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)

Aflatoxins become an economical problem in our country due to its contamination in agricultural commodities for export. The toxin may also cause hepatoma and liver diseases in the Thais as well. It is, therefore, necessary to search for and to develop efficient technology to combat and control such dangerous mold and mycotoxins. This paper is a collection of our previous and present studies towards reduction of risk from aflatoxins in foods and feedstuffs. The investigation of mold and aflatoxin contamination in local foods and feedstuffs in Chiang Mai area was made. The inhibitory effect of garlic extract on growth of Aspergillus flavus and its aflatoxin production was demonstrated. Detoxification of aflatoxins by chemicals such as ammonium carbonate, ammonium bicarbonate and ammonium benzoate was also shown. Preventions of toxigenic mold growth and its aflatoxin production by means of some food preservative were reported. Modifications of such effective chemicals were investigated for safety in future application.
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PMID:Studies of aflatoxins in Chiang Mai, Thailand. 147 82

Regulation of intracellular pH (pHi) was studied in Fu5, a rat hepatoma cell line that maintains a variety of differentiated functions. Microspectrofluorimetry of the pH-sensitive dye 2',7'-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF) was used to measure pHi in 10-15 cells growing on cover glasses that were mounted in a flow-through chamber on the stage of a microscope. In N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered solutions, pHi was 7.14, and intrinsic buffer capacity was inversely related to pHi. Amiloride (0.1 mM) caused pHi to decrease by 0.33 pH units in 4 min. Recovery from an acid load (using either NH4 prepulse technique or Na-free solutions) was completely blocked by amiloride. In HCO3-CO2-buffered solutions, pHi was 7.15, and buffer capacity was relatively insensitive to pHi between pHi of 6.6 and 7.2. Amiloride caused pHi to decrease by only 0.09 units. Recovery from an acid load was Na dependent, occurred in Cl-free solutions, and was totally blocked by the combination of amiloride plus 0.5 mM dihydro-4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (H2DIDS); recovery occurred when either amiloride or H2DIDS was removed. Removal of external Cl caused a rapid, H2DIDS-blockable alkalinization that was faster in HCO3-CO2 than in HEPES. The apparent Km for Clout for relaxation of Cl-free alkalinization was 4.5 mM. Rate of HCO3 transport during Cl-free treatment increased at alkaline resting pHi. It is concluded that Fu5 cells have two Na-dependent base-loading mechanisms and an acid-loading Cl-HCO3 exchanger. In solutions containing HCO3-CO2, the Na-H exchanger accounts for approximately 40% of recovery from an acid load, and a Na-HCO3 cotransporter accounts for the remainder. Recovery from an alkaline load appears to occur through the activity of the Cl-HCO3 exchanger.
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PMID:pH regulation in hepatoma cells: roles for Na-H exchange, Cl-HCO3 exchange, and Na-HCO3 cotransport. 255 Nov 79

Glucocorticoid hormones induced a stringent dependence on serum for the in vitro proliferation of Fu5 rat hepatoma cells by suppressing the growth rate and final quiescent cell density. Treatment of dexamethasone-suppressed quiescent Fu5 with serum plus insulin caused a rapid reinitiation of cellular proliferation and DNA synthesis that peaked at 16 h. RNA dot blot analysis of this time course showed that the transcript levels for the proto-oncogenes c-fos, c-myc, and c-rasKi peaked at 0.5, 2, and 4 h, respectively, while expression of c-rasHa and ornithine decarboxylase transcripts rose steadily during 16 h. Microspectrofluorimetric measurements of cytosolic calcium (Ca2+i) with fura-2 showed that insulin and serum, alone or in combination, elicited no changes in Ca2+i over a 50-min time course, although ATP, which is not a mitogen, induced large increases in Ca2+i. Cytosolic pH, pHi, was also measured using 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. Insulin and serum, alone or in combination, did not cause pHi to increase in either 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) (pHi 7.17)- or HCO3/CO2 (pHi 7.19)- buffered media. Acid-loading of cells with NH4Cl indicated that both quiescent and proliferating Fu5 cells have equally active, amiloride-sensitive Na/H exchangers. Therefore, induction of DNA synthesis and proto-oncogene expression occurs in Fu5 epithelial tumor cells in the absence of any short term increases of pHi or Ca2+i.
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PMID:Glucocorticoids confer normal serum/growth factor-dependent growth regulation to Fu5 rat hepatoma cells in vitro. Sequential expression of cell cycle-regulated genes without changes in intracellular calcium or pH. 305 98

Inorganic deposits in the wall of human and animal arteries and in experimental tumor (Morris hepatoma 7777) were examined using proton induced X-ray emission (PIXE) and PIXE in combination with proton microprobe (micro-PIXE) techniques. The sections adjacent to the irradiated ones part were submitted to histological investigations and one part of the material was additionally investigated by infrared (IR) spectroscopy. For identification of mineral deposits, the micro-PIXE method appeared the most sensitive. The mineral deposits were detected in the artery samples, even in those without visible morphological changes, as well as in tumor samples. The deposites showed different localization and composition, depending on age and type of vessel. There were also differences between human and animal arteries. IR spectroscopy revealed the presence of carbonate apatite within the artery samples from old individuals. Matching of histological observations with data obtained by micro-PIXE method allows a better correlation of morphological and analytical results.
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PMID:Investigation of inorganic deposits in selected organic matrices. 322 Jan 41

In previous communications the growth-suppressive effect of gamma-linolenic acid (GLA) dissolved in sodium carbonate in the culture media of malignant cells has been reported. In this study we show that linoleic acid (LA), the fatty acid precursor of GLA, had no growth-suppressive effect on human hepatoma cells in culture while a similar concentration of GLA suppressed malignant cell growth in culture by 69% after 10 days. This growth-suppressive effect must therefore be seen as an effect of GLA and not as a 'soap' effect. It has also been shown that the growth rate of human hepatoma cells in culture to which GLA was added daily for 5 consecutive days remained suppressed after the withdrawal of GLA from the growth medium for a further 5-day period. The striking difference between GLA and LA as regards growth suppression of human hepatoma cells in culture appears to imply a metabolic block in the hepatoma cells, involving the enzyme delta-6-desaturase, in the conversion of LA to GLA and thence via dihomo-gamma-linolenic acid to the prostaglandins of the 1 series.
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PMID:Some effects of linoleic acid and gamma-linolenic acid on the proliferation of human hepatoma cells in culture. 632 95

The transport system for inorganic anions has been investigated in hepatocytes and hepatoma tissue culture cells. Sulfate transport in hepatocytes is temperature sensitive and occurs against an electrochemical gradient. Uptake was shown to occur by a sodium-dependent and a sodium-independent route with Km values of 2.3 and 33 mM and Vmax values of 2.1 and 10 nmol/mg of protein/min, respectively. An analysis of the sodium dependency indicates a Hill coefficient of 1.05 suggesting an equimolar stoichiometry for sodium and sulfate transport. The transport of sulfate was decreased by metabolic and sodium transport inhibitors. Bicarbonate was shown to effect the transport of sulfate, where uptake was accelerated by intracellular bicarbonate and competitively inhibited by extracellular bicarbonate. In addition, sulfate efflux was stimulated by extracellular bicarbonate. These results suggested that bicarbonate is a substrate for the sulfate transport system and can accelerate uptake and efflux by an anion exchange mechanism. Inhibition of bicarbonate uptake by extracellular sulfate and by the anion transport inhibitor 4,4'-diisothiocyano-2,2'-stilbene disulfonate demonstrates that bicarbonate does not enter the cell exclusively by CO2 diffusion but can be transported in part as an anionic species. These results are consistent with its role in the sulfate-bicarbonate exchange system. This inorganic anion transport system was shown to be inhibited by approximately 80% in hepatoma tissue culture cells where altered sodium dependency, Km, and Vmax values reflect possible alterations in the structure and/or membrane content of the carrier.
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PMID:Analysis of the transport system for inorganic anions in normal and transformed hepatocytes. 706 40

For many years after Warburg's classic work, it was generally assumed that tumors produced large amounts of lactic acid and consequently had an acidic intracellular pHi. However, with the advent of Magnetic Resonance Spectroscopy (MRS), a non-invasive in vivo measure of tissue pH became available and demonstrated that in both human and animal tumors, pHi was higher (> 7.0) than pH epsilon (< 6.8), in contrast to normal tissues (e.g., liver) in which pHi (approximately 7.2) is lower than pH epsilon (approximately 7.4). This result has been confirmed in animal tumors using an MRS-visible extracellular marker, 3-aminopropyl phosphonate. The pH gradient across the tumor cell membrane is part of an interrelated system of ionic gradients and measurements made by both 31P MRS and by conventional analysis in Morris hepatoma 9618a and in livers demonstrated that the following ions also changed: compared with liver the Na+ content was 2-fold higher, K+ was 20% lower, total Ca2+ was 8-fold higher (7.4 mumol/g wet wt) and total Pi 2-fold higher (8.5 mumol/g wet wt), suggesting the presence of insoluble calcium phosphate, HCO3- was lower, total Mg2+ was similar in both tissues, but free [Mg2+] (calculated by two different methods) was approximately 5-fold lower in the hepatoma, as was [ATP]/[ADP][P(i)]. Because of an inadequate blood supply, tumors are often hypoxic with impaired Krebs cycle activity, low [ATP]/[ADP][P(i)] and rely mainly on glycolysis for energy. The rapid production and subsequent export of anionic lactate-from the tumor cell would be accompanied by H+. This would account for reversal of the proton gradient and activation of the Na+/H+ exchange. The elevated [Na+]i would decrease the Na+/Ca2+ exchange, which would in turn tend to cause the accumulation of Ca2+ (and P(i)). Such calcification is a very common feature of tumor pathology. The data indicate the change in gradient of one ion (H+) involves alterations in the linked equilibria of many ions and also of energy metabolites and offers new insights into properties of tumors important both diagnostically and therapeutically.
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PMID:Tumor metabolism: the lessons of magnetic resonance spectroscopy. 757 38

Intracellular pH (pHi) plays an important role in the metabolic activation of quiescent cells after a proliferative stimulus, and Na+/H+ exchange activity is required for growth in some extrahepatic tumors. To investigate intracellular acid/base homeostasis in hepatoma cells and the effects of putative liver growth factors on Na+/h+ exchange activity, we have studied intracellular pH (pHi) regulation in Hep G2 cells, a well-differentiated hepatoma cell line, both in resting conditions and after administration of epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), and insulinlike growth factor-II (IGF-II). The effects of fetal calf serum, TGF alpha, and amiloride on 3H-Thymidine incorporation were also studied. Amiloride (1 mmol/L) and external Na+ removal decreased baseline pHi in both HEPES and KRB. In HEPES, cells recovered from an acid load (20 mmol/L NH4Cl) by an amiloride inhibitable Na+/H+ exchange. In KRB, an additional, DIDS-inhibitable, Na(+)- and HCO3- dependent, but Cl(-)-independent acid extruder (Na:HCO3 cotransport) was activated. No evidence was found for a Cl/HCO3 exchange acting as acid loader. Administration of EGF and TGF alpha, but not of IGF-II, induced a dose-dependent, amiloride-inhibitable increase in baseline pHi, together with an increase in Na+/H+ exchange activity, shifting to the right the JH/pHi curve. Finally, 3H-thymidine incorporation in Hep G2 cells, in the presence of FCS or TGF alpha, was strongly inhibited by amiloride. In conclusion, in Hep G2 cells, pHi is mainly regulated by Na+/H+ exchange, which activity can be stimulated by EGF and TGF alpha, but not by IGF-II. Administration of TGF alpha stimulates DNA synthesis, an effect that is blocked by amiloride, an inhibitor of Na+/H+ exchanger. These data suggest that Na+/H+ exchange activation may play a critical role in the growth of some hepatic tumors.
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PMID:Intracellular pH regulation in Hep G2 cells: effects of epidermal growth factor, transforming growth factor-alpha, and insulinlike growth factor-II on Na+/H+ exchange activity. 763 29

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

We previously reported the preparation and characterization of an antibody against membrane fraction of autolysosomes from rat liver (J. Histochem. Cytochem. 38, 1571-1581, 1990). Immunoblot analyses of total membrane fraction of a rat hepatoma cell line, H-4-II-E cells by this antibody suggested that H-4-II-E cells expressed several autolysosomal proteins, including a protein with apparent molecular weight of 60 kDa. It was suggested that this 60 kDa protein was a peripheral membrane protein, because it was eluted from the membrane by sodium carbonate treatment. We prepared an antibody against this 60 kDa protein by affinity purification method, and examined its behavior during induction of autophagy. Autophagy was induced by transferring the cells from Dulbecco's modified Eagle medium (DMEM) containing 12% fetal calf serum into Hanks' balance salt solution. In DMEM, the 60 kDa protein showed diffused immunofluorescence pattern, and immunoelectron microscopy suggested that this protein was located on the extracellular side of the plasma membrane. After inducing autophagy, the immunofluorescence configuration of the 60 kDa protein changed from the diffused pattern to a granulous one. Immunoelectron microscopy showed that the 60 kDa protein was localized on the luminal side of the limiting membrane of autolysosomes and endosomes. In the presence of bafilomycin A1 which prevents fusion between autophagosomes and lysosomes, the 60 kDa protein was localized on the limiting membrane of the autophagosomes and endosomes. These results suggest that the 60 kDa protein is transported from the plasma membrane to the autophagosome membrane through the endosomes.
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PMID:A 60 kDa plasma membrane protein changes its localization to autophagosome and autolysosome membranes during induction of autophagy in rat hepatoma cell line, H-4-II-E cells. 1036 69


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