• The Effect of Polysialic Acid Expression on Glioma Cell Nano-mechanics

      Grant, Colin A.; Twigg, Peter C.; Saeed, Rida F.; Lawson, G.; Falconer, Robert A.; Shnyder, Steven D. (2016-03-01)
      Polysialic acid (PolySia) is an important carbohydrate bio-polymer that is commonly over-expressed on tumours of neuroendocrine origin and plays a key role in tumour progression. PolySia exclusively decorates the neural cell adhesion molecule (NCAM) on tumour cell membranes, modulating cell-cell interactions, motility and invasion. In this preliminary study, we examine the nano-mechanical properties of isogenic C6 rat glioma cells - transfected cells engineered to express the enzyme polysialyltransferase ST8SiaII, which synthesises polySia (C6-STX cells) and wild type cells (C6-WT). We demonstrate that polySia expression leads to reduced elastic and adhesive properties but also more visco-elastic compared to non-expressing wild type cells. Whilst differences in cell elasticity between healthy and cancer cells is regularly assigned to changes in the cytoskeleton, we show that in this model system the change in properties at the nano-level is due to the polySia on the transfected cell membrane surface.
    • The use of thermographic imaging to evaluate therapeutic response in human tumour xenograft models

      Hussain, Nosheen; Connah, David; Ugail, Hassan; Cooper, Patricia A.; Falconer, Robert A.; Patterson, Laurence H.; Shnyder, Steven D. (2016-08-05)
      Non-invasive methods to monitor tumour growth are an important goal in cancer drug development. Thermographic imaging systems offer potential in this area, since a change in temperature is known to be induced due to changes within the tumour microenvironment. This study demonstrates that this imaging modality can be applied to a broad range of tumour xenografts and also, for the first time, the methodology’s suitability to assess anti-cancer agent efficacy. Mice bearing subcutaneously implanted H460 lung cancer xenografts were treated with a novel vascular disrupting agent, ICT-2552, and the cytotoxin doxorubicin. The effects on tumour temperature were assessed using thermographic imaging over the first 6 hours post-administration and subsequently a further 7 days. For ICT-2552 a significant initial temperature drop was observed, whilst for both agents a significant temperature drop was seen compared to controls over the longer time period. Thus thermographic imaging can detect functional differences (manifesting as temperature reductions) in the tumour response to these anti-cancer agents compared to controls. Importantly, these effects can be detected in the first few hours following treatment and therefore the tumour is observable non-invasively. As discussed, this technique will have considerable 3Rs benefits in terms of reduction and refinement of animal use.