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Download Cox-2: a new target for cancer prevention and treatment by Joseph R. Bertino, Andrew J. Dannenberg, Raymond N. DuBois PDF

By Joseph R. Bertino, Andrew J. Dannenberg, Raymond N. DuBois

Quite a few investigators have discovered elevated degrees of cyclooxygenase-2 (COX-2) in either pre-malignant and malignant tissues. additionally, animals engineered to be COX-2 poor or taken care of with a selective COX-2 inhibitor confirmed diminished tumor formation and development. the current booklet experiences those findings suggesting that COX-2 is a legitimate molecular aim for the prevention and remedy of melanoma. the 1st chapters are dedicated to the epidemiology of nonsteroidal anti inflammatory medicinal drugs (NSAIDs) and melanoma, the pharmacology of COX-2 inhibitors and the legislation of COX-2 expression in human cancers. in addition to, the ebook encompasses a sequence of chapters reading the hyperlink among COX-2 and melanoma in particular organs (e.g. pores and skin, breast, cervix, digestive tract, lung, etc.). in addition, a number of scientific trials assessing the potential for COX-2 inhibitors for fighting and treating melanoma are defined.

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1%) [38]. , history of MI, angina, cerebrovascular accident, transient ischemic attack, angioplasty or coronary artery disease) but were not taking low-dose aspirin. This high-risk population accounted for 38% of the patients who suffered from MI during the study [38]. It is possible that the higher incidence of MI observed in the VIGOR trial was a consequence of a possible cardioprotective effect of naproxen, and the lack of aspirin prophylaxis in a high-risk subset of the study population taking rofecoxib.

Edu Baron 24 Dannenberg AJ, DuBois RN (eds): COX-2. Prog Exp Tum Res. Basel, Karger, 2003, vol 37, pp 25–51 Pharmacology of COX-2 Inhibitors Peter C. , USA Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used as analgesics in one form or another for centuries. Extracts and preparations from plants such as the willow tree Salix alba have been used for hundreds of years for relief from pain and fever. Derivatives of salicylic acid were characterized as the active components of these plants in the 18th century and were chemically synthesized for the first time in 1860.

The incorporation of a hydrophilic side chain on COX-2-specific inhibitors encourages binding in the hydrophilic side pocket of the COX-2 isoform. Isakson 28 Tyr 385 Val 434 Phe 518 Val 523 Ser 530 Arg 513 Arg 120 Arg 516 His 90 SIDE POCKET Fig. 3. Binding of COX-selective inhibitors to the COX-2 isoform. A COX-2-specific inhibitor (a prototype of celecoxib), depicted in yellow, is shown inside the hydrophobic channel of the catalytic domain of the COX-2 enzyme. The smaller valine residue at position 523 makes the hydrophilic side pocket accessible to the bulky side chain of COX-2-specific inhibitors.

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