Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined 21 patients with focal lesions of the liver. Routinely we used T1 weighted, proton weighted and T2 weighted measurement modes, mainly with repetition times of 1.6 sec and echo delay times of 35 or 120 msec. Using these parameters we can see characteristic changes of the signals of the liver tumours. Cystic lesions usually show a strong decrease of the signal in the T1 weighted images in comparison with the normal liver pattern, in the proton weighted images a weak decrease but also in some cases a weak increase of the signal; in the T2 weighted images they show signals of very great intensity. We can differentiate haemangioma of cystic lesions because of the very strong signal in the proton weighted images in comparison with the normal liver pattern, which we could not see in any other focal liver disease. Metastases and hepatoma produced low signal intensity in the T1 weighted image. The proton weighted and the T2 weighted images show signals with a slightly greater intensity compared with the normal pattern, i.e. a very good possibility to distinguish hepatoma and metastases from cystic lesions or haemangioma. The differentiation from hepatoma and metastases cannot be made with NMR up to now. We are also not able to differentiate the focal nodular hyperplasia (FNH) from metastases. We used a 0.35 T supraconductive magnetic system.
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PMID:[Initial experiences with MR in liver tumors]. 299 37

Investigations with the fluorinated spermidine analogues show clearly that these compounds have significant potential for studying the metabolism and functions of the polyamines. However, the biochemical and biological properties of these analogues are dissimilar. This is due to the influence of the fluorine substituent(s) on the basicity of the amine function proximal to the fluoromethylene group, this effect being amplified by geminal disubstitution. The monofluorinated spermidine analogues compare well with the natural amine in their ability to regulate the expression of the decarboxylase enzymes, to be substrates of spermine synthase and to support growth of polyamine-deficient cells. It is also likely that 6-monofluorospermine, formed biochemically in situ, shares with spermine similar functions. These findings raise the possibility of using these spermidine analogues to study the metabolism and pharmacology of polyamines in vivo but also to provide more insight into the regulatory role of spermidine in ODC and SAM-DC expression. Another potential application may be the use of these analogues as probes in tumor imaging and therapy control. This indication has been inferred by studies in tumor-bearing animals, using 19F-NMR spectroscopy determination of tissue fluorospermidine and fluorospermine, formed biochemically from the precursors 2-fluoro or 2,2-difluoroputrescine, and which demonstrate preferential accumulation in tumor versus normal tissue. Finally, these monofluorinated spermidine analogues may exert beneficial effects in pathological states associated with polyamine deficiency. These diseases remain however to be identified. Among the difluorinated spermidine analogues, 7,7-difluorospermidine possesses the most interesting properties. This spermidine analogue still possesses ODC and SAM-DC repressing activities although at much higher concentration than spermidine. More importantly it is a potent inhibitor of spermine synthesis both in cultured cells and in vivo due to its efficient competition with spermidine in the spermine synthase reaction. This compound not only depletes tumor cell of its spermine content but, in addition, appears to exert by itself and/or via 6,6-difluorospermine, the product of its metabolism, polyamine antagonist effects. Combined with MAP but also with DFMO, two potent irreversible inhibitors of ODC which block the synthesis of the natural endogenous polyamines, 7,7-difluorospermidine causes an immediate decrease of viability in cultured HTC cells and promotes tumor regression and stabilization in hepatoma-bearing rats.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Fluorine-containing polyamines: biochemistry and potential applications. 307 45

A model for studying the 31P NMR spectrum of rat skin without contribution from other tissue signals has been developed by creating a skin pedicle. 31P NMR spectra were obtained with a solenoidal coil, which was separated from the flank of the rat by a Faraday shield. Phosphomonoesters, inorganic phosphate (Pi) (1.63 +/- 0.12 mumols per g wet wt), phosphodiesters, phosphocreatine (PCr) (1.4 +/- 0.12 mumols per g wet wt) and ATP (1.35 +/- 0.22 mumols per g wet wt) were observed, superimposed on broader signals, probably due to phospholipids. Extracts of freeze-clamped pedicles contained concentrations of phosphorus metabolites similar to those seen by NMR. The exception was Pi which was twofold higher in the extract. The presence of the broader phospholipid contribution suggests that the signals did not arise solely from the panniculus carnosus muscle of rat skin, although this muscle was evident on histological examination of the pedicles. In extracts of normal rat skin levels of creatine, ATP, ADP and Pi were similar to those of pedicles, whereas PCr was about twofold higher. Signals from rat skin are likely to contribute to spectra of subcutaneous organs and tumours. Two kinds of rat hepatoma that contained no PCr frequently gave PCr signals from the overlying skin, whereas in three other subcutaneous tumours the contribution from skin was negligible.
NMR Biomed 1988 Feb
PMID:Phosphate metabolites in rat skin. 327 23

Rat stomach gangliosides were purified and their distribution in the different tissue compartments was established. Three major monosialogangliosides were found: GM3, GM1, and a ganglioheptaosylceramide carrying a blood group B determinant. This latter structure was characterized by exoglycosidase degradation, immunostaining with a monoclonal anti-blood group B antibody on thin layer chromatogram, permethylation analysis, electron-impact mass spectrometry of the permethylated-reduced and trimethylsilylated molecule, and 1H NMR spectroscopy of the native ganglioside. It was found to be (Formula: see text) i.e. a GM1 structure substituted with the blood group B determinant and was called B-GM1. A similar structure has been previously identified in precancerous rat liver and chemically induced rat hepatoma (Holmes, E. H., and Hakomori, S. (1982) J. Biol. Chem. 257, 7698-7703). Fucosyl-GM1 was also detected as a minor ganglioside in rat gastric mucosa. The ganglioside profile was modified during the postnatal development. The contribution of GM3 and GD3, which accounted for 95% of the ganglioside sialic acid at birth, decreased during the first 3 weeks of life. GM1, fucosyl-GM1, and B-GM1 were not detected at birth. The concentration of the fucogangliosides increased during the 2nd and 3rd weeks after birth, was stable during the 4th week and then decreased, whereas that of GM1 increased steadily between 6 days and 2 months of age. B-GM1, which has been defined as a tumor-associated ganglioside in the rat liver, was found to be a developmentally regulated antigen of the normal rat stomach.
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PMID:Developmental changes of gangliosides of the rat stomach. Appearance of a blood group B-active ganglioside. 368 Feb 54

Glycoprotein MII2, the major cell surface glycoprotein (molecular mass 110 kDa) of Zajdela hepatoma ascites cells, contains about 25 O-glycosidic oligosaccharide chains per molecule. They were released as oligosaccharide-alditols by alkaline borohydride treatment of MII2, and purified by gel filtration on Bio-Gel P-6 followed by high-voltage paper electrophoresis. Four oligosaccharide-alditol fractions (A-D) were obtained in relative yields of 8:6:3:3. The structure of the components of fractions A-C was determined by 500-MHz 1H-NMR spectroscopy in combination with sugar composition analysis, to be as follows. (A) NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)]GalNAc-ol; (B1) NeuAc alpha(2----3)Gal beta(1----3)[Gal beta(1----4)GlcNAc beta(1----6)]GalNAc-ol; (B2) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)]GalNAc-ol; (C) NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol. On the basis of sugar composition and characteristics on Bio-Gel P-6 filtration, paper electrophoresis and thin-layer chromatography, the structure of the carbohydrate component of fraction D is proposed to be as follows. (D) NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol
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PMID:The structure of the O-glycosidic oligosaccharide chains of the major Zajdela hepatoma ascites-cell-membrane glycoprotein. 375 66

We have identified an unusual resonance at 16.5 ppm in the 31P NMR spectrum of a Morris (7777) hepatoma grown in the inguinal fossa of a Buffalo rat as myoinositol 1,2-(cyclic) phosphate. This compound has been observed in all of the 32 tumors examined as well as in cultured cells derived from the tumor, but it has not been observed in normal rat tissues. Its level in the aqueous phase of chloroform/methanol/water extracts of the tumor is 70 +/- 40 nmol/g, wet weight (n = 4). The presence of a breakdown product of phosphatidylinositol at such high levels in a fast growing tumor may provide an important clue for understanding the metabolic defect that results in the malignant growth of this tumor.
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PMID:Observation of myo-inositol 1,2-(cyclic) phosphate in a Morris hepatoma by 31P NMR. 379 28

A glutathione conjugate of aflatoxin B1 (AFB1) which has previously been identified as 8,9-dihydro-8-(S-glutathionyl)-9-hydroxy aflatoxin B1 (AFB1-GSH) (E.J. Moss, D.J. Judah, M. Przybylski and G.E. Neal, Biochem. J., 210 (1983) 227-233) has been degraded in vitro to all of the intermediates of the mercapturic acid pathway (MAP) and the chromatographic and spectral characteristics of each of these compounds investigated. The cysteinylglycyl conjugate (AFB1-Cys.Gly) was prepared by incubating the AFB1-GSH conjugate with a rat hepatoma cell line rich in gamma-glutamyl-transpeptidase (GGT). Incubations of the AFB1-Cys.Gly conjugate with dipeptidase produced a metabolite, which was purified and characterized by 1H-NMR spectroscopy as 8,9-dihydro-8-(S-cysteinyl)-9-hydroxy aflatoxin B1 (AFB1-Cys). The N-acetyl derivative of the AFB1-Cys conjugate resulted from the incubation of the AFB1-GSH conjugate in vitro with isolated rat kidney cells. Mass spectral data were consistent with the compound being 8,9-dihydro-8-(S-cysteinyl-(N-acetyl))-9-hydroxy aflatoxin B1 (AFB1-Nac.Cys). A chromatographically identical compound was obtained by the chemical acetylation of AFB1-Cys.
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PMID:The mercapturic acid pathway metabolites of a glutathione conjugate of aflatoxin B1. 393 41

To help understand which tissue parameters best account for the water proton NMR relaxation times, the longitudinal relaxation time (T1), the transverse relaxation time (T2), and the water content of 16 tissues from normal adult rats were measured at 10.7 MHz and 29 degrees C. Regression analyses between the above and other tissue parameters were performed. These other tissue parameters included: the amounts of various organic and inorganic components, protein synthetic rate, oxygen consumption rate, and morphological composition. In addition, the differences in T1, T2, and water content values between normal liver and malignant tumor (Morris #7777 a transplantable hepatoma) were studied to help understand how a disease state can be detected and characterized by NMR spectroscopy. The results of this study and information from the literature allow the following generalizations to be made about tissue T1 and T2 values: (1) Each normal tissue has rather consistent and characteristic T1 and T2 relaxation times which are always shorter than the T1 and T2 of bulk water; (2) tissues with higher water content tend to have longer T1 relaxation times; (3) tissue T2 values are not, however, as well correlated with water content as T1 values; (4) tissues with shorter T1 values have higher calculated hydration fractions, greater amounts of rough endoplasmic reticulum, and a greater rate of protein synthetic activity; (5) tissues with higher lipid content, associated with intracellular non-membrane bounded lipid droplets, tend to have longer T2 values; (6) tissues with greater overall surface area, whether in the form of cellular membranes or intracellular or extracellular fibrillar macromolecules, tend to have shorter T2 values; (7) the differences between T1 and T2 values between tumor and normal tissues correlated with differences in the volume fraction (amounts) of extracellular fluid volumes and in the amounts of membrane and fibrillar surface area in the cells. The above generalizations should be useful in predicting T1 and T2 changes associated with specific tissue pathologies.
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PMID:Characterization of proton NMR relaxation times in normal and pathological tissues by correlation with other tissue parameters. 653 Sep 24

The 1H NMR spin-lattice relaxation time (T1), spin-spin relaxation time (T2), and spin-lattice relaxation time in the rotating frame (T1rho) were determined for Novikoff hepatoma, Walker-256 Carcinosarcoma, Sarcoma-180 and Ehrlich Ascites tumor as well as for 7 normal tissues in the rat at 2.18 MHz. T1 values yielded improved discrimination of normal and malignant tissue compared to previous results at higher frequencies.
Physiol Chem Phys Med NMR 1984
PMID:Improved discrimination of normal and malignant tissue using 1H NMR relaxation time measurements at 2.18 MHz. 654 47

Using serial lectin-affinity chromatography, glycosidase digestion, and NMR and methylation analysis, the structures of complex N-linked glycan chains (M(r) range 2000-3500) of rat hepatocytes and poorly differentiated chemically transformed Zajdela ascites hepatoma cells were determined and compared. The results revealed considerable differences between the two cell types: (i) hepatoma cells only expressed tri- and/or tetra-antennary complex N-linked glycan chains, whereas hepatocytes displayed large amounts of bi-antennary N-linked structures and smaller amounts of tri-/tetra-antennary structures; (ii) 20% of the glycan chains in hepatoma cells contained a bisecting GlcNAc residue which was beta (1,4)-linked to the beta-mannosyl residue of the core and was not detected in the hepatocytes; (iii) hepatoma cells expressed a high proportion of the fucosylated or not GlNAc beta (1,6) Man alpha 1-->branch, whereas hepatocytes only contained a little of this branch; (iv) hepatoma cells, but not hepatocytes, exhibited a repeating (Gal beta(1,4) GlcNAc beta (1,3)) sequence characteristic of poly-N-acetyllactosaminoglycans. These glycans were capped by both alpha-galactosyl and sialyl residues; (v) The alpha (2,3)/alpha (2,6)-linkage ratio of sialic acid was significantly higher in hepatoma cells (4/1 vs. 2/1 in hepatocytes); (vi) Only hepatocytes expressed an unusual structure in which a sialyl residue was alpha (2,6)-linked to a GlcNAc residue located within a NeuAc alpha (2,3) Gal beta (1,3) GlcNAc branch which was beta (1,4)-linked to Man alpha 1,3-->. The differences between these complex N-linked glycan chains in hepatocytes and hepatoma cells seem to be both quantitative and qualitative, since some glycan structures were only present in one cell type.
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PMID:Structural differences between complex-type Asn-linked glycan chains of glycoproteins in rat hepatocytes and Zajdela hepatoma cells. 776 66


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