Supplemental Figure 1 and 2 from Cytoplasmic Cyclin E Mediates Resistance to Aromatase Inhibitors in Breast Cancer
Iman DoostanCansu KarakaşMehrnoosh KohansalKwang-Hui LowMatthew J. EllisJohn A. OlsonVera J. SumanKelly K. HuntStacy L. MoulderKhandan Keyomarsi
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<p>Supplemental Figure 1: Nuclear and cytoplasmic scoring system for cyclin E. Supplemental Figure 2: Breast cancer recurrence-free interval in patients with estrogen receptor-positive comparing positive and negative staining for Ki67</p>Keywords:
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In about one-third of advanced breast cancers, estrogen deprivation causes tumor regression. Estrogen concentrations in tumor tissue seem to depend largely on local production. The aromatase enzyme complex is thought to be the key enzyme in this respect. In the present study, the effect of the new third-generation nonsteroidal aromatase inhibitor vorozole (Rivizor) on tumor tissue aromatase activity and estrogen concentrations was evaluated. During 7 days preceding mastectomy, 11 postmenopausal breast cancer patients were treated with 2.5 mg of vorozole once daily. Eight patients could be evaluated. Intratumoral aromatase activity and estrone and estradiol levels were measured and compared to the values of nine untreated postmenopausal breast cancer patients. In treated patients, median tissue aromatase activity was 89% lower than that in controls (P < 0.001). Similarly, median tissue estrone and estradiol concentrations were 64 and 80% lower, respectively, in treated patients (P = 0.001 and P < 0.05, respectively). These results support the hypothesis that depleting the tumor of estrogens, thus impairing estrogenic stimulation, is an important mechanism in the antitumor activity of aromatase inhibitors.
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Histoculture drug response assay (HDRA) systems have been used in evaluating the cytotoxic effects of chemotherapeutic agents for many kinds of advanced cancers. We have adapted the HDRA system to estimate the antitumor effect of aromatase (estrogen synthetase) inhibitors on breast cancer. Small pieces of breast cancer tissue specimens were placed onto a collagen-matrix filled with medium containing testosterone (a substrate for aromatase) or testosterone plus an aromatase inhibitor. At the end of culture, [3H]-thymidine incorporation was measured in aliquots of the histocultured specimens after 10 days culture. The increment of thymidine incorporation in testosterone-treated specimens to that of control provides an index of existence of aromatase and estrogen-dependency, since converted estradiol from added testosterone by aromatase stimulates the incorporation. The decrease in the index of "testosterone + aromatase inhibitor"/"testosterone" indicates the antitumor effect of the aromatase inhibitor on breast cancer. Twenty-one 25 breast cancer surgical specimens were successfully cultured, and 6 showed the increased incorporation of [3H]-thymidine by testosterone. Aromatase inhibitor blocked this stimulation in these 6 specimens. These results suggested that this antitumor effect is related to the inhibition of aromatase and the aromatase inhibitor would be effective for individual patients with breast cancer which responds to testosterone in this histoculture assay system. The histoculture technique we used here is therefore expected to be useful in predicting the efficacy of aromatase inhibitors for individual patients with breast cancer.
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OBJECTIVE: To summarize the aspect of clinical application and progress on aromatase inhibitor.METHODS:To collecte medical literatures in recent years at home and abroad.RESULTS CONCLUSION:Advance in synthetise of the aromatase inhibitor(AI)has been swiftly in rencent years, with higher selectivity to aromatase.Position for the treatment of late breast cancer and postoperative adjuvant treatment of early breast cancer is made certain.The new aromatase inhibitor have more advantages compared with early ones,the founding of aromatase inhibitor makes treatment of breast cancer easier. It plays an important roles in palliative treatment patients with breast cancer.
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