激活细胞外signal-regulated激酶:协会与表皮生长因子受体/转化生长因子α表达在头颈部鳞状细胞癌和抑制抗表皮生长因子受体的治疗方法。
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Albanell J, Codony-Servat J,红色的F, Del Campo JM Sauleda年代,Anido J, Raspall G, Giralt J, Rosello J,尼科尔森RI, Mendelsohn J, Baselga J
激活细胞外signal-regulated激酶:协会与表皮生长因子受体/转化生长因子α表达在头颈部鳞状细胞癌和抑制抗表皮生长因子受体的治疗方法。
癌症研究》2001年9月1;61 (17):6500 - 10。
- PubMed ID
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11522647 (在PubMed]
- 文摘
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激活增殖激酶/细胞外的表达signal-regulated激酶(erk) ERK1 ERK2特点是101年humanhead和颈部鳞状细胞癌标本。激活ERK1/2were发现在大多数的这些肿瘤的不同层次,化验的疣状与抗体特定双重磷酸化,激活ERK1 ERK2。ERK1/2激活水平高与先进的肿瘤区域淋巴结转移(P = 0.048)和复发肿瘤(P = 0.021)。表皮生长因子(EGF)受体的表达(P = 0.037),转化生长因子α(是;HER2 (P < 0.001), P = 0.066;积极的趋势)与ERK1/2激活。在多变量分析,是(P < 0.0001)和HER2 (P = 0.045)是独立与ERK1/2激活。反过来,激活ERK1/2与更高的ki - 67增殖指数(P = 0.002)。在EGF receptor-dependent模型细胞(A431和DiFi),一个特定的表皮生长因子受体酪氨酸激酶抑制剂(“艾瑞莎”;ZD1839)和嵌合anti-EGF受体抗体(“西妥昔单抗”; C225) inhibited ERK 1/2 activation at concentrations that inhibited autocrine cell proliferation. In patients on treatment with C225, the activation of ERK1/2 in skin, an EGF receptor-dependent tissue, was lower compared with control skin. Parallel changes were seen in keratinocyte Ki67 proliferation indexes in skin from C225-treated patients. Taken together, these studies provide support for a role of activation of ERK1/2 in head and neck squamous carcinoma and a correlation with EGF receptor/TGF-alpha expression. The inhibition of ERK1/2 activation in vitro and in vivo by compounds targeting the EGF receptor points to the interest of ERK1/2 as potential surrogate markers of EGF-receptor signaling in clinical therapeutic studies.