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)

Chromogranin A is a cellular marker forneuroendocrine tumors. Elevated levels of chromogranin A are also found in patients with cancers of epithelial origin when neuroendocrine differentiation occurs, which is associated with a poor prognosis. We investigated the prevalence of serum levels of chromogranin A in patients with primary liver cancer. Seventy-nine patients (65 males, mean age 67.6 years, range 48-88 years) with liver cirrhosis and hepatocellular carcinoma were studied. The etiology of cirrhosis was identified as due to hepatitis C virus infection in 47 patients, to hepatitis C virus and alcohol in 7, to alcohol alone in 14, to hepatitis C and B virus in 2, and to hepatitis B virus alone in 4. Of the remaining patients, 2 suffered from hemochromatosis and 3 had cryptogenic cirrhosis. According to the Child-Pugh's score, 54 patients belonged to class A, 22 to class B, and 3 to class C. The concentration of chromogranin A was measured in serum with a commercial solid-phase two-site immunoradiometric assay. Elevated serum levels of chromogranin A were found in 32 of 79 patients (43%). Levels over 600 ng/ml were present in 7 of 76 patients (9.2%), all of whom had very high serum levels of alpha-fetoprotein. Hence, elevated serum levels of chromogranin A are present in over one third of patients with hepatocellular carcinoma. It is therefore possible that some hepatocellular carcinomas could acquire a neuroendocrine differentiation. We propose further studies to ascertain whether serum levels of chromogranin A are useful as a prognostic marker for hepatocellular carcinoma as in prostate cancer.
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PMID:Elevated serum chromogranin A in patients with hepatocellular carcinoma. 1244 8

Primary hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the viral-chemical etiology as well as molecular mechanisms of HCC pathogenesis remains largely unknown. Recent studies in our laboratory have identified several potential factors that may contribute to the pathogenesis of HCC. Oxidative stress and chronic inflammation have been linked to an increased risk of liver cancer. For example, oxyradical overload diseases such as Wilson disease and hemochromatosis result in the generation of oxygen/nitrogen species that can cause mutations in the p53 tumor suppressor gene. The Hepatitis B virus X gene (HBx), a viral transactivator with oncogenic potentials, has been shown to bind to and inactivate p53-mediated apoptosis. HBx mutants derived from HCC have a diminished ability to act as a transactivator. However, they still retain the ability to bind to and abrogate p53-mediated apoptosis. The comparison of gene expression profiles between HBx-expressing primary human hepatocytes and HBV-infected liver samples by cDNA microarrays indicate a unique alteration of a subset of oncogenes and tumor suppressor genes including p53. Our studies implicate both viral and endogenous chemical processes in the etiology of HCC, and p53 may be a common target for the inactivation during liver carcinogenesis.
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PMID:Molecular pathogenesis of human hepatocellular carcinoma. 1250 83

Primary hepatocellular carcinoma (HCC) is one of the most common malignancies and has the fourth highest mortality rate worldwide. The major risk factors, including chronic infections with the hepatitis B or C virus, are exposure to dietary aflatoxin B1(AFB1), vinyl chloride, or alcohol consumption. Southern China and sub-Saharan Africa have the highest dietary AFB1 exposure, making it and hepatitis B virus (HBV) the major causes of cancer mortality in these geographic areas. Recent studies have discovered genetic and epigenetic changes involved in the molecular pathogenesis of HCC, including somatic mutations in the p53 tumor suppressor gene (TP53). AFB1 induces typical G:C to T:A transversions at the third base in codon 249 of p53. Chronic active hepatitis B and C (HCV) infection, and further inflammatory and oxyradical disorders including Wilson disease (WD) or hemochromatosis, generate reactive oxygen/nitrogen species that can damage DNA and mutate the p53 gene. The X gene of HBV (HBx) is the most common open reading frame integrated into the host genome in HCC. The integrated HBx is frequently mutated and has a diminished ability to function as a transcriptional cotransactivator and to activate the NF-kappa B pathway. However, the mutant HBx proteins still retain their ability to bind to and abrogate p53-mediated apoptosis. In summary, both viruses and chemicals are implicated in the etiology and molecular pathogenesis of HCC. The resultant molecular changes in the ras and Wnt signal-transduction pathways, and the p53 and Rb tumor suppressor pathways significantly contribute to liver carcinogenesis
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PMID:TP53 and liver carcinogenesis. 1261 6

Hereditary hemochromatosis is a prevalent genetic disorder of iron hyperabsorption leading to hyperferremia, tissue iron deposition and complications including cirrhosis, hepatocarcinoma, cardiomyopathy and diabetes. Most individuals affected with hereditary hemochromatosis are homozygous with respect to a missense mutation that disrupts the conformation of HFE, an atypical HLA class I molecule (ref. 1; OMIM 235200). Mice lacking Hfe or producing a C282Y mutant Hfe protein develop hyperferremia and have high hepatic iron levels. In both humans and mice, hereditary hemochromatosis is associated with a paucity of iron in reticuloendothelial cells. It has been suggested that HFE modulates uptake of transferrin-bound iron by undifferentiated intestinal crypt cells, thereby programming the absorptive capacity of enterocytes derived from these cells; however, this model is unproven and controversial. Hepcidin, a peptide hormone (HAMP; OMIM 606464), seems to act in the same regulatory pathway as HFE. Although expression of mouse Hamp is normally greater during iron overload, Hfe-/- mice have inappropriately low expression of Hamp. We crossed Hfe-/- mice with transgenic mice overexpressing Hamp and found that Hamp inhibited the iron accumulation normally observed in the Hfe-/- mice. This argues against the crypt programming model and suggests that failure of Hamp induction contributes to the pathogenesis of hemochromatosis, providing a rationale for the use of HAMP in the treatment of this disease.
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PMID:Constitutive hepcidin expression prevents iron overload in a mouse model of hemochromatosis. 1270 88

The aim of this study was to evaluate the efficacy of and tolerance for radiofrequency thermoablation (RFTA) in patients with hepatocellular carcinoma (HCC). From March 1999 to September 2001, a total of 56 patients (46 men and 10 women) whose mean age was 67.8 years (range 51 to 76 years) underwent RFTA for 71 HCCs at our institution. RFTA was carried out in 45 patients with one lesion less than 6 cm in diameter, in seven patients with two lesions less than 4 cm in diameter each, and in four patients with three lesions less than 3 cm in diameter each. The mean diameter of the lesions was 4.1 cm (range 0.8 to 6.0 cm). The etiology of the cirrhosis was alcoholism in 31 patients, post-hepatitis C in 19 patients, post-hepatitis B in four patients, and hemochromatosis in two patients. Forty-five patients were classified as Child stage A and 11 were Child stage B. No ascites, prothrombin time >60%, and platelet count <60,000/mm(3) were needed. Two types of cooled needles were used depending on the size of the lesion (a needle 15 cm in length was used for 2 or 3 cm tumors, and a cluster of needles was used for tumors larger than 4 cm). Helical computed tomography was performed 8 weeks after treatment. The main criterion for a complete response was the presence of a hypodense lesion without contrast enhancement. Mean follow-up was 14 months. Complete tumor destruction was achieved in 50 (89.2%) of 56 patients after one session and in 52 (92.8%) of 56 after two sessions. Twelve months later, a complete response was confirmed in 45 patients (80.3%), four patients had a local recurrence and new liver nodules, and three patients had died (one of bone metastasis, one of acute alcoholic hepatitis, and one of bronchial carcinoma). Thirty-nine patients (69.6%) were still in complete remission 36 months later, and a new HCC had developed in six patients. At 36 months 49 of 56 patients were alive and 39 of 56 were free of disease. Patients with HCCs that developed following viral cirrhosis had a worse prognosis than those with HCCs that occurred after alcoholic cirrhosis (2-year survival, 57.7% vs. 77.7%; P=0.0241). It was concluded that radiofrequency ablation is an effective treatment for HCC, although the prognosis is better in patients who develop HCC after alcoholic cirrhosis compared to those in whom HCC occurs after viral cirrhosis.
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PMID:Treatment of hepatocellular carcinoma using percutaneous radiofrequency thermoablation: results and outcomes in 56 patients. 1312 58

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world with an extremely poor prognosis. The major etiologic risk factors for HCC development include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, toxins (alcohol, aflatoxin B1) and various inherited metabolic liver diseases, such as hemochromatosis and alpha-1-antitrypsin deficiency. Central to the molecular pathogenesis of HCC are mutations of various genes and genetic/chromosomal instability that result from chronic liver disease and the associated enhanced liver cell regeneration and mitotic activity. Alterations in the structure or expression of several tumor suppressor genes and oncogenes have been described. In addition, mechanisms leading to genetic instability due to mismatch repair deficiency or chromosomal instability and aneuploidy due to defective chromosomal segregation appear to be involved. The prognosis of HCC patients is generally very poor. Most studies have shown a five-year survival rate of less than 5% in symptomatic patients. HCC has been found to be quite resistant to radio- or chemotherapy. Investigations of the natural history and clinical course of HCC revealed a long-term survival of patients only with small asymptomatic HCC that could be treated surgically or nonsurgically. For patients with advanced symptomatic HCC, novel therapeutic strategies such as gene therapy are urgently needed. Apart from exploring and refining new HCC treatment strategies, the implementation of the existing measures or the development of novel measures to prevent HCC is most important. Primary HCC prevention could have a major impact on the incidence of HCC. Further, secondary prevention of a local recurrence or of new HCC lesions in patients after successful surgical or nonsurgical HCC treatment is of paramount importance and is expected to significantly improve disease-free and overall survival rates of patients. Based on rapid scientific advances, molecular diagnosis, gene therapy and molecular prevention are becoming increasingly part of our patient management and will eventually complement or in part replace the existing diagnostic, therapeutic and preventive strategies. Overall, this should result in a reduced HCC incidence and an improved clinical outcome for patients with HCC, one of the most devastating malignancies worldwide.
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PMID:Molecular therapy and prevention of hepatocellular carcinoma. 1459 23

Several types of aggressive cancers, including hepatocellular carcinoma (HCC), often arise as a multifocal primary tumor. This suggests a high rate of premalignant changes in noncancerous tissue before the formation of a solitary tumor. Examination of the messenger RNA expression profiles of tissue samples derived from patients with cirrhosis of various etiologies by complementary DNA (cDNA) microarray indicated that they can be grossly separated into two main groups. One group included hepatitis B and C virus infections, hemochromatosis, and Wilson's disease. The other group contained mainly alcoholic liver disease, autoimmune hepatitis, and primary biliary cirrhosis. Analysis of these two groups by the cross-validated leave-one-out machine-learning algorithms revealed a molecular signature containing 556 discriminative genes (P <.001). It is noteworthy that 273 genes in this signature (49%) were also significantly altered in HCC (P <.001). Many genes were previously known to be related to HCC. The 273-gene signature was validated as cancer-associated genes by matching this set to additional independent tumor tissue samples from 163 patients with HCC, 56 patients with lung carcinoma, and 38 patients with breast carcinoma. From this signature, 30 genes were altered most significantly in tissue samples from high-risk individuals with cirrhosis and from patients with HCC. Among them, 12 genes encoded secretory proteins found in sera. In conclusion, we identified a unique gene signature in the tissue samples of patients with cirrhosis, which may be used as candidate markers for diagnosing the early onset of HCC in high-risk populations and may guide new strategies for chemoprevention. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
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PMID:Cancer-associated molecular signature in the tissue samples of patients with cirrhosis. 1476 6

The incidence rate of hepatocellular carcinoma (HCC) has been increasing over the last 20 years. HCC is a worldwide, but the incidence is very high in countries of South East Asia, China, sub-Saharan Africa and southern Europe. Liver cirrhosis is the most important risk factor for the development of HCC, through necrotic-proliferative and dysplastic activity. HBV is indicated as a carcinogen agent, while it is unknown the real role of HCV in hepatocarcinogenesis. The role played by aflatoxins, ethanol, hemochromatosis, familiarity and sex hormones is still undefined. The clinical presentation of HCC is similar to that of chronic hepatitis and cirrhosis indicating the need of a periodic screening (even 4-6 months) with alpha-fetoprotein determination and abdominal ultrasound scan. Hepatic resection, liver transplantation and percutaneous ethanol injection are the options more frequently chosen for treating patients with HCC.
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PMID:[Hepatitis viruses and development of hepatocellular carcinoma]. 1496 92

Iron overload in the liver may occur in clinical conditions such as hemochromatosis and nonalcoholic steatohepatitis, and may lead to the deterioration of the normal liver architecture by mechanisms not well understood. Although a relationship between the expression of ICAM-1, and classical major histocompatibility complex (MHC) class I molecules, and iron overload has been reported, no relationship has been identified between iron overload and the expression of unconventional MHC class I molecules. Herein, we report that parameters of iron metabolism were regulated in a coordinated-fashion in a human hepatoma cell line (HepG2 cells) after iron loading, leading to increased cellular oxidative stress and growth retardation. Iron loading of HepG2 cells resulted in increased expression of Nor3.2-reactive CD1d molecules at the plasma membrane. Expression of classical MHC class I and II molecules, ICAM-1 and the epithelial CD8 ligand, gp180 was not significantly affected by iron. Considering that intracellular lipids regulate expression of CD1d at the cell surface, we examined parameters of lipid metabolism in iron-loaded HepG2 cells. Interestingly, increased expression of CD1d molecules by iron-loaded HepG2 cells was associated with increased phosphatidylserine expression in the outer leaflet of the plasma membrane and the presence of many intracellular lipid droplets. These data describe a new relationship between iron loading, lipid accumulation and altered expression of CD1d, an unconventional MHC class I molecule reported to monitor intracellular and plasma membrane lipid metabolism, in the human hepatoma cell line HepG2.
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PMID:Altered expression of CD1d molecules and lipid accumulation in the human hepatoma cell line HepG2 after iron loading. 1563 40

HH is a common inherited disorder of iron metabolism affecting about 1 out of 250 individuals of Northern European decent. Many of these patients do not have evident phenotypic expression and do not develop significant iron loading. Some patients, however, develop progressive iron overload and cirrhosis. These individuals are at risk of developing HCC. Cirrhotics with hemochromatosis should undergo regular screening for HCC. If HCC is identified early, treatment with either resection or liver transplantation is optimal. Palliative measures, including ablative therapy and chemoembolization, can be used. With increasing clinical recognition,hemochromatosis should be diagnosed earlier and progression to cirrhosis and HCC should be minimized.
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PMID:Relation of hemochromatosis with hepatocellular carcinoma: epidemiology, natural history, pathophysiology, screening, treatment, and prevention. 1565 32


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