Project description:A retrospective observational study to evaluate immunohistochemical expression of Inhibin Beta A (INHBA) in 60 cases of Colorectal Carcinoma, and compare levels of its expression to different clinicopathological criteria.
Project description:This study will be conducted in subjects with refractory colorectal carcinoma with unresectable liver metastases. The purposes of the study are:
* to evaluate the safety and any harmful effects of an intravenous injection of Ad.hIFN-β;
* help determine whether the virus carrying the interferon-beta gene will enter the bloodstream and liver tumor cells and cause the cancer cells to die.
Project description:Coordinated communication among pancreatic islet cells is necessary for the maintenance of glucose homeostasis. In diabetes, chronic exposure to pro-inflammatory cytokines has been shown to perturb β-cell communication and function. Compelling evidence has implicated extracellular vesicles (EVs) in modulating physiological and pathological responses to β-cell stress. We report that pro-inflammatory β-cell small EVs (cytoEV) induce β-cell dysfunction, promote a pro-inflammatory islet transcriptome, and enhance recruitment of CD8+ T-cells and macrophages. Proteomic analysis of cytoEV revealed an enrichment of the chemokine, CXCL10, with surface topological analysis depicting CXCL10 as membrane-bound on cytoEV to facilitate direct binding to CXCR3 receptors on the surface of β-cells. CXCR3 receptor inhibition reduced CXCL10-cytoEV binding and attenuated β-cell dysfunction, inflammatory gene expression, and leukocyte recruitment to islets. Collectively, this work implicates the significant role of pro-inflammatory β-cell derived small EVs in modulating β-cell function, global gene expression, and antigen presentation through activation of the CXCL10/CXCR3 axis.
