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International Journal of Molecular... Nov 2020Aspirin, synthesized and marketed in 1897 by Bayer, is one of the most widely used drugs in the world. It has a well-recognized role in decreasing inflammation, pain and... (Review)
Review
Aspirin, synthesized and marketed in 1897 by Bayer, is one of the most widely used drugs in the world. It has a well-recognized role in decreasing inflammation, pain and fever, and in the prevention of thrombotic cardiovascular diseases. Its anti-inflammatory and cardio-protective actions have been well studied and occur through inhibition of cyclooxygenases (COX). Interestingly, a vast amount of epidemiological, preclinical and clinical studies have revealed aspirin as a promising chemopreventive agent, particularly against colorectal cancers (CRC); however, the primary mechanism by which it decreases the occurrences of CRC has still not been established. Numerous mechanisms have been proposed for aspirin's chemopreventive properties among which the inhibition of COX enzymes has been widely discussed. Despite the wide attention COX-inhibition has received as the most probable mechanism of cancer prevention by aspirin, it is clear that aspirin targets many other proteins and pathways, suggesting that these extra-COX targets may also be equally important in preventing CRC. In this review, we discuss the COX-dependent and -independent pathways described in literature for aspirin's anti-cancer effects and highlight the strengths and limitations of the proposed mechanisms. Additionally, we emphasize the potential role of the metabolites of aspirin and salicylic acid (generated in the gut through microbial biotransformation) in contributing to aspirin's chemopreventive actions. We suggest that the preferential chemopreventive effect of aspirin against CRC may be related to direct exposure of aspirin/salicylic acid or its metabolites to the colorectal tissues. Future investigations should shed light on the role of aspirin, its metabolites and the role of the gut microbiota in cancer prevention against CRC.
Topics: Animals; Aspirin; Chemoprevention; Colorectal Neoplasms; Cyclooxygenase Inhibitors; Gastrointestinal Microbiome; Humans; Prostaglandin-Endoperoxide Synthases
PubMed: 33260951
DOI: 10.3390/ijms21239018 -
Proceedings of the National Academy of... Mar 2019Inflammation in the tumor microenvironment is a strong promoter of tumor growth. Substantial epidemiologic evidence suggests that aspirin, which suppresses inflammation,...
Inflammation in the tumor microenvironment is a strong promoter of tumor growth. Substantial epidemiologic evidence suggests that aspirin, which suppresses inflammation, reduces the risk of cancer. The mechanism by which aspirin inhibits cancer has remained unclear, and toxicity has limited its clinical use. Aspirin not only blocks the biosynthesis of prostaglandins, but also stimulates the endogenous production of anti-inflammatory and proresolving mediators termed aspirin-triggered specialized proresolving mediators (AT-SPMs), such as aspirin-triggered resolvins (AT-RvDs) and lipoxins (AT-LXs). Using genetic and pharmacologic manipulation of a proresolving receptor, we demonstrate that AT-RvDs mediate the antitumor activity of aspirin. Moreover, treatment of mice with AT-RvDs (e.g., AT-RvD1 and AT-RvD3) or AT-LXA inhibited primary tumor growth by enhancing macrophage phagocytosis of tumor cell debris and counter-regulating macrophage-secreted proinflammatory cytokines, including migration inhibitory factor, plasminogen activator inhibitor-1, and C-C motif chemokine ligand 2/monocyte chemoattractant protein 1. Thus, the pro-resolution activity of AT-resolvins and AT-lipoxins may explain some of aspirin's broad anticancer activity. These AT-SPMs are active at considerably lower concentrations than aspirin, and thus may provide a nontoxic approach to harnessing aspirin's anticancer activity.
Topics: Animals; Antineoplastic Agents; Aspirin; Chemokine CCL2; Chemokines; Cytokines; Disease Models, Animal; Docosahexaenoic Acids; Eicosanoids; Fatty Acids, Unsaturated; Female; Inflammation; Lipoxins; Macrophages; Metabolomics; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microtubule-Associated Proteins; Neoplasm Metastasis; Neoplasms; Nerve Tissue Proteins; Phagocytosis; Plasminogen Inactivators; Prostaglandins
PubMed: 30862734
DOI: 10.1073/pnas.1804000116 -
British Medical Journal (Clinical... Jun 1986
Topics: Adolescent; Arthritis, Juvenile; Aspirin; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Reye Syndrome
PubMed: 3087507
DOI: 10.1136/bmj.292.6535.1543 -
International Journal of Molecular... Sep 2019Uncomplicated healthy pregnancy is the outcome of successful fertilization, implantation of embryos, trophoblast development and adequate placentation. Any deviation in... (Review)
Review
Uncomplicated healthy pregnancy is the outcome of successful fertilization, implantation of embryos, trophoblast development and adequate placentation. Any deviation in these cascades of events may lead to complicated pregnancies such as preeclampsia (PE). The current incidence of PE is 2-8% in all pregnancies worldwide, leading to high maternal as well as perinatal mortality and morbidity rates. A number of randomized controlled clinical trials observed the association between low dose aspirin (LDA) treatment in early gestational age and significant reduction of early onset of PE in high-risk pregnant women. However, a substantial knowledge gap exists in identifying the particular mechanism of action of aspirin on placental function. It is already established that the placental-derived exosomes (PdE) are present in the maternal circulation from 6 weeks of gestation, and exosomes contain bioactive molecules such as proteins, lipids and RNA that are a "fingerprint" of their originating cells. Interestingly, levels of exosomes are higher in PE compared to normal pregnancies, and changes in the level of PdE during the first trimester may be used to classify women at risk for developing PE. The aim of this review is to discuss the mechanisms of action of LDA on placental and maternal physiological systems including the role of PdE in these phenomena. This review article will contribute to the in-depth understanding of LDA-induced PE prevention.
Topics: Animals; Aspirin; Biomarkers; Exosomes; Extracellular Vesicles; Female; Humans; Molecular Targeted Therapy; Placenta; Pre-Eclampsia; Pregnancy; Treatment Outcome
PubMed: 31492014
DOI: 10.3390/ijms20184370 -
European Journal of Vascular and... May 2004Aspirin is effective at reducing the cardiovascular event rate in defined patient groups. The introduction of antiplatelet therapies other than aspirin and the concept... (Review)
Review
BACKGROUND
Aspirin is effective at reducing the cardiovascular event rate in defined patient groups. The introduction of antiplatelet therapies other than aspirin and the concept of aspirin resistance have led to critical reappraisal of current treatment. This review aims to clarify the evidence for aspirin resistance in patients with atherosclerosis.
METHODS
Medline search was performed to identify publications concerned with antiplatelet effects of aspirin and failure of aspirin therapy. Manual cross referencing was also performed.
RESULTS AND CONCLUSION
Wide variations in the rate of aspirin resistance (5.5-75%) have been reported. The lack of consensus on an appropriate definition and the number of different tests used to investigate aspirin resistance needs to be addressed. There are few studies where the primary aim was to document aspirin resistance or aspirin non-response. Further work should aim to investigate if aspirin resistance is clinically important and, if it is, what treatments may be beneficial to the at risk patient.
Topics: Arteriosclerosis; Aspirin; Drug Resistance; Humans; Platelet Aggregation Inhibitors
PubMed: 15079767
DOI: 10.1016/j.ejvs.2003.12.025 -
MBio Apr 2021Aspirin is a chemopreventive agent for colorectal adenoma and cancer (CRC) that, like many drugs inclusive of chemotherapeutics, has been investigated for its effects on...
Aspirin is a chemopreventive agent for colorectal adenoma and cancer (CRC) that, like many drugs inclusive of chemotherapeutics, has been investigated for its effects on bacterial growth and virulence gene expression. Given the evolving recognition of the roles for bacteria in CRC, in this work, we investigate the effects of aspirin with a focus on one oncomicrobe- We show that aspirin and its primary metabolite salicylic acid alter strain Fn7-1 growth in culture and that aspirin can effectively kill both actively growing and stationary Fn7-1. We also demonstrate that, at levels that do not inhibit growth, aspirin influences Fn7-1 gene expression. To assess whether aspirin modulation of may be relevant , we use the mouse intestinal tumor model in which Fn7-1 is orally inoculated daily to reveal that aspirin-supplemented chow is sufficient to inhibit -potentiated colonic tumorigenesis. We expand our characterization of aspirin sensitivity across other strains, including those isolated from human CRC tissues, as well as other CRC-associated microbes, enterotoxigenic , and colibactin-producing Finally, we determine that individuals who use aspirin daily have lower fusobacterial abundance in colon adenoma tissues, as determined by quantitative PCR performed on adenoma DNA. Together, our data support that aspirin has direct antibiotic activity against strains and suggest that consideration of the potential effects of aspirin on the microbiome holds promise in optimizing risk-benefit assessments for use of aspirin in CRC prevention and management. There is an increasing understanding of the clinical correlations and potential mechanistic roles of specific members of the gut and tumoral microbiota in colorectal cancer (CRC) initiation, progression, and survival. However, we have yet to parlay this knowledge into better CRC outcomes through microbially informed diagnostic, preventive, or therapeutic approaches. Here, we demonstrate that aspirin, an established CRC chemopreventive, exhibits specific effects on the CRC-associated in culture, an animal model of intestinal tumorigenesis, and in human colonic adenoma tissues. Our work proposes a potential role for aspirin in influencing CRC-associated bacteria to prevent colorectal adenomas and cancer, beyond aspirin's canonical anti-inflammatory role targeting host tissues. Future research, such as studies investigating the effects of aspirin on fusobacterial load in patients, will help further elucidate the prospect of using aspirin to modulate for improving CRC outcomes.
Topics: Adenoma; Animals; Aspirin; Bacteria; Carcinogenesis; Cell Transformation, Neoplastic; Colon; Colorectal Neoplasms; Female; Fusobacterium nucleatum; Humans; Male; Mice
PubMed: 33824205
DOI: 10.1128/mBio.00547-21 -
Preventive Medicine Jan 2022We undertook a systematic review to synthesise the data on attitudes and behaviour towards the use of aspirin for cancer prevention, and healthcare providers' attitudes... (Review)
Review
We undertook a systematic review to synthesise the data on attitudes and behaviour towards the use of aspirin for cancer prevention, and healthcare providers' attitudes towards implementing aspirin in practice. Searches were carried out across 12 databases (e.g. MEDLINE, EMBASE). We used the Mixed Methods Appraisal Tool to evaluate study quality, and conducted a narrative synthesis of the data. The review was pre-registered (PROSPERO: CRD42018093453). Thirty-eight studies were identified. Uptake and adherence data were all from trials. Trials recruited healthy participants, those at higher risk of cancer, and those with cancer. Four studies reported moderate to high (40.9-77.7%) uptake to an aspirin trial among people who were eligible. Most trials (18/22) reported high day-to-day adherence (≥80%). Three trials observed no association between gender and adherence. One trial found no association between adherence and colorectal cancer risk. Three studies reported moderate to high (43.6-76.0%) hypothetical willingness to use aspirin. Two studies found that a high proportion of healthcare providers (72.0-76.0%) perceived aspirin to be a suitable cancer prevention option. No qualitative studies were identified. The likelihood that eligible users of aspirin would participate in a trial evaluating the use of aspirin for preventive therapy was moderate to high. Among participants in a trial, day-to-day adherence was high. Further research is needed to identify uptake and adherence rates in routine care, the factors affecting aspirin use, and the barriers to implementing aspirin into clinical care.
Topics: Aspirin; Attitude of Health Personnel; Health Personnel; Humans; Neoplasms
PubMed: 34762964
DOI: 10.1016/j.ypmed.2021.106872 -
Annals of Internal Medicine Jun 2016Cancer is the second leading cause of death in the United States. (Review)
Review
BACKGROUND
Cancer is the second leading cause of death in the United States.
PURPOSE
To conduct systematic reviews of aspirin and 1) total cancer mortality and incidence in persons eligible for primary prevention of cardiovascular disease (CVD) and 2) colorectal cancer (CRC) mortality and incidence in persons at average CRC risk.
DATA SOURCES
MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials through January 2015 and relevant references from other reviews.
STUDY SELECTION
Trials comparing oral aspirin versus placebo or no treatment in adults aged 40 years or older were included. Two investigators independently reviewed abstracts and articles against inclusion and quality criteria.
DATA EXTRACTION
Data from 20 good- or fair-quality trials were abstracted by one reviewer and checked by another.
DATA SYNTHESIS
In CVD primary prevention trials, cancer mortality (relative risk [RR], 0.96 [95% CI, 0.87 to 1.06]) (10 trials; n = 103 787) and incidence (RR, 0.98 [CI, 0.93 to 1.04]) (6 trials; n = 72 926) were similar in aspirin and control groups over 3.6 to 10.1 years. In CVD primary and secondary prevention trials, 20-year CRC mortality was reduced among persons assigned to aspirin therapy (RR, 0.67 [CI, 0.52 to 0.86]) (4 trials; n = 14 033). Aspirin appeared to reduce CRC incidence beginning 10 to 19 years after initiation (RR, 0.60 [CI, 0.47 to 0.76]) (3 trials; n = 47 464).
LIMITATIONS
Most data were from clinically and methodologically heterogeneous CVD prevention trials. Outcome assessment and follow-up length varied across studies. Data on non-CRC cancer types and subgroups were limited.
CONCLUSION
In CVD primary prevention populations, aspirin's effect on total cancer mortality and incidence was not clearly established. Evidence from CVD primary and secondary prevention studies suggested that aspirin therapy reduces CRC incidence and perhaps mortality approximately 10 years after initiation.
PRIMARY FUNDING SOURCE
Agency for Healthcare Research and Quality.
Topics: Adult; Anticarcinogenic Agents; Aspirin; Cardiovascular Diseases; Colorectal Neoplasms; Humans; Incidence; Neoplasms; Primary Prevention; United States
PubMed: 27064482
DOI: 10.7326/M15-2117 -
Gut Apr 1982Aspirin and paracetamol consumption have been compared in 346 matched pairs of patients with haematemesis and melaena, and control individuals in the general community.... (Comparative Study)
Comparative Study
Aspirin and paracetamol consumption have been compared in 346 matched pairs of patients with haematemesis and melaena, and control individuals in the general community. Both aspirin and paracetamol intake were more common in patients than in controls, but the association for aspirin was stronger and was apparent with both recent and habitual intake, whereas for paracetamol the association was not detectable for habitual intake. The results for paracetamol suggests that patients with bleeding take analgesic drugs in part because of symptoms associated with bleeding, and such intake is not necessarily causal of bleeding. Failure to control investigations to take account of this point has exaggerated the possible risks of aspirin consumption.
Topics: Acetaminophen; Adolescent; Adult; Aged; Aspirin; Female; Hematemesis; Humans; Male; Melena; Middle Aged; Risk
PubMed: 7076011
DOI: 10.1136/gut.23.4.340 -
International Journal of Molecular... Sep 2022Aspirin resistance describes a phenomenon where patients receiving aspirin therapy do not respond favorably to treatment, and is categorized by continued incidence of... (Review)
Review
Aspirin resistance describes a phenomenon where patients receiving aspirin therapy do not respond favorably to treatment, and is categorized by continued incidence of adverse cardiovascular events and/or the lack of reduced platelet reactivity. Studies demonstrate that one in four patients with vascular disease are resistant to aspirin therapy, placing them at an almost four-fold increased risk of major adverse limb and adverse cardiovascular events. Despite the increased cardiovascular risk incurred by aspirin resistant patients, strategies to diagnose or overcome this resistance are yet to be clinically validated and integrated. Currently, five unique laboratory assays have shown promise for aspirin resistance testing: Light transmission aggregometry, Platelet Function Analyzer-100, Thromboelastography, Verify Now, and Platelet Works. Newer antiplatelet therapies such as Plavix and Ticagrelor have been tested as an alternative to overcome aspirin resistance (used both in combination with aspirin and alone) but have not proven to be superior to aspirin alone. A recent breakthrough discovery has demonstrated that rivaroxaban, an anticoagulant which functions by inhibiting active Factor X when taken in combination with aspirin, improves outcomes in patients with vascular disease. Current studies are determining how this new regime may benefit those who are considered aspirin resistant.
Topics: Anticoagulants; Aspirin; Clopidogrel; Factor X; Humans; Platelet Aggregation Inhibitors; Point-of-Care Testing; Rivaroxaban; Ticagrelor; Vascular Diseases
PubMed: 36232618
DOI: 10.3390/ijms231911317