Background: Tumor-associated macrophages (TAMs) are critical components of the tumor microenvironment (TME) in prostate cancer. Commonly used orthotopic models do not accurately reflect the complete TME of a human patient or the natural initiation and progression of a tumor. Therefore, genetically engineered mouse models are essential for studying the TME as well as advancing TAMtargeted therapies. Two common transgenic (TG) models of prostate cancer are Hi-Myc and transgenic adenocarcinoma of the mouse prostate (TRAMP), but the TME and TAM characteristics of these models have not been well characterized.Methods: To advance the Hi-Myc and TRAMP models as tools for TAM studies, macrophage infiltration and characteristics were assessed using histopathologic, flow cytometric, and expression analyses in these models at various timepoints during tumor development and progression.Results: In both Hi-Myc and TRAMP models, macrophages adopt a more pro-tumor phenotype in higher histological grade tumors and in older prostate tissue. However, the Hi-Myc and TRAMP prostates differ in their macrophage density, with Hi-Myc tumors exhibiting increased macrophage density and TRAMP tumors exhibiting decreased macrophage density compared to age-matched wild type mice. Conclusions:The macrophage density and the adenocarcinoma cancer subtype of Hi-Myc appear to better mirror patient tumors, suggesting that the Hi-Myc model is the more appropriate in vivo TG model for studying TAMs and TME-targeted therapies.
Objective To investigate the circulating tumour cells (CTCs) capture abilities of two technologies that are not dependent on cell‐surface marker expression: a selection‐free platform [AccuCyte®‐CyteFinder® system (Rarecyte)] and a size‐based platform [fluid‐assisted separation technology (FAST)]. In addition, the combination of the two systems to more completely assess CTCs was investigated. Patients and methods In all, 28 patients with metastatic prostate cancer were included. Two 6 mL peripheral blood samples were taken from each patient at the same time‐point. The samples were then subjected to the two different technology platforms in parallel. An additional group of samples was acquired by applying the waste chamber material from the FAST‐group tests (flow‐through that goes through the FAST filter membrane) to the Rarecyte system for the detection any CTCs that were not captured by FAST. Results The three groups had significantly different putative CTC‐positive tests, with positive rates of 29% for Rarecyte, 57% for FAST, and 79% for the combination. We also assessed CTC phenotype: 56.6% of the CTCs were cytokeratin (CK)+/epithelial cell adhesion molecule (EpCAM)−, 3.1% were CK−/EpCAM+, and 40.3% were CK+/EPCAM+. The captured CTCs diameter ranged from 5.2 to 16.9 µm. The mean CTC size from the FAST waste chamber was significantly smaller. The diameters for each of the phenotypic groups were significantly different. Conclusions These data highlight disparities in the positive rates and enumerated CTC numbers detected by the two techniques. Notably, the combination of the two technologies resulted in the highest CTC‐capture rates. Smaller CTCs were more likely to be missed by the FAST as they passed through the filter system. Sizes of CTCs varied with different cell surface marker phenotypes.
In this paper, Cu-6 wt%Ag alloy sheets were prepared using vacuum induction melting, heat treatment, and cold working rolling. We investigated the influence of the aging cooling rate on the microstructure and properties of Cu-6 wt%Ag alloy sheets. By reducing the cooling rate of the aging treatment, the mechanical properties of the cold-rolled Cu-6 wt%Ag alloy sheets were improved. The cold-rolled Cu-6 wt%Ag alloy sheet achieves a tensile strength of 1003 MPa and an electrical conductivity of 75% IACS (International Annealing Copper Standard), which is superior to the alloy fabricated with other methods. SEM characterization shows that the change in properties of the Cu-6 wt%Ag alloy sheets with the same deformation is due to a precipitation of the nano-Ag phase. The high-performance Cu-Ag sheets are expected to be used as Bitter disks for water-cooled high-field magnets.
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