Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Localized hydrogen-1 magnetic resonance (MR) spectroscopy and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) were employed to obtain metabolic information from intracranial gliomas. Advantages and difficulties associated with comparison of results from the two modalities were realized. Forty patients were studied with H-1 MR spectroscopy. MR signal intensities from lactate, N-acetylaspartate (NAA), choline, and creatine from a volume of interest containing the tumor and a contralateral volume were obtained and evaluated. NAA signal intensities were generally decreased in the tumor spectra, and choline signal intensities were elevated. H-1 MR spectroscopy was unsuccessful in eight patients, and FDG PET scans were not obtained in four of the patients with successful MR spectroscopic examinations. Lactate signal intensity was detected in 10 of the 28 patients who had successful H-1 MR spectroscopic and FDG PET studies. Lactate signal intensities were observed in lesions shown at FDG PET to be hypermetabolic, as well as in lesions found to be hypometabolic.
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PMID:Metabolism of human gliomas: assessment with H-1 MR spectroscopy and F-18 fluorodeoxyglucose PET. 224 60

In situ fluorine NMR imaging has been used to measure vascularity in subcutaneously implanted mammary tumors. Oxyferol, a perfluorinated blood substitute comprised of an emulsion of 25% w/v perfluorotributylamine, was used as a tracer. Following iv administration, this perfluorocarbon emulsion remains primarily in the vasculature during the image acquisition period. The distribution of the PFTA in the 19F NMR image gives a map of tissue regions with intact vascularity. This technique has been used to demonstrate decreased blood flow in necrotic regions of R3230AC mammary tumors in which vasculature had been damaged either as a result of spontaneous necrosis or by photodynamic therapy (PDT). Damage to tumor vascularity following PDT was observed prior to the development of necrosis.
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PMID:In situ assessment of tumor vascularity using fluorine NMR imaging. 232 42

Experiments on the P 388 D1 cell line (48 h exposure) demonstrate that [1,2-bis-(fluorophenyl)ethylenediamine]platinum(II) complexes are comparably active on the cell number and 3H-thymidine incorporation, irrespective of the position of the fluorine atom (ortho, meta, or para) and the nature of the "leaving group" (Cl- or H2O). However, the compounds of the R,R/S,S series are more active than those of the R,S series and comparable to cisplatin. In the "tumor colony forming assay" the R,R/S,S configurated compounds are about ten times as active as cisplatin. The R,R/S,S configurated diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II) salts reach their half maximum effect more readily (t1/2 approximately equal to 1.6 h) than their R,S configurated analogues (t1/2 approximately equal to 20 h). A time limited contact of the cells with R,R/S,S configurated diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II) salts (-1h) leads to a similar inhibition like a permanent drug exposure indicating a fast uptake of the complex by the tumor cell. In experiments on the Ehrlich ascites tumor of the mouse and on the L 1210 leukemia cell line R,R/S,S-[1,2-bis(4-fluorophenyl)ethylenediamine]dichloroplatinum(II) turns out to be equipotent with cisplatin.
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PMID:Tumor inhibiting [1,2-bis(fluorophenyl)ethylenediamine]platinum(II) complexes. Part II: Biological evaluation-in vitro studies on the P 388 D1 leukemia cell line. 234 59

Deuterium and fluorine nuclear magnetic resonance spectroscopy have been employed for quantification of regional blood flow in concert with nonradiative, exogenous, freely diffusible tracers such as D2O and freon gas. Typically, the tracer residue washout was monitored by NMR over time following tracer administration by bolus injection or inhalation. The theory, including compartmental analysis, required to quantitatively derive volumetric tissue blood flow and perfusion is reviewed herein. Applications of NMR tissue blood flow measurement techniques to tumor, muscle, liver, and brain are presented with discussion of the advantages and disadvantages of NMR methods.
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PMID:Quantification of regional blood flow by monitoring of exogenous tracer via nuclear magnetic resonance spectroscopy. 234 7

The intrinsic resolution of the Donner 600-crystal positron emission tomograph (PET 600) is 2.6 mm full width at half maximum (FWHM) in-plane and 6 mm FWHM axially. More than 100 patients with glioma, radiation necrosis, Alzheimer disease, or epilepsy have been studied with this system. Approximately 1 million events are acquired in 15 minutes, starting 1 hour after injection of 10 mCi (370 MBq) of fluorine-18-fluorodeoxyglucose. Normal structures as small as the superior colliculi and the external capsule have been resolved. Improved separation of the cortical ribbon from adjacent white matter has allowed more accurate determination of cortical metabolic rate. In two of 15 patients undergoing evaluation for recurrent glioma, the PET 600 images showed tumor uptake that was not apparent on a lower-resolution study. A high-activity orbiting transmission source with electronic collimation allows accurate, short-duration transmission measurements to be made after radiopharmaceutical administration. The anatomic detail seen on the transmission images can be used for reproducible patient positioning with an accuracy of 1-2 mm perpendicular to the image plane. These findings demonstrate the practicality and clinical effectiveness of high-resolution positron emission tomography.
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PMID:Clinical evaluation of a high-resolution (2.6-mm) positron emission tomography. 238 37

Hydrogen-1 magnetic resonance (MR) spectroscopic images of patients with intracranial tumors were obtained. Metabolite maps of N-acetyl aspartate, choline, lactate, and creatine concentrations were reconstructed with a nominal spatial resolution of 7 mm and a section thickness of 25 mm. The metabolite maps showed variations in metabolite concentrations across the tumor. In one patient, it was observed that choline concentration was increased in one part of the tumor but decreased in another part. In another patient, the concentration of N-acetyl aspartate was extremely low in one part of the tumor but only slightly increased in another part of the tumor. Lactate was observed in all patients. In one patient, a combined measurement made with positron emission tomography (PET) and MR spectroscopic imaging was performed. This demonstrated that increased lactate concentration measured with H-1 MR spectroscopic imaging corresponded topographically with increased glucose uptake measured with fluorine-18 fluoro-2-deoxyglucose PET. Combined MR spectroscopic and PET measurements provide an opportunity to investigate, in greater detail than before, glucose uptake and catabolism by intracranial tumors.
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PMID:Metabolic imaging of patients with intracranial tumors: H-1 MR spectroscopic imaging and PET. 238 38

The cellular metabolism of 9-beta-D-arabinofuranosyl-2-fluoroadenine 5'monophosphate (F-araAMP), a soluble nucleoside analog with proven antileukemic activity in animal and human tumors, has been studied in mice bearing P388 leukemia. Earlier studies showed markedly less in vivo accumulation of F-ara ATP the principal active metabolite, in gastrointestinal mucosa (GI) and bone marrow (BM) compared with P388 after F-araA or F-araAMP administration. To elucidate the mechanism of toxicity this work has examined the pharmacodynamics of F-araAMP anabolites, F-araATP and F-ATP, in P388 cells, BM and GI mucosa tissues after nontoxic (LD1) and toxic (LD50) doses of F-araAMP. F-araATP was the major triphosphate metabolite in acid-soluble extracts from P388 cells, BM, and GI mucosa tissues. F-araATP accumulated to approximately 1 mM in P388 cells after either LD1 or LD50 treatment of F-araAMP and was eliminated with a t1/2,el of approximately 5 h. The ratio of the area under the concentration-time curve (AUC 0----infinity) of F-araATP was 1.01 after the LD50 over the LD1 doses of F-araAMP. BM and GI mucosa tissues accumulated 40-fold less F-araATP than the concentration in P388 cells. 2-Fluoro-ATP, a second toxic anabolite, accumulated in P388 cells to 156 +/- 39 microM and 447 +/- 79 microM after the two doses of the drug, respectively. The ratio of area under the curve (AUC) of F-ATP in P388 cells after the two doses of F-araAMP was 38.77, which approaches the ratio of % lethality (LD50/LD1 = 50). F-ATP was also quantitated in BM and GI mucosa reaching one-fifth to one-half the concentration of F-araATP after the LD50 dose of F-araAMP. The AUC values of F-ATP (0----24 h) were 9.5- to 12.5-fold higher after the LD50 than after the LD1 dose of F-araAMP. These results suggest that there is a selective therapeutic action of F-araAMP against P388 and that the increased cellular concentration of F-ATP in both the tumor cells and the host tissues (BM and GI mucosa) could explain the mode of toxicity of F-araAMP.
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PMID:Pharmacodynamics and proposed mechanism of therapeutic action and host toxicity of 9-beta-D-arabinofuranosyl-2-fluoroadenine monophosphate (F-araAMP) in P388 murine leukemia-bearing mice. 247 18

A fluorine-containing anthracycline, ME2303, given intravenously once a week for 4 weeks at the maximum tolerated doses showed better therapeutic effects against 2 gastric, 3 lung and 2 human breast tumor xenografts than did adriamycin (ADM) at the maximum tolerated dose. Among the tumors, ME2303 showed a better effect against St-40, a well-differentiated human gastric adenocarcinoma, against which ADM showed only a marginal effect. Likewise, ME2303 was more effective against Lu-24 human small cell carcinoma and MX-1 human medullary tubular adenocarcinoma than ADM. Notably, the Lu-24 tumor, developed in nude mice, disappeared after the treatment in 3 out of 6 mice. ME2303 would be an interesting compound for phase I and II clinical studies in the future.
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PMID:Antitumor activity of ME2303, a fluorine-containing anthracycline, against human tumors implanted in nude mice. 250 92

The effects of fluorine substitution on benzo[b]fluoranthene (B[b]F) DNA adduct formation and tumorigenicity in mouse epidermis were investigated. Fluoro derivatives studied included 1-, 6-, 7-, 8-, 9- and 11-fluoroB[b]F as well as 1,9- and 6,9-difluoroB[b]F. Each compound was applied topically to mice and hydrocarbon/DNA adduct formation was assessed using the 32P-post-labelling technique. All of the fluorinated compounds bound to DNA to a lesser extent than B[b]F. Among the fluorinated compounds, the greatest binding was observed for 8-fluoroB[b]F. Lowest levels of hydrocarbon/DNA adduct formation from the fluoro derivatives were observed for 1-, 7-, 11- and 6,9-difluoroB[b]F. The tumor-initiating activities on mouse skin of 7-, 9- and 11-fluoroB[b]F were determined. All three compounds were significantly less tumorigenic than B[b]F. The results of this study are discussed with respect to possible mechanisms of metabolic activation of B[b]F.
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PMID:Effects of fluorine substitution on the DNA binding and tumorigenicity of benzo[b]fluoranthene in mouse epidermis. 259 3

Multiresonance perfluorocarbon emulsions (Oxypherol and Fluosol-DA) were imaged in tumor-bearing mice using 19F spin-echo magnetic resonance imaging in vivo. Multiple thin-slice fluorine images free of chemical shift artifacts were obtained in 13 minutes and these were correlated with proton images obtained during the same experiment to delineate the anatomic distribution of perfluorocarbons. Sequential images were used to determine the time course of the distribution and the retention of the compounds in tumors and organs. 19F MR spectroscopy was used ex vivo to determine with high sensitivity the relative concentration of perfluorocarbons in different tissues and organs and to confirm the results obtained from imaging experiments. The fluorine images visually demonstrated the preferential localization of the perfluorocarbons in the liver and spleen; shortly after injection, the images also revealed the highly vascularized tumor-chest wall interface. Imaging and spectroscopy together showed that the perfluorocarbons were removed from the blood pool within hours and remained sequestered in tissues at later times; the highest concentrations were found in the spleen and liver, where the agents were retained without spectral changes for the duration of these studies. The perfluorocarbons accumulated within tumors at dose-dependent concentrations, one to two orders of magnitude smaller than those observed in the spleen and liver.
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PMID:Perfluorocarbon imaging in vivo: a 19F MRI study in tumor-bearing mice. 260 98


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