Cuzick, J. et al. Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. Lancet Oncol. 10, 501-507

Cancer Research UK Centre for Epidemiology, Mathematics, and Statistics, Queen Mary University of London, London UK.
The Lancet Oncology (Impact Factor: 24.69). 06/2009; 10(5):501-7. DOI: 10.1016/S1470-2045(09)70035-X
Source: PubMed


Evidence clearly shows a chemopreventive effect for aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) on colorectal cancer and probably other cancer types; however, data on the risk-benefit profile for cancer prevention are insufficient and no definitive recommendations can be made. Aspirin has emerged as the most likely NSAID for use in chemoprevention because of its known cardiovascular benefit and available safety and efficacy data. Other traditional NSAIDs, particularly sulindac, and selective COX-2 inhibitors are now given to patients at high risk of colorectal cancer, although these drugs do not provide cardioprotection. More studies of aspirin and cancer prevention are needed to define the lowest effective dose, the age at which to initiate therapy, the optimum treatment duration, and the subpopulations for which the benefits of chemoprevention outweigh the risks of adverse side-effects. Although it might be possible to answer some of these questions with longer follow-up of existing clinical trials, randomised controlled trials with new study designs will be needed. Future projects should investigate the effects of aspirin treatment on multiple organ systems. Cancers of interest are colorectal, breast, prostate, lung, stomach, and oesophageal. The main side-effect of aspirin is peptic ulcers; therefore coadministration of aspirin with a proton-pump inhibitor is an attractive option and is under investigation in the AspECT trial.

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Available from: Florian Otto, May 11, 2014
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    • "Our results showed that there were significant correlations between COX2 protein expression and the recurrence-free or OS rate of oral cancer, suggesting that COX2 protein expression may have a prognostic significance in oral cancer. It is widely recognized that the use of nonsteroid anti-inflammatory drugs (NSAIDs) is closely correlated with a reduced risk of cancer [32]. Exactly, COX2 is the best known target of NSAIDs, which is considered as a critical rate-limiting enzyme in the arachidonic acid metabolism that is implicated in the biosynthesis of prostaglandins [33]. "
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    ABSTRACT: The prognostic significance of COX2 for survival of patients with oral cancer remains controversial. Thus, the meta-analysis was performed in order to identify COX2 expression impact on prognosis of oral cancer. Method. Relevant literatures were searched using the following electronic databases without any language restrictions: Web of Science, the Cochrane Library Database, PubMed, EMBASE, CINAHL, and CBM. Version 12.0 STATA software (Stata Corporation, College Station, Texas, USA) was used for the current meta-analysis. Odds ratios (ORs) and hazard ratios (HRs) with their corresponding 95% confidence interval (95% CI) were also calculated to clarify the correlation between COX2 expression and prognosis of oral cancer. Results. Final analysis of 979 oral cancer patients from 12 clinical cohort studies was performed. The meta-analysis results show that COX2 expression in cancer tissues was significantly higher than those in normal and benign tissues (all P < 0.05). Combined HR of COX2 suggests that positive COX2 expression has a shorter overall survival (OS) than those of negative COX2 expression ( P < 0.05). Conclusion. The meta-analysis study shows that elevated COX2 expression may be associated with the pathogenesis of oral cancer and with a worse prognosis in oral cancer patients.
    Full-text · Article · Jun 2014 · BioMed Research International
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    • "As we mentioned existing epidemiological data suggest that NSAIDs, the most common of which are aspirin or ibuprofen, naproxen, and indomethacin, vastly lower the incidence and motility of breast, colorectal, and lung cancer [44]. NSAIDs are known as potent anti-inflammatory agents that act through the inhibition of the COX enzyme and the subsequent inhibition of prostaglandins which are catalysed by COX enzymes at the site of inflammation [45]. This type of drug is usually accompanied by side effects; however, some studies have suggested that selective COX-2 inhibitors such as celecoxib may produce superior anti-inflammatory drugs with substantial safety advantages over existing NSAIDs [46]. "
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    ABSTRACT: Toad glandular secretions and skin extractions contain many natural agents which may provide a unique resource for novel drug development. The dried secretion from the auricular and skin glands of Chinese toad (Bufo bufo gargarizans) is named Chansu, which has been used in Traditional Chinese Medicine (TCM) for treating infection and inflammation for hundreds of years. The sterilized hot water extraction of dried toad skin is named Huachansu (Cinobufacini) which was developed for treating hepatitis B virus (HBV) and several types of cancers. However, the mechanisms of action of Chansu, Huachansu, and their constituents within are not well reported. Existing studies have suggested that their anti-inflammation and anticancer potential were via targeting Nuclear Factor (NF)- κ B and its signalling pathways which are crucial hallmarks of inflammation and cancer in various experimental models. Here, we review some current studies of Chansu, Huachansu, and their compounds in terms of their use as both anti-inflammatory and anticancer agents. We also explored the potential use of toad glandular secretions and skin extractions as alternate resources for treating human cancers in combinational therapies.
    Full-text · Article · Mar 2014 · Evidence-based Complementary and Alternative Medicine
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    • "Efficacy and safety are the prime considerations in the evaluation of anticancer agents [34], and the latter is especially paramount in chemoprevention. Extensive epidemiological and clinical evidence supports a beneficial role of aspirin in the prevention of breast, colon, and lung cancers [35]; however, its gastrointestinal toxicity is limiting. Our results demonstrated that PA-2, with the novel phospho-modification, is superior to aspirin both in terms of efficacy in TNBC, as well as safety [9]. "
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    ABSTRACT: The anticancer properties of aspirin are restricted by its gastrointestinal toxicity and its limited efficacy. Therefore, we synthesized phospho-aspirin (PA-2; MDC-22), a novel derivative of aspirin, and evaluated its chemotherapeutic and chemopreventive efficacy in preclinical models of triple negative breast cancer (TNBC). Efficacy of PA-2 was evaluated in human breast cancer cells in vitro, and in orthotopic and subcutaneous TNBC xenografts in nude mice. Mechanistic studies were also carried out to elucidate the mechanism of action of PA-2. PA-2 inhibited the growth of TNBC cells in vitro more potently than aspirin. Treatment of established subcutaneous TNBC xenografts (MDA-MB-231 and BT-20) with PA-2 induced a strong growth inhibitory effect, resulting in tumor stasis (79% and 90% inhibition, respectively). PA-2, but not aspirin, significantly prevented the development of orthotopic MDA-MB-231 xenografts (62% inhibition). Mechanistically, PA-2: 1) inhibited the activation of epidermal growth factor receptor (EGFR) and suppressed its downstream signaling cascades, including PI3K/AKT/mTOR and STAT3; 2) induced acetylation of p53 at multiple lysine residues and enhanced its DNA binding activity, leading to cell cycle arrest; and 3) induced oxidative stress by suppressing the thioredoxin system, consequently inhibiting the activation of the redox sensitive transcription factor NF-kappaB. These molecular alterations were observed in vitro and in vivo, demonstrating their relevance to the anticancer effect of PA-2. Our findings demonstrate that PA-2 possesses potent chemotherapeutic efficacy against TNBC, and is also effective in its chemoprevention, warranting further evaluation as an anticancer agent.
    Full-text · Article · Feb 2014 · BMC Cancer
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