Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of menaquinone-4 (MK-4, vitamin K2) was studied on des-gamma-carboxy prothrombin (DCP or PIVKA-II) levels in three subjects with vitamin K deficiency and five patients with hepatocellular carcinoma (HCC) with positive DCP. The half-life of DCP in HCC patients after intravenous MK-4 administration (50 mg daily for 14 days) was determined to be 60 hours, identical to that found in vitamin K-deficient subjects who received MK-4. When a single dose of MK-4 (10 mg) was given intravenously to three patients with HCC and elevated DCP, the levels decreased with a reduction rate identical to that in vitamin K-deficient subjects for the first 1 to 3 days, followed by an increase reaching the previous level in 7 to 10 days. Changes in plasma coagulant activity were compared between subjects with vitamin K deficiency and those with HCC before and after a single dose of MK-4 (10 mg). The activity increased in DCP-positive patients with HCC as in vitamin K-deficient subjects who received the same single dose of MK-4. The increase was greater in HCC patients with higher DCP levels. These results suggest that the level of plasma DCP in patients with HCC responded to vitamin K with the same sensitivity as that in vitamin K-deficient subjects. When patients with HCC underwent effective tumor therapy (resection or arterial embolization), the reduction rate (slope of DCP decline) was found to be identical to that in vitamin K-deficient subjects given with MK-4. In patients with less effective therapy, the reduction rate was smaller, or there was an increase in DCP. These observations strongly suggest that sequential measurements of the DCP reduction rate after treatment for HCC are useful for assessing therapeutic effects.
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PMID:Changes of plasma des-gamma-carboxy prothrombin levels in patients with hepatocellular carcinoma in response to vitamin K. 130 8

The clinical significance of des-gamma-carboxy prothrombin (PIVKA-II) in hepatocellular carcinoma (HCC) was investigated in 112 patients with and without vitamin K administration. The positivity rate of PIVKA-II was significantly decreased in patients receiving vitamin K (28.5%), compared with those without vitamin K administration (54.5%, p less than 0.05). The plasma levels of vitamin K derivatives [phylloquinone (VK1), menaquinone-4 (MK4), and menaquinone-7 (MK7)] measured were not decreased in patients with HCC, but were significantly increased in MK4 and VK1 + MK4 + MK7. The amount of PIVKA-II in plasma did not correlate with the plasma levels of vitamin K derivatives. However, PIVKA-II was decreased by the administration of vitamin K, and all of the six patients with more than 5.0 ng/ml of VK1 + MK4 + MK7 were within normal limits, whereas half of 32 patients with less than that had abnormal levels of PIVKA-II. Thus, it was suggested that PIVKA-II was not elevated due to vitamin K deficiency, but might result from the impaired metabolism or availability of vitamin K in the tumor. Therefore, PIVKA-II should be measured without vitamin K administration.
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PMID:The effects of vitamin K on the generation of des-gamma-carboxy prothrombin (PIVKA-II) in patients with hepatocellular carcinoma. 170 89

A new clotting method is described to assay des-gamma-carboxyprothrombin (DCP), using staphylocoagulase and adsorbed undiluted citrated plasma. The thrombin-coagulase formed was tested with a chromogenic substrate. The results were expressed in milliunits (m.u.). All 96 normal plasmas had less than 15 m.u. (mean 3.58 m.u.). Out of 56 non-hepatectomized cellular hepatocarcinomas, 40 had DCP levels between 20 and 420 m.u. (average between 40 and 60 m.u.); 71.4% of cellular hepatocarcinoma had an increased DCP and 90% were positive either in alpha-foetoprotein or in DCP. Ten cases of non-cellular hepatocarcinomas had normal DCP levels. We found no cases of cirrhosis or chronic hepatitis, whether active or persistent, with abnormal level of DCP. Out of 127 patients tested, no case was found with a high DCP and a low level of "total factor II", which could be interpreted as a vitamin K deficiency. Only one case of hepatocarcinoma had 25 m.u. of DCP and a low total factor II (20%) and 2 had less than 10% total factor II with no detectable DCP.
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PMID:Assay of des-gamma-carboxyprothrombin using staphylocoagulase. Application to the diagnosis of cellular hepatocarcinoma. 242 13

Serum decarboxy-prothrombin (DCP) was raised in 70.7% of histologically confirmed cases of hepatocellular carcinoma and, with alpha foetoprotein, constitutes a complementary biochemical marker for this disease. It is usually normal in other hepatic diseases but pathological values of DCP have been observed in a few cases of cirrhosis and in some pancreatic carcinomas with hepatic metastases. The differential diagnosis may be established by administering 20 mg of Vitamin K1 by slow intravenous injection: if the DCP remains pathological 15 days after Vitamin K1 the diagnosis of hepatocellular carcinoma is very probable. On the other hand, if the DCP is normal a Vitamin K deficiency may be diagnosed.
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PMID:[Assay of decarboxy-prothrombin: its value in the diagnosis of hepatocellular carcinoma]. 283 88

Protein C, one of the vitamin K-dependent plasma proteins synthesized in the liver, was measured immunologically in normal subjects (n = 20), patients with hepatocellular carcinoma (n = 60), liver cirrhosis (n = 60), acute hepatitis (n = 16), chronic hepatitis (n = 19), malignant neoplasms other than hepatocellular carcinoma (n = 35) and patients on warfarin treatment (n = 20). We also assayed gamma-carboxyglutamic acid-complete (carboxylated) protein C in these population by using a monoclonal antibody directed against human protein C, JTC-1, which recognizes the gamma-carboxyglutamic acid domain-related conformational change induced by metal ions. We demonstrated that the plasma of patients with hepatocellular carcinoma contains considerable amounts of gamma-carboxyglutamic acid-incomplete protein C, evidenced by the significantly reduced protein C:gamma-carboxyglutamic acid/protein C:antigen ratios in hepatocellular carcinoma as compared to those seen in normal controls, other liver diseases and other malignant neoplasms (p less than 0.01). In two patients with hepatocellular carcinoma with the reduced protein C:gamma-carboxyglutamic acid/protein C:antigen ratios, successful treatment (transcatheter hepatic arterial embolization or lipiodolization of antitumor agent) led to the very rapid normalization of the ratios. Intravenous administration of vitamin K, however, induced no such effects in three other patients with hepatocellular carcinoma with the abnormality. We conclude that the impaired vitamin K-dependent gamma-carboxylation observed in patients with hepatocellular carcinoma involves not only prothrombin, but also protein C, and that the impairment is not due to vitamin K deficiency.
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PMID:The acquired vitamin K-dependent gamma-carboxylation deficiency in hepatocellular carcinoma involves not only prothrombin, but also protein C. 283 89

A new method for assaying the activity of des-gamma-carboxyprothrombin (DCP), using staphylocoagulase on undiluted adsorbed plasma, is described. The thrombin-coagulase formed is measured on a chromogenic substrate, and the results are expressed in milliunits per milliliter of increment of the optical density following the release of p-nitroaniline. Levels of DCP in 96 normal subjects were under 10 mU/ml (mean, 3.58 mU/ml). Of 70 nonhepatectomized patients with hepatocellular carcinomas, 74% had increased DCP levels of between 20 and 420 mU/ml (most of the values were between 20 and 100 mU/ml). Des-carboxyprothrombin and alpha-fetoprotein measurements gave complementary information, one marker or the other being positive in 87% of hepatocellular carcinoma. Fourteen of 15 patients with metastatic carcinoma of the liver had normal DCP levels, as did 95 patients with liver cirrhosis and 13 patients with chronic hepatitis. When the level of "total factor II" is below 40%, it is recommended that a second determination of DCP be performed 5 days after the injection of vitamin K, to exclude any vitamin K deficiency (in the case of hepatocellular carcinoma the DCP level will remain elevated). The DCP assay appears more sensitive and more specific than the alpha-fetoprotein assay for the diagnosis of hepatocellular carcinoma; furthermore, both tests are complementary.
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PMID:A new method to assay des-gamma-carboxyprothrombin. Results obtained in 75 cases of hepatocellular carcinoma. 301 18

We detected des-gamma-carboxy prothrombin, an abnormal prothrombin, in the serum of 69 of 76 patients (91 per cent) with biopsy-confirmed hepatocellular carcinoma (the mean level of the abnormal prothrombin was 900 ng per milliliter). In contrast, levels of the abnormal prothrombin were low in patients with chronic active hepatitis (mean, 10 ng per milliliter) or metastatic carcinoma involving the liver (mean, 42 ng per milliliter), and undetectable in normal subjects. In five patients treated with vitamin K there was no reduction in abnormal prothrombin, indicating that its presence was not due to vitamin K deficiency. Surgical resection of tumors in two patients and chemotherapy in one patient markedly reduced abnormal-prothrombin concentrations, which later increased with recurrence of disease. Serum alpha-fetoprotein levels correlated poorly with abnormal-prothrombin levels. Together, the assay for abnormal prothrombin and the alpha-fetoprotein assay identified 64 of 76 patients with hepatoma (84 per cent). Abnormal prothrombin may be useful in the laboratory diagnosis of primary hepatocellular carcinoma.
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PMID:Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. 620 41

Based on studies in intact animals, the presence of humoral factors, "coagulopoietins", which regulate the synthesis of vitamin K-dependent plasma proteins has been proposed. These proposed factors are produced in response to vitamin K deficiency, coumarin treatment, or specific antibody depletion of vitamin K-dependent clotting factors. The production of prothrombin by rat hepatoma H4IIEC3 cells has now been shown to be dependent on the source of bovine serum in the media. Cells grown in serum from cows treated with dicoumarol produce about 20% more prothrombin in 24 h than those cells grown in control serum. The humoral factor causing this response is present early in the course of dicoumarol treatment, and the increase in prothrombin production is dependent on the amount of serum from a dicoumarol-treated cow in the media. Based on membrane filtration studies, the factor appears to be associated with the protein fraction of serum.
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PMID:Prothrombin synthesis in rat hepatoma H4IIEC3 cells: response to the proposed "coagulopoietin factor". 768 32

Des-gamma-carboxyprothrombin (DCP) appears to be a useful tumor marker for the evaluation of patients with HCC. DCP is produced by the malignant hepatocyte and appears to result from an acquired posttranslational defect in the vitamin K-dependent carboxylase system. DCP production is independent of vitamin K deficiency, although pharmacological doses of vitamin K can transiently suppress DCP production in some tumors. DCP levels greater than 0.1 AU/ml (100 ng/ml) on ELISA are highly suggestive of HCC or tumor recurrence. Normalization of DCP levels correlates well with successful tumor resection and appears to be an excellent marker of tumor activity. Plasma DCP does not correlate with AFP levels. However, when used together, DCP and AFP assays increase the sensitivity to HCC in more than 85% of patients. The specificity of the DCP assay appears to be superior to that of AFP; fewer than 5% of patients with nonmalignant liver disorders have DCP levels in excess of 100 ng/ml. In patients with medium to large HCC, DCP levels do correlate with tumor size. In tumors of less than 3 cm, DCP levels are increased in only 20% of patients. However, the diagnostic threshold for the DCP assay may be improved by newer assays that can detect partially carboxylated DCP species not measured by the monoclonal antibody-based ELISA.
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PMID:Des-gamma-carboxy (abnormal) prothrombin and hepatocellular carcinoma: a critical review. 840 74

Serum protein induced in vitamin K absence-II (PIVKA-II) is used as a tumor marker because it increases at a notably higher rate in patients with hepatocellular carcinoma. To clarify the mechanism causing the elevation of serum PIVKA-II, we measured the contents of vitamins K1 (phylloquinone, PK) and K2 (menaquinone, MK) (MK-4, MK-5, MK-6, MK-7, MK-8, MK-9, MK-10) in liver tissue resected from 21 hepatic cancer patients (12 patients with hepatocellular carcinoma and 9 patients with metastatic hepatic cancer), using HPLC combined with coulometric reduction and fluorometric detection. In the cancerous tissue of hepatocellular carcinoma patients, PK, MK-7, MK-8, and MK-10 were significantly lower than that found in the noncancerous tissue. Furthermore, MK-6, MK-7, MK-8, and MK-10 in the cancerous tissue of hepatocellular carcinoma patients were significantly lower than that in the cancerous tissue of metastatic hepatic cancer patients. These data suggested that one of the mechanisms of the elevation of serum PIVKA-II levels in hepatocellular carcinoma patients is a vitamin K deficiency in the local cancerous tissue.
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PMID:Vitamin K contents in liver tissue of hepatocellular carcinoma patients. 1074 46


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