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)

Combined hepatocellular-cholangiocarcinoma is a rare form of primary liver cancer showing features of both hepatocellular and biliary epithelial differentiation. In a review of 24 cases of this tumor, three histologic types were encountered. Four cases were Type I or "collision tumors," apparently a coincidental occurrence of both hepatocellular carcinoma and cholangiocarcinoma in the same patient. Twelve cases were Type II or "transitional tumors," in which there were areas of intermediate differentiation and an identifiable transition between hepatocellular carcinoma and cholangiocarcinoma. Eight cases were Type III or "fibrolamellar tumors" which resembled the fibrolamellar variant of hepatocellular carcinoma but which also contained mucin-producing pseudoglands. Type III tumors differ from other combined tumors, occurring at a younger age, in the absence of cirrhosis, and having a slightly longer survival. Immunohistochemical (immunoperoxidase) staining for intracellular antigens showed that alpha-fetoprotein is a fairly specific, although insensitive, marker of hepatocellular differentiation in primary liver cancers, being present in 50% of typical hepatocellular carcinomas and in hepatocellular areas in 29% of combined tumors, but in no cholangiocarcinomas or cholangiocellular areas of combined tumors. Keratin is a good marker of biliary epithelial differentiation, being found in 90% of cholangiocarcinomas and in 52% of combined hepatocellular cholangiocarcinomas, but in no hepatocellular carcinomas. Alpha-1-antitrypsin, fibrinogen, IgG, and carcinoembryonic antigen may be found in both hepatocellular carcinoma, cholangiocarcinoma, and in combined tumors; these antigens are therefore of limited use in differential diagnosis.
 ...
PMID:Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study. 257 78

Alpha-1-antitrypsin (AAT) is the major protease inhibitor in human serum and is primarily expressed in the liver. We have studied AAT expression in fusion hybrids between a rat hepatoma line and either human fetal liver fibroblasts (series XXII) or human skin fibroblasts (series XIX). While the human AAT gene was always activated in series XXII hybrids when it was present, it was only rarely activated in series XIX hybrids. RFLP analysis revealed that both parental AAT alleles in series XIX hybrids were capable of being activated. Molecular analysis of the AAT gene in expressing and nonexpressing hybrids revealed that active AAT genes were hypomethylated, while inactive AAT genes were highly methylated. However, differences in methylation patterns were confined to the 5' end of the gene, on both sides of the first exon. DNaseI sensitivity revealed no hypersensitive sites close to active or inactive AAT genes.
 ...
PMID:Activation of human alpha 1-antitrypsin genes in rat hepatoma x human fibroblast hybrid cell lines is correlated with demethylation. 282 94

Alpha-1-antitrypsin (A1AT) has been shown to be a useful tumor marker for hepatocellular carcinoma (HCC) and some other neoplasms. No studies of alpha-1-antichymotrypsin (A1AChy) in HCC have been reported. A comparative study of A1AT and A1AChy in HCC was undertaken. While 19/33 HCC were positive for A1AT, all 33 HCC contained immunoreactive A1AChy. Cells showing positive immunoreaction for both A1AT and A1AChy were more numerous in moderately differentiated HCC than in well differentiated or poorly differentiated HCC. Although the pattern of staining with both antisera was similar, in cases showing positive staining for both antisera, A1AChy-positive cells were more numerous than A1AT-positive cells. The results suggest a useful role for A1AChy as a marker of HCC.
 ...
PMID:Comparison of alpha-1-antitrypsin and alpha-1-antichymotrypsin in hepatocellular carcinoma: an immunoperoxidase study. 609 53

An increased frequency of alpha-1-antitrypsin deficiency (AATD) has been reported in patients with hepatocellular carcinoma (HCC) in Scandinavia and England. Using a specific immunoperoxidase technique for alpha-1-antitrypsin (AAT) and periodic acid-Schiff (PAS) with and without diastase predigestion, the authors examined nonneoplastic autopsy liver tissue from 58 black southern African patients with HCC and from 54 controls. No periportal PAS-positive diastase-resistant globules containing AAT (specific for AATD) were found in liver tissue from either group. A finely granular diffuse cytoplasmic AAT staining (not removed by diastase predigestion) was present in hepatocytes in a "checkerboard" pattern within the lobule in 33 (57%) HCC patients and in 20 (37%) controls (P greater than 0.1), and was particularly prominent adjacent to tumor in 11 HCC patients. Alpha-1-antitrypsin was present in neoplastic cells in 18 of the 40 HCC examined (45%). These findings suggest no major role for AATD in the etiology of HCC in southern Africa.
 ...
PMID:Alpha-1-antitrypsin deficiency in Southern African hepatocellular carcinoma patients. An immunoperoxidase and histochemical study. 628 Aug 44

Alpha-1-antitrypsin (AAT) deficiency resulting from the homozygous protease inhibitor (Pi) ZZ and the heterozygous Pi Z states has been reported to be aetiologically associated with hepatocellular carcinoma (HCC). We studied the phenotype distribution of AAT variants (Pi) by iso-electric focusing on polyacrylamide gel and measured serum AAT concentrations by rocket immuno-electrophoresis in 80 unselected southern African Black patients with HCC and 103 age-, sex- and tribally matched control subjects. Aberrant (non-MM) phenotypes were present in 7 HCC patients (8,7%) and 13 controls (12,6%), an insignificant difference. None of the patients or controls had the Pi ZZ phenotype, while 4 HCC patients (5,0%) and 2 controls (1,9%) (P greater than 0,05) were found to be heterozygous carriers of the Z gene. No HCC patient had a subnormal serum AAT value, and the values in the patients were not lower than those in the controls. We conclude that AAT deficiency does not play an aetiological role in HCC in southern African Blacks. The 4 patients with the heterozygous Z phenotype did not have fibrolamellar carcinomas.
 ...
PMID:Alpha-1-antitrypsin deficiency and hepatocellular carcinoma. Determination of Pi phenotypes using iso-electric focusing. 631 69

Alpha-1-antitrypsin (alpha(1)-antitrypsin) is the archetypal member of the serine proteinase inhibitor or serpin superfamily. The most common severe deficiency variant is the Z allele, which results in the accumulation of mutant protein within hepatocytes. This 'protein overload' causes neonatal hepatitis, cirrhosis and hepatocellular carcinoma. The lack of circulating plasma alpha(1)-antitrypsin results in early-onset panlobular emphysema. The mechanism underlying the deficiency of Z alpha(1)-antitrypsin is due to an aberrant conformational transition within the protein and the formation of chains of polymers that tangle within the secretory pathway of hepatocytes. This mechanism also underlies the plasma deficiency of other members of the serpin superfamily to cause a class of diseases called the serpinopathies. Specifically mutant alleles of antithrombin, C1-inhibitor and alpha(1)-antichymotrypsin have been reported that favour the spontaneous formation of polymers and the retention of protein within hepatocytes. The consequent lack of plasma antithrombin, C1-inhibitor and alpha(1)-antichymotrypsin results in thrombosis, angio-oedema and emphysema, respectively. Moreover, the polymerisation of mutants of neuroserpin results in the retention of polymers within neurones to cause the inclusion body dementia, familial encephalopathy with neuroserpin inclusion bodies or FENIB. We review here the genetic and molecular basis and clinical features of alpha(1)-antitrypsin deficiency, and show how this provides a platform to understand the other serpinopathies.
 ...
PMID:Practical genetics: alpha-1-antitrypsin deficiency and the serpinopathies. 1469 55

Alpha-1-antitrypsin (AT) deficiency was first described in the late 1960s in patients with severe pulmonary emphysema. The recognition of AT deficiency as a cause of emphysema then led to what is still the prevailing theory for the pathogenesis of emphysema, the protease-antiprotease theory. Soon it was found that AT deficiency accounted for a significant number of cases of neonatal liver disease that were previously categorized as idiopathic. We now know that AT deficiency is the most common genetic cause of neonatal liver disease and the most frequent diagnosis necessitating liver transplantation. It has also been shown to cause chronic liver disease, cryptogenic cirrhosis, and hepatocellular carcinoma in adults never previously known to have liver disease in infancy or childhood. Observations indicate that genetic traits unlinked to the AT gene or environmental factors predispose to or protect AT-deficient individuals from liver disease.
 ...
PMID:Alpha-1-antitrypsin deficiency: diagnosis and treatment. 1546 58

Alpha-1-antitrypsin (AT) deficiency is the most common genetic cause of liver disease in children. In addition to chronic liver inflammation and injury, it has a predilection to cause hepatocellular carcinoma later in life. The deficiency is caused by a mutant protein, ATZ, which is retained in the endoplasmic reticulum (ER) in a polymerized form rather than secreted into the blood in its monomeric form. The histologic hallmark of the disease is ATZ-containing globules in some, but not all, hepatocytes. Liver injury results from a gain-of-toxic function mechanism in which mutant ATZ retained in the ER initiates a series of pathologic events, but little is known about the mechanism by which this leads to carcinogenesis. Several recent observations from my laboratory have led to a novel hypothetical paradigm for carcinogenesis in AT deficiency in which globule-containing hepatocytes are "sick," relatively growth suppressed, but also elaborating trans-acting regenerative signals. These signals are received and transduced by globule-devoid hepatocytes, which, because they are younger and have a lesser load of accumulated ATZ, have a selective proliferative advantage. Chronic regeneration in the presence of tissue injury leads to adenomas and ultimately carcinomas. Aspects of this hypothetical paradigm may also explain the proclivity for hepatocarcinogenesis in other chronic liver diseases, including other genetic diseases, viral hepatitis, and nonalcoholic steatohepatitis.
 ...
PMID:Pathogenesis of chronic liver injury and hepatocellular carcinoma in alpha-1-antitrypsin deficiency. 1686 11

Alpha-1-antitrypsin (AAT) is an important serine protease inhibitor in humans. Hereditary alpha-1-antitrypsin deficiency (AATD) affects lungs and liver. Liver disease caused by AATD in paediatric patients has been previously well documented. However, the association of liver disease with alpha-1-antitrypsin gene polymorphisms in adults is less clear. Therefore, we aimed to study AAT polymorphisms in adults with liver disease. We performed a case-control study. AAT polymorphisms were investigated by isoelectric focusing in 61 patients with liver cirrhosis and 9 patients with hepatocellular carcinoma. The control group consisted of 218 healthy blood donors. A significant deviation of observed and expected frequency of AAT phenotypes from Hardy-Weinberg equilibrium (chi-square = 34.77, df 11, P = 0.000) in the patient group was caused by a higher than expected frequency of Pi ZZ homozygotes (f = 0.0143 and f = 0.0005, respectively, P = 0.000). In addition, Pi M homozygotes were more frequent in patients than in controls (63% and 46%, respectively, P = 0.025). Our study results show that Pi ZZ homozygosity in adults could be associated with severe liver disease. Presence of Pi M homozygosity could be associated with liver disease via some mechanism different from Z allele-induced liver damage through accumulation of AAT polymers.
 ...
PMID:Alpha-1-antitrypsin phenotypes in adult liver disease patients. 1996 Dec 68

Here we report on a patient with a primary hepatocellular carcinoma in a non-cirrhotic liver, in whom heterozygosity for an AAT-deficiency allele was found (PiMZ). Based on this observation and the current literature, the possible mechanisms for an eventual contribution of a heterozygosity of a heterozygous AAT-deficiency for a hepatocellular carcinoma are discussed. Alpha-1-antitrypsin (AAT)-deficiency (Laurell-Eriksson syndrome) is a genetic disorder, in which individuals who are homozygous for a deficiency allele are at an increased lifetime risk for pulmonary emphysema, liver cirrhosis, and primary hepatocellular carcinoma. It has been controversially discussed whether the heterozygous form (PiMZ) is also associated with an increased risk for liver diseases. Hepatocarcinogenesis for AAT-deficiency is probably based on a series of toxic events. Precipitation of AAT aggregates in hepatocytes is the initial step. These accumulate in the endoplasmic reticulum and cannot be eliminated from all hepatocytes by proteasomal and non-proteasomal mechanisms. AAT aggregates induce proinflammatory pathways and may be a stimulus for hepatocarcinogenesis. This hypothesis is based mostly on studies of individuals homozygous for a deficiency allele (PiZZ). The mechanism may also play a role in heterozygous patients. Since not all patients with precipitates of AAT-aggregates are develop a hepatocellular carcinoma related comorbidities such as chronic hepatitis B, C, chronic alcohol abuse, or so far unknown genetic and environmental factors may be crucial.
 ...
PMID:[Heterozygous alpha-1-antitrypsin deficiency (PiMZ): risk factor in the development of primary liver carcinoma in non-cirrhotic liver?]. 2088 26


1 2 Next >>