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At least 973 records · Page 54Linked to original sources
PubMed1989

Extraction of intracellular nucleosides and nucleotides with acetonitrile.

Extraction of intracellular nucleosides and nucleotides with acetonitrile (ACN) and water was compared with extraction with 60 g/L perchloric acid (PCA), followed by neutralization with KOH, 1 mol/L. Freshly isolated rat bone-marrow and intestinal cells were incubated with radiolabeled 5-fluorouracil (FUra) and 5-fluorodeoxyuridine. The ribose and deoxyribose nucleosides and nucleotides of FUra, and ADP and ATP in the soluble extracts were separated by HPLC and measured by scintillation counting or ultraviolet absorbance. The insoluble precipitates were digested in 1 mol/L NaOH and analyzed for the radioactive macromolecule-bound nucleotides. Both extraction methods yielded the same total (i.e., soluble and insoluble) amount of radioactivity. However, the ACN method yielded significantly more FUra nucleosides and triphosphate nucleotides and ATP in the soluble fraction, and more proteins and macromolecule-bound nucleotides in the insoluble fraction. In the PCA method, the soluble fraction contained more monophosphate nucleotides and ADP than in the ACN method. The PCA extraction procedure promoted decomposition of ATP to ADP and interfered with the ion-pairing reversed-phase HPLC assay. The ACN extraction is faster (less than 5 min) than the PCA extraction (greater than 10 min). Moreover, the ACN in the soluble extract fraction can be removed by evaporation and thus does not interfere with the HPLC analysis. Thus the ACN method evidently is suitable for extraction of nucleosides and nucleotides.

Acetonitriles↗
PubMed1998

1H MRS markers of tumour growth in intrasplenic tumours and liver metastasis induced by injection of HT-29 cells in nude mice spleen.

We have characterized, by in vitro magnetic resonance spectroscopy (MRS), the metabolite pattern of perchloric acid (PCA) extracts of intrasplenic tumours and hepatic metastasis, produced by intra-spleen injection of the human colorectal carcinoma cell line HT-29 and its metastatic variant HT-29 MMM into nude mice. Our aim was to gain further understanding of colorectal tumour metabolism as a basis for future in vivo studies of human colon cancer by 1H MRS. Metabolite PCA extract analysis showed a good reproduction of the spectral pattern observed in human primary colon tumours, while they were very different from the spectral pattern of the host tissues (spleen and liver). The main differences between host and tumour tissues involved taurine, phosphocholine (PC), phosphoethanolamine (PE), creatine, glycogen and glucose. Creatine is the most promising marker to follow tumour growth because of its practical absence in the nude mice host tissues. Detection of variable levels of this compound and of taurine in hepatic foci in man, are suggested as possible diagnostic markers. No correlation could be found between spectral pattern differences and the different ability to metastasize of the two HT-29 cell lines used. Furthermore, indirect evidence for a functional link between taurine and myo-inositol in colon tumour cells is presented. In summary, our data suggest that the nude mice model may be a suitable system for the MRS study of the changes taking place in host tissues upon tumour progression.

Animals↗
PubMed1969

Control of respiration and metabolism in growing Klebsiella aerogenes. The role of adenine nucleotides.

1. A rapid-sampling technique was used to obtain perchloric acid extracts of cells growing in a chemostat culture, so that meaningful values for ATP content could be obtained in spite of the fact that the turnover time for the total ATP content was about 1sec. 2. For steady-state growth, it was found that, in a glucose-limited chemostat culture, the ATP/ADP concentration ratio was approximately constant with changes in dissolved-oxygen tensions above the critical value, but fell when the culture was grown under oxygen-limited conditions and was at a minimum in anaerobically grown cultures. The steady-state ATP content was lower in cells growing under nitrogen-limited conditions with glucose in excess than in glucose-limited cells. The steady-state ATP content was independent of growth rate at growth rates over 0.1hr.(-1). 3. When the respiration rate of the cells was stimulated by lowering the oxygen tension the ATP content did not increase, indicating either an increased turnover rate of ATP or a fall in the P/O ratio. The sudden addition of extra glucose or succinate to a glucose-limited culture increased the respiration rate of the cells, but the ATP content quickly returned to the steady-state value after initial perturbations. This control over ATP content is explained in terms of regulation by adenine nucleotides of the catabolism and anabolism of glucose. An exception to this control over ATP content was found when the respiration rate was stimulated by addition of an antifoam.

Adenine Nucleotides↗
PubMed1997

Fructose-3-phosphate production and polyol pathway metabolism in diabetic rat hearts.

Previous studies have suggested that polyol-pathway and nonenzymatic glycation may be involved in the development of cardiac myopathy, a well-known manifestation of diabetes. Although the exact etiology of this complication is not fully understood, it is likely to be multifactorial. In this study, we investigated the metabolic consequences of diabetes and the effect of aldose reductase inhibitor (ARI) treatment on cardiac tissues of Sprague-Dawley rats. Perchloric acid (PCA) extracts of hearts from the animals were examined using 31P-nuclear magnetic resonance (NMR), gas chromatography/mass spectrometry (GC/MS), and high-performance liquid chromatography (HPLC). In 31P-NMR spectra of diabetic animals, a peak resonating at the chemical shift of 5.8 ppm with a coupling constant of 10 Hz was identified as fructose-3-phosphate (F3P). Undetectable in controls (< approximately 20 nmol/g), this metabolite was present at a concentration of 81.3 +/- 16.3 nmol/g wet weight (n = 4) in diabetic rat hearts. GC/MS analysis of these extracts from diabetics also identified a decomposition product of F3P, 3-deoxyglucosone (3DG), at a concentration of 9.4 +/- 3.5 nmol/g (n = 3), compared with 0.98 +/- 0.43 nmol/g (n = 3) in controls. No evidence was found for the expected detoxification products of 3-DG, 3-deoxyfructose and 2-keto 3-deoxygluconate. Concomitant with the elevation of F3P and 3DG, fructose and sorbitol levels were also elevated in diabetic animals. Surprisingly, ARI treatment was found to have no effect on the levels of these metabolites. These data suggest that either the heart may be unique in its production of fructose or it may not readily transport the ARI sorbinil. Production of the potent glycating agents F3P and 3DG in diabetics suggests that these compounds may be contributing factors in the glycation of cardiac proteins in the diabetic rat heart.

Administration, Oral↗
PubMed2003

Metabolite changes in BT4C rat gliomas undergoing ganciclovir-thymidine kinase gene therapy-induced programmed cell death as studied by 1H NMR spectroscopy in vivo, ex vivo, and in vitro.

Programmed cell death was induced by HSV-tk gene therapy in rat BT4C glioma cells, and metabolite changes associated with cell damage were monitored in vivo by 1H NMR spectroscopy and ex vivo by high resolution magic angle spinning (HRMAS) 1H NMR, and in vitro in perchloric acid extracts of tumors. Metabolite concentrations, as quantified in vivo using water as an internal reference and in vitro in extracts, were correlated with cell density. The results showed that both in vivo and in vitro glycine and creatine concentrations followed volume-averaged cell density, whereas that of total choline-containing compounds was unaffected by a cell loss approaching 60%. Meanwhile, both saturated and unsaturated 1H NMR visible lipids increased. HRMAS 1H NMR spectroscopy of the tumor samples at 14.1 tesla demonstrated the presence of nucleotide peaks from adenosine and uridine nucleotides in glioma samples ex vivo. The assignment of a doublet at 7.95 ppm to UDP was confirmed by spiking experiments of tumor extracts in conjunction with 1H and 31P NMR spectroscopy. HRMAS also resolved the choline-containing peak at 3.2 ppm in vivo into resonances from choline (3.20 ppm), phosphocholine (3.22 ppm), glycerophosphocholine (3.24 ppm), and taurine (3.26 ppm). These resonances were uncorrelated with temporal progression through programmed cell death. Our results show that 1H NMR-detected lipids and some of the small molecular weight metabolites respond to gene therapy. However, the choline-containing compounds are unaffected by severe decline in cell density. The latter observation supports the idea that triacylglycerols, rather than membrane phospholipids, are the key components of 1H NMR visible lipids, and it also casts doubt on the validity of resonance of choline-containing compounds as a diagnostic marker of programmed cell death in vivo.

Animals↗
PubMed1984

P-31 nuclear magnetic resonance analysis of brain: II. Effects of oxygen deprivation on isolated perfused and nonperfused rat brain.

Phosphatic metabolite (perchloric acid extractable) concentrations of cerebral tissues were analyzed by phosphorus-31 nuclear magnetic resonance (P-31 NMR) spectroscopy following external perfusion of the isolated rat brain (30 min or 60 min) under the following conditions: (a) constant perfusion pressure with either fluorocarbon- or erythrocyte-based medium, and (b) constant perfusate flow rate (3 ml/min) with the erythrocyte-based medium. Metabolite concentrations of control perfused brains were compared with those in nonperfused controls to provide a basis for detecting any qualitative or quantitative changes in cerebral metabolite composition. Metabolic responses of perfused brains to ischemia (incomplete ischemia, 83% reduction in flow for 10 min; transient complete ischemia for 1.5 or 2 min) were evaluated immediately after the ischemic episode and at selected time points during reperfusion (3 and 15 min). Alterations in cerebral metabolite levels induced by hypoxia were analyzed using a nonperfused rat brain model. Irrespective of the perfusion method employed, the phosphatic metabolites of control perfused rat brains were identical quantitatively to those of the nonperfused controls. Cerebral ischemia resulted in significantly increased levels of ADP, AMP + IMP, Pi, fructose 1,6-diphosphate, and glycerol 3-phosphate (global ischemia only), whereas ATP and phosphocreatine (PCr) levels declined significantly. The magnitude of these changes varied with the severity of the ischemia; however, following 15 min of control reperfusion metabolite levels had reverted to preischemic values. Significant perturbations in tissue phosphoethanolamine (3.84 delta resonance) content were evident at various time points during ischemia and postischemic recovery, which varied according to the perfusion conditions. In contrast to the changes observed in response to ischemia, hypoxia affected only cerebral high-energy phosphate levels. ATP and PCr levels were reduced, while a concomitant, essentially equimolar, increase in Pi and ADP was observed. The present studies indicate that in terms of phosphatic metabolites, the control equilibrated isolated perfused rat brain is quantitatively and qualitatively indistinguishable from the nonperfused rat brain in vivo regardless of the perfusion conditions (constant flow versus constant pressure). The metabolic responses to ischemia and hypoxia, as measured by P-31 NMR, were consistent with the pattern of changes reported elsewhere. Overall, P-31 NMR spectroscopic evaluation of the intact rat brain provides a potential experimental context for dynamic measures of cerebral metabolism under exogenously controlled conditions. Th

Animals↗
PubMed1984

Metabolic status of fresh v eye-bank-processed corneas. A phosphorus nuclear magnetic resonance study.

The concentrations of corneal phosphatic metabolites in fresh and eye-bank-processed corneas were measured by phosphorus 31 nuclear magnetic resonance of perchloric acid corneal extracts to determine whether metabolic differences exist between these two corneal preparations. Cat corneas were prepared using an eye-bank protocol, including specular microscopic examination and transport to a distant location. Fresh cat corneas were used as controls. The hexose 6-phosphate resonance band, the nucleoside monophosphate band, the phosphodiesters, and adenosine triphosphate of eye-bank-processed corneas were significantly decreased relative to fresh control corneas. Phosphatic metabolites that significantly increased relative to control corneas included inorganic orthophosphate and phosphocreatine. A calculated corneal tissue-energy index was significantly decreased for eye-bank-processed corneas relative to control. This decline demonstrates a compromise in the metabolic energy status of the tissue and is indicative of a diminished ability of the cornea to maintain its complement of high-energy phosphates.

Adenosine Triphosphate↗
PubMed1997

Column-switching high-performance liquid chromatography combined with ionspray tandem mass spectrometry for the simultaneous determination of the platelet inhibitor Ro 44-3888 and its pro-drug and precursor metabolite in plasma.

A liquid chromatographic/mass spectrometric (LC/MS) assay was developed for the simultaneous determination of a pro-drug (Ro 48-3657), its active metabolite (platelet inhibitor, Ro 44-3888) and precursor metabolite (Ro 48-3656) in human, dog and rat plasma, utilizing on-line column-switching solid-phase extraction (SPE) for clean-up and high-performance liquid chromatography (HPLC) for separation of the analytes, with on-line detection by ionspray (pneumatically assisted electrospray) tandem mass spectrometry in the selected reaction monitoring (SRM) mode. The assay was validated for the quantification of all three analytes. The method involves protein precipitation with perchloric acid, enrichment of the analytes on a standard bore trapping column (i.d. 4.6 mm) and separation on a narrow-bore analytical column (i.d. 2 mm). Except for the plasma precipitation step, the assay was fully automated, allowing unattended operation. The lower limits of quantification were 0.20 ng ml-1 (Ro 48-3657, Ro 44-3888) and 0.50 ng ml-1 (Ro 48-3656) using a 0.5 ml plasma aliquot. The mean inter-assay precision and accuracy derived from quality control samples were 5.3% and 101%, respectively, utilizing the calibration range 0.2-200 ng ml-1. Using the unique features of column-switching HPLC combined with MS/MS, it was possible to develop the method in a short period of time. The method has been successfully applied to map complete concentration-time courses for the kinetic evaluation of the drug and its metabolites in man, dog and rat. This LC/MS assay is sensitive, specific, accurate, precise and robust.

Amidines↗
PubMed2000

Quantitative determination of alpha-cyclodextrin in human plasma by liquid chromatography/positive ion electrospray mass spectrometry.

A sensitive and selective method for the determination of alpha-cyclodextrin in human plasma is described using beta-cyclodextrin as an internal standard. After protein precipitation with perchloric acid, the analytes were isolated from human plasma by solid-phase extraction on Bond Elut C18 cartridges. The compounds were chromatographed on a narrow-bore aminopropyl column (125 x 2 mm i.d., 5 microm) and analyzed by electrospray ionization mass spectrometry in the positive selected-ion mode using the [M+NH4]+ ion. The lower limit of quantitation was 5 ng ml(-1) of human plasma. Linear calibration curves were obtained over the concentration range 5-1000 ng ml(-1) of human plasma. The intra- and inter-assay precisions were <18% and the accuracy was <10.5% over the entire concentration range. During the method development, the ionization efficiencies of the analytes in plasma samples originating from different sources were examined to overcome the matrix effect problems caused by co-eluting endogenous compounds. The method was successfully applied to pharmacokinetic studies in human volunteers.

Blood Chemical Analysis↗
PubMed1997

Beta-thymosins from marine invertebrates: primary structure and interaction with actin.

The beta-thymosins are distributed throughout the vertebrate phyla, and all known vertebrate beta-thymosins bind actin monomers. To determine whether beta-thymosin-like peptides function as actin-binding proteins in invertebrates, we fractionated perchloric acid extracts of the gonads of both the sea urchin, Arbacia punctulata, and the scallop, Argopecten irradians, and screened the fractions for proteins which could be crosslinked to actin. In each case a peptide was isolated which crosslinks to actin from both rabbit skeletal muscle and scallop cross-striated adductor muscle; both peptides were sequenced and each was found to consist of 40 amino acid residues, compared with 41-43 residues for the vertebrate beta-thymosins. The sequences of the scallop and sea urchin beta-thymosins are 80% identical to each other, 75% identical to residues 1-40 of thymosin beta4, and 72-80% identical to residues 1-40 of other vertebrate beta-thymosins. The sea urchin peptide was found to inhibit actin polymerization and nucleotide exchange. The affinity of the sea urchin peptide for rabbit muscle actin is apparently lower than that of thymosin beta4, since about twice the concentration of sea urchin peptide is required to give inhibition of actin polymerization or nucleotide exchange equivalent to thymosin beta4.

Actins↗
PubMed2000

Characterization of dansylated glutathione, glutathione disulfide, cysteine and cystine by narrow bore liquid chromatography/electrospray ionization mass spectrometry.

A method using reversed phase high performance liquid chromatography/electrospray ionization-mass spectrometry (RP-LC/ESI-MS) has been developed to confirm the identity of dansylated derivatives of cysteine (C) and glutathione (GSH), and their respective dimers, cystine (CSSC) and glutathione disulfide (GSSG). Cysteine, GSH, CSSC and GSSG are present at low concentrations in rainbow trout (Oncorhynchus mykiss) liver cells. Initially, hepatic cells were sampled from a suspension culture and disrupted upon addition of 10% perchloric acid. The reduced thiols present in the cell extracts were acetylated to prevent dimerization and then the C and GSH species were derivatized with dansyl chloride for fluorescence detection. An LC system using a weak anion exchange column (AE) with fluorescence detection (FLD) was used for sensitive routine analysis; however, it produced peaks of unknown origin in addition to the expected analytes. Analytes were then separated on a C18 RP-LC system using a water/acetonitrile gradient with 0.2% formic acid, and detected using LC/ESI-MS at 3.5 KV which produced an intense ion with a minimum limit of detection of less than 0.5 pmole injected (>10:1 signal-to-noise (S/N). Subsequently, fractions of effluent from the AE-LC/FLD system were analyzed by LC/ESI-MS to confirm the presence of the target analytes in routine cell extracts. Monodansylated GSSG was identified as a product that could possibly affect the quantification of GSH and GSSG.

Animals↗
PubMed1999

In vivo nuclear magnetic resonance studies of glycolytic kinetics in Lactococcus lactis.

The metabolism of glucose by nongrowing cells of L. lactis strain MG5267 was studied under controlled conditions of pH, temperature, and gas atmosphere (anaerobic and aerobic) using a circulating system coupled to nuclear magnetic resonance (NMR) detection that allowed a noninvasive determination of intracellular pools of intermediate metabolites by 13C-NMR with a time resolution of 30 seconds. In addition, intracellular parameters, such as pH, NTP levels, and concentration of inorganic phosphate in the cytoplasm, could be monitored on-line by 31P-NMR with a time resolution of approx. 3 min. The time course for the concentrations of intracellular fructose 1,6-bisphosphate (FBP), 3-phosphoglycerate (3-PGA), and phosphoenolpyruvate (PEP), together with kinetic measurements of substrate consumption and endproducts formation, were used as a basis for the construction of a mechanistic model for glycolysis. In vivo measurements were complemented with determinations of phosphorylated metabolites in perchloric acid extracts. A top-down model was developed by simplifying the metabolism to the resolution allowed by the experimental data collected by in vivo NMR (grouped in seven metabolic steps). This simplified mechanistic model was adjusted to the metabolite concentrations determined by in vivo NMR. The results obtained led to the rationalization of the dynamics of glucose metabolism as being driven largely by ATP surplus. This excess causes accumulation of FBP due to NAD+ limitation, whose regeneration is dependent on downstream pyruvate reduction. The model was capable of predicting qualitative shifts in the metabolism of glucose when changing from anaerobic to aerobic conditions.

Glycolysis↗
PubMed1999

Direct chromatographic resolution and isolation of the four stereoisomers of meta-hydroxyphenylpropanolamine.

Methods for the direct chiral chromatographic separation of the four stereoisomers of meta-hydroxyphenylpropanolamine (MHPA) on an analytical and preparative scale are described. Separations were carried out on a Crownpak CR (+) chiral column with 113 mM aqueous perchloric acid as the mobile phase. Baseline resolution of the more retained (+)-stereoisomers (1S configuration) and partial resolution of the less retained (-)-stereoisomers (1R configuration) were obtained under these chromatographic conditions. Removal of the bulk of the (1R,2S)-stereoisomer (metaraminol) from the initial crude mixture by fractional crystallization as the (+)-bitartarate salt substantially improved the peak resolution factors (Rs) of the remaining three stereoisomers. Semipreparative chromatographic resolution of the latter isomeric mixture provided milligram quantities of each stereoisomer in >97% enantiomeric excess. Subsequent recrystallization of their bitartarate or fumarate salts gave enantiomeric purities >99%.

Chromatography, Ion Exchange↗
PubMed1975

Quantification of carcinoembryonic antigen-like activities in normal, human gastrointestinal secretions.

The secretion of carcinoembryonic antigen-like (CEA-like) material into the gastrointestinal tract of 28 fasting normal men was quantified by using intestinal perfusion techniques. CEA-like material was recovered from all levels of the gastrointestinal tract. The highest secretory rate was in the colon (mean +/- SE, 2.41 +/- 2.0 mug/minute per colon), followed by pancreatobiliary secretion and pancreatic secretion. The secretory rate from the stomach, duodenum, jejunum, and ileum was less than 20 ng/minute. After perchloric acid extraction, the CEA-like material from the colon had the same chromatographic and radioimmunologic properties as [125I] CEA. These data suggest that the CEA-like material is normally secreted into the gastrointestinal tract and particularly into the colon.

Adult↗
PubMed1979

Occurrence of a thermostable antigen of ovarian carcinoma in normal tissues and secretions.

Thermostable antigen (TA) occurs in ovarian carcinoma and in certain specialized tissues. High titers of TA were found in nineteen of twenty endocervical extracts but not in myometrium, endometrium, or exocervix. TA was present in all of sixteen cervical mucus samples. Antibodies to perchloric acid extract of bronchus showed cross-reaticity with TA from ovarian carcinoma and cervix. Immunofluorescence with frozen sections revealed TA to be present in the columnar epithelium of ovarian neoplasms, and endocervical glands, in bronchial seromucous glands and in hepatic bile canaliculi. Immunofluorescence and immunodiffusion were used to test for cancer patient antibodies against TA. All sera tested negative. An immunofluorescence inhibition test for circulating TA also tested negative in sera of ovarian and cervical cancer patients.

Adult↗
PubMed1980

Assessment of serial CEA determinations in urine of patients with bladder carcinoma.

Carcinoembryonic antigen (CEA) levels in urine and serum from 294 patients with bladder cancer in varying stages have been clinically evaluated. All urine samples were obtained from patients with intact renal function and without bacterial infection in the bladder. The samples were collected before, during, and at follow-up examination after radiotherapy. They were perchloric acid extracted before being assayed in a double-antibody radioimmunoassay. The geometric mean of urine CEA levels for patients with primary tumors of Stage T1 or T2 was significantly lower than that for those with Stage T3 or T4 disease. The urine CEA levels for patients with tumors of various histologic grades did not differ. The urine CEA levels decreased from before to after radiation treatment of the primary tumor. Patients with recurrence within six months after undergoing primary treatment had higher initial mean urine CEA levels than did those without evidence of recurrence. The prognostic information for recurrence was limited to the more advanced tumors. Differences were also found between the means of samples taken before recurrence and after treatment of recurrent tumors; with regression of the tumor, a lower mean urine CEA level was found; with progression, a higher value. Urine CEA levels before any treatment were higher when the patients had a short survival time. Serum CEA levels were not related to stage or grade of the primary bladder tumor but levels were slightly elevated with metastases. The determination of urine CEA levels seems to be useful in the follow-up of patients with bladder carcinoma because when initially high, it adds to the information of the T classification and predicts early recurrence, and the monitoring of individual patients after primary treatment is useful for detecting recurrence.

Aged↗
PubMed1981

Isolation, characterization and clinical evaluation of a pancreas cancer-associated antigen.

A pancreas cancer-associated antigen (PCAA) was identified and isolated from ascites fluid of human pancreatic cancer. Purified PCAA was homogeneous as determined by polyacrylamide gel electrophoresis. PCAA was a glycoprotein with a molecular weight of approximately 1,000,000 and consisted of 20% carbohydrates and 80% peptides, had an isoelectric point of 4.7, and migrated to alpha 2-beta region. It possessed a sedimentation coefficient of 14S and appeared to be a fibrous or fibroglobular protein. Immunoreactivity of PCAA was sensitive to proteolytic enzymes, perchloric acid, KSCN, glycine-HCl at pH 2.5, urea and lithium diiodosalicylate; and insensitive to neuraminidase or beta-glucosidase. Immunohistochemical technique revealed that PCAA was located in the cytoplasm of ductal epithelial cells of malignant pancreas. Using heteroantiserum raised against purified PCAA, horseradish peroxidase and CNBr-activated Sepharose 4B, an enzyme-immunoassay (EIA) for circulating PCAA has been developed. From a group of 40 healthy blood donors, an upper limit of 16.2 micrograms of PCAA/ml of serum has been tentatively determined. An elevated PCAA was shown in 67% (29/43) of patients with pancreas cancer, as well as in 30% (11/36) of lung cancer patients, 27% (10/37) of colonic cancer patients, and in 16% (6/36) of breast cancer patients. The reactive antigen in sera of these cancers was shown to be immunologically identical. PCAA also was detected in extracts of various human tissues, particularly pancreatic tumors, colonic tumors, and in a normal colon. Further, PCAA exhibited heterogeneity in molecular weight, isoelectric point, and electrophoretic mobility.

Animals↗
PubMed1991

Phosphate metabolites and steroid hormone receptors of benign and malignant breast tumors. A Nuclear Magnetic Resonance study.

Phosphorous 31 (31P) nuclear magnetic resonance (NMR) spectra were recorded from perchloric acid extracts of benign and malignant breast tumors. The spectra were correlated with the histopathologic diagnosis and the steroid receptor status of the tumor. Higher relative content of the lipid-derived metabolite glycerolphosphoethanolamine (GPE), the high-energy nucleoside phosphates (nucleoside-diphosphate [NDP], nucleoside-triphosphate [NTP]), and sugar esters of uridine diphosphate (UDPS) appeared in the carcinomas. Malignant tumors also showed a lower ratio of phosphoethanolamine to phosphocholine (PE/PC) than benign conditions. Lower content of the lipid-derived metabolite glycerolphosphocholine (GPC) and high content of the high-energy compound phosphocreatine (PCr) were associated with malignant tumors having high content of estrogen receptors (ER). High PCr content was also associated in the carcinomas with high progesterone receptors (PgR) content. In the benign tumors NDP and NTP were higher in tumors with high PgR content. The authors suggest that 31P magnetic resonance spectroscopy (MRS) of the breast can provide additional variables to diagnose malignancy, and when combined with magnetic resonance imaging (MRI), invasive procedures may be avoided. It also seems that levels of PCr and GPC obtained from the spectra can serve as markers to hormonal receptor status of breast carcinomas, and may be used in addition to the ER and PgR content to improve prediction of the response to hormonal therapy. Additional development requires in situ MRI and MRS combined studies.

Breast↗