Until recently, tamoxifen, a nonsteroidal antiestrogen, was the mainstay of endocrine treatment of breast cancer. However, new aromatase inhibitors that are many times more potent and specific than the first such agent, aminoglutethimide, are changing the management of breast cancer in postmenopausal women. This review discusses the role of aromatase inhibitors such as letrozole, anastrozole, and exemestane in the treatment of breast cancer.

Aromatase Inhibitors in Breast Cancer

The Methylation Effect in Medicinal Chemistry Eliezer J. Barreiro,* Arthur E. K€ummerle, and Carlos A. M. Fraga Laborat orio de Avaliac-~ao e Síntese de Subst̂ancias Bioativas (LASSBio), Faculdade de Farm acia, Universidade Federal do Rio de Janeiro, CCS, Cidade Universit aria, CP 68.006, 21941-902 Rio de Janeiro, RJ, Brazil Programa de P os-Graduac-~ao em Farmacologia e Química Medicinal, Instituto de Cîencias Biom edicas, Universidade Federal do Rio de Janeiro, Cidade Universit aria, Ilha do Fund~ao, Rio de Janeiro, RJ, Brazil Programa de P os-Graduac-~ao em Química, Instituto de Química, Universidade Federal do Rio de Janeiro, Cidade Universit aria, Ilha do Fund~ao, Rio de Janeiro, RJ, Brazil

The methylation effect in medicinal chemistry.

During development, the genotype of the zygote determines the nature of the gonad, which then determines the male or female phenotype. The molecular events underlying this process are just beginning to be defined. A single treatment of chicken embryos with an aromatase inhibitor (which blocks the synthesis of estrogen from testosterone) at a stage when their gonads were bipotential caused genetic females to develop a permanent male phenotype. These sex-reversed females developed bilateral testes that were capable of complete spermatogenesis and had the physical appearance and behavior of normal males. This result identifies aromatase as a key developmental switch in the sex determination of chickens.

http://science.sciencemag.org/content/sci/255/5043/467.full.pdf

Aromatase enzyme activity and sex determination in chickens

Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) advocated for use in painful and inflammatory rheumatic and certain non-rheumatic conditions. It is available in a number of administration forms which can be given orally, rectally or intramuscularly. Conveniently, dosage adjustments are not required in the elderly or in those patients with renal or hepatic impairment. The drug has a relatively short elimination half-life, which limits the potential for drug accumulation. In numerous clinical trials the efficacy of diclofenac is equivalent to that of the many newer and established NSAIDs with which it has been compared. As an analgesic it has a fast onset and long duration of action. When administered intramuscularly it is at least comparable to, and frequently superior to, many narcotic and spasmolytic combinations in renal and biliary colic. Extensive clinical experience has been gained with diclofenac, clearly establishing its safety profile. It is well tolerated compared with other NSAIDs and rarely produces gastrointestinal ulceration or other serious side effects. Thus, diclofenac can be considered as one of the few NSAIDs of 'first choice' in the treatment of acute and chronic painful and inflammatory conditions.

Jong M. Wasvary

Papers

In vitro and in vivo studies demonstrating potent and selective estrogen inhibition with the nonsteroidal aromatase inhibitor CGS 16949A.

Diclofenac sodium (GP 45840, voltaren), a potent inhibitor of prostaglandin synthetase

Reduction of cardiovascular and thyroxine-suppressing activities of L-T3 by liver targeting with cholic acid.

Inhibition of prostaglandin synthase by pirprofen: Studies with sheep seminal vesicle enzyme

Demonstration of potent lipid-lowering activity by a thyromimetic agent devoid of cardiovascular and thermogenic effects