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)

The rate of protein synthesis in vivo was assessed in tumor tissue, skeletal muscle, liver, and the whole body of rats bearing either the Yoshida sarcoma or Novikoff hepatoma after 18 days of tumor growth and compared to tumor-free controls. Changes in size of the whole animal and tumor (i.e., growth) were measured, and fractional rates of growth, synthesis, and degradation were estimated. Muscle protein synthesis and whole-body growth were significantly reduced in both groups of tumor-bearing rats after 18 days of tumor growth. In addition to reductions in muscle protein synthesis, whole-body protein synthesis was significantly reduced in the Yoshida tumor-bearing group (587 +/- 36 versus 401 +/- 40 mg/h; mean +/- SEM; control versus Yoshida group, respectively, P less than 0.01). Tumor protein synthesis was not statistically different between the Yoshida tumor (76 +/- 21 mg/h) and the Novikoff tumor (50 +/- 8) after 18 days of growth despite the fact that the Yoshida tumors were significantly larger (33.9 +/- 4.2 g versus 11.9 +/- 1.2 g; P less than 0.01). The fractional synthesis rate (Ks) was, in fact, significantly slower in the Yoshida versus the Novikoff tumor (36.8 +/- 7.6 versus 55.1 +/- 4.8%/day). Tumor growth (Kg) followed first order growth rates for both tumor types (r = 0.945, 0.869; Kg = 17.2 +/- 1.6, 15.5 +/- 1.9%/day; Yoshida and Novikoff, respectively). The fractional degradation rate of tumor protein (Kd) was determined as the difference between the two first order rate constants Ks and Kg. The tumor protein degradation rate was significantly reduced in the Yoshida tumors compared to the Novikoff tumors (19.6 +/- 8.2% versus 39.6 +/- 4.2%/day, respectively). The greater size in the Yoshida sarcoma can be attributed to reduction in fractional protein degradation rather than change in synthesis rates, which supports the theory that some tumors can regulate their growth by alteration in tumor protein degradation rates (J. A. Tayek et al., Cancer Res., 46:5649-5654, 1986).
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PMID:Alterations in whole body, muscle, liver, and tumor tissue protein synthesis and degradation in Novikoff hepatoma and Yoshida sarcoma tumor growth studied in vivo. 334 28

Hypercalcemia has not previously been recognized as a complication of advanced chronic liver disease without hepatoma. During a five-year period, 16 patients evaluated in the liver transplantation program at the University of Pittsburgh developed hypercalcemia. All had advanced chronic liver disease with mean total bilirubin concentration of 29.5 +/- 4.6 mg/dL (50.1 +/- 78.2 mumol/L) (mean +/- SEM) and prothrombin time 16.8 +/- 0.8s. The highest serum calcium level was 17.2 mg/dL (4.3 mmol/L). The mean serum calcium level was 11.7 +/- 0.3 mg/dL (2.93 +/- 0.075 mmol/L) with an ionized calcium level of 5.41 +/- 0.35 mg/dL (1.35 +/- 0.088 mmol/L) and a phosphorus level of 4.2 +/- 0.4 mg/dL (1.4 +/- 0.1 nmol/L). Mild to moderate renal insufficiency was present in 14 (87%) patients; the mean serum creatinine level was 2.8 +/- 0.4 mg/dL (247 +/- 35 mumol/L). In five (38%) patients parathyroid hormone was completely suppressed and in an additional five (38%) patients, it was in a range most compatible with nonhyperparathyroid hypercalcemia. The 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D levels were normal or low in the 11 patients in whom determinations were made. Hypercalcemia that is not due to hyperparathyroidism or hypervitaminosis D is a potential complication of advanced chronic liver disease.
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PMID:Hypercalcemia. A complication of advanced chronic liver disease. 381 45

We developed a specific RIA for a somatomedin (Sm)-binding protein, with an approximate mol wt of 35-40,000, purified from midgestational human amniotic fluid (AF) and termed AF-binding protein (AFBP). After Sephadex G-200 chromatography AFBP-RIA activity was found in fractions of fetal and cord serum only at a kav corresponding to a mol wt of +/- 40,000. Whole serum or plasma dilutions in a range of 1:20 to 1:600 showed parallelism with the standard curve. Sm-binding activity in fetal serum was found solely at a mol wt of 30-40,000; in cord serum additionally at a mol wt range of 150-200,000. AFBP serum or plasma concentrations determined by RIA were influenced by several factors: AFBP values in eight adults were highest in the morning (mean +/- SEM, 0.7 +/- 0.1 mu geq/ml) and lowest at night (0.3 +/- 0.1). AFBP values in pre- and postnatal serum showed a gradual decline with increasing age: fetal serum: mean +/- SEM, 36.7 +/- 15.7 (n = 17); adults: 0.6 +/- 0.07 mu geq/ml (n = 19). In serum from GH-deficient children AFBP concentrations were significantly higher than in an age-matched control group (P less than 0.05). Elevated values also were found in serum of children with end-stage renal failure and in serum of pregnant women at 36 weeks of gestation. AFBP was found in urine of preterm infants (mean +/- SEM, 0.04 +/- 0.005 mu geq/ml; n = 31). AFBP immunoreactivity was demonstrable in serum of three orangoutan mothers and their three children and in medium of a hepatoma cell line (PLC/PRF/5) but not in bovine, porcine, rabbit, or rat serum or in medium of cell cultures of (pre-)term placentae. We conclude that AFBP immunoreactivity is present in pre- and postnatal serum and has striking similarity to an unsaturated serum Sm-binding protein with a mol wt of +/- 40,000.
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PMID:Immunoassay of a somatomedin-binding protein from human amniotic fluid: levels in fetal, neonatal, and adult sera. 620

Attachment of the cells of mouse ascitic hepatoma to various substrata was examined with the aid of SEM. Ascitic cells did not attach themselves in vitro to the mesothelium-covered surface of peritoneum. However, these cells were attached to the surface of peritoneum from which mesothelial layer had been removed. In the course of growth of ascitic tumor in vivo attached ascitic cells on the peritoneal surface were seen only in the areas of stomata but not in the mesothelium-covered areas. Ascitic cells taken from the peritoneal fluid adhered poorly to the glass surface in culture. However, adhesiveness of these cells to the glass and their ability to spread on the glass surface increased considerably after cultivation in vitro. This alteration of adhesiveness was completely reversible: the cultured cells transplanted intraperitoneally restored their poor adhesive properties. It is suggested that non-adhesiveness of mesothelial surface is the main factor preserving suspended state of intraperitoneally growing ascitic cells. Depending on the environment, ascitic cells may undergo reversible changes of adhesiveness.
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PMID:SEM study of the attachment of mouse ascitic hepatoma cells to various substrata. 741 96

We describe a case of recurrent hypoglycaemia associated with a hepatoma. During hypoglycaemia serum insulin was undetectable. Plasma insulin-like growth factor II (IGF-II) was not elevated although 71% of plasma IGF-II was present as big IGF-II (molecular weight 11 kDa) which probably represents a non-glycated form of pro-IGF-II. The GH response to hypoglycaemia was impaired and plasma levels of both IGF-I and the GH-dependent IGF binding protein (IGFBP-3) were low. A recently described unextracted assay directed against the first 21 amino acids of the E-domain (E-21) of proinsulin-like growth factor-II (pro-IGF-II) allows direct plasma estimation (plasma E-21) of larger molecular forms of IGF-II without interference from normal IGF-II and IGF binding proteins. Basal values were grossly elevated (23.7 and 23.8 nmol/l). Treatment with GH led to an increase in the mean plasma glucose across 24 hours (4.25 +/- 0.21 mol/l (mean +/- SEM) before treatment, compared with 4.86 mmol/l +/- 0.17 following GH (P < 0.01)) and a reduction in hypoglycaemic attacks. The treatment was associated with a rise in IGFBP-3 and small increases in insulin like growth factors. Subsequent treatment with the somatostatin analogue octreotide did not produce a significant change in plasma glucose levels or insulin-like growth factors. Two courses of intrahepatic adriamycin restored elevated levels of E-21 to normal. Total IGF-II remained normal and IGF-I increased. GH treatment was successfully withdrawn with no effect on plasma glucose or growth factor levels. The patient remained free from hypoglycaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A case of hepatoma associated with hypoglycaemia and overproduction of IGF-II (E-21): beneficial effects of treatment with growth hormone and intrahepatic adriamycin. 752 21

It has been shown previously that erythropoietin expression in vitro by hepatoma cells increases in response to hypoxia. To verify whether hypoxia of the tumor might result in hepatic release of erythropoietin in vivo, serum erythropoietin concentrations were measured immunoenzymatically in 12 patients (5 women, 7 men) who underwent transarterial chemoembolization for hepatocellular carcinoma. Peripheral blood samples were collected at baseline, and after 6 hours and 1, 2, 3, and 7 days after the procedure. In a second set of experiments, performed in three male patients also undergoing chemoembolization for hepatocellular carcinoma, paired blood samples were collected after catheterization of the hepatic veins and of the right antecubital vein. None of the patients had erythrocytosis. In comparison with a baseline mean value +/- SEM of 100.6 +/- 12.6 micrograms/L, serum erythropoietin concentrations were the following; +6 hours, 55.4 +/- 18.0 (P < .001); +1 day, 102.4 +/- 24.7 (P = NS), +2 days, 183.0 +/- 31.1 (P < .05); +3 days, 155.0 +/- 26.0 (P < .05); +7 days, 153.3 +/- 27.4 (P < .05) (matched Student's t-test). The ratio of hepatic vein/antecubital vein serum erythropoietin concentrations increased from 0.85 at baseline to 1.30 at +2 days, paralleling the increase of aspartate transaminase (r = .914, P < .005). After chemoembolization, no correlation was found between serum erythropoietin and alpha-1-fetoprotein concentrations. The concentration of the latter, stable initially, decreased 7 days after the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic release of erythropoietin induced by transarterial chemoembolization in patients with hepatocellular carcinoma. 760 7

We have previously demonstrated (M. Stubbs, Z. M. Bhujwalla, G. M. Tozer, L. M. Rodrigues, R. J. Maxwell, R. Morgan, F. A. Howe, and J. R. Griffiths, NMR Biomed., 5: 351, 1992) that the intracellular pH (pHi) of several rat tumors is higher (> pH 7.0) than that of the tumor extracellular fluid (pHe), in contrast to normal tissues (e.g., liver) in which pHi is lower than pHe. In this paper we confirm a pHe of 6.8 +/- 0.07 (SEM) in Morris hepatoma 9618a by an independent method and report the tissue content of other ions by both 31P magnetic resonance spectroscopy and by conventional analysis in hepatomas and livers in rats. Compared with liver, tissue Na+ was 2-fold higher and tissue K+ was lower. Tissue Ca2+ was 8-fold higher (7.4 +/- 4.3 mumol/g wet weight) and tissue Pi was 2-fold higher (8.5 +/- 1.3 mumol/g wet weight) suggesting the presence of insoluble calcium phosphate. Cl- was unchanged (approximately 40 mumol/g wet weight), whereas HCO3- was lower in the hepatoma (12.4 +/- 0.83 compared to 15.5 +/- 0.76 mumol/g wet weight). Total tissue Mg2+ was similar in both tissues, but free [Mg2+] (calculated by two different methods) was approximately 5-fold lower in the hepatoma. The ATP values were 3.5-fold and [NAD]/[NADH] 9-fold lower in the hepatoma. The results are compatible with the hypothesis that the chronic partial hypoxia of tumor tissue involves changes in the linked equilibria of many ions and metabolites and may help explain such pathologies as calcification.
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PMID:Metabolic consequences of a reversed pH gradient in rat tumors. 803 32

In order to provide a device releasing drugs in a controlled manner and having targetability to specific organs or cells, chitosan-gel microspheres, CMS, crosslinked with glutaraldehyde, immobilizing 1-[N-(5-aminopentyl) carbamoyl]-5-fluorouracil, 1, coated with anionic polysaccharides, such as 6-O-carboxymethyl-N-acetyl-alpha-1,4-polygalactosamine (CM-NAPGA), 6-O-carboxymethyl-chitin, alginic acid and heparin, by polyelectrolyte complex membrane formation were prepared. When chitosan was crosslinked with glutaraldehyde, 1 was simultaneously immobilized into CMS by Schiff's base formation. Average diameter of CMS obtained was estimated to be about 0.5-1.0 micron by SEM observation. In physiological saline media, only free 5-FU was released from the CMS but 1 and any 5-FU derivative was not. Release rate of 5-FU from the CMS was reduced by coating with polyelectrolyte complex membrane of cationic chitosan and anionic polysaccharides. CMS coated with CM-NAPGA showed a lectin-mediated specific aggregation phenomenon by addition of Abrus precatorius agglutinin. Moreover, the CMS immobilizing 1 coated with CM-NAPGA showed higher growth-inhibitory effect against SK-Hep-1 (human hepatoma) cells in vitro than the CMS coated with other polysaccharides.
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PMID:Release behaviour of 5-fluorouracil from chitosan-gel microspheres immobilizing 5-fluorouracil derivative coated with polysaccharides and their cell specific recognition. 838 99

The effect of tumor resection on protein metabolism in cancer-bearing subjects is poorly documented. We explored changes in nitrogen (N) and protein metabolism after excision of tumors both at the whole body level (N balance) and at the tissue level, including skeletal muscle, small intestine, and liver. Sixteen male Sprague-Dawley rats (approximately 375 g) bearing subcutaneous Morris hepatoma 7777 for 6 weeks were either operated for tumor excision and studied for 10 days postoperatively (n = 10) or sacrificed on the day of surgery as tumor-bearing controls; operated and unoperated tumor-bearing rats were compared with healthy rats (n = 16). Tumors, which grew to a mass of 74 +/- 7 g (mean +/- SEM), induced significant loss of body mass (-27 +/- 13 g) and protein depletion in epitrochlearis muscle (EPI) (-38%) and small intestine (-42%) vs healthy rats. Tumor significantly decreased muscle protein synthesis vs healthy rats (7.14 +/- 0.5 vs 10.7 +/- 0.5 nmol phenylalanine (Phe)/EPI/3 hr), net degradation (21.7 +/- 2.9 vs 30.6 +/- 2.5 nmol Phe/EPI/3 hr) and degradation (28.8 +/- 2.7 vs 41.4 +/- 2.5 nmol Phe/EPI/3 hr). In 50% of operated rats, tumor removal was followed immediately by increased food intake, body weight, and N balance; in other rats, this was delayed by 2-4 days. By 6 days postoperative, all rats were gaining weight and had normal food intake; wasting was abolished in small intestine, but not in skeletal muscle (protein mass -43% vs healthy rats, P < 0.05). Postoperative rats maintained lower muscle protein degradation (28.2 +/- 2.0 vs 41.4 +/- 2.5 nmol Phe/EPI/3 hr, P < 0.05) than healthy rats; protein synthesis was no longer reduced. In skeletal muscle, protein synthesis and protein deposition were related to levels of postoperative food intake (r = 0.91 and 0.98, respectively; P < 0.05). Following tumor excision, reversal of cancer cachexia appeared to be highly dependent on the level of postoperative food intake.
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PMID:Protein metabolism in cachectic tumor-bearing rats: effect of tumor excision. 859 16

Quantitative analysis of lysozyme- and CD68-positive Kupffer cells was carried out in connection with diethylnitrosamine-induced hepatocarcinogenesis in non-human primates. The number of Kupffer cells/mm2 was determined in 28 cases of hepatocellular carcinoma (HCC) and seven age-matched controls. The Kupffer cell counts (mean +/-SEM) gradually decreased in the following order, irrespective of the histochemical markers (lysozyme or CD 68) used: healthy control liver (101.7 +/- 13.5 and 103.2 +/- 11.9 respectively), non-cirrhotic and non-neoplastic host liver (54.3 +/- 13.6 and 50.5 +/- 15.4), cirrhotic host liver (26.2 +/- 8.2 and 27.2 +/- 3.3), HCC tissue (20.7 +/- 4.4 and 19.3 +/- 4.1) and metastatic foci in the lung (9.8 +/- 1.8 and 9.7 +/- 2.8). The difference between the normal liver and the non-neoplastic, non-cirrhotic portions of the HCC-bearing liver was significant (P < 0.05). A highly significant difference was found between the number of Kupffer cells found in healthy control or non-neoplastic liver and those found in HCC nodules (P < 0.0001 and P < 0.0005 respectively). The results obtained by hematoxylin and eosin staining and lysozyme/CD68 immunohistochemistry were highly similar, indicating that this decrease was attributable primarily to numeric loss of Kupffer cells. The results suggest that the reduction in the number of Kupffer cells in HCC is a constant feature of hepatocarcinogenesis not only in rodent models, but also in non-human primates.
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PMID:Quantitative evaluation of lysozyme- and CD68-positive Kupffer cells in diethylnitrosamine-induced hepatocellular carcinomas in monkeys. 860 89


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