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肝素对结直肠癌的抗肿瘤作用:文献综述

The Antineoplastic Effect of Heparin on Colorectal Cancer: A Review of the Literature.

作者信息

Giannas Emmanuel, Kontovounisios Christos

机构信息

Department of Surgery and Cancer, Imperial College London, London SW7 2BX, UK.

Department of General Surgery, Chelsea and Westminster Hospital, London SW10 9NH, UK.

出版信息

J Clin Med. 2023 Nov 19;12(22):7173. doi: 10.3390/jcm12227173.

Abstract

Heparin and derivatives are commonly used for thrombophylaxis in surgical colorectal cancer (CRC) patients. Recent studies have suggested that, besides its protective effect on the incidence of venous thromboembolism, heparin has an anti-cancer effect. The aim of this review was to explore the literature and report the antineoplastic effect of heparin and derivatives on CRC. MEDLINE and EMBASE databases were searched for relevant articles. Nineteen studies were included ( = 19). Fifteen were lab studies conducted in vivo or in vitro on CRC cell lines and/or mice ( = 15). Four were in vivo clinical studies ( = 4). CRC tumor growth was reduced by 78% in one study, ( < 0.01), while tumorigenesis was suppressed in heparin-treated mice in seven studies. A high dose of low molecular weight heparin for extended duration significantly reduced post-operative VEGF, suggesting that such a regime may inhibit tumor angiogenesis and distant metastasis. A randomized trial demonstrated the antineoplastic effect of nadroparin as the 6 month survival in palliative patients increased. Another study has reported that disease-free survival of CRC patients was not affected by a similar tinzaparin regime. The anti-cancer properties of heparin and derivatives are promising, especially in lab studies. Further clinical trials are needed to investigate the anti-cancer benefit of heparin on CRC.

摘要

肝素及其衍生物常用于结直肠癌(CRC)手术患者的血栓预防。最近的研究表明,除了对静脉血栓栓塞发生率有保护作用外,肝素还具有抗癌作用。本综述的目的是检索文献并报告肝素及其衍生物对CRC的抗肿瘤作用。检索MEDLINE和EMBASE数据库以查找相关文章。纳入了19项研究(n = 19)。15项是在CRC细胞系和/或小鼠上进行的体内或体外实验室研究(n = 15)。4项是体内临床研究(n = 4)。一项研究中CRC肿瘤生长减少了78%(P < 0.01),而在7项研究中肝素治疗的小鼠肿瘤发生受到抑制。高剂量的低分子量肝素延长使用时间可显著降低术后VEGF,表明这种方案可能抑制肿瘤血管生成和远处转移。一项随机试验表明那屈肝素具有抗肿瘤作用,因为姑息患者的6个月生存率提高。另一项研究报告称,类似的替扎肝素方案对CRC患者的无病生存期没有影响。肝素及其衍生物的抗癌特性很有前景,尤其是在实验室研究中。需要进一步的临床试验来研究肝素对CRC的抗癌益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2366/10671867/c5cd57693968/jcm-12-07173-g001.jpg

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