Project description:We found the bone marrow stromal-derived neural progenitor cells secretome have the neural protection effect. Proteomic analysis was performed nn order to analyze the protection factor in the secretome. Keywords: Neural protection, secretome
Project description:Desmoplastic small round cell tumor (DSRCT) is an aggressive malignancy that occurs predominantly in young adult males and is characterized by abdominopelvic sarcomatosis exhibiting multi-lineage cellular nests of epithelial, muscular, mesenchymal, and neural differentiation admixed with desmoplastic stroma. Prior to the recognition of the disease as a distinct clinical entity, DSRCT was invariably misclassified as poorly differentiated atypical cancer of the testes, ovary, mesentery, or gastrointestinal tract, and the chemotherapies used for those malignancies elicited poor clinical response. As previously reported, a tectonic shift in the treatment of these patients occurred after researchers made two astute observations: 1) DSRCT microscopically resembles other small round “blue cell” sarcoma subtypes (e.g., ES, rhabdomyosarcoma, synovial sarcoma), and 2) DSRCT and ES have the same N-terminal EWSR1 fusion partner. Proteomic analysis using a reverse-phase protein lysate array (RPPA) was used to elucidate biomarkers that distinguish DSRCT from adjacent normal tissue and Ewing sarcoma. This proteomic analysis revealed novel proteins, such as the androgen receptor and Syk, that may be susceptible to drug targeting, as well as oncogenic pathways like Akt-PI3K that are highly expressed in DSRCT.
Project description:Therapeutic neo-vasculogenesis in vivo can be achieved by the co-transplantation of human endothelial colony-forming progenitor cells (ECFCs) with mesenchymal stem/progenitor cells (MSPCs).The underlying mechanism is not completely understood thus hampering the development of novel stem cell therapies.We hypothesized that proteomic profiling could be used to retrieve the in vivo signaling signature during the initial phase of human neo-vasculogenesis. ECFCs and MSPCs were therefore either transplanted alone or co-transplanted subcutaneously into immune deficient mice. Early cell signaling, occurring within the first 24 hours in vivo, was analyzed using antibody microarray proteomic profiling.Vessel formation and persistence were verified in parallel transplants for up to 24 weeks. Proteomic analysis revealed significant alteration of regulatory components including caspases, calcium/calmodulin-dependent protein kinase, DNA protein kinase,human ErbB2 receptor-tyrosine kinase as well as mitogen-activated protein kinases.Therapeutic candidate caspase-4 was selected from array results for targeting vascular network formation in vitro as well as modulating therapeutic vasculogenesis in vivo. As a proof-of-principle, caspase-4 and general caspase-blocking led to diminished endothelial network formation in vitro and significantly decreased vasculogenesis in vivo. Proteomic profiling ex vivo thus unraveled a signaling signature which can be targeted to modulate neo-vasculogenesis in vivo.