George L. May

Proteolipid identified by magnetic resonance spectroscopy in plasma of a patient with borderline ovarian tumour

Magnetic resonance spectroscopy (MRS) can identify abnormal lipoproteins in the plasma of patients with premalignant and malignant tumours. Proteolipid complexes, 8-11 nm and 25-28 nm in size, were isolated from the plasma of a patient with a borderline ovarian tumour. These complexes, which generated a characteristically long MRS T2 relaxation value (greater than 400 ms), were disrupted by ribonuclease. None of the conventional lipoproteins had a T2 value above 160 ms. Chemical analysis of the proteolipid complexes showed a 20% glycolipid component, and MRS identified a fucosylated molecule as the origin of the long T2 value. 9 months after resection of all tumour, a visible lipoprotein band, possibly lipoprotein (a), persisted in the plasma but neither the long T2 relaxation value nor the 8-11 nm or 25-28 nm particles were present. The long T2 relaxation value in the MRS profile, found in isolated proteolipid and unfractionated plasma and serum of other patients with carcinoma of the ovary and colon, provides a non-invasive method of assaying for cancer.

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.

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 T 1 experiments, the lipids in HDL and LDL are shown to be in diffusive exchange. In contrast, the lipids ofchylomicra 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 T 2 relaxation value observed for neutral lipid methylenes in metastatic cancer cells (>00 ms) was not observed for any of the 4 lipoproteins studied. None of the lipoprotein classes gave a T 2 longer than 250 ms.

Two-Dimensional Proton Magnetic Resonance Spectroscopy for Tissue Characterization of Thyroid Neoplasms

Abstract. We have previously demonstrated that one dimensional (1D) proton ( 1 H) magnetic resonance spectroscopy (MRS) can distinguish normal thyroid tissue from thyroid carcinoma using a spectral ratio of peak intensity at 1.7 ppm/0.9 ppm. Two dimensional (2D) 1 H-MRS allows identification of specific molecules that have overlapping peaks in the 1D-MR spectrum. Specimens from 93 consecutive thyroid nodules were examined using 2D 1 H-MRS on a Bruker AM-360 wide-bore spectrometer. There was a progressive increase in lipid cross peaks assigned to di-/triglycerides when comparing colloid/hyperplastic nodules to follicular adenoma, and adenoma to carcinoma. A specific cross peak attributable to cholesterol/cholesteryl esters was commonly seen in carcinomas. In contrast, two unassigned cross peaks unique to the thyroid were more prevalent in benign lesions. There was an overall increase in cross peaks attributable to cell surface fucosylation in carcinoma when compared to benign lesions, although the fucose spectral pattern was not specific for cancer. On this basis, a spectral ratio of peak intensity at 2.05 ppm/0.9 ppm more clearly distinguished benign follicular adenoma from carcinoma. 2D 1 H-MRS thus identifies chemical changes that allow more specific tissue characterization of thyroid neoplasms.

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 metastasise 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 T 2 relaxation value (⪢ 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 T 2 relaxation value and the diminished numbers of metastases in animals suggests that the plasma membrane particle is involved in the metastatic process.

GMP-140 (P-selectin) inhibits human neutrophil activation by lipopolysaccharide: Analysis by proton magnetic resonance spectroscopy

Proton magnetic resonance spectroscopy has been used to monitor the effect of GMP-140 on the stimulation of human peripheral blood neutrophils. Stimulation of neutrophils by lipopolysaccharide gives rise to a high resolution lipid spectrum from the intact cells. Fluid phase GMP-140, which prevents adhesion and development of inflammatory responses of neutrophils, was found to inhibit these changes in the lipid spectrum by up to 40%. Anti-GMP-140 Fab fragments reversed this effect while non-immune Fab fragments did not affect the observed inhibition by GMP-140.

Vinblastine sensitivity of leukaemic lymphoblasts modulated by serum lipid

The high‐resolution proton magnetic resonance spectrum of leukaemic lymphoblasts is characteristic of neutral lipid in an isotropic environment. When such lymphoblasts are selected for resistance to the anticancer drug vinblastine, the intensity of this spectrum increases with increasing drug resistance. A reversal of this trend can be achieved by growing cells in delipidated serum, whereby lipid spectrum and drug resistance are diminished. However, both can be restored by subsequent regrowth in normal medium. Thus, although detectable genetic changes accompany the development of vinblastine resistance, the expression of these changes can be modulated by environmental lipid.