- Clotting mechanisms and cancer: implications in thrombus formation and tumor progression.
- The Interplay between Hemostasis and Malignancy: The Oral Cancer Paradigm
- Hemostatic Mechanism In Extracorporeal Circulation | JAMA Surgery | JAMA Network
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Try searching for "tissue factor" on PubMed and see how many hits you get! You can also try alternate names for tissue factor, which are coagulation factor III F3 and tissue thromboplastin - these really help narrow the search.
Tissue factor is the main trigger of the complex coagulation cascade. It is a transmembrane protein that is constitutively expressed lining blood vessels. Coagulation is normally activated when endothelial cells are injured. Once bound to tissue factor, FVII becomes activated and together the two proteins form an enzymatic complex, which binds to and activates another coagulation factor, factor X FX.
FX is the lead protein of the common pathway of coagulation, whose end-result is the generation of the potent enzyme, thrombin, from prothrombin factor II. Thrombin is the ultimate enzyme responsible for clot or thrombus formation, since it directly cleaves fibrinogen into fibrin, which forms the basis of thrombi Figure 1. With respect to thrombosis, I am studying the role of tissue factor and platelets in two main diseases - one affecting horses I own a lovely Arabian gelding - see above - so I clearly have a personal agenda here and one affecting dogs really and truly man's best friend.
My interest in this area arose from my professional diagnostic service responsibilities as a clinical pathologist, in which I frequently make a diagnosis of cancer from aspirates of tissues of animals. My desire to understand the biology of cancer and to help animals led to this research focus in my laboratory. I am currently studying the role of tissue factor in cancer metastasis in humans and animals.
Tissue factor is upregulated in cancer cells and is thought to be a marker of oncogenic transformation. Activation of coagulation, with thrombus formation, is a common consequence of cancer in people. We have shown that various different cancer cells from dogs express tissue factor. These studies have been extended by Lauren Witter and Erika Gruber a clinical pathology resident.do05.makkie.com/faithless-1.php
Clotting mechanisms and cancer: implications in thrombus formation and tumor progression.
They have been working on thrombin generation by cancer cells and have data showing that these cells generate thrombin in plasma in a tissue factor-dependent manner manuscripts in preparation. We have also been looking at how tissue factor helps tumor cells metastastize. To facilitate these studies, I established a collaboration with the Department of Biomedical Engineering at Cornell University. With the assistance of Dr. Michael Shuler, members of my laboratory Drs.
Mandy Esch and James Camp have developed a unique microfluidic device, consisting of small less than 70 um semi-cylindrical "vascular" channels fabricated into a synthetic transparent polymer, called PDMS. Endothelial cells can be grown within the channels and can be exposed to fluid shear forces, similar to what they experience in blood Figure 2. Sara Che, a graduate student in my laboratory, is using this device to explore how cancer cells interact proteins or endothelial cells to form metastatic tumors.
The Interplay between Hemostasis and Malignancy: The Oral Cancer Paradigm
Sara has found that high tissue factor-expressing cancer cells can bind to the natural inhibitor of tissue factor called tissue factor pathway inhibitor under static and fluidic conditions using the above device , suggesting that this tissue factor-inhibitor binding could help capture circulating tumor cells to promote tumor metastasis, particularly in sites of low blood flow.
Sara is now looking at how tissue factor-expressing microvesicles generated by cancer cells can affect endothelial cells to promote metastasis and she has had lots of help with this from great under-graduate students like Jeannie Park and Linda Wang. I am a veterinary clinical pathologist and am dedicated to advancing my field through investigative studies. Anything clinical pathology-related is fair research game, as can be seen from my varied research publications.
Hemostatic Mechanism In Extracorporeal Circulation | JAMA Surgery | JAMA Network
My main clinical pathologic interests are hemostatic disorders and hematopoietic neoplasia. Wright's-stained smear of a lymph node aspirate from a dog with a metastatic transitional cell carcinoma. A tumor cell with a purple intracytoplasmic inclusion is seen amongst lymphocytes. Wright's stained smear of a skin lesion from a cat with Histoplasmosis.
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Many encapsulated yeast are seen within both macrophages in this image. Wright's stained blood from a dog with acute megakaryoblastic leukemia.
Register Login. Hematology Meeting Reports formerly Haematologica Reports. Article Sidebar PDF. Published: Jun 3, Abstract Views: 89 PDF: Degen, J.