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)

Biosynthesis of cholesteryl 14-methylhexadecanoate, cholesteryl palmitate and cholesteryl stearate was studied in the liver of rats bearing the Walker 256 carcinoma. Zajdela hepatoma and during chemical carcinogenesis following the administration of benzo[a]-pyrene. An up to 9-fold enhanced production of all these esters was found in liver homogenate during the 10--16th day after Walker tumor transplantation. Only the enzyme system esterifying cholesterol in the cytosol at pH 6.5 was stimulated while the activity of similar enzymes in mitochondria, microsomes and cytosol at an acid pH were not affected. Activity of the cytosol enzyme esterifying cholesterol at pH 6.5 was also enhanced during the active growth of Zajdela hepatoma and during the period of chemical carcinogenesis characterized by the appearance of first palpable subcutaneous tumors. Enhanced activity of cholesterol esterifying enzymes in the liver exactly coincided with periods of elevated levels of cholesteryl 14-methylhexadecanoate in the liver and blood plasma as described earlier. An increased demand of the tumor-bearing host for this cholesteryl ester utilized as a co-factor for enhanced protein synthesis is obviously met by its stimulated production in the liver tissue.
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PMID:Biosynthesis of cholesteryl 14-methylhexadecanoate in the liver of rats bearing transplantable tumors and during chemical carcinogenesis. 43 54

It was shown that 1-phenylethylbiguanide (phenformin) administered orally to mice at a dose of 2 mg/day potentiated the antitumor effect of cyclophosphamide on transplantable squamous cell cervical carcinoma, hepatoma-22a and Lewis lung tumor, but did not alter the effect of cyclophosphamide on sarcoma-180 and L-1210. Oral administration of phenformin (5 mg/day) to rats with transplanted Walker 256 carcinoma enhanced the antitumor effect of hydrazine sulfate.
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PMID:Potentiation of antitumor effect of cyclophosphamide and hydrazine sulfate by treatment with the antidiabetic agent, 1-phenylethylbiguanide (phenformin). 50 14

Spin-lattice relaxation times (T1) for 31P were determined in normal and malignant tissues by a saturation technique employing a 90 degree -tau-90 degrees pulse sequence. Results for five normal tissues from rat were (in seconds): 2.33 +/- .14 for liver; 2.19 +/- .05 for muscle; 1.13 +/- .05 for brain; 1.43 +/- .15 fro kidney; and 1.97 +/- .12 for intestine. Results for two rat malignancies, Novikoff hepatoma and Walker sarcoma, were 5.98 +/- .57 and 5.38 +/- .68, respectively, and for Crocker sarcoma of mouse, 5.19 +/- 1.42. No individual measurement of malignant tissue overlapped any of the normal measurements; probabilities of insignificance ranged from .029 for Crocker sarcoma to .000184 for Novikoff hepatoma. The data call attention to another nucleus of potential value for NMR detection of internal malignancies in humans. Also suggested, because of the strategic placement of the 31P nucleus in the nucleic acid molecule, is a possible new probe for exploring the mechanism of carcinogenesis.
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PMID:NMR in cancer: VIII. Phosphorus-31 as a nuclear probe for malignant tumors. 61 35

The results of studies conducted on 355 white nonpedigree male rats (268 experimental and 87 intact animals) indicated that nephrogenic hypertension: a) potentiates the development of benz(a) pyrene induced blastomas; b) enhances, as a rule, the growth of transplantable tumors: carcinoma RS-1 and sarcoma 45; c) results in a tendency to more frequent metastasization of the tumors (Walker carcinosarcoma and Zajdela ascites hepatoma).
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PMID:[Nephrogenic hypertension and carcinogenesis]. 70 95

Protein synthesis was significantly enhanced in subcellular systems containing ribosomes and cytosol from the liver of Walker tumor-bearing rats from the second week following the tumor transplantation and this enhancement persisted for the whole period of tumor growth. Homologous systems from Zajdela hepatoma and host liver showed a markedly increased poly(U)-dependent peptide elongation when compared with normal liver tissue. A stimulation of polyphenylalanine synthesis resulted from the addition of cytosols from tumors or host liver to ribosomes from normal rat liver. Similar results were found for the binding of phenylalanyl-tRNA to ribosomes. Ribosomes from tumors and host liver are more active in peptide elongation than particles from normal liver tissue. A more than 10-fold stimulation of phenylalanine polymerization resulted from the addition of poly(U) to ribosomes from Zajdela hepatoma whereas only less than 2-fold enhancement was found when using ribosomes from normal or host liver. Hepatoma ribosomes apparently contain only a low proportion of polyribosomes carrying natural message. Enhanced protein synthesis in tumors and host liver is apparently due, in particular, to an increased activity of soluble factors required for protein synthesis and less due to an increased activity of ribosomes.
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PMID:Protein synthesis in tumor host. I. Enhanced peptide elongation in transplantable tumors and host liver. 74 61

1H spectra of tumours or normal tissues, which include signals from all hydrogen-containing metabolites, are too complex for the human eye to interpret. We have studied 58 1H spectra from perchloric acid extracts of three normal tissues (liver, kidney and spleen) and five rat tumours (GH3 pituitary, fibrosarcoma, Morris Hepatomas 7777 and 9618a and Walker carcinosarcoma). Instead of editing them or quantifying individual metabolites, we have used statistical pattern recognition techniques to classify them into groups. This automatic, objective method differentiated spectra from normal and malignant rat tissue biopsies, and from different types of cancer. It seems likely that this technique can be applied to human tissues and thus used for cancer diagnosis.
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PMID:Classification of tumour 1H NMR spectra by pattern recognition. 132 Mar 91

The contribution of extracellular components to the measurement of pHMRS of a variety of rat tumours (nitrosomethyl urea induced mammary tumours, GH3 prolactinomas, Hepatoma 9618a, UA hepatomas and Walker sarcomas) has been assessed. Acid extractable P(i) was between 2.6 and 12.5 mumol/G wet wt depending on tumour type, and of this 53 +/- 4.8% (mean +/- SEM) was MRS-visible. The P(i) content of tumour exudate was 2-3 mM, of interstitial fluid (sampled from a micropore chamber incorporated within a tumour) 1.7 mM, and of blood plasma 1.95 mM. The mean extracellular volumes of the tumours, measured by distribution of 3H2O and [14C]inulin, were 49-55% depending on tumour type and were at least twice that found in normal liver. Calculations suggested that for most tumours with an extracellular volume not exceeding 55%, at least 65% of the P(i)(MRS) signal was derived from intracellular P(i), and thus that pH(MRS) is a measure of pHi. For each tumour type, pHMRS was measured both in 'pulse-acquire' mode at 1.9 T which may include signals from surrounding tissue, and in localized mode at 4.7 T where the signal came uniquely from tumour tissue. The steady state pHMRS was either neutral or on the alkaline side of neutrality (pH range 7.04-7.37). Raised lactate content and decreased buffering capacity (compared to normal tissues) accompanied these neutral to alkaline pH values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An assessment of 31P MRS as a method of measuring pH in rat tumours. 148 71

DT diaphorase (NAD(P)H dehydrogenase (quinone), EC 1.6.99.2) isolated from Walker 256 rat carcinoma cells can convert CB 1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) to a cytotoxic DNA interstrand cross-linking agent. This is achieved by reduction of the 4-nitro group of CB 1954 to produce the hydroxylamino species, a bioactivation which accounts for the much greater sensitivity of Walker cells to CB 1954 when compared with other cells which are unable to carry out this reduction (Knox et al., Biochem Pharmacol 37: 4661-4669 and 4671-4677, 1988). As predicted from their measured DT diaphorase activities a number of rat hepatoma and hepatocyte cell lines were also shown to be sensitive to CB 1954. However, no CB 1954-sensitive cell lines of human origin were found, although levels of DT diaphorase similar to those in the sensitive rat cells were present in these cells. The human cells were as sensitive as rat cells to the active form of CB 1954 (5-(aziridin-1-yl)-4-hydroxyla mino-2-nitrobenzamide). DT diaphorase, purified to homogeneity from human Hep G2 cells, did metabolize CB 1954 to this 4-hydroxylamino product, but the rate of CB 1954 reduction and thus production of the cytotoxic product, was much lower than that of purified Walker enzyme (ratio of Kcat = 6.4). In addition, CB 1954 could be considered an inhibitor of, rather than a substrate for, the human form of DT diaphorase. The purified rat and human DT diaphorases possessed otherwise similar biochemical and molecular properties. These findings explain the decreased sensitivity towards CB 1954 of human cell lines when compared to rat cell lines.
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PMID:The differences in kinetics of rat and human DT diaphorase result in a differential sensitivity of derived cell lines to CB 1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) 190 Dec 7

Sensitivity to phenylephrine, isoproterenol, serotonin, oxytocin, acetylcholine and barium chloride of vas deferens uterus und fundus strip was studied comparatively in hepatectomized and sarcoma-45, sarcoma-M1, Walker carcinosarcoma and Zajdela ascites hepatoma bearing rats. The contractile response to monoamines and oxytocin was considerably lower or absent at certain periods after hepatectomy or tumour grafting. Effects of biogenic amine antagonists were also substantially altered. The response to isoproterenol, acetylcholine and barium chloride remained unchanged. Apparently a selective alteration of a response of visceral smooth muscles mediated through alpha-adrenergic and D-serotonin receptors occurred not only during the tumour growth but also in the case of active (extensive) proliferation of the normal tissue.
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PMID:[The monoaminergic receptors of the internal organs in rats with a tumor and after partial hepatectomy]. 217 98

31P-NMP, surface coil spectra of three subcutaneously implanted rat tumours (Morris hepatoma 7777, GH3 prolactinoma, Walker carcinosarcoma) and an N-methyl-N-nitrosourea induced rat mammary adenocarcinoma at different stages of growth were obtained and compared with histological sections taken immediately after NMR acquisitions. Metabolite ratios (phosphocreatine (PCr)/beta nucleoside triphosphate (beta NTP), PCr/Pi, beta NTP/Pi) calculated from the NMR spectra were compared with ratios obtained from acid extracts of tumours of similar size. Measurements of creatine and ADP were also made. Three of the tumours showed positive correlations between increasing tumour size and decreasing metabolite ratios measured both by NMR and in extracts, whereas the Walker carcinosarcoma showed no correlation between size and any parameters measured. Phosphorus metabolite ratios, measured in extracts of skin overlying the tumours, indicated a fall in high energy phosphate when there was histological evidence of skin invasion by the tumour. Surface coil 31P-NMR spectra of subcutaneously grown or induced tumours in the rat represent a slowly changing steady state as the tumour increases in size. We conclude that increasing numbers of hypoxic tumour cells, rather than large areas of necrotic tissue, contribute largely to the NMR spectrum.
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PMID:Growth studies of subcutaneous rat tumours: comparison of 31P-NMR spectroscopy, acid extracts and histology. 280 46


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