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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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在哺乳動物繁殖所涉及的過程，從出生一直到排卵，明確涉及大規(guī)模組織重構(gòu)，在佛羅里達州的一些ammatory進程密切類比。這樣一個過程是對排卵卵泡破裂。人類濾泡佛羅里達州的uid已發(fā)現(xiàn)含有硫酸乙酰肝素與異常強大的抗凝血活性，由于3 - O型硫酸氨基葡萄糖含量高[49]。事實上，小鼠缺乏3 - O型轉(zhuǎn)磺酶酶被發(fā)現(xiàn)有正常止血，但展出的生殖異常[50]。曠日持久的勞動是為緊急剖腹產(chǎn)的主要原因之一。 通過該婦女誰正在經(jīng)歷低分子量肝素治療對血栓形成勞動時間較短和實驗，低分子量肝素增加子宮收縮，并可使宮頸癌科幻broblasts增加白細胞介素-8的合成科幻ndings臨床觀察 [51]，非肝素抗凝血劑是目前在第一階段的預防和治療的臨床試驗的長期勞動[52]。這一機制的行為，在此適應癥肝素目前還不清楚。宮頸癌和宮頸擴張成熟，被稱為是一個炎性事件[53,54]和肝素可能對這一過程的影響。 血栓往往是相關(guān)的，如胰臟癌侵略性癌癥，而又有很多調(diào)查肝素和很低的發(fā)病率和死亡率的癌癥患者心率分子量肝素的臨床試驗。 Meta分析表明，肝素治療不改善這個存活率組病人。此外，有證據(jù)表明，除了作為一種抗血栓形成，也可能具有肝素的抗腫瘤作用的屬性。在細胞和動物模型為基礎(chǔ)，梅勒等人。 [55]表明，非抗凝血劑肝素找出所有科幻吸光度抑制乳腺癌細胞的遷移和抗凝血劑肝素可以降低移植癌細胞的轉(zhuǎn)移和擴散。 抗腫瘤轉(zhuǎn)移作用可能是由于它能夠抑制生長因子對細胞表面結(jié)合，導致血管生成的抑制作用。肝素還可以抑制對L -及P -選擇素[56]的粘附作用 |
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