An internalizing antibody targeting of cell surface GRP94 effectively suppresses tumor angiogenesis of colorectal cancer.

Colorectal cancer (CRC) is one of the life-threatening malignancies worldwide. Thus, novel potential therapeutic targets and therapeutics for the treatment of CRC need to be identified to improve the clinical outcomes of patients with CRC. In this study, we found that glucose-regulated protein 94 (GRP94) is overexpressed in CRC tissues, and its high expression is correlated with increased microvessel density. Next, through phage display technology and consecutive in vitro functional isolations, we generated a novel human monoclonal antibody that specifically targets cell surface GRP94 and shows superior internalizing activity comparable to trastuzumab. We found that this antibody specifically inhibits endothelial cell tube formation and simultaneously promotes the downregulation of GRP94 expression on the endothelial cell surface. Finally, we demonstrated that this antibody effectively suppresses tumor growth and angiogenesis of HCT116 human CRC cells without causing severe toxicity in vivo. Collectively, these findings suggest that cell surface GRP94 is a novel potential anti-angiogenic target in CRC and that antibody targeting of GRP94 on the endothelial cell surface is an effective strategy to suppress CRC tumor angiogenesis.

Influence of Volumetric Damage Parameters on Patch Antenna Sensor-Based Damage Detection of Metallic Structure.

Antenna sensors have been employed for crack monitoring of metallic materials. Existing studies have mainly focused on the mathematical relationship between the surface crack length of metallic material and the resonant frequency. The influence of the crack depth on the sensor output and the difference of whether the crack is depth-penetrated remains unexplored. Therefore, in this work, a numerical simulation method was used to investigate the current density distribution characteristics of the ground plane (metallic material) with different crack geometric parameters. The data reveals that, compared with the crack length, the crack depth has a greater influence on the resonant frequency. The relationship between the frequency and the crack geometric parameters was discussed by characterizing the current density and sensor output under different crack lengths and depths. Therefore, the feasibility of monitoring another common damage of metallic materials, i.e., corrosion pit, was explored. Furthermore, the influences of crack and corrosion pit geometric parameters on the output results were validated by experiments.

Characterization of a Patch Antenna Sensor's Resonant Frequency Response in Identifying the Notch-Shaped Cracks on Metal Structure.

Patch antenna sensor is a novel sensor that has great potential in structural health monitoring. The two resonant frequencies of a patch antenna sensor are affected by the crack on its ground plane, which enables it to sense the crack information. This paper presents a detailed characterization of the relationship between the resonant frequencies of a patch antenna sensor and notch-shaped cracks of different parameters, including the length, the orientation, and the center location. After discussing the principle of crack detection using a patch antenna sensor, a parametric study was performed to understand the response of the sensor's resonant frequencies to various crack configurations. The results show that the crack parameters affect the resonant frequencies in a way that can be represented by the crack's cutting effect on the sensor's current flow. Therefore, we introduced a coefficient φ to comprehensively describe this interaction between the crack and the current distribution of the antenna radiation modes. Based on the definition of coefficient φ , an algorithm was proposed for predicting the resonant frequency shifts caused by a random notch-shaped crack and was verified by the experimental measurements. The presented study aims to provide the foundation for the future use of the patch antenna sensor in tracking the propagation of cracks of arbitrary orientation and location in metal structures.