The protein C anticoagulant pathway.

Esmon, Charles T.

doi:10.1161/01.atv.12.2.135

Cited by 296 publications

(159 citation statements)

References 88 publications

Supporting

Mentioning

155

Contrasting

Unclassified

Order By: Relevance

“…The protein C pathway is a primary regulator of coagulation and inflammation events [37]. Protein C is activated on endothelial cells by the concerted activities of thrombin, thrombomodulin and the endothelial protein C receptor (EPCR).…”

Section: Discussionmentioning

confidence: 99%

A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: A Gynecologic Oncology Group study

McMeekin

Sill

Benbrook

et al. 2007

Gynecologic Oncology

View full text Add to dashboard Cite

Objectives-A phase II trial was conducted to evaluate the anti-tumor activity and adverse effects of thalidomide in persistent or recurrent endometrial cancer refractory to cytotoxic chemotherapy, and to correlate angiogenesis biomarker expression with clinical outcome.Methods-Consenting patients were treated until progression or intolerable toxicity with an oral starting dose of 200 mg thalidomide/day that was to increase by 200 mg every 2 weeks to a target dose of 1000 mg/day. Vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF), and soluble endothelial protein C receptor (sEPCR) were analyzed by ELISA in pre and post-treatment specimens.Results-Twenty-four of 27 patients enrolled in the study were eligible, of whom 2 reached the target dose, 8 progressed before achieving the target dose and 14 refused or had toxicity that prohibited escalation. Two patients (8.3%) remained progression-free ≥ 6 months. There were 3 (12.5%) with partial responses, 2 (8.3%) with stable disease, 15 (62.5%) with increasing disease, and 4 (16.7%) who were inevaluable for response. Median progression-free survival and overall survival Précis: Thalidomide has minimal activity in chemo-refractory endometrial cancer as judged by the ability to prolong progression-free survival greater than 6 months.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Section: Discussionmentioning

confidence: 99%

A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: A Gynecologic Oncology Group study

McMeekin

Sill

Benbrook

et al. 2007

Gynecologic Oncology

View full text Add to dashboard Cite

show abstract

“…␥-Carboxyglutamic acid-mediated calcium ion binding in these proteins is necessary for their association with phospholipid surfaces and is critical for their hemostatic function (1,2). Prothrombin and factors VII, IX, and X are involved in the coagulant response leading to the generation of thrombin at sites of injury, whereas PC and PS play roles in an antithrombotic pathway that limits coagulation by inactivating the important coagulation cofactors Va and VIIIa (3). Protein Z (PZ) is a 62-kDa, vitamin K-dependent plasma protein whose structure is similar to that of factors VII, IX, and X and PC.…”

mentioning

confidence: 99%

Prothrombotic phenotype of protein Z deficiency

Yin

Huang

Cui

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

152

160

View full text Add to dashboard Cite

Protein Z (PZ) is a vitamin K-dependent plasma protein whose function has been uncertain. The structure of PZ is very similar to that of the coagulation-related factors VII, IX, and X and PC, but PZ differs from these other proteins in that it is not the zymogen of a serine protease. We have shown recently that PZ forms a calcium ion-dependent complex with activated factor X at phospholipid surfaces and that this interaction leads to the inhibition of activated factor X activity through, in part, the action of a previously unidentified plasma protein named PZ-dependent protease inhibitor. Herein, we report that the presence of PZ dampens the coagulation response in human plasma and that concomitant PZ deficiency dramatically increases the severity of the prothrombotic phenotype of factor VLeiden mice. The results indicate that PZ plays a physiologically important role in the regulation of coagulation.

show abstract

“…3 Finally, the propagation phase is regulated by the protein C anticoagulant pathway. 4 As thrombin is generated, it binds to endothelial cell surface thrombomodulin, and its specificity is redirected from fibrinogen cleavage to protein C activation. Activated protein C, with its essential cofactor protein S, is able to inactivate FVa (and possibly FVIIIa), thereby downregulating any burst of thrombin generation.…”

mentioning

confidence: 99%

Correcting the hemophilic imbalance

Lane

2017

Blood

View full text Add to dashboard Cite

In this issue of Blood, Polderdijk et al design and evaluate a therapeutic inhibitor of activated protein C.1 They have produced a recombinant variant of a1- antitrypsin (a1AT) incorporating 3 residue changes within the P2-P19 sequence of its reactive loop. This variant (termed KRK a1AT) exhibits high specificity and inhibitory efficiency toward activated protein C. It is able to restore thrombin generation in normal and in hemophilia plasmas, when these are supplemented with soluble thrombomodulin. It is able to restore hemostasis in challenged hemophilia mice. KRK a1AT is therefore a potentially valuable future therapeutic agent for the human hemophilias

show abstract

The protein C anticoagulant pathway.

Cited by 296 publications

References 88 publications

A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: A Gynecologic Oncology Group study

A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: A Gynecologic Oncology Group study

Prothrombotic phenotype of protein Z deficiency

Correcting the hemophilic imbalance

Contact Info

Product

Resources

About