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)

Optimum cutoff levels for plasma des-gamma-carboxy (abnormal) prothrombin (DCP) and serum alpha-fetoprotein (AFP) were determined by analyzing receiver operating characteristic (ROC) curves to discriminate between hepatocellular carcinoma (HCC) and benign hepatic conditions. Plasma DCP levels in 200 patients with HCC and 197 control patients with benign liver diseases were measured by an enzyme immunoassay with anti-DCP monoclonal antibodies, while serum AFP levels for both groups were measured by radioimmunoassay. From ROC curves and tangential lines with a slope of 1.0, the cutoff levels of DCP and AFP were determined to be 0.11 AU/ml and 150 ng/ml, respectively. Lowered cutoff levels of DCP did not improve the sensitivity, in contrast to the increased sensitivity obtained by lowering the specificity of AFP. The sensitivities and specificities determined in this study were close to the currently used values of 0.1 AU/ml for DCP and 200 ng/ml for AFP, justifying these cutoff levels for the differentiation of benign and malignant liver diseases.
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PMID:Determination of optimum cutoff levels of plasma des-gamma-carboxy prothrombin and serum alpha-fetoprotein for the diagnosis of hepatocellular carcinoma using receiver operating characteristic curves. 128 27

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

Angiotensinogen is the precursor molecule of one of the most potent vasoactive substances, angiotensin-II. Angiotensinogen is normally synthesized in the liver and secreted into the plasma where it is converted into angiotensin-II by the combined proteolytic action of renin and angiotensin converting enzyme. Angiotensinogen levels in the plasma are modulated by a number of pathological and physiological factors. In order to understand the regulation of angiotensinogen gene expression, we have constructed an expression vector in which 688 bp of the 5'-flanking region of the rat angiotensinogen gene were attached to the chloramphenicol acetyl transferase (CAT) coding sequence. We have also obtained 5'-sequential deletion mutants from the rat angiotensinogen promoter attached to the CAT gene, and have identified multiple cis-acting DNA sequences involved in the regulation of angiotensinogen gene expression by transient transfection of these recombinant DNA molecules in human hepatoma cell lines, Hep3B, and HepG2.
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PMID:Identification of cis-acting DNA elements involved in the regulation of angiotensinogen gene expression. 155 46

We have recently found presence of a high concentration of a novel type of kinin, hydroxyprolyl3-bradykinin (Hyp3-BK) in human tumor ascites in addition to conventional bradykinin (BK). Because of their potential physiological activity, it is of interest to know how these bradykinins can be degraded in ascites. Degradation of two synthetic kinins, BK and Hyp3-BK, added to the ascitic fluid from patients with ovarian carcinoma and hepatoma, were analyzed by reversed phase HPLC. Both kinins were degraded into their desArg9-BK or -Hyp3-BK and desPhe8-Arg-9-BK or -Hyp3-BK products following incubation with the ascitic fluid. The rate of the degradation of BK and Hyp3-BK was the same. The formation of desArg9-BK was completely inhibited by kininase I inhibitor, while the formation of desPhe8-Arg9-BK was not completely inhibited by a kininase II inhibitor. The degradation of both kinins was inhibited completely by EDTA. The results indicate the presence of other metalloprotease(s) which cleaves kinins in the ascitic fluid, in addition to kininase I and kininase II. The carboxypeptidase A and carboxypeptidase B inhibitor, benzyl malic acid, failed to block degradation of both kinins. A rapid cleave of Phe-Arg into Phe and Arg was also found in the ascitic fluid. Thus, the major degradation products of kinins in the ascitic fluid were demonstrated to be either desArg9-BK or Hyp3-BK, desPhe8-Arg9-BK or -Hyp3-BK, phenylalanine and arginine. Lysyl-BK and lysylhydroxyprolyl3-BK were rapidly converted into BK and hydroxyprolyl3-BK by the ascitic fluid.
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PMID:Degradation pathway of kinins in tumor ascites and inhibition by kininase inhibitors: analysis by HPLC. 216 Jan 86

Des-gamma-carboxy prothrombin [DCP], a protein induced by vitamin K absence or antagonist-II and also abbreviated PIVKA-II, was evaluated as a serologic marker for hepatocellular carcinoma (HCC). Its plasma levels were measured by enzyme immunoassay (E-1023) using an anti-DCP monoclonal antibody in 514 patients with various diseases. Of 120 patients with HCC, 76 (63%) had abnormal DCP levels greater than 0.1 arbitrary unit (AU)/ml and 58 (48%) showed levels greater than 0.3 AU/ml. When a diagnostic minimum level of 0.3 AU/ml was applied for DCP, false-positive cases of HCC were virtually eliminated. In some patients with HCC, plasma DCP levels normalized after surgical resection of the tumor. However, they rose again later with recurrence of the disease. The sensitivity of DCP in the diagnosis and monitoring of HCC was increased by serial and simultaneous determinations of alpha-fetoprotein (AFP), because high DCP levels were observed more often in low AFP-producing HCC patients. Elevated plasma DCP 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 DCP levels. These results suggested strongly that DCP was synthesized by the hepatoma cells.
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PMID:Plasma abnormal prothrombin (des-gamma-carboxy prothrombin) as a marker of hepatocellular carcinoma. 245 Jun 34

Over the last few years, many tumor markers have been proposed to clinicians but only a limited number of them meet the necessary criteria to be useful for either screening, diagnosis, prognosis or follow-up of gastrointestinal (GI) tumors. Both CEA and Ca 19-9 have proven to be clinically useful for the detection of recurrent tumors. AFP remains the most useful marker for the follow-up of hepatocellular carcinoma (HCC). Its interest for the early detection of primary tumor is debated. Recent data suggest that assays based on monoclonal antibodies to AFP could be used for detection HCC in high risk populations. Decarboxy-prothrombin assay may be a complement to the AFP test in this localization. In addition to GI hormones, serotonin and urinary 5HIAA, Neuron Specific Enolase appears to be a valuable marker for the follow-up of neuroendocrine tumors of the GI tract. Only a few of the new tumor-associated antigens detected by monoclonal antibodies, appear to be promising clinical ly e.g. Ca50 TAG-72, PAO. Monoclonal antibodies to tumor-associated markers have also been used with other techniques: Immunohistochemistry: this technique is useful to the pathologist for the diagnosis of undifferentiated tumors by demonstrating the presence of specific antigens on tissue samples. Immunoscintigraphy: it can be useful for the detection of either metastases of recurrences of colorectal cancer by using anti-ACE antibodies labeled with Iodine 131 iodine 123 or indium 111. However immunoscintigraphy is less sensitive than both ultrasonography and CT scan for localizing hepatic metastases. At the present time the best indication of this method remains the diagnosis of pelvic recurrences.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The value of tumor markers in digestive oncology]. 269 5

We measured plasma abnormal prothrombin (des-gamma-carboxy prothrombin; DCP) levels in normal subjects and in patients with hepatocellular carcinoma and other various diseases using the enzyme-linked immunosorbent assay developed by Motohara et al. (Pediatr Res 1985; 19: 354-357). Fifty-eight percent of 52 patients with hepatocellular carcinoma had elevated DCP levels; 24 of 28 patients with advanced or moderately advanced hepatocellular carcinoma were positive. By contrast, 50 normal controls, 13 pregnant women and 10 patients with acute hepatitis had normal levels. Three of 55 patients with chronic liver disease, and 6 of 32 patients with other malignancies, showed a slight increase. Thus, increased plasma DCP appears useful for the diagnosis of hepatocellular carcinoma. To elucidate the mechanism for the increase of DCP in hepatocellular carcinoma, we cultured a human hepatoma cell line, huH-2, and measured the levels of this abnormal prothrombin in the medium. The huH-2 cells produced large amounts of DCP in the medium without added vitamin K. It increased in a cell concentration- and time-dependent fashion. These cells produced no detectable amount of DCP in the medium with added vitamin K. Thus, human hepatoma cell line huH-2 produces DCP, and its production is dependent on the amount of vitamin K available in the medium. Des-gamma-carboxy prothrombin may be a useful tumor marker for the diagnosis of hepatocellular carcinoma.
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PMID:Production of abnormal prothrombin (des-gamma-carboxy prothrombin) by hepatocellular carcinoma. A clinical and experimental study. 303 40

To clarify the mechanism of production of des-gamma-carboxy (abnormal) prothrombin (DCP) by hepatocellular carcinoma (HCC), we measured the levels of vitamin K, DCP, immunoreactive prothrombin and the activity of gamma-glutamyl carboxylase in liver tissues from HCC patients and in the medium of cultured human hepatoma cells. There was no significant difference in vitamin K (K1, MK-4) contents between HCC and non-HCC cirrhotic liver tissues. The activity of gamma-glutamyl carboxylase per unit amount of endogenous microsomal prothrombin precursor was decreased in HCC tissue compared with non-HCC liver tissue (positive plasma DCP: 335 +/- 72 vs 372 +/- 67, negative plasma DCP: 370 +/- 84 vs 393 +/- 56 nmol/min per mg prothrombin precursor, P > 0.05), although the total incorporation of 14COOH into microsomal precursor protein was higher in the former. By contrast, levels of DCP and immunoreactive prothrombin in HCC tissue were greater (P < 0.05) than those in non-HCC cirrhotic liver tissue. Furthermore, production of large amounts of immunoreactive prothrombin was observed in human hepatoma cells huH-1 and huH-2, which produced large amounts of DCP. These results suggest that there was excessive synthesis of prothrombin precursors by human HCC tissue and hepatoma cell lines huH-1 and huH-2. Thus, excessive synthesis of prothrombin precursors seems to be the main mechanism of DCP production by HCC.
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PMID:Levels of vitamin K, immunoreactive prothrombin, des-gamma-carboxy prothrombin and gamma-glutamyl carboxylase activity in hepatocellular carcinoma tissue. 762 Jan 13

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 a 48-year-old man, using imaging methods, the presence was shown of a tumour in the right hepatic lobe. The serum AFP and DCP concentrations--the serological markers of hepatocellular cancer--were significantly increased, however, the histological examination of liver biopsy specimen demonstrated the structure of a cancer originating from the bile canaliculi. The material for study obtained during laparotomy and autopsy made possible the demonstration of the structure typical of both cholangiocellular carcinoma and hepatocellular carcinoma in separate foci. The mixed form of hepatocholangiocellular carcinoma is extremely rare and difficult for diagnosis which induced us to report own case.
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PMID:[Hepatocholangiocarcinoma]. 797 26


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