Hypoxic cell radiosensitizers as potential adjuvants to conventional chemotherapy for the treatment of cancer.
Hypoxic cell radiosensitizers as potential adjuvants to conventional chemotherapy for the treatment of cancer.
复制标题
缺氧细胞放射增敏剂作为治疗癌症的常规化疗的潜在佐剂。
DOI：
10.1016/0006-2952(82)90051-x
复制
发表时间：
1982
影响因子：
5.8
通讯作者：
B. C. Millar
中科院分区：
文献类型：
--
作者：
B. C. Millar
在讨论低氧细胞放射增敏剂作为化疗辅助治疗人类肿瘤的可能性之前，有必要考虑与正常组织相比，肿瘤中氧气的有效性以及开发放射增敏剂的原理。在正常组织和肿瘤组织中，氧分压依赖于通过血管系统的供应和组织中新陈代谢的局部清除。与正常组织不同，肿瘤的血管供应经历了持续的变化。随着肿瘤大小的增大，血管网成比例地减少。相对于肿瘤质量，血管变得更大，但更短。毛细血管交换表面积减小，毛细血管间距离增加。因此，随着肿瘤的生长，单位质量的氧气供应减少，这导致远离毛细血管的部位出现缺氧和坏死。低氧细胞比氧气充足的细胞更能抵抗电离辐射的致命影响。如果在人类肿瘤中存在这样的细胞，它们可能会在分次放射治疗后形成病灶重新生长，这可能会导致局部复发。放射增敏剂的发展是基于辐射化学的考虑，即具有高电子亲和力的模拟氧化合物应该选择性地修复缺氧细胞中的辐射损伤，而在有氧条件下不起作用[I]。硝基杂环化合物，如硝基呋喃和硝基咪唑受到特别关注，因为这些基团中的几个成员已经在临床上用于治疗厌氧菌感染。将它们引入临床放射治疗的理由是，它们应该缓慢代谢，从而有足够的时间到达肿瘤组织中的靶细胞，它们应该通过细胞与细胞的接触被动扩散，并且由于它们无法敏化需氧细胞，不应增加正常组织的毒性。现在，从生化和生物学证据来看，尽管放射增敏剂代谢缓慢，但在低氧条件下产生的某些产物对缺氧和需氧细胞都是有毒的。1974年，Sutherland[2]证明了甲硝唑对多细胞球体中低氧细胞的毒性，并提出了低氧事件产生的某些产物(S)扩散到有氧细胞，导致细胞死亡。
Before discussing the possibility that hypoxic cell radiosensitizers may be useful as adjuvants to chemotherapy in the treatment of human tumours it is worth considering the availability of oxygen in tumour compared with normal tissues and the rationale for the development of radiosensitizers. In both normal and tumour tissue oxygen tension is dependent on the supply through the vascular system and local removal by metabolism in the tissues. Unlike normal tissue, the vascular supply of tumours undergoes continuous change. As the tumour increases in size the vascular network proportionally decreases. Vessels become larger relative to tumour mass but shorter. There is a decrease in the exchange surface area of the capillaries accompanied by an increase in the intercapillary distance. Thus, as tumours grow the oxygen supply per unit mass decreases and this leads to areas of hypoxia and necrosis at sites distant from the capillaries. Hypoxic cells are much more resistant to the lethal effects of ionising radiation than well oxygenated cells. If such cells are present in human tumours the possibility that they may form foci for regrowth after fractionated radiotherapy could lead to local recurrence. The development of radiosensitizers was based on radiation chemical considerations that oxygen mimetic compounds with a high electron affinity should selectively fix radiation damage in hypoxic cells whilst having no effect in aerobic conditions [I]. Nitroheterocyclic compounds such as nitrofurans and nitroimidazoles have received particular attention because several members of these groups were already in use clinically for the treatment of anaerobic infections. The rationale for their introduction into clinical radiotherapy was that they should be metabolised slowly and thereby have ample time to reach target cells in tumour tissue, that they should diffuse passively via cell-cell contact and that by virtue of their inability to sensitize aerobic cells should not increase normal tissue toxicity.It is now apparent from biochemical and biological evidence that although radiosensitizers are metabolised slowly, certain products produced in hypoxia are toxic to both hypoxic and aerobic cells. In 1974 Sutherland [2] showed that metronidazole was toxic to hypoxic cells in multicellular spheroids and proposed that some product (s) produced by events in hypoxia diffused into aerobic cells and caused cell
登录
查看更多内容
KHT 肉瘤对放射增敏剂和 BCNU 联合化疗的体内反应。
影响因子：
8.8
作者：
Mulcahy,RT;Siemann,DW;Sutherland,RM
通讯作者：
Sutherland,RM
厌氧菌和缺氧中国仓鼠肺成纤维细胞 (V-79-473) 细胞中米索硝唑代谢的比较。
影响因子：
5.8
作者：
Koch,RL;Rose,C;Rich,TA;Goldman,P
通讯作者：
Goldman,P
长期接触米索硝唑后抗肿瘤药物的细胞毒性增强。
影响因子：
8.8
作者：
Roizin-Towle,LA;Hall,EJ
通讯作者：
Hall,EJ
米索硝唑对 RIF-1 肿瘤对环磷酰胺反应的增强作用。
影响因子：
8.8
作者：
Law,MP;Hirst,DG;Brown,JM
通讯作者：
Brown,JM
米索硝唑和化疗剂 CCNU 的体内组合。
影响因子：
8.8
作者：
Siemann,DW
通讯作者：
Siemann,DW