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 changes in the plasma level of PIVKA-II (Protein Induced by Vitamin K Absence or Antagonist-II) following the treatment or progress of the disease was studied in 60 patients with hepatocellular carcinoma. The positivity rate determined by the changes in PIVKA-II was 58.4 percent (35/60 cases) and was about the same as those reported so far, all of which were obtained by a single determination of PIVKA-II. Plasma PIVKA-II was elevated in 61.9 percent (13/21 cases) of alpha-fetoprotein negative patients and it was almost identical with the overall positivity rate. In parallel with serum alpha-fetoprotein, the plasma level of PIVKA-II was decreased after the surgery or transcatheter arterial embolization and was increased when the recurrence or progress of the disease was observed. Furthermore, the nonspecific elevation of PIVKA-II due to the associated liver cirrhosis or chronic hepatitis was infrequent compared with that of alpha-fetoprotein. In 18 cases positive with both PIVKA-II and alpha-fetoprotein, a close correlation (R = 0.91) was observed between the changes of these markers during the progress or treatment of the disease. Thus, it was suggested that determination of PIVKA-II in blood might be useful not only in the diagnosis but in monitoring the progress or the effectiveness of treatments in hepatocellular carcinoma.
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PMID:[The clinical significance of PIVKA-II determination in patients with hepatocellular carcinoma: a comparative study with alpha-fetoprotein]. 169 80

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

Prothrombin synthesis and secretion were studied in a human hepatoma cell line (Hep G2) incubated with 35S-methionine for 2 to 24 hours at 37 degrees C. Extracellular and intracellular prothrombin were detected by immunoprecipitation with affinity-purified antiprothrombin antibody. Incorporation of 35S-methionine into prothrombin was monitored by counting specific bands excised from 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Prothrombin represented 0.3% to 0.7% of total newly synthesized protein secreted into the media. Warfarin had no effect on total prothrombin synthesis (extracellular plus intracellular). However, warfarin inhibited secretion of newly synthesized prothrombin by 58% to 73% over a 2 to 4 hour period. This was accompanied by the intracellular accumulation of an immunoprecipitable species of prothrombin of 78 kd, 6 kd less than extracellular prothrombin. At the end of the 4-hour incubation with warfarin, intracellular prothrombin increased from 44% to 82% (twofold) of total prothrombin, whereas extracellular prothrombin decreased from 56% to 19% (threefold) of total prothrombin. After 24-hour incubation with warfarin, intracellular and extracellular immunoprecipitable prothrombin approached control values. Deglycosylation of extracellular and intracellular prothrombin with hydrofluoric acid (HF) resulted in a decrease in mol wt for both species to 66 kd. Endoglycosidase-H treatment, which digests "early mannosyl" residues, resulted in a decrease in the mol wt of the intracellular species of 8 kd with no effect on the extracellular species. Thus, the lower mol wt intracellular species that accumulates following early warfarin treatment is due to the presence of incompletely processed carbohydrate chain. The data are compatible with the hypothesis that optimum glycosylation and secretion require Vitamin K-dependent carboxylation.
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PMID:Effect of warfarin on prothrombin synthesis and secretion in human Hep G2 cells. 304 Jan 56

Vitamin K is required for the posttranslational formation of gamma-carboxyglutamyl residues in a number of plasma clotting factors. Interference with vitamin K action results in the appearance of abnormal (des-gamma-carboxy) forms of prothrombin in human plasma. Vitamin K-sufficient patients with primary hepatocellular carcinoma also secrete significant quantities of abnormal prothrombin; this response has now been studied in a rat model. Normal Buffalo strain rats had 9 micrograms/mL of circulating plasma abnormal prothrombin, whereas Buffalo strain rats carrying the transplantable Morris hepatoma tumor no. 7777 had 33 micrograms/mL at 3 weeks after transplant. Vitamin K-dependent carboxylase activity was normal in the liver of these rats, but very low in the tumor tissue. Rats carrying Morris hepatoma tumors no. 9618A and 5123D did not secrete significant amounts of abnormal prothrombin. Carboxylase activity in these tumors was 15 times that of the 7777 tumor. The data suggest that the secretion of abnormal prothrombin by hepatocellular tumors is the result of normal expression of the prothrombin gene by those tumors and a failure of the tumor to express the carboxylase gene.
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PMID:Abnormal prothrombin in the plasma of rats carrying hepatic tumors. 381 18

The human hepatoma cell line, Hep G2, was analyzed for the ability to synthesize and secrete several coagulation proteins. Using specific radioimmunoassays, factor X, prothrombin, and antithrombin III were present in 8-day culture supernatants at 62, 405, and 1,220 ng/mL, respectively. Factor IX was not detected, either in supernatants or in cell extracts. Intrinsically labeled factor X was secreted as a single-chain polypeptide of 66,000 daltons, as measured by sodium dodecylsulfate-polyacrylamide gels under nonreduced and reduced conditions. Immunoblots of Hep G2 supernatants and normal human plasma also indicate the presence of single-chain factor X. These findings support the hypothesis of a postsecretion proteolytic cleavage of factor X into the two-chain form. Prothrombin and antithrombin represented their plasma protein counterparts structurally, with molecular weights of 73,000 and 61,000, respectively. Secreted factor X, prothrombin, and antithrombin III were biologically active, as determined in coagulation or chromogenic assays, and all three activities were neutralized by monospecific antibodies. Vitamin K increased the quantity of prothrombin secreted by twofold, without affecting the rate of secretion over a five-day culture period, and had an apparent transient inhibitory effect on secretion of antithrombin III. Warfarin caused a three to fourfold decrease in the rate and quantity of secreted prothrombin, but did not affect intracellular concentrations. The intracellular and extracellular concentrations and rate of secretion of antithrombin III were not modulated by warfarin. These data suggest that the Hep G2 cell line may provide a useful model for assessing the regulation of biosynthesis and secretion of human coagulation proteins.
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PMID:Human hepatoma cells secrete single chain factor X, prothrombin, and antithrombin III. 632 78

This is the first reported case of magnetic resonance imaging (MRI) findings of cranial metastasis from hepatocellular carcinoma. A 53-year-old male was admitted to our hospital on August 23, 1994, complaining of severe headache and a subcutaneous mass on the forehead. He was diagnosed as hepatocellular carcinoma in February, 1994, at another hospital. Because of multiple intrahepatic metastasis, he was inoperable and received transarterial embolization (TAE) on February 15, 1994. He had noticed the subcutaneous mass two months prior to admission, and its recent rapid growth, and morning headache. On admission, there was no abnormality observed by neurological and physical examination except the subcutaneous mass on his forehead, 5 x 7 cm in size. It was elastic soft and unmovable, and he felt tenderness. Laboratory examination showed only mild liver dysfunction. HBsAg was negative, and alpha-fetoprotein and PIVKA-II (Protein Induced by Vitamin K Antagonists) were within normal limit. Skull X-ray showed a round bone defect in the frontal bone. Computerized tomographic (CT) scan showed bone destruction and a well-circumscribed high density mass extending from the frontal subcutaneous region into the cranial cavity. MRI showed the tumor compressing the left frontal lobe on T1 weighted image as isointense and T2 weighted image showed a slight low intense mass. The tumor was clearly enhanced on both CT scan and MRI. Left external carotid angiogram demonstrated that the hypervascular tumor mainly fed by a frontal branch of the left superficial temporal artery in the frontal region. Tumor and bone scintigram revealed multiple bone metastasis. Lung CT scan showed no metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A rare case of cranial metastasis from hepatocellular carcinoma]. 747 23

Fourteen patients with unrespectable HCC were treated with various interventional radiology (IVR) procedures. The initial therapeutic response was determined using computed tomography (CT) findings, and determinations of serum alpha-fetoprotein (AFP) and protein induced by Vitamin K absence or antagonist-II (PIVKA-II) levels. When CT studies of the initial response to IVR were compared with changes in the serum AFP and PIVKA-II levels, the AFP level was found to correlate more closely than the PIVKA-II levels. The PIVKA-II level correlated more closely than the AFP level in cases with poor response to IVR. Both of these tumor markers should be measured in combination with the diagnostic imagings for follow-up studies of IVR.
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PMID:Clinical evaluation of serum alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels in patients with hepatocellular carcinoma following interventional radiology. 751 71

Synthesis of metallothionein-I (MT-I) and heme oxygenase mRNAs is rapidly and transiently induced by H2O2 in mouse hepatoma cells (Hepa) and this effect is blocked by catalase. Menadione, which generates free radicals, also induces these mRNAs. Deletion mutagenesis revealed that a region between -42 and -153 in the mouse MT-I promoter was essential for induction of a CAT reporter gene. A multimer of a 16 bp sequence (-101 to -86) that includes an antioxidant response element and overlapping adenovirus major late transcription factor binding site elevated basal expression and allowed induction by H2O2 when inserted upstream of a minimal promoter. However, deletion of this region (-100 to -89) from the intact MT-I promoter (-153) did not completely eliminate response. Multiple copies of a metal response element also permitted response to H2O2. These results suggest that induction of MT-I gene transcription by H2O2 is mediated by at least two different elements within the proximal MT-I gene promoter and suggest a previously undescribed function of the MRE. Induction of MT gene transcription by ROS and the subsequent scavenging of ROS by the MT peptide is reminiscent of the metal regulatory loop and is consistent with the hypothesized protective functions of MT.
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PMID:Transcriptional induction of the mouse metallothionein-I gene in hydrogen peroxide-treated Hepa cells involves a composite major late transcription factor/antioxidant response element and metal response promoter elements. 780 Apr 94

Vitamin K is a substrate for the enzyme catalyzing the carboxylation of specific glutamyl residues to gamma-carboxyglutamyl residues in hepatic precursors of a limited number of plasma proteins, including prothrombin. The gamma-carboxylation of these proteins can be blocked by the anticoagulant warfarin; and in the bovine and human, warfarin treatment results in the secretion of under-gamma-carboxylated forms of prothrombin into plasma. In the rat, this response is not seen, but plasma prothrombin concentrations are drastically decreased. This response has now been studied in rat hepatoma (H-35) cells in which prothrombin secretion is decreased 90% by incubation in the presence of warfarin. Neither prothrombin mRNA levels nor the apparent rate of prothrombin message translation were decreased when cells were cultured in the presence of warfarin rather than of vitamin K. The pool of intracellular prothrombin precursors is increased threefold by warfarin treatment, and this pool is rapidly secreted when vitamin K is administered. In contrast, continued incubation in the presence of warfarin resulted in the degradation of 60% of this pool in 24 hours. When transport of secretory proteins to the golgi apparatus was blocked with Brefeldin A, this precursor pool was gamma-carboxylated in the presence of vitamin K and no degradation occurred. Lysosomal enzyme inhibitors did not block the degradation, and the data suggest that, in rat hepatocytes, under-gamma-carboxylated prothrombin is specifically targeted to a pathway of protein degradation located in the endoplasmic reticulum.
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PMID:Prothrombin synthesis and degradation in rat hepatoma (H-35) cells: effects of warfarin. 801 15

Ultrasonically guided fine needle (21 gauge) aspiration biopsy (FNAB) was performed on a patient with a hepatocellular carcinoma (HCC) measuring 1.5 x 1.5 cm in segment VI of the liver. The tumour was located just beneath the liver surface. Subsegmentectomy of segment VI was performed. Twelve months after the biopsy and 10 months after the operation, levels of alpha-fetoprotein (AFP) and protein induced by Vitamin K absence or antagonist-II (PIVKA-II) increased gradually without any evidence of recurrence of HCC in the liver. Thirteen months after the biopsy, the patient palpated a hard subcutaneous nodule 1.5 cm in diameter in the right lower anterior chest wall at the insertion site of the biopsy needle. A subcutaneous tumour was excised and histological examination revealed moderately differentiated HCC. The levels of AFP and PIVKA-II normalized thereafter. These tumour markers were therefore useful for diagnosing the subcutaneous nodule as a metastatic HCC. The patient is currently doing well without further recurrence of HCC or needle-tract seeding 23 months after subsegmentectomy and 11 months after excision of the subcutaneous tumour.
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PMID:Subcutaneous seeding of small hepatocellular carcinoma after fine needle aspiration biopsy. 838 23


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