C1 inhibitor (C1 INH) is a member of the serine protease inhibitor (serpin) superfamily. It is the only physiological inhibitor of protease C1r and C1s in the complement system. C1 INH is a single chain glycoprotein with apparent molecular weight of 105 KDa, consisting of 478 amino acids. C1 INH N-terminal domain includes first 98 amino acids with 10 definite and 7 potential glycosylation site. Various of carbohydrates are present on the cell surface and component of ECM (extracellular matrix) in every eukaryotic cell, including both cancer cells and cells that are important for tumur survival. Carbohydrates on the cancer cell surface have been shown to be important in many aspects of cancer cell physiological processes, involved in cell growth and cell adhesion. Carbohydrates are also able to bind and interact with growth factors and other proteins that trigger signal transduction. Interfere carbohydrates maybe offer a useful therapeutic approach for treating cancers. In order to understand whether the C1 INH NT98 polypeptides can influences cancer or not, we amplified a DNA fragment encoding C1 INH N-terminal domain 98 residues (C1 INH NT98) by PCR, and transfer to the plasmid pGEX-2T, than use E.coli (BL21 strain) to express the non-glycosylated polypeptides, and further analyze the influence of the effective roles exhibited by the polypeptides non-glycosylated on breast cancer cell MDA-MB-435s. Proliferation and migration assays in our experiment showed that non-glycosylated C1 INH NT98 can inhibited breast cancer cell growth and migration, and the mechanism needed to be clarified clearly through extensive research.

C1-esterase inhibitor (C1-inh) can inhibitor the first complement protein as C1s and C1r activity to reach adjust classical pathway, avoid excessive activation of the complement system to cause disease. C1-inhibitor protein composed of 478 amino acids with two domains: C terminal domain (serpin domain) and N terminal domain. The early focus has been to angioedema associated with cancer found so far. So the purpose of the study was to investigate whether the C1-inh cause for the breast cancer cell proliferation and migration. We use recombinant gene transform Escherichia coli strain BL21(DE3) and expression. Recombinant protein was purified using affinity column. Influence of proliferation and migration on breast cancer cells were tested by purified recombinant C1-inh. In breast cancer cell proliferation results showed, C1-inh significant proliferation of breast cancer, and when the higher concentration, the longer the incubation time, the remarkable effect of promoting proliferation is even more obvious. The results in breast cancer cell migration is also significant in the C1-inh to promote breast cancer cell migration, and when the higher concentration of the longer incubation time, the significant increased migration is more effective. Therefore, this study does note C1-inh to promote breast cancer cell proliferation and migration.

The physiological role of the plasma contact system still remains a partial enigma. The aim of the presented work was to expand our understanding of the plasma contact system, focusing on its physiological activation and function, principally from a hemostatic perspective. It also explored contact system activation under pathological conditions. We found that when human platelets become activated in blood, plasma proteins of the contact system bind to platelets and initiate contact activation. The platelet-triggered contact activation contributed to clot formation by shortening the clotting time and enhancing clot stability. We demonstrated that the regulation of contact activation elicited by activated platelets differed from the previously described contact activation elicited by negatively charged material surfaces. Platelet-triggered contact activation and activation propelled by clotting blood were found to be regulated by antithrombin, whereas material-induced activation was regulated by C1 inhibitor. We also showed that the fibrin fibers that are formed during the clot process further enhance and propagate the contact activation initially induced by activated platelets. Fibrin not only activated factor XII but also seemed to increase the affinity of antithrombin for the proteases of the contact system, leading to the generation of contact enzyme-antithrombin complexes during clot formation. To determine whether the contact system might be involved in the inflammation and vascular disease associated with systemic lupus erythematosus (SLE), we analyzed plasma samples from SLE patients. These patients were found to have altered levels of contact enzyme-serpin complexes, supporting the concept that the contact system may be involved in the pathophysiology of SLE. The contact enzyme-antithrombin complexes were clearly linked to platelet activation in vivo. Altered levels of both FXIIa-antithrombin and FXIIa-C1 inhibitor were found to be correlated with previous vascular disease and may therefore be potential biomarkers for assessing the risk of thrombotic events in SLE patients. These findings add to our knowledge of how the plasma contact system is activated and functions in vivo and will help us to understand the role of the contact system, not only in hemostasis but also in vascular disease and thrombotic conditions.

The complement system is a long and complicated event of reactions where activation leads to cleavage of different factors and ends with either inflammation or cell lysis.     Recent studies have shown that the complement system and coagulation have some elements in common. Therefore in this study it was relevant to look at the inhibition of the complement system in two different whole blood analyses of coagulation activation, thromboelastography and impedance aggregometry. Thromboelastography, or TEG®, measures the clot forming properties of whole blood and the impedance aggregometry, or Multiplate®, measures platelets’ ability to adhere and aggregate to an electrode. Four different inhibitors where used: Eculizumab, C1 inhibitor, Compstatin and OMS721, which all inhibits different parts of the complement system.     The curves from Multiplate® was presented in standard deviation and the number of reduction, while the results from TEG® was presented in before and after added inhibitor in graphs.     In conclusion, impedance aggregometry show a more specific and secure results of the inhibitors effect, which was seen by that both C1 inihibitor and Compstatin had a major influence on the area under the curve (AUC). In TEG® there were no detectable difference, which could mean TEG® is not specific enough for platelets efficiency, which is affected by the complement inhibition.