Abstract:
Barrett's oesophagus is a complication of gastro-oesophageal reflux disease and is
the single most important predisposing factor for the development of
adenocarcinoma of the oesophagus. New molecular markers are needed for early
diagnosis and to monitor disease progression.
Telomerase is a ribonuclear protein with reverse transcriptase activity, which
uses its own RNA component as a template for the addition of telomeric repeats
to the end of chromosomes. Telomerase activity has been studied during the
neoplastic progression of Barrett's oesophagus using a TRAP based ELISA
technique, which found telomerase to be reactivated early during
.
disease
progression. A non-isotopic method of in situ hybridisation for the detection of the
RNA component of telomerase has also been successfully developed.
Plasminogen activation is an inducible extracellular proteolytic system involved
in the regulation of cellular interactions and invasion. The components of the
urokinase-type Plasminogen Activator system have been fully investigated
during the progression of Barrett's oesophagus to adenocarcinoma utilising
immunohistochemistry and ELISA techniques. Changes in the expression of this
invasive phenotype were found to occur late during disease progression in
malignant tissues.
Two-oesophageal cell-lines have been characterised using molecular biological
techniques to detect a range of molecular markers to produce ex vivo models of
oesophageal adenocarcinoma and oesophageal squamous cell carcinoma. In order
to assess the effects of bile salts and acidity on oesophageal tissues these celllines
were then utilised as ex vivo models. Exposure to acidic conditions both
alone and with bile salts altered the morphological appearance of the cells and
disrupted adhesion molecules in the cellular membrane.
Investigations into both telomerase reactivation and the plasminogen activator
system have provided new information concerning the nature and timing of
molecular changes during the Barrett's metaplasia/dysplasia/ adenocarcinoma
sequence.
