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)

A mutation in the gene encoding for the liver mitochondrial aldehyde dehydrogenase (ALDH2-2), present in some Asian populations, lowers or abolishes the activity of this enzyme and results in elevations in blood acetaldehyde upon ethanol consumption, a phenotype that greatly protects against alcohol abuse and alcoholism. We have determined whether the administration of antisense phosphorothioate oligonucleotides (ASOs) can mimic the low-activity ALDH2-2 Asian phenotype. Rat hepatoma cells incubated for 24 h with an antisense oligonucleotide (ASO-9) showed reductions in ALDH2 mRNA levels of 85% and ALDH2 (half-life of 22 h) activity of 55% equivalent to a >90% inhibition in ALDH2 synthesis. Glutamate dehydrogenase mRNA and activity remained unchanged. Base mismatches in the oligonucleotide rendered ASO-9 virtually inactive, confirming an antisense effect. Administration of ASO-9 (20 mg/kg/day for 4 d) to rats resulted in a 50% reduction in liver ALDH2 mRNA, a 40% inhibition in ALDH2 activity, and a fourfold (P < 0.001) increase in circulating plasma acetaldehyde levels after ethanol (1 g/kg) administration. Administration of ASO-9 to rats by osmotic pumps led to an aversion (-61%, P < 0.02) to ethanol. These studies provide a proof of principle that specific inhibition of gene expression can be used to mimic the protective effects afforded by the ALDH2-2 phenotype.
 ...
PMID:Eliciting the low-activity aldehyde dehydrogenase Asian phenotype by an antisense mechanism results in an aversion to ethanol. 1153 26

Hepatocellular carcinoma (HCC) is a common cancer. Its incidence is higher in countries where hepatitis B is endemic. HCC is substantially a complication of liver cirrhosis. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the predominant causes of cirrhosis, and as such, HCC. The link between HCC and alcoholic cirrhosis is less strong. Other less common forms of chronic liver disease can also lead to HCC. HBV is the HCC-determining disease worldwide. In endemic regions, it tends to be acquired early in life. The largest strides in prevention of HCC have been made with the HBV vaccine. HCV has a lower global prevalence than HBV, but HCV causes the most HCC in economically developed regions. In these areas, where the incidence of HCC is low, HCV now accounts for more than 50% of HCCs. There is no vaccine for HCV, so prevention of HCV-associated HCC will focus on prevention of initial infection and elimination of infection through antiviral therapies. HBV-HCV coinfection, and the combination of either with alcohol abuse or aflatoxin exposure seems to raise the risk of HCC development further. Liver transplantation and other adjuvant therapies may offer better options for secondary prevention of HCC than resection alone.
 ...
PMID:The epidemiology and prevention of hepatocellular carcinoma. 1168 37

Macrocytosis is most commonly associated with vitamin B(12) and folic acid deficiency, followed by alcoholism, liver disease, and other pathologic conditions. We studied the red cell and vitamin status in 423 consecutive patients with various liver diseases, including 31 with acute viral hepatitis (AVH), 105 with chronic hepatitis (CH), and 134 with alcoholic liver disease (ALD), who consisted of 84 with non-cirrhotic alcoholic liver disease (NCALD) and 50 with alcoholic liver cirrhosis (ALC), 60 with non-alcoholic liver cirrhosis (NALC), and 93 with hepatocellular carcinoma (HCC). The mean corpuscular volume (MCV) and red cell distribution width (RDW) were significantly higher in patients with ALD and NALC, and among them macrocytosis occurred more frequently in patients with ALC. Macrocytic anemia was mostly found in cirrhotic patients, in which the Child-Pugh score was closely related to the development of macrocytic anemia. In ALD, the MCV was significantly correlated with the estimated alcohol consumption and inversely correlated with the serum folic acid level, which, however, was often maintained within the normal range in patients with macrocytic ALC. After abstinence from alcohol, the MCV and RDW were reduced significantly and were associated with an increasing serum folic acid level. This suggests that macrocytic anemia was a common feature of alcoholic and non-alcoholic liver cirrhosis and that alcohol abuse and folic acid deficiency play a secondary role in macrocytosis.
 ...
PMID:Red blood cell status in alcoholic and non-alcoholic liver disease. 1170 57

Liver cirrhosis is the end-stage of chronic liver disease with a prevalence of 0.5-0.8 percent in the German population. The main causes are chronic viral hepatitis B and C and alcohol abuse. Liver cirrhosis is often oligosymptomatic and frequently only diagnosed when complications occur (laboratory tests, ultrasound, computertomography or nuclear resonance imaging and histology). Complications include portal hypertension, gastrointestinal bleeding, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatopulmonary syndrome, hepatic encephalopathy and hepatocellular carcinoma. Therapeutic management should mainly focus on the treatment of the underlying chronic liver disease in a precirrhotic stage. In the case of cirrhosis, prevention and treatment of complications are clinically most important.
 ...
PMID:[Clinical aspects of liver cirrhoses and its complications and diagnostic problems]. 1171 75

A retrospective multicenter analysis of 652 patients with chronic hepatitis C who have been treated with interferon (IFN) was performed to assess the effects of IFN on the clinical course and development of HCC. During a mean follow-up of 54.8 months, hepatocellular carcinoma (HCC) developed in 7.0% of the patients. The rate was significantly higher in the patients who did not respond to IFN treatment than in those with sustained virological response and those who obtained a normalization of alanine aminotransferase levels despite the presence of HCV RNA (incomplete response) (P < 0.01). Using multivariate Cox's proportional hazard model, alcohol abuse (P < 0.05) and a higher level of fibrosis (P < 0.05) before treatment were the significant background factors associated with HCC development in the patients who did not respond to IFN. Interestingly, a significant increase in the rate of HCC development occurred in patients who had a histological finding of progressive fibrosis (F3). In addition, patients with low histological staging scores were likely to have an incomplete response, even if a sustained virological response was not obtained. IFN produced an improvement in histological activity and fibrosis stage in the second biopsy specimens irrespective of the clinical outcome when compared against untreated subjects.
 ...
PMID:Interferon inhibits progression of liver fibrosis and reduces the risk of hepatocarcinogenesis in patients with chronic hepatitis C: a retrospective multicenter analysis of 652 patients. 1183 20

Colchicine decreases liver fibrosis in experimental and human disease, but a meta-analysis recently concluded that colchicine should not be used for liver fibrosis or cirrhosis irrespective of the aetiology. In this issue, Cortez-Pinto et al. confirm such negative conclusions in their series of 55 outpatients with biopsy-proven alcoholic cirrhosis followed for a median of 3.5 years. Although well tolerated, colchicine did not affect either the annual incidence rate of complications or liver function tests. Current treatment of alcoholic cirrhosis includes correction of nutritional deficiencies, exogenous administration of antioxidants (notably S-adenosylmethionine and polyenylphosphatidylcholine), and liver transplantation. In the future, preventive/therapeutic strategies will include campaigns to decrease alcohol abuse aimed at subjects genetically prone to develop alcoholic liver injury, prevention of liver fibrosis via inhibition of the Na+/H+ exchange, stimulation of apoptosis of stellate cells, antagonism of cytokines involved in liver injury, degradation of extracellular matrix, and reversal of ethanol-induced inflammatory and fibrotic changes via increased nitric oxide levels. On the grounds that it renders the hepatocyte more vulnerable to necrosis, steatosis has a key role in the pathogenesis of alcoholic and non-alcoholic liver disease. Conditions associated with insulin resistance have been recognized as risk factors for chronic liver disease and hepatocellular carcinoma in the alcoholic. This suggests that, through steatosis, insulin resistance could be a co-factor of alcoholic liver disease. Were such a hypothesis confirmed, it would unify our view of the pathogenesis of alcoholic and non-alcoholic liver disease, with all its inherent therapeutic implications.
 ...
PMID:Of liver, whisky and plants: a requiem for colchicine in alcoholic cirrhosis? 1194 49

Unresectable hepatocellular carcinoma (HCC) are associated with a poor prognosis. Recently, one controlled study reported a strikingly prolonged survival of patients with HCC who were treated with octreotide. Until other randomised controlled trials become available, this multicentric retrospective study therefore assesses the outcome of HCC-patients who received octreotide treatment. 63 patients (53 males, 10 females) who had been treated with octreotide at 13 participating German centres were included in the analysis. In 54 cases liver cirrhosis was present (25 Child-Pugh A, 20 Child-Pugh B, 7 Child-Pugh C, 2 unknown). The liver disease was associated with alcohol abuse in 19 patients, alcohol and viral hepatitis in four patients, while 12 patients had only markers of past or present hepatitis B infection, 11 patients suffered of chronic hepatitis C infection, and four patients were seropositive for both hepatitis B and hepatitis C markers. The Okuda stage was stage I in 23, stage II in 33, and stage III in 7 patients. The patients initially received octreotide as a long-acting release formula (20-30 mg/month) in 43 cases or through subcutaneous injection (dose 3 x 50-3 x 300 ug/day) in the remaining cases. 11 of the patients receiving subcutaneous treatment were later converted to the long-acting release form of the drug. At three months, a partial remission was achieved in two patients, while 22 tumours showed no change and 26 tumours progressed. At six months, 11 tumours showed no change, while 15 tumours progressed. The patients' median survival was 9 months (Okuda stage I 16 months, stage II 9 months, stage III 4 months). In conclusion, octreotide treatment did not result in markedly prolonged survival in this retrospective series of 63 patients.
 ...
PMID:[Clinical outcome of a cohort of 63 patients with hepatocellular carcinoma treated with octreotide]. 1205 62

Approximately 400,000 individuals in the United States are co-infected with hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) and it is likely that almost one in two of these subjects consumes alcohol. The majority of these patients suffer an accelerated course of liver disease as manifested by the onset of cirrhosis within 5 to 10 years of developing HCV infection, as well as an increased risk of developing hepatocellular carcinoma (HCC). It is thought that chronic alcohol abuse mediates liver damage as a result of increased production of free radicals and proinflammatory cytokines. In the setting of chronic HCV infection, alcohol ingestion has an additional effect of diminishing immune clearance and increasing viral burden to hasten the onset of cirrhosis and HCC. Likewise, chronic HCV and HIV-1 co-infection results in a net increase in HCV burden; higher prevalence rates of HCV transmission to sexual partners and offspring, as well as an accelerated progression to end stage liver disease as compared to individuals with HCV infection alone. Thus, the synergistic effects of alcohol abuse and HIV-1 greatly impact on the morbidity and mortality for patients with HCV coinfection. Ultimately, this cumulative disease process will require far more aggressive management with abstinence and counseling for alcohol abuse; highly active antiretroviral therapy (HAART) for HIV infection and combination anti-viral therapy for HCV infection to stem the rapid progression to end stage liver disease.
 ...
PMID:Hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infections in alcoholics. 1208 18

Hepatocellular carcinoma (HCC) is a major type of primary liver cancer and one of the rare human neoplasms etiologically linked to viral factors. Chronic infections with the hepatitis B virus (HBV) and the hepatitis C virus (HCV) have been implicated in about 80% of cases worldwide, and other known environmental risk factors, including alcohol abuse and dietary intake of aflatoxin B1, might synergize with viral infections. Recent insight into the molecular mechanisms leading to HCC development has been provided by the identification of major genetic abnormalities revealed by genomewide allelotype studies and molecular cytogenetic analysis. Moreover, several oncogenic pathways have been implicated in malignant transformation of liver cells. Inactivation of the p53 tumor suppressor gene by mutations and allelic deletions in about 30% of HCC cases has been associated predominantly with exposure to aflatoxin B1 and HBV infection. By contrast, a mutation in the beta-catenin gene in around 22% of HCCs is more rare in HBV-associated tumors. Activation of cyclin D1 and disruption of the Rb pathway are also commonly involved in liver tumorigenesis. New major challenges include the identification of candidate genes located in frequently altered chromosomal regions and that of oncogenic pathways driven by different risk factors. This search might shed some light on the tumorigenic role of HBV and HCV. It might also permit accurate evaluation of major targets for prognostic and therapeutic intervention.
 ...
PMID:Genetic alterations and oncogenic pathways in hepatocellular carcinoma. 1209 25

Ten percent of patients who undergo resection for hepatocellular carcinoma (HCC) associated with chronic liver disease have no detectable cause for this underlying liver disease. Recent studies have shown that patients with cryptogenic chronic liver disease frequently have risk factors for nonalcoholic fatty liver disease (NAFLD). This study examines the incidence of risk factors for NAFLD in patients with chronic liver disease who underwent resection for HCC. Among 210 patients with chronic liver disease who underwent resection for HCC, 18 (8.6%) had no identifiable cause for the underlying liver disease. These patients were assessed for obesity, diabetes mellitus, and histological features of the tumor and the adjacent liver parenchyma. Comparisons were made with matched patients with alcohol- and chronic-viral-hepatitis-related HCC. The prevalence of obesity (50% vs. 17% vs. 14%), diabetes (56% vs. 17% vs. 11%), aspartate aminotransferase/alanine aminotransferase ratio<1 (50% vs. 19% vs. 17%), and steatosis>20% (61% vs. 17% vs. 19%) was significantly higher in patients with cryptogenic liver disease than in patients with alcohol abuse and chronic viral hepatitis (P<0.0001 for each). Well-differentiated tumors were significantly more common in patients with cryptogenic liver disease (89% vs. 64% in patients with alcohol-related HCC vs. 55% in patients with chronic viral hepatitis-related HCC, P<0.0001). In conclusion, the hypothesis that obesity and diabetes mellitus may be important risk factors for cryptogenic chronic liver disease in patients with HCC is supported by the analysis of surgically treated patients. Whether HCC is primarily related to obesity and diabetes mellitus or secondarily to a NAFLD-like parenchymal lesions remains to be clarified.
 ...
PMID:Obesity and diabetes as a risk factor for hepatocellular carcinoma. 1476 43


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>