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)

Soluble proteoglycans (SPG) were extracted from bovine (BCC) and human (HCC) costal cartilages by the dissociative method using 4 M guanidinium chloride (GuHCl). Proteoglycans which are resistant to extraction (RPG) were obtained following collagenase digestion or hydroxylamine treatment of the cartilage residues. Similarly, SPG were extracted from bovine metaphyseal and cortical bone using EDTA. The RPG were extracted from the bones using hydroxylamine. Density gradient fractionation under dissociative conditions of cartilage SPG and RPG followed by chromatography on Sepharose 2B revealed that A1D1 RPG are smaller than the SPG. SPG reacted with either collagenase or hydroxylamine are also smaller than the parent SPG. A1D1 fractions obtained from BCC-SPG and RPG or from mixtures of SPG and acid-soluble collagen are free of hydroxyproline. Hydroxyproline is not completely separated from HCC-RPG. Density gradient fractionation of bone proteoglycans and Sepharose chromatography of the A1 and A1D1 fractions showed that those obtained from metaphysis are larger than those from cortical bone. This was attributed to the presence of calcified cartilage in metaphyseal bone. The A1D1 fractions of the metaphyseal proteoglycans seemed to undergo self-association since this fraction is larger than the A1 fraction from which it is derived. Cortical bone proteoglycans do not behave similarly. Density gradient purification under dissociative conditions failed to separate hydroxyproline from the proteoglycans obtained from bone. It is hypothesized that in bone proteoglycans and collagen might be linked.
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PMID:Studies on extractable and resistant proteoglycans from metaphyseal and cortical bone and cartilage. 626 Mar 14

The human hepatocellular carcinoma cell line PLC/PRF/5, which synthesizes and secretes hepatitis B surface antigen, was grown under optimal conditions in tissue culture, using Eagle's minimal essential medium supplemented with 10% fetal bovine serum and 10(-11) M triiodothyronine on collagen rafts. Injection s.c. of the PLC/PRF/5 cell line into athymic BALB/c nude mice resulted in the growth of a well-circumscribed, moderately differentiated hepatocellular carcinoma. The intervals until tumor appearance and tumor "take" rates were dependent on inoculum dose. Four to 5 x 10(6) cells induced tumor growth in 29% of 14 injected mice within 29 to 40 days, while 7 to 13 X 10(6) cells induced tumors in all 15 mice within 10 to 12 days after inoculation. Hepatitis B surface antigen was detected in the nude mouse serum and tumor tissue, and its concentration roughly correlated with tumor weight. A low level of antibody against hepatitis B surface antigen was detected in five tumor-bearing animals, as well as in one mouse which did not produce a tumor. Hepatitis B core antigen and its antibody and hepatitis B e antigen and its antibody were not detected in 26 mice, using immunohistochemical and radioimmunoassay methods. alpha-Fetoprotein, carcinoembryonic antigen, and alpha-antitrypsin were detected in nude mice tumors, using the peroxidase-antiperoxidase technique. Finally, hepatitis B virus DNA, identified in the nude mouse tumor by molecular hybridization techniques, was compared to PLC/PRF/5 cell line hepatitis B virus DNA.
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PMID:Tumorigenicity in nude mice of a human hepatoma cell line containing hepatitis B virus DNA. 626 Mar 36

This paper describes the isolation and partial characterization of a collagen cell attachment protein from the spent culture medium of rat hepatoma cells. When compared with serum fibronectin, this attachment protein differed in several biochemical parameters. The hepatoma attachment protein was partially purified by adsorbing and eluting from an inorganic gel, magnesium oxide. Cell adhesive activity may routinely recovered at levels of 10 to 30%, and a 2000-fold purification was attained. The hepatoma attachment protein was shown to be sensitive to trypsin and chymotrypsin, to be heat inactivated at 61 degrees, to have a molecular weight of 58,000, to have an isoelectric point of 4.1, to show an electrophoretic mobility on cellulose acetate of approximately one-half that of fibronectin, and not to cross-react with antifibronectin antisera.
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PMID:Collagen cell attachment protein from rat hepatoma cells. 626 32

Serum immunoreactive prolyl hydroxylase protein (S-IRPH), galactosylhydroxylysyl glucosyltransferase activity (S-GGT) and the amino-terminal propeptide of type III procollagen [S-Pro(III)-N-P] were studied in 24 patients with primary hepatocellular carcinoma, 18 with secondary liver neoplasms and 35 with other malignant diseases but no evidence of liver involvement; this latter group included 13 patients with Burkitt's lymphoma, 11 with breast cancer and 11 with other neoplasms. Control values were determined for 60 apparently healthy Nigerians, S-IRPH and S-GGT were above the upper normal limit, defined as the mean + 2 SD of the controls, in all the patients with primary hepatocellular carcinoma and all but one with secondary liver neoplasms, whereas only one S-IRPH value and three S-GGT values exceeded this limit in the patients with other malignant diseases. The mean S-Pro(III)-N-P was even more elevated than S-IRPH and S-GGT in the primary and secondary liver neoplasm cases, but was also elevated in other malignant neoplasms; about one third of the patients with no evidence of liver involvement had a concentration exceeding the upper normal limit. A high correlation was found between the values for the three assays both in primary hepatocellular carcinoma and in the whole series of malignant diseases. The data suggest that primary and secondary malignant neoplasms of the liver have a high rate of collagen synthesis. The three assays may be of some value in the diagnosis of primary hepatocellular carcinoma and secondary liver involvement in other malignant diseases, and in monitoring the treatment provided.
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PMID:Enzymes of collagen synthesis and type III procollagen amino-propeptide in serum from Nigerians with hepato-cellular carcinoma and other malignant diseases. 628 64

The clinical and pathologic features of 23 cases of hepatocellular carcinoma occurring in patients younger than age 35 years (mean age, 17.4 years) were analyzed. Ten of these (43%) were the fibrolamellar oncocytic variant (FLO), characterized by large polygonal neoplastic hepatocytes and lamellar bundles of collagen. The remainder (non-FLO) showed the usual wide range of gross and histologic patterns typical of hepatocellular carcinoma in older age groups. Overall, hepatocellular carcinoma was more common in females than in males. The FLO variant was characterized by a longer duration of symptoms prior to diagnosis, increased frequency of resectability of the tumor, and infrequency of mitoses. Of particular importance is the fact that 5 of 10 patients with the FLO variant are alive and clinically free of disease 1 1/2 to 8 years postoperatively, while none of the 13 patients with non-FLO hepatocellular carcinoma is alive and free of disease. There was no significant difference between the two groups in mean age at diagnosis, presence of single versus multiple hepatic tumors, vascular invasion, or tumor necrosis. Although cirrhosis was present in three non-FLO patients and none of the FLO patients, the difference was not statistically significant. The prognosis of hepatocellular carcinoma in young patients does not appear to differ from that in older patients, with the exception of the fibrolamellar oncocytic variant, a variant which is common in younger patients.
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PMID:Hepatocellular carcinoma in young people. 631 97

The activity of L-GGT (EC 2.4.1.66), an enzyme catalyzing the intracellular biosynthesis of collagen, was determined in human primary hepatic cancer, acute viral hepatitis and cirrhotic liver tissues and compared to the mean level of enzyme activity in normal human liver tissues. The mean levels of L-GGT activity in primary hepatocellular carcinoma (PHC), acute viral hepatitis and cirrhotic tissues were 7.78, 2.69 and 2.16 times the mean level of enzyme activity in normal human liver tissues. The mean level of L-GGT activity in PHC was 3.61 times the mean level of L-GGT activity in cirrhosis and 2.90 times the mean value of liver enzyme activity in acute viral hepatitis. The findings in this study provide a basis for the highly elevated serum values of this intracellular enzyme in patients with primary hepatic cancer and the data indicate that L-GGT activity may be increased in primary liver cancer to compensate for an increased rate of collagen synthesis.
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PMID:Elevation of liver-galactosylhydroxylysyl glucosyltransferase activity in human primary hepatocellular carcinoma. 631 46

Total prolyl hydroxylase protein was measured in hepatic tissues of 8 patients with primary hepatocellular (PHC), 5 with acute viral hepatitis, and 5 with cirrhosis (3 alcoholic and 2 with secondary biliary cirrhosis). The mean values were compared with the mean value of 10 normal hepatic tissues. The mean values were all highly significantly elevated (P less than 0.001) in PHC, acute viral hepatitis and the cirrhotic patients, respectively. The mean L-IRPH value in PHC was about 9.50 times the control mean, while in acute viral hepatitis, and cirrhosis the mean L-IRPH values were about 3.00 and 2.30 times the control mean respectively. The mean level of L-IRPH in PHC was 4.06 times the mean level of L-IRPH in cirrhosis and 3.14 times the mean value in acute viral hepatitis. The findings of this study provide a basis for the elevated serum values of this intracellular enzyme of collagen synthesis in patients with primary hepatocellular carcinoma and the data indicate that this enzyme may be elevated to compensate for an increased rate of collagen synthesis in the malignant liver tissue.
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PMID:Liver immunoreactive prolyl hydroxylase protein in human primary hepatocellular carcinoma. 632 76

The distribution of collagen types I, III, and V in normal and fibrotic human livers and hepatocellular carcinoma was studied by indirect immunofluorescence procedure using type specific antibodies. Type I collagen as well as type III collagen was present in normal liver within the portal tracts and along the perisinusoidal spaces. Basement membrane collagen, type V collagen, was demonstrated only around the bile ducts and vessels of the portal tracts and central veins. In fibrotic liver, both type I and III collagens were found in increased amounts in fibrotic areas. In fibrous septa of active cirrhosis, however, type I collagen as well as type III collagen was abundant, whereas in inactive cirrhosis type I fibers were predominant. Type V collagen was observed in the walls of proliferative bile ductules and vessels in the fibrotic liver, and also along the sinusoids in the periportal areas. In hepatocellular carcinoma, each type of collagen was distributed regularly along the sinusoid-like vascular channels within the tumor.
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PMID:Distribution of collagen types I, III, and V in fibrotic and neoplastic human liver. 632 63

A test of the mitogenic activity of greater than 40 purified and crude sources of hormones and growth factors revealed that epidermal growth factor, high density lipoprotein, an extract of bovine pituitary, hypothalamus, or whole brain, and the medium conditioned by differentiated human hepatoma cells were mitogenic for cultured endothelial cells derived from human umbilical vein. The four active agents combined with an improved nutrient medium and a collagen- or fibronectin-coated culture surface supported the growth of the endothelial cell population at a rate of 0.70-0.80 generations per day at both low and high cell densities in serum-free medium. The brain-derived activity exhibited properties reported by Maciag et al. [Maciag, T., Hoover, A. & Weinstein, R. (1982) J. Biol. Chem. 257, 5333-5336] and Gordon et al. [Gordon, P. B., Sussman, I. I. & Hatcher, V. B. (1983) In Vitro 19, 661-671]. The liver cell-derived activity was a specific product of differentiated hepatoma cells. The medium from HeLa cells, relatively undifferentiated rat liver cell lines, and human fibroblasts was inactive. Purified plasma proteins of liver origin could not substitute for the hepatoma cell-conditioned medium. The hepatoma cell-derived activity was non-dialyzable, heat-labile, stable between pH 4 to 11, inactivated by trypsin and mercaptoethanol treatment, and stable after treatment with 6 M urea and phenylmethylsulfonyl fluoride. The results provide a simplified model for elucidation of the endocrinology of human endothelial cell growth, function, and aging. We suggest an endocrine role of both the nervous system and liver in the regeneration of endothelial cells.
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PMID:Brain- and liver cell-derived factors are required for growth of human endothelial cells in serum-free culture. 633 82

The use of bovine lens capsule basement membrane as a model substratum for studies of invasion and extravasation by metastatic tumor cells is described. The abilities of three independently isolated pairs of metastatic variant cell lines to digest the purified substrates, laminin, type IV collagen, and type I collagen, were compared with their abilities to solubilize isotope from 125I-labeled lens capsule basement membrane matrix. The cell lines used were +SA and -SA mouse mammary adenocarcinoma cells, RT7-4bs and RT7-4b-Ls rat hepatocarcinoma cells, and B16-F1 and B16-F10 mouse melanoma cells. In general, imperfect correlations of lytic activity with metastatic ability were found for the purified substrate digestions, but, for each pair of variants, the more metastatic tumor cell line was always able to solubilize more surface-bound isotope from the lens capsule. Visual evidence of tumor cell-associated digestion of lens capsule basement membrane was obtained using transmission electron microscopy. Mouse mammary carcinoma cells attached more rapidly to lens capsule than to endothelial cell monolayers or tissue culture plastic. We next added endothelial cells to the model substrate. Aortic endothelial cells grew well on lens capsules without apparent synthesis of additional basement membrane matrix. In additional studies, the lens capsule was used in a chamber apparatus to demonstrate that cellular invasion of the full thickness of this basement membrane structure could be demonstrated and readily quantitated. Our results indicate that bovine lens capsule is a particularly versatile basement membrane structure useful for studies of tumor cell invasion and extravasation. In addition, the comparison of purified substrate digestions with lens capsule matrix digestion indicates the desirability of also using a matrix digest when correlating lytic abilities of tumor cells with their metastatic abilities.
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PMID:Interaction of metastatic tumor cells with bovine lens capsule basement membrane. 670 69


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