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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to identify changes in 31P nuclear magnetic resonance (NMR) spectra associated with multiple drug resistance (MDR), a number of wild type and drug-resistant cancer cell lines were studied. The resistant cells included cells selected with various drugs, mainly Adriamycin, as well as cells transfected with the human multidrug resistance gene (MDR1 gene), which encodes P-glycoprotein. In most cases, 31P NMR spectra were significantly different from those of parental, drug-sensitive lines. The spectra of resistant cells generally indicated increased levels of ATP and phosphocreatine in the cytoplasm. These changes are compatible with the increased glucose utilization rate previously described for resistant cells. Major changes were also observed in the levels of glycerophosphocholine and glycerophosphoethanolamine. Changes in cellular metabolism reflected by 31P NMR spectra depend on the drug used to select the cells for MDR. The direction of these changes was not consistent for all cell lines studied and could not be directly attributed to expression of P-glycoprotein, suggesting that the changes may be related to alterations in metabolism and membrane function associated with other mechanisms of MDR. The results demonstrate the suitability of 31P NMR for studies of biochemical changes associated with MDR. The toxicity of 2-deoxyglucose, a glucose antimetabolite, was investigated in addition to the NMR studies and was found to be consistently higher in multidrug-resistant cells than in the parental drug-sensitive lines. For MCF-7 breast cancer cells, where several sublines with different levels of resistance were available, the toxicity was highest for the most resistant lines.
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PMID:The multidrug resistance phenotype: 31P nuclear magnetic resonance characterization and 2-deoxyglucose toxicity. 199 55

The glycolytic inhibitor 2-deoxyglucose (2-DG) was tested as a potential chemotherapeutic agent for drug-resistant cancer cells. Previously it was found that Adriamycin-resistant human MCF-7 breast cancer cells (ADR) exhibit an enhanced rate of glycolysis compared to their parent wild-type (WT) cell line (R. C. Lyon et al., Cancer Res., 48: 870-877, 1987). We now describe a specific toxic effect of 2-DG on the ADR cells, which is more than 15-fold greater than for WT cells. Using 31P magnetic resonance spectroscopy of perfused MCF7 cells we continuously monitored the accumulation of 2-deoxyglucose 6-phosphate together with concomitant changes in other phosphate-containing metabolites. Kinetic measurements demonstrated that ADR cells accumulated 2-deoxyglucose 6-phosphate faster and to a greater extent than WT cells, while their depletion of high energy compounds (ATP, phosphocreatine) was more pronounced and became irreversible earlier. The phosphorylation of 2-DG could be followed more effectively by the use of 13C magnetic resonance spectroscopy of 2-DG enriched with 13C at C-6, since the signals of 2-DG and 2-deoxyglucose 6-phosphate are clearly resolved and, unlike 31P magnetic resonance spectroscopy, there are no other interfering signals. With the use of this technique with ADR and WT cells the rate of phosphorylation of 2-DG was found to be 11.2 x 10(-4) and 6.5 x 10(-4) mmol/min/mg protein, respectively. The results of these studies indicate that differences in the biochemistry of energy metabolism of resistant cells may make them targets for energy antimetabolites.
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PMID:Effects of 2-deoxyglucose on drug-sensitive and drug-resistant human breast cancer cells: toxicity and magnetic resonance spectroscopy studies of metabolism. 229 96

Combined analysis of both 1H and 31P NMR spectra of extracts of drug-sensitive and multidrug-resistant MCF-7 human breast cancer cells enabled quantitative comparisons between the concentrations of major metabolites, as well as of their precursors. In resistant cells high energy phosphorus compounds, phosphocreatine and ATP, and also their precursors, creatine and ADP, were elevated compared to the sensitive cells. In phospholipid metabolism, the sensitive cells showed higher phosphocholine and phosphoethanolamine concentrations than the resistant cells, but choline levels were similar. These results delineated the differences in control of metabolic pathways between drug-sensitive and drug-resistant cells.
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PMID:Information from combined 1H and 31P NMR studies of cell extracts: differences in metabolism between drug-sensitive and drug-resistant MCF-7 human breast cancer cells. 235 12

The effects of 17 beta-estradiol treatment versus tamoxifen on the metabolism of human breast cancer T47D-clone 11 cells were studied by noninvasive 31P and 13C nuclear magnetic resonance techniques. 31P nuclear magnetic resonance spectra revealed differences between estrogen and tamoxifen treated cells. The steady state content of phosphorylcholine and of the nucleoside diphosphates was higher in the tamoxifen treated cells by 33 and 140%, respectively, relative to estrogen treated cells. The intracellular pH of 7.2 and the content of the nucleoside triphosphates, Pi, phosphocreatine, glycerolphosphorylcholine, and glycerolphosphorylethanolamine and uridine diphosphoglucose remained the same in both treatments. Glucose utilization and subsequent lactate, glutamate, alanine, and glycerol 3-phosphate synthesis were monitored on line following administration of specifically labeled [13C]glucose. In estrogen treated cells the rate of lactate production via glycolysis was 560 fmol/cell/h and the initial rate of 13C labeling of the glutamate pool via the Krebs cycle was 6.8 fmol/cell/h. In the tamoxifen treated cells these rates were 2-fold lower, at 250 and 2.9 fmol/cell/h for lactate and glutamate labeling, respectively. In estrogen treated cells, the calculated content of glutamate (19 fmol/cell), alanine (11 fmol/cell), and glycerol 3-phosphate (8 fmol/cell) was higher than in tamoxifen treated cells, where only glutamate labeling was detected (13 fmol/cell). The observed differences in the in vivo kinetics of glucose metabolism may provide a sensitive measure for detecting the response of human breast cancer cells to estrogen versus tamoxifen treatments.
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PMID:Metabolic studies of estrogen- and tamoxifen-treated human breast cancer cells by nuclear magnetic resonance spectroscopy. 256 27

A recently developed method for image-selected localized hydrogen-1 magnetic resonance (MR) spectroscopy was assessed in the differential diagnosis of nine primary and secondary cerebral tumors, including four gliomas, two meningiomas, one neurilemoma, one arachnoid cyst, and one metastasis of breast cancer. Well-resolved H-1 MR spectra of these tumors were obtained in vivo with a conventional 1.5-T whole-body MR imaging system. All tumor spectra were remarkably different from spectra from normal brain tissue. Spectra obtained from different tumors exhibited reproducible differences, while histologically similar tumors yielded characteristic spectra with only minor differences. The observed spectral alterations reflect variations in concentrations and relaxation times of the H-1 MR sensitive pool of free (mobile) metabolites within the tissues. In most cases, the concentrations of N-acetyl-aspartate and creatine/phosphocreatine are reduced below detectability, whereas choline-containing compounds are generally enhanced. The spectral differences between the tumors are mainly due to the differing concentrations of lipids, lactic acid, and carbohydrates. Localized H-1 MR spectroscopy may become an important clinical tool for the differentiation of tumors as well as for therapeutic control.
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PMID:Noninvasive differentiation of tumors with use of localized H-1 MR spectroscopy in vivo: initial experience in patients with cerebral tumors. 274 10

To assess the potential of in vivo magnetic resonance (MR) spectroscopy for breast cancer, hydrogen-1 and phosphorus-31 MR spectra of five malignant human breast tumors were compared with those of unaffected breast tissue. The water-to-fat ratio was high in the tumors (average, 2.2) but low in the unaffected tissue (average, 0.3). The P-31 spectrum of normal breast tissue showed low levels of phosphomonoesters (PMEs), inorganic phosphate, phosphodiesters (PDEs), and ATP. In addition, an intense phosphocreatine (PCr) signal was observed in breast tissue of young women: The relative intensities of the PCr and ATP signals had a mean value of 1.9. The tumor spectrum showed elevated levels of PMEs, Pi, and PDEs, while no PCr was seen (PCr/ATP less than 0.2). In two breast cancers treated with radiation therapy, resulting in a decrease of tumor volume of more than 50%, a similar change in the tumor P-31 spectrum was observed: An intense PCr signal developed (PCr/ATP = 1.1). Control experiments indicated that the appearance of PCr after radiation therapy was the result of a radiation-induced metabolic change in the tumor itself.
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PMID:Human breast cancer in vivo: H-1 and P-31 MR spectroscopy at 1.5 T. 284 30

The concentration of phosphates and the kinetics of phosphate transfer reactions were measured in the human breast cancer cell line, T47D, using 31P-NMR spectroscopy. The cells were embedded in agarose filaments and perifused with oxygenated medium during the NMR measurements. The following phosphates were identified in spectra of perifused cells and of cell extracts: phosphorylcholine (PC), phosphorylethanolamine (PE), the glycerol derivatives of PC and PE, inorganic phosphate (Pi), phosphocreatine (PCr), nucleoside triphosphate (primarily ATP) and uridine diphosphate glucose. The rates of the transfers: PC----gamma ATP (0.2 mM/s), Pi----gamma ATP (0.2 mM/s) and the conversion beta ATP----beta ADP (1.3 mM/s) were determined from analysis of data obtained in steady-state saturation transfer and inversion recovery experiments. Data from spectrophotometric assays of the specific activity of creatine kinase (approx. 0.1 mumol/min per mg protein) and adenylate kinase (approx. 0.4 mumol/min per mg protein) suggest that the beta ATP----beta ADP rate is dominated by the latter reaction. The ratio between the rate of ATP synthesis from Pi and the rate of consumption of oxygen atoms (4 X 10(-3) mM/s) was approx. 50. This high value and preliminary measurements of the rate of lactate production from glucose, indicated that aerobic glycolysis is the main pathway of ATP synthesis.
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PMID:31P-NMR studies of phosphate transfer rates in T47D human breast cancer cells. 362 May 15

31P magnetic resonance spectra of perfused human breast cancer cells with the phenotype of pleiotropic drug resistance exhibit striking differences in the levels of phosphate metabolites from the wild-type, drug-sensitive parent cell line. Resistant cells demonstrated elevated levels of phosphocreatine and depressed levels of phosphomonoesters, phosphodiesters, and diphosphodiesters. These differences may reflect significant alterations in the control of bioenergetic metabolism between drug-resistant and -sensitive cells.
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PMID:Differences in phosphate metabolite levels in drug-sensitive and -resistant human breast cancer cell lines determined by 31P magnetic resonance spectroscopy. 373 Oct 76

We have used 31P- and 13C-nuclear magnetic resonance spectroscopy to measure key metabolite levels and fluxes through enzymes regulating phospholipid and mitochondrial metabolism in normal human mammary epithelial cells. We have compared these values to those found in a progression series of breast cancer cell lines of varying metastatic potential established from a single patient. We find a 16-19-fold increase in phosphocholine content in two primary breast cancer cell lines (21PT and 21NT) and a 27-fold increase in phosphocholine content in the metastatic breast cancer cell line (21MT-2) compared with the normal breast epithelial cell strain 76N. Thus, phosphocholine may serve as a metabolic marker for the human breast cell progression state. A 30% decrease in ATP levels, a 83% decrease in phosphocreatine levels, along with a 2-fold increase in NAD(+) + NADH levels in 21PT, 21NT, and 21MT-2 cells compared to the normal breast cells further suggests impaired mitochondrial metabolism in the breast carcinoma cell lines. Consistent with this suggestion is our finding that the primary breast cancer cell lines (21PT and 21NT) and the metastatic breast cell line (21MT-2) showed a 50 and 89% relative reduction, respectively, in the flux of pyruvate utilized for mitochondrial energy generation compared to pyruvate utilized to replenish tricarboxylic acid cycle intermediates. These results demonstrate that diminished mitochondrial energy generation may be quantitatively related to the progression state of human breast cells.
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PMID:Pyruvate utilization, phosphocholine and adenosine triphosphate (ATP) are markers of human breast tumor progression: a 31P- and 13C-nuclear magnetic resonance (NMR) spectroscopy study. 758 61

The effect of estrogen withdrawal on energy metabolism was studied in four human breast cancer xenografts: the estrogen-dependent MCF-7 and ZR75-1 and the estrogen-independent ZR75/LCC-3 and MDA-MB-231. The tumors were grown in ovariectomized nude mice with a s.c. implanted estrogen pellet. After Gompertzian growth was verified, the estrogen pellet was removed from half of the animals. In vivo 31P magnetic resonance spectroscopy of the tumors was performed 1 day before and on days 2, 6, and 14 after estrogen removal. Estrogen withdrawal induced a significant increase in the nucleoside triphosphate:Pi ratio in the two estrogen-dependent xenografts, whereas this ratio remained unchanged in the estrogen-independent tumors. In ZR75/LCC-3 tumors a slight decrease in nucleoside triphosphate:Pi was observed following onset of estrogen stimulation after initial growth without estrogen. Extracts of freeze-clamped tumors prepared 14 days after estrogen removal were analyzed for ATP and phosphocreatine content. Our findings suggest a correlation between estrogen withdrawal and the steady-state concentrations of ATP, phosphocreatine, and Pi in human breast cancer xenografts. Discrimination analysis of the pretherapeutic spectra enabled us to identify the tumor line and the estrogen dependence of the tumors in 80-90% of all cases.
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PMID:Effect of estrogen withdrawal on energy-rich phosphates and prediction of estrogen dependence monitored by in vivo 31P magnetic resonance spectroscopy of four human breast cancer xenografts. 771 72


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