Micro-porous titanium is coated with silver nanoparticles by using a simple chemical reduction method that exhibits excellent antibacterial ability. Scanning electron microscopy (SEM) shows that the silver nanoparticles with average sizes of about 100 nm are formed homogeneously on the micro-porous titanium surface. After the micro-porous Ti coated with silver nano particles is treated by heating, the average size of the silver nano particles is slightly increased, but the nano particles are more uniformly dispersed on the surface of the micro-porous titanium. X-ray diffraction (XRD) indicates that those nanoparticles are metallic silver produced on the micro-porous titanium surface. The samples of micro-porous titanium coated with silver nanoparticles inhibit the growth of Escherichia coli. Our results show that the electrical double layer of the samples play an important role in the antibiosis and this study opens a new window for antibacterial mechanism which may be suitable for the other antibacterial metallic materials.
Cancer-associated fibroblasts play a key role in tumor progression. It is conceivable that the breaking of immune tolerance of "self-antigens" associated with tumor cells and tumor stromal is an attractive approach for tumor immunotherapy. To test this concept, we used basic fibroblast growth factor (bFGF) to activate normal fibroblasts and used these activated fibroblasts as one vaccine against tumor.
The lung squamous cell carcinoma survival rate is very poor despite multimodal treatment. It is urgent to discover novel candidate biomarkers for prognostic assessment and therapeutic targets to lung squamous cell carcinoma (SCC).
Etsrp/Etv2 (Etv2) is an evolutionarily conserved master regulator of vascular development in vertebrates. Etv2 deficiency prevents the proper specification of the endothelial cell lineage, while its overexpression causes expansion of the endothelial cell lineage in the early embryo or in embryonic stem cells. We hypothesized that Etv2 alone is capable of transdifferentiating later somatic cells into endothelial cells. Using heat shock inducible Etv2 transgenic zebrafish, we demonstrate that Etv2 expression alone is sufficient to transdifferentiate fast skeletal muscle cells into functional blood vessels. Following heat treatment, fast skeletal muscle cells turn on vascular genes and repress muscle genes. Time-lapse imaging clearly shows that muscle cells turn on vascular gene expression, undergo dramatic morphological changes, and integrate into the existing vascular network. Lineage tracing and immunostaining confirm that fast skeletal muscle cells are the source of these newly generated vessels. Microangiography and observed blood flow demonstrated that this new vasculature is capable of supporting circulation. Using pharmacological, transgenic, and morpholino approaches, we further establish that the canonical Wnt pathway is important for induction of the transdifferentiation process, whereas the VEGF pathway provides a maturation signal for the endothelial fate. Additionally, overexpression of Etv2 in mammalian myoblast cells, but not in other cell types examined, induced expression of vascular genes. We have demonstrated in zebrafish that expression of Etv2 alone is sufficient to transdifferentiate fast skeletal muscle into functional endothelial cells in vivo. Given the evolutionarily conserved function of this transcription factor and the responsiveness of mammalian myoblasts to Etv2, it is likely that mammalian muscle cells will respond similarly.
VEGF receptor 2 (VEGFR2) inhibitors, as efficient antiangiogenesis agents, have been applied in the cancer treatment. However, currently most of these anticancer drugs suffer some adverse effects. Discovery of novel VEGFR2 inhibitors as anticancer drug candidates is still needed.
Tumor neovascularization is a highly complex process including multiple steps. Understanding this process, especially the initial stage, has been limited by the difficulties of real-time visualizing the neovascularization embedded in tumor tissues in living animal models. In the present study, we have established a xenograft model in zebrafish by implanting mammalian tumor cells into the perivitelline space of 48 hours old Tg(Flk1:EGFP) transgenic zebrafish embryos. With this model, we dynamically visualized the process of tumor neovascularization, with unprecedented high-resolution, including new sprouts from the host vessels and the origination from VEGFR2(+) individual endothelial cells. Moreover, we quantified their contributions during the formation of vascular network in tumor. Real-time observations revealed that angiogenic sprouts in tumors preferred to connect each other to form endothelial loops, and more and more endothelial loops accumulated into the irregular and chaotic vascular network. The over-expression of VEGF165 in tumor cells significantly affected the vascularization in xenografts, not only the number and size of neo-vessels but the abnormalities of tumor vascular architecture. The specific inhibitor of VEGFR2, SU5416, significantly inhibited the vascularization and the growth of melanoma xenografts, but had little affects to normal vessels in zebrafish. Thus, this zebrafish/tumor xenograft model not only provides a unique window to investigate the earliest events of tumoral neoangiogenesis, but is sensitive to be used as an experimental platform to rapidly and visually evaluate functions of angiogenic-related genes. Finally, it also offers an efficient and cost-effective means for the rapid evaluation of anti-angiogenic chemicals.
Primary tumors and metastases have been thought to initiate avascularly as multicellular aggregates and later induce angiogenesis or initiate vascularly by co-opting pre-existing host blood vessels without inducing angiogenesis. These two distinct concepts of microtumor vascularization have raised significant controversies. To clarify intratumoral vascularization and tumor cell behaviors at single-cell level during the earliest stage of microtumor initiation, we established primary and metastatic microtumor models in Tg(flk1:EGFP) transgenic zebrafish. We found that tumor cells preferred to initiate avascularly as multicellular aggregates and only later (50-100 cells in size) induced angiogenesis in blood-supply-sufficient microenvironments. In blood-supply-deficient microenvironments, less tumor cells (20-30 cells per fish) managed to co-opt and migrate along host vessels, whereas more tumor cells (100-300 cells per fish) could immediately induce angiogenesis without obvious cell migration. In a metastatic model, we clearly observed that tumor cells co-opted, migrated along and proliferated on the surface of host vessels at an early stage after they extravasated from host vessels and induced angiogenesis later when micromatastases comprised only 15-30 tumor cells. Moreover, the inducement of neovessels accelerated the growth of micromatastases in size, meanwhile, decreased the migration of tumor cells on the surface of host vessels. These results suggest that vessel co-option and angiogenesis have distinct contributions during the initiation of microtumors. Microtumors initiated reasonably through co-opting host vessels or inducing angiogenesis, depending on the differences of local microenvironments and cell numbers in microtumors. The results in this study may have important implications for the therapeutic application of antiangiogenic strategies.
Epidermal growth factor receptor (EGFR) plays an important role in the growth and metastasis of many solid tumors. Strategies that target EGFR hold promising therapeutic potential for the treatment for non-small cell lung cancer (NSCLC), as EGFR is normally overexpressed in these tumors. This study was designed to determine whether an anti-EGFR immunotoxin has anti-tumor activity against NSCLC, and if so, to further investigate the possible mechanisms of cytotoxicity.
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