Therapeutic Effects of Long-Term Administration of Tranilast in an Animal Model for the Treatment of Fibroids.
Therapeutic Effects of Long-Term Administration of Tranilast in an Animal Model for the Treatment of Fibroids.
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DOI：
10.3390/ijms241310465
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发表时间：
2023-06-21
影响因子：
5.6
通讯作者：
Khorram, Omid
中科院分区：
文献类型：
--
作者：
Chuang, Tsai-Der;Munoz, Leslie;Quintanilla, Derek;Boos, Drake;Khorram, Omid
曲尼司特（N-3，4-二甲氧基肉桂酰基邻氨基苯甲酸）是一种口服药物，具有抗过敏特性，在日本和韩国被批准用于治疗哮喘和增生性瘢痕。先前的体外研究表明曲尼司特通过其对细胞增殖的抑制作用和对细胞凋亡的诱导作用来减少肌瘤的生长。本研究的目的是确定曲尼司特在小鼠模型中治疗人源性子宫肌瘤的疗效。SCID小鼠（卵巢切除，补充雌激素和孕激素）植入纤维瘤外植体，并治疗两个月曲尼司特（50 m/kg/天）或车辆。处死后，切除异种移植物并进行分析。曲尼司特耐受性良好，无不良副作用。在曲尼司特处理的小鼠中，肿瘤重量沿着减少37%，Ki 67、CCND 1和E2 F1的染色显著减少;裂解的半胱天冬酶3的核染色显著增加; TGF-β3和Masson三色染色减少。在曲尼司特处理的小鼠的异种移植物中，纤连蛋白、COL 3A 1、CCND 1、E2 F1和TGF-β3的mRNA和蛋白表达受到显著抑制。曲尼司特的这些有希望的治疗效果需要额外的动物研究和人体临床试验来评估其治疗子宫肌瘤的疗效。
Tranilast (N-3, 4-dimethoxycinnamoyl anthranilic acid) is an orally administered drug with antiallergic properties and approved in Japan and the Republic of Korea for the treatment of asthma and hypertrophic scars. Previous in vitro studies indicated that tranilast reduced fibroid growth through its inhibitory effects on cell proliferation and induction of apoptosis. The objective of this study was to determine the efficacy of tranilast for treatment of human-derived fibroids in a mouse model. SCID mice (ovariectomized, supplemented with estrogen and progesterone) were implanted with fibroid explants and treated for two months with tranilast (50 m/kg/daily) or the vehicle. After sacrifice, xenografts were excised and analyzed. Tranilast was well tolerated without adverse side effects. There was a 37% reduction in tumor weight along with a significant decrease in staining for Ki67, CCND1, and E2F1; a significant increase in nuclear staining for cleaved caspase 3; and reduced staining for TGF-β3 and Masson’s trichrome in the tranilast treated mice. There was a significant inhibition of mRNA and protein expression of fibronectin, COL3A1, CCND1, E2F1, and TGF-β3 in the xenografts from the tranilast-treated mice. These promising therapeutic effects of tranilast warrant additional animal studies and human clinical trials to evaluate its efficacy for treatment of fibroids.
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DOI：
10.1016/j.xfss.2022.04.005
发表时间：
2022-11
期刊：
F&S science
影响因子：
--
作者：
Chuang, Tsai-Der;Quintanilla, Derek;Boos, Drake;Khorram, Omid
通讯作者：
Khorram, Omid
影响因子：
5.6
作者：
通讯作者：
--
影响因子：
3.9
作者：
Chuang TD;Panda H;Luo X;Chegini N
通讯作者：
Chegini N
影响因子：
3.7
作者：
Chuang TD;Khorram O
通讯作者：
Khorram O
影响因子：
1.9
作者：
Kim, Seung Joon;Kim, Jin Woo;Kim, Young Kyoon
通讯作者：
Kim, Young Kyoon