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Title: In vitro modelling of lymphoma : potential for exploring experimental therapies
Author: Shamash, Jonathan
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1996
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The development of new therapies for the treatment of lymphoma has been hampered by the lack of reproducible and faithful in vitro models. This has been a particular problem with the relatively slow growing types of which two broad groups are considered here - namely the low grade B cell non-Hodgkin's lymphomas and Hodgkin's disease. This thesis describes the development of a culture system using a stromal cell layer, anti-CD40 and two cytokines - human interleukin 3 (IL3) and human interleukin 10 (IL10) which has resulted in the in vitro expansion of low grade B cell malignancies with retention of the morphological and immunophenotypical features of the parent tumour and in addition a growth rate similar to that found in vivo. This system was able to support the growth of Hodgkin's lymphoma - both lymphocyte predominant and non lymphocyte predominant types. Molecular analysis of these cells suggested a B cell origin in most cases and cell sorting using flow cytometry for CD30 positive (CD30+ve) cells revealed the presence of Reed Sternberg cells (RS cells) or lymphocytic and/or histiocytic (L + H) cells in the CD30+ve cell sorts. The knowledge that the anti-apopotic protein Bcl-2 prevented intracellular repartitioning of calcium led to the assessment of calcium channel blocking drugs acting at two sites (1) the cell membrane (nimodipine) and (2) the endoplasmic reticulum (dantrolene and azumolene). These were initially tested in various lymphoma cell lines with differing levels of bcl-2 expression and then in primary lymphoma culture. The effect of these drugs alone and in combination with cytotoxic agents was compared and the in vitro cytotoxic activity of dantrolene and azumolene described.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available