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)

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

Balloon occluded arterial infusion (BOAI) is an ideal and widely accepted method for augmentation of the intrahepatic tissue level of anticancer drugs. But this method nakes repeated infusion very difficult because the Seldinger method is needed to cannulate into the hepatic artery. Recently, we made an intrahepatic artery catheter attached with an implantable reservoir, consisting of an intra-arterial catheter, reservoir and cylinder-like device which has a small balloon on its inner part. The cannulation is done at laparotomy. With this method, five cases of nonresectable hepatocellular carcinoma, one metastatic liver cancer and one noncurative hepatocellular carcinoma were treated. Intrahepatic vessels were quite visible by DSA using CO2 gas. Serum concentration level of adriamycin was lower and undetectable at 120 minutes after infusion. No side effects nor catheter complications were observed. Intra-arterial infusion therapy using this device will be a most useful routine method for cancer control in the outpatient clinic.
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PMID:[Fabrication and clinical application of intrahepatic arterial catheter facilitating repeated infusion therapy and experience]. 284 6

Methacetin undergoes rapid O-dealkylation by hepatic microsomal enzyme systems, and the resultant CO2 is present in the expired air. The rate of O-dealkylation of methacetin was assessed by the [13C]methacetin breath test in seven healthy volunteers and 30 patients with histologically proven chronic liver diseases. The 30-min recovery of orally administered [13C]methacetin as 13CO2 in the exhaled air was significantly reduced in patients with chronic aggressive hepatitis and in those with liver cirrhosis but not in patients with chronic persistent hepatitis or healthy controls. Patients with either advanced cirrhosis or hepatocellular carcinoma showed significantly lower values than those with well-compensated cirrhosis. The levels in two patients with late primary biliary cirrhosis were reduced. These results show that the severity of liver damage can be effectively evaluated by [13C]methacetin breath test. In addition, this test is simple, safe, and time efficient.
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PMID:[13C]methacetin breath test for evaluation of liver damage. 303 Jun 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

Viable tissue slices from rat liver and Morris hepatoma 3924A were compared as to their ability to incorporate carbons from [U-14 C]pyruvate into newly synthesized cholesterol versus CO2. By 4 h, the tumor slice incubation had incorporated over 6-fold more pyruvate carbons into the sterol than into CO2, relative to the normal liver slice incubation, per g tissue protein. However, the presence of the mitochondrial citrate exchange carrier inhibitor 1,2,3-benzenetricarboxylate in the incubation inhibited the formation of [14C]cholesterol, while simultaneously leading to an increase in the rate of 14CO2 production in the tumor. In the normal liver system by contrast, benzenetricarboxylate also inhibited [14C]cholesterol formation, but had hardly any effect on the already high rate of 14CO2 production. The ability of benzenetricarboxylate to inhibit the rapid carbon flux from pyruvate to cholesterol, and to steer the metabolic flow of carbons toward oxidative decarboxylation via the Krebs cycle in whole, viable tumor tissue, indirectly emphasizes the importance of the mitochondrial citrate exchange carrier in supporting the decontrol of cholesterogenesis de novo in tumors by accelerating the supply of lipogenic precursor carbons to the tumor cytosol. These studies may be therefore interpreted as extensions, to the level of whole-cell metabolism, of the concept of a persistent 'truncated' Krebs cycle in the mitochondria of metastatic cancer tissue. This concept states, in part, that a rapid efflux of mitochondrially generated citrate would operate preferentially in tumors, and thus provide carbons continuously to the cytoplasmic compartment where the well-established deregulated pathway of cholesterogenesis occurs (Parlo, R.A. and Coleman, P.S. (1984) J. Biol. Chem. 259, 9997-10003; Coleman, P.S. and Lavietes, B.B. (1981) CRC Crit. Rev. Biochem. 11, 341-393).
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PMID:Continuous pyruvate carbon flux to newly synthesized cholesterol and the suppressed evolution of pyruvate-generated CO2 in tumors: further evidence for a persistent truncated Krebs cycle in hepatomas. 308 71

The CO2-ratios method is applied to the analysis of abnormalities of TCA (tricarboxylic acid)-cycle metabolism in AS-30D rat ascites-hepatoma cells. This method utilizes steady-state 14CO2-production rates from pairs of tracers of the same compound to evaluate TCA-cycle flux patterns. Equations are presented that quantitatively convert CO2 ratios into estimates of probability of flux through TCA-cycle-related pathways. Results of this study indicated that the ratio of 14CO2 produced from [1,4-14C]succinate to 14CO2 produced from [2,3-14C]succinate was increased by the addition of glutamine (5 mM) to the medium. An increase in the succinate CO2 ratio is quantitatively related to an increased flux of unlabelled carbon into the TCA-cycle-intermediate pools. Analysis of 14C distribution in [14C]citrate derived from [2,3-14C]succinate indicated that flux from the TCA cycle to the acetyl-CoA-derived carbons of citrate was insignificant. Thus the increased succinate CO2 ratio observed in the presence of glutamine could only result from an increased flux of carbon into the span of the TCA cycle from citrate to oxaloacetate. This result is consistent with increased flux of glutamine to alpha-oxoglutarate in the incubation medium containing exogenous glutamine. Comparison of the pyruvate CO2 ratio, steady-state 14CO2 production from [2-14C]pyruvate versus [3-14C]pyruvate, with the succinate 14CO2 ratio detected flux of pyruvate to C4 TCA-cycle intermediates in the medium containing glutamine. This result was consistent with the observation that [14C]aspartate derived from [2-14C]pyruvate was labelled in C-2 and C-3. 14C analysis also produced evidence for flux of TCA-cycle carbon to alanine. This study demonstrates that the CO2-ratios method is applicable in the analysis of the metabolic properties of AS-30D cells. This methodology has verified that the atypical TCA-cycle metabolism previously described for AS-30D-cell mitochondria occurs in intact AS-30D rat hepatoma cells.
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PMID:Analysis of tricarboxylic acid-cycle metabolism of hepatoma cells by comparison of 14CO2 ratios. 312 Jun 98

The effect of isoflurane on cerebrospinal fluid pressure (CSFP) was determined in 20 patients undergoing craniotomy for intracranial supratentorial neoplasm or hepatoma. In 15 of these patients, following endotracheal intubation, hyperventilation sufficient to result in PaCO2 25-30 torr was begun simultaneously with the introduction of 1 per cent isoflurane. In the remaining five patients ventilation was equivalent, but normocapnia was maintained by adding CO2 to the inspired gases. In the hypocapnic patients CSFPs did not increase above awake values (range 5-45 torr) following isoflurane administration. In the normocapnic patients (CSFPs consistently increased. In three of these five patients the increases were precipitous, but were corrected rapidly by establishment of hypocapnia. The authors conclude that the known cerebral vasodilator properties of isoflurance can be countered effectively by hypocapnia. Furthermore, unlike the situation with halothane, it is not necessary to establish hypocapnia prior to introducing isoflurane in order to avoid CSFP increases.
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PMID:Isoflurane and cerebrospinal fluid pressure in neurosurgical patients. 678 82

Nocturnal intragastric feeding of patients with certain hepatic forms of glycogen storage disease has been advocated as an effective treatment, resulting in improved blood chemical values and linear growth. We are reporting the long-term follow-up of five patients with glycogen storage diseases; three with type Ia, one with type Ib, and one with type III disease. All had improvement in one or more of the following: linear growth, serum glutamic oxaloacetate transaminase, total lipids, cholesterol, phospholipids, or triglycerides. None had significant improvement in venous CO2, serum lactate or urate. One of the patients in this study died after 1.1 years of treatment, and another patient developed hepatocellular carcinoma after 4.4 years of treatment. Nocturnal intragastric feeding, in conjunction with appropriate daytime feeding, is helpful in the management of patients with glycogen storage disease but response to treatment is variable, and it remains to be determined whether the ultimate prognosis of the diseases can be improved.
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PMID:Glycogen storage disease: long-term follow-up of nocturnal intragastric feeding. 680 87

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

Hepatocellular carcinoma (HCC) is considered to develop either on a background of preneoplastic lesions as multistep carcinogenesis or on a liver without such a lesion as de novo. The latter course can be assumed by our clinical experience of imaging diagnosis and by follow up studies of alpha fetoprotein (AFP) producing HCCs. Although serial checkup of AFP is important, serological or genetic approach is little use for early detection of HCC. At present, imaging diagnosis especially ultrasound is the best modality for detecting early developing HCC. The most reliable way for the final diagnosis of the detected mass is done by aspiration histology using a 21G needle with ultrasound guidance. Recent new imaging modalities such as contrast enhanced ultrasound using CO2 microbubbles or CTAP are not so reliable as aspiration histology, especially in tumors less than 15 mm in diameter.
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PMID:[Early diagnosis of hepatocellular carcinoma]. 750 20


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