Comparison of cisplatin sensitivity and the 18F fluoro-2-deoxy 2 glucose uptake with proliferation parameters and gene expression in squamous cell carcinoma cell lines of the head and neck.

Comparison of cisplatin sensitivity and the 18F fluoro-2-deoxy 2 glucose uptake with proliferation parameters and gene expression in squamous cell carcinoma cell lines of the head and neck.
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头颈鳞状细胞癌细胞系中顺铂敏感性和 18F 氟-2-脱氧 2 葡萄糖摄取与增殖参数和基因表达的比较。

DOI:
10.1186/1756-9966-28-17
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发表时间:
2009-02-13
期刊:
Journal of experimental & clinical cancer research : CR
影响因子:
--
通讯作者:
Wahlberg P
Wahlberg P
中科院分区:
其他
文献类型:
--
作者:
Henriksson E;Kjellén E;Baldetorp B;Bendahl PO;Borg A;Brun E;Mertens F;Ohlsson T;Rennstam K;Wennerberg J;Wahlberg P

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局部晚期头颈癌患者的生存率仍然很差,5年生存率为24- 35%。在分子和细胞水平上识别预后和预测标志物,可能会发现新的治疗靶点,并提供“泰勒制造”的治疗。已建立的人鳞状细胞癌(HNSCC)细胞系是用于鉴定此类标志物的有价值的模型。本研究的目的是建立和表征一系列的细胞系,并比较顺铂的敏感性和18F氟-2脱氧2葡萄糖(18F-FDG)摄取这些细胞系与其他细胞特性,如增殖参数和TP 53和CCND 1状态。培养新鲜肿瘤组织的外植体培养物,并从18例HNSCC病例中建立了6个新的永久细胞系。分析成功生长的细胞系的临床参数,组织学分级,核型,DNA倍性,指数和S期分数(SPF)。细胞系的进一步特征在于他们的18F-FDG的摄取,顺铂的敏感性,通过活力测试(结晶紫),和他们的TP 53和CCND 1的状态,荧光原位杂交(FISH),聚合酶链反应单链构象多态性(PCR-SSCP)与DNA测序,细胞周期蛋白D1,免疫组织化学。当用Kaplan-Meier方法和对数秩检验进行分析时,可以在体外培养的肿瘤患者的无病期和总生存时间比那些肿瘤不在体外生长的患者短。他们的肿瘤也显示出比不能建立细胞系的肿瘤更复杂的核型。TP 53或CCND 1状态与18F-FDG摄取或顺铂敏感性之间无相关性。然而,肿瘤细胞倍增时间和18F-FDG摄取之间呈负相关。HNSCC细胞的体外生长似乎是一个独立的预后因素,细胞系更容易从侵袭性肿瘤中建立,这种现象更依赖于肿瘤细胞的分子遗传特征,而不是肿瘤位置或TNM状态。
The survival of patients with locally advanced head and neck cancer is still poor, with 5-year survival rates of 24–35%. The identification of prognostic and predictive markers at the molecular and cellular level could make it possible to find new therapeutic targets and provide "taylor made" treatments. Established cell lines of human squamous cell carcinoma (HNSCC) are valuable models for identifying such markers. The aim of this study was to establish and characterize a series of cell lines and to compare the cisplatin sensitivity and 18F fluoro-2 deoxy 2 glucose (18F-FDG) uptake of these cell lines with other cellular characteristics, such as proliferation parameters and TP53 and CCND1 status. Explant cultures of fresh tumour tissue were cultivated, and six new permanent cell lines were established from 18 HNSCC cases. Successfully grown cell lines were analysed regarding clinical parameters, histological grade, karyotype, DNA ploidy, and index and S-phase fraction (Spf). The cell lines were further characterized with regard to their uptake of 18F-FDG, their sensitivity to cisplatin, as measured by a viability test (crystal violet), and their TP53 and CCND1 status, by fluorescence in situ hybridization (FISH), polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) with DNA sequencing and, for cyclin D1, by immunohistochemistry. Patients with tumours that could be cultured in vitro had shorter disease-free periods and overall survival time than those whose tumours did not grow in vitro, when analysed with the Kaplan-Meier method and the log-rank test. Their tumours also showed more complex karyotypes than tumours from which cell lines could not be established. No correlation was found between TP53 or CCND1 status and 18F-FDG uptake or cisplatin sensitivity. However, there was an inverse correlation between tumour cell doubling time and 18F-FDG uptake. In vitro growth of HNSCC cells seem to be an independent prognostic factor, with cell lines being more readily established from aggressive tumours, a phenomenon more dependent on the molecular genetic characteristics of the tumour cells than on tumour location or TNM status.
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影响因子: 8.8
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期刊: CANCER
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