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尤因肉瘤的靶向治疗:异质性的意义。

Targeted therapy for Ewing's sarcoma: significance of heterogeneity.

机构信息

Department of Medical Oncology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands.

出版信息

Anticancer Res. 2010 Sep;30(9):3715-9.

PMID:20944159
Abstract

BACKGROUND

Survival in Ewing's sarcoma (ES) is limited. Experience with insulin-like growth factor targeting drugs, which require specific molecular tumour alterations, herald a major breakthrough. We screened for tumour heterogeneity within patients by DNA quantification.

MATERIALS AND METHODS

DNA image cytometry (IC) was performed on 41 samples from 21 patients, evaluating if ploidy state remained constant over time and between different lesions within patients and the prognostic value of ploidy was assessed.

RESULTS

DNA content varied over time and different ploidy states were found to coexist at a single timepoint. Non-diploid DNA content was associated with shorter overall survival (median, 19 vs. 84 months, p=0.047).

CONCLUSION

We encountered a change and heterogeneity of ploidy state. This implies that screening for targets on a single tumour sample is insufficient and may lead to under- or overtreatment. The fact that non-diploid DNA content was associated with an adverse outcome confirms that this technique discriminates biologically different tumour clones.

摘要

背景

尤因肉瘤(ES)患者的生存率有限。具有特定分子肿瘤改变的胰岛素样生长因子靶向药物的应用带来了重大突破。我们通过 DNA 定量对患者的肿瘤异质性进行了筛选。

材料与方法

对 21 名患者的 41 个样本进行了 DNA 图像细胞计量学(IC)分析,评估了倍性状态是否随时间和患者内不同病变而保持稳定,以及倍性的预后价值。

结果

DNA 含量随时间变化,并且在单个时间点发现存在不同的倍性状态。非整倍体 DNA 含量与总生存期较短相关(中位数,19 个月与 84 个月,p=0.047)。

结论

我们发现了倍性状态的变化和异质性。这意味着在单个肿瘤样本上筛选靶点是不够的,可能导致治疗不足或过度。非整倍体 DNA 含量与不良预后相关,这证实了该技术可区分生物学上不同的肿瘤克隆。

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1
Targeted therapy for Ewing's sarcoma: significance of heterogeneity.尤因肉瘤的靶向治疗:异质性的意义。
Anticancer Res. 2010 Sep;30(9):3715-9.
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Flow and image cytometric DNA analysis in Ewing's sarcoma.尤因肉瘤的流式细胞术和图像细胞术DNA分析
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