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Special Issue "Cyclooxygenase(COX) Inhibitors"

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A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (20 September 2012)

Special Issue Editor

Guest Editor
Dr. Tilo Grosser

Department of Pharmacology, Institute for Translational Medicine and Therapeutics, Translational Research Center, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA
Phone: ++1-215-573-7600
Interests: study on the translational therapeutics of benefit and risk of drugs targeting the cyclooxygenase system using cellular systems; model organisms and mechanistic phenotyping studies in humans

Special Issue Information

Dear Colleagues,

Cyclooxygenase (COX) inhibitors are commonly used to alleviate pain, inflammation and fever. They inhibit the formation of prostanoids, which reduce the threshold to stimulation of peripheral nociceptors, increase the excitability of spinal sensory neurons and stimulate thermo sensitive neurons in the preoptic area of the brain. Low dose aspirin is the preferred antiplatelet regimen for cardiovascular prophylaxis. Perhaps more than 60 million people in the United States consume a COX inhibitor regularly. Over 40 distinct compounds are marketed as almost 1000 brands, formulations, and doses. The major side effects of these drugs are caused by coincident inhibition of cytoprotective and homeostatic prostanoids. Thus, all COX inhibitors may be associated with gastrointestinal complications, including serious bleeds. COX-2 selective compounds have been shown to reduce the incidence of these bleeding events, but are more likely to cause serious cardiovascular events than nonselective drugs. All COX inhibitors have been reported to elevate blood pressure and/or cause salt retention and edema, although they do so to variable degrees amongst individuals, if at all. Evidence from human pharmacology and genetics, genetically manipulated rodents and other animal models and randomized trials indicates that these cardiovascular adverse events are consequent to suppression of COX-2 dependent cardioprotective prostanoids, particularly, prostacyclin.

It has long been appreciated that the response to any COX inhibitor may vary substantially from patient to patient. Can we predict which patients are likely to benefit from treatment with a particular compound and which patients are likely to develop complications, such as heart attack and stroke? Does the cardiovascular risk extend to some or several or all of the older, non-isoform selective COX inhibitors? What are the relative roles of inhibition of COX-1 and COX-2 in therapeutic efficacy and risk? A much more detailed understanding of the biology of the prostanoid biosynthetic-response system, the molecular mechanisms and pharmacoepidemiology of therapeutic benefit and risk of COX inhibitors, their human pharmacology, and genetic and non-genetic factors that cause variability in these drugs is a necessary prerequisite to development of an evidence based paradigm to personalize therapy with COX inhibitors.

This special issue presents an opportunity to create a readily accessible collection of insightful reviews of current knowledge, evolving concepts, provocative ideas and original research articles in these very topics as a resource for students and trainees in our laboratories and for those who are interested in this field.

Sincerely,

Dr. Tilo Grosser
Guest Editor

Keywords

  • cyclooxygenase-1
  • cyclooxygenase-2
  • prostaglandins
  • prostanoids
  • nonsteroidal antiinflammatory drugs

Published Papers (2 papers)

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Review

Open AccessReview Mechanistic and Pharmacological Issues of Aspirin as an Anticancer Agent
Pharmaceuticals 2012, 5(12), 1346-1371; doi:10.3390/ph5121346
Received: 6 November 2012 / Revised: 16 November 2012 / Accepted: 30 November 2012 / Published: 5 December 2012
Cited by 16 | PDF Full-text (446 KB) | HTML Full-text | XML Full-text
Abstract
Recent findings have shown that aspirin, taken for several years, reduces the long-term risk of some cancers, particularly colorectal cancer. The result that aspirin benefit is detectable at daily low-doses (at least 75mg), the same used for the prevention of cardiovascular disease, [...] Read more.
Recent findings have shown that aspirin, taken for several years, reduces the long-term risk of some cancers, particularly colorectal cancer. The result that aspirin benefit is detectable at daily low-doses (at least 75mg), the same used for the prevention of cardiovascular disease, positions the antiplatelet action of aspirin at the center of its antitumor efficacy. At low-doses given every 24 h, aspirin is acting by a complete and persistent inhibition of cyclooxygenase (COX)-1 in platelets (in the pre-systemic circulation) while causing a limited and rapidly reversible inhibitory effect on COX-2 and/or COX-1 expressed in nucleated cells. Aspirin has a short half-life in human circulation (approximately 20 min); nucleated cells have the ability to resynthesize the acetylated COX-isozymes within a few hours, while platelets do not. COX-independent mechanisms of aspirin, such as the inhibition of Wnt/ b-catenin and NF-kB signaling and the acetylation of extra-COX proteins, have been suggested to play a role in its chemo-preventive effects, but their relevance remains to be demonstrated in vivo at clinical doses. In conclusion, the results of clinical pharmacology and the analysis of randomized and epidemiological studies suggest that colorectal cancer and atherothrombosis share a common mechanism of disease, i.e. enhanced platelet activation in response to injury at distinct sites. Full article
(This article belongs to the Special Issue Cyclooxygenase(COX) Inhibitors)
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Open AccessReview Cyclooxygenase (COX) Inhibitors and the Newborn Kidney
Pharmaceuticals 2012, 5(11), 1160-1176; doi:10.3390/ph5111160
Received: 17 August 2012 / Revised: 28 September 2012 / Accepted: 15 October 2012 / Published: 25 October 2012
Cited by 3 | PDF Full-text (488 KB) | HTML Full-text | XML Full-text
Abstract
This review summarizes our current understanding of the role of cyclo-oxygenase inhibitors (COXI) in influencing the structural development as well as the function of the developing kidney. COXI administered either during pregnancy or after birth can influence kidney development including nephronogenesis, and [...] Read more.
This review summarizes our current understanding of the role of cyclo-oxygenase inhibitors (COXI) in influencing the structural development as well as the function of the developing kidney. COXI administered either during pregnancy or after birth can influence kidney development including nephronogenesis, and can decrease renal perfusion and ultrafiltration potentially leading to acute kidney injury in the newborn period. To date, which COX isoform (COX-1 or COX-2) plays a more important role in during fetal development and influences kidney function early in life is not known, though evidence points to a predominant role for COX-2. Clinical implications of the use of COXI in pregnancy and in the newborn infant are also evaluated herein, with specific reference to the potential effects of COXI on nephronogenesis as well as newborn kidney function. Full article
(This article belongs to the Special Issue Cyclooxygenase(COX) Inhibitors)

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