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)

The high prevalence of hepatocellular carcinoma (HCC) in genetic hemochromatosis (GH) and the association between increased body iron stores and occurrence of HCC in subjects with iron overload unrelated to GH, and the experimental evidence of a co-carcinogenic role of iron strongly support that iron is involved in the development of HCC.
 ...
PMID:Iron and hepatocellular carcinoma. 1135 May 42

Hepatocellular carcinoma (HCC) is a well-known complication of genetic hemochromatosis (GH). However, the frequency of primary liver carcinoma (PLC) with biliary differentiation, such as cholangiocarcinoma (CC) and combined hepatocholangiocarcinoma (CHCC), in GH remains unclear We analyzed the histologic type of 20 PLCs occurring in the background of GH; all patients were homozygotic for the C282Y mutation. Ten were depleted of iron by successive phlebotomies, while the remaining 10 were untreated. Histologically, 13 cases were classified as HCC, 3 as CC, and 4 as CHCC. Immunohistochemical detection of Hep Par 1, cytokeratin 19 (CK19), and MUC1 supported this classification; PLC with biliary differentiation was immunoreactive for MUC1 in 86% (6/7) of cases and for CK19 in 100% (7/7) of cases. The nontumoral liver exhibited no cirrhosis or extensive fibrosis in 6 cases. Von Meyenburg complexes were present in 11 cases and intraparenchymal bile duct adenomas in 3. These data suggest that PLCs in patients with GH present a wide histologic spectrum, with tumors showing frequent biliary differentiation; may arise on a nonfibrotic or a cirrhotic liver; and often are associated with Von Meyenburg complexes and to a lesser extent with bile duct adenomas.
 ...
PMID:Primary liver carcinoma in genetic hemochromatosis reveals a broad histologic spectrum. 1171 Jun 92

Hepatocellular carcinoma (HCC) is the most common malignant tumor of males in the world, with an incidence of 1,000,000 new cases a year. It is endemic in Southeast Asia and Sub-Saharan Africa. Risk factors include chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), Aflatoxin B1 uptake, hemochromatosis, and alpha1 -antitripsin deficiency. Epidemiological studies provide evidence for the association of HCC with HBV infection. The incidence of HCC is high in regions hyperendemic for HBV. Chronic carrier state and maternal-infant transmission are important factors in the development of HCC. Evidence of direct oncogenic effect of H BV is well established, HCCs contain viral DNA sequences integrated into hepatocyte DNA that act as random insertional mutagens, and these sites are near genes involved in the control of proliferation and differentiation. The mechanism of hepatitis C virus in hepatocarcinogenesis is still imprecise but a high percentage of cases are related to this virus. Chronic alcohol consumption and cirrhosis are cofactors that increase the development of HCC in patients with chronic viral infection. In experimental carcinogenesis a multipotential element called oval cell proliferates in the early stages. The cellular events are accompanied by increased expression of several growth factors that enhance the survival of carcinogen-activated cells by suppressing apoptosis and increasing elements entering the cell cycle. Hepatic carcinogenesis is a complex process associated with accumulation of genetic and epigenetic changes that run through steps of initiation, promotion and progression. Activation of oncogenes of the "ras" family and others has been detected during chemically-induced HCC in rodents, but there is little evidence of such activation in human tumors. The role of tumor supressor genes such as retinoblastoma (RB) and P53 genes has been documented. Aflatoxin B1 that contaminates foods in endemic areas has a clear role in hepatocarcinogenesis. Metabolites of this toxin promote apurinic sites and G to T mutations in chromosomal DNA, the third base of codon 249 of the P53 gene is preferentially targeted to form aducts with aflatoxin B1, and this mutation has been specifically identified in HBV infection. Histological and cytological criteria for the diagnosis of HCC are well established and are based in architectural and cytological changes. An important issue is the diagnosis of liver "nodules" detected by image, from which small biopsies or aspiration material is obtained. Special studies such as reticulin, CD34, cytokeratin profile, and MOC-31 can be very useful for the differential diagnosis of primary and metastatic tumors. Telomerase activity has been found in HCC and negative in pericancerous tissue. It is more pronounced in poorly differentiated tumors and correlates with factors of clinical importance, such as prognosis and recurrences. Cells of well-differentiated HCC have an ultrastructural appearance similar to normal hepatocytes. During the process of dedifferentiation, there is progressive loss of organization of intracellular organelles. The cell cohesion is lost, intercellular gaps with microvilli appear, the sinusoids become capillarized, and reparative changes are seen in the spaces of Disse. A variety of inclusions, such as Mallory bodies, granular material, secondary lysosomes, and Dubin-Johnson pigment, have been described. Fibrolamellar carcinoma has a characteristic histological picture and ultrastructurally oncocytic features. Neuroendocrine granules and combination of HCC with bile duct carcinoma are seen by electron microscopy.
 ...
PMID:Hepatocellular carcinoma: an update. 1178 14

The appearance of the cirrhotic liver on computed tomography can be difficult to evaluate and can frustrate the radiologist distinguishing benign from malignant lesions. Hepatic edema, fibrosis, atrophy, and vascular abnormalities are common in the cirrhotic liver and produce derangements in morphology, attenuation, and perfusion, limiting the accurate characterization of hepatic masses. With the development of fast magnetic resonance (MR) sequences and dynamic postgadolinium-enhanced imaging, most hepatic lesions with uncertain etiology on computed tomography can be accurately characterized on MR imaging. We describe MR imaging techniques useful for imaging cirrhosis and its complications. We also illustrate the spectrum of findings in the cirrhotic liver on dynamic gadolinium-enhanced MR imaging, including reticular and confluent fibrosis, fatty infiltration, hemochromatosis, regenerating nodules, dysplastic nodules, hepatocellular carcinoma, and sequela of portal hypertension.
 ...
PMID:Cirrhosis: spectrum of findings on unenhanced and dynamic gadolinium-enhanced MR imaging. 1190 25

Hepatocellular carcinoma (HCC) accounts for 80-90% of liver cancers and is one of the most frequent carcinomas throughout the world. The disease is more prevalent in parts of Africa and Asia than in North and South America and Europe, with a strong etiological association with viral hepatitis, hemochromatosis, known liver (hepatic) carcinogens, and toxins (mycotoxins). Clinical and molecular medical analyses have yielded a considerable amount of information about liver carcinogenesis. Many genes undergo somatic aberrations, with a tendency to cluster at genes involved in cell cycle regulation, in the p53 and Wnt/catenin pathways of signal transduction and cellular adhesion, and in the TGF-beta/IGF axis. Since HCC may arise both in liver cirrhosis and in noncirrhotic liver, one may speculate that different hepatocarcinogenetic pathways exist. Recent results of high-output gene analysis using cDNA microarrays support the idea of different genetic alterations in HCC with or without cirrhosis.
 ...
PMID:Genes involved in hepatocellular carcinoma: deregulation in cell cycling and apoptosis. 1195 13

The incidence of hepatocellular carcinoma is increasing in many countries. The estimated number of new cases annually is over 500,000, and the yearly incidence comprises between 2.5 and 7% of patients with liver cirrhosis. The incidence varies between different geographic areas, being higher in developing areas; males are predominantly affected, with a 2:3 male/female ratio. The heterogeneous geographic distribution reflects the epidemiologic impact of the main etiologic factors and environmental risk, which are the hepatitis B (HBV) and hepatitis C (HCV) viruses. The percentage of cases of hepatocellular carcinoma attributable to HBV worldwide is 52.3% and is higher in Asia where the seroprevalence of HBsAg in the population is high. However, the vaccination campaign against this virus in some eastern countries has tended to lower the incidence of new cases of hepatocellular carcinoma. The percentage of cases of hepatocellular carcinoma attributable to HCV is 25%, and it is more prevalent in Japan, Spain, and Italy where the association between hepatocellular carcinoma and antibodies to HCV ranges between 50 and 70%. In most cases hepatocellular carcinoma develops in cirrhotic livers, where the persistent proliferation of liver cells represents the key factor of progression to hepatocellular carcinoma independent of the etiology. Another minor risk factor is aflatoxin B1 consumption, which is responsible for most cases of hepatocellular carcinoma in Africa, where the consumption of contaminated foods is common. Other known risk factors are some hereditary diseases, such as hemochromatosis, porphyria cutanea tarda, hereditary tyrosinemia, and alpha1 anti-trypsin deficiency. The natural history of hepatocellular carcinoma is heterogeneous and is influenced by nodule dimension, the mono- or plurifocality of lesions at diagnosis, the growth rate of the tumor, and the stage of the underlying cirrhosis. Available data to date suggest that tumor growth in a cirrhotic liver is variable and that the time in which a lesion in undetectable until it becomes 2 cm is between 4 and 12 months. Therefore, the suggested interval for surveillance screening with ultrasound in patients with liver cirrhosis has been set at 6 months. Patients who should benefit from screening programs are those who would be treated with curative therapy if diagnosed with hepatocellular carcinoma. Thus, the ideal target population should be limited to Child-Pugh's class A cirrhotic patients without significant comorbidity.
 ...
PMID:Epidemiology, risk factors, and natural history of hepatocellular carcinoma. 1209 24

Pituitary changes in the case of a 69-year-old man with hemochromatosis are reported. The patient died of complications of hepatocellular carcinoma. The pituitary removed at autopsy was studied by histology, histochemistry, immunocytochemistry, electron microscopy, and X-ray diffraction. Preferential localization of iron deposits was demonstrated within gonadotrophs, which, at the ultrastructural level, displayed selective, severe cellular injury. X-ray diffraction revealed the deposition of iron-accumulated lysosomes. Iron storage also was noted in stellate cells. We consider selective injury of pituitary gonadotrophs to be the basis of hypogonadism in iron-overloaded states.
 ...
PMID:The Anterior Pituitary in Hemochromatosis. 1211 44

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 toxins (alcohol, aflatoxin B1), androgens and estrogens, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection as well as various inherited metabolic disorders, such as alpha-1-antitrypsin deficiency and hemochromatosis. The molecular pathogenesis of HCC development is very complex and involves alterations in the structure or expression of several tumor suppressor genes, oncogenes and, possibly, mechanisms leading to a genetic instability due to mismatch repair deficiency or chromosomal instability and aneuploidy due to defective chromosomal segregation. Central to the molecular pathogenesis of HCCs are mutations of various genes and a genetic instability which in most cases result from chronic liver disease and the associated enhanced liver cell regeneration and mitotic activity. The prognosis of HCC patients is generally very poor. Most studies report a five year survival rate of less than 5% in symptomatic HCC patients. Furthermore, these tumors have been shown to be quite resistant to radio- or chemotherapy. Investigations of the natural history and clinical course of HCCs revealed long-term survival of patients only with small asymptomatic HCCs that could be treated surgically or by non-surgical interventions. Apart from exploring and refining new HCC treatment strategies, the implementation of existing and the development of novel measures to prevent HCC development are most important. Primary HCC prevention includes among others universal hepatitis B vaccination, antiviral therapy of patients with chronic hepatitis B or C, reduction of food contamination with aflatoxins, elimination of excessive alcohol etc. Also for some genetic diseases there is the potential for HCC prevention by identifying affected family members at risk, such as patients with precirrhotic hemochromatosis. Reduction of iron overload by phlebotomy has been shown to eliminate the progression hemochromatosis to liver cirrhosis and HCC. Preventive measures, therefore, should have a major impact on the incidence of HCCs in patients with acquired and inherited liver diseases. Further, the prevention of a local recurrence or the development of new HCC lesions in patients after successful surgical or non-surgical HCC treatment (secondary prevention) is of paramount importance and is expected to significantly improve disease-free and overall patient survival. Based on rapid scientific advances, molecular diagnosis, gene therapy and molecular prevention are becoming increasingly part of our patient management and will eventually complement and in part replace existing diagnostic, therapeutic and preventive strategies. Overall, this should result in a reduction of the incidence of HCCs, one of the most devastating malignancies worldwide.
 ...
PMID:Molecular targets for prevention of hepatocellular carcinoma. 1214 24

Cirrhosis of the liver has to be regarded as a premalignant condition independent of its etiology. The annual risk of developing HCC in cirrhosis is between 1% and 6%. Surveillance-programs have been introduced to detect early stages of HCC in order to improve mortality. However, only controlled trials will answer the question of the efficacy of such programs. Studies on the potential benefit of surveillance-programs comparing survival in surveilled and unsurveilled patients are so far lacking. It seems clear, however, that surveillance-programs can detect small tumors, often unfocal and potentially treatable by a curative approach. Moreover, the etiology (HBV, HCV, genetic hemochromatosis) and activity of liver cirrhosis as measured by serum-transaminases, liver histology (small-cell dysplasia and atypical regenerative nodules), Child-Pugh-stage and the concentration of alpha-fetoprotein at the beginning of a surveillance-program--all these factors reflect a high risk of developing HCC in an individual patient. Until programs are introduced on the basis of randomized, controlled trials of surveillance vs. usual care (with liver-related, specific deaths and all-cause-mortality as end-points) it seems reasonable to screen high-risk patients semi-annually by liver ultrasound and determination of AFP-concentration in the serum.
 ...
PMID:[Hepatocellular carcinoma: risk groups--screening]. 1223 79

Hepatocellular carcinoma (HCC) is the most common hepatic malignancy worldwide. The primary risk factor for the development of HCC is cirrhosis. Even patients without cirrhosis who develop HCC are typically found to have some underlying hepatic abnormality, such as steatohepatitis or chronic viral hepatitis. Although cirrhosis of any cause increases the risk of developing HCC, cirrhosis associated with chronic hepatitis B or C virus infection or hemochromatosis carries the greatest risk. Additional factors such as patient age and sex, duration and severity of liver disease, concurrent alcohol or aflatoxin exposure, liver histology, and alpha-fetoprotein levels also contribute to the relative risk of developing HCC. Vaccination programs aimed at preventing hepatitis B virus infection have been very successful in lowering the incidence of HCC in some areas of the world. Interferon-based therapy, which may control the inflammatory activity in chronic hepatitis C, also holds promise in preventing HCC. Other novel chemopreventative agents, such as glycyrrhizin and polyprenoic acid, may also have a role in preventing HCC, but they require further study before they can be recommended for widespread use.
 ...
PMID:Hepatocellular carcinoma: the high-risk patient. 1239 10


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