Joiner B, Hirst V K, McKeown S R, McAleer J J, Hirst D G
CRC Gray Laboratory, Mount Vernon Hospital, Northwood, Middx, UK.
Br J Cancer. 1993 Oct;68(4):720-6. doi: 10.1038/bjc.1993.417.
Recombinant human erythropoietin (rHuEpo) has recently become available for the treatment of chronic anaemia, including that associated with cancer. Carcinoma NT in CBA mice causes a progressive anaemia which can be overcome by daily injections of recombinant human erythropoietin (rHuEpo). This model was used to study the effect of haematocrit on tumour blood flow, growth rate and radiosensitivity, in mice with haematocrits ranging from approximately 38% (control) to 65% (20 U/day rHuEpo). Tumours showed a small but significant slowing in growth rate with higher haematocrit. In vitro studies showed rHuEpo had no direct effect on the growth of NT cells. Tumour blood flow was measured by two methods in each mouse (133Xe clearance and 86Rubidium uptake). Blood flow showed a tendency to decrease with increasing blood viscosity although this effect was not significant despite the large differences in haematocrit. Although tumour doubling time was prolonged despite the large differences in haematocrit. Although tumour doubling time was prolonged with increasing radiation dose, from 0 (sham irradiated) to 35 Gy, haematocrit was not found to influence the growth delay. This was attributed to adaptation of the tumour during the relatively slow change in the haematocrit. rHuEpo is being considered for clinical use in anaemic cancer patients. Our data suggest that this treatment will correct haematocrit with no effect on tumour radiosensitivity.
重组人促红细胞生成素(rHuEpo)最近已可用于治疗慢性贫血,包括与癌症相关的贫血。CBA小鼠中的NT癌会导致进行性贫血,每日注射重组人促红细胞生成素(rHuEpo)可克服这种贫血。该模型用于研究血细胞比容对肿瘤血流、生长速率和放射敏感性的影响,所用小鼠的血细胞比容范围从约38%(对照)到65%(20 U/天rHuEpo)。血细胞比容较高时,肿瘤生长速率虽有小幅但显著的减慢。体外研究表明,rHuEpo对NT细胞的生长没有直接影响。通过两种方法测量每只小鼠的肿瘤血流(133Xe清除率和86铷摄取)。尽管血细胞比容差异很大,但随着血液粘度增加,血流呈下降趋势,不过这种影响并不显著。尽管血细胞比容差异很大,但肿瘤倍增时间延长。随着辐射剂量从0(假照射)增加到35 Gy,肿瘤倍增时间延长,但未发现血细胞比容会影响生长延迟。这归因于在血细胞比容相对缓慢变化期间肿瘤的适应性。rHuEpo正在考虑用于贫血癌症患者的临床治疗。我们的数据表明,这种治疗将纠正血细胞比容,而对肿瘤放射敏感性没有影响。