Florian, Catarina Ligia; (1996) Proton nuclear magnetic resonance studies of human glioma cell lines. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The object of this research was to investigate profiles of human brain and nervous system tumours using cell culture techniques combined with 1H-MRS and chromatographic analysis of cell extracts. In assessing the reliability of these techniques it was found that when the culture medium, timing and procedure of extraction were carefully controlled, reproducible results were obtained both within a given passage number, and across passages of a cell line. The hypothesis that transformed cells, while being distinguishable from normal brain cells, will share some 1H-NMR spectroscopic features specific to their cell of origin was proposed, and tested in studies of human meningioma cell lines and normal rat meningeal cell cultures. Some attributes characteristic to meningeal cells were shared by the meningioma cell lines, relating meningioma cells to their tissue of origin. Other features of the spectra discriminated the transformed from normal cells. The hypothesis that types of human nervous system tumours could be distinguished by their characteristic 1H-NMR spectra was tested on meningioma, neuroblastoma and glioblastoma/astrocytoma cell lines. In addition to similarities, there were qualitative and quantitative discriminating spectral features which allowed the identification of the tumour type. A few spectral characteristics distinguished between astrocytomas and glioblastoma multiforme, but there were similarities between spectra from human astrocytomas and previously published spectra from rat astrocytes. Studies on cell lines from human primitive neuroectodermal tumours (PNETs) revealed a characteristic metabolite pattern for cerebellar medulloblastomas, which reflects their derivation form neural progenitor cells. This pattern discriminates cerebellar medulloblastomas from PNETs of other locations in the central nervous system, from normal human cerebellum, and from other human brain tumours. Metabolite profiles were obtained at key ages during postnatal development and maturation, from anatomical regions of rat brain where different types of normal brain cell populations are expressed in certain proportions. These revealed that the qualitative and quantitative aspects of the presence of metabolites in each anatomical region studied was related to the cellular composition of that region.

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