New insights into the function of the APC/C subunit, APC5 And Development of a spheroid model to investigate heterogeneity in glioblastoma

O’Connor, Leigh (2014). New insights into the function of the APC/C subunit, APC5 And Development of a spheroid model to investigate heterogeneity in glioblastoma. University of Birmingham. M.Res.

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Abstract

Glioblastoma (GBM) is the most common and most aggressive form of brain cancer. Current treatment involves concomitant radiotherapy and chemotherapy with the drug Temozolomide (TMZ), but the median survival is still only around a year. Transcriptional profiling studies revealed different subtypes of GBM with distinct patterns of gene expression that are linked to specific genetic alterations. In this study, cell lines were used to represent the different subtypes. They were cultured as 3D spheroids, which have been shown to be more representative of GBM tumours than monolayers. Confocal imaging of polyclonal spheroids showed the subtypes form distinct populations that reflect their preference for different positions within the spheroid, suggesting an arrangement that confers a survival advantage to the cells. The effect of TMZ treatment was studied, with different effects seen both between 2D and monoclonal spheroid culture, and between the different subtypes with varying morphological changes following treatment. The results show that spheroid culture is a promising method in GBM model development. However, problems were encountered that hindered imaging of polyclonal spheroids. More work is needed to optimise the method to improve spheroid size uniformity and fluorescent signal of the cell lines.

Type of Work:

Thesis (Masters by Research > M.Res.)

Award Type:

Masters by Research > M.Res.

Supervisor(s):