Intravital FLIM-FRET imaging reveals dasatinib-induced spatial control of src in pancreatic cancer.

Cancer invasion and metastasis occur in a complex three-dimensional (3D) environment, with reciprocal feedback from the surrounding host tissue and vasculature-governing behavior. In this study, we used a novel intravital method that revealed spatiotemporal regulation of Src activity in response to the anti-invasive Src inhibitor dasatinib. A fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer (FLIM-FRET) Src biosensor was used to monitor drug-targeting efficacy in a transgenic p53-mutant mouse model of pancreatic cancer.

Organotypic collagen I assay: a malleable platform to assess cell behaviour in a 3-dimensional context.

Cell migration is fundamental to many aspects of biology, including development, wound healing, the cellular responses of the immune system, and metastasis of tumor cells. Migration has been studied on glass coverslips in order to make cellular dynamics amenable to investigation by light microscopy. However, it has become clear that many aspects of cell migration depend on features of the local environment including its elasticity, protein composition, and pore size, which are not faithfully represented by rigid two dimensional substrates such as glass and plastic.

Spatial regulation of RhoA activity during pancreatic cancer cell invasion driven by mutant p53.

The ability to observe changes in molecular behavior during cancer cell invasion in vivo remains a major challenge to our understanding of the metastatic process. Here, we demonstrate for the first time, an analysis of RhoA activity at a subcellular level using FLIM-FRET (fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer) imaging in a live animal model of pancreatic cancer. In invasive mouse pancreatic ductal adenocarcinoma (PDAC) cells driven by mutant p53 (p53(R172H)), we observed a discrete fraction of high RhoA activity at both the leading edge and rear of cells in vivo which was absent in two-dimensional in vitro cultures.

Reduced expression of multiple gap junction proteins is a feature of cervical dysplasia.

Cervical dysplasia is a premalignant lesion associated with human papillomavirus (HPV) infection which, over time, can turn cancerous. Previous studies have indicated that loss of gap junctions may be a feature of cervical cancer and premalignant dysplasia. Loss of the gap junction protein connexin43 has been demonstrated in dysplastic cervix, but other connexins have not been investigated.

Liver cell lines for the study of hepatocyte functions and immunological response.

Background: Liver cell lines closely resembling primary hepatocyte are essential for research on hepatitis viruses and hepatocyte function. Currently used cell lines are derived from hepatic tumours and have altered gene expression.

Aims: The generation and characterisation of novel human hepatocyte lines (HHLs) derived from healthy human liver, retaining the primary hepatocyte phenotype.