A pilot phase II study of valproic acid for treatment of low-grade neuroendocrine carcinoma.
A pilot phase II study of valproic acid for treatment of low-grade neuroendocrine carcinoma.
复制标题
丙戊酸的II期研究，用于治疗低度神经内分泌癌。
DOI：
10.1634/theoncologist.2011-0031
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Loconte NK
中科院分区：
文献类型：
--
作者：
Mohammed TA;Holen KD;Jaskula-Sztul R;Mulkerin D;Lubner SJ;Schelman WR;Eickhoff J;Chen H;Loconte NK
Notch 1已被证明是神经内分泌肿瘤（NETs）的肿瘤抑制因子。以前在NET细胞系中的体外研究也表明，丙戊酸（VPA），一种组蛋白脱乙酰酶抑制剂，可以诱导Notch 1，并且Notch 1激活与NET肿瘤标志物的减少相关。因此，本研究旨在评价丙戊酸在治疗NET中的作用，以及VPA是否诱导体内Notch信号传导途径。8例低级别NET（类癌和胰腺）患者接受丙戊酸500 mg口服治疗，每日2次，调整剂量以维持目标VPA水平在50-100 mcg/mL之间。所有患者随访12个月或直至疾病进展。Notch 1信号传导在治疗前的所有肿瘤中均不存在，并且用VPA上调。一名患者有未经证实的PR，并注意到Notch 1 mRNA水平增加了40倍。4例患者的最佳缓解为疾病稳定。5/7例患者的肿瘤标志物改善。总体而言，VPA治疗耐受性良好。丙戊酸在体内激活Notch 1信号传导，并可能在治疗低度NET中发挥作用。
Notch1 has been shown to be a tumor suppressor in neuroendocrine tumors (NETs). Previous in-vitro studies in NET cell lines have also suggested that valproic acid (VPA), a histone deacetylase inhibitor, can induce Notch1, and that Notch1 activation correlates with a decrease in tumor markers for NET. Thus, this study aimed to evaluate the role of valproic acid in treating NETs and if VPA induced the Notch signaling pathway signaling in-vivo‥ Eight patients with low grade NETs (carcinoid and pancreatic) were treated with valproic acid 500 mg orally twice a day with dosing adjusted to maintain a goal VPA level between 50–100 mcg/mL. All patients were followed for 12 months or until disease progression. Notch1 signaling was absent in all tumors prior to treatment, and was upregulated with VPA. One patient had an unconfirmed PR and was noted to have a 40-fold increase in Notch1 mRNA levels. Four patients had stable disease as best response. Tumor markers improved in 5/7 patients. Overall, treatment with VPA was well tolerated. Valproic acid activates Notch1 signaling in-vivo and may have a role in treating low grade NET.
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影响因子：
5.8
作者：
Kunnimalaiyaan, Muthusamy;Chen, Herbert
通讯作者：
Chen, Herbert
影响因子：
158.5
作者：
MOERTEL, CG;LEFKOPOULO, M;KLAASSEN, D
通讯作者：
KLAASSEN, D
影响因子：
6.2
作者：
Modlin, IM;Lye, KD;Kidd, M
通讯作者：
Kidd, M
影响因子：
9.8
作者：
Massironi, Sara;Conte, Dario;Peracchi, Maddalena
通讯作者：
Peracchi, Maddalena
DOI：
10.1097/01.coc.0000054535.19808.f4
发表时间：
2004-06-01
影响因子：
2.6
作者：
Ansell, SM;Mahoney, MR;Rubin, J
通讯作者：
Rubin, J