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p53突变和细胞周期蛋白D1扩增与头颈部人鳞状细胞癌异种移植瘤中的顺铂敏感性相关。

p53 mutation and cyclin D1 amplification correlate with cisplatin sensitivity in xenografted human squamous cell carcinomas from head and neck.

作者信息

Henriksson Eva, Baldetorp Bo, Borg Ake, Kjellen Elisabeth, Akervall Jan, Wennerberg Johan, Wahlberg Peter

机构信息

Department of Otorhinolaryngology, University Hospital of Malmö, Sweden.

出版信息

Acta Oncol. 2006;45(3):300-5. doi: 10.1080/02841860600547380.

Abstract

To investigate the response of tumour growth to cisplatin treatment, in relation to p53 mutation and cyclin D1 dysregulation on DNA and protein level, biopsies from seven xenografted human squamous cell carcinomas from the head and neck were analysed with immunohistochemistry for p53 expression and cyclin D1 expression. Polymerase chain reaction-singlestranded conformation polymorphism was used to determine p53 mutations. Fluorescence in situ hybridization was performed to analyse cyclin D1 amplification. The mice were injected i.p. with NaCl (controls) or cisplatin. After injection the tumour volume were measured. The inhibition of tumour growth by cisplatin was defined as the area under the growth curves, and compared with the growth curves of the tumours in the control group. Xenografts with p53 mutation showed significantly higher resistance to cisplatin (p < 0.001) and also tumours with cyclin D1 amplification showed significantly higher resistance (p < 0.001).

摘要

为了研究肿瘤生长对顺铂治疗的反应,以及p53突变和细胞周期蛋白D1失调在DNA和蛋白质水平上的关系,对7例头颈部人鳞状细胞癌异种移植瘤进行活检,采用免疫组织化学分析p53表达和细胞周期蛋白D1表达。采用聚合酶链反应-单链构象多态性方法检测p53突变。进行荧光原位杂交分析细胞周期蛋白D1扩增情况。给小鼠腹腔注射氯化钠(对照组)或顺铂。注射后测量肿瘤体积。将顺铂对肿瘤生长的抑制作用定义为生长曲线下的面积,并与对照组肿瘤的生长曲线进行比较。具有p53突变的异种移植瘤对顺铂的耐药性显著更高(p<0.001),具有细胞周期蛋白D1扩增的肿瘤对顺铂的耐药性也显著更高(p<0.001)。

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