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 broad-range proteinase inhibitor alpha 1-inhibitor III (alpha 1I3), a member of the complement C3/alpha 2-macroglobulin protein family, is the prototype of a negatively regulated acute phase protein. During an acute inflammatory reaction alpha 1I3 plasma protein and liver mRNA concentrations are decreased three- to fourfold in rats, and in chronic inflammations the protein concentration is reduced between ten- and 20-fold. In search of a cell culture model to study the regulation of the alpha 1I3 gene by mediators of inflammation, five well-established rat hepatoma cell lines were examined. All five lines constitutively expressed the gene, a marker for a highly differentiated hepatic phenotype, although at less than one-tenth the level of its expression in vivo. In the three hepatoma lines FAZA, FTO2B and FAO1, alpha 1I3 mRNA was decreased by treatment with interleukin 6 (IL6) and glucocorticoids. Among these lines untreated FAO1 cells produced the highest constitutive concentrations of alpha 1I3 mRNA and in FAO1 cells alpha 1I3 mRNA concentrations were decreased up to fourfold in a dose-responsive and time-dependent manner after treatment with IL6 alone or with combinations of IL6 and the synthetic glucocorticoid dexamethasone. Thus, IL6 alone was sufficient to negatively regulate alpha 1I3 mRNA levels in hepatoma cells with similar characteristics as occur during an inflammatory response in the liver. A number of other acute phase mRNA species, including alpha 1-acid glycoprotein, T2-kininogen, gamma-fibrinogen and alpha 2-macroglobulin were induced to higher levels by the same hormonal treatments in FAO1 cells. The fourfold reduction of alpha 1I3 mRNA concentrations in FAO1 cells could be reversed by treatment with 1 microM of a water-soluble derivative of forskolin, an activator of the cyclic AMP pathway. Thus, the effect of IL6 on the expression of the alpha 1I3 gene may involve the activation of the cyclic AMP pathway. In contrast, T2 kininogen mRNA levels were not altered by treatment of FAO1 cells with forskolin, suggesting that IL6 may act on this gene through a different mechanism.
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PMID:Interleukin 6 is a negative regulator of the acute phase alpha 1-inhibitor III gene. 169 10

Combination therapy with hyperthermia and immuno-targeting chemotherapy was studied using conjugate of anti-AFP-antibody and adriamycin on AFP producing hepatocellular carcinoma (HC-4) in nude mice. Experimental groups were designed as follows; A. Control B. Adriamycin alone C. Conjugate alone D. Hyperthermia alone E. Adriamycin and hyperthermia F. Conjugate and hyperthermia. Hyperthermia was performed immediately after administration of ADM-conjugate (8.0 mg/kg as ADM) or ADM alone (8.0 mg/kg). Heating in the water bath was continued for 30 minutes at 42 degrees C or 40 degrees C and drug was injected intraperitoneally. Hyperthermic therapy at 42 degrees C along with ADM-conjugate completely inhibited the tumor growth compared with others. The serum AFP was undetectable level. The effectiveness of this treatment was also histologically confirmed. Tumor concentration of ADM remained at a significantly higher level for a prolonged period comparing other groups. Growth of HC-4 was completely suppressed by the combination therapy of hyperthermia and immuno-targeting chemotherapy. One of the probable causes of this antitumor effect may be due to prolonged and high level of ADM concentration in the tumor.
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PMID:[Effects of combination therapy with hyperthermia and immuno-targeting chemotherapy using anti-AFP antigen on hepatocellular carcinoma]. 169 58

A 64 kilodalton (kDa) surface protein was isolated from the water-extracted materials from Mycobacterium bovis strain BCG, the determinants of which are antigenically shared by a 64 kDa major surface antigenic component of line 10 hepatoma cells. The 64 kDa protein showed anti-line 10 tumor activity in pre-immunized guinea pigs, and this suggest that the BCG 64 kDa protein is probably identical with the tumor specific antigen.
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PMID:A 64 kDa protein from Mycobacterium bovis BCG shares the same antigenic determinants with line 10 hepatoma cells and has anti-line 10 tumor activity. 171 93

Menadione (vitamin K3, 2-methyl-1,4-naphthoquinone) is a synthetic derivative of napthoquinone. Its ability to inhibit cell growth in a wide variety of and human tumor cell types, and in rat hepatocytes has been recognized. Using a rat transplantable hepatoma model, we have evaluated the cytotoxic activity of menadione in hepatoma cells. Tumor cells in culture were sensitive to menadione treatment. The ID50 of drug is 3.4 microM as shown by a colorimetric MTT (3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Tumor-bearing rats were randomized into the treatment (n = 16) and control (n = 15) groups. Rats in the treatment group received intraperitoneal injection of menadione (10 mg/2 ml) once a week for four times; the control group received 2 ml water instead. None of the control rats survived after the 17th day following the start of treatment, while 5 out of the 16 treated rats responded well and survived long-term (greater than 60 days). Medadione was shown to inhibit actively the growth of hepatoma cells in vitro as well as in vivo.
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PMID:The in vitro and in vivo cytotoxicity of menadione (vitamin K3) against rat transplantable hepatoma induced by 3'-methyl-4-dimethyl-aminoazobenzene. 177 38

Various contrast agents are applied in both CT and MR imaging to improve the detection as well as the differentiation of focal liver lesions. In detecting hepatocellular carcinoma, the accuracy of Lipiodol-enhanced CT is comparable to that of CT during arterial portography. Tissue-specific contrast agents for the liver are superparamagnetic iron oxide particles, which are characterized by uptake in the reticuloendothelial system, and the paramagnetic hepatobiliary contrast agent manganese (II)-N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5'-bis(phosphate). Both substances have the potential for markedly improving the detection of malignant liver tumors. The already good differentiation of focal hepatic lesions on plain MR images can be further improved by dynamic gadolinium diethylenetriamine penta-acetic acid-enhanced MR imaging. In the diagnosis of bile duct disorders, contrast-enhanced CT continues to be the method of choice. Water applied as a gastrointestinal contrast agent improves the staging of rectal carcinoma by CT. The development of suitable orally applied gastrointestinal contrast agents has now also improved the differentiation of the intestine from other abdominal structures on MR images, and this will lead to a general improvement of abdominal MR imaging.
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PMID:Contrast material for computed tomography and magnetic resonance imaging of the gastrointestinal tract. 185 83

The PLHC-1 fish hepatoma cell line (Poeciliopsis lucida) was used in the neutral red assay to evaluate the acute cytotoxicities of direct-acting (alkylbenzenes, phthalate diesters, and pesticides) and metabolism-mediated (benzo[a]pyrene) toxicants. The sequence of cytotoxic potencies for the alkylbenzenes and phthalate diesters appeared to be a direct function of their hydrophobicity (as described by logarithmic octanol/water partition coefficients). The organochlorine pesticides (alachlor and p,p'-methoxychlor) were more cytotoxic than the organophosphorus pesticides (EPN, diazinon, and malathion). The PLHC-1 cell line apparently maintained sufficient xenobiotic-metabolizing capacity, as the hepatoma cells were able to metabolize benzo[a]pyrene to cytotoxic intermediates. Xenobiotic-metabolizing capacity was temperature dependent, with enzymatic activity increasing as the temperature was increased from 28 to 34 to 37 degrees C, was inducible by Aroclor 1254 (a chemical inducer of cytochrome P450-dependent monooxygenase activity), and was reduced by EPN (an inhibitor of P450 activity).
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PMID:In vitro cytotoxicity studies with the fish hepatoma cell line, PLHC-1 (Poeciliopsis lucida). 186 89

Residents in the endemic area of blackfoot disease (BFD), a unique peripheral artery disease associated with long-term arsenic exposure, have been reported to have a significantly high mortality from hepatocellular carcinoma (HCC). A total of 129 BFD patients and 374 age-sex-residence-matched community controls were studied to examine their hepatitis B surface antigen (HBsAg) carrier status by radioimmunoassays. Residents in the endemic area had a HBsAg carrier rate (20.2%) similar to that of the general population in Taiwan. The rate was the same among BFD patients (20.9%) and matched controls (20.1%). There was no significant difference in HBsAg carrier rate among subjects who have consumed high-arsenic artesion well water for different periods of time. The rate was also similar in villages with differences in blackfoot disease prevalence, in type of wells for drinking water, as well as in arsenic content in well water. Arsenic seems to increase HCC risk of residents in this endemic area where the HBsAg carrier status is homogeneously prevalent with a rate similar to that of the general population in Taiwan.
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PMID:Prevalence of hepatitis B surface antigen carrier status among residents in the endemic area of chronic arsenicism in Taiwan. 201 56

The level of certain water-soluble hydrocarbon conjugates, such as benzo[a]pyrene sulfates (BP-SO4), is a direct measure of carcinogenic polycyclic aromatic hydrocarbon metabolism and an indication of exposure. A new method, based on continuous-flow high-resolution fast atom bombardment mass spectrometry, has been developed for the analysis of BP-SO4 in the medium of cell cultures treated with benzo[a]pyrene. An organic solvent extract of medium from cultures of the human hepatoma cell line (HepG2) was fractionated by reversed-phase SEP-PAK chromatography and microbore high-performance liquid chromatography (HPLC). The HPLC fraction containing BP-SO4 was collected, dried, and injected into a stream of acetonitrile/water/glycerol that was continuously flowing to the tip of the sample probe which was being bombarded continuously by a beam of high-energy xenon atoms. Molecular anions of BP-SO4 (m/z 347) desorbed from the liquid were analyzed by a high-resolution (m/delta m 5000) mass spectrometer and recorded as a function of time. As little as 1.5 pg of BP-SO4 could be detected with a S/N ratio of 8. The mass spectrometer response was linear with respect to the quantity of BP-SO4 injected over the range from 15 to 625 pg. The results obtained with this method show that the HepG2 cultures metabolized 3% of the benzo[a]pyrene into the BP-SO4 conjugate in 24 h. This procedure, which was used to detect and quantify directly BP-SO4 in culture medium without the use of a radiolabeled precursor, should be generally applicable for analyses of sulfated conjugates resulting from the metabolism of different hydrocarbons.
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PMID:Determination of benzo[a]pyrene sulfate conjugates from benzo[a]pyrene-treated cells by continuous-flow fast atom bombardment mass spectrometry. 206 9

In previous publications, one of us demonstrated that variation in paramagnetic-ion contents is a major contributing factor to the different NMR relaxation times, T1 and T2, of water protons among normal mouse tissues; and between normal tissues and cancer cells. The nature of the paramagnetic ions involved was not determined. In the present communication, we report results of analysis of the contents of three biologically prominent paramagnetic ions (manganese, iron and copper) in 9 normal mouse tissues (brain, heart, small intestine, kidney, liver, lung, voluntary muscle, spleen and stomach); one strain of rat cancer cells (As-30, rat hepatoma); and 6 strains of mouse cancer cells (Ehrlich mammary adenocarcinoma, LSA lymphoma, Krebs carcinoma of the inguinal region; sarcoma 180; Klein TA3 mammary adenocarcinoma; P815 mast cell leukemia). Our data indicate that manganese and iron are by far the two most important paramagnetic ions contributing to the diversity of NMR relaxation times. The average manganese content of all the normal mouse tissues studied (29.6 +/- 4.99 mu mole/kg) is 24 times higher than the average manganese contents of all the cancer cells studied (1.22 +/- 0.27 mu moles/kg) and there is essentially no overlap between the two groups of data. The average iron content of the normal mouse tissues (281.6 +/- 51.2 mumoles/kg) is 4 times the average in cancer cells (66.7 +/- 7.74 mumoles/kg) but there is some overlap here. The observed differences in both the manganese and iron contents are statistically highly significant, with P's below 0.0001. The copper contents of the cancer cells is lower than the average of normal mouse tissues but only by some 20%. The difference is statistically insignificant at the 0.05 level but significant at the 0.2 level.
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PMID:Low paramagnetic-ion content in cancer cells: its significance in cancer detection by magnetic resonance imaging. 159 62

The influence of eicosanoids on the proliferation of hepatoma (HTC) cells was studied in culture and in tumor-bearing rats. The cells in culture demonstrated a capacity to metabolize arachidonic acid to eicosanoids including thomboxane B2 and the prostaglandins E2 and F2 alpha a. An effect of these eicosanoids on cell proliferation was suggested by the decreased cell division seen with an inhibitor of cyclooxygenase, flurbiprofen. A biphasic effect on the proliferation of HTC cells was observed with increasing concentrations of prostaglandin F2 alpha. These studies were extended to tumor-bearing rats where inhibitory effects on the early stages of tumor growth were seen with flurbiprofen. Bleeding times were decreased in tumor-bearing rats but were restored to control values by treatment with flurbiprofen and an inhibitor of thromboxane synthetase, OKY 046. These drugs and a thromboxane/endoperoxide receptor antagonist, SQ 29, 548, were not observed to have statistically significant effects on isotope-labeled water distribution but they had substantial effects on the maintenance of body weight by tumor-bearing rats. The data suggested that the cachexia of tumor-bearing animals may be mediated at least in part by the action of eicosanoids.
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PMID:Influence of inhibitors of eicosanoid metabolism on proliferation of rat hepatoma cells and on tumor-host interaction. 211 60


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