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M Dyne

Publications and source records attributed to M Dyne.

27 records · Page 2Linked to original sources
PubMed1987

A comparison of the chemical analyses of cell lipids with their complete proton NMR spectrum.

Whole cells are made up of molecules in different environments to which NMR spectroscopy is sensitive. In particular, malignant and transformed cells contain lipids not only in bilayers but in isotropically tumbling domains which give rise to high-resolution spectra. We have recently developed a technique for simultaneously analyzing broadline and high-resolution signals (M. Bloom, K. T. Holmes, C. E. Mountford, and P. G. Williams, J. Magn. Reson., in press) and we report here its application to a range of rat, mouse, and human cell lines. Some selected features of the NMR spectra were compared with the chemical analysis of the whole-cell lipid. We found that in general the proportion of protons in the narrow methylene resonance at 1.3 ppm increased with the neutral lipid content of the cells. This peak was chosen because its T2 relaxation behavior correlates with metastatic potential in a rat model system. This new technique could be applied to other high-resolution components both in healthy and in diseased states.

Animals↗
PubMed1986

A proteolipid in cancer cells is the origin of their high-resolution NMR spectrum.

High-resolution proton nuclear magnetic resonance studies show that the spectrum of a proteolipid complex, isolated from the serum of patients with malignant diseases, is directly comparable with that obtained from intact cancer cells and solid tumours. These NMR signals have previously been shown to reveal differences between cancer cells with various biological characteristics such as metastatic capacity and drug sensitivity. The proteolipid contains cholesterol, phospholipid, triglyceride, glycolipids, ether-linked lipids, and an apoprotein of unusual electrophoretic mobility. We have yet to confirm the presence of the mRNA reported by others. NMR spectroscopy could be used as a rapid method of identifying the presence of this proteolipid complex in human serum and aiding the diagnosis of malignant disease.

Female↗
PubMed1986

Cell surface involvement in cancer metastasis: an NMR study.

NMR spectroscopy is one of the few techniques which has the sensitivity to detect subtle changes to the surface chemistry of cells. It has previously been demonstrated that high resolution 1H NMR methods can distinguish tumour cells with the capacity to metastasis and this information appears to arise from a type of proteolipid in or attached to the plasma membrane. Here we report that the 1H NMR signal, which we have used to identify metastatic cells in rat tumours, is significantly reduced in intensity after cultured cells are treated with trypsin/EDTA. The long T2 relaxation value (greater than 350 ms) observed in metastatic cells is absent after enzyme treatment. 2D scalar correlated NMR (COSY) spectra of these treated cells show that a cross peak normally associated with malignancy and metastatic disease is markedly reduced. These findings indicate that the plasma membrane lipid particle which generates the high resolution spectrum is directly affected by trypsin/EDTA. Alterations to the cell surface properties were also demonstrated in vivo since reduced numbers of metastases were observed in animals injected with enzyme-treated cells. The correlation between the absence of a long T2 relaxation value and the diminished numbers of metastases in animals suggests that the plasma membrane particle is involved in the metastatic PROCESS.

Adenocarcinoma↗
PubMed1986

Cellular resistance to vinblastine is associated with altered respiratory function.

Human leukaemic T lymphoblasts made resistant to low levels (20-40 ng/ml) of vinblastine have altered respiratory capacity. Cellular oxygen uptake was greater in resistant cells compared with sensitive cells, and vinblastine (40 ng/ml) caused immediate inhibition of oxygen uptake in sensitive cells, but not in resistant cells. Isolated mitochondria reflected the changes observed in the intact cells. Rates of oxidation of cytochrome c, succinate and glutamine were higher in mitochondria from resistant cells and were little affected by challenge with vinblastine, whereas vinblastine at 40 ng/ml was completely inhibitory for sensitive cell mitochondria. Azide inhibited vinblastine efflux from sensitive and resistant cells in both the presence and absence of glucose. Levels of protein, total lipid, free cholesterol and cardiolipin were elevated in vinblastine-resistant lymphoblasts.

Cell Line↗
PubMed1985

Phospholipid and ether linked phospholipid content alter with cellular resistance to vinblastine.

The phospholipid and ether linked phospholipid content of leukaemic lymphocytes alters when the cells become resistant to low levels of the anti-cancer drug, vinblastine. Sphingomyelin and cardiolipin increase, and phosphatidyl ethanolamine and serine decrease in resistant cells. In addition, increases in 1-alkyl-2-acyl phosphatidyl choline and 1-alkenyl-2-acyl-phosphatidyl ethanolamine are concomitant with decreased 1,2-diacyl phosphatidyl choline and ethanolamine. Changes to the ultrastructure of the inner half of the plasma membrane bilayer, as a consequence of drug resistance, are illustrated by freeze-fracture electron microscopy.

Binding Sites↗
PubMed1985

Lipid domain in cancer cell plasma membrane shown by 1H NMR to be similar to a lipoprotein.

Human blood lipoproteins have been characterised by 1H NMR methods and chemical analysis, and comparisons made with the properties of the triglyceride-rich plasma membrane domain found in cancer cells. By means of selective and non-selective T1 experiments, the lipids in HDL and LDL are shown to be in diffusive exchange. In contrast, the lipids of chylomicra and VLDL do not exhibit lipid diffusion, and therefore resemble the neutral lipids of cancer cell plasma membranes. 2D scalar correlated NMR (COSY) spectra of cancer cells or solid tumours are similar to those obtained from VLDL and LDL. The long T2 relaxation value observed for neutral lipid methylenes in metastatic cancer cells (greater than 300 ms) was not observed for any of the 4 lipoproteins studied. None of the lipoprotein classes gave a T2 longer than 250 ms.

Adenocarcinoma↗