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)

Proteins coupled to colloidal gold particles have been widely used to visualize the uptake and intracellular transport of specific ligands by receptor-mediated endocytosis. The intracellular route of lysosome-directed ligands such as asialoglycoproteins (ASGP) are apparently unaltered by conjugation to gold, but the pathway of transferrin, a ligand that normally recycles to the cell surface, was reported to be altered by conjugation to 15-20 nm gold. In this study, we sought to determine whether a smaller transferrin-gold probe would recycle, and whether it might enter the same endosomal and lysosomal compartments as does a larger, lysosome-directed ASGP gold probe by visualizing their simultaneous uptake in human hepatoma (HepG2) cells. In the same cells, endocytosis of fluid-phase protein was followed using the soluble tracer native ferritin; lysosomal compartments were identified by acid phosphatase cytochemistry; and cell surfaces were labeled with ruthenium red or cationized ferritin. During the first 10 min of uptake at 37 degrees C, specific receptor-bound ferrotransferrin (FeTf)-8 nm gold and asialoorosomucoid (ASOR)-20 nm gold were clustered together in coated pits and entered the same coated vesicles, smooth vesicles, and tubules in the peripheral cytoplasm. At later times, however, transferrin-gold did not return to the cell surface; unlike native transferrin, this gold probe accompanied ASOR-gold into multivesicular bodies (MVB). The MVBs that contained probes were at first devoid of acid phosphatase activity, but at 30 min, enzyme activity was detected in a few MVBs. Native ferritin was present, along with gold probes, in all compartments of the endocytic pathway. We conclude that the normal intracellular pathway of transferrin is altered by its association with a colloidal gold particle.
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PMID:Intracellular transport of transferrin- and asialoorosomucoid-colloidal gold conjugates to lysosomes after receptor-mediated endocytosis. 299 27

The relationship of serum ferritin and transferrin levels to risk of cancer was examined in a population of 21,513 Chinese male government workers in Taiwan who have been followed prospectively since 1975. On the basis of a previous study in the Solomon Islands, increased ferritin and decreased transferrin levels were predicted for those men who developed cancer. The results were consistent with the prediction. The mean serum ferritin was higher at the start of the study in 192 men who had died of cancer or who had developed primary hepatocellular carcinoma (PHC) as of July 1983, as compared to their controls. The mean serum transferrin level was lower in men who had died of cancers other than PHC. The estimate of relative risk of cancer death for a man with 200 ng ferritin/ml and 200 mg transferrin/dl, as compared to a man with levels of 20 ng/ml and 400 mg/dl, respectively, is 2.9. These serum iron-binding protein levels are at the extremes of the "normal" range. Men who subsequently died of cancer had lower hemoglobin, lower hematocrit, lower albumin, and higher globulin levels at the start of the study than did the controls. These results are consistent with the hypothesis that increased iron stores increase the risk of cancer. However, direct assessment of iron stores prior to disease was not possible, and the same constellation of findings may be consistent with other explanations.
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PMID:Iron-binding proteins and risk of cancer in Taiwan. 300 43

We examined hematopoietic disorders in 74 patients with various malignancies. The proportions of patients with anemia in the case of esophageal carcinoma, gastric carcinoma, colorectal carcinoma, hepatoma, and pancreatic carcinoma were 75%, 87.5%, 77%, 64% and 87.5%, respectively. Hypochromic microcytic anemia was mainly observed in showed patients with carcinoma of the gastro-intestinal tract which showed severe bleeding. The major proportion of patients with hepatoma and pancreatic carcinoma showed normochromic normocytic anemia. The WBC count was usually within the normal range except for patients with liver cirrhosis or generalized metastasis who showed decreased WBC counts. The mean lymphocyte count in the peripheral blood, which is thought to be correlated with the prognosis of cancer patients, was less than 1,500/microliter except for patients with gastric carcinoma, whose five-year survival rate was 28.6%. Monocytosis was mainly observed in patients with colorectal carcinoma and pancreatic carcinoma, accounting for 24.5% of the total cases. This finding may suggest some relationship between cancer and monocytes. Thrombocytosis was seen in patients with severe bleeding, but thrombocytopenia was seen in patients with liver cirrhosis. Most cancer patients showed normo-cellular marrow and normal M/E. We also examined the ferrokinetics and ferritin levels in cancer patients.
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PMID:[Hematological disorders in malignancy]. 301 96

Over 100 patients have received cyclic treatment with polyclonal 131I labeled anti-ferritin and anti-carcinoembryonic antigen (CEA) antibodies from different animal species (rabbit, pig, cynomolgous monkey, bovine, and baboon). Because survival was prolonged from original cyclic treatment, retreatment with original antibodies (recycling) became a necessary consideration. An assay using autoradiography of Ouchterlony gels, with diffusion of patients' sera against the varied radiolabeled antibodies, was developed to detect anti-antibody precipitin bands. Anti-antibody could be detected with a sensitivity to the 60 ng level. Sera from 35 patients given from 1 to 7 separate cycles (2 injections/week, total antibody 6 mg/cycle) of radiolabeled foreign antibody were studied for the production of anti-antibodies. Anti-antibodies were detected in 11 of 22 primary hepatoma patients studied, 3 of 4 intrahepatic biliary cancer patients, and 0 of 9 Hodgkin's disease patients. In all but two of the patients, the anti-antibodies produced were specific for the species used in the treatment of the patient. Eight patients were reinjected (recycled) with previously used antibodies and the presence or absence of precipitin bands correlated with the ability of these antibodies to deposit in the tumor or to be rapidly degraded. The importance of this assay is its simplicity, sensitivity, and the rapid detection of anti-antibody activity for patients requiring treatment with radiolabeled antibodies.
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PMID:Detection of specific anti-antibodies in patients treated with radiolabeled antibody. 301 17

In 67 patients (mean age 51 years, range 26-79), at diagnosis of primary haemochromatosis (PH), grade III or IV liver iron overload was present in all cases, cirrhosis in 85%, transferrin saturation greater than 80% in 75%, serum ferritin greater than 1000 micrograms/l in 84%, and overt diabetes in 48%. Alcohol intake was greater than 150 g/day in 11 patients; six were chronic hepatitis B surface antigen (HBsAg) carriers. HLA-A3 and B7 antigens were present in 64% and 23% versus respectively 22% (p less than 0.01) and 9% (p less than 0.025) in controls. Iron overload was found in the stomach, duodenum, skin and bone marrow in 57, 43, 45 and 59% of the patients studied. Sixty-three patients were followed for 1-260 months (median 24); 43 received regular iron-depleting treatment and 20 did not because of liver failure, cancer or refusal. Cumulative survival was 79%, 67% and 61% at 1, 4 and 10 years, respectively. Ten patients died from hepatocellular carcinoma and two from extrahepatic cancer. The early high mortality rate was due to some cases of advanced disease or cancer. Cumulative survival in the regularly treated group was 95% at 1 year and 91% at 4 and 10 years, which was higher than in the untreated group.
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PMID:Clinical, biochemical and histological features of primary haemochromatosis: a report of 67 cases. 302 81

The mRNAs for the heavy and light subunits of the iron-storage protein ferritin occur in cells largely as inactive ribonucleoprotein particles, which are recruited for translation when iron enters the cell. Cytoplasmic extracts from rat tissues and hepatoma cells were shown by an electrophoretic separation procedure to form RNA-protein complexes involving a highly conserved sequence in the 5' untranslated region of both ferritin heavy- and light-subunit mRNAs. The pattern of complex formation was affected by pretreatment of rats or cells with iron. Crosslinking by UV irradiation showed that the complexes contained an 87-kDa protein interacting with the conserved sequence of the ferritin mRNA. We propose that intracellular iron levels regulate ferritin synthesis by causing changes in specific protein binding to the conserved sequence in the ferritin heavy- and light-subunit mRNAs.
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PMID:Cytoplasmic protein binds in vitro to a highly conserved sequence in the 5' untranslated region of ferritin heavy- and light-subunit mRNAs. 312 26

Hepatocellular carcinoma cells of the PLC/PRF/5 cell line had 1.9 x 10(5) transferrin receptors per tumor cell with a Kd of 1.5 x 10(-8) M. At high concentrations of transferrin the binding was not saturable. Transferrin internalization by hepatoma cells was shown by time and temperature-dependent binding studies and by pronase experiments. Transferrin recycling was confirmed by the demonstration of a progressive increase in the cellular molar ratios of iron to transferrin and by chase experiments. Ammonium chloride interfered with iron unloading. The vinca alkaloid vincristine inhibited iron and transferrin uptake. The hepatocarcinoma cells appeared to lack asialoglycoprotein receptors and therefore internalized partially desialated transferrin by the regular route. Iron uptake from transferrin was markedly inhibited by the hydrophobic ferrous chelator 2,2' bipyridine but was relatively unaffected by the hydrophilic ferric chelator desferroxamine. The implication that ferrous iron was involved in postendocytic transvesicular membrane iron transport was supported by a study in which hepatoma cells were shown to take up large amounts of ferrous iron suspended in 270 mM sucrose at pH 5.5. The interaction at this pH between surface labeled hepatoma cell extracts and ferrous iron on a Sephacryl S-300 column suggested that the postendocytic transvesicular transport of iron through the membrane was in part protein mediated. The endocytosed iron in hepatoma cells was found in association with ferritin (33%), transferrin (31%) and a low molecular weight fraction (21%).
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PMID:Transferrin iron interactions with cultured hepatocellular carcinoma cells (PLC/PRF/5). 316 34

Localization of ferritin using a pre-embedding diffusion technique and an indirect localization sequence has been made in 34 cases of human liver under normal and several pathological conditions. With light microscopic observation, positive immuno-staining for ferritin was demonstrated as diffuse deposits in the hepatocytes and Kupffer cells. Intensity of the positive immuno-staining for ferritin in these cells appeared to roughly coincide with serum ferritin levels of each patient, but showed no disease specificity, although hepatoma cells contained weak deposits or were negative from immuno-staining for ferritin. With electron microscopic studies, intracellular antigen was well preserved in the hepatocytes and Kupffer cells in most cases with the positive immuno-staining for ferritin being observed in cytosol and a few cisternae of rough endoplasmic reticulum. Content of the positive immuno-staining for ferritin differed considerably from one case to another and one cell to another even in the same case. There was no immuno-staining for ferritin in hemosiderin pigment, lysosome, most of rough endoplasmic reticulum, Golgi complexes, and nucleus in both cells.
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PMID:Localization of ferritin in human liver diseases studied by immuno-histochemical and immuno-electron microscopic procedures. 331 30

Purified recombinant human ferritin composed solely of H subunit was radiolabeled and incubated with proerythroleukemic K562 human cells. A specific binding was detected, and it could be displaced only by ferritins, natural or recombinant, containing large proportion of the H subunit. The specific ferritin H-chain binding was saturable, and cells showed 17,000 to 23,000 binding sites per cell. The affinity constant measured at 37 degrees C was of 3 x 10(8) M-1. Treatment with pronase eliminated the specific binding. The binding sites were expressed in a high number during the cellular exponential phase of growth and progressively decreased to disappear when cells reached the plateau phase. Treatment of the cells with desferrioxamine increased recombinant H-ferritin binding, while iron had little effect. K562 cells induced to differentiate by hemin failed to bind ferritin H. Ferritin H-chain binding capacity is present on various cell lines such as HL60, lung cancer, and hepatoma cells. Analysis of the binding sites by western blotting showed a peptide with apparent mol wt of about 100 kd.
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PMID:Characteristics and expression of binding sites specific for ferritin H-chain on human cell lines. 342 30

Serum ferritin is present in two forms--a glycosylated form that results from active secretion by cells and a nonglycosylated form that is directly released by damaged cells. Glycosylated ferritin binds to concanavalin A (Con A) through the glucose and/or mannose residues of the molecule. Patients with neuroblastoma frequently present at diagnosis with abnormally elevated levels of serum ferritin. The ferritin levels will, however, return to normal with clinical remission, suggesting that the tumor is the origin of the elevated ferritin. With the use of a Con A binding assay, an investigation was made as to whether the increased levels of serum ferritin at diagnosis in neuroblastoma patients resulted from active secretion by the tumor or were the consequence of direct release of ferritin from damaged tissue. Serum samples were collected at diagnosis from 36 children with neuroblastoma and from 16 normal healthy subjects. Tissue ferritins were purified from normal human liver, placenta, HeLa cells, human neuroblastoma, and hepatoma cells grown in culture. Serum and tissue ferritins were measured before and after binding with Con A. Sixty-three percent of serum ferritin from neuroblastoma patients and 66% of serum ferritin from normal subjects were bound to Con A, suggesting that they were glycosylated and were likely to have been secreted. On the other hand, only 28% of tissue ferritin were bound to Con A. Furthermore, most patients showed abnormally elevated levels of serum ferritin, and 63% of these ferritins were bound to Con A. These results are compatible with the hypothesis that much of the elevated ferritin in sera of patients with neuroblastoma seen at diagnosis is the result of secretion of ferritin by the tumor.
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PMID:Source of increased ferritin in neuroblastoma: studies with concanavalin A-sepharose binding. 345 40


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