分类: 生物学 >> 生物物理学 >> 肿瘤学 提交时间: 2016-05-11
摘要: Dasatinib-based therapy is often used as a second-line therapeutic strategy for imatinib-resistance gastrointestinal stromal tumors (GISTs); however, acquired aberrant activation of dasatinib target proteins, such as c-KIT and PDGFR13, attenuates the therapeutic efficiency of dasatinib. Combination therapy which inhibits the activation of dasatinib target proteins may enhance the cytotoxicity of dasatinib in GISTs. Bortezomib, a proteasome inhibitor, significantly inhibited cell viability and promoted apoptosis of dasatinib-treated GIST-TI cells, whereas GIST-TI cells showed little dasatinib cytotoxicity when treated with dasatinib alone, as the upregulation of c-KIT caused by dasatinib itself interfered with the inhibition of c-KIT and PDGFRI3 phosphorylation by dasatinib. Bortezomib induced internalization and degradation of c-KIT by binding c-KIT to Cbl, an E3 ubiquitin-protein ligase, and the subsequent release of Apaf-1, which was originally bound to the c-KIT-Hsp903-Apaf-1 complex, induced primary apoptosis in GISTTI cells. Combined treatment with bortezomib plus dasatinib caused cell cycle arrest in the G1 phase through inactivation of PDGFRP and promoted bortezomib-induced apoptosis in GIST-TI cells. Our data suggest that combination therapy exerts better efficiency for eradicating GIST cells and may be a promising strategy for the future treatment of GISTs. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
分类: 核科学技术 >> 粒子加速器 提交时间: 2023-06-18 合作期刊: 《Nuclear Science and Techniques》
摘要: Differing from radiography without lens system, the high-energy proton radiography (PRAD) uses Zumbro lens system to focus the penetrating protons. Since the Zumbro lens system is able to limit the range of multiple Coulomb scattering angles of the protons, the low-energy PRAD with Zumbro lens system is also feasible, although the attenuation of probing protons in the object is negligible. Low-energy PRAD is superior to the high-energy PRAD for diagnosing the objects of small thicknesses. To verify the imaging principle of Zumbro lens system, 11 MeV PRAD experiments were performed at the China Academy of Engineering Physics (CAEP) recently. The experiment results demonstrated that this 11 MeV PRAD was able to radiograph objects of area density less than 2.7�10-2 g/cm2 and the area density discrepancy less than 2.3% could be distinguished.
分类: 核科学技术 >> 粒子加速器 提交时间: 2023-06-18 合作期刊: 《Nuclear Science and Techniques》
摘要: Proton radiography experiment with a Zumbro lens system was carried out on an 11 MeV proton cyclotron. The experimental results show that the image blurring is improved markedly. Clear images and good spatial resolution of the density step edges are obtained, which is important for hydrotest experiments, and the spatial resolution can achieve 100 m.