Arsenaulttodd2477

The Mycobacterium Bacillus Calmette-Guérin cell wall skeleton (BCG-CWS), the main immune active center of BCG, is a potent candidate non-infectious immunotherapeutic drug and an alternative to live BCG for use against urothelial carcinoma. However, its application in anticancer therapy is limited, as BCG-CWS tends to aggregate in both aqueous and non-aqueous solvents. To improve the internalization of BCG-CWS into bladder cancer cells without aggregation, BCG-CWS was nanoparticulated at a 180 nm size in methylene chloride and subsequently encapsulated with conventional liposomes (CWS-Nano-CL) using an emulsified lipid (LEEL) method. In vitro cell proliferation assays showed that CWS-Nano-CL was more effective at suppressing bladder cancer cell growth compared to nonenveloped BCG-CWS. In an orthotopic implantation model of luciferase-tagged MBT2 bladder cancer cells, encapsulated BCG-CWS nanoparticles could enhance the delivery of BCG-CWS into the bladder and suppress tumor growth. Treatment with CWS-Nano-CL induced the inhibition of the mammalian target of rapamycin (mTOR) pathway and the activation of AMP-activated protein kinase (AMPK) phosphorylation, leading to apoptosis, both in vitro and in vivo. Furthermore, the antitumor activity of CWS-Nano-CL was mediated predominantly by reactive oxygen species (ROS) generation and AMPK activation, which induced endoplasmic reticulum (ER) stress, followed by c-Jun N-terminal kinase (JNK) signaling-mediated apoptosis. Therefore, our data suggest that the intravesical instillation of liposome-encapsulated BCG-CWS nanoparticles can facilitate BCG-CW cellular endocytosis and provide a promising drug-delivery system as a therapeutic strategy for BCG-mediated bladder cancer treatment.A better understanding of the impact of molecular size and linkers is important for PEG-based hyperbranched polymers (HBPs) intended as tailored drug delivery vehicles. This study aimed to evaluate the effects of crosslinker chemistry (cleavable disulphide versus non-cleavable ethylene glycol methacrylate (EGDMA) linkers) and molecular weight within the expected size range for efficient renal elimination (22 vs. 48 kDa) on the intravenous pharmacokinetic and biodistribution properties of 89Zr-labelled HBPs in rats. All HBPs showed similar plasma pharmacokinetics over 72 h, despite differences in linker chemistry and size. A larger proportion of HBP with the cleavable linker was eliminated via the urine and faeces compared to a similar-sized HBP with the non-cleavable linker, while size had no impact on the proportion of the dose excreted. The higher molecular weight HBPs accumulated in organs of the mononuclear phagocyte system (liver and spleen) more avidly than the smaller HBP. These results suggest that HBPs within the 22 to 48 kDa size range show no differences in plasma pharmacokinetics, but distinct patterns of organ biodistribution and elimination are evident.Ingredients of brown seaweed like fucoidans are often described for their beneficial biological effects, that might be interesting for a medical application. In this study, we tested an extract from Dictyosiphon foeniculaceus (DF) to evaluate the effects in glioblastoma and uveal melanoma, looking for a possible anti-cancer treatment. LY2780301 We investigated toxicity, VEGF (vascular endothelial growth factor) secretion and gene expression of tumor and non-tumor cells. SVGA (human fetal astrocytes), the human RPE (retinal pigment epithelium) cell line ARPE-19, the tumor cell line OMM-1 (human uveal melanoma), and two different human primary glioblastoma cultures (116-14 and 118-14) were used. Tests for cell viability were conducted with MTS-Assay (3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium), and the proliferation rate was determined with cell counting. VEGF secretion was assessed with ELISA (enzyme-linked immunosorbent assay). The gene expression of VEGF receptor 1 (VEGFR1), VEGF receptor 2 (VEGFR2) and VEGF-A was determined with real-time qPCR (quantitative polymerase chain reaction). DF lowered the cell viability of OMM-1. Proliferation rates of ARPE-19 and OMM-1 were decreased. The VEGF secretion was inhibited in ARPE-19 and OMM-1, whereas it was increased in SVGA and 116-14. The expression of VEGFR1 was absent and not influenced in OMM-1 and ARPE-19. VEGFR2 expression was lowered in 116-14 after 24 h, whereas VEGF-A was increased in 118-14 after 72 h. The extract lowered cell viability slightly and was anti-proliferative depending on the cell type investigated. VEGF was heterogeneously affected. The results in glioblastoma were not promising, but the anti-tumor properties in OMM-1 could make them interesting for further research concerning cancer diseases in the human eye.High-strength aluminum alloy (mainly refers to the 7xxx series) is the optimum material for lightweight military equipment. However, this type of aluminum alloy is a wrought aluminum alloy. If it is directly formed by traditional casting methods, there will inevitably be problems such as coarseness, unevenness, looseness, and hot cracking in the structure, which will greatly affect the final performance of the part. Based on the internal cooling with annular electromagnetic stirring (IC-AEMS) method, a new technology of rheological die forging is developed in this paper, and the scale-reduced parts of a brake hub of Al-6.54Zn-2.40Cu-2.35Mg-0.10Zr aluminum alloy were prepared. The influence of IC-AEMS and the addition of rare element Sc on the structure and mechanical properties of the parts was studied. An optical microscope and scanning electron microscope (SEM) were used to observe the microstructure evolution, energy dispersive spectroscopy (EDS) was used to analyze the phase distribution and composition, and the mechanical properties of the parts were tested by uniaxial tensile tests. The results show that the addition of Sc element can effectively refine the grains and improve the strength and elongation of the material; the application of IC-AEMS improves the cooling rate of the melt, increases the effective nucleation rate, and the grains are further refined. Through process optimization, scale-reduced parts of a brake hub with good formability and mechanical properties can be obtained, the ultimate tensile strength is 597.2 ± 3.1 MPa, the yield strength is 517.8 ± 4.3 MPa, and the elongation is 13.7 ± 1.3%.