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Assessment of breast cancer progression and metastasis during a hypercoagulable state induced by silencing of antithrombin in a xenograft mouse model
Local coagulation activation has been shown to impact both primary tumor growth and metastasis in mice. It is well known that components of the blood clotting cascade such as tissue factor and thrombin play a role in tumor progression by activating cellular receptors and local formation of fibrin. However, whether venous thromboembolism (VTE) or a hypercoagulable state has a direct impact on cancer progression is unknown. Here we have combined an orthotopic murine breast cancer model, using female Nod-SCID mice, with siRNA-mediated silencing of antithrombin (siAT) leading to the induction of a systemic hypercoagulable state.
Source: Thrombosis Research - November 24, 2022 Category: Hematology Authors: J.T. Buijs, B. Ünlü, E.H. Laghmani, M. Heestermans, B.J.M. van Vlijmen, H.H. Versteeg Tags: Full Length Article Source Type: research

Knockdown of liver-derived factor XII by GalNAc-siRNA ALN-F12 prevents thrombosis in mice without impacting hemostatic function
Plasma coagulation Factor XII (FXII) plays a crucial role in contact activation, ultimately regulating both the kinin-kallikrein system and the intrinsic pathway of coagulation. A growing body of evidence suggests that inhibition of FXII can prevent thrombosis. Given FXII does not appear to modulate hemostasis, targeting FXII is a promising strategy for the prevention of pathological thrombus formation without the hemostatic risks typically associated with anticoagulants. To this end, a subcutaneously administered investigational RNAi therapeutic targeting liver F12 mRNA (ALN-F12) was developed.
Source: Thrombosis Research - August 26, 2020 Category: Hematology Authors: Jingxuan Liu, Brian C. Cooley, Akin Akinc, James Butler, Anna Borodovsky Tags: Full Length Article Source Type: research

P14. Abstract Title: Modulating Fibrinolysis using siRNA against Coagulation Factor XIII
High specificity, easy reversibility, and a half-life on the order of weeks; these are all major advantages that gene therapy has over traditional anticoagulants, add to that a strategy that weakens clots rather than preventing clotting altogether and prophylaxis of thrombosis may become much safer. Currently, anticoagulant drugs are used as a preventative measure for people susceptible to developing disease causing thrombi (which manifest as heart attacks, strokes, and pulmonary embolism), but they require frequent administration and their strict inhibition of clotting increases the risk of uncontrolled bleeding.
Source: Thrombosis Research - September 30, 2019 Category: Hematology Authors: A. Strilchuk, E. Conway, E. Pryzdial, P. Cullis, C. Kastrup Source Type: research

The cell-membrane prothrombinase, fibrinogen-like protein 2, promotes angiogenesis and tumor development
The aim of the study was to further investigate the role of fibrinogen-like protein 2 (FGL-2), a transmembrane prothrombinase that directly cleaves prothrombin to thrombin, in angiogenesis and tumor development and the mechanism(s) underlying these processes. To study angiogenesis HUVEC clones with decreased fgl-2 mRNA were generated by specific siRNA. To study tumorigenesis SCID mice were implanted with intact (wild type) and fgl-2-silenced PC-3 clones. IFN-γ treated HUVEC expressing increased fgl-2 mRNA exhibited significant capillary sprouting that was not inhibited by hirudin, whereas fgl-2 silencing completely inhibi...
Source: Thrombosis Research - December 4, 2014 Category: Hematology Authors: Esther Rabizadeh, Izhack Cherny, Doron Lederfein, Shany Sherman, Natalia Binkovsky, Yevgenia Rosenblat, Aida Inbal Tags: Regular Article Source Type: research

Oestrogen induced downregulation of TFPI expression is mediated by ERα
Conclusion: Our data establish a direct and time dependent regulation of TFPI expression by oestrogens through the ERα at the transcriptional level.
Source: Thrombosis Research - April 30, 2014 Category: Hematology Authors: Huda Omar Ali, Benedicte Stavik, Elisabeth Dørum, Nina Iversen, Per Morten Sandset, Grethe Skretting Tags: Coagulation and Fibrinolysis Source Type: research

siRNA down-regulation of FGA mRNA in HepG2 cells demonstrated that heterozygous abnormality of the Aα-chain gene does not affect the plasma fibrinogen level
Conclusions: Our results suggest that FGG mRNA levels limit fibrinogen expression in normal liver and HepG2 cells and that 50% reduction of FGA mRNA levels would not limit fibrinogen expression in normal liver and HepG2 cells.
Source: Thrombosis Research - February 15, 2013 Category: Hematology Authors: Yuka Takezawa, Kazuyuki Matsuda, Fumiko Terasawa, Mitsutoshi Sugano, Takayuki Honda, Nobuo Okumura Tags: Coagulation and Fibrinolysis Source Type: research