Neoadjuvant treatment of endometrial cancer using anastrozole: A randomised pilot study

Thangavelu, Amudha; Hewitt, Matthew J.; Quinton, Naomi; Duffy, Sean

doi:10.1016/j.ygyno.2013.09.023

Cited by 36 publications

(34 citation statements)

References 36 publications

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“…(Ghosh et al, 2010;Kim et al, 2012;Yoshimoto et al, 2014). When it comes to the expression of aromatase in normal endometrium and whether it has activity, it is commonly considered that endometrial cancer is an estrogen-dependent disease and aromatase is widely expressed in endometrial cancer tissues (Hosono et al, 2011;Liu et al, 2013;Thangavelu et al, 2013). This research confirms that aromatase is expressed in both endometrial epithelial cells and endometrial stromal cells.…”

Section: Discussionmentioning

confidence: 52%

Functional Investigation on Aromatase in Endometrial Hyperplasia in Polycystic Ovary Syndrome Cases

Zhao

Zhang²,

Yan³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Objective: To explore the possible significance of aromatase P450 in endometrial hyperplasia with a background of polycystic ovary syndrome (PCOS). Methods: Immunohistochemistry was used to determine the expression of aromatase P450 in endometrium of PCOS patients. Semiquantitative analysis of aromatase P450 expression of mRNA and protein level wasalso carried out by real-time quantitative RT-PCR method. After endometrial cells were stimulated by testosterone and letrozole in vitro, the estradiol (E 2 ) level was determined, and the expression of cell aromatase P450 mRNA was assessed. Results: The aromatase P450 mRNA level was increased in endometria of PCOS patients. When endometrial cells were cultured with 10 -6 M testosterone, the E 2 level in the culture medium increased. An inhibitory effect on E 2 generation and expression of aromatase P450 mRNA was observed when the endometrial cells were treated with 10 -5 M letrozole. Conclusions: There is an increased expression of aromatase P450 in PCOS patient endometrium. Androgen stimulation could enhance the synthesis of aromatase P450 mRNA and the production of E 2 in endometrial cells in vitro while letrozole could do the reverse.

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Section: Discussionmentioning

confidence: 52%

Functional Investigation on Aromatase in Endometrial Hyperplasia in Polycystic Ovary Syndrome Cases

Zhao

Zhang²,

Yan³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Nordic Society of Gynecologic Oncology Study (NSGO) reported similar results (Lindemann et al 2014). Thangavelu and coworkers examined the biological changes in human endometrial carcinoma tissues before and after aromatase inhibitor treatment (Thangavelu et al 2013). Patients were randomized to receive anastrozole or placebo before definitive surgery.…”

Section: Androgen Action From the Viewpoint Of Therapeutic Targetmentioning

confidence: 99%

In situ androgen and estrogen biosynthesis in endometrial cancer: focus on androgen actions and intratumoral production

Itō¹,

Miki²,

Suzuki³

et al. 2016

Endocrine-Related Cancer

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In situ estrogen biosynthesis is considered to play pivotal roles in the development and progression of human endometrial carcinoma. However, the biological roles of androgen have remained virtually unknown. Various epidemiological studies have revealed that elevated serum androgen levels are generally associated with an increased risk of developing endometrial carcinoma; however, studies directly examining androgens in carcinoma tissues are relatively rare and reviews summarizing this information are scarce. Therefore, we summarized recent studies on androgens in endometrial carcinoma, especially focusing androgen actions and in situ androgen biosynthesis. Among the enzymes required for local biosynthesis of androgen, 17β-hydroxysteroid dehydrogenase type 5 (conversion from androstenedione to testosterone) and 5α-reductase (reduction of testosterone to dihydrotestosterone (DHT)) are the principal enzymes involved in the formation of biologically most potent androgen, DHT. Both enzymes and androgen receptor were expressed in endometrial carcinoma tissues, and in situ production of DHT has been reported to exist in endometrial carcinoma tissues. However, testosterone is not only a precursor of DHT production, but also a precursor of estradiol synthesis, as a substrate of the aromatase enzyme. Therefore, aromatase could be another key enzyme serving as a negative regulator for in situ production of DHT by reducing amounts of the precursor. In an in vitro study, DHT was reported to exert antiproliferative effects on endometrial carcinoma cells. Intracrine mechanisms of androgens, the downstream signals of AR, which are directly related to anticancer progression, and the clinical significance of DHT-AR pathway in the patients with endometrial carcinoma have, however, not been fully elucidated.

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“…Aromatase activity is demonstrated also in EC, at variance with normal endometrial tissue [30][31][32][33]. Endometrial cancer tissue mimics an endocrine organ, and it can convert the androgens in active estrogen by the action of aromatase in a paracrine way [8,13]. In EC, the activity of aromatase is associated with stromal invasion and aromatase enzymes are expressed during the process of carcinoma-stromal interaction [29].…”

Section: Role Of Aromatase Enzyme and Pharmacological Inhibitionmentioning

confidence: 99%

“…At present, only a single randomized work reports on the neo-adjuvant use of AI in EC patients [13]. Thangavelu et al [13] showed a reduction of endometrial proliferation in 16 EC patients subjected to anastrozole therapy for 14 days, against 8 patients treated with placebo.…”

Section: Use Of Ai In the Therapy Of Localized Ecmentioning

confidence: 99%

“…Recently, anti-angiogenic and receptorial inhibitor agents have been introduced in the treatment of advanced or recurrent EC as a single agent or in association with platinum-based regimes of chemotherapy [10][11][12]. Moreover, since the EC tissue mimics an endocrine organ by the action of aromatase, the use of aromatase inhibitors (AI) seem to have a rational basis in the treatment of type I EC [3,13].…”

Section: Introductionmentioning

confidence: 99%

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Effectiveness of aromatase inhibitors in the treatment of advanced endometrial adenocarcinoma

Bogliolo

Gardella

Dominoni

et al. 2015

Arch Gynecol Obstet

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Neoadjuvant treatment of endometrial cancer using anastrozole: A randomised pilot study

Cited by 36 publications

References 36 publications

Functional Investigation on Aromatase in Endometrial Hyperplasia in Polycystic Ovary Syndrome Cases

Functional Investigation on Aromatase in Endometrial Hyperplasia in Polycystic Ovary Syndrome Cases

In situ androgen and estrogen biosynthesis in endometrial cancer: focus on androgen actions and intratumoral production

Effectiveness of aromatase inhibitors in the treatment of advanced endometrial adenocarcinoma

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