Formation and repair kinetics of Pt-(GpG) DNA adducts in extracted circulating tumour cells and response to platinum treatment

被引：13
作者：
Nel, I. [1 ]
Gauler, T. C. [2 ,4 ]
Eberhardt, W. E. [2 ,4 ]
Nickel, A-C [1 ]
Schuler, M. [2 ,4 ]
Thomale, J. [3 ]
Hoffmann, A-C [1 ,2 ]
机构：
[1] Univ Duisburg Essen, West German Canc Ctr, Dept Med Oncol, D-45122 Essen, Germany
[2] Univ Duisburg Essen, West German Canc Ctr, Dept Med Oncol, D-45122 Essen, Germany
[3] Univ Duisburg Essen, Sch Med, Inst Cell Biol Canc Res, D-45122 Essen, Germany
[4] Univ Hosp Essen, Ruhrlandklin, Div Thorac Oncol, D-45122 Essen, Germany
来源：
BRITISH JOURNAL OF CANCER | 2013年 / 109卷 / 05期
关键词：
Pt-(GpG) DNA adducts; circulating tumour cells; pre-therapeutic; ex vivo; non-small-cell lung cancer; platinum-based chemotherapy; LUNG-CANCER; EXPRESSION; CHEMOTHERAPY; LYMPHOCYTES; CAPACITY; EXCISION; TRIAL;
D O I：
10.1038/bjc.2013.419
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Background: Pt-(GpG) intrastrand crosslinks are the major DNA adducts induced by platinum-based anticancer drugs. In the cell lines and mouse models, the persistence of these lesions correlates significantly with cell damage. Here we studied Pt-(GpG) DNA adducts in circulating tumour cells (CTC) treated with cisplatin in medium upfront to systemic therapy from patients with advanced non-small-cell lung cancer (NSCLC). Methods: Blood was drawn before systemic treatment and the CD45/CD15-depleted fraction of mononuclear cells was exposed to cisplatin, verified for the presence of CTC by pan-cytokeratin (pCK) staining and immunoanalysed for the level of Pt-(GpG) in DNA. Results: Immunostaining for pCK, CD45 and subsequently for Pt-(GpG) adducts in the cisplatin-exposed cells (ex vivo) at different time points depicted distinct differences for adduct persistence in CTC between responders vs non-responders. Conclusion: Pt-(GpG) adducts can be detected in CTC from NSCLC patients and assessing their kinetics may constitute a clinically feasible biomarker for response prediction and dose individualisation of platinum-based chemotherapy. This functional pre-therapeutic test might represent a more biological approach than measuring protein factors or other molecular markers.
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页码：1223 / 1229
页数：7
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