Murine bioluminescent hepatic tumour model.

This video describes the establishment of liver metastases in a mouse model that can be subsequently analysed by bioluminescent imaging. Tumour cells are administered specifically to the liver to induce a localised liver tumour, via mobilisation of the spleen and splitting into two, leaving intact the vascular pedicle for each half of the spleen. Lewis lung carcinoma cells that constitutively express the firefly luciferase gene (luc1) are inoculated into one hemi-spleen which is then resected 10 minutes later. The other hemi-spleen is left intact and returned to the abdomen. Liver tumour growth can be monitored by bioluminescence imaging using the IVIS whole body imaging system. Quantitative imaging of tumour growth using IVIS provides precise quantitation of viable tumour cells. Tumour cell death and necrosis due to drug treatment is indicated early by a reduction in the bioluminescent signal. This mouse model allows for investigating the mechanisms underlying metastatic tumour-cell survival and growth and can be used for the evaluation of therapeutics of liver metastasis.

Ex vivo culture of patient tissue & examination of gene delivery.

This video describes the use of patient tissue as an ex vivo model for the study of gene delivery. Fresh patient tissue obtained at the time of surgery is sliced and maintained in culture. The ex vivo model system allows for the physical delivery of genes into intact patient tissue and gene expression is analysed by bioluminescence imaging using the IVIS detection system. The bioluminescent detection system demonstrates rapid and accurate quantification of gene expression within individual slices without the need for tissue sacrifice. This slice tissue culture system may be used in a variety of tissue types including normal and malignant tissue and allows us to study the effects of the heterogeneous nature of intact tissue and the high degree of variability between individual patients. This model system could be used in certain situations as an alternative to animal models and as a complementary preclinical mode prior to entering clinical trial.

Electrochemotherapy as an adjunct or alternative to other treatments for unresectable or in-transit melanoma.

Treatment of recurrent or in-transit unresectable melanoma continues to be a major therapeutic challenge. Electrochemotherapy (ECT) is a therapeutic option for those patients whose lesions are not suitable for surgical resection and who have exhausted all other treatment modalities. ECT combines electroporation of tumor cells with the administration either of intravenous or intratumoral antineoplastic drugs, such as bleomycin or cisplatin. The cell membranes are thus rendered permeant to these impermeant hydrophilic drugs with a several hundred-fold increase in intracellular delivery and cytotoxicity. ECT is an effective treatment in the palliative management of unresectable recurrent disease with overall objective response rates of approximately 80-90%. ECT technology continues to evolve allowing application to deeper lesions. By combining ECT with tumor-specific immunostimulating approaches, such as perilesional IL-2, CpG oligonucleotides or prior immunogene therapy, there is a promise of both local and systemic control of this disease.