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西妥昔单抗治疗在鳞状细胞癌中的效果。

Effect of cetuximab treatment in squamous cell carcinomas.

作者信息

Nestor Marika

机构信息

Unit of Otolaryngology and Head & Neck Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

出版信息

Tumour Biol. 2010 Apr;31(2):141-7. doi: 10.1007/s13277-010-0018-8. Epub 2010 Feb 24.

Abstract

The purpose of this study was to assess the effects of the monoclonal antibody cetuximab in a panel of cultured squamous cell carcinoma cell lines. This antibody, targeting the epidermal growth factor receptor (EGFR), is emerging as a promising agent for treatment of several cancers. As this antibody comes into clinical use, the identification of predictive markers of therapeutic benefit remains a pressing issue. Cells were first characterized according to EGFR expression, cell doubling time, and BRAF and K-ras mutations. The effects of cetuximab on cell-cycle distribution, proliferation, as well as cell growth rate were then evaluated. Cetuximab decreased cell proliferation in three out of four cell lines in a time-dependent manner, and all cell lines were found to exhibit wild type K-ras and BRAF genes. A possible correlation between EGFR expression and cetuximab effect on growth inhibition rate was observed, whereas reduction of cell doubling time seemed to be more dependent on initial growth rate. In addition, other factors may further influence the long-term treatment response of cetuximab. Moreover, the time-dependent manner of cetuximab response demonstrates the importance of long-term measurements for this substance.

摘要

本研究的目的是评估单克隆抗体西妥昔单抗在一组培养的鳞状细胞癌细胞系中的作用。这种靶向表皮生长因子受体(EGFR)的抗体正成为治疗多种癌症的一种有前景的药物。随着这种抗体进入临床应用,确定治疗获益的预测标志物仍然是一个紧迫的问题。首先根据EGFR表达、细胞倍增时间以及BRAF和K-ras突变对细胞进行表征。然后评估西妥昔单抗对细胞周期分布、增殖以及细胞生长速率的影响。西妥昔单抗以时间依赖性方式降低了四分之三细胞系中的细胞增殖,并且发现所有细胞系均表现出野生型K-ras和BRAF基因。观察到EGFR表达与西妥昔单抗对生长抑制率的影响之间可能存在相关性,而细胞倍增时间的缩短似乎更依赖于初始生长速率。此外,其他因素可能会进一步影响西妥昔单抗的长期治疗反应。而且,西妥昔单抗反应的时间依赖性方式证明了对该物质进行长期测量的重要性。

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