Serum cytochrome c to indicate the extent of ongoing tumor cell death
Serum cytochrome c to indicate the extent of ongoing tumor cell death
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DOI：
10.1111/j.1751-553x.2008.01033.x
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发表时间：
2009-06
影响因子：
3
通讯作者：
A. Osaka;H. Hasegawa;K. Tsuruda;N. Inokuchi;K. Yanagihara;Y. Yamada;M. Aoyama;T. Sawada;S. Kamihira
中科院分区：
文献类型：
--
作者：
A. Osaka;H. Hasegawa;K. Tsuruda;N. Inokuchi;K. Yanagihara;Y. Yamada;M. Aoyama;T. Sawada;S. Kamihira
尽管细胞凋亡在肿瘤发生中具有重要意义，但目前尚无生物标志物来评估血液恶性肿瘤体内细胞凋亡的程度。我们研究了血清细胞色素c（cyto-c）作为细胞凋亡生物标志物的潜力。体外实验中，肿瘤坏死因子相关凋亡诱导配体（TNF-related apoptosis inducing ligand，TNF-related apoptosis inducing ligand，TNF-相关凋亡诱导配体）诱导凋亡细胞释放Cyto-c和乳酸脱氢酶（lactate dehydrogenase，LD）进入培养液中，呈时间依赖性，并具有不同的动力学模式。在153例恶性血液病患者中，只有三分之一的患者显示血清cyto-c水平较高（>20 ng/ml）。虽然血清cyto‐c水平与血清LD活性大致相关，但它们与系列测量的不同动力学模式表明，血清cyto‐c而不是LD是跟踪肿瘤状态变化的更敏感指标。此外，血清cyto‐c水平将急性成人T细胞白血病患者分为有利和不利亚组，5年生存率分别为67%和11%。总之，血清cyto‐c可以提供一种快速的真实的时间生物标志物，用于跟踪涉及凋亡细胞死亡的肿瘤状态变化，但缺乏疾病或细胞类型特异性。
Despite the significant implication of apoptosis in tumorigenesis, there is no biomarker to assess the extent of ongoing apoptosis in vivo for hematological malignancies. We investigated the potential of serum cytochrome c (cyto‐c) as a biomarker for apoptosis. Cyto‐c and lactate dehydrogenase (LD) were released into the culture medium from apoptotic cells induced by tumor necrosis factor‐related apoptosis‐inducing ligand in a time‐dependent manner in vitro, with different kinetic patterns. Only one‐third of 153 patients with hematological malignancies showed high levels of serum cyto‐c (>20 ng/ml). Although serum cyto‐c level was roughly correlated to serum LD activity, their different kinetic patterns from serial measurements indicated that serum cyto‐c rather than LD is a more sensitive indicator for tracking changes of tumor status. Furthermore, serum cyto‐c level stratified patients with acute adult T‐cell leukemia into favorable and unfavorable subgroups with 5‐year survival rates of 67%vs. 11%. In conclusion, serum cyto‐c may provide a fast real‐time biomarker for tracking changes of tumor status involved in apoptotic cell death, but lacking disease or cell‐type specificity.