Molecular design and characterization of recombinant long half-life mutants of human tissue factor pathway inhibitor

Bai, Hao; Ma, Ding; Zhang, Yu Gao; Zhang, Nong; Kong, De Sheng; Guo, Hong Shen; Mo, Wei; Tang, Qi; Song, Hou Yan

doi:10.1160/th04-11-0721

Cited by 4 publications

(1 citation statement)

References 20 publications

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“…In vivo, recombinant human TFPI is cleared from the circulation in a biphasic manner with a rapid a-phase half-life (t 1/2a ) of 2.4 minutes and a terminal b-phase half-life (t 1/2b ) of 19.5 minutes. 26 From a therapeutic standpoint, this quick clearance is clinically inconvenient and potentially costly in conditions such as cancer for which continuous or regular administration would be required.…”

Section: Hemostatic Functions Of Tfpimentioning

confidence: 99%

The Role of Tissue Factor Pathway Inhibitor in Tumor Growth and Metastasis

Amirkhosravi

Meyer

Amaya

et al. 2007

Semin Thromb Hemost

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Clotting activation occurs frequently in cancer. Tissue factor (TF), the most potent initiator of coagulation, is expressed aberrantly in many types of malignancy and is involved not only in tumor-associated hypercoagulability but also in promoting tumor angiogenesis and metastasis via coagulation-dependent and coagulation-independent (signaling) mechanisms. Tissue factor pathway inhibitor (TFPI) is the natural inhibitor of TF coagulant and signaling activities. Studies have shown that TFPI exhibits antiangiogenic and antimetastatic effects in vitro and in vivo. In animal models of experimental metastasis, both circulating and tumor cell-associated TFPI are shown to significantly reduce tumor cell-induced coagulation activation and lung metastasis. Heparins and heparin derivatives, which induce the release of TFPI from the vascular endothelium, also exhibit antitumor effects, and TFPI may contribute significantly to those effects. Indeed, a non-anticoagulant low-molecular-weight heparin with intact TFPI-releasing capacity has been shown to have significant antimetastatic effect in a similar experimental mouse model. The evidence supporting the dual inhibitory functions on TF-driven coagulation and signaling strengthen the rationale for considering TFPI as a potential anticancer agent. This article primarily summarizes the evidence for antiangiogenic and antimetastatic effects of TFPI and describes its potential mechanisms of action. The possible application of TFPI and other inhibitors of TF as potential anticancer agents is described, and information regarding potential antitumor properties of TFPI-2 (which has structural similarities to TFPI) is also included.

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Section: Hemostatic Functions Of Tfpimentioning

confidence: 99%

The Role of Tissue Factor Pathway Inhibitor in Tumor Growth and Metastasis

Amirkhosravi

Meyer

Amaya

et al. 2007

Semin Thromb Hemost

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Identification of genes differentially expressed by calorie restriction in the rotifer (Brachionus plicatilis)

Kaneko

Hirayama

et al. 2009

J Comp Physiol B

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A monogonont rotifer Brachionus plicatilis has been widely used as a model organism for physiological, ecological studies and for ecotoxicology. Because of the availability of parthenogenetic mode of reproduction as well as its versatility to be used as live food in aquaculture, the population dynamic studies using the rotifer have become more important and acquired the priority over those using other species. Although many studies have been conducted to identify environmental factors that influence rotifer populations, the molecular mechanisms involved still remain to be elucidated. In this study, gene(s) differentially expressed by calorie restriction in the rotifer was analyzed, where a calorie-restricted group was fed 3 h day(-1) and a well-fed group fed ad libitum. A subtracted cDNA library from the calorie-restricted rotifer was constructed using suppression subtractive hybridization (SSH). One hundred sixty-three expressed sequence tags (ESTs) were identified, which included 109 putative genes with a high identity to known genes in the publicly available database as well as 54 unknown ESTs. After assembling, a total of 38 different genes were obtained among 109 ESTs. Further validation of expression by semi-quantitative reverse transcription-PCR showed that 29 out of the 38 genes obtained by SSH were up regulated by calorie restriction.

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