The erythroleukaemic K562 cell line and its adriamycin resistant counterpart were used to study resistance, its reversion and their consequences on the levels and localisation of lipids detected in proton nuclear magnetic resonance (NMR) spectra. On whole cells, the mobile lipids giving rise to a NMR signal were significantly decreased in the resistant cells when compared to the sensitive ones; these lipids recovered partially in the reverting cells. According to the spinlattice relaxation times (T1), the lipids detected appeared to be in a similar environment in sensitive and reverting cells. In membrane-enriched fractions, mobile lipid levels were not significantly different in the sensitive and reverting cell lines but decreased in resistant ones. Moreover, lipid droplets stained with a fluorescent Nile red lipophilic probe showed the presence of highly fluorescent particles in the samples in which NMR detected high levels of mobile lipids. These results suggest the participation of cytosolic lipid droplets in NMR signals in drug sensitive and reverting cells and open the question of the relative roles of these droplets and of the membrane lipids in the lipid metabolic pathways associated with drug resistance in cancer cells.

Drug Resistance, Multiple↗

PubMedDate not supplied

Differentiation of the P-gp and MRP1 multidrug resistance systems by mobile lipid 1H-NMR spectroscopy and phosphatidylserine externalization.

We have previously demonstrated that proton NMR spectra of fatty acid chains in erythroleukemia K562 wild-type cells and their MDR1 counterparts show variations related to the phenotype over-expressing the P-glycoprotein (P-gp). Human lung cancer cells whose multidrug resistance (MDR) counterparts over-express the multidrug resistance-associated protein MRP1 have not yet been studied by NMR. Both P-gp and MRP1 belong to the same ATP-binding cassette transporter superfamily. A comparison of NMR spectra from both these multidrug-resistance phenotypes showed that the results previously obtained on the MDR1 family are not valid for MRP1. Furthermore, flow cytofluorimetry studies with external phosphatidylserine labelling showed that P-gp and MRP1 overexpressions have strong but differentiated effects on cell lipid pools.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

[Tracheotomy in a case of tetanus].

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Humans↗

PubMedDate not supplied

Proton NMR spectroscopy of plasma lipoproteins in the experimental Lewis lung carcinoma.

Plasma and fractionated lipoproteins from 40 Lewis Lung Carcinoma grafted mice were tested from the first day up to the fatal issue by biochemical analyses and water suppressed 1H NMR spectroscopy. We have confirmed first, that the 1H NMR spectra of plasma lipoproteins are modified by the tumoral state and could provide a useful marker of the disease as long as they are used for individual follow-up with appropriate spectral parameters. Using fractionated lipoproteins we have demonstrated secondly, that the observed spectral modifications do not result from a specific cancer lipoprotein but from quantitatively modified ratio between Very Light Density Lipoproteins and High Density Lipoproteins.

Animals↗

PubMedDate not supplied

Proton NMR spectroscopy of plasma lipoproteins: a marker of the immune function in cancer disease?

1H-NMR spectroscopy of cancer plasma statistically detects significant narrowing of the methyl and methylene line widths. This change is due to relative increase in light density lipoproteins (VLDL and LDL) compared to heavy density lipoproteins (HDL). This observation had raised great hopes for a simple and universal screening test of cancer patients. Furthermore, the same signal can be observed in the plasma of pregnant women and heart transplanted patients undergoing an immunosuppressive treatment. This signal disappears after child's birth and during graft rejection processes. These observations suggest that the test initially proposed by Fossel in 1986 reveals a specific immunological status developed by the organism in "symbiosis" with "foreign" cells, rather than a cancerous disease.

Adjuvants, Immunologic↗

PubMedDate not supplied

Proton nuclear magnetic resonance spectroscopy of plasma lipoprotein: technical problems and potential interest in cancer disease.

This paper reviews several methods presently available for analysing lipoprotein NMR spectra. Two main steps can be distinguished: NMR signal processing and data analysis. Time domain (wavelet transform) and frequency domain (curve fitting) signal processing methods are compared. Statistical methods of data analysis (Ascending Hierarchical Classification, Correspondence Analysis and Principal Component Analysis) have been tested on simulated NMR data of plasma lipoprotein with different numbers of sampling points and different noise levels. These few examples clearly attest that the NMR approach to complex "mixture" (such as body fluids) analysis is emerging from its infancy. New interest in plasma lipoprotein analysis in cancer biology is finally discussed in the light of previous clinical and experimental results and of understanding of lipid metabolism in cancer.

Humans↗