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Title: Apoptosis, cell proliferation and role of oncogenes in lymphoreticular malignancies
Author: Kiberu, Samuel
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 1998
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This study was conducted using paraffin embedded material of randomly selected lymphoma cases from the archives of Leicester Royal Infirmary. The cases had been confirmed by immunophenotyping and immunocytogenetic analysis of B and T cell gene rearrangements using PCR (Polymerase chain reaction). These included 20 each of low grade and high grade non Hodgkin's lymphomas of both sexes and age groups 4-84 yrs. Prognostic information was obtained from the case notes. An in situ End labelling technique was used to study apoptotic indices. Cell proliferation rates were studied by in situ hybridisation method to detect histone using mRNA digoxigenin-11-dUTP probe. Bcl-2 expression was assessed using antigen retrieval and an immunoperoxidase technique. Apoptotic indices, proliferation rates, Bcl-2 expression and tumour grade were correlated to each other. Flowcytometric study of four cell lines (HL-60, Raji, C88 and DP16-1) was also undertaken as regards apoptosis, cell proliferation and oncogene expression. Apoptosis was assessed using existing techniques on thymocytes. Cell proliferation was assessed using proliferation markers like Ki-67, PCNA and BrdUrd. The study showed that the high grade lymphomas had the highest apoptotic indices and proliferation rates. More of the low grade tumours were Bcl-2 positive. Most mortalities occurred in tumours which had high proliferation rates and were Bcl-2 negative suggesting that those two parameters were bad prognostic indicators. A larger and extended study would be required to confirm my observations. For the cell lines apoptosis showed an inverse correlation with cell proliferation. There appeared to be a link between apoptosis and cell differentiation and the role of oncogenes was established. The information derived from cell lines could be exploited in designing drugs which produce apoptosis, cell differentiation and counteracting cell proliferation thus reducing tumour load.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available