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"Ann Arbor, MI - New laboratory research suggests that the COX-2 inhibitor celecoxib (Celebrex, Pfizer), might impede the action of "baby" aspirin [1]. Dr Gilad Rimon (University of Michigan, Ann Arbor) and colleagues found evidence that this was the case in a dog model and say that "it will be important to determine" whether the same is true in humans. The report was published online December 1, 2009 in the Proceedings of the National Academy of Medicine. Celecoxib is the only COX-2 inhibitor to have remained on the market in the US, and doctors who recommend this painkiller often coprescribe a daily low dose of 81 mg of aspirin (known as a "baby" dose) to counteract any possible prothrombotic effects of the coxib, while minimizing potential gastrointestinal toxicity of the aspirin. Senior author of the new work, Dr William L Smith (University of Michigan, Ann Arbor), explained to heartwire that previous studies in humans have shown that celecoxib does not interfere with the effect of a standard dose of aspirin (325 mg), but any potential interaction of celecoxib with the lower dose has not been examined. Stagger dosing to avoid any potential problems First, Smith explained that he and his colleagues looked in vitro at celecoxib and found that it binds to one of two available sites on the COX-1 enzyme. "This surprised us," he commented. "It appears to interfere with the ability of some other drugs to affect COX-1, most notably aspirin." Second, in beagles, they administered the dog-equivalent of a baby dose of aspirin in humans and then gave some of the animals the equivalent of 100 mg of celecoxib twice daily in addition. "Celecoxib plus aspirin interfered with the normal effect of low-dose aspirin on platelets," he notes. Smith says this observation obviously requires confirmation in humans, but in the meantime he suggests "getting around the problem" by patients taking the low-dose aspirin at least 15 to 30 minutes before the celecoxib is taken, "because

Cyclooxygenase (COX) is an enzyme (EC 1.14.99.1) that is responsible for formation of important biological mediators called prostanoids (including prostaglandins, prostacyclin and thromboxane). Pharmacological inhibition of COX can provide relief from the

"ScienceDaily (Jan. 13, 2010) - For those who do not drink, researchers have found that six essential oils -from thyme, clove, rose, eucalyptus, fennel and bergamot -- can suppress the inflammatory COX-2 enzyme, in a manner similar to resveratrol, the chemical linked with the health benefits of red wine. They also identified that the chemical carvacrol was primarily responsible for this suppressive activity."

Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential Cox-2 inhibition on systemic syndromes in patients with advanced lung cancer. Cerchietti LC, Navigante AH, Castro MA. Nutr Cancer. 2007;59(1):14-20. PMID: 17927497

The present study, thus, raises the possibility that DHA may exert pro-apoptotic and antitumoral effects through proteasomal regulation of beta-catenin levels and alterations in the expression of TCF-beta-catenin target genes. Docosahexaenoic acid induces proteasome-dependent degradation of beta-catenin, down-regulation of survivin and apoptosis in human colorectal cancer cells not expressing COX-2. Calviello G, Resci F, Serini S, Piccioni E, Toesca A, Boninsegna A, Monego G, Ranelletti FO, Palozza P. Carcinogenesis. 2007 Jun;28(6):1202-9. Epub 2006 Dec 20. PMID: 17183061 doi:10.1093/carcin/bgl254

The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential. Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D, Steward W, Dennison A. Eur J Cancer. 2009 Aug;45(12):2077-86. Epub 2009 Jun 1. Review. PMID: 19493674 Omega-3 fatty acid (omega-3 FA) consumption has long been associated with a lower incidence of colon, breast and prostate cancers in many human populations. Human trials have demonstrated omega-3 FA to have profound anti-inflammatory effects in those with cancer. In vitro and small animal studies have yielded a strong body of evidence establishing omega-3 FA as having anti-inflammatory, anti-apoptotic, anti-proliferative and anti-angiogenic effects. This review explores the evidence and the mechanisms by which omega-3 FA may act as angiogenesis inhibitors and identifies opportunities for original research trialling omega-3 FAs as anti-cancer agents in humans. The conclusions drawn from this review suggest that omega-3 FAs in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found principally in oily fish have potent anti-angiogenic effects inhibiting production of many important angiogenic mediators namely; Vascular Endothelial Growth Factor (VEGF), Platelet-Derived Growth Factor (PDGF), Platelet-Derived Endothelial Cell Growth Factor (PDECGF), cyclo-oxygenase 2 (COX-2), prostaglandin-E2 (PGE2), nitric oxide, Nuclear Factor Kappa Beta (NFKB), matrix metalloproteinases and beta-catenin

Effects of dietary flaxseed on intestinal tumorigenesis in Apc(Min) mouse. Bommareddy A, Zhang X, Schrader D, Kaushik RS, Zeman D, Matthees DP, Dwivedi C. Nutr Cancer. 2009;61(2):276-83. PMID: 19235044 DOI: 10.1080/01635580802419764

Egg consumption, serum cholesterol, and cause-specific and all-cause mortality: the National Integrated Project for Prospective Observation of Non-communicable Disease and Its Trends in the Aged, 1980 (NIPPON DATA80). Nakamura Y, Okamura T, Tamaki S, Kadowaki T, Hayakawa T, Kita Y, Okayama A, Ueshima H; NIPPON DATA80 Research Group. Am J Clin Nutr. 2004 Jul;80(1):58-63. PMID: 15213028 Results: The subjects were categorized into 5 egg consumption groups on the basis of their responses to a questionnaire (≥2/d, 1/d, 1/2 d, 1-2/wk, and seldom). There were 69, 1396, 1667, 1742, and 315 women in each of the 5 groups, respectively. Age-adjusted total cholesterol (5.21, 5.04, 4.95, 4.91, and 4.92 mmol/L in the 5 egg consumption categories, respectively) was related to egg consumption (P < 0.0001, analysis of covariance). In women, unadjusted IHD mortality and all-cause mortality differed significantly between the groups [IHD mortality: 1.1, 0.5, 0.4, 0.5, and 2.0 per 1000 person-years, respectively (P = 0.008, chi-square test); all-cause mortality: 14.8, 8.0, 7.5, 7.5, and 14.5 per 1000 person-years, respectively (P < 0.0001, chi-square test)]. In men, egg consumption was not related to age-adjusted total cholesterol. Cox analysis found that, in women, all-cause mortality in the 1-2-eggs/wk group was significantly lower than that in the 1-egg/d group, whereas no such relations were noted in men. Conclusion: Limiting egg consumption may have some health benefits, at least in women in geographic areas where egg consumption makes a relatively large contribution to total dietary cholesterol intake.

Mice fed fish oil and curcumin showed a significantly reduced tumor volume, 25% (P < 0.04) and 43% (P < 0.005), respectively, and importantly, a combination of curcumin and fish oil diet showed > 72% (P < 0.0001) tumor volume reduction. Expression and activity of iNOS, COX-2, and 5-LOX are downregulated, and p21 is upregulated in tumor xenograft fed curcumin combined with fish oil diet when compared to individual diets. The preceding results evidence for the first time that curcumin combined with omega-3 fatty acids provide synergistic pancreatic tumor inhibitory properties. Prevention and treatment of pancreatic cancer by curcumin in combination with omega-3 fatty acids. Swamy MV, Citineni B, Patlolla JM, Mohammed A, Zhang Y, Rao CV. Nutr Cancer. 2008;60 Suppl 1:81-9. PMID: 19003584

Prostacyclin (or PGI2) is a member of the family of lipid molecules known as eicosanoids.\nAs a drug, it is also known as "epoprostenol".[1] The terms are sometimes used interchangeably Prostacyclin (PGI2) chiefly prevents formation of the platelet plug involved in primary hemostasis (a part of blood clot formation). It is also an effective vasodilator. Prostacyclin's interactions in contrast to thromboxane (TXA2), another eicosanoid, strongly suggest a mechanism of cardiovascular homeostasis between the two hormones in relation to vascular damage.

Li N, Sood S, Wang S, Fang M, Wang P, Sun Z, Yang CS, Chen X. Overexpression of 5-lipoxygenase and cyclooxygenase 2 in hamster and human oral cancer and chemopreventive effects of zileuton and celecoxib. Clin Cancer Res. 2005 Mar 1;11(5):2089-96. PMID

Rosmarinic acid antagonizes activator protein-1-dependent activation of cyclooxygenase-2 expression in human cancer and nonmalignant cell lines. Scheckel KA, Degner SC, Romagnolo DF. J Nutr. 2008 Nov;138(11):2098-105. PMID: 18936204

Ursolic acid inhibits cyclooxygenase-2 transcription in human mammary epithelial cells. Subbaramaiah K, Michaluart P, Sporn MB, Dannenberg AJ. Cancer Res. 2000 May 1;60(9):2399-404. PMID: 10811116

Fish oil-derived fatty acids, docosahexaenoic acid and docosapentaenoic acid, and the risk of acute coronary events: the Kuopio ischaemic heart disease risk factor study. Rissanen T, Voutilainen S, Nyyssönen K, Lakka TA, Salonen JT. Circulation. 2000 Nov 28;102(22):2677-9. PMID: 11094031 Methods and Results-We studied this association in the Kuopio Ischaemic Heart Disease Risk Factor Study, a prospective population study in Eastern Finland. Subjects were randomly selected and included 1871 men aged 42 to 60 years who had no clinical coronary heart disease at baseline examination. A total of 194 men had a fatal or nonfatal acute coronary event during follow-up. In a Cox proportional hazards' model adjusting for other risk factors, men in the highest fifth of the proportion of serum DHA+DPA in all fatty acids had a 44% reduced risk (P=0.014) of acute coronary events compared with men in the lowest fifth. Men in the highest fifth of DHA+DPA who had a low hair content of mercury (2.0 µg/g). There was no association between proportion of eicosapentaenoic acid and the risk of acute coronary events. Conclusions-Our data provide further confirmation for the concept that fish oil-derived fatty acids reduce the risk of acute coronary events. However, a high mercury content in fish could attenuate this protective effect.

Egg consumption in relation to cardiovascular disease and mortality: the Physicians' Health Study. Djoussé L, Gaziano JM. Am J Clin Nutr. 2008 Apr;87(4):964-9. PMID: 18400720 Results: In an average follow-up of 20 y, 1550 new myocardial infarctions (MIs), 1342 incident strokes, and 5169 deaths occurred. Egg consumption was not associated with incident MI or stroke in a multivariate Cox regression. In contrast, adjusted hazard ratios (95% CI) for mortality were 1.0 (reference), 0.94 (0.87, 1.02), 1.03 (0.95, 1.11), 1.05 (0.93, 1.19), and 1.23 (1.11, 1.36) for the consumption of < 0.0001). This association was stronger among diabetic subjects, in whom the risk of death in a comparison of the highest with the lowest category of egg consumption was twofold (hazard ratio: 2.01; 95% CI: 1.26, 3.20; P for interaction = 0.09). Conclusions: Infrequent egg consumption does not seem to influence the risk of CVD in male physicians. In addition, egg consumption was positively related to mortality, more strongly so in diabetic subjects, in the study population.

Targeting lipoxygenases with care. de Souza PM, Newson J, Gilroy DW. Chem Biol. 2006 Nov;13(11):1121-2. PMID: 17113992 doi:10.1016/j.chembiol.2006.11.002  

Prostate tumor growth and recurrence can be modulated by the omega-6:omega-3 ratio in diet: athymic mouse xenograft model simulating radical prostatectomy. Kelavkar UP, Hutzley J, Dhir R, Kim P, Allen KG, McHugh K. Neoplasia. 2006 Feb;8(2):112-24. PMID: 16611404

Sun Z, Sood S, Li N, Ramji D, Yang P, Newman RA, Yang CS, Chen X. Involvement of the 5-lipoxygenase/leukotriene A4 hydrolase pathway in 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch, and inhibition of carcinoge

Bushinsky DA, Parker WR, Alexander KM, Krieger NS. Metabolic, but not respiratory, acidosis increases bone PGE(2) levels and calcium release. Am J Physiol Renal Physiol. 2001 Dec;281(6):F1058-66. PMID: 11704556 [PubMed - indexed for MEDLINE]