Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation
Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation
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DOI：
10.1054/bjoc.2001.1803
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发表时间：
2001-05-18
影响因子：
8.8
通讯作者：
de Vries, EGE
中科院分区：
文献类型：
--
作者：
Schröder, CP;Wisman, GBA;de Vries, EGE
大剂量化疗和外周血造血干细胞移植（PBSCT）可加速造血干细胞端粒长度丢失。由于缺乏包括治疗前和治疗后样本的数据，我们研究了乳腺癌患者治疗前后的白细胞端粒长度和端粒酶活性，这些患者随机接受5个辅助疗程FEC（5-FU、表阿霉素和环磷酰胺）（n = 17），或4 x FEC，然后接受高剂量环磷酰胺、塞替派、卡铂和自体PBSCT（n = 16）。血红蛋白。在化疗前（t（0））、化疗后5个月（t（1））和化疗后9个月（t（2））评估MCV、白细胞和血小板数量;与t（0）相比，这些参数在t（1）和t（2）时降低（高剂量：所有参数;标准剂量：白细胞和血小板），高剂量治疗后的所有参数在t（1）时低于标准剂量治疗。t（0）和t（1）的成对个体白细胞样本显示端粒长度变化（通过端粒限制性片段（TRF）测定确定）范围为（+）0.8至-2.2kb，两组中有9名患者的TRF长度减少。在t（0）和t（1）的白细胞样本中，端粒酶活性（通过TRAP测定）低于检测限。因此，在这种情况下，标准和高剂量化疗会对血液重建产生负面影响。在个体患者中，端粒长度可以在治疗后的血液增殖应激后显著改变。(C)2001年癌症研究运动。
High-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT) may accelerate telomere length loss in haematopoietic stem cells. As data including pre-and post-treatment samples are lacking, we studied leukocyte telomere length and telomerase activity before and after treatment in breast cancer patients randomized to receive 5 adjuvant courses FEC (5-FU, epirubicin and cyclophosphamide) (n = 17), or 4 x FEC followed by high-dose cyclophosphamide, thiotepa, carboplatin and autologous PBSCT (n = 16). Haemoglobin. MCV, leukocyte-and platelet numbers were assessed prior to (t(0)), 5 months after (t(1)) and 9 months after chemotherapy (t(2)); these parameters were decreased at t(1) and t(2) compared to t(0) (high-dose: all parameters; standard-dose: leukocytes and platelets), and all parameters were lower after high-dose than standard-dose treatment at t(1). Paired individual leukocyte samples of t(0) and t(1) showed telomere length change (determined by telomere restricted fragment (TRF) assay) ranging from (+)0.8 to -2.2 kb, with a decreased TRF length in 9 patients of both groups. Telomerase activity (determined by TRAP assay) was below detection limit in leukocyte samples of t(0) and t(1). Thus, standard-and high-dose chemotherapy negatively affect haematological reconstitution in this setting. In individual patients, telomere length can be remarkably changed following haematological proliferative stress after treatment. (C) 2001 Cancer Research Campaign.