327 research outputs found

    Learning-by-doing as an approach to teaching social entrepreneurship

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    Many studies have explored the use of learning-by-doing in higher education, but few have applied this to social entrepreneurship contexts and applications: this paper addresses this gap in the literature. Our programme involved students working with different stakeholders in an interactive learning environment to generate real revenue for social enterprises. Our results show that learning-by-doing enables students to develop their entrepreneurial skills and enhance their knowledge of social businesses. The findings also show that students became more effective at working in teams and in formulating and applying appropriate business strategies for the social enterprises. Overall, the learning-by-doing approach discussed in this paper is capable of developing the entrepreneurial skills of students, but there are challenges that need to be addressed if such an approach is to be effective

    Supernatants from lymphocytes stimulated with Bacillus Calmette-Guerin can modify the antigenicity of tumours and stimulate allogeneic T-cell responses

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    BACKGROUND: Reduced expression of class 1 human leucocyte antigens (HLA1) is often a mechanism by which tumours evade surveillance by the host immune system. This is often associated with an immune function that is unable to mount appropriate responses against disease, which can result in a state that favours carcinogenesis. METHODS: In the current study, we have explored the effects of Bacillus Calmette-Guerin (BCG) on the cytokine output of leucocytes, which is a key determinant in generating antitumour action, and have also assessed the effect of these cytokine cocktails on HLA1 expression in solid tumour cell lines. RESULTS: BCG potently activated a broad range of leucocytes, and also enhanced the production of cytokines that were Th(1)-predominant. Supernatants from BCG-treated leucocytes significantly increased the expression of HLA1 on the surface of cancer cell lines, which correlated with increased cytolytic T-cell activity. We also showed that the increased HLA1 expression was associated with activation of intracellular signalling pathways, which was triggered by the increases in the Th(1)-cytokines interferon-γ and tumour necrosis factor-α, as counteracting their effects negated the enhancement. CONCLUSION: These studies reaffirm the role of BCG as a putative immunotherapy through their cytokine-modifying effects on leucocytes and their capacity to enhance tumour visibility

    Expression and DNA methylation of TNF, IFNG and FOXP3 in colorectal cancer and their prognostic significance.

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    BACKGROUND: Colorectal cancer (CRC) progression is associated with suppression of host cell-mediated immunity and local immune escape mechanisms. Our aim was to assess the immune function in terms of expression of TNF, IFNG and FOXP3 in CRC. METHODS: Sixty patients with CRC and 15 matched controls were recruited. TaqMan quantitative PCR and methylation-specific PCR was performed for expression and DNA methylation analysis of TNF, IFNG and FOXP3. Survival analysis was performed over a median follow-up of 48 months. RESULTS: TNF was suppressed in tumour and IFNG was suppressed in peripheral blood mononuclear cells (PBMCs) of patients with CRC. Tumours showed enhanced expression of FOXP3 and was significantly higher when tumour size was >38 mm (median tumour size; P=0.006, Mann-Whitney U-test). Peripheral blood mononuclear cell IFNG was suppressed in recurrent CRC (P=0.01). Methylated TNFpromoter (P=0.003) and TNFexon1 (P=0.001) were associated with significant suppression of TNF in tumours. Methylated FOXP3cpg was associated with significant suppression of FOXP3 in both PBMC (P=0.018) and tumours (P=0.010). Reduced PBMC FOXP3 expression was associated with significantly worse overall survival (HR=8.319, P=0.019). CONCLUSIONS: We have detected changes in the expression of immunomodulatory genes that could act as biomarkers for prognosis and future immunotherapeutic strategies

    The correlation between colorectal cancer rates of proliferation and apoptosis and systemic cytokine levels; plus their influence upon survival

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    Colorectal cancer development is associated with a shift in host immunity with suppression of the cell-mediated immune system (CMI) and a predominance of humoral immunity (HI). Tumour progression is also associated with increased rates of cell proliferation and apoptosis. The aim of this study was to investigate whether these factors correlate and have an influence upon prognosis. Long-term follow-up was performed on 40 patients with colorectal cancer who had levels of tumour necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-10 measured from stimulated blood cultures before surgery. Their archived tumour specimens were analysed to determine a Ki-67-derived proliferation index (PI) and a M30-derived apoptosis index (AI). Tumour necrosis factor-α levels negatively correlated to tumour proliferation (ρ=−0.697, P=0.01). Interleukin-10 levels had a positive correlation with tumour proliferation (ρ=0.452, P=0.05) and apoptosis (ρ=0.587, P=0.01). Patient survival correlates to tumour pathological stage (P=0.0038) and vascular invasion (P=0.0014). An AI⩽0.6% and TNF-α levels ⩾8148 pg ml−1 correlate to improved survival (P=0.032, P=0.021). Tumour proliferation and apoptosis correlate to progressive suppression of the CMI-associated cytokine TNF-α and to and higher levels of IL-10. Survival is dependent upon the histological stage of the tumour, vascular invasion, rates of apoptosis and proliferation and systemic immunity which are all interconnected
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