ARIMIDEX: A new oral, once-a-day aromatase inhibitor

ARIMIDEX® is a potent and selective aromatase inhibitor undergoing evaluation as a treatment for postmenopausal women with advanced breast cancer. Studies examining the pharmacology of ARIMIDEX were conducted in both animals and humans. In animals, ARIMIDEX elicits maximal aromatase suppressive activity at a dose of approx. 0.1 mg/kg, does not alter adrenal steroid hormone biosynthesis, and at a dose of 1 mg/kg, has no other pharmacologic effects other than aromatase inhibition. In this overview, the pharmacodynamic, pharmacokinetic, and safety profiles of single and multiple daily doses of ARIMIDEX are reported in humans. Daily doses of 1–10 mg of ARIMIDEX suppressed estradiol levels to the maximum degree measurable using sensitive estrogen assays. ARIMIDEX had no clinically significant effects on the response of cortisol and aldosterone to ACTH stimulation. Absorption of ARIMIDEX was rapid, with maximum plasma concentrations occurring within 2 h after oral administration. Plasma concentrations of ARIMIDEX rose with increasing doses of the drug. The elimination half-life of ARIMIDEX in humans ranged from 30 to 60 h. Consistent with the long plasma half-life, steady state plasma concentrations were 3–4-fold higher than plasma concentrations observed after single administration of 1, 3, 5, or 10 mg doses. Long term treatment of breast cancer patients with 10 mg/day has continued in 17 patients without an escape of estradiol suppression. Previously, these patients had received on average 2.6 systemic treatments for breast cancer and had significant metastatic disease. Three of the 17 patients continued ARIMIDEX treatment for 20 months and beyond. Given the number of previous treatments and tumor burden at the start of treatment, the response to ARIMIDEX treatment is encouraging. Phase III studies are now underway to assess the efficacy and safety of ARIMIDEX in the treatment of advanced breast cancer.     

Effects of aromatase inhibition with aminoglutethimide in men with benign prostatic hypertrophy [Poster 28]

Fourteen men with benign prostatic hypertrophy were treated with the aromatase inhibitor aminoglutethimide for periods of up to 3 months. LH, FSH and testosterone levels rose within one week and remained elevated, while estradiol levels decreased. Despite significant changes in these hormones there was no change in urine flow rates or prostatic size over the study period.     

Closely related species of Drosophila can contain different libraries of middle repetitive DNA sequences

Very few of the middle repetitive DNA sequences found in Drosophila melanogaster are present in all of the species of the D. melanogaster subgroup. One member of the subgroup, D. erecta, lacks most of the families of repetitive elements from D. melanogaster (including copia and 412) but possesses many other families not present in the D. melanogaster genome. Other species in the subgroup possess some families in these two species and lack others. From this we conclude that most individual middle repetitive families are highly unstable components of the Drosophila genome over short periods of evolutionary time.     

Human breast tumour-induced osteolysis and prostaglandins

Osteolysis effected in vitro by breast carcinomas can be inhibited by aspirin. Some prostaglandins stimulate bone resorption. Our results indicate that whilst osteolytically active PGE and PGF are released by the carcinomas in most cases, some other osteolytic principle is released as well.     

Exchange of ribosomal proteins among the ribosomes of Escherichia coli.

Summary The exchange of ribosomal proteins among ribosomes of E. coli has been measured, using a density label technique. As expected most of the proteins do not exhange appreciably. However a substantial fraction of each of proteins S1, S2, S21, L7/L12, L9, L10, L11, L26 and L33 is found to exchange, but exchange of S1, S2, L7/L12, L10, L11 and L26 is found to occur in vitro after lysis of the cells, and therefore it is not possible to say whether or not these proteins also exchange in vivo. In contrast S21, L9 and L33 do not exchange after lysis of the cells and we therefore conclude that these proteins exchange in vivo. The maximum level of exchange of S21, L9 and L33 is attained so rapidly that we were unable to show whether or not it was dependent on protein synthesis.