Reference

Letrozole: an updated review of its use in postmenopausal women with advanced breast cancer

Some chemicals with cas registry numbers like 112809-51-5 and 9039-48-9 are also used. Letrozole: an updated review of its use in postmenopausal women with advanced breast cancer. Keating, Gillian M.; Jarvis, Blair (Adis International Inc., Langhorne, PA, USA). American Journal of Cancer (Auckland, New Zealand), 1(5), 351-371 (English) 2002 Adis International Ltd. CODEN: AJCMCB. ISSN: 1175-6357. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review. Letrozole is a highly selective nonsteroidal aromatase inhibitor. In postmenopausal women with advanced breast cancer, letrozole inhibits whole body aromatization by >98% and reduces plasma levels of estrone, estradiol and estrone sulfate by 74 to >95%. It also significantly inhibits aromatase activity and significantly reduces endogenous estrogen levels within breast tumors. Letrozole is superior to tamoxifen in the first-line treatment of postmenopausal women with advanced breast cancer. In a large, well designed trial, letrozole recipients were significantly less likely than tamoxifen recipients to experience disease progression or treatment failure and significantly more likely to experience an objective response or clin. benefit. The survival rate was significantly higher in letrozole than in tamoxifen recipients at 1 and 2 yr. In the second-line treatment of postmenopausal women with advanced breast cancer, letrozole was at least as effective as megestrol and was superior to aminoglutethimide, according to the results of three large, well designed trials. Letrozole 2.5 mg/day recipients were significantly more likely than letrozole 0.5 mg/day recipients or megestrol recipients to achieve an objective response in one trial, while no difference between the three treatment groups was seen in a second study. However, in this study, a significantly lower risk of disease progression and treatment failure was seen in letrozole 0.5 mg/day than in megestrol recipients. In the other trial, letrozole 2.5 mg/day, compared with megestrol, recipients were significantly less likely to experience treatment failure and had significantly longer durations of objective response and clin. benefit. Compared with aminoglutethimide recipients, letrozole recipients were significantly less likely to experience disease progression or treatment failure, and had significantly prolonged survival. Second-line therapy with letrozole was assocd. with a significantly higher overall response rate than anastrozole in postmenopausal women with advanced breast cancer. Letrozole was generally well tolerated in postmenopausal women with advanced breast cancer with adverse events tending to be of mild-to-moderate severity. Letrozole had similar tolerability to tamoxifen in the first-line treatment of advanced breast cancer. In terms of second-line treatment, letrozole appeared to be better tolerated than megestrol, aminoglutethimide or anastrozole. Conclusion: Letrozole is an effective option in the first- and second-line treatment of postmenopausal women with advanced breast cancer who have hormone receptor-pos. disease or disease of unknown receptor status. Letrozole is superior to tamoxifen in the first-line treatment of advanced breast cancer and at least as effective as megestrol, with better tolerability, in the second-line treatment of advanced breast cancer. .

Expression and purification of a recombinant form of human aromatase from Escherichia coli

Expression and purification of a recombinant form of human aromatase from Escherichia coli. Zhang, Fangming; Zhou, Dujin; Kao, Yeh-Chih; Ye, Jingjing; Chen, Shiuan (Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA). Biochemical Pharmacology, 64(9), 1317-1324 (English) 2002 Elsevier Science Inc. CODEN: BCPCA6. ISSN: 0006-2952. DOCUMENT TYPE: Journal CA Section: 7 (Enzymes) Aromatase converts androgen to estrogen, a hormone that plays an important role in the development of breast cancer. Aromatase inhibitors have been shown to be a useful endocrine regimen for estrogen-dependent breast cancer.Chemicals with cas numbers 112809-51-5 and 120511-73-1 also play role. Structure-function studies of aromatase can generate crit. structural information for designing highly potent and specific inhibitors. However, aromatase structure-function studies have been hampered by a lack of purified protein. In this report, we describe the construction and expression of a recombinant deriv. of human aromatase in Escherichia coli using the pET vector system, and the purifn. of the enzyme by means of nickel-agarose affinity chromatog. We examd. the expression of the full-length, Del-38, C-6xHis-tagged Del-38, and NC-6xHis-tagged Del-38 forms of aromatase. The recombinant aromatase without the first 38 amino acids from the amino-terminus (i.e. Del-38) was found to have a higher activity than the full-length enzyme. Moreover, the addn. of two sep. hexameric histidine tags at both the amino and the carboxyl-termini (i.e. NC-6xHis-tagged Del-38) increased the binding affinity of the recombinant enzyme to the nickel-agarose. The expressed aromatase (i.e. NC-6xHis-tagged Del-38 aromatase) was eluted from the nickel-agarose with 80 mM EDTA. The total aromatase activity of the 80 mM EDTA-eluted fractions was significantly higher than the detergent-solubilized protein ext., indicating a renaturation process during the nickel-agarose affinity chromatog. Purified aromatase exhibited a single band when analyzed by SDS-PAGE, and activity up to 5.8 nmol/mg/min was obtained using the tritiated water release assay. The Km value for androstenedione was detd. to be 62±24 nM by enzyme kinetic anal. The recombinant aromatase prepn. was also characterized by reduced CO-difference spectral anal., reaction product extn. assay, and inhibition studies using two aromatase inhibitors (letrozole and anastrozole). The results indicate that the recombinant aromatase from E. coli has catalytic properties identical to those of the enzyme expressed in human tissue and will be very useful for further structure-function studies of aromatase. .