文献库 文献相关信息
- 题目:
- Targeting Cyclin-Dependent Kinases in Synovial Sarcoma: Palbociclib as a Potential Treatment for Synovial Sarcoma Patients.
- 作者:
- Vlenterie(Myrella),Hillebrandt-Roeffen(Melissa H S),Schaars(Esther W M),Flucke(Uta E),Fleuren(Emmy D G),Navis(Anna C),Leenders(William P J),Versleijen-Jonkers(Yvonne M H),van der Graaf(Winette T A)
- 状态:
- 发布时间2016-08-04 , 更新时间 2016-08-18
- 期刊:
- Ann Surg Oncol
- 摘要:
- In synovial sarcomas alterations in the cyclin D1-CDK4/6-Rb axis have been described. Also, β-catenin, a cyclin D1 regulator, is often overexpressed. Additionally, studies have shown that the t(X;18) translocation influences tumor behavior partly through cyclin D1 activation. We investigated how alterations in the cyclin D1-CDK4/6-Rb axis impact prognosis and studied effects of targeting this axis with the CDK4/6 inhibitor palbociclib.,Synovial sarcoma samples (n = 43) were immunohistochemically stained for β-catenin, cyclin D1, p16, p21, p27, Rb, and phospho-Rb. Fluorescent in situ hybridization (FISH) was performed to detect CCND1 amplification or translocation. In 4 synovial sarcoma cell lines sensitivity to palbociclib was investigated using cell viability assays, and effects on the sensitive cell lines were evaluated on protein level and by cell cycle arrest.,Expression of nuclear phospho-Rb and nuclear β-catenin in the patient samples was associated with poor survival. FISH showed a sporadic translocation of CCND1 in a subset of tumors. An 8-fold CCND1 amplification was found in 1 cell line, but not in the patient samples investigated. Palbociclib effectively inhibited Rb-phosphorylation in 3 cell lines, resulting in an induction of a G1 arrest and proliferation block.,In this series nuclear phospho-Rb and nuclear β-catenin expression were negative prognostic factors. In vitro data suggest that palbociclib may be a potential treatment for a subset of synovial sarcoma patients. Whether this effect can be enhanced by combination treatment deserves further preclinical investigations.
- 语言:
- eng
- DOI:
DataTable pData
微信公众号
关注微信订阅号，实时查看信息，关注医学生物学动态。
版权所有 © 2025.Genelibs 济南弘晖生物技术有限公司 鲁ICP备13024435号-2
