The thromboxane A2 pathway and its components are implicated in the regulation of tumor cell angiogenesis, migration, invasion, metastasis and apoptosis. Scientific studies report cyclooxygenase-2 is up-regulated in many different types of cancer including breast, cervix, colon, esophagus, glioma, head and neck, lung, melanoma, pancreas, prostate, stomach and thyroid. Levels of urinary 11-dehydrothromboxane B2 reflect activity of components of the thromboxane A2 pathway impacting thromboxane A2 generation. Test results may be of use to the healthcare provider in the diagnosis, prognosis and therapeutic management of patients with cancer.

Role of Cox-2/PGE2 Mediated inflammation in Oral Squamous Cell Carcinoma

"Oral cancer include malignancy of the oral cavity and oropharynx, 90% of which are squamous cell carcinoma.  Oral and oropharyngeal squamous cell carcinoma (OSCCP) is a very aggressive neoplasm and is often diagnosed late in the disease.  Extensive research has demonstrated a relationship between chronic inflammation and a variety of cancer types, including OSCC."

"A significant amount of research indicates that the cyclooxygenase/prostaglandin E2 (PGE2) pathway of inflammation contributes to the development and progression of a variety of cancers, including squamous cell carcinoma of the oral cacity and oropharynx (OSCC). Although there have been promising results from studies examining the utility of anti-inflammatory drugs in the treatment of toxicities, this strategy has been met with only variable success and may make them inappropriate for some OSCC patients.  Improved inflammation-targeting therapies require continued study of the mechanisms linking inflammation and progression of OSCC.  In this review, a synopsis of OSCC biology will be provided, and recent insights into inflammation related mechanisms of OSCC pathobiology will be discussed  The roles of prostaglandin E2 and cluster of differentiation factor 147 (CD147) will be presented, and evidence for their interactions in OSCC will be explored.  Through continued investigation into the protumourigenic pathways of OSCC, more treatment modalities targeting inflammation-related pathways can be designed with the hope of slowing tumour progression and improving patient prognosis in patients with this aggressive form of cancer."

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Oxidant Stress as a major determinant of platelet activation in invasive breast cancer

“Breast cancer (BC) is the most common female cancer and the second leading cause of cancer-related death in women, worldwide."  Recent data have clearly demonstrated that type 2 diabetes (T2D) and obesity are among the most important risk factors for postmenopausal estrogen-dependent BC, also suggesting that oxidative stress might represent a shared mechanism for BC initiation and/or progression.

 “The results obtained showed that presurgical urinary excretion of both biomarkers was enhanced in BC patients compared to controls and was associated with patients’ estrogen receptor (ER) expression, but not HER2 status or Ki67 proliferation index. Accordingly, both urinary biomarkers were increased in patients with luminal-like BC molecular subtypes compared with triple negative or HER2-enriched tumors. "The prognostic value of 11-dehydro-TXB2 was then evaluated showing a significant correlation with BC pathological response to neoadjuvant treatment. Furthermore, among relapsing patients, those with elevated urinary biomarker levels were more likely to develop distant metastasis rather than local recurrence."

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Inhibiting breast cancer by targeting the thromboxane A2 pathway

“Cyclooxygenases have been implicated in mammary tumorigenesis. We sought to identify the key prostaglandin responsible for the pro-neoplastic effect of cyclooxygenases and develop prostaglandin-targeted strategies for breast cancer chemoprevention or therapy."

“Clinically, the thromboxane A2 pathway might be associated with HER2- positive and axillary lymph node metastasis in human breast cancer. We found that the thromboxane A2 pathway was required for breast cancer cell growth, anchorage-independent growth and invasion capabilities."

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Aspirin use and reduced risk of pancreatic cancer

"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.  

"Regular use of aspirin thus appears to reduce risk of pancreatic cancer by almost half."

"People who take aspirin for prevention of other diseases likely also reduce their risk of pancreatic cancer.  Aside from benefits for both cardiovascular disease and certain cancers, long term aspirin use entails some risks of bleeding complications, which necessitates risk-benefit analysis for individual decisions about use."

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Curcumin anticancer studies in pancreatic cancer

"Pancreatic cancer is one of the deadliest cancers woldwide.  Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis"

"We also demonstrated that curcumin inhibited the proliferation and enhanced the apoptosis of MIA PaCA-2 cells, through the suppression of NF-kB-activation."

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Targeting arachidonic pathway by natural products for cancer prevention and therapy

Arachidonic acid (AA) pathway, a metabolic process, plays a key role in carcinogensis.  Hence, AA pathway metabolic enzymes phospholipase A2s (PLA2S), cyclooxygenases (COXs) and lipoxygenases (LOXs) and their metabolic products, such as prostaglandins and leukotrienes, have been considered novel preventive and therapeutic targets in cancer."

"Curcumin, resveratrol, apigenin, anthocyans, berberine, ellagic acid, eugenol, fisetin, ursolic acid, [6]-gingerol, guggulsteone, lycopene and genistein are well known cancer chemopreventive agents which act by targeting multiple pathways, including COX-2."

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Aspirin and Cancer

"The place of aspirin in primary prevention remains controversial, with North American and European organizations issuing contradictory treatment guidelines.  More recently, the U.S. Preventive Services Task Force recommended "initiating low-dose aspirin use for the primary prevention of cardiovascular disease and colorectal cancer in adults aged 50-59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years."  This recommendation reflects increasing evidence for a chemopreventive effect of low-dose aspirin against colorectal (and other) cancer.  The intent of this paper is to review the evidence supporting a chemopreventive effect of aspirin, discuss its potential mechanism (s) of action, and provide a conceptual framework for assessing current guidelines in the light of ongoing studies."

"The protective effects of low-dose aspirin against cancer appear to reflect the prevention of early neoplastic transformation throughout the alimentary tract, as well as an antimetastatic action. Both effects may be explained by the antiplatelet effect of low-dose aspirin."

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Obstructive Sleep Apnea Syndrome (OSA) and Cancer: Current Insights

"The obstructive sleep apnea syndrome (OSA) is an independent risk factor for atherosclerosis.  Chronic intermittent hypoxia (CHI) causes atherosclerosis in the occurrence of a pre-existing hyperlipidemia.  A new pathway, in animal models has been demonstrated that CIH significantly increased atherosclerotic lesion sizes, mRNA levels of Cox-1 and thromboxane synthase (TXBS).  Lesion size is correlated to COX-1 and TXBS mRNA levels.  COX-1 inhibition reduced lesion progression in intermittent hypoxia mice.  This study demonstrated for the first time, that the activation of the COX pathway exposed to CIH is associated with increased atherosclerotic lesions in mice, highlighting early atherosclerosis markers in OSA patients."

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Citrus flavanoids and human cancers

"Nowadays cancers pose a great threat to the health of human beings.  Based on studies on the flavonoids and other bioactive compounds of citrus fruits in current literature, it was widely suggested that the consumption of citrus fruits is beneficial to the prevention and treatment of human chronic diseases including cancers. In the past decades, the study concerning citrus flavonoids has covered various areas including the type, content and distribution of flavonoids in fruits; their variation between wild and cultivated genotypes; their antioxidant, anti-inflammation, anti-aging, antimicrobial and anticarcinogenic activities."

"Nuclear factor kappa B (NF-κB) transcription factors regulate several important physiologic processes of the cell, e.g., cell growth, and apoptosis. Thus, inhibition of NF-κB activation offers a potential strategy for treatment of different malignancies."

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Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical Significance

"Colorectal cancer (CRC) represents the third leading cause of cancer-related death in the United States.  Lack of reliable biomarkers remain a critical issue for early detection of Colorectal cancer.  In this study, we investigated the potential predictive values of circulating prostaglandin biosynthes in CRC risk."

“CRC progression is accompanied by a pronounced elevation of systemic TXA2 biosynthesis.” 

“Measurement of urinary TXA2 metabolites such as 11-dehydro TXB2 might provide the best estimate of systemic TXA2 biosynthesis in vivo”

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