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)

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.
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PMID:Alpha-1-antitrypsin deficiency in Southern African hepatocellular carcinoma patients. An immunoperoxidase and histochemical study. 628 Aug 44

A case of primary hepatocellular carcinoma is described in a patient with long-standing sarcoidosis of the liver associated with chronic active hepatitis, and the MZ alpha-1-antitrypsin phenotype. This association appears to be unique. The respective roles of alpha-1-antitrypsin deficiency, sarcoidosis and chronic active hepatitis in the development of hepatocellular carcinoma in this case are uncertain.
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PMID:Hepatocellular carcinoma in a patient with sarcoidosis-associated chronic active hepatitis and the MZ alpha-1-antitrypsin phenotype. 630 80

Human factor I is a two-chain plasma glycoprotein composed of disulfide-linked 50,000- and 38,000-dalton subunits. Analysis of its biosynthesis and postsynthetic processing demonstrated that factor I is synthesized as a single chain precursor (pro-I) that undergoes glycosylation and limited proteolysis to generate the native protein. One of three human hepatoma cell lines, HepG2 , secreted factor I predominantly (70-90%) in a single chain pro-I form. The other cell lines secrete factor I predominantly in its two chain native form. The defect in conversion of pro-I to I in HepG2 was protein specific since other multichain proteins, derived from single chain precursors, the third, fourth, and fifth components of complement were processed normally. Further analysis of the inefficient pro-I to I conversion by HepG2 revealed that Xenopus oocytes injected with HepG2 mRNA secreted factor I in a predominantly two-chain form. In addition, the apparent sizes of native factor I, transferrin, and alpha-1-antitrypsin secreted by the three hepatoma lines differed due to differences in postsynthetic processing.
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PMID:Biosynthesis and postsynthetic processing of human C3b/C4b inactivator (factor I) in three hepatoma cell lines. 632 81

Transplantation of Yoshida sarcoma (solid type) and Zajdela ascites hepatoma tumors in rats induces a biphasic change in the concentration of the following five acute-phase proteins: alpha-1-acid glycoprotein; alpha-1-antitrypsin; haptoglobin; hemopexin; and ceruloplasmin. These proteins and other plasma proteins were quantitated by two-dimensional immunoelectrophoresis relative to normal serum concentrations. The elevation of most of these acute-phase proteins was greater in the second phase, during which serum levels increased continuously as the tumor burden increased until the animals died. The increase in haptoglobin concentration during the second phase was much higher in rats bearing Yoshida sarcoma than in rats bearing Zajdela tumors. Rats receiving irradiated tumor cells showed neither tumor growth nor second-phase protein changes. Significant increases in uptake of 3H-amino acids by isolated perfused livers of tumor-bearing rats provided evidence for an increase in the hepatic synthesis rates of the acute-phase proteins. Removal of the solid tumor resulted in a gradual decrease of acute-phase protein concentrations with concomitant increase in serum albumin concentration. These alterations in serum acute-phase proteins during tumor growth and after removal of the tumor may make their use attractive as biological markers of the response of the tumor-bearing animal to its tumor.
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PMID:Kinetics of the acute-phase reaction in rats after tumor transplantation. 697 53

Percutaneous needle biopsy specimens of the liver from three elderly persons (aged 77, 71, and 66) demonstrated eosinophilic intracytoplasmic globules within hepatocytes, particularly in the periportal and periseptal areas. These globules were periodic acid-Schiff positive and diastase resistant, and were identified as alpha-1-antitrypsin by immunofluorescence technics. Two of the patients had cirrhosis, and identification of protease inhibitor (Pi) type by acid starch electrophoresis and crossed immunoelectrophoresis demonstrated SZ and MZ genotypes. The patient with SZ genotype also had a long history of chronic obstructive pulmonary disease. Pi-typing was not performed for the third patient, who did not have cirrhosis. The morphologic identification of alpha-1-antitrypsin disease in liver biopsies of persons of any age is important because of (1) possible multisystem involvement (hepatic and pulmonary), (2) increased frequency of hepatocellular carcinoma, and (3) implications for genetic counseling for other family members.
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PMID:Alpha-1-antitrypsin globules in hepatocytes of elderly persons with liver disease. 701 69

Seven cases of ovarian yolk sac tumor (endodermal sinus tumor) with patterns resembling those of hepatocellular carcinoma were encountered in patients 7-43 years of age. Two of the patients had gonadal dysgenesis with a 46XY karyotype. At operation three tumors were confined to the ovary and four were associated with intra-abdominal metastases. Two of the Stage I tumors recurred within one year. The hepatoid pattern was a prominent feature of all the tumors and was exclusive in four of them. In one specimen it merged almost imperceptibly with a polyvesicular vitelline pattern. The hepatoid component of the tumors was characterized by discrete masses, nests and/or broad bands of large polyhedral cells with central nuclei and prominent nucleoli; gland-like spaces, some of which contained mucin, were occasionally evident. Each tumor contained numerous PAS-positive, diastase-resistant intracytoplasmic and extracytoplasmic hyaline bodies. Alpha-fetoprotein and alpha-1-antitrypsin were identified by immunoperoxidase and immunofluorescence techniques in four tumors and albumin in two. Immunoperoxidase stains for chorionic gonadotropin were negative in four cases. Ultrastructural analysis of two specimens disclosed features similar to those of hepatocellular carcinoma.
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PMID:Hepatoid yolk sac tumor of the ovary (endodermal sinus tumor with hepatoid differentiation): a light microscopic, ultrastructural and immunohistochemical study of seven cases. 713 31

One hundred and twenty-four infants admitted to hospitals in Norway between 1955 and 1974 during the first 3 months of life with cholestatic jaundice were studied retrospectively. Sixty-four infants had had extrahepatic atresia of the biliary tree and 60 had had intrahepatic cholestasis. This gives an incidence of about 1:9000 live births for cholestasis. In 4 of the 64 infants with extra-hepatic atresia a bile duct-to-bowel anastomosis had been performed but this was successful in only 2. Sixty of these infants had died by their 2nd birthday. Twenty-six of the infants with intrahepatic cholestasis had died by 1978 and the most common causes of death were cholestasis complicated by infection, bleeding, or hepatoma. The survivors aged between 4 and 23 years were followed up in 1978. In about two-thirds of them aetiological factors--such as alpha-1-antitrypsin deficiency, arteriohepatic dysplasia, cholestasis with lymphoedema--and other familial or genetic factors, or infections were found. Four of the 34 survivors are known to have cirrhosis. Twenty patients had biochemical abnormalities, and 12 had normal liver function tests. Two patients could not be examined. Of the 19 patients with familial or genetic aetiological factors, 4 had cirrhosis, 14 had biochemical abnormalities, and only 5 had normal liver function tests. Of 11 survivors with idiopathic disease or septicaemia, none had cirrhosis and only 4 had abnormal liver function tests.
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PMID:Cholestatic jaundice in infancy. The importance of familial and genetic factors in aetiology and prognosis. 727 1

The Hep G2 hepatoma cell line synthesizes the inter-alpha-trypsin inhibitor (ITI). This protease inhibitor and the other proteins of this family include four polypeptides chains: three heavy chains (HC1, HC2, HC3) and one light chain (bikunin). In the present study, we have demonstrated by immunofluorescence that ITI is detected mainly in perinuclear cytoplasmic zones comparable to those of albumin or alpha-1-antitrypsin. The presence of the mRNAs of the four polypeptide chains in all Hep G2 cells of a non-synchronized culture have been demonstrated by in situ hybridization. An evaluation of the transcription of the four ITI genes through an analysis of markings brings to the fore a clearly much higher rate of mRNAs from the light chain than from the heavy chains. The mRNAs corresponding to the HC2 chains are more heavily represented than are those corresponding to the HC1 and HC3 chains. In Hep G2 cells in culture, a quantification of mRNAs based on the in situ hybridization technique shows that their relative quantities, in decreasing order, are those of L, HC2, HC3 and HC1.
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PMID:Light microscopical detection of inter-alpha-trypsin inhibitor and its different mRNAs in cultured hepatoma Hep G2 cells using immunocytochemical and in situ hybridization techniques. 751 68

Insulin-like growth factor II (IGF II) regulated tissue-specific gene expression in hepatoma cell lines, but had no effect on expression of tissue-specific genes in primary cultures of E14 and newborn rat liver cells depleted of erythroid cells. No change was observed in these primary cultures with respect to alpha-fetoprotein (alpha-FP), albumin, cytokeratin 19 (CK19), gamma-glutamyltranspeptidase (GGT), and IGF II receptors. Two well-differentiated hepatoma, HepG2 and FTO-2B, and a poorly differentiated hepatoma, H4AzC2, did not show increased proliferation in the presence of IGF II, yet showed gene expression changes in response to IGF II. In HepG2 cells, IGF II increased albumin mRNA levels and resulted in a shift from clusters of cells positive to 100% of the cells expressing immunohistochemically detectable albumin. The transcription factor HNF-3 beta mRNA and protein levels of the bile duct markers, CK19 and GGT, were also increased in the presence of IGF II. Other genes tested were not affected, including alpha-1-antitrypsin, and two liver-specific transcription factors, HNF-4 and HNF-3 alpha. In FTO-2B cells, IGF II increased the expression of albumin, CK19, and GGT, without accompanying changes in albumin and GGT mRNAs. In H4A7C2 cells, IGF II reduced CK19 and OC.3 protein levels and GGT, transferrin, and HNF-3 beta mRNAs. The effects of IGF II on H4AZC2 cells were not blocked in the presence of an anti-rat IGF II receptor antibody. We conclude that IGF II affects tissue-specific gene expression of hepatomas and qualitative and quantitative aspects of its influence on the hepatomas is dependent on their degree of differentiation.
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PMID:Insulin-like growth factor II regulation of gene expression in rat and human hepatomas. 752 37

Serum levels of alpha-1-antitrypsin were measured by radial immunodiffusion, and phenotypes were determined by electrofocusing in acrylamide gel in 160 subjects who were used as controls in a case-control study of hepatocellular carcinoma (HCC). The results were studied in relation to age, sex, diagnostic category, tobacco smoking, consumption of alcoholic beverages, presence of hepatitis B surface antigen (HBsAg), and serum levels of alphafetoprotein (AFP) by modeling the data through multiple regression. There was no relation of serum alpha-1-antitrypsin values with sex, HBsAg, AFP, consumption of alcoholic beverages, and diagnostic category (p > 0.25). By contrast, there were statistically significant dose-dependent positive associations of serum alpha-1-antitrypsin with age and tobacco smoking (p < 0.01 in both instances). The positive association of serum alpha-1-antitrypsin with tobacco smoking and the previously reported excessive elevation of serum alpha-1-antitrypsin in hepatitis B-negative tobacco-related cases of HCC suggest that alpha-1-antitrypsin is intimately related to the pathogenetic process linking tobacco smoking to HCC.
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PMID:Tobacco smoking and other factors in relation to serum alpha-1-antitrypsin. 768 28


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