ASIA unversity:Item 310904400/112907
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    题名: Preclinical Evaluation of Exemestane as a Novel Chemotherapy for Gastric Cancer
    作者: 楊顓丞;張寧;吳登強;鄭維中;鍾瑋敏;張維君;Liu, C-J;Liu, C-J;吳宜珍;賴學洲;馬文隆;Ma, Wen-Lung
    贡献者: 護理學系
    关键词: aromatase;exemestane;gastric cancer.
    日期: 2019-11
    上传时间: 2020-09-02 16:00:48 (UTC+8)
    出版者: 亞洲大學
    摘要: CYP19A1/aromatase (Ar) is a prognostic biomarker of gastric cancer (GCa). Ar is a critical enzyme for converting androstenedione to oestradiol in the steroidogenesis cascade. For decades, Ar has been targeted with Ar inhibitors (ARIs) in gynaecologic malignancies; however, it is unexplored in GCa. A single-cohort tissue microarray examination was conducted to study the association between Ar expression and disease outcome in Asian patients with GCa. The results revealed that Ar was a prognostic promoter. Bioinformatics analyses conducted on a Caucasian-based cDNA microarray databank showed Ar to be positively associated with GCa prognosis for multiple clinical modalities, including surgery, 5-Fluorouracil (5-FU) for adjuvant chemotherapy, or HER2 positivity. These findings imply that targeting Ar expression exhibits a potential for fulfilling unmet medical needs. Hence, Ar-targeting compounds were tested, and the results showed that exemestane exhibited superior cancer-suppressing efficacy to other ARIs. In addition, exemestane down-regulated Ar expression. Ablating Ar abundance with short hairpin (sh)Ar could also suppress GCa cell growth, and adding 5-FU could facilitate this effect. Notably, adding oestradiol could not prevent exemestane or shAr effects, implicating a nonenzymatic mechanism of Ar in cancer growth. Regarding translational research, treatment with exemestane alone exhibited tumour suppression efficacy in a dose-dependent manner. Combining subminimal doses of 5-FU and exemestane exerted an excellent tumour suppression effect without influencing bodyweight. This study validated the therapeutic potentials of exemestane in GCa. Combination of metronomic 5-FU and exemestane for GCa therapy is recommended.
    關聯: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
    显示于类别:[護理學系] 期刊論文

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