Hejna M, Raderer M, Zielinski C C
Department of Medicine I, University Hospital, Vienna, Austria.
J Natl Cancer Inst. 1999 Jan 6;91(1):22-36. doi: 10.1093/jnci/91.1.22.
Metastasis involves several distinct steps, including one in which the tumor cell, after entry into the bloodstream, comes to rest in a capillary located at the distant site where a metastatic tumor will ultimately form. Components of the blood-clotting pathway may contribute to metastasis by trapping cells in capillaries or by facilitating adherence of cells to capillary walls. Conceivably, anticoagulants could interfere with this step in the metastatic process. In this review, we have summarized current knowledge on the interaction of malignant cells, clotting factors, and anticoagulants. We used computerized (MEDLINE) and manual searches to identify studies done in humans, in animals, and in in vitro systems that were published in English between 1952 and 1998. We found many reports that the formation of metastatic tumors could be inhibited by heparin, a vitamin K antagonist (warfarin), and inhibitors of platelet aggregation (prostacyclin and dipyridamole). Despite these encouraging preliminary results and a compelling biochemical rationale, only limited information exists on the clinical use of anticoagulants for the prevention or treatment of metastatic cancer because there have been so few controlled and prospectively randomized studies on this topic. In view of the preliminary results, anticoagulants may hold promise for the prevention and treatment of metastases. We believe that larger controlled investigations are strongly warranted to evaluate the clinical potential of anticoagulants for the prevention and treatment of metastases in humans.
转移涉及几个不同的步骤，其中包括肿瘤细胞进入血液后，在远处最终形成转移瘤的部位的毛细血管中停留。凝血途径的成分可能通过将细胞困在毛细血管中或促进细胞与毛细血管壁的黏附而促进转移。可以想象，抗凝剂可能会干扰转移过程中的这一步骤。在这篇综述中，我们总结了关于恶性细胞、凝血因子和抗凝剂相互作用的现有知识。我们使用计算机检索（MEDLINE）和人工检索，以识别1952年至1998年间以英文发表的关于人类、动物和体外系统的研究。我们发现许多报告称，肝素、维生素K拮抗剂（华法林）和血小板聚集抑制剂（前列环素和双嘧达莫）可以抑制转移瘤的形成。尽管有这些令人鼓舞的初步结果和令人信服的生化理论依据，但关于抗凝剂在预防或治疗转移性癌症方面的临床应用的信息仍然有限，因为关于这个主题的对照和前瞻性随机研究很少。鉴于初步结果，抗凝剂可能在预防和治疗转移方面具有前景。我们认为，强烈需要进行更大规模的对照研究，以评估抗凝剂在人类预防和治疗转移方面的临床潜力。
