The arachidonic acid (AA) pathway plays a key role in cardiovascular biology, carcinogenesis, and many inflammatory diseases, such as asthma, arthritis, etc. Esterified AA on the inner surface of the cell membrane is hydrolyzed to its free form by phospholipase A2 (PLA2), which is in turn further metabolized by cyclooxygenases (COXs) and lipoxygenases (LOXs) and cytochrome P450 (CYP) enzymes to a spectrum of bioactive mediators that includes prostanoids, leukotrienes (LTs), epoxyeicosatrienoic acids (EETs), dihydroxyeicosatetraenoic acid (diHETEs), eicosatetraenoic acids (ETEs), and lipoxins (LXs). Many of the latter mediators are considered to be novel preventive and therapeutic targets for cardiovascular diseases (CVD), cancers, and inflammatory diseases. This review sets out to summarize the physiological and pathophysiological importance of the AA metabolizing pathways and outline the molecular mechanisms underlying the actions of AA related to its three main metabolic pathways in CVD and cancer progression will provide valuable insight for developing new therapeutic drugs for CVD and anti-cancer agents such as inhibitors of EETs or 2J2. Thus, we herein present a synopsis of AA metabolism in human health, cardiovascular and cancer biology, and the signaling pathways involved in these processes. To explore the role of the AA metabolism and potential therapies, we also introduce the current newly clinical studies targeting AA metabolisms in the different disease conditions.

/pdf/metabolism-pathways-of-arachidonic-acids-mechanisms-and-26csrabpai.pdf

Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets.

Purpose
The objective of this study was to describe trends in the prevalence of regular aspirin and nonsteroidal anti-inflammatory drug (NSAID) use among adults in the United States during 2005 and 2010, and to identify characteristics of regular users.

Methods
Data from the 2005 and 2010 National Health Interview Survey (NHIS) were analyzed to estimate the prevalence of regular use of aspirin and NSAIDs among U.S. adults aged 18 years and older. Results were stratified by demographics and self-reported medical conditions and extrapolated to provide U.S. population estimates.

Results
In 2010, around 43 million adults (19.0%) took aspirin at least three times per week for more than 3 months (i.e. regular users), and more than 29 million adults (12.1%) were regular users of NSAIDs. Compared with 2005, this was an overall increase of 57% in aspirin use and 41% in NSAID use. These increases were consistent across the strata of age, sex, race, and selected medical conditions, including cardiovascular disease (CVD), arthritis, peptic ulcers, cancer, and severe headache, except for Asian Americans.

Conclusion
Large increases in the use of both aspirin and NSAIDs were observed over a 5 year period. The increase may be the result of increasing media attention reporting that regular aspirin use lowers the risk of CVD and related deaths, and may also prevent cancer. Moreover, safety concerns related to alternative medications such as acetaminophen and selective COX-2 inhibitors may influence users of these drugs to switch to aspirin and NSAIDs. Copyright © 2013 John Wiley & Sons, Ltd.

Trends in the use of aspirin and nonsteroidal anti‐inflammatory drugs in the general U.S. population

Epidemiological studies have clarified the potential associations between regular aspirin use and cancers. However, it remains controversial on whether aspirin use decreases the risk of cancers risks. Therefore, we conducted an updated meta-analysis to assess the associations between aspirin use and cancers. The PubMed, Embase, and Web of Science databases were systematically searched up to March 2017 to identify relevant studies. Relative risks (RRs) with 95% confidence intervals (CIs) were used to assess the strength of associations. A total of 218 studies with 309 reports were eligible for this meta-analysis. Aspirin use was associated with a significant decrease in the risk of overall cancer (RR = 0.89, 95% CI: 0.87–0.91), and gastric (RR = 0.75, 95% CI: 0.65–0.86), esophageal (RR = 0.75, 95% CI: 0.62–0.89), colorectal (RR = 0.79, 95% CI: 0.74–0.85), pancreatic (RR = 0.80, 95% CI: 0.68–0.93), ovarian (RR = 0.89, 95% CI: 0.83–0.95), endometrial (RR = 0.92, 95% CI: 0.85–0.99), breast (RR = 0.92, 95% CI: 0.88–0.96), and prostate (RR = 0.94, 95% CI: 0.90–0.99) cancers, as well as small intestine neuroendocrine tumors (RR = 0.17, 95% CI: 0.05–0.58). These findings suggest that aspirin use is associated with a reduced risk of gastric, esophageal, colorectal, pancreatic, ovarian, endometrial, breast, and prostate cancers, and small intestine neuroendocrine tumors.

/pdf/associations-between-aspirin-use-and-the-risk-of-cancers-a-4araipz2sy.pdf

Associations between aspirin use and the risk of cancers: a meta-analysis of observational studies

With few exceptions, epidemiological studies have found that individuals who take nonsteroidal antiinflammatory drugs (NSAIDs) have a reduced risk of colorectal adenomas and carcinoma. Similarly, randomized studies in patients with familial adenomatous polyposis have uniformly found that NSAIDs can lead to polyp regression and prevention of new polyps, and trials in patients with sporadic adenomas document that aspirin reduces the risk of adenoma recurrence. Together these data provide convincing evidence for the chemopreventive efficacy of NSAIDs in the large bowel.

Aspirin and cancer risk: a summary review to 2007.

https://engagedscholarship.csuohio.edu/cgi/viewcontent.cgi?article=1197&context=scichem_facpub

From COX-2 Inhibitor Nimesulide to Potent Anti-Cancer Agent: Synthesis, In Vitro, In Vivo and Pharmacokinetic Evaluation

We investigated the risk of lung cancer in relation to non-steroidal anti-inflammatory drugs (NSAIDs) among 573 cases and 857 sex- and age-matched controls for whom we had information on use of NSAIDs, from a prescription database covering all pharmacies in Denmark since 1995, and self-reported NSAID use, smoking habits and other potential confounders Associations were expressed as odds ratios, assessed by logistic regression in unmatched analyses After controlling for smoking habits, length of education and concomitant use of acetaminophen, we found a slightly decreased relative risk of 086 (95% confidence intervals, 065–114) for lung cancer associated with any use of NSAIDs The risk decreased significantly (P=002) with increasing numbers of dispensed prescriptions per year during the 1–3 years before the index date with a relative risk of 049 (028–084) among those with four or more prescriptions per year during this period Our findings suggest that regular use of NSAIDs is associated with a slightly or moderately reduced risk for lung cancer

/pdf/use-of-nsaids-smoking-and-lung-cancer-risk-2prj1xn6ep.pdf

Use of NSAIDs, smoking and lung cancer risk.

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Use of NSAIDs, smoking and lung cancer risk.