Aspirin and non-aspirin non-steroidal anti-inflammatory drug use and risk of lung cancer

Saw Swee Hock School of Public Health, National University of Singapore, MD3, 16 Medical Drive, Singapore 117597, Singapore. wei-yen
Lung cancer (Amsterdam, Netherlands) (Impact Factor: 3.74). 04/2012; 77(2):246-51. DOI: 10.1016/j.lungcan.2012.03.005
Source: PubMed

ABSTRACT There is evidence that aspirin and non-aspirin non-steroidal anti-inflammatory drug (NSAID) have anti-carcinogenic properties, but their effect on lung cancer, in particular in never-smokers, is unclear. Information on past or current use of anti-inflammatory medication was obtained in 398 Chinese female primary lung cancer cases and 814 controls in a hospital-based study in Singapore. 65% of cases and 88% of controls were never-smokers. Controls were excluded if they had been admitted for conditions associated with aspirin or NSAID use (n=174). Regular aspirin use (twice a week or more, for a month or more) was associated with a reduced risk of lung cancer (adjusted odds ratio [OR] 0.50, 95% confidence intervals [95%CI] 0.31-0.81 in non-smokers; OR 0.38, 95%CI 0.16-0.93 in smokers). Regular use of non-aspirin NSAID, paracetamol, steroid creams and steroid pills was uncommon and no association with lung cancer was detected. Our results suggest that aspirin consumption may reduce lung cancer risk in Asian women and are consistent with current understanding of the role of cyclooxygenase in lung carcinogenesis.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with rheumatoid arthritis (RA) appear to be at a higher risk of lung cancer (LC). Although the connection between RA and LC has been an active area of research for many years, the molecular pathogenesis of the disease process remains unclear. The cyclooxygenase (COX)-2/thromboxane A2 (TxA2) pathway has been shown to play a potential role in LC development through an auto-regulatory feedback loop. An increased level of TxA2 has been found in RA patients, and intriguingly, the positive feedback loop for the COX-2/TxA2 pathway was shown to have a potential function in RA fibroblast-like synoviocytes (RA-FLS). Thus, the molecular basis of LC development in patients with RA has been at least in partly described. It is possible that COX-2-derived TxA2 could be monitored for the early detection of LC in RA patients, and targeting this molecular may decrease the risk of LC in patients with RA.
    Cancer Letters 08/2014; 354(1). DOI:10.1016/j.canlet.2014.08.024 · 5.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Inflammatory stimuli clearly contribute to lung cancer development and progression, but the underlying pathogenic mechanisms are not fully understood. We found that the pro-inflammatory cytokine IL-1β is dramatically elevated in the serum of patients with non-small cell lung cancer (NSCLC). In vitro studies showed that IL-1β promoted the proliferation and migration of NSCLC cells. Mechanistically, IL-1β acted through the COX-2/HIF-1α pathway to repress expression of miR-101, a microRNA with an established role in tumor suppression. Lin28B was identified as critical effector target of miR-101 with its repression of Lin28B a critical aspect of tumor suppression. Overall, IL-1β upregulated Lin28B by downregulating miR-101. Interestingly, COX-2 inhibition by aspirin or celecoxib abrogated IL-1β-mediated repression of miR-101 and IL-1β-mediated activation of Lin28B, along with their stimulatory effects on NSCLC cell proliferation and migration. Together, our findings defined a IL-1β/miR-101/Lin28B pathway as a novel regulatory axis of pathogenic inflammatory signaling in NSCLC.
    Cancer Research 06/2014; 74(17). DOI:10.1158/0008-5472.CAN-14-0960 · 9.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Resistance and non-response to aspirin dramatically decreases its therapeutic efficacy. To overcome this issue, a small-molecule thrombus-targeting drug delivery system, aspirin-Arg-Gly-Asp-Val (A-RGDV), is developed by covalently linking Arg-Gly-Asp-Val tetrapeptide with aspirin. The 2D ROESY NMR and ESI-MS spectra support a molecular model of A-RGDV tetramer. Transmission electron micros¬copy images suggest that the tetramer spontaneously assembles to nanoparticles (ranging from 5 to 50 nm in diameter) in water. Scanning electron microscopy images and atomic force microscopy images indicate that the smaller nanoparticles of A-RGDV further assemble to bigger particles that are stable in rat blood. The delivery investigation implies that in rat blood A-RGDV is able to keep the molecular integrality, while in thrombus it releases aspirin. The in vitro antiplatelet aggregation assay suggests that A-RGDV selectively inhibits arachidonic acid induced platelet aggregation. The mechanisms of action probably include releasing aspirin, modifying cyclic oxidase, and decreasing the expression of GPIIb/IIIa. The in vivo assay demonstrates that the effective anti-thrombotic dose of A-RGDV is 16700 folds lower than the non-responsive dose of aspirin.
    ACS Nano 08/2013; 7(9). DOI:10.1021/nn402171v · 12.03 Impact Factor