Aspirin Nonsteroidal Anti-inflammatory Drugs Research Articles

Recategorization of Non-Aspirin Nonsteroidal Anti-inflammatory Drugs According to Clinical Relevance: Abandoning the Traditional NSAID Terminology

Non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to treat pain, fever, and inflammation. Historically, NSAIDs have been categorized as traditional NSAIDs and newer cyclooxygenase (COX)-2 inhibitors (coxibs). However, traditional NSAIDs also inhibit the COX-1 and COX-2 enzyme isoforms to a varying degree. This diversity of COX-1 and COX-2 selectivity within the class of traditional NSAIDs has proven clinically important, with evidence accumulating on the cardiovascular risks associated with selective COX-2 inhibition. Thus, the relative COX-2 selectivity of traditional NSAIDs correlates with their cardiovascular risk profile, being more favourable for non-selective NSAIDs, such as naproxen and low-dose ibuprofen, and less favourable for more COX-2 selective agents, such as diclofenac. To enhance clinically relevant terminology, we advocate categorizing all non-aspirin NSAIDs—including traditional NSAIDs—according to their relative COX-1 and COX-2 selectivity as either COX-1 inhibitors, non-selective NSAIDs, or COX-2 inhibitors. We further recommend subcategorizing COX-2 inhibitors as newer COX-2 inhibitors (coxibs) or older COX-2 inhibitors. Finally, we recommend examining the effects of the individual NSAIDs included in each of the proposed categories. Adhering to these recommendations will align future studies, advance interpretation of COX-specific adverse cardiovascular effects, and provide better guidance to clinicians prescribing NSAIDs.

Potential role of acetylsalicilic acid and other non-steroidal anti-inflammatory drugs in cancer risk reduction (literature review)

The aim of this review is to analyze and summarize the existing evidence regarding the possibilities of using acetylsalicylic acid (ASA) and other non-steroidal anti-inflammatory drugs (NSAIDs) to reduce cancer risk. Conclusions. Chronic inflammation facilitates the onset and progress of tumour growth. Anti-cancer properties of acetylsalicylic acid and other non-steroidal anti-inflammatory drugs are mediated via cyclooxygenase COX-dependent mechanisms, as well as other tumorigenic pathways. Current systematic review addresses potential role of ASA and other NSAIDs in reduction of cancer risk for the following localizations: head and neck, lungs, gastrointestinal tract, breast, ovaries, prostate, and skin. The role of ASA in primary prevention of colorectal cancer in specific populations is presented in 2016 U. S. Preventive Services Task Force guidelines. Studies indicate heterogeneous protective potential of ASA against different cancer types, depending on studied population, duration of intake and dose. Influence of non-aspirin NSAIDs on cancer morbidity and mortality is more controversial.

Non-aspirin NSAIDs use is associated with lowering of liver fibrosis scores in patients with fatty liver disease

Only a few studies are available with appropriate data on the effects of non-aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) use in patients with fatty liver disease. We performed a retrospective study of 1347 patients with imaging studies that showed fatty liver disease from 2016 through 2019. We then determined the change in validated indices using Fibrosis-4 (FIB4) and NAFLD fibrosis score (NFS). Patient clinical information, including NSAIDs use, was collected at baseline and then yearly. Using generalized linear models, we estimated the association between non-aspirin NSAIDs use and change in baseline indices. Non-aspirin NSAIDs use was found to be associated with significant lowering of FIB-4 score (0.596 units lower, p-value <0.0001) and NFS (0.431 units lower, p-value 0.0027) every year. In this retrospective study of patients with fatty liver disease found on imaging, non-aspirin NSAID use was associated with lowering of fibrosis scores, suggesting that NSAID use might be associated with a lower risk for advanced fibrosis in fatty liver disease.

Non-aspirin NSAIDs use is associated with lowering of liver fibrosis scores in patients with fatty liver disease

Non-aspirin NSAIDs use is associated with lowering of liver fibrosis scores in patients with fatty liver disease

Anti-inflammatory chemoprevention attenuates the phenotype in a mouse model of esophageal adenocarcinoma.

Barrett's esophagus (BE) is the main known precursor condition of esophageal adenocarcinoma (EAC). BE is defined by the presence of metaplasia above the normal squamous columnar junction and has mainly been attributed to gastroesophageal reflux disease and chronic reflux esophagitis. Thus, the rising incidence of EAC in the Western world is probably mediated by chronic esophageal inflammation, secondary to gastroesophageal reflux disease in combination with environmental risk factors such as a Western diet and obesity. However, (at present) risk prediction tools and endoscopic surveillance have shown limited effectiveness. Chemoprevention as an adjunctive approach remains an attractive option to reduce the incidence of neoplastic disease. Here, we investigate the feasibility of chemopreventive approaches in BE and EAC via inhibition of inflammatory signaling in a transgenic mouse model of BE and EAC (L2-IL1B mice), with accelerated tumor formation on a high-fat diet (HFD). L2-IL1B mice were treated with the IL-1 receptor antagonist Anakinra and the nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin or Sulindac. Interleukin-1b antagonism reduced tumor progression in L2-IL1B mice with or without a HFD, whereas both NSAIDs were effective chemoprevention agents in the accelerated HFD-fed L2-IL1B mouse model. Sulindac treatment also resulted in a marked change in the immune profile of L2-IL1B mice. In summary, anti-inflammatory treatment of HFD-treated L2-IL1B mice acted protectively on disease progression. These results from a mouse model of BE support results from clinical trials that suggest that anti-inflammatory medication may be effective in the chemoprevention of EAC.

The Effects of Non-Steroidal Anti-Inflammatory Drugs and Anti-Platelet Therapy on the Incidence and Recurrence of Hepatocellular Carcinoma: A Meta-Analysis

Background: Chemoprevention with NSAIDs, including aspirin, and anti-platelet therapy (APT), has been suggested to reduce the incidence and recurrence of hepatocellular carcinoma (HCC). This meta-analysis aimed to determine whether NSAIDs and APT use affected HCC incidence, HCC recurrence and liver-related mortality in at-risk populations with chronic liver disease. Method: Electronic databases including Pubmed, Scopus, Medline, Embase and Cochrane Library were searched (from inception to 1 October 2020) for eligible studies evaluating the impacts of NSAID or APT use on HCC incidence, recurrence and mortality. Data on HCC incidence, recurrence, liver-related mortality or bleeding complications had to be available. Studies were included if they evaluated adults with newly diagnosed HBV, HCV, ALD or NASH that were administered at least one NSAID or APT for a defined period of time and were followed for at least six-months. The primary outcome was HCC incidence. Secondary outcomes included: HCC recurrence, liver-related mortality and bleeding complications. Data were pooled using a random effects model with hazards ratios (HR) or odds ratio (OR), and 95% confidence intervals (CI) presented. Results: Of 3614 articles screened, 16 studies were included, with a total of 111,096 participants. Aspirin use significantly reduced the risk of HCC incidence (HR: 0.47, 95% CI: 0.32-0.71); and improved liver-related mortality (OR: 0.38, 95% CI: 0.29-0.49), with a small increased risk of gastrointestinal bleeding events (OR: 1.141, 95% CI: 1.06-1.23). With respect to HCC recurrence following treatment, analysis of all NSAID treatment (including aspirin-only, non-aspirin NSAIDs-only and combination NSAIDs groups) were associated with a decreased risk of HCC recurrence (HR: 0.80, 95% CI: 0.75-0.86). By stratified analysis, only the non-aspirin NSAID group showed statistical significance in risk reduction (HR: 0.73, 95% CI: 0.63-0.84). Conclusion: This study supports the use of aspirin in at-risk individuals to reduce the incidence of HCC and liver-related mortality. Funding Statement: NSW Cancer Council Linkage grant RG163222. Declaration of Interests: None of the authors declare any conflict of interest.

Non-aspirin NSAID use and mortality of endometrial cancer. A nationwide cohort study.

Laboratory studies have shown anti-neoplastic properties of non-aspirin NSAID; however, no studies have examined the influence of non-aspirin NSAIDs as potential adjuvant cancer therapy in women with endometrial cancer. We therefore examined the association between post-diagnostic use of non-aspirin NSAIDs and endometrial cancer mortality in Denmark. We identified all women with a primary endometrial cancer diagnosis between 2000 and 2012, who were alive one year after the diagnosis. Information on drug use, cause-specific mortality and potential confounders was obtained from nationwide health- and demographic registries. Cox regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between post-diagnostic non-aspirin NSAID use and endometrial cancer mortality. Among 6 694 endometrial cancer patients with a maximum follow-up of 13years, 753 women died from endometrial cancer. Post-diagnostic non-aspirin NSAID use (≥ 1 filled prescription) was associated with an overall HR of 1.15 (95% CI; 0.97-1.36) for endometrial cancer mortality, with higher HRs for the highest intensity of use (HR; 1.40, 95% CI; 1.11-1.77) and largest cumulative amount (HR; 1.56, 95% CI; 1.14-2.14). Our findings yielded no evidence that use of non-aspirin NSAIDs was associated with reduced endometrial cancer. Rather, we observed that high-intensity and large cumulative amount of non-aspirin NSAID use may be associated with increased endometrial cancer mortality.

Candidate drugs for preventive treatment of unruptured intracranial aneurysms: A cross-sectional study.

Background and purposeEstablishment of drug therapy to prevent rupture of unruptured intracranial aneurysms (IAs) is needed. Previous human and animal studies have gradually clarified candidate drugs for preventive treatment of IA rupture. However, because most of these candidates belong to classes of drugs frequently co-administered to prevent cardiovascular diseases, epidemiological studies evaluating these drugs simultaneously should be performed. Furthermore, because drugs included in the same class may have different effects in terms of disease prevention, drug-by-drug assessments are important for planning intervention trials.Materials and methodsWe performed a cross-sectional study enrolling patients diagnosed with IAs between July 2011 and June 2019 at our institution. Patients were divided into ruptured or unruptured groups. The drugs investigated were selected according to evidence suggested by either human or animal studies. Univariate and multivariate logistic regression analyses were performed to assess the association of drug treatment with rupture status. We also performed drug-by-drug assessments of the association, including dose-response relationships, with rupture status.ResultsIn total, 310 patients with ruptured and 887 patients with unruptured IAs were included. Multivariate analysis revealed an inverse association of statins (odds ratio (OR), 0.54; 95% confidence interval (CI) 0.38–0.77), calcium channel blockers (OR, 0.41; 95% CI 0.30–0.58), and angiotensin II receptor blockers (ARBs) (OR, 0.67; 95% CI 0.48–0.93) with ruptured IAs. Moreover, inverse dose-response relationships with rupture status were observed for pitavastatin and rosuvastatin among statins, benidipine, cilnidipine, and amlodipine among calcium channel blockers, and valsartan, azilsartan, candesartan, and olmesartan among ARBs. Only non-aspirin non-steroidal anti-inflammatory drugs were positively associated with ruptured IAs (OR, 3.24; 95% CI 1.71–6.13).ConclusionsThe present analysis suggests that several types of statins, calcium channel blockers, and ARBs are candidate drugs for preventive treatment of unruptured IAs.

Associations of Aspirin and Non-Aspirin Non-Steroidal Anti-Inflammatory Drugs With Colorectal Cancer Mortality After Diagnosis.

Aspirin use reduces colorectal cancer (CRC) incidence, but there is limited evidence regarding associations of aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) with CRC-specific survival. This prospective analysis includes women and men from the Cancer Prevention Study-II Nutrition Cohort who were cancer free at baseline (1992 or 1993) and diagnosed with CRC during incidence follow-up through 2015. Detailed information on aspirin and non-aspirin NSAID use was self-reported on questionnaires at baseline, in 1997, and every 2 years thereafter. Pre- and postdiagnosis data were available for 2686 and 1931 participants without distant metastases, respectively, among whom 512 and 251 died from CRC during mortality follow-up through 2016. Secondary analyses examined associations between prediagnosis aspirin use and stage at diagnosis (distant metastatic vs localized or regional). All statistical tests were 2-sided. Long-term regular use of aspirin (>15 times per month) before diagnosis was associated with lower CRC-specific mortality (multivariable-adjusted hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.52 to 0.92). Postdiagnosis regular aspirin use was not statistically significantly associated with risk of CRC-specific mortality overall (HR = 0.82, 95% CI = 0.62 to 1.09), although participants who began regular aspirin use only after their diagnosis were at lower risk than participants who did not use aspirin at both the pre- and postdiagnosis periods (HR = 0.60, 95% CI = 0.36 to 0.98). Long-term aspirin use before diagnosis was also associated with lower odds of diagnosis with distant metastases (multivariable-adjusted odds ratio = 0.73, 95% CI = 0.53 to 0.99). Our results suggest that long-term aspirin use before a diagnosis of nonmetastatic colorectal cancer may be associated with lower CRC-specific mortality after diagnosis, consistent with possible inhibition of micrometastases before diagnosis.

Hollow fiber coated Fe3O4@Maleamic acid-functionalized graphene oxide as a sorbent for stir bar sorptive extraction of ibuprofen, aspirin, and venlafaxine in human urine samples before determining by gas chromatography–mass spectrometry

The present work proposes the application of stir bar sorptive extraction (SBSE), followed by gas chromatography–mass spectrometry for the determination of trace levels of the non-steroidal anti-inflammatory and serotonin-norepinephrine reuptake inhibitor drugs (Ibuprofen, Aspirin, and Venlafaxine) in human urine samples. In the method, a new and simple device for the SBSE procedure was prepared using a hollow fiber and Fe wire into the HF lumen. A new sorbent (Fe3O4@Maleamic acid-functionalized graphene oxide) was synthesized and ultrasonically penetrated in the outer surface pores of the HF in the presence of a nonionic surfactant (Triton X-140). Effective main factors on the SBSE procedure were optimized by the design of experiment approach. The proposed analytical methodology demonstrated suitable detection limits (≤ 0.12 ng mL−1), high preconcentration factor (≥ 238), and wide linear dynamic ranges with excellent determination coefficients higher than 0.9971 for the measurement of the analytes. Intra-day and inter-day relative standard deviations (RSDs, n = 5) for the determination of the drugs were lower than 2.63 and 4.73%, respectively. Assays of the human urine samples were shown the average recoveries between 97.2 and 103% for all drugs with RSDs lower than 4.57% under the optimum extraction conditions. The methodology has high advantages such as cheapness, fastness, low solvent desorption, high recovery, and no memory effect with good recoveries and proper RSDs for the determination of the ibuprofen, aspirin, and venlafaxine in human urine samples.

Nonaspirin nonsteroidal anti-inflammatory drugs and gastric cancer risk after Helicobacter pylori eradication: A territory-wide study.

Despite Helicobacter pylori (HP) eradication, individuals can still develop gastric cancer (GC). Prior studies have demonstrated that nonaspirin nonsteroidal anti-inflammatory drugs (NA-NSAIDs) reduce the risk of GC, but this may be caused by immortal time bias and failure to adjust for HP status. The objective of this study was to investigate whether NA-NSAIDs reduced the risk of GC in patients who undergo H. pylori eradication. Adult patients who had received clarithromycin-based triple therapy between 2003 and 2016 were identified from a territory-wide health care database. Exclusion criteria included prior GC or GC diagnosed <6 months after HP eradication, prior gastrectomy, gastric ulcer after HP eradication, and failure of triple therapy. Covariates included age, sex, prior peptic ulcer disease, other comorbidities, and concurrent medications (aspirin, proton pump inhibitors, statins, and metformin). To avoid immortal time bias, NA-NSAID use (≥90 days) was treated as a time-dependent variable in a multivariable Cox model (time-dependent analysis). Time-independent analysis was also performed. During a median follow-up of 8.9 years (interquartile range, 5.4-12.6 years), 364 of 92,017 patients (0.4%) who underwent HP eradication developed GC. NA-NSAID use was associated with a significant reduction in the risk of GC in time-fixed analysis (adjusted hazard ratio [aHR], 0.65; 95% CI, 0.47-0.90), but not in time-dependent multivariable analysis (aHR, 1.35; 95% CI, 0.97-1.87). Time-dependent subgroup analyses also did not indicate any significant association between NA-NSAID use and either cardia GC (aHR, 0.75; 95% CI, 0.27-2.06) or noncardia GC (aHR, 1.28; 95% CI, 0.83-1.98). NA-NSAID use was not associated with a reduced risk of GC among patients who underwent HP eradication. The chemopreventive effect of NA-NSAIDs observed in prior studies may have been confounded by immortal time bias.

Association of aspirin and nonaspirin NSAIDs therapy with the incidence risk of hepatocellular carcinoma: a systematic review and meta-analysis on cohort studies.

According to the current research evidence, the therapy of nonsteroidal anti-inflammatory drugs (NSAIDs) might effectively decrease the risk of hepatocellular carcinoma (HCC) incidence. Investigations have been conducted on the relationship between NSAIDs (aspirin and nonaspirin NSAIDs) and the risk of HCC incidence. We searched the PubMed, Web of Science, Embase and Cochrane Library databases for cohort studies published prior to 15 March 2020 and screened eligible studies. There were a total of 12 eligible studies (published between 2012 and 2020). We observed a lower risk of HCC among aspirin users [hazard ratio 0.53; 95% confidence interval (CI), 0.43-0.65]. However, there were no statistically significant associations discovered between nonaspirin NSAID use and the risk of HCC incidence (hazard ratio 0.95; 95% CI, 0.79-1.15). Furthermore, aspirin use has also been found to reduce the risk of HCC in patients with cirrhosis or viral hepatitis compared to that in the general population (hazard ratio 0.15; 95% CI, 0.10-0.23; hazard ratio 0.65; 95% CI, 0.56-0.76, respectively). Moreover, no statistical associations were found between aspirin use and a higher risk of bleeding risk, with a hazard ratio value of 0.76 (95% CI, 0.51-1.13). In summary, the conducted meta-analysis reveals that aspirin, rather than nonaspirin NSAIDs, can significantly decrease the risk of HCC, particularly in patients with cirrhosis or viral hepatitis.

Safety of select headache medications in patients with cerebral and spinal cavernous malformations

Background: Patients with cerebral or spinal cavernous malformations (CM) and a primary headache disorder are often limited in medication options due to concern for bleeding risk. Methods: From a prospective cohort of CM patients (2015–2020), demographics, mode of clinical presentation, and radiographic data were collected. Follow up of patients was performed with electronic medical record review, in person visits and/or written surveys. Select medication use was ascertained from the time of the CM diagnosis to a censor date of first prospective symptomatic hemorrhage, complete surgical excision of sporadic form CM, or death. The influence of non-aspirin NSAID (NA-NSAID), triptan, or OnabotulinumtoxinA on prospective hemorrhage risk was assessed. Results: As of August 20, 2020, 329 patients with spinal or cerebral CM (58% female; 20.1% familial; 42.2% initial presentation due to hemorrhage; 27.4% brainstem) were included. During a follow-up of 1799.9 patient years, 92 prospective hemorrhages occurred. Use of NA-NSAIDs, triptans, and OnabotulinumtoxinA after the diagnosis of CM was unassociated with an increased risk of prospective hemorrhage. Conclusions: Use of triptans and NA-NSAIDs, does not precipitate CM hemorrhage. Similarly, we did not find that OnabotulinumtoxinA precipitated CM hemorrhage in a limited number of patients at doses &lt;200 units per session.

791. Evaluation of NSAID Exposure as a Risk Factor for Clostridium difficile infection: A Propensity-Score-Matched Case-Control Study

BackgroundExposure to certain medications, particularly antibiotics and proton pump inhibitors, has been associated with increased risk for Clostridium difficile infection (CDI). Studies have suggested an increased risk for CDI associated with exposure to certain non-steroidal anti-inflammatory drugs (NSAIDs). We conducted a retrospective case-control study to evaluate the risk for CDI associated with NSAID use.MethodsThe population included 1338 patients tested for CDI from February–December 2016 at the University of Michigan. NSAID use within 30 days of CDI testing was determined by chart review. Both scheduled and as-needed NSAID use met the definition for exposure, but aspirin use alone did not. Additional clinical data such as comorbid disease and baseline laboratory parameters were extracted through electronic query. A random forest model imputed missing data. A propensity score for NSAID use was developed via logistic regression and included gender, back pain, baseline serum creatinine, osteoarthritis, rheumatoid arthritis, serum albumin, and use of anticoagulant or antiplatelet medications. Cases were matched 1:1 with C. difficile negative controls by propensity score, with a matching caliper of 0.2 x standard deviation of the logit of the score. The final study population consisted of 1256 cases and their matched controls, however 6 cases could not be matched to controls as none had scores within the matching caliper. Conditional logistic regression was used to compare cases to controls.ResultsNSAID use was similar between the two groups on unadjusted analyses. The adjusted, multivariable model demonstrates that non-aspirin NSAID use is not a significant risk factor for CDI (P =.816), after adjustment for comorbid disease burden, age, and history of prior CDI (Table). Older age and prior CDI were independent risk factors for CDI (Table). Table Study population and modeling results ConclusionIn this retrospective case-control study, non-aspirin NSAID use was not associated with an increased risk of CDI. To our knowledge, this is the first study of NSAID use as a risk factor for CDI that accounted for bias due to treatment assignment using a propensity score. Future studies should account for frequency or chronicity of NSAID use, which may affect the results.DisclosuresKrishna Rao, MD, MS, Bio-K+ International, Inc. (Consultant)Merck and Co., Inc. (Research Grant or Support)Roche Molecular Systems, Inc. (Consultant)

Unraveling the Role of Drug-Lipid Interactions in NSAIDs-Induced Cardiotoxicity.

Cardiovascular (CV) toxicity is nowadays recognized as a class effect of non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs). However, their mechanisms of cardiotoxicity are not yet well understood, since different compounds with similar action mechanisms exhibit distinct cardiotoxicity. For instance, diclofenac (DIC) is among the most cardiotoxic compounds, while naproxen (NAP) is associated with low CV risk. In this sense, this study aimed to unravel the role of drug-lipid interactions in NSAIDs-induced cardiotoxicity. For that, DIC and NAP interactions with lipid bilayers as model systems of cell and mitochondrial membranes were characterized by derivative spectrophotometry, fluorometric leakage assays, and synchrotron X-ray scattering. Both DIC and NAP were found to have the ability to permeabilize the membrane models, as well as to alter the bilayers’ structure. The NSAIDs-induced modifications were dependent on the lipid composition of the membrane model, the three-dimensional structure of the drug, as well as the drug:lipid molar ratio tested. Altogether, this work supports the hypothesis that NSAIDs-lipid interactions, in particular at the mitochondrial level, may be another key step among the mechanisms underlying NSAIDs-induced cardiotoxicity.

Nonsteroidal Anti-Inflammatory Drugs: Updates on Dosage Formulations and Adverse Effects.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used medications due to their prescription and nonprescription availability, various dosage formulations, and therapeutic efficacy. Although NSAIDs have many known benefits, their effects on gastrointestinal, cardiovascular, bone, and renal physiology limit their widespread and long-term use. This article provides an update on dosage formulations, product availability, and pertinent adverse effects and warnings regarding the use of NSAIDs, with an emphasis on nonaspirin NSAIDs.

Breast Cancer Risk and Use of Nonsteroidal Anti-inflammatory Agents After a Benign Breast Biopsy.

Over one million women in the United States receive biopsy diagnoses of benign breast disease (BBD) each year, which confer a 1.5-4.0-fold increase in breast cancer risk. Studies in the general population suggest that nonsteroidal anti-inflammatory agents (NSAID) lower breast cancer risk; however, associations among women with BBD are unknown. We assessed whether NSAID use among women diagnosed with BBD is associated with lower breast cancer risk. Participants included 3,080 women (mean age = 50.3 ± 13.5 years) in the Mayo BBD surgical biopsy cohort diagnosed between January 1, 1992 and December 31, 2001 who completed breast cancer risk factor questionnaires that assessed NSAID use, and whose biopsies underwent detailed pathology review, masked to outcome. Women were followed from date of BBD biopsy to breast cancer diagnosis (main outcome) or censoring (death, prophylactic mastectomy, reduction mammoplasty, lobular carcinoma in situ or last contact). Median follow-up time was 16.4 ± 6.0 years. Incident breast cancer was diagnosed among 312 women over a median follow-up of 9.9 years. Regular non-aspirin NSAID use was associated with lower breast cancer risk [HR = 0.63; 95% confidence interval (CI) = 0.46-0.85; P = 0.002] with trends of lower risk (highest tertiles of use vs. nonuse) for greater number of years used [HR = 0.55; 95% CI = 0.31-0.97; P trend = 0.003), days used per month (HR = 0.51; 95% CI = 0.33-0.80; P trend = 0.001) and lifetime number of doses taken (HR = 0.53; 95% CI = 0.31-0.89; P trend = 0.003). We conclude that nonaspirin NSAID use is associated with statistically significant lower breast cancer risk after a BBD biopsy, including a dose-response effect, suggesting a potential role for NSAIDs in breast cancer prevention among patients with BBD.

Aspirin alleviates denervation-induced muscle atrophy via regulating the Sirt1/PGC-1α axis and STAT3 signaling.

BackgroundOur prior studies have shown that inflammation may play an important triggering role during the process of denervated muscle atrophy. The nonsteroidal anti-inflammatory drug aspirin exhibits the effect of anti-inflammatory factors. This study will investigate the protective effect of aspirin on denervated muscle atrophy and the underlying mechanism.MethodsMouse models of denervated muscle atrophy were established. The protective effect of aspirin (20 mg/kg/d, i.p.) on denervated muscle atrophy was analyzed using the wet weight ratio of tibialis anterior (TA) muscle and muscle fiber cross-sectional area (CSA). The levels of inflammatory factors were detected using quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Sirtuins1 (SIRT1)/Peroxisome Proliferator-Activated Receptor γ Co-Activator 1α (PGC-1α) and Signal transducer and activator of transcription 3 (STAT3) signaling pathway and the muscle fiber type related proteins in TA muscle after denervation were analyzed by western blot assay.ResultsIntraperitoneal injection of aspirin (20 mg/kg/d) effectively alleviated denervation-induced muscle atrophy. This mainly manifested as follows: The wet weight ratio of TA muscle and muscle fiber CSA of mice treated with aspirin were significantly greater compared with mice treated with normal saline. The level of myosin heavy chain (MHC) increased, and the levels of muscle specific E3 ubiquitin ligase Muscle-specific RING finger-1 (MuRF-1) and muscle atrophy F-box (MAFbx) were decreased. Mitochondrial vacuolation and autophagy were inhibited, as evidenced by reduced level of autophagy related proteins PINK1, BNIP3, LC3B and Atg7 in mice treated with aspirin compared with mice treated with saline. In addition, aspirin treatment inhibited the slow-to-fast twitch muscle fiber conversion, which were related with triggering the expression of Sirt1 and PGC-1α. Moreover, aspirin reduced the levels of inflammatory factors interleukin-6, interleukin-1β and tumor necrosis factor-α and decreased the activation of STAT3 signaling pathway.ConclusionsThis is the first study to find that aspirin can alleviate denervation-induced muscle atrophy and inhibit the type I-to-type II muscle fiber conversion and mitophagy possibly through regulating the STAT3 inflammatory signaling pathway and Sirt1/PGC-1α signal axis. This study expands our knowledge regarding the pharmacological function of aspirin and provides a novel strategy for prevention and treatment of denervated muscle atrophy.

SMAR1 repression by pluripotency factors and consequent chemoresistance in breast cancer stem-like cells is reversed by aspirin.

The high abundance of drug efflux pumps in cancer stem cells (CSCs) contributes to chemotherapy resistance. The transcriptional regulator SMAR1 suppresses CSC expansion in colorectal cancer, and increased abundance of SMAR1 is associated with better prognosis. Here, we found in breast tumors that the expression of SMAR1 was decreased in CSCs through the cooperative interaction of the pluripotency factors Oct4 and Sox2 with the histone deacetylase HDAC1. Overexpressing SMAR1 sensitized CSCs to chemotherapy through SMAR1-dependent recruitment of HDAC2 to the promoter of the gene encoding the drug efflux pump ABCG2. Treating cultured CSCs or 4T1 tumor-bearing mice with the nonsteroidal anti-inflammatory drug aspirin restored SMAR1 expression and ABCG2 repression and enhanced tumor sensitivity to doxorubicin. Our findings reveal transcriptional mechanisms regulating SMAR1 that also regulate cancer stemness and chemoresistance and suggest that, by restoring SMAR1 expression, aspirin might enhance chemotherapeutic efficacy in patients with stem-like tumors.

An Overview of Cancer Prevention: Chemoprevention and Immunoprevention

Cancer prevention encompasses a broad spectrum of strategies designed to lower the chance of developing cancer and reduce the morbidity of established cancer. There are three levels of cancer prevention. Eliminating or mitigating cancer risk factors by adopting healthy behaviors and lifestyles, such as avoiding tobacco and alcohol use, exercising, eating a healthy diet, and applying sunscreen to protect against UV exposure, belongs to primary prevention and is the easiest and most effective way of preventing cancer for the general public. Secondary prevention includes screening to identify precancerous lesions and taking intervention measures to prevent disease progression to malignancy. Tertiary prevention refers to reducing or controlling the symptoms and morbidity of established cancer or the morbidity caused by cancer therapy. For high-risk populations, chemopreventive agents, such as selective estrogen receptor modulators (including tamoxifan and raloxifene) in breast cancer prevention and non-steroidal anti-inflammatory drugs (aspirin) in colorectal cancer prevention, and immunoprevention using human papillomavirus and hepatitis B virus vaccines in infection-related cancers have shown clear clinical benefits of reducing cancer incidences. In this review, we will summarize the current status of cancer prevention, focusing on the major agents that are clinically used for chemoprevention and immunoprevention.