Journal ArticleDOI
Anti-inflammatory drugs and their mechanism of action
John R. Vane,Regina M. Botting +1 more
TLDR
Selective COX-2 inhibitors may demonstrate new important therapeutic benefits as anticancer agents, as well as in preventing premature labor and perhaps even retarding the progression of Alzheimer's disease.Abstract:
Nonsteroidal anti-inflammatory drugs (NSAIDs) produce their therapeutic activities through inhibition of cyclooxygenase (COX), the enzyme that makes prostaglandins (PGs). They share, to a greater or lesser degree, the same side effects, including gastric and renal toxicity. Recent research has shown that there are at least two COX isoenzymes. COX-1 is constitutive and makes PGs that protect the stomach and kidney from damage. COX-2 is induced by inflammatory stimuli, such as cytokines, and produces PGs that contribute to the pain and swelling of inflammation. Thus, selective COX-2 inhibitors should be anti-inflammatory without side effects on the kidney and stomach. Of course, selective COX-2 inhibitors may have other side effects and perhaps other therapeutic potential. For instance, COX-2 (and not COX-1) is thought to be involved in ovulation and in labor. In addition, the well-known protective action of aspirin on colon cancer may be through an action on COX-2, which is expressed in this disease. Moreover, NSAIDs delay the progress of Alzheimer's disease. Thus, selective COX-2 inhibitors may demonstrate new important therapeutic benefits as anticancer agents, as well as in preventing premature labor and perhaps even retarding the progression of Alzheimer's disease.read more
Citations
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Journal ArticleDOI
Risk of cardiovascular events associated with selective COX-2 inhibitors.
TL;DR: The results from VIGOR showed that the relative risk of developing a confirmed adjudicated thrombotic cardiovascular event with rofecoxib treatment compared with naproxen was higher than that in the placebo group of a recent meta-analysis of 23 407 patients in primary prevention trials.
Journal ArticleDOI
Human pharmaceuticals in the aquatic environment: a challenge to Green Chemistry.
Journal Article
Chronic inflammation and cancer.
TL;DR: The contribution of reactive oxygen and nitrogen intermediates, prostaglandins, and inflammatory cytokines to carcinogenesis is discussed, which can lead to novel approaches to the prevention and treatment of cancer.
Journal ArticleDOI
Nonsteroidal Anti-inflammatory Drugs and the Risk of Parkinson Disease
Honglei Chen,Shumin M. Zhang,Miguel A. Hernán,Michael A. Schwarzschild,Walter C. Willett,Graham A. Colditz,Frank E. Speizer,Alberto Ascherio +7 more
TL;DR: Findings are consistent with the hypothesis that use of NSAIDs may delay or prevent the onset of PD.
Journal ArticleDOI
Inflammatory Mechanisms in Alzheimer's Disease: Inhibition of β-Amyloid-Stimulated Proinflammatory Responses and Neurotoxicity by PPARγ Agonists
TL;DR: The efficacy of NSAIDs in the treatment of AD may be a consequence of their actions on PPARγ rather than on their canonical targets the cyclooxygenases, and the efficacy of these agents in inhibiting a broad range of inflammatory responses suggestsPPARγ agonists may provide a novel therapeutic approach to AD.
References
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Journal ArticleDOI
Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs
TL;DR: Experiments with guinea-pig lung suggest that some of the therapeutic effects of sodium salicylate and aspirin-like drugs are due to inhibition of the synthesis of prostaglandins.
Journal ArticleDOI
An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation.
TL;DR: A balance between formation of anti- and pro-aggregatory substances by enzymes could also contribute to the maintenance of the integrity of vascular endothelium and explain the mechanism of formation of intra-arterial thrombi in certain physiopathological conditions.
Journal ArticleDOI
Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides.
TL;DR: Evidence is presented that the more unstable and major component of rabbit aorta contracting substance (RCS) formed in platelets and guinea pig lung is also thromboxane A2.
Journal ArticleDOI
Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas
Charles E. Eberhart,Robert J. Coffey,Aramandla Radhika,Francis M. Giardiello,Suzanne Ferrenbach,Raymond N. DuBois +5 more
TL;DR: COX-2, but not COX-1, gene expression is markedly elevated in most human colorectal cancers compared with accompanying normal mucosa, and COx-2 expression seems to be increased in a subset of adenomas.
Journal ArticleDOI
Suppression of Intestinal Polyposis in ApcΔ716 Knockout Mice by Inhibition of Cyclooxygenase 2 (COX-2)
Masanobu Oshima,Joseph E. Dinchuk,Stacia Kargman,Hiroko Oshima,Bruno C. Hancock,Elizabeth Kwong,James M. Trzaskos,Jilly F. Evans,Makoto Mark Taketo,Makoto Mark Taketo +9 more
TL;DR: Results provide direct genetic evidence that COX-2 plays a key role in tumorigenesis and indicate that COx-2-selective inhibitors can be a novel class of therapeutic agents for colorectal polyposis and cancer.
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