Heparin and Cancer
Heparin and Cancer
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肝素与癌症
DOI：
--
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发表时间：
1998
影响因子：
6.7
通讯作者：
D. Ornstein
中科院分区：
文献类型：
--
作者：
L. Zacharski;D. Ornstein
肝素作为一种治疗性抗凝剂，几十年来一直是基础和临床科学家深入研究的主题(1)。然而，除了对凝血的作用外，肝素还表现出许多与抗凝作用无关的其他活性(2)。1930年，当Goerner在实验动物中证明肝素抑制肿瘤生长时，他首次观察到肝素对恶性肿瘤自然史的影响(3)。在随后的几十年里，大量关于肝素和癌症的文献得到了发展。最近，在前瞻性随机临床试验中，人们对未分离肝素（UH）和低分子量肝素（LMWH）预防和治疗静脉血栓栓塞（VTE）的观察结果越来越感兴趣。一些研究表明，接受低分子肝素治疗的癌症患者的中短期生存得到改善。两项已发表的荟萃分析（4,5）强调了这一改善的结果，最近一项前瞻性研究的结果也支持了这一趋势(6)。在任何一项研究中，癌症预后的改善都不能归因于静脉血栓栓塞的预防；因此，有理由假设肝素的有益作用可能是由独立于抗凝的机制介导的。肝素有几个特性可以合理地解释它对实验和人类恶性肿瘤的影响。本文就肝素与肿瘤的关系进行综述，并对肝素发挥抗肿瘤作用的机制进行综述。目的是鼓励肝素对癌症结局的明确临床试验和对人类恶性肿瘤药物机制的进一步研究。低分子肝素具有良好的药代动力学特性，适合慢性门诊用药，是进一步研究的优秀候选者。这种与传统的实验性细胞毒性化疗的背离为开发新型生长调节疗法提供了希望，这种疗法可以中断癌症进展的途径。在本文中，“肝素”是指未分离肝素（UH），“UH”和“低分子肝素”将用于区分这两种分子形式。
Summary Heparin has been the subject of intensive investigation for decades by both basic and clinical scientists because of its usefulness as a therapeutic anticoagulant (1). In addition to its effects on coagulation, however, heparin exhibits many other activities which seem to have little to do with anticoagulation (2). Goerner first observed an effect on the natural history of malignancy in 1930 when he demonstrated that heparin inhibited tumor growth in experimental animals (3). A substantial body of literature on heparin and cancer has developed during the ensuing decades. A recent increase in interest has resulted from observations made during prospective, randomized clinical trials which compared unfractionated heparin (UH) with low molecular weight heparin (LMWH) for the prevention and treatment of venous thromboembolism (VTE). Several studies have shown improvement in short to intermediate term survival in the subset of patients with cancer who received LMWH. This improved outcome has been emphasized in two published meta-analyses (4, 5), and the trend is supported by the results of a more recent prospective study (6). The improved cancer outcome could not be attributed to prevention of VTE in any of the studies; therefore, it is reasonable to hypothesize that a beneficial effect of heparin may be mediated by mechanisms independent of anticoagulation. Heparin has several properties that may plausibly explain its effect on experimental and human malignancy. The purpose of this paper is to summarize the literature on heparin and cancer and review mechanisms by which heparin may exert antineoplastic activity. The goal is to encourage both definitive clinical trials of heparin on cancer outcome and further studies of drug mechanisms in human malignancy. LMWH, with its favorable pharmacokinetic attributes, is suitable for chronic outpatient administration and is an excellent candidate for further investigation. Such a departure from conventional experimental cytotoxic chemotherapy holds promise for development of novel forms of growth regulatory therapy that interrupt pathways of cancer progression. In this review, “heparin” will refer to unfractionated heparin (UH), and “UH” and “LMWH” will be used to distinguish between the two molecular forms.
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DOI：
10.1042/bj2760785
发表时间：
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期刊：
The Biochemical journal
影响因子：
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DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
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作者：
Pratt,CW;Tobin,RB;Church,FC
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DOI：
10.1172/jci119454
发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
Griffin,JH
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DOI：
10.1152/jappl.1983.55.4.1284
发表时间：
1983
期刊：
Journal of applied physiology: respiratory, environmental and exercise physiology
影响因子：
--
作者：
Flick,MR;Hoeffel,JM;Staub,NC
通讯作者：
Staub,NC