receptor. Canser Res 54 : 1695-1701, 1994.
– reference: 19) Dassonville O, Formento JL, Francoual M, et al : Expression of epidermal growth factor receptor and survival in upper aerodigestive tract cancer. J Clin Oncol 11 : 1873-1878, 1993.
– reference: 34) Perez-Soler R, Donato NJ, Shin DM, et al Tumor epidermal growth factor receptor studies in patients with non-small cell lung cancer or head and neck cancer treated with monoclonal antibody RG 83852. J Clin Oncol 12 : 730-739, 1994.
– reference: 17) Stanton P, Richards S, Reeves J, et al : Epidermal growth factor expreesion by human squamous cell carcinomas of the head and neck, cell lines and xenografts. Br J Cancer 70 : 427-433, 1994.
– reference: 20) Starkey RH, Orth DN : Radioimmunoassay of human epidermal growth factor (urogastrone). J Clin Endocr Metab 45 : 1144-1153, 1987.
– reference: 31) Bonner JA, Maihle NJ, Folven BR : The inteaction of epidermal growth factor and radiation in human head and neck squamous cell carcinoma cell lines with vastly different radiosensitivities. Int J Radiat Oncol Biol Phys 29 : 243-247, 1994.
– reference: 1) Cohen S : Isoration of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem 237 : 1555-4562, 1962.
– reference: 18) Ohi K, Suzuki M, Koike S, et al : Expression of epidermal growth factor receptor in squamous cell carcinoma of the head and neck. J Otolaryngol Jpn 96 : 2039-2043, 1993.
– reference: 22) Irish JC, Bernstein A : Oncogenes in head and neck cancer. Laryngoscope 103 : 42-52, 1993.
– reference: 35) Jose B, Larry N, Hideo M, et al : Antitumor effects of doxorubicin in combination with anti-epidermal growth factor receptor monoclonal antibodies. J Natl Cancer Inst 85 : 1327-1333, 1993.
– reference: 7) 蒲生 忍, 清水信義 : 上皮増殖因子とそのレセプター.日本臨床50 : 193-200, 1992.
– reference: 16) Ozanne B, Schum A, Richards CS, et al : Evidence for increased EGF receptor in epidermal malignancies. Cancer Cells 3 : 41-49, 1985.
– reference: 29) Mochimatsu M, Tsukuda M, Furukawa S, et al : The sensitivity of head and neck squamous cell carcinomas to tumor necrosis factor-α. Biotherapy 6 : 239-244, 1994.
– reference: 4) Carpenter G : Receptors for epidermal growth factor and other polypeptide mitogens. Ann Rev Biochem 56 : 881-914, 1987.
– reference: 10) Shoyab M, Plowman GD, McDonald VL, et al : Structure and function of human amphiregulin : a member of the epidermal growth factor family. Science 243 : 1074-1076, 1989.
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Snippet 頭頸部扁平上皮癌培養細胞に対する上皮成長因子 (Epidermal Growth Factor;EGF) の作用, またこれらの細胞のEGFリセプター (EGFR) 発現, 抗EGFR抗体の作用,...
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Title 頭頸部扁平上皮癌培養細胞に対するEpidermal Growth Factorの影響
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