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)

Altered expression of protooncogenes/oncogenes is believed to be involved in hepatocarcinogenesis of the chemically induced, transplantable Morris hepatoma 7777. We compared the mRNA expression of c-N-ras and v-erb B mRNA of normal rat liver with that of Morris hepatoma 7777 using Northern blot analysis and in situ hybridization. Northern blot analysis revealed a strong overexpression of the v-erb B related mRNA, while the c-N-ras mRNA was only slightly increased. In situ hybridization using a c-N-ras mRNA probe also showed only a slightly increased number of silver grains in the hepatoma cells compared with normal rat liver. On the other hand, the v-erb B related mRNA was strongly overexpressed in the hepatoma cells, while the connective-tissue capsule, the blood vessels, blood cells and the necrotic foci did not show an elevated v-erb B related gene mRNA expression. Similar results were obtained in liver metastases. The detectable v-erb B hybridization signal was lost by pretreatment with RNase A. We conclude that the c-N-ras gene is of minor importance in the chemically induced, transplantable Morris hepatoma 7777, while the increased expression of the v-erb B related mRNA is due to a selection of ligand-independent tyrosine kinase activity.
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PMID:Expression of the erb B oncogene in the Morris hepatoma 7777. 786 26

Immunohistochemical methods have been used to localize an HCV antigen on paraffin embedded liver tissue sections by means of monoclonal antibodies to C100-3 nonstructural protein. Peroxidase-antiperoxidase, alkaline phosphatase-antialkaline phosphatase, biotin-streptavidin-peroxidase and immunogold silver staining methods showed a nuclear staining of the hepatocytes in cases of chronic hepatitis with positive HCV serology, alcoholic liver disease and hepatocarcinoma. No cross reactions were observed with viral hepatitis B and delta antigens. The strongest reaction without background staining was obtained with immunogold silver staining. Nuclear localization was compared to the cytoplasmic staining described in the literature.
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PMID:Nuclear immunostaining of hepatitis C infected hepatocytes with monoclonal antibodies to C100-3 nonstructural protein. Comparison of immunogold silver staining with other immunohistochemical methods. 787 66

Using the Colloid silver staining technique to reveal AgNOR and immunostaining for anti-PCNA monoclonal antibody, 23 resected specimens with hepatocellular carcinoma (HCC, < or = 3.5cm in diameter) were examined. These cases were divided into two groups; Group A [9 cases without vascular invasion and a satellite nodule] and Group B [14 cases with satellite nodules]. Comparison of AgNOR score, the morphological features of AgNOR (the area and roundness factor of AgNOR) and PCNA labeling index between Group A and Group B was made by a image analyzer (SP-500). The AgNOR scores and PCNA labeling indices of HCCs in Group B were significantly higher than those of HCCs in Group A. And a close correlation was shown between AgNOR score and PCNA labeling index. Further more, the area, form, and distribution of AgNORs within the nucleus were also different in the two study groups. In Group A, many AgNORs were regular and medium-sized brown dots (AgNOR-roundness factor; > or = 80%, AgNOR-area; 1.5-4.5 microns 2). But in Group B, AgNORs showed marked variation in size and form. These results suggest that HCCs with multiple, smaller, irregular, and widely dispersed AgNOR in combination with high AgNOR scores have a more aggressive potential. The morphological features of AgNOR may be useful indicators for evaluating the proliferative activity of HCC.
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PMID:[Evaluation of the biological malignancy in hepatocellular carcinoma by argyrophilic nucleolar organizer region (AgNOR) staining--morphological study of AgNOR using image analyzer]. 790 44

Human hepatic stimulator substance (hHSS) was purified from fetal liver with 6,000-fold decrease in protein content and 840-fold increase in specific growth stimulative activity. Purification procedures included the heating of a homogenate in 35% (W/V) Tris-HCL at 95 degrees C for 20 min, high and ultra speed centrifugation, passage over Sephadex G100 gel filtration, DEAE-cellulose ion exchange, TSK G3000 SWG high performance liquid chromatography (HPLC) and YWG C-18 reverse phase HPLC techniques. The most purified material (HP-HSS) revealed cell-specific and dose dependent increase in 3H-TdR incorporation into cellular DNA. As little as 38 ng of the HP-HSS per ml of culture medium produced a 2.5-fold increase in DNA synthesis. Further studies indicate that HP-HSS in combination with insulin and epidermal growth factor stimulate DNA synthesis 16-fold compared with serum and hormone free controls and nearly 3-fold over hepatoma growth with HP-HSS alone. Sodium dedecyl sulfate polyacrylamide gel electrophoresis with silver stain and ultrascan XL laser densitrometer quantitative scanning revealed only one band at 12,800.
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PMID:Purification and characterization of human hepatic stimulator substance. 824 25

A 77-year-old man, diagnosed with a liver tumor, was referred to our hospital. Abdominal ultrasonography demonstrated a low echoic mass in the liver S2 region, and abdominal CT confirmed the presence of a round low-density mass 7 cm in diameter. Enhanced angio-computed tomography (CT) showed a ring-like form with a pale periphery. In the delayed phase of angio-CT, the inside of the mass was enhanced, showing septal stricture. Abdominal magnetic resonance imaging (MRI) revealed a heterogenous low intensity area in T1-weighted images, with a clear high intensity border becoming apparent in T2-weighted images. Stretching of the hepatic artery was evident on the arterial phase of angiography, while an avascular area was apparent in the lateral segment of the liver in the portal phase. Lateral segmentectomy was performed. The size of the tumor was 6 x 6 x 5 cm. On macroscopic cross section, it was white and clearly demarcated from the surrounding tissue. Microscopic observation of H&E-stained specimens did not show any glandular formation. The tumor consisted of an irregular fascicular arrangement of spindle-shaped and round cells with poor intercellular adhesion. While there was no region containing differentiated epithelial components, silver impregnation staining revealed structures resembling regenerating bile ducts. The tumor cells were positive for wide-keratin, and for vimentin staining. Tumor cells were carcinoembryonic antigen (CEA)-positive and alpha-feto protein (AFP)-negative. From the above findings, the tumor was judged to have originated from epithelium rather than from mesenchymal elements. The final diagnosis was intrahepatic cholangiocarcinoma with secondary sarcomatous transformation, rather than hepatocellular carcinoma.
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PMID:Intrahepatic sarcomatous cholangiocarcinoma. 857 44

Computerized morphometrical measurements were made of liver cells and their nuclei taken from biopsy specimens of primary biliary cirrhosis (PBC), alcoholic cirrhosis, posthepatitic cirrhosis (HBV-related), and hepatocellular carcinoma (HCC). The specimens were stained with hematoxylin-eosin (HE), Mallory's stain for collagen fibers, orcein method, periodic acid Schiff (PAS) reaction, and silver impregnation. Light microscopic views were then selected and original liver cells were magnified x 1000. The size of liver cell nuclei, distance between corresponding liver cell nuclei and distribution pattern of hepatocytes were calculated by computer. Variation in regenerative activity among the four disease groups was noted. Regenerative features of liver cells were mild in degree in PBC. In alcoholic cirrhosis, regenerative features of liver cells were less prominent than in posthepatitic cirrhosis. In posthepatitic cirrhosis, regenerative liver cells were well developed, showing remarkable pleomorphism of liver cell nuclei and expansive arrangement of liver cell cords. This tendency towards regenerative activity suggests that the possibility of HCC occurring is greater in posthepatitic cirrhosis than in PBC or alcoholic cirrhosis. It was concluded that morphologically, there is a greater possibility of occurrence of HCC in posthepatitic cirrhosis than in any other type of cirrhosis, because of its high regenerative hepatocytic activity. Also etiological factors of liver diseases are more important in the development of liver cell regeneration. Furthermore, regenerative activity can be measured by computerized morphometry as an established methodology.
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PMID:Regenerative pattern of liver cells in primary biliary cirrhosis, alcoholic cirrhosis, posthepatitic cirrhosis (HBV-related) and hepatocellular carcinoma: comparative analysis by computerized morphometry. 872 50

Genomic stability was investigated in Chinese hamster ovary (CHO) and human hepatocellular carcinoma HepG2 cells selected for growth in the presence of cytotoxic concentrations of N-(phosphonacetyl-L-asparate) (PALA). In CHO cells selected with 9 x LD50 PALA the carbamyl p-synthetase, aspartate transcarbamylase and dihydroorotase (CAD) gene complex was amplified two-fold while in HepG2 cells selected at comparable PALA concentrations a 7- to 10-fold increase in the CAD gene was observed. Concomitant with amplification of the CAD gene were increases in CAD mRNA and protein expression in both CHO and HepG2 cells. In long-term cultures of HepG2 cells the CAD gene underwent spontaneous amplification (5-fold) in the absence of PALA treatment with increasing passage number. In an attempt to define proteins and/or family of proteins that may either directly or indirectly influence DNA amplification potential through a mechanism of enhanced genomic instability, immobilized pH gradient-two-dimensional polyacrylamide gel electrophoresis (IPG 2-D PAGE) analysis of silver-stained nuclear cytoplasmic polypeptides concomitant with PALA resistance and CAD amplification was performed. Analysis of silver-stained polypeptides from 3 x LD50 PALA-selected CHO and HepG2 cells revealed no significant alterations in polypeptide expression. In CHO cells selected at 5 x and 7 x PALA LD50, and HepG2 cells selected at 5 x and 9 x PALA LD50, one subset of 4-8 polypeptides (pl: pI 7.2-7.6/36-38 kDa) were increased 2- to 3-fold in both 5 x and 7 x- and 5 x and 9 x LD50 PALA-selected CHO and HepG2, respectively, while five relatively neutral-to-basic, low M(r) polypeptides (p2: 18/7.30; p3: 16/7.00; p4: 14/7.00; p5: 14/7.40; and p6: 13.5/7.00) were markedly increased in CHO cells selected at 7 x LD50 PALA. In addition to these PALA-associated increases, four polypeptides (p7a: pI 6.50/40 kDa; p7b: 6.55/40; p7c: 6.60/40; and p7d: 6.65/40) were significantly increased in high-passage (p159) HepG2 cells undergoing spontaneous CAD gene amplification in the absence of PALA exposure. In CHO cells, polypeptides p7 a, b, d were increased while the expression of p7c (pI 6.60/40 kDa) was unaltered in 7 x LD50-treated CHO cells. Although neither the identity nor biological function of polypeptides 1-7 is known, a proposed mechanism involving interaction with certain growth regulatory proteins such as p53 for mediating genomic instability is given.
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PMID:Protein alterations associated with gene amplification in cultured human and rodent cells. 885 14

The soluble interleukin-6 receptor (sIL-6R) consists of the extracellular domain of the membrane-bound IL-6 receptor (gp80) found on many types of cells. Contrary to most other soluble cytokine receptors, it possesses in vitro agonistic properties, yet its physiologic role remains unknown. We have generated a cDNA encoding the rat sIL-6R and have expressed and purified the protein using Escherichia coli and baculovirus systems. Analysis of purified protein by electrophoresis and silver staining showed a single band migrating at 35 kDa for E. coli (nonglycosylated) and at 47 kDa for baculovirus-derived material. The purified protein is biologically active, as determined by the ability to convert human hepatoma cells (HepG2) from nonresponsive to responsive to rat IL-6 and induce acute-phase protein synthesis. Most important, we show that rat sIL-6R directly induces proliferation of the IL-6-dependent murine hybridoma cell line (B9) in an IL-6-like manner, with 50% proliferation induced by 100 ng/ml of baculovirus-derived receptor protein. Physiologic concentrations of sIL-6R dramatically enhance the sensitivity of B9 cells to IL-6, indicating that the bioassay for IL-6 is susceptible to modulation by the presence of sIL-6R in rodent serum samples. This sIL-6R-dependent B9 cell proliferation is fully abrogated by antibodies directed against rodent IL-6 and indicates autocrine production of low amounts of IL-6 by the B9 cell line.
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PMID:Characterization and biologic activities of recombinant rat soluble interleukin-6 receptor. 893 75

Gastric carcinoid tumors were found in seven of 135 striped field mice (Apodemus agrarius) by routine histopathologic examination. All these carcinoids occurred in mature striped field mice aged 72-100 weeks. Six animals were females and only one was male. Only two of seven tumors were detectable by gross examination. Grossly, tumors were located in the fundus of the glandular stomach. All seven tumors were microscopically single in the stomach and two mice exhibited extragastric metastasis. Tumors from all the mice were characterized by densely packed sheets of round to polygonal cells, subdivided into packets by a fine fibrovascular stroma. The cytoplasm of all tumor cells from all the mice contained argyrophil granules when stained by Grimelius and Sevier-Munger silver procedures. All seven mice with gastric carcinoids exhibited positive immunoreactivity to neuron specific enolase. Psammoma bodies, concentrically laminated microcalcification, were characteristic findings in gastric carcinoids from five mice. There were also a concomitant and independent hepatocellular adenoma in one case and hepatocellular carcinoma in two cases. The present cases provide the first description of spontaneous gastric carcinoid tumors in the striped field mice.
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PMID:Spontaneous gastric carcinoid tumors in the striped field mouse (Apodemus agrarius). 930 Mar 68

The method of surface-enhanced Raman microspectroscopy was developed for direct detection of membrane-bound enzymes in cells. Cells were cultured, fixed, and incubated with specific primary antibodies and their corresponding labeled secondary antibodies, and surface-enhanced Raman scattering (SERS) was detected directly in the wells of a multiwell plate. First, specific primary antibodies were separately bound to enzymes in cells. Then, the peroxidase-labeled secondary antibodies were added to bind these primary antibodies. Peroxidase substrates, o-phenylenediamine and hydrogen peroxide, were added and reacted for 15 min at room temperature to form azoaniline, a compound with strong Raman scattering. Then, Raman scattering of this enzymatic product was enhanced by silver colloids. Samples were excited with a He/Ne laser at 632.8 nm and SERS was detected by a CCD camera. The SERS spectrum of this product showed an intense peak at 1370 cm-1 and its intensity was used for assessment of cellular enzymes. The observed amount of enzyme was normalized to protein content in each well. The method was successfully used to detect prostaglandin H synthase-1 and -2 (PGHS-1 and -2) in normal human hepatocytes and human hepatocellular carcinoma (HepG2) cells. The detection limit of these PGHS enzymes by this method was about 0.1 pg per well. An immunohistochemical staining was also used to detect the expression of both PGHS isozymes in these cells.
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PMID:Detection of membrane-bound enzymes in cells using immunoassay and Raman microspectroscopy. 961 99


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