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Background: Androgen receptor (AR)-targeted treatments improve the survival of castration-resistant prostate cancer (CRPC) patients; however, secondary resistance to these agents ultimately occurs in virtually all patients. Therefore, alternative therapeutic targets are urgently needed. Since growing evidence demonstrates that WNT/β-catenin signaling plays an important role in CRPC, the antitumor activity and mechanism of action of CWP232291, a small molecule β-catenin inhibitor, were investigated in prostate cancer. Methods: We assessed the antitumor activity of CWP232291 in prostate cancer cell lines and primary cells derived from CRPC patients. The effect of CWP232291 on apoptotic cell death, endoplasmic reticulum (ER) stress, cell viability, and WNT/β-catenin signaling was evaluated by flow cytometry, western blotting, luciferase reporter assay, and fluorescence microscopy. Antitumor efficacy was assessed in two CRPC xenograft mouse models. Results: CWP232291 induced ER stress, resulting in upregulation of the proapoptotic protein CHOP and activation of caspase-3-dependent apoptosis. In addition, CWP232291 suppressed the expression of β-catenin by affecting WNT-dependent transcriptional activity, and downregulated AR and its splice variants in prostate cancer cells. Antitumor activity was observed in prostate cancer cells in vitro and ex vivo, and antitumor efficacy was observed in vivo. Conclusions: Beyond providing preclinical evidence of therapeutic efficacy for the novel small molecule β-catenin inhibitor CWP232291 in CRPC, our results show that inducing ER stress and targeting WNT/β-catenin signaling may be a novel strategy against CRPC. [ABSTRACT FROM AUTHOR]

In this study, a time-dependent corrosion depth estimation method using atmospheric corrosion monitor (ACM) sensor data to evaluate time-dependent corrosion behaviors is proposed. For the time-dependent corrosion depth estimation of uncoated carbon steel and weathering steel, acceleration corrosion tests were conducted in salt-spray corrosion environments and evaluated with a corrosion damage estimation method using ACM sensing data and corrosion loss data of the tested steel specimens. To estimate the time-dependent corrosion depth using corrosion current by an ACM sensor, the relationship between the mean corrosion depth calculated from the weight loss method and the corrosion current was evaluated. The mean corrosion depth was estimated by calculating the corrosion current and evaluating the relationship between the mean corrosion depth and corrosion current during the expected period. From the test and estimation results, the corrosion current demonstrated a good linear correlation with the mean corrosion depth of carbon steel and weathering. The calculated mean corrosion depth is nearly the same as that of the tested specimen, which can be well used to estimate corrosion rate for the uncoated carbon steel and weathering steel. [ABSTRACT FROM AUTHOR]

Magnesium (Mg) and its alloys have attracted much attention as a promising candidate for degradable implant applications however the rapid corrosion of magnesium inside the human body greatly limits its use as an implant material. Therefore, coating the alloy surface with a multifunctional film is a promising way to overcome the drawbacks. Here we propose for the first time a multifunction layer coating to enhance the cell viability, antibacterial property and decelerated corrosion rates to act as a novel material to be used for degradable implant Applications. For that, the magnesium alloy (AZ31) was first treated with hydrofluoric acid (HF) and then dopamine tris Hydrochloric acid (tris-HCL) solution. The reducing catechol groups in the polydopamine (PD) layer subsequently immobilize silver/gold ions in situ to form uniformly dispersed Ag/Au nanoparticles on the coating layer. The successful formation of Ag/Au nanoparticles on the HF-PD AZ31 alloy was confirmed using XPS and XRD, and the morphology of all the coated samples were investigated using SEM images. The alloy with HF-PDA exhibit enhanced cell attachment and proliferation. Moreover, the nanoparticle immobilized HF-PD alloy exhibited dramatic corrosion resistance enhancement with superior antibacterial properties and accountable biocompatibility. Thus the result suggest that HF-PD Ag/Au alloy has great potential in the application of degradable implant and the surface modification method is of great significance to determine its properties. [ABSTRACT FROM AUTHOR]