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Phosphorus magnetic resonance spectroscopy of human breast cancer and therapeutic modulation

Kalra, Radhika; (1993) Phosphorus magnetic resonance spectroscopy of human breast cancer and therapeutic modulation. Doctoral thesis (M.D), UCL (University College London). Green open access

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Abstract

This thesis examines the use of 31P MRS to monitor the response to therapy in human breast cancer, and ways of modulating drug resistance that would be suitable for monitoring with 31P MRS. Patients with breast cancer were studied using 31P MRS with the aim of elucidating the mechanism for therapy induced changes in phosphomonoester (PME). There was a strong relationship between tumour proliferation and PME/ γATP due to a significant correlation for aneuploid tumours. The source of PME is unlikely to be due to cell signalling as there was no relationship between PME and EGFr. 31P MRS of perchloric acid extracts of both malignant and normal breast demonstrated that a large contribution to the PME peak is from phosphoethanolamine (PE) and to a lesser extent from phosphocholine (PC). As the concentration of PE and PC varied markedly between tumours, PME relative to γATP may be indicative of intracellular levels, particularly as cellular ATP is tightly regulated. There was no relationship between the concentration of PE and PC and the respective phospholipids, phosphatidylcholine (PtdC) and phosphatidylethanolamine (PtdE) measured from 31P MR spectra of chloroform/methanol extracts. The technical limitations of 31P MRS indicate that it may only be applicable for monitoring therapy in large tumours, assessing novel agents and their metabolic effects. Studies with cultured human breast cancer cells are useful for identifying factors that could be important in determining chemosensitivity in vivo. Transient adriamycin resistance induced by hypoxia in rodent V79 cells was not observed in both human MCF-7 breast cancer lines with markedly different adriamycin sensitivity. For MCF-7/AdrR and MDA-468 expressing high levels of EGFr, sensitivity to adriamycin was not modulated by EGF, although the growth of MDA-468 was inhibited by EGF.

Type: Thesis (Doctoral)
Qualification: M.D
Title: Phosphorus magnetic resonance spectroscopy of human breast cancer and therapeutic modulation
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Breast cancer; Phosphocholine
URI: https://discovery.ucl.ac.uk/id/eprint/10104000
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