Effect Of Aspirin In Prevention Research Articles

Prophylactic Effect of Aspirin and Other Medicine on Cerebral Infarction for Patients with Cardiovascular Diseases Risk Factors: A Systemic Review and Meta-Analysis.

Stroke, as a type of cardiovascular disease (CVD) and cerebrovascular disease, has the risk of causing death or disability in patients. Aspirin, as an antipyretic and analgesic drug, can also treat or prevent CVDs. Previous studies have had conflicting results on the preventive effect of aspirin on cerebral infarction for patients with CVD risk factors. This review was carried out through a meticulous search of the Web of Science and PubMed databases. Articles were included or excluded based on predefined criteria. In terms of heterogeneity, a fixed effect model was utilized when I2 was less than 50%. Conversely, if the studies were deemed clinically comparable, a random effect model was implemented. The findings suggest that medical intervention significantly mitigates the risk of cerebral infarction in patients predisposed to CVDs [odds ratio (OR), 0.85; 95% confidence interval (CI), 0.74-0.98; P = 0.03]. Interestingly, the preventive efficacy of medication appears to be higher in men (OR, 0.82; 95% CI, 0.72-0.94; P = 0.004) than in women (OR, 0.84; 95% CI, 0.69-1.01; P = 0.06). However, in terms of stroke prevention, no significant difference was observed between the use of aspirin (OR, 0.90; 95% CI, 0.76-1.06; P = 0.19) and other medications (OR, 0.65; 95% CI, 0.31-1.38; P = 0.26).

Effect of aspirin on blood pressure in hypertensive patients: a systematic review and meta-analysis

IntroductionAspirin is widely used for secondary prevention in patients with hypertension. However, previous studies mainly focused on the preventive effects of aspirin, and there has been a lack of reliable evidence on whether taking aspirin affects blood pressure This study aimed to investigate whether aspirin would affect the blood pressure in patients with hypertension.MethodsPubMed, Cochrane database, Embase, Scopus and Medline databases were searched until September 2023. For continuous variables (e.g., blood pressure reduction), the mean difference (MD) was selected as the effect magnitude indices. We used the Cochrane Collaboration’s Risk of Bias tool to assess the risk of bias.ResultA total of five studies were included, comprising 20,312 patients. We found that aspirin did not affect SBP (MD = -0.78, 95% CI: − 2.41, 0.84). A similar result was found for DBP (MD = -0.86, 95% CI: − 2.14, 0.42).ConclusionThis study showed no significant difference in blood pressure between the aspirin and control groups, suggesting that aspirin does not affect blood pressure.

Preventive effect of aspirin on peripherally inserted central catheter-related vein thrombosis in patients with malignant tumors

AbstractThe majority of patients receiving chemotherapy undergo PICC catheterization. However, PICCs are significantly associated with catheter related complications, including deep vein thrombosis, blood infection, fibrin sheath, catheter prolapse, catheter displacement and blockage. Of all the risks, PICC-related VT was the most prevailing clinic symptom and resulted in a high risk of death. AimThe study aimed to investigate the preventive efficacy and safety of aspirin for patients with malignant tumors receiving venous thrombosis (VT) related with peripherally inserted central catheters (PICC) treatment. Patients and MethodsA randomized controlled trial was conducted. Participants with malignant tumors receiving chemotherapy who accepted PICC insertion operation were randomly allocated to the aspirin treatment group (n = 235) or the control group (n = 246). The patients in the aspirin group were administrated aspirin (100mg) for 30 days, whereas the patients in control group were administrated a placebo drug. The incidence of PICC-related VT in both groups and the aspirin related adverse effects were evaluated. ResultsThe incidence of PICC-related VT was 0.4% in the aspirin group, compared with 3.3% in the control group (P = 0.038). In addition, aspirin related bleeding was not observed. ConclusionPICC-related VT could be effectively prevented by aspirin in patients with malignant tumors.

The preventive effects of aspirin on preeclampsia based on network pharmacology and bioinformatics.

This study aimed to reveal the key targets and molecular mechanisms of aspirin in preventing preeclampsia. We used bioinformatics databases to collect the candidate targets for aspirin and preeclampsia. The biological functions and signaling pathways of the intersecting targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then, the hub targets were identified by cytoscape plugin cytoHubba from the protein-protein interaction network. We collected 90 targets for aspirin in preventing preeclampsia. The biological processes of the intersecting targets are mainly involved in xenobiotic metabolic process, inflammatory response, negative regulation of apoptotic process, and protein phosphorylation. The highly enriched pathways were FoxO signaling pathway, circadian rhythm, insulin resistance, arachidonic acid metabolism, and drug metabolism-cytochrome P450. The hub targets for aspirin in preventing preeclampsia were tumor protein p53 (TP53), C-X-C motif chemokine ligand 8 (CXCL8), mitogen-activated protein kinase 3 (MAPK3), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 14 (MAPK14), epidermal growth factor receptor (EGFR), estrogen receptor (ESR1), and prostaglandin-endoperoxide synthase 2 (PTGS2). Molecular docking results showed good bindings between the proteins and aspirin. In conclusion, these findings highlight the key targets and molecular mechanisms of aspirin in preventing preeclampsia.

A randomized controlled trial on Aspirin and complex regional pain syndrome after radius fractures.

Complex regional pain syndrome (CRPS) is often diagnosed in patients who are recovered with surgery or injury. CRPS is usually diagnosed in patients recovering from distal radius fractures. The aim of study was the effects of aspirin in prevention of the complex regional pain syndrome (CRPS) following a fracture of distal radius. In a double-blind, randomized controlled trial, 91 patients with unilateral extra-articular distal radius fractures were randomly allocated to receive either placebo (PLA) or 500 mg of aspirin (ASA) daily for 7 days. The effect of aspirin on the occurrence of CRPS was evaluated. The patients were assessed clinically and radiographically in the second, fourth and twelfth weeks by a physician who was unaware of the treatment allocation. Ninety-one patients (ASA, n=44; PLA, n=47) were enrolled in the study. The prevalence of CRPS in all patients was 16.5%. The prevalence of CRPS in the aspirin group was lower (13.6%) than the placebo group (19.1%), but this difference was not statistically significant. The only significant difference was the lower rate of regional osteoporosis seen in the radiographs of aspirin group. Mean age was significantly higher in the patients with CRPS. Also, comminuted distal radius fractures (A3-type) were significantly more common in the patients with CRPS. Administration of aspirin in patients with a distal radius fracture was associated with a lower incidence of CRPS, but, not statistically significant. Further investigations needs to be done with a larger sample size, longer follow-up period and multi-center design.

Abstract 720: Aspirin plus FOLFOX for colorectal cancer management: A promising alternative for clinical trial in Africans with the disease

Abstract Colorectal cancer (CRC) has disproportionately overburden Africans with advanced stage at diagnosis and higher mortality rate due in part to issues that include grossly inadequate resources for management and poor understanding of the pathobiology of the disease. Accumulating evidences support the effectiveness of Aspirin in prevention and inhibition of CRC occurrence and cellular growth respectively. The utilisation of 5-fluorouracil (5-FU)-based regimens which include folinic acid, 5-FU and oxaliplatin (FOLFOX) combination in CRC management have not completely halt the distant recurrences and poor prognosis of CRC. In this study, we highlighted evidences that prove Aspirin plus FOLFOX to be promising alternative for clinical trial in Black men with CRC. Our study aims in this research were: to identify the expression pattern of BIRC7 in human CRC cells, SW480 cell line and N-methyl-N-nitrosourea (NMU)-induced CRC in rat; to determine the relationship between BIRC7 and BCL2, p53, PDL-1, MSH1, PMS2, DARC and Annexin V expression in CRC. to examine the efficacy of Aspirin plus neoadjuvant FOLFOX on the BIRC7 in CRC cells in-vivo in rat. Results show significant (P = 0.0001) expression of the BIRC7 in the CRC tissues compared to normal sections. When comparing this expression with Data from TCGA data bank, we observed a significant increase in BIRC7 expression in Caucasian than the Black and Indian and The expression pattern of the BIRC7 was significantly higher (P = 0.0001) in CRC not otherwise specified compared to mucinous CRC histology. The SW480 cell line show increased expression of the BIRC7 protein in-vitro. There was significant expression of the BIRC7 in the NMU-induced CRC cells compared the normal colonic lesion. There was increased expression of the BCL-2 and reduced expression of p53 in the human CRC cases and in the NMU-induced CRC cells model. There was increased expression of the Annexin V, absence of the MSH1, PMS2, PDL1 and DARC protiens in the CRC sections. Aspirin plus FOLFOX may serve as an important adjuvant treatment component for colorectal cancer metastasis and local recurrence in Blacks, Caucasian and Asians. There is need to explore the potential of Aspirin plus FOLFOX for clinical trial in colorectal cancer management in Blacks and other population using approach from our findings. Citation Format: Faruk Mohammed, Sani Ibrahim, Sirajo Mohammed Aminu, Ahmed Adamu, Adamu Abdullahi, Abdulmumini Hassan Rafindadi, Yawale Iliyasu, John Idoko, Abdullahi Jubril Randawa, Mohammed Sani Shehu, Atara Ntekim, Abdullahi Mohammed, Aishatu Maude Suleiman, Yahaya Ukwenya, Khalid Zahir Shah, Ahmad Bello, Sani Abubakar, Kasimu Umar Adoke, Cheh Augustin Awasum, Ahmad Mai, Hussaini Yusuf Maitama, Dauda Maigatari. Aspirin plus FOLFOX for colorectal cancer management: A promising alternative for clinical trial in Africans with the disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 720.

Aspirin for Evidence-Based Preeclampsia Prevention trial: influence of compliance on beneficial effect of aspirin in prevention of preterm preeclampsia

The Aspirin for Evidence-Based Preeclampsia Prevention trial was a multicenter study in women with singleton pregnancies. Screening was carried out at 11-13 weeks' gestation with an algorithm that combines maternal factors and biomarkers (mean arterial pressure, uterine artery pulsatility index, and maternal serum pregnancy-associated plasma protein A and placental growth factor). Those with an estimated risk for preterm preeclampsia of >1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg/d) vs placebo from 11-14 until 36 weeks' gestation. Preterm preeclampsia with delivery at <37 weeks' gestation, which was the primary outcome, occurred in 1.6% (13/798) participants in the aspirin group, as compared with 4.3% (35/822) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74). We sought to examine the influence of compliance on the beneficial effect of aspirin in prevention of preterm preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial. This was a secondary analysis of data from the trial. The proportion of prescribed tablets taken was used as an overall measure of compliance. Logistic regression analysis was used to estimate the effect of aspirin on the incidence of preterm preeclampsia according to compliance of <90% and ≥90%, after adjustment for the estimated risk of preterm preeclampsia at screening and the participating center. The choice of cut-off of 90% was based on an exploratory analysis of the treatment effect. Logistic regression analysis was used to investigate predictors of compliance ≥90% among maternal characteristics and medical history. Preterm preeclampsia occurred in 5/555 (0.9%) participants in the aspirin group with compliance ≥90%, in 8/243 (3.3%) of participants in the aspirin group with compliance <90%, in 22/588 (3.7%) of participants in the placebo group with compliance ≥90%, and in 13/234 (5.6%) of participants in the placebo group with compliance <90%. The odds ratio in the aspirin group for preterm preeclampsia was 0.24 (95% confidence interval, 0.09-0.65) for compliance ≥90% and 0.59 (95% confidence interval, 0.23-1.53) for compliance <90%. Compliance was positively associated with family history of preeclampsia and negatively associated with smoking, maternal age <25 years, Afro-Caribbean and South Asian racial origin, and history of preeclampsia in a previous pregnancy. The beneficial effect of aspirin in the prevention of preterm preeclampsia appears to depend on compliance.

Aspirin for Evidence-Based Preeclampsia Prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history

The Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention trial demonstrated that in women who were at high risk for preterm preeclampsia with delivery at <37 weeks' gestation identified by screening by means of an algorithm that combines maternal factors and biomarkers at 11-13 weeks' gestation, aspirin administration from 11 to 14 until 36 weeks' gestation was associated with a significant reduction in the incidence of preterm preeclampsia (odds ratio 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). We sought to examine whether there are differences in the effect of aspirin on the incidence of preterm preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial in subgroups defined according to maternal characteristics and medical and obstetrical history. This was a secondary analysis of data from the Aspirin for Evidence-Based Preeclampsia Prevention trial. Subgroup analysis was performed to assess evidence of differences in the effect of aspirin on incidence of preterm preeclampsia in subgroups defined by maternal age (<30 and ≥30 years), body mass index (<25 and ≥25 kg/m2), racial origin (Afro-Caribbean, Caucasian and other), method of conception (natural and assisted), cigarette smoking (smoker and non-smoker), family history of preterm preeclampsia (present and absent), obstetrical history (nulliparous, multiparous with previous preterm preeclampsia and multiparous without previous preterm preeclampsia), history of chronic hypertension (present and absent). Interaction tests were performed on the full data set of patients in the intention to treat population and on the data set of patients who took ≥ 90% of the prescribed medication. Results are presented as forest plot with P values for the interaction effects, group sizes, event counts and estimated odds ratios. We examined whether the test of interaction was significant at the 5% level with a Bonferroni adjustment for multiple comparisons. There was no evidence of heterogeneity in the aspirin effect in subgroups defined according to maternal characteristics and obstetrical history. In participants with chronic hypertension preterm preeclampsia occurred in 10.2% (5/49) in the aspirin group and 8.2% (5/61) in the placebo group (adjusted odds ratio, 1.29; 95% confidence interval, 0.33-5.12). The respective values in those without chronic hypertension were 1.1% (8/749) in the aspirin group and 3.9% (30/761) in the placebo group (adjusted odds ratio, 0.27; 95% confidence interval, 0.12-0.60). In all participants with adherence of ≥90% the adjusted odds ratio in the aspirin group was 0.24 (95% confidence interval, 0.09-0.65); in the subgroup with chronic hypertension it was 2.06 (95% confidence interval, 0.40-10.71); and in those without chronic hypertension it was 0.05 (95% confidence interval, 0.01-0.41). For the complete data set the test of interaction was not significant at the 5% level (P= .055), but in those with adherence ≥90%, after adjustment for multiple comparisons, the interaction was significant at the 5% level (P= .0019). The beneficial effect of aspirin in the prevention of preterm preeclampsia may not apply in pregnancies with chronic hypertension. There was no evidence of heterogeneity in the aspirin effect in subgroups defined according to maternal characteristics and obstetrical history.

Aspirin and the Primary Prevention of Cardiovascular Diseases: An Approach Based on Individualized, Integrated Estimation of Risk.

While the use of aspirin in the secondary prevention of cardiovascular (CVD) is well established, aspirin in primary prevention is not systematically recommended because the absolute CV event reduction is similar to the absolute excess in major bleedings. Recently, emerging evidence suggests the possibility that the assumption of aspirin, may also be effective in the prevention of cancer. By adding to the CV prevention benefits the potential beneficial effect of aspirin in reducing the incidence of mortality and cancer could tip the balance between risks and benefits of aspirin therapy in the primary prevention in favour of the latter and broaden the indication for treatment with in populations at average risk. While prospective and randomized study are currently investigating the effect of aspirin in prevention of both cancer and CVD, clinical efforts at the individual level to promote the use of aspirin in global (or total) primary prevention could be already based on a balanced evaluation of the benefit/risk ratio.

Aspirin prevents TNF-α-induced endothelial cell dysfunction by regulating the NF-κB-dependent miR-155/eNOS pathway: Role of a miR-155/eNOS axis in preeclampsia

Preeclampsia is an inflammatory disease with endothelial cell dysfunction that occurs via decreased endothelial nitric oxide synthase/nitric oxide (eNOS/NO) activity. Aspirin reduces the incidence of hypertensive pregnancy complications. However, the underlying mechanism has not been clearly explained. Here, we found that tumor necrosis factor (TNF)-α, microRNA (miR)−155, and eNOS levels as well as endothelial redox phenotype were differentially regulated in preeclamptic patients, implying the involvement of TNF-α- and redox signal-mediated miR-155 biogenesis and eNOS downregulation in the pathogenesis of preeclampsia. Aspirin prevented the TNF-α-mediated increase in miR-155 biogenesis and decreases in eNOS expression and NO/cGMP production in cultured human umbilical vein endothelial cells (HUVECs). Similar effects of aspirin were also observed in HUVECs treated with H2O2. The preventive effects of aspirin was associated with the inhibition of nuclear factor-κB (NF-κB)-dependent MIR155HG (miR-155 host gene) expression. Aspirin recovered the TNF-α-mediated decrease in wild-type, but not mutant, eNOS 3′-untranslated region reporter activity, whose effect was blocked by miR-155 mimic. Moreover, aspirin prevented TNF-α-mediated endothelial cell dysfunction associated with impaired vasorelaxation, angiogenesis, and trophoblast invasion, and the preventive effects were blocked by miR-155 mimic or an eNOS inhibitor. Aspirin rescued TNF-α-mediated eNOS downregulation coupled with endothelial dysfunction by inhibiting NF-κB-dependent transcriptional miR-155 biogenesis. Thus, the redox-sensitive NF-κB/miR-155/eNOS axis may be crucial in the pathogenesis of vascular disorders including preeclampsia.

General practitioner attitudes towards prescribing aspirin to carriers of Lynch Syndrome: Findings from a national survey

A dose non-inferiority study comparing 100 mg, 300 mg and 600 mg of aspirin for cancer prevention among Lynch Syndrome carriers is underway (Colorectal Adenoma/Carcinoma Prevention Programme trial 3, CaPP3). To guide implementation of the findings, we investigated general practitioner (GP) attitudes towards aspirin prescribing for Lynch Syndrome carriers. We surveyed 1007 UK GPs (9.6% response rate). Using a within-subjects design, GPs read a statement on harms and benefits of aspirin and indicated their willingness to prescribe aspirin at three doses (100 mg, 300 mg, 600 mg). Approximately two-thirds (70.8%) of GPs had heard of Lynch Syndrome or its associated names, and among those 46.7% were aware of the cancer preventive effects of aspirin among carriers. Two-thirds (68.1%) of GPs reported feeling comfortable discussing harms and benefits of aspirin with a Lynch Syndrome patient. Willingness to prescribe was 91.3% at 100 mg, and declined to 81.8% at 300 mg and 62.3% at 600 mg (p < 0.001). In multivariable analyses, willingness to prescribe (600 mg) was higher among GPs ≥50 years (OR 1.46, 95% CI 1.03-2.07), more experienced GPs (OR 1.50, 95% CI 1.10-2.04), GPs who were aware of the cancer preventive effects of aspirin (OR 1.58, 95% CI 1.20-2.09), and those who reported seeing a Lynch Syndrome patient in practice (OR 1.44, 95% CI 1.01-2.05, p = 0.045). GPs report limited awareness of Lynch Syndrome and the preventive effects of aspirin among carriers. To ensure the optimal dose identified in the CaPP3 trial is readily available to patients, prescribing guidance and strategies to educate GPs should be developed.

Effects of aspirin in the prevention of cardiovascular events for patients with hypertension

Objective To study the effect of aspirin in the prevention of cardiovascular events for patients with hypertension. Methods 105 patients with hypertensive disease were randomly divided into group A,B,C,35 cases in each group, and group A was dealed with nifedipine tablets treatment, group B were treated with nifedipine tablets and aspirin,group C was given nifedipine tablets and dipyridamole. The antihypertensive effects of the three groups were observed,three years through regular follow-up for all patients, the effects of prevention of cardiovascular events in patients with essential hypertension were observed. Results The occurrence probability of myocardial infarction, cerebral infarction and cerebral hemorrhage in the group B were 2.85%,2.85%,0.00%, respectively, which were statistically significant less than those in the group A and C group(F=19.4,P<0.05). Conclusion The preventive effect of aspirin is better for cardiovascular events in hypertensive patients, which is worthy to be popularized and used in clinical studies, aspirin for this kind of disease is a kind of ideal. Key words: Aspirin; Hypertension

Reducing Cardiovascular and Cancer Risk: How to Address Global Primary Prevention in Clinical Practice.

Emerging evidence suggesting the possibility that interventions able to prevent cardiovascular disease (CVD) may also be effective in the prevention of cancer have recently stimulated great interest in the medical community. In particular, data from both experimental and observational studies have demonstrated that aspirin may play a role in preventing different types of cancer. Although the use of aspirin in the secondary prevention of CVD is well established, aspirin in primary prevention is not systematically recommended because the absolute cardiovascular event reduction is similar to the absolute excess in major bleedings. By adding to its cardiovascular prevention benefits, the potential beneficial effect of aspirin in reducing the incidence of mortality and cancer could tip the balance between risks and benefits of aspirin therapy in primary prevention in favor of the latter and broaden the indication for treatment with aspirin in populations at average risk. Prospective and randomized studies are currently investigating the effect of aspirin in prevention of both cancer and CVD; however, clinical efforts at the individual level to promote the use of aspirin in global (or total) primary prevention already could be made on the basis of a balanced evaluation of the benefit/risk ratio.

Aspirin and intracerebral hemorrhage: Where are we now?

For the past 3 decades, aspirin has been widely used for prevention of ischemic stroke and myocardial infarction. Although the evidence supporting the effectiveness of aspirin in prevention of vascular events is clear, data regarding the risk of acute and recurrent intracerebral hemorrhage related to the use of this medication have been conflicting. We review past and contemporary data on aspirin use in relation to intracerebral hemorrhage.

Abstract C49: A randomized phase II trial of low-dose aspirin versus placebo in high-risk individuals with CT screen-detected subsolid lung nodules

Abstract Lung cancer screening by spiral low-dose CT scan (ld-CT) is a noninvasive test with low radiation exposure and no contrast medium and offers the opportunity to serially examine the peripheral lung for the first time, albeit with the limitation that small lesions cannot be biopsied, leaving their identity unknown. However, the incidence of undetermined nodules detected with ld-CT is more than 50% in high-risk individuals. The nature of these nodules remains uncertain but some of them could represent precancerous lesions. Particularly, ground glass opacities (GGO), compared with solid nodules, can represent localized bronchioloalveolar carcinoma without foci of active fibroblastic proliferation or atypical adenomatous hyperplasia, a putative adenocarcinoma precursor lesion. Two screening programs with annual ld-CT in current and former smokers are run at the EIO and they may represent suitable cohorts of at-risk subjects to be enrolled in a chemopreventive study. Aspirin, the first nonsteroidal anti-inflammatory drug (NSAID) identified, may have anti-cancer properties, especially for diseases whose etiology implicates chronic inflammation including lung cancer. The anti-inflammatory effect of NSAIDs operates through inhibition of prostaglandins via suppression of cyclooxygenase-1 (COX-1) and COX-2. Evidence of this effect is derived from several recently published meta-analyses of aspirin in the prevention of cardiovascular events showing that daily aspirin reduced the incidence of several cancers and reduced metastases. In 2011, Rothwell et al. pooled data from 8 double-blind randomized controlled trials of daily aspirin and analyzed the effect of aspirin on cancer mortality as secondary endpoints. The 20-year risk of death due to all cancers was lower in the aspirin than in the control group and the benefit increased with treatment duration. Lung cancer-specific mortality rates were reduced by 29% (95% CI, 11-42) in the aspirin group in the 20-year period after the trial commenced. No trend with dose (above 75 mg/day) was observed, but the effect on all cancers was more evident in adenocarcinomas and was present in both smokers and nonsmokers. Several further observational studies have been published confirming a lower lung cancer risk in aspirin users. Based on the growing evidence on the potential preventive effect of Aspirin on lung cancer, we will conduct a monoinstitutional, double-blind, placebo-controlled phase IIb study in which 128 participants enrolled in a ld-CT annual screening program will be randomized to receive either low dose Aspirin (100 mg/day) or placebo for 12 month. The primary endpoint will be the shrinkage of GGO and partially solid nodules after one-year treatment in a per-lesion and per-subject analysis. Secondary endpoints will be the modulation of biological markers and their potential correlation with modification of lung nodules shrinkage. In particular, we will evaluate the effect of Aspirin on a signature of serum miRNA correlated to subsolid nodules. Other secondary endpoints will be the evaluation of lung nodule density before and after treatment and the number and size of non-target lesions. Additional circulating biomarkers will include the modulation of hs-CRP as a marker of inflammation, the evaluation of urinary cotinine as marker of tobacco exposure and investigation of the potential effect of aspirin according to its concentration, the measurement of urinary prostaglandin metabolites (PGEM) and urine LTE4. Tolerability of low dose Aspirin will be also evaluated. The study is expected to start by December 2013. Supported by NCI, DCP Contract HHSN261201200034I to the UT MD Anderson Cancer Prevention Agent Development Program: Early Phase Clinical Research Citation Format: Aliana Guerrieri-Gonzaga, Giulia Veronesi, Pier Paolo Di Fiore, Matteo Lazzeroni, Massimo Bellomi, Eva Szabo, Lana A. Vornik, Powel H. Brown, Bernardo Bonanni. A randomized phase II trial of low-dose aspirin versus placebo in high-risk individuals with CT screen-detected subsolid lung nodules. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C49.

Effect of aspirin in prevention of adverse pregnancy outcome in women with elevated alpha-fetoprotein

Background: To evaluate the effect of low-dose aspirin in prevention of adverse pregnancy outcomes (APO) in women with second trimester alpha-fetoprotein (AFP) >2.5 multiple of median (MOM) and to compare aspirin effect on women with normal and abnormal uterine artery (UtA) Doppler. The primary outcome was the adverse pregnancy outcome.Methods: This randomized controlled trial was conducted in singleton pregnant women, who had unexplained AFP >2.5 MOM and gestational age between 15 and 18 weeks of gestation. They were assigned randomly to receive either aspirin (N = 65) or control (N = 68). UtA Doppler velocimetry studies were performed at the time of targeted ultrasonographic exam.Results: Two groups were comparable regarding the maternal characteristics. The frequency of APO in aspirin and control groups were 26.1% versus 44.1% (p = 0.045), the frequency of preterm delivery before 34 weeks were 3.2% versus 22.0% in aspirin and control group, p = 0.001. Other outcomes were similar in both groups. The frequency of adverse outcomes in women with abnormal UtA Doppler was 39.1% in aspirin and 60.0% in control group, p = 0.556.Conclusion: Low-dose aspirin reduces APO and delivery before 34 weeks of gestation in pregnant women with unexplained elevated AFP.

Aspirin prevents growth and differentiation of breast cancer cells: lessons from in vitro and in vivo studies

Aspirin, a classical non‐steroidal anti‐inflammatory drug (NSAID) is widely used to reduce pains and fever. Epidemiological and experimental studies suggested that Aspirin use reduces the risk of different cancers including breast cancer and may be used as a chemopreventive agent against breast cancer and other carcinogenesis. These studies have raised the tempting possibility that Aspirin could serve as a preventive medicine for breast cancer. However lack of in‐depth knowledge of the mechanism of action of Aspirin reshapes the debate of risk and benefit of Aspirin in prevention of breast cancer. Our aim is to investigate effects of Aspirin on pathophysiological events like epithelial to mesenchymal transition (EMT), migration, stemness of cell in breast cancer cells. Our studies using in vitro and in vivo tumor xenograft model show a strong beneficial effects of Aspirin in prevention of breast carcinogenesis. We find Aspirin not only prevents breast tumor cell proliferation in vitro and tumor growth in xenograft mouse model, it also significantly inhibits other pathophysiological events in breast cancer such as EMT, cell migration as well as reprogramming of stemness in breast cancer cells. Collectively our studies suggest that intake of an ASPIRIN a day might offer additional avenues for breast cancer prevention and treatment.(Support: VA Merit Grants ;S. Banerjee and S.K. Banerjee)

Positive influence of aspirin on coronary endothelial function: Importance of the dose

To investigate the effects of different doses of aspirin on coronary endothelial function. The study included 139 Japanese subjects (mean age, 60 years; 53 women) with angiographically normal coronary arteries. Patients were distributed into Group I (n = 63), who was administered aspirin and Group II (n = 76), the control, who were not administered aspirin. Group I was further divided into Group Ia (n = 50, low-dose aspirin, 100 mg) and Group Ib (n = 13, high-dose aspirin, 500 mg). After a routine coronary angiography, acetylcholine (ACh; 3 and 30 μg/min successively) and nitroglycerin (NTG) were infused into the left coronary ostium over 2 min. The change in the diameter of the coronary artery in response to each drug was expressed as the percentage change from baseline values. The patient characteristics did not differ between the two groups. The change in coronary diameter in response to ACh was greater in Group I than in Group II (P = 0.0043), although the NTG-induced coronary vasodilation was similar between groups. ACh-induced dilation was greater in Group Ia than in Group Ib (P = 0.0231). Multivariate regression analysis showed that a low-dose of aspirin (P = 0.0004) was one of the factors associated with ACh-induced dilation at 30 μg/min. In subjects with angiographically normal coronary arteries, aspirin only had a positive influence on coronary endothelial function at the low dose of 100 mg. This improvement of coronary endothelial function may be involved in the preventive effect of aspirin against future coronary events.

P07.08: The effect of aspirin in prevention of preeclampsia and its complications in women with abnormal uterine artery Doppler ultrasound

P07.08: The effect of aspirin in prevention of preeclampsia and its complications in women with abnormal uterine artery Doppler ultrasound

Suppressive effect of post- or pre-treatment of aspirin metabolite on mitomycin C-induced genotoxicity using the somatic mutation and recombination test in Drosophila melanogaster

In our previous paper, we found that aspirin suppressed in a somatic mutation and recombination test (SMART) of mitomycin C (MMC) in Drosophila melanogaster. In order to reveal the mechanism of bio-antimutagenicity and/or preventive effect of aspirin, we evaluated the suppressive ability of each aspirin metabolite, such as salicylic acid (SA), salicyluric acid (SUA), gentisic acid (GA), gentisuric acid (GUA) and 2,3-dihydroxybenzoic acid (DHBA), in SMART in D. melanogaster using post- and pre-treatments. As for the post-treatment, SA reduced the numbers of large single and twin spots. GA reduced the small single and large single spots, and GUA reduced the single spots, large single and twin spots. The inhibition of GUA is slightly stronger than that of any other metabolites; the inhibition percentage is 49 at the dose of 5 mg/bottle. On the other hand, as for the pre-treatment, aspirin, SUA, GA and DHBA reduced the numbers of small single spots. SUA, GE and DHBA reduced the number of large single spots. Aspirin and its metabolites did not reduce the number of twin spots. The results of the present study suggest that SA, GA and GUA repair or replicate DNA-damage by MMC and SUA, GA, GUA and DHBA prevent DNA-damage by MMC. It is suggested that secondary cancer is prevented by aspirin post-treatment without losing the medicinal effectiveness (anti-tumor activity). Therefore, we consider there are effective doses and/or administration timing of aspirin and MMC to prevent secondary cancer.