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Decidualization Resistance
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Irene Muñoz-Blat, Nerea Castillo-Marco, Teresa Cordero, Carlos Simón, Tamara Garrido-Gómez
Our transcriptomic results revealed altered gene expression during in vitro decidualization of hESCs from former patients with sPE. Among the 129 genes with altered expression, the gene encoding Annexin A2 (ANXA2) was further analyzed (26). This gene is associated with the first steps of embryo adhesion during the implantation process (48). ANXA2 is widely expressed in the placenta and its defective activity could cause fibrinolytic deficiency linked with increasing thrombosis and PE predisposition (49). We studied the role of ANXA2 in defective decidualization to evaluate its potential for being a maternal biomarker for sPE prediction (50). Deficient decidualization was detected in an in vitro model using small interfering RNA (siRNA) for ANXA2 in hESCs from control individuals. In addition, blocking ANXA2 expression during pregnancy in an in vivo knockout mouse model resulted in deficient implantation and placentation. Thus, these results support the occurrence of decidualization resistance in women with sPE at the time of delivery and propose ANXA2 as a possible biomarker to determine the risk of PE (50). Together, these results support the maternal contribution to PE.
Enzymatic Degradation of Bradykinin
Published in Sami I. Said, Proinflammatory and Antiinflammatory Peptides, 2020
Randal A. Skidgel, Ervin G. Erdös
Because carboxypeptidase U is a relatively new member of the metallocarboxypeptidase family, its functions are still being explored. However, it is likely important in the fibrinolytic pathway by regulating lysine-mediated plasminogen binding to proteins and cells, for example, by cleaving C-terminal lysine residues from α2-antiplasmin, histidine-rich glycoprotein, fibrin, annexin II, or a-enolase (Redlitz et al., 1995). Recently, it was shown to regulate clot lysis in dogs in vivo (Redlitz et al., 1996).
Gene Expression and Function of the Cellular Receptor for u-PA (u-PAR)
Published in Pia Glas-Greenwalt, Fibrinolysis in Disease Molecular and Hemovascular Aspects of Fibrinolysis, 2019
Vincent Ellis, Michael Ploug, Torben Plesner, Keld Danø
Although the cellular binding of plasminogen is crucial for the activity of this system, the nature of the cellular binding sites involved is incompletely elucidated and the abundance of these sites makes it almost certain that they are heterogenous in character. Although a number of proteins (e.g., α-enolase55 and annexin II56), and also nonproteins (gangliosides),57 have been demonstrated as cellular components binding plasminogen, none of these have been directly demonstrated to have any functional role in cellular plasminogen activation. Consequently reference to any of these components, or other potential plasminogen binding components, as “receptors” currently seems unfounded. The abundance and heterogeneity of the plasminogen binding sites invites speculation that a discrete subpopulation of the total binding is involved in u-PAR-mediated plasminogen activation. There is circumstantial evidence to support this kind of model, which is discussed later in this chapter.
Characteristics of fibrinolytic disorders in acute promyelocytic leukemia
Published in Hematology, 2018
Ping Wang, Yingmei Zhang, Huiyuan Yang, Wenyi Hou, Bo Jin, Jinxiao Hou, Haitao Li, Hongli Zhao, Jin Zhou
Annexin II on the surface of peripheral blood leukocytes was detected in the patients and healthy controls of this study. Before treatment, patients’ annexin II levels on the surface of peripheral blood leukemic cells was not significantly higher than that of the controls, which is in contrast to the data of bone marrow cells in other studies [11,12,27]. Compared with bone marrow cells, peripheral blood cells may have a more direct effect on fibrinolytic activity. Annexin II is also expressed on endothelial cells, peripheral blood monocytes, macrophages and neutrophils in healthy people [28,29]. Results from this study could not conclude that the increased fibrinolytic activity in patients with APL patients was caused by annexin II. Further research will be required to investigate this relationship.
Orlistat as a FASN inhibitor and multitargeted agent for cancer therapy
Published in Expert Opinion on Investigational Drugs, 2018
Alejandro Schcolnik-Cabrera, Alma Chávez-Blanco, Guadalupe Domínguez-Gómez, Lucia Taja-Chayeb, Rocio Morales-Barcenas, Catalina Trejo-Becerril, Enrique Perez-Cardenas, Aurora Gonzalez-Fierro, Alfonso Dueñas-González
Annexin A2 (also called p36, calpactin I, lipocortin II, chromo bindin VIII, or placental anticoagulant protein IV) is a 36 kDa protein. It has been reported that annexin A2 (ANXA2) plays a role in exocytosis, endocytosis, and membrane trafficking. Its depletion correlates with apoptotic death induced by p53-mediated pathways [91]. Annexin A is over-expressed in at least a dozen of malignancies [92]. Based on its role in cancer development and progression, its targeting has been evaluated in preclinical models. In fact, the anti-ANXA2 monoclonal antibody has shown in a preclinical model of breast carcinoma, a potent and durable antitumor effect lasting up to 172 days, with a 76% tumor growth inhibition with no adverse effects [93]. These data encourage the development of agents targeting ANXA2 for cancer treatment.
Prostate cancer proteomics: clinically useful protein biomarkers and future perspectives
Published in Expert Review of Proteomics, 2018
Paula Intasqui, Ricardo P. Bertolla, Marcus Vinicius Sadi
In another study, 320 proteins extracted from biopsies were identified, and annexin A2 (ANXA2) levels during initial diagnosis provided a good prediction of the metastasis risk [23]. A biomarker assay was then developed after a screening of several potential proteins in prostate biopsies from different medical centers. Proteins were analyzed by quantitative multiplex proteomics imaging, and results were correlated with the prostate pathology and attributed a Gleason score. A biomarker panel including eight proteins: cullin-2 (CUL2), derlin-2 (DERL2), RNA-binding protein FUS (FUS), stress-70 protein, mitochondrial (HSPA9), decaprenyl-diphosphate synthase subunit 2 (PDSS2), phospho-S6-ribosomal protein (pS6), mothers against decapentaplegic homolog 4 (SMAD4), and nuclease-sensitive element-binding protein 1 (YBX1), was proposed. This set of biomarkers was validated in a separate cohort and was capable of distinguishing samples according to tumor invasiveness (AUC = 0.68) and Gleason score (AUC = 0.65) [24]. The authors also report the use of a multiplex proteomics imaging platform, which they discuss avoids dilution of affected tissue during homogenization for proteomics analysis, and thus allows observation of the affected region. This also deals with the inherently heterogeneous and multifocal nature of prostate cancers, as it allows for observation of the affected region [24].