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You searched for +publisher:"University of North Carolina" +contributor:("Mackman, Nigel"). Showing records 1 – 3 of 3 total matches.

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University of North Carolina

1. McEachron, Troy Anthony. Regulation of urokinase plasminogen activator and plasminogen activator inhibitor-1 in murine breast cancer cells.

Degree: Pathology and Laboratory Medicine, 2011, University of North Carolina

Proteases are indispensable for tumor growth, angiogenesis, and metastasis. These proteases are produced by tumor cells, stromal cells, and by the host coagulation cascade. Protease-activated receptor-1 (PAR-1) and PAR-2 are G protein-coupled receptors that serve as the cellular receptors for several of these proteases, including activated coagulation factor VII (FVIIa), activated coagulation factor X (FXa), and thrombin. PAR-1 and PAR-2 have been found to be overexpressed in breast cancer and activation of these receptors contributes to the malignant phenotype of the cells. Activation of PAR-1 or PAR-2 by coagulation proteases increases the expression of urokinase plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1). uPA and PAI-1 are overexpressed in breast cancer patients and contribute to tumor angiogenesis, tumor growth, and metastasis. Using the highly metastatic 4T1 murine mammary adenocarcinoma model, I examined the effects of coagulatio Advisors/Committee Members: McEachron, Troy Anthony, Mackman, Nigel, University of North Carolina at Chapel Hill.

Subjects/Keywords: School of Medicine; Department of Pathology and Laboratory Medicine

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

McEachron, T. A. (2011). Regulation of urokinase plasminogen activator and plasminogen activator inhibitor-1 in murine breast cancer cells. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:fa79f55d-2f3c-432c-aea1-cd55446f04c9

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

McEachron, Troy Anthony. “Regulation of urokinase plasminogen activator and plasminogen activator inhibitor-1 in murine breast cancer cells.” 2011. Thesis, University of North Carolina. Accessed October 30, 2020. https://cdr.lib.unc.edu/record/uuid:fa79f55d-2f3c-432c-aea1-cd55446f04c9.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

McEachron, Troy Anthony. “Regulation of urokinase plasminogen activator and plasminogen activator inhibitor-1 in murine breast cancer cells.” 2011. Web. 30 Oct 2020.

Vancouver:

McEachron TA. Regulation of urokinase plasminogen activator and plasminogen activator inhibitor-1 in murine breast cancer cells. [Internet] [Thesis]. University of North Carolina; 2011. [cited 2020 Oct 30]. Available from: https://cdr.lib.unc.edu/record/uuid:fa79f55d-2f3c-432c-aea1-cd55446f04c9.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

McEachron TA. Regulation of urokinase plasminogen activator and plasminogen activator inhibitor-1 in murine breast cancer cells. [Thesis]. University of North Carolina; 2011. Available from: https://cdr.lib.unc.edu/record/uuid:fa79f55d-2f3c-432c-aea1-cd55446f04c9

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of North Carolina

2. Geddings, Julia. The Role of Tumor Microvesicles in Cancer-Associated Thrombosis.

Degree: Pathology and Laboratory Medicine, 2015, University of North Carolina

Cancer patients have a ~4 -fold increased risk of venous thromboembolism (VTE) compared with the general population, and cancer patients with VTE have reduced survival compared with non-VTE patients. Microvesicles (MVs), also known as microparticles (MPs), are small membrane vesicles that are constitutively released from tumors, and tumor cell-derived, tissue factor (TF)-positive (TF+) MVs may contribute to thrombosis in cancer patients. I tested the hypothesis that tumor cell-derived, TF+ TMVs activate platelets in vitro and in vivo, and this contributes to cancer-associated VTE. For this study I first had to establish a reproducible model of cancer-associated thrombosis. The in vivo model chosen for this purpose was the inferior vena cava (IVC) stenosis model in mice. This model was chosen because it mimics certain features of human deep vein thrombosis, including the triggering of thrombosis with minimal endothelial damage, maintenance of blood flow at the site of thrombosis, and chronic thrombus development that can be followed over time in vivo. The strengths and weaknesses of this model are summarized in chapter 2 of this dissertation. The IVC stenosis model of thrombosis was used to evaluate the role of TF+ TMVs in the enhancement of thrombosis. In the study included as chapter 3 in this dissertation, I found that TF+ TMVs isolated from two human pancreatic cell carcinoma cells lines activate isolated human platelets in a TF- and thrombin-dependent manner in vitro. TF+ TMV-mediated platelet activation was also inhibited by the ADP scavenger apyrase and the P2Y12 receptor inhibitor 2MesAMP. Further, TF+ TMVs enhanced thrombosis in two mouse models of venous thrombosis in a TF-dependent manner. TF+ TMV-enhanced thrombosis was reduced in Par4 deficient mice and in wild-type mice treated with the platelet inhibitor clopidogrel, suggesting that TF+ TMV-enhanced thrombosis in mice was, in part, dependent on platelets. These studies identify TF+ TMV-induced platelet activation as a possible mechanism of thrombosis in cancer and suggest that platelet inhibitors, such as aspirin and clopidogrel, may be considered for the prevention of VTE in high risk cancer patients. Advisors/Committee Members: Geddings, Julia, Mackman, Nigel, Homeister, Jonathon, Kasthuri, Raj, Key, Nigel, Weissman, Bernard, Bergmeier, Wolfgang.

Subjects/Keywords: Medicine; Biology; Pathology; School of Medicine; Department of Pathology and Laboratory Medicine

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Geddings, J. (2015). The Role of Tumor Microvesicles in Cancer-Associated Thrombosis. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:3d55e13e-65a0-47b3-885e-91787f00f01f

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Geddings, Julia. “The Role of Tumor Microvesicles in Cancer-Associated Thrombosis.” 2015. Thesis, University of North Carolina. Accessed October 30, 2020. https://cdr.lib.unc.edu/record/uuid:3d55e13e-65a0-47b3-885e-91787f00f01f.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Geddings, Julia. “The Role of Tumor Microvesicles in Cancer-Associated Thrombosis.” 2015. Web. 30 Oct 2020.

Vancouver:

Geddings J. The Role of Tumor Microvesicles in Cancer-Associated Thrombosis. [Internet] [Thesis]. University of North Carolina; 2015. [cited 2020 Oct 30]. Available from: https://cdr.lib.unc.edu/record/uuid:3d55e13e-65a0-47b3-885e-91787f00f01f.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Geddings J. The Role of Tumor Microvesicles in Cancer-Associated Thrombosis. [Thesis]. University of North Carolina; 2015. Available from: https://cdr.lib.unc.edu/record/uuid:3d55e13e-65a0-47b3-885e-91787f00f01f

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of North Carolina

3. Blatt, Tasha. Role of the P2Y1 receptor in platelet activation.

Degree: Pharmacology, 2016, University of North Carolina

Understanding and manipulating thrombosis and blood hemostasis is critical for the effective treatment of patients at risk for heart attack and stroke. ADP is an important modulator of platelet function and vascular tone that acts by binding to and activating the P2Y1 and P2Y12 receptors. Deletion or inhibition of either receptor results in nearly a total loss of ADP-promoted aggregation. Interestingly, the P2Y1 receptor desensitizes extremely rapidly, with a half-life of approximately 18 sec, whereas the P2Y12 receptor continuously signals minutes after initial activation. We hypothesized that the rapid desensitization of the P2Y1 receptor in platelets prevents excess thrombosis and unwanted aggregation at lower concentrations of ADP. We have used ex vivo platelet activation experiments to demonstrate that the observed desensitization is specific to the P2Y1 receptor compared to other Gq-coupled receptors in platelets and is recapitulated in mouse platelets. We focused on serine and threonine residues on the C-terminus because of the involvement of various Ser and Thr phosphorylation on the regulation of the P2Y1 receptor in cell culture systems. Using an optimized viral transduction model to introduce variants of the P2Y1 receptor into bone marrow, we show preliminary data suggesting that mutating multiple serine and threonine residues in the C-terminus of the P2Y1 receptor (ā€œ340-0Pā€) results in prolonged activation of platelets in the absence of the P2Y12 receptor pathway, thus eliminating the observed desensitization in the wild type P2Y1 receptor. Furthermore, creation of a knock-in mouse for the 340-0P variant of the P2Y1 receptor revealed a loss of desensitization in platelets upon ADP stimulation in 340-0P heterozygous mice. These data suggest that the loss of Ser and Thr residues on the C-terminus of the P2Y1 receptor nullifies the observed desensitization and provides insights regarding the physiological relevance of this process in platelets. Advisors/Committee Members: Blatt, Tasha, Nicholas, Robert, Harden, T. Kendall, Bergmeier, Wolfgang, Mackman, Nigel, Parise, Leslie, Roth, Bryan.

Subjects/Keywords: School of Medicine; Department of Pharmacology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Blatt, T. (2016). Role of the P2Y1 receptor in platelet activation. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:44ab11e3-9091-4cfa-820f-93f471aaed92

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Blatt, Tasha. “Role of the P2Y1 receptor in platelet activation.” 2016. Thesis, University of North Carolina. Accessed October 30, 2020. https://cdr.lib.unc.edu/record/uuid:44ab11e3-9091-4cfa-820f-93f471aaed92.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Blatt, Tasha. “Role of the P2Y1 receptor in platelet activation.” 2016. Web. 30 Oct 2020.

Vancouver:

Blatt T. Role of the P2Y1 receptor in platelet activation. [Internet] [Thesis]. University of North Carolina; 2016. [cited 2020 Oct 30]. Available from: https://cdr.lib.unc.edu/record/uuid:44ab11e3-9091-4cfa-820f-93f471aaed92.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Blatt T. Role of the P2Y1 receptor in platelet activation. [Thesis]. University of North Carolina; 2016. Available from: https://cdr.lib.unc.edu/record/uuid:44ab11e3-9091-4cfa-820f-93f471aaed92

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.