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Title: The investigation of the properties and behaviour of superficial bladder cancer by an in vitro explant tumour system, and its use in the response to conventional and novel intravesical cytotoxic agents
Author: Crook, Timothy John
ISNI:       0000 0001 3397 4731
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2004
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Aim: To produce a four-dimensional model of superficial transitional cell carcinoma of the bladder in vitro for the assessment of therapeutic agents used as intravesical therapy, and which is consistent and amenable to rationalised experiments. Introduction: Superficial transitional cell carcinoma of the bladder is more common compared to the invasive type, but has a high probability of recurrence. The various modalities of control include cytoscopic resection or diathermy ablation, as well as intravesical chemotherapeutic adjuncts such as the anthracyclines, Mitomycin C and immunotherapy with BCG. The laboratory investigation of these intravesical agents is by assays on monolayers of tumour cell lines. Animal models are able to give more accurate representations of clinical tumours in certain cancer types. However, there is no reliable animal model of superficial transitional cell carcinoma because of the difficulty in keeping the tumour both non-invasive and consistent in size and tumour grade. Methods: The MGH-U1 cell line was transfected with green fluorescent protein in its parental and resistant forms. Rat bladder explant cultures were established, and the explants seeded with the transfected cell lines. Visualisation of the resulting colonies was by fluorescent confocal microscopy. Fluorescence intensity and area of the colonies were recorded for each time point. Cytotoxic drugs were applied to the tumour colonies for 1 hour and the effects observed over several days. Results: The MGH-U1 cell line stably expressed Green Fluorescent Protein, and maintained its characteristics. Tumour colonies were successfully established on the explants, and visualised for up to 11 days after seeding. Mean area of the colony was used as a measure of colony growth. Experiments with cytotoxic agents showed that high concentrations of drugs similar to those in use clinically could be applied to the model, with continuing growth of the colonies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available