17β-estradiol was reported to inhibit melanoma cells proliferation however, clinical trials did not provide the expected survival benefits. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. ERβ is the predominant ER in melanoma, and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Estrogens exert their effects through estrogen receptors (ERα and ERβ) that affect cancer growth in an opposite way: ERα is associated with a proliferative action and ERβ with an anticancer effect. Melanoma incidence is higher in males than in females, and females have a significant survival advantage over men. Increasing evidence supports that melanoma is a hormone-related cancer. However, treatment resistance and side effects are common events of these therapeutic strategies. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. 2Department of Medical Biotechnologies and Translational Medicine, Università degli Studi di Milano, Milano, ItalyĬutaneous melanoma is an aggressive tumor its incidence has been reported to increase fast in the past decades.1Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy.Roberta Manuela Moretti 1 and Patrizia Limonta 1*
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Kesempatan itu membuat mereka berdua menjadi sangat dekat. Ternyata, putri sekolah yang paling dicintai sebenarnya adalah seorang Otaku kelas berat. Tapi dengan tiba-tiba nasib, kunjungan acak Yuuto ke perpustakaan sekolah membawa rahasia Haruka yang paling gelap terungkap, yang berpotensi merusak reputasinya saat ini. Seperti banyak lainnya, dia mengagumi Haruka dari kejauhan, bahkan tidak pernah bermimpi mendekatinya. Yuuto Ayase adalah anak laki-laki pemalu yang memiliki keberuntungan luar biasa duduk di kelas bersama Haruka setiap hari. Haruka Nogizaka is the most popular student in the prestigious Hakujo Academy, possessing unparalleled beauty, talent, and influence. Popularitasnya begitu hebat sehingga teman sekelasnya kadang-kadang memberinya julukan Prancis untuk lebih mengungkapkan kegemaran mereka. Read reviews on the anime Nogizaka Haruka no Himitsu (Haruka Nogizakas Secret) on MyAnimeList, the internets largest anime database. 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