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 distribution of fibronectin (FN), laminin (LAM), and collagen IV (Coll IV), three components of the basement membranes (BM), was investigated in human hepatocellular carcinoma (HCC) and the surrounding uninvolved liver and was compared with the grade of differentiation of the tumor. The following three patterns of BM antigens were observed in HCC: (1) peritrabecular or periacinar, (2) pericellular, and (3) stromal-vascular. In the more differentiated tumors, FN, LAM, and Coll IV were observed in a peritrabecular or periacinar pattern whereas a pericellular pattern was only seen with anti-FN antisera that occasionally stained the content of acini. Double staining showed that the four antigens were usually codistributed. Occasionally, however, there was a different distribution along the BM suggesting an heterogeneity in the composition of BM. In the more anaplastic tumors and in the intrahepatic metastasis, BM components were seen around vessels and in the stroma and they were usually fragmented. The finding that FN can be located pericellularly or within acini supports the concept that FN is synthesized, at least in part, by hepatoma cells. The peritrabecular and periacinar location of Coll IV and LAM suggests a sinusoidal cell derivation of these two antigens. The immunohistochemical staining patterns for BM in HCC reflect the differentiation of the tumor, with differentiated tumors showing a relatively intact BM and poorly differentiated tumors showing a sharply defective BM.
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PMID:Distribution of basement membrane components in human hepatocellular carcinoma. 253 55

ED-A and ED-B are facultative type III homologies of fibronectin, encoded by alternatively spliced exons, described in man and in rat. A hybrid alpha-globin-fibronectin minigene containing the ED-B region from the human gene has been transfected in human cell lines derived from various tissues, in order to study the processing of the generated precursor RNA in the different cell environments. In most tested lines the pre-RNA is alternatively spliced and produces two mature RNAs, with and without the ED-B exon, in different ratios that closely resemble the corresponding endogenous fibronectin RNAs. In a hepatoma cell line, Hep 3B, only one RNA is produced, in which the ED-B exon is absent; the same pattern of splicing is observed in liver. The data show that all the information required to produce accurate and regulated alternative splicing of the ED-B exon is contained in the fragment used and cell specific factors are necessary for the pre-RNA to be differentially spliced in the various cell lines. In contrast, expression in Hep 3B of a similar gene containing the ED-A area failed to reproduce the liver specific splicing pattern. Therefore regulation of ED-A processing is likely to involve different mechanisms to those responsible for control of ED-B splicing.
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PMID:Cell type specific trans-acting factors are involved in alternative splicing of human fibronectin pre-mRNA. 254 40

Basic fibroblast growth factor (FGF) is synthesized as a phosphoprotein by both bovine capillary endothelial and human hepatoma cells in culture. Because basic FGF is characterized by its high affinity for heparin and its association in vivo with the extracellular matrix, we examined the possibility that the phosphorylation of this growth factor by purified protein kinase C (PK-C) and the catalytic subunit of cAMP-dependent protein kinase-A (PK-A) can be modulated by components of the extracellular matrix. Heparin and other glycosaminoglycans (GAGs) inhibit the ability of PK-C to phosphorylate basic FGF. In contrast, heparin can directly increase the phosphorylation of basic FGF by PK-A. While fibronectin, laminin, and collagen IV have no effect on the ability of PK-C to phosphorylate basic FGF, they all can inhibit the effects of PK-A. Thus, there is a differential effect of extracellular matrix-derived proteins and GAGs on the phosphorylation of basic FGF. The enhanced phosphorylation of basic FGF that is mediated by heparin is associated with a change in the kinetics of the reaction and the identity of the amino acid targeted by this enzyme. The amino acids that are targeted by PK-C and PK-A have been identified by phosphopeptide analyses as Ser64 and Thr112, respectively. In the presence of heparin, basic FGF is no longer phosphorylated by PK-A at the usual PK-A consensus site (Thr112), but instead is phosphorylated at the canonical PK-C site (Ser64). Accordingly, heparin inhibits the phosphorylation of basic FGF by PK-C presumably by masking the PK-C dependent consensus sequence surrounding Ser64. Thus, when basic FGF is no longer phosphorylated by PK-A in the receptor binding domain (Thr112), it loses the increased receptor binding ability that characterizes PK-A phosphorylated basic FGF. The results presented here demonstrate three novel features of basic FGF. First, they identify a functional effect of the binding of heparin to basic FGF. Second, they establish that the binding of heparin to basic FGF can induce structural changes that alter the substrate specificity of protein kinases. Third, and perhaps most important, the results demonstrate the existence of a novel interaction between basic FGF, fibronectin, and laminin. Although the physiological significance of this phosphorylation is not known, these results clearly suggest that the biological activities of basic FGF are regulated by a complex array of biochemical interactions with the proteins, proteoglycans, and glycosaminoglycans present in the extracellular milieu and the cytoplasm.
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PMID:Differential effects of heparin, fibronectin, and laminin on the phosphorylation of basic fibroblast growth factor by protein kinase C and the catalytic subunit of protein kinase A. 259 18

This paper presents the case report of the coincidental presence of an adenocarcinoma of the rectum and fibrolamellar hepatocellular carcinoma in a 76 year-old man. The tumours were successfully removed by simultaneous resection. The characteristics of hepatocellular carcinoma of the fibrolamellar type are discussed in detail on the basis of the presented case and a survey of the literature. This variant of hepatocellular carcinoma is predominantly found in younger patients. It appears in non-cirrhotic livers and is preferentially localized in the right lobe. Histologically, fibrolamellar hepatocellular carcinoma is characterized by large eosinophilic tumour cells. The cells show trabecular or solid arrangement separated by fibrous septa. Cytoplasmic globules are often found in the tumour cells. In the literature, fibrinogen, CEA, alpha-1-antitrypsin, copper binding protein and copper have been demonstrated in the tumour cells by immunohistochemistry and histochemistry. The fibronectin content is increased in the tumour and seems to correlate with a higher degree of differentiation, as well as a better prognosis. The serum alpha-fetoprotein levels of patients with fibrolamellar carcinomas are normal, in contrast to those in patients with other types of hepatocellular carcinomas. The serum vitamin B12 binding-capacity, as well as neurotensin concentrations are increased. Patients with fibrolamellar carcinomas have a much better prognosis than patients with ordinary hepatocellular carcinomas because of the earlier onset of symptoms, slower tumour progression with late metastasis, and better operability. Two-year survivals of 82% and five-year survivals of 63% have been reported. The prognosis is also better after total hepatectomy followed by liver transplantation.
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PMID:[76-year-old patient with adenocarcinoma of the rectum and fibrolamellar hepatocellular 2d carcinoma. Case report with literature review of hepatocellular carcinoma of the fibrolamellar type]. 282 Jan 56

We studied fibronectin concentration in the ascitic fluid of 102 patients, 71 with cirrhosis, 13 with hepatocellular carcinoma, 12 with malignant peritonitis, and six with miscellaneous disease. Fibronectin concentrations in the first three groups were 45 +/- 45 mg/l, 54 +/- 84 mg/l, and 144 +/- 123 mg/l, respectively. The difference between patients with cirrhosis and malignant peritonitis was significant (p less than 0.01). However, fibronectin concentration greater than 100 mg/l had a sensitivity of 58 per cent and a specificity of 86 per cent for the diagnosis of malignant peritonitis. Ascitic fluid protein content over 30 g/l had the same sensitivity and specificity was 90 per cent. Among cirrhotic patients, high fibronectin concentrations were demonstrated in those with long-standing ascites (m = 134 +/- 58 mg/l) whereas the lowest concentrations were found in patients with severe hepatocellular failure (m = 12 +/- 9 mg/l). Concentrations were significantly different, according to whether or not spontaneous bacterial peritonitis occurred later (20 +/- 13 mg/l versus 52 +/- 49 mg/l); 83 per cent of patients with spontaneous bacterial peritonitis during their clinical course had initial fibronectin concentrations above 30 mg/l in their ascites. We conclude that: 1) measurement of fibronectin concentration in ascitic fluid is of poor diagnostic value for discrimination between malignant and non malignant ascitic, 2) low concentrations of fibronectin are associated with the occurrence of spontaneous bacterial peritonitis in cirrhotic patients. Hypothetically, the quantitative defect of fibronectin could be responsible for bacterial opsonization impairment in these patients.
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PMID:[Fibronectin in the ascitic fluid: its diagnostic significance]. 282 81

The ascitic fluid concentrations of cholesterol and fibronectin and the serum-ascites albumin difference were compared with two conventional tests of ascitic fluid, total protein and LDH, in their diagnostic ability for detection of malignancy in ascitic samples from 69 patients with ascites: 54 with ascites due to liver disease and 15 whose ascites was caused by peritoneal metastases. Sixteen cirrhotic patients with superimposed hepatocellular carcinoma in whom ascites was of uncertain etiology were considered separately. The mean ascitic fluid total protein, LDH, cholesterol, and fibronectin values in the peritoneal metastases group were 3.70 +/- 1.20 g/dl, 247.26 +/- 148.14 units/liter, 109.06 +/- 29.85 mg/dl, and 91.57 +/- 41.52 micrograms/ml, respectively, and all were significantly higher than the corresponding values in the liver disease group (P less than 0.001), which were 1.37 +/- 0.59 g/dl, 75.40 +/- 110.70 units/liter, 23.75 +/- 11.22 mg/dl, and 31.86 +/- 10.51 micrograms/ml, respectively. Mean serum-ascites albumin difference in the peritoneal metastases group was 0.62 +/- 0.38 g/dl, which was significantly different from the corresponding value in the liver disease group (1.92 +/- 0.41 g/dl, P less than 0.001). Both ascitic cholesterol above 46 mg/dl and an ascitic fibronectin concentration greater than 50 micrograms/ml had high diagnostic accuracy (97%) for malignancy, being higher than that achieved using a serum-ascites albumin difference under 1.1 g/dl and an ascitic total protein above 2.5 g/dl, which had accuracies of 94% and 93%, respectively. Ascitic fluid LDH was the least reliable test. No differences in the ascitic fluid analysis were found between cirrhotic patients with and without hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diagnosis of malignant ascites. Comparison of ascitic fibronectin, cholesterol, and serum-ascites albumin difference. 283 70

The effects on human hepatoblastoma (HuH-6) and hepatoma (HuH-7) cell lines of collagen type I (CI), type IV (CIV), fibronectin (FN) and laminin (LAM) were investigated. CI and CIV promoted almost equally the attachment of both cell lines more strikingly than did FN or LAM. CI and CIV were also superior to FN or LAM in supporting the growth of HuH-6. These substrates, however, had no appreciable effect on the growth of HuH-7. The amount of alpha-fetoprotein (AFP) and albumin secreted in HuH-6 was found to be higher on FN- and LAM- coated substrates than on the other matrix material- coated ones. HuH-7 exhibited increased levels of AFP on LAM- coated substrates 4 days after plating. These results indicate that the ability of extracellular matrix materials to enhance attachment and/or growth is different from that to enhance AFP and albumin production in HuH-6 and probably in HuH-7.
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PMID:Effects of various substrates on human hepatoblastoma and hepatoma cell culture. 284 Feb 8

A new human hepatocellular carcinoma (HCC) cell line, KYN-2, has been established from a surgical specimen obtained from a 52-year-old Japanese male HCC patient. The originally resected HCC was classified as pleomorphic HCC corresponding to Edmondson-Steiner's grade III with a thick trabecular to solid arrangement. The cell line has been maintained for 17 months through 35 passages. Morphologically, the KYN-2 cells have retained the characteristics of the original HCC, being pleomorphic and composed of various types such as cells with relatively small, polygonal, eosinophilic cytoplasm and oval-shaped nuclei with a marked tendency to pile up, flat cells with abundant clear cytoplasm and oval-shaped nuclei, and many multinucleated giant cells, proliferating in a pavement-like cell arrangement. Some junctional complexes and a number of microvilli are evident between the cells by electron microscopy. Functionally, these cells were found to secrete albumin, alpha 1-acid glycoprotein, alpha 1-antitrypsin, ceruloplasmin, transferrin, complement C, fibrinogen, fibronectin, prothrombin, retinol-binding protein (serum type), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), ferritin and beta 2-microglobulin in chemically defined medium (CDM). The secretion of AFP and CEA is apparently dependent upon culture medium and passage. The doubling time of cells growing in serum-containing medium at the 14th passage was 84 h, and those of cells in serum-containing medium, HB101 (serum-free medium) and CDM at late passage were 28, 68, and 42 h, respectively. Chromosome analysis revealed that the chromosome number ranged from 56 to 69 without a mode, and the presence of marker chromosomes. HB virus DNA sequence was not detected by hybridization analysis. The tumorigenicity of KYN-2 cells was identified by development of tumors in nude mice after subcutaneous injection of the cells; the tumors showed an appearance basically similar to that of the original HCC. Thus, these findings suggest that the KYN-2 cell line is available as a new human HCC cell line and should be useful for various studies on HCC.
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PMID:A new human pleomorphic hepatocellular carcinoma cell line, KYN-2. 284 82

The authors evaluated the diagnostic accuracy of sialic acid and its lipid-bound fraction in ascites and compared these tests with others (fibronectin, cholesterol) recently claimed as valuable in the differential diagnosis of ascites. Fibronectin yielded the best diagnostic accuracy (85%) with no false-positive and 37% of false-negative (10/27). The authors also found higher concentration of sialic acid in malignant ascites than in nonmalignant ascites (P less than 0.001) and, taking 300 mg/l as the cutoff value, the false-positive rate was 10% (four of 40), the false-negative rate 30% (eight of 27), and the overall diagnostic accuracy 82%, comparable to that of the fibronectin. The authors conclude that both fibronectin and sialic acid determinations in ascites may be regarded as accurate markers of neoplastic involvement of the peritoneum, although no test is useful in the ascites with hepatocellular carcinoma and cirrhosis of the liver.
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PMID:Diagnostic accuracy of sialic acid in the diagnosis of malignant ascites. 291 98

A method for culturing endothelial cells (HCC-EC) from surgical specimens of human corpus cavernosum has been developed. The approach involves selective endothelial outgrowth from explants and may be generally applicable to tissues whose endothelium is not amenable to isolation by routine mechanical or enzymatic methods. The tissue is minced into pieces which are placed onto gelatin- or fibronectin-coated tissue culture plastic, and grown in medium suitable for microvascular endothelial cell growth (Carson and Haudenschild, In Vitro 22:344-354, 1986). By Days 5 to 7 EC colonies are found. Within a day or two after the appearance of the EC colonies, a non-EC cell type appears and, if undisturbed, quickly overgrows the EC. An exploitable temporal separation between the emergence of EC and non-EC is obtained when both conditioned medium (from bovine aortic endothelium) and retinal extract are present during the outgrowth period. Explants are removed by pipetting at the first sign of the emergence of the non-EC cell type. Once isolated, HCC-EC do not require conditioned medium but do require either retinal extract or acidic fibroblast growth factor for survival and growth. Approximately 60% of the first passage cultures are at least 80% EC as judged by DiI-Ac-LDL labeling. One corpus (0.3 x 0.3 x 0.5 cm) usually produces 120 cm2 of primary culture within 2 wk. These EC form contact-inhibited monolayers and stain positively for Factor VIII. They have a doubling time at 6th passage of 48 h and a plateau density of 5 to 7 x 10(4) cells/cm2. The availability of such cultures should facilitate the study of endothelium-mediated responses which play an important role in the erectile function of human penile corpus cavernosum.
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PMID:Culture of human corpus cavernosum endothelium. 292 64


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