1H magnetic resonance spectroscopy metabolites as biomarkers for cell cycle arrest and cell death in rat glioma cells

Mirbahai, Ladan; Wilson, Martin; Shaw, Christopher S.; McConville, Carmel; Malcomson, Roger D. G.; Griffin, Julian L.; Kauppinen, Risto A.; Peet, Andrew C.

doi:10.1016/j.biocel.2010.07.002

Cited by 35 publications

(35 citation statements)

References 32 publications

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“…The above changes translate into clear decreases in the PC/GPC and PC/Cho ratios ( Figure 5), the former having been related to cell growth arrest prior to apoptosis. 48 The distinctly different signature observed for MTX comprises a more marked decrease in PC than for DOX, reflecting a further decrease in PTC synthesis, and no meaningful changes in GPC or Cho (no significant membrane breakdown) in accordance with reports on MTX-treated breast cancer cells 25 and imatinib-treated leukemia cells. 49 These changes originate steadier decreases for PC/GCP and PC/Cho (Figure 5b), which establish a clear signature for MTX reflecting lower PTC synthesis (as for DOX) without concomitant membrane degradation (contrary to DOX).…”

Section: Journal Of Proteome Researchsupporting

confidence: 84%

Metabolic Markers of MG-63 Osteosarcoma Cell Line Response to Doxorubicin and Methotrexate Treatment: Comparison to Cisplatin

Lamego

Duarte

Marques³

et al. 2014

J. Proteome Res.

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A high resolution magic angle spinning NMR metabolomics study of the effects of doxorubicin (DOX), methotrexate (MTX) and cisplatin (cDDP) on MG-63 cells is presented and unveils the cellular metabolic adaptations to these drugs, often used together in clinical protocols. Although cDDP-treated cells were confirmed to undergo extensive membrane degradation accompanied by increased neutral lipids, DOX-and MTX-treated cells showed no lipids increase and different phospholipid signatures, which suggests that (i) DOX induces significant membrane degradation, decreased membrane synthesis, and apparent inhibition of de novo lipid synthesis, and (ii) MTX induces decreased membrane synthesis, while no membrane disruption or de novo lipid synthesis seem to occur. Nucleotide signatures were in apparent agreement with the different drug action mechanisms, a link having been found between UDPGlcNAc and the active pathways of membrane degradation and energy metabolism, for cDDP and DOX, with a relation to oxidative state and DNA degradation, for cDDP. Correlation studies unveiled drug-specific antioxidative signatures, which pinpointed m-and s-inositols, taurine, glutamate/ glutamine, and possibly creatine as important in glutathione metabolism. These results illustrate the ability of NMR metabolomics to measure cellular responses to different drugs, a first step toward understanding drug synergism and the definition of new biomarkers of drug efficacy.

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Section: Journal Of Proteome Researchsupporting

confidence: 84%

Metabolic Markers of MG-63 Osteosarcoma Cell Line Response to Doxorubicin and Methotrexate Treatment: Comparison to Cisplatin

Lamego

Duarte

Marques³

et al. 2014

J. Proteome Res.

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“…Two other studies in adult gliomas did not find a correlation between total choline and Ki67 [27,28]. The reason for these conflicting results has been postulated to be that PCh and GPC both contribute to total choline but it is the ratio PCh/GPC which is related to tumour growth [46,47]. In the current study, a positive correlation was found between Ki67 and PCh but not GPC, supporting this assertion.…”

Section: Discussionsupporting

confidence: 73%

Metabolite Levels in Paediatric Brain Tumours Correlate with Histological Features

Orphanidou-Vlachou

Kohe²,

Bründler³

et al. 2018

Pathobiology

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Aims: Metabolite levels can be measured non-invasively using in vivo ¹H magnetic resonance spectroscopy (MRS). These tumour metabolite profiles are highly characteristic for tumour type in childhood brain tumours; however, the relationship between metabolite values and conventional histopathological characteristics has not yet been fully established. This study systematically tests the relationship between metabolite levels detected by MRS and specific histological features in a range of paediatric brain tumours. Methods: Single-voxel MRS was performed routinely in children with brain tumours along with the clinical imaging prior to treatment. Metabolites were quantified using LCModel. Histological features were assessed semi-quantitatively for 27 children on H&E and immunostained slides, blind to the metabolite values. Statistical analysis included 2-tailed independent-samples t tests and 2-tailed Spearman rank correlation tests. Results: Ki67, cellular atypia, and mitosis correlated positively with choline metabolites, and phosphocholine in particular. Apoptosis and necrosis were both associated with lipid levels, with the relationship dependent on the use of long or short echo time MRS acquisitions. Neuronal components correlated negatively and glial components positively with N-acetyl-aspartate. Glial components correlated positively with myoinositol. Conclusion: Metabolite levels in children's brain tumours measured by MRS are closely associated with key histological features routinely assessed by histopathologists in the diagnostic process. This further elucidates our understanding of this important non-invasive diagnostic tool and strengthens our understanding of the relationship between metabolites and histological features.

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“…Using 31 P MRSI, it is possible to determine 1) phospholipid cell membrane turnover, as one of the major indicators for tumor growth, by quantifying concentrations of glycerophosphocholine (GPC), phosphocholine (PCho), glycerophosphoethanolamine (GPE), and phosphoethanolamine (PEth); and 2) cellular energy status, by quantifying concentrations of inorganic phosphate (Pi), phosphocreatine (PCr), and ATP, and by determining intracellular pH. Studies on tumor models in cell culture showed decreased PCho and increased GPC concentrations upon treatment with antimitotic drugs, a modification not visible using the integrated 1 H Cho signal used in standard MR spectroscopy (20)(21)(22). 31 P MRSI offers the discrimination between two cholinecontaining compounds and adds their ethanolamine analogues PEth to the detectable parameters, providing a much more comprehensive characterization of lipid membrane metabolism compared to 1 H MRSI (23).…”

Section: Introductionmentioning

confidence: 99%

Intratumoral Concentrations and Effects of Orally Administered Micellar Curcuminoids in Glioblastoma Patients

Dützmann

Schiborr

Kocher

et al. 2016

Nutrition and Cancer

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1H magnetic resonance spectroscopy metabolites as biomarkers for cell cycle arrest and cell death in rat glioma cells

Cited by 35 publications

References 32 publications

Metabolic Markers of MG-63 Osteosarcoma Cell Line Response to Doxorubicin and Methotrexate Treatment: Comparison to Cisplatin

Metabolic Markers of MG-63 Osteosarcoma Cell Line Response to Doxorubicin and Methotrexate Treatment: Comparison to Cisplatin

Metabolite Levels in Paediatric Brain Tumours Correlate with Histological Features

Intratumoral Concentrations and Effects of Orally Administered Micellar Curcuminoids in Glioblastoma Patients

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