ArticleCancer research2014
Thrombin drives tumorigenesis in colitis-associated colon cancer.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Review
- Effects of Prothrombin on Podocytopathy and Proteinuria in Glomerular Disease.Journal of the American Society of Nephrology : JASN · 2025Article
- PARs in the inflammation-cancer transformation of CRC.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Macrophages and platelets in liver fibrosis and hepatocellular carcinoma.Frontiers in immunology · 2023Review
- Biological Evaluation, Molecular Docking Analyses, and ADME Profiling of Certain New Quinazolinones as Anti-colorectal Agents.ACS omega · 2022Article
- Survival outcomes with warfarin compared with direct oral anticoagulants in cancer-associated venous thromboembolism in the United States: A population-based cohort study.PLoS medicine · 2022Article
- Platelet and Cancer-Cell Interactions Modulate Cancer-Associated Thrombosis Risk in Different Cancer Types.Cancers · 2022Review
- Overall survival with warfarin vs. low-molecular-weight heparin in cancer-associated thrombosis.Journal of thrombosis and haemostasis : JTH · 2021Article
- The Activation of Prothrombin Seems to Play an Earlier Role than the Complement System in the Progression of Colorectal Cancer: A Mass Spectrometry Evaluation.Diagnostics (Basel, Switzerland) · 2020Article
- The Immune Microenvironment and Cancer Metastasis.Cold Spring Harbor perspectives in medicine · 2020Review
- Cell type-specific mechanisms coupling protease-activated receptor-1 to infectious colitis pathogenesis.Journal of thrombosis and haemostasis : JTH · 2020Article
- Article
- Soft fibrin matrix downregulates DAB2IP to promote Nanog-dependent growth of colon tumor-repopulating cells.Cell death & disease · 2019Article
- Review
- Protease-Activated Receptors in the Intestine: Focus on Inflammation and Cancer.Frontiers in endocrinology · 2019Review
- [Effect of natural hirudin on angiogenesis of human microvascular endothelial cells].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2018Article
- Article
- Coagulation induced by C3aR-dependent NETosis drives protumorigenic neutrophils during small intestinal tumorigenesis.Nature communications · 2016Article
- Mechanistic roles of epithelial and immune cell signaling during the development of colitis-associated cancer.Cancer research frontiers · 2016Article
- Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
The established association between inflammatory bowel disease and colorectal cancer underscores the importance of inflammation in colon cancer development. On the basis of evidence that hemostatic proteases are powerful modifiers of both inflammatory pathologies and tumor biology, gene-targeted mice carrying low levels of prothrombin were used to directly test the hypothesis that prothrombin contributes to tumor development in colitis-associated colon cancer (CAC). Remarkably, imposing a modest 50% reduction in circulating prothrombin in fII+/- mice, a level that carries no significant bleeding risk, dramatically decreased adenoma formation following an azoxymethane/dextran sodium sulfate challenge. Similar results were obtained with pharmacologic inhibition of prothrombin expression or inhibition of thrombin proteolytic activity. Detailed longitudinal analyses showed that the role of thrombin in tumor development in CAC was temporally associated with the antecedent inflammatory colitis. However, direct studies of the antecedent colitis showed that mice carrying half-normal prothrombin levels were comparable to control mice in mucosal damage, inflammatory cell infiltration, and associated local cytokine levels. These results suggest that thrombin supports early events coupled to inflammation-mediated tumorigenesis in CAC that are distinct from overall inflammation-induced tissue damage and inflammatory cell trafficking. That prothrombin is linked to early events in CAC was strongly inferred by the observation that prothrombin deficiency dramatically reduced the formation of very early, precancerous aberrant crypt foci. Given the importance of inflammation in the development of colon cancer, these studies suggest that therapeutic interventions at the level of hemostatic factors may be an effective means to prevent and/or impede colitis-associated colon cancer progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.