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)

Phospholipase A2 (PLA2) modifications were investigated in patients with acute and chronic liver diseases, PLA2 variations were related to indices of liver function as well as to parameters of the acute phase response. Serum PLA2 activity modifications were fluorimetrically measured in 105 patients affected by acute and chronic liver diseases or extra-hepatic diseases. One-way ANOVA demonstrated a significant difference among groups (F = 4.53, P < 0.001); Bonferroni's test for pairwise comparisons showed that patients with hepatocellular carcinoma had higher mean values than subjects with benign extra-hepatic diseases (P < 0.01) and mild chronic liver disease (P < 0.05). Multiple regression analysis, performed choosing PLA2 as the dependent variable and blood urea nitrogen, C-reactive protein, alkaline phosphatase and alpha 1-fetoprotein as predictor variables was significant (multiple R = 0.7056, multiple R2 = 0.4978, F = 15.36, P = < 0.0001). The standardized regression coefficients found to be significant were those of C-reactive protein, blood urea nitrogen and alpha 1-fetoprotein. In conclusion, in patients with chronic liver disease, serum PLA2 activity increases parallel to disease severity and accompanies the expression of proteins of the acute phase response that, like PLA2 activity, increase in serum while liver synthesis declines.
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PMID:Increased serum phospholipase A2 activity in advanced chronic liver disease as an expression of the acute phase response. 826 31

721 patients with liver cirrhosis were regularly screened by sonography and determination of alpha fetoprotein during a period of eleven years (1.1.1982-1.1.1993). In 137 of them hepatocellular carcinoma (HCC) was diagnosed; 28 (20.4%) had a unilocular HCC with a diameter up to 5 cm. Diagnosis was regularly verified by sonographic guided puncture, in rare cases by laparoscopy and biopsy. Beside a diameter of 5 cm the tumor should be localized at least 5 mm from the main structures in the hilus, and not in the centre of the liver; furthermore multilocular hepatocellular carcinomas and intra- and extrahepatic metastases were contraindications. Child-Pugh-classification should be A+B and urea synthesis rate at least 6 g per day. In 21 patients (75%) a portal hypertension was diagnosed; 19 (68%) had bled from esophageal varices; in case of one bleeding a therapeutic sclerotherapy and in case of recurrent variceal hemorrhage an elective shunt operation were performed. Surgical resection was carried out with controlled hypotension and temporary occlusion of the hepatoduodenal ligament. Tumor was removed by segmentectomy or bisegmentectomy and in rare cases by enucleation. There were 3 clinical deaths (10.7%); causes of death were liver failure and (2) sepsis (1). All patients could be followed up to January 1, 1993; there were 12 further deaths of liver failure, tumor recurrence or second tumor. 13 patients are still living. Thus the live expectancy for one year was 80, for 5 years 50 and for 10 years 30%. There is no doubt, that it is possible to detect hepatocellular carcinoma in patients with liver cirrhosis early by regular sonography and determination of alpha-fetoprotein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Single hepatocellular carcinoma (phi < or = 5 cm) in liver cirrhosis. Early diagnosis and surgical removal]. 826 41

The growing success of liver transplantation and the shortage of donor livers has turned attention to the possibility of utilizing hepatocytes within artificial liver support systems to allow time for donor livers to become available and to improve the condition of patients with hepatic failure. This study evaluated encapsulated hepatocytes, a technology which might allow the possibility of using xenogenic or human hepatoma cells. Rabbit hepatocytes were encapsulated using the ionic polysaccharides carboxymethylcellulose, chondroitin sulfate A, chitosan, and polygalacturonic acid. Encapsulated cells were maintained in perfusion culture for at least 6 days in heparinized, normal human plasma or in a defined culture medium. Parallel cultures of plated hepatocytes were also conducted. The metabolic capability of the cells was evaluated by following the rates of urea, albumin, and transferrin synthesis and the transformation rate of the drug antipyrine. Protein synthesis and ureogenesis in plasma were depressed from the levels expressed in defined culture medium. Drug detoxification as measured by antipyrine metabolism appeared to be enhanced in plasma. We conclude that encapsulated rabbit hepatocytes retain significant levels of function for at least 6 days of perfusion with human plasma, suggesting the feasibility of this technology as a potential method of short-term liver support.
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PMID:Performance of plasma-perfused, microencapsulated hepatocytes: prospects for extracorporeal liver support. 830 53

An 87-year old woman was admitted with a clinical picture of hypovolemic shock, preceded by a few weeks of abdominal pain. On admission, blood urea was high, the hemoglobin 5 g% and the CT scan revealed a large mass in the right hepatic lobe and free fluid in the abdominal cavity. A tentative diagnosis of ruptured hepatoma with spontaneous intraperitoneal bleeding was made. The diagnosis was confirmed by angiography and selective embolization of the hepatic artery stopped the bleeding. The patient left hospital a few days later.
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PMID:[Spontaneous rupture of a hepatocellular carcinoma successfully managed by embolization of the hepatic artery]. 838 82

In the rat, the gene (rOAT) encoding ornithine aminotransferase (OAT) is expressed in all cell types examined; however, regulation of rOAT expression is complex and cell-type specific. Various regions of the rOAT 5' flanking domain were cloned upstream from the cat reporter gene, and the expression of these OAT::cat fusions was examined following transfection into rat kidney epithelial cells (NRK-52E), human embryonic kidney cells (293), and rat hepatoma cells (H-4-II-E). Although these experiments suggested the presence of one or more positive regulatory elements between nucleotides -661 and -158, and one or more negative elements upstream from nt -897, none of these putative elements appeared to function in a cell-type-specific manner. The nt sequence of 2531 bp of the rOAT domain flanking the promoter revealed several putative promoter/enhancer elements in positions analogous to the human OAT gene, numerous AGGTCA-like motifs related to the binding sites for the estrogen and thyroid hormone receptors, and multiple motifs resembling a putative regulatory element associated with genes encoding enzymes of the urea cycle. Finally, sensitivity of the 5' end of rOAT to cleavage by DNase I was examined, as DNase-I-hypersensitive sites (DHS) are often found in association with cis-acting regulatory elements. Two DHS were identified; one DHS approximately 140 bp upstream, and the second DHS approximately 300 bp downstream, of the transcription start point (tsp). These data provide the foundation upon which to base future studies aimed at elucidating the molecular mechanisms through which rOAT expression is regulated in a cell-type specific manner.
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PMID:Promoter region of the rat gene encoding ornithine aminotransferase: transcriptional activity, sequence, and DNase-I-hypersensitive sites. 846 71

We previously reported that polymyxin B (PMB) enhances cellular catabolism of low density lipoproteins (LDLs) through a non-LDL receptor-mediated endocytotic pathway. These data were obtained mainly by using Hep G2 cells, a well differentiated human hepatoma cell line. In the current study, we explore the mechanisms of PMB-mediated endocytotic catabolism of LDL. We found that PMB enhanced LDL catabolism also in homozygous familial hypercholesterolemia fibroblasts, thereby establishing that PMB-mediated cellular catabolism of LDL does not involve LDL receptors. By using [14C]sucrose, and ligands for the asialoglycoprotein (ASGP) receptors, possibilities were excluded that PMB enhances cellular endocytosis of LDL, by inducing a general increase of cellular pinocytic activity or by causing endocytosis of LDL via the ASGP receptors in Hep G2 cells. We further show, by using polymyxin B coupled Sepharose 4B (PMB-Sepharose 4B) beads, that PMB binds to LDL to form a complex. This binding was tight, and changes in pH and salt concentrations had no significant effect on the binding, but unlabelled LDL competed with 125I-LDL to bind to PMB-Sepharose 4B. Urea and endotoxins decreased this binding, suggesting that PMB binds to LDL at least partially through hydrophobic interactions. Agarose gel electrophoresis of PMB-LDL indicates that PMB cationizes LDL. In conclusion, PMB binds to LDL to form a PMB-LDL complex presumably through interactions between lipid groups. This endows LDL with positive charges, which enhances LDL binding to negatively charged cell membranes, and such bound LDL is rapidly internalized through absorptive endocytosis.
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PMID:Polymyxin B complexes with and cationizes low density lipoproteins. The cause of polymyxin B-induced enhancement of endocytotic catabolism of low density lipoproteins. 849 42

It is currently in discussion whether or not established liver cell lines can be used for an extracorporeal liver assist device. Thus, metabolic features of primary hepatocytes, immortalized hepatocytes, and hepatoma cells were compared. The ability of these cells to process toxic blood of patients with hepatic failure was investigated by testing their viability in toxin enriched medium that was obtained by toxin separation from patients' blood via a molecular adsorbents recirculating system (MARS). In addition, glucose metabolism, urea synthesis, P450 dependent verapamil metabolism using high performance liquid chromatography, and interleukin-6 induced "acute phase" reaction by sulfodesoxysalicylic acid-polyacrylamide gel electrophoresis detected changes of albumin synthesis were determined in primary hepatocytes and in established liver cells. The viability of hepatoma cells after contact with the toxic compounds coming from the patients' blood was significantly decreased in comparison to that of immortalized hepatocytes and primary hepatocytes. Immortalized hepatocytes and hepatoma cells showed a significantly higher consumption of glucose associated with a significantly higher lactate synthesis. A basic urea synthesis rate could be measured in immortalized hepatocytes and hepatoma cells, but it was significantly lower than that of primary cells. P450 with its subenzyme CYP2C was inducible only in primary hepatocytes and in immortalized cells, but in the latter the enzymatic activity was lower than that of primary cells. The incubation with acute phase mediators resulted in a decrease of albumin synthesis in primary hepatocytes and in hepatoma cells, but it increased the albumin synthesis in immortalized hepatocytes. Summarizing these data, partially beneficial effects can be assumed if established cells are used in an extracorporeal liver assist device. These might include synthesis of some compounds and basic metabolic activities, such as urea synthesis. However, established liver cells showed clearly altered metabolic characteristics. The sufficient removal of toxic compounds requires additional strategies for detoxification by primary hepatocytes in sufficient amounts.
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PMID:Primary or established liver cells for a hybrid liver? Comparison of metabolic features. 857 14

The prognosis of patients with hepatocellular carcinoma is dismal. Long-term survival and cure of patients with hepatocellular carcinoma (HCC) can be expected only after resection or hepatectomy followed by transplantation. Thus, prognosis primarily depends on the possibility of resective surgery, which is determined predominantly by anatomic extent of disease. This survey deals with factors that become effective after resection or transplantation and that have prognostic significance in univariate or multivariate analyses. Several studies have shown that resection for cure (R classification) and anatomical extent of the tumors (TNM) were the most important prognostic factors. Prognostic factors other than TNM and R can be grouped into clinical findings and pathological features. As to clinical findings, performance status is an important prognostic factor in one multivariate analysis. The effects of other factors as age, sex, tumor site, and hepatomegaly on prognosis were discussed controversially. As might be expected, studies on pathological factors yielded different results. Histological grade had an influence in one study, but not in another. Histological type and coexisting cirrhosis were important in multivariate analysis only in resected patients. The majority of factors (capsule formation, dysplasia of adjacent liver tissue, mitotic activity, bile production) were only investigated in univariate analyses. There are only few studies evaluating the prognostic importance of molecular pathology factors. None of them has shown convincing evidence that these parameters may give information more important than TNM and R classification. The prognostic importance of TNM for patients not treated by resective surgery is emphasized in many studies. Ascites, toxic syndrome, and laboratory variables as bilirubin, blood urea nitrogen, and serum albumin were independent predictors of survival. The prognosis of patients with cholangiocarcinoma is even worse than that of HCC-patients and only 25% patients resected with stage-II-tumors can be expected to survive for five years.
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PMID:[Prognostic factors in liver tumors]. 860 Jun 73

To evaluate serum alpha-1-antitrypsin (A1AT) as a prognostic factor in hepatocellular carcinoma, we studied 75 consecutive patients (60 male, 15 female, mean age +/- SD 63.0 +/- 9.3 years) in whom hepatocellular carcinoma developed with pre-existing cirrhosis. Median survival time was 245 days (range 4-1568+). 30 patients had serum A1AT concentration of < or = 2.20 g/l (Group A) while 45 (Group B) had alpha-1-antitrypsin > 2.20 g/l. Median survival was 518 days in Group A and 81 days in Group B (Mantel-Cox 20.95, P < 0.0001; hazard ratio 0.26, 95% confidence limits 0.15-0.46). By stepwise survival analysis, alpha-1-antitrypsin together with bilirubin, tumour size and blood urea nitrogen were chosen among 17 variables as the only independent predictors of survival. We conclude that measurement of serum A1AT concentration might be useful as an inexpensive, widely available prognostic marker of hepatocellular carcinoma.
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PMID:Prognostic value of serum alpha-1-antitrypsin in hepatocellular carcinoma. 866 31

Effect of glutathione (GSH) depletion on paraquat (PQ) toxicity in the liver and kidneys of mice was examined. Glutamic-pyruvate transaminase (GPT) and blood urea nitrogen (BUN) levels in plasma of mice were hardly changed by treatment with 150 micro mol/kg of PQ. However, significant increases in the plasma GPT and BUN levels after PQ injection were observed in mice which were pretreated with L-buthionine-SR-sulfoximine (BSO), an inhibitor of GSH synthesis, at 4 hr prior to PQ administration. This result supports the previous observation that hepatotoxicity of PQ was enhanced in diethyl maleate-pretreated mice (Cagen and Gibson, 1977). In the present study, lipid peroxidation evaluated by thiobarbituric acid-reactive substances (TBA-RS) level in the liver of mice given PQ was elevated by pretreatment with BSO. Moreover, enhancement of PQ cytotoxicity by BSO pretreatment was also observed in cultured mouse hepatoma cell line (NCTC clone 1469). Vitamin E, an antioxidant, and Desferal, an iron chelator, significantly prevented mice from the BSO-enhanced hepato- and nephrotoxicity of PQ. These findings suggest that the tissues or cells of low GSH concentration are highly vulnerable to PQ toxicity and GSH may play a major role in diminishing the toxic action of PQ exerted through oxidative stress.
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PMID:Enhancement of paraquat toxicity by glutathione depletion in mice in vivo and in vitro. 872 Jan 62


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