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Anastrozole

Manufactured by AstraZeneca
Sourced in United Kingdom

Anastrozole is a laboratory product manufactured by AstraZeneca. It is an aromatase inhibitor, a class of compounds that block the activity of the aromatase enzyme, which is responsible for the production of estrogen. The core function of Anastrozole is to inhibit the aromatase enzyme.

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7 protocols using anastrozole

1

Crossover Study of Anastrozole Effects

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This was a double-blind, randomized, placebo-controlled, balanced crossover study in healthy male volunteers. Ethical approval was obtained from the Lothian Research Ethics Committee and informed written consent was obtained from participants.
After a screening visit, participants received 6 weeks of anastrozole (1 mg daily; Astra Zeneca) and 6 weeks of placebo, administered in identical capsules (Tayside Pharmaceuticals), in random order with a 2-week washout period.
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2

Testosterone Metabolism Modulation in Mice

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To block the conversion of testosterone to estradiol (aromatization), the aromatase inhibitor, anastrozole (AstraZeneca, London, UK), was dissolved in 0.3% hydroxypropylcellulose and 0.9% NaCl, added to an osmotic mini-pump (Alzet, Cupertino, CA), and delivered under the skin via an indwelling catheter in the back of 4-week-old castrated mice (the continuous infusion rate of anastrozole was adjusted to 200 μg/day). To adjust the blood testosterone levels to a steady state, a testosterone pellet (15 mg/tablet) (Nacalai Tesque, Kyoto, Japan) was simultaneously implanted under the neck skin of 4-week-old castrated mice using a precision trochar (a placebo pellet was implanted in control mice). This testosterone treatment produces maximal stimulation of spermatogenesis [38 (link)]. Glucose and lipid metabolism were similarly evaluated in 7-week-old mice, at which time the blood estradiol levels were also measured to confirm that they were below the level of sensitivity.
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3

Testosterone, Aromatase Inhibitor, and Bone Density

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This was a double-blind, randomized, placebo-controlled trial of 12 months duration conducted at the National Institute on Aging (NIA) Intramural Research Unit (MedStar Harbor Hospital, Baltimore) (NCT00104572). Men aged ≥65 years with fasting morning (7–10 am) total T levels <350 ng/dl were enrolled. Subjects were randomized to 3 groups: transdermal testosterone (TT) gel 5 g/day and placebo tablet (TT-group, N = 13); oral aromatase inhibitor (Anastrozole, AstraZeneca) 1 mg/day and placebo gel (AI-group, N = 13); placebo tablet and placebo gel daily (Placebo, N = 9). The primary outcome of the trial was change in bone density over the course of 1-year intervention [11 (link)]. Evaluation of GH axis was one of the secondary outcomes (determined a priori); GH secretion and pulsatility were measured at baseline and 3 months; IGF-1 was measured at baseline, 3 and 6 months. The eligibility criteria of the trial have been published previously [11 (link)].
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4

PARAGON: Anastrozole for Gynecological Oncology

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The PARAGON study was coordinated by the National Health and Medical Research Council (NHMRC) Clinical Trials Centre, University of Sydney, in collaboration with Australian New Zealand Gynaecological Oncology Group (ANZGOG). Anastrozole was supplied by Astra Zeneca. This study was conducted according to the principles of the Declaration of Helsinki and was prospectively registered (ACTRN12610000796088).
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5

Radiolabeled Steroid Quantification

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Radiolabeled [3H]-pregnenolone, [7(N)-3H]-pregnenolone (12.6 Ci/mmol), and [3H]-androstenedione: Andros-4-ene-3, 17-dione, [1β-3H(N)]-, 250 µCi (9.25 MBq) were purchased from PerkinElmer (Waltham, MA, USA). [3H]-17α-OH progesterone [1, 2, 6, 7-3H] (60-120 Ci/mmol 2.22-4.44 TBq/mmol) was obtained from American Radiolabeled Chemicals Inc. (St. Louis, MO, USA). Silica gel-coated aluminum backed TLC plates were purchased from Macherey-Nagel (Oensingen, Switzerland). The tritium-screens used for the autoradiography were purchased from Fujifilm (Dielsdorf, Switzerland). Turmeric extract capsules (from Curcuma longa) were obtained from the Finest Natural (Item: 943.17, Deerfield, IL, USA). Trilostane was extracted in absolute ethanol (EtOH) from tablets commercially available as Modrenal® (Bioenvision, NY, USA). Abiraterone was purchased from Selleckchem (Houston, TX, USA). Anastrozole was obtained from AstraZeneca (Cambridge, UK).
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6

Endocrine-Resistant Breast Cancer Cell Lines

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Endocrine-sensitive MCF-7 (American Type Culture Collection (ATCC) Virginia, USA ) and tamoxifen-resistant LY2 cells (kind gift from R. Clarke, Georgetown, DC, USA) were grown as previously described [21 (link)]. MCF7-derived AI-sensitive cells (Aro) were developed in house. MCF7 Aro-derived letrozole-resistant cells (LetR) and anastrozole-resistant cells (AnaR) were created by long-term treatment of Aro with letrozole (Novartis, Basel, Switzerland) or anastrozole (AstraZeneca, Macclesfield, UK) [21 (link)]. LY2, LetR and AnaR cells were utilised to model endocrine resistance developed through long-term adaptation to hormonal therapy. MDA-MB-453, SKBR3 and LNCaP cells were acquired from ATCC and maintained as recommended. Cells were maintained in steroid-depleted medium for 72 hours before treatment with hormones. All cells were incubated at 37 °C under 5 % CO2 in a humidified incubator. All in-house cells were authenticated and are routinely verified as endocrine resistant.
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7

Combination Therapy Cytotoxicity Assay

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A total of 104 cells/well were plated in a 96-well plate and treated for 4 days with 25 nM of AD combined with letrozole, anastrozole (AstraZeneca, London, UK) or MK-2206 (Merck Sharp & Dohme, Whitehouse Station, NJ, USA). Cell viability was assessed as previously described [29 (link)].
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