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.

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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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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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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The role of aspirin in cancer prevention

“Recently published secondary analyses of cardiovascular trials provide the first randomized evidence that daily aspirin use may also reduce the incidence of all cancers combined, even at low doses (75-100 mg daily)”

“10% reduction in overall cancer incidence beginning during the first 10 years of treatment could tip the balance of benefits and risks favourably in average-risk populations.”

"This Review considers the general mechanism of action that defines aspirin and other non-steroidal anti inflammtory drugs (NSAIDs) as a class, the specific advantages of aspirin over other NSAIDs for prophylactic use, the current evidence concerning the main health outcomes affected by aspirin use, and the hypothesis that inhibition of platelet activiation may mediate both the cardioprotective and cancer preventive effects of low-dose aspirin."

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Platelet activation in patients with colorectal cancer

“Enhanced platelet activation occurs in colorectal cancer patients. Permanent inactivation of platelet COX-1 by low dose aspirin might restore anti tumor reactivity.”

"Thus we aimed to address whether enhanced platelet activation, as assessed by the measurement of the urinary excretion of 11-dehydro-TXB(2) (a major enzymatic metabolite of TXB(2), occurs in patients with colorectal cancer.  In 10 patients with colorectal cancer, the urinary excretion of 11-dehydro-TXB(2) was significantly higher than in 10 controls, matched for sex, age and cardiovascular risk factors"

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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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The thromboxane synthase and receptor signaling pathway in cancer: an emerging paradigm in cancer progression and metastasis

“Increased cyclooxygenase (COX)-2 expression has been described in a variety of human cancers, which has focused attention on TXA2 as a downstream metabolite of the COX-2-derived PGH2.”

“It is a great importance to further determine whether and how prostanoids, such as TXA2, mediate the effects of COX-2 in cancer, potentially leading to a more targeted approach for cancer prevention and treatment."

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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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