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Chronic Diseases

The thromboxane A2 pathway through its end product thromboxane A2 is implicated in the development and progression of many chronic diseases. There is clear clinical and/or experimental evidence platelet thromboxane A2 release is greatly enhanced in a number of chronic diseases. Frequently in these diseases, the balance between thromboxane A2 and prostacyclin is significantly altered, resulting in excessive vasoconstriction and disorders of hemostasis. Levels of urinary 11-dehydrothromboxane B2 reflect activity of components of the thromboxane A2 pathway resulting in thromboxane A2 generation.

Role of platelets in inflammation and cancer; novel therapeutic strategies

“The results of clinical studies have shown that the antiplatelet drug aspirin reduces the incidence of vascular events and colorectal cancer.”

“Low-dose aspirin treatment (which is associated with a preferential inhibition of platelet COX-1) causes a 70-80% reduction of urinary 11-dehydro-TXB2  and 2,3-din-or-TXB2 excretion.”

"Moreover, the results of clinical studies have shown that the antiplatelet drug aspirin reduces the incidence of vascular events and colorectal cancer.  All these pieces of evidence support the notion that colorectal cancer and atherothrombosis may share a common mechanism of disease, that is, platelet activation in response to epithelial (in tumourigensis) and endothelial (in tumourgenesis and atherothrombosis) injury."

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Communicating clinical research to reduce cancer risk through diet: Walnuts as a case example

"The connection between diet and cancer has been well established, as affirmed by the considerable international consistency among dietary and lifestyle recommendations for reducing risk of cancer and other chronic diseases. The World Cancer Research Fund, American Institute for Cancer Research, and the American Cancer Society guidance each emphasize a plant-based diet, a physically active lifestyle, limited alcohol, and maintaining a healthy weight."

“Both the walnut and fish diets inhibited prostaglandin E metabolite (PGEM) and 11-dehydro thromboxane B2, but had no effect on IL-1β, IL-6, TNF-α, CRP, or the number of circulating lymphocyte subsets.”

“A plant-based diet is associated with decreased risk for cancer and other chronic diseases, due in part to reduced chronic inflammation.”

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Glycyrrhizin suppresses lung adenocarcinoma cell growth through inhibition of thromboxane synthase

The effects of glycyrrhizin treatment in lung cancer remain undetermined, despite extensive studies of the anti-tumor activities of glycyrrhizin."

"Our study has revealed anti-tumor effects of glycyrrhizin on lung adenocarcinoma, and these effects are, to some extent, TAS-dependent.  TxAS has been shown to be a therapeutic target in lung cancer."

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Thromboxane A2 exerts promoting effects on cell proliferation through mediating cyclooxygenase-2 signal in lung adenocarcinoma cell

"Background: Lung cancer concerns a woldwide health problem and the efficacy of available treatments is unsatisfactory.  Recently, thromboxane A2 (TXA2) synthase (TXAS) and receptor (TXA2R) have been documented to play a role in lung cancer development.  Therefore dual TXA2R modulator may be more efficacious to kill lung tumor cells than single TXAS inhibitor or TXA2R antagonism.  The close relationship between cyclooxgenase (COX-2) and TXAS also raises the question whether or how TXA2 contributes to the oncogenic activity of Cox-2. This study is therefore conducted to answer these questions."

"The present study has for the first time shown that dual TXA2 modulators and the single blocker of TXAS or TXA2R offer a similar inhibitory role in lung adenocarcinoma cell proliferation and that the tumor-promoting effects of COX-2 can largely be relayed by TXA2."

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Platelets, cyclooxygenases and colon cancer

"A growing body of evidence supports the central role of platelets in early events of tumorigenesis and metastasis.  Activated platelets, in response to tissue damage, induce a proinflammatory program involving the aberrant expression of cyclooxygenase (COX)-2 which leads to increased tissue concentrations of the proinflammatory and protumorigenic prostaglandin E2.  The central role of platelet activation in cancer development is sustained by the analysis of clinical studies with aspiring showing an anti-cancer efficacy by the drug, even at the low doses used for the prevention of atherothrombosis."

"Activated platelets, in response to tissue damage, induce a proinflammatory program involving the aberrant expression of cyclooxygenase (COX)-2.”

“The central role of platelet activation in cancer development is sustained by the analysis of clinical studies with aspirin showing an anticancer efficacy by the drug, even at the low doses used for the prevention of atherothrombosis."

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The cyclooxygenase-2/thromboxane A2 pathway; a bridge from rheumatoid arthritis to lung cancer?

"It is possible that COX-2 derived TxA2 could be monitored for the early detection of LC in RA patients, and targeting this molecular pathway may decrease the risk of LC in patients with RA."

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Case-Control study of aspirin use and risk of pancreatic cancer

"Pancreas-cancer prognosis is dismal, with 5-year survival less than 5%.  Significant relationships between aspirin use and decreased pancreas-cancer incidence and mortality have been shown in four of 13 studies."

"Few Options besides the avoidance of smoking and obesity are available to prevent pancreatic cancer  The association between aspirin use and risk of pancreatic cancer has been inconsistent across studies."

"We observed a significant inverse relationship between aspirin use and risk of pancreatic cancer."

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Thromboxane synthase expression and correlation with VEGF and angiogenesis in non-small cell lung cancer

"This study confirms previous observations of the role of TXS in NSCLC using an in-vivo model, providing further support for the potential of TXS inhibition as a therapeutic strategy in the disease."

"Thromboxane synthase (TXS) overexpression increases tumor growth in NSCLC in-vivo."

"Increased TXS, VEGF, and CD-31 in tissue from TXS overexpressing xenografts."

"TXS associated with VEGF and vessel density in patient serum and tissue samples."

"No association with survival alone or in combination with VEGF."

"Novel anti-angiogenic role is NSCLC alone or in combination with other agents."

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Platelet thromboxane (11-dehydro-Thromboxane B2) and aspirin response in patients with diabetes and coronary artery disease

"Aspirin (ASA) irreversibly inhibits platelet cyclooxygenase-1 (COX-1) leading to decreased thromboxane-mediated platelet activation.  The effect of ASA ingestion on thromboxane generation was evaluated in patients with diabetes (DM) and cardiovascular disease."

“Patients with DM and CAD have significantly higher mean baseline levels of urinary 11-DHTXB2 than healthy controls likely indicating a higher platelet activation and risk for CVD.”

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Neuroblastoma-related inflammation

"The daily intake of low-dose aspirin lowers the risk of several cancers among the adults.  The continuous administration of low-dose aspirin to TH-MYCN mice (a model of pediatric neuroblastoma) delays tumor outgrowth and decreases tumor-promoting inflammation by inhibiting regulatory cells of the innate immune system as well as immunosuppressive mediators such as transforming growth factor B and thromboxane A2.  These findings pave novel avenues for the clinical management of neuroblastoma."

"The anticancer effects of aspirin have been suggested to depend on the inhibition of platelet activation, directly stemming from a reduction in TXA2 levels. This would be paralleled by a reduction in the metastatic potential of cancer cells and in the levels of COX2, by angiogenesis inhibition as well as by the attenuation of pro-inflammatory pathways involving, among several mediators, PGE2."

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