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 effects of various cytokines on synthesis and microheterogeneity of carbohydrate structure of alpha 1-proteinase inhibitor (PI) and alpha-fetoprotein (AFP) in the human hepatoma cell lines Hep 3B and Hep G2 were studied. In both lines, crude cytokine preparations from LPS-activated human monocytes (CM) and several cell lines led to increased PI and decreased AFP synthesis, while recombinant interleukin 1 (IL-1), recombinant tumor necrosis factor (TNF) and hepatocyte stimulating factor preparations (HSF) affected AFP but not PI production. Several of the crude cytokine preparations, but not IL-1, TNF, or HSF, caused Hep 3B cells to secrete forms of PI and AFP showing increased reactivity with Con A upon testing by affinity electrophoresis, while decreased reactivity with Con A was seen in these proteins secreted by Hep G2 cells. Determination of molecular size of PI inducing activity in CM showed a sharp peak at about 17 kD while AFP inhibiting activity was present in a very broad range of molecular size fractions maximal at 17-30 kD. Changes in patterns of glycosylation of these proteins were attributable to cytokines of about 30 kD in Hep 3B and 44 kD in Hep G2 cells. These findings demonstrate the existence of a family of glycosylation regulating cytokines, and suggest that distinct mechanisms within hepatocytes, responsive to different cytokines, may lead to increased or decreased Con A binding of glycoproteins and to altered gene expression.
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PMID:Effect of cytokines on glycosylation of acute phase proteins in human hepatoma cell lines. 246 70

Plasma abnormal prothrombin (protein induced by vitamin K absence or antagonist-II: PIVKA-II) was evaluated as a serological marker for hepatocellular carcinoma (HCC). Its plasma levels were measured by enzyme immunoassay using an anti-PIVKA-II monoclonal antibody in 1010 patients with various diseases. Of 192 patients with HCC, 116 (60%) had abnormal PIVKA-II levels greater than 0.1 AU/ml. Elevation of PIVAK-II levels was observed rarely in chronic hepatitis, liver cirrhosis and other malignant tumors. Plasma PIVKA-II levels in HCC increased with tumor size. Normal levels were observed in patients with tumors measuring 2 cm or less in diameter. As a result, diagnostic application of plasma PIVKA-II levels to small liver tumors is limited. The sensitivity of PIVKA-II in the diagnosis and monitoring of HCC was increased by serial and simultaneous determinations of AFP, because high PIVKA-II levels were observed more often in low AFP-producing HCC patients. In some patients with HCC, plasma PIVKA-II levels decreased after surgical resection of the tumor or chemoembolization with cisplatin suspended in Lipiodol (LPS), but later rose again with recurrence of the disease. Elevated plasma PIVKA-II levels were not related to low vitamin K concentration in the serum. In fact, in many patients vitamin K administration resulted in only a moderate reduction of PIVKA-II levels. From these results, plasma PIVKA-II assay by the EIA method using a monoclonal antibody is a useful tool for the diagnosis and monitoring of HCC, particularly in HCC patients with low AFP levels.
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PMID:[Clinical usefulness of plasma PIVKA-II assay and its limitations in patients with hepatocellular carcinoma]. 247 53

A method to prepare cisplatin suspended in an oily lymphographic agent, Lipiodol (LPS), has been established to deliver cisplatin to hepatocellular carcinoma (HCC) by the hepatic artery. Seventy-one patients, one Stage I, 16 Stage II, 16 Stage III, and 38 Stage IV, were treated with LPS therapy. A partial response was obtained in 33 cases (46.5%), a minor response in 20 cases (28.2%), and no change in 18 cases (25.3%). In 34 patients whose serum alpha-fetoprotein (AFP) levels were greater than 400 ng/ml, the serum AFP levels decreased in 31 patients (91.2%). The AFP decreased by more than 50% in 25 cases (73.5%) and more than 75% in 19 cases (55.9%). The plasma des-gamma-carboxy prothrombin (DCP) levels decreased in all of the 26 DCP-positive patients. The survival rate was 77% at 6 months and the 1-year survival rate was estimated to be 55%. The patients treated with LPS therapy survived longer compared with patients given Lipiodol containing neocarzinostatin by the hepatic artery. Complications such as acute gastroduodenal mucosal lesions (24%), cholecystitis (2.8%), pancreatitis (7%), delayed jaundice (7%), and hepatic encephalopathy (4.2%) were observed after therapy. The peak plasma platinum (Pt) concentrations determined as ultrafilterable Pt occurred 5 to 20 minutes, and 5 to 60 minutes as total Pt after the end of LPS injection. The Pt concentrations in the tumor tissues were 42 times higher in four operated cases and 7.1 times higher in six autopsy cases than those in the nontumorous tissue. These results suggest that LPS selectively accumulates in the HCC, is long-lasting and gradually releases the drug. In addition it is effective as a new anti-cancer therapy for hepatocellular carcinoma.
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PMID:Hepatic arterial injection chemotherapy with cisplatin suspended in an oily lymphographic agent for hepatocellular carcinoma. 247 31

We established a preparation method for the suspension of cisplatin in Lipiodol (LPS) and applied it by intra-hepatic artery injection for the treatment of advanced hepatocellular carcinoma. We defined that stage IV carcinoma as characterized by tumor spread more than one lobe (H4) or by tumor emboli in the major branches of the portal vein (Vp3) or by distant metastasis (M1). According to this definition, 20 patients of stage IV were treated by this therapy, and evaluated the survival using Kaplan-Meier method. A reduction in tumor size more than 25% was observed in 11 of 20 patients (55%). In 4 of these cases (20%), over 50% of tumor reduction was obtained. In 15 patients whose serum alpha-fetoprotein (AFP) levels were higher than 400 ng/ml, a decrease more than 50% was noted in 9 of the 15 patients (60%). Sixty per cent survival rate was obtained at 6 month. A statistical by significant difference was obtained in the survival patterns between this therapy and other intra-arterial chemotherapy. The factors that influenced on the survival significantly were AFP levels (over 10,000 ng/ml), Vp3 and M1. However, tumor size and intrahepatic metastasis, etc. were not significant factors. LPS therapy seemed to be effective to even stage IV hepatocellular carcinoma and could be applied further.
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PMID:[Intra-arterial injection of cisplatin suspension in lipiodol (LPS) for the treatment of advanced hepatocellular carcinoma (stage IV)]. 253 53

Cisplatin suspension in Lipiodol (LPS) was prepared for the treatment of hepatocellular carcinoma by intra-hepatic arterial injection. In a rabbit liver cancer model, concentrations of cisplatin in tumor were more than 20 times higher than those in a nontumorous part of the liver at 5 min after LPS injection into the hepatic artery. Cisplatin at high concentrations was detected at 7 days after injection. The concentrations in other organs were lower except in the gall-bladder. In clinical trials for 71 patients with hepatocellular carcinoma, partial response was observed in 33 cases (46.5%) and minor response in 20 cases (28.2%). The survival rate was 77% at 6 month and 55% at one year. Although fever, nausea, vomiting and epigastralgia were observed as side effects, these were temporary. Acute gastroduodenal mucosal lesions, cholecystitis, pancreatitis, delayed jaundice and hepatic encephalopathy were observed as complications and super selective cannulation was necessary for their prevention.
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PMID:[Intra-arterial injection of cisplatin suspension in Lipiodol (LPS) in the treatment of hepatocellular carcinoma]. 255 Dec 47

We have looked for IL-6, a cytokine that has immunomodulating and inflammation-associated activities, in joint exudates (fluid and mononuclear cells) from patients with rheumatoid arthritis and other arthritides using both biologic and biochemical assays. IL-6 was assessed by its ability to stimulate alpha 1-antichymotrypsin secretion from the human hepatoma cell line Hep3B clone 2, an activity which is blocked by an antiserum to Escherichia coli derived IL-6, and by the growth of the IL-6-dependent murine hybridoma 7TD1 cell line. IL-6 isoforms in synovial fluid were characterized by immunoaffinity chromatography followed by Western blotting. The presence of IL-1 in synovial fluids and its production by synovial fluid mononuclear cells was monitored by Western blotting and indirect immunofluorescence with polyclonal anti-IL-1 beta antisera. In an analysis of 30 effusions from 27 rheumatoid patients with acutely inflamed joints, abundant quantities of IL-6 (greater than 2 ng/ml) were detected in 23 by the alpha 1-antichymotrypsin bioassay. Several rheumatoid synovial fluids also had elevated IL-6 levels in the 7TD1 bioassay. Seven of nine nonrheumatoid effusions also contained high levels of IL-6 (greater than 2 ng/ml). No IL-1 (less than 0.25 ng/ml) could be detected by Western blotting in 10 rheumatoid effusions even though eight of these contained high levels of IL-6. The IL-6 activity could be neutralized with a rabbit antiserum to rIL-6. Multiple IL-6 isoforms (25, 30, 45 kDa) were present in two rheumatoid and one traumatic effusion studied. Fresh mononuclear cells isolated from various synovial effusions did not appear to make IL-6 constitutively, as no IL-6 could be detected in the media of cells cultured for 12 to 18 h after isolation. Similarly, there was no constitutive production of IL-1 by these cells. However, synovial fluid mononuclear cells could be induced to secrete both IL-6 and IL-1 after stimulation with LPS. The LPS-responsive cells were monocytes and not lymphocytes or dendritic cells. These findings suggest that IL-6 is involved in inflammatory joint disease. However, the primary cells synthesizing it may be located in the synovial lining instead of the joint exudate.
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PMID:IL-6/IFN-beta 2 in synovial effusions of patients with rheumatoid arthritis and other arthritides. Identification of several isoforms and studies of cellular sources. 278 56

Haptoglobin is a plasma protein scarcely present in fetal but abundant in adult serum, where it is present at a concentration of approximately 150 mg/100 ml. In this paper we show by run-on experiments that the haptoglobin (Hp) gene is actively transcribed in adult but not in fetal liver nuclei. Studies with established cell lines indicate that the Hp gene is expressed in the hepatoma cells HepG2 but not in the hepatoma cell line Hep3B nor in HeLa cells. Plasmids carrying various segments of the 5' flanking region of the Hp gene fused to the chloramphenicol acetyl transferase (CAT) gene direct CAT transcription when introduced into HepG2 but are inactive in Hep3B and in HeLa cells, thus behaving like the resident chromosomal Hp gene. Deletion analysis defines a region, upstream to the transcription initiation site, essential for cell-specific expression. The Hp gene is induced in Hep3B cells by treatment with supernatant from LPS-stimulated monocytes (SMS), in a manner mimicking the acute phase reaction. We characterize the DNA segment necessary and sufficient for cell-specific expression of the Hp-CAT constructions in HepG2 and show that the same segment is also sufficient for acute phase induction in Hep3B.
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PMID:The human haptoglobin gene: transcriptional regulation during development and acute phase induction. 282 Jul 12

alpha 1-acid glycoprotein (alpha AGP) is a well-characterized human plasma protein. Its structural properties have been studied for many years but little is known about its function. Amino acid sequence analysis of purified human alpha AGP from plasma pooled from several individuals showed considerable heterogeneity. We have cloned the genomic DNA segment encoding alpha AGP and we show that it contains three adjacent alpha AGP coding regions, AGP-A, B and B', identical in exon--intron organization but with slightly different coding potential. These results account for the heterogeneity observed by protein sequencing. Southern blot analysis indicates that the cloned cluster contains all the alpha AGP coding sequences present in the human genome. The larger majority of alpha AGP mRNA in human liver is transcribed from AGP-A, whose promoter and cap site have been determined while the level of AGP-B and B' mRNA in human liver is very low. Using Hep3B hepatoma cells as a model system for the in vitro study of the acute phase reaction, we show that only AGP-A is strongly induced by treatment with culture medium of LPS stimulated monocytes.
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PMID:Structure and expression of the genes coding for human alpha 1-acid glycoprotein. 282 85

TNF-stimulated gene-14 (TSG-14) encodes a secreted glycoprotein with significant sequence homology to C-reactive protein (CRP) and serum amyloid P component (SAP), members of the pentraxin family of acute phase proteins. TSG-14 mRNA was elevated in human FS-4 fibroblasts by treatment with TNF, IL-1, or bacterial LPS, and weakly by dexamethasone. Abs to recombinant TSG-14 immunoprecipitated a 42-kDa protein from the culture supernatants of TNF- or IL-1-stimulated FS-4 cells. TSG-14 protein was also inducible in the Hep3B human hepatoma cell line by TNF, IL-1, IL-6, or dexamethasone. CRP protein, identified by immunoprecipitation of a 25-kDa band with Abs to CRP, was induced in Hep3B cells by IL-1, IL-6, or dexamethasone. Immunoprecipitations with polyclonal Abs to TSG-14 and CRP suggested that the two proteins are immunologically cross-reactive. Appearance of TSG-14 protein was demonstrated in the serum of mice after injection with LPS. No TSG-14 mRNA was detected in the liver of LPS-injected mice, suggesting that hepatocytes are not the major site of TSG-14 synthesis. Thus, in the intact organism the main cellular sources of TSG-14 and classical acute phase proteins appear to be different.
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PMID:Relationship of TSG-14 protein to the pentraxin family of major acute phase proteins. 752 2

Tenidap is a novel anti-inflammatory and anti-arthritic agent that lowers intracellular pH and suppresses anion transport when applied to cells in vitro. Both of these parameters are known to influence pro-inflammatory cell function. To investigate whether tenidap can modulate cellular responses to cytokine stimulation, several in vitro cytokine-driven assays were characterized with respect to their tenidap sensitivity. Human monocytes treated with granulocyte-macrophage colony stimulating factor (GM-CSF) demonstrated an increased production of IL-6 as well as an increased total translational activity. Tenidap dose-dependently inhibited both cytokine-induced responses; the effect on IL-6, however, occurred at lower tenidap concentrations than those required to prevent the increase in total translational activity. In contrast, the known translational inhibitor cycloheximide did not demonstrate selectivity for IL-6; this agent decreased the GM-CSF-induced increase in total translational activity in parallel with its effects on IL-6. GM-CSF-treated monocytes also produced greater amounts of IL-1 beta in response to LPS stimulation than did non-GM-CSF-treated cells, and tenidap again suppressed this cytokine-induced activation. Human Hep3B cells treated with a combination of interleukin (IL)-1 beta and IL-6 demonstrated an acute phase-type of response. These hepatoma cells increased production of the positive acute phase protein serum amyloid A (SAA) while they decreased production of a negative acute phase protein human serum albumin (HSA). Tenidap dose-dependently inhibited the cytokine-induced increase in SAA production without effecting synthesis of HSA or total TCA-precipitable macromolecules. Importantly, the ability of tenidap to alter these various cytokine responses was not shared with piroxicam, a potent cyclooxygenase inhibitor. Finally, human neutrophils treated with either GM-CSF or tumor necrosis factor (TNF)-alpha demonstrated an increased chloride conductance as measured by the loss of radioactive chloride from 36Cl-loaded cells. When tenidap was included within the medium during cytokine stimulation, loss of radioactive chloride was prevented. Thus, tenidap inhibited the cytokine-induced increase in anion transport. Together, these results indicate that tenidap can suppress cellular activation processes induced by a variety of cytokines. This functional antagonism is not dependent on cyclooxygenase inhibition but, rather, appears to link to tenidap's unique ability to alter ionic homeostasis. These in vitro observations, therefore, may help to explain how this novel anti-inflammatory agent acts to lower acute phase proteins and IL-6 levels in man.
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PMID:Inhibition of cytokine activation processes in vitro by tenidap, a novel anti-inflammatory agent. 778 40


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