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Cancer Metastasis Reviews Jun 2017After more than a century, aspirin remains one of the most commonly used drugs in western medicine. Although mainly used for its anti-thrombotic, anti-pyretic, and... (Review)
Review
After more than a century, aspirin remains one of the most commonly used drugs in western medicine. Although mainly used for its anti-thrombotic, anti-pyretic, and analgesic properties, a multitude of clinical studies have provided convincing evidence that regular, low-dose aspirin use dramatically lowers the risk of cancer. These observations coincide with recent studies showing a functional relationship between platelets and tumors, suggesting that aspirin's chemopreventive properties may result, in part, from direct modulation of platelet biology and biochemistry. Here, we present a review of the biochemistry and pharmacology of aspirin with particular emphasis on its cyclooxygenase-dependent and cyclooxygenase-independent effects in platelets. We also correlate the results of proteomic-based studies of aspirin acetylation in eukaryotic cells with recent developments in platelet proteomics to identify non-cyclooxygenase targets of aspirin-mediated acetylation in platelets that may play a role in its chemopreventive mechanism.
Topics: Animals; Anticarcinogenic Agents; Aspirin; Blood Platelets; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Humans; Neoplasms
PubMed: 28762014
DOI: 10.1007/s10555-017-9675-z -
Frontiers in Endocrinology 2023Colorectal cancer (CRC) is a highly prevalent digestive system malignancy. Aspirin is currently one of the most promising chemopreventive agents for CRC, and the...
The underlying regulatory mechanisms of colorectal carcinoma by combining Vitexin and Aspirin: based on systems biology, molecular docking, molecular dynamics simulation, and study.
INTRODUCTION
Colorectal cancer (CRC) is a highly prevalent digestive system malignancy. Aspirin is currently one of the most promising chemopreventive agents for CRC, and the combination of aspirin and natural compounds helps to enhance the anticancer activity of aspirin. Natural flavonoids like vitexin have an anticancer activity focusing on colorectal carcinoma.
METHODS
This study investigated the potential mechanism of action of the novel combination of vitexin and aspirin against colorectal cancer through network pharmacology, molecular docking, molecular dynamics simulation, and experiments.
RESULTS
The results of network pharmacology suggested that vitexin and aspirin regulate multiple signaling pathways through various target proteins such as NFKB1, PTGS2 (COX-2), MAPK1, MAPK3, and TP53. Cellular experiments revealed that the combined effect of vitexin and aspirin significantly inhibited HT-29 cell growth. Vitexin dose-dependently inhibited COX-2 expression in cells and enhanced the down-regulation of COX-2 and NF-κB expression in colorectal cancer cells by aspirin.
DISCUSSION
This study provides a pharmacodynamic material and theoretical basis for applying agents against colorectal cancer to delay the development of drug resistance and improve the prognosis of cancer patients.
Topics: Humans; Aspirin; Molecular Docking Simulation; Cyclooxygenase 2; Molecular Dynamics Simulation; Colorectal Neoplasms; Molecular Biology
PubMed: 37564983
DOI: 10.3389/fendo.2023.1147132 -
The Journal of Medical Investigation :... 2023Platelets play an important role in physiological hemostatic mechanisms. In contrast, platelet activation has been implicated in pathological conditions, such as...
Platelets play an important role in physiological hemostatic mechanisms. In contrast, platelet activation has been implicated in pathological conditions, such as atherosclerosis, angiogenesis, and inflammation. Thrombin is considered to be of particular pathological importance as a platelet-activating substance, and thrombin-activated platelets are detected in the blood of patients with advanced occlusive arterial disease. Ca acts as a second messenger in platelet activation, and the regulation of intracellular Ca concentrations ([Ca]i) is important for controlling platelet functions. However, changes in [Ca]i by antiplatelet agents remain unclear. Therefore, we herein investigated the relationship between [Ca]i and the intensity of platelet aggregation after a thrombin stimulation, the relationship between [Ca]i and the intensity of platelet aggregation by antiplatelet agents, and the effects of antiplatelet agents on thrombin-activated platelets as a surrogate platelet model for arterial occlusive disease. Fura2-loaded platelets were treated with phosphate-buffered saline or a low concentration of thrombin (0.005 U/mL), followed by antiplatelet agents (aspirin or cilostazol), and changes in [Ca]i and the intensity of platelet aggregation by the thrombin stimulation were measured using fluorescence spectrophotometry. Changes in [Ca]i and the intensity of platelet aggregation after the thrombin stimulation as well as the relationship between [Ca]i and the intensity of platelet aggregation by antiplatelet agents indicated that cilostazol exerted stronger antiplatelet effects than aspirin and also that antiplatelet effects may be attenuated in thrombin-activated platelets. The present results also suggest the utility of thrombin-activated platelets as a surrogate platelet model for arterial occlusive disease. These results may contribute to future drug development for antiplatelet therapy. J. Med. Invest. 70 : 94-100, February, 2023.
Topics: Humans; Blood Platelets; Aspirin; Platelet Aggregation Inhibitors; Cilostazol; Thrombin
PubMed: 37164750
DOI: 10.2152/jmi.70.94 -
Molecules (Basel, Switzerland) Dec 2022Acetylsalicylic acid (ASA) is one of the first drugs to be obtained by synthesis while being the most used. It has experienced the longest lasting commercial success and... (Review)
Review
Acetylsalicylic acid (ASA) is one of the first drugs to be obtained by synthesis while being the most used. It has experienced the longest lasting commercial success and is considered the most popular drug of the modern era. ASA, originally used as an anti-inflammatory medication, nowadays is predominantly used as an antiplatelet agent for prophylaxis in cardiac patients. Many studies show that the benefits of using ASA far outweigh the potential risk of side effects. With particular emphasis on the possibility of ASA repositioning for new therapies, extending the indications for use beyond the diseases from the spectrum of atherosclerotic diseases, such as cancer, requires shifting the benefit-risk ratio, although very good, even more towards safety. Interesting activities consisting not only of changing the formulation but also modifying the drug molecule seem to be an important goal of the 21st century. ASA has become a milestone in two important fields: pharmacy and medicine. For a pharmacist, ASA is a long-used drug for which individual indications are practically maintained. For a doctor, acetylsalicylic acid is primarily an antiplatelet drug that saves millions of lives of patients with coronary heart disease or after a stroke. These facts do not exempt us from improving therapeutic methods based on ASA, the main goal of which is to reduce the risk of side effects, as well as to extend effectiveness. Modified acetylsalicylic acid molecules already seem to be a promising therapeutic option.
Topics: Humans; Aspirin; Platelet Aggregation Inhibitors; Stroke
PubMed: 36500502
DOI: 10.3390/molecules27238412 -
British Journal of Anaesthesia Jan 1991
Topics: Analgesia, Epidural; Analgesia, Obstetrical; Aspirin; Female; Hematoma, Epidural, Cranial; Humans; Pregnancy; Risk Factors
PubMed: 1997043
DOI: 10.1093/bja/66.1.1 -
International Journal of Cancer Mar 2021Aspirin has been associated with a reduced risk of colorectal and other selected digestive tract cancers, but the evidence for other neoplasms is still controversial. To... (Meta-Analysis)
Meta-Analysis
Aspirin has been associated with a reduced risk of colorectal and other selected digestive tract cancers, but the evidence for other neoplasms is still controversial. To provide an up-to-date quantification of the role of aspirin on lung, breast, endometrium, ovary, prostate, bladder, and kidney cancer, we conducted a systematic review and meta-analysis of all observational studies published up to March 2019. We estimated pooled relative risk (RR) of cancer or cancer death for regular aspirin use vs non-use by using random-effects models, and, whenever possible, we investigated dose- and duration-risk relations. A total of 148 studies were considered. Regular aspirin use was associated to a reduced risk of lung (RR = 0.88, 95% confidence interval [CI] = 0.79-0.98), breast (RR = 0.90, 95% CI = 0.85-0.95), endometrial (RR = 0.91, 95% CI = 0.84-0.98), ovarian (RR = 0.91, 95% CI = 0.85-0.97) and prostate (RR = 0.93, 95% CI = 0.89-0.96) cancer. However, for most neoplasms, nonsignificant risk reductions were reported in cohort and nested case-control studies and there was between-study heterogeneity. No association was reported for bladder and kidney cancer. No duration-risk relations were observed for most neoplasms, except for an inverse duration-risk relation for prostate cancer. The present meta-analysis confirms the absence of appreciable effect of regular aspirin use on cancers of the bladder and kidney and quantifies small and heterogeneous inverse associations for other cancers considered.
Topics: Aspirin; Humans; Neoplasms; Observational Studies as Topic
PubMed: 32984948
DOI: 10.1002/ijc.33311 -
WMJ : Official Publication of the State... Oct 2022Inappropriate aspirin use can lead to increased frequency of bleeding events and poor patient outcomes.
BACKGROUND
Inappropriate aspirin use can lead to increased frequency of bleeding events and poor patient outcomes.
OBJECTIVES
Compare current aspirin prescribing to guideline recommendations and analyze the impact of pharmacist education for clinicians with provision of patient-specific recommendations.
METHODS
Internal medicine residents received 1 educational session on appropriate aspirin use. Over a 5-month period post-education, 100 patients on aspirin with a clinic appointment were screened and their charts reviewed. Aspirin use was classified based on guideline recommendations as follows: (1) recommended, (2) weigh the risk and benefits, (3) not recommended, (4) dose change recommended, or (5) outside of guideline recommendation. A recommendation for aspirin deprescribing was then communicated to the clinician prior to the patient's appointment. Prescriber practice following the appointment was collected and analyzed.
RESULTS
Inappropriate aspirin use occurred in 29% (n = 29) of patients prior to their appointment. Of these, aspirin was not recommended in 65.5% (n = 19), and a dose reduction from 325 mg to 81 mg was recommended in 34.5% (n = 10). Of the 81 patients who kept their appointment, pharmacist recommendations to deprescribe aspirin were communicated to the clincian for 20 patients (24.7%) and resulted in a 55% aspirin deprescription.
CONCLUSIONS
The majority of patients identified as using aspirin inappropriately fell into 3 groups: (1) patients taking 325 mg aspirin, (2) patients taking aspirin for primary prevention, and (3) patients taking aspirin concomitantly with an anticoagulant. Strategies that may lead to optimization of aspirin use include lectures and patient-specific chart reviews with pharmacist recommendation.
Topics: Humans; Aspirin; Deprescriptions; Pharmacists
PubMed: 36301649
DOI: No ID Found -
Journal of Vascular Surgery Dec 2009Atherothrombosis, characterized by atherosclerotic plaque rupture and subsequent occlusive or subocclusive thrombus formation is the primary cause of acute ischemic... (Review)
Review
Atherothrombosis, characterized by atherosclerotic plaque rupture and subsequent occlusive or subocclusive thrombus formation is the primary cause of acute ischemic syndromes involving all vascular beds and accounts for more than one-third of all deaths in the developed world. Platelet activation and aggregation constitute the most critical component in the pathophysiology of atherothrombotic disease. Aspirin is currently the most commonly used antiplatelet agent and one of the most frequently prescribed drugs, with as many as 30 million Americans on chronic aspirin regimens. Multiple well-designed prospective randomized clinical trials have demonstrated aspirin's efficacy in both primary and secondary prevention of a wide variety of entities that the atherothrombotic disease spectrum encompasses, such as cerebrovascular, coronary artery, and peripheral vascular disease. Despite its proven benefit, however, a growing body of evidence suggests that up to 70% of aspirin-takers may still be at risk for atherothrombotic complications due to resistance. Patients with laboratory-confirmed aspirin resistance seem to have an almost fourfold increase in their risk for acute thrombotic episodes, which underlines the magnitude of the problem for the vascular specialist. In this article, we review the physiology of platelet activation and the role of aspirin as an antiplatelet agent; the various laboratory assays used in assessing aspirin effectiveness; and current data on aspirin resistance and its clinical implications in patients with cardiovascular disease. We also review the studies that explore this phenomenon in patients with peripheral arterial disease and discuss the optimal management options in aspirin-resistant individuals. Suggestions are advanced for the direction of future trials evaluating aspirin resistance in patients with vascular disease.
Topics: Aspirin; Bleeding Time; Cardiovascular Diseases; Drug Resistance; Evidence-Based Medicine; Fibrinolytic Agents; History, 18th Century; History, 19th Century; History, 20th Century; History, Ancient; Humans; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Predictive Value of Tests; Vascular Surgical Procedures
PubMed: 19679423
DOI: 10.1016/j.jvs.2009.06.023 -
Aging Sep 2023Diabetic cystopathy (DCP) is one of the most common and troublesome urologic complications of diabetes mellitus, characterized by chronic low-grade inflammatory...
Diabetic cystopathy (DCP) is one of the most common and troublesome urologic complications of diabetes mellitus, characterized by chronic low-grade inflammatory response. However, the correlation between inflammation and disease progression remains ambiguous and effective drugs interventions remain deficient. Herein, during 12-week study, 48 male Sprague-Dawley rats were randomly assigned to four groups: negative control (NC), NC treated with aspirin (NC+Aspirin), DCP, and DCP treated with aspirin (DCP+Aspirin). Type 1 diabetes mellitus was established by intraperitoneal injection of streptozotocin (65 mg/kg). After 2 weeks modeling, the rats in treatment groups received daily oral aspirin (100 mg/kg/d). After 10 weeks of treatment, aspirin ameliorated pathological weight loss and bladder weight increase in diabetic rats, accompanied by a 16.5% decrease in blood glucose concentrations. H&E, Masson, immunohistochemistry and transmission electron microscopy revealed that a dilated bladder with thickened detrusor smooth muscle (DSM) layer, inflammatory infiltration, fibrosis and ultrastructural damage were observed in diabetic rats, which were obviously ameliorated by aspirin. The dynamic investigations at 4, 7 and 10 weeks revealed inflammation gradually increased as the disease progresses. After 10 weeks of treatment, the expression of TNF-α, IL-1β, IL-6, and NF-κB has been decreased to 78%, 39.7%, 44.1%, 33.3% at mRNA level and 67.6%, 76.7%, 71.4%, 67.1% at protein level, respectively (DCP+Aspirin vs. DCP, p < 0.01). Aspirin partially restored the increased expression of inflammatory mediators in bladder DSM of diabetic rats. The study provided insight into long-term medication therapies, indicating that aspirin might serve as a potential strategy for DCP treatment.
Topics: Male; Animals; Rats; Rats, Sprague-Dawley; Aspirin; Diabetes Mellitus, Experimental; Inflammation; Diabetes Mellitus, Type 1
PubMed: 37702622
DOI: 10.18632/aging.205021 -
The Oncologist Jan 2024Previous meta-analyses have indicated that aspirin could affect breast cancer outcomes, particularly when taken post-diagnostically. However, several recent studies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous meta-analyses have indicated that aspirin could affect breast cancer outcomes, particularly when taken post-diagnostically. However, several recent studies appear to show little to no association between aspirin use and breast cancer mortality, all-cause mortality, or recurrence.
AIMS
This study aims to conduct an updated systematic review and meta-analysis on the associations of pre-diagnostic and post-diagnostic aspirin use with the aforementioned breast cancer outcomes. It also looks, through subgroup analyses and meta-regressions, at a range of variables that could explain the associations between aspirin use and breast cancer outcomes.
RESULTS
In total, 24 papers and 149 860 patients with breast cancer were included. Pre-diagnostic aspirin use was not associated with breast-cancer-specific mortality (HR 0.98, 95% CI, 0.80-1.20, P = .84) or recurrence (HR 0.94, 95% CI, 0.88-1.02, P = .13). Pre-diagnostic aspirin was associated with non-significantly higher all-cause mortality (HR 1.27, 95% CI, 0.95-1.72, P = .11). Post-diagnostic aspirin was not significantly associated with all-cause mortality (HR 0.87, 95% CI, 0.71-1.07, P = .18) or recurrence (HR 0.89, 95% CI, 0.67-1.16, P = .38). Post-diagnostic aspirin use was significantly associated with lower breast-cancer-specific mortality (HR 0.79, 95% CI, 0.64-0.98, P = .032).
CONCLUSIONS
The only significant association of aspirin with breast cancer outcomes is lower breast-cancer-specific mortality in patients who used aspirin post-diagnostically. However, factors such as selection bias and high inter-study heterogeneity mean that this result should not be treated as conclusive, and more substantial evidence such as that provided by RCTs is needed before any decisions on new clinical uses for aspirin should be made.
Topics: Humans; Female; Aspirin; Breast Neoplasms
PubMed: 37358878
DOI: 10.1093/oncolo/oyad186