文章：

癌症的贫血：千刀万剐的死亡

The anaemia of cancer: death by a thousand cuts

原文发布日期：2005-06-20

DOI: 10.1038/nrc1648

类型: Review Article

开放获取: 否

要点：

1. Anaemia is the most common cancer-associated morbidity.
2. Cancer-associated anaemia is an adverse prognostic factor for survival independent of tumour type.
3. The mechanisms for cancer-associated anaemia are diverse, but the most important is suppression of production of the essential erythroid-cell growth factor erythropoietin.
4. Erythropoietin serves as a survival factor for late-stage erythroid cells by coordinating the expression of both anti-apoptotic and pro-apoptotic proteins in these cells during their differentiation.
5. Tumour cells also have erythropoietin receptors.
6. Anaemia causes tissue hypoxia, which is tumour promoting through activation of genes in addition to erythropoietin that facilitate angiogenesis, glucose metabolism and cell proliferation, as well as selecting for p53-defective cells. Tissue hypoxia also enhances the resistance of tumour cells to radiotherapy or antimetabolites.
7. Recombinant human erythropoietin can alleviate cancer-associated anaemia and tissue hypoxia, but two recent clinical trials indicated that recombinant erythropoietin might also act as a tumour promoter, whereas the use of tumour-necrosis factor-α (TNFα) and TNF-related apoptosis-inducing ligand as antitumour agents could favour the activity of pro-apoptotic proteins during differentiation of erythoid cells.

要点翻译：

1. 贫血是癌症最常见的并发症。
2. 癌症相关贫血是生存的不良预后因素，与肿瘤类型无关。
3. 癌症相关贫血的机制多样，但最重要的是抑制必需的红系细胞生长因子——促红细胞生成素的产生。
4. 促红细胞生成素通过协调晚期红系细胞分化过程中抗凋亡和促凋亡蛋白的表达，作为这些细胞的生存因子。
5. 肿瘤细胞也具有促红细胞生成素受体。
6. 贫血导致组织缺氧，这种缺氧状态除了通过促红细胞生成素激活基因外，还会促进肿瘤生长，这些基因促进血管生成、葡萄糖代谢和细胞增殖，并选择p53缺陷细胞。组织缺氧还增强肿瘤细胞对放疗或抗代谢药物的耐药性。
7. 重组人促红细胞生成素可缓解癌症相关贫血和组织缺氧，但最近两项临床试验表明，重组促红细胞生成素也可能作为肿瘤促进因子，而使用肿瘤坏死因子-α（TNFα）和TNF相关凋亡诱导配体作为抗肿瘤剂，可能有利于红系细胞分化过程中促凋亡蛋白的活性。

英文摘要：

Cancer has a negative systemic impact on its host in addition to its local or metastatic effects, and no cancer complication is more ubiquitous than anaemia, a condition for which there is now a specific remedy, the recombinant growth factor erythropoietin. This is not a trivial therapeutic consideration, because cancer-associated anaemia has an adverse influence on survival regardless of tumour type. However, the pharmacological correction of anaemia with recombinant erythropoietin could promote tumour growth, whereas the use of tumour-necrosis factor-α (TNFα) and TNF-related apoptosis-inducing ligand as antitumour agents could exacerbate anaemia, thereby perpetuating tissue hypoxia and tumour progression.

摘要翻译： 

癌症除局部或转移效应外，对宿主还具有全身性负面影响，而最常见的并发症莫过于贫血。如今，这种贫血已有特异性治疗手段——重组生长因子促红细胞生成素。这一治疗选择并非无足轻重，因为无论肿瘤类型如何，癌相关贫血都会对生存产生不利影响。然而，用重组促红细胞生成药物纠正贫血可能促进肿瘤生长；相反，使用肿瘤坏死因子-α（TNFα）及其相关凋亡诱导配体作为抗肿瘤药物又可能加重贫血，从而持续组织缺氧并推动肿瘤进展。

原文链接：

The anaemia of cancer: death by a thousand cuts