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The Journal of Clinical Investigation May 2023Fibrinogen-like protein 1 (FGL1) has been associated with improved survival in hepatocellular carcinoma (HCC). However, recent evidence suggests that FGL1 may bind to...
Fibrinogen-like protein 1 (FGL1) has been associated with improved survival in hepatocellular carcinoma (HCC). However, recent evidence suggests that FGL1 may bind to surface receptors on lymphocytes and induce immune senescence. In this issue of the JCI, Lin and co-authors show that FGL1 may be acetylated by aspirin and targeted for degradation, which is associated with increased antitumor immunity and improved survival. Similar findings were obtained with inhibitors of sirtuin 2 (SIRT2), a histone deacetylase. These findings expand our current understanding of the role of FGL1 in cancer and provide an impetus for the evaluation of alternative immunotherapy combinations in HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Aspirin; Fibrinogen; Immunotherapy
PubMed: 37115694
DOI: 10.1172/JCI169598 -
Cancer Research Jul 2021Preclinical and clinical studies provide evidence for aspirin as a preventative agent for cancer. Compelling direct evidence supports a chemopreventive effect of aspirin... (Review)
Review
Preclinical and clinical studies provide evidence for aspirin as a preventative agent for cancer. Compelling direct evidence supports a chemopreventive effect of aspirin in individuals at high risk of developing colorectal cancer due to Lynch syndrome, while indirect evidence indicates that aspirin may reduce the risk of and mortality from sporadic colorectal cancer. There is weaker evidence for a protective effect of aspirin against all cancers taken as a group. Nevertheless, the results of recent retrospective cohort studies consistently indicate a beneficial effect of aspirin as a chemopreventive or adjuvant chemotherapeutic agent in hepatocellular carcinoma (HCC). Epidemiologic studies conducted in the general population or in selected populations at higher risk for HCC reveal that regular aspirin use is associated with reduced HCC incidence. In addition, aspirin may act as an adjuvant to other therapies in reducing HCC recurrence. According to studies in animal models, the cancer-preventative effect of aspirin may be related to its antiplatelet and anti-inflammatory activities. Prospective studies are warranted to determine whether aspirin should be recommended to diverse populations of patients at risk for HCC.
Topics: Aspirin; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Retrospective Studies
PubMed: 33893087
DOI: 10.1158/0008-5472.CAN-21-0758 -
Annual Review of Medicine Jan 2021High-quality evidence indicates that regular use of aspirin is effective in reducing the risk for precancerous colorectal neoplasia and colorectal cancer (CRC). This has... (Review)
Review
High-quality evidence indicates that regular use of aspirin is effective in reducing the risk for precancerous colorectal neoplasia and colorectal cancer (CRC). This has led to US and international guidelines recommending aspirin for the primary prevention of CRC in specific populations. In this review, we summarize key questions that require addressing prior to broader adoption of aspirin-based chemoprevention, review recent evidence related to the benefits and harms of aspirin use among specific populations, and offer a rationale for precision prevention approaches. We specifically consider the mechanistic implications of evidence showing differences in aspirin's effects according to age, the potential role of modifiable mechanistic biomarkers for personalizing prevention, and emerging evidence that the gut microbiota may offer novel aspirin-associated preventive targets to reduce high-risk neoplasia.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Chemoprevention; Colorectal Neoplasms; Humans; Precision Medicine
PubMed: 33035431
DOI: 10.1146/annurev-med-060319-120913 -
Wiley Interdisciplinary Reviews.... Sep 2020Epidemiological data indicate that long-term low dose aspirin administration has a protective effect against the occurrence of colorectal cancer, both in sporadic and in... (Review)
Review
Epidemiological data indicate that long-term low dose aspirin administration has a protective effect against the occurrence of colorectal cancer, both in sporadic and in hereditary forms of the disease. The mechanisms underlying this protective effect, however, are incompletely understood. The molecular events that lead to protection have been partly defined, but remain to be fully characterized. So far, however, approaches based on evolutionary dynamics have not been discussed much, but can potentially offer important insights. The aim of this review is to highlight this line of investigation and the results that have been obtained. A core observation in this respect is that aspirin has a direct negative impact on the growth dynamics of the cells, by influencing the kinetics of tumor cell division and death. We discuss the application of mathematical models to experimental data to quantify these parameter changes. We then describe further mathematical models that have been used to explore how these aspirin-mediated changes in kinetic parameters influence the probability of successful colony growth versus extinction, and how they affect the evolution of the tumor during aspirin administration. Finally, we discuss mathematical models that have been used to investigate the selective forces that can lead to the rise of mismatch-repair deficient cells in an inflammatory environment, and how this selection can be potentially altered through aspirin-mediated interventions. This article is categorized under: Models of Systems Properties and Processes > Mechanistic Models Analytical and Computational Methods > Analytical Methods Analytical and Computational Methods > Computational Methods.
Topics: Aspirin; Cell Cycle Checkpoints; Cell Proliferation; Evolution, Molecular; Humans; Models, Theoretical; Neoplasms
PubMed: 32163237
DOI: 10.1002/wsbm.1487 -
Cancer Epidemiology, Biomarkers &... Mar 2021Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a...
BACKGROUND
Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk.
METHODS
Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL ( = 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium ( = 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls).
RESULTS
Altered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2, and ARFIP2 expression, and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR: 1.08, 95% CI, 1.03-1.13; OR: 3.33, 95% CI, 2.46-4.50; and OR: 1.15, 95% CI, 1.02-1.29, respectively).
CONCLUSIONS
MCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation, indicating a possible role in aspirin's reduction of metastasis.
IMPACT
Our approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.
Topics: Aspirin; Colorectal Neoplasms; Humans; Mendelian Randomization Analysis; Proteomics; Risk Factors
PubMed: 33318029
DOI: 10.1158/1055-9965.EPI-20-1176 -
The Journal of Infection Apr 2023
Topics: Humans; Aspirin; COVID-19; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Signal Transduction; Receptors, Interleukin-1
PubMed: 36690213
DOI: 10.1016/j.jinf.2023.01.025 -
The British Journal of Ophthalmology May 1992
Topics: Aspirin; Cataract; Humans
PubMed: 1390503
DOI: 10.1136/bjo.76.5.257 -
BMJ (Clinical Research Ed.) May 1994
Topics: Aspirin; Female; Humans; Meta-Analysis as Topic; Pre-Eclampsia; Pregnancy
PubMed: 8205012
DOI: 10.1136/bmj.308.6939.1250 -
British Journal of Pharmacology Jan 2023
Topics: Aspirin; Blood Platelets
PubMed: 36325602
DOI: 10.1111/bph.15975 -
The Journal of Headache and Pain Feb 2007Acetylsalicylic acid (ASA, Aspirin) is among the most used drugs worldwide. At present, Aspirin represents a quite versatile drug employed in the control of pain... (Review)
Review
Acetylsalicylic acid (ASA, Aspirin) is among the most used drugs worldwide. At present, Aspirin represents a quite versatile drug employed in the control of pain symptomatologies and in situations such as prevention of both ischaemic stroke and cardiovascular events. Aspirin causes inhibition of prostaglandin (PG) synthesis by inactivation of the cyclooxygenase (COX) enzyme. ASA constitutes the focus of new researches explaining more widely Aspirin's control of inflammation. The induction of the endogenous epimers lipoxins (Aspirin-triggered 15-epi-lipoxins, ATLs) represents one of the most recent achievements. This particular feature of Aspirin is not shared by other NSAIDs. ASA is well known as a headache medication, figuring as a possible treatment choice in tension-type headache but also in acute migraine attacks. Furthermore, a new Aspirin formulation with a greater rapidity of action has been introduced. In conclusion, little information exists on the subject and more studies are required.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Humans; Tension-Type Headache
PubMed: 17192817
DOI: 10.1007/s10194-006-0357-4