Endothelial cell proliferation as a novel approach to targeting tumour therapy.
Endothelial cell proliferation as a novel approach to targeting tumour therapy.
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内皮细胞增殖作为靶向肿瘤治疗的新方法。
DOI：
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发表时间：
1982
影响因子：
8.8
通讯作者：
J. Denekamp
中科院分区：
文献类型：
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作者：
J. Denekamp
肿瘤中血管内皮细胞的增殖率比大多数成人正常组织中的增殖率高出一个非常大的系数，通常大于20（图）。这种巨大的差异提供了一种潜在的途径，通过靶向全身毒素将肿瘤治疗瞄准实体瘤，对大多数正常组织几乎没有损伤的风险。长期以来，人们已经认识到，实体瘤和成人正常组织之间的主要差异之一是血管网络的发展模式和速度。肿瘤中的新血管形成是快速的，但它不足以，特别是在三维排列中，为所有肿瘤细胞提供足够的营养供应（Hirst等人，1982年）。由于这个原因，许多肿瘤细胞由于营养缺乏而不增殖，并且由于每个毛细血管周围的代谢肿瘤细胞的氧气耗尽而缺氧。这会对化疗和放疗产生耐药性。大量的研究致力于寻找改善这种肿瘤中的氧合、增殖状态和药物递送的方法。认识到肿瘤细胞通过肿瘤血管生成因子（TAF）促进新血管形成的特殊能力。他们提出了通过干扰血管生成来防止肿瘤生长的方法，包括通过产生抗TAF抗体来灭活TAF的免疫技术，该抗体将防止进一步的毛细血管增殖。在其他地方，很少有人注意到肿瘤血管系统和正常组织血管系统的增殖特性之间的巨大差异。Tannock（1970）、Hirst & Denekamp（1979）和Hirst等人（1982）比较了肿瘤中毛细血管内皮细胞的增殖率与肿瘤细胞本身的增殖率。他们的结论是，内皮细胞增殖的速度限制了肿瘤细胞的产生，即使多达18%的内皮细胞可以在任何一个时间进行DNA合成。其他研究集中在各种正常组织中内皮细胞的非常低的增殖率上（参见Tannock和Hayashi，1972; Hirst等人，1980年）。然而，肿瘤和正常组织中内皮细胞之间的增殖速率的显著差异似乎以前没有被评论或确定为用于指导肿瘤治疗的潜在途径。该表总结了正常组织和肿瘤内皮的已发表标记指数（LI），并说明了它们之间的巨大差异。显示的数值是通过对自动射线照片进行评分获得的。
THE proliferation rate of vascular endo-thelial cells in tumours exceeds that in most adult normal tissues by a very large factor, often greater than 20 (Figure). This enormous differential offers a potential route for aiming tumour therapy at solid tumours by means of a targeted systemic toxin, with little risk of damage to most of the normal tissues. It has long been recognized that one of the major differences between solid tumours and adult normal tissues is the pattern and rate of development of the vascular network. New vessel formation in tumours is rapid, but it is insufficient, particularly in a 3-dimensional arrangement , to provide an adequate nutrient supply to all the tumour cells (Hirst et al., 1982). For this reason many tumour cells are non-proliferating because of nutrient deprivation, and hypoxic because of oxygen depletion by the metabolizing tumour cells around each capillary. This produces resistance to both chemotherapy and radiotherapy. A great deal of research is devoted to finding ways of improving the oxygenation, proliferative status and drug delivery in such tumours. recognized the special ability of tumour cells to promote new vessel formation via the tumour angiogenesis factor (TAF). They have proposed methods ofpreventing tumour growth by interfering with angio-genesis, including an immunological technique for inactivating TAF by producing an anti-TAF antibody which would prevent further capillary proliferation. Elsewhere, little attention has been paid to the enormous differential between the proliferation characteristics of the tumour vasculature and the normal tissue vasculature. Tannock (1970), Hirst & Denekamp (1979) and Hirst et al. (1982) have compared the proliferation rate of the capillary endothelium in tumours with that of the tumour cells themselves. They concluded that the rate of endothelial proliferation limits tumour cell production even though as many as 18% of the endothelial cells can be in DNA synthesis at any one time. Other studies have concentrated on the very low proliferation rate of endothelial cells in a variety of normal tissues (see reviews by Tannock & Hayashi, 1972; Hirst et al., 1980). However, the remarkable difference in proliferation rates between endothelium in tumours and in normal tissues does not seem to have been previously commented upon or identified as a potential route for directing therapy at a tumour. The Table summarizes the published labelling index (LI) for normal tissue and tumour endothelium, and illustrates the large difference between them. The values shown were obtained by scoring auto-radiographs …