2,083 research outputs found
Collagen receptors as potential targets for novel anti-platelet agents
No full textPlatelets have important roles in atherosclerosis and thrombosis and their inhibition reduces the risk of these disorders. There is still a need for platelet inhibitors affecting pathways that reduce thrombosis and atherosclerosis while leaving normal hemostasis relatively unaffected, thus reducing possible bleeding complications. Although combinations show progress in achieving these goals none of the present inhibitors completely fulfill these requirements. Collagen receptors offer attractive possibilities as alternative targets at early stages in platelet activation. Three major collagen receptors are assessed in this review; the alpha2beta1 integrin, responsible primarily for platelet adhesion to collagen; GPVI, the major signaling receptor for collagen; and GPIb-V-IX, which is indirectly a collagen receptor via von Willebrand factor. Several thrombosis models and experimental approaches suggest that all three are interesting targets and merit further investigation
American Society of Hematology--48th Annual Meeting and Exposition. Updates on therapies. 9-12 December 2006 Orlando, FL, USA
No full textThe origins of major platelet receptor nomenclature.
No full textThe nomenclature of the major platelet receptors may appear complex, but in fact there are logical reasons why it developed in the way it did. In this short review, I describe the origins of this nomenclature, how it developed as more information became available and as relationships were established with receptors on other types of cells. Difficulties have also arisen with alternative nomenclature systems and the various equivalences with these are described and listed. There remain areas such as immunology and transfusion where the accepted nomenclature leaves something to be desired, but it is unlikely that major changes will occur
Platelet GPIb complex as a target for anti-thrombotic drug development
No full textSpecific inhibition of platelet function is a major target of anti-thrombotic drug research. Platelet receptors are both accessible and specific but have multiple functions often linked to a wide range of ligands. GPIb complex is best known as a major platelet receptor for von Willebrand factor essential for platelet adhesion under high shear conditions found in arteries and in thrombosis. Recent animal studies have supported inhibition of GPIb as a good candidate for anti-thrombotic drug development with several classes of proteins showing important specific effects and the required discrimination between roles in haemostasis and thrombosis is important to protect against bleeding complications. These include antibodies, several classes of snake venom proteins, mutant thrombin molecules and peptides affecting subunit interactions. However, due to the nature of its receptor-ligand interactions involving large protein-protein interfaces, the possibility of developing classic pharmaceutical inhibitors for long term (and perhaps oral) treatment is still unclear, and additional information about structural interactions and signalling mechanisms is essential
Snake venom proteins affecting platelets and their applications to anti-thrombotic research
No full textSnake venoms are very complex mixtures of biologically active proteins and peptides that may affect hemostasis in many ways, by activating or inhibiting coagulant factors or platelets, or by disrupting endothelium. They have been classified into various families, including serine proteases, metalloproteinases, C-type lectins, disintegrins and phospholipases. The various members of a particular family act selectively on different blood coagulation factors, blood cells or tissues. Venom proteins affect platelet function in particular by binding to and blocking or clustering and activating receptors or by cleaving receptors or von Willebrand factor. They may also activate protease-activated receptors or modulate ADP release or thromboxane A(2) formation. L-amino acid oxidases activate platelets by producing H(2)O(2). Many of these purified components are valuable tools in platelet research, providing new information about receptor function and signaling
Evolution of cooperation among tumor cells
No full textThe evolution of cooperation has a well established theoretical framework based on game theory. This approach has made valuable contributions to a wide variety of disciplines, including political science, economics, and evolutionary biology. Existing cancer theory suggests that individual clones of cancer cells evolve independently from one another, acquiring all of the genetic traits or hallmarks necessary to form a malignant tumor. It is also now recognized that tumors are heterotypic, with cancer cells interacting with normal stromal cells within the issue microenvironment, including endothelial, stromal, and nerve cells. This tumor cell???stromal cell interaction in itself is a form of commensalism, because it has been demonstrated that these nonmalignant cells support and even enable tumor growth. Here, we add to this theory by regarding tumor cells as game players whose interactions help to determine their Darwinian fitness. We marshal evidence that tumor cells overcome certain host defenses by means of diffusible products. Our original contribution is to raise the possibility that two nearby cells can protect each other from a set of host defenses that neither could survive alone. Cooperation can evolve as byproduct mutualism among genetically diverse tumor cells. Our hypothesis supplements, but does not supplant, the traditional view of carcinogenesis in which one clonal population of cells develops all of the necessary genetic traits independently to form a tumor. Cooperation through the sharing of diffusible products raises new questions about tumorigenesis and has implications for understanding observed phenomena, designing new experiments, and developing new therapeutic approaches.Author manuscript. Published in final edited form as: Proc Natl Acad Sci U S A. 2006 September 5; 103(36): 13474-13479.The final published version of this article is located at: www.pnas.org/cgi/doi/10.1073/pnas.0606053103NIH U56 CA113004; to David E. AxelrodR.A. was supported by National Science Foundation (NSF) Grant SES-0240852. D.E.A. was supported by NSF Grant IIS-0312953, National Institutes of Health (NIH) Grant U56 CA113004, and New Jersey Commission on Cancer Research Grant 1076-CCR-SO. K.J.P. is an American Cancer Society Clinical Research Professor and is supported by NIH Grants CA69568, CA102872, and CA093900.NIH CA69568; to Kenneth J. PientaNIH CA102872; to Kenneth J. PientaNIH CA093900; to Kenneth J. PientaNSF SES-0240852; to Robert AxelrodNJ Commission on Cancer Research 1076-CCR-SO; to David E. AxelrodAlso available in PubMed Central. PMCID: PMC155738
Primary haemostasis: sticky fingers cement the relationship
No full textPlatelet aggregation to form a haemostatic plug, or thrombus, plays a key role in preventing bleeding from a wound. Recent studies have provided new insights into how platelet receptors are deployed during the interactions with the vascular subendothelial matrix that lead to haemostatic plug formation
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