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)

To determine the clinical significance of plasma endothelin-1 in chronic liver disease, these levels were measured by radioimmunoassay. The plasma endothelin-1 levels in patients with cirrhosis (N = 16) (2.04 +/- 0.25 pg/ml) and patients with hepatocellular carcinoma (N = 22) (2.23 +/- 0.17 pg/ml) increased significantly compared with controls (N = 16) (1.17 +/- 0.17 pg/ml) and patients with chronic hepatitis (N = 11) (1.09 +/- 0.19 pg/ml) (P < 0.01). The presence of ascites rather than tumor volume was associated with a significant elevation of endothelin-1. Endothelin-1 showed significant negative correlations with parameters of hepatic function, including indocyanine green clearance, serum albumin, and prothrombin time. Although endothelin-1 was not correlated with plasma renin activity and plasma endotoxin, it demonstrated a significant positive correlation with the plasma level of atrial natriuretic peptide (r = 0.42, P < 0.01). These findings demonstrate that plasma endothelin-1 increased in proportion to the severity of liver damage and may be causally related with the derangement of systemic/renal hemodynamics and fluid and electrolyte homeostasis seen in advanced liver disease.
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PMID:Clinical significance of plasma endothelin-1 in patients with chronic liver disease. 799 94

The coagulation parameters of fourteen patients with advanced liver cirrhosis (3 in Child class B and 11 in class C) were prospectively determined quarterly for one year in order to evaluate the possible relationship between high D-dimer levels and incidence of disseminated intravascular coagulation (DIC) and of gastrointestinal bleeding. The values of D-dimer, fibrin(ogen) degradation products, platelets, fibrinogen, prothrombin activity and antithrombin III were fairly stable in almost all patients and no patient developed an overt DIC; one patient had a significant increase in D-dimer three months after the first control. During the one year follow-up, four patients died, one by the occurrence of hepatocellular carcinoma and three by digestive bleeding. Overall, four patients had upper digestive tract bleeding, three from esophageal varices and one from hemorrhagic gastritis. Hemorrhage was more frequent in patients with high D-dimer levels (3/7, 43%) than in patients with normal D-dimer levels (1/7, 14%). In conclusion, the detection of high D-dimer levels in patients with advanced cirrhosis is not predictive for the occurrence of a overt DIC but seems to be related with an increased risk of gastrointestinal bleeding.
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PMID:High D-dimer levels: a possible index of risk of overt disseminated intravascular coagulation and/or digestive bleeding in advanced liver cirrhosis? 801 48

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

Primary hepatocellular carcinoma can be revealed by recurrent pulmonary embolism as observed in this case of a 63-year-old woman initially hospitalized for abdominal pain and shortness of breath. The clinical diagnosis was confirmed by laboratory findings, a ventilation perfusion scan and pulmonary angiography which demonstrated peripheral basal artery cut-off and slow filling with delayed washout. The patient was treated with heparin then with nicoumarol and responded well. One month after discharge the patient again complained of shortness of breath and was readmitted. Anticoagulation was adequate as evidenced by a prothrombin time of 1.39 INR and the physical examination and laboratory tests again suggested pulmonary emboli, confirmed by a ventilation perfusion scan. Computed tomography of the chest and abdomen revealed multiple hypodense masses filling half of the liver volume and needle biopsy led to the diagnosis of hepatocellular carcinoma. Hypercoagulability in malignancy is well-known although cases of migratory thrombophlebitis are extremely rare. Pulmonary embolism has not been described as a presenting feature of hepatocellular carcinoma. In this case, there was no evidence of hepatic dysfunction and the pulmonary embolism occurred despite adequate anticoagulation. Clinicians should include occult carcinoma among the possible causes of recurrent pulmonary embolism and when searching for malignancy can include hepatocellular carcinoma among the causes of hypercoagulation.
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PMID:Pulmonary embolism as the presenting feature of hepatocellular carcinoma. 802 23

To evaluate whether neutrophil bactericidal function, the ability to produce oxygen-derived free radicals, is altered in patients with chronic liver disease, we measured chemiluminescence amplified by a luciferin analog (Cypridina luciferin analog-dependent chemiluminescence) and luminol (luminol-dependent chemiluminescence) in response to N-formyl-Met-Lue-Phe by neutrophils from patients with chronic liver diseases due to C and/or B type hepatitis: chronic active hepatitis, cirrhosis and hepatocellular carcinoma. Both Cypridina luciferin analog-dependent chemiluminescence and luminol-dependent chemiluminescence were significantly decreased in neutrophils from patients with chronic liver disease (hepatocellular carcinoma < cirrhosis < chronic active hepatitis) when they were compared with normal healthy subjects. The reduction of Cypridina luciferin analog-dependent chemiluminescence in chronic active hepatitis and cirrhosis was more sensitive than Cypridina luciferin analog-dependent chemiluminescence; however, in hepatocellular carcinoma, luminol-dependent chemiluminescence was more reduced than luminol-dependent chemiluminescence. Although there were not significant correlations between glutamic pyruvic transaminase and Cypridina luciferin analog-dependent chemiluminescence/luminol-dependent chemiluminescence, there were significant negative correlations between total bilirubin and Cypridina luciferin analog-dependent chemiluminescence/luminol-dependent chemiluminescence. Furthermore, there were significant positive correlations between albumin/prothrombin time and Cypridina luciferin analog-dependent chemiluminescence/luminol-dependent chemiluminescence. These data suggest that an impaired ability to produce oxygen-derived free radicals may contribute to the susceptibility to infection in patients with chronic liver disease.
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PMID:Impaired ability of neutrophils to produce oxygen-derived free radicals in patients with chronic liver disease and hepatocellular carcinoma. 804 92

A 65-year-old male with hepatocellular carcinoma was admitted to our hospital. Hepatic angiography showed a hypervascular tumor 8 cm in diameter in the right lobe of the liver with tumor emboli in the inferior vena cava and right atrium. Then, two chemoembolization treatments using gelform and cisplatin suspended in Lipiodol were performed. Although the size of the main tumor in the liver and tumor emboli was reduced, 6 months after the initial chemoembolization the serum levels of alfa-fetoprotein (AFP) and plasma des-gamma-carboxy prothrombin (DCP) rose to 14,000 ng/ml and 6.4 AU/ml, respectively, and multiple lung metastases were detected by CT scan. Then, 200 mg/day of UFT was administered orally. Four months after the administration, the levels of AFP and DCP markedly decreased to 95 ng/ml and 0.0 AU/ml, respectively, and the lung metastases and tumor emboli disappeared. Moreover, there were no side-effects including liver dysfunction.
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PMID:[A case of hepatocellular carcinoma whose lung metastases and tumor emboli in the inferior vena cava disappeared by oral administration of UFT]. 806 Jan 44

Prognostic factors of the outcome of upper gastrointestinal bleeding in patients with cirrhosis are insufficiently defined. Pertinent clinical, biochemical, and endoscopic data of 332 upper gastrointestinal bleedings in 268 patients with cirrhosis observed in the participating centers during 31 months were recorded. Clinical data were analyzed until 40 days after bleeding. A further set of 82 bleedings was used as a validation group. Ninety-two of the 268 patients died within the time of the study, and 28 of the 82 patients of the validation group died. According to a stepwise logistic regression analysis, s-creatinine, ascites on admission, previous diagnosis of hepatocellular carcinoma, s-bilirubin, prothrombin index, varices as definite or probable source of bleeding, gender, and presentation with hemathemesis were the best set of covariates for predicting outcome. From them a prognostic index was developed and validated in the 82 further bleedings. Sensitivity and specificity in the cumulated training and test sets were 75 and 80%, respectively. In the present material, the prognostic index was significantly more efficient than Child-Pugh score or the prognostic index proposed by Garden et al. These data show that it is possible to predict the outcome of upper gastrointestinal bleeding in cirrhosis on the basis of few easily available data. The prognostic index we proposed and validated may become useful to predict the outcome of a bleeding and to select or stratify patients in clinical trials.
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PMID:Development and validation of a prognostic index predicting death after upper gastrointestinal bleeding in patients with liver cirrhosis: a multicenter study. 807 32

Urinary gamma-carboxyglutamic acid (gamma-Gla) levels were determined in healthy subjects of all ages. The urinary gamma-Gla levels were highest in infants (0-1 years), then fell in an age-dependent manner, again in subjects reaching a minimum value in adults, then gradually increased over 60 years of age. Urinary gamma-Gla levels therefore change markedly with aging. The relationships between the urinary gamma-Gla excretion and plasma levels of prothrombin and protein C in patients with various hepatic diseases or diabetes mellitus were examined and compared with those in healthy adults. Both plasma prothrombin and protein C levels were decreased in all patients with liver disease compared with healthy adults. In patients with hepatitis and liver cirrhosis, the decrease did not, however, affect the gamma-Gla excretion. In addition, in patients with hepatoma or carcinoma with liver metastases, the urinary gamma-Gla levels were increased. In patients with diabetes mellitus, the urinary gamma-Gla levels and plasma levels of prothrombin and protein C tended to increase, but this was not significant. The present results indicate that simultaneous measurement of the levels of urinary gamma-Gla and plasma prothrombin and protein C is a useful tool for the diagnosis of liver diseases and diabetes mellitus.
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PMID:Urinary levels of gamma-carboxyglutamic acid and its clinical significance. 814 4

The presence of under-gamma-carboxylated forms of plasma prothrombin is a marker for human primary hepatocellular carcinoma. A rat hepatoma cell line (7777) which was previously shown to secrete undercarboxylated prothrombin when grown as a solid tumor has now been grown in monolayer culture. This cell line has a decreased activity of the microsomal vitamin K-dependent carboxylase when compared to a control (H4IIEC3) hepatoma line, does not increase intracellular prothrombin concentrations in response to vitamin K depletion, and secretes undercarboxylated prothrombin even when grown in vitamin K supplemented media. Prothrombin gene expression in the 7777 cell line, as measured by prothrombin mRNA levels, was not altered in the 7777 cell line. This cell line appears to be a model for assessing the cellular alterations responsible for undercarboxylated prothrombin excretion by human hepatocellular tumors.
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PMID:Vitamin K-dependent carboxylase activity, prothrombin mRNA, and prothrombin production in two cultured rat hepatoma cell lines. 837 93

Microwave coagulo-necrotic therapy (MCN) was performed in 21 patients with small hepatocellular carcinoma less than 5cm in diameter and this therapeutic method was determined to be effective from the following results. 1) A marked low density area was seen in the region receiving the therapy and no enhanced findings were observed by enhanced CT one month postoperatively. 2) Recurrence appeared in 5 patients (23.8%) and only one patient died 1 year and 6 months after the operation. However, the other 20 patients survived for a maximum of 3 years and 2 months postoperatively. 3) The levels of total bilirubin and GOT in these patients were similar to those of patients who underwent hepatectomy. However, the levels of prothrombin time and hepaplatin test in patients with MCN changed less than in those who received hepatectomy. 4) Tendency of the renal failure was seen in 2 patients, and the other 19 patients did not have any complication postoperatively.
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PMID:[Investigation of microwave coagulo-necrotic therapy for 21 patients with small hepatocellular carcinoma less than 5 cm in diameter]. 839 31


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