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The processes involved in mammalian reproduction, from ovulation through to birth, clearly involve large-scale tissue remodelling, with some close analogies to in fl ammatory processes. One such process is the rupture of the ovarian follicle on ovulation. Human follicular fl uid has been found to contain heparan sulphate with unusually strong anticoagulant activity, due to a high content of 3-O-sulphated glucosamine [49]. Indeed, mice lacking the 3-O- sulfotransferase enzyme were found to have normal haemostasis but exhibited reproductive abnormalities [50]. Protracted labour is one of the major reasons for emergency caesarean section. Through clinical observations that women who were undergoing low molecular heparin treatment for thrombophilia had shorter labour time and experimental fi ndings that low molecular weight heparin increases myometrial contractility and induces increased synthesis of interleukin 8 in cervical fi broblasts [51], a non-anticoagulant heparin is now in Phase I clinical trial for the prevention and treatment of protracted labour [52]. The mechanism by which heparin acts in this indication is unclear. Human cervical ripening and cervical dilation is known to be a proinflammatory event [53,54] and heparin may have an effect on this process. Thrombosis is often associated with aggressive cancers such as pancreatic cancer and there are numerous clinical trials investigating the effect of heparin and low molecular weight heparin on the morbidity and mortality rate of cancer patients. Meta-analysis has shown that heparin therapies do improve survival rate for this group of patients. In addition, there is evidence to show that apart from acting as an antithrombotic, heparin may also possess antineoplastic properties. In cell based and animal models, Mellor et al.[55] demonstrated that non-anticoagulant heparin signi fi cantly inhibits the migration of breast cancer cells and that anticoagulant heparin can reduce migration and metastatic spread of cancer cells. The anti-metastatic effect may be due to its ability to inhibit the binding of growth factor on cell surface, leading to inhibition of angiogenesis. Heparin can also inhibit the adhesion by acting on L- and P-selectin [56] |
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xing2007(金币+8, 翻译EPI+1):谢谢 2010-08-23 07:39:50
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在哺乳动物繁殖所涉及的过程，从出生一直到排卵，明确涉及大规模组织重构，在佛罗里达州的一些ammatory进程密切类比。这样一个过程是对排卵卵泡破裂。人类滤泡佛罗里达州的uid已发现含有硫酸乙酰肝素与异常强大的抗凝血活性，由于3 - O型硫酸氨基葡萄糖含量高[49]。事实上，小鼠缺乏3 - O型转磺酶酶被发现有正常止血，但展出的生殖异常[50]。旷日持久的劳动是为紧急剖腹产的主要原因之一。 通过该妇女谁正在经历低分子量肝素治疗对血栓形成劳动时间较短和实验，低分子量肝素增加子宫收缩，并可使宫颈癌科幻broblasts增加白细胞介素-8的合成科幻ndings临床观察 [51]，非肝素抗凝血剂是目前在第一阶段的预防和治疗的临床试验的长期劳动[52]。这一机制的行为，在此适应症肝素目前还不清楚。宫颈癌和宫颈扩张成熟，被称为是一个炎性事件[53,54]和肝素可能对这一过程的影响。 血栓往往是相关的，如胰脏癌侵略性癌症，而又有很多调查肝素和很低的发病率和死亡率的癌症患者心率分子量肝素的临床试验。 Meta分析表明，肝素治疗不改善这个存活率组病人。此外，有证据表明，除了作为一种抗血栓形成，也可能具有肝素的抗肿瘤作用的属性。在细胞和动物模型为基础，梅勒等人。 [55]表明，非抗凝血剂肝素找出所有科幻吸光度抑制乳腺癌细胞的迁移和抗凝血剂肝素可以降低移植癌细胞的转移和扩散。 抗肿瘤转移作用可能是由于它能够抑制生长因子对细胞表面结合，导致血管生成的抑制作用。肝素还可以抑制对L -及P -选择素[56]的粘附作用 |
2楼2010-08-22 07:49:03