Chapter title |
Mode of Action of Aspirin as a Chemopreventive Agent
|
---|---|
Chapter number | 3 |
Book title |
Prospects for Chemoprevention of Colorectal Neoplasia
|
Published in |
Recent results in cancer research Fortschritte der Krebsforschung Progrès dans les recherches sur le cancer, August 2012
|
DOI | 10.1007/978-3-642-30331-9_3 |
Pubmed ID | |
Book ISBNs |
978-3-64-230330-2, 978-3-64-230331-9
|
Authors |
Melania Dovizio, Annalisa Bruno, Stefania Tacconelli, Paola Patrignani, Dovizio, Melania, Bruno, Annalisa, Tacconelli, Stefania, Patrignani, Paola |
Abstract |
Aspirin taken for several years at doses of at least 75 mg daily reduced long-term incidence and mortality due to colorectal cancer. The finding of aspirin benefit at low-doses given once daily, used for cardioprevention, locates the antiplatelet effect of aspirin at the center of its antitumor efficacy. In fact, at low-doses, aspirin acts mainly by an irreversible inactivation of platelet cyclooxygenase (COX)-1 in the presystemic circulation, which translates into a long-lasting inhibition of platelet function. Given the short half-life of aspirin in the human circulation(approximately 20 min) and the capacity of nucleated cells to resynthesize the acetylated COX-isozyme(s), it seems unlikely that a nucleated cell could be the target of aspirin chemoprevention. These findings convincingly suggest that colorectal cancer and atherothrombosis may share a common mechanism of disease, i.e. platelet activation in response to epithelial(in tumorigenesis) and endothelial(in tumorigenesis and atherothrombosis) injury. Activated platelets may also enhance the metastatic potential of cancer cells (through a direct interaction and/or the release of soluble mediators or exosomes) at least in part by inducing the overexpression of COX-2. COX-independent mechanisms of aspirin, such as the inhibition of NF-kB signaling and Wnt/β-catenin signaling and the acetylation of extra-COX proteins, have been suggested to play a role in its chemopreventive effects. However, their relevance remains to be demonstrated in vivo at clinical doses. |
Mendeley readers
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Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 13 | 22% |
Researcher | 9 | 15% |
Student > Bachelor | 8 | 14% |
Student > Doctoral Student | 4 | 7% |
Student > Master | 4 | 7% |
Other | 8 | 14% |
Unknown | 13 | 22% |
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Veterinary Science and Veterinary Medicine | 1 | 2% |
Other | 3 | 5% |
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