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Title: In vitro augmentation of carcinoembryonic antigen expression in colorectal cancer cells
Author: Collie, M. H. S.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1999
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Carcinoembryonic antigen (CEA) is an oncofoetal antigen heterogeneously expressed by colorectal cancer cells, which may provide a useful target for antibody guided tumour localisation and therapy. Recent work in the Royal Free Hospital Department of Surgery demonstrated significant augmentation of CEA expression by certain Colorectal cancer cell lines on exposure to various chemical agents or to changing physicochemical environments. Specifically, Lovo, HT29 and Colo cell lines which are high, low and non-expressors of CEA respectively were grown in the presence of Butyric acid, gamma-interferon, Theophylline, 5-Azacytidine, Retinoic Acid or phorbol esters. All the agents caused reversible inhibition of cell growth and proliferation. Butyric acid and gamma-Interferon only caused significant augmentation of CEA expression in Lovo and HT29 cell lines but had no such effect on Colo cells. The aim of this work is to further systematically explore the effects of differentiating agents (Butyric acid, gamma-Interferon and 5-Azacytidine and Theophylline), altering environmental factors (pH, temperature, oxygen supply and nutritional content of medium), a range of commonly used cytotoxic drugs and radiation on the growth, differentiation and CEA expression of three cell lines - Lovo, HT29 and Colo. According to the observed effects of these factors used singly, combinations of chemical and physicochemical factors will also be tested for synergistic reactions. The growth, differentiation characteristics and CEA expression parameters will be measured by a combination of Electro Microscopy, Immunocytochemistry and Fluorescein Activated Cell Sorting. It is anticipated that Fluorescein-Activated Cell Sorting may prove more sensitive than Immunocytochemistry. Membrane CEA expression and total CEA content will be compared. In addition, the degree of release of CEA by the growing cells into their medium will be measured by Radioimmunoassay. An investigation of the genetic events which accompany observed differentiation and CEA expression will be conducted by indirect Immunocytochemistry. The aim is to establish whether genetically determined changes in the cell cycle accompany perceived changes in CEA expression and differentiation. Treated cells will be immunostained for oncogene products known to be associated with proliferation, apoptosis or tumour progression, e.g., p53, Bcl-2, K-ras, and c-myc.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available