Regulation of cell survival by HUNK mediates breast cancer resistance to HER2 inhibitors
BREAST CANCER RESEARCH AND TREATMENT
Authors: Yeh, Elizabeth S.; Abt, Melissa A.; Hill, Elizabeth G.
Abstract
Breast cancer patients who are HER2-positive receive targeted inhibitors to HER2, including trastuzumab and lapatinib. While patients benefit from the use of HER2 inhibitors, many fail therapy and almost all patients become resistant to treatment, indicating a critical need to prevent treatment failure. Several recent studies indicate that activation of autophagy contributes to trastuzumab and lapatinib resistance and demonstrate that impairing autophagy in breast cancer cells is therapeutically beneficial. Moreover, autophagy is mechanistically linked through signaling crosstalk to apoptotic pathways, where activation of one process impacts the other. Therefore, understanding the molecular mechanisms that control these processes may uncover novel areas of therapeutic intervention to combat or prevent resistance in breast cancer. We previously characterized the protein kinase HUNK as a breast cancer-promoting factor in HER2/neu-induced mammary tumor models, in which HUNK supported the survival of HER2/neu-positive tumor cells, likely through the regulation of apoptosis. Because significant crosstalk exists between apoptotic and autophagy proteins, we now examine if HUNK is also able to regulate cell survival through modulation of autophagy using HER2 inhibitor sensitive and resistant breast cancer models. Furthermore, we investigate whether inhibiting HUNK impairs in vivo tumor growth that is initiated by HER2 inhibitor-resistant breast cancer cells. Our findings indicate that therapeutically targeting HUNK is a potential strategy for overcoming resistance and that resistant breast cancer cells maintain HUNK expression to drive tumorigenesis, an observation that is consistent with a pro-survival role for this kinase.
Low frequency microwave absorption property of CIPs/ZnO/Graphene ternary hybrid prepared via facile high-energy ball milling
POWDER TECHNOLOGY
Authors: Yin, Pengfei; Zhang, Limin; Wang, Jian; Feng, Xing; Wang, Kaiming; Rao, Hanbing; Wang, Yanying; Dai, Jianwu
Abstract
CIPs/ZnO/Graphene ternary lamelliform hybrid with good microwave absorbing properties in low frequency band was prepared via facile high-energy ball milling method. The different components of CIPs, ZnO and graphene are combined tightly as well as the NPs of CIPs and ZnO dispersed on graphene present the polycrys-talline characteristics. The addition of ZnO and graphene can improve the low frequency absorption intensity of ball milled CIPs and reduce the corresponding matching absorption thickness. The maximum reflection loss of -45.57 dB at 0.48 GHz with a - 10 dB bandwidth over the frequency range of 030-0.71 GHz can be achieved at the thickness of 4 mm. The excellent absorption performance of this ternary hybrid is owing to the external planar anisotropy, outstanding dielectric properties, hunk eddy current loss, multiple Debye relaxation processes, superior attenuation characteristics and better impedance matching. In addition, the preparation method used here is pretty simple, thus the as-prepared ternary hybrid is probable for using as a candidate in the absorption of low frequency microwave. (C) 2019 Elsevier B.V. All rights reserved.