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)

Specific binding sites for angiotensin II (Ang II) were identified in a human hepatoma cell line, HepG2. Binding of [125I]-Sar1 Ang II to these cells showed a high-affinity site with a Kd of 2.4 +/- 0.2 nmol/l. This specific binding was not changed during the cell cycle and showed no alteration after 24 h of treatment with Sar1-Ang II (10(-8) mol/l). Exposure of HepG2 cells to the Ang II agonist Sar1-Ang II caused a dose-dependent decrease in angiotensinogen production. The maximal inhibitory effect was at a dose of 10(-6) mol/l Sar1-Ang II which elicited 67% inhibition of angiotensinogen production after 24 h (control: 2.015 +/- 0.5 micrograms angiotensinogen/mg DNA; Sar1-Ang II 10(-6) mol/l: 0.68 +/- 0.03 micrograms angiotensinogen/mg DNA). Fifty per cent inhibition was obtained at a dose of 10(-9) mol/l Sar1-Ang II. Angiotensin II had a less marked effect, showing maximal inhibition of 40%. This study shows that the HepG2 cells possess specific Ang II binding sites and that Ang II analogues induce a dose-dependent inhibition of angiotensinogen production in cell culture.
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PMID:Regulation of angiotensinogen production by angiotensin II analogues. 324 Dec 35

The cyclic nucleotide-independent protein kinase which is separated from poly(A) polymerase during its purification from nuclei of rat liver and Morris hepatoma 3924A was purified essentially to homogeneity. Liver nuclear poly(A) polymerase was dissociated from protein kinase by phosphocellulose column chromatography. In contrast, protein kinase copurified with the hepatoma poly(A) polymerase on the phosphocellulose column. Neither liver nor hepatoma kinase was stimulated by spermine or inhibited by heparin. These enzymes did not utilize GTP as phosphoryl donor, or histones or tyrosine-containing [Val5]-angiotensin II as phosphoryl acceptors. The apparent Km with respect to ATP was similar for the liver (4.7 microM) and hepatoma (11 microM) kinases, and the apparent Km with respect to casein was identical (0.6 microgram/microliter) for these enzymes. Both enzymes were capable of phosphorylating poly(A) polymerase and stimulating both tumor and liver poly(A) polymerase activity. However, in addition to their different chromatographic properties, the two kinases differed in molecular weight (liver, 37,000; hepatoma, 56,000), in their response to various divalent metal ions, and in their ability to phosphorylate hepatoma poly(A) polymerase (Km 7.9 and 30 microgram/microliter for liver and hepatoma enzymes, respectively). These latter characteristics distinguished the liver and hepatoma protein kinases from each other as well as from the previously described NI protein kinase.
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PMID:Purification and characterization of a nuclear protein kinase from rat liver and a hepatoma that is capable of activating poly(A) polymerase. 609 60

Elevation of the mean arterial blood pressure to approximately 150 mmHg by infusion of angiotensin II resulted in an approximate 5.7-fold selective increase in blood flow in tumor tissue without increasing blood flow in normal tissue. This finding of no autoregulation of blood flow in tumor tissue was made in an experiment on inbred DONRYU rats with sc transplanted AH109A solid tumors (Yoshida ascites hepatoma). Changes in tissue blood flow were measured by a thermoelectrical method. In another experiment in which DONRYU rats with sc transplanted AH272 solid tumors were used, the chemotherapeutic effect of mitomycin C on main tumors and lymph node metastatic foci was markedly enhanced in rats with angiotensin-induced hypertension, as compared to its effect in rats without angiotensin-induced hypertension. Thus a new approach to cancer chemotherapy has been demonstrated in which the delivery to tumor tissue of systemically administered anticancer drugs can be selectively enhanced.
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PMID:A new approach to cancer chemotherapy: selective enhancement of tumor blood flow with angiotensin II. 694 36

The effect of angiotensin II (Ang II) on the transport of cationic amino acids has been examined in vascular smooth muscle cells (VSMC) isolated from rat aortae. Ang II stimulated the uptake rates of radiolabeled arginine and lysine in a time- and concentration-dependent manner. The stimulated arginine uptake could be blocked by pretreatments with cycloheximide and actinomycin D or co-treatment with valsartan, an antagonist specific for Ang II receptor subtype-1. The modulation by Ang II was bidirectional as the efflux of arginine was also stimulated, 5-fold over basal. Using reverse transcription-coupled polymerase chain reaction methodology, a partial cDNA with 94% sequence identity to that of cationic amino acid transporter subtype-1 (CAT-1) of mouse fibroblasts was obtained from VSMC. This sequence also exhibited 14 base changes compared with the sequence of ecotropic retrovirus receptor (ERR)/CAT-1 from rat hepatoma. Northern analyses with this partial CAT-1 cDNA and CAT-2 cDNA of mouse T-lymphocytes showed that Ang II rapidly stimulated the expression of both CAT-1 and CAT-2 in VSMC. Both signals peaked at 2 h after exposure to Ang II. The CAT-1 signal decayed over the next 6 h to levels 3-fold above basal, which are maintained up until 24 h. The induced CAT-2 mRNA concentration also decayed rapidly but increased again between 16 and 24 h to levels comparable with those observed at 2 h.
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PMID:Angiotensin II stimulates system y+ and cationic amino acid transporter gene expression in cultured vascular smooth muscle cells. 749 19

Astrocytes have been identified as the primary source of brain angiotensinogen (Ao), but the regulation of the secretion of this protein from astrocytes is poorly defined. In this study, the rat C6 glioma cell line was used as an astrocyte model to investigate the regulation of Ao secretion. C6 cultures secreted Ao at a rate of 4.05 +/- 1.52 (mean +/- SD) ng of Ao/10(6) cells/24 h as determined by a direct radioimmunoassay. This rate was not significantly altered by the hormones thyroxine, estradiol, angiotensin II, growth hormone, and prostaglandins or by increased levels of intracellular cyclic AMP. Treatment with the synthetic glucocorticoid dexamethasone (DEX; 10(-6) M) reduced the rate of Ao secretion to 1.82 +/- 0.28 ng of Ao/10(6) cells/24 h. By comparison, the basal secretion rate for rat H4 hepatoma cells was 142.4 +/- 10.0 ng of Ao/10(6) cells/24 h, and this increased fourfold (572.4 +/- 173.1 ng/10(6) cells/24 h) in the presence of 10(-6) M DEX. Both these inhibitory (C6) and stimulatory (H4) actions of DEX were dose related. The inhibition observed in C6 cells was mimicked by RU28362, a pure glucocorticoid agonist, and reversed by the antagonist RU486, demonstrating that DEX was functioning as a true glucocorticoid. The action of DEX was also antagonized by the cyclic AMP analogue N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (dBcAMP) (control, DEX, and DEX + dBcAMP, 3.58 +/- 0.73, 1.69 +/- 0.82, and 4.93 +/- 1.88 ng of Ao/10(6) cells/24 h, respectively, and by the beta-adrenergic agonist isoprenaline, which stimulates cyclic AMP production.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A novel inhibitory role for glucocorticoids in the secretion of angiotensinogen by C6 glioma cells. 751 Jul 76

The effects of different steroids on the expression of angiotensin AT1 receptors by the human hepatoma cell line, PLC-PRF-5 was studied. Dexamethasone and aldosterone decreased the specific binding of [3H]angiotensin II to intact PLC-PRF-5 cells by 57 +/- 4% and 54 +/- 2%, respectively, compared to control, untreated cells. EC50 values for dexamethasone, cortisol and aldosterone were 1.8 +/- 0.6, 40 +/- 6, and 310 +/- 20 nM, respectively, suggesting that these effects were mediated via a glucocorticoid receptor. Scatchard analysis revealed that dexamethasone decreased the number of angiotensin AT1 receptors expressed (50 +/- 4% relative to control) with no change in receptor affinity. Treating cells with dexamethasone in the presence of either an angiotensin converting enzyme inhibitor or an angiotensin II receptor antagonist did not prevent the reduction in angiotensin AT1 receptor expression, ruling out a mechanism involving a dexamethasone induced increase in endogenous angiotensin II production. A ribonuclease protection assay established that the steady state level of angiotensin AT1 receptor mRNA in dexamethasone treated cells was reduced to 34.7 +/- 8.4% of untreated cells. The decrease in the number of angiotensin AT1 receptors expressed on the cell surface after treatment with dexamethasone therefore seems likely to reflect the decreased steady state level of the mRNA coding for this receptor.
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PMID:Glucocorticoids regulate the expression of angiotensin AT1 receptors, in the human hepatoma cell line, PLC-PRF-5. 777 81

In general, chemotherapy does not play an essential role in hepatocellular carcinoma (HCC) because of the low sensitivity to antitumor agents in cancer cells. Additionally, the vast majority of patients with HCC have chronic liver disease, notably cirrhosis, so it is virtually impossible to administer a large amount of antitumor agents. In fact, chemotherapy plays an important part in multimodal treatment for HCC. Whenever chemotherapy is used for patients in the advanced stage, it should be aimed to improve prognosis without impairment of their quality of life. Regarding prognostic factors of chemotherapy for unresectable patients, both reserved hepatic function and tumor advancement are important. Intra-arterial infusion chemotherapy using MMC, ADM, CDDP and/or 5-FU via hepatic artery is appropriately used to improve the therapeutic efficacy. The response rate by one shot injection seems to be approximately 10-20% in general. Although it is not clear which medicine and means of administration are most effective, oral administration is used as a subsidiary treatment for HCC in general. In order to enhance the efficacy of antitumor agents, various drug delivery systems including selective enhancement of tumor blood flow with angiotensin II and drug carriers such as Lipiodol have been applied. Recently, totally implantable arterial access devices have been used for intermittent intra-arterial infusion chemotherapy. It seems to make life easier for the treated patients. Further trials are planned to develop new modes of chemotherapy such as overcoming multidrug resistance by calcium antagonists.
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PMID:[The present status of chemotherapy for hepatocellular carcinoma]. 838 60

The effects of angiotensin II and other six vasoactive agents on tissue blood flow of Yoshida rat ascites hepatoma AH109A and normal liver were measured by the hydrogen clearance method. The mean blood flow in the tumor peripheral part under normotensin was 11.9 +/- 8.2 ml/min/100 g tissue and was not influenced by tumor size. Tumor blood flow was more significantly increased in infusion angiotensin II than 0.5 mg/ml methoxamine; however, normal liver blood flow of tumor-bearing rats was unchanged in contrast to an increase seen in the tumor. A Pronounced reduction of tumor blood flow was found after administration of epinephrine, norepinephrine and ethylphenylephrine. In addition, metaraminol, phenylephrine as well as 1.0 and 2.5 mg/ml methoxamine were not found to significantly change the blood flow of the tumor.
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PMID:[The effects of angiotensin II and other vasoactive agents on the blood flow in Yoshida ascites hepatoma]. 838 31

We quantitatively measured blood flow in liver parenchyma and hepatic tumors in two patients using 15O-carbon dioxide (steady state) and 15O-water (dynamic) PET imaging. Images were acquired before and during administration of angiotensin-II to achieve a hypertensive state. Blood flow in the hepatocellular carcinoma was greater than that of the parenchyma. Blood flow in the colon metastasis was similar to that in the parenchyma and lower in the center than in the periphery. During a hypertensive state induced by angiotensin II, blood flow in both the primary and secondary liver tumors did not change, while blood flow in the liver parenchyma decreased. As a result, there was a relative increase in tumor blood flow during the hypertensive state on PET images. Furthermore, blood flow to the spleen decreased to 55% of baseline during the hypertensive state. These findings suggest that hypertensive cancer chemotherapy may protect normal tissue. Furthermore, PET imaging may be able to predict the efficacy of hypertensive cancer chemotherapy in the patients with liver tumors.
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PMID:Angiotensin-II-induced hypertension chemotherapy: evaluation of hepatic blood flow with oxygen-15 PET. 879 Feb 7

Angiotensinogen is the precursor protein of angiotensin II that is involved in regulating blood pressure and electrolyte homeostasis, and it is mainly synthesized in the liver. In the present study, we analyzed the human angiotensinogen proximal promoter region by means of Chloramphenicol acetyltransferase assays, and suggested that the region from -106 to +44 is sufficient for hepatoma cell line (HepG2)-specific expression. Electrophoretic mobility shift assays using ALE (ATF-like element, -102 to -87) fragment identified CREB/ATF family nuclear factors and novel ones, ALF (ALE-binding factor). The deletion and in vivo competition of ALE decreased the human angiotensinogen promoter activity. Furthermore, the heterologous promoter analysis demonstrated that ALE acts as a HepG2-dependent activating element. These results indicate that ALE plays an important role in hepatic expression of human angiotensinogen gene.
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PMID:ATF-like element contributes to hepatic activation of human angiotensinogen promoter. 926 49


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