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)

The biosynthesis and post-translational processing of the insulin-like growth factor II (IGF-II) receptor has been studied in H-35 hepatoma cells using a specific polyclonal anti-receptor immunoglobulin preparation. Cells were pulse-labeled with [35S]methionine followed by incubation with excess unlabeled methionine (chase). Gel electrophoresis of the immunoadsorbed receptors shows that the receptor is first synthesized as a 245-kDa precursor which is transformed to the mature 250-kDa form with a half-time of about 2 h. The 245-kDa precursor could also be labeled biosynthetically with [3H]mannose, only one-half of which was ultimately found associated with the 250-kDa product. Neuraminidase converts the 250-kDa receptor species to a 245-kDa form. Whereas the 250-kDa receptor is insensitive to detectable cleavage by endoglycosidase H, digestion of the 245-kDa species with this enzyme produces a 232-kDa form. A similar 232-kDa receptor species accumulates in H-35 cells incubated with tunicamycin (2 micrograms/ml). This tunicamycin-induced aglyco-receptor is not further processed to the 250-kDa form. Monensin (50 nM) blocks receptor processing at the 245-kDa stage. Endoglycosidase H treatment of the monensin-induced 245-kDa species indicates that this is a mixture of partially processed precursors having equivalent Mr. No evidence was obtained for the presence of O-linked oligosaccharides on the IGF-II receptor. The IGF-II binding activity of the three different biosynthetic forms of the receptor was assessed by affinity cross-linking of 125I-IGF-II to the receptors using disuccinimidyl suberate. Both the mature 250-kDa receptor and the neuraminidase-digested 245-kDa form specifically bound 125-I-IGF-II. However, the 232-kDa aglyco-receptor had no detectable IGF-II binding activity using this method. In summary, these studies show: 1) that the H-35 cell IGF-II receptor is synthesized first as a 245-kDa precursor having 4-6 high-mannose oligosaccharide side chains, 2) processing of the receptor oligosaccharides by mannose removal and terminal sialylation converts the 245-kDa precursor to the 250-kDa mature product which has been previously identified as the functional receptor in the plasma membrane, 3) the apparent molecular mass of the receptor in the absence of N-glycosylation is 232-kDa, and 4) glycosylation of the IGF-II receptor is required for the acquisition of IGF-II binding activity.
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PMID:Biosynthesis and processing of the type II insulin-like growth factor receptor in H-35 hepatoma cells. 299 8

The insulin-like growth factor II (rIGFII) is a mitogenic polypeptide, the expression of which is high in most rat tissues during embryonic development, yet is barely detectable in adult tissues except for some of neurogenic origin. The gene is present as a single copy in the genome but has three alternative leader exons, E1, E2 and E3, thereby with three independent transcriptional promoters. We analysed the expression of rIGFII and the relative efficiency of each promoter in hepatocarcinogen-treated livers, primary hepatomas and established hepatoma lines. The E3-specific product was first detected after 6 weeks of 3'-methyl-4-dimethylaminoazobenzene treatment and those of E1 and E2 also after 9 weeks. The levels gradually increased according to the sum of the treatment period, but reactivation was nil in the regenerating liver. Consistently high levels of expression were observed in all primary tumors, but the relative promoter activity varied with the tumor. The significance of rIGFII reactivation was discussed in the light of the hepatocarcinogenesis.
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PMID:Reactivation of rat insulin-like growth factor II gene during hepatocarcinogenesis. 316 58

We describe a case of recurrent hypoglycaemia associated with a hepatoma. During hypoglycaemia serum insulin was undetectable. Plasma insulin-like growth factor II (IGF-II) was not elevated although 71% of plasma IGF-II was present as big IGF-II (molecular weight 11 kDa) which probably represents a non-glycated form of pro-IGF-II. The GH response to hypoglycaemia was impaired and plasma levels of both IGF-I and the GH-dependent IGF binding protein (IGFBP-3) were low. A recently described unextracted assay directed against the first 21 amino acids of the E-domain (E-21) of proinsulin-like growth factor-II (pro-IGF-II) allows direct plasma estimation (plasma E-21) of larger molecular forms of IGF-II without interference from normal IGF-II and IGF binding proteins. Basal values were grossly elevated (23.7 and 23.8 nmol/l). Treatment with GH led to an increase in the mean plasma glucose across 24 hours (4.25 +/- 0.21 mol/l (mean +/- SEM) before treatment, compared with 4.86 mmol/l +/- 0.17 following GH (P < 0.01)) and a reduction in hypoglycaemic attacks. The treatment was associated with a rise in IGFBP-3 and small increases in insulin like growth factors. Subsequent treatment with the somatostatin analogue octreotide did not produce a significant change in plasma glucose levels or insulin-like growth factors. Two courses of intrahepatic adriamycin restored elevated levels of E-21 to normal. Total IGF-II remained normal and IGF-I increased. GH treatment was successfully withdrawn with no effect on plasma glucose or growth factor levels. The patient remained free from hypoglycaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A case of hepatoma associated with hypoglycaemia and overproduction of IGF-II (E-21): beneficial effects of treatment with growth hormone and intrahepatic adriamycin. 752 21

We characterized 8 human hepatocellular-carcinoma cell lines established from the primary tumors of Korean patients. All lines showed substrate adherence and one line from anaplastic tumor also grew as floating aggregates. Most cultured cells maintained many morphological characteristics of the original tumors from which they were derived. Doubling times varied from 34 to 72 hr. All lines showed relatively high viability and were not contaminated with Mycoplasma or bacteria. All lines showed aneuploidy and were proven to be unique by DNA fingerprinting analysis. Hepatitis-B-virus (HBV) DNA was integrated in the genomes of all lines. Two of the cell lines (SNU-354, SNU-368) showed expression of HBV and HBVx (HBx) transcripts. SNU-354 strongly expressed albumin, and SNU-368 expressed transferrin and insulin-like growth factor II. No lines produced alpha-fetoprotein at the RNA and protein level. These cell lines represent useful tools for in vitro studies related to hepatocellular carcinoma.
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PMID:Characterization of cell lines established from human hepatocellular carcinoma. 754 80

In order to study the role of insulin-like growth factor II (IGF-II) in the development of hepatocarcinoma (HCC), the expression of IGF-II, IGF-II receptor (IGF-IIR) and HBxAg in HCC was studied with immunohistochemistry (PAP method). Meanwhile DNA ploidy and S-phase fraction of hepatocytes were analyzed with flow cytometry. The results were as follows: (1) IGF-II, IGF-IIR and HBxAg showed positive staining simultaneously in the tumor tissues of 93% (n = 15) of the HCC cases with chronic liver disease and with positive evidence of HBV; (2) The mean S-phase incidence in tissues of IGF-II positive HCC was 28.6 +/- 6.4%; this was higher than 12.8 +/- 2.4% in the IGF-II negative tumors (P < 0.05); (3) The incidence of DNA-aneuploidy in IGF-II positive liver tissues was 100% (10/10); this was higher than 60% (6/10) in IGF-II negative liver tissues (P < 0.05). It is suggested that IGF-II might play an important role in the development of HCC when there is evidence of HBV and chronic liver disease involvement. IGF-II positive staining HCC have increased proliferative activity as compared with IGF-II negative staining tumors.
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PMID:[A study of the relationship between expression of IGF-II, IGF-IIR, HBxAg and the DNA ploidy, cell cycle of hepatocytes in hepatocarcinoma]. 760 Aug 62

In the present study we investigated the expression of transforming growth factor alpha and insulin-like growth factor II to explain the role of these growth factors in the development of hepatocellular carcinoma from chronic active hepatitis B and cirrhosis. The expression of transforming growth factor alpha and insulin-like growth factor II was tested in 38 tissue samples from patients with chronic active hepatitis B, 32 cirrhosis and 31 hepatocellular carcinoma, by immunohistochemical staining using monoclonal anti-transforming growth factor alpha and anti-insulin-like growth factor II. All patients were seropositive for HBsAg. Transforming growth factor alpha was expressed in 26 (68.4%) of 38 chronic active hepatitis B, 18 (56.3%) of 32 cirrhosis and 16 (51.6%) of 31 hepatocellular carcinoma tissue samples. Transforming growth factor alpha was found in the periportal hepatocytes of chronic active hepatitis B and in regenerating hepatocytes of cirrhotic nodules. In hepatocellular carcinoma tissues, transforming growth factor alpha-containing tumor cells were evenly distributed within the tumor tissues but focal distribution limited to a part of tumor tissues was also observed. The expression of insulin-like growth factor II was observed in 30 (93.8%) of 32 cirrhosis and all the 31 hepatocellular carcinoma tissue samples tested, but not in chronic active hepatitis B samples. Insulin-like growth factor II was expressed in most hepatocytes of regenerating nodules and in tumorous as well as non-tumorous hepatocytes of hepatocellular carcinoma tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential expression of transforming growth factor alpha and insulin-like growth factor II in chronic active hepatitis B, cirrhosis and hepatocellular carcinoma. 760 79

In this study we investigated the expression of insulin-like growth factor II (IGf-II) to explain a role for this growth factor in concert with hepatitis B virus (HBV) involvement in the development of hepatocellular carcinoma (HCC) from chronic hepatitis type B (CAH-B) and liver cirrhosis (LC). The expressions of IGF-II and HBsAg were tested in tissue samples from 38 patients with CAH-B, 32 with LC, and 31 with HCC, by immunohistochemical staining using monoclonal anti IGF-II and anti HBs. All patients were seropositive for the presence of HBsAg. The expression of IGF-II was observed in 30 out of 32 (93.8%) LC and all 31 (100%) HCC tissue samples tested. IGF-II was expressed in most hepatocytes of regenerating nodules and in tumorous as well as nontumorous cells of HCC tissues. Neither normal liver tissues nor CAH-B tissue samples expressed IGF-II. HBsAg was expressed in 34 out of 38 (89.5%) CAH-B, 24 out of 32 (75%) LC and 13 out of 31 (41.9%) HCC tissue samples. The expression sites of HBsAg were not correlated with those of IGF-II in any tissue samples tested. The present study indicates that IGF-II plays a role in cell proliferation of regenerating nodules as well as in the development of hepatocellular carcinomas. In addition, there was no direct evidence of HBV involvement in the overexpression of this growth factor.
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PMID:Expression of insulin-like growth factor II in chronic hepatitis B, liver cirrhosis, and hepatocellular carcinoma. 766

Expression of insulin-like growth factor II in two human hepatocellular carcinoma cell lines and in hepatitis B, cirrhosis and hepatocellular carcinoma in 419 cases were investigated, and its relationship with the expression of hepatitis B virus X gene was studied by means of immunohistochemical and electron microscopic techniques. The results demonstrated that hepatocellular carcinoma cells (SMMC 7721 and QGY 7703) in culture could express insulin-like growth factor II. Expression seemed to be regulated by cell density, which was suggested as the molecular basis of the contact inhibition of cell proliferation. In tissue sections, cells with high expression of insulin-like growth factor II were observed not only in hepatocellular carcinoma (93%) but also in 95% of the pericancerous liver tissues, 72% of cirrhotic livers, 64% of chronic active hepatitis and 37% of chronic persistent hepatitis. In most cases of hepatocellular carcinoma, insulin-like growth factor II was localized in the cytoplasm of the cancer cells. In the benign liver disorders, four types of cells that highly expressed insulin-like growth factor II were observed: (a) a kind of small liver cell we named the small polygonal liver cell; (b) multinuclear giant hepatocytes; (c) hepatocytes in most of hyperplastic and neoplastic nodules, small hepatocyte nodules and some of regenerative nodules; and (d) some proliferating ductular cells. Even more interestingly, insulin-like growth factor II expression was shown to be closely related to the expression of hepatitis B virus X gene product. We suggest that the activation of insulin-like growth factor II gene and its overexpression may be a crucial step in the processes of hepatitis B virus-associated hepatocarcinogenesis and that the X gene product may activate the insulin-like growth factor II gene through a transactivation mechanism. In addition, we studied the characteristics of small polygonal liver cells, and the roles they may play in the regeneration and carcinogenesis of hepatitis B virus-infected liver are discussed.
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PMID:Expression of insulin-like growth factor II in hepatitis B, cirrhosis and hepatocellular carcinoma: its relationship with hepatitis B virus antigen expression. 792 18

We have used human procathepsin D isolated from supernatant of human breast cancer cell line ZR-75-1 to test its mitogenic activity for a broad spectrum of human-derived cell lines. These cell lines included: breast cancer cell lines ZR-75-1, MDA-MB-436, MBA-MD-483 and MDA-MB-231, B lymphoblastoid cell line Raji, the monocytoid cell line U937, T lymphoblastoid cell line 8402, epitheloid carcinoma cell line HELA, hepatocellular carcinoma cell line Hep G2, breast milk epithelial cell line HBL-100 and angiosarcoma cell line HAEND-1. We have tested the level of proliferation of these cell lines depending on the presence of procathepsin D in the medium. In parallel we have also measured the effect of insulin-like growth factor II under the same experimental conditions. We have found a significant difference between the influence of IGF II and that of procathepsin D. While IGF II promoted in practically the same way the proliferation of all cell lines tested, procathepsin D had a very pronounced effect on breast cancer cell lines only. This finding might help to explain some contradictory results of prognostic significance of procathepsin D in human breast cancer.
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PMID:Effect of human procathepsin D on proliferation of human cell lines. 801 70

Recent results obtained using molecular biology techniques have suggested a possible role for insulin-like growth factor II (IGF-II) in the pathogenesis of hepatocellular carcinoma (HCC). To investigate this phenomenon, a monoclonal antibody was used against IGF-II to study 54 patients with HCC. The presence of HBsAg was also tested both in serum and liver tissue. A positive immunoreaction was found in 9/15 (60%) of the HCC arising in cirrhotic livers of patients who had serum markers for HBV (HBV + positive patients). These results provide further evidence that HBV might play a role in the expression of IGF-II. In HCC of patients without any markers of HBV infection (HBV- negative patients), IGF-II was detected in 10/39 (25.6%) of the tumors, and in some benign neoplastic lesions. It was found not only in neoplastic cells but also in some dysplastic nodules. The speculation arises that IGF-II expression may play a role in some steps of hepato-carcinogenesis.
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PMID:Expression of insulin-like growth factor II (IGF-II) in human hepatocellular carcinomas: an immunohistochemical study. 802 52


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